Annual Scientific Report 2011

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Annual Scientific Report 2011 The mission of IDIBAPS is to combine high-quality clinical research with high-level basic research in order to achieve a more effective transfer of scientific results in the prevention and treatment of the most common health issues in our country.

AnnuAl Scientific RepoRt

Hospital Clínic – Fundació Clínic University of Barcelona – Faculty of Medicine CSIC – Institut d’Investigacions Biomèdiques de Barcelona (IIBB) (Spanish National Scientific Research Council – Barcelona Institute of Biomedical Research) Rosselló, 149-153 Generalitat de Catalunya – Departament d’Economia i Coneixement 08036 Barcelona (Catalan Autonomous Government – Ministry for the Economy www.idibaps.org and Knowledge) Published by: IDIBAPS Rosselló, 149-153 – 08036 Barcelona

Editorial Board: Dr Ramon Gomis, IDIBAPS Director Dr Joan Rodés, Member of the IDIBAPS Scientific Council Dr Pastora Martínez, IDIBAPS Managing Director Mrs Teresa Peña, Fundació Clínic Research Management Office Mrs Sandra Vidal, Fundació Clínic Technical Office Mrs Gemma Pedrola, IDIBAPS Assistant to the Director Mr Àlex Argemí, IDIBAPS Communication Officer

Production and design: BPMO Edigrup C/ Guitard, 43, 1ª planta 08014 Barcelona Tel.: 933 637 840 www.bpmoedigrup.com

Legal Deposit: B-47.798-2005

Centres de recerca de Catalunya IDIBAPS is accredited as a Health This centre has been cofinanced by the European Union through Care Research Institute by the the European Regional Development Fund (ERDF) Carlos III Health Institute inDeX

foreword iDiBApS

• introduction ...... 8 • idiBaps research and innovation ...... 14 • scientific core facilities ...... 30 • networking ...... 38 • training ...... 51 • idiBaps and society ...... 55

1 AReA 1 Biological aggression and response mechanism ...... 56

2 AReA 2 respiratory, cardiovascular, renal and pathoBiology Bioengineering ...... 96

3 AReA 3 liver, digestive system and metaBolism ...... 140

4 AReA 4 clinical and eXperimental neuroscience ...... 196

5 AReA 5 oncology and haematology ...... 254

transversal research groups ...... 308

index

• team leaders indeX ...... 321 6 August Pi i Sunyer (Barcelona 1879 – Mexico 1965), eminent doctor and politician who changed the entire course of biomedicine and politics in this country, after whom this Institute is named.

The Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) is a public research centre dedicated to translational research in the field of biomedicine. It aims to integrate state-of-the-art basic research and quality clinical research in order to acquire and transfer knowledge concerning the main health problems present in our society, with the final purpose of improving their prevention and treatment. Inno- vation and technological progress are therefore essential lines of activity at IDIBAPS. The IDIBAPS task force combines more than 460 researchers, making IDIBAPS probably one of the most powerful translational research centres in Spain.

IDIBAPS is located in a melting pot for biomedical research, Barcelona Clinic Campus. The University of Barcelona School of Medicine and Barcelona’s Hospital Clínic are found in the same area. This institutional combination is ideal for creating powerful synergies and ensuring that the IDIBAPS research is efficiently transferred to the patient and included in the training of new health professionals.

The Centre’s research activities are divided into five different areas which group over 59 top-level research teams and over 460 investigators. IDIBAPS’ researchers are distributed into the following fields of activity: Biological Aggression and Response Mechanisms (Area 1), Respiratory, Cardiovascular and Renal Pathobiology and Bio- engineering (Area 2), Liver, Digestive System and Metabolism (Area 3), Clinical and Experimental Neuroscience (Area 4), and Oncology and Haematology (Area 5).

The data presented in this Annual Scientific Report detail the ever-growing scientific output led by IDIBAPS’ investigators, and their capacity for attracting public and private funding. In 2011, they reached a new record, with 906 original articles published in high-impact-factor scientific journals. This is only possible thanks to hard work, enthusiasm and infrastructures such as the recently built Esther Kop- lowitz Research Centre or the soon-to-be-finished CELLEX Research Centre. This enormous potential for capturing resources and their conversion into results ap- plicable to clinical practice constitute the best guarantee for securing the future of the Institute.

Scientific breakthroughs are never the result of chance. They are long-term com- mitments that involve not only researchers, but also society as a whole. IDIBAPS is a consortium that undertakes such a commitment in Catalonia: to encourage translational research, innovation and technological progress in the field of biomedicine through different programmes addressing diseases with a high prevalence, and high morbidity and mortality rates.

7 INTRODUCTION

Esther Koplowitz Research Centre (CEK) – Patronage to continue innovating

In order to guarantee financial stability and ensure con- Salud Carlos III) and the University of Barcelona (Uni- tinuity, IDIBAPS recognizes that the financing of R&D versitat de Barcelona), as well as the support of other and research institutes should not only come from patrons such as the Esther Koplowitz Foundation, public agencies but also from private funding institu- the Cellex Private Foundation, Sardà Farriol Action for tions. Therefore, fundraising is extremely important Diabetes Research (Acción Sardà Farriol para la Inves- at two levels: at the researcher level to finance their tigación en Diabetes) and Laboratoris Esteve. own research and at the institutional level to be able to finance strategic infrastructures and interventions. The Funded with a capital contribution of €15 million from ability to obtain private funds is also a reflection of the the Esther Koplowitz Foundation to the Clínic Foun- quality and prestige of the institution and its research- dation, the investment in the building exceeds €50 ers. In this aspect, IDIBAPS and its researchers also million. With space for more than 350 researchers, have a good track record of obtaining private funds. In the CEK receives international scientists and PhD stu- recent years, around €35 million has been obtained at dents, thus fostering the exchange of experience and the institutional level, enabling the acquisition of new professional cooperation. In 2011, it reached its full equipment, the construction of new lab facilities and operating capacity. the modernisation of the old ones. The CEK building houses a large number of the The Esther Koplowitz Research Centre (CEK) is a IDIBAPS teams, covering a massive range of research wonderful example of public and private co-respon- lines. The biomedical progress achieved in the CEK sibility, since it benefits from the participation of the has its grounds in the history and the top-level re- Catalan Autonomous Government (Generalitat de search developed by IDIBAPS over the years. The Catalunya), the Spanish Ministry for the Economy and multitude of international researchers that combine Competitiveness (Ministerio de Economía y Competi- their efforts in the new facilities allows us to look to tividad), the Carlos III Health Institute (Instituto de the future with hope and enthusiasm. 8 INTRODUCTION

Management Report

1. Funding of IDIBAPS. IDIBAPS funding in 2011 to- 2. Resource volume generated by the IDIBAPS re- talled more than €21 million. Twenty-seven percent searchers. This is a very significant aspect. The resourc- of this amount corresponded to the contribution of es generated by IDIBAPS researchers during the finan- the Ministry of Economy and Knowledge (Departa- cial year 2011 totalled €39,325,319. These resources ment d’Economia i Coneixement) and the Ministry have been managed by different institutions: IDIBAPS of Health (Departament de Salut) of the Catalan itself (€12,857,082) and the Clínic Foundation (Fundació Autonomous Government (Generalitat de Catalu- Clínic per a la Recerca Biomèdica) (€26,468,237). It is nya). The rest of the funding executed by IDIBAPS important to mention that 63% of the resources ex- in 2011 corresponded to calls for research funding ecured by IDIBAPS researchers in 2011 (more than €24 (58%), as well as contracts and cooperation agree- million) corresponded to competitive research projects ments with private entities (12%) and financial in- or were provided on a grant basis (calls for funding). The come sources (3%). remaining 37% was distributed as follows: contracts with private entities (21%); clinical trials managed by the Clinic Foundation (3%); donations (11%); and teaching contracts (3%). IDIBAPS FUNDING 2011

COMPETITIVE RESoURcES ExEcURED By PROJECTS IDIBAPS RESEARchERS IN 2011 (APPLICATIONS FOR FUNDING) COMPETITIVE RESEARCH 12,594,000 : 58% PROJECTS 24,680,246 : 62.8% M. ECONOMY AND KNOWLEDGE CONTRIBUTION 5,006,000 : 24% PRIVATE ENTITIES 8,146,038 : 20.7%

PRIVATE FUNDING DONATIONS 2,496,000 : 12% 4,230,853 : 10.7% M. HEALTH CONTRIBUTION CLINICAL TRIALS 600,000 : 3% 1,168,849 : 3% FINANCIAL INCOME TEACHING 585,000 : 3% 1,099,333 : 2.8%

Keeping our focus on translational research and innovation

IDIBAPS has a very clear mission statement that There is no question that 2011 was a challenging focuses all its efforts in research on achieving both year due to the difficult and unpredictable economic a clinical and medical approach. That means that environment. In spite of that, IDIBAPS kept its focus IDIBAPS has a unique strength in clinical re- on translational research and high-impact cooperation search and a clear mandate to orientate its ba- with relevant stakeholders, including other research sic research projects to relevant clinical ques- and innovation centres, industrial companies and tions. Additionally, there is an increasing focus on technology-driven small and medium-sized enterprises developing capabilities to bring our biomedical and (SMEs). This was reflected in the fact that 8 additional health-care knowledge to the market, in close co- patents were submitted (including PCT extensions) in operation with both local and international research 2011, two of them jointly with industrial partners, two and health-care centres and biotech and medtech with large national research organisations and one with industrial partners. All this is being developed SMEs. In addition, 4 technology transfer agreements jointly with the Direction of Innovation of Hospital were closed with biotech and medtech SMEs, raising Clínic de Barcelona and the Innovation Manage- the number of Hospital Clínic and IDIBAPS innovation ment Offices of Clinic Foundation. and transfer deals in the period 2007-2011 to 66.

9 Organisational Chart

Board of GovernorS Scientific council chAIRMAN Jesús Ávila, Josep Maria Martorell, Severo Ochoa Molecular Biology Centre, Madrid Director General for Research, Catalan Autonomous José A. Berciano, Government (Generalitat de Catalunya) Neurology Department, Hospital Universitario Marqués de Valdecilla, Santander VIcE-chAIRMAN Lisardo Boscá, cristina Suñol, Biochemical Institute, Universidad Complutense, Madrid Director of Barcelona Biomedical Research Institute - CSIC Roberto Gallego, Neuroscience Institute, Universidad Miguel Hernández, BoARD MEMBERS Alicante Jordi Alberch, Francisco Javier García-Sancho, Research Vice-Dean of University of Barcelona Biology and Molecular Genetics Institute, School of Joan Bigorra, Medicine, Valladolid Innovation Director of Hospital Clínic of Barcelona Roberto Groszmann, Lluís calvo, Hepatic Hemodinamic Lab. Yale University School of Institutional Coordinator of the CSIC in Catalonia Medicine, West Haven Francesc cardellach, José López Barneo, Dean of the University of Barcelona School of Medicine Department of Medical Physiology and Biophysics, School carles constante, of Medicine, Seville Director General for Healthcare Regulation, Planning and carlos López otín, Resources – Catalan Autonomous Government (Generalitat Department of Biochemistry and Molecular Biology, de Catalunya) University of Oviedo, Oviedo Ramon Gomis, José M. Mato, Director of IDIBAPS Cooperative Bioscience Research Centre (CIC bioGUNE), Josep Maria Piqué, Biscay General Manager of Hospital Clínic of Barcelona Federico Mayor, Severo Ochoa Molecular Biology Centre, Madrid SEcREtARy Ginés Morata, Pastora Martínez, Severo Ochoa Molecular Biology Centre, Madrid Managing director of IDIBAPS Miguel Ángel del Pozo, Integrin Signalling Laboratory, National Cardiovascular Research Centre (CNIC), Madrid ciril Rozman, Haematology Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona Margarita Salas, Severo Ochoa Molecular Biology Centre, Madrid Jesús San Miguel, Haematology Department, Hospital Clínico de Salamanca, Salamanca Francisco Sánchez-Madrid, Immunology Department, Hospital La Princesa, Madrid Eugenio Santos, Cancer Research Centre, Salamanca

10 INTRODUCTION

director’S adviSory committee MANAGEMENt coMMIttEE tEAchING cooRDINAtoR Ramon Gomis, Neus Agell, Director of IDIBAPS University of Barcelona School of Medicine cristina Suñol, Director of Barcelona Biomedical Research Institute - CSIC GUESt MEMBERS Francesc cardellach, Joan Rodés, Dean of the University of Barcelona School of Medicine Member of the IDIBAPS Scientific Council Antonio Sisó, PERSoNS REPRESENtING thE INStItUtIoNS CAPSE-GESCLINIC Research Coordinator Manel Ramos, Joan Bigorra, Hospital Clínic de Barcelona Doctors’ Representatives Hospital Clínic Innovation Director Guadalupe Mengod, Jaume Bosch Researcher at Barcelona Biomedical Research Institute - CSIC CIBERehd Scientific Director Josep M. Gatell, PERSoNS REPRESENtING thE AREAS National Coordinator of the RETIC on AIDS Area 1 Àlvar Agustí, Jordi Vila Estapé, Coordinator CIBERres Scientific Director Ana Angulo, Representative Elías campo Hospital Clínic Research Director Area 2 Ramón Farré, Coordinator SEcREtARy Joan Albert Barberà, Representative Albert Barberà, Scientific Manager of IDIBAPS Area 3 Julià Panés, Coordinator Jorge Ferrer, Representative

Area 4 Anna Planas, Coordinator Pablo Villoslada, Representative

Area 5 Dolors colomer, Coordinator cristina Nadal, Representative

11 INTRODUCTION

IDIBAPS Organisational Chart

The organisational charts for IDIBAPS and the Clinic Foun- dation are shown in the following graphics. With a view to ensuring smooth functioning, the research structure of IDIBAPS is supported by the Management and Administra- tion Departments offered by the Fundació Clínic.

Biobank Biosecurity Bioinformatics Biostatistics and Knowledge Data Management Management Flow Cytometry and Cell Separation Scientific Laboratories core Scientific Management Facilities Management Functional Genomics Scientific Manager Medical Imaging

Director’s Advisory committee Director

Ethical committee in clinical Research Governing Scientific Board council Ethical committee in Animal Biological Experimentation Aggression and Response Mechanisms Research Areas Managing Clinical and Director Experimental Neurosciences

Administra- tion Units Liver, Digestive System and Metabolism

Oncology and Hematology

Respiratory, Cardiovascular and Kidney Transversal Bioengineering and Research Groups Biopathology

12 INTRODUCTION

Clinic Foundation Organisational Chart

Financial Management Accounting of Grants Controlling Invoices Management

Accounting & Finance Department

technical Managing office Director Human Public Contracts Resources Management

Purchasing Fellowship Puchasing Director human Management and General Resources Services General Service

Governing Board

International cooperation Project Manager office Research Management International office Competitive Grants Administration National Competitive Grants Agreements, Innovation Mnagement Contracts and office Patronage

13 IDIBAPS ReSeARCh AND INNOvATION

Since its creation in 1996, IDIBAPS has shown constant An original paper is taken to be an article contributing new growth of the principal quality indicators for a research knowledge as a result of experiments performed by inves- centre: the number of scientific publications; the total im- tigators of the Institute. In order to be considered as such, pact factor; the financial resources; and the contracting of the article must have among its signing authors at least qualified personnel. one member of IDIBAPS pertaining to one of the research teams reflected in this Report, with specific mention of A full description of how these indicators and other suc- IDIBAPS or of the entities within the IDIBAPS Consortium. cess factors have evolved over time is presented below with graphs to provide clarity.

Scientific Output

The number of publications and their impact factor represent one of the most reliable indicators of the competitiveness of a research centre. Both parameters show a clear rising trend in IDIBAPS. In 2011 alone, there were 906 original publications in scientific journals with an impact factor greater than 0.5.

oriGinal articleS 2003-2011

2011: 906

2010: 846 2009: 840

2008: 736

2007: 686

2006: 577

2005: 537 2004: 531

2003: 475

14 IDIBAPS RESEARCH AND INNOVATION

The investigators working for the different institutions It should be noted that the sum of the articles per area is that form part of IDIBAPS are distributed into 5 ﬁ elds of higher than the institutional total because publications re- activity. Each area is divided into different teams that sulting from collaboration between teams in two different combine in-house research conducted with their own areas have been counted once for each area. The graph lines of research and cooperation with other teams. Apart shows that production in all the areas was of a very high from the 5 IDIBAPS areas, this report contains a speciﬁ c level, and collaboration among areas increased considera- section dedicated to transversal groups doing research bly compared with the previous year. in Primary Care, Nursing, Pharmacology and Clinical Trials, which also play a very important role in translational research.

The areas reported on are listed below, with graphs showing each area’s scientiﬁ c output – once again, original papers only.

ORIGINAL ARTICLES 2009-2011

1. Biological aggression and response mechanisms 2. Respiratory, cardiovascular and renal pathobiology and bioengineering 3. Liver, digestive system and metabolism 4. Clinical and experimental neuroscience 5. Oncology and haematology 232 221 223 212 210 210 200 197 192

200 187 162 163 161

160 156 138

2009 120 2010

2011 80

0 Area 1 Area 2 Area 3 Area 4 Area 5

15 IDIBAPS ReSeARCh AND INNOvATION IMPACT FACTOR 2002-2011

The impact factor (IF) of the journals in which the articles are published provides a measure or marker of the influence of the research carried out in a given centre. It is based on statistical data from the number of times 2011: 4,725 articles published in a particular journal are cited. Although there are many factors that may be just as, or even more, 2010: important in terms of analysing the work carried out by 4,177 our researchers, the IF is an objective measurement that 2009: 3,879 serves as a guide. In this Report, IF considered are those indicated at the Journal Citation Report 2010 (ISI Web of Knowledge). 2008: 3,051

The progress made in terms of the total IF for IDIBAPS 2007: 3,062 publications in recent years is shown in the figure on the right side. In 2011, the 906 articles published by IDIBAPS 2006: 2,625 investigators reached a total of 4,725.06 IF points. This means that the mean IF per article published by IDIBAPS 2005: 2,242 in 2011 is 5.22 - a figure that implies a significant increase 2004: 2,183 with respect to the 4.94 recorded in 2010. Added to this, close to 60% of these original papers appeared in journals 2003: 2,101 in the upper quartile of impact in their field. Thus, while 2002: 1,888 the number of publications increases yearly, there has been no drop in quality.

mean impact factor / oriGinal article 5.2 4.9 4.5 4.4 4.4 4.4 4.5 4.3 4.2 4.2

2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

16 IDIBAPS ReSeARch AnD InnovAtIon

Journals Index

This list reflects the 50 journals with the highest Impact Factors in which IDIBAPS investigators published original articles during 2011.

Total Original Total Original Journal IF Journal IF Articles Articles NEW ENGL J MED 53.49 3 PLOS GENET 9.54 1 NAT GENET 36.38 5 J HEPATOL 9.33 9 NATURE 36.10 4 J ALLERGY CLIN IMMUN 9.27 1 LANCET 33.63 2 BRAIN 9.23 1 JAMA-J AM MED ASSOC 30.01 1 ANN RHEUM DIS 9.08 10 LANCET NEUROL 21.66 2 CELL DEATH DIFFER 9.05 1 J CLIN ONCOL 18.97 8 LEUKEMIA 8.97 2 LANCET ONCOL 17.76 3 BIOL PSYCHIAT 8.67 3 J EXP MED 14.78 2 ARTHRITIS RHEUM-US 8.44 3 CIRCULATION 14.43 3 SCHIZOPHRENIA BULL 8.27 3 J CLIN INVEST 14.15 2 CANCER RES 8.23 2 BRIT MED J 13.47 1 CLIN INFECT DIS 8.19 3 PLOS BIOL 12.47 1 HUM MOL GENET 8.06 2 GASTROENTEROLOGY 12.03 6 NEUROLOGY 8.02 6 AM J HUM GENET 11.68 1 ANN SURG 7.47 2 HEPATOLOGY 10.89 7 CLIN CANCER RES 7.34 6 ARCH GEN PSYCHIAT 10.78 1 J NEUROSCI 7.27 2 ANN NEUROL 10.75 3 J PATHOL 7.27 2 ARCH INTERN MED 10.64 1 DIABETES CARE 7.14 3 GUT 10.61 8 ARCH NEUROL-CHICAGO 7.11 2 BLOOD 10.56 22 J BONE MINER RES 7.06 1 AM J RESP CRIT CARE 10.19 4 DIABETOLOGIA 6.97 1 EUR HEART J 10.05 5 CLIN CHEM 6.89 2 CURR BIOL 10.03 1 EMERG INFECT DIS 6.86 1 P NATL ACAD SCI USA 9.77 1 CEREB CORTEX 6.84 1

The number of editorials (70) and reviews (112) has also Total IF: Mean IF: 906 originals been outstanding. This reflects the role of the members of 4,725.06 5.22 IDIBAPS as opinion leaders. Moreover, also documented in 112 reviews 588.94 5.26 this report are 51 multicentre studies in which IDIBAPS 70 editorials 442.44 6.32 researchers have actively participated, but without being 17 guidelines 64.71 3.81 the main signing authors. These researchers are specifically 51 multicentre 715.54 14.03 mentioned in some section or annex of the article as for- studies ming part of the study group.

17 IDIBAPS ReSeARCh AND INNOvATION

Since the impact factor (IF) refers to the journals and not The total is 182,487 citations received by IDIBAPS studies specifically to the published articles, the graph below in the last five years. This figure confirms the international shows the number of citations received by the studies pu- projection of the work carried out by this Institute. blished by IDIBAPS investigators (data calculated through the ISI Web of Knowledge): Another important aspect to be taken into account is the type of research reflected in the original works published by our investigators. Of note is the fact that 28% of the original publications listed in this report were the result of collabo- citationS ration between two or more IDIBAPS teams.

39,974

39,236

38,267

35,978

29,032

2007 2008 2009 2010 2011

18 IDIBAPS ReSeARCh AND INNOvATION

Clinical Guidelines

To provide a general overview of IDIBAPS’ impact on soci- The list below reflects the participation of IDIBAPS investi- ety, it is important to mention the fact that every year, our gators in clinical guidelines published in 2011 in international researchers participate in the elaboration of international journals subject to peer review. In addition to contributing clinical guidelines. These guidelines are not only published in new data for improving patient treatment, the influence of high-impact peer-reviewed journals but also have a tremen- the IDIBAPS investigators places them at the head of expert dous impact on patient care and on society in general. Con- committees that establish the new trends to be followed in sequently, IDIBAPS researchers are responsible for setting medical practice. The names of the IDIBAPS investigators new trends to be followed in medical practice. are shown in capital letters under the section Authors:

Associated Journal title Reference IF Authors Short text

Cavo M; Rajkumar SV; Palumbo A; Moreau International Myeloma Working P; Orlowski R; BLADE J; Sezer O; Ludwig Group consensus approach to the H; Dimopoulos MA; Attal M; Sonneveld P; treatment of multiple myeloma 117 (23): Boccadoro M; Anderson KC; Richardson BLOOD 10.56 patients who are candidates 6063-6073 PG; Bensinger W; Johnsen HE; Kroeger N; for autologous stem cell Gahrton G; Bergsagel PL; Vesole DH; Einsele transplantation H; Jagannath S; Niesvizky R; Durie BGM; San Miguel J; Lonial S

Tendera M; Aboyans V; Bartelink ML; ESC Guidelines on the diagnosis Baumgartner I; Collet JP; Cremonesi A; and treatment of peripheral artery De Carlo M; Erbel R; HERAS M; Kownator diseases: Document covering S; Minar E; Ostergren J; Poldermans D; atherosclerotic disease of RIAMBAU V; Roffi M; Sievert H; van Sambeek extracranial carotid and vertebral, EUR HEART J 32(22):2851-906 10.05 M; Zeller T; Bax J; Auricchio A; Baumgartner mesenteric, renal, upper and H; Ceconi C; Dean V; Deaton C; Fagard R; lower extremity arteries: the Funck-Brentano C; Hasdai D; Hoes A; Knuuti Task Force on the Diagnosis and J; Kolh P; McDonagh T; Moulin C; Popescu B; Treatm Reiner Z; Sechtem U; Sirnes PA; Torbicki A; Vahanian A; Windecker S

Treatment of muscle-invasive and Stenzl A, Cowan NC, De Santis M, Kuczyk metastatic bladder cancer: update EUR UROL 59(6):1009-18 8.84 MA, Merseburger AS, Ribal MJ, Sherif A, of the EAU guidelines Witjes JA.

Comprehensive risk reduction in patients with atrial fibrillation: Kirchhof P; Lip GYH; Van Gelder IC; Bax J; Emerging diagnostic and Hylek E; Kaab S; Schotten U; Wegscheider K; THROMB therapeutic options Executive 106 (6): 1012-1019 4.70 Boriani G; Ezekowitz M; Diener H; Heidbuchel HAEMOSTASIS summary* of the report from H; Lane D; MONT L; Willems S; Dorian P; the 3rd AFNET/EHRA consensus Vardas P; Breithardt G; Camm AJ conference

19 IDIBAPS ReSeARCh AND INNOvATION

Associated Journal title Reference IF Authors Short text

New treatment guidelines for acute Nivoli AMA; COLOM F; Murru A; Pacchiarotti bipolar depression: A systematic J AFFECT DISORDERS 129 (1-3): 14-26 3.74 I; Castro-Loli P; Gonzalez-Pinto A; Fountoulakis review KN; VIETA E

Guidelines for emergency management of acute heart Llorens P; MIRO O; Sanchez FJM; Puente failure: consensus of the Acute EMERGENCIAS 23 (2): 119-139 3.09 PH; Rodriguez JJ; Gil V; Perello R; Aguirre A; Heart Failure Working Group of Valero A the Spanish Society of Emergency Medicine (ICA-SEMES) in 2011

Comments on the 2011 ESC/EAS guidelines for the management Anguita M; Alegria E; Barrios V; Casasnovas of dyslipidemias. A report of the REV ESP CARDIOL 64 (12): 1090-1095 2.16 JA; Escobar C; Leon M; Luengo E; Llisterri JL Task Force of the Clinical Practice (HERAS M) Guidelines Committee of the Spanish Society of Cardiology

Management of patients with Raviele A; Giada F; Bergfeldt L; Blanc JJ; palpitations: a position paper EUROPACE 13 (7): 920-934 1.84 Blomstrom-Lundqvist C; MONT L; Morgan from the European Heart Rhythm JM; Raatikainen MJP; Steinbeck G; Viskin S Association

National consensus document by GESIDA/National Aids Plan on antiretroviral treatment in ENFERM INFEC MICR Panel de expertos de GESIDA y Plan Nacional 29(3):209.e1-103. 1.66 adults infected by the human CL sobre el Sida (GATELL JM, MALLOLAS J) immunodeficiency virus (January 2011 update)

Alobid I; Anton E; Armengot M; Chao J; Colas C; del Cuvillo A; Davila I; Dordal MT; Escobar C; Fernandez-Parra B; Gras- Cabrerizo JR; Ibanez MD; Lluch M; Mateu V; SEAIC-SEORL. Consensus Montoro J; Gili JR; MULLOL J; Navarro AM; J INVEST ALLERG Document on Nasal Polyposis. 21 Suppl 1:1-58 1.49 Pumarola F; Rondon C; Sanchez-Hernandez CLIN POLINA Project MC; Sarandeses A; Soler R; Valero AL; Rhinoconjunctivitis Committee; Spanish Society of Allergy and Clinical Immunology; Rhinology and Allergy Commission; Spanish Society of Otorhinolaryngology

20 IDIBAPS ReSeARCh AND INNOvATION

Associated Journal title Reference IF Authors Short text

Alobid I; Alonso JR; Barrot C; Benitez P; Canizares S; Castanyer T; Centellas S; Civeira MED CLIN- E; Climent B; Duenas A; FERNANDEZ-SOLA J; Multiple chemical sensitivity 136(15):683-7 1.41 BARCELONA Ferrer A; Gene M; Godas T; Gomez E; Montori E; Munne P; NOGUE S; PICADO C; Rovira E; SANZ P; Valero A

Garcia Del Muro X; Martin J; MAUREL J; Cubedo R; Bague S; de Alava E; Pousa AL; Soft tissue sarcomas: clinical MED CLIN- 136(9):408.e1-8 1.41 Narvaez JA; Ortiz E; Pomes J; Poveda A; practice guidelines BARCELONA Romasanta LP; Tendero O; Viñals JM; Grupo Español de Investigacion en Sarcomas (GEIS)

SEOM clinical guidelines for the MAUREL J; Fernandez-Martos C; Feliu J; CLIN TRANSL ONCOL 13 (8): 525-527 1.25 treatment of anal cancer Isla D

Hepatocellular and biliary tract carcinomas: SEOM clinical CLIN TRANSL ONCOL 13 (8): 536-544 1.25 Feliu J; Sastre J; MAUREL J; Isla D guidelines

SEOM guidelines on thrombosis CLIN TRANSL ONCOL 13 (8): 592-596 1.25 Munoz AJ; VINOLAS N; Cubedo R; Isla D in cancer patients

Barberan J; MENSA J; Llamas JCV; Ramos IJ; Ruiz JCG; Marin JRC; Tello PB; Massana MB; Vidal JB; Vinas JMC; Huelva FJC; Pons EC; Mediavilla JD; Morfa MLD; Barrigon FE; Avellan PF; Lopez SG; Garcia CG; Maraver DH; Recommendations for the de la Guia AL; JIMENEZ JL; Chacon EM; Rubio treatment of invasive fungal REV ESP QUIM 24 (4): 263-270 0.67 MO; de Oteyza JP; Ramirez GR; Contreras RR; infection caused by filamentous Barbero AR; Tarrats MR; Felix DR; Godoy PS; fungi in the hematological patient Salinas AS; Alonso MA; Torroba JD; Ferreiras DV; Lopez LV; Garcia JMA; Perea JRA; Moreno RC; Cancer RC; Abete JF; Rodriguez JG; Gomez JG; de la Pedrosa EGG; Baranda JMM; Garcia FJP; Camps IR; Lleti MS; Cisneros JD

Blanquer J; Aspa J; Anzueto A; FERRER M; SEPAR Guidelines for Nosocomial ARCH 47 (10): 510-520 0 Gallego M; Rajas O; Rello J; de Castro FR; Pneumonia BRONCONEUMOL TORRES A

21 IDIBAPS ReSeARCh AND INNOvATION

Research Funding

Funding obtained from open calls for funding is one of the main driving forces of research. The table below shows the large number of projects granted in 2011 by different entities that help make the excellence of the IDIBAPS possible:

Public funding Funding Institutions Number of Projects Instituto de Salud Carlos III (ISCIII) 26 Ministerio de Economía y Competitividad (MINECO) - Plan Nacional I+D+i [Ministry of the Economy and 24 Competitiveness – National R&D Plan] European Commission 13 Ministerio de Sanidad, Política Social e Igualdad [Ministry of Health, Social Policy and Equality] 10 National Institute of Health (NIH) 6 Generalitat de Catalunya [Catalan Autonomous Government] - ACC10 i AGAUR 5 Agence Nationale Français de recherches sur le sida et les hépatites virales 1

Private funding Funding Institutions Number of Projects Fundación Mutua Madrileña 3 Asociación Española Contra el Cáncer (AECC) [Spanish Association against Cancer] 2 FIPSE 2 Fundació Marató TV3 2 La Caixa “Obra Social” 1 COIB - Col.legi Oficial Infermeria de Barcelona [Barcelona Official College of Nursing] 1 Caja Navarra 1 MAPFRE 1 Michael J. Fox Foundation for Parkinson 1 Premi Fund. Roche Transplant. 1 Lymphoma Research Foundation 1

22 IDIBAPS ReSeARCh AND INNOvATION

IDIBAPS Researchers and Technical Personnel

In the area of human Resources, it should be mentioned that many of the IDIBAPS professionals come from the different institutions that make up the IDIBAPS consortium. The table below shows the origin of the 461 accredited investigators:

Investigators accredited by IDIBAPS Hospital Clínic and University of Barcelona 142 Hospital Clínic de Barcelona 184 CSIC - IIBB 34 University of Barcelona 33 IDIBAPS 47 Fundació Clínic 16 ICREA 5 totAL: 461

Funding obtained in 2011for hiring researchers and technical personnel can come from different sources:

No. of Aid Agreements Sources of Funding type and contracts Instituto de Salud carlos III (IScIII) Pre-doctoral Research Grants (FI) 3 Post-doctoral Research Grants (Sara Borrell) 3 Senior Researcher Grants - ISIS 1 Post-residency (Rio Hortega) 6 Support Technician 1 Extension of Studies (BAE) 2 Ministry of Science and Innovation (MIcINN) Pre-doctoral Research Grants (FPI) 5 Pre-doctoral Research Grants (FPU) 5 Post-doctoral Research Grants (Juan Cierva) 1 Senior Researcher Grants (Ramon y Cajal) 1 Support Technician 2 Short Stays 4 Generalitat de catalunya Pre-doctoral Research Grants (FI) 3 Post-doctoral Research Grants (BP) 1 Senior Research Grants - ICREA 1 Pre-doctoral Research Grants (FI) 1 others Post-doctoral Research Grants 3 IDIBAPS calls IDIBAPS Pre-doctoral Research Grants 6 Post-doctoral Research Grants BIOTRACK 4

23 IDIBAPS ReSeARCh AND INNOvATION Institució Catalana de Recerca i Estudis Avançats (ICREA)

The Catalan Institute for Research and Advanced Studies (Departament d’Economia i Coneixement) that aims to recruit (Institució Catalana de Recerca i Estudis Avançats, ICREA) is top scientists for the Catalan R&D system. IDIBAPS has five a foundation supported by the Catalan Autonomous Govern- ICREA investigators that contribute knowledge, experience and ment through the Catalan Ministry of Economy and Knowledge leadership to the teams into which they are incorporated:

Dr. Josep M. Dr. Josep Llovet Dalmau Translational Autoimmunity against research group synaptic antigens in liver oncology

The Translation research group in liver oncology was created The Autoimmunity against Synaptic Antigens team is led in 2006 by Dr Josep M. Llovet, ICREA Research Professor for by Dr Josep Dalmau i Obrador, ICREA Research Professor IDIBAPS and Professor of Medicine at the Mount Sinai School at IDIBAPS and Professor of Neurology at the University of of Medicine. The group is composed of 8 people from IDIBAPS Pennsylvania in Philadelphia. Dr Dalmau is a clinical neuro- and leads an international consortium on genomic research oncologist trained and working as Associate Professor of in liver cancer, the HCC Genomic Consortium, with about 30 Neurology in the Memorial Sloan-Kettering Cancer Center in investigators. In 2009, it received the AACR-Landon Interna- New York. His research focuses on a group of diseases locat- tional Innovator Award, and was recognised as an Outstanding ed at the intercrossing of autoimmunity, cancer and synaptic Research Group by the Catalan Autonomous Government. In proteins. This includes the description of new syndromes, the 2010, the group started the coordination of a European FP7- associated immune mechanisms, isolation of the target anti- HEALTH project, the HEPTROMIC consortium, involving the gens, and the development of diagnostic tests and treatment coordination of 6 academic centres and 2 companies, with the strategies. These studies have identified 17 autoantigens and purpose of identifying new oncogenes and treatment targets. have led to diagnostic tests, some of which are used all over In 2011, the group was awarded a grant from the Spanish As- the world. sociation against Cancer (Asociación Española contra el Cancer, In the last 5 years, Dr Dalmau has discovered a new category AECC). Finally, during this year Dr Llovet has been nominated of autoimmune processes resulting in memory, behaviour as President of the International Liver Cancer Association and cognition alterations, and which may cause psychosis. (ILCA). These processes are associated with autoimmune responses The following are the main contributions made by the group characterised by antibodies targeted at synaptic proteins and over these last few years: receptors, such as the glutamate receptors (NMDA, AMPA) • Definition of a molecular classification of hepatocellular or the GABA(B) receptors, or synaptic proteins related with carcinoma (Chang, Can Res, 2008; Hoshida, Cancer Res epilepsy (LGI1, Caspr2). Once the antigens have been identi- 2009; Villanueva, Gastroenterology 2011; Minguez, J fied, Dr Dalmau’s group’s studies focus on the cellular and Hep 2011) molecular mechanisms whereby the antibodies alter the func- • Identification of key oncogenes in hepatocarcinogenesis, tion of the synaptic proteins and receptors and produce the such as miRNA Let-7 (Viswanathan, Nature Genetics 2009; symptoms. The results of these studies have had an impact Toffanin, Gastroenterology 2011), EGF and c-MET (Keng, on many medical disciplines and on neuroscience, since they Nature Biotech 2009), AEG-1 (Yoo, J Clin Invest, 2009) and offer a link between immune processes and synaptic activity the signalling pathway of IGFR1 (Tovar, J Hepatol 2010). related to memory, behaviour, psychosis, epilepsy and neuron • Leadership of EASL-EORTC Guidelines: Dr Llovet has degeneration. been working as Chair of the Clinical Practice Guidelines on Management of HCC endorsed by EASL and EORTC and published in J Hepatology 2012 and European Journal of Cancer 2012.

24 IDIBAPS ReSeARCh AND INNOvATION

Dr. Albert Dr. Maria v. Dr. Antonio Pol Sánchez-vives Postigo Cell Cortical networks Group on Regulation proliferation and EVENT Lab of Gene Expression in and signalling (Virtual Environments Cell Differentiation in Neuroscience and and Cancer Technology)

The aim of Dr Pol’s group is to characterize – Dr Sánchez-Vives joined IDIBAPS in 2008 Dr Postigo’s laboratory investigates the in health and in illness – the cellular proces- and is the head of the Systems Neuro- molecular mechanisms involved in the ses that are regulated or altered due to lipid sciences Group, recognised by AGAUR regulation of gene expression during cell accumulation within the cells. All prokaryote (Agency for Management of University and differentiation and in cancer. To that effect, and eukaryote cells maintain the evolutive Research Grants) as a Consolidated Re- our research focuses on ZEB1 (deltaEF1) competence of accumulating lipids in orga- search Group. and ZEB2 (SIP1) factors, key modulators of nelles known as intracellular lipid droplets. Understanding how the brain processes cell differentiation, stemness maintenance In healthy cells, a small population of lipid information and how brain activity is gener- in normal and cancer stem cells, oncogenic droplets is present at all times, though the- ated and modulated in neuronal networks transformation, and tumour invasion and se organelles become abundant in response is crucial for intervening in cerebral function metastasis. to different pathophysiological conditions when this function has been altered. The group uses in vitro and in vivo models such as obesity, diabetes, fatty liver disease Neuron connectivity and cellular and syn- to address the following two main research (steatosis), liver cirrhosis, viral hepatitis, ar- aptic properties make up brain activity and lines: teriosclerosis and even cancer. Globally, the- this, in turn, has effects upon the network. • Study of the mechanisms by which se disorders affect over half of the popula- The objective of Dr Sánchez-Vives group ZEB1 and ZEB2 regulate tumorigenesis tion in Western countries. Recent advances is to determine how these processes take and the epithelial-mesenchymal transi- in the cellular biology of lipid droplets have place, particularly as regards the generation (EMT) during cancer progression. shown the latter to be multifunctional orga- tion of brain rhythms; how information is • Role of ZEB1 and ZEB2 in the regula- nelles that are metabolically very active and generated, synchronized or encoded. These tion of normal hematopoietic differen- thus constitute key elements in the complex activity patterns are altered under pathologi- tiation and its malignant transformation exchange of lipids and proteins in constant cal conditions, and their restoration may The group’s research at IDIBAPS has been movement within the cells. In this scenario, contribute to recovering function. The mod- funded by, among other sources, grants the group is particularly focused on the cost els of diseases in genetically-modified mice from the Spanish Ministry for the Economy to the cell of the accumulation of cholesterol allow us to carry out such studies. and Competitiveness (formerly, of Science in organelles and the role of the caveolin Another of the group’s lines of research and Innovation), the European Union, Span- protein in the regulation of these fluxes. concerns the integration of information ish Association Against Cancer (AECC), La in the brain cortex, resulting in body rep- Caixa Foundation, O. Torres Foundation and resentation. They use virtual reality and AVON Cosmetics SAU. brain-computer interfaces with a view to understanding and acting upon these processes. At present, and within the setting of an integrated project in the European Union, the group is studying the usefulness of body representation in virtual reality for the treatment of pain and the restoration of motor function.

25 IDIBAPS ReSeARCh AND INNOvATION

ISIS

IDIBAPS is a research Institute accredited through the Spanish gramme. This initiative includes the ISIS contracts to attract Sen- Government’s Health Research Institutes Accreditation Pro- ior researchers with a proven experience leading research teams.

Dr. Cristina Dr. Pere Fillat Santamaria Gene Therapy and Pathogenesis and Cancer Group Treatment of Autoimmunity

The Gene Therapy and Cancer Group led Dr Santamaria’s laboratory has two dis- by Cristina Fillat started up at the IDIBAPS tinct components: one for purely basic in September 2011 with the support of the biomedical research which studies the role Instituto de Salud Carlos III ISIS Programme. of particular genes and molecules in the It has been recognised by the Catalan Au- development and functioning of the immune tonomous Government as an Outstanding system; and another, more applied, based Research Group. on the study of the immunological effects Dr Fillat’s group’s research focuses on the of a new therapeutic platform they have study of the molecular and cellular basis of developed for the treatment of autoimmune pancreatic ductal adenocarcinoma and the diseases, which include type 1 diabetes, lu- development of novel experimental thera- pus and autoimmune diseases of the central pies based on gene transfer and virotherapy. nervous system. This treatment, based on The main research lines are: nanotechnology, works by way of an immu- • To identify specific cellular pathways nological mechanism for protection against and molecular determinants altered in autoimmunity designed by mother nature, pancreatic tumours. which they have learned to manipulate by • Development of antitumour therapies using a new type of drug, also discovered based on oncolytic adenovirus. The by Santamaria’s group. One of the main main interest is devoted to the search objectives is to start using this therapeutic for sensitizers of adenoviral oncolysis platform with patients through the conduct- and to study their mechanisms of syn- ing of clinical trials. ergy. Special emphasis is also applied to engineering tumour-selective oncolytic adenoviruses. • To explore novel non-viral experimental therapies for pancreatic tumours. Preclinical testing of the newly developed therapies is studied in genetically-modified mouse models and in orthotopic xenografts. Some of the animal models are specially designed to allow for the non-invasive imaging of tumour progression and metastatic processes.

26 IDIBAPS ReSeARCh AND INNOvATION

Innovation and Transference

With the aim of improving people’s health, IDIBAPS is firmly Taking innovation into consideration is not an additional task committed to innovation in the healthcare sector. Above in the routine work of researchers, but is a philosophy that is and beyond evaluating research and protecting knowledge, present in all the activities they carry out. It is important for IDIBAPS is concerned with promoting the use of new medi- researchers, for patients and for the Institute. cal technologies that will improve patients’ state of health, A list is provided below of the patents that have been devel- their quality of life and the efficiency of healthcare processes. oped in 2011:

Patents applied for: Number Inventors owners title type Europath Biosciences S.L., Methods for prognosis of diffuse large EP11382290.2 Elías Campo, Luis Colomo Fundació Clínic per a la Recerca Prognostic B-cell lymphoma Biomèdica Chimeric polypeptides derived from Raimon Sanmartí, Isabel CSIC, Fundació Clínic per a la P201131310 the protein vimentin with utility for the Diagnostic Haro, Mª José Gómara Recerca Biomèdica diagnosis of rheumatoid arthritis Use of photolyase for the reduction or ISDIN, IDIBAPS, Hospital Clínic improvement of the subclinical field P201130965 Susana Puig Treatment de Barcelona cancerization associated with actinic keratosis Use of photolyase for the reduction or ISDIN, IDIBAPS, Hospital Clínic improvement of the subclinical field P201131696 Susana Puig Treatment de Barcelona cancerization associated with actinic keratosis Fundació Clínic per a la Recerca New compounds derived from the Francisco Lozano, Vanessa Biomèdica, Hospital Clínic EP11382172 scavenger-like lymphocyte receptors Treatment Martínez, Rafael Fenutria de Barcelona, Universitat de for use in immunotherapy Barcelona Sonsoles Sánchez- Fundació Clínic per a la Recerca Non-replicative virions of the human Palomino, Montserrat Biomèdica, IDIBAPS, Instituto EP 11382103.7 immunodeficiency virus and their Prophylaxis Plana Prades, José Alcamí de Investigaciones Sanitarias therapeutic applications Pertejo Carlos III Julián Panés Díaz, Elena Hospital Clínic de Barcelona, Tolerogenic dendritic cells and their use EP11382174.8 Ricart Gómez, Daniel Treatment CIBERehd in cell therapy Benítez Ribas Universitat de Ramon Farré, Daniel Barcelona,Hospital Clínic Device for generating upper airway P201031183 Navajas, Josep M. de Barcelona, CIBER de Experimental obstruction in animals Montserrat Enfermedades Respiratorias, IDIBAPS Julián Panés Díaz, Elena Hospital Clínic de Barcelona, Tolerogenic dendritic cells and their use EP11382174.8 Ricart Gómez, Daniel CIBER de Enfermedades Treatment in cell therapy Benítez Ribas Hepáticas y Digestivas Francesc Balaguer, Meritxell Gironella, Juan Baylor Research Institute, MicroRNAs (miRNA) as biomarkers for José Lozano, Leticia Hospital Clínic de Barcelona, US2011/055391 the identification of familial and non- Diagnostic Moreira, Antoni Castells, CIBER de Enfermedades familial colorectal cancer Ajay Goel, Richard C. Hepáticas y Digestivas Boland US Application Ajay Goel, Richard C. LINE-1 hypomethylation as a biomarker Serial Number: Baylor Research Institute Diagnostic Boland, Francesc Balaguer for early-onset colorectal cancer 13/419,744 Gene-expression signature of Antoni Castells, Luis tumor recurrence in patients with US PTO LaSalvia, Aurea Mira, Hospital Clínic de Barcelona, stage II and III colon cancer treated Diagnostic 61/604,058 Míriam Cuatrecasas, Siemens Healthcare with 5’fluoruracil-based adjuvant Christoph Petry chemotherapy

27 IDIBAPS ReSeARCh AND INNOvATION

Number Inventors owners title type Andrés Pablo Montefeltro, Gabriel Alvarado Urbina, Compositions and methods for PCT/ Analía Bortolozzi Biassoni, Nlife Therapeutics selective delivery of oligonucleotide Treatment EP2011/056270 Francesc Artigas Pérez, molecules to specific neuron types Miquel Vila Bover Meritxell Gironella, Antoni CIBER de Enfermedades Castells, Juan José Lozano Plasma microRNAs for the detection of US 61/550,148 Hepáticas y Digestivas, Hospital Diagnostic Salvatella, Maria Dolores early colorectal cancer. Clínic de Barcelona Giráldez

Patent cooperation treaty (Pcts): Number Inventors owners title type Albert Sanchez-Fueyo, Juan José Lozano, Marc Method and kit for the diagnosis of PCT/ Martínez Llordella, Antoni HCB, CIBERehd tolerance in liver transplantation using Diagnostic EP2011/053127 Rimola Castella, Felix liver tissue Bohne

Patents in course of transference: Licence Number Inventors owners title type holder Miguel Morales, Xavier Peptides for the treatment of Gasull, Francesc Rabanal, Universitat de Barcelona, ES200902164 ocular hypertension and/or Biotech ProRetina Ángel Acebes, Alberto CSIC, IDIBAPS, UCM, CIBIR glaucoma Ferrús, Jesús Pintor B-3774-09 Raimundo Lozano Raví Hospital Clínic de Barcelona OntoDDB Software Setting Fundació Clínic per a New compounds derived Francisco Lozano, Vanessa la Recerca Biomèdica, from the scavenger-like Immunovative EP11382172 Biotech Martínez, Rafael Fenutria. Hospital Clínic de Barcelona, lymphocyte receptors for use Developments Universitat de Barcelona in immunotherapy. Fundació Clínic per a Eduard Gratacós Solsona la Recerca Biomèdica, AQUA characterization Secreto Transmural AF0962029 Ivan Amat Roldan Hospital Clínic de Barcelona, software Industrial Biotech Universitat de Barcelona F. Sanchez-Madrid, Carlos Martinez-A, D Sancho Madrid, P Engel, Universidad Autónoma de Immune regulation based on Albor Biologics US 7867475 Biotech E. Esplugues Artola, J Madrid the depletion of CD69+ cells (USA) Vega Ramos, P Lauzurica Gómez F. Sanchez-Madrid, Carlos Martinez-A, D Immune regulation based on Sancho Madrid, P Engel, Universidad Autónoma de the depletion of CD69+ cells. Albor Biologics US 20110081292 Biotech E. Esplugues Artola, J Madrid Methods of Treating Viral (USA) Vega Ramos, P Lauzurica Hepatitis. Gómez. F. Sanchez-Madrid, Carlos Martinez-A, D Immune regulation based on Sancho Madrid, P Engel, Universidad Autónoma de Albor Biologics US 20110165071 the depletion of CD69+ cells. Biotech E. Esplugues Artola, J Madrid (USA) Methods of Treating Cancer. Vega Ramos, P Lauzurica Gómez

28 IDIBAPS ReSeARCh AND INNOvATION

Spin-off companieS

The knowledge generated by IDIBAPS usually completes its LINkcARE (2009) cycle when transferred to industry. In other cases, the link with Linkcare HS administers a Patient-Centred, Case-Manage- the centre is maintained through the creation of spin-off compa- ment oriented Open Health Care model that has been desig- nies. Spin-off companies created by IDIBAPS researchers are: ned as a joint effort of several leading medical care research centres in Europe led by Hospital Clínic. It was launched IMMUNNoVAtIVE DEVELoPMENtS S.L. (2010) by Dr Josep Roca. Linkcare’s Open Source platform links This spin-off company launched by Dr Francisco Lozano was clinical data from different systems such as Primary Care created in February 2010, based on the transference of two Information (PCIS), Hospital Information (HIS), Electronic patents pertaining to the University of Barcelona, Hospital Health Record (EHR) and Enterprise Resource Programming Clínic de Barcelona and the Clínic Foundation for Biomedical (ERP) Systems with a library of customized patient profile Research. IND’s activity focuses on the development of new protocols. Linkcare application main areas are: Chronicity, biological therapies for the prevention and treatment of in- Fragility, End of Life Care, Reproduction and Perinatology, flammatory disorders with an immune basis. Wellness and Clinical Research. For further information: www.immunnovative.com For further information: [email protected]

BIoNURE (2009) NEURotEc PhARMA (2006) Spin-off from Hospital Clínic/IDIBAPS and CSIC for the deve- This R&D company founded by Dr Nicole Mahy centres its lopment of new neuroprotective drugs for the treatment of activity on the development of new diagnostic and therapeu- multiple sclerosis and other neurological diseases. Bionure tic tools for acute and chronic central nervous system disea- was launched by Dr Pablo Villoslada. ses that occur with inflammation and/or neurodegeneration, For further information: www.bionure.com such as Stroke, Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Parkinson’s Disease (PD) and Alzheimer’s tRANSMURAL BIotEch (2009) Disease (AD). Spin-off from Hospital Clínic and UB, created by Dr Eduard For further information: www.neurotec-pharma.com Gratacós, for the development and commercialization of different diagnostic devices in the gynaecology field. For further information: www.transmuralbiotech.com

Clinical Trials

IDIBAPS is the ideal setting for completing a number of the cru- The table below summarizes the number of clinical trials cial steps in the development of new medicinal products. Basic approved by the Ethical Committee in Clinical Research biomedical research and applied clinical research, together with (ECCR) in the past years. Of note is the large number of quality specialised healthcare practice, are aspects of IDIBAPS clinical trials designed and sponsored by the IDIBAPS inves- that can be very useful for the development of drugs. tigators themselves: clinical trialS approved By tHe iec clinical trials presented to clinical trials promoted by IDIBAPS year the EccR investigators 2010 219 12 2011 232 26

clinical trial type Approved in 2011 Single-centre trial 16 Multicentre (reference ethics committee) 39 Multicentre (concerned ethics committee) 123 Observational/non-comparative phase IV study 32 Medical devices 20 Other 2 total 232

29 SCIeNTIFIC CORe FACILITIeS

High-level biomedical research requires the use of high-cost IDIBAPS has 6 scientific core facilities of its own, mostly techniques and equipment. In addition, the high complex- located in the CEK building: ity of many of these techniques requires the dedication of specialised personnel. In many cases a given technique is • Biobank of Hospital Clínic – IDIBAPS (Page 30) applied by different research teams without any of them re- • Bioinformatics (Page 33) quiring exclusive and permanent use of the methodology. • Biostatistics and Data Management (Page 34) • Cytometry and Cell Sorting (Page 35) IDIBAPS promotes the setting up of common service core • Functional Genomics (Page 36) facilities to support research for use by all researchers, with • Medical Imaging (Page 37) the purpose of improving the performance and profitability of investments and efficiency in the use of available resources.

Biobank of Hospital Clínic - IDIBAPS

introduction

The Biobank is a centralised institutional support core facil- 1. Neurological tissue Bank ity for coordinating the collection, processing, storage and transfer of human biological samples to promote biomedical A nervous tissue repository (brain and spinal cord) created from research of the highest standard. donations from cadavers with or without neurological conditions, helping to facilitate research into neurological illnesses in With the aim of optimizing the human resources and equip- order to improve diagnoses and enhance patient care. ment in the Biobank, this facility offers a wide range of services for the processing and analysis of the samples col- 2. tumour Bank and Anatomical Pathology collections lected by the research groups. A Repository of tumour and non-tumour tissue samples All the procedures performed at the Biobank are carried out from patients affected by a neoplasia, as well as tissue under ISO9001 certification. samples from other diseases, all surplus to diagnostic requirements from the Department of Anatomical Pathology in When it was first set up, the Biobank had a dual mission: Hospital Clínic. This material is essential to providing current large-scale tissue research projects with the samples they • To provide the scientific community with standard, well- require. characterised biological samples with high added value, in order to promote, foster and develop biomedical research 3. Blood and Fluid Bank in accordance with current legislation • To standardise all the Institute’s research sample collec- This repository contains samples of, among others, metabo- tions (in accordance with article 67 of Law 14/2007 and lic, inflammatory bowel, oncological, digestive, psychiatric Royal Decree RD1716/2011 related to Biomedical Re- and maternal and foetal diseases. It houses a large range search with human samples) of samples of scientific interest, primarily DNA, serum and plasma, which are provided by doctors’ surgeries and labo- The Biobank’s catalogue of samples is formed by the sam- ratories where blood and fluid are taken for lab tests and ples collected by three large banks, all of which have exten- blood and fluid donation. sive experience in research with human samples and which Visit the web: www.clinicbiobanc.org are available for scientific purposes for the consolidation of personalised medicine:

30 SCIeNTIFIC CORe FACILITIeS

ServiceS MoLEcULAR tEchNIQUES • DNA extraction from peripheral blood. The Biobank of Hospital Clínic – IDIBAPS offers a wide va- • DNA/RNA/protein extraction from tissue (frozen and paraf- riety of human biological samples along with services. The fin-embedded). scientific community may make full use of the bank’s equip- • WGA. ment and professional staff to achieve their most ambitious • Serum and plasma isolation. goals. The work of the biobank goes beyond simply provid- • Immunohistochemistry. ing samples; they offer support to researchers during the various stages of projects requiring the use of biological equipment samples. • -20ºC, -80ºC and -150ºC freezers with safety systems. hUMAN BIoLoGIcAL SAMPLE PRoVISIoN • Vapour phase liquid nitrogen tanks. • Nerve tissue from cadaveric donors affected by neurologic diseases. NEURoLoGIcAL tISSUE BANk • Frozen and paraffin-embedded tissues representing the • Cubicles for obtaining the material under sterile conditions. most common neoplasms. • Instruments for preparing samples for the microscope. • DNA, serum, plasma and PBMCs from different diseases • Filing cabinets for collecting paraffined samples. as well as from control donors. • Gas filtration cabinet. • Automated immunostaining appliance. tEchNIcAL AND ScIENtIFIc ADVIcE • Combination refrigerator and -40ºC freezer for preserving • Creation and management of new collections. fungibles. • Methodology (technical guidance). • Autoclave for sterilising surgical material. • Experimental design with human and animal tissue samples. tUMoUR BANk • Design and interpretation of immunohistochemical • Equipment for preparing tissue microarrays (TMAs): TMA studies. Master (3Dhistech) (UB Faculty of Medicine / FEDER). • Quality management programmes. • LaserTissue microdissection microscope with laser • Harmonization of quality procedures for the handling of LMD7000 (Leica Microsystems). DNA samples. • Microtomes and cryostat (Leica Microsystems). • Technical assessment for the handling of the Biobank • Tissue processor (Leica Microsystems). equipment (laser microdissector, multiobserver micro- • Bond Max III for automated immunohistochemistry (Leica scope with software for morphometric analysis and a Microsystems). histological slide scanner with analysis software). • Digital slide scanner Pannoramic Desk (3Dhistech). • Multiobserver microscope BX43 with a 12Mpx photo- PRIVAtE coLLEctIoNS MANAGEMENt graphic camera and the morphometric analysis software • Collection management for multicentre studies. CellSens Dimension (Olympus). • Storage of pre-existing collections. BLooD AND FLUID BIoBANk hIStoLoGIcAL tEchNIQUES • Programmable freezer with a controlled freezing ramp. • Processing of frozen and paraffin-embedded tissues • “Chemagic MSM1®” automated device for obtaining DNA (macroscopy, cryopreservation, paraffin blocks, histologi- from large volumes of blood. cal sections). • “Tecan EVO150®” automated station for the aliquoting of • Lasser microdissection. samples. • Tissue microarray construction (TMA). • “CoulterZ1®” cells and particles counter. • Histological staining. • TC Automated Cell Counter (Bio Rad). • Definitive neuropathological diagnosis of neurological • Cabinets for isolating cells under sterile conditions. diseases. • Cell immortalisation platform. • Slide scan and morphometric analysis. • Computer systems for managing samples and related data. cELLULAR tEchNIQUES • ABF500 Automated Blood Fractionation system (RTS). • Purification and cryopreservation of mononuclear cells. • Immortalization of B lymphocytes. • Erythrocyte isolation from whole blood. • Cell counting.

31 SCIeNTIFIC CORe FACILITIeS

LOcatiOn

Neurological tissue Bank Faculty of Medicine UB South wing, floor 0

tumour Bank CEK building c/ Rosselló, 149-153, planta -1 Servei d’Anatomia Patològica (Hospital Clínic) c/ Villarroel, 170. Escala 3, planta 5

Blood and Fluid Bank CEK building c/ Rosselló, 149-153, planta -1

Contact: [email protected]

PEOPLE

ScIENtIFIc cooRDINAtoR Neurological tissue Bank Manager: Ellen Gelpí, MD, PhD (IDIBAPS) • Maria Jesús Rey, MD, PhD (UB) Neuropathologist. Senior Technician • carina Antiga (IDIBAPS) Secretary • Sara charif (IDIBAPS) Laboratory Technician Anna Bosch comas, PhD (IDIBAPS) • Rosa Rivera (UB) Specialised Technician StAFF • Abel Muñoz (Fundació Clínic) • Joan Albert Barberà, MD, PhD (Hospital Clínic) Autopsy Assistant Director • Leire Etxarri (Fundació Clínic) • Meritxell Rufet (Fundació Clínic) Autopsy Assistant Assistant Manager • Ángela Martín (Fundació Clínic) tumour Bank Informed Consent Manager Manager: Miriam cuatrecasas, MD, PhD (Hospital Clínic) • Esther Barnadas (IDIBAPS) • Laura Gelabert (Fundació Clínic) Lab Manager Laboratory Technician • Mónica Marín (Hospital Clínic) Laboratory Technician • Raquel Bermudo Gascón, PhD (Fundació Clínic) Tumour Bank Manager • Blanca Noemí Luján, MD, PhD (Hospital Clìnic - IDIBAPS) Pathologist and Website Manager for the Catalan Tumour Bank Network (Xarxa de Bancs de Tumors de Catalunya)

Blood and Fluid Bank Manager: Verónica Fernandez Pascual, PhD (IDIBAPS) • Anna Morales (IDIBAPS) Laboratory Technician • Regina cañaveras (Fundació Clínic) Laboratory Technician

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Bioinformatics introduction equipment

The Bioinformatics Unit is mainly devoted to analysis and sup- • 2 rack Servers HP ProLiant DL580 G7 4P Intel® Xeon® E7- port in the interpretation of data coming from OMICS disciplines 4870 10-cores, 2,40GHz, Hyper-Threading Technology (80 (genomics, proteomics and metabolomics). The integration of threads per node), 30 MB CPU cache, 192 GB RAM. Internal data from these fields requires huge efforts in the development Hard disk: 2 x 300GB 6G SAS 10K SFF. O.S.: 64b Suse of common languages, tools, and specific databases. Linux Enterprise Server configured with SGE System (Sun Differential expression or classification studies in every OMICS Grid Engine). field usually face two big challenges: the high dimensionality and • Rack Server HP ProLiant DL580 G7 4P Intel® Xeon® E7- the small number of samples. Furthermore, biomedical research 4850 10-cores, 2,00GHz, Hyper-Threading Technology (80 is frequently aimed at understanding very complex biological threads per node), 24 MB CPU cache, 128 GB RAM. Inter- problems for the discovery of specific biological markers. It is nal Hard disk: 2 x 300GB 6G SAS 10K SFF. O.S.: 64b Suse then necessary to use sophisticated tools with complex statisti- Linux Enterprise Server configured with SGE System (Sun cal methodologies to derive information from the usual condi- Grid Engine). tions of high-throughput experiments. At present, the emerging • Rack Server HP ProLiant DL580 G7 2P Intel® Xeon® E7- field of Systems Biology is aimed at analysing and integrating 4830 8-cores, 2,13GHz, Hyper-Threading Technology (32 data from the entire OMICS field to ultimately create working threads per node), 24 MB CPU cache, 64 GB RAM. Internal models of entire biological systems. Hard disk: 2 x 300GB 6G SAS 10K SFF. O.S.: 64b Suse Linux Visit the web: bioinformatics.fcrb.es Enterprise Server. • IBM eServer BladeCenter HS21 Server. 1P Intel® Xeon® ServiceS E5-345 4-cores, 2,33 GHz. 8 MB CPU cache, 16GB RAM. At- tached Hard Disk DAS: 500 GB (Raid 5). O.S.: 64b Suse Linux Bioinformatics support different areas of biomedical research, Enterprise Server. particularly in OMICS technologies; development of new tools • Rack Server HP ProLiant DL580 G5 4P Intel® Xeon® X7350 and diffusion: 4-cores, 2,93GHz, 8 MB CPU cache, 32 GB RAM. Internal • consultancy and Analysis: counselling in experimental de- Hard disk: 2 x 146GB 6G SAS 10K SFF. O.S.: 64b Red Hat sign; low-level and quality-control analyses; orientation on bio- Enterprise Linux Server. statistical resources; assistance in tools utilisation; intensive • High Performance Storage System (HPSS) for High Perfor- analysis of OMICS technology data in collaborative settings; mance Computing (HPC) EMC-Isilon, 3 nodes X200, 24 TB interpretation of results. (72 Tb, Raid 5), 12GB CPU cache, with internal infiniband con- • Administration of Bioinformatic resources and devel- nection. Scalability up to 15PB. O.S.: OneFS configured with opment of new tools: access to proprietary computer Parallel NFS. resources on Linux servers (especially in NGS projects); • External SAS storage HP MSA60, 8 TB 2U Serial Attach SCSI. software management; development of customized tools and • Back up rack-mount tape autoloader - HP LTO-5 Ultrium. Ca- databases, particularly in web settings. pable up to 24TB of compressed capacity with hp p212/256 • Dissemination: course and seminar organisation. smart array controller.

LOcatiOn PEOPLE

CEK building ScIENtIFIc cooRDINAtoR C/ Roselló 149-153, -1 Floor. Susana kalko, PhD. (IDIBAPS) Bioinformatics Core Facility CEK [email protected] StAFF • Joan Protasio (IDIBAPS) Technician

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Biostatistics and Data Management

introduction A maximum duration of 2 hours is established for each session and service may be provided for a maximum of 2 The Biostatistics and Data Management Platform provides sessions. Consultations requiring additional attention shall methodological and statistical support for research projects receive the same consideration as a project. carried out by IDIBAPS and allied institutions. Depending on projects and availability, the platform may provide support to PRoJEctS external public and private entities. Any services required by the client above and beyond those specified in the section on consulting services shall be ren- The platform’s main objective is to promote cutting edge dered upon formal acceptance of the estimate and timetable clinical research and to facilitate the necessary resources to provided. carry it out. Sample projects: • Creation and maintenance of a clinical trial data base: (a) crea- The platform’s tasks are conducted in compliance with the tion of the eCRF (electronic case report form); (b) creation and International Conference of Harmonisation guidelines, Euro- consensus of Data Management and Validation Plans with the pean and local laws, as well as with the regulatory recom- research team; (c) traceable data export to analysis systems. mendations. Standard Operating Procedures (SOPs) are in • Statistical analysis of clinical trials or other projects: (a) place to fulfil those standards. creation and consensus of the most appropriate Statistical Analysis Plan depending on data type and study objective; (b) ServiceS creation of the most appropriate statistical program according to the objective of the study, with emphasis on the traceability coNSULtING SERVIcES of results; (c) creation of a statistical report and collaboration in Short-term consulting services in methodology and statis- writing and supervising subsequent follow-up articles. tics. Specific consultations are free to departments and institutes of Hospital Clínic and similar institutions. They equipment include, but are not limited to: (a) statistical study design; (b) sample size calculation; (c) consulting on information collec- • Equipment includes a personal computer and statistics and tion methods for analysis; (d) methodological and statistical data management programmes: nQuery, SAS, SPSS, EAST, consulting for research projects. JMP, MACRO.

LOcatiOn PEOPLE

Biostatistics and Data Management ScIENtIFIc DIREctoR: core Facility Ferran torres MD, PhD. (IDIBAPS) IDIBAPS (Institut d’investigacions Scientific Director Biomèdiques August Pi i Sunyer) Hospital Clinic Barcelona StAFF 183, Mallorca Street, floor -1, 08036 Barcelona • José Ríos (IDIBAPS) [email protected] Scientific Coordinator Training and Consultancy Manager • Abiguei torrents (Fundació Clínic – CAIBER) Junior Statistician • José Fernández Sardiña (Fundació Clínic – CAIBER) Data Management Manager • Sandra Serrano (Fundació Clínic – CAIBER) Data Management

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Cytometry and Cell Sorting introduction ServiceS

Flow cytometry is a technique for multiparametric analysis • Analysis of population of interest. of particles, such as cells , by suspending them in a stream • Apoptosis. of fluid and passing them through a LASER. It allows for • Cell cycle, proliferation. the simultaneous multiparametric analysis of the physical • Functional analysis. and/or chemical characteristics of up to thousands of parti- • Stem cells. cles per second. Each suspended particle passing through • Viability. the beam scatters the LASER, and fluorescent chemicals • Analysis of microorganisms. found in the particle or attached to the particle may be • Multiparameter quantitative trials on soluble molecules and excited into emitting light at a longer wavelength than the phosphoproteins (CBA and CBA Flex Set), cell signalling. light source. • Cell sorting. • Microparticles. Fluorescence-activated cell sorting is a specialised type of • High resolution microscopy in flow (cell signalling and flow cytometry. It provides a method for sorting a heteroge- molecular translocation, internalization, co-localization, neous mixture of biological cells, one cell at a time, based cell-cell Interaction, morphology analysis, cell death and on the specific light-scattering and fluorescent characteris- autophagy, cell cycle and mitosis, DNA damage and repair). tics of each cell. It provides fast, objective and quantitative • User training. recording of fluorescent signals from individual cells as well as physical separation of cells of particular interest. equipment

This technology has applications in molecular biology, pa- • BD FACSCalibur: 2 LASER, Up to 4 fluorescence. thology, immunology, plant biology and marine biology. It • BD FACSCantol : 2 LASER, Up to 6 fluorescence. has broad application in medicine (especially in transplanta- • BD FACSCantoII: 3 LASER, Up to 8 fluorescence. tion, haematology, tumour immunology and chemotherapy, • BD LSRFortessa SORP + HTS: 4 LASER, Up to 16 prenatal diagnosis, genetics, etc.). fluorescence. • BD LSRFortessa SORP: 5 LASER, Up to 18 fluorescence. The Facility is subdivided into three rooms: FACS analysis • AMNIS ISX : 2 digital cameras, Up to 12 fluorescence and high-resolution images in flow room; data analysis room; channels. and cell sorting room. • BD FACSAriaII: 3 LASER, Up to 9 fluorescence. • BD FACSAria SORP: 5 LASER, Up to 18 fluorescence. • Magnetic cell sorter autoMACSPro. LOcatiOn • Data analysis: DIVA v6.1.3, CellQuestPro v6.0.3, ModFit LT v3.2, FlowJo v7.6.1, FCAPArray v1.0.1. CEK building C/ Roselló 149-153, -1 Floor. PEOPLE [email protected] ScIENtIFIc cooRDINAtoR AND hEAD oF FAcILIty: Isabel crespo (IDIBAPS)

StAFF • cristina López (IDIBAPS) Specialist Technician • Laia Llinas (IDIBAPS) Specialist Technician

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Functional Genomics

introduction equipment

The IDIBAPS Genomic Unit provides access to different • NanoDrop. genome-wide protocols. • Sinergy2. The platform manages samples for genomic projects start- • Bioanalyzer 2100 (Agilent). ing from quantitative and qualitative analysis of nucleic acids • Viia7 (Applied Biosystems). up to genome-wide gene expression, genotyping and gene- • Fluidigim (BioMark). dose analysis using different platforms including real-time • GeneChip Affymetrix genetic analysis system. PCR and microarrays. • GeneTitan Affymetrix genetic analysis system. • Agilent platform. ServiceS • Axon 4000B scanner. • PyroMark Q96 ID. • Quantification of nucleic acids. • GenomeAnalyzer IIx (Illumina). • Qualitative analysis of nucleic acids. • Expression analysis by Real-time PCR. • Genotyping analysis by Real-time PCR. • Digital PCR (Fluidigm). • Genome-wide expression analysis (Affymetrix microarrays). • Genome-wide genotyping analysis (Affymetrix microarrays). • High-throughput expression analysis (GeneTitan Affy- metrix). • High-throughput genotyping analysis (GeneTitan Affy- metrix). • CGH-Arrays (Agilent). • Scanner Axon 4000B. PEOPLE • Pyrosequencing. • Next-generation sequencing (Illumina). ScIENtIFIc cooRDINAtoR: In addition to these services, the Core Facility offers advice Pedro Jares, PhD. (HC-UB) on experimental design for transcriptomic studies, on ex- tracting RNA and on analysis of microarray data. StAFF • Elías campo, MD, PhD. (HC-UB) Scientific Director LOcatiOn • Magda Pinyol, PhD. (IDIBAPS) Unit Manager CEK building • Montse Sánchez (IDIBAPS) C/ Roselló 149-153, -1 Floor. Technician [email protected] • Laura Plà (IDIBAPS) Technician • helena Suárez, PhD. (IDIBAPS) Specialist Technician • Anna Enjuanes, PhD. (IDIBAPS) Specialist Technician

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Medical Imaging introduction • Experimental Imaging Research (7T MRI Unit): - Bruker BioSpec 70/30 (gradient system of 400 mT/m) The main objectives of this Core Facility are: - Imaging volume coils for mice, rat and small cats or rabbits • To provide services related to medical imaging techniques - Surface coil for rat and mouse brain imaging for researchers from IDIBAPS and other institutions, and to - Surface coil for rat heart imaging (with CINE acquisition industries connected with health. sequence) • To perform first-rate basic and clinical research into medical - Volume coils for 1H/13C, 1H/31P and 1H/19F imaging using structural and functional magnetic resonance spectroscopy imaging, magnetic resonance spectroscopy, molecular imag- - Surface coil for 1H/13C spectroscopy ing, other types of medical imaging and image processing. - Electric stimulator for fMRI • Researcher training in techniques and basic research to - Inhalation anaesthetic system including animal monitoring enable them to conduct experimental and clinical studies, - 4 PC for image processing and analysis thereby allowing them to explore the advantages of transla- • Image Processing Lab: tional research. - 3 dedicated workstations (1 Mac, 2 linux) and 7 high performance ServiceS - PC (5 dual windows-linux, 2 windows) for image post- processing • Clinical Imaging Research (3T MRI Unit). - 10 standard PC • Experimental Imaging Research (7T MRI Unit). - Software licences: 10 Matlab, 2 LcModel, 1 AnalyzeDirect • Imaging Processing Lab. equipment PEOPLE

• Clinical Imaging Research (3T MRI Unit): ScIENtIFIc cooRDINAtoR - RM 3T- Siemens 3T TRIO, B17 software Clinical Imaging Research - 32 phased-array head coil (3T MRI Unit): - 8 phased-array head coil Núria Bargalló Alabart, MD, PhD. - Body coil, (Hospital Clínic) - Others phase array coil StAFF Experimental Imaging Research (7T MRI Unit) LOcatiOn • Guadalupe Soria Rodríguez, PhD. (IDIBAPS)

3t MRI Unit 7t MRI Unit: Hospital Clinic de Barcelona, floor 0, 3a stairs [email protected] [email protected] Post-processing Imaging Lab: CEK building C/ Roselló 149-153, -1 Floor. [email protected] Image Analysis Advisor • Raúl tudela, PhD. (CIBER-BBN, GIB-UB) CIBER-BBN, GIB-UB

Image Processing Lab • carles Falcón Falcón, PhD. (IDIBAPS)

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The IDIBAPS collaboration network is wide-reaching, span- • IDIBAPS’ researchers also participate in 11 National ning the five continents and over 40 countries. IDIBAPS’ IScIII Networks, and 2 of them are coordinated by researchers participate in hundreds of national and interna- IDIBAPS: AIDS and Multiple Sclerosis National Networks. tional consortiums: • In the 7th Framework Programme and Executive Agency • IDIBAPS participates in all nine Spanish Biomedical for health and consumer Protection Programme, Research centres of the Instituto de Salud carlos IDIBAPS participates in 56 projects, coordinating 14 of them. III (IScIII). A total of 27 research groups from IDIBAPS participate in these national networks and 3 of them are • IDIBAPS’ researchers also participate in many interna- coordinated by an IDIBAPS researcher: CIBER of Dia- tional consortiums such as: Colorectal Cancer Genetics betes and Metabolic Diseases; CIBER of Hepatic and (COGENT); International Cancer Genome Consortium Gastrointestinal Diseases; and CIBER of Respiratory (ICGC); International Consortium for Inflammatory Bowel Diseases. Disease Genetics; European Clinical Research Infrastruc- tures Network (ECRIN); and Hepatocellular Carcinoma International (HCC) Genomic Consortium.

Spanish Biomedical Networks (CIBERS, RETICS and CAIBER)

In the last few years, much of the financial support pro- IDIBAPS participates in most of these virtual research vided by the Instituto de Salud Carlos III (Spanish Ministry structures and leads a number of them. Investigators of the of the Economy and Competitiveness) has been geared IDIBAPS direct the following networks: towards the consolidation of the Spanish National Re- • Networked Biomedical Research Centre for Hepatic and search Networks, an initiative that includes the Networked Digestive Diseases (Centro de Investigación Biomé- Biomedical Research Centres (Centros de Investigación dica en Red de Enfermedades Hepáticas y Digestivas, Biomédica en Red, CIBERs), Cooperative Research Topic CIBERehd). Networks (Redes Temáticas de Investigación Cooperativa • Spanish Biomedical Research Centre in Diabetes and en Salud, RETICs), and the Networked Biomedical Re- Associated Metabolic Disorders (Centro de Investi- search Support Consortium – Spanish Clinical Trials Plat- gación Biomédica en Red de Diabetes y Enfermedades form (Consorcio de Apoyo a la Investigación Biomédica en Metabólicas Asociadas, CIBERDEM). Red - Plataforma Española de Ensayos Clínicos, CAIBER), • Networked Biomedical Research Centre for Respiratory which represent a new way of understanding cooperative Diseases (CIBERES). biomedical research that has given excellent results over • AIDS Research Network (RIS). recent years. • Spanish Multiple Sclerosis Network (REEM).

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networked Biomedical reSearcH centre for Hepatic and diGeStive diSeaSeS (centro de investigación Biomédica en red de enfermedades Hepáticas y digestivas, ciBerehd)

Director: Dr Jaume Bosch

www.ciberehd.org

CIBERehd was created on 29 November 2006, and is pres- CIBERehd has 6 major research programmes: ently composed of 45 groups (and six others on ad honorem • Portal hypertension and mechanisms of transition to basis), corresponding to 31 centres in 10 Autonomous Re- cirrhosis. gions throughout Spain. Its Scientific Director is Prof. Jaume • Hepatitis viruses. Bosch, and its activities are supervised by an External Advi- • Cholestasis and metabolic disorders. sory Board and Scientific Committee. Its central facilities are • Liver immunology, cell therapy and transplantation. located in Calle Córcega 180, in Barcelona. • Liver and digestive cancer. • Gastrointestinal inflammation and motility. The objectives of the CIBER for Hepatic and Digestive Dis- eases are: Its budget, totalling €5.3 million in 2011, covers the sala- • To promote top level research in liver and digestive dis- ries of the investigators integrated in its different groups, eases in an international context, fostering interaction scientific infrastructure, training programmes and strategic among the best Spanish groups. actions – involving the implementation of large research • To focus on translational research, in order to facilitate projects that can only be addressed through firm coopera- a rapid transferral of the results to clinical practice and tive action. biotechnological applications. CIBERehd’s activity is reflected in its annual report, which CIBERehd’s scientific activity is essentially focused on its includes the publication of over 200 articles per year in top research programmes and strategic actions, and is comple- journals (first upper quartile of the SCI) and clinical guide- mented by the training programme, the scientific and tech- lines, as well as the conducting of over 50 clinical trials. nological platforms and common resources. CIBERehd has Sixty-four cooperative studies are ongoing at present. its own platforms in genomics, transcriptomics, proteomics, metabolomics, gene silencing and bioinformatics, as well as a biobank (integrated within the IDIBAPS biobank), a bank of steatotic livers and telemedicine platforms for diagnostic and therapeutic support in liver cancer, genetic counselling in colorectal cancer, a database of chronic hepatitis B patients and a national registry of patients with Vascular Liver Diseases.

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networked Biomedical reSearcH centre in diaBeteS and aSSociated metaBolic diSorderS (centro de investigación Biomédica en red de diabetes y enfermedades metabólicas asociadas, ciBerdem)

Director: Dr Ramon Gomis

www.ciberdem.org www.investigaladiabetes.org

The CIBER in Diabetes and Associated Metabolic Disorders diabetes. Worthy of special note in 2011 was the launch of is made up of 31 elite research groups in 19 associate in- the ‘Amicus Canis’ and ‘Pilchardus’ projects (both in collabo- stitutions. It represents the biggest network of scientific ration with IDIBAPS) and diabetesalacarta.org (in collabora- diabetes research in Spain. Its objectives are to achieve the tion with the Alícia Foundation). highest standards of research practice and to accelerate the translation of scientific results into clinical applications. At CIBERdem, despite the recession, researchers have With the aim of achieving pioneering biomedical advances, battled on with their projects and have made significant CIBERdem promotes the development of projects in col- achievements, even though they have been obliged to laboration with other national and international institutes and restructure or downsize their teams or be much more it has two of its own technological platforms: the Biobank sparing in their use of materials. It was extraordinary and and the Metabolomics Platform. highly stimulating to see how, year after year, we were able to discuss new proposals and, in the majority of The consortium seeks to involve not only the scientific com- cases, give a positive answer. However, countries with a munity, but also the business sector, in R&D investment. solid scientific tradition show us that now is the time to It offers companies the possibility of working together on make better use of our scientific structures, to put a little research projects, scientific consultancy, organisation of extra effort into our work, be more rigorous in our priori- scientific events and socially-responsible corporate actions. ties and sharpen our wits, in order to make the most of Furthermore, it disseminates and divulges its scientific work the results we have obtained. It is also a time to look out- through multiple actions such as the periodic organisation of side our frontiers to Europe and try to obtain funding from scientific seminars and its annual Science Open Day, always beyond our own borders. with the active collaboration of patients’ associations. CIBERdem has made significant advances which are of In its effort to continue supporting the work of its research great importance to our health system, such as the Di@ groups, CIBERdem has implemented a strategic fundraising bet.es Study, which provides us with accurate information plan (investigaladiabetes.org) to generate active participation on the prevalence of diabetes in the Spanish population, from the business world and society in general, with the ob- and the results obtained by researchers using the Metabo- jective of collecting funds which will enable us to continue lomics Platform. They are collective achievements, a gen- to promote and finance scientific activity in order to find eral effort made by all our researchers. new means of preventing, diagnosing, treating and curing

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networked Biomedical reSearcH centre for reSpiratory diSeaSeS (centro de investigación Biomédica en red de enfermedades respiratorias, ciBereS)

Director: Dr Àlvar Agustí

www.ciberes.org

The CIBER for respiratory diseases (CIBERES) is a net- In parallel to these PCIs, CIBERES has organised a series worked, multidisciplinary and multicentre research institu- of research support platforms, such as: (1) Pulmonary tion integrating basic, clinical and populational research in Biobank; (2) Technological Development and Transfer- respiratory illnesses. CIBERES is composed of 34 research ence; (3) Training Programme; and (4) Communications groups, 60% of which belong to hospitals and 40% to uni- Department. CIBERES organises annual scientific ses- versities and research centres. The Scientific director of sions and a number of different monographic research CIBERES is Dr Alvar Agustí (Chest Institute, Hospital Clinic). seminars. The administrative centre of CIBERES is in the Fundació Caubet-Cimera in Mallorca.

CIBERES’ research activity is structured on the basis of Cor- porate Research Programmes (Programes Corporatius de Investigació - PCI). Each PCI comprises a series of projects that in a cooperative and integrated manner addresses a relevant healthcare problem in the field of respiratory disease. At present, CIBERES has 10 active PCIs: • Asthma. • Pulmonary fibrosis. • Chronic obstructive pulmonary disease (COPD). • Lung Cancer – Thoracic Neoplasms. • Acute lung injuries. • Sleep Apnea Hypopnea Syndrome. • Tuberculosis. • Pneumonia and sepsis of respiratory origin. • Pathogen-Host Interactions. • H1N1 influenza.

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aidS reSearcH network (red de investigación en Sida, riS)

Director: Dr Josep Maria Gatell

www.retic-ris.net

The AIDS Research Network (Red de Investigación en through network-based efforts and the creation of dif- SIDA - RIS) was created in 2003 and established the basis ferent platforms. A large cohort has been defined, for driving original and innovative research in the field of corresponding to different groups of patients with ho- AIDS. In its second operating period (2007-2011), the Net- mogeneous characteristics, which allows us to evaluate work became consolidated and focused its activity on the the efficacy of new treatment protocols and intervention creation of common platforms (Cohorts, Biobank, Labo- strategies and to carry out studies on toxicity, resistance ratories and Resistance) that generate data and biological and pathogenesis. The particular characteristics of the samples on which the research strategies are founded HIV epidemic in our country allow for the study of par- (clinico-epidemiological, clinico-therapeutic, immunopatho- ticular pathologies associated with HIV infection, such as genesis and vaccines). The network’s priorities are pro- hepatitis C coinfection. jects that require a network in order to be implemented, and issues that are relatively specific to Spain, or in which The AIDS network is composed of 19 core research we are able to make high-level original contributions. groups and 17 associate clinical groups. It includes groups with different experience in virology, immunology and cel- The AIDS network aims to address original problems lular and molecular biology that contribute complementary through novel technological approaches. A series of points of view and techniques in order to globally address large-scale projects have been defined. The strategies complex problems relating to the pathogenesis of HIV in- used to achieve the established objectives are based on fection, such as immune reconstitution, virus-host interac- important breakthroughs which can only be addressed tions and the mechanisms underlying cell damage.

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SpaniSH multiple ScleroSiS network (red española de esclerosis múltiple, reem)

Director: Dr Pablo Villoslada

www.reem.es

The Spanish Multiple Sclerosis Network (Red Española de • Promotion of the creation of shared resources among Esclerosis Múltiple, REEM) was created in 2008. REEM is the different centres participating in REEM, such as composed of basic and clinical investigators at national level, biobanks and clinical databases. interested in the aetiopathogenesis of multiple sclerosis and • Training of young investigators in understanding multi- in the development of new diagnostic and treatment meth- ple sclerosis, based on courses, conferences and spells ods with which to combat the disease. The Director of the in other laboratories. network is Dr Pablo Villoslada, Head of the IDIBAPS Neuro- immunology team. Multiple sclerosis presently affects over two million people throughout the world and our greatest challenge is to im- REEM has three objectives: prove the quality of life of affected patients. • Development of a cooperative research programme on the aetiology, diagnosis and treatment of multiple sclerosis.

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CIBERs and RETICs in which IDIBAPS takes part

IDIBAPS also actively participates in other CIBER and RETIC research networks through its research teams:

Networked Biomedical Research centres (cIBERs)

cIBER IDIBAPS team Principal investigator CIBERdem - Diabetes y enfermedades Diabetes: metabolic and molecular networks Anna Maria Novials Sardà metabolicas CIBERdem - Diabetes y enfermedades Genomic Programming of Beta Cells and Diabetes Jorge Pedro Ferrer Marrades metabólicas CIBERdem - Diabetes y enfermedades Diabetes: metabolic and molecular networks Ramon Gomis Barbarà metabólicas CIBERehd - Enfermedades hepáticas y Physiopathology and treatment of ascites and Vicente Arroyo Pérez digestivas altered renal function in liver cirrhosis CIBERehd - Enfermedades hepáticas y Liver hemodynamics and portal hypertension. Jaime Bosch Genover digestivas Digestive bleeding secondary to ruptured esophageal varicose veins CIBERehd - Enfermedades hepáticas y Hepatic oncology Jordi Bruix Tudó digestivas CIBERehd - Enfermedades hepáticas y Gastrointestinal and pancreatic oncology Antoni Castells Garangou digestivas CIBERehd - Enfermedades hepáticas y Viral hepatitis in the immune competent host and Xavier Forns Bernhardt digestivas in liver transplant patients CIBERehd - Enfermedades hepáticas y Inflammatory bowel disease (IBD) Julián Panés Díaz digestivas CIBERehd - Enfermedades hepáticas y Cholestasis and bone pathology Albert Parés Darnaculleta digestivas CIBERehd - Enfermedades hepáticas y Liver transplantation and graft viability Antonio Rimola Castellà digestivas CIBERehd - Enfermedades hepáticas y Mitochondrial regulation of cell death and José Carlos Fernández-Checa digestivas steatohepatitis CIBERned - Enfermedades Neurodegenerative diseases: Clinical and Eduard Tolosa Sarró neurodegenerativas experimental research CIBERned - Enfermedades Neuropharmacology and experimental Guadalupe Mengod neurodegenerativas neuropathology. CIBERned - Enfermedades Cellular biology of pathological processes Jordi Alberch neurodegenerativas CIBERned - Enfermedades Neurobiology Unit Ramon Trullas Oliva neurodegenerativas CIBERned - Enfermedades Neuropharmacology and experimental Eduard Rodríguez Farré neurodegenerativas neuropathology. CIBERer - Enfermedades raras Secondary lesions due to chronic alcohol Francesc Cardellach López ingestion, muscle pathology CIBERer - Enfermedades raras Fetal and perinatal medicine Eduard Gratacós Solsona CIBERer - Enfermedades raras Genetics Montserrat Milà Recasens CIBERer - Enfermedades raras Hereditary metabolic diseases Maria Antònia Ribes Rubio CIBERer - Rare Diseases Gene Therapy and Cancer Cristina Fillat CIBERes - Enfermedades respiratorias Physiopathological mechanisms of respiratory Joan Albert Barberà Mir illnesses CIBERes - Enfermedades respiratorias Applied research in infectious respiratory José María Montserrat Canal diseases, critically ill patients and lung cancer

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cIBER IDIBAPS team Principal investigator CIBERes - Enfermedades respiratorias Clinical and Experimental Respiratory César Picado Vallés Immunoallergy (IRCE) CIBERes - Enfermedades respiratorias Applied research in infectious respiratory Antoni Torres Martí diseases, critically ill patients and lung cancer CIBERes - Enfermedades respiratorias Respiratory biophysics and bioengineering Ramón Farré Neuropharmacology and experimental CIBEResp - Epidemiología y Salud Pública Eduard Rodríguez Farré neupathology CIBERobn - Fisiopatología de la obesidad y Hypertension, lipids and cardiovascular risk Emili Ros Rahola nutrición CIBERobn - Fisiotatología de la obesidad y Secondary lesions due to chronic alcohol Ramon Estruch Riba nutrición ingestion, muscle pathology CIBERsam - Salud Mental Biological bases of psychiatric disorders and Miguel Bernardo Arroyo nuclear psychiatry CIBERsam - Salud Mental Biological bases of psychiatric disorders and Eduard Vieta Pascual nuclear psychiatry CIBERsam - Salud Mental Neuropharmacology and experimental Francesc Artigas neuropathology CIBER-BBN - Bioingeniería, Biomateriales y Respiratory biophysics and bioengineering Ramón Farré Nanomedicina (Grupo Asociado) CIBER-BBN - Bioingeniería, Biomateriales y Respiratory biophysics and bioengineering Javer Pavia Nanomedicina cooperative health Research thematic Networks (REtIcs)

REtIc IDIBAPS team Principal investigator REDINSCOR - Red de Investigación en Arrhythmias, resynchronization and cardiac Josep Brugada Terradellas Insuficiencia Cardíaca en España imaging RIS - Red Española de Investigación en SIDA Infectious diseases and AIDS Josep Maria Gatell Artigas REIPI - Red española de investigación en Immune receptors of the innate and adaptive Francisco Lozano Soto patología infecciosa (REIPI) system HERACLES - Determinantes Genéticos y Atherosclerosis and coronary disease Maria Magdalena Heras Fortuny Ambientales de la Disfunción Vascular en la Hipertensión y Cardiopatía Isquémica HERACLES - Determinantes genéticos y Hemotherapy - hemostasis Ginés Escolar Albaladejo ambientales de la disfunción vascular Red de Terapia Celular Cellular biology of pathological processes Josep Mª Canals Coll RETICEF - Red temática de investigación Neuropharmacology and experimental Coral Sanfeliu Pujol cooperativa en envejecimiento y fragilidad neuropathology RECAVA - Factores de Riesgo, Evolución Diagnosis and therapy in oncology Maria Àfrica Muxí Pradas y Tratamiento de las Enfermedades Cardiovasculares y sus Mecanismos REDINREN - Red de Investigación en Nephro-urological diseases and kidney Esteban Poch López de Briñas Enfermedades Renales transplantation REDINREN - Red de Investigación en Nephro-urological diseases and kidney Josep Maria Campistol Plana Enfermedades Renales transplantation

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REtIc IDIBAPS team Principal investigator RED DE CANCER - Red temática de Hematological oncology Francisco Cervantes Requena investigación cooperativa de cáncer RED DE CANCER - Red temática de Hematological oncology Juan Bladé Creixenti investigación cooperativa de cáncer RED DE CANCER - Red temática de Cell proliferation and signaling Oriol Bachs Valldeneu investigación cooperativa de cáncer RED DE CANCER - Red temática de Hematopoietic progenitor cell transplantation Álvaro Urbano Ispizúa investigación cooperativa de cáncer RED DE CANCER - Red temática de Physiopathology and molecular bases in Dolors Colomer Pujol investigación cooperativa de cáncer hematology RED DE CANCER - Red temática de Diagnosis and therapy in oncology Francisca Eugenia Pons Pons investigación cooperativa de cáncer RED DE CANCER - Red temática de Human and experimental functional Elias Campo Guerri investigación cooperativa de cáncer oncomorphology RED DE CANCER - Red temática de Hematological oncology Emili Montserrat Costa investigación cooperativa de cáncer RED DE CANCER - Red tematica de Molecular and translational oncology Pedro Gascón Vilaplana investigación cooperativa de cancer. RED DE CANCER - Red tematica de Cell proliferation and signaling Carles Enrich investigación cooperativa de cancer REEM - Red Española de Esclerosis Múltiple Clinical and experimental neuroimmunology Pablo Villoslada Díaz REEM - Red Española de Esclerosis Múltiple Clinical and experimental neuroimmunology Francesc Graus Ribas RIRAAF - Red de Investigación de Reacciones Clinical and Experimental Respiratory Joan Bartra Tomàs Adversas a Alérgenos y Fármacos Immunoallergy (IRCE) RIER - Red de investigación en inflamación y Inflammatory joint diseases (IJDs) Juan de Dios Cañete Crespillo enfermedades reumáticas RETIC de Biobancos Biobank Joan Albert Barberà Mir / Anna Bosch RETICS INNOVACIÓN - RETICS de Innovación Direction of Innovation, Hospital Clínic of Juan Bigorra Llosas en Tecnologías Médicas y Sanitarias Barcelona OFTARED - RETIC en Oftalmología Neurophysiology and functional studies of the Arcadi Gual nervous system

Consortium to Support Network Biomedical Research - Spanish Clinical Trials Platform (CAIBER)

The aim of CAIBER is to empower the development of both tate and promote multi-centre clinical trials which are safe, internal and network-based clinical research programmes rigorous, controlled and guaranteed to preserve the quality and clinical trials. It places special focus on those with no of the study, patient safety and the reliability of the data. commercial interest or which are oriented towards prevention, diagnosis, treatment and services in the subject areas IDIBAPS, through the Clínic Foundation, is one of the nodes reflected in the Strategic Action on Health as relevant social in the CAIBER consortium. This node is led by Dr A. Trilla and public health interest groups. The objective is to facili- and Dr X. Carné.

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International Projection

International projection is one of IDIBAPS’ strategic objec- A good example of this is the increasing presence of IDIBAPS tives, with a view both to establishing collaborative ties with investigators in research projects financed by the European entities of reference in other countries and gaining access Commission. At present, we are participating in 84 such pro- to international calls for research funding. More and more jects (FPVI and FPVII), of which, we are responsible for co- researchers from this Institute are participating in major in- ordinating a total of 14; in 70 we are participating as partners ternational projects. and we have 7 monocontract Marie Curie projects.

PrOjEcts cOOrdinatEd by idibaPs rEsEarchErs

The 14 European projects coordinated by IDIBAPS hEPtRoMIc - Genomic predictors and oncogenic researchers are presented below: drivers in hepatocellular carcinoma Dr Josep M. Llovet cooPERAtIoN 2010 - 2013 Call: CE-FP7-HEALTH-2ST-10 NExES - Supporting healthier and independent living Official code: 259744 for chronic patients and elderly Dr Josep Roca oDhIN - optimizing delivery of health care 2008 - 2012 interventions Call: CE-CIP-ICTPSP2007-1 Dr Antoni Gual Official code: 225025 2011 - 2014 Call: CE-FP7-HEALTH-2ST-10 tRocAR - translational Research on combating Official code: 259268 Antimicrobial Resistance Dr Jordi Vila ALIcE RAP - Addictions and Lifestyles in 2009 - 2012 contemporary Europe - Reframing Addictions Call: CE_FP7_Health_B_07 Project Official code: 223031 Dr Antoni Gual 2011 - 2016 AMPhoRA - Alcohol Measures for Public health Call: CE_FP7-SSH-2010-1 Research Alliance Official code: 266813 Dr Antoni Gual 2009 - 2012 Call: CE_FP7_Health_B_07 Official code: 223059

47 NeTwORkINg

PrOjEcts cOOrdinatEd by idibaPs rEsEarchErs

PEoPLE SANco - EAhc

FEtAL-MED - Multidisciplinary Research training EU-LIVING-DoNoR - European Living Donation and Programme in Fetal Medicine and health Public health Dr Eduard Gratacós Dr Martí Manyalich 2006 - 2011 2007 - 2012 Call: CE_Marie_C_06 Call: CE_SANCO05 Official code: MEST-CT-2005-019707 Official code: 2006211

uVoLUMES - Novel Ultrasound-based tridimensional ELIPSy - European Living tools for Structural and Functional Evaluation of Donor Psychosocial Follow-up Volumes of Interest in human organs Dr Martí Manyalich Dr Eduard Gratacós 2009 - 2012 2008 - 2012 Call: CE_SANCO08 Call: CE_FP7_07_3_1_IAPP Official code: 20081104 Official code: 217911 ENERcA III - European reference network of expert ADIBEt - the role of adipose tissue in obesity: beta centres in rare anaemias cell crosstalk Dr Juan Luis Vives-Corrons Dr Ramon Gomis 2009 - 2012 2008 - 2012 Call: CE_SANCO08 Call: CE_FP7_07_3_1_IAPP Official code: 20081210 Official code: PIAP-GA-2008-218130

ENDo-VV - EndoVascularVision: new endoscopic tools for real time vascular assisted vision Dr Eduard Gratacós 2010 - 2014 Call: CE_FP7_PPOLE_09_IAPP Official code: 251356

REPRotRAIN - Reproductive Biology Early Research training Dr Rafael Oliva 2012 - 2015 Call: CE-FP7-PEOPLE-ITN-11 Official code: 289880

48 NeTwORkINg

Biotrack - Professional Training and Career Development in Biomedicine

IDIBAPS’ institutional mobility action www.idibaps.org/biotrack

BIOTRACK, Professional Training and Career Develop- ment in Biomedicine, is an IDIBAPS initiative co-funded by the Marie Curie Actions of the European Commission, 7th Framework Programme. This is an institutional mobility action that aims to increase scientific output and quality by strengthening and reinforcing the centre’s previously-existing research programmes.

This programme comprises two different forms of life-long • Reintegration schemes: Additional start-up incentive training and career development: IDIBAPS participates in a number of reintegration programmes directed at Senior Researchers. BIOTRACK • In-coming mobility scheme: Post-doctoral programme provides accomplished scientists, who wish to reinte- This BIOTRACK scheme aims to recruit outstanding grate but have mobility requirements, with additional young researchers with a good track record in scientific resources to increase the initial start-up funding granted publications who have acquired experience in other within the framework of these schemes. It is hoped countries. that this additional incentive will help to enhance their excellent research. IDIBAPS’ Group Leaders offer the applicants the chance to find out more about the research frameworks they may Present and future of the programme work within if they are selected. This part is dynamic as, in each call, the research lines available may be modified. In 2011, the community of BIOTRACK researchers in IDIBAPS continued to grow: In 2011, a new timetable was introduced for this scheme. Four 3-month calls were offered instead of • Eight post-doctoral fellows have been working in the one annual call. This structure makes BIOTRACK more centre since their acceptance in the previous in-coming visible to the scientific community and attracts more mobility calls: four were selected in 2010 and four in talented researchers every time (see Figure 1). 2011.

• Three researchers were reintegrated into IDIBAPS thanks to the above Reintegration Schemes and BI- OTRACK grants. 450 400 350 IDIBAPS has declared its commitment to the principles of 300 The European Charter for Researchers and The Code of 250 Conduct for the Recruitment of Researchers proposed by 200 the European Commission. Therefore, the selection pro- 150 cesses are transparent; there is no discrimination by gender, 100 nationality or any other aspects. 50 0 2009 2010 2011

Figure 1. One call per year was opened in 2009 and 2010, receiving 156 and 116 applications respectively. In 2011, a new structure was operated, with four 3-month calls instead of one annual call. As a result, in one year, 411 applicants presented their candidatures for the post-doctoral programme. This amounted to nearly four times the number of candidatures received in previous years.

49 TRAININg

Research Seminars

As well as being orientated towards the creation of net- • VEGF, HIF-1-alpha and the lung structure maintenance program works, the research seminars organised by IDIBAPS are a Monday 21st March clear demonstration of the institute’s dedication to teaching. Dr Norbert Voelkel The speakers always offer added value that contributes to Director, Victoria Johnson Center for Obstructive Lung the knowledge of our investigators. The goal is to share Diseases/Virginia Commonwealth University, Richmond, knowledge as it becomes available, with the consolidation of Virginia, USA alliances all over the world in order to obtain better research. • Linking of the Allergic Environment to Autoimmunity: The following institutional seminars were organised by the IgE and basophils as amplifiers in lupus management of IDIBAPS in 2011: Monday 11th April Dr Juan Rivera • Brain imaging and neuropathological aspects of medial National Institutes of Arthritis and Musculoskeletal and temporal lobe atrophy in aged patients Skin Diseases, National Institutes of Health (USA) Monday 24th January Prof Alphonse Probst • Advances in colorectal cancer genetics: fine mapping Emeritus Professor, Department of Neuropathology, of known regions, novel variants and associations with University of Basel, and Memory Clinic assessor cancer initiation Monday 27th June • Advances in endoscopic imaging; towards Dr Luis carvajal-carmona “endopathology” Wellcome Trust Centre for Human Genetics, University Monday 14th February of Oxford Dr Michael Wallace Mayo Clinic College of Medicine, Director of Research • Genetic architecture of diabetes: the present and the future for the Department of Medicine, Director of the Monday 17th October Gastroenterology and Hepatology Division Dr Valeriya Lyssenko Associate Professor at Lund University • Somatic reprogramming of adult ovaries to testes Monday 21st February • The visual system in Multiple Sclerosis and Prof. Mathias treier neurodegenerative disease Director of the Institute for Molecular Endocrinology/ Monday 17th October Medical Faculty, University Hospital of Cologne Prof Ari Green (Germany) Department of Neurology, University of California, San Francisco

• The role of telomerase in cancer and aging Monday 21st November Dr María Blasco Director of the Spanish National Cancer Research Centre (CNIO), Madrid

• Neuroprotection and Cell Therapy in Parkinson’s Disease Monday 19th December Dr José López Barneo Professor at Seville Biomedicine Institute (Instituto de Biomedicina de Sevilla (IBiS)), Hospital Universitario Virgen del Rocío/CSIC/University of Seville

In addition, two new lines of seminars were started in 2011. The “In house” Seminars aim to share in-house knowledge through presentations of research and challenges led by IDIBAPS investigators. The “core Facility” Seminars have become a tool for introducing new techniques and services offered by the IDIBAPS Core Facilities.

50 TRAININg

Doctoral Theses

IDIBAPS’ dedication to training is also reflected by A list is provided below of the 84 doctoral theses directed the large number of doctoral theses that are directed by investigators from this centre in 2011: and supported by the IDIBAPS integrated members.

thesis Author title thesis Directors Neuronal basis of auditory adaptation and temporal discrimination in Juan Manuel Abolafia Moya Sanchez-Vives MV the auditory cortex of the awake, freely-moving rat Evaluation of the efficacy of acupuncture in the prevention of migraine Jerusa Alecrim Andrade Carne X attacks Gomis R, Parrizas M, Felicia Alexandra Hanzu Molecular determinants of adipose tissue crosstalks Diaz-Ricart M Isabel Alfany Fernández Differential role of Angiotensin II in liver resections and liver transplant Peralta C Combined therapy with uric acid and RTPA in acute ischaemic stroke: pharmacokinetics, clinical safety and biological activity of the Sergio Amaro Delgado Chamorro A, Planas A intravenous administration of uric acid in ischaemic stroke treated with RTPA Albert Antolín Santaliestra Living will, chronically-ill patient and A&E Sanchez M, Miro O Prevalence and factors associated with non-alcoholic hepatic steatosis Maria Antònia Auladell Llorens Pares A in the general population Involvement of G-proteins and PKA in local regulation of the sonic María de las Mercedes Barzi Diéguez Bachs O hedgehog pathway in the primary cilium Mercedes Barzy Dieguez Role of Gi and PKA in Shh signalling Pons S Early-onset of chronic cannabis use: effects on cognitive function and Ana Beatriz Fagundo Martin R brain activity Lluïsa Benito Serrano Utility of early detection of atrial fibrillation Coll-Vinent B Jordi Berenguer de Felipe MicroRNA regulation of neuronal proliferation Pons S Study of the effects of vasodilator drugs on gaseous exchange and Isabel Blanco Vich Barbera JA pulmonary haemodynamics in chronic respiratory diseases Psychosocial functioning in bipolar disorder: factors involved and Caterina del Mar Bonnin Roig Vieta E, Martinez A follow-up at 4 years Effects of organochlorine pesticides on glutamatergic Victor Briz neurotransmission in primary neuronal cultures: interactions with the Suñol C neuroendocrine system Early biomarkers for platelet hyperactivity: characteristics of the Lucas Brunso Welker Diaz-Ricart M, Escolar G mechanisms of contraction and secretion in horses Analysis of single-nucleotide polymorphisms (SNPs) as factors Marc Campayo predictive of relapse in patients with surgically-resected non-small cell Vinolas N lung cancer Study of the alteration in signalling pathways involved in the neuronal Olga Carretón Gómez dysfunction Huntington’s Disease: evaluation of its application as Alberch J therapy in prevention of cognitive deterioration Arani Casillas Ramírez Strategies to protect the steatotic graft in liver transplant Peralta C Osteoporosis in the postmenopausal woman: fracture risk in Dacia Cerdà Gabaroi Guañabens N cholestatic disease and prevalence of other associated disorders Community-acquired pneumonia: prospective study of aetiology and Catia Cillóniz Campos Torres A clinical progress in a 12-year study period Cardiac dysfunction by tissue doppler in early-and late-onset fetal Montserrat Comas Rovira Gratacos E, Crispi F growth restriction

51 TRAININg

thesis Author title thesis Directors Effects of the laparoscopic “Roux-en-Y” bypass as a bariatric surgery Ricard Corcelles Codina technique in the treatment of metabolic syndrome associated with Lacy A morbid obesity Effectiveness of two interventions in the prescribing of antibiotics in Josep M Cots Yago Coca A respiratory tract infections in Primary Care in Spain Gerardo Dambrava Rodríguez Povilas Characterization of community-acquired pneumonia Torres A Clinical and neuropsychological characteristics in children and Elena de la Serna Gómez Castro J, Baeza I adolescents at high risk of schizophrenia Brain reorganization in an experimental model of intrauterine growth Elisenda Eixarch Roca Gratacos E, Figueras F restriction Rafael Fenutria Aumesquet Immunomodulatory properties of the CD5 extracellular region Lozano F Complete remission in multiple myeloma: prognostic impact of the Carlos José Fernández de Larrea oligoclonal bands, serum free light-chain ratio and residual plasma Blade J Rodríguez cells in bone marrow Pulmonary vascular changes induced by exposure to cigarette smoke Elisabet Ferrer Andrés Barbera JA, Peinado VI in an animal model of COPD The inflammatory process triggered by activation of the TLR4 Míriam Aurora Font Nieves de la Vega innate immune receptor, and natural autoregulation mechanisms in Planas A, Petegnief V astrocytes Multimodal magnetic resonance imaging and cerebrospinal fluid Molinuevo JL, Bartres- Juan Fortea Ormaechea analysis in preclinical familial and sporadic Alzheimer’s Disease Faz D Prevalence and clinical and neuropathological phenotype of Carles Gaig Ventura Tolosa E Parkinsonism associated with LRRK2 gene mutations Clinical significance of the microRNAs of the p53 pathway in non- Elena Gallardo Martín Vinolas N small-cell lung cancer: miR-34a and miR-16 In-vivo reflectance confocal microscopy in dermatology: application in Reyes Gamo Puig S the diagnosis of skin tumours Magnetic resonance imaging study of the musculoskeletal system in Ana Isabel García Díez the assessment of Lipodystrophy Syndrome in patients infected by Oleaga L, Mallolas J the human immunodeficiency virus Study of cardiac electromechanics by signal post-processing Silvia García Etelvino and cardiac imaging: application of a clinical model of cardiac Sitges M resynchronization therapy Clemente García Rizo Metabolism and inflammation in first episode psychosis Bernardo M Characterization of the types of activation of different populations Sabrina Gea Sorlí of macrophages during experimental acute pancreatitis and their Closa D relationship with the severity of the disease Thomas Gener Modulation of spatial processing by somatosensory inputs in the rat Sanchez-Vives MV Elena González Moreno Biogenesis of lipid bodies Pol A Immaculada Grau Corral Analysis of the virtual communities in the ForumClinic portal forums Siso A Physiological and immunological changes after natural orifice Lacy A, Fernandez- Carlos Guarner Argente transluminal endoscopic surgery (NOTES) using three different access Esparrach G routes versus laparoscopy: comparative study in a porcine model Study of the immunomodulatory effect of statins. In vitro and in vivo David Guillen Tunica Brunet M studies Biological and prognostic characterization of diffuse large-cell Gonzalo Gutiérrez García Lopez-Guillermo A lymphoma during immunochemotherapy cAMP specific-phosphodiesterases: mRNA variations and sex-related Emily Johansson Mengod G differences in mouse brain following immune response Júlia Calvo Castillo Molecular changes in metastatic transition of breast cancer Fernandez PL, Thomson T Adam Kassan The study of lipid droplet biogenesis Pol A

52 TRAININg

thesis Author title thesis Directors Study of myocardial regeneration in alcoholic cardiomyopathy and Meritxell Lluis Padierna its relationship with the functional damage and myocardial structure, Fernandez-Sola J activation of apoptosis and myostatin activity Utility of pretransplant MELD and sodium in the short-term prognosis Maria Carlota Londoño Hurtado Gines P for liver transplant Characterization of natural killer response to human cytomegalovirus- Giuliana Magri Angulo A, Lopez-Botet M infected dendritic cells Dopamine Transporter (DAT) and schizophrenia prognosis: prospective Anna Mané Santacana study of a cohort evaluated by DATSCAN, volumetric MRI and the Bernardo M, Parellada E DAT gene polymorphism -67 A/T Revascularization of Chronically-Occluded Coronary Arteries: Victoria Martín Yuste Predictors of Angiographic Success and Role of the New Imaging Sabate M, Cinca J Techniques in Patient Selection Participation of 5- and 12/15 - lipoxygenase in the development and Marcos Martínez Clemente Claria J progression of hepatic inflammation and steatosis Analysis of fibrinolysis as a new thrombotic pathogenic mechanism Balasch J, Carmona F, Mª Ángeles Martínez Zamora in early and advanced gestational disease. Relationship with Tassies D antiphospholipid antibodies Modulation of the monoaminergic systems in the prefrontal cortex: Mercè Masana Nadal Bortolozzi A, Artigas F implications in schizophrenia and depression Sílvia Maya Enero Safety in resuscitation in the extremely-premature neonates ward Botet F Changes in prenatal and postnatal cytogenetic diagnosis with the Mª Carme Morales Peydró implementation of new molecular biology techniques and the Sanchez A, Bachs O repercussions on genetic counselling Sporadic and familial porphyria cutanea tarda: observational study of Carlos Muñoz Santos Herrero C the clinical and biochemical characteristics and the risk factors Clinical significance of the presence of autoantibodies in primary Norma Nardi Siso A, Ramos-Casals M Sjögren’s Syndrome: implications for routine practice Expression of mucines and related molecules in mucoepidermoid Blanca Noemi Luján carcinomas of the salivary glands: diagnostic and prognostic Alos L, Cardesa A implications Natalia Nuño Lambarri, Universidad Hepatocyte growth factor and c-Met: role of hypercholesterolaemia Fernandez-Checa JC, Autónoma Metropolitana, Mexico DF and signal transduction Gomez L The combination of different pathology criteria enhances the J. Osorio effectiveness of node involvement as a prognostic factor in stomach Fuster J cancer Isabella Pacchiarotti Treatment outcomes of antidepressant use in bipolar disorder Vieta E, Colom F Raffaella Pippa P27kip1 regulates the transcription of genes involved in tumorigenesis Bachs O Renal involvement in systemic lupus erythematosus and Guillermo Javier Pons-Estel Silvestre antiphospholipid syndrome: clinical/epidemiological, anatomical Cervera R pathology study including predictive factors for morbidity/mortality Improvement in the clinical safety of the poisoned patient following Jordi Puiguriguer Ferrando Nogue S compliance with the quality indicators in Clinical Toxicology Ignacio Revuelta Vicente Molecular characterization of neoplasms in solid-organ transplant Campistol JM Evaluation of Compton scattering in SPECT studies with 123-I-labelled Núria Roé Vellvé radiotracers and quantification of small-animal neurotransmission Ros D studies Role of the Kruppel-like factor 2 transcription factor in hepatic Lucía Russo endothelial dysfunction associated with portal hypertension and Bosch J, Gracia J ischaemia- and reperfusion-related damage Prevalence, clinical correlates and factors associated with course and Regina Sala Cassola Castro J outcome of anxiety disorders in adolescents with bipolar disorder Noelia Salvador Marcos SAPKs in the DNA replication checkpoint Agell N

53 TRAININg

thesis Author title thesis Directors cAMP and neuroinflammation: identification of proteins involved Cristina Sanabra Palau in the regulation of cAMP levels in experimental autoimmune Mengod G encephalomyelitis Dermatoscopic characteristics of the melonocytic lesions in atypical Sonia Segura multiple-mole melanoma in different anatomical areas and of Puig S melanomas on trunk and lower limbs In-vivo reflectance confocal microscopy in dermatology: application in Sonia Segura Tigell Puig S the diagnosis of skin tumours Signalling pathways and potential therapeutic agents in an in vitro Javier Selva Sánchez Egea G model of foetal alcoholic syndrome Expression and functional role of CD84 and CD229 receptors in innate Jordi Sintes Castro Engel P and adaptive immunity Ivonne Torres Atencio, Autònoma de Regulatory role of Prostaglandin E2 in osmotic activation in mast cells Picado C, Martin M Barcelona (UAB) Left ventricular hypertrophy and prediction of cardiovascular risk in Francisco Javier Tovillas Morán Coca A people with hypertension in our setting Chronic kidney disease and renal replacement therapy in patients with Miro JM, Moreno A, Joan Carles Trullàs Vila human immunodeficiency virus infection. Prevalence and survival in Barril G renal replacement therapy and kidney transplant Mauricio Valencia Arango Prevention of complications associated with mechanical ventilation Torres A, Ferrer M Van Arensbergen, Joris The role of polycomb-mediated gene repression in beta-cell identity Ferrer J Benefits of calmodulin binding to RAC 1: implications in clathrin- Mª Teresa Vidal-Quadras de Soto Tebar F independent endocytosis Description and evaluation of the dermatoscopic parameters and Puig S, Malvehy J, Pedro Zaballos Diego patterns of non-melanocytic skin lesions and their differential Estrach MT diagnosis with melanoma

54 IDIBAPS AND SOCIeTy IDIBAPS AND SOCIeTy

IDIBAPS understands that new biomedical discoveries must reach the citizens not only through medical and scientific benefits, but also through high-quality information. It is our obligation to inform society of advances, of basic and healthcare novelties and of the principal research lines being pur- sued. The responsibility of informing society is based on the principle that a well-informed person is a healthier person.

http://www.facebook.com/idibaps https://twitter.com/idibaps/

Mass media play an important role in the communication of laboratory designed to become an educational support in the research results. That is why IDIBAPS investigators work classrooms which explains scientific concepts and everyday together with the IDIBAPS Communication Office in press activity in clinical and basic laboratories. This activity, which releases and press meetings to provide reliable and relevant was started with a grant from the Generalitat de Catalunya data to journalists. In 2011, over 20 press releases were (ACDC 2010) and had the support of the Obra Social “la launched, adding to the individual news items, where inves- Caixa”, is now available in Spanish, Catalan and English and tigators from this Institute are interviewed as independent at www.ambientech.org. experts expressing their opinion about other issues. Lastly, IDIBAPS is exploring the context of social networks Multimedia applications are also an ideal tool for stimulat- as a channel for communication with society. The Face- ing learning and explaining complex concepts. With this in book and Twitter profiles are a new way to interact with mind, IDIBAPS joined forces with Ambientech, an institution IDIBAPS and learn more about what is going on inside its specialising in educational websites. The result is a virtual laboratories:

AReA 1 Team involved in:

Biological aggression and response mechanisms

Inflammatory joint diseases (IJDs) StrateGic oBjectiveS gROUP MeMBeRS Promotion of research into the most prevalent chronic forms of arthritis: rheumatoid arthritis (RA) and spon- dyloarthritis, including psoriatic arthritis.

main lineS of teAM leADeR reSearcH Raimon Sanmartí (Hospital clínic) tel.: 93 227 54 00 (ext.: 2236/2604) 1. Prognostic factors in initial arthritis e-mail: [email protected] • Prognostic factors (clinical and immunogenetic) in patients with initial iDiBApS MeMBeRS: rheumatoid arthritis. Juan D. cañete (Hospital clínic) • Production of new synthetic citrullinated peptides for the design of poStDoctoRAl fellowS: immunoassays with diagnostic and Raquel celis (fundació clínic) prognostic value in recent-onset Maria Victoria Hernández (fundació clínic) rheumatoid arthritis. • Effect of tobacco on the phenotype ReSeARcH fellowS: of recent-onset rheumatoid arthritis Virginia Ruiz-esquide (fundació clínic) 2. Pharmacogenomics of chronic ar- Julio Ramírez (fundació clínic) thritis • Genetic biomarkers associated to collABoRAtoRS: TNF antagonists response in rheu- Guadalupe ercilla (Hospital clínic) matoid arthritis and psoriatic arthritis Jaume pomés (Hospital clínic) 3. Immunopathology of synovitis in Xavier tomas (Hospital clínic) chronic arthritis odette Viñas (Hospital clínic) • Utility in differential diagnosis and J.A. Gómez-puerta (fundació clínic) prognosis. Immunopathological changes related to biological treatments. Synovial response biomarkers. 4. Role of autoinflammatory genes in the pathogenesis of chronic arthritis • MEFV gene mutations in intermittent arthritis.

58 AReA 1 BioloGicAl AGGReSSion AnD ReSponSe MecHAniSMS inflAMMAtoRy Joint DiSeASeS (iJDS)

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 45.44 11 6 3 oRiGinAlS in ankylosing spondylitis: results of a i.f.: 36.45 12-week randomized, double blind, 2010 10.06 3 2 1 controlled multicentre study (LOADET 2011 36.45 8 5 3 1 Haro I, Gomara MJ, Perez ML, study). RHEUMATOLOGY. 50:1828- Vinas O, Ercilla G, Gomez-Puerta JA, 1837. I.F.: 4.17. Sanmarti R. Antibodies against beta- fibrin synthetic peptides: A study of 6 Narvaez J, Diaz-Torne C, Ruiz JM, their association with the immunoge- Hernandez MV, Torrente-Segarra V, Ros GRAntS foR ReSeARcH netic background and disease course S, DeLaSerna AR, Diaz-Lopez C, San- in pRoGReSS of rheumatoid arthritis patients. marti R, Nolla JM. Predictors of respon- EUR J MED CHEM. 46:1095-1102. se to rituximab in patients with active Cañete J. Red de Inflamación y Enfer- I.F.: 3.19. rheumatoid arthritis and inadequate medades Reumáticas. Sponsored by: response to anti-TNF agents or traditio- Instituto de Salud Carlos III (ISCIII), 2 Villa MD, Jimenez-Jorquera C, nal DMARDs. CLIN EXP RHEUMATOL. RETICS RD08/0075/0006 “RIER”. Dura- Haro I, Gomara MJ, Sanmarti R, 29:991-997. I.F.: 2.36. tion: 01/01/2009-31/01/2012. Fernandez-Sanchez C, Mendoza E. Carbon nanotube composite peptide- 7 Izquierdo E, Canete JD, Celis R, Cañete J. Subtipos de células T sinovia- based biosensors as putative diag- DelRey MJ, Usategui A, Marsal S, San- les (Th1, Th2, Th17 y Treg) y actividad nostic tools for rheumatoid arthritis. marti R, Criado G, Pablos JL. Synovial y gravedad de la artritis psoriásica. BIOSENS BIOELECTRON. 27:113- Fibroblast Hyperplasia in Rheumatoid Sponsored by: Instituto de Salud 118. I.F.: 5.36. Arthritis Clinicopathologic Correlations Carlos III (ISCIII), PI080206. Duration: and Partial Reversal by Anti-Tumor 01/01/2009-31/12/2011. 3 Canete JD, Albaladejo C, Hernan- Necrosis Factor Therapy. ARTHRITIS dez MV, Lainez B, Pinto JA, Ramirez RHEUM-US. 63:2575-2583. I.F.: 8.44. Sanmarti R. Estudio comparativo fe- J, Lopez-Armada MJ, Rodriguez-Cros notípico, genotípico e inmunohistoló- JR, Engel P, Blanco FJ, Sanmarti R. 8 Malakoutikhah M, Gomara MJ, Go- gico. Sponsored by: Instituto de Salud Clinical significance of high levels of mez-Puerta JA, Sanmarti R, Haro I. The Carlos III (ISCIII), PI080207. Duration: soluble tumour necrosis factor-alpha Use of Chimeric Vimentin Citrullinated 01/01/2009-31/12/2011. receptor-2 produced by alternative Peptides for the Diagnosis of Rheuma- splicing in rheumatoid arthritis: a toid Arthritis. J MED CHEM. 54:7486- Cañete J. Asociación de polimorfismo longitudinal prospective cohort stu- 7492. I.F.: 5.21. de un sólo nucleótido (SNPs) de los dy. RHEUMATOLOGY. 50:721-728. genes de las vias de señalización intra- I.F.: 4.17. celular NFkB, MAPK y JAK/STAT con ReViewS la artritis reumatoide y con diferentes 4 Ruiz-Esquide V, Gomez-Puerta i.f.: 4.74 fenotipos de la enfermedad. Sponsored JA, Canete JD, Graell E, Vazquez I, by: Instituto de Salud Carlos III (ISCIII), Ercilla MG, Vinas O, Gomez-Centeno 1 Narvaez J, Diaz-Torne C, Ruiz JM, PI041023. Duration: 01/01/2005- A, Haro I, Sanmarti R. Effects of Hernandez MV, Torrente-Segarra V, Ros 30/12/2011. Smoking on Disease Activity and Ra- S, DeLaSerna AR, Diaz-Lopez C, San- diographic Progression in Early Rheu- marti R, Nolla JM. Comparative Effec- matoid Arthritis. J RHEUMATOL. tiveness of Rituximab in Combination 38:2536-2539. I.F.: 3.55. with Either Methotrexate or Lefluno- mide in the Treatment of Rheumatoid 5 Navarro-Sarabia F, Fernandez- Arthritis. SEMIN ARTHRITIS RHEU. Sueiro JL, Torre-Alonso JC, Gratacos 41:401-405. I.F.: 4.74. J, Queiro R, Gonzalez C, Loza E, Linares L, Zarco P, Juanola X, Roman- Ivorra J, Martin-Mola E, Sanmarti R, Mulero J, Diaz G, Armendariz Y, Collantes E. High-dose etanercept

59 AReA 1

Biological aggression and response mechanisms

Systemic autoimmune diseases StrateGic oBjectiveS gROUP MeMBeRS The Systemic Autoimmune Diseases research group promotes basic, clinical and translational research in these diseases in a multidisciplinary manner, with the participation of members of teAM leADeR the following Departments: Autoimmu- Dr. Ricard cervera Segura (Hospital clínic) ne Diseases, Ophthalmology, Internal tel.: 93 227 57 74 Medicine, Nephrology, Immunology, fax: 93 227 17 07 Hemostasis, Hepatology, Obstetrics and e-mail: [email protected] Dermatology, among others. These activities are carried out in close iDiBApS MeMBeRS: María Soledad Retamozo collaboration with different international Gerard espinosa Garriga (Hospital (Hospital clínic) work groups, of which the team mem- clínic) bers are national and/or international Miguel ingelmo Morín (Hospital clínic) ADMiniStRAtiVe StAff: coordinators: European Working Party Manuel Ramos casals (Hospital clínic) isabel chaves (Hospital clínic) on Systemic Lupus Erythematosus Alfredo Adán (Hospital clínic) (EWPSLE), European Forum on Antiphos- Albert Bové (uB) collABoRAtoRS: pholipid Antibodies (EFAPL), Catastrophic Ricardo p. casaroli (Hospital clínic) Xavier Bosch Aparici (Hospital clínic) Antiphospholipid Syndrome (CAPS) Maria cinta cid (Hospital clínic) María teresa Sainz de la Maza (Hos- Registry Project Group, International José Hernández Rodríguez (Hospital pital clínic) Pediatric Register of Antiphospholipid clínic) Antoni Sisó (GeSclinic) Syndrome (Ped-APS Register), Systemic elena Millá (Hospital clínic) Lupus International Collaborative Centers ViSitinG ScientiStS: (SLICC), Sjögren’s Syndrome-Hepatitis C ReSeARcH fellowS: Marta pérez de lis (Vigo) Virus (SS-HCV) Study Group, HISPAMEC Joan plaza nicolau (Hospital clínic) Roberto pérez-Alvarez (Vigo) Study Group, Systemic Autoimmune Ana García Martínez (Hospital clínic) Rafael Belenguer (València) Disease Study Group – Use of Biological Sergio prieto (Hospital clínic) Miriam Akasbi (Madrid) Therapies (BIOGEAS), Spanish Sjögren’s Georgina espígol (iDiBApS) Miriam Gandía (cádiz) Syndrome Multicenter Study Group (GE- Marc corbera (iDiBApS) norma nardi (Buenos Aires, Argentina) MESS), European Vasculitis Study Group Montserrat Butjosa (Hospital clínic) patrícia patrício (lisboa, portugal) (EUVAS), European League Against Miguel Angel plasín (Hospital clínic) claudia Mendoza (puebla, Méxic) Rheumatism (EULAR) Systemic Vasculitis Guillermo pons-estel (iDiBApS) Horacio Berman (tucumán, Argentina) Task Force, EULAR Standing Committee Juan carlos Mejía (Hospital clínic) Verônica Vilela (Río de Jainero, Brasil) for International Clinical Studies Including cándido Díaz-lagares (Hospital clínic) Therapeutics, and the American College ester planas (iDiBApS) of Rheumatology (ACR) Work Group for Rosa Serrano (Hospital clínic) Development of Classification Criteria for itziar tavera (Hospital clínic) Rheumatic Polymyalgia, among others. Marco Alba (Hospital clínic) main lineS of reSearcH

1. Systemic lupus erythematosus, antiphospholipid syndrome and systemic sclerosis: • Epidemiological multicenter studies on the clinical manifestations and long-term evolution of these diseases. • Clinical trials in new biological therapies.

60 AReA 1 BioloGicAl AGGReSSion AnD ReSponSe MecHAniSMS SySteMic AutoiMMune DiSeASeS

implicated in the perpetuation of inflammation and in vascular remodelling. • Study of the prevalence of large vessel inflammatory involvement at the start and during the course of giant cell arteritis. • Clinical trials promoted fundamentally for investigating new biological therapies in the management of systemic vasculitis. • Spanish systemic vasculitis registry. • Spanish Behçet’s disease registry. 4. Autoimmune ophthalmopathy: • Clinical trials in new biological therapies. • Study of genetic polymorphisms in uveitis as risk factors of the diffe- Renal thrombotic microangiopathy associated with antiphospholipid antibodies. rent clinical manifestations of such ophthalmological disorders. • Study of genetic polymorphisms as vascular remodelling (occlusion or • Treatment with anti-Vascular En- risk factors of the different clinical dilatation) and its clinical conse- dothelial Growth Factor (VEGF) manifestations of these diseases. quences. drugs for choroid neovasculari- • Study of the cardiovascular and • Development of an organ cultu- zation and cystic macular edema endothelial damage risk factors re model for studying the factors secondary to uveitis. found in these diseases. • Basic research in animal models eMeRgeNT gROUP on the mechanism of action of an- autoimmune opHtHalmopatHy tiphospholipid antibodies. 2. Sjögren’s syndrome, autoimmune Group Leader: Alfredo Manuel Adan (hospital clínic) manifestations of hepatitis c virus infection and biological therapies: This group studies the clinical, diagnostic and therapeutic as- • Epidemiological multicenter studies pects of autoimmune diseases. The scientific contribution of on the clinical manifestations and this line of research is very competitive and is internationally long-term evolution of these diseases. renowned. The group also studies the genetic polymorphisms of uveitis as risk factors for the different clinical manifestations of the disease, • Study of lymphomas associated and participates in different clinical trials involving novel biological treatments. with Sjögren’s syndrome. • Study of the cardiovascular and endothelial damage risk factors ReSeARCh gROUP found in this syndrome. SyStemic vaSculitiS • Clinical and basic studies in mixed Cryoglobulinemia. Group Leader: Maria cinta cid (hospital clínic) • International registry of treatments This group studies the clinical, diagnostic and therapeutic with biological drugs for systemic aspects of systemic vasculitic disorders, as well as the autoimmune disorders (BIOGEAS). mechanisms producing vascular damage in these diseases. 3. Systemic vasculitis: The scientific contribution of this line of research is very • Investigation of the mechanisms in- competitive and is internationally renowned. Clinical studies are also made volved and the clinical consequences of the systemic vascular lesions characterizing giant cell arteritis, exploring of the persistence of vascular inflam- the mechanisms that produce these vascular lesions in this disease, and par- mation in giant cell arteritis. Identifi- ticipating in different clinical trials involving new biological treatments. The cation of new therapeutic targets. group also coordinates the Spanish registries of vasculitis associated with • Study of the mechanisms involved antineutrophil cytoplasmic antibodies (ANCA) and Behçet’s disease. in the development of abnormal

61 BIOLOgICAL AggReSSION AND ReSPONSe MeChANISMS Systemic autoimmune diseases

PUBLICATIONS

oRiGinAlS 4 Diaz-Gallo L, Gourh P, Broen J, Si- D, Peschken C, Farewell V, Thompson i.f.: 185.01 meon C, Fonollosa V, Ortego-Centeno K, Theriault C, Merrill JT. Autoantibo- N, Agarwal S, Vonk MC, Coenen M, dies as biomarkers for the prediction of 1 Furie R, Petri M, Zamani O, Cerve- Riemekasten G, Hunzelmann N, neuropsychiatric events in systemic lu- ra R, Wallace DJ, Tegzova D, Sanchez- Hesselstrand R, Tan FK, Reveille JD, pus erythematosus. ANN RHEUM DIS. Guerrero J, Schwarting A, Merrill JT, Assassi S, Garcia-Hernandez FJ, Ca- 70:1726-1732. I.F.: 9.08. Chatham WW, Stohl W, Ginzler EM, rreira P, Camps MT, Fernandez-Nebro Hough DR, Zhong ZJ, Freimuth W, A, DeLaPena PG, Nearney T, Hilda D, 7 Ramos-Casals M, Diaz-Lagares C, VanVollenhoven RF. A phase III, rando- Gonzalez-Gay MA, Airo P, Beretta L, Khamashta MA. B-cell-depletion thera- mized, placebo-controlled study of be- Scorza R, Herrick A, Worthington J, py in systemic autoinmune diseases. limumab, a monoclonal antibody that Pros A, Gomez-Gracia I, Trapiella L, Es- Recommendations for use in clinical inhibits B lymphocyte stimulator, in pinosa G, Castellvi I, Witte T, DeKeyser practice. MED CLIN-BARCELONA. patients with systemic lupus erythe- F, Vanthuyne M, Mayes MD, Radstake 136:257-263. I.F.: 1.41. matosus. ARTHRITIS RHEUM-US. TRDJ, Arnett FC, Martin J, Rueda B. 63:3918-3930. I.F.: 8.44. Analysis of the influence of PTPN22 8 Pelegrin L, Mesquida M, Adan A, gene polymorphisms in systemic scle- Cervera C, Bosch-Mestres J, Esteban- 2 Bossini-Castillo L, Broen JCA, rosis. ANN RHEUM DIS. 70:454-462. Redondo C, Juiz-Gonzalez P, Llorenc Simeon CP, Beretta L, Vonk MC, I.F.: 9.08. V, Miro JM. Candida dubliniensis Ortego-Centeno N, Espinosa G, endophthalmitis in a HIV-infected in- Carreira P, Camps MT, Navarrete 5 Carmona FD, Simeon CP, Beretta travenous drug abuser. MYCOSES. N, Gonzalez-Escribano MF, Vicente- L, Carreira P, Vonk MC, Rios-Fernandez 54:E856-E858. I.F.: 1.67. Rabaneda E, Rodriguez L, Tolosa C, R, Espinosa G, Navarrete N, Vicente- Roman-Ivorra JA, Gomez-Gracia I, Rabaneda E, Rodriguez-Rodriguez L, 9 Alba MA, Espigol-Frigole G, Garcia-Hernandez FJ, Castellvi I, Ga- Tolosa C, Garcia-Hernandez FJ, Castellvi Prieto-Gonzalez S, Tavera-Bahillo I, Gar- llego M, Fernandez-Nebro A, Garcia- I, Egurbide MV, Fonollosa V, Gonzalez- cia-Martinez A, Butjosa M, Hernandez- Portales R, Egurbide MV, Fonollosa V, Gay MA, Rodriguez-Carballeira M, Diaz- Rodriguez J, Cid MC. Central Nervous DeLaPena PG, Pros A, Gonzalez-Gay Gonzalez F, Saez-Comet L, Hesselstrand System Vasculitis: Still More Questions MA, Hesselstrand R, Riemekasten R, Riemekasten G, Witte T, Voskuyl AE, than Answers. CURR NEUROPHARMA- G, Witte T, Coenen MJH, Koeleman Schuerwegh AJ, Madhok R, Shiels P, COL. 9:437-448. I.F.: 2.78. BP, Houssiau F, Smith V, DeKeyser F, Fonseca C, Denton C, Nordin A, Palm Westhovens R, DeLanghe E, Voskuyl O, Hoffmann-Vold AM, Airo P, Scorza 10 Bossini-Castillo L, Simeon CP, AE, Schuerwegh AJ, Chee MM, Mad- R, Lunardi C, VanLaar JM, Hunzelmann Beretta L, Vonk MC, Callejas-Rubio hok R, Shiels P, Fonseca C, Denton N, Kreuter A, Herrick A, Worthington J, JL, Espinosa G, Carreira P, Camps MT, C, Claes K, Padykov L, Nordin A, Koeleman BPC, Radstake TRDJ, Martin Rodriguez-Rodriguez L, Rodriguez- Palm O, Lie BA, Airo P, Scorza R, Van- J. Association of a non-synonymous Carballeira M, Garcia-Hernandez FJ, Laar JM, Hunzelmann N, Kreuter A, functional variant of the ITGAM gene Lopez-Longo FJ, Hernandez-Hernandez Herrick A, Worthington J, Radstake with systemic sclerosis. ANN RHEUM V, Saez-Comet L, Egurbide MV, Hessels- TRDJ, Martin J, Rueda B. A replica- DIS. 70:2050-U203. I.F.: 9.08. trand R, Nordin A, Hoffmann-Vold AM, tion study confirms the association Vanthuyne M, Smith V, DeLanghe E, of TNFSF4 (OX40L) polymorphisms 6 Hanly JG, Urowitz MB, Su L, Bae Kreuter A, Riemekasten G, Witte T, Hun- with systemic sclerosis in a large SC, Gordon C, Clarke A, Bernatsky S, zelmann N, Voskuyl AE, Schuerwegh European cohort. ANN RHEUM DIS. Vasudevan A, Isenberg D, Rahman A, AJ, Lunardi C, Airo P, Scorza R, Shiels 70:638-641. I.F.: 9.08. Wallace DJ, Fortin PR, Gladman D, P, VanLaar JM, Fonseca C, Denton C, Romero-Dirz J, Sanchez-Guerrero J, Herrick A, Worthington J, Koeleman 3 Casaroli-Marano R, Adan A, Dooley MA, Bruce I, Steinsson K, Kha- BP, Rueda B, Radstake TRDJ, Martin Gomez-Ulla F, Diaz JM. Age-related mashta M, Manzi S, Ramsey-Goldman J. Confirmation of association of the macular degeneration: Analysis of the R, Sturfelt G, Nived O, VanVollenhoven macrophage migration inhibitory factor results of ranibizumab therapy. MED R, Ramos-Casals M, Aranow C, Mackay gene with systemic sclerosis in a large CLIN-BARCELONA. 136:128-129. M, Kalunian K, Alarcon GS, Fessler BJ, European population. RHEUMATOLOGY. I.F.: 1.41. Ruiz-Irastorza G, Petri M, Lim S, Kamen 50:1976-1981. I.F.: 4.17.

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original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 134.58 34 11 15 11 Illei GG, Cervera R, Burt RK, Doria consensus patient index for primary A, Hiepe F, Jayne D, Pavletic S, Martin Sjogren’s syndrome. ANN RHEUM 2010 173.60 33 15 13 T, Marmont A, Saccardi R, Voskuyl AE, DIS. 70:968-972. I.F.: 9.08. 2011 185.01 37 19 13 Farge D. Current state and future direc- tions of autologous hematopoietic stem 16 Perez-Alvarez R, Diaz-Lagares cell transplantation in systemic lupus C, Garcia-Hernandez F, Lopez-Roses erythematosus. ANN RHEUM DIS. L, Brito-Zeron P, Perez-De-Lis M, Re- 21 Noval S, Ortiz-Perez S, Sanchez- 70:2071-2074. I.F.: 9.08. tamozo S, Bove A, Bosch X, Sanchez- Dalmau BF, Ruiz-Ares G, Arpa J, Adan Tapias JM, Forns X, Ramos-Casals M. A. Neuro-Ophthalmological Features 12 Mosca M, Tani C, Aringer M, Hepatitis B Virus (HBV) Reactivation of Primary Diffuse Leptomeningeal Bombardieri S, Boumpas D, Cervera R, in Patients Receiving Tumor Necrosis Gliomatosis. J NEURO-OPHTHALMOL. Doria A, Jayne D, Khamashta MA, Kuhn Factor (TNF)-Targeted Therapy Analysis 31:299-305. I.F.: 1.06. A, Gordon C, Petri M, Schneider M, of 257 Cases. MEDICINE. 90:359-371. Shoenfeld Y, Smolen JS, Talarico R, Tin- I.F.: 4.26. 22 Carmona FD, Serrano-Lopera A, cani A, Ward MM, Werth VP, Carmona Lopez-Isac E, Simeon CP, Carreira P, L. Development of quality indicators to 17 Garcia-Carrasco M, Mendoza- Rios-Fernandez R, Espinosa G, Camps evaluate the monitoring of SLE patients Pinto C, Riebeling C, Sandoval-Cruz M, MT, Navarrete N, Gonzalez-Escribano in routine clinical practice. AUTOIM- Nava A, Etchegaray-Morales I, Jime- MF, Vicente-Rabaneda E, Rodriguez- MUN REV. 10:383-388. I.F.: 6.56. nez-Hernandez M, Montiel-Jarquin A, Rodriguez L, Tolosa C, Beltran E, Lopez-Colombo A, Cervera R. Influen- Gomez-Garcia I, Fernandez-Castro M, 13 Marcos M, Fernandez C, Soria- ce of Prevalent Vertebral Fractures Lopez-Longo FJ, Garcia-Hernandez no A, Marco F, Martinez JA, Almela on the Quality of Life of Patients with FJ, Castellvi I, Trapiella L, Fernandez- M, Cervera R, Mensa J, Espinosa G. Systemic Lupus Erythematosus. ISR Nebro A, Garcia-Portales R, Egurbide Epidemiology and clinical outcomes of MED ASSOC J. 13:333-337. I.F.: 0.95. MV, Fonollosa V, DeLaPena PG, Pros A, bloodstream infections among lupus Rodriguez-Carballeira M, Diaz-Gonzalez patients. LUPUS. 20:965-971. I.F.: 2.60. 18 Perez-Alvarez R, Perez-De-Lis F, Saez-Comet L, Gonzalez-Gay MA, M, Diaz-Lagares C, Pego-Reigosa JM, Martin J. No evidence for association 14 VanAssen S, Agmon-Levin N, Retamozo S, Bove A, Brito-Zeron P, between the CCR5/Delta32CCR5 po- Elkayam O, Cervera R, Doran MF, Bosch X, Ramos-Casals M. Interstitial lymorphism and systemic sclerosis. Dougados M, Emery P, Geborek P, Lung Disease Induced or Exacerbated CLIN EXP RHEUMATOL. 29:895-896. Ioannidis JPA, Jayne DRW, Kallenberg by TNF-Targeted Therapies: Analysis of I.F.: 2.36. CGM, Muller-Ladner U, Shoenfeld Y, 122 Cases. SEMIN ARTHRITIS RHEU. Stojanovich L, Valesini G, Wulffraat 41:256-264. I.F.: 4.74. 23 Llorenc V, Keller J, Pelegrin L, NM, Bijl M. EULAR recommendations Adan A. Pars Plana Vitrectomy for for vaccination in adult patients with 19 Arevalo JF, Adan A, Berrocal MH, Vitreo-Retinal Complications of Birdshot autoimmune inflammatory rheumatic Espinoza JV, Maia M, Wu L, Roca JA, Chorioretinopathy. OCUL IMMUNOL diseases. ANN RHEUM DIS. 70:414- Quiroz-Mercado H, Ruiz-Moreno JM, INFLAMM. 19:346-352. I.F.: 0.95. 422. I.F.: 9.08. Serrano MA. Intravitreal bevacizumab for inflammatory choroidal neovascu- 24 DeVita S, Soldano F, Isola M, 15 Seror R, Ravaud P, Mariette larization. Results from the Pan-Ame- Monti G, Gabrielli A, Tzioufas A, Ferri C, X, Bootsma H, Theander E, Han- rican Collaborative Retina Study Group Ferraccioli GF, Quartuccio L, Corazza L, sen A, Ramos-Casals M, Dorner T, at 24 Months. RETINA-J RET VIT DIS. DeMarchi G, Ramos M, Voulgarelis M, Bombardieri S, Hachulla E, Brun JG, 31:353-363. I.F.: 2.77. Lenzi M, Saccardo F, Fraticelli P, Mascia Kruize AA, Praprotnik S, Tomsic M, MT, Sansonno D, Cacoub P, Tomsic Gottenberg JE, Devauchelle V, Devita 20 Silvarino R, Sant F, Espinosa G, M, Tavoni A, Pietrogrande M, Zignego S, Vollenweider C, Mandl T, Tzioufas Pons-Estel G, Sole M, Cervera R, Arri- AL, Scarpato S, Mazzaro C, Pioltelli P, A, Carsons S, Saraux A, Sutcliffe zabalaga P. Nephropathy associated Steinfeld S, Lamprecht P, Bombardieri N, Vitali C, Bowman SJ. EULAR with antiphospholipid antibodies in pa- S. Preliminary classification criteria for Sjogren’s Syndrome Patient Reported tients with systemic lupus erythemato- the cryoglobulinaemic vasculitis. ANN Index (ESSPRI): development of a sus. LUPUS. 20:721-729. I.F.: 2.60. RHEUM DIS. 70:1183-1190. I.F.: 9.08.

63 BIOLOgICAL AggReSSION AND ReSPONSe MeChANISMS Systemic autoimmune diseases

25 Casaroli-Marano R, Pinero A, IN, Steinsson K, Khamashta M, Alarcon Segarra M, Lozano E, Espigol-Frigole Adan A, Castro J, Armada F, Cervera GS, Fessler B, Petri M, Manzi S, Nived G, Hernandez-Rodriguez J, Cid MC. E, Llopis MD, Abreu P, Esteban E, O, Sturfelt G, Ramsey-Goldman R, Doo- Tissue and serum markers of inflam- Arias L, Fernandez-Arias I, Kim HK, ley MA, Aranow C, VanVollenhoven R, mation during the follow-up of patients Acebes X, Acosta B, Bahaya Y, Ba- Ramos-Casals M, Zoma A, Kalunian K, with giant-cell arteritis-a prospective rrios M, Blazquez A, Bueno R, Bures Farewell V. SF-36 summary and subs- longitudinal study. RHEUMATOLOGY. A, Carnota P, Castanos A, Cubillas M, cale scores are reliable outcomes of 50:2061-2070. I.F.: 4.17. Degollada N, Fernandez C, Fuste C, neuropsychiatric events in systemic lu- Garcia P, Gil MA, Graell X, Granados pus erythematosus. ANN RHEUM DIS. 33 Prieto-Gonzalez S, Cardellach F, M, Guerra P, Hernandez A, Kalitovics 70:961-967. I.F.: 9.08. Estruch R, Miguel R, Grau JM, Cid MC. N, Llorente S, Mesa JC, Molina JJ, Type 1 autoimmune hepatitis in a patient Mones A, Montero J, Nadal E, Na- 29 Cervera R, Tektonidou MG, Espi- with microscopic polyangiitis: challenges varro M, Ortiz JV, Ortiz S, Otxoa I, nosa G, Cabral AR, Gonzalez EB, Erkan in diagnosis and treatment. MED CLIN- Pereira E, Perez JR, Planas N, Prades D, Vadya S, Adrogue HE, Solomon M, BARCELONA. 136:345-348. I.F.: 1.41. S, Rodriguez E, Rosal F, Ruiz A, San- Zandman-Goddard G, Shoenfeld Y. Task chez A, Udaondo P, Vargas JC, Villota Force on Catastrophic Antiphospholipid 34 VanAssen S, Elkayam O, Agmon- E, Zarallo J. Prevalence of age-related Syndrome (APS) and Non-criteria APS Levin N, Cervera R, Doran MF, Douga- macular degeneration in Spain. Manifestations (I): catastrophic APS, dos M, Emery P, Geborek P, Ioannidis BRIT J OPHTHALMOL. 95:931-936. APS nephropathy and heart valve le- JP, Jayne DR, Kallenberg CG, Müller- I.F.: 2.93. sions. LUPUS. 20:165-173. I.F.: 2.60. Ladner U, Shoenfeld Y, Stojanovich L, Valesini G, Wulffraat NM, Bijl M. 26 Ramos-Casals M, Perez-Alvarez 30 Cervera R, Tektonidou MG, Espi- Vaccination in adult patients with auto- R, Perez-De-Lis M, Xaubet A, Bosch nosa G, Cabral AR, Gonzalez EB, Erkan immune inflammatory rheumatic di- X. Pulmonary Disorders Induced by D, Vadya S, Adrogue HE, Solomon M, seases: A systematic literature review Monoclonal Antibodies in Patients Zandman-Goddard G, Shoenfeld Y. Task for the EULAR evidence-based recom- with Rheumatologic Autoimmune Force on Catastrophic Antiphospholipid mendations for vaccination in adult pa- Diseases. AM J MED. 124:386-394. Syndrome (APS) and Non-criteria APS tients with auto-immune inflammatory I.F.: 5.12. Manifestations (II): thrombocytope- rheumatic diseases. AUTOIMMUN nia and skin manifestations. LUPUS. REV. 10:341-352. I.F.: 6.56. 27 Diaz-Lagares C, Perez-Alvarez 20:174-181. I.F.: 2.60. R, Garcia-Hernandez FJ, Ayala-Gutie- 35 Agmon-Levin N, Blank M, rrez MM, Callejas JL, Martinez-Berrio- 31 Mosca M, Govoni M, Tomietto Zandman-Goddard G, Orbach H, Me- txoa A, Rascon J, Caminal-Montero P, Aringer M, Boumpas D, Cervera R, roni PL, Tincani A, Doria A, Cervera L, Selva-O’callaghan A, Oristrell J, Conti F, D’cruz D, Doria A, DeLaFuente R, Miesbach W, Stojanovich L, Barak Hidalgo C, Gomez-De-La-Torre R, D, Galeazzi M, Houssiau F, Huizinga V, Porat-Katz BS, Amital H, Shoenfeld Saez L, Canora-Lebrato J, Camps MT, TWJ, Khamashta MA, Ines L, Duarte Y. Vitamin D: an instrumental factor Ortego-Centeno N, Castillo-Palma C, Couto M, Meroni P, Montecucco C, in the anti-phospholipid syndrome MJ, Ramos-Casals M. Rates of, and Norkuviene E, Riemekasten G, Rios by inhibition of tissue factor expres- risk factors for, severe infections in V, Schneider M, Shoenfeld Y, Steup- sion. ANN RHEUM DIS. 70:145-150. patients with systemic autoimmune Beekman GM, Szmyrka-Kaczmarek M, I.F.: 9.08. diseases receiving biological agents Tani C, Tincani A, Tzioufas AG, Voll R, off-label. ARTHRITIS RES THER. 13:-. Bencivelli W, Salaffi F, Bombardieri S. 36 Font C, Vidal L, Espinosa G, Tas- I.F.: 4.36. The development of a simple ques- sies D, Monteagudo J, Farrus B, Visa L, tionnaire to screen patients with SLE Cervera R, Gascon P, Reverter JC. Solid 28 Hanly JG, Urowitz MB, Jackson for the presence of neuropsychiatric cancer, antiphospholipid antibodies, and D, Bae SC, Gordon C, Wallace DJ, symptoms in routine clinical practice. venous thromboembolism. AUTOIM- Clarke A, Bernatsky S, Vasudevan LUPUS. 20:485-492. I.F.: 2.60. MUN REV. 10:222-227. I.F.: 6.56. A, Isenberg D, Rahman A, Sanchez- Guerrero J, Romero-Diaz J, Merrill 32 Visvanathan S, Rahman MU, 37 Pons-Estel GJ, Salerni GE, Serra- JT, Fortin PR, Gladman DD, Bruce Hoffman GS, Xu S, Garcia-Martinez A, no RM, Gomez-Puerta JA, Plasin MA,

64 AReA 1 BioloGicAl AGGReSSion AnD ReSponSe MecHAniSMS SySteMic AutoiMMune DiSeASeS

Aldasoro E, Lozano M, Cid J, Cervera 7 O’neill S, Cervera R. Systemic lupus Markers Associated with Clinical Phe- R, Espinosa G. Therapeutic plasma ex- erythematosus. BEST PRACT RES CL notypes of Systemic Sclerosis through change for the management of refrac- RH. 24:841-855. I.F.: 3.30. a Genome-Wide Association Strategy. tory systemic autoimmune diseases: PLOS GENET. 7:-. I.F.: 9.54. Report of 31 cases and review of the 8 Engel P, Gomez-Puerta JA, Ramos- literature. AUTOIMMUN REV. 10:679- Casals M, Lozano F, Bosch X. Therapeu- 2 Dooley MA, Jayne D, Ginzler EM, 684. I.F.: 6.56. tic Targeting of B Cells for Rheumatic Isenberg D, Olsen NJ, Wofsy D, Eit- Autoimmune Diseases. PHARMACOL ner F, Appel GB, Contreras G, Lisk L, REV. 63:127-156. I.F.: 18.86. Solomons N. Mycophenolate versus ReViewS Azathioprine as Maintenance Therapy i.f.: 57.54 for Lupus Nephritis. NEW ENGL J eDitoRiAlS MED. 365:1886-1895. I.F.: 53.49. 1 Bosch X, Lozano F, Cervera R, Ra- i.f.: 5.20 mos-Casals M, Min B. Basophils, IgE, 3 Pfeiffer N. Timolol versus brinzola- and Autoantibody-Mediated Kidney 1 Vasconcelos C, Cervera R, Khamas- mide added to travoprost in glaucoma Disease. J IMMUNOL. 186:6083-6090. hta M. “So this is Lupus” FOREWORD. or ocular hypertension. GRAEF ARCH I.F.: 5.75. LUPUS. 20:339-339. I.F.: 2.60. CLIN EXP. 249:1065-1071. I.F.: 2.16.

2 Pons-Estel GJ, Serrano R, Plasin 2 Cervera R. ‘ASIA’: a new systemic MA, Espinosa G, Cervera R. Epidemio- autoimmune syndrome?. LUPUS. GRAntS foR ReSeARcH logy and management of refractory 20:665-666. I.F.: 2.60. in pRoGReSS lupus nephritis. AUTOIMMUN REV. 10:655-663. I.F.: 6.56. Adan AM. Estudio aleatorizado y MulticentRicS abierto de la eficacia, seguridad y 3 Espinosa G, Berman H, Cervera R. i.f.: 65.19 tolerabilidad de dosis repetidas de be- Management of refractory cases of vacizumab intravítreo en pacientes con catastrophic antiphospholipid syndro- 1 Gorlova O, Martin JE, Rueda B, edema macular uveítico refractario. me. AUTOIMMUN REV. 10:664-668. Koeleman BPC, Ying J, Teruel M, Diaz- Sponsored by: Instituto de Salud Car- I.F.: 6.56. Gallo LM, Broen JC, Vonk MC, Simeon los III (ISCIII), EC08/00096. Duration: CP, Alizadeh BZ, Coenen MJH, Voskuyl 01/01/2008-31/12/2011. 4 Bosch X, Saiz A, Ramos-Casals M. AE, Schuerwegh AJ, VanRiel PLCM, Monoclonal antibody therapy-associa- Vanthuyne M, Van’tSlot R, Italiaander A, Cid MC. Mecanismos implicados ted neurological disorders. NAT REV Ophoff RA, Hunzelmann N, Fonollosa V, y consecuencias clínicas de la per- NEUROL. 7:165-172. I.F.: 6.51. Ortego-Centeno N, Gonzalez-Gay MA, sistencia de la inflamación vascular Garcia-Hernandez FJ, Gonzalez-Escriba- en la arteritis de células gigantes. 5 Ramos-Casals M, Diaz-Lagares no MF, Airo P, VanLaar J, Worthington Identificación de dianas terapéuticas. C, Soto-Cardenas MJ, Brito-Zeron P, J, Hesselstrand R, Smith V, DeKeyser Sponsored by: Ministerio de Ciencia Cuadrado MJ, Sanna G, Bertolaccini F, Houssiau F, Chee MM, Madhok R, e Innovación (Plan Nacional I+D), L, Khamashta MA. Rituximab The- Shiels PG, Westhovens R, Kreuter SAF 08/04328. Duration: 01/01/2009- rapy in Lupus Nephritis: Current Cli- A, DeBaere E, Witte T, Padyukov L, 31/12/2011. nical Evidence. CLIN REV ALLERG Nordin A, Scorza R, Lunardi C, Lie BA, IMMU. 40:159-169. I.F.: 3,44. Hoffmann-Vold AM, Palm O, DeLaPena Ramos M. Alteraciones genéticas del PG, Carreira P, Varga J, Hinchcliff M, sistema inmunitario innato y estado 6 Garcia-Carrasco M, Jimenez- Lee AT, Gourh P, Amos CI, Wigley FM, protrombótico como factores predispo- Hernandez C, Jimenez-Hernandez M, Hummers LK, Hummers J, Nelson JL, nentes de arteriosclerosis subclínica y Voorduin-Ramos S, Mendoza-Pinto C, Riemekasten G, Herrick A, Beretta L, enfermedad cardiovascular en pacien- Ramos-Alvarez G, Montiel-Jarquin A, Fonseca C, Denton CP, Gregersen PK, tes con síndrome de Sjögren primario. Rojas-Rodriguez J, Cervera R. Susac’s Agarwal S, Assassi S, Tan FK, Arnett Sponsored by: Instituto de Salud syndrome: An update. AUTOIMMUN FC, Radstake TRDJ, Mayes MD, Mar- Carlos III (ISCIII), PI080103. Duration: REV. 10:548-552. I.F.: 6.56. tin J. Identification of Novel Genetic 01/01/2009-30/06/2012.

65 BIOLOgICAL AggReSSION AND ReSPONSe MeChANISMS Systemic autoimmune diseases

Casaroli R. Análisis celular y mole- Adan AM. Estudio de factores pre- cular de las células progenitoras me- dictores para el desarrollo de recu- senquimales estromales de la medu- rrencias en la toxoplasmosis ocular. la ósea humana y su potencial en la Sponsored by: Instituto de Salud en la terapia celular para la superficie Carlos III (ISCIII), 010PI10/00479. ocular. Sponsored by: Instituto de Duration: 01/01/2011-31/12/2013. Salud Carlos III, PI09/0992. Duration: 01/01/2010-31/12/2012. Cid MC. Grup de Recerca sobre Inflamació Vascular (vasculitis). Ramos M. Multilingual Organic Sponsored by: AGAUR_SGR09, Information Management in the 2009_SGR_1301. Duration: Medical Domain. Sponsored by: 15/09/2009-31/12/2013. European Comission, Coordinador: Kentro Erevnon Notioanatolikis Evropis Astiki Mi Kerdoskopiki, DoctoRAl tHeSeS 250534. Duration: 01/03/2010- 31/08/2012. Siso A, Ramos-Casals M. Signi- ficado clínico de la presencia de Ramos M. Susceptibilitat immuno- autoanticuerpos en el síndrome de genètica i alteracions metabòliques Sjögren primario: implicaciones en com a factors etiopatogènics de la práctica diaria. PhD student: Nor- dolor crònic en pacients amb sín- ma Nardi, Universitat de Barcelona. drome de Sjögren en comparació amb pacients atesos a l’àmbit Cervera R. Afectación renal en el de l’atenció primària. Sponsored lupus eritematoso sistémico y el by: Fundació La Marató de TV3, síndrome antifosfolipídico: Estudio 071810. Duration: 13/02/2008- clínco-epidemiológico, anátomo- 12/08/2012. patológico y de factores predictivos de morbi-mortalidad. PhD student: Casaroli R. Medicina Regenerativa Guillermo Javier Pons-Estel Silves- en la Superfície Ocular: Aplicación tre (Universitat de Barcelona). de terapia celular para la reparación de la superficie oculr mediante amplificación ex vivo de éclulas progenitoras autólogas del limbo es- clerocorneal sobre membrana am- niótica. Sponsored by: Ministerio de Sanidad, Politica Social e Igualdad, TRA-072. Duration: 01/01/2010- 31/12/2011.

Cervera R. Grup de recerca de malalties autoimmunes sistèmi- ques. Sponsored by: AGAUR_ SGR09, 2009_SGR_1421. Duration: 15/09/2009-31/12/2013.

Ramos M. Grup de Recerca en la Síndrome de Sjögren (GRESS). Sponsored by: AGAUR_SGR09, 2009_SGR_1357. Duration: 28/09/2009-31/12/2013.

66 AReA 1

Team involved in: Biological aggression and response mechanisms

Infectious diseases and AIDS gROUP MeMBeRS

teAM leADeR Josep M. Gatell (Hospital clínic) tel.: 93 227 54 30 fax: 93 451 44 38 e-mail: [email protected]

iDiBApS MeMBeRS: Mireia Arnedo (iDiBApS) Miguel caballero (Hospital clínic) felipe García (Hospital clínic) Montserrat laguno (fundació clínic) Josep Mallolas (Hospital clínic) esteban Martínez (Hospital clínic) José Antonio Martínez (Hospital clínic) José Mensa (Hospital clínic) carmen Álvarez (fundació clínic) laura Zamora (fundació clínic) José M. Miró (Hospital clínic) cristina Rovira (fundació clínic) María Martínez (iDiBApS) Asunción Moreno (Hospital clínic) Alberto Merino (iDiBApS) Víctor Sánchez-Merino Montserrat plana (iDiBApS) (fundació clínic) M. eloisa yuste (iDiBApS) nuRSinG StAff: cristina García de la María Alex Soriano (Hospital clínic) emmanuela fernandez (fundació clínic) (fundació clínic) Ana Muñoz (fundacio clinic) ReSeARcH fellowS: Ana Gonzalez (fundacio clínic) christian Manzardo ADMiniStRAtiVe StAff: florencia etcheverry (fundació clínic) carmen Mensa (iDiBApS) (fundacio clínic) Hodei Arneras (fundacio clinic) irene Ruíz (fundació clínic) luisa Benito Serrano (GeSclinic) laura linares (iDiBApS) Zoe Herreras pérez (cApSe) Gemma Sanclemente StAtiSticiAn: ignacio Menacho pascual (Hospital clínic) Jose ignacio pérez (fundació clínic) (GeSclinic) irma Hoyo (uB) Marta Mari (fundacio clínic) ethel Sequeira Aymar (cApSe) carolina ferreira (iDiBApS) olga Barba (cApSe) collABoRAtoRS: Mª Angeles Moreno ubiedo (cApSe) tecHniciAnS: José luis Blanco (Hospital clínic) Marta catalan (cApSe) pilar callau (fundació clínic) Marta calvo (fundació clinic) Valentin Araunde (cApSe) tuixent escriba (iDiBApS) carlos cervera (Hospital clínic) Ana picas (GeSclinic) Ana García (fundació clínic) nuria climent (iDiBApS) Jordi Hoyo (GeSclinic) Maria teresa García Ana del Rio (Hospital clínic) Mª Jose Giner (GeSclinic) (fundació clínic) teresa Gallart (Hospital clínic) Dani cararach (GeSclinic) carmen Hurtado (fundació clínic) cristina Gil (iDiBApS) eloisa Molés (GeSclinic) M. José Maleno (fundació clínic) Joan Joseph (fundació clínic) Mª luisa Moro (GeSclinic) laia Miralles (iDiBApS) Agathe león (fundació clínic) pilar Arrabal (GeSclinic) Sara nieto (iDiBApS) Montserrat loncà (fundació clínic) yolanda Armero (fundació clínic) Sonsoles Sánchez-palomino ViSitinG ScientiStS: Alberto crespo (iDiBApS) (fundació clínic) Sebastien lyonnais (iDiBApS) Manuel enric Bargalló (iDiBApS) narcís Saubí (iDiBApS) Gilles Mirambeau (uB)

67 BIOLOgICAL AggReSSION AND ReSPONSe MeChANISMS Infectious diseases and AIDS

StrateGic • Infection in solid-organ transplant nophenotyping and the evaluation of oBjectiveS recipients. CD4+ lymphocyte proliferation in res- • Interactions between nosocomial ponse to antigens of the HIV virus. 1. In the AIDS field: infections and antibiotic use. Techniques for the determination of • Immunotherapy of the disease and drug levels have also been developed natural and acquired defense mecha- main lineS of in collaboration with the clinical phar- nisms, including the development of reSearcH macology group. Having ruled out therapeutic and preventive vaccines. the possibility of eradicating the HIV • Efficacy and resistance and tolerance 1. In the AIDS field: virus, the working hypothesis is to mechanisms of new antiretrovirals. • The most important line focuses on see whether it is possible to almost • Immunopathogenesis, treatment the peripheral (blood) and central completely suppress HIV replication response and resistance mecha- response (lymphatic tissue and over the long term, recover the host nisms of certain opportunistic cerebrospinal fluid)to different immune system and quantify the infections, including tuberculosis, antiretroviral therapies when degree of such recovery. The inte- pneumocystis carinii pneumonia administered in very early evolutive rruption of treatment leads to a rapid (PCP) and toxoplasmosis. stages (CD4 > 500 mm3). We disease rebound effect, which could • Complications related to aging have developed ultrasensitive tech- be avoided partially or totally (functio- 2. In the general infections field: niques for the determination of viral nal recovery). • Prevention and treatment support load in plasma and tissues, as well as • The mechanism by which the in endocarditis due to multiresistant techniques for the determination of virus is able to escape the germs, including animal models. genotypic resistance and for immu- cytotoxic immune response is

ReSeARCh gROUP endocarditiS. cardiovaScular infectionS. experimental model

Group Leader: Josep Maria Miro (hospital clínic)

This group studies the epidemiological, clinical, diagnostic, preventive and therapeutic aspects of infectious endocarditis. This is done based on studies of local, national or international cohorts (ICE) that have revealed an increase in endocarditis produced by methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA,

Levels of a-defensins 1-3 produced by imMDDC from HIV-infected individuals. (A) Comparison respectively). Studies using the experimental between the secreted levels of a-defensins 1-3 by imMDDC from HIV-controllers (elite con- model of endocarditis due to MRSA and glyco- trollers and viremic controllers; n = 19) and HIV non-controllers (viremic non-controllers and patients with HAART; n = 20). (B) Secreted levels of a-defensins 1-3 by imMDDC from healthy peptide intermediate-resistant Staphylococcus non-infected (NI; n = 15), elite controllers (ELITE; n = 4), viremic controllers (VC; n = 15), viremic aureus (GISA) have evaluated the activity of non-controllers (VNC; n = 11) and patients receiving HAART (HAART; n = 9). Dots indicate each patient, and lines represent median 6 interquartile ranges (Rodriguez-Garcia M, et al. PloS ONE new antibiotic combinations (phosphomycin and 2010;5:1-10). imipenem), or new antibiotics such as daptomycin and telavancin.

68 AReA 1 BioloGicAl AGGReSSion AnD ReSponSe MecHAniSMS infectiouS DiSeASeS AnD AiDS

subject to study, and could corres- on the administration of autologous • Response to treatment, resistance pond to the selection of quasispe- dendritic cells stimulated ex vivo and transmission of tuberculosis. cies different from the reservoirs with the virus of the patient. The • Prognostic factors of community- (immunological resistance). For first two Phase I clinical trials have acquired and nosocomial respira- this reason we have started a already been finished and publis- tory infections in both immuno- research line aimed at developing hed. The third study is now practi- competent and immune depressed techniques for stimulating the im- cally finished. individuals. mune system, with a view to as- • We are developing different im- • The genetic fundaments of host sociating them with antiretroviral munogens which may be potential susceptibility and the biochemical, therapy. Cyclic interruption of the candidates for therapeutic or pre- molecular and replicative capacity treatment and therapeutic vacci- ventive vaccines. bases of the resistant strains. nes can induce recovery of the 2. In the general infections field: specific immune response to HIV • Clinical and experimental endocar- antigens, associated with a spon- ditis, including endocarditis in illegal For further information: taneous decrease in viral load, drug abusers (Dr. J.M. Miró). www.idibaps.org/aidsresearch which is correlated to the degree • Infections in transplant recipients. of proliferative and specific cyto- Microbiological diagnosis and prog- toxic response against HIV-1 in a nostic markers (Dr. A. Moreno). small percentage of patients. • Predictive factors and markers of • We have also developed an immu- treatment response in nosocomial notherapeutic technique based infections (Dr. J. Mensa).

ReSeARCh gROUP ReSeARCh gROUP eMeRgeNT gROUP infectionS in Solid-orGan aidS and Hiv infection noSocomial infection tranSplant recipientS Study Group Group Leader: Josep Maria Gatell Group Leader: Group Leader: (hospital clínic) Asuncion Moreno Alex Soriano (hospital clínic) (hospital clínic) This group studies the clinical, diag- In the last years, this group has This group stud- nostic, therapeutic and preventive studied the clinical and evolutive ies the clinical, aspects of HIV infection. The scientific characteristics of bacteremias in patients subjected diagnostic, therapeutic and pre- contribution of this line of research is to different solid organ transplants (kidney, liver, ventive aspects of nosocomial very competitive and is internationally heart and renal-pancreatic). We have shown that (in-hospital) infections. The sci- renowned. This group of investigators mannose binding to lectin polymorphisms (MBL) entific contribution is particularly focuses on exploration of the potential condition an increase in the prevalence of cyto- notorious in the treatment and for eradicating HIV infection and on megalovirus (CMV) disease, and have analyzed the management of bacteremia, in- reconstruction of the immune system, mortality risk factors of pneumonia in transplant pa- fections in Intensive Care Units, including the development of preven- tients. Studies have been made of the prevalence and infections related to orthope- tive and therapeutic vaccines. Since of other viruses of the herpes group (HHV-6 and -7) dic implants. Its components are its start in 2002, Dr. Gatell has coordi- in the transplant population, as well as their patho- members of the REIPI (Spanish nated the Spanish network of research genic role in the post-transplantation period. These Research Network in Infectious groups in AIDS (RIS), funded by the studies have been made jointly with investigators Disease), and participate actively FIS, and since 2007 has coordinated specialized in Microbiology and Immunology, and in multicenter projects financed the HIVACAT project on research into with the different Transplantation Units (Institutes by the FIS. of Digestive, Renal and Thoracic Diseases). vaccines against HIV infection.

69 BIOLOgICAL AggReSSION AND ReSPONSe MeChANISMS Infectious diseases and AIDS

PUBLICATIONS

oRiGinAlS 6 Garcia F, Climent N, Assoumou L, Wang A. Association Between Valvular i.f.: 359.35 Gil C, Gonzalez N, Alcami J, Leon A, Surgery and Mortality Among Patients Romeu J, Dalmau J, Martinez-Picado With Infective Endocarditis Complica- 1 Pelegrin L, Mesquida M, Adan A, J, Lifson J, Autran B, Costagliola D, ted by Heart Failure. JAMA-J AM MED Cervera C, Bosch-Mestres J, Este- Clotet B, Gatell JM, Plana M, Gallart T. ASSOC. 306:2239-2247. I.F.: 30.01. ban-Redondo C, Juiz-Gonzalez P, Llo- A Therapeutic Dendritic Cell-Based Vac- renc V, Miro JM. Candida dubliniensis cine for HIV-1 Infection. J INFECT DIS. 12 Medina-Ramirez M, Sanchez- endophthalmitis in a HIV-infected 203:473-478. I.F.: 6.29. Merino V, Sanchez-Palomino S, intravenous drug abuser. MYCOSES. Merino-Mansilla A, Ferreira CB, Perez 54:E856-E858. I.F.: 1.67. 7 Tomas X, Bori G, Garcia S, Garcia- I, Gonzalez N, Alvarez A, Alcocer-Gon- Diez AI, Pomes J, Soriano A, Rios J, zalez JM, Garcia F, Gatell JM, Alcami 2 Marcos M, Fernandez C, Soriano Almela M, Mensa J, Gallart X, Martinez J, Yuste E. Broadly Cross-Neutralizing A, Marco F, Martinez JA, Almela M, JC, Riba J. Accuracy of CT-guided joint Antibodies in HIV-1 Patients with Un- Cervera R, Mensa J, Espinosa G. aspiration in patients with suspected detectable Viremia. J VIROL. 85:5804- Epidemiology and clinical outcomes infection status post-total hip arthro- 5813. I.F.: 5.19. of bloodstream infections among plasty. SKELETAL RADIOL. 40:57-64. lupus patients. LUPUS. 20:965-971. I.F.: 1.39. 13 Pinilla MI, Cobos-Trigueros N, I.F.: 2.60. Soriano A, Martinez JA, Zboromyrska 8 Martinez-Navio JM, Casanova V, Y, Almela M, Mensa J. Burkholderia ce- 3 Sanchez-Palomino S, Massanella Pacheco R, Naval-Macabuhay I, Cli- pacia bacteremia: a prospective analy- M, Carrillo J, Garcia A, Garcia F, Gon- ment N, Garcia F, Gatell JM, Mallol J, sis of 33 episodes. REV ESP QUIM. zalez N, Merino A, Alcami J, Bofill M, Gallart T, Lluis C, Franco R. Adenosine 24:209-212. I.F.: 0.67. Yuste E, Gatell JM, Clotet B, Blanco deaminase potentiates the generation J. A cell-to-cell HIV transfer assay of effector, memory, and regulatory 14 Ortega M, Marco F, Soriano A, Al- identifies humoral responses with CD4(+) T cells. J LEUKOCYTE BIOL. mela M, Martinez JA, Lopez J, Pitart C, broad neutralization activity. VACCI- 89:127-136. I.F.: 4.63. Mensa J. Candida species bloodstream NE. 29:5250-5259. I.F.: 3.57. infection: epidemiology and outcome in 9 Freitas P, Carvalho D, Santos AC, a single institution from 1991 to 2008. J 4 Reekie J, Reiss P, Ledergerber B, Mesquita J, Correia F, Xerinda S, HOSP INFECT. 77:157-161. I.F.: 3.08. Sedlacek D, Parczewski M, Gatell J, Marques R, Martinez E, Sarmento A, Katlama C, Fatkenheuer G, Lundgren Medina JL. Assessment of body fat 15 Ortega M, Marco F, Soriano A, JD, Mocroft A. A comparison of the composition disturbances by bioimpe- Almela M, Martinez JA, Lopez J, Pitart long-term durability of nevirapine, dance analysis in HIV-infected adults. J C, Mensa J. Cefotaxime resistance and efavirenz and lopinavir in routine ENDOCRINOL INVEST. 34:E321-E329. outcome of Klebsiella spp bloodstream clinical practice in Europe: a Euro- I.F.: 1.48. infection. EUR J CLIN MICROBIOL. SIDA study. HIV MED. 12:259-268. 30:1599-1605. I.F.: 2.63. I.F.: 3.58. 10 Labarga P, Soriano V, Caruz A, Poveda E, DiLello F, Hernandez-Quero 16 Marcos M, Soriano A, Inurrieta A, 5 Leon A, Caceres C, Fernandez J, Moreno S, Bernal E, Miro JM, Leal Martinez JA, Romero A, Cobos N, Her- E, Chausa P, Martin M, Codina C, M, Gutierrez F, Portilla J, Pineda JA. nandez C, Almela M, Marco F, Mensa Rousaud A, Blanch J, Mallolas J, Association between IL28B gene poly- J. Changing epidemiology of central Martinez E, Blanco JL, Laguno M, morphisms and plasma HCV-RNA levels venous catheter-related bloodstream Larrousse M, Milinkovic A, Zamora L, in HIV/HCV-co-infected patients. AIDS. infections: increasing prevalence of Canal N, Miro JM, Gatell JM, Gomez 25:761-766. I.F.: 6.35. Gram-negative pathogens. J ANTI- EJ, Garcia F. A New Multidisciplinary MICROB CHEMOTH. 66:2119-2125. Home Care Telemedicine System 11 Kiefer T, Park L, Tribouilloy C, I.F.: 4.66. to Monitor Stable Chronic Human Cortes C, Casillo R, Chu V, Delahaye F, Immunodeficiency Virus-Infected Durante-Mangoni E, Edathodu J, Falces 17 Llibre JM, Arribas JR, Domingo P, Patients: A Randomized Study. PLOS C, Logar M, Miro JM, Naber C, Tripodi Gatell JM, Lozano F, Santos JR, Rivero ONE. 6:-. I.F.: 4.41. MF, Murdoch DR, Moreillon P, Utili R, A, Moreno S, Clotet B. Clinical implica-

70 AReA 1 BioloGicAl AGGReSSion AnD ReSponSe MecHAniSMS infectiouS DiSeASeS AnD AiDS

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 299.30 60 41 10 tions of fixed-dose coformulations of M, Blanco J, Woods M, Gunthard HF, antiretrovirals on the outcome of HIV-1 DeBakker P, Douek DC, Silvestri G, 2010 207.37 47 24 7 therapy. AIDS. 25:1683-1690. I.F.: 6.35. Martinez-Picado J, Telenti A. Compara- 2011 359.35 91 37 19 tive transcriptomics of extreme pheno- 18 Miro JM, Manzardo C, Zamora L, types of human HIV-1 infection and SIV Pumarola T, Herreras Z, Gallart T, Gatell infection in sooty mangabey and rhesus JM. Clinical management of acute and macaque. J CLIN INVEST. 121:2391- 28 Martinez E. Disorders of fat chronic human immunodeficiency virus 2400. I.F.: 14.15. partitioning in treated HIV-infection. infection before starting antiretroviral BEST PRACT RES CL EN. 25:415- treatment. ENFERM INFEC MICR CL. 24 Munoz-Mahamud E, Garcia S, 427. I.F.: 4.19. 29:759-772. I.F.: 1.66. Bori G, Martinez-Pastor JC, Zumba- do JA, Riba J, Mensa J, Soriano A. 29 Berenguer J, VonWichmann 19 Perello R, Calvo M, Miro O, Casta- Comparison of a low-pressure and a MA, Quereda C, Miralles P, Mallolas neda M, Saubi N, Camon S, Foix A, Ga- high-pressure pulsatile lavage during J, Lopez-Aldeguer J, Alvarez-Pellicer tell JM, Masotti M, Mallolas J, Sanchez debridement for orthopaedic implant J, DeMiguel J, Crespo M, Guardiola M, Martinez E. Clinical presentation of infection. ARCH ORTHOP TRAUM SU. JM, Tellez MJ, Galindo MJ, Arponen acute coronary syndrome in HIV infec- 131:1233-1238. I.F.: 1.20. S, Barquilla E, Bellon JM, Gonzalez- ted adults: A retrospective analysis of Garcia J. Effect of accompanying a prospectively collected cohort. EUR J 25 Papagno L, Alter G, Assoumou L, antiretroviral drugs on virological INTERN MED. 22:485-488. I.F.: 1.66. Murphy RL, Garcia F, Clotet B, Larsen response to pegylated interferon and M, Braibant M, Marcelin AG, Costaglio- ribavirin in patients co-infected with 20 Marcos MA, Ramon S, Anton A, la D, Altfeld M, Katlama C, Autran B. HIV and hepatitis C virus. J ANTIMI- Martinez E, Vilella A, Olive V, Cilloniz Comprehensive analysis of virus-specific CROB CHEMOTH. 66:2843-2849. C, Moreno A, Torres A, Pumarola T. T-cells provides clues for the failure of I.F.: 4.66. Clinical relevance of mixed respiratory therapeutic immunization with ALVAC- viral infections in adults with influenza HIV vaccine. AIDS. 25:27-36. I.F.: 6.35. 30 Tural C, Sola R, Alvarez NP, A H1N1. EUR RESPIR J. 38:739-742. Molto J, Sanchez M, Zamora AM, Or- I.F.: 5.92. 26 Blasco AJ, Arribas JR, Clotet B, nelas A, Laguno M, Gonzalez J, Von- Domingo P, Gonzalez-Garcia J, Lopez- Wichmann MA, Tellez MJ, Paredes 21 Cervera C, Castaneda X, Pericas Bernaldo JC, Llibre JM, Lozano F, Po- R, Clotet B. Effect of an induction JM, DelRio A, DeLaMaria CG, Mestres dzamczer D, Santamaria JM, Tuset M, period of pegylated interferon-alpha C, Falces C, Marco F, Moreno A, Miro Zamora L, Lazaro P, Gatell JM. Costs 2a and ribavirin on early virological JM. Clinical utility of daptomycin in and cost effectiveness analysis of response in HIV-HCV-coinfected infective endocarditis caused by Gram- preferred GESIDA regimens for initial patients: results from the CORAL-2 positive cocci. INT J ANTIMICROB AG. antiretroviral therapy. ENFERM INFEC study. ANTIVIR THER. 16:833-841. 38:365-370. I.F.: 3.79. MICR CL. 29:721-730. I.F.: 1.66. I.F.: 3.77.

22 Cilloniz C, Ewig S, Ferrer M, Pol- 27 Mothe B, Llano A, Ibarrondo J, 31 Viasus D, Pano-Pardo JR, Cor- verino E, Gabarrus A, DeLaBellacasa Daniels M, Miranda C, Zamarreno J, dero E, Campins A, Lopez-Medrano F, JP, Mensa J, Torres A. Community- Bach V, Zuniga R, Perez-Alvarez S, Ber- Villoslada A, Farinas MC, Moreno A, acquired polymicrobial pneumonia in ger CT, Puertas MC, Martinez-Picado J, Rodriguez-Bano J, Oteo JA, Martinez- the intensive care unit: aetiology and Rolland M, Farfan M, Szinger JJ, Hilde- Montauti J, Torre-Cisneros J, Segura prognosis. CRIT CARE. 15:-. I.F.: 4.60. brand WH, Yang OO, Sanchez-Merino F, Carratala J. Effect of immunomo- V, Brumme CJ, Brumme ZL, Hecker- dulatory therapies in patients with 23 Rotger M, Dalmau J, Rauch A, man D, Allen TM, Mullins JI, Gomez pandemic influenza A (H1N1) 2009 Mclaren P, Bosinger SE, Martinez R, G, Goulder PJ, Walker BD, Gatell JM, complicated by pneumonia. J INFEC- Sandler NG, Roque A, Liebner J, Ba- Clotet B, Korber BT, Sanchez J, Brander TION. 62:193-199. I.F.: 3.81. ttegay M, Bernasconi E, Descombes C. Definition of the viral targets of pro- P, Erkizia I, Fellay J, Hirschel B, Miro tective HIV-1-specific T cell responses. 32 Cervera C, DelRio A, Garcia L, JM, Palou E, Hoffmann M, Massanella J TRANSL MED. 9:-. I.F.: 3.51. Sala M, Almela M, Moreno A, Falces C,

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Mestres CA, Marco F, Robau M, Ga- of autologous whole inactivated HIV-1 logy (SEIMC). 2011 Update. ENFERM tell JM, Miro JM. Efficacy and safety for clinical use in therapeutic vaccines. INFEC MICR CL. 29:435-454. I.F.: 1.66. of outpatient parenteral antibiotic VACCINE. 29:5711-5724. I.F.: 3.57. therapy for infective endocarditis: 42 Lee A, Chalfine A, Daikos GL, Ga- a ten-year prospective study. EN- 38 Viasus D, Pano-Pardo JR, Pa- rilli S, Jovanovic B, Lemmen S, Martinez FERM INFEC MICR CL. 29:587-592. chon J, Campins A, Lopez-Medrano F, JA, Aumatell CM, Mcewen J, Pittet D, I.F.: 1.66. Villoslada A, Farinas MC, Moreno A, Rubinovitch B, Sax H, Harbarth S. Hand Rodriguez-Bano J, Oteo JA, Martinez- hygiene practices and adherence deter- 33 Vilchez F, Martinez-Pastor JC, Montauti J, Torre-Cisneros J, Segura F, minants in surgical wards across Europe Garcia-Ramiro S, Bori G, Tornero E, Gudiol F, Carratala J. Factors associated and Israel: A multicenter observational Garcia E, Mensa J, Soriano A. Effica- with severe disease in hospitalized study. AM J INFECT CONTROL. 39:517- cy of debridement in hematogenous adults with pandemic (H1N1) 2009 520. I.F.: 3.04. and early post-surgical prosthetic in Spain. CLIN MICROBIOL INFEC. joint infections. INT J ARTIF OR- 17:738-746. I.F.: 4.78. 43 Etcheverry MF, Lum PJ, Evans JL, GANS. 34:863-869. I.F.: 1.50. Sanchez E, DeLazzari E, Mendez-Arancibia 39 Reekie J, Gatell JM, Yust I, E, Sierra E, Gatell JM, Page K, Joseph J. 34 Cervera C, Fernandez-Ruiz M, Bakowska E, Rakhmanova A, Losso HIV vaccine trial willingness among injec- Valledor A, Linares L, Anton A, Mar- M, Krasnov M, Francioli P, Kowalska tion and non-injection drug users in two cos MA, Sanclemente G, Hoyo I, Co- JD, Mocroft A. Fatal and nonfatal AIDS urban centres, Barcelona and San Francis- fan F, Ricart MJ, Perez-Villa F, Navasa and non-AIDS events in HIV-1-positive co. VACCINE. 29:1991-1996. I.F.: 3.57. M, Pumarola T, Moreno A. Epidemio- individuals with high CD4 cell counts logy and risk factors for late infection according to viral load strata. AIDS. 44 Bohlius J, Schmidlin K, Boue F, in solid organ transplant recipients. 25:2259-2268. I.F.: 6.35. Fatkenheuer G, May M, Caro-Murillo TRANSPL INFECT DIS. 13:598-607. AM, Mocroft A, Bonnet F, Clifford G, I.F.: 2.04. 40 DeLaTorre-Cisneros J, Farinas Paparizos V, Miro JM, Obel N, Prins M, MC, Caston JJ, Aguado JM, Cantisan Chene G, Egger M. HIV-1-related Hodg- 35 Carcelero E, Tuset M, Martin S, Carratala J, Cervera C, Cisneros JM, kin lymphoma in the era of combination M, DeLazzari E, Codina C, Miro J, Cordero E, Crespo-Leiro MG, Fortun antiretroviral therapy: incidence and Gatell JM. Evaluation of antiretroviral- J, Frauca E, Gavalda J, Gil-Vernet S, evolution of CD4(+) T-cell lymphocytes. related errors and interventions by Gurgui M, Len O, Lumbreras C, Marcos BLOOD. 117:6100-6108. I.F.: 10.56. the clinical pharmacist in hospitalized MA, Martin-Davila P, Monforte V, Mon- HIV-infected patients. HIV MED. tejo M, Moreno A, Munoz P, Navarro D, 45 Lopez-Medrano F, Fernandez-Ruiz 12:494-499. I.F.: 3.58. Pahissa A, Perez JL, Rodriguez-Bernot M, Morales JM, San-Juan R, Cervera A, Rumbao J, Juan RS, Santos F, Varo C, Carratala J, Torre-Cisneros J, Gaval- 36 Gil C, Garcia MT, Garcia F, Miro E, Zurbano F. GESITRA-SEIMC/REIPI re- da J, Munoz P, Len O, Martin-Davila JM, Aguero F, Alos L, Zamora L, commendations for the management of P, Ramos A, Montejo M, Lumbreras Capon A, Costa J, Pumarola T, Gatell cytomegalovirus infection in solid-organ C, Moreno A, Aguado JM. Impact JM. Evaluation of the Roche COBAS transplant patients. ENFERM INFEC of Hepatitis C Virus Infection on the (R) TaqMan (R) HIV-1 test for quanti- MICR CL. 29:735-758. I.F.: 1.66. Risk of Infectious Complications After fying HIV-1 RNA in infected cells and Kidney Transplantation: Data From the lymphoid tissue. J VIROL METHODS. 41 Fortun J, Carratala J, Gavalda J, RESITRA/REIPI Cohort. TRANSPLANTA- 174:69-76. I.F.: 2.14. Lizasoain M, Salavert M, DeLaCamara TION. 92:543-549. I.F.: 3.68. R, Borges M, Cervera C, Garnacho J, 37 Gil C, Climent N, Garcia F, Lassaleta A, Lumbreras C, Sanz MA, 46 Freitas P, Carvalho D, Souto S, Hurtado C, Nieto-Marquez S, Leon Ramos JT, Torre-Cisneros J, Aguado Santos AC, Xerinda S, Marques R, Mar- A, Garcia MT, Rovira C, Miralles L, JM, Cuenca-Estrella M. Guidelines for tinez E, Sarmento A, Medina JL. Impact Dalmau J, Pumarola T, Almela M, the Treatment of Invasive Fungal Disea- of Lipodystrophy on the prevalence and Martinez-Picado J, Lifson JD, Zamora se by Aspergillus spp. and Other Fungi components of metabolic syndrome in L, Miro JM, Brander C, Clotet B, Ga- Issued by the Spanish Society of Infec- HIV-infected patients. BMC INFECT DIS. llart T, Gatell JM. Ex vivo production tious Diseases and Clinical Microbio- 11:-. I.F.: 2.83.

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47 Ferrer E, DelRio L, Martinez E, 53 Sterzik H, Soriano A, Mohamad in HIV-Infected Patients Correlates Curto J, Domingo P, Ribera E, Negre- AM, Martinez JA, Fernandez J, Cobos With the Imbalance Between Ma- do E, Rosales J, Saumoy M, Ordonez N, Morata L, Mensa J. Is linezolid a risk trix Metalloproteinases and Their J, Gatell JM, Podzamczer D. Impact of factor for Gram-negative bacillus infec- Inhibitors. J INFECT DIS. 203:810- Switching from Lopinavir/Ritonavir to tions in intensive care unit patients? A 813. I.F.: 6.29. Atazanavir/Ritonavir on Body Fat Re- comparative study with vancomycin. distribution in Virologically Suppressed SCAND J INFECT DIS. 43:765-770. 59 Cilloniz C, Ewig S, Polverino E, HIV-Infected Adults. AIDS RES HUM I.F.: 1.56. Marcos MA, Esquinas C, Gabarrus A, RETROV. 27:1061-1065. I.F.: 2.08. Mensa J, Torres A. Microbial aetiolo- 54 Martina MN, Cofan F, Suarez A, gy of community-acquired pneumonia 48 Letang E, Miro JM, Nhampossa Masso E, Trullas JC, Cervera C, Moreno and its relation to severity. THORAX. T, Ayala E, Gascon J, Menendez C, A, Oppenheimer F, Miiro JM, Campistol 66:340-346. I.F.: 6.53. Alonso PL, Naniche D. Incidence and JM. Kidney Transplantation and Waiting Predictors of Immune Reconstitution List for Renal Transplantation for Hu- 60 Garrabou G, Lopez S, Moren C, Inflammatory Syndrome in a Rural man Immunodeficiency Virus Patients. Martinez E, Fontdevila J, Cardellach Area of Mozambique. PLOS ONE. 6:-. TRANSPL P. 43:2179-2181. I.F.: 0.99. F, Gatell JM, Miro O. Mitochondrial I.F.: 4.41. damage in adipose tissue of untrea- 55 Antinori A, Coenen T, Costagiola ted HIV-infected patients. AIDS. 49 Linares L, Sanclemente G, Cer- D, Dedes N, Ellefson M, Gatell J, Gi- 25:165-170. I.F.: 6.35. vera C, Hoyo I, Cofan F, Ricart MJ, rardi E, Johnson M, Kirk O, Lundgren Perez-Villa F, Navasa M, Marcos MA, J, Mocroft A, Monforte AD, Phillips A, 61 Garcia AI, Milinkovic A, Tomas X, Anton A, Pumarola T, Moreno A. In- Raben D, Rockstroh JK, Sabin C, Son- Rios J, Perez I, Vidal-Sicart S, Pomes fluence of Cytomegalovirus Disease nerborg A, DeWolf F. Late presentation J, DelAmo M, Mallolas J. MRI signal in Outcome of Solid Organ Transplant of HIV infection: a consensus definition. changes of the bone marrow in HIV- Patients. TRANSPL P. 43:2145-2148. HIV MED. 12:61-64. I.F.: 3.58. infected patients with lipodystrophy: I.F.: 0.99. correlation with clinical parameters. 56 Gomez J, Canovas E, Banos V, SKELETAL RADIOL. 40:1295-1301. 50 Martinez E, Marcos MA, Hoyo- Martinez L, Garcia E, Hernandez-Torres I.F.: 1.39. Ulloa I, Anton A, Sanchez M, Vilella A, A, Canteras M, Ruiz J, Medina M, Mar- Larrousse M, Perez I, Moreno A, Trilla tinez P, Canovas A, Soriano A, Clavel 62 Saubi N, Im EJ, Fernandez- A, Pumarola T, Gatell JM. Influenza M. Linezolid plus Rifampin as a Salvage Lloris R, Gil O, Cardona PJ, Gatell J, A H1N1 in HIV-infected adults. HIV Therapy in Prosthetic Joint Infections Hanke T, Joseph J. Newborn Mice MED. 12:236-245. I.F.: 3.58. Treated without Removing the Implant. Vaccination with BCG.HIVA(222) plus ANTIMICROB AGENTS CH. 55:4308- MVA.HIVA Enhances HIV-1-Specific 51 Bori G, Munoz-Mahamud E, Gar- 4310. I.F.: 4.67. Immune Responses: Influence of cia S, Mallofre C, Gallart X, Bosch J, Age and Immunization Routes. CLIN Garcia E, Riba J, Mensa J, Soriano A. 57 Saumoy M, Ordonez-Llanos J, DEV IMMUNOL. :-. I.F.: 2.26. Interface membrane is the best sam- Martinez E, Barragan P, Ribera E, Bo- ple for histological study to diagnose net R, Knobel H, Negredo E, Lonca 63 Ortiz M, Poloni ES, Furrer H, prosthetic joint infection. MODERN M, Curran A, Gatell JM, Podzamczer Kovari H, Martinez R, Arnedo M, Elzi L, PATHOL. 24:579-584. I.F.: 4.18. D. Low-density lipoprotein size and Bernasconi E, Vernazza P, Hirschel B, lipoprotein-associated phospholipase Cavassini M, Ledergerber B, Gunthard 52 Garcia-Vidal C, Barba P, Arnan A2 in HIV-infected patients switching HF, Telenti A, Tarr PE. No Longitudinal M, Moreno A, Ruiz-Camps I, Gudiol C, to abacavir or tenofovir. ANTIVIR THER. Mitochondrial DNA Sequence Changes Ayats J, Orti G, Carratala J. Invasive 16:459-468. I.F.: 3.77. in HIV-infected Individuals With and Aspergillosis Complicating Pande- Without Lipoatrophy. J INFECT DIS. mic Influenza A (H1N1) Infection in 58 Diaz A, Garcia F, Mozos A, Ca- 203:620-624. I.F.: 6.29. Severely Immunocompromised Pa- ballero M, Leon A, Martinez A, Gil C, tients. CLIN INFECT DIS. 53:E16-E19. Plana M, Gallart T, Gatell JM, Alos L. 64 Cervera C, Fernandez-Aviles F, I.F.: 8.19. Lymphoid Tissue Collagen Deposition DeLaCalle-Martin O, Bosch X, Rovira

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M, Plana M, Moreno A, Garcia F, Miro 69 Pett SL, Carey C, Lin E, 74 Mogollon MV, Anguita MP, JM, Martinez A, Gallart T, Carreras E, Wentworth D, Lazovski J, Miro Aguado JM, Tornos P, Miro JM, Gal- Blade J, Gatell JM. Non-myeloabla- JM, Gordin F, Angus B, Rodriguez- vez-Acebal J, Munoz-Sanz A, Farinas tive hematopoietic stem cell trans- Barradas M, Rubio R, Tambussi G, MD, Fernandez-Guerrero M, Vilacos- plantation in the treatment of severe Cooper DA, Emery S. Predictors of ta I, Munoz P, Montejo-Baranda JM, idiopathic CD4+lymphocytopenia. bacterial pneumonia in Evaluation Hidalgo-Tenorio C, Falco V, DelRio EUR J HAEMATOL. 87:87-91. of Subcutaneous Interleukin-2 in A, Arnaiz AM, San-Feliu I, DeAlarcon I.F.: 2.79. a Randomized International Trial A. Q fever endocarditis in Spain. (ESPRIT). HIV MED. 12:219-227. Clinical characteristics and outcome. 65 Vilchez F, Martinez-Pastor JC, I.F.: 3.58. ENFERM INFEC MICR CL. 29:109- Garcia-Ramiro S, Bori G, Macule 116. I.F.: 1.66. F, Sierra J, Font L, Mensa J, Soria- 70 Font-Vizcarra L, Lozano no A. Outcome and predictors of L, Rios J, Forga MT, Soriano A. 74 Font-Vizcarra L, Zumbado A, treatment failure in early post-surgical Preoperative nutritional status and Garcia S, Bosch J, Mensa J, Soriano prosthetic joint infections due to Sta- post-operative infection in total A. Relationship between haematoma phylococcus aureus treated with de- knee replacements: A prospective in femoral neck fractures contamina- bridement. CLIN MICROBIOL INFEC. study of 213 patients. INT J ARTIF tion and early postoperative prosthetic 17:439-444. I.F.: 4.78. ORGANS. 34:876-881. I.F.: 1.50. joint infection. INJURY. 42:200-203. I.F.: 2.27. 66 Trullas JC, Cofan F, Barril G, 71 Orcau A, Cayla JA, Martinez Martinez-Castelao A, Jofre R, Rivera JA. Present epidemiology of tuber- 76 Font-Vizcarra L, Tornero E, Bori M, Martinez-Ara J, Ros S, Perez I, culosis. Prevention and control pro- G, Bosch J, Mensa J, Soriano A. Moreno A, Miro JM. Outcome and grams. ENFERM INFEC MICR CL. Relationship between intraoperative Prognostic Factors in HIV-1-Infected 29:2-7. I.F.: 1.66. cultures during hip arthroplasty, obe- Patients on Dialysis in the cART sity, and the risk of early prosthetic Era: a GESIDA/SEN Cohort Study. 72 Romero A, Sued O, Puig T, joint infection: A prospective study of JAIDS-J ACQ IMM DEF. 57:276-283. Esteve A, Pumarola T, Casabona J, 428 patients. INT J ARTIF ORGANS. I.F.: 4.26. Gonzalez V, Matas L, Tural C, Rodri- 34:870-875. I.F.: 1.50. go I, Margall N, Domingo P, Casano- 67 Martinez-Rebollar M, Lonca va A, Ferrer E, Caballero E, Ribera 77 Sierra JM, Garcia S, Martinez- M, Perez I, Soy D, Brunet M, Martin E, Farre J, Amengual MJ, Navarro Pastor JC, Tomas X, Gallart X, Vila J, R, Coll O, Hernandez S, Laguno M, G, Prat JM, Masabeu A, Simo JM, Bori G, Macule F, Mensa J, Riba J, Milinkovic A, Larrousse M, Calvo M, Villaverde CA, Barrufet P, Sauca Soriano A. Relationship between the Blanco JL, Martinez E, Gatell JM, MG, Ortin X, Orti A, Navarro R, Eu- degree of osteolysis and cultures ob- Mallolas J. Pharmacokinetic Study ras JM, Vilaro J, Villa MC, Montull tained by sonication of the prosthe- of Saquinavir 500 mg Plus Ritonavir S, Vilanova C, Pujol F, Diaz O, Miro ses in patients with aseptic loosening (1000/100 mg Twice a Day) in HIV-Po- JM. Prevalence of Transmitted of a hip or knee arthroplasty. ARCH sitive Pregnant Women. THER DRUG Antiretroviral Resistance and Dis- ORTHOP TRAUM SU. 131:1357- MONIT. 33:772-777. I.F.: 3.13. tribution of HIV-1 Subtypes Among 1361. I.F.: 1.20. Patients with Recent Infection in 68 Viasus D, Pano-Pardo JR, Pa- Catalonia (Spain) between 2003 and 78 Lejeune M, Miro JM, DeLazzari chon J, Riera M, Lopez-Medrano F, 2005. ENFERM INFEC MICR CL. E, Garcia F, Claramonte X, Martinez Payeras A, Farinas MC, Moreno A, 29:482-489. I.F.: 1.66. E, Ribera E, Arrizabalaga J, Arribas Rodriguez-Bano J, Oteo JA, Martinez- JR, Domingo P, Ferrer E, Plana M, Montauti J, Torre-Cisneros J, Segura 73 Garcia-Oltra E, Garcia-Ramiro Valls ME, Podzamczer D, Pumarola F, Gudiol F, Carratala J. Pneumonia S, Pastor JCM, Tibau R, Bori G, T, Jacquet A, Mallolas J, Gatell JM, Complicating Pandemic (H1N1) 2009 Bosch J, Mensa J, Soriano A. Gallart T. Restoration of T Cell Res- Risk Factors, Clinical Features, and Prosthetic joint infection by Candida ponses to Toxoplasma gondii after Outcomes. MEDICINE. 90:328-336. spp.. REV ESP QUIM. 24:37-41. Successful Combined Antiretroviral I.F.: 4.26. I.F.: 0.67. Therapy in Patients with AIDS with

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Previous Toxoplasmic Encephali- 83 Gomez CE, Najera JL, Perdiguero With Fluconazole for the Prevention tis. CLIN INFECT DIS. 52:662-670. B, Garcia-Arriaza J, Sorzano COS, Jime- of Early Invasive Fungal Infection I.F.: 8.19. nez V, Gonzalez-Sanz R, Jimenez JL, in Low-Risk Liver Transplant Re- Munoz-Fernandez MA, DeQuiros JCLB, cipients. TRANSPLANTATION. 79 Arenas-Pinto A, Grant A, Bhas- Guardo AC, Garcia F, Gatell JM, Plana 92:346-350. I.F.: 3.68. karan K, Copas A, Carr A, Worm SW, M, Esteban M. The HIV/AIDS Vaccine Martinez E, Reiss P, Dunn D, Weber R, Candidate MVA-B Administered as a 88 Perello R, Miro O, Miro JM, Hoy J, Weller I. Risk factors for fatality Single Immunogen in Humans Triggers Masso E, Sanchez M, Camon S, De- in HIV-infected patients with dideoxynu- Robust, Polyfunctional, and Selective LaBellacasa JP, Moreno A, Marcos cleoside-induced severe hyperlactatae- Effector Memory T Cell Responses to MD. Urgent pneumococcal urinary mia or lactic acidosis. ANTIVIR THER. HIV-1 Antigens. J VIROL. 85:11468- antigen, importance in the diagnosis 16:219-226. I.F.: 3.77. 11478. I.F.: 5.19. of acquired pneumonia in HIV-1 patients. EUR J EMERG MED. 18:50- 80 Garcia F, DeQuiros JCLB, Gomez 84 Viasus D, Pano-Pardo JR, Pachon 54. I.F.: 0.90. CE, Perdiguero B, Najera JL, Jimenez J, Riera M, Lopez-Medrano F, Payeras V, Garcia-Arriaza J, Guardo AC, Perez A, Farinas MC, Moreno A, Rodriguez- 89 Sousa R, Lopez R, Martinez- I, Diaz-Brito V, Conde MS, Gonzalez N, Bano J, Oteo JA, Ortega L, Torre-Cis- Pastor JC, Cervera C, Bori G, Alvarez A, Alcami J, Jimenez JL, Pich J, neros J, Segura F, Carratala J. Timing Garcia-Ramiro S, Mensa J, Soriano Arnaiz JA, Maleno MJ, Leon A, Munoz- of Oseltamivir Administration and A. Usefulness of monitoring line- Fernandez MA, Liljestrom P, Weber J, Outcomes in Hospitalized Adults With zolid trough serum concentration Pantaleo G, Gatell JM, Plana M, Este- Pandemic 2009 Influenza A(H1N1) Vi- in prolonged treatments. REV ESP ban M. Safety and immunogenicity of rus Infection. CHEST. 140:1025-1032. QUIM. 24:151-153. I.F.: 0.67. a modified pox vector-based HIV/AIDS I.F.: 6.52. vaccine candidate expressing Env, Gag, 90 Fuster D, Soriano A, Garcia Pot and Nef proteins of HIV-1 subtype 85 Martina MN, Cervera C, Esforzado S, Piera C, Suades J, Rodriguez B (MVA-B) in healthy HIV-1-uninfected N, Linares L, Torregrosa V, Sanclemen- D, Martinez JC, Mensa J, Campos volunteers: A phase I clinical trial te G, Hoyo I, Cofan F, Oppenheimer F, Pons F. Usefulness of Tc-99m- (RISVAC02). VACCINE. 29:8309-8316. F, Miro JM, Campistol JM, Moreno A. ciprofloxacin scintigraphy in the I.F.: 3.57. Toxoplasma gondii primary infection in diagnosis of prosthetic joint in- renal transplant recipients. Two case fections. NUCL MED COMMUN. 81 San-Juan R, Aguado JM, Lumbre- reports and literature review. TRANSPL 32:44-51. I.F.: 1.37. ras C, Fortun J, Len O, Munoz P, Mon- INT. 24:e6-e12. I.F.: 3.21. tejo M, Moreno A, Cordero E, Blanes 91 Viard JP, Souberbielle JC, M, Ramos A, Torre-Cisneros J, Lopez- 86 Garcia F, Perez-Cachafeiro S, Kirk O, Reekie J, Knysz B, Losso Medrano F, Carratala J, Moreno E. Se- Guillot V, Alvarez M, Perez-Romero M, Gatell J, Pedersen C, Bogner lective Intestinal Decontamination With P, Perez-Elias MJ, Viciana I, Blanco JR, Lundgren JD, Mocroft A. Fluoroquinolones for the Prevention of JR, Lopez-Dieguez M, DeMendoza Vitamin D and clinical disease pro- Early Bacterial Infections After Liver C. Transmission of HIV drug resis- gression in HIV infection: results Transplantation. LIVER TRANSPLANT. tance and non-B subtype distribution from the EuroSIDA study. AIDS. 17:896-904. I.F.: 3.07. in the Spanish cohort of antiretro- 25:1305-1315. I.F.: 6.35. viral treatment naive HIV-infected 82 Miro JM, Manzardo C, Mussini individuals (CoRIS). ANTIVIR RES. C, Johnson M, Monforte AD, Antinori 91:150-153. I.F.: 4.44. ReViewS A, Gill MJ, Sighinolfi L, Uberti-Foppa C, i.f.: 27.41 Borghi V, Sabin C. Survival Outcomes 87 San-Juan R, Aguado JM, Lum- and Effect of Early vs. Deferred cART breras C, Fortun J, Len O, Munoz P, 1 Albert M, Benito J, Bhagani Among HIV-Infected Patients Diagno- Montejo M, Moreno A, Cordero E, S, Boesecke C, Deterding K, Do- sed at the Time of an AIDS-Defining Blanes M, Ramos A, DeLaTorre-Cis- minguez S, Fisher M, Fontanet Event: A Cohort Analysis. PLOS ONE. neros J, Lopez-Medrano F, Carratala A, Garcia D, Gilson R, Guiguet M, 6:-. I.F.: 4.41. J, Moreno E. Universal Prophylaxis Hoepelman AIM, Horban A, Katla-

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ma C, Mallolas J, Page E, Peters 6 Guaraldi G, Fontdevila J, Christen- MulticentRicS L, Pozniak A, Prins M, Puoti M, sen LH, Orlando G, Stentarelli C, Carli F, i.f.: 165.68 Rauch A, Rodger A, Rockstroh JK, Zona S, DeSantis G, Pedone A, DeFazio Soriano V, Stephan C, Thibault V, D, Bonucci P, Martinez E. Surgical co- 1 Cain LE, Logan R, Robins JM, Tural C, Valantin MA, VanDeLaar rrection of HIV-associated facial lipoa- Sterne JAC, Sabin C, Bansi L, Justice T, VanDerMeer J, Vella S, Vogel trophy. AIDS. 25:1-12. I.F.: 6.35. A, Goulet J, VanSighem A, DeWolf F, M, DeWit S, Autran B, Clotet B, Bucher HC, VonWyl V, Esteve A, Casa- Danta M, Journiac M, Matthews bona J, DelAmo J, Moreno S, Seng R, G, Meyer-Olson D, Nelson M, eDitoRiAlS Meyer L, Perez-Hoyos S, Muga R, Lodi Schmidt R, Wedemeyer H. Acute i.f.: 8.19 S, Lanoy E, Costagliola D, Hernan MA. hepatitis C in HIV-infected indivi- When to Initiate Combined Antiretro- duals: recommendations from the 1 Gatell JM. Antiretroviral Therapy for viral Therapy to Reduce Mortality and European AIDS Treatment Network HIV: Do Subtypes Matter?. CLIN IN- AIDS-Defining Illness in HIV-Infected (NEAT) consensus conference The FECT DIS. 53:1153-1155. I.F.: 8.19. Persons in Developed Countries An Ob- European AIDS Treatment Network servational Study. ANN INTERN MED. (NEAT) Acute Hepatitis C Infection 154:509-W173. I.F.: 16.73. Consensus Panel. AIDS. 25:399- clinicAl GuiDelineS 409. I.F.: 6.35. i.f.: 2.33 2 Nienaber JJC, Kuinkel BKS, Clarke-Pearson M, Lamlertthon S, 2 Garcia F, Routy JP. Challenges in 1 Barberan J, Mensa J, Llamas JCV, Park L, Rude TH, Barriere S, Woods dendritic cells-based therapeutic vac- Ramos IJ, Ruiz JCG, Marin JRC, Tello CW, Chu VH, Marin M, Bukovski S, cination in HIV-1 infection Workshop PB, Massana MB, Vidal JB, Vinas JMC, Garcia P, Corey GR, Korman T, Doco- in dendritic cell-based vaccine clinical Huelva FJC, Pons EC, Mediavilla JD, Lecompte T, Murdoch DR, Reller LB, trials in HIV-1. VACCINE. 29:6454- Morfa MLD, Barrigon FE, Avellan PF, Fowler VG. Methicillin-Susceptible 6463. I.F.: 3.57. Lopez SG, Garcia CG, Maraver DH, Staphylococcus aureus Endocarditis DeLaGuia AL, Jimenez JL, Chacon EM, Isolates Are Associated With Clonal 3 Martinez-Rebollar M, Larrousse Rubio MO, DeOteyza JP, Ramirez GR, Complex 30 Genotype and a Distinct M, Calvo M, Munoz A, Gonzalez A, Contreras RR, Barbero AR, Tarrats MR, Repertoire of Enterotoxins and Ad- Lonca M, Martinez E, Blanco JL, Felix DR, Godoy PS, Salinas AS, Alonso hesins. J INFECT DIS. 204:704-713. Mallolas J, Laguno M. Current status MA, Torroba JD, Ferreiras DV, Lopez LV, I.F.: 6.29. of acute hepatitis C. ENFERM INFEC Garcia JMA, Perea JRA, Moreno RC, MICR CL. 29:210-215. I.F.: 1.66. Cancer RC, Abete JF, Rodriguez JG, 3 Yuan J, Guo S, Hall D, Cammett Gomez JG, DeLaPedrosa EGG, Baranda AM, Jayadev S, Distel M, Stor- 4 Vidal F, Domingo P, Vilades C, Pe- JMM, Garcia FJP, Camps IR, Lleti MS, fer S, Huang ZM, Mootsikapun P, raire J, Arnedo M, Alcami J, Leal M, Cisneros JD. Recommendations for the Ruxrungtham K, Podzamczer D, Haas Villarroya F, Gatell JM. Pharmacoge- treatment of invasive fungal infection DW. Toxicogenomics of nevirapine- netics of the lipodystrophy syndrome caused by filamentous fungi in the associated cutaneous and hepatic associated with HIV infection and hematological patient. REV ESP QUIM. adverse events among populations combination antiretroviral therapy. 24:263-270. I.F.: 0.67. of African, Asian, and European des- EXPERT OPIN DRUG MET. 7:1365- cent. AIDS. 25:1271-1280. I.F.: 6.35. 1382. I.F.: 3.37. 2 PanelDeExpertosDeGesidaYPlan- NacionalSobreEl SIDA. National con- 4 English S, Katzourakis A, Bonsall 5 Trullas JC, Cofan F, Tuset M, sensus document by GESIDA/National D, Flanagan P, Duda A, Fidler S, We- Ricart MJ, Brunet M, Cervera C, Aids Plan on antiretroviral treatment in ber J, Mcclure M, Phillips R, Frater Manzardo C, Lopez-Dieguez M, Op- adults infected by the human immu- J. Phylogenetic analysis consistent penheimer F, Moreno A, Campistol nodeficiency virus (January 2011 up- with a clinical history of sexual JM, Miro JM. Renal transplanta- date). ENFERM INFEC MICR CL. 29:-. transmission of HIV-1 from a single tion in HIV-infected patients: 2010 I.F.: 1.66. donor reveals transmission of highly update. KIDNEY INT. 79:825-842. distinct variants. RETROVIROLOGY. I.F.: 6.11. 8:-. I.F.: 5.24.

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5 Millet JP, Orcau A, Rius C, Casals issues, main findings and losses to Miro JM. Tratamiento antiretroviral M, DeOlalla PG, Moreno A, Nelson JL, follow-up. ENFERM INFEC MICR CL. una vez al dia en pacientes con Cayla JA. Predictors of Death among 29:645-653. I.F.: 1.66. infecciones por el VIH-1 no tratados Patients Who Completed Tuberculosis previamente y con cifras de linfo- Treatment: A Population-Based Cohort 11 Paredes R, Puertas MC, Bannister citos CD4+ inferiores a 100 céls/ Study. PLOS ONE. 6:-. I.F.: 4.41. W, Kisic M, Cozzi-Lepri A, Pou C, Belli- MM3. Estudio prospectivo alea- do R, Betancor G, Bogner J, Gargalia- torizado, multicéntrico y abierto. 6 Trevino A, DeMendoza C, Caba- nos P, Banhegyi D, Clotet B, Lundgren Estudio advanz-3. Sponsored by: llero E, Rodriguez C, Parra P, Benito J, Menendez-Arias L, Martinez-Picado Instituto de Salud Carlos III (ISCIII), R, Cabezas T, Roc L, Aguilera A, J. A376S in the Connection Subdomain EC07/90642. Duration: 29/10/2007- Soriano V. Drug resistance mutations of HIV-1 Reverse Transcriptase Confers 30/06/2012. in patients infected with HIV-2 living Increased Risk of Virological Failure in Spain. J ANTIMICROB CHEMOTH. to Nevirapine Therapy. J INFECT DIS. Caballero M. Desarrollo de un mo- 66:1484-1488. I.F.: 4.66. 204:741-752. I.F.: 6.29. delo experimental en cobaya de enfermedad de vías aéreas superiores 7 Yebra G, DeMulder M, Martin L, 12 Castro H, Judd A, Gibb DM, por exposición al humo de tabaco. Perez-Cachafeiro S, Rodriguez C, Butler K, Lodwick RK, VanSighem A, Estudio de los cambios anatomo- Labarga P, Garcia F, Tural C, Jaen A, Ramos JT, Warsawski J, Thorne C, No- patológicos y de los marcadores de Navarro G, Holguin A. Sensitivity of guera-Julian A, Obel N, Costagliola D, inflamación. Sponsored by: Ministe- seven HIV subtyping tools differs Tookey PA, Colin C, Kjaer J, Grarup J, rio Sanidad y Consumo, PI070434. among subtypes/recombinants in the Chene G, Phillips A. Risk of triple-class Duration: 26/11/2007-30/06/2012. Spanish cohort of naive HIV-infected virological failure in children with HIV: patients (CoRIS). ANTIVIR RES. 89:19- a retrospective cohort study. LANCET. Yuste E. Optimización como inmu- 25. I.F.: 4.44. 377:1580-1587. I.F.: 33.63. nógeno de la proteína de la envuel- ta del virus de la inmunodeficiencia 8 Sterling TR, Villarino ME, Borisov 13 Wittkop L, Gunthard HF, DeWolf humana tipo 1. Sponsored by: Fun- AS, Shang N, Gordin F, Bliven-Sizemo- F, Dunn D, Cozzi-Lepri A, DeLuca A, Ku- dación para la Investigación y Pre- re E, Hackman J, Hamilton CD, Men- cherer C, Obel N, VonWyl V, Masque- vención del Sida en España (FIPSE), zies D, Kerrigan A, Weis SE, Weiner lier B, Stephan C, Torti C, Antinori A, 36780/08. Duration: 30/10/2008- M, Wing D, Conde MB, Bozeman L, Garcia F, Judd A, Porter K, Thiebaut R, 31/08/2012. Horsburgh CR, Chaisson RE. Three Castro H, VanSighem AI, Colin C, Kjaer Months of Rifapentine and Isoniazid J, Lundgren JD, Paredes R, Pozniak A, Arnedo M. Factores genéticos for Latent Tuberculosis Infection. Clotet B, Phillips A, Pillay D, Chene G. implicados en el desarrollo de dis- NEW ENGL J MED. 365:2155-2166. Effect of transmitted drug resistance lipemia en pacientes infectados I.F.: 53.49. on virological and immunological res- por VIH-1 que inician tratamiento ponse to initial combination antiretrovi- antiretroviral de gran actividad. 9 Kruk A, Bannister W, Podlekarev ral therapy for HIV (EuroCoord-CHAIN Sponsored by: Fundación para la DN, Chentsova NP, Rakhmanova AG, joint project): a European multicohort Investigación y Prevención del Sida Horban A, Domingo P, Mocroft A, study. LANCET INFECT DIS. 11:363- en España (FIPSE), PS09/00396. Lundgren JD, Kirk O. Tuberculosis 371. I.F.: 16.14. Duration: 30/10/2008-29/10/2011. among HIV-positive patients across Europe: changes over time and risk Climent N. Evaluación de la adeno- factors. AIDS. 25:1505-1513. I.F.: 6,35. GRAntS foR ReSeARcH sina desaminasa como molécula in pRoGReSS coestimuladora de la actividad lin- 10 Sobrino-Vegas P, Gutierrez F, focitaria en una vacuna terapéutica Berenguer J, Labarga P, Garcia F, Gatell JM. NoE - European AIDS del VIH. Sponsored by: Fundación Alejos-Ferreras B, Munoz MA, Moreno Treatment Network. Sponsored para la Investigación y la Preven- S, DelAmo J. The cohort of the spa- by: European Commission, LSHP- ción del Sida en España (FIPSE), nish hiv research network (coris) and CT-2006-037570. Duration: 01/02/2007- 36750/08. Duration: 11/12/2008- its associated biobank; organizational 31/01/2012. 31/12/2011.

77 BIOLOgICAL AggReSSION AND ReSPONSe MeChANISMS Infectious diseases and AIDS

Miro JM. Optimización farma- Gatell JM. Evaluación del impacto de Moreno A. Infecciones en el Trasplante cocinética/farmacodinámica del nuevos sistemas de información en de órgano sólido (INFTOS). Sponsored tratamiento con vancomicina de el cuidado de pacientes VIH crónicos. by: AGAUR_SGR09, 2009_SGR_1341. la endocarditis experimental por Sponsored by: Instituto de Salud Car- Duration: 15/09/2009-31/12/2013. Staphylococcus aureus resistente los III (ISCIII), PI09/90897. Duration: o no a la meticilina causada por 01/01/2010-31/12/2012. Gatell JM. European Network of HIV/ cepas con una CMI a la vancomi- AIDS Cohort Studies to Coordinate at cina de 0.5, 1 o 2 mcg/mL. Spon- Miro JM. Supervivencia de los pacien- European and International level Clini- sored by: Instituto de Salud Carlos tes con infección por el VIH en terapia cal. Sponsored by: European Commis- III (ISCIII), PI080268. Duration: renal sustitutiva o trasplante renal en sion, CE_FP7_Health_1st_10. 260694. 01/01/2009-30/12/2011. España. Sponsored by: Fundación para Duration: 01/01/2011-31/12/2015. la Investigación y Prevención del Sida Miro JM. Estudio FIPSE de trasplante en España (FIPSE), 24-0858-09. Dura- Gatell JM. Red de investigación hepático en pacientes infectados tion: 04/01/2010-03/01/2012. en sida. Sponsored by: Institu- por el VIH en España. Sponsored by: to de Salud Carlos III (ISCIII), Fundación para la Investigación y Pre- Gatell JM. Premio Fundación Lilly RD06/0006/0000. Duration: vención del Sida en España (FIPSE), de Investigación Clínica. Sponsored 01/01/2007-31/12/2012. TOH/VIH-08. Duration: 01/01/2009- by: Fundación Lilly, 10/104. Duration: 15/01/2012. 01/05/2010-30/04/2012. Gatell JM. Programa HIVACAT. Sponsored by: Conveni Generalitat Garcia F. Desarrollo de una vacuna Caballero M. Estudio del cambio de de Catalunya, Fundació La Caixa, La- frente a VIH: Estudio de los cambios eficacia y la seguridad de la bleomicina boratorios Esteve, RD06/0006/0000. de la biología de células dendríticas aplicada con electroquimioterapia en Duration: 01/01/2007-31/12/2012. humanas tras interacción dcon distin- el tratamiento de neoplasias de cabeza tos inmunógenos. Sponsored by: Ins- y cuello.. Sponsored by: Ministerio Gatell JM. Simposio internacional tituto de Salud Carlos III, PS09/01297. de Sanidad, Política Social e Igualdad, sobre la NucleoCápside Retroviral. Duration: 01/01/2010-31/12/2012. EC10-067. Duration: 01/01/2011- Sponsored by: Ministerio de Ciencia 31/12/2011. e Innovación, SAF2011-13586-E. Du- Arnedo M. Factores genéticos ration: 20/12/2011-19/12/2012. implicados en el desarrollo de Garcia F. Estudio en fase I abierto para dislipemia en pacientes infectados evaluar la seguridad e inmunogenici- Laguno M. Hipertensión Portal Idio- por VIH-1 que inician tratamiento dad de la vacuna frente a VIH-1 MVA- pática en el paciente infectado por el antiretroviral de gran actividad. B en pacientes infectados por VIH VIH. Prevalencia, curso clínico, iden- Sponsored by: Instituto de Salud crónicos en tratamiento antirretroviral tificación de métodos diagnósticos Carlos III (ISCIII), PI09/0396. Dura- (RISVAC03). Sponsored by: Ministerio no invasivos y factores pronóstico. tion: 01/01/2010-31/12/2012. de Sanidad, Política Social e Igualdad, Sponsored by: Fipse, 36-0963. Dura- TRA-094. Duration: 01/01/2010- tion: 16/02/2011-15/02/2014. Eloisa Yuste. Desarrollo de una 31/12/2011. vacuna frente al VIH: aislamiento Eloisa Yuste. Diseño, síntesis y estu- y caracterización de nuevos anti- Moreno A. Evaluar la eficacia y la dio anti-HIV-1 de dominios peptídicos cuerpos neutralizantes de amplio seguridad de la combinación de fosfo- del GB virus C. Sponsored by: Fun- espectro. Diseño de inmunóge- micina (F) e imipenem (I) para el trata- dación para la Investigación y Pre- nos capaces de generar dichos miento de la endocarditis (EI) sobre la vención del Sida en España (FIPSE), anticuerpos. Sponsored by: Ins- válvula nativa o protésica por S.aureus 36-0735-09. Duration: 09/03/2010- tituto de Salud Carlos III (ISCIII), resistente a meticilina (MRSA). Spon- 08/03/2013. PI09/1459. Duration: 01/01/2010- sored by: Instituto de Salud Carlos III, 31/12/2012. EC08/00190. Duration: 01/01/2009- 30/06/2012.

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Garcia F. Design of multifunctional DoctoRAl tHeSeS nanoparticles targeting TLR or Nod receptors for dendritic cell immune Miro JM, Moreno A, Barril G. Enfer- therapy. Sponsored by: Instituto de medad renal crónica y terapia renal Salud Carlos III, PI10/02984 (NO- sustitutiva en pacientes con infec- NO-MED). Duration: 01/01/2011- ción por el virus de la inmunodefi- 31/12/2013. ciencia humana. Prevalencia y supervivencia en terapia renal sustitutiva y Gatell JM. Grup de recerca VIH/ trasplante renal. PhD student: Joan sida. Sponsored by: AGAUR_ Carles Trullàs Vila. SGR09, 2009_SGR_1159. Duration: 23/09/2009-31/12/2013. Mallolas J. Estudio del sistema mus- culoesquelético mediante resonancia Gatell JM. 8th International Retrovi- magnética en la valoración del sín- ral NC Symposium. Sponsored by: drome de lipodistrofia en pacientes AGAUR_ARCS11, JG075298. Dura- infectados por el virus de la inmu- tion: 18/09/2011-21/09/2011. nodeficiencia humana. PhD student: Ana Isabel García Díez. Gatell JM. Nanopartículas de ácido poli-láctico (PLA) recubiertas de antígenos VIH y vectores poxvi- rus que expresan proteína Gag o proteínas reguladoras del ciclo del VIH como inmunógenos para una vacuna contra el SIDA: Interacción con células dendríticas. Sponsored by: Ministerio de Ciencia e Innova- ción (Plan Nacional I+D), SAF2008- 04395. Duration: 01/01/2009- 31/12/2011.

Miro JM. A Phase III multi-center, randomized, open-label, comparative study to assess the efficacy of a treatment algorithm to reduce the use of vancomycin in patients with intravenous catheter-associated bloodstream infections (BSI) due to Staphylococci. Sponsored by: Duke University, NIHAI2008025. Dura- tion: 23/05/2011-30/06/2012.

79 AReA 1

Team involved in: Biological aggression and response mechanisms

Immune receptors of the innate and adaptive system

gROUP MeMBeRS

teAM leADeR francisco lozano (Hospital clínic/uB) tel.: 93 227 42 17 fax: 93 451 80 38 e-mail: [email protected]

iDiBApS MeMBeRS: ReSeARcH fellowS: tecHniciAnS: Ana Angulo (iDiBApS) lyzette Bonet (fundació clínic) Adriana lázaro (fundació clínic) pablo engel (uB) Rafael fenutría (fundació clínic) noelia Armiger Borràs (iDiBApS) carles Serra (Hospital clínic) elena isern (iDiBApS) Ricardo Bastos (iDiBApS) Jordi Sintes (uB) cristina Miró (Mec/fpu) poStDoctoRAlS fellowS: cristina escoda (Mec/fpi) esther carrasco Miguel (Jdc) natalia pérez carmona (uB) Mario Martínez florensa (AGAuR) Jose de Salort (uB) Vanesa G. Martínez (Jdc) M. carmen Diaz-Ramos (iDiBApS) Xavier Romero (iDiBApS) Marta consuegra (AGAuR) esther carreras Margalef (Biotrack) Marc orta (Micinn/fpi) Ángela Zarama (iDiBApS) inês Simoês (fcyt)

80 AReA 1 BioloGicAl AGGReSSion AnD ReSponSe MecHAniSMS iMMune ReceptoRS of tHe innAte AnD ADAptiVe SySteM

StrateGic oBjectiveS

1. Genetic and molecular characterization of receptors of both the innate and adaptive immune system. 2. Functional characterization of the ligand- receptor interactions responsible for intercellular communication between the innate and adaptive immune system components.

3. Molecular characterization of patho- Immunohistochemical staining of a normal tonsil specimen exhibiting secondary folicles. Brown, CD279/PD-1 gen-host interactions. (Programmed death-1) positive cells (activated T and B lymphocytes). Red, CD23 positive cells (activated B cells and Follicular Dendritic Cells). 4. Molecular characterization of the biology, pathogenesis and immunology of cytomegalovirus (CMV). 3. Immunogenetics of receptors and 6. Characterization of the genic re- molecules implicated in the regula- gulation mechanisms of CMV and tion of innate and adaptive immune identification of functions encoded main lineS of responses. for by CMV. reSearcH 4. Study of the role of the CD5 and 7. Study of CMV mediated modulation CD6 receptors in lymphocyte activa- of immune response and immune 1. Study of the structure and function tion and differentiation. evasion strategies. of the SLAM (Signaling Lympho- 5. Molecular and functional cha- cytic Activation Molecule) and SAP racterization of nonlymphoid (SLAM-Associated Protein) leukocy- members of the superfamily te molecule families. of receptors with extracellular 2. Study of the molecules that interve- domains rich in cysteine (SRCR, ne in leukocyte adhesion and inflam- Scavenger Receptor Cysteine- mation. Rich) residues.

eMeRgeNT gROUP molecular mecHaniSmS of tHe patHoGeneSiS of cmv diSeaSe

Group Leader: Ana Angulo (IDIBAPS)

Cytomegalovirus (CMV) is an ubiquitous pathogen that establishes latent infections for life – with serious consequences for immune-compromised individuals. The group studies different aspects of the interactions between CMV and the host, with special emphasis on the mechanisms that regulate viral genic expression, the determination of new functions encoded by the virus, and the identification of processes of interference with the immune system.

81 BIOLOgICAL AggReSSION AND ReSPONSe MeChANISMS

Immune receptors of the innate and adaptive system

PUBLICATIONS

oRiGinAlS 6 Blanc M, Hsieh WY, Robertson 11 Matesanz-Isabel J, Sintes J, i.f.: 92.77 KA, Watterson S, Shui GH, Lacaze P, Llinas L, DeSalort J, Lazaro A, Engel Khondoker M, Dickinson P, Sing G, P. New B-cell CD molecules. IMMU- 1 Canete JD, Albaladejo C, Her- Rodriguez-Martin S, Phelan P, Forster NOL LETT. 134:104-112. I.F.:2.51. nandez MV, Lainez B, Pinto JA, T, Strobl B, Muller M, Riemersma Ramirez J, Lopez-Armada MJ, R, Osborne T, Wenk MR, Angulo A, 12 Magri G, Muntasell A, Romo Rodriguez-Cros JR, Engel P, Blanco Ghazal P. Host Defense against Viral N, Saez-Borderias A, Pende D, FJ, Sanmarti R. Clinical significance Infection Involves Interferon Mediated Geraghty DE, Hengel H, Angulo A, of high levels of soluble tumour Down-Regulation of Sterol Biosynthe- Moretta A, Lopez-Botet M. NKp46 necrosis factor-alpha receptor-2 sis. PLOS BIOL. 9:-. I.F.: 12.47. and DNAM-1 NK-cell receptors drive produced by alternative splicing in the response to human cytomegalo- rheumatoid arthritis: a longitudinal 7 Engel P, Perez-Carmona N, Alba virus-infected myeloid dendritic cells prospective cohort study. RHEU- MM, Robertson K, Ghazal P, Angulo overcoming viral immune evasion MATOLOGY. 50:721-728. I.F.: 4.17. A. Human cytomegalovirus UL7, strategies. BLOOD. 117:848-856. a homologue of the SLAM-family I.F.: 10.56. 2 Bamberger M, Santos AM, receptor CD229, impairs cytokine Goncalves CM, Oliveira MI, James production. IMMUNOL CELL BIOL. 13 Kropp KA, Robertson KA, Sing JR, Moreira A, Lozano F, Davis SJ, 89:753-766. I.F.: 3.74. G, Rodriguez-Martin S, Blanc M, Carmo AM. A New Pathway of Lacaze P, Hassim MF, Khondoker CD5 Glycoprotein-mediated T Cell 8 Pascual-Garcia M, Carbo JM, MR, Busche A, Dickinson P, Forster Inhibition Dependent on Inhibitory Leon T, Matalonga J, Out R, VanBer- T, Strobl B, Mueller M, Jonjic S, Phosphorylation of Fyn Kinase. J kel T, Sarrias MR, Lozano F, Celada Angulo A, Ghazal P. Reversible In- BIOL CHEM. 286:30324-30336. A, Valledor AF. Liver X Receptors hibition of Murine Cytomegalovirus I.F.: 5.33. Inhibit Macrophage Proliferation Replication by Gamma Interferon through Downregulation of Cyclins (IFN-gamma) in Primary Macropha- 3 Keszei M, Detre C, Rietdijk D1 and B1 and Cyclin-Dependent ges Involves a Primed Type I ST, Munoz P, Romero X, Berger Kinases 2 and 4. J IMMUNOL. IFN-Signaling Subnetwork for Full SB, Calpe S, Liao GX, Castro W, 186:4656-4667. I.F.: 5.75. Establishment of an Immediate-Early Julien A, Wu YY, Shin DM, Sancho Antiviral State. J VIROL. 85:10286- J, Zubiaur M, Morse HC, Morel L, 9 Miro-Julia C, Rosello S, Marti- 10299. I.F.: 5.19. Engel P, Wang NH, Terhorst C. A nez VG, Fink DR, Escoda-Ferran C, novel isoform of the Ly108 gene Padilla O, Vazquez-Echeverria C, 14 Lacaze P, Forster T, Ross A, ameliorates murine lupus. J EXP Espinal-Marin P, Pujades C, Garcia- Kerr LE, Salvo-Chirnside E, Lisnic MED. 208:811-822. I.F.: 14.78. Pardo A, Vila J, Serra-Pages C, VJ, Lopez-Campos GH, Garcia-Rami- Holmskov U, Yelamos J, Lozano F. rez JJ, Messerle M, Trgovcich J, An- 4 DeSalort J, Sintes J, Llinas Molecular and Functional Charac- gulo A, Ghazal P. Temporal Profiling L, Matesanz-Isabel J, Engel P. terization of Mouse S5D-SRCRB: of the Coding and Noncoding Muri- Expression of SLAM (CD150) cell- A New Group B Member of the ne Cytomegalovirus Transcriptomes. surface receptors on human B-cell Scavenger Receptor Cysteine- J VIROL. 85:6065-6076. I.F.: 5.19. subsets: From pro-B to plasma Rich Superfamily. J IMMUNOL. cells. IMMUNOL LETT. 134:129- 186:2344-2354. I.F.: 5.75. 15 Isern E, Gustems M, Mes- 136. I.F.: 2.51. serle M, Borst E, Ghazal P, Angulo 10 Romo N, Magri G, Muntasell A. The Activator Protein 1 Binding 5 Llinas L, Lazaro A, DeSalort J, A, Heredia G, Baia D, Angulo A, Motifs within the Human Cytome- Matesanz-Isabel J, Sintes J, Engel Guma M, Lopez-Botet M. Natural galovirus Major Immediate-Early En- P. Expression profiles of novel cell killer cell-mediated response to hancer Are Functionally Redundant surface molecules on B-cell sub- human cytomegalovirus-infected and Act in a Cooperative Manner sets and plasma cells as analyzed macrophages is modulated by their with the NF-kappa B Sites during by flow cytometry. IMMUNOL functional polarization. J LEUKOCY- Acute Infection. J VIROL. 85:1732- LETT. 134:113-121. I.F.: 2.51. TE BIOL. 90:717-726. I.F.: 4.63. 1746. I.F.: 5.19.

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original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 50.14 11 9 1 16 Diaz-Ramos MC, Engel P, Bas- GRAntS foR ReSeARcH tos R. Towards a comprehensive in pRoGReSS 2010 55.45 11 8 1 human cell-surface immunome data- 2011 92.77 16 11 0 base. IMMUNOL LETT. 134:183-187. Angulo A. Regulación transcripcional I.F.: 2.51. y funciones de los genes principales inmediatamente tempranos: implicaciones en la patogénesis viral. Rich). Sponsored by: Ministerio de ReViewS Sponsored by: Ministerio de Ciencia Ciencia e Innovación (Plan Nacional i.f.: 53.61 e Innovación (Plan Nacional I+D). I+D), SAF2007-62197. Duration: Duration: 01/01/2008-31/12/2011. 1/12/2007-30/4/2011. 1 Bosch X, Lozano F, Cervera R, Ra- mos-Casals M, Min B. Basophils, IgE, Lozano F. Implicaciones funcionales Lozano F. Nova bioteràpia en sepsis and Autoantibody-Mediated Kidney y terapéuticas del reconocimiento fúngica i polimicrobiana. Sponsored Disease. J IMMUNOL. 186:6083-6090. de ligandos exógenos y endógenos by: CIDEM VALTEC08-2-0034. Dura- I.F.: 5.75. por parte de receptores linfoci- tion: 31/10/2008-31/10/2011. tarios tipo scavenger. Sponsored 2 Engel P, Gomez-Puerta JA, by: Ministerio de Ciencia e Inno- Lozano F. Immunoreceptores del Ramos-Casals M, Lozano F, Bosch vación, SAF2010-19717. Duration: Sistema Inmunitario Innato y Adap- X. Therapeutic Targeting of B Cells 01/01/2011-31/12/2013. tativo. Sponsored by: Agència de for Rheumatic Autoimmune Disea- Gestió d’Ajuts Universitaris i de ses. PHARMACOL REV. 63:127-156. Lozano F. Análisis de los factores Recerca (AGAUR), 2009/SGR/00252. I.F.: 18.86. del sistema inmunitario innato impli- Duration: 01/01/2009-31/12/2012. cados en la respuesta a la infección 3 Martinez VG, Moestrup SK, Holm- por el Virus Influenza A/H1N1 2009 Lozano F. Papel modulador de recepto- skov U, Mollenhauer J, Lozano F. Sponsored by: Instituto de Salud res linfocitarios tipo scavenger (CD5 y The Conserved Scavenger Receptor Carlos III (ISCIII), Programa de in- CD6) en la patofisiología de la infección Cysteine-Rich Superfamily in Therapy vestigación del MICINN ante la Gri- por el virus de la inmunodeficiencia and Diagnosis. PHARMACOL REV. pe A/H1N1 (GR09/0013). Duration: humana 1 (VIH-1). Sponsored by: FIPSE- 63:967-1000. I.F.: 18.86. 24/11/2009-31/10/2012. Fundación para la Investigación y Pre- vención del Sida en España, 36-0773-09. 4 Soldevila G, Raman C, Lozano F. Engel P. Estudio de las moléculas Duration: 04/01/2010-03/01/2013. The immunomodulatory properties CD150/SLAM en la función efectora of the CD5 lymphocyte receptor in de los linfocitos B de tipo innato. health and disease. CURR OPIN IM- Sponsored by: Ministerio de Cien- DoctoRAl tHeSeS MUNOL. 23:310-318. I.F.: 10.14. cia e Innovación (Plan Nacional I+D) SAF2009-07071. Duration: Lozano F. Propiedades inmunomodu- 01/01/2010-31/12/2011. ladoras de la región extracelular de eDitoRiAlS CD5. PhD student: Rafael Fenutria i.f.: 6.25 Lozano F. Red española de inves- Aumesquet. tigación en patología infecciosa 1 Sintes J, Engel P. Bacterial (REIPI). Sponsored by: Instituto Engel P. Expression and functional recognition SLAM (CD150) is a de Salud Carlos III (ISCIII), RE- role of CD84 and CD229 receptors multitasking immunoreceptor: from TIC07 RD06/0008/1013. Duration: in innate and adaptive immunity. cosignalling to bacterial recognition. 29/2/2008-31/12/2012. PhD student: Jordi Sintes Castro. IMMUNOL CELL BIOL. 89:161-163. I.F.: 3.74. Lozano F. Estudio de las propieda- Angulo A, Lopez-Botet M. Charac- des inmunomoduladoras de miem- terization of natural killer response 2 Engel P. Editorial HLDA9 special bros linfoides y no linfoides de la to human cytomegalovirus infected issue. IMMUNOL LETT. 134:103-103. superfamilia de receptores SRCR dendritic cells. PhD student: Giuliana I.F.: 2.51. (Scavenger Receptor Cysteine- Magri.

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Musculoskeletal repair and plasticity StrateGic oBjectiveS gROUP MeMBeRS Our research group, which was incorporated to the IDIBAPS in 2007, aims to agglutinate and generate synergies among specialists in different disciplines that work in the field of the teAM leADeR locomotor system. This is a field with Joaquim forés i Viñeta a growing social and technological de- (Hospital clínic) mand, but with scant incidence in the tel.: 93 227 93 14 research setting of this institution. e-mail: [email protected] There are many aspects of new knowledge related to the musculoske- iDiBApS MeMBeRS: Joan Xavier fontdevila letal system: cellular, genic and pharma- Jesús Benito (Hospital clínic) (Hospital clínic) cological therapies; new materials and Andrés combalía (Hospital clínic) Salvador fuster (Hospital clínic) implants; robotics; top-level surgical francisco Maculé (Hospital clínic) Xavier Gallart (Hospital clínic) and anesthetic technology; and sophis- Montserrat nuñez (Hospital clínic) eloy M. García Díez (Hospital clínic) ticated imaging techniques. The lack of Jaume pomés (Hospital clínic) Ruben García elvira (Hospital clínic) clinical scientific evidence relating to Josep M. Segur (Hospital clínic) Raquel García tarriño (Hospital clínic) much of the new knowledge, and the Sebastián García (Hospital clínic) Anna lópez Gutiérrez (Hospital clínic) great volume of patients in our setting, Sergi Sastre (Hospital clínic) felipe orient (Hospital clínic) with limited resources, represent an Santiago Suso (Hospital clínic) lluis peidro (Hospital clínic important source of work from which to Daniel poggio (Hospital clínic) derive intellectual benefit. Working with ADMiniStRAtiVe StAff: Dragos popescu (Hospital clínic) humbleness but “thinking big” seems Antònia Bayo (Hospital clínic) Salvi prat (Hospital clínic) to us to be the best strategy for rea- Josep Riba (Hospital clínic) ching the objective of being a reference collABoRAtoRS: Moisés Rios (Hospital clínic) group in our setting. M.ª teresa Anglada (Hospital clínic) Xavier Sala (Hospital clínic) Jordi Asunción (Hospital clínic) isabel Sañudo (Hospital clínic) Misericordia Basora (Hospital clínic) Xavier tomás (Hospital clínic) Guillem Bori (Hospital clínic) pere torner (Hospital clínic) Xavier carné (Hospital clínic) Antoni trilla (Hospital clínic) Ana carreño (Hospital clínic) Raquel Vilarrasa (Hospital clínic) Adela faulí (Hospital clínic) Josep M. Serra (Hospital clínic) Jenaro A. fernández-Valencia Alex Soriano (Hospital clínic) (Hospital clínic)

Navigation and robotics applied to skeletal grafts.

84 AReA 1 BioloGicAl AGGReSSion AnD ReSponSe MecHAniSMS MuSculoSkeletAl RepAiR AnD plASticity

PUBLICATIONS original publications from 2009 to 2011 main lineS of Year IF Total Q 1 Q 2 reSearcH oRiGinAlS 2009 43.02 15 8 4 27.31 11 5 3 1. Bone physiopathology, pathological i.f.: 62.94 2010 variation with age, evaluation of 2011 62.94 21 7 6 fracture setting techniques and 1 Marcos M, Fernandez C, Soriano bone substitutes. A, Marco F, Martinez JA, Almela M, 2. Cartilage, degeneration and repair Cervera R, Mensa J, Espinosa G. through tissue engineering. Epidemiology and clinical outcomes cacy of debridement in hematogenous 3. Evaluation and design of new of bloodstream infections among and early post-surgical prosthetic joint prosthetic implants. lupus patients. LUPUS. 20:965-971. infections. INT J ARTIF ORGANS. 4. Minimally invasive surgery with I.F.: 2.60. 34:863-869. I.F.: 1.50. new technology and instruments. 5. Infections of the locomotor appara- 2 Tomas X, Bori G, Garcia S, Garcia- 7 Bori G, Munoz-Mahamud E, Gar- tus, their prevention and treatment. Diez AI, Pomes J, Soriano A, Rios J, cia S, Mallofre C, Gallart X, Bosch J, 6. Acute postoperative pain and chro- Almela M, Mensa J, Gallart X, Marti- Garcia E, Riba J, Mensa J, Soriano nic musculoskeletal pain. nez JC, Riba J. Accuracy of CT-guided A. Interface membrane is the best 7. Functional re-adaptation, prevalen- joint aspiration in patients with sample for histological study to ce and evaluation of health results suspected infection status post-total diagnose prosthetic joint infection. in degenerative arthropathies. hip arthroplasty. SKELETAL RADIOL. MODERN PATHOL. 24:579-584. 8. Biology of autologous adipose tis- 40:57-64. I.F.: 1.39. I.F.: 4.18. sue grafts. 9. Musculoskeletal system tissue 3 Ortega M, Marco F, Soriano A, 8 Sterzik H, Soriano A, Mohamad AM, bank. Almela M, Martinez JA, Lopez J, Martinez JA, Fernandez J, Cobos N, 10. Imaging diagnosis, new technolo- Pitart C, Mensa J. Candida species Morata L, Mensa J. Is linezolid a risk gies in diagnosis and follow-up. bloodstream infection: epidemiology factor for Gram-negative bacillus infec- 11. Collaboration in joint projects with and outcome in a single institution tions in intensive care unit patients? A the UASP. from 1991 to 2008. J HOSP INFECT. comparative study with vancomycin. 12. Acute-phase response in open 77:157-161. I.F.: 3.08. SCAND J INFECT DIS. 43:765-770. fractures. Use of IL-6, C-reactive I.F.: 1.56. protein and CK in predicting results, 4 Marcos M, Soriano A, Inurrieta and correlation with the Gustilo A, Martinez JA, Romero A, Cobos 9 Vilchez F, Martinez-Pastor JC, Gar- classification. N, Hernandez C, Almela M, Marco cia-Ramiro S, Bori G, Macule F, Sierra J, 13. Vascular anatomy of the upper F, Mensa J. Changing epidemiology Font L, Mensa J, Soriano A. Outcome extremity applied to reconstructive of central venous catheter-related and predictors of treatment failure in procedures. bloodstream infections: increasing early post-surgical prosthetic joint in- 14. Surgical management of facial prevalence of Gram-negative patho- fections due to Staphylococcus aureus lipoatrophy based on the injection gens. J ANTIMICROB CHEMOTH. treated with debridement. CLIN MI- of autologous adipose tissue in HIV- 66:2119-2125. I.F.: 4.66. CROBIOL INFEC. 17:439-444. I.F.: 4.78. infected patients. 15. Nervous system: 5 Munoz-Mahamud E, Garcia S, 10 Garcia-Oltra E, Garcia-Ramiro S, • Tubulization repair of peripheral Bori G, Martinez-Pastor JC, Zumba- Pastor JCM, Tibau R, Bori G, Bosch J, nervous system damage. do JA, Riba J, Mensa J, Soriano A. Mensa J, Soriano A. Prosthetic joint • Experimental reimplantation of Comparison of a low-pressure and a infection by Candida spp.. REV ESP nerve root preganglionic avul- high-pressure pulsatile lavage during QUIM. 24:37-41. I.F.: 0.67. sions. debridement for orthopaedic implant infection. ARCH ORTHOP TRAUM 11 Font-Vizcarra L, Zumbado A, SU. 131:1233-1238. I.F.: 1.20. Garcia S, Bosch J, Mensa J, Soriano A. Relationship between haematoma in fe- 6 Vilchez F, Martinez-Pastor JC, moral neck fractures contamination and Garcia-Ramiro S, Bori G, Tornero E, early postoperative prosthetic joint in- Garcia E, Mensa J, Soriano A. Effi- fection. INJURY. 42:200-203. I.F.: 2.27.

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Musculoskeletal repair and plasticity

12 Sierra JM, Garcia S, Martinez- 18 Nunez M, Lozano L, Nunez E, European AIDS Treatment Network Pastor JC, Tomas X, Gallart X, Vila J, Sastre S, DelVal JL, Suso S. Good Qua- (NEAT) consensus conference The Bori G, Macule F, Mensa J, Riba J, lity of Life in Severely Obese Total Knee European AIDS Treatment Network Soriano A. Relationship between the Replacement Patients: A Case-Control (NEAT) Acute Hepatitis C Infection degree of osteolysis and cultures obtai- Study. OBES SURG. 21:1203-1208. Consensus Panel. AIDS. 25:399-409. ned by sonication of the prostheses in I.F.: 3.08. I.F.: 6.35. patients with aseptic loosening of a hip or knee arthroplasty. ARCH ORTHOP 19 Munoz-Mahamud E, Popescu TRAUM SU. 131:1357-1361. I.F.: 1.20. D, Nunez E, Lozano LM, Nunez M, MulticentRicS Sastre S, Torner P, Segur JM, Macule i.f.: 2.51 13 Sousa R, Lopez R, Martinez- F. Secondary patellar resurfacing in the Pastor JC, Cervera C, Bori G, Gar- treatment of patellofemoral pain after 1 Kovacs FM, Seco J, Royuela A, cia-Ramiro S, Mensa J, Soriano A. total knee arthroplasty. KNEE SURG Pena A, Muriel A. The Correlation Bet- Usefulness of monitoring linezolid SPORT TR A. 19:1467-1472. I.F.: 1.86. ween Pain, Catastrophizing, and Disabi- trough serum concentration in pro- lity in Subacute and Chronic Low Back longed treatments. REV ESP QUIM. 20 Herrera A, Carpintero P, Fernan- Pain A Study in the Routine Clinical 24:151-153. I.F.: 0.67. dez-Perez C, Hernandez-Vaquero D, Practice of the Spanish National Health Martinez AA, Suso S. Secondary pre- Service. SPINE. 36:339-345. I.F.: 2.51. 14 Fuster D, Soriano A, Garcia S, vention in osteoporotic fractures. The Piera C, Suades J, Rodriguez D, Mar- GIOS project. MED CLIN-BARCELONA. tinez JC, Mensa J, Campos F, Pons 136:50-55. I.F.: 1.41. GRAntS foR ReSeARcH F. Usefulness of Tc-99m-ciprofloxacin in pRoGReSS scintigraphy in the diagnosis of 21 Penas C, Pascual-Font A, Man- prosthetic joint infections. NUCL cuso R, Fores J, Casas C, Navarro X. Soriano A. Estudio aleatorizado y do- MED COMMUN. 32:44-51. I.F.: 1.37. Sigma Receptor Agonist 2-(4-Morpholi- ble ciego para establecer el momen- nethyl) 1 Phenylcyclohexanecarboxylate to más apropiado de la administra- 15 Penas C, Font-Nieves M, Fo- (Pre084) Increases GDNF and BiP ción de la proxilaxis antibiótica en la res J, Petegnief V, Planas A, Nava- Expression and Promotes Neuroprotec- artroplastia total de rodilla cuando se rro X, Casas C. Autophagy, and BiP tion after Root Avulsion Injury. J NEU- realiza bajo isquemia. Sponsored by: level decrease are early key events ROTRAUM. 28:831-840. I.F.: 3.43. Ministerio de Sanidad y Consumo, in retrograde degeneration of mo- EC07/90330. Duration: 29/10/2007- toneurons. CELL DEATH DIFFER. 30/06/2011. 18:1617-1627. I.F.: 9.05. ReViewS i.f.: 6.35 Nuñez M. Calidad de vida relacionada 16 Ruiz-Gaspa S, Martinez-Ferrer con la salud, dependencia física y cos- A, Guanabens N, Dubreuil M, Peris P, 1 Albert M, Benito J, Bhagani S, tes en pacientes con artrosis después Enjuanes A, DeOsaba MJM, Alvarez Boesecke C, Deterding K, Dominguez de artroplastia total de rodilla. Estudio L, Monegal A, Combalia A, Pares A. S, Fisher M, Fontanet A, Garcia D, Gil- prospectivo. Sponsored by: Fondo de Effects of Bilirubin and Sera from son R, Guiguet M, Hoepelman AIM, Investigacion Sanitaria (FIS) Instituto Jaundiced Patients on Osteoblasts: Horban A, Katlama C, Mallolas J, Page de Salud Carlos III, PS09/01148. Dura- Contribution to the Development of E, Peters L, Pozniak A, Prins M, Puoti tion: 01/01/2010-31/12/2012. Osteoporosis in Liver Diseases. HEPA- M, Rauch A, Rodger A, Rockstroh JK, TOLOGY. 54:2104-2113. I.F.: 10.89. Soriano V, Stephan C, Thibault V, Tural Fores J. Eficacia del tratamiento con C, Valantin MA, VanDeLaar T, VanDer- condroitin sulfato en la rizartrosis. 17 Nunez M, Lozano L, Nunez E, Meer J, Vella S, Vogel M, DeWit S, Medicion con test sensoriales y fun- Segur JM, Sastre S. Factors Influen- Autran B, Clotet B, Danta M, Journiac cionales cuantitativos y analisis de cing Health-related Quality of Life M, Matthews G, Meyer-Olson D, concordancia con escalas subjetivas after TKA in Patients who are Obese. Nelson M, Schmidt R, Wedemeyer H. de dolor. Sponsored by: Instituto de CLIN ORTHOP RELAT R. 469:1148- Acute hepatitis C in HIV-infected indi- Salud Carlos III, EC08/00079. Duration: 1153. I.F.: 2.12. viduals: recommendations from the 01/01/2009-30/12/2011.

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Garcia S. Estudio aleatorizado y abierto para determinar si la administración de un antibiótico puede reducir la incidencia de infección en pacientes con cultivos positivos durante una artroplastia de cadera. Sponsored by: Instituto de Salud Carlos III, EC08/00182. Duration: 01/01/2009-30/12/2011.

Soriano A. Estudio comparativo de la eficacia de pautas ‘’cortas’’ y ‘’largas’’ de la combinación rifampicina-levo- floxacino en la infección estafilocócica postquirúrgica precoz y hematógena de prótesis articular. Sponsored by: Insti- tuto de Salud Carlos III, EC08/00189. Duration: 01/01/2009-30/12/2011.

Sastre S. Determinación de los niveles plasmáticos de substancia P en pacientes afectos de patología tendinosa degenerativa del hombro tributarios de cirugía. Sponsored by: Fund_Esp_Ar- troscop11, AEA2011-SASTRE. Dura- tion: 04/05/2011-03/05/2012.

Soriano A. Grup de patologia sèptica de l’aparell locomotor. Sponsored by: Gen- eralitat de Catalunya, AGAUR, SGR09 2009_SGR_906. Duration: 15/09/2009- 31/12/2013.

Soriano A. Estudio para determinar la presencia de microorganismos en la superfície de prótesis articulares retiradas por un aflojamiento aséptico. Sponsored by: Instituto de Salud Carlos III (ISCIII), FIS10 PI10/02245. Duration: 01/01/2011-31/12/2013.

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Immunogenetics of the autoinflammatory response StrateGic oBjectiveS gROUP MeMBeRS In the field ofautoinflammatory diseases: Promotion of basic, clinical and translation research in the physiopathology of autoinflammatory diseases as a model teAM leADeR for gaining in-depth knowledge of the Jordi yagüe (Hospital clínic) regulation of the normal inflammatory tel.: 93 227 54 00 (ext: 2155) response, its dysfunctions, and its reper- fax: 93 451 80 38 cussions upon the immune response. e-mail: [email protected] In the field ofimmune response: iDiBApS MeMBeRS: Determination of the components of Juan ignacio Aróstegui (Hospital clínic) normal and pathological inflammatory Manel Juan (Hospital clínic) response is essential for modulating the specific recognition phenomena of ReSeARcH fellowS: the immune response. emma Garcia Melchor (Agaur) main lineS of collABoRAtoRS: reSearcH eva Gonzalez Roca (Hospital clínic) In the field ofautoinflammatory diseases: • Determination of the genetic and molecular bases of the autoinflammatory process. • Characterization of the regulatory mechanisms of the inflammasome and its dysfunction. • Characterization of the specific transcriptional profiles of autoinflammatory diseases. • Isolation of new genes responsible for hereditary autoinflammatory diseases and identification of genetic susceptibility factors for the development of polygenic autoinflammatory processes. • Definition of new therapeutic targets for the treatment of autoinflammatory diseases.

In the field ofimmune response: • Assessing the role of HLA-DRB3/4/5 loci in the immune response against infection, transplantation and autoimmune response. • Assessing the role of the mutation E52del in MyD88 in normal population as well as in relation to the lack of MyD88.

88 AReA 1 BioloGicAl AGGReSSion AnD ReSponSe MecHAniSMS iMMunoGeneticS of tHe AutoinflAMMAtoRy ReSponSe

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 41.69 7 5 2 oRiGinAlS 5 Azmanov DN, Dimitrova S, Florez L, i.f.: 70.42 Cherninkova S, Draganov D, Morar B, 2010 19.96 4 3 1 Saat R, Juan M, Arostegui JI, Ganguly S, 2011 70.42 9 5 1 1 Pedrosa E, Carretero-Iglesia Soodyall H, Chakrabarti S, Padh H, Lopez- L, Boada A, Colobran R, Faner R, Nevot MA, Chernodrinska V, Anguelov B, Pujol-Autonell I, Palou E, Esteve A, Majumder P, Angelova L, Kaneva R, Mac- Pujol-Borrell R, Ferrandiz C, Juan key DA, Tournev I, Kalaydjieva L. LTBP2 caramis G, Jares P, Bea S, Gonzalez-Diaz M, Carrascosa JM. CCL4L Polymor- and CYP1B1 mutations and associated M, Bassaganyas L, Baumann T, Juan phisms and CCL4/CCL4L Serum ocular phenotypes in the Roma/Gypsy M, Lopez-Guerra M, Colomer D, Tubio Levels Are Associated with Psoriasis founder population. EUR J HUM GENET. JMC, Lopez C, Navarro A, Tornador C, Severity. J INVEST DERMATOL. 19:326-333. I.F.: 4.38. Aymerich M, Rozman M, Hernandez 131:1830-1837. I.F.: 6.27. JM, Puente DA, Freije JMP, Velasco G, 6 DeLarrea CF, Tovar N, Rozman M, Ro- Gutierrez-Fernandez A, Costa D, Carrio 2 Ferrer G, Hodgson K, Pereira sinol L, Arostegui JI, Cibeira MT, Rovira A, Guijarro S, Enjuanes A, Hernandez A, Juan M, Elena M, Colomer D, M, Yague J, Blade J. Multiple Myeloma L, Yague J, Nicolas P, Romeo-Casabona Roue G, Aymerich M, Baumann T, in Serologic Complete Remission after CM, Himmelbauer H, Castillo E, Dohm Montserrat E, Moreno C. Combined Autologous Stem Cell Transplantation: JC, DeSanjose S, Piris MA, DeAlava E, analysis of levels of serum B-cell Impact of Bone Marrow Plasma Cell As- Miguel JS, Royo R, Gelpi JL, Torrents D, activating factor and a proliferation- sessment by Conventional Morphology Orozco M, Pisano DG, Valencia A, Guigo inducing ligand as predictor of di- on Disease Progression. BIOL BLOOD R, Bayes M, Heath S, Gut M, Klatt P, sease progression in patients with MARROW TR. 17:1084-1087. I.F.: 3.28. Marshall J, Raine K, Stebbings LA, Fut- chronic lymphocytic leukemia. LEU- real PA, Stratton MR, Campbell PJ, Gut KEMIA LYMPHOMA. 52:2064-2068. 7 Fortea J, Llado A, Clarimon J, Lleo A, I, Lopez-Guillermo A, Estivill X, Montser- I.F.: 2.49. Oliva R, Peri J, Pintor L, Yague J, Blesa rat E, Lopez-Otin C, Campo E. Whole- R, Molinuevo JL, Sanchez-Valle R. PICO- genome sequencing identifies recurrent 3 DeLarrea CF, Tovar N, Cibeira MT, GEN: Five years experience with a ge- mutations in chronic lymphocytic leukae- Arostegui JI, Rosinol L, Elena M, Fi- netic counselling program for dementia. mia. NATURE. 475:101-105. I.F.: 36.10. lella X, Yague J, Blade J. Emergence NEUROLOGIA. 26:143-149. I.F.: 0.59. of oligoclonal bands in patients with multiple myeloma in complete remis- 8 Abraira V, Alvarez-Cermeno JC, GRAntS foR ReSeARcH sion after induction chemotherapy: Arroyo R, Camara C, Casanova B, Cubi- in pRoGReSS association with the use of novel llo S, DeAndres C, Espejo C, Fernandez agents. HAEMATOL-HEMATOL J. O, Ferrer J, Figueredo MA, Garcia- Yague J. Análisis de las vías de se- 96:171-173. I.F.: 6.53. Merino A, Garcia-Sanchez MI, Garcia- ñalización TOLL/IL-1 receptor (TIR), Trujillo JA, Gomez M, Gonzalez-Oria C, NOD-LIKE receptor (NLR) y NF-kB en 4 Tanaka N, Izawa K, Saito MK, Gosis A, Izquierdo G, Jimenez J, Lopez- las formas hereditarias y no hereditarias Sakuma M, Oshima K, Ohara O, Nis- Trascasa M, Montalban X, Moreno MJ, de las enfermedades autoinflamatorias. hikomori R, Morimoto T, Kambe N, Munoz D, Nunez V, Muriel A, Navarro Sponsored by: FIS, PS09/01182. Dura- Goldbach-Mansky R, Aksentijevich I, J, Olascoaga J, Oreja-Guevara C, Prada tion: 01/01/2010-30/12/2012. DeSaintBasile G, Neven B, VanGijn A, Ramil E, Ramo-Tello C, Rodriguez C, M, Frenkel J, Arostegui JI, Yague J, Rodriguez E, Rodriguez-Frias F, Rodri- Otero MJ. Reevaluación del papel de Merino R, Ibanez M, Pontillo A, Taka- guez-Antiguedad A, Rodriguez-Molina HLA-DRB3 (DR52) en la respuesta de da H, Imagawa T, Kawai T, Yasumi T, JJ, Ruiz E, Saiz A, Sarasola E, Simo M, los linfocitos T CD4+. Sponsored by: Nakahata T, Heike T. High Incidence Yague J, Villar LM. Utility of oligoclonal FIS PI10/01404. Duration: 01/01/2011- of NLRP3 Somatic Mosaicism in Pa- IgG band detection for MS diagnosis 31/12/2013. tients With Chronic Infantile Neuro- in daily clinical practice. J IMMUNOL logic, Cutaneous, Articular Syndrome METHODS. 371:170-173. I.F.: 2.34. Yagüe J. Immunogenètica en la res- Results of an International Multicen- posta autoinflamatòria. Sponsored by: ter Collaborative Study. ARTHRITIS 9 Puente XS, Pinyol M, Quesada V, AGAUR SGR09 2009_SGR_1260. Dura- RHEUM-US. 63:3625-3632. I.F.: 8.44. Conde L, Ordonez GR, Villamor N, Es- tion:23/9/2009-31/12/2013.

89 AReA 1

Biological aggression and response mechanisms

Emergencies: Processes and pathologies StrateGic oBjectiveS gROUP MeMBeRS The group has a general interest in the study of all processes and pathologies inherent to the emergency setting - in all cases adopting a patient – centered approach and focusing on the acute teAM leADeR process leading to emergency con- oscar Miró Andreu (Hospital clínic) sultation. This approach is absolutely tel.: 93 227 54 00 (ext. 3153) unique in Catalonia and in Spain, in fax: 93 227 56 93 view of the topic involved and the e-mail: [email protected] perspective from which it is addressed. The processes seen in the Emergency iDiBApS MeMBeRS: nuRSinG StAff: Department are exclusive and unique, Santiago nogué Xarau (Hospital clínic) Montserrat Amigó tadín (Hospital clínic) and improvement in their knowledge Miguel Sánchez Sánchez (Hospital clínic) eva Gómez Rodríguez (Hospital clínic) leads to healthcare and organizational Blanca coll-Vinent puig (Hospital clínic) carolina fuenzalida inostroza (facultat implications with considerable scope Sònia Jiménez Hernández (Hospital clínic) Medicina) and repercussion. While the transverse characteristics of emergency disease ReSeARcH fellowS: collABoRAtoRS: conditions cause them to be dealt with emilio Salgado García (Hospital clínic) elisenda Gómez Angelats (Hospital clínic) by other disciplines, in the first few Beatriz lópez Barbeito (Hospital clínic) Josep Ramon Alonso Viladot hours of their presentation they are ex- núria corominas García (Hospital clínic) (Hospital clínic) clusively addressed by the Emergency María teresa Ruiz (Hospital clínic) Albert Antolín Santaliestra (Hospital clínic) Department, where clinical research Victor Gil espinosa (Hospital clínic) Miguel Galicia paredes (Hospital clínic) has not classically been considered. As Sira Aguiló Mir (Hospital clínic) francesc Xavier Jiménez fábrega (SeM) a result, the possibilities for gaining in- Rafel perelló carbonell (Hospital clínic) Mar ortega Romero (Hospital clínic) depth and new knowledge on the part Rosa escoda turón (Hospital clínic) of the group are immense. francesc Xavier escalada Roig (SeM) núria Díaz Miranda (pedagoga, escola main lineS Molina, Barcelona) of reSearcH Alba Riesgo (uB) Maria luisa Benito (cAp les corts) 1. Functional aspects of hospital francisco Javier Jacob Rodríguez Emergency Departments. Since (facultat Medicina) 1997, the group has dedicated an important part of its research effort to exploring the fundamental functional mechanisms of a Hos- pital Emergency Department. In a series of studies, the group has demonstrated that the most important limiting element regarding the efficacy, effectiveness and quality of the Emergency Department is fundamented upon extrinsic rather than upon intrinsic factors (service demand). Among the intrinsic factors, those dependent upon the Hospital rather than on the Emergency De- partment as such are the most deci- sive in determining the functionality of a given Emergency Department.

90 AReA 1 BioloGicAl AGGReSSion AnD ReSponSe MecHAniSMS eMeRGencieS: pRoceSSeS AnD pAtHoloGieS

2. clinical aspects of intoxicated pa- the year 2000, has involved diffe- the context of the acute heart failure tients. This is a line of long tradition rent professionals (physicians and working group of the Spanish Socie- and history in our research group. nurses in both out- and in-hospital ty of Emergency Care Medicine and The Clinic Hospital is a reference emergency services, with pedago- Urgencies. centre in Catalonia for healthcare gical support). Its main objective is and research in relation to intoxi- to explore all the possibilities and 8. Attention to infectious diseases cations of all kinds. It is a member difficulties for diffusing knowledge in Emergency Departments. This of the SEMES-TOX group, which is of cardiopulmonary resuscitation new research line brings together the toxicology working group of the maneuvers among the general po- different approaches to infections, Spanish Society of Emergency Care pulation. The setting in which the focusing on the clinical data and Medicine and Urgencies, and of the research activity has been most diagnostic or therapeutic actions STC-AETOX group of the Spanish intense is among students in se- performed during the first hours of Association of Toxicology. condary education (14-16 years of the patients at the hospital, which age), where the approach is made use to occur in the Emergency De- 3. treatment of arrhythmias in the through a specific program, the partment. The research is focused emergency room. For over 10 years PROCES (Programa de Reanimació on prevalent infections, life-threa- the group has participated in a coordi- cardiopulmonar Orientat a Centres tening infections (especially sepsis) nated manner with the cardiologists d’Ensenyament Secundari, or car- and infections associated with HIV. of the center, with primary care diopulmonary resuscitation program physicians working in clinics in their oriented towards secondary educa- 9. Dynamics of teaching and re- corresponding reference areas, and tion centres) designed exclusively search in Emergency Medicine. In with other investigators in Spain who for application in the current Cata- Spain Emergency Medicine is not work in Emergency Departments lan educational model, which has officially recognized as a specialty. (the group forms part of the arrhyth- been fully developed by members Therefore there is a lack of teaching mias chapter of the Spanish Society of the group (Òscar Miró i Andreu, and research which demands a of Emergency Care Medicine and Miquel Sánchez-Sánchez, and Núria deep analysis. At the same time, it Urgencies), in the investigation of Díaz-Miranda). would be interesting to gain a better disorders of this kind. The most re- understanding of the characteris- levant contributions of the group in 6. Emergency medical care for tics that drive these activities and this setting have been in reference to problems caused by drug abuse. compare them with the results of ATRIAL FIBRILLATION. Originally conceived as a toxicolo- the activity recorded in other spe- gical variant, the importance and cialties with long experience and 4. Evaluation of chest pain in the specificity of research in this field recognition. In addition, bibliometric Emergency Department. The group made it possible in 2001 to create tools are becoming very powerful, coordinates and conducts important this line of research. The advanta- allowing detailed examination of the research work in the only structural ges derived as a result of research research activity as well as opening chest pain unit currently operating in from the emergency care perspec- new research possibilities around Spain, which began its activities in tive has made it possible to clearly these tools. 2002. From the start, the group has improve our knowledge of this centered its efforts on taking advan- group of disorders. At present, the tage of this fact to investigate the group works in collaboration with medical care of these patients, and other groups in Spain and in other to further knowledge of a subgroup countries. of these subjects who had not been diagnosed at the time with acute 7. Acute heart failure. This research coronary disease, and had therefore line focuses on the differential as- not been sufficiently investigated. pects (both clinical and epidemiological) of acute decompensated heart 5. Diffusion of the teaching of car- failure. Investigation of this syndro- diopulmonary resuscitation ma- me – highly prevalent in Emergency neuvers among the general po- Departments – is carried out in com- pulation. This is an interdisciplinary bination with other Emergency De- line of work which, from its start in partments throughout Spain, within

91 BIOLOgICAL AggReSSION AND ReSPONSe MeChANISMS Emergencies: Processes and pathologies PUBLICATIONS

oRiGinAlS 7 Rodriguez JJ, Puente PH, San- 13 Moren C, Noguera-Julian A, Rovi- i.f.: 49.13 chez FJM, Llorens P, Miro O, Perello ra N, Corrales E, Garrabou G, Hernan- R. EAHFE (Epidemiology Acute dez S, Nicolas M, Tobias E, Cardellach 1 Lopez B, Sanchez M, Bragulat E, Heart Failure Emergency) study: F, Miro O, Fortuny C. Mitochondrial im- Jimenez S, Coll-Vinent B, Ortega M, analysis of the patients with echo- pact of human immunodeficiency virus Gomez-Angelats E, Miro O. Validation cardiography performed prior to an and antiretrovirals on infected pediatric of a triage flowchart to rule out acute emergency visit due to an episode patients with or without lipodystrophy. coronary syndrome. EMERG MED J. of acute heart failure. REV CLIN PEDIATR INFECT DIS J. 30:992-995. 28:841-846. I.F.: 1.27. ESP. 211:329-337. I.F.: 0.76. I.F.: 3.06.

2 Perello R, Calvo M, Miro O, Cas- 8 Guitian PP, Xarau SN, Guiller- 14 Garrabou G, Inoriza JM, Moren taneda M, Saubi N, Camon S, Foix mo JR, Tejero IN, Viladot JRA. C, Oliu G, Miro O, Marti MJ, Carde- A, Gatell JM, Masotti M, Mallolas Evaluation of acute poisonings llach F. Mitochondrial Injury in Human J, Sanchez M, Martinez E. Clinical due to chemical agents treated in Acute Carbon Monoxide Poisoning: presentation of acute coronary an Emergency Department. MED The Effect of Oxygen Treatment. J syndrome in HIV infected adults: A CLIN-BARCELONA. 136:149-152. ENVIRON SCI HEAL C. 29:32-51. retrospective analysis of a prospecti- I.F.: 1.41. I.F.: 4.84. vely collected cohort. EUR J INTERN MED. 22:485-488. I.F.: 1.66. 9 Jimenez S, Aguilo S, Antolin A, 15 Miro O, Jacob J, Martin-Sanchez Coll-Vinent B, Miro O, Sanchez M. FJ, Herrero P, Pavon J, Perez-Dura 3 Garrabou G, Lopez S, Moren C, Home hospitalization directly from MJ, Noval A, Segura F, Richard F, Martinez E, Fontdevila J, Cardellach emergency department: an efficient Gimenez A, Gil C, Alonso H, Ruiz M, F, Gatell JM, Miro O. Mitochondrial alternative to standard inpatient Garrido M, Roman JJG, Aguirre A, damage in adipose tissue of un- hospitalization. MED CLIN-BARCE- Torres JM, Ruiz F, Perello R, Villena treated HIV-infected patients. AIDS. LONA. 137:587-590. I.F.: 1.41. H, Gil V, Llorens P. Prognostic implica- 25:165-170. I.F.: 6.35. tions of emergency department deter- 10 Galicia M, Nogue S, Miro O. mination of B-type natriuretic peptide 4 Perello R, Miro O, Miro JM, Masso Liquid ecstasy intoxication: clinical in patients with acute heart failure: E, Sanchez M, Camon S, DeLaBellaca- features of 505 consecutive emer- the PICASU-2 study. EMERGENCIAS. sa JP, Moreno A, Marcos MD. Urgent gency department patients. EMERG 23:437-446. I.F.: 3.09. pneumococcal urinary antigen, im- MED J. 28:462-466. I.F.: 1.27. portance in the diagnosis of acquired 16 Jacob J, Llorens P, Martin-San- pneumonia in HIV-1 patients. EUR J 11 Sanchez M, Bauset JL, Cuer- chez FJ, Herrero P, Alvarez A, Perez- EMERG MED. 18:50-54. I.F.: 0.90. vo R, Carbajosa J, Oria MC, Povar Dura MJ, Noval A, Segura F, Richard F, J, Santalo M. Management of Gimenez A, Miro O. Prognostic value 5 Benito L, Hoyo J, Montroig A, For- non-ST-segment elevation acute of emergency department testing for nes B, Fluxa G, Marti D, Pedros M, coronary syndromes in emergency de- N-terminal fragment of brain natriuretic Siso A, Mont L, Miro O, Coll-Vinent partments according to hospital size: peptide in patients with acute heart B. Adverse effects of antiarrhythmic cases from the Emergency Manage- failure: the PICASU-1 study. EMER- drugs in patients with atrial fibrillation ment of Acute Coronary Syndrome GENCIAS. 23:183-192. I.F.: 3.09. in Primary Care. MED CLIN-BARCE- (MUSICA) registry. EMERGENCIAS. LONA. 137:241-246. I.F.: 1.41. 23:447-454. I.F.: 3.09. 17 Côté HC, Gerschenson M, Walker UA, Miro O, Garrabou G, Hammond E, 6 Riesgo A, Miro O, Lopez-De-Sa E, 12 Moren C, Noguera-Julian A, Rovi- Villarroya J, Giralt M, Villarroya F, Cin- Sanchez M. Comparison of the Ma- ra N, Garrabou G, Nicolas M, Cardellach que P, Garcia-Arumi E, Andreu AL, Pinti nagement of Non-ST Segment Ele- F, Martinez E, Sanchez E, Miro O, For- M, Cossarizza A. Quality assessment vation Myocardial Infarction During tuny C. Mitochondrial assessment in of human mitochondrial DNA quantifi- Emergency Care According to Sex asymptomatic HIV-infected paediatric cation: MITONAUTS, an international of the Patient. REV ESP CARDIOL. patients on HAART. ANTIVIR THER. multicentre survey. MITOCHONDRION. 64:1060-1064. I.F.: 2.16. 16:719-724. I.F.: 3.77. 11:520-527. I.F.: 3.24.

92 AReA 1 BioloGicAl AGGReSSion AnD ReSponSe MecHAniSMS eMeRGencieS: pRoceSSeS AnD pAtHoloGieS

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 24.46 8 3 3 18 Salmeron JM, Jimenez L, 4 Sanz-Gallen P, Nogue S, Herrera- Miro O, Sanchez M. Safety and Mozo I, Delclos GL, Valero A. Occupa- 2010 40.83 21 1 7 efficacy of hospital emergency tional contact allergy to omeprazole and 2011 49.13 20 4 5 department discharge from triage fluoxetine. CONTACT DERMATITIS. by nurses accredited to use an al- 65:118-119. I.F.: 3.67. gorithmic aid for the Spanish Triage System without physician evalua- 5 Miro O. Project EMERGER: the fifth tion. EMERGENCIAS. 23:346-355. year. EMERGENCIAS. 23:1-2. I.F.: 3.09. DoctoRAl tHeSeS I.F.: 3.09. 6 Sanchez M. Treatment of myocardial Coll-Vinent B. Utilitat de la detecció 19 Riesgo A, Sant E, Benito L, infarction with ST-segment elevation: a precoç de la fibril·lació auricular. PhD Hoyo J, Miro O, Mont L, Bragulat war between the sexes?. EMERGEN- student: Lluïsa Benito Serrano. E, Coll-Vinent B. Sex Differences in CIAS. 23:83-84. I.F.: 3.09. the Treatment of Patients With Atrial Sanchez M, Miro O. Testamento vital, Fibrillation: Population-Based Study enfermo crónico y urgencias. PhD stu- in a Local Health District. REV ESP clinicAl GuiDelineS dent: Albert Antolín Santaliestra. CARDIOL. 64:233-236. I.F.: 2.16. i.f.: 3.09 Nogue S. Mejora de la seguridad clí- 20 Antolin A, Sanchez M, Miro O. 1 Llorens P, Miro O, Sanchez FJM, nica del paciente intoxicado a partir Temporal trend in understanding of Puente PH, Rodriguez JJ, Gil V, Perello del cumplimiento de los indicadores and attitudes to advance directives R, Aguirre A, Valero A. Guidelines for de calidad en Toxicología Clínica. PhD in patients with chronic diseases. emergency management of acute heart student: Jordi Puiguriguer Ferrando. GAC SANIT. 25:412-418. I.F.: 1.11. failure: consensus of the Acute Heart Failure Working Group of the Spanish Society of Emergency Medicine (ICA- ReViewS SEMES) in 2011. EMERGENCIAS. i.f.: 3.09 23:119-139. I.F.: 3.09.

1 Nogue S, Corominas N, Soy D, Cino J. Intravenous lipid emulsion: GRAntS foR ReSeARcH in a new antidote for use in resuscita- pRoGReSS tion. EMERGENCIAS. 23:378-385. I.F.: 3.09. Coll-Vinent B. Utilidad de la detec- ción precoz de la fibrilación auricular. Sponsored by: Instituto de Salud eDitoRiAlS Carlos III (ISCIII), PI070278. Duration: i.f.: 19.12 26/11/2007-30/06/2011.

1 Miro O. 3,085 EDITORIAL. EMER- Miro O. Grup de recerca consolidat. GENCIAS. 23:261-263. I.F.: 3.09. Sponsored by: Generalitat de Ca- talunya, SGR 2009-1385. Duration: 2 Miro O. Another year without recog- 01/01/2009-31/12/2013. nition for emergency medical training in Spain. EMERGENCIAS. 23:421-422. Miro O. Comparación de dos metodo- I.F.: 3.09. logías diferentes para la difusión de la enseñanza de la reanimación cardiopul- 3 Julian-Jimenez A, Miro O. Emer- monar básica durante la escolarización gencias: results of a readership opinion obligatoria. Sponsored by: Instituto de survey. EMERGENCIAS. 23:341-343. Salud Carlos III (ISCIII), PI 07/0073. Du- I.F.: 3.09. ration: 26/11/2007-30/06/2011.

93 AReA 1

Biological aggression and response mechanisms Molecular and cellular bases of inflammation. StrateGic Structural and biological mass spectrometry oBjectiveS gROUP MeMBeRS 1. Molecular and cellular bases of inflammation: Study of inflammatory response in general.

teAM leADeR 2. Structural and biological mass Daniel closa (iiBB-cSic) spectrometry: tel.: 93 363 83 43 Development of techniques for fax: 93 363 83 01 solving problems in proteomics and e-mail: [email protected] in the analysis of biomolecules in general. Application to the study of antigen presentation in autoimmune diseases and to the investigation of therapeutic targets and markers of the disease.

main lineS of reSearcH

1. Molecular and cellular bases of inflammation: • Mechanisms involved in the development of systemic inflammatory processes. • New therapies for idiopathic pulmonary fibrosis. • Study of the lipid alterations associated associated with pancreatitis.

2. Structural and biological mass spectrometry: • Phosphoproteomics of the human T lymphocyte. • Diagnostic and prognostic markers in cancer and other diseases. iDiBApS MeMBeRS: tecHniciAnS: • External scientific-technical ser- oriol Bulbena (iiBB-cSic) l. ignacio Sanchez vices. Proteomics Services and emili Gelpí (iiBB-cSic) V. Sirenko (iDiBApS) Coordination of Proteored Net- Joaquín Abián (iiBB-cSic-uAB) edita Bueno (JAe-tec) work. Montserrat carrascal (iiBB-cSic) Joan Villanueva (proteored) emma folch (iBB-cSic) Ana González (proteored) D. ovelleiro (proteored) ReSeARcH fellowS: V. casas (tS- Micinn) Gemma Gay S. Gea (tS) collABoRAtoRS: c. lebrero (GenAMe) f. pí (iiBB-cSic) R. Guillamat (ciBeReS) A. Salas (Rc) A. Serrano (iiBB-cSic) M. Gay (JAe-Doc) n. franco (ciBeReHD)

94 AReA 1 BioloGicAl AGGReSSion AnD ReSponSe MecHAniSMS MoleculAR AnD cellulAR BASeS of inflAMMAtion. StRuctuRAl AnD BioloGicAl MASS SpectRoMetRy

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 oRiGinAlS GRAntS foR ReSeARcH 2009 38.98 9 8 1 i.f.: 24.86 in pRoGReSS 2010 51.15 9 8 0 2011 24.86 5 3 0 1 Morina D, Puig P, Rios J, Vilella A, Abian J. La activación linfocitaria a Trilla A. A statistical model for hos- través del análisis del fosfoproteo- pital admissions caused by seasonal ma. Determinación de perfiles de diseases. STAT MED. 30:3125-3136. fosforilación in vivo. Sponsored by: I.F.:2.33. MICINN, BIO2009-11735. Duration: Abian J. Desarrollo de una vacuna 01/01/2010-31/12/2012. global frente a Brachyspira hyodysen- 2 Gea-Sorli S, Guillamat R, Serrano- teriae y Brachyspira pilosicoli median- Mollar A, Closa D. Activation of Closa D. Trasplante de macrófagos te análisis pan-genómico estructural lung macrophage subpopulations in reprogramados ex vivo como terapia y funcional combinado con tecnolo- experimental acute pancreatitis. J para la pancreatitis aguda experi- gías de producción de proteínas re- PATHOL. 223:417-424. I.F.:7.27. mental. Sponsored by: Ministerio combinantes (brachVac). Sponsored Ciencia e Innovación, SAF2009- by: Proyectos INNPACTO 2011, MI- 3 Balasa M, Gelpi E, Antonell A, 07605. Duration: 01/01/2010- CINN. Laboratorios Dr. Larrasa S.L. Rey MJ, Sanchez-Valle R, Molinuevo 31/12/2011. Duration: 01/01/2011-31/12/2014. JL, Llado A. Clinical features and APOE genotype of pathologically Closa D. Derivados lipídicos como Montserrat Carrascal. Caracterización proven early-onset Alzheimer disea- agentes moduladores de la res- del secretoma y fosfosecretoma del se. NEUROLOGY. 76:1720-1725. puesta hiperinflamatoria sistémica. linfocito T CD4+ primario humano I.F.:8.02. Sponsored by: Ministerio Ciencia e mediante herramientas proteómicas. Innovación, 201022002. Duration: Sponsored by: MICINN. Duration: 4 Gay M, Pares A, Carrascal M, 01/06/2010-01/06/2011. 01/01/2011-31/12/2012. Bosch-I-Crespo P, Gorga M, Mas A, Abian J. Proteomic Analysis of Bulbena O. Trasplante de células al- Closa D. Regulació de la Inflama- Polypeptides Captured from Blood veolares tipo II, derivadas de células ció Aguda i Crónica. Sponsored during Extracorporeal Albumin Dialy- madre adultas, para el tratamiento de by: Generalitat de Catalunya, sis in Patients with Cholestasis and la fibrosis pulmonar idiopática. Spon- AGAUR, 2009_SGR_966. Duration: Resistant Pruritus. PLOS ONE. 6:-. sored by: FIS, PS09/02362. Duration: 16/09/2009-31/12/2013. I.F.:4.41. 01/01/2010-31/12/2013.

5 Quero C, Colome N, Rodriguez Abian J. Desarrollo de una herra- DoctoRAl tHeSeS C, Eichhorn P, DeLaPaz MP, Gelpi mienta de diagnóstico molecular para E, Abian J. Proteomics of toxic oil la obtención de aves con mayor valor Closa D. Caracterització del tipus syndrome in humans: Phenotype dis- añadido. Sponsored by: Proyectos d’activació de diferents poblacions tribution in a population of patients. INNPACTO 2011, MICINN. Labo- de macròfags durant la pancreatitis CHEM-BIOL INTERACT. 192:129-135. ratorios Dr. Larrasa S.L. Duration: aguda experimental i la seva relació I.F.:2.83. 01/01/2011-31/12/2014. amb la severitat del procés. PhD student: Sabrina Gea Sorlí, Universitat de Barcelona.

AReA 2 Team involved in:

Respiratory, cardiovascular and renal pathobiology and bioengineering Atherosclerosis, coronary disease and heart failure StrateGic oBjectiveS gROUP MeMBeRS • To identify the pathophysiological mechanisms involved in the process of accelerated atherosclerosis. The research focuses on the area of cardiovascular biology. teAM leADeR • To evaluate the clinical efficacy of re- Manel Sabaté (Hospital clínic) generative cell therapy and carry out tel.: 93 227 93 05 further in-depth study of the regulatory fax: 93 227 93 05 mechanisms of the exogenous and en- e-mail: [email protected] dogenous stem cells in ischaemic heart disease and heart failure. xxxxxx iDiBApS MeMBeRS: ADMiniStRAtiVe StAff: • To gain an increased understanding Magda Heras fortuny (Hospital clínic) MªAngeles Alvarez (Hospital clínic) of the genetics, pathophysiology, Amadeu Betriu (Hospital clínic) eva trellísó Areny (fcRB) diagnosis and treatment of heart fail- Xavier Bosch (Hospital clínic) ure in the areas of basic and clinical Ana paula Dantas (iDiBApS) collABoRAtoRS: research, imaging techniques, bio- carles paré (Hospital clínic) Montserrat Batlle (iDiBApS) markers, risk factors and advances in félix pérez Villa (Hospital clínic) Mònica Masotti (Hospital clínic) both medical treatment and treatment José luis pomar (Hospital clínic) África Muxí (Hospital clínic) with medical devices. The research Montserrat Rigol (iDiBApS) núria Solanes (fcRB) focuses on patients with advanced Mercè Roqué (Hospital clínic) José ortiz pérez (Hospital clínic) heart failure and patients with heart laura novensà (iDiBApS) failure in the community. ReSeARcH fellowS: Rut Andrea (Hospital clínic) • To gain an increased understanding of luis Álvarez contreras Manel Azqueta (Hospital clínic) the organisational models for the care Montserrat cardona (Hospital clínic) of cardiovascular patients in the com- tecHniciAnS: carles falces (Hospital clínic) munity: integration between cardiology nadia castillo (fundació clínic) Victoria Martín yuste (Hospital clínic) and primary care, cardiovascular pre- Sussanna prat (Hospital clínic) vention and care of the chronic patient. nuRSinG StAff: Mª José pulgarín (iDiBApS) • To gain a more in-depth understand- Anna Barrabés (fundació clínic) Salvatore Brugaletta (Hospital clínic) ing of the pathophysiology, diagnostic elisabet de Mingo (iDiBApS) Ana García Álvarez (Hospital clínic) methods and results of new treatments for acute and chronic ischaemic heart disease. The research focuses on basic in vitro studies, studies on animal models, clinical studies of the pathophysiology and safety and efficacy studies on the different treatments for coronary heart disease. The aim is to further con- centrate on the effects of the risk factors on the development of ischaemic heart disease. • To evaluate the repercussions of the new diagnostic techniques and types of treatment in structural heart disease, including valvular disease and congenital and acquired structural disease. • To study the applicability of the invasive and non-invasive imaging techniques in ischaemic heart disease, heart failure, structural heart disease and cell therapy.

98 AReA 2 ReSpiRAtoRy, cARDioVASculAR AnD RenAl pAtHoBioloGy AnD BioenGineeRinG AtHeRoScleRoSiS, coRonARy DiSeASe AnD HeARt fAiluRe

main lineS of • Study of the impact of gender differ- cardiovascular disease in the reSearcH ences on ischaemic heart disease. community: Evaluation of the characteristics of • Study of the integrated care models cardiovascular Biology: cardiovascular disease in women and between cardiology and primary care for • Study of the mechanisms of hyperpla- the different factors affecting the improving clinical practice in patients with sia of the intima following coronary prognosis. chronic heart disease. revascularisation procedures in mu- • Clinical studies evaluating the efficacy • Outpatient characterisation of new- rine and porcine experimental models and safety of drug-eluting stents onset heart failure using high-resolution with the aim of developing pharmaco- coated with everolimus in patients imaging. logical prevention strategies. with ST-segment elevation myocardial • Study of interventions in chronic patients • Study of the biocompatibility of the infarction (EXAMINATION Study). for improving prognosis and prevention materials in the design of intracoro- • Clinical evaluation of the fully biore- of readmissions due to heart failure. nary devices. sorbable coronary device (Absorb) • Study of impedance during the en- in patients with ischaemic heart Structural heart disease dothelialisation process of a coronary disease. • Study of the efficacy and efficiency, and stent. Development of the “smart • Chronic total occlusion of coronary the repercussions on quality of life, of stent”. arteries in humans: from the patho- surgical and transcatheter treatment of • Study of the influence of hormonal physiology to the clinical implications aortic valve disease. factors and aging on the regulation of successful recanalisation through • Percutaneous closure of the left atrial of the nitric oxide and superoxide percutaneous coronary intervention. appendage in patients with non-valvular systems in the healthy population and Utility of imaging techniques in the atrial fibrillation requiring anticoagulant the population with cardiovascular indications and treatment of patients treatment who have a recent history of disease. with chronic coronary artery occlu- gastrointestinal bleeding. • Determination of the mechanisms sions and assessment of results and • Evaluation of the impact of the use of involved in the regulation of the ni- follow-up. MitraClip in patients with functional mi- tric oxide and superoxide systems tral regurgitation in different population through steroid receptors and their heart failure: groups. role in regulating the development of • Study of neurohormonal activation and • Role of cardiac imaging in the indications, cardiovascular diseases such as ath- the fibrotic process associated with diagnosis, treatment and follow-up of pa- erosclerosis, hypertension, diabetes ventricular remodelling in idiopathic or tients with structural heart disease. and metabolic syndrome. ischaemic dilated cardiomyopathy us- • Advances in diagnostic imaging for and ing molecular biology and immunohis- treatment of heart valve diseases and cell therapy: tochemical techniques on myocardial complications such as infectious endo- • Study of the efficacy of cell therapy in tissue and through neurohormonal carditis. patients with chronic refractory angina determinations. and non-revascularisable coronary dis- • Genetic study of familial idiopathic chagas heart Disease ease and the regulation of endothelial cardiomyopathy. • Utility of the new imaging techniques and progenitor cell activation in acute myo- • Prevention of ventricular dysfunction biomarkers for the early diagnosis of car- cardial infarction. At an experimental in chemotherapy patients. Evaluation diac involvement in Chagas disease. level, we are analysing the regulatory of drugs for the prevention of ventric- • Research into early markers of response mechanisms and the efficacy of the ular dysfunction in oncology patients to antiparasitic treatment. administration of mesenchymal stem undergoing chemotherapy. cells on myocardial regeneration in an • Study of heart failure with normal Pulmonary hypertension and right ven- experimental pig model. ejection fraction: role of biomarkers tricular dysfunction and imaging techniques in the diagno- • Utility of cardiac magnetic resonance im- Ischaemic heart disease: sis, relationship between myocardial aging in the estimation and monitoring of • Pathophysiology and improvement remodelling biomarkers in diagnosis haemodynamic parameters in pulmonary in the diagnosis and treatment of and prognosis of outpatients and hypertension. acute coronary syndrome. Role of the study of lung function in these pa- • Utility of magnetic resonance imaging mechanisms of vascular inflammation tients. for the early detection of right ventricular and thrombosis. Evaluation of the • Evaluation of mechanical circulatory dysfunction. circulating endothelial cells and the support devices: ventricular assist de- • Research into new pharmacological treat- progenitor endothelial cells. vice as bridge to transplant. ments in pulmonary hypertension.

99 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Atherosclerosis, coronary disease and heart failure

PUBLICATIONS

oRiGinAlS Survival Rates in Myocardial Infarc- 10 Freixa X, Masotti M, Palomo i.f.: 97.59 tion Patients. REV ESP CARDIOL. M, Diaz-Ricart M, Escolar G, Guasch 64:96-104. I.F.: 2.16. E, Regueiro A, Jimenez M, Betriu A, 1 Cervera C, Fernandez-Ruiz M, Heras M. Endothelin-1 levels predict Valledor A, Linares L, Anton A, Mar- 6 Anguita M, Beiras AC, Cobo E, endothelial progenitor cell mobilization cos MA, Sanclemente G, Hoyo I, Co- Coca A, DeTeresa E, Diez J, Lopez after acute myocardial infarction. MI- fan F, Ricart MJ, Perez-Villa F, Navasa B, Cebollada J, Diaz B, Galve E, CROVASC RES. 82:177-181. I.F.: 2.39. M, Pumarola T, Moreno A. Epidemiol- Gonzalez-Juanatey JR, Jimenez- ogy and risk factors for late infection Navarro M, Lopez I, Lupon J, Martin 11 Sanchis J, Bodi V, Nunez J, Nun- in solid organ transplant recipients. C, Monserrat L, Narejos S, Figal DAP, ez E, Bosch X, Pellicer M, Heras M, TRANSPL INFECT DIS. 13:598-607. Perez-Calvo JI, Querejeta R, Ridocci Bardaji A, Marrugat J, Llacer A. Iden- I.F.: 2.04. F, Rodriguez A, Rodriguez M, Roig E, tification of very low risk chest pain Roure J, Ruiz S, Sanchez PL, Terns using clinical data in the emergency 2 Linares L, Sanclemente G, Cer- M, Toran P, Munoz-Tuduri M. Effects department. INT J CARDIOL. 150:260- vera C, Hoyo I, Cofan F, Ricart MJ, of Prolonged-Release Torasemide 263. I.F.: 6.80. Perez-Villa F, Navasa M, Marcos MA, Versus Furosemide on Myocardial Fi- Anton A, Pumarola T, Moreno A. In- brosis in Hypertensive Patients with 12 Sabate S, Mases A, Guilera N, fluence of Cytomegalovirus Disease Chronic Heart Failure: A Randomized, Canet J, Castillo J, Orrego C, Sabate A, in Outcome of Solid Organ Transplant Blinded End Point, Active-Controlled Fita G, Parramon F, Paniagua P, Rodri- Patients. TRANSPL P. 43:2145-2148. Study. CLIN THER. 33:1204-1213. guez A, Sabate M. Incidence and pre- I.F.: 0.99. I.F.: 2.55. dictors of major perioperative adverse cardiac and cerebrovascular events in 3 Novensa L, Novella S, Medina P, 7 Roque M, Sitges M, Sala J, Delgado non-cardiac surgery. BRIT J ANAESTH. Segarra G, Castillo N, Heras M, Her- V, Morales M, Marrugat J, Vila J, Subi- 107:879-890. I.F.: 4.22. menegildo C, Dantas AP. Aging Nega- rana I, Tassies D, Reverter JC, Castro tively Affects Estrogens-Mediated M, Duran M. Effects of Raloxifene on 13 Sanchis J, Nunez J, Bodi V, Nunez Effects on Nitric Oxide Bioavailability Endothelial Function and Hemostasis E, Garcia-Alvarez A, Bonanad C, Regue- by Shifting ER alpha/ER beta Balance in Women With Ischemic Heart Dis- iro A, Bosch X, Heras M, Sala J, Bielsa in Female Mice. PLOS ONE. 6:-. ease. REV ESP CARDIOL. 64:572-578. O, Llacer A. Influence of Comorbid I.F.: 4.41. I.F.: 2.16. Conditions on One-Year Outcomes in Non-ST-Segment Elevation Acute Coro- 4 Mohr FW, Rastan AJ, Serruys 8 Martin-Yuste V, Alvarez-Contreras nary Syndrome. MAYO CLIN PROC. PW, Kappetein AP, Holmes DR, L, Brugaletta S, Ferreira-Gonzalez 86:291-296. I.F.: 5.71. Pomar JL, Westaby S, Leadley K, I, Cola C, Garcia-Picart J, Marti V, Dawkins KD, Mack MJ. Complex Sabate M. Emergent Versus Elective 14 Falces C, Andrea R, Heras M, Vehi coronary anatomy in coronary ar- Percutaneous Stent Implantation in C, Sorribes M, Sanchis L, Cevallos J, tery bypass graft surgery: Impact the Unprotected Left Main: Long- Menacho I, Porcar S, Font D, Sabate of complex coronary anatomy Term Outcomes from a Single-Center M, Brugada J. Integration Between in modern bypass surgery? Les- Registry. J INVASIVE CARDIOL. Cardiology and Primary Care: Impact on sons learned from the SYNTAX 23:392-397. I.F.: 1.78. Clinical Practice. REV ESP CARDIOL. trial after two years. J THORAC 64:564-571. I.F.: 2.16. CARDIOV SUR. 141:130-140. 9 Garcia-Alvarez A, Sitges M, I.F.: 3.61. Heras M, Poyatos S, Posada E, 15 Garcia-Alvarez A, Sitges M, Pinazo MJ, Regueiro A, Gascon J, Regueiro A, Poyatos S, Pinazo MJ, 5 Bosch D, Masia R, Sala J, Vila Sanz G. Endothelial Function and Posada E, Bijnens B, Heras M, Gascon J, Ramos R, Elosua R, Subirana High-Sensitivity C-reactive Protein J, Sanz G. Myocardial Deformation I, Heras M, Sanchis J, Grau M, Levels in Patients With Chagas Dis- Analysis in Chagas Heart Disease With Brugada R, Marrugat J. Effect of ease Living in a Nonendemic Area. the Use of Speckle Tracking Echocardi- Opening a New Catheterization REV ESP CARDIOL. 64:891-896. ography. J CARD FAIL. 17:1028-1034. Laboratory on 30-Day and 2-Year I.F.: 2.16. I.F.: 3.36.

100 AReA 2 ReSpiRAtoRy, cARDioVASculAR, RenAl pAtHoBioloGy AnD BioenGineeRinG AtHeRoScleRoSiS, coRonARy DiSeASe, AnD HeARt fAiluRe

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 89.11 21 13 3 16 Bueno H, Betriu A, Heras M, Alon- Lambert JL, Blasco T, DeLaFuente L, so JJ, Cequier A, Garcia EJ, Lopez-Sen- Pascual D, Rabago G. Risk factors as- 2010 131.29 33 16 9 don JL, Macaya C, Hernandez-Antolin sociated with cytomegalovirus infection 2011 97.59 26 6 12 R. Primary angioplasty vs. fibrinolysis in in heart transplant patients: a prospec- very old patients with acute myocardial tive, epidemiological study. TRANSPL infarction: TRIANA (TRatamiento del In- INFECT DIS. 13:136-144. I.F.: 2.04. farto Agudo de miocardio eN Ancianos) eDitoRiAlS randomized trial and pooled analysis 22 Guasch E, Sionis A, Reverter JC, i.f.: 15.63 with previous studies. EUR HEART J. Andrea R, Loma-Osorio P, Freixa X, 32:51-60. I.F.: 10.05. Heras M. Safety issues of adjunctive 1 DiMario C, James S, Dudek D, Sa- clopidogrel in patients discharged after bate M, Degertekin M. Commentary: 17 Castel MA, Farrero M, Vallejos percutaneous coronary intervention The risk of over-regulation. BRIT MED I, Cardona M, Regueiro A, Perez-Villa with stent placement and requiring J. 342:-. I.F.: 13.47. F. Primary Immunosuppression and oral anticoagulation. INT J CARDIOL. Outcome Differences After Heart 146:E1-E4. I.F.: 6.80. 2 Martin-Yuste V, Alvarez-Contreras Transplantation: Tacrolimus Versus Cy- L, Cola C, Brugaletta S, Picart JG, closporine. TRANSPL P. 43:2244-2246. 23 Loma-Osorio P, Peñafiel P, Doltra Marti V, Masotti M, Sabate M. Use- I.F.: 0.99. A, Sionis A, Bosch X. Shoshin beriberi fulness of the Tornus (R) Catheter mimicking a high-risk non-ST-segment in Nondilatable Coronary Chronic 18 Aros F, Heras M, Vila J, Sanz H, elevation acute coronary syndrome Total Occlusion. REV ESP CARDIOL. Ferreira-Gonzalez I, Permanyer-Miralda with cardiogenic shock: when the ar- 64:935-938. I.F.: 2.16. G, Cunat J, Lopez-Bescos L, Cabades teries are not guilty. J EMERG MED. A, Loma-Osorio A, Marrugat J. Reduc- 41:e73-e77. I.F.: 1.55. tion in 28 Days and 6 Months of Acute clinicAl GuiDelineS Myocardial Infarction Mortality From 24 Diaz JF, DeLaTorre JM, Sabate i.f.: 12.21 1995 to 2005. Data From PRIAMHO I, M, Goicolea J. Spanish Cardiac Cath- II and MASCARA Registries. REV ESP eterization and Coronary Intervention 1 Anguita M, Alegria E, Barrios V, CARDIOL. 64:972-980. I.F.: 2.16. Registry. 20th Official Report of the Casasnovas JA, Escobar C, Leon M, Spanish Society of Cardiology Working Luengo E, Llisterri JL. Comments on 19 Esteban V, Mendez-Barbero N, Group on Cardiac Catheterization and the 2011 ESC/EAS guidelines for the Jimenez-Borreguero LJ, Roque M, No- Interventional Cardiology (1990-2010). management of dyslipidemias. A report vensa L, Garcia-Redondo AB, Salaices REV ESP CARDIOL. 64:1012-1022. of the Task Force of the Clinical Prac- M, Vila L, Arbones ML, Campanero MR, I.F.: 2.16. tice Guidelines Committee of the Span- Redondo JM. Regulator of calcineurin 1 ish Society of Cardiology. REV ESP mediates pathological vascular wall re- 25 Freixa X, Heras M, Ortiz JT, Ar- CARDIOL. 64:1090-1095. I.F.: 2.16. modeling. J EXP MED. 208:2125-2139. giro S, Guasch E, Doltra A, Jimenez I.F.: 14.78. M, Betriu A, Masotti M. Usefulness 2 Tendera M, Aboyans V, Bartelink of Endothelin-1 Assessment in Acute ML, Baumgartner I, Collet JP, Cre- 20 Gimenez M, Gilabert R, Mon- Myocardial Infarction. REV ESP CAR- monesi A, DeCarlo M, Erbel R, Heras teagudo J, Alonso A, Casamitjana R, DIOL. 64:105-110. I.F.: 2.16. M, Kownator S, Minar E, Ostergren Pare C, Conget I. Repeated Episodes of J, Poldermans D, Riambau V, Roffi Hypoglycemia as a Potential Aggravat- 26 Sanchis J, Bodi V, Nunez J, M, Sievert H, VanSambeek M, Zeller ing Factor for Preclinical Atherosclero- Bosch X, Heras M, Bonanad C, Pel- T, Bax J, Auricchio A, Baumgartner sis in Subjects With Type 1 Diabetes. licer M, Merlos P, Minana G, Llacer H, Ceconi C, Dean V, Deaton C, DIABETES CARE. 34:198-203. I.F.: 7.14. A. Usefulness of pain presentation Fagard R, Funck-Brentano C, Has- characteristics for predicting out- dai D, Hoes A, Knuuti J, Kolh P, 21 Delgado JF, Manito N, Almenar come in patients presenting to the Mcdonagh T, Moulin C, Popescu L, Crespo-Leiro M, Roig E, Segovia hospital with chest pain of uncertain B, Reiner Z, Sechtem U, Sirnes PA, J, DePrada JAV, Lage E, Palomo J, origin. EMERG MED J. 28:847-850. Torbicki A, Vahanian A, Windecker Camprecios M, Arizon JM, Rodriguez- I.F.: 1.27. S. ESC Guidelines on the diagnosis

101 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Atherosclerosis, coronary disease and heart failure

and treatment of peripheral artery 4 Ahmed WH, Mendiz OA, Thomas canal Kv1.3. Sponsored by: Gen- diseases: Document covering ath- MR. Usage Patterns and 1-Year eralitat de Catalunya (VALTEC), erosclerotic disease of extracranial Outcomes With the TAXUS Liberte VALTEC09-1-0042. Duration: carotid and vertebral, mesenteric, Stent: Results of the TAXUS OLYM- 01/01/2009-31/12/2011. renal, upper and lower extremity PIA Registry. CATHETER CARDIO arteries: the Task Force on the Di- INTE. 77:979-992. I.F.: 2.40. Sabate M. Chronic total occlu- agnosis and Treatm. EUR HEART J. sions of human coronary arteries: 32:2851-2906. I.F.: 10.05. 5 Fraser AG, Daubert JC, VanDeW- from pathophysiology to long-term erf F, Estes NAM, Smith SC, Krucoff clinical implications of success- MW, Vardas PE, Komajda M. Clinical ful recanalization by means of MulticentRicS evaluation of cardiovascular devices: percutaneous coronary interven- i.f.: 66.23 principles, problems, and propos- tion. Sponsored by: Fundació La als for European regulatory reform Marató de TV3, 082130. Duration: 1 Grube E, Chevalier B, Smits P, Report of a policy conference of 29/04/2010-04/03/2012. Dzavik V, Patel TM, Mullasari AS, the European Society of Cardiol- Wohrle J, Stuteville M, Dorange ogy. EUR HEART J. 32:1673-1686D. Roque M. VALTEC09-1-0042 aport- C, Kaul U. The SPIRIT V Study A I.F.: 10.05. ación de la Universidad de Navarra Clinical Evaluation of the XIENCE al proyecto CIDEM. Sponsored by: V Everolimus-Eluting Coronary VALTEC09, PI040823. Duration: Stent System in the Treatment of GRAntS foR ReSeARcH 30/06/2009-30/09/2011. Patients With De Novo Coronary in pRoGReSS Artery Lesions. JACC-CARDIO- VASC INTE. 4:168-175. I.F.: 5.86. Heras M. HERACLES - Determi- DoctoRAl tHeSeS nantes Genéticos y Ambientales de 2 Urban P, Abizaid A, Banning A, la Disfunción Vascular en la Hiperten- Sabate M, Cinca J. Revascularización Bartorelli AL, Baux AC, Dzavik V, sión y Cardiopatía Isquémica. Spon- de las Arterias Coronarias Ocluidas Ellis S, Gao RL, Holmes D, Jeong sored by: Instituto de Salud Carlos III Crónicamente. Predictores de éxito MH, Legrand V, Neumann FJ, (ISCIII), RETIC06 RD06/0009/0008. Angiográfico y Papel de las Nuevas Nyakern M, Spaulding C, Worthley Duration: 01/01/2007-31/12/2012. Técnicas de Imagen en la Selección S. Stent Thrombosis and Bleeding de los Pacientes. PhD student: Victo- Complications After Implantation of Dantas AP. Regulación hormonal del ria Martín Yuste. Sirolimus-Eluting Coronary Stents perfil proteómico y la función vas- in an Unselected Worldwide Popu- cular durante el envejecimiento y la lation A Report From the e-SELECT evolución de enfermedades cardio- (Multi-Center Post-Market Surveil- vasculares. Sponsored by: Instituto lance) Registry. J AM COLL CAR- de Salud Carlos III (ISCIII), PI08/0176. DIOL. 57:1445-1454. I.F.: 14.29. Duration: 01/01/2009-31/12/2011.

3 Jolly SS, Yusuf S, Cairns J, Heras M. Células endoteliales circu- Niemela K, Xavier D, Widimsky P, lantes y células progenitoras endote- Budaj A, Niemela M, Valentin V, liales en la enfermedad cardiovascu- Lewis BS, Avezum A, Steg PG, lar aguda. Correlación con la función Rao SV, Gao P, Afzal R, Joyner CD, endotelial y la evolución clínica. Chrolavicius S, Mehta SR. Radial Sponsored by: Instituto de Salud versus femoral access for coro- Carlos III (ISCIII), PI080272. Duration: nary angiography and intervention 01/01/2008-31/12/2011. in patients with acute coronary syndromes (RIVAL): a randomised, Roque M, Heras M, Novensà L, Rigol parallel group, multicentre M, Solanes N. Prevenció i tracta- trial. LANCET. 377:1409-1420. ment de la hiperplàsia de l’íntima I.F.: 33.63. mitjançant l’ús de bloquejants del

102 AReA 2

Respiratory, cardiovascular and renal pathobiology Team involved in: and bioengineering Arrhythmias, resynchronization and cardiac imaging gROUP MeMBeRS

teAM leADeR Josep Brugada (Hospital clínic) tel.: 93 227 55 51 e-mail: [email protected]

iDiBApS MeMBeRS: Silvia Montserrat Silvia Vidorreta lluis Mont (Hospital clínic) (Hospital clínic - fundació clínic) (fundació clínic - icARDeA) Marta Sitges (Hospital clínic) Juan fernández-Armenta Sara Hevia teresa M. de caralt (Hospital clínic) (fundació clínic - cvReMoD) (fundació clínic - ReDinScoR) Vidal, Bárbara (Hospital clínic) Ada Doltra José tomás ortiz (Hospital clínic) (fundació clínic - cvReMoD) ADMiniStRAtiVe StAff: Rosario Jesús perea (Hospital clínic) naiara calvo (Hospital clínic) neus portella (fundació clínic) pablo Ramos (Hospital clínic) Gemma pros (Hospital clínic) poStDoctoRAl fellowS: esther Guiu (fundació clínic) Gemma Gay-Jordi (fiS) felipe Bisbal Van Bylen StAtiSticiAn: Montserrat Batlle (fundació clínic) (Hospital clínic) Roger Borras (fundació clínic) Montserrat Rigol (fundació clínic) núria Solanes (fundació clínic) tecHniciAnS: collABoRAtoRS: cira Rubies (fundació cinic - Mª Àngels castel ReSeARcH fellowS: fiS inst. de Salut carles iii) (Hospital clínic) etel Silva (fundació clínic - nadia castillo (fundació clínic) José Mª tolosana cvReMoD) (Hospital clínic) paola Berne (cnic) nuRSinG StAff: elena Arbelo laínez eduard Guasch (Rio ortega- Mariona Matas (Hospital clínic) (Hospital clínic) iDiBApS-iSc iii) Silvia poyatos (fundació clínic) Susanna prat David Andreu (fundació clínic) Anna Barrabes (fundació clínic) (Hospital clínic) Antonio Berruezo (Hospital clínic)

ViSitinG ScientiStS: Reinder evertz (Beca eHRA, european Heart Rhythm Association) Malek khatib (Beca eHRA, european Heart Rhythm Association) franco Merschon (fellow Argentina) M emilce trucco (fellow Argentina) philippe taghji (fellow france)

103 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Arrhythmias, resynchronization and cardiac imaging

StrateGic main lineS of oBjectiveS reSearcH

The aims for the coming year are fun- 1. cardiovascular genetic diseases: damentally to go further in the six main • This year patients continue to be in- research lines of the group: genetic cluded in the multicenter study ‘Sudden cardiovascular diseases, atrial fibrillation, cardiac death: Translating basic science cardiac resynchronization, ventricular into clinical care’, in collaboration with tachycardias, and experimental models Dr. Ramon Brugada of the Cardiovas- of etiological factors in atrial fibrillation, cular Genetics Center UdG-IDIBGI, in and Sports Cardiology. Furthermore, we Girona. wish to continue promoting prospective 2. Experimental models for the study of multicenter projects allowing the obtain- etiological factors in atrial fibrillation: ment of transcendental clinical results, • We wish to continue analyzing the without abandoning practical clinical re- mechanisms conditioning the appear- search, with a view to improving patient ance of atrial and ventricular fibrosis in care. On the other hand, we will keep on the rat model of resistance exercise. working with the Bioengineering team • We are continuing collaboration with at the UPF in modeling and software de- the Pneumology Sleep Unit and the velopment for image processing. Department of Physical Medicine of

(A) Map of atrial fibrillation: Atrial fibrillation ablation procedure. We see the ablation scheme and integration of the 3D reconstruction of a CAT scan within the navigator. This system allows real time catheter localization within the heart of the patient.

(B) Map of ventricular tachycardia: Ventricular tachycardia ablation procedure. In this case we see an epicardial map of the left ventricle in a patient with structural heart disease (right). The 3D reconstruction derived from an MRI scan with gadolinium contrast injection allows noninvasive characterization of the tissue and planning of the intervention (left).

ReSeARCh gROUP cardiac imaGinG

team Leader: Marta Sitges (hospital clínic)

Our group has a pluridisciplinary team of people • Study of right ventricular morphology and function in elite dedicated to non-invasive cardiac imaging and its athletes at rest and exercising. Project funded by the Spanish application in the knowledge of and research into National Plan for R&D&i. cardiovascular pathophysiology and therapy with- • Detection of latent ventricular dysfunction in different disor- in the field of cardiac mechanics and cardiac arrhythmias, as well ders such as Chagas disease, cirrhosis of the liver and cardio- as other cardiovascular diseases. Our lines of research include: toxicity caused by chemotherapy in blood disorders. Projects • Application of cardiac imaging in the study of cardiac mechan- funded by the FIS. ics in patients with cardiac dyssynchrony treated with resyn- • Analysis of post-infarction remodelling using three-dimensional chronisation therapy. Application of an experimental porcine echocardiography and cardiac magnetic resonance imaging. model as part of the cvREMOD project funded by the Centro Project funded by the Spanish Cardiology Society para el Desarrollo Tecnológico e Industrial (CDTI) [Centre for • Utility of multi-slice CT in the diagnosis of chest pain in Acci- Technological and Industrial Development]. dent and Emergency. Project funded by FIS • Study of atrial morphology and function in patients with atrial • Non-invasive analysis of endothelial function through ultra- fibrillation and elite sportsmen and women. Project funded by sound of the humeral artery in myocardial infarction patients FIS and the Spanish National Plan for R&D&i. with pulmonary hypertension. Projects funded by the FIS.

104 AReA 2 ReSpiRAtoRy, cARDioVASculAR, RenAl pAtHoBioloGy AnD BioenGineeRinG ARRHytHMiAS, ReSyncHRoniZAtion AnD cARDiAc iMAGinG

PUBLICATIONS the Faculty of Medicine of Barcelona • SARA study (Spanish Atrial Fibril- University, with the purpose of studying lation vs Antiarrhythmic Drugs). original publications from 2009 to 2011 the repercussions of obstructive apnea Comparative multicenter study of Year IF Total Q 1 Q 2 upon the heart, using an experimental the efficacy of ablation versus drug 2009 66.31 17 13 1 model in rats. treatment. Once the recruitment 2010 93.71 27 13 4 • We keep working on the experimental was completed we started analys- 2011 120.18 27 11 8 murine model of cardiac adaptation to ing the results. chronic training that we developed to • Recruitment has been completed in study the pathophysiology of atrial fibril- two randomized, prospective stud- lation. Our research focuses specially in ies designed to compare different oRiGinAlS the adaptation of the right ventricle ablation techniques. i.f.: 120.18 3. Atrial fibrillation (AF): • We are about to start several mul- • On one hand we are continuing the ticentric studies about new ablation 1 Benito L, Hoyo J, Montroig A, study of etiological factors in primary techniques and new antiarrhythmic Fornes B, Fluxa G, Marti D, Pedros M, atrial fibrillation, specifically with the FU- drugs: EAST, FIRE AND ICE and Siso A, Mont L, Miro O, Coll-Vinent TURE study, which analyzes the role of RAFAELLO. B. Adverse effects of antiarrhythmic undetected hypertension and physical 4. Ventricular tachycardia (Vt): drugs in patients with atrial fibrillation exercise. • Multicenter study of antiarrhythmic in Primary Care. MED CLIN-BARCELO- drugs versus ablation in ischemic NA. 137:241-246. I.F.: 1.41. patients with automated implantable defibrillators. 2 Riesgo A, Sant E, Benito L, Hoyo J, ReSeARCh gROUP • A prospective study evaluating the Miro O, Mont L, Bragulat E, Coll-Vinent cardiac ejection fraction following ventricu- B. Sex Differences in the Treatment of reSyncHroniSation lar extrasystolia ablation in patients Patients With Atrial Fibrillation: Popula- with ventricular extrasystoles and tion-Based Study in a Local Health Dis- team Leader: Lluis Mont structural heart disease. trict. REV ESP CARDIOL. 64:233-236. (hospital clínic) • Different prospective studies are I.F.: 2.16. being conducted, evaluating the Our group is car- clinical usefulness of epicardial abla- 3 Roque M, Sitges M, Sala J, Delgado V, rying out research tion in different substrates. Morales M, Marrugat J, Vila J, Subirana I, into the application and results of • Software has been developed to Tassies D, Reverter JC, Castro M, Duran cardiac resynchronisation tech- delimit the slow conduction zones M. Effects of Raloxifene on Endothelial niques. Several studies are cur- within myocardial scars by means Function and Hemostasis in Women rently underway: of magnetic resonance studies and With Ischemic Heart Disease. REV ESP • Following recruitment in the their fusion with images obtained CARDIOL. 64:572-578. I.F.: 2.16. SPARE III study, which is from three-dimensional navigation analysing the results of AV-node ablation in patients with atrial sysems. 4 Garcia-Alvarez A, Sitges M, Heras fibrillation receiving resynchroni- • Siemens has has sponsored a pro- M, Poyatos S, Posada E, Pinazo MJ, sation. Subsidy: Fondo de Inves- spective study to evaluate remodel- Regueiro A, Gascon J, Sanz G. En- tigación Sanitaria (FIS) [Health ling and sudden death risk predictive dothelial Function and High-Sensitivity Research Fund], Instituto de capacity with MRI and biomarker C-reactive Protein Levels in Patients Saludo Carlos III (PS09/01500). levels in patients with structural With Chagas Disease Living in a Non- • TRICHAMPION multicentre heart disease. endemic Area. REV ESP CARDIOL. study on ablation and desynchro- 64:891-896. I.F.: 2.16. nisation in patients with hypertrophic cardiomyopathy. 5 Falces C, Andrea R, Heras M, Vehi • Studies on optimisation of C, Sorribes M, Sanchis L, Cevallos J, electrocardiographic resyn- Menacho I, Porcar S, Font D, Sabate chronisation: BEST. Subsidy: Fondo de Investigación Sanitaria M, Brugada J. Integration Between (FIS) [Health Research Fund], Cardiology and Primary Care: Impact on Instituto de Saludo Carlos III Clinical Practice. REV ESP CARDIOL. (PS10/01569). 64:564-571. I.F.: 2.16.

105 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Arrhythmias, resynchronization and cardiac imaging

6 Garcia-Alvarez A, Sitges M, Reguei- therapy in patients undergoing atrioven- 18 Tamborero D, Vidal B, Tolosana ro A, Poyatos S, Pinazo MJ, Posada E, tricular junction ablation for permanent JM, Sitges M, Berruezo A, Silva E, Bijnens B, Heras M, Gascon J, Sanz atrial fibrillation: a randomized trial. EUR Castel M, Matas M, Arbelo E, Rios G. Myocardial Deformation Analysis in HEART J. 32:2420-2429. I.F.: 10.05. J, Villacastin J, Brugada J, Mont L. Chagas Heart Disease With the Use Electrocardiographic versus Echocar- of Speckle Tracking Echocardiography. 13 Doltra A, Vidal B, Silva E, Mont diographic Optimization of the Inter- J CARD FAIL. 17:1028-1034. I.F.: 3.36. L, Tamborero D, Castel MA, Tolosana ventricular Pacing Delay in Patients JM, Berruezo A, Brugada J, Sitges M. Undergoing Cardiac Resynchroniza- 7 Freixa X, Heras M, Ortiz JT, Argiro Comparison of Hemodynamic versus tion Therapy. J CARDIOVASC ELEC- S, Guasch E, Doltra A, Jimenez M, Dyssynchrony Assessment for Interven- TR. 22:1129-1134. I.F.: 3.29. Betriu A, Masotti M. Usefulness of tricular Delay Optimization with Echocar- Endothelin-1 Assessment in Acute diography in Cardiac Resynchronization 19 Zeljko HM, Mont L, Sitges M, Myocardial Infarction. REV ESP CAR- Therapy. PACE. 34:984-990. I.F.: 1.35. Tolosana JM, Nadal M, Castella M, DIOL. 64:105-110. I.F.: 2.16. Brugada J. Entrapment of the circular 14 Nagarakanti R, Ezekowitz MD, Old- mapping catheter in the mitral valve 8 Duchateau N, DeCraene M, Piella gren J, Yang S, Chernick M, Aikens TH, in two patients undergoing atrial G, Silva E, Doltra A, Sitges M, Bijn- Flaker G, Brugada J, Kamensky G, Parekh fibrillation ablation. EUROPACE. ens BH, Frangi AF. A spatiotemporal A, Reilly PA, Yusuf S, Connolly SJ. Dabi- 13:132-133. I.F.: 1.84. statistical atlas of motion for the gatran Versus Warfarin in Patients With quantification of abnormal myocardial Atrial Fibrillation An Analysis of Patients 20 DellaBella P, Brugada J, Zep- tissue velocities. MED IMAGE ANAL. Undergoing Cardioversion. CIRCULA- penfeld K, Merino J, Neuzil P, Maury 15:316-328. I.F.: 4.36. TION. 123:131-136. I.F.: 14.43. P, Maccabelli G, Vergara P, Baratto F, Berruezo A, Wijnmaalen AP. Epicardi- 9 Berruezo A, DePotter T, Sitges M, 15 Lubinski A, Bissinger A, Boersma al Ablation for Ventricular Tachycardia Mansour F, Mont L, Brugada J. Bifo- L, Leenhardt A, Merkely B, Oto A, Pro- A European Multicenter Study. CIRC- cal Right Ventricular Resynchroniza- clemer A, Brugada J, Vardas PE, Wolpert ARRHYTHMIA ELEC. 4:653-659. tion for the Failing Right Ventricle. C. Determinants of geographic variations I.F.: 4.81. PACE. 34:E78-E81. I.F.: 1.35. in implantation of cardiac defibrillators in the European Society of Cardiology 21 Boriani G, Auricchio A, Klersy C, 10 Berruezo A, Vatasescu R, Mont member countries-data from the Euro- Kirchhof P, Brugada J, Morgan J, Var- L, Sitges M, Perez D, Papiashvilli G, pean Heart Rhythm Association White das P. Healthcare personnel resource Vidal B, Francino A, Fernandez-Ar- Book. EUROPACE. 13:654-662. I.F.: 1.84. burden related to in-clinic follow-up of menta J, Silva E, Bijnens B, Gonzalez- cardiovascular implantable electronic Juanatey JR, Brugada J. Biventricular 16 Moya A, Garcia-Civera R, Croci F, devices: a European Heart Rhythm pacing in hypertrophic obstructive Menozzi C, Brugada J, Ammirati F, Del- Association and Eucomed joint cardiomyopathy: A pilot study. HEART Rosso A, Bellver-Navarro A, Garcia-Sac- survey. EUROPACE. 13:1166-1173. RHYTHM. 8:221-227. I.F.: 4.25. ristan J, Bortnik M, Mont L, Ruiz-Granell I.F.: 1.84. R, Navarro X. Diagnosis, management, 11 Benito B, Gay-Jordi G, Serrano- and outcomes of patients with syncope 22 Andreu D, Berruezo A, Ortiz- Mollar A, Guasch E, Shi YF, Tardif JC, and bundle branch block. EUR HEART J. Perez JT, Silva E, Mont L, Borras R, Brugada J, Nattel S, Mont L. Cardiac 32:1535-1541. I.F.: 10.05. DeCaralt TM, Perea RJ, Fernandez- Arrhythmogenic Remodeling in a Rat Armenta J, Zeljko H, Brugada J. Inte- Model of Long-Term Intensive Exer- 17 Montserrat S, Sitges M, Calvo gration of 3D Electroanatomic Maps cise Training. CIRCULATION. 123:13- N, Silva E, Tamborero D, Vidal B, and Magnetic Resonance Scar Char- U61. I.F.: 14.43. Berruezo A, Bernado C, Mont L, Bru- acterization Into the Navigation Sys- gada J. Effect of Repeated Radiof- tem to Guide Ventricular Tachycardia 12 Brignole M, Botto G, Mont L, requency Catheter Ablation on Left Ablation. CIRC-ARRHYTHMIA ELEC. Iacopino S, DeMarchi G, Oddone Atrial Function for the Treatment of 4:674-683. I.F.: 4.81. D, Luzi M, Tolosana JM, Navazio A, Atrial Fibrillation. AM J CARDIOL. Menozzi C. Cardiac resynchronization 108:1741-1746. I.F.: 3.68.

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23 Bosch X, Esteve J, Sitges M, ReViewS clinicAl GuiDelineS DeCaralt TM, Domenech A, Ortiz JT, i.f.: 2.49 i.f.: 6.54 Monzo M, Morales-Ruiz M, Perea RJ, Rovira M. Prevention of Chemothera- 1 VanGelder IC, Haegeli LM, Brandes 1 Raviele A, Giada F, Bergfeldt L, py-Induced Left Ventricular Dysfunc- A, Heidbuchel H, Aliot E, Kautzner J, Blanc JJ, Blomstrom-Lundqvist C, tion With Enalapril and Carvedilol: Szumowski L, Mont L, Morgan J, Wil- Mont L, Morgan JM, Raatikainen MJP, Rationale and Design of the OVER- lems S, Themistoclakis S, Gulizia M, Steinbeck G, Viskin S. Management COME Trial. J CARD FAIL. 17:643-648. Elvan A, Smit MD, Kirchhof P. Rationale of patients with palpitations: a posi- I.F.: 3.36. and current perspective for early rhythm tion paper from the European Heart control therapy in atrial fibrillation. EU- Rhythm Association. EUROPACE. 24 Macedo PG, Brugada J, Leinveber ROPACE. 13:1517-1525. I.F.: 1.84. 13:920-934. I.F.: 1.84. P, Benito B, Molina I, Sert-Kuniyoshi F, Adachi T, Bukartyk J, VanDerWalt C, 2 Oliva A, Brugada R, D›aloja E, Boschi 2 Kirchhof P, Lip GYH, VanGelder IC, Konecny T, Maharaj S, Kara T, Mont- I, Partemi S, Brugada J, Pascali VL. Bax J, Hylek E, Kaab S, Schotten U, serrat J, Somers V. Sleep-Disordered State of the Art in Forensic Investiga- Wegscheider K, Boriani G, Ezekowitz Breathing in Patients With the Brugada tion of Sudden Cardiac Death. AM J M, Diener H, Heidbuchel H, Lane D, Syndrome. AM J CARDIOL. 107:709- FOREN MED PATH. 32:1-16. I.F.: 0.65. Mont L, Willems S, Dorian P, Vardas 713. I.F.: 3.68. P, Breithardt G, Camm AJ. Compre- hensive risk reduction in patients with 25 Sarkozy A, Sorgente A, Boussy eDitoRiAlS atrial fibrillation: Emerging diagnostic T, Casado R, Paparella G, Capulzini L, i.f.: 23.05 and therapeutic options Executive Chierchia GB, Yazaki Y, DeAsmundis summary* of the report from the 3rd C, Coomans D, Brugada J, Brugada P. 1 Arbelo E, Hindriks G, Maggioni A, AFNET/EHRA consensus conference. The value of a family history of sudden Morgan J, Tavazzi L, Vardas P, Brugada THROMB HAEMOSTASIS. 106:1012- death in patients with diagnostic type J. Atrial Fibrillation Ablation Pilot Study: 1019. I.F.: 4.70. I Brugada ECG pattern. EUR HEART J. a new feature of the EURObservational 32:2153-2160. I.F.: 10.05. Research Programme. EUR HEART J. 32:1173-1174. I.F.: 10.05. MulticentRicS 26 Rollin A, Maury P, Guilbeau-Frugier i.f.: 59.84 C, Brugada J. Transient ST Elevation 2 Brugada J, Brugada R, Brugada P. After Ketamine Intoxication: A New Electrophysiologic testing predicts events 1 Bogale N, Priori S, Gitt A, Alings Cause of Acquired Brugada ECG Pat- in Brugada syndrome patients. HEART M, Linde C, Dickstein K. The Europe- tern. J CARDIOVASC ELECTR. 22:91-94. RHYTHM. 8:1595-1597. I.F.: 4.25. an cardiac resynchronization therapy I.F.: 3.29. survey: patient selection and im- 3 Sitges M, Mont L. Identification of plantation practice vary according to 27 Calvo N, Mont L, Vidal B, Nadal M, optimal candidates for heart resynchro- centre volume. EUROPACE. 13:1445- Montserrat S, Andreu D, Tamborero D, nization therapy: an ongoing search. 1453. I.F.: 1.84. Pare C, Azqueta M, Berruezo A, Brugada MED CLIN-BARCELONA. 137:113-114. J, Sitges M. Usefulness of transoe- I.F.: 1.41. 2 Bogale N, Witte K, Priori S, Cle- sophageal echocardiography before cir- land J, Auricchio A, Gadler F, Gitt A, cumferential pulmonary vein ablation in 4 Brugada J, Brugada R, Brugada P. Limbourg T, Linde C, Dickstein K. The patients with atrial fibrillation: is it really Rebuttal to EP testing does not predict European Cardiac Resynchronization mandatory?. EUROPACE. 13:486-491. cardiac events in patients with Brugada Therapy Survey: comparison of out- I.F.: 1.84. syndrome. HEART RHYTHM. 8:1796- comes between de novo cardiac re- 1796. I.F.: 4.25. synchronization therapy implantations and upgrades. EUR J HEART FAIL. 5 Brugada J. Role of emergency medi- 13:974-983. I.F.: 4.51. cine physicians in identifying patients at risk of sudden death. EMERGENCIAS. 23:5-7. I.F.: 3.09.

107 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Arrhythmias, resynchronization and cardiac imaging

3 Yusuf S, Healey JS, Pogue J, Brugada J. iCARDEA: An Intelligent DoctoRAl tHeSeS Chrolavicius S, Flather M, Hart RG, Platform for Personalized Remote Hohnloser SH, Joyner CD, Pfef- Monitoring of the Cardiac Patients Sitges M. Estudio de la electrome- fer MA, Connolly SJ. Irbesartan with Electronic Implant Devices. Spon- cánica cardíaca mediante postpro- in Patients with Atrial Fibrillation. sored by: SRDC YAZILIM ARASTIRMA cesado de señal e imagen cardiaca: NEW ENGL J MED. 364:928-938. VE GELISTIRME VE DANISMANLIK Aplicación de un modelo clínico de I.F.: 53.49. TICARET, Ref.: 248240. Duration: terapia de resincronización cardíaca. 01/02/2010-31/01/2013. PhD student: Silvia García Etelvino.

GRAntS foR ReSeARcH Mont L. Estudio del remodelado mio- in pRoGReSS cárdico en un modelo animal crónico de síndrome de apnea-hipoapnea del Brugada J. REDINSCOR - Red sueño. Sponsored by: Instituto de Sa- de Investigación en Insuficiencia lud Carlos III, PI10/00834. Duration: Cardíaca en España. Sponsored 01/01/2011-31/12/2013. by: Instituto de Salud Carlos III (ISCIII), RD06/0003/0008. Duration: Brugada J. Sudden cardiac death: 01/01/2007-31/12/2012. definig clinical algorithms for a thorough investigation. Sponsored Mont L. Estudi de la terapia de by: CNIC, CNIC-03-2008. Duration: resincronització a Catalunya (TRC- 21/11/2008-20/11/2012. CAT). Sponsored by: AATRM (Agencia d’Avaluació de Tecnología Sitges M. Efecto del entrenamiento i Recerca Mèdiques, 154/4/2008. crónico sobre el ventrículo derecho: Duration: 01/01/2009-31/12/2012. Análisis por imagen. Sponsored by: Ministerio de Ciencia e Inno- Brugada J. Mecanismos y rever- vación, DEP2010/20565. Duration: sibilidad de la fibrosis miocárdica 01/01/2010-31/12/2013. asociada al ejercicio. Sponsored by: Ministerio de Ciencia e Inno- Berruezo A. Utilidad de la resonancia vación, DEP2009-12455. Duration: magnética con realce tardío como 01/01/2010-31/12/2012. guía para la ablación de taquicardias ventriculares. Sponsored by: Instituto Brugada J. Arítmies i Estimulació de Salud Carlos III (ISCIII), PI08/0243. Cardíaca. Sponsored by: Agèn- Duration: 01/01/2009-31/12/2011. cia de Gestió d’Sponsored bys Universitaris i de Recerca, 2009 Brugada J. cvREMOD: Convergencia de SGR 1104. Duration: 01/01/2009- tecnologías médicas para la gestión inte- 31/12/2013. gral del remodelado vascular. Sponsored by: Centro para el Desarrollo Tecnoló- Ortiz JT. Utilidad de la angiografía gico Industrial (CDTI), CENIT09 09/370. coronaria no invasiva mediante Duration: 09/09/2009-31/12/2012. tomografía computerizada multide- tector en el diagnóstico del síndro- Castel MA. Optimización de la tera- me coronario agudo en urgencias. pia de resincronización cardiaca me- Sponsored by: Instituto de Salud diante el QRS: valoración del efecto Carlos III, PI09/90513. Duration: agudo y la respuesta a medio plazo. 01/01/2010-31/12/2012. Sponsored by: Instituto de Salud Car- los III (ISCIII), PI10/01569. Duration: 01/01/2011-31/12/2013.

108 AReA 2

Team involved in: Respiratory, cardiovascular and renal pathobiology and bioengineering Nephro-urological diseases and kidney transplantation gROUP MeMBeRS StrateGic oBjectiveS

The multidisciplinary nature of our research group stems from well-balan- teAM leADeR ced collaboration between clinicians Josep Mª campistol (Hospital clínic) and medical researchers, biologists, tel.: 93 227 54 00 (ext.: 3395) biochemists, veterinarians and specia- fax: 93 227 93 46 list technicians with extensive expe- e-mail: [email protected] rience in all areas of the research into the natural history of renal disease iDiBApS MeMBeRS: Miquel Blasco (Hospital clínic) (clinical nephrology, dialysis and trans- pilar Arrizabalaga Maria n. Martina (Hospital clínic) plant). This creates the perfect setting (Hospital clínic) Sebastián Azorín (Hospital clínic) for translational research, with a two- Albert Botey (Hospital clínic) Sara Herrero (fundació clínic) way flow of communication between Aleix cases (Hospital clínic) Marta lazo (fundació clínic) bench and bedside. Guadalupe ercilla Since the setting up 5 years ago of (Hospital clínic) tecHniciAnS: the Laboratori Experimetal en Nefrolo- Georgina Hotter (iiBB-cSic) Maite del Hierro (iiBB-cSic) gia i Transplantament (LENIT) [Experi- Jaume Martorell (Hospital clínic) Daniel Moya-Rull (fundació clínic) mental Laboratory for Nephrology and eduard Mirapeix natalia Hierro (iDiBApS) Transplantation] the clinical research (Hospital clínic) and the different clinical trials have federico oppenheimer collABoRAtoRS: moved towards focusing on more (Hospital clínic) celia Bádenas (fundació clínic) fundamental aspects and concen- esteban poch (Hospital clínic) Anna Sola (iiBB-cSic) trating on a translational approach. José luis Viñas (iiBB-cSic) Our research focuses on the study poStDoctoRAl fellowS: eugenia Vinuesa (iiBB-cSic) of fibrosis mechanisms, regenerative elisenda Banón-Maneus nestor fontseré (Hospital clínic) techniques and the search for biomar- (fundació clínic) francesc Maduell (Hopsital clínic) kers through urinary proteomics in Jordi Rovira (fundació clínic) ignacio Revuelta (Hospital clínic / chronic kidney disease and interstitial María José Ramírez-Bajo iDiBApS) fibrosis and tubular atrophy in renal (iDiBApS) fritz Diekmann (Hospital clínic) transplant. We are also studying the luis f. Quintana (Hospital clínic) impact of the immunosuppressive ReSeARcH fellowS: federico cofán (Hospital clínic) medication used in renal transplant, Joan nistal (fundació clínic) nuria esforzado (Hospital clínic) both in terms of the nephrotoxicity Michaela Jung (iiBB-cSic) Vicenç torregrosa (Hospital clínic) induced by calcineurin inhibitors and Marina Ventayol (iiBB-cSic) Maria J. Ricart (Hospital clínic) the beneficial and harmful effects of chrysa Mastora (iiBB-cSic) Manel Vera (Hospital clínic) mTOR inhibitors on left ventricular Marta Arias (Hospital clínic) hypertrophy and proteinuria respectively. The strategic objectives of our research group are complemented by study of the importance of cardiovascular disease and cancer in renal and solid-organ transplant patients.

109 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg

Nephro-urological diseases and kidney transplantation

main lineS of 3. Influence of mtoR inhibition on • Role of the dendritic cells in the de- reSearcH renal function and humoral response velopment of skin cancer induced by in renal transplant patients and experi- the immunosuppressive treatment in the 1. cardiovascular and Renal Disease mental models of renal disease. renal transplant population. • Evaluation of cardiovascular risk and • the role of mtoR inhibition in the • Post-transplant kaposi’s sarcoma: Stu- accelerated atherosclerosis in renal development of proteinuria and his- dy of expression of different oncogenic patients. tological lesions in an experimental signalling pathways in tumour tissue and • Study of left ventricular hypertrophy model of renal failure (5/6 nephrec- a virological study evaluating the relation- in chronic kidney disease using an tomy). Study of the influence of mTOR ship with oncoviruses (HV8). experimental model of chronic kid- inhibition, introduced at different times, • Nanotechnology in post-transplant ney disease (5/6 nephrectomy). on renal function, proteinuria, histolo- cancers. Impact on tumour progression • Effect of the use of mTOR inhibitors gical lesions, VEGF expression and its and development of metastasis. on the prevention of atherosclerosis receptors. and left ventricular hypertrophy. • Analysis of the harmful side effects 5. Identification of new uremic toxins • Dyslipidaemia and cardiovascular risk associated with the use of mTOR inhi- • The main objective of this study is the in renal transplant. Apolipoprotein bitors: formation of oedema, anaemia, detection of new uremic toxins and the polymorphisms. lung involvement, testicular dystrophy, analysis of depurative abilities of diffe- • Endothelial dysfunction and effect diabetes. The group has various expe- rent dialytic technics. These solutes in of the uraemic environment on en- rimental models for determining the patients with end-stage chronic kidney dothelial cells. mechanisms that lead to each of these disease are responsible of uremic syn- • Vascular calcification according to pathophysiological situations. drome, only identified 90 of them. For diet and the different pharmacolo- • Study of the effect of mTOR inhibitors identify them, we are performing proteo- gical strategies for the control of in the humoral immune response in mic analysis through 2D DIGE and mass- calcium/phosphorus metabolism and renal transplant through study of the spectrometry. renal osteodystrophy. effect of a number of immunomodu- • Evaluation of different hemodialysis tech- • Anaemia of renal origin and erythro- lating drugs, alone or in combination nics in depurative ability of these solutes. poiesis-stimulating proteins in uraemia. with rapamycin, on the B-lymphocyte • Different prospectives studies evalu- and humoral rejection. In vitro and in ation the impact of high-flux or on-line 2. Fibrosis mechanisms and the search vivo experimental models of chronic hemodiafiltration in end-stage chronic for biomarkers in chronic kidney disease humoral rejection in rats and in an kidney disease patient survival, the (CKD) and interstitial fibrosis and tubular experimental model of systemic lupus effect of nocturan, every other day on-li- atrophy (IFTA) in renal transplant. erythematosus. ne hemodiafiltration, or the use of bioim- • Molecular mechanisms of fibro- pedance ant the measure of plasmatic genesis. 4. cancer and renal transplant volume in the prevention of hypotension • Etiopathogenic factors using a P- • clinical and molecular characterisa- and adjust the weight on dialysis. glycoprotein knockout mouse model tion of post-transplant cancers. Study and by culture of tubular epithelial of tumour behaviour according to the 6. other lines of research cells in an attempt to define the role immunosuppressive regimen used, as • Study of hereditary kidney diseases, esof P-glycoprotein in the development well as the direct oncogenic effect of pecially polycystic kidney disease, Alport of calcineurin inhibitor-induced ne- the immunosuppressive drugs, using syndrome and benign familial haematuria. phrotoxicity. the immunohistochemical characteri- • Amyloidosis associated with dialysis or • Diagnostic Approach: Through sation of the tumours in a renal trans- beta-2 microglobulin and other types of the analysis of the urinary proteo- plant population compared to a control hereditary and non-hereditary amyloidosis me using 2D-gel and fingerprinting population. Differences between the with renal involvement. techniques, we are attempting to two populations in the TGF-, VEGF and find early markers of renal fibrosis PI3K/AKT/mTOR pathways in adeno- Our researchers also work on research lines and IFTA, as well as in primary renal carcinoma of the colon and skin cancer shared with other Institut d’Investigacions diseases such as systemic lupus and the existence of KRAS mutations in Biomèdiques August Pi i Sunyer (IDIBAPS) erythematosus and membranous ne- the former and alteration in p53 expres- [August Pi i Sunyer Biomedical Research phropathy. Study of proteomics in the sion in the latter, according to treatment Institute] teams, primarily in the fields of dialysis patient under different renal with calcineurin or mTOR inhibitors. hypertension, endothelial dysfunction, dia- purification techniques. • ko mouse experimental model for betes, systemic autoimmune diseases with • therapeutic Strategies. p53. renal involvement and cancer.

110 AReA 2 ReSpiRAtoRy, cARDioVASculAR, RenAl pAtHoBioloGy AnD BioenGineeRinG nepHRo-uRoloGicAl DiSeASeS AnD kiDney tRAnSplAntAtion

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 80.92 23 18 1 oRiGinAlS tes R, DeLaCruz-Troca JJ, Natarajan i.f.: 63.97 A, Batlle D. Baseline characteristics of 2010 117.61 30 12 3 patients with chronic kidney disease 2011 63.97 20 7 6 1 Haro I, Gomara MJ, Perez ML, stage 3 and stage 4 in spain: the MER- Vinas O, Ercilla G, Gomez-Puerta JA, ENA observational cohort study. BMC Sanmarti R. Antibodies against beta- NEPHROL. 12:-. I.F.: 2.14. 12 Lloberas N, Torras J, Cruza- fibrin synthetic peptides: A study of do JM, Andreu F, Oppenheimer F, their association with the immunoge- 7 Grinyo JM, Saval N, Campistol JM. Sanchez-Plumed J, Gentil MA, Brunet netic background and disease course Clinical assessment and determinants M, Ekberg H, Grinyo JM. Influence of of rheumatoid arthritis patients. EUR J of chronic allograft nephropathy in MRP2 on MPA pharmacokinetics in re- MED CHEM. 46:1095-1102. I.F.: 3.19. maintenance renal transplant patients. nal transplant recipients-results of the NEPHROL DIAL TRANSPL. 26:3750- Pharmacogenomic Substudy within 2 Ruiz-Esquide V, Gomez-Puerta JA, 3755. I.F.: 3.56. the Symphony Study. NEPHROL DIAL Canete JD, Graell E, Vazquez I, Ercilla TRANSPL. 26:3784-3793. I.F.: 3.56. MG, Vinas O, Gomez-Centeno A, Haro 8 Novoa PA, Grinyo JM, Ramos FJP, I, Sanmarti R. Effects of Smoking on Errasti P, Franco A, Aldana G, Pefaur J, 13 Tavira B, Coto E, Diaz-Corte C, Disease Activity and Radiographic Marti-Cuadros AM, Otero AB, Saval N, Ortega F, Arias M, Torres A, Diaz JM, Progression in Early Rheumatoid Ar- Oppenheimer F. De Novo Use of Evero- Selgas R, Lopez-Larrea C, Campistol thritis. J RHEUMATOL. 38:2536-2539. limus With Elimination or Minimization JM, Ruiz-Ortega M, Alvarez V. KCNQ1 I.F.: 3.55. of Cyclosporine in Renal Transplant gene variants and risk of new-onset Recipients. TRANSPL P. 43:3331-3339. diabetes in tacrolimus-treated renal- 3 Silvarino R, Sant F, Espinosa G, I.F.: 0.99. transplanted patients. CLIN TRANS- Pons-Estel G, Sole M, Cervera R, Arri- PLANT. 25:E284-E291. I.F.: 1.75. zabalaga P. Nephropathy associated 9 Coto-Llerena M, Perez-Del-Pulgar with antiphospholipid antibodies in pa- S, Crespo G, Carrion JA, Martinez SM, 14 Alberu J, Pascoe MD, Campistol tients with systemic lupus erythema- Sanchez-Tapias JM, Martorell J, Navasa JM, Schena FP, Rial MD, Polinsky M, Ne- tosus. LUPUS. 20:721-729. I.F.: 2.60. M, Forns X. Donor and Recipient IL28B ylan JF, Korth-Bradley J, Goldberg-Alberts Polymorphisms in HCV-Infected Patients R, Maller ES. Lower Malignancy Rates 4 Martina MN, Cofan F, Suarez A, Undergoing Antiviral Therapy before in Renal Allograft Recipients Converted Masso E, Trullas JC, Cervera C, More- and after Liver Transplantation. AM J to Sirolimus-Based, Calcineurin Inhibitor- no A, Oppenheimer F, Miiro JM, Cam- TRANSPLANT. 11:1051-1057. I.F.: 6.05. Free Immunotherapy: 24-Month Results pistol JM. Kidney Transplantation and From the CONVERT Trial. TRANSPLAN- Waiting List for Renal Transplantation 10 Seron D, Moreso F, Arias M, TATION. 92:303-310. I.F.: 3.68. for Human Immunodeficiency Virus Campistol JM, Curto J, Hernandez D, Patients. TRANSPL P. 43:2179-2181. Morales JM, Sanchez-Fructuoso A, 15 Martina MN, Sole M, Masso E, I.F.: 0.99. Abraira V. Estimation of renal allograft Perez N, Campistol JM, Quintana LF. half-life: fact or fiction? (vol 26, pg 3013, Mixed cryoglobulinaemia not related 5 Martina MN, Cervera C, Esforzado 2011). NEPHROL DIAL TRANSPL. 26:-. to hepatitis C virus, mesangiocapillary N, Linares L, Torregrosa V, Sancle- I.F.: 3.56. glomerulonephritis and lymphoplas- mente G, Hoyo I, Cofan F, Oppen- mocytic lymphoma. NEFROLOGIA. heimer F, Miro JM, Campistol JM, 11 Alcaraz A, Musquera M, Peri L, 31:743-746. I.F.: 0.74. Moreno A. Toxoplasma gondii primary Izquierdo L, Garcia-Cruz E, Huguet infection in renal transplant recipients. J, Alvarez-Vijande R, Campistol JM, 16 Tavira B, Garcia EC, Diaz-Corte C, Two case reports and literature Oppenheimer F, Ribal MJ. Feasibility Ortega F, Arias M, Torres A, Diaz JM, review. TRANSPL INT. 24:e6-e12. of Transvaginal Natural Orifice Trans- Selgas R, Lopez-Larrea C, Campistol JM, I.F.: 3.21. luminal Endoscopic Surgery-Assisted Alvarezca V. Pharmacogenetics of tacro- Living Donor Nephrectomy: Is Kidney limus after renal transplantation: analysis 6 Martinez-Castelao A, Gorriz JL, Vaginal Delivery the Approach of the of polymorphisms in genes encoding 16 Portoles JM, DeAlvaro F, Cases A, Future?. EUR UROL. 59:1019-1025. drug metabolizing enzymes. CLIN CHEM Luno J, Navarro-Gonzalez JF, Mon- I.F.: 8.84. LAB MED. 49:825-833. I.F.: 2.07.

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Nephro-urological diseases and kidney transplantation

17 Fontsere N, Blasco M, Maduell 2 Epailly E, Albanell J, Andreassen A, de órganos sólidos al tratamiento in- F, Vera M, Arias-Guillen M, Herranz Bara C, Campistol JM, Delgado JF, Ei- munosupresor. Sponsored by: Instituto S, Blanco T, Barrufet M, Burrel M, sen H, Fiane AE, Mohacsi P, Schubert de Salud Carlos III (ISCIII), PI080300. Montana J, Real MI, Mestres G, S, Sebbag L, Turazza FM, Valantine H, Duration: 01/01/2008-31/12/2011. Riambau V, Campistol JM. Practical Zuckermann A, Potena L. Proliferation Utility of On-Line Clearance and Blood signal inhibitors and post-transplant Poch E. Análisis de biomarcadores Temperature Monitors as Noninvasive malignancies in heart transplantation: predictores de insuficiencia renal aguda Techniques to Measure Hemodialysis practical clinical management ques- post cirugía cardíaca. Sponsored by: Blood Access Flow. BLOOD PURIFI- tions. CLIN TRANSPLANT. 25:E475- Instituto de Salud Carlos III, PI08/0140. CAT. 31:1-8. I.F.: 1.52. E486. I.F.: 1.75. Duration: 01/01/2009-30/12/2011.

18 Vodenik B, Rovira J, Diek- 3 Dominguez-Gil B, Andres A, Campis- Campistol JM. Análisis de biomarca- mann F, Revuelta I, Oppenheimer F, tol JM, Morales JM. Should we be using dores urinarios en la disfunción cró- Campistol JM. Preemptive Use of kidneys from hepatitis C virus-infected nica del injerto: estudio de validación Mammalian Target of Rapamycin Inhi- donors?. CURR OPIN NEPHROL HY. e implicación de la vía WNT/BETA- bitors in Living Donor Transplantation. 20:599-604. I.F.: 4.46. CATENINA. Sponsored by: Instituto TRANSPL P. 43:2568-2573. I.F.: 0.99. de Salud Carlos III (ISCIII), PI09/0281. Duration: 01/01/2010-31/12/2012. 19 Sola A, Weigert A, Jung M, Vin- MulticentRicS uesa E, Brecht K, Weis N, Brune B, i.f.: 3.68 Campistol JM. Proteomic analysis of Borregaard N, Hotter G. Sphingosine- transthyretin post-translational modifica- 1-phosphate signalling induces the 1 Holdaas H, Rostaing L, Seron D, tions as a disease activity marker in TTR- production of Lcn-2 by macrophages Cole E, Chapman J, Fellstrom B, Strom hereditary amyloidosis: a case-control to promote kidney regeneration. J EH, Jardine A, Midtvedt K, Machein U, study. Sponsored by: Fundació la Marató PATHOL. 225:597-608. I.F.: 7.27. Ulbricht B, Karpov A, O’connell PJ. Con- de TV3, TV3_EMinoritarias_10 101430. version of Long-Term Kidney Transplant Duration: 03/02/2011-02/02/2014. 20 Vanrenterghem Y, Bresnahan Recipients From Calcineurin Inhibitor B, Campistol J, Durrbach A, Grinyó Therapy to Everolimus: A Randomized, Campistol JM. LENIT (Laboratori J, Neumayer HH, Lang P, Larsen Multicenter, 24-Month Study. TRANS- Experimental de Nefrologia i Trans- CP, Mancilla-Urrea E, Pestana JM, PLANTATION. 92:410-418. I.F.: 3.68. plantament). Sponsored by: AGAUR_ Block A, Duan T, Glicklich A, Gujrathi SGR09, 2009_SGR_1125. Duration: S, Vincenti F. Belatacept-based regi- 20/07/2009-31/12/2013. mens are associated with improved GRAntS foR ReSeARcH cardiovascular and metabolic risk in pRoGReSS Campistol JM. Remodelación tisular factors compared with cyclosporine en el rechazo crónico. Sponsored in kidney transplant recipients (BEN- Poch E. REDINREN - Red de Investiga- by: Fundación Mutua Madrileña, EFIT and BENEFIT-EXT studies). ción en Enfermedades Renales. Spon- AP92582011. Duration: 26/11/2011- TRANSPLANTATION. 91(9):976-83. sored by: nstituto de Salud Carlos III 25/11/2014. I.F.: 3.68. (ISCIII), FIS_RETIC06 RD06/0016/0015. Duration: 01/01/2007-30/04/2011. Hotter G. Bioregeneració i micromo- nitorització hipóxica. Sponsored by: ReViewS Campistol JM. Red de Investigación en AGAUR_SGR09, 2009_SGR_1074. i.f.: 12.32 Enfermedades Renales (REDINREN). Duration: 29/07/2009-31/12/2013. Sponsored by: Instituto de Salud Carlos 1 Trullas JC, Cofan F, Tuset M, Ricart III (ISCIII), FIS_RETIC07 RD06/0016/1002. MJ, Brunet M, Cervera C, Manzardo Duration: 29/02/2008-31/12/2012. DoctoRAl tHeSeS C, Lopez-Dieguez M, Oppenheimer F, Moreno A, Campistol JM, Miro JM. Brunet M. Estudio multicéntrico para Campistol JM. Caracterización mole- Renal transplantation in HIV-infected la validación de los biomarcadores de cular de las neoplasias en trasplante patients: 2010 update. KIDNEY INT. elección que reflejen la respuesta indi- de órgano sólido. PhD student: Ignacio 79:825-842. I.F.: 6.11. vidual de los pacientes trasplantados Revuelta Vicente.

112 AReA 2

Team involved in: Respiratory, cardiovascular and renal pathobiology and bioengineering Hypertension, lipids and cardiovascular risk gROUP MeMBeRS

teAM leADeR emili Ros (Hospital clínic) tel.: 93 227 93 83 fax: 93 453 78 29 e-mail: [email protected]

iDiBApS MeMBeRS: nuRSinG StAff: Ramón estruch (Hospital clínic) Antonio coca (Hospital clínic) Anna lópez (iSciii) Rosa Gilabert (Hospital clínic) Daniel Zambón (Hospital clínic) isabel núñez (Hospital clínic) cristina Sierra (Hospital clínic) DietiStS: Miquel camafort (Hospital clínic) Ana Mª pérez-Heras (fundació clínic) poStDoctoRAl fellowS: Mercè Serra (iSciii) ViSitinG ScientiStS: Montserrat cofán (iSciii) nagila R. teixeira Damasceno Aleix Sala-Vila (iSciii) StAtiSticiAn: (university of Sao paulo) emili corbella (iDiBell) ReSeARcH fellowS: Mònica Doménech collABoRAtoRS: (iSciii/fundació clínic) núria Bargalló (Hospital clínic) cinta Valls (iSciii) Maria teresa de caralt (Hospital clínic)

113 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg

Hypertension, lipids and cardiovascular risk

StrateGic main lineS of 7. Cholesterol absorption and synthesis oBjectiveS reSearcH evaluated by the determination of plasma non-cholesterol sterol levels The general aim of our group is to gain 1. External arterial ultrasound of femoral using gas chromatography: measure- in-depth knowledge of the epidemiology, and carotid arteries, coronary cal- ment, genetic conditioning factors, pathogenesis, diagnosis, treatment and cium by CT and carotid plaque MRI. influence on cardiovascular risk and prevention of arterial hypertension, dyslipi- Relationship between preclinical relationship with lipid response to demia and associated cardiovascular risk. atherosclerosis and conventional phytosterols, ezetimibe and statins. The research lines we wish to continue and emergent risk factors and bio- 8. Influence of polyunsaturated consolidating are the following: markers of the usual diet, including long-chain fatty acids (plant and 1. Mechanisms and consequences unsaturated fatty acids and in plasma marine omega-3) on preclinical ath- of silent lesions in target organs of phospholipids, circulating vitamins erosclerosis of the carotid arteries, hypertension. and phytosterols. Influence of diet on evaluated by high-resolution ultra- 2. Interaction of environmental deter- carotid atheroma plaque vulnerability sound and MRI. xxxxxx minants in cardiovascular disease, evaluated by sequential MRI. Correla- 9. Associations of the fatty acids profile such as salt intake and the salt sen- tion of plaque composition by MRI in whole plasma, whole blood and sitivity phenomenon. with histology. circulating phospholipid fraction with 3. Candidate genes of hypertension 2. Circadian patterns, arterial pressure SCD1 activity; neurodegenerative, and its complications. variability and target organ damage. autoinflammatory and infectious 4. Characterization of genetic dyslipi- Sensitivity to salt in arterial hyperten- diseases; cardiometabolic risk fac- demias. sion. Inflammation in hypertension. tors and non-alcoholic liver steatosis; 5. Detection of preclinical atheroscle- Hypertension and atrial fibrillation dietary determinants of the omega-3 rosis. as manifestation of hypertension- index in whole blood; fatty acids 6. Study of the intestinal absorption induced cardiac damage. composition of the “lipid rafts”; and and synthesis of cholesterol. 3. Candidate genes for cerebrovascular effect upon intracellular signaling. 7. Phytosterolemia as a cardiovascular stroke risk in hypertensive patients. 10. Effect of diet supplementation with risk factor. Candidate genes for the develop- nuts for 2 years on cognitive func- 8. Determination of the fatty acids ment of left ventricular hypertrophy tion, the integrity of the retina, the profile in phospholipids and blood and heart failure in hypertensive length of telomeres and different cell membranes, and their as- patients. markers of inflammation, oxidation sociations with diet, metabolic 4. Functionality of dietary patterns and and cardiovascular risk in old people. syndrome, cardiovascular risk phe- whole foods: influence upon arterial notypes and preclinical arterioscle- pressure evaluated by ambulatory rosis. and home monitoring, insulin resist- 9. Study of the cardiovascular function- ance, biological markers of choles- ality of foods, including the effects terol absorption and synthesis and of foods rich in omega-3 fatty acids vascular risk, dietary biomarkers upon carotid atheroma plaque char- (unsaturated fatty acids in whole acteristics. blood, carotenes and vitamin E in 10. Effects of the Mediterraenan diet on plasma, polyphenols in urine) and carotid atheroma plaque vulnerability physicochemical properties of the evaluated by MRI. low-density lipoproteins (LDLs) and 11. Identification of genetic variants as- high-density lipoproteins (HDLs). sociated with different responses to 5. Mild age-associated cognitive foods and nutrients (nutrigenetics). impairment in participants in the 12. Influence of the components of PREDIMED study after two years the Mediterranean on degenerative of intervention with Mediterranean diseases and cognitive impairment diets or a low-fat diet. in older people. 6. Effect of hypercholesterolemia of 13. Effects of Mediterranean diet on different origin and severity on cogni- blood pressure assessed by am- tive function as assessed by neu- bulatory and home blood pressure ropsychological tests and functional monitoring. brain MRI.

114 AReA 2 ReSpiRAtoRy, cARDioVASculAR, RenAl pAtHoBioloGy AnD BioenGineeRinG nepHRo-uRoloGicAl DiSeASeS AnD kiDney tRAnSplAntAtion

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 70.61 22 9 11 oRiGinAlS and general obesity and abdominal i.f.: 78.21 obesity in an elderly population at high 2010 97.91 21 14 5 cardiovascular risk. PREV MED. 53:155- 2011 78.21 22 9 10 1 Anguita M, Beiras AC, Cobo E, 161. I.F.: 3.30. Coca A, DeTeresa E, Diez J, Lopez B, Cebollada J, Diaz B, Galve E, 5 Cofan M, Escurriol V, Garcia-Otin AL, Gonzalez-Juanatey JR, Jimenez- Moreno-Iribas C, Larranaga N, Sanchez Navarro M, Lopez I, Lupon J, MJ, Tormo MJ, Redondo ML, Gonzalez 10 Sala-Vila A, Harris WS, Cofan M, Martin C, Monserrat L, Narejos CA, Corella D, Pocovi M, Civeira F, Ros Perez-Heras AM, Pinto X, Lamuela- S, Figal DAP, Perez-Calvo JI, Que- E. Association of plasma markers of Raventos RM, Covas MI, Estruch R, rejeta R, Ridocci F, Rodriguez cholesterol homeostasis with metabolic Ros E. Determinants of the omega-3 A, Rodriguez M, Roig E, Roure syndrome components. A cross-sectio- index in a Mediterranean population at J, Ruiz S, Sanchez PL, Terns M, nal study. NUTR METAB CARDIOVAS. increased risk for CHD. BRIT J NUTR. Toran P, Munoz-Tuduri M. Effects 21:651-657. I.F.: 3.44. 106:425-431. I.F.: 3.07. of Prolonged-Release Torasemide Versus Furosemide on Myocardial 6 Sala-Vila A, Cofan M, Nunez I, Gi- 11 Sola R, Fito M, Estruch R, Salas- Fibrosis in Hypertensive Patients labert R, Junyent M, Ros E. Carotid Salvado J, Corella D, DeLaTorre R, with Chronic Heart Failure: A Ran- and femoral plaque burden is inversely Munoz MA, Lopez-Sabater MD, domized, Blinded End Point, Acti- associated with the alpha-linolenic acid Martinez-Gonzalez MA, Aros F, Ruiz- ve-Controlled Study. CLIN THER. proportion of serum phospholipids in Gutierrez V, Fiol M, Casals E, Warnberg 33:1204-1213. I.F.: 2.55. Spanish subjects with primary dyslipide- J, Buil-Cosiales P, Ros E, Konstantinidou mia. ATHEROSCLEROSIS. 214:209-214. V, Lapetra J, Serra-Majem L, Covas MI. 2 Cenarro A, Garcia-Otin AL, Tejedor I.F.: 4.09. Effect of a traditional Mediterranean diet MT, Solanas M, Jarauta E, Junquera on apolipoproteins B, A-I, and their ratio: C, Ros E, Mozas P, Puzo J, Pocovi M, 7 Murie-Fernandez M, Irimia P, Toledo A randomized, controlled trial. ATHE- Civeira F. A presumptive new locus E, Martinez-Vila E, Buil-Cosiales P, Serra- ROSCLEROSIS. 218:174-180. I.F.: 4.09. for autosomal dominant hypercholes- no-Martinez M, Ruiz-Gutierrez V, Ros E, terolemia mapping to 8q24.22. CLIN Estruch R, Martinez-Gonzalez MA. Caro- 12 Casas-Agustench P, Lopez-Uriarte GENET. 79:475-481. I.F.: 2.94. tid intima-media thickness changes with P, Bullo M, Ros E, Cabre-Vila JJ, Salas- Mediterranean diet: A randomized trial Salvado J. Effects of one serving of 3 Schroder H, Fito M, Estruch R, (PREDIMED-Navarra). ATHEROSCLERO- mixed nuts on serum lipids, insulin Martinez-Gonzalez MA, Corella D, SIS. 219:158-162. I.F.: 4.09. resistance and inflammatory markers in Salas-Salvado J, Lamuela-Raventos R, patients with the metabolic syndrome. Ros E, Salaverria I, Fiol M, Lapetra J, 8 Barrios V, Calderon A, Coca A, Gon- NUTR METAB CARDIOVAS. 21:126-135. Vinyoles E, Gomez-Gracia E, Lahoz C, zalez-Juanatey JR, Sarria A, Rodriguez- I.F.: 3.44. Serra-Majem L, Pinto X, Ruiz-Gutierrez Padial L. Computerized interpretation of V, Covas MI. A Short Screener Is Valid the electrocardiogram in the diagnosis 13 Sala-Vila A, Cofan M, Mateo- for Assessing Mediterranean Diet of left ventricular hypertrophy. The Gallego R, Cenarro A, Civeira F, Ortega Adherence among Older Spanish Men ELECTROPRES project. REV CLIN ESP. E, Ros E. Inverse association between and Women. J NUTR. 141:1140-1145. 211:391-399. I.F.: 0.76. serum phospholipid oleic acid and insu- I.F.: 4.30. lin resistance in subjects with primary 9 Casas-Agustench P, Bullo M, Ros dyslipidaemia. CLIN NUTR. 30:590-592. 4 Bullo M, Garcia-Aloy M, Martinez- E, Basora J, Salas-Salvado J. Cross- I.F.: 3.41. Gonzalez MA, Corella D, Fernandez- sectional association of nut intake with Ballart JD, Fiol M, Gomez-Gracia E, adiposity in a Mediterranean population. 14 Bosch X, Foix A, Jordan A, Coca A, Estruch R, Ortega-Calvo M, Francisco NUTR METAB CARDIOVAS. 21:518-525. Lopez-Soto A. Outpatient Quick Diagno- S, Flores-Mateo G, Serra-Majem L, I.F.: 3.44. sis Units for the evaluation of suspected Pinto X, Covas MI, Ros E, Lamuela- severe diseases: an observational, Raventos R, Salas-Salvado J. Asso- descriptive study. CLINICS. 66:737-741. ciation between a healthy lifestyle I.F.: 1.42.

115 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Hypertension, lipids and cardiovascular risk

15 Sobrino J, Domenech M, Cama- case-control study in the Spanish EPIC GRAntS foR ReSeARcH fort M, Vinyoles E, Coca A. Prevalence cohor. J NUTR BIOCHEM. 22:487-494. in pRoGReSS of masked hypertension in a cohort I.F.: 4.54. of controlled hypertensive patients Coca A. NoE - Integrated Genom- in Spain. MED CLIN-BARCELONA. 20 Redon J, Olsen MH, Cooper ics, Clinical Research and Care 136:607-612. I.F.: 1.41. RS, Zurriaga O, Martinez-Beneito in Hypertension. Sponsored by: MA, Laurent S, Cifkova R, Coca European Commission, Istituto 16 Ascaso JF, Millan J, Mateo-Ga- A, Mancia G. Stroke mortality and Auxolico Italiano, CE_FPVI06 llego R, Ruiz A, Suarez-Tembra M, trends from 1990 to 2006 in 39 coun- LHSM-CT-2006-037093. Duration: Borrallo RM, Zambon D, Gonzalez- tries from Europe and Central Asia: 01/11/2006-31/01/2011. Santos P, Peres-De-Juan M, Ros E. implications for control of high blood Prevalence of metabolic syndrome pressure. EUR HEART J. 32:1424- Ros E. Contribución de la variabili- and cardiovascular disease in a 1431. I.F.: 10.05. dad en el promotor del gen del re- hypertriglyceridemic population. ceptor LDL a la hipercolesterolemia EUR J INTERN MED. 22:177-181. 21 Medina-Remon A, Zamora- poligénica. Subproyecto 5: Análisis I.F.: 1.66. Ros R, Rotches-Ribalta M, Andres- de biomarcadores de absorción y Lacueva C, Martinez-Gonzalez MA, síntesis de colesterol. Sponsored 17 DeCastro-Oros I, Pampin S, Covas MI, Corella D, Salas-Salvado by: Instituto de Salud Carlos III Cofan M, Mozas P, Pinto X, Salas- J, Gomez-Gracia E, Ruiz-Gutierrez V, (ISCIII), PI09/1292. Duration: Salvado J, Rodriguez-Rey JC, Ros E, DeLaCorte FJG, Fiol M, Pena MA, 01/01/2010-31/12/2012. Civeira F, Pocovi M. Promoter variant Saez GT, Ros E, Serra-Majem L, Pinto -204A > C of the cholesterol 7 alpha- X, Warnberg J, Estruch R, Lamuela- Ros E. Subproject: Effects of a hydroxylase gene: Association with Raventos RM. Total polyphenol 2-year Mediterranean diet interven- response to plant sterols in humans excretion and blood pressure in tion on 3T MRI-monitored carotid and increased transcriptional activ- subjects at high cardiovascular risk. plaque progression and vulnerability in transfected HepG2 cells. CLIN NUTR METAB CARDIOVAS. 21:323- ity. A randomized study. Sponsored NUTR. 30:239-246. I.F.: 3.41. 331. I.F.: 3.44. by: Centro Nacional de Investigacio- nes Cardiovasculares (CNIC), MSC_ 18 Salas-Salvado J, Bullo M, Babio 22 Sierra C, Coca A, Schiffrin EL. CNIC07-S02. Duration: 01/01/2008- N, Martinez-Gonzalez MA, Ibarrola- Vascular Mechanisms in the Pathoge- 31/12/2011. Jurado N, Basora J, Estruch R, Covas nesis of Stroke. CURR HYPERTENS MI, Corella D, Aros F, Ruiz-Gutierrez REP. 13:200-207. I.F.: 2.24. V, Ros E. Reduction in the Incidence DoctoRAl tHeSeS of Type 2 Diabetes With the Medi- terranean Diet Results of the PRE- eDitoRiAlS Coca A. Hipertrofia ventricular DIMED-Reus nutrition intervention i.f.: 2.82 izquierda y prediccion del riesgo randomized trial. DIABETES CARE. cardiovascular del hipertenso en 34:14-19. I.F.: 7.14. 1 Camafort M, Coca A. Resistant nuestro medio. PhD student: Fran- hypertension: beyond a bad control of cisco Javier Tovillas Morán. 19 Corella D, Portoles O, Arriola L, blood pressure. MED CLIN-BARCELO- Chirlaque MD, Barricarte A, Frances NA. 137:444-445. I.F.: 1.41. Coca A. Efectivitat de dues in- F, Huerta JM, Larranaga N, Martinez tervencions en la prescripció C, Martinez-Camblor P, Molina E, 2 Hernandez-Hernandez R, Coca A. d’antibiòtics en infeccions del trac- Navarro C, Quiros JR, Rodriguez L, The paradox of obesity in heart failure: te respiratori en Atenció Primària Sanchez MJ, Ros E, Sala N, Gonzalez Is more weight better?. MED CLIN- a Espanya. PhD student: Josep M CA, Moreno-Iribasd C. Saturated fat BARCELONA. 137:689-690. I.F.: 1.41. Cots Yago. intake and alcohol consumption modulate the association between the APOE polymorphism and risk of future coronary heart disease: a nested

116 AReA 2

Team involved in: Respiratory, cardiovascular and renal pathobiology and bioengineering & Respiratory biophysics and bioengineering gROUP MeMBeRS

teAM leADeR Ramon farré (universitat de Barcelona) tel.: 93 402 45 15 fax: 93 403 52 78 e-mail: [email protected]

iDiBApS MeMBeRS: foteini popota (iDiBApS) Javier pavía (Hospital clínic) Aida niñerola (ciBeR-BBn) Domènec Ros (uB) tecHniciAnS: poStDoctoRAl fellowS: Miguel Rodríguez (uB) theodora tsapikouni (ciBeReS) Rocío nieto (ciBeReS) elena Garreta (Marie curie - iDiBApS) collABoRAtoRS: laura chimenti (Marie curie - carles falcón (iDiBApS) european Respiratory Society) Raúl tudela (ciBeR-BBn) Albert cot (uB-ciBeR-BBn) ReSeARcH fellowS: Jordi Alcaraz (uB) Berta Martí (iBec) Xavier trepat (uB-iBec) esther Melo (Mec) Daniel navajas (uB-iBec) Valentina isetta (ue)

117 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Respiratory biophysics and bioengineering

StrateGic oBjectiveS

The general objectives of the group are the study of the biophysical mechanisms determining respiratory function, and the development of models and methods for the processing of biomedical images and signals. The work of the group is based on an interdisciplinary approach, with integration between basic and clinical research. In parallel to the scientific objectives, our group promotes transfer to the industrial setting of the technological advances derived from the research work.

main lineS of reSearcH

1. Respiratory mechanics. The aim of research in respiratory mechanics is to investigate the vis- coelastic properties of the airways and lung tissues. At present, the work fundamentally focuses on the study of upper airway collapsibility in obstructive apnea-hypopnea during sleep and in the monitoring of noninvasive mechanical ventilation during respiratory failure. The clinical aim of this research is to obtain improved

noninvasive diagnostic techniques, De-cellularized rat lung. and to optimize the treatment methods based on ventilation assist measures. process, and of the way in which of photon emission tomography 2. Molecular and cellular mechanical stimuli can enhance (SPECT) and positron emission nanomechanics. differentiation towards the alveolar tomography (PET) images, with the The introduction of nanotechnolo- epithelial phenotype. One of our pro- purpose of securing more precise gies allowing the manipulation of jects in this setting focuses on organ quantification of gammagraphic materials on the nanometric and pico- regeneration. Specifically, work is (scintigraphic) studies. With this Newton scale has opened up new done on the bioartificial production of objective in mind, iterative algo- perspectives for the investigation of functional rat lungs by means of the rithms are being developed for the individual biomolecules and cells. Our re-cellularization of the extracellular three-dimensional reconstruction group uses atomic force microscopy, matrix of the organ with stem cells, of images and for the fusion of magnetic microspheres and traction and recreation of the mechanical pul- SPECT and magnetic resonance force microscopy to study cell adhe- monary micro-nano environment, to imaging (MRI) images. sion and the mechanical properties optimize cell differentiation. of lung cells and leukocytes. Studies are also made of the mechanical 3. Biomedical imaging analysis. For further information: properties of embryonic and adult Research in imaging analysis cur- www.ub.edu/biofisica stem cells during the differentiation rently focuses on the processing

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PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 26.03 9 6 3 oRiGinAlS 7 Iranzo A, Valldeoriola F, Lomena F, i.f.: 56.27 Molinuevo JL, Serradell M, Salamero 2010 48.63 11 7 3 M, Cot A, Ros D, Pavia J, Santamaria 2011 56.27 11 8 2 1 Mane A, Gallego J, Lomena F, Ma- J, Tolosa E. Serial dopamine transpor- teos JJ, Fernandez-Egea E, Horga G, ter imaging of nigrostriatal function Cot A, Pavia J, Bernardo M, Parellada in patients with idiopathic rapid-eye- E. A 4-year dopamine transporter movement sleep behaviour disorder: a (DAT) imaging study in neuroleptic- prospective study. LANCET NEUROL. Ros D. Desarrollo del proyecto naive first episode schizophrenia 10:797-805. I.F.: 21.66. “Tecnologías de Imagen Molecular patients. PSYCHIAT RES-NEUROIM. Avanzada (AMIT)”. Sponsored by: 194:79-84. I.F.: 2.06. 8 Munoz E, Iranzo A, Rauek S, Lome- CDTI - CETIR, CENTRE MEDIC, na F, Gallego J, Ros D, Santamaria J, S.A., 10/192. Duration: 01/01/2010- 2 Cagido VR, Zin WA, Ramirez J, Tolosa E. Subclinical nigrostriatal dopa- 01/01/2013. Navajas D, Farre R. Alternating ven- minergic denervation in the cerebellar tilation in a rat model of increased subtype of multiple system atrophy Ros D. Cuantificación de estudios de abdominal pressure. RESP PHYSIOL (MSA-C). J NEUROL. 258:2248-2253. SPECT cerebral utilizando ligandos NEUROBI. 175:310-315. I.F.: 2.38. I.F.: 3.85. del transportador de dopamina en modelos animales y en diagnóstico 3 Pino F, Roe N, Orero A, Falcon C, 9 Dellaca R, Montserrat JM, Govo- clínico. Sponsored by: Ministerio Rojas S, Benlloch JM, Ros D, Pavia ni L, Pedotti A, Navajas D, Farre R. de Ciencia e Innovación, SAF2009- J. Development of a variable-radius Telemetric CPAP titration at home in 08076. Duration: 01/01/2010- pinhole SPECT system with a porta- patients with sleep apnea-hypopnea 31/12/2012. ble gamma camera. REV ESP MED syndrome. SLEEP MED. 12:153-157. NUCL. 30:286-291. I.F.: 0.77. I.F.: 3.43. Pavia J. Estudios de neuroimá- gen. Sponsored by: Centro para el 4 Horga G, Parellada E, Lomena F, 10 Almendros I, Farre R, Planas AM, Desarrollo Tecnológico Industrial Fernandez-Egea E, Mane A, Font Torres M, Bonsignore MR, Navajas D, (CDTI), CENIT10 10/157. Duration: M, Falcon C, Konova AB, Pavia J, Montserrat JM. Tissue Oxygenation in 18/05/2010-31/12/2013. Ros D, Bernardo M. Differential Brain, Muscle, and Fat in a Rat Model brain glucose metabolic patterns in of Sleep Apnea: Differential Effect antipsychotic-naive first-episode schi- of Obstructive Apneas and Intermit- DoctoRAl tHeSeS zophrenia with and without auditory tent Hypoxia. SLEEP. 34:1127-1133. verbal hallucinations. J PSYCHIATR I.F.: 5.49. Ros D. Evaluation of Compton scatte- NEUROSCI. 36:312-321. I.F.: 4.89. ring in spect studies with 123-I-labe- 11 Masa JF, Gonzalez MT, Pereira R, led rediotracers and quantification of 5 Almendros I, Farre R, Torres Mota M, Riesco JA, Corral J, Zamorano small animal neurotransmission stu- M, Bonsignore MR, Dalmases M, J, Rubio M, Teran J, Farre R. Validity of dies. PhD student: Núria Roé Vellvé. Ramirez J, Navajas D, Montserrat spirometry performed online. EUR RES- JM. Early and mid-term effects of PIR J. 37:911-918. I.F.: 5.92. obstructive apneas in myocardial injury and inflammation. SLEEP MED. 12:1037-1040. I.F.: 3.43. GRAntS foR ReSeARcH in pRoGReSS 6 Carreras A, Wang Y, Gozal D, Montserrat JM, Navajas D, Farre R. Farré R. Efecto de los estímulos me- Non-invasive system for applying cánicos en la diferenciación de células airway obstructions to model obs- madres hacia el fenotipo epitelial alveo- tructive sleep apnea in mice. RESP lar. Sponsored by: Ministerio de Ciencia PHYSIOL NEUROBI. 175:164-168. e Innovación, SAF2008-02991. Dura- I.F.: 2.38. tion: 01/01/2009-31/12/2011.

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Respiratory, cardiovascular and renal Team involved in: pathobiology and bioengineering Applied research in infectious respiratory diseases, critically ill patients and lung cancer gROUP MeMBeRS

teAM leADeR Antoni torres (Hospital clínic) tel.: 93 227 55 49 fax: fax: 93 227 98 13 e-mail: [email protected]

iDiBApS MeMBeRS: ReSeARcH fellowS: nuRSinG StAff: carles Agustí (Hospital clínic) Mariano esperatti (fiS) patrícia fernández (fiS) Joan Ramon Badia Arnoldo Guerrero encarnación Moreno (fundació clínic) (Hospital clínic) (Hospital clínic) isabel Martín (fundació clínic) Miquel ferrer (Hospital clínic) Arturo Huerta (fiS) Rebeca Domingo (fiS) Ramon Marrades (Hospital clínic) catia cillóniz (SGR) néstor Soler (Hospital clínic) Gema tirado (SepAR) ADMiniStRAtiVe StAff: Dolors Soy (Hospital clínic) laia fernàndez (cibeRes) elisabet Sancho (ciberes) Josep Mª Montserrat Hugo loureiro (Hospital clínic) Marc Miravitlles carmen lucena (Hospital clínic) StAtiSticiAn: (fundació clínic) Zinka Matkovic (eRS) Albert Gabarrús Barri (ciberes) Marta torres (ciberes) poStDoctoRAl fellowS: Joan Daniel Martí (fundació clínic) collABoRAtoRS: Jacob Sellarés (Hospital clínic) Beatriz Herrero (fundació clínic) núria Sànchez (cApSe) eva polverino (Hospital clínic) Valeria Giunta (Hospital de Milano) pilar Martínez (clínica platón) Gianluigi li Bassi (iDiBApS) otavio Ranzani (eRS) Montserrat Rigol (iDiBApS) laura Guerrero (iDiBApS) elena prina Rosanel Amaro (Hospital clínic) isaac Almendros (ciberes) (Hospital de Milano) Mariano Rinaudo (clínica del pilar)

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StrateGic oBjectiveS

• Study of community-acquired respiratory infections, nosocomial infections and infections in immune depressed patients. • Study of invasive and noninasive mechanical ventilation in acute respiratory failure, particularly in weaning from artificial ventilation. • Study of the exacerbation of chronic obstructive pulmonary disease (COPD) and the implication of bacterial, viral and fungal infectious agents. • Physiopathological and treatment studies in an animal model of ventilation associated pneumonia. Noninvasive ventilation after extubation significantly improves patient survival in relation to conventional treatment with oxygen therapy (Lancet; 374: 1082–88). • Epidemiology, diagnosis and treatment of adult bronchiectasia not associated with cystic fibrosis: Study of inflammatory response, new sistances of microorganisms. Study 4. Etiopathogenesis, bronchial infec- treatment modalities and immuno- of biofilms in endotracheal tubes. tion and inflammation in the pa- globulin replacement therapy. Local and systemic inflammatory tient with chronic obstructive pul- • Human and animal model research response. monary disease (COPD). Role of in sleep apnea syndrome. 2. Epidemiology and diagnosis of infections in exacerbation of the • Multicenter studies in relation to community-acquired pneumonia. disease. Study of bronchial and sleep respiratory pathology and car- Multicenter studies in the setting associated systemic response. diovascular disease. of community-acquired pneumonia. Analysis of the risk and prog- New methods for fast diagnosis. New nostic factors in acute episodes. main lineS treatments. Resistances of microor- Smoking. Epidemiology and of reSearcH ganisms. Local and systemic inflam- diagnosis of alpha-1-antitrypsin matory response. S. pneumoniae in deficiency. 1. Epidemiology, prevention and new the context of new vaccines. 5. Chronic pulmonary infections: treatmentsof pneumonias associ- 3. Study of the risk factors, microbiol- bronchiectasia not associated ated with artificial ventilation and ogy and prognosis of Health Care with cystic fibrosis, immune new methods of fast diagnosis . Re- Associated Pneumonia (HCAP). deficiencies and cystic fibrosis in the adult. Control of bronchial colonization. Study of bronchial ReSeARCh gROUP inflammatory and associated sys- BreatHinG diSturBanceS in Sleep temic response. New treatment modalities (nebulizer antibiotic team Leader: Josep M. Montserrat (hospital clínic) treatment). Replacement therapy with immunoglobulins. The main research line of this group is the analysis of re- 6. Infectious lung complications spiratory disturbances in sleep. Specifically, the two most in immune depressed patients. important lines are the following: the study of diagnostic Evaluation of the etiological fac- methods and effects of treatment in a population of apneic patients in which the indication is not clear; and the study of animal mod- tors. Optimization of the diagnostic els for exploring the mechanisms underlying the origin and consequences techniques. Study of bronchial of the disorder. Both lines are carried out in the context of national multi- inflammatory and associated sys- center clinical trials. temic response. Analysis of prognostic factors.

121 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Applied research in infectious respiratory diseases, critically ill patients and lung cancer PUBLICATIONS 7. Invasive and noninvasive mechanical ventilation: epidemiology, cost-effectiveness and physi- oRiGinAlS 7 Carreras A, Wang Y, Gozal D, Montse- opathology. New techniques. i.f.: 160.67 rrat JM, Navajas D, Farre R. Non-invasive Weaning from mechanical ven- system for applying airway obstructions tilation: role of the inflammatory 1 Martin-Loeches I, Diaz E, Vidaur L, to model obstructive sleep apnea in mice. response and respiratory failure Torres A, Laborda C, Granada R, Bonas- RESP PHYSIOL NEUROBI. 175:164-168. following extubation. tre J, Martin M, Insausti J, Arenzana A, I.F.: 2.38. 8. Study of the pharmacokinetics Guerrero JE, Navarrete I, Bermejo-Mar- of antibiotics and other drugs in tin J, Suarez D, Rodriguez A. Pandemic 8 Dellaca R, Montserrat JM, Govoni L, the ventilated and non-ventilated and post-pandemic Influenza A (H1N1) Pedotti A, Navajas D, Farre R. Telemetric patient. infection in critically ill patients. CRIT CPAP titration at home in patients with 9. Porcine model of acute pulmo- CARE. 15:-. I.F.: 4.60. sleep apnea-hypopnea syndrome. SLEEP nary damage due to methicillin- MED. 12:153-157. I.F.: 3.43. resistant P. aeruginosa, S. aureus 2 Marcos MA, Ramon S, Anton A, and S. pneumoniae: study of Martinez E, Vilella A, Olive V, Cilloniz C, 9 Almendros I, Farre R, Planas AM, new coadjuvant drugs in the Moreno A, Torres A, Pumarola T. Clinical Torres M, Bonsignore MR, Navajas D, treatment of pneumonia, study relevance of mixed respiratory viral in- Montserrat JM. Tissue Oxygenation in of new antibiotics, prevention of fections in adults with influenza A H1N1. Brain, Muscle, and Fat in a Rat Model of ventilator-associated pneumonia EUR RESPIR J. 38:739-742. I.F.: 5.92. Sleep Apnea: Differential Effect of Obs- (VAP), and new forms of mechan- tructive Apneas and Intermittent Hypoxia. ical ventilation. 3 Cilloniz C, Ewig S, Ferrer M, Polve- SLEEP. 34:1127-1133. I.F.: 5.49. 10. European studies of respiratory rino E, Gabarrus A, DeLaBellacasa JP, infections. Participation in the Mensa J, Torres A. Community-acquired 10 Guerrero L, Pinazo MJ, Posada E, GRACE, MOSAR and THERAE- polymicrobial pneumonia in the intensive Gascon J, Ribas J, Soy D. A high-perfor- DGE projects, which respectively care unit: aetiology and prognosis. CRIT mance liquid chromatographic method for investigate community-acquired CARE. 15:-. I.F.: 4.60. benznidazole quantitation in plasma of pa- respiratory infections, in-hospital tients with Chagas disease. CLIN CHEM respiratory infections and new 4 Cilloniz C, Ewig S, Polverino E, LAB MED. 49:77-82. I.F.: 2.07. diagnostic methods. Marcos MA, Esquinas C, Gabarrus A, 11. Chronic sleep apnea models. Mensa J, Torres A. Microbial aetiology 11 Wood J, Butler CC, Hood K, Kelly 12. Multicenter Study to assess the of community-acquired pneumonia and MJ, Verheij T, Little P, Torres A, Blasi effect of CPAP on cardiovascular its relation to severity. THORAX. 66:340- F, Schaberg T, Goossens H, Nuttall J, diseases in patients with sleep 346. I.F.: 6.53. Coenen S. Antibiotic prescribing for adults apnea. with acute cough/lower respiratory tract 13. Telematic control of CPAP treat- 5 Martinez-Rebollar M, Lonca M, Pe- infection: congruence with guidelines. ment in sleep apnea syndrome. rez I, Soy D, Brunet M, Martin R, Coll EUR RESPIR J. 38:112-118. I.F.: 5.92. O, Hernandez S, Laguno M, Milinkovic A, Larrousse M, Calvo M, Blanco JL, 12 Butler CC, Kelly MJ, Hood K, Scha- For further information: Martinez E, Gatell JM, Mallolas J. berg T, Melbye H, Serra-Prat M, Blasi F, www.idibapsrespiratoryresearch.org Pharmacokinetic Study of Saquinavir Little P, Verheij T, Molstad S, Godycki- 500 mg Plus Ritonavir (1000/100 mg Cwirko M, Edwards P, Almirall J, Torres Twice a Day) in HIV-Positive Pregnant A, Rautakorpi UM, Nuttall J, Goossens Women. THER DRUG MONIT. 33:772- H, Coenen S. Antibiotic prescribing for 777. I.F.: 3.13. discoloured sputum in acute cough/lower respiratory tract infection. EUR RESPIR J. 6 Almendros I, Farre R, Torres M, 38:119-125. I.F.: 5.92. Bonsignore MR, Dalmases M, Ramirez J, Navajas D, Montserrat JM. Early and 13 Bordon J, Kapoor R, Martinez C, mid-term effects of obstructive apneas Portela D, Duvvuri P, Klochko A, Ayesu in myocardial injury and inflammation. K, Peyrani P, Cilloniz C, Wiemken T, Parra SLEEP MED. 12:1037-1040. I.F.: 3.43. A, Torres A, Rello J, Ramirez J. CD4+cell

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original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 212.64 34 28 3 counts and HIV-RNA levels do not predict taxel-Carboplatin Followed by Concurrent 197.85 39 21 12 outcomes of community-acquired pneu- Radiation Therapy and Weekly Paclitaxel 2010 monia in hospitalized HIV-infected pa- and Consolidation Paclitaxel-Carboplatin 2011 160.67 33 22 6 tients. INT J INFECT DIS. 15:E822-E827. in Stage III Non-small Cell Lung Cancer. J I.F.: 2.53. THORAC ONCOL. 6:79-85. I.F.: 4.04.

14 Miravitlles M, Izquierdo I, Herrejon 20 Fietze I, Penzel T, Alonderis A, Barbe A, Torres JV, Baro E, Borja J, Esfera IN- F, Bonsignore MR, Calverly P, DeBacker G, Benchetrit G, Rioseco ML, Ayesu K, VESTIGATORS. COPD severity score as W, Diefenbach K, Donic V, Eijsvogel MM, Klotchko A, Marzoratti L, Raya M, Figue- a predictor of failure in exacerbations of Franklin KA, Gislason T, Grote L, Hedner J, roa S, Saavedra F, Pryluka D, Inzunza C, COPD. The ESFERA study. RESP MED. Jennum P, Lavie L, Lavie P, Levy P, Lom- Torres A, Alvare P, Fernandez P, Barros M, 105:740-747. I.F.: 2.53. bardi C, Mallin W, Marrone O, Montserrat Gomez Y, Contreras C, Rello J, Bordon JM, Papathanasiou ES, Parati G, Plywac- J, Feldman C, Arnold F, Nakamatsu R, 15 Alia I, DeLaCal MA, Esteban A, Abe- zewski R, Pretl M, Riha RL, Rodenstein D, Riquelme J, Blasi F, Aliberti S, Cosentini lla A, Ferrer R, Molina FJ, Torres A, Gordo Saaresranta T, Schulz R, Sliwinski P, Stei- R, Lopardo G, Gnoni M, Welte T, Saad M, F, Elizalde JJ, DePablo R, Huete A, Anzue- ropoulos P, Svaza J, Tomori Z, Tonnesen Guardiola J, Ramirez J. Predicting mortali- to A. Efficacy of Corticosteroid Therapy in P, Varoneckas G, Verbraecken J, Vesely ty in hospitalized patients with 2009 H1N1 Patients With an Acute Exacerbation of J, Vitols A, Zielinski J, Mcnicholas WT. influenza pneumonia. INT J TUBERC Chronic Obstructive Pulmonary Disease Management of obstructive sleep apnea LUNG D. 15:542-546. I.F.: 2.56. Receiving Ventilatory Support. ARCH IN- in Europe. SLEEP MED. 12:190-197. TERN MED. 171:1939-1946. I.F.: 10.64. I.F.: 3.43. 25 Sellares J, Ferrer M, Cano E, Lourei- ro H, Valencia M, Torres A. Predictors of 16 Martinez R, Menendez R, Reyes 21 Gasa M, Salord N, Fortuna AM, prolonged weaning and survival during S, Polverino E, Cilloniz C, Martinez A, Mayos M, Vilarrasa N, Dorca J, Montse- ventilator weaning in a respiratory ICU. IN- Esquinas C, Filella X, Ramirez P, Torres rrat JM, Bonsignore MR, Monasterio C. TENS CARE MED. 37:775-784. I.F.: 5.00. A. Factors associated with inflammatory Obstructive sleep apnoea and metabolic cytokine patterns in community-acquired impairment in severe obesity. EUR RES- 26 Miravitlles M, Naberan K, Cantoni pneumonia. EUR RESPIR J. 37:393-399. PIR J. 38:1089-1097. I.F.: 5.92. J, Azpeitia A. Socioeconomic Status and I.F.: 5.92. Health-Related Quality of Life of Patients 22 Garcia-Rio F, Soriano JB, Miravitlles with Chronic Obstructive Pulmonary 17 Ramirez P, Ferrer M, Marti V, Reyes M, Munoz L, Duran-Tauleria E, Sanchez G, Disease. RESPIRATION. 82:402-408. S, Martinez R, Menendez R, Ewig S, To- Sobradillo V, Ancochea J. Overdiagnosing I.F.: 2.54. rres A. Inflammatory biomarkers and pre- Subjects With COPD Using the 0.7 Fixed diction for intensive care unit admission in Ratio: Correlation With a Poor Health- 27 Kessler R, Partridge MR, Miravitlles severe community-acquired pneumonia. Related Quality of Life. CHEST. 139:1072- M, Cazzola M, Vogelmeier C, Leynaud D, CRIT CARE MED. 39:2211-2217. I.F.: 6.25. 1080. I.F.: 6.52. Ostinelli J. Symptom variability in patients with severe COPD: a pan-European cross- 18 Riquelme R, Torres A, Rioseco ML, 23 Sanchez-De-La-Torre M, Barcelo A, sectional study. EUR RESPIR J. 37:264- Ewig S, Cilloniz C, Riquelme M, Inzun- Pierola J, Esquinas C, DeLaPena M, Du- 272. I.F.: 5.92. za C, Polverino E, Gomez Y, Marcose ran-Cantolla J, Capote F, Masa JF, Marin MA, Contreras C, Gabarrus A, Fasce JM, Vila M, Cao G, Martinez M, DeLecea 28 Rubinstein E, Lalani T, Corey GR, Ka- R. Influenza pneumonia: a comparison L, Gozal D, Montserrat JM, Barbe F. Plas- nafani ZA, Nannini EC, Rocha MG, Rahav between seasonal influenza virus and ma levels of neuropeptides and metabolic G, Niederman MS, Kollef MH, Shorr AF, the H1N1 pandemic. EUR RESPIR J. hormones, and sleepiness in obstructive Lee PC, Lentnek AL, Luna CM, Fagon JY, 38:106-111. I.F.: 5.92. sleep apnea. RESP MED. 105:1954-1960. Torres A, Kitt MM, Genter FC, Barriere SL, I.F.: 2.53. Friedland HD, Stryjewski ME. Telavancin 19 Casas F, Vinolas N, Ferrer F, Agusti versus Vancomycin for HospitalAcqui- C, Sanchez M, Gimferrer JM, Lomena F, 24 Riquelme R, Jimenez P, Videla AJ, red Pneumonia due to Gram-positive Campayo M, Jeremic B. Long-Term Re- Lopez H, Chalmers J, Singanayagam A, Pathogens. CLIN INFECT DIS. 52:31-40. sults of a Phase II Trial of Induction Pacli- Riquelme M, Peyrani P, Wiemken T, Arbo I.F.: 8.19.

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29 Miravitlles M, Sotgiu G, Dimo- ReViewS eDitoRiAlS poulos G, Rohde G, Centis R, Ferrara i.f.: 26.78 i.f.: 13.97 G, Ewig S, Blasi F, Migliori GB. The best on infections: update from the 1 Nogue S, Corominas N, Soy D, Cino J. 1 Ewig S, Torres A. Healthcare-associa- 2010 ERS Congress. EUR RESPIR J. Intravenous lipid emulsion: a new antidote ted pneumonia: meeting the yeti. EUR 38:450-455. I.F.: 5.92. for use in resuscitation. EMERGENCIAS. RESPIR J. 38:755-757. I.F.: 5.92. 23:378-385. I.F.: 3.09. 30 Hedner J, Grote L, Bonsignore 2 Ferrer M. Respiratory High-Depen- M, Mcnicholas W, Lavie P, Parati G, 2 Polverino E, Torres A. Community- dency Care Units in Italy. RESP CARE. Sliwinski P, Barbe F, DeBacker W, acquired pneumonia. MINERVA ANESTE- 56:1215-1216. I.F.: 1.53. Escourrou P, Fietze I, Kvamme JA, SIOL. 77:196-211. I.F.: 2.58. Lombardi C, Marrone O, Masa JF, 3 Torres A, Ewig S. The Strange Case Montserrat JM, Penzel T, Pretl M, 3 Ewig S, Torres A. Community-acquired of Community-Acquired Pneumonia in Riha R, Rodenstein D, Saaresranta pneumonia as an emergency: time for an COPD. CHEST. 139:483-485. I.F.: 6.52. T, Schulz R, Tkacova R, Varoneckas aggressive intervention to lower mortality. G, Vitols A, Vrints H, Zielinski J. The EUR RESPIR J. 38:253-260. I.F.: 5.92. European Sleep Apnoea Database MulticentRicS (ESADA): report from 22 European 4 Miravitlles M. Cough and sputum i.f.: 3.00 sleep laboratories. EUR RESPIR J. production as risk factors for poor outco- 38:635-642. I.F.: 5.92. mes in patients with COPD. RESP MED. 1 Llaurado M, Labeau S, Vandijck D, Re- 105:1118-1128. I.F.: 2.53. llo J, Rosa A, Riera A, Gallart E, Moreno R, 31 Masa JF, Corral J, Pereira Vandewoude K, Piner R, Benitez ML, Blot R, Duran-Cantolla J, Cabello M, 5 Decramer M, Miravitlles M, Price D, S. Southern European Intensive Care Nur- Hernandez-Blasco L, Monasterio C, Roman-Rodriguez M, Llor C, Welte T, ses’ Knowledge of Evidence-Based Guide- Alonso A, Chiner E, Zamorano J, Aiz- Buhl R, Dusser D, Samara K, Siafakas lines for Preventing Ventilator-Associated puru F, Montserrat JM. Therapeutic N. New horizons in early stage COPD Pneumonia. MED INTENSIVA. 35:6-12. Decision-making for Sleep Apnea and - Improving knowledge, detection and I.F.: 1.50. Hypopnea Syndrome Using Home treatment. RESP MED. 105:1576-1587. Respiratory Polygraphy A Large I.F.: 2.53. 2 Rodriguez A, Martin-Loeches I, Bo- Multicentric Study. AM J RESP CRIT nastre J, Olaechea P, Alvarez-Lerma F, CARE. 184:964-971. I.F.: 10.19. 6 Ferrer M, Sellares J, Torres A. The use Zaragoza R, Guerrero J, Blanco J, Gordo F, of non-invasive ventilation by Italian phy- Pozo F, Lorente J, Carratala J, Cordero M, 32 Masa JF, Jimenez A, Duran J, sicians in the clinical practice. MINERVA Rello J, Esteban A, Leon C. First influenza Carmona C, Monasterio C, Mayos M, ANESTESIOL. 77:941-942. I.F.: 2.58. season after the 2009 pandemic influenza: Teran J, Barbe F, Rubio M, Failde I, report of the first 300 ICU admissions Mota M, Montserrat JM. Visual analo- 7 Ewig S, Woodhead M, Torres A. in Spain. MED INTENSIVA. 35:208-216. gical well-being scale for sleep apnea Towards a sensible comprehension of se- I.F.: 1.50. patients: validity and responsiveness vere community-acquired pneumonia. IN- A test for clinical practice. SLEEP TENS CARE MED. 37:214-223. I.F.: 5.00. BREATH. 15:549-559. I.F.: 1.68. GRAntS foR ReSeARcH 8 Bassi GL, Torres A. Ventilator-associa- in pRoGReSS 33 Ferrer M, Menendez R, Amaro ted pneumonia: role of positioning. CURR R, Torres A. The Impact of Guidelines OPIN CRIT CARE. 17:57-63. I.F.: 2.55. Ferrer M. Eficacia de los glucocorticoides on the Outcomes of Community- en la neumonía asociada a la ventilación acquired and Ventilator-associated mecánica estudio clínico aleatorizado. Pneumonia. CLIN CHEST MED. Sponsored by: Ministerio Sanidad y Con- 32:491-505. I.F.: 3.11. sumo, EC07/90390. Duration: 29/10/2007- 31/12/2012.

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Torres A. Genomics to combat resistance Montserrat JM. Efectos sistémicos del against antibiotics in Community-acquired síndrome de las apneas durante el sueño. LRTI in Europe. Sponsored by: European Análisis mediante modelos animales y es- Comission, LSHM-CT-2005-518226. Dura- tudios cognitivos en humanos. Sponsored tion: 01/03/2007-28/02/2011. by: Instituto de Salud Carlos III, PI08/0277. Duration: 31/12/2008-30/12/2011. Torres A. An integrated platform enabling Theranostic applications at the Point of Soler N. Impacto de la infección vírica Primary Care. Sponsored by: European en las agudizaciones de la enfermedad Comission, FP7-ICT07-01-216027. Dura- pulmonar obstructiva crónica (AEPOC): tion: 01/03/2008-29/02/2012. caracterización clínica, gravedad y factores pronósticos. Sponsored by: Instituto de Torres A. Health Care Associated Pneu- Salud Carlos III, PI10/01504. Duration: monia (HCAP). Sponsored by: Fondo de 01/01/2011-31/12/2013. Investigación Sanitaria, PI080240. Dura- tion: 01/01/2009-31/12/2012. Garcia C. Complicaciones pulmonares en pacientes receptores de trasplante Torres A. Fisiopatologia i tractament de les de progenitores hematopoyéticos. Spon- malalties respiratòries. Sponsored by: Ge- sored by: Instituto de Salud Carlos III neralitat de Catalunya, AGAUR, SGR/911. (ISCIII), PI10/00507. Duration: 01/01/2011- Duration: 01/01/2009-31/12/2013. 31/12/2013.

Ferrer M. Papel de la respuesta inflama- toria y el estrés oxidativo sistémico en la DoctoRAl tHeSeS retirada de la ventilación mecánica invasiva. Sponsored by: Fondo de Investigación Torres A, Ferrer M. Prevención de com- Sanitaria, PI080232. Duration: 01/01/2009- plicaciones asociadas a la ventilación 30/09/2012. mecánica. PhD student: Mauricio Valencia Arango. Torres A. Efectos de los flujos insipartorio- respiratorio y la presión positiva al final Torres A. Neumonía adquirida en la comu- de la espiración en el aclaramiento de nidad: Estudio prospectivo de etiología y secreciones y la neumonía asociada al evolución clínica en un período de 12 años ventilador. Sponsored by: INSTITUTO DE de estudio. PhD student: Catia Cillóniz SALUD CARLOS III, PI09/1249. Duration: Campos. 01/01/2010-31/12/2012. Torres A. Caracterización de la neumonía Soler N. Utilidad del tratamiento antibióti- adquirida fuera del hospital. PhD student: co en las agudizaciones de la enfermedad Gerardo Dambrava Rodríguez Povilas. pulmonar obstructiva crónica (EPOC) sin purulencia en el esputo: ensayo clinico aleatorizado, controlado y doble ciego de eficacia y seguridad. Sponsored by: Instituto de Salud Carlos III, EC08/00061. Duration: 01/01/2009-31/12/2012.

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Team involved in: Respiratory, cardiovascular and renal pathobiology and bioengineering Physiopathological mechanisms of respiratory illnesses

gROUP MeMBeRS StrateGic oBjectiveS

1. Investigation of the molecular and cellular bases of chronic respiratory diseases, with special emphasis on pulmonary circulatory disorders and teAM leADeR systemic manifestations. Joan Albert Barberà (Hospital clínic) 2. Study of the physiopathological and pathogenic tel.: 93 227 57 47 mechanisms related to acute and chronic respira- fax: 93 227 54 55 tory failure, focusing on chronic obstructive dis- e-mail: [email protected] eases, hepatopulmonary disorders and obesity. 3. Evaluation of the potential of cell therapy and tis- iDiBApS MeMBeRS: Maite Simó (Hospital clínic) sue engineering applied to respiratory diseases. Josep Roca (Hospital clínic) Maria palomo (fundació clínic) 4. Development of artificial and bioartificial lung Robert Rodríguez-Roisín Xavier Alsina (Hospital clínic) models for the support of patients with acute and (Hospital clínic) Beatriz Valeiro (fundació clínic) chronic respiratory failure. elizabeth Zavala (Hospital clínic) 5. Study of the determining factors of the clinical Graciela Martínez-pallí ADMiniStRAtiVe StAff: course and healthcare resource utilization in chron- (Hospital clínic) Mirjam Hillenius (fundació clínic) ic respiratory diseases. Julio Más (fundació clínic - poStDoctoRAl fellowS: ciBeReS) main lineS of reSearcH Melina Musri (iDiBApS) Verónica Amado (fundació clínic) pHySiotHeRApiStS: 1. Biopathology and physiopathology of pulmonary Anael Barberan (fundació clínic) circulation disorders ReSeARcH fellowS: Ane Arbillaga (fundació clínic) 2. Physical activity, cell bioenergetics and systemic elisabeth ferrer (fiS) effects of chronic obstructive pulmonary disease Diego Rodríguez (eRS-SepAR) collABoRAtoRS: (COPD) ebymar Arismendi (fundació clínic) Albert Alonso (fundació clínic) 3. Physiopathological mechanisms underlying gas ex- Jéssica Garcia (fundació clínic) isabel Blanco (Hospital clínic) change alterations in airway obstructive diseases David Domínguez (fundació clínic) felip Burgos (Hospital clínic) 4. Interaction between systemic and pulmonary Borja lobo (fundació clínic) federico Gómez (uB) inflammation in COPD and morbid obesity Roberto del pozo (fundació clínic) carme Hernández (Hospital clínic) 5. Tissue engineering and bioartificial lung models Victor i. peinado (ciBeReS) 6. Prognostic and determining factors of healthcare tecHniciAnS: Jordi Vilaró (fundació clínic) resource utilization in chronic respiratory disease Raquel puig-pey (iDiBApS) elena Gimeno (iDiBApS) 7. Analysis of inflammation and oxidative stress bio- núria coll (fundació clínic) Marta cascante (uB) markers in exhaled air in the study of respiratory eva Rivas (Hospital clínic) diseases nuRSinG StAff: conchi Gistau (Hospital clínic) yolanda torralba (ciBeReS)

View of two precursor vascular cells with inter-differential technology. One of the cells maintains the precursor phenotype, while the other has acquired a smooth muscle cell phenotype.

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PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 99.63 18 12 oRiGinAlS Kovacs G, Hamid AM, Jais X, Simon- i.f.: 91.96 neau G. Chronic Thromboembolic Pul- 2010 121.18 16 11 1 monary Hypertension (CTEPH) Results 2011 91.96 21 10 3 1 Villar J, Perez-Mendez L, Basaldua From an International Prospective Re- S, Blanco J, Aguilar G, Toral D, Zavala gistry. CIRCULATION. 124:1973-1981. E, Romera MA, Gonzalez-Diaz G, I.F.: 14.43. DelNogal F, Santos-Bouza A, Ramos 11 Blanco I, Ribas J, Xaubet A, Go- L, Macias S, Kacmarek RM. A Risk 6 DeMas IM, Selivanov VA, Marin S, mez FP, Roca J, Rodriguez-Roisin R, Tertiles Model for Predicting Mortali- Roca J, Oresic M, Agius L, Cascante Barbera JA. Effects of inhaled nitric ty in Patients With Acute Respiratory M. Compartmentation of glycogen oxide at rest and during exercise in Distress Syndrome: Age, Plateau metabolism revealed from C-13 isoto- idiopathic pulmonary fibrosis. J APPL Pressure, and P-aO2/F-IO2 at ARDS pologue distributions. BMC SYST BIOL. PHYSIOL. 110:638-645. I.F.: 4.24. Onset Can Predict Mortality. RESP 5:-. I.F.: 3.57. CARE. 56:420-428. I.F.: 1.53. 12 Guarner-Argente C, Cordova H, 7 Martinez-Palli G, Hirose R, Liu T, Martinez-Palli G, Navarro-Ripoll R, 2 Turan N, Kalko S, Stincone A, Xu FY, Dang K, Feiner J, Serkova NJ, Rodriguez-D’jesus A, DeMiguel CR, Clarke K, Sabah A, Howlett K, Cur- Niemann CU. Donor pre-treatment with Beltran M, Fernandez-Esparrach G. now SJ, Rodriguez DA, Cascante M, everolimus or cyclosporine does not Gastrotomy closure with a new tissue O’neill L, Egginton S, Roca J, Falciani reduce ischaemia-reperfusion injury anchoring device: A porcine survival F. A Systems Biology Approach Iden- in a rat kidney transplant model. NE- study. WORLD J GASTROENTERO. tifies Molecular Networks Defining PHROL DIAL TRANSPL. 26:1813-1820. 17:1732-1738. I.F.: 2.24. Skeletal Muscle Abnormalities in I.F.: 3.56. Chronic Obstructive Pulmonary Di- 13 Garcia-Aymerich J, Gomez FP, Be- sease. PLOS COMPUT BIOL. 7:-. 8 Otero R, Oribe M, Ballaz A, Jimenez net M, Farrero E, Basagana X, Gayete I.F.: 5.52. D, Uresandi F, Nauffal D, Conget F, A, Pare C, Freixa X, Ferrer J, Ferrer A, Rodriguez C, Elias T, Jara L, Cayuela A, Roca J, Galdiz JB, Sauleda J, Monso E, 3 Moran I, Blanch L, Fernandez R, Blanco I, Barbera J. Echocardiographic Gea J, Barbera JA, Agusti A, Anto JM. Fernandez-Mondejar E, Zavala E, assessment of pulmonary arterial pres- Identification and prospective validation Mancebo J. Acute physiologic effects sure in the follow-up of patients with of clinically relevant chronic obstructive of a stepwise recruitment maneu- pulmonary embolism. THROMB RES. pulmonary disease (COPD) subtypes. ver in acute respiratory distress 127:303-308. I.F.: 2.37. THORAX. 66:430-437. I.F.: 6.53. syndrome. MINERVA ANESTESIOL. 77:1167-1175. I.F.: 2.58. 9 Olea E, Ferrer E, Prieto-Lloret J, 14 Guarner-Argente C, Beltran M, Gonzalez-Martin C, Vega-Agapito V, Martinez-Palli G, Navarro-Ripoll R, Mar- 4 Nunez B, Sauleda J, Anto JM, Ju- Gonzalez-Obeso E, Agapito T, Peinado tinez-Zamora MA, Cordova H, Comas lia MR, Orozco M, Monso E, Noguera V, Obeso A, Barbera JA, Gonzalez C. J, DeMiguel CR, Rodriguez-D’jesus A, Gomez FP, Garcia-Aymerich J, Effects of cigarette smoke and chronic A, Almela M, Hernandez-Cera C, Lacy Agusti A. Anti-Tissue Antibodies Are hypoxia on airways remodeling and AM, Fernandez-Esparrach G. Infection Related to Lung Function in Chronic resistance. Clinical significance. RESP during Natural Orifice Transluminal Obstructive Pulmonary Disease. AM PHYSIOL NEUROBI. 179:305-313. Endoscopic Surgery Peritoneoscopy: J RESP CRIT CARE. 183:1025-1031. I.F.: 2.38. A Randomized Comparative Study in a I.F.: 10.19. Survival Porcine Model. J MINIM IN- 10 Ferrer E, Peinado VI, Castaneda J, VAS GYN. 18:741-746. I.F.: 1.56. 5 Pepke-Zaba J, Delcroix M, Lang I, Prieto-Lloret J, Olea E, Gonzalez-Martin Mayer E, Jansa P, Ambroz D, Treacy MC, Vega-Agapito MV, Diez M, Domin- 15 Bader A, Lorenz K, Richter A, C, D’armini AM, Morsolini M, Snijder guez-Fandos D, Obeso A, Gonzalez C, Scheffler K, Kern L, Ebert S, Giri S, Be- R, Bresser P, Torbicki A, Kristensen Barbera JA. Effects of cigarette smoke hrens M, Dornseifer U, Macchiarini P, B, Lewczuk J, Simkova I, Barbera and hypoxia on pulmonary circulation in Machens HG. Interactive Role of Trau- JA, DePerrot M, Hoeper MM, Gaine the guinea pig. EUR RESPIR J. 38:617- ma Cytokines and Erythropoietin and S, Speich R, Gomez-Sanchez MA, 627. I.F.: 5.92. Their Therapeutic Potential for Acute

127 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Physiopathological mechanisms of respiratory illnesses

and Chronic Wounds. REJUV RES. 21 Chappell SL, Daly L, Lotya J, cerbations Reliability and Validity of 14:57-66. I.F.: 4.23. Alsaegh A, Guetta-Baranes T, Roca J, a Patient-reported Diary. AM J RESP Rabinovich R, Morgan K, Millar AB, CRIT CARE. 183:323-329. I.F.: 10.19. 16 Maier D, Kalus W, Wolff M, Ka- Donnelly SC, Keatings V, Macnee W, lko SG, Roca J, DeMas IM, Turan N, Stolk J, Hiemstra PS, Miniati M, Monti 2 Jones PW, Chen WH, Wilcox TK, Cascante M, Falciani F, Hernandez S, O’connor CM, Kalsheker N. The Sethi S, Leidy NK. Characterizing and M, Villa-Freixa J, Losko S. Knowled- role of IREB2 and transforming growth Quantifying the Symptomatic Featu- ge management for systems bio- factor beta-1 genetic variants in COPD: res of COPD Exacerbations. CHEST. logy a general and visually driven a replication case-control study. BMC 139:1388-1394. I.F.: 6.52. framework applied to translational MED GENET. 12:-. I.F.: 2.44. medicine. BMC SYST BIOL. 5:-. 3 Barst RJ, Oudiz RJ, Beardswor- I.F.: 3.57. ReViewS th A, Brundage BH, Simonneau G, i.f.: 8.06 Ghofrani HA, Sundin DP, Galie N. 17 Cremona G, Barbara JA, Mel- Tadalafil monotherapy and as add-on gosa T, Appendini L, Roca J, Casadio 1 Martinez-Palli G, Cardenas A. Pre to background bosentan in patients C, Donner CF, Rodriguez-Roisin R, operative cardio pulmonary assessment with pulmonary arterial hypertension. J Wagner PD. Mechanisms of gas of the liver transplant candidate. ANN HEART LUNG TRANSPL. 30:632-643. exchange response to lung volume HEPATOL. 10:421-433. I.F.: 1.87. I.F.: 3.43. reduction surgery in severe emphy- sema. J APPL PHYSIOL. 110:1036- 2 Ram FS, Rodriguez-Roisin R, Gra- 4 Vogelmeier C, Hederer B, Glaab 1045. I.F.: 4.24. nados-Navarrete A, Garcia-Aymerich J, T, Schmidt H, Rutten-VanMolken Barnes NC. WITHDRAWN: Antibiotics MPMH, Beeh KM, Rabe KF, Fabbri 18 Gambus PL, Jensen EW, for exacerbations of chronic obstructive LM. Tiotropium versus Salmeterol for Jospin M, Borrat X, Martinez-Palli pulmonary disease. COCHRANE DB the Prevention of Exacerbations of G, Fernandez-Candil J, Valencia SYST REV. 1:-. I.F.: 6.19. COPD. NEW ENGL J MED. 364:1093- JF, Barba X, Caminal P, Troconiz IF. 1103. I.F.: 53.49. Modeling the Effect of Propofol and Remifentanil Combinations for eDitoRiAlS 5 Kett DH, Azoulay E, Echeverria Sedation-Analgesia in Endoscopic i.f.: 16.11 PM, Vincent JL. Candida bloodstream Procedures Using an Adaptive Neuro infections in intensive care units: Fuzzy Inference System (ANFIS). 1 Barbera JA, Peinado VI. Disruption Analysis of the extended prevalence ANESTH ANALG. 112:331-339. of the lung structure maintenance pro- of infection in intensive care unit I.F.: 3.27. gramme: a comprehensive view of em- study. CRIT CARE MED. 39:665-670. physema development. EUR RESPIR J. I.F.: 6.25. 19 Selivanov VA, Votyakova TV, 37:752-754. I.F.: 5.92. Pivtoraiko VN, Zeak J, Sukhomlin T, Trucco M, Roca J, Cascante M. 2 Zock JP, Rodriguez-Trigo G, Pozo- GRAntS foR ReSeARcH Reactive Oxygen Species Production Rodriguez F, Barbera JA. Health Effects in pRoGReSS by Forward and Reverse Electron of Oil Spills: Lessons from the Prestige. Fluxes in the Mitochondrial Respi- AM J RESP CRIT CARE. 184:1094- Roca J. IP - Healthcare by Biosensor ratory Chain. PLOS COMPUT BIOL. 1096. I.F.: 10.19. Measurements And Networking. 7:-. I.F.: 5.52. Sponsored by: European Commision, CE_FPVI05. Duration: 01/11/2005- 20 Llinas L, Peinado VI, Goni JR, MulticentRicS 30/04/2011. Rabinovich R, Pizarro S, Rodriguez- i.f.: 79.88 Roisin R, Barbera JA, Bastos R. Barbera JA. Estudio de los efectos Similar gene expression profiles in 1 Leidy NK, Wilcox TK, Jones PW, de sildenafilo sobre el intercambio smokers and patients with moderate Roberts L, Powers JH, Sethi S. Stan- gaseoso, la hemodinámica pulmonar y COPD. PULM PHARMACOL THER. dardizing Measurement of Chronic la tolerancia al esfuerzo en pacientes 24:32-41. I.F.: 2.09. Obstructive Pulmonary Disease Exa- con hipertensión pulmonar asociada a

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la enfermedad pulmonar obstructiva Bastos R. Estudio de la pérdida de crónica. Sponsored by: Fondo de In- masa muscular en pacientes con Enfer- vestigación Sanitaria (FIS), EC0790049. medad Pulmonar Obstructiva Crónica Duration: 29/10/2007-31/12/2011. mediante técnicas de genómica y proteómica. Sponsored by: Instituto de Roca J. Supporting Healthier and Inde- Salud Carlos III (ISCIII), PI08/0320. Du- pendent Living for Chronic Patients and ration: 01/01/2009-30/06/2012. Elderly - NEXES. Sponsored by: Unión Europea, FP7 (CIP-ICT) 225025. Dura- Roca J. Desarrollo de un sistema tion: 01/05/2008-31/05/2011. de rehabilitación física domiciliario. Sponsored by: Ministerio de Ciencia e Peinado V. Mecanismos moleculares de Innovación, IPT-2011-1193-900000. Du- la diferenciación de células progenitoras ration: 04/05/2011-31/12/2013. endoteliales durante la reparación del endotelio en la hipertensión pulmonar. Spon- Roca J. STREP - Knowledge Sharing sored by: Fundació Marató TV3, 08/1310. and Decision Support for Health- Duration: 20/02/2009-19/12/2012. care Professionals. Sponsored by: Unió Europea, CE_FPVI01. Duration: Barbera JA. Estudio de nuevas dianas 01/01/2004-30/11/2011. terapéuticas en el tratamiento de la hipertensión pulmonar asociada a la Roca J. Despliegue de nuevos servicios enfermedad pulmonar obstructiva cró- sanitarios soportados por tecnolo- nica. Sponsored by: Instituto de Salud gías de la información y comunica- Carlos III (ISCIII), PI09/0536. Duration: ción (DENSSA-TIC). Sponsored by: 01/01/2010-31/12/2012. Ministerio de Ciencia e Innovación, IPT-2011-1333-900000. Duration: Roca J. Servicios innovadores de aten- 05/05/2011-31/12/2014. ción integrada para pacientes crónicos. Sponsored by: Instituto de Salud Car- los III (ISCIII), PI09/90634. Duration: DoctoRAl tHeSeS 01/01/2010-31/12/2012. Barbera JA. Estudio de los efectos de Rodriguez R. Obesidad mórbida e los agentes vasodilatadores sobre el inflamación sistématica y pulmonar. intercambio de gases y la hemodinámi- Sponsored by: Instituto de Salud Car- ca pulmonar, en las enfermedades res- los III (ISCIII), PI08/0311. Duration: piratorias crónicas. PhD student: Isabel 31/12/2008-30/12/2011. Blanco Vich.

Roca J. Synergy – Modelling and simu- Barbera JA, Peinado VI. Alteracions lation for systems medicine (COPD as vasculars pulmonars induïdes per a use case). Sponsored by: Unión Euro- l’exposició a fum de tabac en un mo- pea, FP7-ICT-2009-6. 270086. Duration: del animal de MPOC. PhD student: 28/02/2011-31/01/2014. Elisabet Ferrer Andrés, Universitat de Barcelona. Gomez F. Biomarcadores inflamatorios, de estrés oxidativo y metabonómicos en el aire exhalado en la EPOC y el cán- cer de pulmón. Sponsored by: Minis- terio Sanidad y Consumo, PI08/0283. Duration: 01/01/2009-31/12/2011.

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Respiratory, cardiovascular and renal pathobiology Team involved in: and bioengineering & Clinical and Experimental Respiratory Immunoallergy (IRCE)

gROUP MeMBeRS

teAM leADeR césar picado (Hospital clínic, uB) tel.: 93 227 26 34 fax: 93 227 98 13 e-mail: [email protected]

iDiBApS MeMBeRS: Jaume Sánchez lópez ADMiniStRAtiVe StAff: Joaquim Mullol (iDiBApS) (fundació clínic) elena Arrufat (fundació clínic) Antoni Xaubet (Hospital clínic) Maria Rueda (fundació clínic) Joan Bartra (Hospital clínic) liliana carbalho collABoRAtoRS: Antonio Valero (Hospital clínic) (erasmus portugal) Assumpció Martínez-Antón laura pujols tarrés (fundació clínic) franklin Mariño Sánchez (ccMD niH) isam Alobid (Hospital clínic) (Hospital clínic) yvonne torres (Ministeri d’educació, erola Ainsua enrich (fpi) Govern de panamà) poStDoctoRAl fellowS: esteban cano (Hospital clínic) Rosa torres (fiS) Josep Maria Guilemany (fiS - SeoRl) María del carmen Vennera (ciBeRes) Jordi Roca-ferrer (uB) tecHniciAnS: Joaquim ensenyat nora Mireia fuentes prado (Hospital clínic) ReSeARcH fellowS: (fundació clínic) Margarita Martin Andorrà Rosa Maria Muñoz-cano (fiS) María pérez Gonzalez (fundació clínic) francisco Garcia Garcia (fiS) (fundació clínic) Damiana Alvarez errico laura fernández-Bertolin (iDiBApS) (Juan de la cierva) francisco de Borja callejas (fiS) nuRSinG StAff: Manuel Bernal Sprekelsen Marta Gabasa (ciBeReS) Sílvia centellas (Hospital clínic) (Hospital clínic) Suha Jabr (Ministeri Assuumptes Sarai Sánchez fuentes exteriors i cooperació) (fundació clínic)

130 AReA 2 ReSpiRAtoRy, cARDioVASculAR, RenAl pAtHoBioloGy AnD BioenGineeRinG clinicAl AnD eXpeRiMentAl ReSpiRAtoRy iMMunoAlleRGy (iRce)

Immunofluorescent analysis showing StrateGic the differentiation of human nasal oBjectiveS polyp pseudostratified epithelium from epithelial stem cells in Air Liquid Inter- face (ALI) culture. At day 0, epithelial 1. Investigation of the mechanisms cells form a monolayer of undifferen- regulating inflammatory response tiated basal stem cells (p63+, basal stem cell marker), while at days 14 and remodelling in bronchial asthma, and 28 of culture, epithelial cells form rhinosinusitis and pulmonary intersti- a polarized and well-differentiated pseudo-stratified epithelium including tial diseases. ciliated cells (b-tubulin IV+, ciliated cell 2. Investigation of the mechanisms un- marker) and goblet cells (MUC5B+, goblet cell marker). DAPI (4’,6-dia- derlying food allergies. midino-2-phenylindole) was used for 3. Investigation of the mechanisms nucleus staining. Immunofluerescence was analysed using a epifluorescence involved in anaphylaxis of complex microscope (magnification ×63). etiopathogenesis. 4. Investigation of the mechanisms involved in loss of smell. 5. Study of the mechanisms regulat- inhibitors; prostaglandin E2 receptor ing the response to glucocorticoid 3 agonists) in asthma, rhinosinusitis main lineS treatment in inflammatory respiratory and pulmonary interstitial diseases of reSearcH diseases. based on in vitro models and animal 6. Study of the mechanisms involved in models of asthma and pulmonary 1. Molecular and cellular bases of the severe asthma and relationship with fibrosis. inflammatory response in asthma, alterations in glucocorticoid receptor 10. Study of the mechanisms of ana- rhinosinusitis and pulmonary intersti- function. phylactic reactions of multiple origin tial diseases. 7. Study of the relationship between (indolent mastocytosis, predisposing 2. Role of the MUC genes in the upper airway disorders (nasal and genetic alterations). modulation of mucosal secretion in sinuses) and alterations of the 11. Study of quality of life in nasosinusal respiratory diseases, remodeling of lower airway (asthma, bronchiecta- pathology. respiratory diseases and their regula- sia, chronic obstructive pulmonary 12. Loss of smell: role of nasosinusal tion with glucocorticoids. disease). inflammation, Parkinson’s disease 3. Role of arachidonic acid metabolites 8. Study of the mechanisms regulating and congenital alterations. (prostaglandins and leukotrienes) in the response to food allergens and 13. Identification and characterization of the etiopathogenesis of asthma, rhi- relationship with nonsteroidal anti- adapter molecules in the signaling nosinusitis and pulmonary interstitial inflammatory drugs and arachidonic of IgE high affinity receptor and KIT diseases. acid metabolism. receptor 4. Role of the angiotensin system in 9. New therapeutic modalities (en- lung fibrosis. dothelin, proteosome and COX-2

ReSeARCh gROUP naSoSinuSal inflammatory and olfactory reSearcH Group (inGenio)

Group Leader: Joaquim Mullol (IDIBAPS)

In this group we investigate dif- • We evaluate olfactory alterations and their ferent aspects of inflammatory mechanisms of action as diagnostic and severity nasosinusal disorders (allergic and markers. We have validated a proprietary olfac- non-allergic rhinitis, chronic rhino- tometric test (BAST-24), and have carried out an sinusitis, nasal polyposis): epidemiological study (OLFACAT) on olfactory • We explore the physiopathological mechanisms function in the Catalan population. of nasosinusal mucosal hypersecretion and the • We use an eosinophil and epithelial cell regulation of mucins and MUC genes. culture model for testing and comparing • We analyze the physiopathological and clinical the antiinflammatory action of different association of nasosinusal disorders with asth- drugs employed in situations of respiratory ma, atopy, NSAID intolerance and bronchiecta- inflammation, such as corticosteroids, sia, and their impact upon patient quality of life. antihistamines and antileukotrienes.

131 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Clinical and Experimental Respiratory Immunoallergy (IRCE)

PUBLICATIONS

oRiGinAlS 7 Navarro A, Valero A, Rosales MJ, 14 Soria G, Aguilar E, Tudela R, i.f.: 81.17 Mullol J. Clinical Use of Oral Antihista- Mullol J, Planas AM, Marin C. In mines and Intranasal Corticosteroids vivo magnetic resonance imaging 1 Alvarez-Errico D, Oliver-Vila I, in Patients With Allergic Rhinitis. J characterization of bilateral structural Ainsua-Enrich E, Gilfillan AM, Pica- INVEST ALLERG CLIN. 21:363-369. changes in experimental Parkinson’s do C, Sayos J, Martin M. CD84 Ne- I.F.: 1.49. disease: a T2 relaxometry study gatively Regulates IgE High-Affinity combined with longitudinal diffusion Receptor Signaling in Human Mast 8 Sanchez-Lopez J, Asturias JA, Enri- tensor imaging and manganese-en- Cells. J IMMUNOL. 187:5577-5586. que E, Suarez-Cervera M, Bartra J. Cu- hanced magnetic resonance imaging I.F.: 5.75. pressus arizonica Pollen: A New Pollen in the 6-. EUR J NEUROSCI. 33:1551- Involved in the Lipid Transfer Protein 1560. I.F.: 3.66. 2 Ramos-Casals M, Perez-Alvarez Syndrome?. J INVEST ALLERG CLIN. R, Perez-De-Lis M, Xaubet A, Bosch 21:522-526. I.F.: 1.49. 15 Alobid I, DePablo J, Mullol J, Cen- X. Pulmonary Disorders Induced by tellas S, Parramon G, Carrasco J, Arma- Monoclonal Antibodies in Patients 9 Valero A, Chivato T, Justicia JL, rio A, Bernal-Sprekelsen M. Increased with Rheumatologic Autoimmune Navarro AM. Diagnosis and treatment Cardiovascular and Anxiety Outcomes Diseases. AM J MED. 124:386-394. of grass pollen-induced allergic rhinitis but Not Endocrine Biomarkers of Stress I.F.: 5.12. in specialized current clinical practice During Performance of Endoscopic in Spain. ALLERGY ASTHMA PROC. Sinus Surgery A Pilot Study Among No- 3 Blanco I, Ribas J, Xaubet A, Go- 32:384-389. I.F.: 1.74. vice Surgeons. ARCH OTOLARYNGOL. mez FP, Roca J, Rodriguez-Roisin R, 137:487-492. I.F.: 1.57. Barbera JA. Effects of inhaled nitric 10 Vennera MD, Picado C, Mullol J, oxide at rest and during exercise Alobid I, Bernal-Sprekelsen M. Effica- 16 Videler WJ, Badia L, Harvey RJ, in idiopathic pulmonary fibrosis. cy of omalizumab in the treatment of Gane S, Georgalas C, VanDerMeu- J APPL PHYSIOL. 110:638-645. nasal polyps. THORAX. 66:824-825. len FW, Menger DJ, Lehtonen MT, I.F.: 4.24. I.F.: 6.53. Toppila-Salmi SK, Vento SI, Hytonen M, Hellings PW, Kalogjera L, Lund VJ, 4 Wang DY, Wardani RS, Singh K, 11 Valero A, Justicia JL, Anton E, Scadding G, Mullol J, Fokkens WJ. Thanaviratananich S, Vicente G, Xu Dordal T, Fernandez-Parra B, Lluch M, Lack of efficacy of long-term, low-dose G, Zia MR, Gulati A, Fang SY, Shi L, Montoro J, Navarro AM. Epidemiology azithromycin in chronic rhinosinusitis: a Chan YH, Price D, Lund VJ, Mullol of allergic rhinitis caused by grass po- randomized controlled trial. ALLERGY. J, Fokkens WJ. A survey on the llen or house-dust mites in Spain. AM 66:1457-1468. I.F.: 6.30. management of acute rhinosinusitis J RHINOL ALLERGY. 25:E123-E128. among Asian physicians. RHINOLO- I.F.: 1.88. 17 Pujols L, Fuentes-Prado M, GY. 49:264-271. I.F.: 0.80. Fernandez-Bertolin L, Alobid I, Roca- 12 Lopez-Matas MA, Larramendi Ferrer J, Mullol J, Picado C. Lower 5 Lopez-Matas MA, Ferrer A, La- CH, Ferrer A, Huertas AJ, Pagan JA, sensitivity of nasal polyp fibroblasts rramendi CH, Huertas AJ, Pagan JA, Garcia-Abujeta JL, Bartra J, Andreu C, to glucocorticoid anti-proliferative Garcia-Abujeta JL, Bartra J, Andreu Lavin JR, Carnes J. Identification and effects. RESP MED. 105:218-225. C, Lavin JR, Carnes J. Acidic ribo- quantification of tomato allergens: in I.F.: 2.53. somal protein 60S: A new tomato vitro characterization of six different allergen. FOOD CHEM. 127:638-640. varieties. ANN ALLERG ASTHMA IM. 18 Valero A, Mullol J, Herdman M, I.F.: 3.46. 106:230-238. I.F.: 2.80. Rosales MJ. Measuring outcomes in allergic rhinitis: psychometric charac- 6 Morell F, Cruz MJ, Gomez FP, 13 Fernandez-Bertolin L, Mullol J, teristics of a Spanish version of the Rodriguez-Jerez F, Xaubet A, Munoz Alobid I, Roca-Ferrer J, Picado C, Pujols congestion quantifier seven-item test X. Chacinero’s lung - hypersensitivity L. Impact of cell culture methods on (CQ7). HEALTH QUAL LIFE OUT. 9:-. pneumonitis due to dry sausage dust. the outcomes of the in vitro inflam- I.F.: 1.86. SCAND J WORK ENV HEA. 37:349- matory response in nasal polyps. RHI- 356. I.F.: 3.54. NOLOGY. 49:562-569. I.F.: 0.80.

132 AReA 2 ReSpiRAtoRy, cARDioVASculAR, RenAl pAtHoBioloGy AnD BioenGineeRinG clinicAl AnD eXpeRiMentAl ReSpiRAtoRy iMMunoAlleRGy (iRce)

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 72.62 25 11 4 19 Mullol J, Callejas FD, Martinez- 25 Valero A, Sanchez-Lopez J, Anton MA, Mendez-Arancibia E, Bartra J, Serrano C, Munoz-Cano R, 2010 58.14 21 5 7 Alobid I, Pujols L, Valero A, Picado Roca J, Picado C. Safety of Parecoxib 2011 81.17 28 9 11 C, Roca-Ferrer J. Mometasone and in Asthmatic Patients with Aspirin- desloratadine additive effect on eosi- Exacerbated Respiratory Disease. nophil survival and cytokine secretion INT ARCH ALLERGY IMM. 156:221- from epithelial cells. RESP RES. 12:-. 223. I.F.: 2.24. I.F.: 2.86. 2 Sahin G, Klimek L, Mullol J, Hor- 26 Guilemany JM, Marino-Sanchez mann K, Walther LE, Pfaar O. Nitric 20 Alobid I, Cardelus S, Benitez P, FS, Angrill J, Alobid I, Centellas S, Oxide: A Promising Methodological Guilemany JM, Roca-Ferrer J, Picado Pujols L, Berenguer J, Bernal-Spre- Approach in Airway Diseases. INT C, Bernal-Sprekelsen M, Mullol J. Per- kelsen M, Picado C, Mullol J. The ARCH ALLERGY IMM. 156:352-361. sistent asthma has an accumulative importance of smell in patients with I.F.: 2.24. impact on the loss of smell in patients bronchiectasis. RESP MED. 105:44- with nasal polyposis. RHINOLOGY. 49. I.F.: 2.53. 3 Papadopoulos NG, Christodoulou 49:519-524. I.F.: 0.80. I, Rohde G, Agache I, Almqvist C, 27 DeNotaris M, Solari D, Cavallo Bruno A, Bonini S, Bont L, Bossios 21 Castillo JA, Navarro A, Quirce LM, Ensenat J, Alobid I, Soria G, A, Bousquet J, Braido F, Brusselle G, S, Molina J, Garcia-Marcos L, Julia B, Gonzalez JB, Ferrer E, Prats-Galino A. Canonica GW, Carlsen KH, Chanez Valero A, Mullol J. Prevalence and cha- The Use of a Three-Dimensional No- P, Fokkens WJ, Garcia-Garcia M, racteristics of rhinitis in adult asthma- vel Computer-Based Model for Analy- Gjomarkaj M, Haahtela T, Holgate tic patients attending allergist, primary sis of the Endonasal Endoscopic ST, Johnston SL, Konstantinou G, care and pulmonologist settings in Approach to the Midline Skull Base. Kowalski M, Lewandowska-Polak Spain (AIR study). MED CLIN-BARCE- WORLD NEUROSURG. 75:106-113. A, Lodrup-Carlsen K, Makela M, LONA. 136:284-289. I.F.: 1.41. I.F.: 0.68. Malkusova I, Mullol J, Nieto A, Eller E, Ozdemir C, Panzner P, Popov T, 22 Quirce S, Plaza V, Picado C, Ven- 28 Jauregui I, Davila I, Sastre J, Psarras S, Roumpedaki E, Rukhadze nera M, Casafont J. Prevalence of Un- Bartra J, DelCuvillo A, Ferrer M, M, Stipic-Markovic A, Bom AT, Toskala controlled Severe Persistent Asthma Montoro J, Mullol J, Molina X, Valero E, VanCauwenberge P, VanDrunen C, in Pneumology and Allergy Hospital A. Validation of ARIA (Allergic Rhinitis Watelet JB, Xatzipsalti M, Xepapadaki Units in Spain. J INVEST ALLERG and its Impact on Asthma) classifi- P, Zuberbier T. Viruses and bacteria CLIN. 21:466-471. I.F.: 1.49. cation in a pediatric population: The in acute asthma exacerbations - A PEDRIAL study. PEDIAT ALLERG GA2LEN-DARE* systematic review. 23 Roca-Ferrer J, Garcia-Garcia FJ, IMM-UK. 22:388-392. I.F.: 2.87. ALLERGY. 66:458-468. I.F.: 6.30. Pereda J, Perez-Gonzalez M, Pujols L, Alobid I, Mullol J, Picado C. Reduced expression of COXs and production ReViewS eDitoRiAlS of prostaglandin E-2 in patients with i.f.: 10.03 i.f.: 20.40 nasal polyps with or without aspirin- intolerant asthma. J ALLERGY CLIN 1 Dordal MT, Lluch-Bernal M, San- 1 Sanz-Gallen P, Nogue S, Herrera- IMMUN. 128:66-U110. I.F.: 9.27. chez MC, Rondon C, Navarro A, Mozo I, Delclos GL, Valero A. Occupa- Montoro J, Matheu V, Ibanez MD, tional contact allergy to omeprazole and 24 Valero A, Izquierdo I, Giralt J, Fernandez-Parra B, Davila I, Conde J, fluoxetine. CONTACT DERMATITIS. Bartra J, DelCuvillo A, Mullol J. Ru- Anton E, Colas C, Valero A. Allergen- 65:118-119. I.F.: 3.67. patadine Improves Nasal Symptoms, Specific Nasal Provocation Testing: Quality of Life (ESPRINT-15) and Review by the Rhinoconjunctivitis 2 Mullol J, Alobid I. Combined Oral Severity in a Subanalysis of a Cohort Committee of the Spanish Society and Intranasal Corticosteroid Therapy: of Spanish Allergic Rhinitis Patients. of Allergy and Clinical Immunology. An Advance in the Management of J INVEST ALLERG CLIN. 21:229-235. J INVEST ALLERG CLIN. 21:1-12. Nasal Polyposis?. ANN INTERN MED. I.F.: 1.49. I.F.: 1.49. 154:365-U135. I.F.: 16.73.

133 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Clinical and Experimental Respiratory Immunoallergy (IRCE)

clinicAl GuiDelineS GRAntS foR ReSeARcH Martin M. Modulación de la activa- i.f.: 2.90 in pRoGReSS ción mastocitaria por miembros de la superfamilia de receptores CD150, 1 Alobid I, Anton E, Armengot M, Pujols L. Papel de la prostaglandina CD300 y moléculas adaptadoras rela- Chao J, Colas C, DelCuvillo A, Davila E2 en la determinación de la sen- cionadas. Sponsored by: Ministerio de I, Dordal MT, Escobar C, Fernandez- sibilidad de los glucocorticoides en Ciencia e Innovación, SAF2009-07548. Parra B, Gras-Cabrerizo JR, Ibanez enfermedades respiratorias de origen Duration: 01/01/2010-31/12/2012. MD, Lluch M, Mateu V, Montoro J, inflamatorio. Sponsored by: Instituto Gili JR, Mullol J, Navarro AM, Puma- de Salud Carlos III (ISCIII), PI08/0419. Bartra J. Red de Investigación de rola F, Rondon C, Sanchez-Hernandez Duration: 01/01/2009-30/12/2011. Reacciones Adversas a Alérgenos y MC, Sarandeses A, Soler R, Valero Fármacos (RIRAAF). Sponsored by: AL, Rhinoconjunctivitis Committee, Mullol J. Estudio del papel de la in- Instituto de Salud Carlos III (ISCIII), Spanish Society Of Allergy And Clini- flamación neurógenano alérgica en la FIS_RETIC07 RD07/0064/0006. Dura- cal Immunology, Rhinology And Aller- expresión de mucinas y el proceso tion: 29/02/2008-31/12/2012. gy Commission, Spanish Society of de remodelado de la mucosa respi- Otorhinolaryngology. SEAIC-SEORL. ratoria nasosinusal. Sponsored by: Picado C. Inflamació i tractament de Consensus Document on Nasal Po- Ministerio Sanidad y Consumo, PI- les malalties respiratòries. Sponsored lyposis. POLINA Project. J INVEST 0801PI08/0188. Duration: 01/01/2009- by: AGAUR_SGR09 ,2009_SGR_954. ALLERG CLIN. 21:1-58. I.F.: 1.49. 30/12/2012. Duration: 15/09/2009-31/12/2013.

2 Alobid I, Alonso JR, Barrot C, Picado C. Estudio de la regulación Benitez P, Canizares S, Castanyer epigenética del gen de la COX-2 en el DoctoRAl tHeSeS T, Centellas S, Civeira E, Climent asama con intolerancia a los antiinfla- B, Duenas A, Fernandez-Sola J, matorios no esteroideos. Sponsored Picado C, Martin M. Paper regulador Ferrer A, Gene M, Godas T, Gomez by: Ministerio Sanidad y Consumo, de la Prostaglandina E2 en l’activació E, Montori E, Munne P, Nogue S, PI080249. Duration: 01/01/2009- osmòtica en mastòcits. PhD student: Picado C, Rovira E, Sanz P, Valero A. 30/12/2011. Ivonne Torres Atencio, Autònoma de Multiple chemical sensitivity. MED Barcelona (UAB). CLIN-BARCELONA. 136:683-687. Xaubet A. Implicación del sistema de I.F.: 1.41. la angiotensina en la etiopatogenia de la fibrosis pulmonar idiopática. Sponsored by: Instituto de Salud Car- MulticentRicS los III (ISCIII), PI09/00672. Duration: i.f.: 33.63 01/01/2010-30/12/2012.

1 Noble PW, Albera C, Bradford Valero AL. Efecto clínico e inflama- WZ, Costabel U, Glassberg MK, torio nasal tras la aplicación frl factor Kardatzke D, King TE, Lancaster L, de agregación plaquetaria (PAF). Sahn SA, Szwarcberg J, Valeyre D, Sponsored by: Instituto de Salud Car- DuBois RM. Pirfenidone in patients los III (ISCIII), PI0901202. Duration: with idiopathic pulmonary fibrosis 01/01/2010-30/12/2012. (CAPACITY): two randomised trials. LANCET. 377:1760-1769. Bartra J. Anafilaxia por alergia alimen- I.F.: 33.63. taria inducida por AINEs y ejercicio (AAAIA/E): Mecanismos de acción y efecto protector de PGE2. Spon- sored by: Instituto de Salud Carlos III (ISCIII), PI11/01326. Duration: 31/12/2011-31/12/2014.

134 AReA 2

Respiratory, cardiovascular and renal Team involved in: pathobiology and bioengineering Inflammation and repair in respiratory illnesses gROUP MeMBeRS StrateGic oBjectiveS

The general objective of the group is to investigate the inflammatory and tissue repair mechanisms in chronic obstructive pulmo- teAM leADeR nary disease (COPD), their clinical-functional Alvar Agustí García-navarro correlation, the diagnostic, prognostic and (Hospital clínic) therapeutic implications of such knowledge, tel.: 93 227 54 00 (1701) and particularly their relevance in relation to fax: 93 227 98 68 pulmonary oncogenesis. COPD is presently e-mail: [email protected] the fourth most common cause of death in the world, and will rank third within a decade. iDiBApS MeMBeRS: Lung cancer is the most common malignant eugeni Ballester (Hospital clínic) tumor in males (and soon also will be the Abel Gomez-caro (Hospital clínic) most common malignancy in females), and Ramon Marrades (Hospital clínic) involves one of the poorest prognosis with the currently available treatment options. collABoRAtoRS: Dra. Rosa faner (ciBeRes) main lineS of Sra. Gemma Sunyer (ciBeRes) reSearcH nuria Gonzalez (ciBeRes) tamara cruz (ciBeRes) 1. Mechanisms of autoimmunity and auto- inflammation that may contribute to the pathogenesis of acute outbreaks of the disease (in collaboration with the group headed by Dr. J. Yagüe, of the Department of Immunology of the Clinic Hospital). 2. Mechanisms of abnormal catabasis (resolution of the inflammation) that perpetuate the inflammatory response even after smoking cessation (a necessary yet insufficient treatment measure) (in collaboration with Dr. J. Clària, of the Clinic Hospital Biomedical Diag- nostic Center) and Dra. Aina Noguera from Hospital Universitari Son Espases, Mallorca. 3. Mechanisms of oncogenesis in COPD (in collaboration with investigators of the Fun- dació Caubet-Cimera in Mallorca and the CIBER of respiratory diseases (CIBERES): SINECAN project). 4. Application of the methodology of systems biology (“omic” platforms and bioinformatics) to COPD, with a view to integrate the cellular and molecular alterations with clinical data. This line is developed in the setting of the CIBER of respiratory diseases (www.ciberes.org), involving a strategic alliance with the Institute for Systems Biology (Seattle, USA), Harvard University (USA) and the pharmaceutical industry with an interest in COPD.

135 ReSPIRATORy, CARDIOvASCULAR AND ReNAL PAThOBIOLOgy AND BIOeNgINeeRINg Inflammation and repair in respiratory illnesses

PUBLICATIONS

oRiGinAlS 5 Sanchez-Lorente D, Gomez- 10 Jones PW, Rennard SI, Agusti i.f.: 115.32 Caro A, Jimenez MJ, Molins L. A, Chanez P, Magnussen H, Fabbri Apnoeic oxygenation on one-lung L, Donohue JF, Bateman ED, Gross 1 Nunez B, Sauleda J, Anto JM, ventilation in functionally impaired NJ, Lamarca R, Caracta C, Gil EG. Julia MR, Orozco M, Monso E, patients during sleeve lobectomy. Efficacy and safety of once-daily Noguera A, Gomez FP, Garcia- EUR J CARDIO-THORAC. 39:E77- aclidinium in chronic obstructive Aymerich J, Agusti A. Anti-Tissue E79. I.F.: 2.29. pulmonary disease. RESP RES. 12:-. Antibodies Are Related to Lung I.F.: 2.86. Function in Chronic Obstructive 6 Vestbo J, Edwards LD, Scanlon Pulmonary Disease. AM J RESP PD, Yates JC, Agusti A, Bakke P, 11 Sanchez-De-La-Torre M, Pie- CRIT CARE. 183:1025-1031. Calverley PMA, Celli B, Coxson rola J, Vidal C, Barcelo A, DeLaPe- I.F.: 10.19. HO, Crim C, Lomas DA, Macnee na M, Hussain Z, Capote F, Duran W, Miller BE, Silverman EK, Tal- J, Agusti AGN, DeLecea L, Torres 2 Garcia-Aymerich J, Gomez FP, Singer R, Wouters E, Rennard G, Esquinas C, Martinez M, Barbe Benet M, Farrero E, Basagana X, SI. Changes in Forced Expiratory F. Non-synonymous polymorphism Gayete A, Pare C, Freixa X, Ferrer J, Volume in 1 Second over Time in the neuropeptide S precursor Ferrer A, Roca J, Galdiz JB, Sauleda in COPD. NEW ENGL J MED. gene and sleep apnea. SLEEP J, Monso E, Gea J, Barbera JA, 365:1184-1192. I.F.: 53.49. BREATH. 15:403-408. I.F.: 1.68. Agusti A, Anto JM. Identification and prospective validation of clinica- 7 Agusti A, Vestbo J. Current Con- 12 Navarro A, Diaz T, Gallardo lly relevant chronic obstructive pul- troversies and Future Perspectives E, Vinolas N, Marrades RM, Gel monary disease (COPD) subtypes. in Chronic Obstructive Pulmonary B, Campayo M, Quera A, Bandres THORAX. 66:430-437. I.F.: 6.53. Disease. AM J RESP CRIT CARE. E, Garcia-Foncillas J, Ramirez J, 184:507-513. I.F.: 10.19. Monzo M. Prognostic Implications 3 Campayo M, Navarro A, Vinolas of miR-16 Expression Levels in N, Tejero R, Munoz C, Diaz T, Ma- 8 Gomez-Caro A, Garcia S, Re- Resected Non-Small-Cell Lung rrades R, Cabanas ML, Gimferrer guart N, Cladellas E, Arguis P, Cancer. J SURG ONCOL. 103:411- JM, Gascon P, Ramirez J, Monzo Sanchez M, Gimferrer JM. De- 415. I.F.: 2.43. M. A Dual Role for KRT81: A miR- termining the appropriate sleeve SNP Associated with Recurrence lobectomy versus pneumonectomy 13 Campayo M, Vinolas N, Na- in Non-Small-Cell Lung Cancer and ratio in central non-small cell lung varro A, Carcereny E, Casas F, Gel a Novel Marker of Squamous Cell cancer patients: an audit of an ag- B, Diaz T, Gimferrer JM, Marrades Lung Carcinoma. PLOS ONE. 6:-. gressive policy of pneumonectomy RM, Ramirez J, Monzo M. Single I.F.: 4.41. avoidance. EUR J CARDIO-THO- Nucleotide Polymorphisms in To- RAC. 39:352-359. I.F.: 2.29. bacco Metabolism and DNA Repair 4 Agusti A, Sobradillo P, Celli Genes and Prognosis in Resected B. Addressing the Complexity of 9 Puente-Maestu L, Lazaro A, Non-Small-Cell Lung Cancer. J Chronic Obstructive Pulmonary Tejedor A, Camano S, Fuentes M, SURG RES. 167:E5-E12. I.F.: 2.24. Disease From Phenotypes and Bio- Cuervo M, Navarro BO, Agusti markers to Scale-Free Networks, A. Effects of exercise on mito- Systems Biology, and P4 Medicine. chondrial DNA content in skeletal AM J RESP CRIT CARE. 183:1129- muscle of patients with COPD. 1137. I.F.: 10.19. THORAX. 66:121-127. I.F.: 6.53.

136 AReA 2 ReSpiRAtoRy, cARDioVASculAR, RenAl pAtHoBioloGy AnD BioenGineeRinG inflAMMAtion AnD RepAiR in ReSpiRAtoRy illneSSeS

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 ReViewS MulticentRicS 2009 39.11 3 3 0 i.f.: 2.25 i.f.: 2.86 2010 99.55 14 6 5 2011 115.32 13 9 2 1 Silverman EK, Vestbo J, Agusti 1 Dickens JA, Miller BE, Ed- A, Anderson W, Bakke PS, Barnes wards LD, Silverman EK, Lomas KC, Barr RG, Bleecker ER, Boezen DA, Tal-Singer R. COPD associa- HM, Burkart KM, Celli BR, Cho tion and repeatability of blood bio- MH, Cookson WO, Croxton T, Da- markers in the ECLIPSE cohort. ley D, Demeo DL, Gan W, Garcia- RESP RES. 12:-. I.F.: 2.86. Aymerich J, Hall IP, Hansel NN, Hersh CP, Kalsheker N, Kiley JP, Kim WJ, Lambrechts D, Lee SD, GRAntS foR ReSeARcH Litonjua AA, Lomas DA, London in pRoGReSS SJ, Nishimura M, Nørdestgaard BG, O’donnell CJ, Postma DS, Agusti A. Cohorte española de Puhan MA, Tesfaigzi Y, Tobin MD, pacientes con EPOC Avanzada Vogelmeier C, Wilk JB, Wouters (CEPA): Inflamosoma, comorbi- E, Young RP, Ziegler-Heitbrock L, lidad y curso clínico. Sponsored Macnee W, Crapo JD. Opportuni- by: Instituto de Salud Carlos III ties and challenges in the genetics (ISCIII), PI09/0629. Duration: of COPD 2010: an International 01/01/2010-31/12/2012. COPD Genetics Conference report. COPD. 8:121-123. I.F.: 2.25. Agustí A. Inflamasoma, enfermedades auto-inflamatorias y EPOC. Sponsored by: SEPAR, 870. Dura- eDitoRiAlS tion: 01/06/2010-30/06/2011. i.f.: 12.45 Agustí A. Riboleucograma en la 1 Agusti A, Celli B. Avoiding con- Enfermedad Pulmonar Obstruciva fusion in COPD: from risk factors Crónica. Sponsored by: SEPAR, to phenotypes to measures of 133/2011. Duration: disease characterisation. EUR RES- 01/06/2011-30/06/2012. PIR J. 38:749-751. I.F.: 5.92.

2 Fabbri LM, Beghe B, Agusti A. Cardiovascular mechanisms of death in severe COPD exacerbation: time to think and act beyond guidelines. THORAX. 66:745-747. I.F.: 6.53.

137 AReA 2

Respiratory, cardiovascular and renal Team involved in: pathobiology and bioengineering Genetic and urological tumours

gROUP MeMBeRS StrateGic oBjectiveS

At present, the research group in urological oncology is conducting two main teAM leADeR lines of research, based on the two Antonio Alcaraz (Hospital clínic) most frequent urological tumors: urothe- tel.: 93 227 55 45 lial and prostate cancer. fax: 93 227 55 45 The objectives are summarized below: e-mail: [email protected] 1. Identification of noninvasive molecular markers for the diagnosis and progno- iDiBApS MeMBeRS: sis of bladder and prostate cancer. Maria José Ribal (Hospital clínic) 2. Study of molecular markers to Mireia Musquera (Hospital clínic) identify dsseminated tumour cells lourdes Mengual (fundació clínic) and the response to chemotherapy in patients with muscle invasive ReSeARcH fellowS: bladder cancer. Alexandru ciudin (emili letang award) 3. Determination of molecular prog- cristina Gázquez (iDiBApS) nostic factors in upper urinary tract tumors. tecHniciAnS: Mercedes ingelmo-torres main lineS (fundació clínic) of reSearcH

ADMiniStRAtiVe StAff: • Study of gene expression profiles in Maite Dalet (fundació clínic) urine for noninvasive diagnosis and prognosis of bladder tumors. collABoRAtoRS: • Identification of micro-RNA in urine for laura izquierdo (Hospital clínic) the noninvasive diagnosis of bladder Antoni Riera (estudiant en pràctiques) tumors. Antoine G. Van Der Heijden • Determination of disseminated tu- (Radboud university nijmegen Medical center) mor disease in patients with muscle Juan José lozano invasive bladder cancer, based on (plataforma de Bioinformática, ciBeReHD) evaluation of the gene expression of bladder-specific markers in lymph nodes and peripheral blood. • Study of the genic expression profile associated with response to neoadjuvant chemotherapy in patients with muscle invasive bladder cancer. • Study of methylation profiles of urine cells as a method for noninvasive diagnosis of bladder cancer. • Study of the prognostic factors in upper urinary tract tumors PCR. • Study of gene expression and miRNA profiles in urine for noninvasive diagnosis and prognosis of prostate tumors.

138 AReA 2 ReSpiRAtoRy, cARDioVASculAR, RenAl pAtHoBioloGy AnD BioenGineeRinG Genetic AnD uRoloGicAl tuMouRS

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 19.66 7 3 3 oRiGinAlS 6 Madersbacher S, Alcaraz A, Em- i.f.: 28.86 berton M, Hammerer P, Ponholzer 2010 42.53 15 4 4 A, Schroder FH, Tubaro A. The in- 2011 28.86 7 3 3 1 Alcaraz A, Musquera M, Peri L, fluence of family history on prostate Izquierdo L, Garcia-Cruz E, Huguet cancer risk: implications for clinical J, Alvarez-Vijande R, Campistol management. BJU INT. 107:716-721. JM, Oppenheimer F, Ribal MJ. I.F.: 3.19. Feasibility of Transvaginal Natural GRAntS foR ReSeARcH Orifice Transluminal Endoscopic 7 Leveridge M, Musquera M, Evans in pRoGReSS Surgery-Assisted Living Donor A, Cardella C, Pei Y, Jewett M, Robi- Nephrectomy: Is Kidney Vaginal nette M, Finelli A. Renal cell carcino- Alcaraz A. miRNAs para el diag- Delivery the Approach of the Fu- ma in the native allograft kidneys of nóstico no invasivo del carcinoma ture?. EUR UROL. 59:1019-1025. renal transplant recipients. J UROL. urotelial. Sponsored by: Instituto de I.F.: 8.84. 186(1):219-23. I.F.: 3.86 Salud Carlos III (ISCIII) ,PI10/01145. Duration: 01/01/2011-31/12/2013. 2 Bermudo R, Abia D, Mozos A, Garcia-Cruz E, Alcaraz A, Ortiz ReViewS Alcaraz A. Grup de recerca en urolo- AR, Thomson TM, Fernandez PL. i.f.: 8.84 gia oncològica (GRUO). Sponsored Highly sensitive molecular diag- by: AGAUR_SGR09, 2009_SGR_837. nosis of prostate cancer using 1 Catto JWF, Alcaraz A, Bjartell Duration: 20/07/2009-31/12/2013. surplus material washed off from AS, White RD, Evans CP, Fussel S, biopsy needles. BRIT J CANCER. Hamdy FC, Kallioniemi O, Mengual 105:1600-1607. I.F.: 4.83. L, Schlomm T, Visakorpi T. MicroR- NA in Prostate, Bladder, and Kidney 3 Monsalve C, Izquierdo L, Alca- Cancer: A Systematic Review. EUR raz A. Interactions Between He- UROL. 59:671-681. I.F.: 8.84. modynamics and Pharmacology in Kidney Transplantation. TRANSPL P. 43:359-362. I.F.: 0.99. clinicAl GuiDelineS i.f.: 8.84 4 Garcia-Cruz E, Romero Otero J, Martínez Salamanca JI, Leibar 1 Stenzl A, Cowan NC, De San- Tamayo A, Rodríguez Antolin A, tis M, Kuczyk MA, Merseburger Astobieta Odriozola A, Alcaraz A. AS, Ribal MJ, Sherif A, Witjes JA. Linguistic and Psychometric Valida- Treatment of muscle-invasive and tion of the Erection Hardness Score metastatic bladder cancer: update to Spanish. J SEX MED. 8:470-474. of the EAU guidelines. EUR UROL. I.F.: 3.96. 59(6):1009-18. I.F.: 8.84.

5 Alcaraz A, Burgos FJ, Cozar JM, Gomez-Veiga F, Morote J, Solsona eDitoRiAlS E, Unda M, Carballido J. Prostate i.f.: 8.84 cancer in Spain: from guidelines to clinical practice. BJU INT. 108:61- 1 Ribal MJ. Molecular Profiling of 66. I.F.: 3.19. Renal Cancer: The Journey to Clini- cal Application. EUR UROL. 59:731- 733. I.F.: 8.84.

139

AReA 3

Liver, digestive system and metabolism

Gynecological endocrinology and human reproduction StrateGic oBjectiveS gROUP MeMBeRS The global aim of this research group for the coming years is to advance in the knowledge of different aspects relating to the physiopathology of human reproduction: from endocrino- teAM leADeR logical considerations to the most impor- Juan Balasch (Hospital clínic) tant benign and malignant pathological tel.: 93 227 54 36 processes of the female reproductive fax: 93 227 93 25 system, as well as the investigation and e-mail: [email protected] treatment of human reproduction failure. xxxxxx More specifically, the main objectives iDiBApS MeMBeRS: collABoRAtoRS: of our research group are to advance francisco carmona (Hospital clínic) Gemma casals (Hospital clínic) in the existing lines of work, with the camil castelo-Branco (Hospital clínic) Roser casamitjana (Hospital clínic) purpose of: Montserrat creus (Hospital clínic) Salvadora cívico (Hospital clínic) 1. Determining the most relevant Dolors Manau trullás (fundació clínic) Marta Guimerà (Hospital clínic) mechanisms in the pathogenesis Bienvenido puerto (Hospital clínic) José luís Ballescá (Hospital clínic) of reproductive failure (sterility, francisco fábregues (Hospital clínic) Mª Angels Martínez-Zamora repeated miscarriages, repeated Jaume pahisa (Hospital clínic) (Hospital clínic) implant failure after in vitro fertiliza- Aureli torné (Hospital clínic) Joana peñarrubia Alonso tion) and of the principal female (fundació clínic) reproductive disease processes ReSeARcH fellowS: Jaume ordi (Hospital clínic) (endometriosis, uterine myoma, ge- elena Suárez cisneros (iDiBApS) nital cancer). 2. Optimizing and innovating as far as possible the preventive or therapeutic potential in the aforementio- ned situations.

main lineS of reSearcH

1. Reproductive failure markers Analysis of the possible role of new markers of hemostasis alterations as a new pathogenic mechanism of thrombotic disease in early and advanced pregnancy, in patients with or without antiphospholipid syndrome. Study is also made of the usefulness of immunohistochemical and quantitative and qualitative proteomic parameters in the human endo- metrium as markers of endometrial receptiveness. In-depth research of the pathogenic mechanisms involved in the block of pre-implantation embryonic development in vitro. 2. ovarian dysfunction and stimulation/hyperstimulation Investigation of the possibilities of

142 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM GynecoloGicAl enDocRinoloGy AnD HuMAn RepRoDuction

PUBLICATIONS original publications from 2009 to 2011 ultrasound, hormonal, endocrine- Year IF Total Q 1 Q 2 metabolic and genetic markers in 2009 91.94 25 18 2 relation to the prediction of ovarian oRiGinAlS 2010 89.86 26 16 3 response. Study of the role of LH i.f.: 76.25 and the androgens as ovarian sen- 2011 76.25 21 15 2 sitizing factors in relation to ulterior 1 Almog B, Shehata F, Suissa stimulation with FSH. Investigation S, Holzer H, Shalom-Paz E, La- of the possible role of the ovarian Marca A, Muttukrishna S, Blazar follicular cells (granulosum, ma- A, Hackett R, Nelson SM, Cunha crophages) in the pathogenesis of JS, Eldar-Geva T, Margalioth EJ, Rios J, Pahisa J, Balasch J, Ordi J. ovarian hyperstimulation syndrome, Raine-Fenning N, Jayaprakasan K, Does human papillomavirus infec- with the exploration of new ovarian Mcilveen M, Wunder D, Freour T, tion imply a different prognosis in stimulation or endometrial prepa- Nardo LG, Balasch J, Penarrubia J, vulvar squamous cell carcinoma?. ration protocols allowing improved Smeenk J, Gnoth C, Godehardt E, GYNECOL ONCOL. 122:509-514. results in assisted reproduction Lee TH, Lee MS, Levin I, Gamzu R, I.F.: 3.76. techniques. Tulandi T. Age-related normograms 3. optimization of the surgical ma- of serum antimullerian hormone le- 6 Aragao FD, Abrantes CG, nagement of diseases of the re- vels in a population of infertile wo- Gabriel RE, Sousa MF, Castelo- productive apparatus men: a multicenter study. FERTIL Branco C, Moreira MH. Effects of Designed to analyze the role of the STERIL. 95:2359-U280. I.F.: 3.96. body composition and menopause surgical variables allowing improve- characteristics on maximal oxygen ment of the results and reduction 2 Del Pino M, Rodriguez- uptake of postmenopausal women. of the morbidity in the surgical Carunchio L, Alonso I, Torne A, MENOPAUSE. 18:1191-1197. treatment of benign and malignant Rodriguez A, Fuste P, Castillo P, I.F.: 3.32. disorders of the female reproducti- Nonell R, Abu-Lhiga N, Ordi J. Cli- ve apparatus. This also implies de- nical, colposcopic and pathological 7 Fabregues F, Iraola A, Casals fining the prognostic value of HPV characteristics of cervical and G, Creus M, Carmona F, Balasch J. (human papillomavirus) detection vaginal high-grade lesions negati- Evaluation of two doses of recom- and viral typing as prognostic and ve for HPV by Hybrid Capture 2. binant human luteinizing hormone progression markers of precance- GYNECOL ONCOL. 122:515-520. supplementation in down-regulated rous lesions of the cervix, vagina I.F.: 3.76. women of advanced reproductive and vulva. age undergoing follicular stimula- 3 Escudero JM, Auge JM, Filella tion for IVF: a randomized clinical X, Torne A, Pahisa J, Molina R. study. EUR J OBSTET GYN R B. Comparison of Serum Human 158:56-61. I.F.: 1.76. Epididymis Protein 4 with Cancer Antigen 125 as a Tumor Marker in 8 Castelo-Branco C, Martinez MJ, Patients with Malignant and Non- Balasch J. Further data favouring malignant Diseases. CLIN CHEM. hormonal dependency of cerebral 57:1534-1544. I.F.: 6.89. meningiomas: evidence from a patient treated with cabergoline. 4 Valsky DV, Martinez-Serrano GYNECOL ENDOCRINOL. 27:134- MJ, Sanz M, Eixarch E, Acosta 137. I.F.: 1.46. ER, Martinez JM, Puerto B, Grata- cos E. Cord occlusion followed by 9 Comas M, Crispi F, Gomez O, laser cord transection in monocho- Puerto B, Figueras F, Gratacos E. rionic monoamniotic discordant Gestational age- and estimated twins. ULTRASOUND OBST GYN. fetal weight-adjusted reference ran- 37:684-688. I.F.: 3.16. ges for myocardial tissue Doppler Radical cervix resection piece obtained via indices at 24-41 weeks’ gestation. laparoscopic surgery from a young patient 5 Alonso I, Fuste V, DelPino ULTRASOUND OBST GYN. 37:57- with invasive cervical cancer, but with a M, Castillo P, Torne A, Fuste P, 64. I.F.: 3.16. wish to preserve fertility.

143 LIveR, DIgeSTIve SySTeM AND MeTABOLISM

Gynecological endocrinology and human reproduction

10 Molina R, Escudero JM, L, Ordi J, Sigauque B, Cistero P, Infecting Mozambican Pregnant Auge JM, Filella X, Foj L, Torne A, Mandomando I, Alonso PL, Mayor Women. J INFECT DIS. 204:27-35. Lejarcegui J, Pahisa J. HE4 a no- A. Persistence of Plasmodium I.F.: 6.29. vel tumour marker for ovarian can- falciparum Parasites in Infected cer: comparison with CA 125 and Pregnant Mozambican Women after ROMA algorithm in patients with Delivery. INFECT IMMUN. 79:298- ReViewS gynaecological diseases. TUMOR 304. I.F.: 4.10. i.f.: 1.76 BIOL. 32:1087-1095. I.F.: 2.03. 17 Martinez-Zamora MA, Creus 1 Arjona JE, Velasco E, Cervelo P, 11 Kirchner T, Munoz D, Forns M, Tassies D, Reverter JC, Civico S, Espejo E, Pizarro I, Carrasco S, Cas- M, Penarrubia J, Balasch J. Carmona F, Balasch J. Reduced plas- telo-Branco C. Pregnancy following Identifying by means of coping ma fibrinolytic potential in patients radical vulvectomy for carcinoma of typologies and primary appraisal with recurrent implantation failure the vulva: a case report and literatu- the likelihood of positive beta-hCG after IVF and embryo transfer. HUM re review. EUR J OBSTET GYN R B. test results in women undergoing REPROD. 26:510-516. I.F.: 4.36. 158:113-114. I.F.: 1.76. IVF treatment: a preliminary study. HUM REPROD. 26:1138-1143. 18 Martin-Jaular L, Ferrer M, Cal- I.F.: 4.36. vo M, Rosanas-Urgell A, Kalko S, eDitoRiAlS Graewe S, Soria G, Cortadellas N, i.f.: 1.94 12 Bardaji A, Sigauque B, Sanz Ordi J, Planas A, Burns J, Heussler S, Maixenchs M, Ordi J, Aponte V, DelPortillo HA. Strain-specific 1 Castelo-Branco C. Physical JJ, Mabunda S, Alonso PL, Me- spleen remodelling in Plasmodium function in overweight postme- nendez C. Impact of Malaria at the yoelii infections in Balb/c mice nopausal women. CLIMACTERIC. End of Pregnancy on Infant Morta- facilitates adherence and spleen 14:689-690. I.F.: 1.94. lity and Morbidity. J INFECT DIS. macrophage-clearance escape. CELL 203:691-699. I.F.: 6.29. MICROBIOL. 13:109-122. I.F.: 5.63. MulticentRicS 13 Castelo-Branco C, Hidalgo 19 Sabria J, Barcelo-Vidal C, Arigi- i.f.: 4.72 MJC. Isoflavones: effects on bone ta M, Jimenez JM, Puerto B, Borrell health. CLIMACTERIC. 14:204- A. The CUSUM test applied in pros- 1 Gomez-Gil E, DeAntonio IE, Al- 211. I.F.: 1.94. pective nuchal translucency quality maraz MC, Sieso TG, Rabinovich IH, review. ULTRASOUND OBST GYN. Escofet FS. The demand for health 14 Hidalgo MJC, Castelo-Branco 37:582-587. I.F.: 3.16. care services in the gender identity C. Optimizing soy isoflavones units of Andalusia and Catalonia du- effect in postmenopausal women: 20 Fabregues F, Castelo-Branco C, ring the period of 2000 to 2009. REV the impact of timing on climacte- Carmona F, Guimera M, Casamitjana CLIN ESP. 211:233-239. I.F.: 0.76. ric symptoms. GYNECOL ENDO- R, Balasch J. The effect of different CRINOL. 27:696-700. I.F.: 1.46. hormone therapies on anti-mullerian 2 Nnoaham KE, Hummelshoj L, hormone serum levels in anovula- Webster P, D’hooghe T, Nardone FD, 15 Carmona F, Martinez-Zamora tory women of reproductive age. Nardone CD, Jenkinson C, Kennedy MA, Rabanal A, Martinez-Roman GYNECOL ENDOCRINOL. 27:216- SH, Zondervan KT. Impact of endo- S, Balasch J. Ovarian cystectomy 224. I.F.: 1.46. metriosis on quality of life and work versus laser vaporization in the productivity: a multicenter study treatment of ovarian endometrio- 21 Rovira-Vallbona E, Dobano C, across ten countries. FERTIL STE- mas: a randomized clinical trial Bardaji A, Cistero P, Romagosa C, RIL. 96:366-U431. I.F.: 3.96. with a five-year follow-up. FERTIL Serra-Casas E, Quinto L, Bassat STERIL. 96:251-254. I.F.: 3.96. Q, Sigauque B, Alonso PL, Ordi J, Menendez C, Mayor A. Transcription 16 Serra-Casas E, Menendez of var Genes Other Than var2csa in C, Dobano C, Bardaji A, Quinto Plasmodium falciparum Parasites

144 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM GynecoloGicAl enDocRinoloGy AnD HuMAn RepRoDuction

GRAntS foR ReSeARcH DoctoRAl tHeSeS in pRoGReSS Balasch J, Carmona F, Tassies D. Balasch J. Efectos de los fármacos Análisis de la fibrinólisis como nuevo empleados para la estimulación mecanismo patogénico trombótico ovárica sobre las células foliculares. en la patología gestacional precoz y Implicaciones en el síndrome de avanzada. Relación con los anticuer- hiperestimulación ovárica. Spon- pos antifosfolipídicos. PhD student: sored by: Instituto de Salud Carlos Mª Ángeles Martínez Zamora. III (ISCIII), PI070355. Duration: 26/11/2007-31/07/2011.

Balasch J. Caracterización del pro- teoma del epitelio y del estroma endometriales y expresión proteica diferencial en la ventana de implan- tación. Sponsored by: Fundación Salud 2000, PI040634. Duration: 01/01/2009-31/12/2011.

Balasch J. Grup de Fisiopatologia de la Reproducció Humana. Sponsored by: Generalitat de Catalunya, 2009 SGR 1099. Duration: 01/01/2009- 31/12/2013.

Ordi J. Patrones de expresión de miRNA en la progresión y la trans- formación maligna de las lesiones precursoras del cáncer de cérvix uterino. Sponsored by: Instituto de Salud Carlos III (ISCIII), PI09/1084. Duration: 01/01/2010-31/12/2012.

Torne A. Valor clínico de la infección múltiple por virus del papiloma humano (VPH) en pacientes con lesiones premalignas y cáncer de cuello uterino. Sponsored by: Instituto de Salud Carlos III (ISCIII), PI09/1524. Duration: 01/01/2010-31/12/2012.

145 AReA 3 Team involved in: Liver, digestive system and metabolism

Fetal and perinatal medicine

gROUP MeMBeRS

teAM leADeR eduard Gratacós (Hospital clínic) tel.: 93 227 99 46 fax: 93 227 56 05 e-mail: [email protected] xxxxxx iDiBApS MeMBeRS: ADMiniStRAtiVe StAff: Antoni Borrell (Hospital clínic) Maite Aguilera (fundació clínic) francesc Botet (Hospital clínic) estefanía callado (fundació clínic) Vicenç cararach (Hospital clínic) pere lorente (fundació clínic) Xavier carbonell (Hospital clínic) elena casals (Hospital clínic) collABoRAtoRS: francesc figueras (Hospital clínic) Jordi Bellart (Hospital clínic) Josep figueras (Hospital clínic) olga Gómez (Hospital clínic) Josep Maria Martinez-crespo Anna Gonce (Hospital clínic) (Hospital clínic) Xavier Miracle (Hospital clínic) Montserrat palacio (Hospital clínic) Mª Dolors Salvía (Hospital clínic) Josep oriol coll (Hospital clínic) iratxe torre (fundació clínic-Sara Borrell) fátima crispi (iDiBApS) Rogelio cruz (fundació clínic) elisenda eixarch (iDiBApS-Rio Hortega) poStDoctoRAlS fellowS: Joan Junyent (fundació clínic) emilia Ruthy Acosta-Rojas teresa cobo (iDiBApS - Río Hortega) (fundació clínic-ciBeR-eR) Mar Benassar (Hospital clínic) nelly fabiola padilla (fundació clínic) leticia Vinyoles (fundació clínic) Magdalena Sanz (iDiBApS) Alba camacho (fundació clínic) Marta García (fundació clínic) ReSeARcH fellowS: ivan Amat-Roldan (fundació clínic) ViSitinG ScientiStS: Anna González (pre-doc iDiBApS) R. Bartrons Alvaro pérez (iDiBApS) D. Valsky Dafnis Batallé (ciBeR-eR) iosefine Stergitou Jesús Mª Domínguez (ciBeR-eR) Violeta tenorio (fundació clínic) Mónica cruz-lemini (fundació clínic) patricia Garcia (fundació clínic) Stefan Savchev (fundació clínic)

tecHniciAnS: imma Mercade (fundació clínic) Marina coll (fundació clínic) Ariadna Arbat (fundació clínic)

nuRSinG StAff: Angela Arranz (fundació clínic)

146 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM fetAl AnD peRinAtAl MeDicine

PUBLICATIONS StrateGic fraction and MRI- DTI-RMS), neurologi- oBjectiveS cal damage biomarkers, and follow-up of neurological development over the oRiGinAlS The principal strategic objective is to long term. i.f.: 116.03 search for solutions to prenatal di- 2. Cardiac function and cardiovascular seases, identifying the mechanisms programming in the fetus. The aim of 1 Sola R, Fito M, Estruch R, Salas- involved in fetal brain and cardiac repro- this research line is to characterize car- Salvado J, Corella D, DeLaTorre R, gramming, developing new technologies diac function and develop methods for Munoz MA, Lopez-Sabater MD, allowing an early diagnosis, and identi- the prediction and treatment of fetal Martinez-Gonzalez MA, Aros F, fying potential therapeutic targets. programming in the context of cardiac Ruiz-Gutierrez V, Fiol M, Casals E, dysfunction in fetuses and infants. Warnberg J, Buil-Cosiales P, Ros E, Other objectives of the team are the deve- This includes new echocardiographic Konstantinidou V, Lapetra J, Serra-Ma- lopment and consolidation of the existing markers of fetal myocardial function, jem L, Covas MI. Effect of a traditional lines of work in different fields, such as biochemical and genomic markers of Mediterranean diet on apolipoproteins perinatal infections, HIV and neonatal ischemia and immune/endothelial hy- B, A-I, and their ratio: A randomized, infection, fetal therapy and surgery, scree- peractivation. controlled trial. ATHEROSCLEROSIS. ning strategies and prediction of fetal and 3. Fetal therapy and surgery. As mem- 218:174-180. I.F.: 4.09. maternal pathology in large populations, bers of the European Eurofoetus preeclampsia and prematureness. group, we study the fetal surgical 2 Valsky DV, Martinez-Serrano treatment of complications of mono- MJ, Sanz M, Eixarch E, Acosta ER, main lineS chorial gestation and congenital dia- Martinez JM, Puerto B, Gratacos of reSearcH phragmatic herniation, and the tissue E. Cord occlusion followed by laser engineering repair of fetal membranes. cord transection in monochorionic 1. Neurological damage of fetal and pe- Screening of aneuploidy and maternal monoamniotic discordant twins. rinatal origin. Characterization of the disease markers. ULTRASOUND OBST GYN. 37:684- physiopathology and development 4. Perinatal pathology. This is a mixed 688. I.F.: 3.16. of methods for the diagnosis and line that groups projects relating to treatment of prenatal brain damage, prematureness (chorioamnionitis, ag- 3 Comas M, Crispi F, Gomez O, with preferential use of fetal growth gressive nutrition), clinical pathology Puerto B, Figueras F, Gratacos E. retardation as a model. The group (diabetes, autoimmune diseases), Gestational age- and estimated fetal possesses an important interdiscipli- preeclampsia and placental disorders weight-adjusted reference ranges nary structure for the characterization (developing methods for early predic- for myocardial tissue Doppler indi- and prediction of perinatal brain dation), HIV and pregnancy, neonatal res- ces at 24-41 weeks’ gestation. UL- mage, with special attention to the piratory disease (study of pulmonary TRASOUND OBST GYN. 37:57-64. fetal reprogramming mechanisms inflammation and prevention of bron- I.F.: 3.16. secondary to chronic hypoxia. The chopulmonary dysplasia), and investi- line is structured into major inter- gation of neonatal infection (perinatal 4 Sabria J, Barcelo-Vidal C, Arigita related areas: fetal and neonatal brain and nosocomial infections, respiratory M, Jimenez JM, Puerto B, Borrell imaging (ultrasound, moving blood syncytial virus infection, etc.). A. The CUSUM test applied in prospective nuchal translucency quality review. ULTRASOUND OBST GYN. 37:582-587. I.F.: 3.16.

5 Benavides-Serralde A, Hernan- dez-Andrade E, Fernandez-Lara A, Figueras F, Moreno-Alvarez O, Ca- margo-Marin L, Acevedo-Gallegos S, Gallardo-Gaona J, Velazquez- Torres B. Accuracy of Different Equations for Estimating Fetal Weight. GYNECOL OBSTET INVES. 72:264-268. I.F.: 1.03.

147 LIveR, DIgeSTIve SySTeM AND MeTABOLISM Fetal and perinatal medicine

6 Ierullo AM, Fernandez S, Palacio 11 Dadvand P, Basagana X, Sartini growth restriction on brain structure M, Gratacos E, Hernandez-Andrade C, Figueras F, Vrijheid M, DeNazelle and development in preterm infants: E. Cervical blood perfusion asses- A, Sunyer J, Nieuwenhuijsen MJ. A magnetic resonance imaging study. sed using power Doppler-derived Climate Extremes and the Length of BRAIN RES. 1382:98-108. I.F.: 2.62. estimation of fractional moving Gestation. ENVIRON HEALTH PERSP. blood volume: a reproducibility 119:1449-1453. I.F.: 6.09. 18 Salvador J, Arigita M, Carreras study. ULTRASOUND OBST GYN. E, Lladonosa A, Borrell A. Evolution 38:57-61. I.F.: 3.16. 12 Cobo T, Palacio M, Eixarch E, of prenatal detection of neural tube Crispi F, Mercade I, Martinez-Crespo defects in the pregnant population 7 Benavides-Serralde A, Scheier JM, Gratacos E. Clinical and bioche- of the city of Barcelona from 1992 M, Cruz-Martinez R, Crispi F, Fi- mical predictors of very preterm birth to 2006. PRENATAL DIAG. 31:1184- gueras F, Gratacos E, Hernandez- in twin-to-twin transfusion syndrome 1188. I.F.: 2.15. Andrade E. Changes in Central and treated by fetoscopy. AM J OBSTET Peripheral Circulation in Intrauterine GYNECOL. 204:-. I.F.: 3.31. 19 Cruz-Martinez R, Figueras F, Growth-Restricted Fetuses at Di- Hernandez-Andrade E, Oros D, Grata- fferent Stages of Umbilical Artery 13 Cobo T, Palacio M, Martinez- cos E. Fetal Brain Doppler to Predict Flow Deterioration: New Fetal Car- Terron M, Navarro-Sastre A, Bosch Cesarean Delivery for Nonreassuring diac and Brain Parameters. GYNE- J, Filella X, Gratacos E. Clinical and Fetal Status in Term Small-for-Gesta- COL OBSTET INVES. 71:274-280. inflammatory markers in amniotic fluid tional-Age Fetuses. OBSTET GYNE- I.F.: 1.03. as predictors of adverse outcomes in COL. 117:618-626. I.F.: 4.39. preterm premature rupture of mem- 8 Cruz-Martinez R, Moreno-Alvarez branes. AM J OBSTET GYNECOL. 20 DiRenzo GC, Roura LC, Facchi- O, Hernandez-Andrade E, Castanon 205:-. I.F.: 3.31. netti F, Antsaklis A, Breborowicz G, M, Martinez JM, Done E, Deprest Gratacos E, Husslein P, Lamont R, J, Gratacos E. Changes in Lung 14 Borrell A, Robinson JN, Santo- Mikhailov A, Montenegro N, Raduno- Tissue Perfusion in the Prediction of laya-Forgas J. Clinical Value of the vic N, Robson M, Robson SC, Sen C, Survival in Fetuses with Congenital 11- to 13(+6)-Week Sonogram for De- Shennan A, Stamatian F, Ville Y. Gui- Diaphragmatic Hernia Treated with tection of Congenital Malformations: delines for the management of spon- Fetal Endoscopic Tracheal Occlu- A Review. AM J PERINAT. 28:117- taneous preterm labor: identification sion. FETAL DIAGN THER. 29:101- 123. I.F.: 1.12. of spontaneous preterm labor, diagno- 107. I.F.: 0.87. sis of preterm premature rupture of 15 Scazzocchio E, Figueras F. Con- membranes, and preventive tools for 9 Cruz-Martinez R, Figueras F, temporary prediction of preeclampsia. preterm birth. J MATERN-FETAL NEO Hernandez-Andrade E, Oros D, CURR OPIN OBSTET GYN. 23:65-71. M. 24:659-667. I.F.: 2.07. Gratacos E. Changes in myocardial I.F.: 2.33. performance index and aortic isth- 21 Figueras-Aloy J, Salvia-Roiges mus and ductus venosus Doppler 16 Tenorio V, Bonet-Carne E, Botet MD, Rodriguez-Miguelez JM, Miracle- in term, small-for-gestational age F, Marques F, Amat-Roldan I, Gratacos Echegoyen X, Botet-Mussons F, fetuses with normal umbilical E. Correlation Between a Semiauto- Marin-Soria JL, Carbonell-Estrany X. artery pulsatility index. ULTRA- mated Method Based on Ultrasound Impact of Chorioamnionitis on Ex- SOUND OBST GYN. 38:400-405. Texture Analysis and Standard Ultra- haled Nitric Oxide and Endotracheal I.F.: 3.16. sound Diagnosis Using White Matter Aspirate Levels of Nitrites-Nitrates Damage in Preterm Neonates as a and Interleukin-8 in Mechanically Ven- 10 Dadvand P, Basagana X, Fi- Model. J ULTRAS MED. 30:1365- tilated Preterm Neonates. PEDIATR gueras F, Sunyer J, Nieuwenhuijsen 1377. I.F.: 1.25. PULM. 46:595-603. I.F.: 2.24. MJ. Climate and group B strepto- cocci colonisation during pregnan- 17 Padilla N, Falcon C, Sanz-Cortes 22 Eixarch E, Hernandez-Andrade cy: present implications and future M, Figueras F, Bargallo N, Crispi F, E, Crispi F, Illa M, Torre I, Figueras F, concerns. BJOG-INT J OBSTET GY. Eixarch E, Arranz A, Botet F, Gratacos Gratacos E. Impact on fetal mortality 118:1396-1400. I.F.: 3.35. E. Differential effects of intrauterine and cardiovascular Doppler of selec-

148 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM fetAl AnD peRinAtAl MeDicine

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 91.07 34 18 5 tive ligature of uteroplacental vessels 28 Estruch R, Sacanella E, Mota F, 2010 120.82 38 25 4 compared with undernutrition in a Chiva-Blanch G, Antuneza E, Casals E, rabbit model of intrauterine growth Deulofeu R, Rotilio D, Andres-Lacueva 2011 116.03 43 21 11 restriction. PLACENTA. 32:304-309. C, Lamuela-Raventos RM, DeGaeta- I.F.: 2.99. no G, Urbano-Marquez A. Moderate consumption of red wine, but not gin, 23 Cruz-Martinez R, VanMieghem decreases erythrocyte superoxide dis- T, Lewi L, Eixarch E, Cobo T, Martinez mutase activity: A randomised cross- JM, Deprest J, Gratacos E. Inciden- over trial. NUTR METAB CARDIOVAS. ce and clinical implications of early 21:46-53. I.F.: 3.44. 33 Claus F, Sandaite I, Dekoninck inadvertent septostomy after laser P, Moreno O, Martinez RC, Van- therapy for twin-twin transfusion syn- 29 Figueras F, Cruz-Martinez R, Mieghem T, Gucciardo L, Richter J, drome. ULTRASOUND OBST GYN. Sanz-Cortes M, Arranz A, Illa M, Botet Michielsen K, Decraene J, Devlieger 37:458-462. I.F.: 3.16. F, Costas-Moragas C, Gratacos E. R, Gratacos E, Deprest JA. Prenatal Neurobehavioral outcomes in pre- Anatomical Imaging in Fetuses with 24 Borrell A, Santolaya-Forgas J, term, growth-restricted infants with Congenital Diaphragmatic Hernia. Horbaczewski C, Henry RD, Dunn- and without prenatal advanced signs FETAL DIAGN THER. 29:88-100. Albanese L, Robinson JN. Is the of brain-sparing. ULTRASOUND OBST I.F.: 0.87. starting section for 3D volume acqui- GYN. 38:288-294. I.F.: 3.16. sition in the first trimester relevant in 34 Dekoninck P, Gratacos E, Van- the post hoc analysis of aneuploidy 30 Cruz-Martinez R, Figueras F, Mieghem T, Richter J, Lewi P, Ancel screening markers and fetal ana- Hernandez-Andrade E, Benavides- AM, Allegaert K, Nicolaides K, De- tomy?. PRENATAL DIAG. 31:1305- Serralde A, Gratacos E. Normal prest J. Results of Fetal Endoscopic 1310. I.F.: 2.15. reference ranges of fetal regional ce- Tracheal Occlusion for congenital rebral blood perfusion as measured diaphragmatic hernia and the set up 25 Cruz-Martinez R, Figueras F, by fractional moving blood volume. of the randomized controlled TOTAL Jaramillo JJ, Meler E, Mendez A, ULTRASOUND OBST GYN. 37:196- trial. EARLY HUM DEV. 87:619-624. Hernandez-Andrade E, Gratacos E. 201. I.F.: 3.16. I.F.: 1.59. Learning curve for Doppler measurement of fetal modified myocardial per- 31 Roca A, Garcia-Esteve L, Imaz 35 Dadvand P, Basagana X, Figue- formance index. ULTRASOUND OBST ML, Torres A, Hernandez S, Botet F, ras F, Amoly E, Tobias A, DeNazelle GYN. 37:158-162. I.F.: 3.16. Gelabert E, Subira S, Plaza A, Valdes A, Querol X, Sunyer J, Nieuwenhuij- M, Martin-Santos R. Obstetrical and sen MJ. Saharan dust episodes and 26 Oros D, Figueras F, Cruz- neonatal outcomes after prenatal pregnancy. J ENVIRON MONITOR. Martinez R, Meler E, Munmany M, exposure to selective serotonin reup- 13:3222-3228. I.F.: 1.81. Gratacos E. Longitudinal changes in take inhibitors: The relevance of dose. uterine, umbilical and fetal cerebral J AFFECT DISORDERS. 135:208-215. 36 Cruz-Martinez R, Figueras Doppler indices in late-onset small- I.F.: 3.74. F, Benavides-Serralde A, Crispi F, for-gestational age fetuses. ULTRA- Hernandez-Andrade E, Gratacos E. SOUND OBST GYN. 37:191-195. 32 VanMieghem T, Eixarch E, Sequence of changes in myocardial I.F.: 3.16. Gucciardo L, Done E, Gonzales I, performance index in relation to VanSchoubroeck D, Lewi L, Grata- aortic isthmus and ductus venosus 27 Done E, Allegaert K, Lewi P, Jani cos E, Deprest J. Outcome predic- Doppler in fetuses with early-onset J, Gucciardo L, VanMieghem T, Grata- tion in monochorionic diamniotic intrauterine growth restriction. UL- cos E, Devlieger R, VanSchoubroeck twin pregnancies with moderately TRASOUND OBST GYN. 38:179-184. D, Deprest J. Maternal hyperoxyge- discordant amniotic fluid. ULTRA- I.F.: 3.16. nation test in fetuses undergoing SOUND OBST GYN. 37:15-21. FETO for severe isolated congenital I.F.: 3.16. diaphragmatic hernia. ULTRASOUND OBST GYN. 37:264-271. I.F.: 3.16.

149 LIveR, DIgeSTIve SySTeM AND MeTABOLISM Fetal and perinatal medicine

37 Deprest J, Nicolaides K, 43 Arigita M, Borrell A, Mula R, GRAntS foR ReSeARcH Done’ E, Lewi P, Barki G, Largen E, Sanchez A, Mila M, Gratacos E. Use in pRoGReSS Dekoninck P, Sandaite I, Ville Y, Be- of fetal nuchal translucency in the nachi A, Jani J, Amat-Roldan I, Gra- first trimester to predict single-gene Gratacos E. IP- Soft tissue enginee- tacos E. Technical aspects of fetal disorders. PRENATAL DIAG. 31:1164- ring for congenital birth defects in endoscopic tracheal occlusion for 1168. I.F.: 2.15. children: new treatment modalities congenital diaphragmatic hernia. J for spina bifida, urogenital and ab- PEDIATR SURG. 46:22-32. I.F.: 1.31. dominal wall defects (EuroSTEC). ReViewS Sponsored by: European Commision, 38 Moreno R, Martinez I, Petriz i.f.: 5.05 LSHB-CT-2006-037409. Duration: J, Nadal M, Tintore X, Gonzalez JR, 01/01/2007-31/12/2011. Gratacos E, Aran JM. The beta- 1 Deprest JA, Nicolaides K, Gratacos Interferon Scaffold Attachment Re- E. Fetal Surgery for Congenital Dia- Gratacos E. MC - EST - Multidiscipli- gion Confers High-Level Transgene phragmatic Hernia Is Back from Never nary Research Training Programme Expression and Avoids Extinction by Gone. FETAL DIAGN THER. 29:6-17. in Fetal Medicine and Health. Spon- Epigenetic Modifications of Integra- I.F.: 0.87. sored by: European Commision, ted Provirus in Adipose Tissue-De- MEST-CT-2005-019707. Duration: rived Human Mesenchymal Stem 2 Figueras F, Gardosi J. Intrauterine 01/06/2006-31/12/2011. Cells. TISSUE ENG PART C-ME. growth restriction: new concepts in 17:275-287. I.F.: 4.64. antenatal surveillance, diagnosis, and Palacio M. Progesterona vaginal como management. AM J OBSTET GYNE- tratamiento de mantenimiento de ges- 39 Gardosi J, Figueras F, Claus- COL. 204:288-300. I.F.: 3.31. tantes con amenaza de parto pretérmi- son B, Francis A. The customised no. (Promesa). Sponsored by: Instituto growth potential: an international 3 Cruz-Martinez R, Hernandez- de Salud Carlos III (ISCIII), EC07/90023. research tool to study the epide- Andrade E, Moreno-Alvarez O, Done Duration: 29/10/2007-31/12/2012. miology of fetal growth. PAEDIATR E, Deprest J, Gratacos E. Prognostic PERINAT EP. 25:2-10. I.F.: 1.93. Value of Pulmonary Doppler to Predict Gratacos E. Novel ultrasound-based Response to Tracheal Occlusion in Fe- tridimensional tools for structural 40 Botet F, Figueras J, Carbonell- tuses with Congenital Diaphragmatic and fucntional evaluation of interest Estrany X, Narbona E. The impact Hernia. FETAL DIAGN THER. 29:18- in human organs. (Uvolumes). Spon- of clinical maternal chorioamnionitis 24. I.F.: 0.87. sored by: European Commision, on neurological and psychological LSHB-CT-2006-037409. Duration: sequelae in very-low-birth weight 01/08/2008-31/07/2012. infants: a case-control study. J PE- eDitoRiAlS RINAT MED. 39:203-208. I.F.: 1.87. i.f.: 3.02 Gratacos E. A multidisciplinary research programme for the evaluation 41 Comas M, Crispi F, Cruz- 1 Gratacos E. Congenital Diaphrag- of diagnostic techniques and inter- Martinez R, Figueras F, Gratacos E. matic Hernia: One Name for Various vention. Measures for preantal brain Tissue Doppler echocardiographic Diseases. FETAL DIAGN THER. 29:5- damage using growth restriction as a markers of cardiac dysfunction in 5. I.F.: 0.87. model. Sponsored by: Cerebra Foun- small-for-gestational age fetuses. dation, CEREBRA_07_001. Duration: AM J OBSTET GYNECOL. 205:-. 2 Arigita M, Martinez D, Nadal A, Bo- 01/10/2007-30/09/2013. I.F.: 3.31. rrell A. Spina bifida in a 13-week fetus with a normal intracranial translucen- Gratacos E. Clinical use of assesing 42 Baschat A, Chmait RH, De- cy. PRENATAL DIAG. 31:1104-1105. reginal brain circulation perfusion to prest J, Gratacos E, Hecher K, I.F.: 2.15. identify long term neurodevelopmen- Kontopoulos E, Quintero R, Skupski tal anomalies in small for gestational DW, Valsky DV, Ville Y. Twin-to-twin age fetuses (SGA). Sponsored by: transfusion syndrome (TTTS). J PE- Thrasher Research Fund, 02828-7. RINAT MED. 39:107-112. I.F.: 1.87. Duration: 01/04/2009-31/08/2012.

150 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM fetAl AnD peRinAtAl MeDicine

Gratacos E. eVV-endovascular vision. Gratacos E. Diagnóstico precoz en ni- Palacio M. Evaluación del valor pre- Sponsored by: Generalitat de Catalun- ños con daño cerebral y trastornos del dictivo de mal resultado perinatal del ya (ACC1Ó), VALTEC09-1-0048. Dura- aprendizaje. Sponsored by: Fundación perfil proteómico y metabolómico tion: 30/06/2009-30/06/2011. Caja Navarra, 14802-2011. Duration: cérvico-vaginal en pacientes con ame- 01/01/2011-31/12/2011. naza de parto prematuro y rotura pre- Figueras F. Cambios hemodinámicas matura de membranas. Sponsored by: adaptativos a la insuficiencia placenta- Gratacos E. eVV- endoVascularVision: Instituto de Salud Carlos III (ISCIII), ria crónica y relación con la lesión neu- new endoscopic tools for real time PI10/01308. Duration: 01/01/2011- rológica perinatal en modelo animal vascular assisted vision. Sponsored 31/12/2013. de coneja gestante. Sponsored by: by: European Comission, 251356. FIS, PI08/0230. Duration: 01/01/2009- Duration: 01/09/2010-30/08/2014. Gratacos E. Gestión del remodelado 31/12/2011. cardiovascular mediante integración Palacio M. Evaluación de la utilidad de tecnologias de monitorización Gratacos E. Desarrollo de marcadores de la indometacina como trata- ubicua y conceptos del humano predictivos y búsqueda de meca- miento de soporte en pacientes fisiologico virtual. Sponsored by: nismos moleculares responsables con amenaza de parto pretérmico MICINN - Programa CENIT (CV-RE- de la reprogramación cardíaca en y alto riesgo d inflamación intra- MOD), 09/371. Duration: 23/12/2009- la restricción de crecimiento fetal. amniótica: EUDRA-CT. Sponsored 31/12/2012. Sponsored by: Ministerio de Edu- by: INDOGEST 2010-022998-33, cación, SAF2009_08815. Duration: Ministerio de Sanidad, Política Social Gratacos E. Una esperança per a 01/01/2010-31/12/2012. e Igualdad, EC10-065. Duration: families amb problemes d’origen 01/01/2011-31/12/2011. prenatal. Sponsored by: Generalitat Borrell A. Aplicación clínica del geno- de Catalunya, AGAUR-ARCS2011, tipado RHD fetal en sangre materna Palacio M. PROgesterona vaginal EG074749. Duration: 22/11/2011- en una población general de estan- como tratamiento de Mantenimiento 22/11/2012. tes RHD negativas. Sponsored by: en gEStantes con Amenaza de parto Instituto de Salud Carlos III (ISCIII), pretérmino. Ensayo clínico aleatori- PI09/90539. Duration: 01/01/2010- zado, enmascarado a doble ciego y DoctoRAl tHeSeS 31/12/2011. controlado con placebo.. Sponsored by: Ministerio de Sanidad, Política Gratacos E, Figueras F. Brain reorga- Figueras F. Evaluación de frac- Social e Igualdad, TRA-096. Duration: nization in an experimental model of ción sanguínea en movimiento 01/01/2010-31/12/2011. intrauterine growth restriction. PhD como estrategia de cribado de student: Elisenda Eixarch Roca. hipoxia crónica cerebral fetal para Gratacos E. Biomarcadors quantita- la perdicción de alteraciones del tius d’imatge: Nous mètodes per a la Gratacos E, Crispi F. Cardiac dys- neurodesarrollo. Sponsored by: predicció del neurodesenvolupament function by tissue doppler in early-and Instituto de Salud Carlos III (ISCIII), anormal en nens amb retard de crei- late-onset fetal growth restriction. PI09/90391. Duration: 01/01/2010- xement fetal basats en connectòmica. PhD student: Montserrat Comas 31/12/2011. Sponsored by: Caixa d’Estalvis i Pen- Rovira. sions, 10/503. Duration: 03/12/2010- Gratacos E. Evaluación de la eficacia 31/12/2013. Botet F. Seguretat en la reanimació a de un algoritmo combinando varia- la sala dels prematurs extrems. PhD bles biológicas maternas, ecografía Gratacos E. CV-REMOD. Gestión del student: Sílvia Maya Enero. y marcadores bioquímicos para la remodelado Cardiovascular mediante predicción de preeclampsia y retraso integración de tecnologías Monitoriza- de crecimiento intrauterino en primer ción ubicua y Conceptos del Humano trimestre de gestación. Sponsored by: Fisiológico Virtual. Sponsored by: Instituto de Salud Carlos III (ISCIII), MICINN - Programa CENIT (CV- PI09/90404. Duration: 01/01/2010- REMOD), 09/398 - 10/079. Duration: 30/06/2011. 16/09/2009-31/12/2012.

151 AReA 3 Team involved in: Liver, digestive system and metabolism

Viral hepatitis in the immune competent host and in liver transplant patients gROUP MeMBeRS StrateGic oBjectiveS

Investigation of epidemiological, pathogenic, diagnostic and therapeutic aspects of hepatitis virus infections in immune competent patients and liver transplant recipients. teAM leADeR Xavier forns (Hospital clínic) main lineS tel.: 93 227 54 99 of reSearcH fax: 93 227 17 79 e-mail: [email protected] 1. Study of host factors in relation to the xxxxxx natural history and treatment response iDiBApS MeMBeRS: among patients with chronic hepatitis Jose M Sánchez-tapias tecHniciAnS: c. In this setting, mention should be made (Hospital clínic) patricia González (ciBeRehd) of the studies which the group is carrying Josep Maria Barrera (Hospital clínic) out on the influence of polymorphisms Miquel Bruguera (Hospital clínic) nuRSinG StAff: of the IL28B gene (which encodes for Josep costa (Hospital clínic) concepció Bartrés (fundació clínic) interferon lambda-3) upon the natural Miquel navasa (Hospital clínic) history and antiviral treatment response of collABoRAtoRS: chronic hepatitis C (in immune competent ReSeARcH fellowS: Sofia pérez del pulgar (ciBeRehd) individuals and liver transplant recipients). Mairene coto (MAec-Aeci) Georgios koutsoudakis (ciBeRehd) In transplant patients with hepatitis C, our Gonzalo crespo (Hospital clínic) Marta Montero (fundació clínic) group has shown that the presence of a laura Mensa (iDiBApS, Beca pfiS) favorable IL28B polymorphism in the reci- carlos fernández (fundació clínic) pient, if associated with the favorable po- Sabela lens (Hospital clínic) lymorphism in the donor liver, significantly Zoe Mariño (ciBeRehd) increases the antiviral treatment response (Fig. 1). In the coming months, evaluation will be made of the role of this polymorphism in relation to the natural history of chronic hepatitis C virus infection. 2. Development of models for the in vitro study of the hepatitis c virus (hcV). At present there is only a single model for studying the complete life cycle of HCV. This is a limited model, since it is based on the culture of a single cell line, in which only one viral strain grows. Over the last year we have worked on the development of new cell culture systems based on different cell lines with markers genes, allowing the detection of viral replication and the screening of biological samples with considerable rapidity. The ultimate aim of these studies is to establish one or more HCV culture systems allowing the growth and adaptation of viruses from biological samples, and which are therefore more representative of in vivo situations. It is important to note that we have established a collaboration with the Hepatic

152 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM ViRAl HepAtitiS in tHe inMune coMpetent HoSt AnD in liVeR tRAnSplAnt pAtientS

PUBLICATIONS Oncology Group led by Dr. Jordi Bruix 4. Noninvasive diagnosis of chronic he- in order to study the replication of HCV patitis c. In 2011 we obtained the first in hepatocellular carcinoma derived preliminary results of the LiverBiomark oRiGinAlS cell lines isolated and characterized by Project, funded by CIBERehd. The pro- i.f.: 77.73 members of this group. ject applies metabolomics techniques 3. Detection of hcV antigens in liver in an attempt to secure the early identi- 1 Perez-Alvarez R, Diaz-Lagares tissue. This is a project which in a fication of those patients with hepatitis C, Garcia-Hernandez F, Lopez-Ro- sense represents continuity of the C presenting a risk of developing severe ses L, Brito-Zeron P, Perez-De-Lis work started in 2008 with the purpose forms of the disease (in both immune M, Retamozo S, Bove A, Bosch of characterizing the expression of competent individuals and in liver trans- X, Sanchez-Tapias JM, Forns X, HCV penetration receptors (claudin-1, plant recipients). Ramos-Casals M. Hepatitis B Vi- occludin SR-B1 and CD81). Following 5. treatment of chronic hepatitis c. Our rus (HBV) Reactivation in Patients completion of this project, we wish group continues to focus great effort Receiving Tumor Necrosis Factor to detect viral antigens in liver tissue. on improving the efficacy and safety of (TNF)-Targeted Therapy Analysis While this may seem an easy project, antiviral therapy in patients with chronic of 257 Cases. MEDICINE. 90:359- to date it has not been possible to HCV infection. Different aspects are 371. I.F.: 4.26. detect these antigens in a reproducible included within this line of research: 1) manner. Since we have samples from Participation in clinical trials of new anti- 2 Cervera C, Fernandez-Ruiz M, transplant patients with very high viral viral molecules (in both early stages and Valledor A, Linares L, Anton A, loads, and taking advantage of the in pre-marketing phases); and 2) Study of Marcos MA, Sanclemente G, Hoyo experience gained over the past years the predictive factors of treatment res- I, Cofan F, Ricart MJ, Perez-Villa F, with confocal microscopy and immu- ponse and designing of models allowing Navasa M, Pumarola T, Moreno A. nohistochemistry techniques, we aim a reliable prediction of treatment results Epidemiology and risk factors for to evaluate the presence of different – particularly as regards the prediction late infection in solid organ trans- viral antigens in liver biopsies. Success of infection relapse in patients that have plant recipients. TRANSPL INFECT with the project could have clinical been able to achieve negative conver- DIS. 13:598-607. I.F.: 2.04. applications in aspects as relevant as sion of HCV during treatment. In the last the differential diagnosis of rejection year we have found that direct antiviral 3 Gil C, Garcia MT, Garcia F, Miro and the recurrence of hepatitis C after drug treatment (therefore not requiring JM, Aguero F, Alos L, Zamora L, transplantation. One of the predoctoral interferon) is able to definitively eliminate Capon A, Costa J, Pumarola T, fellows in our laboratory will move to HCV, and thus heal the chronic infection. Gatell JM. Evaluation of the Ro- to the U.S. (NIH) to initiate a collabora- This is an important step in the field of che COBAS (R) TaqMan (R) HIV-1 tive study using new generation confo- hepatitis, which will lead to radical chan- test for quantifying HIV-1 RNA in cal microscopy. ges in treatment in the next 10 years. infected cells and lymphoid tissue. J VIROL METHODS. 174:69-76. I.F.: 2.14.

4 Linares L, Sanclemente G, Cer- vera C, Hoyo I, Cofan F, Ricart MJ, Perez-Villa F, Navasa M, Marcos MA, Anton A, Pumarola T, Moreno A. Influence of Cytomegalovirus Disease in Outcome of Solid Or- gan Transplant Patients. TRANSPL P. 43:2145-2148. I.F.: 0.99.

5 Coto-Llerena M, Perez-Del- Pulgar S, Crespo G, Carrion JA, Martinez SM, Sanchez-Tapias JM, Martorell J, Navasa M, Forns Influence of polymorphisms of the interleukin-28B (IL28B) gene upon antiviral X. Donor and Recipient IL28B treatment response in liver transplant patients with hepatitis C. Those patients with a favorable polymorphism (CC) and who receive a liver from an IL28 CC do- Polymorphisms in HCV-Infected nor have a high probability of healing the infection with interferon and ribavirin.

153 LIveR, DIgeSTIve SySTeM AND MeTABOLISM Viral hepatitis in the immune competent host and in liver transplant patients

Patients Undergoing Antiviral The- T, Baliella C, Barcena R, Rodriguez 15 Marcellin P, Forns X, Goeser rapy before and after Liver Trans- M, DeLaMata M, Barrera P, Salcedo T, Ferenci P, Nevens F, Carosi G, plantation. AM J TRANSPLANT. M, Banares R, Otero A, Suarez F, Drenth JP, Serfaty L, DeBacker K, 11:1051-1057. I.F.: 6.05. Banos I, Tome S, Herrero I, Guilera VanHeeswijk R, Luo DH, Picchio G, M. Cyclosporine A-Based Immuno- Beumont M. Telaprevir Is Effective 6 Martinez SM, Fernandez- suppression Reduces Relapse Rate Given Every 8 or 12 Hours With Varo G, Gonzalez P, Sampson E, After Antiviral Therapy in Trans- Ribavirin and Peginterferon Alfa-2a Bruguera M, Navasa M, Jimenez planted Patients With Hepatitis C or-2b to Patients With Chronic He- W, Sanchez-Tapias JM, Forns X. Virus Infection: A Large Multicenter patitis C. GASTROENTEROLOGY. Assessment of liver fibrosis be- Cohort Study. TRANSPLANTATION. 140:459-U159. I.F.: 12.03. fore and after antiviral therapy by 92:334-340. I.F.: 3.68. different serum marker panels in patients with chronic hepatitis C. 11 Marino Z, Carrion JA, Be- ReViewS ALIMENT PHARM THER. 33:138- dini JL, Crespo G, Martinez SM, i.f.: 10.89 148. I.F.: 3.86. Sanchez-Tapias JM, Forns X, Navasa MA. Evaluation of a portable hemog- 1 Martinez SM, Crespo G, Na- 7 Koutsoudakis G, Perez-Del-Pul- lobinometer (HemoCue) to control vasa M, Forns X. Noninvasive gar S, Coto-Llerena M, Gonzalez anemia in hepatitis C liver transplant Assessment of Liver Fibrosis. HEPA- P, Dragun J, Mensa L, Crespo G, recipients undergoing antiviral the- TOLOGY. 53:325-335. I.F.: 10.89. Navasa M, Forns X. Cell Culture rapy. EUR J GASTROEN HEPAT. Replication of a Genotype 1b He- 23:942-947. I.F.: 1.60. patitis C Virus Isolate Cloned from eDitoRiAlS a Patient Who Underwent Liver 12 Balderramo D, Prieto J, i.f.: 6.05 Transplantation. PLOS ONE. 6:-. Cardenas A, Navasa M. Hepatic I.F.: 4.41. encephalopathy and post-transplant 1 Forns X, Navasa M. Cyclosporine hyponatremia predict early calcineu- A or Tacrolimus for Hepatitis C Recu- 8 Dragun J, Perez-Del-Pulgar rin inhibitor-induced neurotoxicity rrence? An Old Debate. AM J TRANS- S, Crespo G, Ramirez S, Coto- after liver transplantation. TRANSPL PLANT. 11:1559-1560. I.F.: 6.05. Llerena M, Mensa L, Garcia- INT. 24:812-819. I.F.: 3.21. Valdecasas JC, Navasa M, Forns X. Characterization of the Cross- 13 Mensa L, Crespo G, Gastinger clinicAl GuiDelineS Neutralizing Antibody Response MJ, Kabat J, Perez-Del-Pulgar S, i.f.: 9.33 Against Hepatitis C Virus in the Miquel R, Emerson SU, Purcell RH, Liver Transplantation Setting. Forns X. Hepatitis C Virus Receptors 1 [ANON]. EASL Clinical Practice AM J TRANSPLANT. 11:767-774. Claudin-1 and Occludin After Liver Guidelines: Management of hepa- I.F.: 6.05. Transplantation and Influence on titis C virus infection. J HEPATOL. Early Viral Kinetics. HEPATOLOGY. 55:245-264. I.F.: 9.33. 9 Balderramo D, Bordas JM, 53:1436-1445. I.F.: 10.89. Sendino O, Abraldes JG, Navasa M, Llach J, Cardenas A. Complica- 14 DiMartino V, Richou C, MulticentRicS tions after ERCP in liver transplant Cervoni JP, Sanchez-Tapias JM, i.f.: 160.47 recipients. GASTROINTEST EN- Jensen DM, Mangia A, Buti M, DOSC. 74:285-294. I.F.: 5.65. Sheppard F, Ferenci P, Thevenot T. 1 Zeuzem S, Andreone P, Pol Response-Guided Peg-Interferon S, Lawitz E, Diago M, Roberts S, 10 Castells L, Campos I, Bilbao Plus Ribavirin Treatment Duration Focaccia R, Younossi Z, Foster I, Navasa M, Carrion J, Forns X, in Chronic Hepatitis C: Meta- GR, Horban A, Ferenci P, Nevens Berenguer M, Aguilera V, Prieto Analyses of Randomized, Contro- F, Mullhaupt B, Pockros P, Terg R, M, Fernandez I, Meneu JC, Ulloa lled Trials and Implications for the Shouval D, VanHoek B, Weiland O, E, Fernandez JR, Suarez MJ, Pas- Future. HEPATOLOGY. 54:789-800. VanHeeswijk R, DeMeyer S, Luo casio JM, Sousa JM, Casanovas I.F.: 10.89. D, Boogaerts G, Polo R, Picchio

154 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM ViRAl HepAtitiS in tHe inMune coMpetent HoSt AnD in liVeR tRAnSplAnt pAtientS

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 106.96 21 12 4 G, Beumont M. Telaprevir for Re- Industrial, Ministerio de Econo- 2010 90.08 15 11 1 treatment of HCV Infection. NEW mía y Competitividad. Duration: ENGL J MED. 364:2417-2428. 01/01/2010-31/12/2013. 2011 77.73 15 8 2 I.F.: 53.49. Forns X. Early identification of seve- Jacobson IM, McHutchison JG, re hepatitis C recurrence after liver Dusheiko G, Di Bisceglie AM, transplantation. Sponsored by: Ro- Reddy KR, Bzowej NH, Marcellin che Organ Transplantation Research P, Muir AJ, Ferenci P, Flisiak R, Foundation (Switzerland), INT_RO- George J, Rizzetto M, Shouval D, TRF_11_01. Duration: 01/10/2011- Sola R, Terg RA, Yoshida EM, Adda 30/09/2012. N, Bengtsson L, Sankoh AJ, Kie- ffer TL, George S, Kauffman RS, Navasa M. Infección del injerto por Zeuzem S; ADVANCE Study Team. el virus de la hepatitis C (VHC) en Telaprevir for previously untreated el trasplante hepático: cinética viral chronic hepatitis C virus infection. precoz, mecanismos de entrada e N ENGL J MED. 364(25):2405-16. histopatología y diagnóstico no in- I.F.: 53.49. vasivo de la fibrosis. Sponsored by: Ministerio de Ciencia e Innovación, Poordad F, McCone J Jr, Bacon BR, PI10/01551. Duration: 01/01/2011- Bruno S, Manns MP, Sulkowski MS, 31/12/2013. Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniu- Navasa M, Forns X. Desarrollo de kiene V, Brass CA, Albrecht JK, Bro- biomarcadores del grado de fibro- nowicki JP; SPRINT-2 Investigators. sis hepática y del pronóstico de Boceprevir for untreated chronic HCV pacientes con enfermedades he- genotype 1 infection. N ENGL J MED. páticas avanzadas mediante el uso 364(13):1195-206. I.F.: 53.49. de herramientas metabolómicas. Sponsored by: Ministerio de Econo- mía y Competitividad (Subprograma GRAntS foR ReSeARcH Innpacto 2010), IPT-010000-2010- in pRoGReSS 013; LIVERBIOMARK. Duration: 01/01/2010-31/12/2012. Forns X. Caracterización de la ex- presión hepática de los receptores Forns X. Hepatitis víriques a l’hoste de entrada del virus de la hepatitis immunocompetent i al trasplantat C y su relación con la cinética de hepàtic. Sponsored by: Generalitat infección del injerto y la evolución de Catalunya, AGAUR_SGR09, clínica después del trasplante he- 2009_SGR_1503. Duration: pático. Sponsored by: Ministerio 23/09/2009-31/12/2013. de Ciencia e Innovación, PI080239. Duration: 01/01/2009-31/12/2011.

Forns X. Estudios de quasiespecies de los virus de la hepatitis B y C (VHB y VHC) y de polimorfismos genómicos asociados a la respuesta al tratamiento antiviral por pirose- cuenciación. Sponsored by: Centro para el Desarrollo Tecnológico

155 AReA 3 Team involved in: Liver, digestive system and metabolism

Pathophysiology and treatment of ascites and altered renal function in liver cirrhosis gROUP MeMBeRS StrateGic oBjectiveS

This is an interdisciplinary group that investigates the mechanisms of progression and treatment of liver fibrotic inflammation leading to cirrho- teAM leADeR sis, as well as the pathogenesis and Vicente Arroyo (Hospital clínic) treatment of the multiorgan compli- tel.: 93 227 57 39 cations derived from the existence of e-mail: [email protected] established liver cirrhosis.

iDiBApS MeMBeRS: oriol Morales (ciBeRehd) main lineS Ramón Bataller (Hospital clínic) José Altamirano (iDiBApS) of reSearcH Joan clària (Hospital clínic) Gustavo Henrique Santos pereira pere Ginès (Hospital clínic) (fundació clinic) 1. Molecular determinants of liver Mónica Guevara (iDiBApS) claudia fagundes Gonçalves inflammation. Role of the Kupffer wladimiro Jiménez (Hospital clínic) (fundació clinic) cells. Manuel Morales-Ruiz elsa Solà (Hospital clinic) 2. Acute bacterial infections in cir- (Hospital clínic) Bibiana Rius Boadas rhosis. Javier fernández-Gómez (fundació clínic) 3. Pathophysiology and treatment (Hospital clínic) Verónica García Alonso (fpi Mec) of hepatorenal syndrome and Daniel Rodrigo torres (fpu-Mec) renal failure associated with bac- poStDoctoRAlS fellowS: Javier Michelena (ciBeRehd) terial infections. Ana González-périz (ciBeRehd) Denisse oro Bozzini (fundació clínic) 4. Evaluation of cirrhotic myocardi- esther titos (ciBeRehd) opathy. Guillermo fernandez Varó (ciBeRehd) tecHniciAnS: pau Sancho (fundació clínic) Montse Bernat (Hospital clínic) Gregori casals (fundació clínic) cristina Díez (Hospital clínic) carmen escofet (Hospital clínic) ReSeARcH fellowS: cristina Millán (iDiBApS) Marta Martín (Hospital clínic) Anabel Martinez (iDiBApS) Montserrat pauta (fpi-Mec) carmen cano (Hospital clínic) Jordi Ribera (ciBeRehd) Marcos Martínez-clemente (Mec) nuRSinG StAff: eva Morán (fpu-Mec) Miriam castro (ciBeRehd) Juan Acevedo (Hospital clínic) Raquel cela (Hospital clínic) Marcella Marinelli (fundació clínic) cristina lópez Vicario (iDiBApS) collABoRAtoRS: Vedrana Reichemback Jordi colmenero (Hospital clínic) (fundació clínic) Marco pavesi (ciBeRehd) Silvia Affò (iDiBApS)

Light microscopic view of hepatocytes from mice with steatohepatitis induced by a fat-rich diet. The interior of the liver cells show lipid vesicles stained with oil red-O.

156 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM pHySiopAtHoloGy AnD tReAtMent of ASciteS AnD AlteReD RenAl function in liVeR ciRRHoSiS

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 92.54 15 14 1 5. Relationship between hepatic oRiGinAlS 2010 240.97 28 23 3 encephalopathy and alterations in i.f.: 94.79 renal function in cirrhosis. 2011 94.79 12 10 2 6. Pathogenesis, clinical implications 1 Bosch X, Esteve J, Sitges M, and treatment of hyponatremia. DeCaralt TM, Domenech A, Ortiz 7. Evaluation of different brain MRI te- JT, Monzo M, Morales-Ruiz M, chniques in cirrhotic patients. Rela- Perea RJ, Rovira M. Prevention tionship to hepatic encephalopathy. of Chemotherapy-Induced Left 8. Role of endogenous cannabinoids Ventricular Dysfunction With Ena- Coulon S, Heindryckx F, DeVos M, in the physiopathology of arterial lapril and Carvedilol: Rationale and Stassen JM, Vinckier S, Altamirano vasodilatation. Design of the OVERCOME Trial. J J, Bataller R, Carmeliet P, VanVlier- 9. Application of genomics and gene CARD FAIL. 17:643-648. I.F.: 3.36. berghe H, Colle I, Morales-Ruiz therapy to liver dysfunction. M. Inhibition of Placental Growth 10. Angiogenesis, endothelial dys- 2 Martinez SM, Fernandez- Factor Activity Reduces the Seve- function, edema and vascular re- Varo G, Gonzalez P, Sampson E, rity of Fibrosis, Inflammation, and modeling in liver cirrhosis. Bruguera M, Navasa M, Jimenez Portal Hypertension in Cirrhotic 11. Pathogenesis of liver fibrosis: cellu- W, Sanchez-Tapias JM, Forns X. Mice. HEPATOLOGY. 53:1629-1640. lar bases and identification of new Assessment of liver fibrosis be- I.F.: 10.89. therapeutic strategies. fore and after antiviral therapy by 12. Physiopathology and treatment of different serum marker panels in 6 Cardenas A, Gines P. Mana- arterial vasodilatation. patients with chronic hepatitis C. gement of patients with cirrhosis 13. Physiopathology and treatment of ALIMENT PHARM THER. 33:138- awaiting liver transplantation. GUT. ascites. 148. I.F.: 3.86. 60:412-421. I.F.: 10.61. 14. Artificial liver support systems. 15. Identification of new therapeutic 3 Guevara M, Baccaro ME, 7 Martin-Llahi M, Guevara M, Torre targets in alcoholic hepatitis. Gomez-Anson B, Frisoni G, Testa A, Fagundes C, Restuccia T, Gilabert C, Torre A, Molinuevo JL, Rami R, Sola E, Pereira G, Marinelli M, L, Pereira G, Sotil EU, Cordoba J, Pavesi M, Fernandez J, Rodes J, Arroyo V, Gines P. Cerebral mag- Arroyo V, Gines P. Prognostic Impor- netic resonance imaging reveals tance of the Cause of Renal Failure marked abnormalities of brain in Patients With Cirrhosis. GAS- tissue density in patients with TROENTEROLOGY. 140:488-U192. cirrhosis without overt hepatic en- I.F.: 12.03. cephalopathy. J HEPATOL. 55:564- 573. I.F.: 9.33. 8 Titos E, Rius B, Gonzalez-Periz A, Lopez-Vicario C, Moran-Salvador 4 Melgar-Lesmes P, Pauta M, E, Martinez-Clemente M, Arroyo V, Reichenbach V, Casals G, Ros J, Claria J. Resolvin D1 and Its Precur- Bataller R, Morales-Ruiz M, Jime- sor Docosahexaenoic Acid Promote nez W. Hypoxia and proinflam- Resolution of Adipose Tissue In- matory factors upregulate apelin flammation by Eliciting Macrophage receptor expression in human ste- Polarization toward an M2-Like llate cells and hepatocytes. GUT. Phenotype. J IMMUNOL. 187:5408- 60:1404-1411. I.F.: 10.61. 5418. I.F.: 5.75.

5 VanSteenkiste C, Ribera J, 9 Moran-Salvador E, Lopez-Parra M, Geerts A, Pauta M, Tugues S, Garcia-Alonso V, Titos E, Martinez- Casteleyn C, Libbrecht L, Olie- Clemente M, Gonzalez-Periz A, vier K, Schroyen B, Reynaert H, Lopez-Vicario C, Barak Y, Arroyo V, VanGrunsven LA, Blomme B, Claria J. Role for PPAR gamma in

157 LIveR, DIgeSTIve SySTeM AND MeTABOLISM Physiopathology and treatment of ascites and altered renal function in liver cirrhosis

obesity-induced hepatic steatosis 3 Gao B, Bataller R. Alcoholic Liver 4 Affo S, Bataller R. RANTES an- as determined by hepatocyte- and Disease: Pathogenesis and New tagonism: A promising approach to macrophage-specific conditional Therapeutic Targets. GASTROENTE- treat chronic liver diseases. J HEPA- knockouts. FASEB J. 25:2538- ROLOGY. 141:1572-1585. I.F.: 12.03. TOL. 55:936-938. I.F.: 9.33. 2550. I.F.: 6.52. 4 Bataller R, Rombouts K, Altami- 10 Martinez-Clemente M, Claria rano J, Marra F. Fibrosis in alcoholic GRAntS foR ReSeARcH J, Titos E. The 5-lipoxygenase/ and nonalcoholic steatohepatitis. in pRoGReSS leukotriene pathway in obesity, BEST PRACT RES CL GA. 25:231- insulin resistance, and fatty liver 244. I.F.: 2.23. Gines P. Efecto de la administración disease. CURR OPIN CLIN NUTR. prolongada de albúmina y midodrina 14:347-353. I.F.: 4.33. 5 Guevara M, Arroyo V. Hepatore- en la prevención de complicaciones nal syndrome. EXPERT OPIN PHAR- en pacientes en lista de espera de 11 Altamirano J, Higuera- MACO. 12:1405-1417. I.F.: 2.40. transplante hepático. Sponsored by: DeLatijera F, Duarte-Rojo A, Instituto de Salud Carlos III (ISCIII), Martinez-Vazquez MA, Abraldes JG, 6 Arroyo V, Fernandez J. Manage- EC07/90077. Duration: 29/10/2007- Herrera-Jimenez LE, Michelena J, ment of hepatorenal syndrome in 31/12/2012. Zapata L, Perez-Hernandez J, Torre patients with cirrhosis. NAT REV NE- A, Gonzales-Gonzalez JA, Cardenas PHROL. 7:517-526. I.F.: 4.75. Guevara M. Estudio Aleatorizado A, Dominguez M, Arroyo V, Gines P, y controlado sobre la eficacia de Caballeria J, Bataller R. The Amount 7 Oliva R, Badenas C, Claria J, la albúmina en la prevención de of Alcohol Consumption Negatively Coll MJ. Molecular genetic reports las complicaciones de pacientes Impacts Short-Term Mortality in in clinical practice: Content and node cirrosis en la lista de espera de Mexican Patients With Alcoholic menclature of mutations. MED CLIN- trasplante hepático. Sponsored by: Hepatitis. AM J GASTROENTEROL. BARCELONA. 136:356-361. I.F.: 1.41. Instituto de Salud Carlos III (ISCIII), 106:1472-1480. I.F.: 6.88. PI070443. Duration: 26/11/2007- 8 Olson JC, Wendon JA, Kramer 30/06/2012. 12 Wong F, Nadim MK, Kellum DJ, Arroyo V, Jalan R, Garcia-Tsao G, JA, Salerno F, Bellomo R, Gerbes A, Kamath PS. Intensive care care of Morales M. Función fisiopatológica Angeli P, Moreau R, Davenport A, the patient with cirrhosis. HEPATO- de la activación de las células en- Jalan R, Ronco C, Genyk Y, Arroyo V. LOGY. 54(5):1864-72. I.F.: 10.89. doteliales hepáticas en la cirrosis. Working Party proposal for a revised Posibles implicaciones terapéuticas. classification system of renal dys- Sponsored by: Ministerio Educa- function in patients with cirrhosis. eDitoRiAlS ción, SAF2007-63069. Duration: GUT. 60:702-709. I.F.: 10.61. i.f.: 31.06 01/10/2007-02/03/2012.

1 Gines P. Hepatorenal Syndrome, Jimenez W. Remodelado tisular y ReViewS Pharmacological Therapy, and Liver disfunción circulatoria en modelos i.f.: 40.82 Transplantation. LIVER TRANS- experimentales de enfermedad PLANT. 17:1244-1246. I.F.: 3.07. hepática. Identificación y caracte- 1 Cardenas A, Gines P. Acute-on- rización de nuevas dianas terapéu- chronic liver failure: the kidneys. 2 Gines P. Pharmacological mana- ticas. Sponsored by: Ministerio de CURR OPIN CRIT CARE. 17:184- gement of hepatorenal syndrome: Ciencia e Innovación, SAF2009- 189. I.F.: 2.55. Lessons from non-responders. J HE- 08839. Duration: 01/01/2010- PATOL. 55:268-269. I.F.: 9.33. 31/12/2012. 2 Altamirano J, Bataller R. Alco- holic liver disease: pathogenesis 3 Morales-Ibanez O, Bataller R. Bataller R. Projecte TRACE 2009. and new targets for therapy. NAT Platelet-derived chemokines: New Desarrollo de un test genético REV GASTRO HEPAT. 8:491-501. targets to treat liver fibrosis. J HE- para predecir la progresión de la I.F.: 4.56. PATOL. 54:581-583. I.F.: 9.33. fibrosis en pacientes con hepatitis

158 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM pHySiopAtHoloGy AnD tReAtMent of ASciteS AnD AlteReD RenAl function in liVeR ciRRHoSiS

crónica C (POLIGEN). Sponsored Jimenez W. Grupo de Investigación by: Ministerio de Ciencia e Inno- traslacional en nuevas estrategias vación, PET2008_0304. Duration: de diagnóstico y tratamiento de la 01/03/2009-02/03/2012. enfermedad hepática. Sponsored by: Generaliat de Catalunya, 2009_ Bataller R. Investigación tras- SGR_1496. Duration: 20/08/2009- lacional en pacientes con he- 31/12/2013. patopatías crónicas: desarrollo de métodos pronósticos e Morales M. Implicaciones básicas identificación de nuevas dia- y traslacionales del estudio de las nas terapéuticas. Sponsored alteraciones funcionales y molecu- by: Instituto de Salud Carlos lares del endotelio hepático en la III (FIS), PI08/0237. Duration: cirrosis. Sponsored by: Ministerio 01/01/2009-31/12/2012. de Economía y Competitividad, SAF 2010-19025. Duration: 01/01/2011- Arroyo V. Investigació hepàtica: 31/12/2013. Recerca bàsica i experimental. Sponsored by: Generaliat de Cata- Fernandez J. Polimorfismos gené- lunya, AGAUR, 2009_SGR_1484 . ticos del sistema inmune innato Duration: 01/01/2009-31/12/2013. (MBL/MASP-2 y TLR2/4) y riesgo de infecciones bacterianas en la cirrosis Gines P. Grup de recerca en he- avanzada. Sponsored by: Instituto patologia clínica. Sponsored by: de Salud Carlos III, PI10/01373. Du- Generalitat de Catalunya, AGAUR, ration: 01/01/2011-31/12/2013. 2009_SGR_1401. Duration: 01/01/2009-31/12/2013. Guevara M. Estudio de la fisiopato- logía de la encepalopatía hepática. Gines P. Disfunción Renal en la Investigación clínica y experimental. cirrosis hepática: Investigación Sponsored by: Instituto de Salud de nuevos métodos diagnósticos Carlos III (ISCIII), PI08/0108. Dura- y terapéuticos. Sponsored by: tion: 01/01/2009-31/12/2012. Ministerio de Ciencia e Innovación Instituto de Salud Carlos III, PI 080126. Duration: 01/01/2010- DoctoRAl tHeSeS 31/12/2012. Gines P. Utilidad del MELD y el so- Claria J. Papel de los mediado- dio pretrasplante en el pronóstico res lipídicos en la inflamación del trasplante hepático a corto plazo. del tejido adiposo y su influencia PhD student: Maria Carlota Londoño sobre la respuesta esteatogénica Hurtado. del higado en la obesidad. Spon- sored by: Ministerio de Educa- Claria J. Participación de la 5- y la ción, SAF2009_08767. Duration: 12/15 - lipooxigenasa en el desarro- 01/01/2010-31/12/2012. llo y progresión de la inflamación y esteatosis hepática. PhD student: Bataller R. Hepatic Microflui- Marcos Martínez Clemente. dic Bioreactor. Sponsored by: Katholieke Universiteit Leuven, FP7-2010-TESTING_1. Duration: 01/01/2011-02/02/2015.

159 AReA 3 Team involved in: Liver, digestive system and metabolism

Hepatic oncology

gROUP MeMBeRS StrateGic oBjectiveS

It is a multidisciplinary team, known internationally as “Barcelona Clinic Liver Cancer (BCLC) group”, which develops an intense teAM leADeR clinical and translational research in liver Jordi Bruix (Hospital clínic) cancer. The aim of the team is to investi- tel.: 93 227 98 03 gate the efficacy of clinical and therapeutic fax: 93 227 57 92 interventions as well as the mechanisms e-mail: [email protected] regulating the disease progression. xxxxxx iDiBApS MeMBeRS: nuRSinG StAff: main lineS M. carmen Ayuso (Hospital clínic) neus llarch (fundació clínic) of reSearcH concepció Bru (Hospital clínic) Josep fuster (Hospital clínic) ADMiniStRAtiVe StAff: At clinical level, work is done in the defi- Josep M. llovet (icReA) núria pérez (fundació clínic) nition of new diagnostic tools and, with Ramon Vilana (Hospital clínic) Ariadna farré (iDiBApS) a view to evaluating treatment efficacy, the optimum criteria for indicating radical ReSeARcH fellowS: collABoRAtoRS: treatment are perfected (surgical resection, clara Alsinet (fundació clínic) loreto Boix (ciBeRehd) transplantation, percutaneous approach María Reig (iDiBApS) Judit peix (ciBeRehd) with ablation) – with the aim of ensuring carlos Rodriguez de lope Manel Solé (Hospital clínic) maximum efficacy in terms of both survival (Hospital clínic) Victoria tovar (iDiBApS) and associated morbidity. In the treatment Helena cornella (iDiBApS) Alejandro forner (ciBeRehd) setting, evaluations are made of the options Silvia tremosini (fundació clínic) Jordi Rimola (cDic) for improving the efficacy of non-curative Marta Burrel (cDic) therapies which have been shown to impro- tecHniciAnS: Maria isabel Real (cDic) ve survival (arterial chemical embolization, Juan M. lópez (fundació clínic) lluís Bianchi (cDic) sorafenib). In this sense, phase 1, 2 and 3 ingrid Rengel (ciBeRehd) Augusto Villanueva (ciberehd) studies are carried out and led at interna- M. Angeles García-criado tional level, with a view to determining the (Hospital clínic) efficacy of new molecular agents. At the same time, evaluations are being made of the efficacy of antiangiogenic treatment to prevent relapse after surgical treatment or ablation. Likewise, cancer prevention studies are being conducted in patients with liver cirrhosis. In relation to translational research, studies are being made of the pathogenesis of hepatocellular carcinoma, together with the analysis of new signaling pathways and genomic aberrations implicated in the development of the tumor, as well as the identification of novel therapeutic targets. An international genomic research consortium has been created in hepatocellular carcinoma, in collaboration with the Mount Sinai Medical School, Harvard University and the Instituto di Tumori in Milan, which has consolidated a tissue bank of capital importance.

160 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM HepAtic oncoloGy

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 oRiGinAlS 162.54 17 13 3 i.f.: 81.94 2009 2010 62.23 11 7 1 2011 81.94 10 8 1 Diagnosis of early stage HCC based on staining 1 Tarocchi M, Hannivoort R, Hos- with GPC3 (A), HSP70 (B) and GS (C). hida Y, Lee UE, Vetter D, Narla G, Villanueva A, Oren M, Llovet JM, Friedman SL. Carcinogen-Induced ReSeARCh gROUP Hepatic Tumors in KLF6+/- Mice 5 Minguez B, Hoshida Y, Villanueva tranSlational reSearcH in Hepatic oncoloGy Recapitulate Aggressive Human A, Toffanin S, Cabellos L, Thung S, Hepatocellular Carcinoma Asso- Mandeli J, Sia D, April C, Fan JB, Group Leader: ciated with p53 Pathway Deregu- Lachenmayer A, Savic R, Roayaie Josep M. Llovet (IDIBAPS) lation. HEPATOLOGY. 54:522-531. S, Mazzaferro V, Bruix J, Schwartz I.F.: 10.89. M, Friedman SL, Llovet JM. Gene- The group was created in the year expression signature of vascular in- 2006 with the purpose of conduct- 2 Villanueva A, Hoshida Y, Bat- vasion in hepatocellular carcinoma. J ing genomic studies in hepatocel- tiston C, Tovar V, Sia D, Alsinet C, HEPATOL. 55:1325-1331. I.F.: 9.33. lular carcinoma and of identifying therapeutic targets Cornella H, Liberzon A, Kobayashi and new molecular treatments. We have established M, Kumada H, Thung SN, Bruix 6 Rimola J, Ordas I, Rodriguez two lines of research in the context of an interna- J, Newell P, April C, Fan JB, Roa- S, Garcia-Bosch O, Aceituno M, tional consortium (HCC Genomic Project), organized yaie S, Mazzaferro V, Schwartz Llach J, Ayuso C, Ricart E, Panes by Dr. Llovet, and involving the participation of the M, Llovet JM. Combining clinical; J. Magnetic Resonance Imaging BCLC-Clínic-IDIBAPS, the Mount Sinai School of pathology; and gene expression for Evaluation of Crohn’s Disease: Medicine (NY), the Dana-Farber Cancer Institute and data to predict recurrence of hepa- Validation of Parameters of Severity the Broad Institute (Boston), and the National Tumor tocellular carcinoma. GASTROEN- and Quantitative Index of Activity. Institute (Milan): TEROLOGY. 140:1501-15012. INFLAMM BOWEL DIS. 17:1759- 1. Genomics. Identification of the genomic altera- I.F.: 12.03. 1768. I.F.: 4.61. tions in hepatocellular carcinoma (HCC), and clarification of their implications in relation to 3 Hessheimer A, Fondevila C, Tau- 7 Bruix J, Poynard T, Colombo M, diagnosis and treatment. Integral analysis of the ra P, Muñoz J, Sanchez O, Fuster Schiff E, Burak K, Heathcote EJ, transcriptome (oligonucleotide microarrays) and J, Rimola A, Garcia-Valdecasas JC. Berg T, Poo JL, Mello CB, Guenther of the genomic aberrations (SNP arrays). Identifi- Decompression of the portal bed R, Niederau C, Terg R, Bedossa P, cation of markers for the early diagnosis of HCC. and twice-baseline portal inflow are Boparai N, Griffel LH, Burroughs 2. Signaling pathways and molecular therapies. necessary for the functional reco- M, Brass CA, Albrecht JK, Epic3S- Identification of the role of the signal transduc- very of a small-for size graft. ANN tudy GROUP. Maintenance therapy tion pathways in the pathogenesis of HCC, and SURG. 253:1201-1210. I.F.: 7.47. with peginterferon alfa-2b does not identification of new therapeutic targets and new prevent hepatocellular carcinoma molecular treatments. We are currently studying 4 Poynard T, Munteanu M, Co- in cirrhotic patients with chronic the signaling pathways corresponding to Akt/ lombo M, Bruix J, Schiff E, Terg hepatitis C. GASTROENTEROLOGY. mTOR, EGFR-Ras-MAPK, IGF and Wnt, in human R, Flamm S, Moreno-Otero R, 140:1990-1999. I.F.: 12.03. samples, cell lines and experimental animals. Carrilho F, Schmidt W, Berg T, Mcgarrity T, Heathcote EJ, Gon- 8 Toffanin S, Hoshida Y, Lachenmayer The group coordinates a European Project, FP-7- cales F, Diago M, Craxi A, Silva M, A, Villanueva A, Cabellos L, Minguez B, HEALTH (HEPTROMIC) with 6 academic centers Boparai N, Griffel L, Burroughs M, Savic R, Ward SC, Thung S, Chiang DY, and two companies, with the purpose of exploring Brass C, Albrecht J. FibroTest is Alsinet C, Tovar V, Roayaie S, Schwartz the prognostic oncogenes and potential treatment an independent predictor of virolo- M, Bruix J, Waxman S, Friedman SL, targets in liver cancer. The group has received gic response in chronic hepatitis C Golub T, Mazzaferro V, Llovet JM. a 5 years grant as a stable group of the Spanish patients retreated with pegylated MicroRNA-based classification of hepa- Association Against Cancer (AECC) to investigate interferon alfa-2b and ribavirin in tocellular carcinoma and oncogenic role about integrated genomic analysis of intrahepatic the EPIC3 program. J HEPATOL. of miR-517a. GASTROENTEROLOGY. colangiocarcionma. 54:227-235. I.F.: 9.33. 140:1618-1628. I.F.: 12.03.

161 LIveR, DIgeSTIve SySTeM AND MeTABOLISM Hepatic oncology

9 Caralt M, Marti J, Cortes J, 2 Villanueva A, Hoshida Y, Llovet Llovet JM. Genomic predictors and Fondevila C, Bilbao I, Fuster J, JM. Hepatocellular carcinoma oncogenic drivers in hepatocellular Garcia-Valdecasas JC, Sapiso- enters the sequencing era. GAS- carcinoma. Sponsored by: European chin G, Balsells J, Charco R. TROENTEROLOGY. 141:1943-1945. Comission, FP7-2010 Health HEP- Outcome of patients following I.F.: 12.03. TROMIC. Proposal nº: 259744 - 2. hepatic resection for metastatic Duration: 01/11/2011-30/10/2013. cutaneous and ocular melanoma. 3 Bruix J. Liver Cancer: Still a Long J HEPATO-BIL-PAN SCI. 18:268- Way To Go. HEPATOLOGY. 54:1-2. Llovet JM. Oncogenic addiction 275. I.F.: 1.96. I.F.: 10.89. and gatekeepper genes in hepatocellular carcinoma. Sponsored by: 10 Fondevila C, Hessheimer 4 Sherman M, Llovet JM. Smo- American Association for Cancer AJ, Flores E, Vendrell M, Munoz king, Hepatitis B Virus Infection, Research, 09-60-27-LLOV. Duration: J, Escobar B, Calatayud D, Taura and Development of Hepatocellular 01/07/2009-30/06/2011. P, Fuster J, Garcia-Valdecasas JC. Carcinoma. J NATL CANCER I. Step-by-Step Guide for a Simpli- 103:1642-1643. I.F.: 14.70. Llovet JM. Integrative genomic fied Model of Porcine Orthotopic análisis of human intrahepatic cho- Liver Transplant. J SURG RES. langiocarcinoma. Sponsored by: Fun- 167:E39-E45. I.F.: 2.24. GRAntS foR ReSeARcH dación Científica Española Contra el in pRoGReSS Cancer, GCA110347LLOV. Duration: 01/09/2011-31/08/2016. ReViewS Bruix J. Identificación y caracteri- i.f.: 33.81 zación de la población de células Llovet JM. Predictores genómicos madre adultas tumorales en líneas pronósticos y nuevas dianas mo- 1 Bruix J, Reig M, Rimola J, celulares derivadas de carcinoma leculares en carcinoma hepático. Forner A, Burrel M, Vilana R, hepatocelular humano. Sponsored Sponsored by: Ministerio de Ciencia Ayuso C. Clinical Decision Making by: Fondo de Investigación Sanitaria, e Innovación, SAF-2010-16055. Du- and Research in Hepatocellular PI080146. Duration: 01/01/2009- ration: 01/01/2011-31/12/2013. Carcinoma: Pivotal Role of Ima- 30/12/2012. ging Techniques. HEPATOLOGY. 54:2238-2244. I.F.: 10.89. Bruix J. Grup de Recerca Consolidat DoctoRAl tHeSeS – Oncologia Hepàtica – Barcelona 2 Bruix J, Sherman M. Manage- Clinic Liver Cancer (BCLC). Spon- Fuster J. La combinación de dife- ment of Hepatocellular Carcino- sored by: Generaliat de Catalunya, rentes criterios anatomopatológicos ma: An Update. HEPATOLOGY. AGAUR, SGR 1100. Duration: potencia la efectividad pronóstica de 53:1020-1022. I.F.: 10.89. 15/09/2009-31/12/2012. la afectación ganglionar en el cáncer gástrico. PhD student: J. Osorio, 3 Villanueva A, Llovet JM. Tar- Llovet JM. Grup de Recerca Sin- Universitat de Barcelona. geted therapies for hepatocellular gular- Recerca Translacional en carcinoma. GASTROENTEROLO- Oncologia Hepàtica. Sponsored by: GY. 140:1410-1426. I.F.: 12.03. Generaliat de Catalunya, AGAUR, SGR 1186. Duration: 22/07/2010- 31/12/2013. eDitoRiAlS i.f.: 49.65 Llovet JM. AACR-Landon INNO- VATION Award for International 1 Tremosini S, Bruix J. Diagnosis Collaborations AACR Annual Mee- of early hepatocellular carcinoma: ting, Denver, USA. Sponsored by: ideal goal, but not yet there. GAS- American Association for Cancer TROENTEROLOGY. 140:358-360. Research. Duration: 01/06/2009- I.F.: 12.03. 01/06/2011.

162 AReA 3 Team involved in: Clinical and experimental neuroscience Liver hemodynamics and portal hypertension. Digestive bleeding secondary to ruptured esophageal varicose veins gROUP MeMBeRS StrateGic oBjectiveS

The gaining of in-depth knowledge of the mechanisms underlying portal hypertension – the main complication of liver diseases – and development of new treatments for teAM leADeR this syndrome, and new noninvasive as- Jaume Bosch (Hospital clínic) sessment techniques. tel.: 93 227 57 90 fax: 93 227 93 48 main lineS e-mail: [email protected] of reSearcH

iDiBApS MeMBeRS: eyal Ashkenazi (ciBeRehd) 1. Factors regulating liver microcirculation Ramon Deulofeu (Hospital clínic) Marco di pascoli (eASl) under normal conditions and in cirrho- Àngels escorsell (Hospital clínic) enric Reverter (fundació clínic) sis, based on isolated liver perfusion Merce fernández lobato (iDiBApS) federica cerini (MRlD) studies and studies in liver sinusoid Joan c. García-pagán (Hospital clínic) cintia de Meireles (MRlD) endothelial cells. Mª Rosa Gilabert (Hospital clínic) Maeva Guillaume 2. Post-transcriptional regulation of en- carles nicolau (Hospital clínic) (Aide Jeunes chercheurs) dothelial nitric oxide synthase (eNOS) Juan González-Abraldes Dinesh Mani tripathi activity. Relevance in the treatment of (Hospital clínic) (Aci-colABoRA 2009-0938) portal hypertension. carolina tiani 3. Regulation of the transcription of liver si- poStDoctoRAlS fellowS: (Beca «Assegno di Ricerca», nusoid endothelial cell protecting genes: Aina Rodríguez (ciBeRehd) università di Bologna) relevance in the physiopathology of por- Vincenzo la Mura (fundació clínic) Sith Siramolpiwat (Hospital clínic) tal hypertension, in ex vivo liver preser- Marc Mejías (SAf) vation and in cirrhosis complications. Jordi Gracia-Sancho (ciBeRehd) tecHniciAnS: 4. Angiogenesis and portal hypertension: esther García (ciBeRehd) contribution to regulation of the develo- ReSeARcH fellowS: Héctor García (ciBeRehd) pment of collateral circulation, hyperdy- Marcos pasarín (fiS) Montse Monclús (idibaps) namic circulation and liver fibrogenesis. Susana Seijó (Beca Río Hortega) 5. New noninvasive methods for evaluating lucía Russo (ciBeRehd) nuRSinG StAff: cirrhosis. Andrea Ribeiro (fundació clínic) Rosa Sáez (ciBeRehd) 6. Randomized clinical studies of novel Giusi Marrone (iSciii) treatments for portal hypertension. Javier Gallego (ciBeRehd) collABoRAtoRS: 7. Hepatic vascular diseases. eugeni Rosado (ciBeRehd) Annalisa Berzigotti (Hospital clínic) 8. Prevention of decompensation of cirrhosis. 9. Discovery of response to treatment diagnostic biomarkers. 10. Role of sinusoidal endothelium in ischemia-reperfusion hepatic injury.

Tracing of liver venous pressure gradient.

163 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe

Liver hemodynamics and portal hypertension. Digestive bleeding secondary to ruptured esophageal varicose veins PUBLICATIONS ReSeARCh gROUP reGulation of liver microcirculation in cirrHoSiS and Hepatic vaScular diSeaSeS oRiGinAlS i.f.: 161.36 Group Leader: Juan carlos García-Pagán (hospital clínic) 1 Gimenez M, Gilabert R, Mon- teagudo J, Alonso A, Casamitjana One of the mechanisms responsible for the development R, Pare C, Conget I. Repeated of portal hypertension and its serious consequences is the Episodes of Hypoglycemia as increase in portal resistance observed within the cirrhotic liver. Part of this in- a Potential Aggravating Factor crease is dynamic and amenable to modification by means of drugs. Therefore, for Preclinical Atherosclerosis in improved knowledge based on experimental models in animals of the cellular, Subjects With Type 1 Diabetes. biochemical and molecular mechanisms regulating this dynamic component DIABETES CARE. 34:198-203. will allow us to design new strategies for the treatment of these disorders. I.F.: 7.14. Liver vascular disorders, particularly Budd-Chiari syndrome and non-cirrhotic portal thrombosis, are infrequent causes of portal hypertension. This compli- 2 Sala-Vila A, Cofan M, Nunez cates progress in our knowledge of these illnesses, their prognosis and treat- I, Gilabert R, Junyent M, Ros E. ments. This circumstance is of particular relevance, since these diseases Carotid and femoral plaque bur- mainly affect young patients with a potentially long life expectancy. For a den is inversely associated with number of years, our group has served as a reference center for these ill- the alpha-linolenic acid proportion nesses – thus allowing us to propose new treatment options and to advance of serum phospholipids in Spa- in furthering our knowledge. nish subjects with primary dys- lipidemia. ATHEROSCLEROSIS. 214:209-214. I.F.: 4.09.

ReSeARCh gROUP 3 Estruch R, Sacanella E, Mota anGioGeneSiS in liver diSeaSeS F, Chiva-Blanch G, Antuneza E, Casals E, Deulofeu R, Rotilio Group Leader: D, Andres-Lacueva C, Lamuela- Mercè Fernadez Lobato (IDIBAPS) Raventos RM, DeGaetano G, Urbano-Marquez A. Moderate We focus our research on the implication and regulation consumption of red wine, but not mechanisms of angiogenesis in the physiopathology of gin, decreases erythrocyte supe- portal hypertension and liver cirrhosis. Our research project is also aimed to roxide dismutase activity: A ran- experimentally evaluate new therapeutic strategies to treat these diseases. domised cross-over trial. NUTR Studies from our group in experimental models of portal hypertension and METAB CARDIOVAS. 21:46-53. cirrhosis have shown that angiogenesis or the formation of new blood ves- I.F.: 3.44. sels is crucial to two of the most important components of the physiopathology of these diseases: the formation of portosystemic collateral vessels and 4 Balderramo D, Bordas JM, the development of hyperdynamic splanchnic circulation. In addition, we Sendino O, Abraldes JG, Navasa found that angiogenesis is closely related to liver cirrhosis inflammation and M, Llach J, Cardenas A. Complica- fibrogenesis and contributes very significantly to the disease progression. tions after ERCP in liver transplant These findings have turned the control of new blood vessels formation into a recipients. GASTROINTEST EN- promising therapeutic target. DOSC. 74:285-294. I.F.: 5.65. These studies may contribute valuable information with a view to improving our knowledge of the molecular and cellular mechanisms involved in the 5 Martin-Llahi M, Guevara M, regulation of angiogenesis and implicated in the physiopathology of portal Torre A, Fagundes C, Restuccia hypertension and chronic liver diseases – these being a leading cause of mor- T, Gilabert R, Sola E, Pereira tality and an important indication for liver transplantation both in this country G, Marinelli M, Pavesi M, Fer- and worldwide. Our aim is that our projects lead to the development of new nandez J, Rodes J, Arroyo V, therapeutic approaches designed to reduce the morbidity and mortality of Gines P. Prognostic Importance patients diagnosed with these disorders. of the Cause of Renal Failure

164 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM liVeR HeMoDynAMicS AnD poRtAl HypeRtenSion. DiGeStiVe BleeDinG SeconDARy to RuptuReD eSopHAGeAl VARicoSe VeinS

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 166.86 28 17 7 in Patients With Cirrhosis. GAS- 11 Berzigotti A, Ashkenazi E, 2010 211.11 30 19 4 TROENTEROLOGY. 140:488-U192. Reverter E, Abraldes JG, Bosch I.F.: 12.03. J. Non-invasive diagnostic and 2011 161.36 22 17 3 prognostic evaluation of liver 6 Altamirano J, Higuera-DeLa- cirrhosis and portal hypertension. tijera F, Duarte-Rojo A, Martinez- DIS MARKERS. 31:129-138. Vazquez MA, Abraldes JG, I.F.: 1.72. Herrera-Jimenez LE, Michelena 17 Nicolau C, Bunesch L, Sebastia J, Zapata L, Perez-Hernandez J, 12 Moize V, Deulofeu R, Torres C. Renal complex cysts in adults: Torre A, Gonzales-Gonzalez JA, F, DeOsaba JM, Vidal J. Nutritional contrast-enhanced ultrasound. Cardenas A, Dominguez M, Arroyo Intake and Prevalence of Nutritional ABDOM IMAGING. 36:742-752. V, Gines P, Caballeria J, Bataller R. Deficiencies Prior to Surgery in a I.F.: 1.95. The Amount of Alcohol Consump- Spanish Morbidly Obese Popula- tion Negatively Impacts Short-Term tion. OBES SURG. 21:1382-1388. 18 Bureau C, Metivier S, D’amico Mortality in Mexican Patients With I.F.: 3.08. M, Peron JM, Otal P, Garcia-Pagan Alcoholic Hepatitis. AM J GAS- JC, Chabbert V, Chagneau-Derrode TROENTEROL. 106:1472-1480. 13 Berzigotti A, Garcia-Tsao G, C, Procopet B, Rousseau H, Bosch I.F.: 6.88. Bosch J, Grace ND, Burroughs AK, J, Vinel JP. Serum bilirubin and Morillas R, Escorsell A, Garcia- platelet count: a simple predictive 7 Nicolau C, Bunesch L, Peri L, Pagan JC, Patch D, Matloff DS, model for survival in patients with Salvador R, Corral JM, Mallofre C, Groszmann RJ. Obesity Is an In- refractory ascites treated by TIPS. J Sebastia C. Accuracy of contrast-en- dependent Risk Factor for Clinical HEPATOL. 54:901-907. I.F.: 9.33. hanced ultrasound in the detection Decompensation in Patients with of bladder cancer. BRIT J RADIOL. Cirrhosis. HEPATOLOGY. 54:555- 19 Luca A, Miraglia R, Caruso S, 84:1091-1099. I.F.: 2.06. 561. I.F.: 10.89. Milazzo M, Sapere C, Maruzzelli L, Vizzini G, Tuzzolino F, Gridelli 8 Gracia-Sancho J, Russo L, 14 Pano B, Sebastia C, Bunesch B, Bosch J. Short- and long-term Garcia-Caldero H, Garcia-Pagan JC, L, Mestres J, Salvador R, Macias effects of the transjugular intra- Garcia-Cardena G, Bosch J. En- NG, Nicolau C. Pathways of Lympha- hepatic portosystemic shunt on dothelial expression of transcription tic Spread in Male Urogenital Pelvic portal vein thrombosis in patients factor Kruppel-like factor 2 and its Malignancies. RADIOGRAPHICS. with cirrhosis. GUT. 60:846-852. vasoprotective target genes in the 31:135-U204. I.F.: 2.76. I.F.: 10.61. normal and cirrhotic rat liver. GUT. 60:517-524. I.F.: 10.61. 15 Llop E, DeJuan C, Seijo S, 20 Garcia-Caldero H, Rodriguez- Garcia-Criado A, Abraldes JG, Bosch Vilarrupla A, Gracia-Sancho J, Divi 9 Berzigotti A, Nicolau C, Bellot J, Garcia-Pagan JC. Portal cholangio- M, Lavina B, Bosch J, Garcia-Pagan P, Abraldes JG, Gilabert R, Garcia- pathy: radiological classification and JC. Tempol administration, a supe- Pagan JC, Bosch J. Evaluation of natural history. GUT. 60:853-860. roxide dismutase mimetic, reduces regional hepatic perfusion (RHP) I.F.: 10.61. hepatic vascular resistance and por- by contrast-enhanced ultrasound in tal pressure in cirrhotic rats. J HEPA- patients with cirrhosis. J HEPATOL. 16 Talens S, Hoekstra J, Dirkx TOL. 54:660-665. I.F.: 9.33. 55:307-314. I.F.: 9.33. SP, Murad SD, Trebicka J, Elias E, Primignani M, Garcia-Pagan JC, 21 Smalberg JH, Koehler E, Mu- 10 Pasarin M, Abraldes JG, Valla DC, Janssen HL, Leebeek rad SD, Plessier A, Seijo S, Trebicka Rodriguez-Vilarrupla A, LaMura V, FW, Rijken DC, ForTheEn-VieStudy J, Primignani M, DeMaat MPM, Garcia-Pagan JC, Bosch J. Insulin GROUP. Proteomic analysis reveals Garcia-Pagan JC, Valla DC, Janssen resistance and liver microcircu- that apolipoprotein a1 levels are de- HLA, Leebeek FWG. The JAK2 46/1 lation in a rat model of early NA- creased in patients with budd-chiari haplotype in Budd-Chiari syndrome FLD. J HEPATOL. 55:1095-1102. syndrome. J HEPATOL. 54:908-914. and portal vein thrombosis. BLOOD. I.F.: 9.33. I.F.: 9.33. 117:3968-3973. I.F.: 10.56.

165 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe

Liver hemodynamics and portal hypertension. Digestive bleeding secondary to ruptured esophageal varicose veins

22 LaMura V, Reverter JC, GRAntS foR ReSeARcH Bosch J. Mecanismos celulares Flores-Arroyo A, Raffa S, Reverter in pRoGReSS y moleculares en la hipertensión E, Seijo S, Abraldes JG, Bosch portal no cirrótica. Sponsored by: J, Garcia-Pagan JC. Von Wille- González-Abraldes J. Insulino resis- Ministerio Ciencia e Innovación brand factor levels predict clinical tencia y disfunción endotelial sinus- (FCCI-ACI-Colabora), ACI2009-0938. outcome in patients with cirrhosis oidal en las hepatopatías crónicas. Duration: 01/12/2009-30/11/2012. and portal hypertension. GUT. Mecanismos moleculares y signifi- 60:1133-1138. I.F.: 10.61. cación clínica. Sponsored by: FIS, Bosch J. Hepatic hemodynamics PI08/0193. Duration: 01/01/2009- and portal hypertension in cirrho- 30/12/2011. sis. Advances in the pathophysio- ReViewS logy, non-invasive evaluation and i.f.: 11.40 Mercè Fernadez Lobato. Regulación therapy. (Clinical & experimental de la angiogénesis en la hiperten- studies). Sponsored by: Insti- 1 Schouten JNL, Garcia-Pagan sión portal y la cirrosis hepática. tuto de Salud Carlos III (ISCIII), JC, Valla DC, Janssen HLA. Evaluación de nuevos enfoques te- PI09/1261. Duration: 01/01/2010- Idiopathic Noncirrhotic Portal rapéuticos. Sponsored by: Ministerio 31/12/2013. Hypertension. HEPATOLOGY. de Ciencia e Innovación, SAF2008- 54:1071-1081. I.F.: 10.89. 02461. Duration: 01/01/2009- Bosch J. Asociación de estatinas al 31/01/2012. tratamiento estándar en la preven- 2 Escorsell A, Bosch J. Self- ción de la recidiva hemorrágica en Expandable Metal Stents in the Mercè Fernadez Lobato. Regulació pacientes con cirrosis y hemorragia Treatment of Acute Esophageal de l’angiogènesi en la hipertensió por varices. Sponsored by: Minis- Variceal Bleeding. GASTROENT portal. Avaluació de noves estratè- terio de Sanidad, Política Social RES PRACT.:-. I.F.: 0.51. gies terapèutiques. Sponsored by: e Igualdad, TRA-074. Duration: Fundació La Marató TV3, MARA- 01/01/2010-31/12/2011. TO-081210. Duration: 01/01/2009- eDitoRiAlS 01/01/2012. Bosch J. Estudio multicéntrico, alea- i.f.: 13.89 torizado, doble-ciego, controlado con Escorsell A. Hemorragia por varices placebo, sobre la eficacia del trata- 1 Garcia-Pagan JC. PORTAL esofágicas: optimización del tratamiento con beta-bloqueantes para HYPERTENSION Nonselective miento en situaciones complejas. la prevención de la descompensa- beta-blockers in patients with Sponsored by: Fondo de Investiga- ción de la cirrosis con hipertensión refractory ascites. NAT REV GAS- ciones Sanitarias de la Seguridad portal (PREDESCI). Sponsored by: TRO HEPAT. 8:10-11. I.F.: 4.56. Social, FIS PI 08/0504. Duration: Instituto de Salud Carlos III (ISCIII), 01/01/2009-31/12/2011. EC08/00091. Duration: 01/01/2009- 2 Bosch J. Soft technique, hard 30/06/2013. end-points. J HEPATOL. 55:955- Bosch J. Grup de Recerca Con- 956. I.F.: 9.33. solidat-AGAUR: Hemodinàmica Bosch J. Desarrollo de biomar- Hepàtica i Hipertensió Protal”. Spon- cadores del grado de fibrosis sored by: Generalitat de Catalunya, hepática y del pronóstico de pa- AGAUR ,2009_SGR_1108. Duration: cientes con enfermedades hepá- 01/01/2009-31/12/2013. ticas avanzadas mediante el uso de herramientas metabolómicas (LIVERBIOMARK). Sponsored by: Ministerio de Ciencia e Innovación, CDTI, INNPACTO 2010. Duration: 01/01/2010-31/12/2012.

166 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM liVeR HeMoDynAMicS AnD poRtAl HypeRtenSion. DiGeStiVe BleeDinG SeconDARy to RuptuReD eSopHAGeAl VARicoSe VeinS

Garcia-Pagan JC. Caracterización y Manipulación de Nuevas Dianas Terapéuticas Involucradas en la Fisiopatología de la Hipertensión Portal en la Cirrosis. Sponsored by: Ministerio de Ciencia e Inno- vación, SAF2010-17043. Duration: 01/01/2010-31/12/2013.

Garcia-Pagan JC. Estudio aleatorizado, doble ciego, controlado con placebo, sobre los efectos de la sapropterina en la hemodinámica hepática y sistémica en pacientes con cirrosis hepática e hipertensión portal. Sponsored by: Ministerio de Sanidad, política Social e Igualdad, EC10-069. Duration: 01/01/2011- 31/12/2012.

Nicolau C. Evaluación funcional de riñón trasplantado mediante eco- grafía con contraste. Sponsored by: Instituto de Salud Carlos III (ISCIII), PI08/0198. Duration: 01/01/2009- 31/12/2012.

DoctoRAl tHeSeS

Bosch J, Gracia J. Papel del factor de transcripción Kruppel-like factor 2 en la disfunción endotelial hepática asociada a la hipertensión portal y al daño por isquemia y reperfusión. PhD student: Lucía Russo.

167 AReA 3 Team involved in: Liver, digestive system and metabolism

Inflammatory bowel disease (IBD)

gROUP MeMBeRS StrateGic oBjectiveS

This IDIBAPS research team has a translational orientation, aimed at generating knowledge to provide a teAM leADeR direct benefit to patients in the near Julián panés (Hospital clínic) future. tel.: 93 227 54 18 The team’s schedule includes three fax: 93 227 93 87 main strategic objectives: e-mail: [email protected] • The development of new treatments for Crohn’s disease and xxxxxx iDiBApS MeMBeRS: ulcerative colitis, focused on cell Josep Mª Bordas (Hospital clínic) tecHniciAnS: therapy and the identification of faust feu (Hospital clínic) carolina españa (ciberhed) new therapeutic targets susceptible Glòria lacima (Hospital clínic) Miriam esteller (ciBeRehd) to pharmacological modulation. Josep llach (Hospital clínic) • Further in-depth knowledge of the Josep M. piqué (Hospital clínic) nuRSinG StAff: genetic and environmental factors Azucena Salas (iDiBApS) Susana pinó (fundació clínic) responsible for susceptibility and elena Ricart (Hospital clínic) Marta Gallego (Hospital clínic) the course of the disease, with Salvadora Delgado (Hospital clínic) Anna Ramírez (ciBeRehd) a view to designing personalized Miquel Sans (iDiBApS) therapies. collABoRAtoRS: • Optimization of the radiological poStDoctoRAlS fellowS: Montserrat Aceituno (Hospital clínic) and biochemical diagnostic tech- elisabeth calderón (iDiBApS) orlando García (Hospital clínic) niques with the aim of adapting isabella Dotti (iDiBApS) ingrid ordás (Hospital clínic) treatment to the needs of each Daniel Benítez (ciBeRehd) individual patient. ReSeARcH fellowS: Maria del carme Masamunt (fundació clínic) Raquel cabezón (fundació clínic) Rut Mora (iDiBApS) núria planell (ciBeRhed)

Culture of intestinal fibroblasts. Vimentin positivity.

168 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM inflAMMAtoRy Bowel DiSeASe (iBD)

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 oRiGinAlS main lineS 82.29 17 8 6 of reSearcH i.f.: 110.31 2009 2010 115.79 19 8 4 1. Hematopoietic stem cell autotrans- 1 Balderramo D, Bordas JM, Sendino 2011 110.31 19 8 6 plantation in refractory Crohn’s O, Abraldes JG, Navasa M, Llach J, disease in conventional treatment Cardenas A. Complications after ERCP and biological therapies. Characte- in liver transplant recipients. GAS- rization of host related and intes- TROINTEST ENDOSC. 74:285-294. Llor X, Carvajal-Carmona L, Villanueva tinal microbiota related factors in I.F.: 5.65. CM, Moreno V, Pique JM, Carracedo the therapeutic response. A, Castells A, Andreu M, Ruiz-Ponte C, 2. Evaluation of the efficacy and safe- 2 Rimola J, Ordas I, Rodriguez S, Castellvi-Bel S. Case-control study for ty of treatment with autologous Garcia-Bosch O, Aceituno M, Llach J, colorectal cancer genetic susceptibility tolerogenic dendritic cells derived Ayuso C, Ricart E, Panes J. Magnetic in EPICOLON: previously identified va- from peripheral blood monocytes Resonance Imaging for Evaluation of riants and mucins. BMC CANCER. 11:-. in refractory Crohn’s disease. Crohn’s Disease: Validation of Parame- I.F.: 3.15. 3. Development and optimization of ters of Severity and Quantitative Index the production and administration of Activity. INFLAMM BOWEL DIS. 6 Montoro MA, Brandt LJ, Santolaria of intestinal epithelium stem cells 17:1759-1768. I.F.: 4.61. S, Gomollon F, Puertolas BS, Vera J, to be applied as a regenerative the- Bujanda L, Cosme A, Cabriada JL, Du- rapy in severe Crohn’s disease and 3 Abuli A, Fernandez-Rozadilla C, ran M, Mata L, Santamaria A, Cena G, ulcerative colitis Giraldez MD, Munoz J, Gonzalo V, Blas JM, Ponce J, Ponce M, Rodrigo L, 4. Optimization of magnetic resonan- Bessa X, Bujanda L, Rene JM, Lanas Ortiz J, Munoz C, Arozena G, Ginard D, ce imaging and ultrasound tech- A, Garcia AM, Salo J, Arguello L, Vilella Lopez-Serrano A, Castro M, Sans M, niques with contrast injection, for A, Carreno R, Jover R, Xicola RM, Llor Campo R, Casalots A, Orive V, Loizate evaluation of the extent, severity X, Carvajal-Carmona L, Tomlinson IPM, A, Tito L, Portabella E, Otazua P, Calvo and prognosis of the inflammatory Kerr DJ, Houlston RS, Pique JM, Ca- M, Botella MT, Thomson C, Mundi lesions in Crohn’s disease and ul- rracedo A, Castells A, Andreu M, Ruiz- JL, Quintero E, Nicolas D, Borda F, cerative colitis. Ponte C, Castellvi-Bel S. A two-phase Martinez B, Gisbert JP, Chaparro M, 5. Characterization of the genetic fac- case-control study for colorectal cancer Bernado AJ, Gomez-Camacho F, Cere- tors determining susceptibility and genetic susceptibility: candidate genes zo A, Nunez EC. Clinical patterns and phenotype in Crohn’s disease and from chromosomal regions 9q22 and outcomes of ischaemic colitis: Results ulcerative colitis. Construction of 3q22. BRIT J CANCER. 105:870-875. of the Working Group for the Study of diagnostic genetic chips. I.F.: 4.83. Ischaemic Colitis in Spain (CIE study). 6. Study of the environmental fac- SCAND J GASTROENTERO. 46:236- tors influencing susceptibility and 4 Scholin J, Buunen M, Hop W, Bon- 246. I.F.: 1.97. the course of inflammatory bowel jer J, Anderberg B, Cuesta M, Delgado disease. S, Ibarzabal A, Ivarsson ML, Janson M, 7 Pariente B, Cosnes J, Danese S, Lacy A, Lange J, Pahlman L, Skullman Sandborn WJ, Lewin M, Fletcher JG, S, Haglind E. Bowel obstruction after Chowers Y, D’haens G, Feagan BG, laparoscopic and open colon resec- Hibi T, Hommes DW, Irvine EJ, Kamm tion for cancer: Results of 5 years of MA, LoftusEv JR, Louis E, Michetti P, follow-up in a randomized trial. SURG Munkholm P, Oresland T, Panes J, Pe- ENDOSC. 25:3755-3760. I.F.: 3.44. yrin-Biroulet L, Reinisch W, Sands BE, Schoelmerich J, Schreiber S, Tilg H, 5 Abuli A, Fernandez-Rozadilla C, Travis S, VanAssche G, Vecchi M, Mary Alonso-Espinaco V, Munoz J, Gonzalo JY, Colombel JF, Lemann M. Develop- V, Bessa X, Gonzalez D, Clofent J, ment of the Crohn’s disease digestive Cubiella J, Morillas JD, Rigau J, Lato- damage score, the Lémann score. IN- rre M, Fernandez-Banares F, Pena E, FLAMM BOWEL DIS. 17:1415-1422. Riestra S, Paya A, Jover R, Xicola RM, I.F.: 4.61.

169 LIveR, DIgeSTIve SySTeM AND MeTABOLISM Inflammatory bowel disease (IBD)

8 Fernandez-Esparrach G, Cordo- 13 Anderson CA, Boucher G, Lees 15 Pellise M, Lopez-Ceron M, va H, Bordas JM, Gomez-Molins CW, Franke A, D’amato M, Taylor KD, DeMiguel CR, Jimeno M, Zabalza I, Gines A, Pellise M, Sendino O, Lee JC, Goyette P, Imielinski M, Latia- M, Ricart E, Aceituno M, Fernandez- Gonzalez-Suarez B, Cardenas A, no A, Lagace C, Scott R, Amininejad Esparrach G, Gines A, Sendino O, Balderramo D, Lacy AM, Delgado S, L, Bumpstead S, Baidoo L, Baldassa- Cuatrecasas M, Llach J, Panes J. Llach J. Endoscopic management no RN, Barclay M, Bayless TM, Brand Narrow-band imaging as an alter- of the complications of bariatric sur- S, Buning C, Colombel JF, Denson LA, native to chromoendoscopy for the gery. Experience of more than 400 DeVos M, Dubinsky M, Edwards C, detection of dysplasia in long-standing interventions. HEPATO-GASTROEN- Ellinghaus D, Fehrmann RSN, Floyd inflammatory bowel disease: a pros- TEROL. 34:131-136. I.F.: 0.68. JAB, Florin T, Franchimont D, Franke pective, randomized, crossover study. L, Georges M, Glas J, Glazer NL, GASTROINTEST ENDOSC. 74:840- 9 Fernandez-Esparrach G, Ayuso- Guthery SL, Haritunians T, Hayward 848. I.F.: 5.65. Colella JR, Sendino O, Pages M, NK, Hugot JP, Jobin G, Laukens D, Cuatrecasas M, Pellise M, Maurel Lawrance I, Lemann M, Levine A, 16 Luna J, Masamunt MC, Llach J, Ayuso-Colella C, Gonzalez-Suarez Libioulle C, Louis E, Mcgovern DP, J, Delgado S, Sans M. Palm oil toco- B, Llach J, Castells A, Gines A. EUS Milla M, Montgomery GW, Morley KI, trienol rich fraction reduces extrace- and magnetic resonance imaging Mowat C, Ng A, Newman W, Ophoff llular matrix production by inhibiting in the staging of rectal cancer: a RA, Papi L, Palmieri O, Peyrin-Biroulet transforming growth factor-beta 1 in prospective and comparative study. L, Panes J, Phillips A, Prescott NJ, human intestinal fibroblasts. CLIN GASTROINTEST ENDOSC. 74:347- Proctor DD, Roberts R, Russell R, NUTR. 30:858-864. I.F.: 3.41. 354. I.F.: 5.65. Rutgeerts P, Sanderson J, Sans M, Schumm P, Seibold F, Sharma Y, 17 Angulo S, Morales A, Danese 10 Chaparro M, Panes J, Garcia Simms LA, Seielstad M, Steinhart AH, S, Llacuna L, Masamunt MC, Pultz V, Manosa M, Esteve M, Merino O, Targan SR, VanDenBerg LH, Vatn M, N, Cifone MG, DeSimone C, Del- Andreu M, Gutierrez A, Gomollon F, Verspaget H, Walters T, Wijmenga gado S, Vila J, Panes J, Donskey C, Cabriada JL, Montoro MA, Mendoza C, Wilson DC, Westra HJ, Xavier RJ, Fernandez-Checa JC, Fiocchi C, Sans JL, Nos P, Gisbert JP. Long-term Zhao ZZ, Ponsioen CY, Andersen V, M. Probiotic sonicates selectively in- durability of infliximab treatment in Torkvist L, Gazouli M, Anagnou NP, duce mucosal immune cells apoptosis Crohn’s disease and efficacy of dose Karlsen TH, Kupcinskas L, Sventorai- through ceramide generation via neu- “escalation” in patients losing res- tyte J, Mansfield JC, Kugathasan S, tral sphingomyelinase. PLOS ONE. ponse. J CLIN GASTROENTEROL. Silverberg MS, Halfvarson J, Rotter 6:e16953-. I.F.: 4.41. 45:113-118. I.F.: 2.75. JI, Mathew CG, Griffiths AM, Gearry R, Ahmad T, Brant SR, Chamaillard M, 18 Vermeire S, Ghosh S, Panes J, 11 Caldelari ACA, Miquel R, Bom- Satsangi J, Cho JH, Schreiber S, Daly Dahlerup JF, Luegering A, Sirotiakova bi JA, Gines A, Fernandez-Esparrach MJ, Barrett JC, Parkes M, Annese J, Strauch U, Burgess G, Spanton G, Ayuso JR, Maurel J, Feu F, Cas- V, Hakonarson H, Radford-Smith G, J, Martin SW, Niezychowski W. The tells A, Fernandez-Cruz L, Navarro S. Duerr RH, Vermeire S, Weersma RK, mucosal addressin cell adhesion Malignancy predictive factors in pan- Rioux JD. Meta-analysis identifies 29 molecule antibody PF-00547,659 in creatic intraductal papillary mucinous additional ulcerative colitis risk loci, ulcerative colitis: a randomised study. neoplasm. MED CLIN-BARCELONA. increasing the number of confirmed GUT. 60:1068-1075. I.F.: 10.61. 137:631-636. I.F.: 1.41. associations to 47. NAT GENET. 43:246-U94. I.F.: 36.38. 19 Luna J, Masamunt MC, Rick- 12 Buchanan J, Wordsworth S, mann M, Mora R, Espana C, Delga- Ahmad T, Perrin A, Vermeire S, Sans 14 Garcia-Iglesias P, Villoria A, do S, Llach J, Vaquero E, Sans M. M, Taylor J, Jewell D. Managing Suarez D, Brullet E, Gallach M, Feu F, Tocotrienols Have Potent Antifibro- the long term care of inflammatory Gisbert JP, Barkun A, Calvet X. Meta- genic Effects in Human Intestinal bowel disease patients: The cost analysis: predictors of rebleeding after Fibroblasts. INFLAMM BOWEL DIS. to European health care providers. endoscopic treatment for bleeding 17:732-741. I.F.: 4.61. J CROHNS COLITIS. 5:301-316. peptic ulcer. ALIMENT PHARM THER. I.F.: 2.63. 34:888-900. I.F.: 3.86.

170 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM inflAMMAtoRy Bowel DiSeASe (iBD)

ReViewS magnetic resonance imaging for the Panes J. Terapia con células dendríti- i.f.: 31.78 diagnosis, assessment of activity and cas tolerogénicas en la enfermedad abdominal complications of Crohn›s de Crohn refractaria. Sponsored by: 1 Sanchez-Delgado J, Gene E, disease. ALIMENT PHARM THER. Ministerio de Innovación y Cien- Suarez D, Garcia-Iglesias P, Brullet 34:125-145. I.F.: 3.86. cia, SAF2009_07272. Duration: E, Gallach M, Feu F, Gisbert JP, 01/01/2010-31/12/2012. Calvet X. Has H. pylori Prevalence 7 VanAssche G, Lewis JD, Lichtens- in Bleeding Peptic Ulcer Been Under- tein GR, Loftus EV, Ouyang Q, Panes Sans M. ECCO Fellowship 2010 estimated? A Meta-Regression. AM J, Siegel CA, Sandborn WJ, Travis Agreement. Prize awarded to Dr. Sans J GASTROENTEROL. 106:398-405. SPL, Colombel JF. The London Posi- for ECCO’s interest in supporting futu- I.F.: 6.88. tion Statement of the World Congress re research in the field of “Molecular of Gastroenterology on Biological determinations of homing of stem 2 Jauregui-Amezaga A, Ricart E, Pa- Therapy for IBD With the European cells in IBD”. Sponsored by: Euro- nes J. Lessons to Learn from Crohn’s Crohn›s and Colitis Organisation: pean Crohn’s & Colitis Organisation Disease Clinical Trials: Implications for Safety. AM J GASTROENTEROL. ECCO, 10/311. Duration: 09/09/2010- Ulcerative Colitis. CURR DRUG TAR- 106:1594-1602. I.F.: 6.88. 09/09/2011. GETS. 12:1467-1477. I.F.: 3.06. Panes J. Tratamiento de la enferme- 3 Rieder F, Lawrance IC, Leite A, eDitoRiAlS dad de Crohn refractaria con células Sans M. Predictors of Fibrostenotic i.f.: 34.67 dendríticas reguladoras: estudio Crohn’s Disease. INFLAMM BOWEL piloto. Sponsored by: Ministerio de DIS. 17:2000-2007. I.F.: 4.61. 1 Pellise M, Panes J. Confocal en- Sanidad, Política Social e Igualdad, domicroscopy in celiac disease. GAS- TRA-097. Duration: 01/01/2010- 4 Daperno M, Castiglione F, De- TROENTEROLOGY. 140:1097-1099. 31/12/2011. Ridder L, Dotan I, Farkkila M, Florhol- I.F.: 12.03. men J, Fraser G, Fries W, Hebuterne Sans M. Estudio de los principales de- X, Lakatos PL, Panes J, Rimola J, 2 Panes J, Benitez-Ribas D, Salas terminantes moleculares implicados Louis E. Results of the 2nd part A. Mesenchymal stem cell therapy en la fibrosis intestinal en la enferme- Scientific Workshop of the ECCO (II): of Crohn’s disease: are the far-away dad de Crohn. Evaluación de estrate- Measures and markers of prediction hills getting closer?. GUT. 60:742-744. gias de tratamiento anti-fibrogénico. to achieve, detect, and monitor intes- I.F.: 10.61. Sponsored by: Ministerio de Ciencia tinal healing in Inflammatory Bowel e Innovación, SAF2010-18434. Dura- Disease. J CROHNS COLITIS. 5:484- 3 Fernandez-Esparrach G, Panes J. tion: 01/01/2011-31/12/2012. 498. I.F.: 2.63. Radiofrequency ablation for nondys- plastic Barrett’s esophagus: to treat or Panes J. Malaltia Inflamatòria Intes- 5 Travis SPL, Higgins PDR, Orchard not to treat?. GASTROENTEROLOGY. tinal. Sponsored by: Generalitat de T, VanDerWoude CJ, Panaccione 140:2130-2132. I.F.: 12.03. Catalunya, AGAUR, 2009_SGR_1206. R, Bitton A, O’morain C, Panes J, Duration: 15/09/2009-31/12/2013. Sturm A, Reinisch W, Kamm MA, D’haens G. Review article: defining GRAntS foR ReSeARcH Salas A. Delivering nanopharma- remission in ulcerative colitis. ALI- in pRoGReSS ceuticals through BIological Barriers MENT PHARM THER. 34:113-124. (BIBA). Sponsored by: Ministerio de I.F.: 3.86. Salas A. New mediators of T effector Economía y Conocimiento. ERANET, responses and therapeutic poten- Euro Nano Med, PI10/02998. Dura- 6 Panes J, Bouzas R, Chaparro M, tial of administration of tolerogenic tion: 01/01/2011-31/12/2013. Garcia-Sanchez V, Gisbert JP, De- dendritic cells in inflammatory bowel Guerenu BM, Mendoza JL, Paredes disease. Sponsored by: Ministerio JM, Quiroga S, Ripolles T, Rimola J. de Ciencia e Innovación, BFU2008- Systematic review: the use of ultraso- 02683/BFI . Duration: 31/12/2008- nography, computed tomography and 31/12/2011.

171 AReA 3 Team involved in: Liver, digestive system and metabolism

Cholestasis and bone pathology

gROUP MeMBeRS StrateGic oBjectiveS

1. Study of the epidemiology, pathogenesis, diagnosis and treatment of adult chronic cho- teAM leADeR lestatic disorders and autoim- Albert parés (Hospital clínic) mune hepatitis. tel.: 93 227 57 53 2. Knowledge of the pathogenic fax: 93 451 55 22 mechanisms underlying pruri- e-mail: [email protected] tus and osteoporosis in primary biliary cirrhosis. xxxxxx 3. Investigation of the pathogenic and therapeutic aspects of metabolic bone diseases 4. Definition of the therapeutic potential of different artificial liver support procedures in teAM leADeR liver failure. núria Guañabens (Hospital clínic) tel.: 93 227 54 00 (ext.: 2235) main lineS e-mail: [email protected] of reSearcH

iDiBApS MeMBeRS: tecHniciAnS: The research lines of this team Antoni Mas (Hospital clínic) Marta Dubreuil (ciBeRehd) are divided into two associated M. lluisa Álvarez (Hospital clínic) groups. pilar peris (Hospital clínic) nuRSinG StAff: Ana Monegal Brancós Rosana Ahuir (ciBeRehd) (Hospital clínic) collABoRAtoRS: ReSeARcH fellowS: Mª Jesús Martinez de osaba pau Bosch (fundació clínic) (Hospital clinic) laia Gifre (Hospital clínic) Àngels Martinez-ferrer (Hospital clínic) Silvia Ruiz-Gaspá (ciBeRehd)

Effect of dialysis with albumin (MARS) on pruritus in patients with chronic cholestasis. VAS: visual analogue scale.

172 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM cHoleStASiS AnD Bone pAtHoloGy

ReSeARCh gROUP cHoleStaSiS PUBLICATIONS

Group Leader: Albert Pares (hospital clínic) oRiGinAlS i.f.: 36.73 1. Epidemiology, natural history and therapeutic response of chronic cholestatic disorders in adults. 1 Ruiz-Gaspa S, Martinez-Ferrer 2. Evaluation of the factors conditioning treatment response, and proposition of A, Guanabens N, Dubreuil M, new treatment regimens in patients showing suboptimum response to ursode- Peris P, Enjuanes A, DeOsaba oxycholic acid. MJM, Alvarez L, Monegal A, 3. Relevance of the anionic exchanger AE2. Combalia A, Pares A. Effects of 4. Diagnosis of autoimmune hepatitis. Development of a new diagnostic procedure Bilirubin and Sera from Jaundi- for autoimmune hepatitis, based on peptide mapping – a project conducted in col- ced Patients on Osteoblasts: laboration with 6 centers in Europe and one in Israel. Contribution to the Development 5. Pruritus in chronic cholestasis and treatment response to albumin dialysis: pro- of Osteoporosis in Liver Disea- teomic analysis. Evaluation of treatment response based on albumin dialysis in ses. HEPATOLOGY. 54:2104- patients with chronic cholestasis and refractory pruritus, and identification of the 2113. I.F.: 10.89. eliminated peptides and proteins using MARS. 6. Pathogenesis of osteoporosis and fracture development in primary biliary cirrho- 2 Gay M, Pares A, Carrascal M, sis and other chronic cholestatic disorders. In collaboration with the Bone Meta- Bosch-I-Crespo P, Gorga M, Mas bolic Diseases group, evaluation of the factors underlying fractures in primary bili- A, Abian J. Proteomic Analysis of ary cirrhosis, and the proposal of new therapeutic modalities for increasing bone Polypeptides Captured from Blood mass. Likewise, investigation is conducted into the repercussion of retained bile during Extracorporeal Albumin acids and bilirubin in cholestasis upon the development of bone disease. Dialysis in Patients with Cholesta- 7. Artificial liver support. Evaluation of the safety and efficacy of different bioartificial sis and Resistant Pruritus. PLOS liver and hepatic support systems in treating acute liver failure and exacerbated ONE. 6:-. I.F.: 4.41. chronic liver failure. An open-label, prospective randomized study versus conventional treatment involving cryopreserved human hepatocytes from organs not apt 3 Cosman F, Eriksen EF, Recknor for transplantation. C, Miller PD, Guanabens N, Kas- perk C, Papanastasiou P, Readie A, Rao H, Gasser JA, Bucci-Rechtweg ReSeARCh gROUP C, Boonen S. Effects of intrave- Bone metaBolic diSeaSe nous zoledronic acid plus subcutaneous teriparatide [rhPTH(1-34)] Group Leader: in postmenopausal osteoporosis. Núria Guañabens (hospital clínic) J BONE MINER RES. 26:503-511. I.F.: 7.06. 1. Osteoporosis in premenopausal women and in males. Study of the clinical characteristics and mechanisms involved in the 4 Torregrosa JV, Fuster D, Mone- development of the disorder. gal A, Gentil MA, Bravo J, Guirado 2. Osteoporosis in primary biliary cirrhosis. Clinical and “in vitro” analysis. Eval- L, Muxi A, Cubero J. Efficacy uation of the key factors in the low development of bone mass and the ap- of low doses of pamidronate in pearance of fractures, and proposal of new therapeutic protocols. In addition, osteopenic patients administered evaluation of the effect of bilirubin and bile acids upon primary osteoblasts in in the early post-renal transplant. culture. OSTEOPOROSIS INT. 22:281-287. 3. Osteoporosis in liver transplantation. Evaluation of the hormonal changes I.F.: 4.86. regulating bone remodeling in this pathology. 4. Analysis of the efficacy of vertebroplasty. Evaluation of the clinical usefulness 5 Cerda D, Peris P, Monegal A, and the complications of this procedure in the treatment of pain secondary to Albaladejo C, DeOsaba MJM, Suris recent vertebral fracture due to osteoporosis. X, Guanabens N. Increase of PTH 5 . Evaluation of bone remodeling regulators. Evaluation of the role of sclerostin in post-menopausal osteoporo- and, through this protein, investigation of the influence of osteocytes upon sis. REV CLIN ESP. 211:338-343. bone loss associated with glucocorticoid treatment and immobilization. I.F.: 0.76.

173 LIveR, DIgeSTIve SySTeM AND MeTABOLISM Cholestasis and bone pathology

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 34.85 9 2 2 6 Gifre L, Peris P, Monegal A, GRAntS foR ReSeARcH MartinezDeOsaba MJ, Alvarez in pRoGReSS 2010 59.69 13 7 1 L, Guañabens N. Osteomalacia 2011 36.73 8 5 1 revisited: a report on 28 cases. Pares A. Enfermedades hepáticas CLIN RHEUMATOL. 30:639-645. autoinmunes. Nuevos procedimien- I.F.: 1.69. tos diagnósticos mediante mapeo peptídico. Sponsored by: Instituto de 7 Sabate M, Ibanez L, Perez Salud Carlos III (ISCIII), PI07/1318E DoctoRAl tHeSeS E, Vidal X, Buti M, Xiol X, Mas (E-RARE). Duration: 01/01/2008- A, Guarner C, Forne M, Sola R, 30/06/2011. Pares A. Prevalença i factors associats Castellote J, Rigau J, Laporte JR. a la presència d’esteatosi hepàtica no Paracetamol in therapeutic dosa- Pares A. Prurito de la colestasis: alcohòlica en la població general. PhD ges and acute liver injury: causality fisiopatología y análisis proteómico. student: Maria Antònia Auladell Llo- assessment in a prospective case Sponsored by: Ministerio de Ciencia rens, Universitat de Barcelona. series. BMC GASTROENTEROL. y Tecnología, SAF200804012. Dura- 11:-. I.F.: 2.47. tion: 01/01/2009-31/12/2011. Guañabens N. Osteoporosis en la mujer posmenopáusica. Riesgo de 8 Peris P, Torra M, Olivares V, Re- Guañabens N. Influencia de la bili- Fractura en la enfermedad colestásica yes R, Monegal A, Martinez-Ferrer rrubina y los ácidos biliares sobre la y prevalencia de otros procesos asocia- A, Guañabens N. Prolonged bisphos- formación ósea. Estudio “in vitro” en dos. PhD student: Dacia Cerdà Gaba- phonate release after treatment in osteoblastos humanos. Sponsored roi, Universitat de Barcelona. women with osteoporosis. Rela- by: Ministerio de Sanidad y Consu- tionship with bone turnover. BONE. mo, PI080105. Duration: 01/01/2009- 49:706-709. I.F.: 4.60. 30/12/2011.

Peris P. Efecte de la vertebroplastia ReViewS percutània en la qualitat de vida dels i.f.: 3.22 pacients amb dolor relacionat amb fractures vertrebals osteroporòti- 1 Ruiz-Esquide V, Peris P, Gifre ques. Comparació amb el tractament L, Guanabens N. Abnormalities of conservador. Sponsored by: Fundació bone metabolism in bariatric surgery. La Marató de TV3 ,071710. Duration: MED CLIN-BARCELONA. 136:215- 13/02/2008-30/08/2011. 221. I.F.: 1.41. Peris P. Prospective study of bone 2 Pares A. Acute Alcoholic He- loss after spinal cord injury. Risk fac- patitis. REV ESP ENFERM DIG. tors and role of osteocyte markers. 103:597-597. I.F.: 1.13. Sponsored by: Fundació La Marató de TV3, Marató TV3. Duration: 3 Guañabens N, Pares A. Manage- 01/01/2011-31/12/2013. ment of osteoporosis in liver disease. HEPATO-GASTROENTEROL. 35:438-445. I.F.: 0.68.

174 AReA 3 Team involved in: Clinical and experimental neuroscience Mitochondrial regulation of cell death and steatohepatitis gROUP MeMBeRS StrateGic main lineS oBjectiveS of reSearcH

1. Determination of intracellular 1. Ischaemia-reperfusion he- teAM leADeR signalling and the role of mito- patocellular damage mecha- José carlos fernández- chondria in cell susceptibility nisms and their regulation checa (iiBB-cSic) in inflammation, hypoxia and based on antioxidant and anti- tel.: 93 227 57 09 chemotherapy, and their rele- inflammatory strategies. (Dr fax: 93 363 83 01 vance in relation to (hepato) Fernández-Checa). e-mail: carcinogenesis. 2. Sphingolipid and mitochondrial [email protected] 2. Determination of the me- oxidative-stress regulation of chanisms behind cholesterol cell death (Dr Fernández-Checa). iDiBApS MeMBeRS: and sphingolipid participation 3. Mechanisms responsible for Joan caballeria (Hospital clínic) in hepatocellular death in cholesterol transport to the Anna colell (iiBB-cSic) different disorders such as mitochondria (Dr Fernández- carmen García Ruíz (iiBB-cSic) non-alcoholic steatohepatitis Checa). Montserrat Marí (iDiBApS) (NASH) or ischaemia/reperfu- 4. Role of cholesterol in hepato- Albert Morales (iiBB-cSic) sion damage. cellular carcinoma response 3. Analysis of the role of free to chemotherapy (Dr Fernán- poStDoctoRAlS fellowS: cholesterol in patients with dez-Checa). laura conde de la Rosa (iiBB-cSic) non-alcoholic steatohepatitis. 5. Development of non-invasive claudia Von Montfort (iiBB-cSic) 4. Contribution of the physico- diagnostic methods for chemical properties of the diagnosis and prognosis in ReSeARcH fellowS: mitochondrial membrane in alcohol-induced liver disease Anna fernández (ciBeRehd) cell death. (Dr J. Caballería). Raquel fucho (ciBeRehd) nuria Matias (Mcyt) nuria tarrats (iiBB-cSic) elisabeth Barbero (Mcyt) cristina Bárcena (iDiBApS) laura Martínez (Mcyt) Milica Stefanovic (cSic) Anna Baulies (Mcyt) Álvaro de Mingo pulido (iSciii-fiS)

tecHniciAnS: Susana núñez pozuelo (ciBeRehd)

In vivo analysis of the liver production of reactive oxygen species (ROS) of mitochondrial origin based on two-photon confocal microscopy. The induction of nutritional liver steatosis was carried out by administering a high-cholesterol (HC) diet or a choline-deficient diet (Lombarda) during 48 hours. The administration of DCF and TMRE was carried out via the portal vein, examining the fluorescence emission of both probes in intact liver in vivo with two-photon confocal microscopy.

175 LIveR, DIgeSTIve SySTeM AND MeTABOLISM Mitochondrial regulation of cell death and steatohepatitis PUBLICATIONS 6. Regulation of cholesterol homeostasis in pa- tion of which in the mitochondria of fatty livers tients and experimental models of non-alcoho- in humans correlates with graft failure, could be lic steatohepatitis (Dr C. García-Ruiz). an effective way of increasing the number of oRiGinAlS 7. Contribution of sphingolipids to non-alcoholic organs available for transplant. Hepatic steatosis i.f.: 46.82 steatohepatitis and resistance to insulin thera- increases ischaemia/reperfusion (I/R) injury and is py (Dr C. García-Ruiz). considered to be one of the main causes of graft 1 Altamirano J, Higuera-DeLatijera 8. Parenchyma-stroma interaction in cancer- failure after liver transplant. Liver transplant is an F, Duarte-Rojo A, Martinez-Vaz- related and ischaemia/reperfusion-induced liver effective treatment for both end-stage chronic quez MA, Abraldes JG, Herrera- damage: lipid therapies (Dr A. Morales) liver disease and acute liver failure. The reduction Jimenez LE, Michelena J, Zapata 9. Role of cholesterol and the mitochondria in in the number and quality of organs available for L, Perez-Hernandez J, Torre A, Alzheimer’s Disease (Dr A. Colell) liver transplantation is a major problem and leads Gonzales-Gonzalez JA, Cardenas A, 10. Contribution of the TNF and cathepsin recep- to the use of grafts of suboptimal quality which Dominguez M, Arroyo V, Gines P, tors to fibrosis and inflammation of the liver can compromise the success of the transplant. Caballeria J, Bataller R. The Amount (Dr M. Marí). Our data indicate that both cholesterol and the of Alcohol Consumption Negatively transport of cholesterol to the mitochondria play Impacts Short-Term Mortality in Three lines in which we have obtained important a critical role in the susceptibility of the fatty liver Mexican Patients With Alcoholic results are: to I/R injury and that intervention on cholesterol Hepatitis. AM J GASTROENTEROL. 1. caveolin-1 deficiency causes cholesterol- levels could provide a unique opportunity to im- 106:1472-1480. I.F.: 6.88. dependent mitochondrial dysfunction and prove liver transplantation. susceptibility to apoptosis. 2 Angulo S, Morales A, Danese Our study demonstrates an unconventional 3. contribution of tNF receptors to fibrosis of S, Llacuna L, Masamunt MC, Pultz function of caveolin-1 both in vivo and in vitro. the liver. N, Cifone MG, DeSimone C, Del- Caveolins are essential components of caveolae. Fibrosis of the liver is the excessive accumulation gado S, Vila J, Panes J, Donskey Caveolin-1 (CAV-1) is found on the plasma mem- of extracellular matrix proteins, such as colla- C, Fernandez-Checa JC, Fiocchi brane as a scaffold protein organising the activity gen, that occurs in most types of chronic liver C, Sans M. Probiotic sonicates se- of multiple signalling molecules in caveolae. CAV- disease. Advanced fibrosis can lead to cirrhosis, lectively induce mucosal immune 1 exhibits binding properties towards fatty acids liver failure and portal hypertension and often cells apoptosis through ceramide and cholesterol and thus plays a role in regulating requires liver transplantation. Activated hepatic generation via neutral sphingomye- lipid homeostasis and transport. A lack of CAV-1 stellate cells (HSCs) have been identified as the linase. PLOS ONE. 6:e16953-. in humans and mice is associated with many major collagen-producing cell-type in the dama- I.F.: 4.41. disorders, including cardiovascular disease, lipo- ged liver. While the inflammatory cytokine TNF dystrophy, diabetes, cancer and pulmonary fibro- has been implicated in the progression of many 3 Bosch M, Mari M, Herms A, sis, but the underlying mechanisms behind this chronic liver diseases leading to fibrosis, its role Fernandez A, Fajardo A, Kassan A, relationship remain unknown. In this study we in fibrogenesis is the subject of debate and the Giralt A, Colell A, Balgoma D, Bar- have characterised an unconventional function of specific contribution of TNF receptors to HSC bero E, Gonzalez-Moreno E, Matias CAV-1, the regulation of mitochondrial function activation has yet to be determined. In this study, N, Tebar F, Balsinde J, Camps M, and metabolism. In the absence of CAV-1, mito- using hepatic stellate cells (HSC) from wild-type Enrich C, Gross SP, Garcia-Ruiz C, chondrial function is lost due to an accumulation (WT), TNF-receptor-1 (TNFR1) knockout, TNF-re- Perez-Navarro E, Fernandez-Checa of cholesterol which leads to impaired oxidative ceptor-2 (TNFR2) knockout, or TNFR1/R2 double JC, Pol A. Caveolin-1 Deficiency phosphorylation, reduced membrane dynamics knockout (TNFR-DKO) mice, we show that loss Causes Cholesterol-Dependent Mi- and consequently, diminished antioxidant defen- of both TNF receptors reduced procollagen a1(I) tochondrial Dysfunction and Apop- ce due to mitochondrial GSH depletion. Under expression, slowed down HSC proliferation and totic Susceptibility. CURR BIOL. conditions of high metabolic flux requiring energy impaired PDGF-induced promitogenic signalling 21:681-686. I.F.: 10.03. production, the failure of the mitochondria to in HSC. Moreover, matrix metalloproteinase-9 meet the demand for energy results in high (MMP-9) expression in HSCs was controlled by 4 Tarrats N, Moles A, Morales A, production of reactive oxygen species causing TNF through TNFR1 and in vivo liver damage and Garcia-Ruiz C, Fernandez-Checa JC, cell death. Consequently, CAV-1 deficiency leads fibrosis following bile duct ligation was reduced Mari M. Critical Role of Tumor Ne- to mitochondrial dysfunction-related conditions in TNFR-DKO and TNFR1 knockout mice com- crosis Factor Receptor 1, but not 2, such as steatohepatitis and neurodegeneration. pared to wild-type mice. These results are indi- in Hepatic Stellate Cell Proliferation, cative of a regulatory role for TNF in extracellular Extracellular Matrix Remodeling, 2. Intervention on cholesterol protects the fatty matrix remodelling and liver fibrosis, suggesting and Liver Fibrogenesis. HEPATOLO- liver against ischaemia/reperfusion injury. that targeting TNFR1 may be of benefit to atte- GY. 54:319-327. I.F.: 10.89. Taking action against cholesterol, the accumula- nuate liver fibrogenesis.

176 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM MitocHonDRiAl ReGulAtion ofcell DeAtH AnD SteAtoHepAtitiS

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 56.28 9 6 3 5 Bosch M, Mari M, Gross SP, Fer- Caballeria J. Desarrollo de méto- nandez-Checa JC, Pol A. Mitochondrial dos diagnósticos no invasivos para 2010 70.69 10 8 0 Cholesterol: A Connection Between el diagnóstico y pronóstico de las 2011 46.82 6 5 0 Caveolin, Metabolism, and Disease. enfermedades hepáticas inducidas TRAFFIC. 12:1483-1489. I.F.: 5.28. por el alcohol. Sponsored by: Ins- tituto de Salud Carlos III (ISCIII), 6 Llacuna L, Fernandez A, Montfort PI09/1164. Duration: 01/01/2010- CV, Matias N, Martinez L, Caballero F, 31/12/2012. Fernández-Checa JC. From gut-deri- Rimola A, Elena M, Morales A, Fernan- ved inflammation to obesity-related dez-Checa JC, Garcia-Ruiz C. Targeting Fernández-Checa JC. Mitocondria liver disease. Sponsored by: European cholesterol at different levels in the y cáncer: papel del colesterol, GSH Commission, JTC_META_2011_001. mevalonate pathway protects fatty li- y cardiolipina en la regulación de la Duration: 07/04/2011-06/04/2014. ver against ischemia-reperfusion injury. permeabilización de la membrana J HEPATOL. 54:1002-1010. I.F.: 9.33. mitocondrial y muerte celular. Spon- sored by: Ministerio de Ciencia e In- DoctoRAl tHeSeS novación, SAF2009-11417. Duration: ReViewS 01/01/2010-31/12/2012. Fernandez-Checa JC, Gomez L. He- i.f.: 4.77 patocyte growth factor and c-Met: Morales A. Interacción parénquima- Role of hypercholesterolemia and 1 Garcia-Ruiz C, Mari M, Colell A, estroma en patologías hepáticas signal transduction. PhD student: Morales A, Fernandez-Checa JC. Me- asociadas al eje inflamación-cáncer Natalia Nuño Lambarri, Universidad tabolic Therapy: Lessons from Liver e isquemia/reperfusión: implicacio- Autónoma Metropolitana, Mexico DF. Diseases. CURR PHARM DESIGN. nes terapéuticas. Sponsored by: 17:3933-3944. I.F.: 4.77. Instituto de Salud Carlos III (ISCIII), PI09/00056. Duration: 01/01/2010- 31/12/2012. GRAntS foR ReSeARcH in pRoGReSS Mari M. Catepsinas en fibrosis he- pática e inflamación. Sponsored by: Garcia C. Papel de los esfingolipidos Instituto de Salud Carlos III (ISCIII), en la esteatohepatitis no alcohólica PI070193. Duration: 26/11/2007- y resistencia a la insulina hepática. 31/03/2011. Sponsored by: Ministerio Educación y Ciencia, SAF2008-02199. Duration: Colell A. Regulacion mitocondrial de 01/01/2009-31/12/2011. la citotoxicidad inducida por beta- amiloide. Sponsored by: Ministerio García C. Papel de la ceramida y los Educación y Ciencia, SAF2010-15760. esfingolípidos en la estetohepatitis. Duration: 01/01/2011-31/12/2013. Sponsored by: Fundación de Inves- tigación Médica Mútua Madrileña. Fernández-Checa JC. Colesterol y Duration: 31/12/2008-30/12/2011. glicoesfingolípidos en la mitocondria hepática y del cerebro y la alteración Fernández-Checa JC. Mitochon- del metabolismo contribuye a la pato- drial USC-UCLA Research Center logía de la enfermedad de Niemann for Alcoholic Liver and Pancreatic Pick tipo C y caveolinopatías. Sponso- Injury Research Project#1. Sponso- red by: Fundació La Marató de TV3, red by: National Institute of Alcohol 050506110015. Duration: 01/05/2011- Abuse and Alcoholism (NIAAA 01/02/2014. -NIH), 5P50AA011999. Duration: 01/01/2007-31/12/2013.

177 AReA 3 Team involved in: Liver, digestive system and metabolism

Liver transplantation and graft viability

gROUP MeMBeRS StrateGic oBjectiveS

Investigation of clinical, mechanis- tic and therapeutic aspects of liver transplantation. teAM leADeR Antoni Rimola (Hospital clínic) main lineS tel.: 93 227 57 53 of reSearcH fax: 93 451 55 22 e-mail: [email protected] 1. Ischemia-reperfusion liver damage in different models: xxxxxx iDiBApS MeMBeRS: ReSeARcH fellowS: warm ischemia; experimental constantino fondevila Amine Zauali (iDiBApS) liver transplantation in the (Hospital clínic) Xavier Muñoz (ciBeRehd) rat with normal, reduced or Juan c. García-Valdecasas isabel Alfany (iDiBApS) steatosic grafts; experimental (Hospital clínic) Ana teresa Menjívar (fundació clínic) liver transplantation in the pig Martí Manyalich (Hospital clínic) Mónica Jiménez (iDiBApS) with whole or partial grafts, or Albert Sánchez fueyo grafts obtained from donors in (Hospital clínic) tecHniciAnS: asystolia; and liver transplanta- Joan Rosselló-catafau (iiBB-cSic) Anna Rodríguez (ciBeReHD) tion in humans. carmen peralta (iDiBApS) Marta Martínez (iDiBApS) 2. Immunosuppression, with spe- Mercedes Brunet cial interest in three fields: im- (Hospital clínic) nuRSinG StAff: mune tolerance of the allogra- pilar Sesé (iDiBApS) ft, biomarkers of the effects of poStDoctoRAlS fellowS: immunosuppressive drugs, and felix Bohne (Deutsche collABoRAtoRS: identification of populations forschungsgemeinschaft) David calatayud (Hospital clínic) with different risks of rejection. Marta Massip (ciBeRehd) Jose fuster (Hospital clínic) Araní casillas (AGAuR) chloë Ballesté (uB) Susana padrissa (Mcyt) olga Millán (ciBeReHD) ViSitinG ScientiStS: Mª carolota londoño (ciBeReHeD) eleonora Boncompagni (eASl)

Exprimental liver transplantation in the rat.

178 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM liVeR tRAnSplAntAtion AnD GRAft ViABility

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 76.07 19 14 1 oRiGinAlS section for metastatic cutaneous and i.f.: 69.84 ocular melanoma. J HEPATO-BIL-PAN 2010 110.83 26 13 4 SCI. 18:268-275. I.F.: 1.96. 2011 69.84 16 10 2 1 Martinez-Rebollar M, Lonca M, Perez I, Soy D, Brunet M, Martin 6 Fondevila C, Hessheimer AJ, R, Coll O, Hernandez S, Laguno Flores E, Vendrell M, Munoz J, M, Milinkovic A, Larrousse M, Escobar B, Calatayud D, Taura P, Calvo M, Blanco JL, Martinez E, Fuster J, Garcia-Valdecasas JC. Gatell JM, Mallolas J. Pharmacoki- Step-by-Step Guide for a Simplified 11 Guillen D, Millan O, Brunet M. netic Study of Saquinavir 500 mg Model of Porcine Orthotopic Liver In vitro studies of the immunomodu- Plus Ritonavir (1000/100 mg Twice Transplant. J SURG RES. 167:E39- latory effects of statins alone and in a Day) in HIV-Positive Pregnant E45. I.F.: 2.24. combination with immunosuppressi- Women. THER DRUG MONIT. ve drugs. EUR J INFLAMM. 9:117- 33:772-777. I.F.: 3.13. 7 Llacuna L, Fernandez A, Montfort 124. I.F.: 4.00. CV, Matias N, Martinez L, Caballero 2 Lloberas N, Torras J, Cruzado F, Rimola A, Elena M, Morales A, 12 Zaouali MA, Reiter RJ, JM, Andreu F, Oppenheimer F, Fernandez-Checa JC, Garcia-Ruiz Padrissa-Altes S, Boncompagni E, Sanchez-Plumed J, Gentil MA, C. Targeting cholesterol at different Garcia JJ, BenAbnennebi H, Freitas Brunet M, Ekberg H, Grinyo JM. levels in the mevalonate pathway I, Garcia-Gil FA, Rosello-Catafau J. Influence of MRP2 on MPA phar- protects fatty liver against ischemia- Melatonin protects steatotic and macokinetics in renal transplant reperfusion injury. J HEPATOL. nonsteatotic liver grafts against cold recipients-results of the Pharma- 54:1002-1010. I.F.: 9.33. ischemia and reperfusion injury. J PI- cogenomic Substudy within the NEAL RES. 50:213-221. I.F.: 5.86. Symphony Study. NEPHROL DIAL 8 Lozano JJ, Pallier A, Martinez- TRANSPL. 26:3784-3793. I.F.: 3.56. Llordella M, Danger R, Lopez M, 13 Casillas-Ramirez A, Alfany- Giral M, Londono MC, Rimola A, Fernandez I, Massip-Salcedo M, 3 Dragun J, Perez-Del-Pulgar S, Soulillou JP, Brouard S, Sanchez- Juan ME, Planas JM, Serafin A, Crespo G, Ramirez S, Coto-Llerena Fueyo A. Comparison of transcrip- Pallas M, Rimola A, Rodes J, Peralta M, Mensa L, Garcia-Valdecasas JC, tional and blood cell-phenotypic C. Retinol-Binding Protein 4 and Navasa M, Forns X. Characteriza- markers between operationally Peroxisome Proliferator-Activated tion of the Cross-Neutralizing Anti- tolerant liver and kidney recipients. Receptor-gamma in Steatotic Liver body Response Against Hepatitis AM J TRANSPLANT. 11:1916-1926. Transplantation. J PHARMACOL EXP C Virus in the Liver Transplantation I.F.: 6.05. THER. 338:143-153. I.F.: 4.02. Setting. AM J TRANSPLANT. 11:767-774. I.F.: 6.05. 9 Jimenez-Castro MB, Casillas- 14 Vidal O, Valentini M, Ginesta Ramirez A, Massip-Salcedo M, Elias- C, Espert JJ, Martinez A, Benarroch 4 Hessheimer A, Fondevila C, Tau- Miro M, Serafin A, Rimola A, Rodes G, Anglada MT, Garcia-Valdecasas ra P, Muñoz J, Sanchez O, Fuster J, Peralta C. Cyclic Adenosine 3 ‘,5 JC. Single-Incision Versus Standard J, Rimola A, Garcia-Valdecasas JC. ‘-Monophosphate in Rat Steatotic Laparoscopic Cholecystectomy: Com- Decompression of the portal bed Liver Transplantation. LIVER TRANS- parison of Surgical Outcomes from a and twice-baseline portal inflow are PLANT. 17:1099-1110. I.F.: 3.07. Single Institution. J LAPAROENDOSC necessary for the functional reco- ADV S. 21:683-686. I.F.: 1.20. very of a small-for size graft. ANN 10 Rafael-Valdivia L, Mendoza SURG. 253:1201-1210. I.F.: 7.47. MA, Martinez-Saldivar B, Sanchez- 15 Fondevila C, Hessheimer AJ, Fueyo A, Brunet M, Garcia-Valdeca- Maathuis MHJ, Munoz J, Taura P, 5 Caralt M, Marti J, Cortes J, sas JC, Rimola A. How long should Calatayud D, Leuvenink H, Rimola A, Fondevila C, Bilbao I, Fuster J, initiation of calcineurin inhibitors be Ploeg RJ, Garcia-Valdecasas JC. Supe- Garcia-Valdecasas JC, Sapisochin delayed to protect renal function in rior Preservation of DCD Livers With G, Balsells J, Charco R. Outcome liver transplantation?. TRANSPL P. Continuous Normothermic Perfusion. of patients following hepatic re- 43:697-698. I.F.: 0.99. ANN SURG. 254:1000-1007. I.F.: 7.47.

179 LIveR, DIgeSTIve SySTeM AND MeTABOLISM

Liver transplantation and graft viability

16 Vidal O, Ginesta C, Valen- 6 Sanchez-Fueyo A, Strom TB. Im- Sanchez A. Effect of rapamycin on tini M, Marti J, Benarroch G, munologic Basis of Graft Rejection tolerance biomarkers in liver trans- Garcia-Valdecasas JC. Suprapubic and Tolerance Following Transplanta- plantation. Sponsored by: Immune single-incision laparoscopic ap- tion of Liver or Other Solid Organs. Tolerance Network (Consorcio pendectomy: a nonvisible-scar GASTROENTEROLOGY. 140:51-+. financiado por el National Institute surgical option. SURG ENDOSC. I.F.: 12.03. of Health, USA), Sirolimus Liver To- 25:1019-1023. I.F.: 3.44. lerance, ITN10238-00SC. Duration: 7 Dominguez-Gil B, Delmonico 01/12/2008-30/12/2011. FL, Shaheen FAM, Matesanz R, ReViewS O’connor K, Minina M, Muller E, Fondevila C. Evaluación de la modifi- i.f.: 32.28 Young K, Manyalich M, Chapman cación farmacológica del flujo portal J, Kirste G, Al-Mousawi M, Coene para prevenir la aparición del síndro- 1 Trullas JC, Cofan F, Tuset M, L, Garcia VD, Gautier S, Hasegawa me small-for-size en el transplante Ricart MJ, Brunet M, Cervera C, T, Jha V, Kwek TK, Chen ZK, Loty hepático en cerdos. Sponsored by: Manzardo C, Lopez-Dieguez M, B, Costa AN, Nathan HM, Ploeg Instituto de Salud Carlos III (ISCIII), Oppenheimer F, Moreno A, Cam- R, Reznik O, Rosendale JD, Tibell PI080273. Duration: 01/01/2009- pistol JM, Miro JM. Renal trans- A, Tsoulfas G, Vathsala A, Noel L. 14/02/2012. plantation in HIV-infected patients: The critical pathway for deceased 2010 update. KIDNEY INT. 79:825- donation: reportable uniformity in Brunet M. Estudio multicéntrico 842. I.F.: 6.11. the approach to deceased dona- para la validación de los biomarca- tion. TRANSPL INT. 24:373-378. dores de elección que reflejen la 2 Elias-Miro M, Massip-Salcedo I.F.: 3.21. respuesta individual de los pacientes M, Jimenez-Castro M, Peralta C. trasplantados de órganos sólidos al Does adiponectin benefit steato- tratamiento inmunosupresor. Spon- tic liver transplantation?. LIVER eDitoRiAlS sored by: Instituto de Salud Carlos TRANSPLANT. 17:993-1004. i.f.: 16.22 III (ISCIII), PI080300. Duration: I.F.: 3.07. 01/01/2008-31/12/2011. 1 Garcia-Valdecasas JC. DCD 3 Peralta C, Brenner C. Endo- donors: A unique source to signi- Peralta C. Una conservación acuosa plasmic reticulum stress inhibi- ficantly increase organ donation. J para la conservación de órganos. tion enhances liver tolerance to HEPATOL. 55:745-746. I.F.: 9.33. Sponsored by: CIDEM, Generalitat ischemia/reperfusion. CURR MED de Catalunya, VALTEC08-2-0033. CHEM. 18:2016-2024. I.F.: 4.63. 2 Brandhorst G, Oellerich M, Duration: 31/10/2008-31/10/2011. Brunet M, Kowalski R, Vinks A, 4 Zaouali MA, BenAbdennebi H, Wallemacq P. Individually Tailored Manyalich M. European living do- Padrissa-Altes S, Alfany-Fernan- Immunosuppression: Is There a nor psychosocial follow-up (ELIP- dez I, Rimola A, Rosello-Catafau Role for Biomarkers?. CLIN CHEM. SY). Sponsored by: Executive J. How Institut Georges Lopez 57:376-381. I.F.: 6.89. Agency for Health and Consumers preservation solution protects (EAHC), European Commission, nonsteatotic and steatotic livers 20081104. Duration: 01/12/2009- against ischemia-reperfusion GRAntS foR ReSeARcH 30/11/2012. injury. TRANSPL P. 43:77-79. in pRoGReSS I.F.: 0.99. Rimola A. Valor predictivo de pará- Sanchez A. Métodos para inducir y metros inmunológicos pretrasplante 5 BenAbdennebi H, Zaouali diagnosticar la tolerancia inmunoló- del receptor y del donante en el de- MA, Alfany-Fernandez I, Tabka gica en el trasplante hepático. Spon- sarrollo de rechazo e infección en el D, Rosello-Catafau J. How to sored by: Ministerio de Educación y trasplante hepático. Sponsored by: protect liver graft with nitric oxi- Ciencia, SAF2008-04092. Duration: Instituto de Salud Carlos III (ISCIII), de. WORLD J GASTROENTERO. 01/01/2009-31/12/2011. PI09/0418. Duration: 01/01/2010- 17:2879-2889. I.F.: 2.24. 31/12/2012.

180 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM liVeR tRAnSplAntAtion AnD GRAft ViABility

Peralta C. Regulación del RBP4 en DoctoRAl tHeSeS trasplante de higados esteatósicos. Sponsored by: Ministerio de Edu- Brunet M. Estudio del efecto inmu- cación, BFU2009_07410. Duration: nomodulador de las estatinas. Estu- 01/01/2010-31/12/2012. dios in vitro e in vivo. PhD student: David Guillen Tunica. Roselló J. Papel del proteasoma dependiente de la ubiquitina en la Peralta C. Papel diferencial de la preservación del hígado graso frente Angiotensina II en resecciones he- a la lesión por isquemia-reperfusión. páticas y trasplante de hígado. PhD Sponsored by: Instituto de Salud student: Isabel Alfany Fernández. Carlos III (ISCIII), PI-081988. Dura- tion: 01/01/2009-31/12/2011. Peralta C. Estrategias para proteger el injerto esteatósico en el trasplan- Manyalich M. Impacto psicosocial te hepático. PhD student: Arani Ca- del proceso de donación en el do- sillas Ramírez. nante vivo de órganos para trasplante. Sponsored by: Instituto de Salud Carlos III (ISCIII), PI10/00949. Dura- tion: 01/01/2011-31/12/2013.

Peralta C. Preservació de l’empelt hepatic. Sponsored by: Gene- ralitat de Catalunya, AGAUR, 2009_SGR_952. Duration: 22/07/2009-31/12/2013.

Sanchez A. Estudio piloto de retirada de la medicación inmunosupresora en pacientes que exhiben marcadores transcripcionales de alta pro- babilidad de tolerancia. Sponsored by: Fundación Mútua Madrileña, AP93762011. Duration: 16/09/2011- 16/09/2013.

Sanchez A. Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipient. Sponsored by: National Institutes of Health (NIH), 5813SC. Duration: 30/09/2009- 31/08/2011.

181 AReA 3 Team involved in: Liver, digestive system and metabolism

Gastrointestinal and pancreatic oncology

gROUP MeMBeRS

teAM leADeR Antoni castells (Hospital clínic) tel.: 93 227 57 39 fax: 93 227 55 89 e-mail: [email protected]

iDiBApS MeMBeRS: tecHniciAnS: ADMiniStRAtiVe StAff: Juan Ramon Ayuso (Hospital clínic) Jennifer Muñoz Sancho Diana Vargas Ríos (Hospital clínic) francesc Balaguer prunes (ciBeRehd, Hospital clínic) (Hospital clínic) Georgina Ramirez Ramal collABoRAtoRS: Sergi castellví (iDiBApS) (fundació clínic) pere Gambús cerillo (Hospital clínic) José ignacio elizalde (Hospital clínic) esther Samper lirola eva Vaquero Raya (Hospital clínic) laureano fernández-cruz (ciBeRehd, Hospital clínic) Virginia Alonso espinaco (ciBeRehd, (Hospital clínic) Hospital clínic) Glòria fernández-esparrach nuRSinG StAff: Meritxell Gironella cos (ciBeRehd. (Hospital clínic) teresa ocaña Bombardo Hospital clínic) cristina fillat (iDiBApS) (Hospital clínic) imma Garrell lluis (cApSe) Àngels Ginès (Hospital clínic) cristina Rodríguez de Miguel Jordi camps (fundació clínic) Antonio lacy (Hospital clínic) (fundació clínic) Salvador navarro (Hospital clínic) Anna Serradesanferm fabregas Maria pellisé (Hospital clínic) (Hospital clínic) oscar Vidal (Hospital clínic) teresa Hospital (fundació clínic)

poStDoctoRAlS fellowS: Maria Victoria Maliandi (iDiBApS) Anabel José (iDiBApS)

ReSeARcH fellowS: Victòria Gonzalo pascual (Hospital clínic) oriol Sendino Garcia (Hospital clínic) Mª Dolores Giráldez Jiménez (Hospital clínic) María lópez-cerón pinilla (fundació clínic) Xavier Borrat (Hospital clínic) leticia Moreira Ruiz (Hospital clínic) laura Visa turmo (Hospital clínic) Xavier Bofill de Ros (fpu) Ana Mato Berciano (fpu) eneko Villanueva Verdejo (fpi Gobierno Vasco) Maria Rovira Rigau (fpi)

182 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM GAStRointeStinAl AnD pAncReAtic oncoloGy

PUBLICATIONS

StrateGic 1. Physiopathology of colorectal cancer: oRiGinAlS oBjectiveS • Hereditary forms of colorectal i.f.: 206.49 cancer, screening and surveillan- The gaining of in-depth knowledge of ce. 1 Guarner-Argente C, Cordova H, the mechanisms underlying the deve- • Genetic susceptibility in colorectal Martinez-Palli G, Navarro-Ripoll R, lopment and progression of gastroin- cancer. Rodriguez-D’jesus A, DeMiguel CR, testinal and pancreatic premalignant • Epigenetics of colorectal cancer. Beltran M, Fernandez-Esparrach and malignant lesions, with a view to 2. Physiopathology of pancreatic G. Gastrotomy closure with a defining new diagnostic, therapeutic cancer: new tissue anchoring device: A and/or preventive strategies. • Implication of microRNAs in pan- porcine survival study. WORLD J creatic cancer. GASTROENTERO. 17:1732-1738. main lineS • Epithelial-mesenchymal transition I.F.: 2.24. of reSearcH in the local and metastatic spread of pancreatic cancer. 2 Guarner-Argente C, Beltran M, The activity of the research group in 3. Research and innovation in endos- Martinez-Palli G, Navarro-Ripoll R, gastrointestinal and pancreatic oncolo- copy: Martinez-Zamora MA, Cordova H, gy is divided into four areas, and these • Endoscopic ultrasound. Comas J, DeMiguel CR, Rodriguez- in turn correspond to different lines of • Advanced diagnostic techniques. D’jesus A, Almela M, Hernandez-Ce- investigation: • Endoscopic therapies. ra C, Lacy AM, Fernandez-Esparrach 4. Research and innovation in surgery: G. Infection during Natural Orifice • Surgery for colorectal cancer. Transluminal Endoscopic Surgery • Surgery for pancreatic cancer. Peritoneoscopy: A Randomized Comparative Study in a Survival Por- cine Model. J MINIM INVAS GYN. 18:741-746. I.F.: 1.56. ReSeARCh gROUP Gene tHerapy and cancer Group 3 Abuli A, Fernandez-Rozadilla C, Giraldez MD, Munoz J, Gonzalo V, Group Leader: Bessa X, Bujanda L, Rene JM, Lanas cristina Fillat (IDIBAPS) A, Garcia AM, Salo J, Arguello L, Vilella A, Carreno R, Jover R, Xicola The Gene Therapy and Cancer Group led by Cristina Fillat RM, Llor X, Carvajal-Carmona L, started at the IDIBAPS in September 2011, with the sup- Tomlinson IPM, Kerr DJ, Houlston port of the ISIS Programme from the Instituto de Salud Carlos III and ac- RS, Pique JM, Carracedo A, Castells knowledged by the Catalan Government as a Singular Research Group. A, Andreu M, Ruiz-Ponte C, Caste- Our research focuses on the study of the molecular and cellular basis of llvi-Bel S. A two-phase case-control pancreatic ductal adenocarcinoma and the development of novel experi- study for colorectal cancer genetic mental therapies based on gene transfer and virotherapy. susceptibility: candidate genes from The main research lines are: chromosomal regions 9q22 and 1. Identify specific cellular pathways and molecular determinants altered in 3q22. BRIT J CANCER. 105:870-875. pancreatic tumors. I.F.: 4.83. 2. Development of antitumoral therapies based on oncolytic adenovirus. Main interest is devoted to the search for sensitizers of adenoviral oncol- 4 Scholin J, Buunen M, Hop W, ysis and to study their mechanisms of synergie. Special emphasis is also Bonjer J, Anderberg B, Cuesta M, applied to engineer tumor-selective oncolytic adenoviruses. Delgado S, Ibarzabal A, Ivarsson ML, 3. Explore novel non-viral experimental therapies for pancreatic tumors. Janson M, Lacy A, Lange J, Pahlman Preclinical testing of the newly developed therapies is studied in genet- L, Skullman S, Haglind E. Bowel obs- ically-modifiedmouse models and in orthotopicxenografts. Some of the truction after laparoscopic and open animal models are specially designed to allow for the non-invasive imag- colon resection for cancer: Results ing of tumor progression and metastatic processes. of 5 years of follow-up in a randomi-

183 LIveR, DIgeSTIve SySTeM AND MeTABOLISM

Gastrointestinal and pancreatic oncology

zed trial. SURG ENDOSC. 25:3755- 9 Pellise M, Lopez-Ceron M, DeMi- 14 Perez-Torras S, Vidal-Pla A, Mi- 3760. I.F.: 3.44. guel CR, Jimeno M, Zabalza M, Ricart quel R, Almendro V, Fernandez-Cruz L, E, Aceituno M, Fernandez-Esparrach Navarro S, Maurel J, Carbo N, Gascon 5 Abuli A, Fernandez-Rozadilla C, G, Gines A, Sendino O, Cuatrecasas P, Mazo A. Characterization of human Alonso-Espinaco V, Munoz J, Gon- M, Llach J, Panes J. Narrow-band pancreatic orthotopic tumor xenografts zalo V, Bessa X, Gonzalez D, Clofent imaging as an alternative to chromoen- suitable for drug screening. CELL ON- J, Cubiella J, Morillas JD, Rigau J, doscopy for the detection of dysplasia COL. 34:511-521. I.F.: 3.18. Latorre M, Fernandez-Banares F, in long-standing inflammatory bowel Pena E, Riestra S, Paya A, Jover R, disease: a prospective, randomized, 15 Huang K, Gutierrez LP, Bulow S, Xicola RM, Llor X, Carvajal-Carmona crossover study. GASTROINTEST EN- Gallinger S, Castells A, Eagle CJ, Church L, Villanueva CM, Moreno V, Pique DOSC. 74:840-848. I.F.: 5.65. JM. Clinical characteristics and outco- JM, Carracedo A, Castells A, Andreu mes in familial adenomatous polyposis M, Ruiz-Ponte C, Castellvi-Bel S. 10 Vidal O, Valentini M, Ginesta patients with a long-term treatment of Case-control study for colorectal C, Espert JJ, Martinez A, Benarroch celecoxib: a matched cohort study. FAM cancer genetic susceptibility in G, Anglada MT, Garcia-Valdecasas CANCER. 10:303-308. I.F.: 2.14. EPICOLON: previously identified JC. Single-Incision Versus Standard variants and mucins. BMC CANCER. Laparoscopic Cholecystectomy: Com- 16 Horndler C, Gallego R, Garcia-Al- 11:-. I.F.: 3.15. parison of Surgical Outcomes from a beniz X, Alonso-Espinaco V, Alonso V, Single Institution. J LAPAROENDOSC Escudero P, Jimeno M, Ortego J, Co- 6 Fernandez-Esparrach G, Cordo- ADV S. 21:683-686. I.F.: 1.20. dony-Servat J, Fernandez-Martos C, va H, Bordas JM, Gomez-Molins Calatrava A, Marin-Aguilera M, Munoz I, Gines A, Pellise M, Sendino O, 11 Jover R, Nguyen TP, Perez-Car- J, Castellvi-Bel S, Castells A, Rubini Gonzalez-Suarez B, Cardenas A, bonell L, Zapater P, Paya A, Alenda C, M, Gascon P, Maurel J. Co-expression Balderramo D, Lacy AM, Delgado Rojas E, Cubiella J, Balaguer F, Morillas of matrix metalloproteinase-7 (MMP- S, Llach J. Endoscopic manage- JD, Clofent J, Bujanda L, Rene JM, 7) and phosphorylated insulin growth ment of the complications of ba- Bessa X, Xicola RM, Nicolas-Perez D, factor receptor I (pIGF-1R) correlates riatric surgery. Experience of more Castells A, Andreu M, Llor X, Boland with poor prognosis in patients with than 400 interventions. HEPATO- CR, Goel A. 5-Fluorouracil Adjuvant wild-type KRAS treated with cetuxi- GASTROENTEROL. 34:131-136. Chemotherapy Does Not Increase mab or panitumumab A GEMCAD stu- I.F.: 0.68. Survival in Patients With CpG Island dy. CANCER BIOL THER. 11:177-183. Methylator Phenotype Colorectal Can- I.F.: 2.91. 7 Fernandez-Esparrach G, Ayuso- cer. GASTROENTEROLOGY. 140:1174- Colella JR, Sendino O, Pages M, 1181. I.F.: 12.03. 17 Balaguer F, Moreira L, Lozano JJ, Cuatrecasas M, Pellise M, Maurel Link A, Ramirez G, Shen Y, Cuatreca- J, Ayuso-Colella C, Gonzalez-Suarez 12 Martinez F, Fernandez-Martos C, sas M, Arnold M, Meltzer SJ, Syngal B, Llach J, Castells A, Gines A. EUS Quintana MJ, Castells A, Llombart A, S, Stoffel E, Jover R, Llor X, Castells and magnetic resonance imaging in Iniguez F, Guillem V, Dasi F. APC and A, Boland CR, Gironella M, Goel A. the staging of rectal cancer: a pros- KRAS mutations in distal colorectal Colorectal Cancers with Microsatelli- pective and comparative study. GAS- polyps are related to smoking habits te Instability Display Unique miRNA TROINTEST ENDOSC. 74:347-354. in men: results of a cross-sectional Profiles. CLIN CANCER RES. 17:6239- I.F.: 5.65. study. CLIN TRANSL ONCOL. 13:664- 6249. I.F.: 7.34. 671. I.F.: 1.25. 8 Caldelari ACA, Miquel R, Bombi 18 Lluis M, Fernandez-Sola J, JA, Gines A, Fernandez-Esparrach G, 13 Sanchez-Tillo E, DeBarrios O, Siles Castellvi-Bel S, Sacanella E, Estruch Ayuso JR, Maurel J, Feu F, Castells L, Cuatrecasas M, Castells A, Postigo R, Urbano-Marquez A. Evaluation of A, Fernandez-Cruz L, Navarro S. A. beta-catenin/TCF4 complex induces Myocyte Proliferation in Alcoholic Malignancy predictive factors in pan- the epithelial-to-mesenchymal transition Cardiomyopathy: Telomerase Enzyme creatic intraductal papillary mucinous (EMT)-activator ZEB1 to regulate tumor Activity (TERT) Compared with Ki-67 neoplasm. MED CLIN-BARCELONA. invasiveness. P NATL ACAD SCI USA. Expression. ALCOHOL ALCOHOLISM. 137:631-636. I.F.: 1.41. 108:19204-19209. I.F.: 9.77. 46:534-541. I.F.: 2.60.

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original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 95.10 19 10 6 19 Castillejo A, Guarinos C, Mar- the clinical practice guidelines of the tinez-Canto A, Barbera VM, Egoavil European Association for Endoscopic 2010 132.71 26 16 4 C, Castillejo MI, Perez-Carbonell L, Surgery (EAES). SURG ENDOSC. 2011 206.49 33 12 10 Sanchez-Heras AB, Segura A, Ochoa 25:2423-2440. I.F.: 3.44. E, Lazaro R, Ruiz-Ponte C, Bujanda L, Andreu M, Castells A, Carracedo A, 24 King CE, Cuatrecasas M, Cas- Llor X, Clofent J, Alenda C, Paya A, tells A, Sepulveda AR, Lee JS, Rustgi Jover R, Soto JL. Evidence for clas- AK. LIN28B promotes colon cancer sification of c.1852_1853AA > GC in progression and metastasis. CANCER 28 Boeckxstaens GE, Annese V, MLH1 as a neutral variant for Lynch RES. 71:4260-4268. I.F.: 8.23. DesVarannes SB, Chaussade S, Cos- syndrome. BMC MED GENET. 12:-. tantini M, Cuttitta A, Elizalde JI, Fuma- I.F.: 2.44. 25 Tomlinson IPM, Carvajal- galli U, Gaudric M, Rohof WO, Smout Carmona LG, Dobbins SE, Tenesa AJ, Tack J, Zwinderman AH, Zaninotto 20 Kupfer SS, Anderson JR, Ludvik A, Jones AM, Howarth K, Palles C, G, Busch OR. Pneumatic Dilation ver- AE, Hooker S, Skol A, Kittles RA, Keku Broderick P, Jaeger EEM, Farring- sus Laparoscopic Heller’s Myotomy TO, Sandler RS, Ruiz-Ponte C, Castell- ton S, Lewis A, Prendergast JGD, for Idiopathic Achalasia. NEW ENGL J vi-Bel S, Castells A, Carracedo A, Ellis Pittman AM, Theodoratou E, Olver MED. 364:1807-1816. I.F.: 53.49. NA. Genetic Associations in the Vita- B, Walker M, Penegar S, Barclay min D Receptor and Colorectal Cancer E, Whiffin N, Martin L, Ballereau 29 Garcia-Albeniz X, Pericay C, in African Americans and Caucasians. S, Lloyd A, Gorman M, Lubbe S, Alonso-Espinaco V, Alonso V, Escudero PLOS ONE. 6:-. I.F.: 4.41. Howie B, Marchini J, Ruiz-Ponte C, P, Fernandez-Martos C, Gallego R, Fernandez-Rozadilla C, Castells A, Gascon P, Castellvi-Bel S, Maurel J. 21 Mongroo PS, Noubissi FK, Carracedo A, Castellvi-Bel S, Duggan Serum matrilysin correlates with poor Cuatrecasas M, Kalabis J, King CE, D, Conti D, Cazier JB, Campbell H, survival independently of KRAS and Johnstone CN, Bowser MJ, Castells Sieber O, Lipton L, Gibbs P, Martin BRAF status in refractory advanced A, Spiegelman VS, Rustgi AK. IMP-1 NG, Montgomery GW, Young J, Baird colorectal cancer patients treated with Displays Cross-Talk with K-Ras and PN, Gallinger S, Newcomb P, Hopper irinotecan plus cetuximab. TUMOR Modulates Colon Cancer Cell Survival J, Jenkins MA, Aaltonen LA, Kerr BIOL. 32:417-424. I.F.: 2.03. through the Novel Proapoptotic Protein DJ, Cheadle J, Pharoah P, Casey G, CYFIP2. CANCER RES. 71:2172-2182. Houlston RS, Dunlop MG. Multiple 30 Diaz-Moralli S, Tarrado-Castellar- I.F.: 8.23. Common Susceptibility Variants near nau M, Alenda C, Castells A, Cascante BMP Pathway Loci GREM1, BMP4, M. Transketolase-Like 1 Expression Is 22 Dumonceau JM, Polkowski and BMP2 Explain Part of the Mis- Modulated during Colorectal Cancer M, Larghi A, Vilmann P, Giovannini sing Heritability of Colorectal Cancer. Progression and Metastasis Forma- M, Frossard JL, Heresbach D, Pujol PLOS GENET. 7:-. I.F.: 9.54. tion. PLOS ONE. 6:-. I.F.: 4.41. B, Fernandez-Esparrach G, Vazquez- Sequeiros E, Gines A. Indications, re- 26 Alonso-Espinaco V, Giraldez MD, 31 Bessa X, Alenda C, Paya A, sults, and clinical impact of endoscopic Trujillo C, VanDerKlift H, Munoz J, Bala- Alvarez C, Iglesias M, Seoane A, ultrasound (EUS)-guided sampling in guer F, Ocana T, Madrigal I, Jones AM, Dedeu JM, Abuli A, Ilzarbe L, Nava- gastroenterology: European Society of Echeverry MM, Velez A, Tomlinson I, rro G, Pellise M, Balaguer F, Castell- Gastrointestinal Endoscopy (ESGE) Cli- Mila M, Wijnen J, Carvajal-Carmona L, vi-Bel S, Llor X, Castells A, Jover R, nical Guideline. ENDOSCOPY. 43:897- Castells A, Castellvi-Bel S. Novel MLH1 Andreu M. Validation Microsatellite 910. I.F.: 6.10. duplication identified in Colombian Path Score in a Population-Based families with Lynch syndrome. GENET Cohort of Patients With Colorectal 23 Siegel R, Cuesta MA, Targarona MED. 13:155-160. I.F.: 5.28. Cancer. J CLIN ONCOL. 29:3374- E, Bader FG, Morino M, Corcelles R, 3380. I.F.: 18.97. Lacy AM, Pahlman L, Haglind E, Bujko 27 Fernandez-Cruz L. Pancreatico- K, Bruch HP, Heiss MM, Eikermann jejunostomy versus pancreaticogas- 32 Fuster D, Ayuso JR, Poveda M, Neugebauer EAM. Laparoscopic trostomy. J HEPATO-BILIARY-PAN. A, Cubedo R, Casado A, Martinez- extraperitoneal rectal cancer surgery: 18:762-768. I.F.: 1.96. Trufero J, Lopez-Pousa A, DelMuro

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Gastrointestinal and pancreatic oncology

XG, Lomena F, Maurel J, Pons F. GRAntS foR ReSeARcH Castells A. Subproductos de la des- Value of FDG-PET for monitoring in pRoGReSS infección y otros determinantes am- treatment response in patients bientales, genéticos y moleculares with advanced GIST refractory to Castells A. Cribado del cáncer colo- del cáncer colorrectal. Sponsored by: high-dose imatinib. A multicenter rrectal en población de riesgo interme- Instituto de Salud Carlos III, PI080533. GEIS study. Q J NUCL MED MOL dio: estudio multicéntrico, aleatorizado Duration: 01/01/2009-31/12/2012. IM. 55:680-687. I.F.: 2.54. y controlado en el que se compara la prueba de detección de sangre Pellise M. Implicación de los focos de 33 Abate-Daga D, Andreu N, oculta en heces mediante método criptas aberrantes en la carcinogénesis Camacho-Sánchez J, Alemany inmunológico y la colonoscopia. Spon- colorrectal: estudio morfológico con R, Herance R, Millán O, Fillat C. sored by: Fundación de la Asociación técnicas de endoscopia avanzada y ca- Oncolytic adenoviruses armed Española Contra el Cáncer (AECC), racterización molecular. Sponsored by: with thymidine kinase can be AECC_07/185. Duration: 01/03/2007- Instituto de Salud Carlos III, PI09/0669. traced by PET imaging and show 30/06/2011. Duration: 01/01/2010-31/12/2012. potent antitumoural effects by ganciclovir dosing. PLOS ONE. Castellvi S, Castells A, Balaguer F, Fillat C. Control transcripcional y por 6(10):e26142-e26142. I.F.: 4.41. Gonzalo V. Genetic study of common microRNAs de adenovirus oncolíti- hereditary bowel cancers in Hispania cos portadores del gen TK: estudios and the Americas (CHIBCHA). Spon- de eficacia terapéutica en células ReViewS sored by: European Commission, 7th troncales neoplásicas de cáncer de i.f.: 4.12 Framework Programme, 223678. Dura- páncreas y en modelos animales. tion: 01/06/2009-30/11/2012. Sponsored by: Ministerio de Ciencia 1 Moreira L, Castells A. Cyclooxyge- e Innovación (MICINN), BIO2008- nase as a Target for Colorectal Cancer Castells A. Grup de Recerca en On- 04692-C03-02. Duration: 15/07/2011- Chemoprevention. CURR DRUG TAR- cología Gastrointestinal i Pancreàtica. 16/04/2012. GETS. 12:1888-1894. I.F.: 3.06. Sponsored by: Agència de Gestió d’Ajuts Universitaris i de Recerca Fillat C. Knockdown of HAS 21-syn- 2 Fernandez-Cruz L, Belli A, Acosta (AGAUR), 2009-SGR-849. Duration: tenic miRNAs in Ts65Dn mice by M, Chavarria EJ, Adelsdorfer W, 01/07/2009-30/06/2014. adeno-associated viral vectors. Lopez-Boado MA, Ferrer J. Which Consequences on hippocampus- is the best technique for pancrea- Castellvi S, Pique JM, Giraldez M, dependent phenotypes. Sponsored by: ticoenteric reconstruction after Ocaña T. Componentes genéticos Fondation Jerome Lejeune. Duration: pancreaticoduodenectomy? A critical comunes y de baja penetrancia impli- 01/01/2009-31/12/2011. analysis. SURG TODAY. 41:761-766. cados en cáncer colorrectal: correla- I.F.: 1.06. ción genotipo-fenotipo e identificación Fillat C. Grup de Recerca Reconegut. de variantes genómicas de riesgo. Sponsored by: Generalitat de Catalun- Sponsored by: Instituto de Salud ya, AGAUR, 2009_SGR_1527. Dura- eDitoRiAlS Carlos III (ISCIII), PI080024. Duration: tion: 01/09/2009-31/12/2013. i.f.: 24.06 01/01/2009-31/12/2013. Castells A. caracterización genómi- 1 Pellise M, Panes J. Confocal Castells A. Cribado del cáncer colo- ca del síndrome de Linch mediante endomicroscopy in celiac disease. rrectal en población de riesgo interme- secuenciación de nueva generación: GASTROENTEROLOGY. 140:1097- dio: estudio multicéntrico, aleatorizado correlación con el perfil transcriptó- 1099. I.F.: 12.03. y controlado en el que se compara la mico y epigenómico. Sponsored by: prueba de detección de sangre oculta. Ministerio de Ciencia e Innovación, 2 Fernandez-Esparrach G, Panes J. Sponsored by: Asociación Española SAF2010-19273. Duration: 01/01/2011- Radiofrequency ablation for nondys- Contra el Cáncer, 08/507. Duration: 31/12/2013. plastic Barrett’s esophagus: to treat 09/10/2008-30/06/2011. or not to treat?. GASTROENTERO- LOGY. 140:2130-2132. I.F.: 12.03.

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Fernández-Esparrach G. Mediastinos- copia transesofágica guiada por un sistema de registro de la imagen versus mediastinoscopia convencional. Estu- dio comparativo en un modelo porcino. Sponsored by: Ministerio de Ciencia e Innovacion, SAF2010-15635. Duration: 01/01/2011-31/12/2013.

Balaguer F. Implicación del metiloma en la patogénesis y diagnóstico del cáncer colorrectal. Sponsored by: Ins- tituto de Salud Carlos III, PI10/00384. Duration: 01/01/2011-31/12/2013.

DoctoRAl tHeSeS

Lacy A. Efectos del Bypass en “Y de Roux” por laparoscopia como técnica de cirugía bariátrica en el tratamiento del síndrome metabólico asociado a la obesidad mórbida. PhD student: Ricard Corcelles Codina.

Lacy A, Fernandez-Esparrach G. Cam- bios fisiológicos e inmunológicos de la cirugía endoscópica transluminal a través de orificios naturales (NOTES) utilizando diferentes vías de acceso versus la laparoscopia: estudio comparativo en un modelo porcino. PhD student: Carlos Guarner Argente.

187 AReA 3 Team involved in: Liver, digestive system and metabolism

Hereditary metabolic diseases

gROUP MeMBeRS StrateGic 4. Cerebral creatine deficiency. Our oBjectiveS group has been a pioneer in the identification of patients with cerebral The strategic objective of our group creatine deficiency. At present we teAM leADeR is to investigate the genetic and bio- are centered on the evaluation of Antonia Ribes chemical bases, as well as the physio- different creatine derivatives with the (Hospital clínic) pathological mechanisms, of hereditary purpose of establishing a treatment tel.: 93 227 54 00 (9340) metabolic diseases. The ultimate aim for creatine transport deficiency. the- fax: 93 227 56 68 is to develop new diagnostic and thera- se creatine uptake studies are carried e-mail: peutic strategies. out in neurons derived from IPI cells [email protected] On the other hand, we conducttransla- and HUVEC and HBMEC cells silen- tional research, stimulating the transfer ced with interference RNA. of knowledge from basic research to the 5. mtDNA depletion. A nucleotide me- clinical practice setting, and vice versa. tabolic defect may give rise to mitochondrial DNA depletion. Since we main lineS have identified patients with these of reSearcH characteristics, without mutations of the genes known to date, our objec- Within the general line of hereditary me- tive is to explore new genes capable tabolic diseases, our concrete research of explaining the disease. lines are based on the following: 6. Type C Niemann-Pick disease. The 1. In vitro therapeutic approaches. . study of patients with this disorder This study involves the testing of has been carried out in a knock-in chemical and peptide libraries. Selec- murine model, with a view to gaining iDiBApS MeMBeRS: tion has been made of disease stop further knowledge of the underlying paz Briones (cSic) mutations and mis-sense mutations physiopathology. On the other hand, laura Gort (Hospital clínic) previously identified by our group. this model will be used to test diffe- teresa pàmpols (Hospital clínic) We make use of fibroblasts IPI cells rent drugs that act upon proteosomal Mª Josep coll (Hospital clínic) and neuron cultures as cell models. degradation. Rosa Mª lópez (Hospital clínic) 2. CoQ10 deficiency. We are carrying 7. Congenital defects of glycosylation out the biochemical selection of pa- (CDG). Our goal is to identify and cha- poStDoctoRAlS fellowS: tients with CoQ10 deficiency, based racterize new cases and phenotypes frederic tort (ciBeRer) on the study of the mitochondrial of these diseases for a better unders- Aleix navarro-Sastre (ciBeRer) respiratory chain and the analysis of tanding of their pathophysiology and Angela Arias (ciBeRer) the metabolic pathways, using sta- finding novel therapeutic targets. ble isotopes in fibroblasts from the ReSeARcH fellowS: previously selected patients. Poste- Judith Macías riorly, in patients that prove negative (fundació niemann pick) for mutations of the genes known nuria Bujan (fiS) to date, an exome analysis will be Aida font (fiS) made to identify the gene causing leslie Matalonga (fundació clínic) the disease. 3. Sanfilippo disease and CoQ10. This collABoRAtoRS: project is studying the relationship Marisa Girós (Hospital clínic) between CoQ10 and Mucopolysac- Judit Garcia-Villoria (Hospital clínic) charidosis III or Sanfilippo disease. José luis Marin (Hospital clínic) We aim to find out whether there is correlation between CoQ10 levels and the disease, and whether treatment of fibroblasts from patients Calculation of the number of mitochondrial with CoQ10 produces any effect. DNA copies, based on real-time PCR.

188 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM HeReDitARy MetABolic DiSeASeS

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 40.42 13 7 4 oRiGinAlS 6 Tural C, Sola R, Alvarez NP, Molto i.f.: 38.49 J, Sanchez M, Zamora AM, Ornelas A, 2010 59.95 17 3 8 Laguno M, Gonzalez J, VonWichmann 2011 38.49 8 4 3 1 Tural C, Sola R, Alvarez NP, Molto MA, Tellez MJ, Paredes R, Clotet B, Co- J, Sanchez M, Zamora AM, Ornelas A, ral-2Study GROUP. Population Pharma- Laguno M, Gonzalez J, VonWichmann cokinetics of Lopinavir/Ritonavir (Kaletra) MA, Tellez MJ, Paredes R, Clotet B. in HIV-Infected Patients. THER DRUG Effect of an induction period of pegyla- MONIT. 33:573-582. I.F.: 3.13. Ribes A. Diagnóstico, fisiopatología y ted interferon-alpha 2a and ribavirin on tratamiento en la deficiencia cerebral early virological response in HIV-HCV- 7 Tort F, DelToro M, Lissens W, Monto- de creatina. Subproyecto 4. Estudios coinfected patients: results from the ya J, Fernandez-Burriel M, Font A, Bujan de captación de creatina, con distintos CORAL-2 study. ANTIVIR THER. 16:833- N, Navarro-Sastre A, Lopez-Gallardo E, preparados de la misma, en neuronas 841. I.F.: 3.77. Arranz JA, Riudor E, Briones P, Ribes A. derivadas de células IPS y en células Screening for nuclear genetic defects HUVEC silenciadas con RNA de IN- 2 Navarro-Sastre A, Tort F, Stehling in the ATP synthase-associated genes TERF. Sponsored by: Instituto de Salud O, Uzarska MA, Arranz JA, DelToro TMEM70, ATP12 and ATP5E in patients Carlos III (ISCIII), PI09/2128. Duration: M, Labayru MT, Landa J, Font A, with 3-methylglutaconic aciduria. CLIN 01/01/2010-31/12/2012. Garcia-Villoria J, Merinero B, Ugarte GENET. 80:297-300. I.F.: 2.94. M, Gutierrez-Solana LG, Campistol J, Coll MJ. Análisis de los mecanismos Garcia-Cazorla A, Vaquerizo J, Riudor E, 8 Ortez C, Villar C, Fons C, Duarte implicados en la enfermedad de Briones P, Elpeleg O, Ribes A, Lill R. A ST, Perez A, Garcia-Villoria J, Ribes A, Niemann-Pick tipo C: generación de Fatal Mitochondrial Disease Is Associa- Ormazabal A, Casado M, Campistol J, un modelo murino de la enfermedad y ted with Defective NFU1 Function in the Vilaseca MA, Garcia-Cazorla A. Unde- valoración de una nueva aproximación Maturation of a Subset of Mitochondrial tectable Levels of CSF Amyloid-beta terapéutica mutación dependiente. Fe-S Proteins. AM J HUM GENET. Peptide in a Patient with 17 beta-Hy- Sponsored by: Instituto de Salud 89:656-667. I.F.: 11.68. droxysteroid Dehydrogenase Deficien- Carlos III, PI10/00936. Duration: cy. J ALZHEIMERS DIS. 27:253-257. 01/01/2011-31/12/2013. 3 Alcaide P, Merinero B, Ruiz-Sala I.F.: 4.26. P, Richard E, Navarrete R, Arias A, Ribes A. European registry and net- Ribes A, Artuch R, Campistol J, Ugarte work for Intoxication type Metabolic M, Rodriguez-Pombo P. Defining the GRAntS foR ReSeARcH Diseases (E-IMD). Sponsored by: Pathogenicity of Creatine Deficiency in pRoGReSS Agència Europea DG-SANCO. Coordi- Syndrome. HUM MUTAT. 32:282-291. nador: Stefan Kölker, A/100886-E-IMD. I.F.: 5.96. Ribes A. Estudio para evaluar la efec- Duration: 01/01/2011-31/12/2013. tividad del tratamiento dietético con 4 Vega AI, Perez-Cerda C, Abia D, Ga- triheptanoina en pacientes con defec- Ribes A. Automatización de métodos mez A, Briones P, Artuch R, Desviat LR, tos graves de la Beta-oxidación mito- de diagnóstico molecular de enferme- Ugarte M, Perez B. Expression analysis condrial. Sponsored by: Instituto de dades mitocondriales. parte 4, hospital revealing destabilizing mutations in Salud Carlos III (ISCIII), EC07/90552. clínic. deplecíon de MTDNA; cálculo phosphomannomutase 2 deficiency Duration: 29/10/2007-31/12/2011. del número de copias de mtdna y ob- (PMM2-CDG): expression analysis of tención de valores de referencia según PMM2-CDG mutations. J INHERIT ME- Briones P. Estudios bioquímicos y edad y tejido. Sponsored by: Instituto TAB DIS. 34:929-939. I.F.: 3.81. mutacionales en pacientes con defi- de Salud Carlos III (ISCIII), PI08/90348. ciencias primarias de CoQ. Selección Duration: 01/01/2009-30/06/2011. 5 Macias-Vidal J, Rodriguez-Pascau L, bioquímica de pacientes y análisis de Sanchez-Olle G, Lluch M, Vilageliu L, la vía metabólica mediante sustratos Grinberg D, Coll MJ. Molecular analysis marcados con isótopos estables. of 30 Niemann-Pick type C patients Sponsored by: Fondo de Investiga- fron Spain. CLIN GENET. 80:39-49. ción Sanitaria, PI08/0307. Duration: I.F.: 2.94. 31/12/2008-30/09/2012.

189 AReA 3 Team involved in: Liver, digestive system and metabolism

Genomic Programming of Beta Cells and Diabetes

gROUP MeMBeRS StrateGic oBjectiveS

1. Use of genomic tools for establishing the genetic and epigenetic mechanisms that modify the risk of develo- teAM leADeR ping diabetes. Jorge ferrer (Hospital clínic) 2. Identification of pathogenic mecha- tel.: 93 227 54 00 nisms and new therapeutic options fax: 93 312 94 09 for monogenic forms of diabetes. e-mail: [email protected] 3. Discovery of new pancreatic regeneration pathways.

main lineS of reSearcH

1. Pancreatic regeneration and programming. 2. Epigenomic regulation of beta cells and diabetes. 3. Monogenic diabetes.

For further information: www.betacellregulation.net

iDiBApS MeMBeRS: tecHniciAnS: ildem Akerman (iDiBApS) Vanessa Grau (ciBeRDeM) poStDoctoRAlS fellowS: Xavier Garcia Miguel Angel Maestro (ciBeRDeM) (ciBeRDeM) Santiago Rodriguez (iDiBApS) natalia castro loris Mularoni (fundació clínic) (fundació clínic) Meritxell Rovira (BiotRAck) Marta Batlle (fundació clínic) ADMiniStRAtiVe StAff: inês cebola (iDiBApS) carme Sanahuja (fundació clínic) ReSeARcH fellowS: Joris van Arensbergen collABoRAtoRS: (fundació clínic) lorenzo pasquali Myriam Solar (fundació clínic) (fundació clínic) ignasi Moran (fundació clínic) Miguel Angel correa (Marie curie, iDiBApS) nikolina nakic (Marie curie, iDiBApS) Immunofluorescence of E13.5 mouse embryonic pancreas. Nuclear staining of ductal cells, hnf1b (blue). Nuclear staining of endocrine cells, nkx2.2 (red). Cytoplasmic staining of acinar cells, CPA1 (green).

190 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM GenoMic pRoGRAMMinG of BetA cellS AnD DiABeteS

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 56.28 4 4 0 oRiGinAlS Ferrer J. Regulación epigenética y i.f.: 46.59 plasticidad de las células beta pan- 2010 64.59 4 4 0 creáticas. Sponsored by: Ministerio 2011 46.59 3 3 0 1 Allen HL, Flanagan SE, Shaw- de Ciencia e Innovación, SAF2008- Smith C, DeFranco E, Akerman I, 03116. Duration: 01/01/2009- Caswell R, Ferrer J, Hattersley AT, 31/12/2011. Ellard S. GATA6 haploinsufficien- cy causes pancreatic agenesis in Ferrer J. Collaborative European DoctoRAl tHeSeS humans. NAT GENET. 44:20-22. Effort to Develop Diabetes Diagno- I.F.: 36.38. sis. Sponsored by: European Com- Ferrer J. The role of polycomb me- mission FP7, 223211. Duration: diated gene repression in beta-cell 2 Kirkpatrick CL, Wiederkehr A, 01/12/2008-30/11/2012. indentity. PhD student: Van Arens- Baquie M, Akhmedov D, Wang HY, bergen, Joris. Gauthier BR, Akerman I, Ishihara Ferrer J. Biology of Liver and Pan- H, Ferrer J, Wollheim CB. Hepa- creatic Development and Disease. tic Nuclear Factor 1 alpha (HNF1 Sponsored by: European Com- alpha) Dysfunction Down-regulates mission FP7, 238821. Duration: X-box-binding Protein 1 (XBP1) and 01/09/2009-31/08/2013. Sensitizes beta-Cells to Endoplasmic Reticulum Stress. J BIOL CHEM. Ferrer J. Empleo de epigenomas 286:32300-32312. I.F.: 5.33. celulares para optimizar la terapia celular a partir de células madre. 3 Hunter CS, Maestro MA, Raum Sponsored by: Ministerio de Cien- JC, Guo M, ThompsonFh 3RD, Ferrer cia e Innovación, PLE2009-0162. J, Stein R. Hnf1α (MODY3) regulates Duration: 01/11/2009-01/11/2012. ß-cell-enriched MafA transcription factor expression. MOL ENDOCRINOL. Ferrer J. Linking non-coding RNAs 25:-339. I.F.: 4.89. to beta-cell programming efforts. Sponsored by: National Institutes of Health (NIH), NIDDK. Duration: eDitoRiAlS 31/01/2011-28/02/2012. i.f.: 32.16 Ferrer J. Epigenetic strategies 1 Ferrer J. Glucose as a Mitogenic for the in vitro generation of re- Hormone. CELL METAB. 13:357-358. placement beta cells. Sponsored I.F.: 18.21. by: National Institute of Health, University of California/San Die- 2 Akerman I, VanArensbergen J, Ferrer go, 1U01DK089567-01. Duration: J. Removing the brakes on cell identity. 01/07/2010-30/12/2012. DEV CELL. 20:411-412. I.F.: 13.95. Ferrer J. Coordinating Center for Beta Cell Biology Consortium GRAntS foR ReSeARcH (VUMC 38271). Sponsored by: in pRoGReSS National Institutes of Health (NIH), 2U01DK072473-06. Duration: Ferrer J. Analysis of the plasticity 01/03/2011-30/05/2013. of pancreatic duct cells. Sponsored by: Juvenile diabetes Research Foundation, 26-2008-633. Duration: 01/08/2008-31/03/2011.

191 AReA 3 Team involved in: Liver, digestive system and metabolism

Diabetes: metabolic and molecular networks

gROUP MeMBeRS

teAM leADeR Josep Vidal (Hospital clínic) tel.: 93 227 98 46 fax: 93 451 66 38 e-mail: [email protected]

iDiBApS MeMBeRS: ReSeARcH fellowS: nuRSinG StAff: Ramon Gomis (Hospital clínic) Andrea Ruiz tarrago (iDiBApS) Judith Viaplana (iDiBApS) Roser casamitjana (Hospital clínic) Joana Duarte (fundació clínic) ignacio conget (Hospital clínic) Miriam ejarque (iDiBApS) DietiStS: enric esmatjes (Hospital clínic) Gemma pujadas (fundació clínic) Serafín Murillo (ciBeRDeM) Rosa Gasa (iDiBApS) Montse Visa (fundació clínic) Marcelina parrizas (iDiBApS) Alba Moreno (iDiBApS) collABoRAtoRS: Joan Marc Servitja (iDiBApS) katerina papageorgiou (iDiBApS) María José coves (ciBeRDeM) Anna novials (iDiBApS) Silvia canivell (iDiBApS) Marga Gimenez (Hospital clínic) Marc claret (iDiBApS) lisa cadavez (iDiBApS) Belén nadal (uB) pablo Miguel García-Roves (iDiBApS) Marc Schneeberger (uB) Alexandra felicia Hanzu (iDiBApS) carles lerin (iDiBApS) Marta pradas (fundació clínic) laura Brugnara (ciBeRDeM) Antonio ceriello (iDiBApS) Mariona Balfego (fundació clínic) lilliam flores (Hospital clínic) emilio ortega (Hospital clínic) Alba González (fundació clínic) pere leyes (Hospital clínic) pere Santamaria (iDiBApS) Hugo Alves (fundació clínic) Miriam Mora (Hospital clínic) pau Serra (iDiBApS) Valeria de nigris irene Halperin (Hospital clínic) (fundació clínic) Antonio Jesús Blanco (Hospital clínic) poStDoctoRAlS fellowS: Mercè Martin (iDiBApS) Maria laura perez (Marie curie) Rebeca fernández (ciBeRDeM) Sandra Rebuffat (ciBeRDeM) Maud Soty (ciBeRDeM) paola casini (iDiBApS) nathalie nicod (iDiBApS) Sara cervantes (iDiBApS) Rita Malpique (iDiBApS) elena Gonzalez (ciBeRDeM) eduardo fernandez (ciBeRDeM) elaine Vieira (ciBeRDeM)

tecHniciAnS: elena lopez (iDiBApS) cesar fandos (iDiBApS) carlos castaño (ciBeRDeM) yaiza esteban (ciBeRDeM) Ainhoa García (ciBeRDeM) lidia Sanchez (ciBeRDeM)

192 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM DiABeteS: MetABolic AnD MoleculAR netwoRkS

StrateGic ReSeARCh gROUP oBjectiveS pancreatic iSletS: BiomarkerS and function

Group Leader: 1. Molecular mechanisms regulating Ramon Gomis (IDIBAPS) plasticity of the islets in diabetes and obesity. 2. Molecular determinants regulating The group headed by Dr. Ramon Gomis investigates the pancreatic beta-cell function: etio- physiology of pancreatic islets and adipose tissue, and the pathogenic role in diabetes. causes leading to dysfunction of these tissues. A central aspect of these 3. Diabetes andobesity as cardiovascu- studies is the determination of the molecular mechanisms implicated in cell lar disease. mass balance at both embryonic development level and as refers to adult age – with special emphasis on cell regeneration and apoptotic processes. main lineS of reSearcH

1. Analysis of the transcriptional circuits ReSeARCh gROUP regulating the beta-cell population molecular and metaBolic alterationS in diaBeteS and its function. Group Leader: 2. Description of the modulating effects Anna Novials (IDIBAPS) of the transcription factors neuroD1 and neurogenin 3 in the embryonic development of the pancreas. The main line of research of the group headed by Dr. No- 3. Description of the molecular vials involves the study of the molecular, genetic and envi- pathways involved in the antiobesity ronmental factors critical to pancreatic beta-cell dysfunction and destruction and antidiabetic effects of sodium in type 2 diabetes. tungstate in experimental animals. 4. Impact of normal blood glucose upon endothelial dysfunction: use of treatments with insulin pumps. ReSeARCh gROUP 5. Determination of the role of the patHoGeneSiS and treatment of autoimmunity hypothalamus in the control of ener- Group Leader: gy homeostasis in obesity. Pere Santamaria (IDIBAPS) 6. Analysis of the epigenetic regulation of adipogenesis. Our laboratory has two distinct components: one for purely basic biomedical research which studies the role of particu- For further information: lar genes and molecules in the development and functioning of the immune www.diabetes-obesity-research.org system; and another, more applied, based on the study of the immunological www.ciberdem.org effects of a new therapeutic platform we have developed for the treatment of autoimmune diseases, which include type 1 diabetes, lupus and autoimmune diseases of the central nervous system. This treatment, based on nanotechnology, works by way of an immunological mechanism for protection against autoimmunity designed by mother nature, which we have learned to manipulate by using a new type of drug, also discovered by us. One of our main objectives is to start using this therapeutic platform with patients through the conducting of clinical trials.

Pancreatic islets transplanted into the eye anterior chamber. Confocal image. Red: vascularization; Blue: alive cells from islets; Green: dead cells from islets). (Authors: Ainhoa García, Rita Malpique; Serveis Cientifico-Tècnics Universitat de Barcelona).

193 LIveR, DIgeSTIve SySTeM AND MeTABOLISM

Diabetes: metabolic and molecular networks

PUBLICATIONS

oRiGinAlS 7 Mcneilly AM, Davison GW, Murphy man pancreatic beta cell hyperactivity in i.f.: 71.18 MH, Nadeem N, Trinick T, Duly E, Novials obesity. DIABETOLOGIA. 54:2856-2866. A, Mceneny J. Effect of alpha-lipoic acid I.F.: 6.97. 1 Gimenez M, Gilabert R, Monteagu- and exercise training on cardiovascular do J, Alonso A, Casamitjana R, Pare C, disease risk in obesity with impaired glu- 13 Soty M, Visa M, Soriano S, Carmona Conget I. Repeated Episodes of Hypogly- cose tolerance. LIPIDS HEALTH DIS. 10:-. MD, Nadal A, Novials A. Involvement of cemia as a Potential Aggravating Factor I.F.: 2.24. ATP-sensitive Potassium (K-ATP) Channels for Preclinical Atherosclerosis in Subjects in the Loss of Beta-cell Function Induced With Type 1 Diabetes. DIABETES CARE. 8 Gomis R, Espadero RM, Jones R, by Human Islet Amyloid Polypeptide. J 34:198-203. I.F.: 7.14. Woerle HJ, Dugi KA. Efficacy and safety BIOL CHEM. 286:40857-40866. I.F.: 5.33. of initial combination therapy with lina- 2 Fabregues F, Castelo-Branco C, gliptin and pioglitazone in patients with 14 Vila L, Serra-Prat M, DeCastro A, Carmona F, Guimera M, Casamitjana R, inadequately controlled type 2 diabetes: Palomera E, Casamitjana R, Legaz G, Balasch J. The effect of different hormo- a randomized, double-blind, placebo-con- Barrionuevo C, Munoz JA, Garcia AJ, ne therapies on anti-mullerian hormone trolled study. DIABETES OBES METAB. Lal-Trehan S, Garcia A, Duran J, Puig-Do- serum levels in anovulatory women of 13:653-661. I.F.: 3.42. mingo M. Iodine nutritional status in preg- reproductive age. GYNECOL ENDOCRI- nant women of two historically different NOL. 27:216-224. I.F.: 1.46. 9 Fernandez-Novell JM, Ballester J, iodine-deficient areas of Catalonia, Spain. Altirriba J, Ramio-Lluch L, Barbera A, NUTRITION. 27:1029-1033. I.F.: 2.73. 3 Moize V, Deulofeu R, Torres F, DeOsa- Gomis R, Guinovart JJ, Rodriguez-Gil JE. ba JM, Vidal J. Nutritional Intake and Pre- Glucose and fructose as functional modu- 15 Pujadas G, Felipe F, Ejarque M, valence of Nutritional Deficiencies Prior lators of overall dog, but not boar sperm Sanchez L, Cervantes S, Lynn FC, Gomis to Surgery in a Spanish Morbidly Obese function. REPROD FERT DEVELOP. R, Gasa R. Sequence and epigenetic de- Population. OBES SURG. 21:1382-1388. 23:468-480. I.F.: 2.55. terminants in the regulation of the Math6 I.F.: 3.08. gene by Neurogenin3. DIFFERENTIA- 10 Wen L, Green EA, Stratmann T, TION. 82:66-76. I.F.: 3.07. 4 Moreno P, Acitores A, Gutierrez-Rojas Panosa A, Gomis R, Eynon EE, Flavell I, Nuche-Berenguer B, ElAssar M, Rodri- RA, Mezquita JA, Mora C. In vivo diabe- 16 Amigo-Correig M, Barcelo-Batllori S, guez-Manas L, Gomis R, Valverde I, Visa togenic action of CD4(+) T lymphocytes Piquer S, Soty M, Pujadas G, Gasa R, Bor- M, Malaisse WJ, Novials A, Gonzalez N, requires Fas expression and is indepen- tolozzi A, Carmona MC, Gomis R. Sodium Villanueva-Penacarrillo ML. Amylin effect dent of IL-1 and IL-18. EUR J IMMUNOL. tungstate regulates food intake and body in extrapancreatic tissues participating in 41:1344-1351. I.F.: 4.94. weight through activation of the hypotha- glucose homeostasis, in normal, insulin- lamic leptin pathway. DIABETES OBES resistant and type 2 diabetic state. PEPTI- 11 Macdonald MR, Petrie MC, Home METAB. 13:235-242. I.F.: 3.42. DES. 32:2077-2085. I.F.: 2.65. PD, Komajda M, Jones NP, Beck-Nielsen H, Gomis R, Hanefeld M, Pocock SJ, 17 Conget I, Battelino T, Gimenez M, 5 Conthe P, Mata M, Orozco D, Pajuelo Curtis PS, Mcmurray JJ. Incidence and Gough H, Castaneda J, Bolinder J. The F, Barreto CS, Anaya SF, Gomis R. Degree prevalence of unrecognized myocardial SWITCH Study (Sensing With Insulin of control and delayed intensification of infarction in people with diabetes: a subs- pump Therapy to Control HbA(1c)): antihyperglycaemic treatment in type tudy of the Rosiglitazone Evaluated for Design and Methods of a Randomized 2 diabetes mellitus patients in primary Cardiac Outcomes and Regulation of Gly- Controlled Crossover Trial on Sensor- care in Spain. DIABETES RES CLIN PR. cemia in Diabetes (RECORD) study. DIA- Augmented Insulin Pump Efficacy in Type 91:108-114. I.F.: 2.13. BETES CARE. 34:1394-1396. I.F.: 7.14. 1 Diabetes Suboptimally Controlled with Pump Therapy. DIABETES TECHNOL 6 Mccluskey JT, Hamid M, Parke HG, 12 Mezghenna K, Pomies P, Chalancon THE. 13:49-54. I.F.: 2.15. Mcclenaghan NH, Gomis R, Flatt PR. De- A, Castex F, Leroy J, Niclauss N, Nadal velopment and functional characterization B, Cambier L, Cazevieille C, Petit P, 18 Hanzu FA, Palomo M, Kalko SG, of insulin-releasing human pancreatic beta Gomis R, Berney T, Gross R, Lajoix AD. Parrizas M, Garaulet M, Escolar G, Gomis cell lines produced by electrofusion. J Increased neuronal nitric oxide synthase R, Diaz-Ricart M. Translational evidence of BIOL CHEM. 286:21982-21992. I.F.: 5.33. dimerisation is involved in rat and hu- endothelial damage in obese individuals:

194 AReA 3 liVeR, DiGeStiVe SySteM AnD MetABoliSM DiABeteS: MetABolic AnD MoleculAR netwoRkS

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 105.88 18 12 3 inflammatory and prothrombotic respon- Gasa R. Cascada transcripcional indu- ses. J THROMB HAEMOST. 9:1236-1245. cida por neurogenina3 en el páncreas: 2010 84.13 19 13 1 I.F.: 5.44. estudio de los factores de transcripción 2011 71.18 18 10 2 math6 y ebf1. Sponsored by: Ministerio de Ciencia e Innovación, BFU2008- GRAntS foR ReSeARcH 02299/BMC. Duration: 01/01/2009- Gomis R. Determinantes moleculares de in pRoGReSS 31/12/2011. la plasticidad de la célula beta en diabetes: efectos del tungstato sódico. Sponsored Servitja JM. Estudio de la respuesta del Novials A. Papel del enzima bace (beta- by: Ministerio de Ciencia e Innovación, islote pancreático a la hipoxia: papel de site amyloid precursor protein cleaving SAF2010-19527. Duration: 01/01/2011- HIF-1. Sponsored by: Ministerio de Educa- enzyme) en la funcionalidad del islote 31/12/2013. ción y Ciencia, BFU2006-09072. Duration: pancreático. Sponsored by: Ministerio de 01/10/2006-30/11/2011. Sanidad, PI080088. Duration: 01/01/2009- Claret M. MicroRNAs hipotalámicos y regu- 31/12/2011. lación del metabolismo energético: posibles Parrizas M. Regulación epigenética de la dianas terapéuticas para el tratamiento de la diferenciación. Sponsored by: Ministerio Parrizas M. Papel de la demetilasa de obesidad y la diabetes. Sponsored by: Insti- de Educación y Ciencia, BFU2006-14251. histonas LSD1 en la adipogénesis. tuto de Salud Carlos III (ISCIII), PI10/01074. Duration: 01/10/2006-31/03/2012. Sponsored by: Ministerio de Educación, Duration: 01/01/2011-31/12/2013. BFU2009-09988. Duration: 01/01/2010- Esmatjes E. Efectos del by-pass gástrico 31/12/2012. Ceriello A. Defective antioxidant response sobre la presión arterial y la disfunción in endothelial cells exposed to oscillating endotelial en personas con obesidad Servitja JM. Epigenetic control of gene glucose: the role of Nrf2. Sponsored by: Ins- grave. Sponsored by: Ministerio de Sa- expression in pancreatic islets. Sponsored tituto de Salud Carlos III (ISCIII), PI10/01256. nidad y Consumo, PI070124. Duration: by: European Foundation for the Study of Duration: 01/01/2011-31/12/2013. 01/01/2007-31/12/2011. Diabetes, EFSD/LILLY_10_001. Duration: 08/05/2010-07/11/2012. Servitja JM. Regulación y función de mi- Gomis R. Dianas moleculares inducidas croRNAs en el islote pancreático. Sponso- por tungstato en la obesidad. Sponsored Claret M. Role of hypothalamic mitochon- red by: Ministerio de Ciencia e Innovación, by: Ministerio de Educación y Ciencia, drial fusion in appetite and body weight BFU2010-17639. Duration: 01/01/2011- SAF2006-07382. Duration: 01/10/2006- control: potential therapeutic target for 31/12/2013. 30/10/2011. the treatment of obesity. Sponsored by: Assoc. Cat. Universitats Públiques - ACUP, Novials A. Seminars on Current Trends Gomis R. FOOD FOR LIFE-Supporting 2010ACUP_00275. Duration: 01/12/2010- in Diabetes and Obesity Research 2011- Healthy Lifestyles in the Mediterranean 30/11/2012. 2012. Sponsored by: Generalitat de Area. Sponsored by: Marie Curie Actions Catalunya, AGAUR, AN076832. Duration: - International Research Staff Exchange Vidal J. GLP-1 y resolución tras el bypass 06/10/2001-12/07/2012. Scheme, FP7- PEOPLE - IRSES - 2008, gástrico de la diabetes tipo 2 asociada 230848. Duration: 01/03/2009-28/02/2013. a obesidad. Sponsored by: Funda- Lerin C. Molecular mechanisms underlying ción de Investigación Médica Mútua, the development of insulin resistance: role Gomis R. The role of adipose tissue in AP62572009. Duration: 03/08/2009- of betaine supplementation. Sponsored obesity: beta cell crosstalk (ADIBET). 31/07/2011. by: European Commission, DG Research Sponsored by: FP7 PEOPLE-2007-3-1- and Innovation, PCIG-GA-2011-293502. IAPP, PIAP-GA-2008-218130. Duration: Vidal J. Estudi aleatoritzat prospectiu sobre Duration: 01/09/2011-31/08/2015. 01/01/2008-31/12/2011. els efectes del tractament mèdic intensiu amb o sense bypass gàstric en Y de Roux, Gomis R. Diabetis experimental, investi- sobre el gruix de la íntima mitja carotídea DoctoRAl tHeSeS gació cel·lular i molecular en models de en malalts amb obesitat grau I. Sponsored diabetis experimental. Sponsored by: Ge- by: Agència d’Avaluació de Tecnologia Mè- Gomis R, Parrizas M. Molecular determi- neralitat de Catalunya, AGAUR, 2009 SGR dica, 401/17/2008. Duration: 01/12/2009- nants of adipose tissue crosstalks. PhD 1426. Duration: 07/08/2009-31/12/2013. 30/11/2012. student: Felicia Alexandra Hanzu.

195

AReA 4

Team involved in: Clinical and experimental neuroscience

Neuropharmacology and experimental neuropathology & gROUP MeMBeRS

teAM leADeR Guadalupe Mengod (iiBB-cSic) tel.: 93 363 83 23 fax: 93 636 83 01 e-mail: [email protected]

iDiBApS MeMBeRS: emily Johansson (fpi-cSic) Anghara Menéndez (iDiBApS) Albert Adell (iiBB-cSic) cristina Sanabra (fpi-iDiBApS) Albert parull (iiBB-cSic) francesc Artigas (iiBB-cSic) Marco Straccia (i3p-cSic) Sara Sánchez-Redondo Analia Bortolozzi (iDiBApS) Anna García-Miralles (fpi-iDiBApS) (ciBeReSp) Anna castañé (iiBB-cSic) Giuseppe Mocci (JAe-cSic) Verónica paz (ciBeRSAM) pau celada (iDiBApS) Susana Revilla (fpu-Micinn) Silvia Serrano (ciBeRneD) Roser cortés (iiBB-cSic) eva troyano (fpi-cSic) noemí Jurado (iiBB-cSic) Rosa cristòfol (iiBB-cSic) Aina palou (fpi-iDiBApS) irene porcar (iiBB-cSic) Sebastià pons (iiBB-cSic) Antonio Herrera-camacho (fpi-iDiBApS) Rosario Ruiz (uB) eduard Rodriguez farré (iiBB-cSic) Guido Dentesano (Marató tV3) Rubén corpas (iiBB-cSic) coral Sanfeliu (iiBB-cSic) núria paúl fernández (iiBB-cSic) Mercedes nuñez (iiBB-cSic) Josep Saura (uB uB) laura Jiménez (iDiBApS) Joan Serratosa (iiBB-cSic) Maurizio Riga (iDiBApS) ADMiniStRAtiVe StAff: carme Solà (iiBB-cSic) Albert ferrés (iDiBApS) María Jaramillo (ciBeRSAM) cristina Suñol (iiBB-cSic) patricia Molina (iiBB-ciSc) Josep Maria tusell (iiBB-cSic) Marta pulido (fpu) collABoRAtoRS: Mª teresa Vilaró (iiBB-cSic) luana Queiroz (cApeS, Brasil) Xavier lópez Gil (iiBB-cSic) laura Vuolo (JAe, cSic) laia lladó (iiBB-cSic) ReSeARcH fellowS: noemí Santana (ciBeRSAM) Mercedes Barzi (fpi-iDiBApS) tecHniciAnS: tamara Romón (iDiBApS) Jordi Berenger (cSic) Mireia Galofré (iDiBApS) tony Valente (iDiBApS) Victor Briz (fpi-iDiBApS) leticia campa (iiBB-cSic) Mercè Masana (iDiBApS) yoelvis García (Marató tV3-iDiBApS) Rocío Martín-Álvarez (ciBeRneD) nair olguin (iiBB-cSic)

198 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience neuRopHARMAcoloGy AnD eXpeRiMentAl neuRopAtHoloGy

ReSeARCh gROUP neuronal proliferation control Group

Group Leader: Sebastián Pons (IIBB-cSIc)

The main goal of our group is to study the mechanisms controlling the proliferation of neural precursors during both normal development and in neoplastic growth. In particular, our research is focused on the molecular and cellular anomalies that contribute to Medulloblastoma formation. This posterior fosse tumor, represents the most frequent brain malignancy in children. Recently, In vivo LPS treatment alters expression of PDE4B3 mRNA in oligodendrocytes. Cellular localization of PDE4B3 mRNA (cluster of dark silver grains), in oligoden- different multicentric genomic studies succeeded drocytes (dark precipitate) in male and female mouse brain parenchyma. Black to distribute Medulloblastomas into 4 different arrowheads point to oligodendrocytes, white arrowheads to radioactively-labeled cells expressing PDE4B3 and double black and white arrowheads to double- groups attending to their expression signatures. labeled cells. Bar = 20 µm. The different groups are commonly associated to a particular histologic type and prognosis. Acti- vating mutations of molecules in Hedgehog and Wnt signaling pathways have been demonstrated StrateGic to be responsible for the initiation of Meulloblas- oBjectiveS tomas of Hedgehog and Wnt groups respectively. Nevertheless, the process occurring between the Furthering of knowledge of the initial mutation and the development of the Medu- physiopathological mechanisms of lloblastoma is mostly unknown. In our laboratory neurological and psychiatric diseases we use in ovo (chicken) and in utero (mouse) elec- and neurotoxic and aging processes troporation systems to express different oncoge- of the central nervous system, with nic mutations of Hedgehog and Wnt pathways a view to identifying new cellular and to study the cellular events occurring during the functional targets and proposing new initial steps of Medulloblastoma formation. treatments.

ReSeARCh gROUP ReSeARCh gROUP SyStemS neuropHarmacoloGy Group neurotoxicity and neurodeGeneration mecHaniSmS Group Group Leader: Francesc Artigas (IIBB-cSIc) Group Leader: cristina Suñol (IIBB-cSIc)

The group studies the neuronal circuits implicated in the physiopathology and treatment The group carries out studies on cytotoxic- of depression and schizophrenia. Special em- ity, oxidative stress, synaptic functions and phasis is placed on the prefrontal cortex and proteomics, for the determination of al- anatomically and functionally related areas. It also explores tered targets in toxicity and aging processes of the central chemical neurotransmission processes and physiology in ani- nervous system. It also focuses on neuroprotective strate- mal models of mental disease, with a view to identifying new gies and the development of in vitro methods for predict- therapeutic targets. ing neurotoxicity.

199 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Neuropharmacology and experimental neuropathology PUBLICATIONS

ReSeARCh gROUP oRiGinAlS molecular i.f.: 68.14 neuropHarmacoloGy Group 1 Amigo-Correig M, Barcelo-Batllori Group Leader: Guadalupe Mengod (IIBB-cSIc) S, Piquer S, Soty M, Pujadas G, Gasa R, Bortolozzi A, Carmona MC, Gomis The group studies neurotransmission and its R. Sodium tungstate regulates food anatomical, cellular and molecular aspects intake and body weight through ac- implicated in neurodegenerative disorders with tivation of the hypothalamic leptin an inflammatory component. The objective is to identify and pathway. DIABETES OBES METAB. characterize new targets for therapeutic action. 13:235-242. I.F.: 3.42.

2 Santana N, Troyano-Rodriguez E, ReSeARCh gROUP Mengod G, Celada P, Artigas F. Acti- cellular neuroBioloGy Group vation of Thalamocortical Networks by the N-methyl-D-aspartate Recep- tor Antagonist Phencyclidine: Rever- Group Leader: Josep Saura (IIBB-cSIc) sal by Clozapine. BIOL PSYCHIAT. 69:918-927. I.F.: 8.67. We study the implication of C/EBP transcription factors and of neuronal-microglial commu- 3 Portella MJ, DeDiego-Adelino J, nication molecules (CD200, CD200R, TREM) in Ballesteros J, Puigdemont D, Oiler glial activation and in the associated neurotoxicity. We conduct S, Santos B, Alvarez E, Artigas F, studies using experimental animals, primary cell cultures (mi- Perez V. Can We Really Accelerate xed glial, astroglial and microglial-enriched, neuronal, mixed and Enhance the Selective Seroto- neuron-glial) and cell lines. nin Reuptake Inhibitor Antidepres- sant Effect? A Randomized Clinical Trial and a Meta-Analysis of Pin- ReSeARCh gROUP dolol in Nonresistant Depression. cneuronal proliferation control Group J CLIN PSYCHIAT. 72:962-969. I.F.: 5.02.

Group Leader: Sebastián Pons (IIBB-cSIc) 4 Watanabe KH, Andersen ME, Basu N, Carvan MJ, Crofton KM, The main goal of our group is to study the me- King KA, Sunol C, Tiffany-Castiglioni chanisms controlling the proliferation of neuro- E, Schultz IR. Defining and modeling nal precursors during both normal development known adverse outcome pathways: and in neoplastic growth. In particular, our re- Domoic acid and neuronal signaling searcg is focused on the molecular and cellular anomalies that as a case study. ENVIRON TOXICOL contribute to Medulloblastoma. We use in ovo (chicken) and in CHEM. 30:9-21. I.F.: 3.03. utero (mouse) electroporation systems to alter Hedgehog and Wnt pathways in order to study the cellular events occurring 5 Briz V, Molina-Molina JM, San- during the initial steps of Medulloblastoma formation. chez-Redondo S, Fernandez MF, Grimalt JO, Olea N, Rodriguez-Farre E, Suñol C. Differential Estrogenic Effects of the Persistent Organochlo- rine Pesticides Dieldrin, Endosulfan, and Lindane in Primary Neuronal Cultures. TOXICOL SCI. 120:413-427. I.F.: 5.09.

200 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience neuRopHARMAcoloGy AnD eXpeRiMentAl neuRopAtHoloGy

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 81.63 20 14 4 6 Romon T, Mengod G, Adell A. Ex- nergic drugs: therapeutic opportunities pression of parvalbumin and glutamic in schizophrenia. INT J NEUROPSY- 2010 105.96 26 16 7 acid decarboxylase-67 after acute admi- CHOPH. 14:53-68. I.F.: 4.70. 2011 68.14 15 9 2 nistration of MK-801. Implications for the NMDA hypofunction model of schi- 13 Vazquez-Borsetti P, Celada P, zophrenia. PSYCHOPHARMACOLOGY. Cortes R, Artigas F. Simultaneous 217:231-238. I.F.: 3.82. projections from prefrontal cortex to dopaminergic and serotonergic nuclei. Artigas F. Estudio del mecanismo de 7 Johansson EM, Sanabra C, Cortes INT J NEUROPSYCHOPH. 14:289-302. acción de la estimulación cerebral pro- R, Vilaro MT, Mengod G. Lipopolysac- I.F.: 4.70. funda sobre la neurotransmisión seroto- charide Administration In Vivo Induces ninérgica y dopaminérgica. Sponsored Differential Expression of cAMP-Speci- 14 Barzi M, Kostrz D, Menendez by: Ministerio de Ciencia e Innovación, fic Phosphodiesterase 4B mRNA Splice A, Pons S. Sonic Hedgehog-induced 201020E046. Duration: 01/01/2010- Variants in the Mouse Brain. J NEU- Proliferation Requires Specific G alpha 03/06/2011. ROSCI RES. 89:1761-1772. I.F.: 2.96. Inhibitory Proteins. J BIOL CHEM. 286:8067-8074. I.F.: 5.33. Bortolozzi A. In vivo silencing of 5-HT2A 8 Hernandez RB, Farina M, Esposito receptor and serotonin transporter by BP, Souza-Pinto NC, Barbosa F, Sunol 15 Sanabra C, Mengod G. Neuroana- RNA interference mechanism. Relevance C. Mechanisms of Manganese-Induced tomical distribution and neurochemical to the cognitive-affective disorder in Neurotoxicity in Primary Neuronal characterization of cells expressing schizophrenia and depression. Sponsored Cultures: The Role of Manganese Spe- adenylyl cyclase isoforms in mouse and by: Instituto de Salud Carlos III, P91C. ciation and Cell Type. TOXICOL SCI. rat brain. J CHEM NEUROANAT. 41:43- Duration: 02/06/2009-02/06/2011. 124:414-423. I.F.: 5.09. 54. I.F.: 2.12 Artigas F. Grup de Recerca Consolidat, 9 Villegas E, Estruch R, Mengod G, Neuroquímica i Neurofarmacologia. Cortes R. NMDA receptors in frontal GRAntS foR ReSeARcH Sponsored by: Generalitat de Catalun- cortex and hippocampus of alcohol in pRoGReSS ya, 2009SGR220. Duration: 01/01/2009- consumers. ADDICT BIOL. 16:163-165. 31/12/2013. I.F.: 4.15. Adell A. Alteraciones de las conexio- nes de la corteza prefrontal en el mo- Artigas F. Novel Methods leading to 10 Garcia-Mesa Y, Lopez-Ramos delo de esquizofrenia de antagonismo New Medications in Depression and JC, Gimenez-Llort L, Revilla S, Guerra NMDA. Sitio de acción y mecanismo Schizophrenia (NEWMEDS). Sponsored R, Gruart A, Laferla FM, Cristofol R, de los fármacos antipsicóticos. Spon- by: IMI JU, (Comisión Europea - CE y Delgado-Garcia JM, Sanfeliu C. Physical sored by: Instituto de Salud Carlos la Federación Europea de Industrias y Exercise Protects Against Alzheimer’s III, PI070111. Duration: 26/11/2007- Asociaciones Farmacéuticas - EFPIA), Disease in 3xTg-AD Mice. J ALZHEI- 30/06/2011. Grant Agreement N° 115008. Duration: MERS DIS. 24:421-454. I.F.: 4.26. 01/09/2009-31/08/2014. Artigas F. Modulación serotoninérgica 11 Straccia M, Gresa-Arribas N, de la corteza prefrontal: relevancia en Solá C. Inhibición de la activación glial Dentesano G, Ejarque-Ortiz A, Tusell el tratamiento de la depresión y la es- como diana terapéutica en enfermeda- JM, Serratosa J, Sola C, Saura J. Pro- quizofrenia. Sponsored by: Ministerio des neurodegenerativas. Sponsored by: inflammatory gene expression and neu- Educación y Ciencia, SAF2007-62378. FIS, PI081396. Duration: 01/01/2009- rotoxic effects of activated microglia Duration: 01/10/2007-04/10/2011. 31/12/2011. are attenuated by absence of CCAAT/ enhancer binding protein beta. J NEU- Celada MP. Actividad cortical y alucina- Cortés R. Expresión de marcadores ROINFLAMM. 8:-. I.F.: 5.79. ciones. nuevo modelo experimental para neuronales en demencias: enfermedad la identificación de dianas terapeuticas de los granos argirófilos y Alzheimer. 12 Masana M, Bortolozzi A, Artigas F. en esquizofrenia. Sponsored by: Institu- Sponsored by: MICINN - Instituto de Selective enhacement of mesocortical to de Salud Carlos III, PS09/01245. Dura- Salud Carlos III, PS09/01087. Duration: dopaminergic transmission by noradre- tion: 01/01/2010-31/12/2012. 01/01/2010-31/12/2012.

201 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Neuropharmacology and experimental neuropathology

Sanfeliu C. Implicación de la sirtuina Bortolozzi A. Papel de los canales de Rodriguez E. Grup de Recerca 1 en procesos neurodegenerativos. potasio-K+ en el mecanismo de ac- Consolidat, Farmacologia i Toxico- Sponsored by: MICINN, SAF2009- ción de los fármacos antidepresivos. logia. Sponsored by: Generalitat de 13093-C02-02. Duration: 01/01/2010- Relevancia del canal TREK-1 y su Catalunya, 2009SGR214. Duration: 31/12/2012. relación con el receptor de seroto- 01/01/2009-31/12/2013. nina 1A. Sponsored by: Instituto de Mengod G. Fármacos innovadores Salud Carlos III, PI10/00290. Duration: Celada MP. Apoyo tecnológico re- para la esclerosis múltiple. Sponsored 01/01/2011-31/12/2013. ferente al proyecto: “Caracterizar la by: Fundación Española para la Ciencia actividad oscilatoria cortical en ratones y Tecnología (FECYT), INC-0367. Dura- Castañé A. Metabotropic glutamate transgénicos PKEHUM0801 y su afec- tion: 01/01/2010-31/12/2011. receptors 2/3 (mGluR2/3) as drug tación por el antipsicótico clozpina. targets to improve cognitive impair- Sponsored by: Ministerio de Economía Bortolozzi A, Artigas F. Modulación ment in schizophrenia. Sponsored y Competitividad, BRAINco Biopharma, de los genes asociados al sistema by: Instituto de Salud Carlos III, CENIT10 10/156. Duration: 18/05/2010- serotonérgico con moléculas RNA 11INT4. Duration: 01/01/2011- 31/12/2013. antisentido (siRNA) y su efecto en 31/12/2012. modelo. Sponsored by: nLife Thera- peutics, 10/166. Duration: 01/07/2010- Pons S. Control de la proliferación de DoctoRAl tHeSeS 31/12/2013. los precursores de neuronas granu- lares del cerebelo. Sponsored by: Suñol C. Efectos de los pesticidas orga- Artigas F. Desarrollo y validación clí- MICINN, BFU2008-024024BFI. Dura- noclorados sobre la neurotransmisión nica de un modelo experimental para tion: 01/01/2009-31/12/2011. glutamatérgica en cultivos primarios identificar dianas terapéuticas en el neuronales. Interacciones con el sistema tratamiento de alucinaciones resisten- Mengod G. El papel de las fosfo- neuroendocrino. PhD student: Victor Briz. tes. Sponsored by: Instituto de Salud diesterasas del AMPc en la evolu- Carlos III, P82. Duration: 21/11/2008- ción y tratamiento de la esclerosis Mengod G. AMPc I neuroinflamació: 21/11/2011. múltiple en el modelo de EAE en Identificació de proteïnes implicades ratón. Nuevas aproximaciones en la regulació dels nivells d’AMPc en Sanfeliu C. Disfunción cerebral du- terapéuticas. Sponsored by: MI- l’encefalomielitis autoimune experimen- rante el envejecimiento: relevancia CINN - Instituto de Salud Carlos III, tal. PhD student: Cristina Sanabra Palau. para la enfermedad de Alzheimer PI10/01874. Duration: 01/01/2011- (BrainAge). Sponsored by: MI- 31/12/2013. Mengod G. cAMP specific-phosphodi- CINN, CSD2010-00045. Duration: esterases: mRNA variations and sex- 27/12/2010-26/12/2015. Saura J. Efecto antiinflamatorio y related differences in mouse brain fol- neuroprotector de la inhibición de C/ lowing immune response. PhD student: Vilaró MT. Efecto de la activación de EBP y C/EBP en un modelo animal Emily Johansson. receptores 5-HT4 de serotonina sobre de esclerosis múltiple. Sponsored la deposición del péptido amiloide Aß‚ by: Instituto de Salud Carlos III, Pons S. Papel de las G i y la PKA en la en un ratón triple transgénico de la PI10/378. Duration: 01/01/2011- señalización de Shh. PhD student: Mer- enfermedad de Alzheimer. Sponsored 31/12/2013. cedes Barzy Dieguez. by: MICINN - Instituto de Salud Carlos III, PS09/00468. Duration: 01/01/2010- Suñol C. Estudio de mecanismos de Pons S. Control de la proliferación 31/12/2012. neurotoxicidad crónica de contami- neuronal por microRNAs. PhD student: nantes tóxicos: papel de los recep- Jordi Berenguer de Felipe. Adell A. Papel de la corteza prefrontal tores GABA-A, de glutamato y de en la fisiopatología y tratamiento de la estrógenos. Posibles intervenciones Bortolozzi A, Artigas F. Modulació dels depresión y esquizofrenia. Estudio con terapéuticas. Sponsored by: MI- sistemes monoaminèrgics a l’escorça modelos animales. Sponsored by: Ins- CINN - Instituto de Salud Carlos III, prefrontal. Implicacions en esquizofrè- tituto de Salud Carlos III, PI10/01103. PS10/00453. Duration: 01/01/2011- nia i depressió. PhD student: Mercè Duration: 01/01/2011-31/12/2013. 31/12/2013. Masana Nadal.

202 AReA 4

Clinical and experimental neuroscience

Brain ischemia: Clinical and experimental studies gROUP MeMBeRS StrateGic oBjectiveS

Study of cerebrovascular pathology from the clinical and basic perspective, with teAM leADeR special emphasis on inflammation and Anna M. planas (iiBB-cSic) immune response, as well as on the tel.: 93 363 83 27 use of neuroimaging techniques. The fax: 93 363 83 01 ultimate aim is to develop therapeutic e-mail: [email protected] strategies in application to stroke.

iDiBApS MeMBeRS: fernando yepes calderón (cSic) Ángel chamorro (Hospital clínic) ester Bonfill (iiBB-cSic, beca fpu) tomàs Santalucia (iDiBApS) Angélica Salas (iDiBApS) lluïsa camón (iiBB-cSic) núria de Vera (iiBB-cSic) tecHniciAnS: emili Martínez (iiBB-cSic) francisca Ruiz (iDiBApS) esther pozas (Ramón y cajal, iDiBApS) cedric Doucerain (iDiBApS) carles Justicia (iiBB-cSic) leonardo J. Márquez (iiBB-cSic) Álvaro cervera (Hospital clínic) Valérie petegnief (iiBB-cSic) collABoRAtoRS: Sergi Amaro (Hospital clínic) Víctor obach (Hospital clínic) Xabier urra (Hospital clínic) Marta Vargas (fundació clínic) francesc Miró (iDiBApS) ReSeARcH fellowS: Guadalupe Soria (iDiBApS) Miriam font (cSic) Gloria Sans (iDiBApS) isabel pérez de puig (iDiBApS) Xavier de la Rosa Siles (cSic)

Study of the rat brain using magnetic resonance imaging. A) Fractional anisotropy map offering information on the magnitude of white matter fibre anisotropy, showing the anatomy of the rat brain. Control of the coronal section at three different levels of the brain. B) The same brain sections, with a colour- code map providing information on the three- dimensional orientation of the white matter fibres using the diffusion tensor imaging (DTI) technique. c) Coronal sections of fractional anisotropy map images of the brain of an animal 7 days after occlusion of the middle cerebral artery during 90 minutes. D) Colour-code map of the same ischemic brain sections.

203 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Brain ischemia: Clinical and experimental studies PUBLICATIONS

main lineS of oRiGinAlS 6 Gorina R, Font-Nieves M, Marquez- reSearcH i.f.: 103.37 Kisinousky L, Santalucia T, Planas AM. Astrocyte TLR4 Activation Induces a Pro- Inflammation and immunity in stroke 1 Penas C, Font-Nieves M, Fores inflammatory Environment Through the • Immunological mechanisms implicated J, Petegnief V, Planas A, Navarro X, Interplay Between MyD88-Dependent NF in the progression of ischemic stroke Casas C. Autophagy, and BiP level kappa B Signaling, MAPK, and Jak1/Stat1 and in the appearance of infectious decrease are early key events in retro- Pathways. GLIA. 59:242-255. I.F.: 5.19. complications. Study of inflammatory grade degeneration of motoneurons. and innate immune responses in CELL DEATH DIFFER. 18:1617-1627. 7 Rojas S, Herance JR, Abad S, Jimenez stroke. Genetic aspects of immune res- I.F.: 9.05. X, Pareto D, Ruiz A, Torrent E, Figueiras ponse. Studies of the lectin pathway. FP, Popota F, Fernandez-Soriano FJ, Pla- • Identification of new antioxidant 2 Bueno H, Betriu A, Heras M, Alonso nas AM, Gispert JD. Evaluation of Hypox- treatments in stroke. Preclinical stu- JJ, Cequier A, Garcia EJ, Lopez-Send- ic Tissue Dynamics with F-18-FMISO PET dies of the protective effects of these on JL, Macaya C, Hernandez-Antolin R. in a Rat Model of Permanent Cerebral treatments and of the mechanisms Primary angioplasty vs. fibrinolysis in Ischemia. MOL IMAGING BIOL. 13:558- involved. Design and conduction of very old patients with acute myocardial 564. I.F.: 3.14. a phase IIb study involving the admi- infarction: TRIANA (TRatamiento del In- nistration of uric acid in stroke treated farto Agudo de miocardio en Ancianos) 8 Soria G, DeNotaris M, Tudela R, Blasco with rtPA. randomized trial and pooled analysis G, Puig J, Planas AM, Pedraza S, Prats- • Use of intraarterial rescue treatments with previous studies. EUR HEART J. Galino A. Improved Assessment of Ex with rtPA in patients previously treated 32:51-60. I.F.: 10.05. Vivo Brainstem Neuroanatomy with High- with intravenous rtPA and selected by Resolution MRI and DTI at 7 Tesla. ANAT multimodal imaging techniques. 3 Almendros I, Farre R, Planas AM, REC. 294:1035-1044. I.F.: 1.40. Torres M, Bonsignore MR, Navajas D, Magnetic Resonance Montserrat JM. Tissue Oxygenation in 9 Obach V, Oleaga L, Urra X, Macho J, • Neuroimaging in brain ischemia: appli- Brain, Muscle, and Fat in a Rat Model of Amaro S, Capurro S, Gomez-Choco M, cation of magnetic resonance (MR) Sleep Apnea: Differential Effect of Ob- SanRoman L, Cervera A, Blasco J, Vargas techniques for the in vivo noninvasive structive Apneas and Intermittent Hy- M, Torres F, Chamorro A. Multimodal CT- monitorization of patients and experi- poxia. SLEEP. 34:1127-1133. I.F.: 5.49. Assisted Thrombolysis in Patients With mental animals in relation to anatomi- Acute Stroke A Cohort Study. STROKE. cal and functional parameters of brain 4 Soria G, Aguilar E, Tudela R, Mullol 42:1129-1131. I.F.: 5.76. damage – including immune response. J, Planas AM, Marin C. In vivo mag- Application in the vascular dementia netic resonance imaging characteriza- 10 Domingo-Espin J, Vazquez E, Ganz model and the studies of functional tion of bilateral structural changes in J, Conchillo O, Garcia-Fruitos E, Cedano recovery after stroke. experimental Parkinson’s disease: a J, Unzueta U, Petegnief V, Gonzalez- T2 relaxometry study combined with Montalban N, Planas AM, Daura X, Neuroprotection longitudinal diffusion tensor imaging Peluffo H, Ferrer-Miralles N, Villaverde A. • Neurological repair and neurogenesis and manganese-enhanced magnetic Nanoparticulate architecture of protein- in brain ischemia: effect of inflam- resonance imaging in the 6-. EUR J based artificial viruses is supported by mation upon neurogenesis. NEUROSCI. 33:1551-1560. I.F.: 3.66. protein-DNA interactions. NANOMEDI- CINE-UK. 6:1047-1061. I.F.: 6.20. clinical trials 5 Martin-Jaular L, Ferrer M, Calvo M, • Combination thrombolysis with antioxi- Rosanas-Urgell A, Kalko S, Graewe S, 11 Marco I, Valhondo M, Martin-Fonte- dants (uric acid). Soria G, Cortadellas N, Ordi J, Planas cha M, Vazquez-Villa H, DelRio J, Planas A, Burns J, Heussler V, DelPortillo HA. A, Sagredo O, Ramos JA, Torrecillas IR, Strain-specific spleen remodelling in Pardo L, Frechilla D, Benhamu B, Lopez- Plasmodium yoelii infections in Balb/c Rodriguez ML. New Serotonin 5-HT1A mice facilitates adherence and spleen Receptor Agonists with Neuroprotective macrophage-clearance escape. CELL Effect against Ischemic Cell Damage. J MICROBIOL. 13:109-122. I.F.: 5.63. MED CHEM. 54:7986-7999. I.F.: 5.21.

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original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 72.94 16 10 4 12 Abilleira S, Davalos A, GRAntS foR ReSeARcH Chamorro A, Alvarez-Sabin J, in pRoGReSS 2010 90.59 14 8 2 Ribera A, Gallofre M. Outcomes 2011 103.37 14 10 2 of Intravenous Thrombolysis Af- Planas A. NoE - Diagnostic Molecular ter Dissemination of the Stroke Imaging. Sponsored by: European Com- Code and Designation of New mission, LSHB-CT-2005-512146. Duration: Referral Hospitals in Catalonia 01/04/2005-30/09/2012. Nacional de Biomedicina (MICINN), SAF2008- The Catalan Stroke Code and 04515-C02-01. Duration: 01/01/2009-31/12/2011. Thrombolysis (Cat-SCT) Moni- Chamorro A. Uricoictus-fase III. Estudio tored Study. STROKE. 42:2001- doble ciego, aleatorizado frente a vehículo de Chamorro A. Estudio de marcadores inmunológi- 2006. I.F.: 5.76. la eficacia clínica del tratamiento combinado cos circulantes y tisulares (tejido linfoide y cere- con ácido úrico y RTPA administrados por bro) y de su relación pronóstica en el paciente 13 Rojas S, Martin A, Pareto via intravenosa en pacientes con ictus is- con ictus isquémico. Sponsored by: Instituto de D, Herance JR, Abad S, Ruiz A, quémico de menos de 3 horas de evolución. Salud Carlos III, PI09/1313. Duration: 01/01/2010- Flotats N, Gispert JD, Llop J, Sponsored by: Ministerio Sanidad y Con- 31/12/2012. Gomez-Vallejo V, Planas AM. Posi- sumo, EC07/90276. Duration: 29/10/2007- tron emission tomography with 30/12/2012. Cervera A. Activación del complemento por la C-11-Flumazenil in the rat shows vía de la lectinas: relevancia clínica. Sponsored preservation of binding sites during Planas A. Affording recovery in Stroke by: FIS, PI10/01898. Duration: 01/01/2011- the acute phase after 2h-Transient (ARISE). Sponsored by: European Commu- 31/12/2013. Focal Ischemia. NEUROSCIENCE. nity. Seventh Framework Programme (Life 182:208-216. I.F.: 3.22. Sciences), HEALTH-2007-2.2.1-1 – nº201024. Planas A. Estudios de neuroimagen. Sponsored Duration: 01/04/2008-01/03/2013. by: Ministerio de Economía y Competitividad, CE- 14 Bousser MG, Amarenco P, NIT10 10/157. Duration: 18/05/2010-31/12/2014. Chamorro A, Fisher M, Ford I, Santalucía T. Efecto de la glucosa sobre Fox KM, Hennerici MG, Mattle la función de HIF-1alfa en neuronas y glía Planas A. Grup d’investigació cerebrovascular. HP, Rothwell PM, DeCordoue A, sometidas a isquemia y estímulos pro- Sponsored by: Generalitat de Catalunya, 2009_ Fratacci MD. Terutroban versus inflamatorios . Sponsored by: Programa SGR_890. Duration: 28/09/2009-31/12/2013. aspirin in patients with cerebral Nacional de Biomedicina (MICINN), ischaemic events (PERFORM): a SAF2008-04515-C02-02. Duration: Planas A. Neurogénesis endógena e inflamación randomised, double-blind, parallel- 01/01/2009-31/12/2011. en la isquemia cerebral en modelos experimen- group trial. LANCET. 377:2013- tales murinos y en pacientes con ictus. Spon- 2022. I.F.: 33.63. Petegnief V. Mecanismos de muerte y sored by: Instituto de Salud Carlos III, PI070917. neuroprotección en la isquemia cerebral. Duration: 01/03/2009-30/09/2011. Efecto de la inflamación y papel de la UPR. ReViewS Sponsored by: Ministerio de Ciencia e Inno- i.f.: 5.76 vación (FIS), PI081932. Duration: 01/01/2009- DoctoRAl tHeSeS 01/12/2011. 1 Amaro S, Chamorro A. Translational Chamorro A, Planas A. Terapia combinada con Stroke Research of the Combination of Justicia C. Estudio de la función cerebral ácido úrico y RTPA en el ictus isquémico agudo: Thrombolysis and Antioxidant Therapy. por resonancia magnética de alto campo Farmacocinética, seguridad clínica y actividad STROKE. 42:1495-1499. I.F.: 5.76. en modelos experimentales de isquemia: biológica de la administración endovenosa de Degeneración y regeneración de la sustancia ácido úrico en el ictus isquémico tratado con blanca. Sponsored by: Ministerio de Ciencia RTPA. PhD student: Sergio Amaro Delgado. eDitoRiAlS e innovación (FIS), PI081880. Duration: i.f.: 5.76 01/01/2009-31/12/2012. Pozas E, Petegnief V. El procés inflamatori desencadenat per l’ activació del receptor de 1 Planas AM, Traystman RJ. Ad- Planas A. Inflamación y respuesta inmune immunitat innata TLR-4, i mecanismes naturals vances in Translational Medicine 2010. innata como dianas terapéuticas en la d’autorregulació en astròcits. PhD student: STROKE. 42:283-284. I.F.: 5.76. isquemia cerebral. Sponsored by: Programa Míriam Aurora Font Nieves de la Vega.

205 AReA 4

Team involved in: Clinical and experimental neuroscience

Neurodegenerative diseases: Clinical and experimental research

gROUP MeMBeRS

teAM leADeR eduardo tolosa (Hospital clínic) tel.: 93 227 57 85 e-mail: [email protected]

iDiBApS MeMBeRS: ReSeARcH fellowS: nuRSinG StAff: Mario ezquerra (iSc3, fundació clínic) claustre pont (ciBeRneD) Rosa Maria Álvarez (fundació clínic) conxita Marín (iDiBApS) teresa Botta Maria Josep Martí (Hospital clínic) Judith navarro (Hospital clínic) collABoRAtoRS: José luís Molinuevo (Hospital clínic) Magda castellví (Hospital clínic) Rubén fernández-Santiago (iDiBApS) esteban Muñoz (Hospital clínic) Mircea Balasa (Hospital clínic) carles Gaig (Hospital clínic) francesc Valldeoriola (Hospital clínic) Jaume olives (fundació clínic) Albert lladó (Hospital clínic) Rebeca Adánez (fundació clínic) Raquel Sánchez del Valle Silvia Gil (iDiBApS) (Hospital clínic) lorena Rami tecHniciAnS: (fundació clínic - Miguel Servet) esther Aguilar (fundació clínic) Mercè Bonastre (ciBeRneD) poStDoctoRAl fellowS: eva caballero (Grup Suport Generalitat) Beatriz Bosch (iDiBApS - pharmacog) Manel fernández (fundació clínic) Anna Antonell (iDiBApS - consolider) Maria teresa Buongiorno cristina Solé padulles (fundació clínic) (fundació clinic) Ana camara (fundació clínic)

206 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience neuRoDeGeneRAtiVe DiSeASeS: clinicAl AnD eXpeRiMentAl ReSeARcH

StrateGic oBjectiveS

1. Development of research projects, with results that may find short term application, with a view to improving the diagnosis and treatment of degenerative neurological diseases. Many of the research lines are linked to clinical research protocols of the Clinic Hospital Department of Neurology. 2. Investigation of the molecular mechanisms implicated in dopaminergic neuron degeneration and in the physiopathology of the motor complications induced by drug treatment, in experimental models of Parkinson’s disease and other movement disorders. Results of a brain transcriptomic study using Heat map analysis showed partial segregation of the expression profiles of controls, idiopathic PD main lineS of (IPD) and LRRK2-associated mutation PD (MPD). IPD and controls have expression patterns that are clearly different, while MPD tissues show reSearcH heterogeneous patterns - two resembling controls and one resembling IPD. This suggests the presence of different transcription processes in the putamen of MPD versus IPD. 1. Genetic analyses, biological markers and experimental therapies in Parkinson’s disease and other movement disorders. Genetic and expression studies in parkinsonisms. 4. Study of the biological and mole- 2. Studies in in vivo and in vitro expe- cular bases of Alzheimer’s disease rimental modelsof the physiopatho- and Parkinson’s disease in precli- logical mechanisms involved in nical stages: mild cognitive impair- Parkinson’s disease and other movement and pre-motor Parkinson’s ment disorders. disease. 3. Genetic and diagnostic and predictive 5. Study of neurogenesis in the sub- marker studies in Alzheimer’s disea- ventricular zone, olfactory bulb and se and other dementias. Experimen- striate nucleus in experimental tal functional neuroimaging studies in models of Parkinson’s disease and healthy and in pathological aging. tardive dyskinesia.

ReSeARCh gROUP parkinSon’S diSeaSe and movement diSorderS

Group Leader: Eduardo tolosa (hospital clínic)

We have consolidated the line of genetics in degenerative disorders, particularly Parkinson’s disease. This year we have explored or published different studies on genetic brain expression of genes potentially implicated in progressive supra- nuclear paralysis (isoforms of tau, CRHR1, IMP5, cdk5, GSK3 and saitohin). In addition, we have determined the frequency of the most common mutations of the LRRK2 gene in patients with Parkinson’s disease seen in our Depart- ment, and in cases of parkinsonism in the Neurological Tissue Bank.

207 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Neurodegenerative diseases: Clinical and experimental research PUBLICATIONS

oRiGinAlS tissue density in patients with cirrhosis 13 Ibarretxe-Bilbao N, Junque C, i.f.: 237.08 without overt hepatic encephalopathy. J Marti MJ, Tolosa E. Brain structural MRI HEPATOL. 55:564-573. I.F.: 9.33. correlates of cognitive dysfunctions in 1 Fortea J, Llado A, Clarimon J, Lleo Parkinson’s disease. J NEUROL SCI. A, Oliva R, Peri J, Pintor L, Yague J, 7 Rascol O, Fitzer-Attas C, Hauser 310:70-74. I.F.: 2.17. Blesa R, Molinuevo JL, Sanchez-Valle R, Jankovic J, Long A, Langston JW, R. PICOGEN: Five years experience Melamed E, Poewe W, Stocchi F, Tolosa 14 Ibarretxe-Bilbao N, Junque C, Marti with a genetic counselling program E, Eyal E, Weiss YM, Olanow CW. A MJ, Tolosa E. Cerebral basis of visual for dementia. NEUROLOGIA. 26:143- double-blind, delayed-start trial of rasagi- hallucinations in Parkinson’s disease: 149. I.F.:0. 59. line in Parkinson›s disease (the ADAGIO Structural and functional MRI studies. J study): prespecified and post-hoc analy- NEUROL SCI. 310:79-81. I.F.: 2.17. 2 Balasa M, Gelpi E, Antonell A, Rey ses of the need for additional therapies, MJ, Sanchez-Valle R, Molinuevo JL, changes in UPDRS scores, and non- 15 Rami L, Fortea J, Bosch B, Sole- Llado A. Clinical features and APOE motor outcomes. LANCET NEUROL. Padulles C, Llado A, Iranzo A, Sanchez- genotype of pathologically proven 10:415-423. I.F.: 21.66. Valle R, Molinuevo JL. Cerebrospinal early-onset Alzheimer disease. NEU- Fluid Biomarkers and Memory Present ROLOGY. 76:1720-1725. I.F.: 8.02. 8 Antonell A, Balasa M, Oliva R, Llado Distinct Associations along the Con- A, Bosch B, Fabregat N, Fortea J, Mo- tinuum from Healthy Subjects to AD 3 Garrabou G, Inoriza JM, Moren linuevo JL, Sanchez-Valle R. A novel Patients. J ALZHEIMERS DIS. 23:1-8. C, Oliu G, Miro O, Marti MJ, Cardel- PSEN1 gene mutation (L235R) associat- I.F.: 4.26. lach F. Mitochondrial Injury in Human ed with familial early-onset Alzheimer›s Acute Carbon Monoxide Poisoning: disease. NEUROSCI LETT. 496:40-42. 16 Fortea J, Llado A, Bosch B, An- The Effect of Oxygen Treatment. J I.F.: 2.06. tonell A, Oliva R, Molinuevo JL, Sanchez- ENVIRON SCI HEAL C. 29:32-51. Valle R. Cerebrospinal Fluid Biomarkers I.F.: 4.84. 9 Wachter T, Minguez-Castellanos in Alzheimer’s Disease Families with A, Valldeoriola F, Herzog J, Stoevelaar PSEN1 Mutations. NEURODEGENER 4 Iranzo A, Valldeoriola F, Lomena F, H. A tool to improve pre-selection DIS. 8:202-207. I.F.: 3.79. Molinuevo JL, Serradell M, Salamero for deep brain stimulation in patients M, Cot A, Ros D, Pavia J, Santamaria with Parkinson›s disease. J NEUROL. 17 Rami L, Valls-Pedret C, Bartres-Faz J, Tolosa E. Serial dopamine trans- 258:641-646. I.F.: 3.85. D, Caprile C, Sole-Padulles C, Castellvi porter imaging of nigrostriatal function M, Olives J, Bosch B, Molinuevo JL. in patients with idiopathic rapid-eye- 10 Beyer K, Ispierto L, Latorre P, Tolo- Cognitive reserve questionnaire. Scores movement sleep behaviour disorder: a sa E, Ariza A. Alpha- and beta-synuclein obtained in a healthy elderly population prospective study. LANCET NEUROL. expression in Parkinson disease with and in one with Alzheimer’s disease. 10:797-805. I.F.: 21.66. and without dementia. J NEUROL SCI. REV NEUROLOGIA. 52:195-201. 310:112-117. I.F.: 2.17. I.F.: 1.22. 5 Munoz E, Iranzo A, Rauek S, Lome- na F, Gallego J, Ros D, Santamaria J, 11 Buongiorno M, Compta Y, Marti 18 Fortea J, Sala-Llonch R, Bartres-Faz Tolosa E. Subclinical nigrostriatal dopa- MJ. Amyloid-beta and tau biomarkers in D, Llado A, Sole-Padulles C, Bosch B, minergic denervation in the cerebellar Parkinson’s disease-dementia. J NEU- Antonell A, Olives J, Sanchez-Valle R, subtype of multiple system atrophy ROL SCI. 310:25-30. I.F.: 2.17. Molinuevo JL, Rami L. Cognitively Pre- (MSA-C). J NEUROL. 258:2248-2253. served Subjects with Transitional Cere- I.F.: 3.85. 12 Sole-Padulles C, Llado A, Bartres- brospinal Fluid beta-Amyloid 1-42 Values Faz D, Fortea J, Sanchez-Valle R, Bosch Have Thicker Cortex in Alzheimer’s Dis- 6 Guevara M, Baccaro ME, Gomez- B, Antonell A, Molinuevo JL, Rami L. ease Vulnerable Areas. BIOL PSYCHIAT. Anson B, Frisoni G, Testa C, Torre A, Association between cerebrospinal 70:183-190. I.F.: 8.67. Molinuevo JL, Rami L, Pereira G, Sotil fluid tau and brain atrophy is not related EU, Cordoba J, Arroyo V, Gines P. to clinical severity in the Alzheimer’s 19 Muxi A, Paredes P, Navales I, Cerebral magnetic resonance imaging disease continuum. PSYCHIAT RES- Valldeoriola F, Gaig C, Lomena F, DeLa- reveals marked abnormalities of brain NEUROIM. 192:140-146. I.F.: 2.06. Cerda A, Sola O, Domenech B, Tolosa

208 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience neuRoDeGeneRAtiVe DiSeASeS: clinicAl AnD eXpeRiMentAl ReSeARcH

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 196.35 43 32 7 E, Pons F. Diagnostic cutoff points for Graff-Radford NR, Dickson DW, Rade- I-123-MIBG myocardial scintigraphy in a makers R, Boeve BF, Pickering-Brown 2010 188.85 27 9 5 Caucasian population with Parkinson’s SM, Snowden J, VanSwieten JC, Heu- 2011 237.08 44 24 10 disease. EUR J NUCL MED MOL I. tink P, Seelaar H, Murrell JR, Ghetti B, 38:1139-1146. I.F.: 5.04. Spina S, Grafman J, Kaye JA, Woltjer RL, Mesulam M, Bigio E, Llado A, Mill- risk of the tauopathy progressive su- 20 Antonell A, Fortea J, Rami L, Bosch er BL, Alzualde A, Moreno F, Rohrer JD, pranuclear palsy. NAT GENET. 43:699- B, Balasa M, Sanchez-Valle R, Iranzo A, Mackenzie IRA, Feldman HH, Hamilton U125. I.F.: 36.38. Molinuevo JL, Llado A. Different profiles RL, Cruts M, Engelborghs S, DeDeyn of Alzheimer’s disease cerebrospinal PP, VanBroeckhoven C, Bird TD, Cairns 28 Marin C, Aguilar E. In vivo 6-OHDA- fluid biomarkers in controls and subjects NJ, Goate A, Frosch MP, Riederer PF, induced neurodegeneration and nigral with subjective memory complaints. Bogdanovic N, Lee VMY, Trojanowski autophagic markers expression. NEU- J NEURAL TRANSM. 118:259-262. JQ, VanDeerlin VM. Genetic and Clini- ROCHEM INT. 58:521-526. I.F.: 3.60. I.F.: 2.60. cal Features of Progranulin-Associated Frontotemporal Lobar Degeneration. 29 Botta-Orfila T, Ezquerra M, Rios J, 21 Molinuevo JL, Berthier ML, Rami ARCH NEUROL-CHICAGO. 68:488-497. Fernandez-Santiago R, Cervantes S, Sa- L. Donepezil provides greater benefits in I.F.: 7.11. maranch L, Pastor P, Marti MJ, Munoz mild compared to moderate Alzheimer’s E, Valldeoriola F, Aguilar M, Calopa M, disease: Implications for early diagno- 25 Compta Y, Ezquerra M, Munoz E, Hernandez-Vara J, Tolosa E. Lack of in- sis and treatment. ARCH GERONTOL Tolosa E, Valldeoriola F, Rios J, Camara teraction of SNCA and MAPT genotypes GERIAT. 52:18-22. I.F.: 1.44. A, Fernandez M, Buongiorno MT, Marti in Parkinson’s disease. EUR J NEUROL. MJ. High cerebrospinal tau levels are 18:E32-E32. I.F.: 3.77. 22 Ibarretxe-Bilbao N, Zarei M, associated with the rs242557 tau gene Junque C, Marti MJ, Segura B, Vendrell variant and low cerebrospinal beta-am- 30 Valls-Pedret C, Olives J, Bosch B, P, Valldeoriola F, Bargallo N, Tolosa E. yloid in Parkinson disease. NEUROSCI Caprile C, Castellvi M, Molinuevo JL, Dysfunctions of cerebral networks LETT. 487:169-173. I.F.: 2.06. Rami L. Landscape test for assessing precede recognition memory deficits in visual memory in Alzheimer’s disease. early Parkinson’s disease. NEUROIM- 26 Valldeoriola F, Gaig C, Muxi A, Na- REV NEUROLOGIA. 53:1-7. I.F.: 1.22. AGE. 57:589-597. I.F.: 5.94. vales I, Paredes P, Lomena F, DeLaCerda A, Buongiorno M, Ezquerra M, Santa- 31 Costa J, Guzman J, Valldeoriola F, 23 Moreno-Lopez C, Santamaria J, cruz P, Marti MJ, Tolosa E. I-123-MIBG Rumia J, Tolosa E, Casanova-Molla J, Salamero M, DelSorbo F, Albanese A, cardiac uptake and smell identification Valls-Sole J. Modulation of the soleus H Pellecchia MT, Barone P, Overeem S, in parkinsonian patients with LRRK2 reflex by electrical subcortical stimuli in Bloem B, Aarden W, Canesi M, Antonini mutations. J NEUROL. 258:1126-1132. humans. EXP BRAIN RES. 212:439-448. A, Duerr S, Wenning GK, Poewe W, I.F.: 3.85. I.F.: 2.30. Rubino A, Meco G, Schneider SA, Bha- tia KP, Djaldetti R, Coelho M, Sampaio 27 Hoglinger GU, Melhem NM, 32 Molinuevo JL, Gomez-Anson B, C, Cochen V, Hellriegel H, Deuschl G, Dickson DW, Sleiman PMA, Wang LS, Monte GC, Bosch B, Sanchez-Valle R, Colosimo C, Marsili L, Gasser T, Tolosa Klei L, Rademakers R, DeSilva R, Litvan Rami L. Neuropsychological profile of E. Excessive Daytime Sleepiness in Mul- I, Riley DE, VanSwieten JC, Heutink prodromal Alzheimer’s disease (Prd- tiple System Atrophy (SLEEMSA Study). P, Wszolek ZK, Uitti RJ, Vandrovcova AD) and their radiological correlates. ARCH NEUROL-CHICAGO. 68:223-230. J, Hurtig HI, Gross RG, Maetzler W, ARCH GERONTOL GERIAT. 52:190-196. I.F.: 7.11. Goldwurm S, Tolosa E, Borroni B, Pas- I.F.: 1.44. tor P, Cantwell LB, Han MR, Dillman A, 24 Chen-Plotkin AS, Martinez-Lage VanDerBrug MP, Gibbs JR, Cookson 33 Molinuevo JL, Hernandez B. Profile M, Sleiman PMA, Hu W, Greene R, MR, Hernandez DG, Singleton AB, of the informal carer associated with the Wood EM, Bing SX, Grossman M, Farrer MJ, Yu CE, Golbe LI, Revesz T, clinical management of the Alzheimer’s Schellenberg GD, Hatanpaa KJ, Weiner Hardy J, Lees AJ, Devlin B, Hakonarson disease patient refractory to symptom- MF, White CL, Brooks WS, Halliday H, Muller U, Schellenberg GD. Identifi- atic treatment of the disease. NEURO- GM, Kril JJ, Gearing M, Beach TG, cation of common variants influencing LOGIA. 26:518-527. I.F.: 0.59.

209 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Neurodegenerative diseases: Clinical and experimental research

34 Tolosa E, Pont-Sunyer C. Prog- K, Manero RM, Aguilar M, Badenes 42 Marin C, Bonastre M, Aguilar E, ress in defining the premotor phase D, Molinuevo JL, Robles A, Barquero Jimenez A. The Metabotropic Gluta- of Parkinson’s disease. J NEUROL MS, Antunez C, Martinez-Parra C, mate Receptor Antagonist 2-Methyl- SCI. 310:4-8. I.F.: 2.17. Frank-Garcia A, Fernandez M, Blesa R. 6-(phenylethynyl) pyridine Decreases Spanish Multicenter Normative Stud- Striatal VGLUT2 Expression in As- 35 Gaig C, Valldeoriola F, Gelpi E, ies (Neuronorma Project): Norms for sociation With an Attenuation of L- Ezquerra M, Llufriu S, Buongiorno the Abbreviated Barcelona Test. ARCH Dopa-Induced Dyskinesias. SYNAPSE. M, Rey MJ, Marti MJ, Graus F, To- CLIN NEUROPSYCH. 26:144-157. 65:1080-1086. I.F.: 2.93. losa E. Rapidly Progressive Diffuse I.F.: 2.30. Lewy Body Disease. MOVEMENT 43 Iranzo A, Frauscher B, Santos H, DISORD. 26:1316-1323. I.F.: 4.48. 40 Arenaza-Urquijo EM, Bosch B, Sa- Gschliesser V, Ratti L, Falkenstetter T, la-Llonch R, Sole-Padulles C, Junque C, Sturner C, Salamero M, Tolosa E, Poewe 36 Cavanillas ML, Fernandez O, Fernandez-Espejo D, Bargallo N, Rami W, Santamaria J, Hogl B. Usefulness of Comabella M, Alcina A, Fedetz M, L, Molinuevo JL, Bartres-Faz D. Spe- the SINBAR electromyographic montage Izquierdo G, Lucas M, Cenit MC, cific Anatomic Associations Between to detect the motor and vocal manifesta- Arroyo R, Vandenbroeck K, Alloza White Matter Integrity and Cognitive tions occurring in REM sleep behavior I, Garcia-Barcina M, Antiguedad Reserve in Normal and Cognitively Im- disorder. SLEEP MED. 12:284-288. A, Leyva L, Gomez CL, Olascoaga paired Elders. AM J GERIAT PSYCHIAT. I.F.: 3.43. J, Otaegui D, Blanco Y, Saiz A, 19:33-42. I.F.: 3.57. Montalban X, Matesanz F, Urcelay 44 Scherfler C, Frauscher B, Schocke E. Replication of top markers of a 41 Mattsson N, Andreasson U, Pers- M, Iranzo A, Gschliesser V, Seppi K, genome-wide association study in son S, Arai H, Batish SD, Bernardini S, Santamaria J, Tolosa E, Hogl B, Poewe multiple sclerosis in Spain. GENES Bocchio-Chiavetto L, Blankenstein MA, W. White and Gray Matter Abnormalities IMMUN. 12:110-115. I.F.: 4.37. Carrillo MC, Chalbot S, Coart E, Chias- in Idiopathic Rapid Eye Movement Sleep serini D, Cutler N, Dahlfors G, Duller Behavior Disorder: A Diffusion-Tensor 37 Trenkwalder C, Kies B, Rudz- S, Fagan AM, Forlenza O, Frisoni GB, Imaging and Voxel-Based Morphometry inska M, Fine J, Nikl J, Honczarenko Galasko D, Galimberti D, Hampel H, Study. ANN NEUROL. 69:400-407. K, Dioszeghy P, Hill D, Anderson T, Handberg A, Heneka MT, Herskovits I.F.: 10.75. Myllyla V, Kassubek J, Steiger M, AZ, Herukka SK, Holtzman DM, Hum- Zucconi M, Tolosa E, Poewe W, pel C, Hyman BT, Iqbal K, Jucker M, Surmann E, Whitesides J, Boroojerdi Kaeser SA, Kaiser E, Kapaki E, Kidd ReViewS B, Chaudhuri KR. Rotigotine Effects D, Klivenyi P, Knudsen CS, Kummer i.f.: 12.21 on Early Morning Motor Function MP, Lui J, Llado A, Lewczuk P, Li QX, and Sleep in Parkinson’s Disease: Martins R, Masters C, Mcauliffe J, 1 Bosch X, Saiz A, Ramos-Casals M. A Double-Blind, Randomized, Pla- Mercken M, Moghekar A, Molinuevo Monoclonal antibody therapy-associated cebo-Controlled Study (RECOVER). JL, Montine TJ, Nowatzke W, O’brien neurological disorders. NAT REV NEU- MOVEMENT DISORD. 26:90-99. R, Otto M, Paraskevas GP, Parnetti ROL. 7:165-172. I.F.: 6.51. I.F.: 4.48. L, Petersen RC, Prvulovic D, DeReus HPM, Rissman RA, Scarpini E, Stefani 2 Molinuevo JL. Memantine: the value 38 Valldeoriola F, Coronell C, Pont A, Soininen H, Schroder J, Shaw LM, of combined therapy. REV NEUROLOGIA. C, Buongiorno MT, Camara A, Gaig Skinningsrud A, Skrogstad B, Spreer 52:95-100. I.F.: 1.22. C, Compta Y. Socio-demographic A, Talib L, Teunissen C, Trojanowski and clinical factors influencing the JQ, Tumani H, Umek RM, VanBroeck 3 Wenning GK, Litvan I, Tolosa E. adherence to treatment in Par- B, Vanderstichele H, Vecsei L, Verbeek Milestones in Atypical and Secondary kinson’s disease: the ADHESON MM, Windisch M, Zhang J, Zetterberg Parkinsonisms. MOVEMENT DISORD. study. EUR J NEUROL. 18:980-987. H, Blennow K. The Alzheimer’s Asso- 26:1083-1095. I.F.: 4.48. I.F.: 3.77. ciation external quality control program for cerebrospinal fluid biomarkers. 39 Quintana M, Pena-Casanova ALZHEIMERS DEMENT. 7:386-395. J, Sanchez-Benavides G, Langohr I.F.: 5.90.

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MulticentRicS parkinsonismos relacionados. Spon- enfermedad de parkinson, parkin- i.f.: 4.26 sored by: Instituto de Salud Carlos sonismo vascular y en pacientes con III, PI09/1038. Duration: 01/01/2010- mutaciones del gen LRRK2. Spon- 1 Frolich L, Ashwood T, Nilsson J, Eck- 31/12/2012. sored by: Instituto de Salud Carlos erwall G. Effects of AZD3480 on Cogni- III, PI070426. Duration: 26/11/2007- tion in Patients with Mild-to-Moderate Tolosa E. European Project on Men- 30/03/2011. Alzheimer’s Disease: A Phase IIb Dose- delian Forms of Parkinson’s Disease. Finding Study. J ALZHEIMERS DIS. Sponsored by: Eberhard-Karls Univer- 24:363-374. I.F.: 4.26. sitaet Tuebingen, 241791. Duration: DoctoRAl tHeSeS 01/04/2010-31/03/2013. Molinuevo JL. Estudios miltimodales GRAntS foR ReSeARcH Molinuevo JL. Disfunción cerebral de reesonancia magnética y de líquido in pRoGReSS durante el envejecimiento: relevancia cefalorraquídeo en la enfermedad para la enfermedad de Alzheimer. de Alzheimer preclínica familiar y Tolosa E. Síntomas no-motores e integ- Sponsored by: Ministerio de Cien- esporádica. PhD student: Juan Fortea ridad de la vía nigroestriatal en portado- cia E Innovacion, CSD2010-00045. Ormaechea. res “asintomáticos” de mutaciones en Duration: 27/12/2010-26/12/2015. el gen LRRK2. Sponsored by: Instituto Tolosa E. Prevalencia, fenotipo clínico de Salud Carlos III, PI080155. Duration: Sanchez R. Estudio portadores de y neuropatológico del Parkinsonismo 01/01/2009-30/06/2012. mutaciones determinantes de demen- asociado a mutaciones en el gen cias monogénicas en fase preclínica: LRRK2. PhD student: Carles Gaig Marti M. Valor predictivo y diagnóstico valoración cognitiva, estudio por RMN Ventura. de demencia en la enfermedad de par- de volúmenes y conectividad cerebral kinson de los marcadores de patología y de marcadores en LCR. Sponsored tau y beta-amiloide en líquido cefalor- by: Instituto de Salud Carlos III, raquídeo y tomografía de emisión de PI080036. Duration: 01/01/2009- positrones. Sponsored by: Instituto de 30/12/2011. Salud Carlos III, PI080236. Duration: 01/01/2009-31/12/2011. Tolosa E. LRRK2 Cohort Consortium 2010 - “Expansion of the ASAP Tolosa E. Grup de recerca de malalties study” (ASymptomatic G2019S/ neurològiques. Sponsored by: AGAUR R1441G LRRK2 mutation carriers and (Agència de Gestió d’Sponsored bys Assessment of factors influencing Universitaris i de Recerca -Generalitat LRRK2-related PD expression study). de Catalunya), 2009 SGR1019. Dura- Sponsored by: Michael J. Fox Founda- tion: 01/01/2009-31/12/2013. tion for Parkinson Disease (MJFF), PI08/90348. Duration: 01/01/2011- Marin C. Disfunción olfativa en la enfer- 31/12/2013. medad de Parkinson y su relación con la neurogénesis en la zona subventricu- Rami L. Evolución cognitiva de un lar: estudio funcional, molecular e in grupo de sujetos con envejecimiento vitro en el parkinsonismo experimental. saludable frente a sujetos con cog- Sponsored by: Instituto de Salud Carlos nición normal a riesgo de la enfer- III, PI080060. Duration: 01/01/2009- medad de Alzheimer. Sponsored by: 31/12/2011. MSPSI_Imserso, 11 197/11. Duration: 23/12/2011-22/12/2012. Ezquerra M. Identificación de biomarcadores de mirnas en el líquido cefalor- Valldeoriola F. Estudio de la enerva- raquídeo con interés diagnóstico para ción simpática cardíaca a través de la enfermedad de Parkinson y otros gammagrafía con 123I-MIBG en la

211 AReA 4

Team involved in: Clinical and experimental neuroscience ReTiC en oftalmología (oFTaRed) Neurophysiology and functional studies of the nervous system

gROUP MeMBeRS

teAM leADeR Josep Valls Solé (Hospital clínic) tel.: 93 227 54 13 fax: 93 227 57 83 e-mail: [email protected]

iDiBApS MeMBeRS: Jordi casanova (iDiBApS) Jonathan Giblin (uB, investigador Mar carreño (Hospital clínic) Merche Morales (iDiBApS) Ramon y cajal) Xavier Gasull (uB) Gerard callejo Martin (uB) Arcadi Gual (uB) Marc Güaita (iDiBApS) ViSitinG ScientiStS: Alejandro iranzo (Hospital clínic) Dylan edwards (Burke institute Joan Santamaria (Hospital clínic) collABoRAtoRS: of Rehabilitation, new york) Antonio Donaire (Hospital clínic) Markus kofler ReSeARcH fellowS: Jordi palés (uB) (Hochzirl neurorehabilitation Germán cuesto Gil (iDiBApS) Xavier Sala Blanch (Hospital clínic) Hospital, Zirl, Austria) Monica Serradell (fundació clínic) carles Gaig (Hospital clínic) Juan M. castellote (instituto de Astrid tulleuda (uB) Javier Aparicio (Hospital clínic) Salud carlos iii, Madrid, españa)

212 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience neuRopHySioloGy AnD functionAl StuDieS of tHe neRVouS SySteM

StrateGic oBjectiveS

Expansion of scientific knowledge on functional aspects of the nervous system, with maximum integration of the basic and clinical aspects, fundamentally using neurophysiological techniques. From the clinical perspective, the principal objectives are the characterization of the neurophysiological aspects of motor control and perception, and the physiopathological aspects of neuromuscular diseases, sleep disturbances, epilepsy, and conditions characterized by neuropathic pain. In basic research, the principal objective is to understand the way that sensory neurons change their excitability in response to injury, inflam- EMG hyperactivity in REM sleep behaviour disorders. Polysomnographic Study (PSG). The mation or other abnormalities, as well figure shows the recording of the electromyographic activity (EMG) of eleven muscles in a patient with REM sleep behaviour disorder (RBD). The aim of the study is to find the cut-off as the role of different ion channels in values for EMG activity during episodes of REM sleep which differentiate patients with RBD the generation of inflammatory and neu- from the controls. In addition to carrying out a conventional PSG set-up (electro-oculogram, electroencephalogram, electrocardiogram, EMG of the mind, nasal flux, chest/abdominal ropathic pain. The ocular research lines effort and posture), an EMG was recorded of the surface of 5 muscle pairs: SCM (sternoclei- study the cellular processes involved domastoid), BIC (biceps brachii), FlexDS (flexor digitorum superficialis - fingers), TA (tibialis anterior) and ExtDB (extensor digitorum brevis - toes), right and left. Thirty seconds of REM in the regulation of intraocular pressure sleep are shown with abnormal increase in EMG activity. and glaucoma pathophysiology. main lineS of somatosensory stimuli. Prepulse 3. Study of sleep and its disturbances reSearcH phenomena. in different disorders. Numbness. 2. Physiology and physiopathology of Sleep multiple latency testing. Rest- 1. The participation of subcortical neuropathic pain. Study of nociceptive less legs syndrome. Periodic leg motor systems in the execution of evoked potentials. Reflex reactions of movements during sleep. movements, postural maintenance the autonomous nervous system in 4. Epileptic phenomena and their and reflex control. Study of the response to nociceptive stimulation. treatment. Status epilepticus. Mo- alarm circuits based on auditory or Conscious sensory perception. nitoring of epileptic seizures. Video- EEG and epidural recording. Epilep- tic crisis recordings with functional ReSeARCh gROUP magnetic resonance imaging. neuropHySioloGy 5. Characterization of ion channels involved in neuronal excitability in Group Leader: xavier Gasull (UB) the sensory nervous system. Study of their role in sensory transduction Within the field of neurophysiology, the group is interested in and the generation of inflammatory establishing the functions of different ion channels in the regu- and neuropathic pain. lation of different cell processes. In particular, at neuron level, 6. Physiology of aqueous humor drai- we are investigating different ion channels implicated in cellular nage and physiopathology of glau- excitability in sensory neurons of the dorsal root ganglia and trigeminal ganglion, coma. Ocular pathology in aging. and their relationship with neuropathic pain. On the other hand, in trabecular Physiology of the cells of the ocular cells that regulate aqueous humor flow in the eye, we are exploring the role of trabecular meshwork. the cytoskeleton and of different ion channels in the functioning of these cells and their relationship with the physiopathology of glaucoma.

213 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Neurophysiology and functional studies of the nervous system PUBLICATIONS

oRiGinAlS Atrophy (SLEEMSA Study). ARCH NEU- 12 Albanese A, Asmus F, Bhatia KP, i.f.: 128.70 ROL-CHICAGO. 68:223-230. I.F.: 7.11. Elia AE, Elibol B, Filippini G, Gasser T, Krauss JK, Nardocci N, Newton A, Valls- 1 Iranzo A, Valldeoriola F, Lomena F, 6 Costa J, Guzman J, Valldeoriola F, Sole J. EFNS guidelines on diagnosis Molinuevo JL, Serradell M, Salamero Rumia J, Tolosa E, Casanova-Molla J, and treatment of primary dystonias. M, Cot A, Ros D, Pavia J, Santamaria Valls-Sole J. Modulation of the soleus EUR J NEUROL. 18:5-18. I.F.: 3.77. J, Tolosa E. Serial dopamine transpor- H reflex by electrical subcortical stimuli ter imaging of nigrostriatal function in in humans. EXP BRAIN RES. 212:439- 13 Fernandez S, Donaire A, Maestro patients with idiopathic rapid-eye-mo- 448. I.F.: 2.30. I, Seres E, Setoain X, Bargallo N, Rumia vement sleep behaviour disorder: a J, Boget T, Falcon C, Carreno M. Func- prospective study. LANCET NEUROL. 7 Iranzo A, Frauscher B, Santos H, tional neuroimaging in startle epilepsy: 10:797-805. I.F.: 21.66. Gschliesser V, Ratti L, Falkenstet- Involvement of a mesial frontoparietal ter T, Sturner C, Salamero M, Tolosa network. EPILEPSIA. 52:1725-1732. 2 Munoz E, Iranzo A, Rauek S, Lom- E, Poewe W, Santamaria J, Hogl B. I.F.: 3.96. ena F, Gallego J, Ros D, Santamaria Usefulness of the SINBAR electromyo- J, Tolosa E. Subclinical nigrostriatal graphic montage to detect the motor 14 Sala-Blanch X, Lopez AM, Pomes dopaminergic denervation in the and vocal manifestations occurring in J, Valls-Sole J, Garcia AI, Hadzic A. No cerebellar subtype of multiple sys- REM sleep behavior disorder. SLEEP Clinical or Electrophysiologic Evidence tem atrophy (MSA-C). J NEUROL. MED. 12:284-288. I.F.: 3.43. of Nerve Injury after Intraneural Injection 258:2248-2253. I.F.: 3.85. during Sciatic Popliteal Block. ANESTHE- 8 Scherfler C, Frauscher B, Schocke SIOLOGY. 115:589-595. I.F.: 5.49. 3 Rami L, Fortea J, Bosch B, M, Iranzo A, Gschliesser V, Seppi K, Sole-Padulles C, Llado A, Iranzo A, Santamaria J, Tolosa E, Hogl B, Poewe 15 Casanova-Molla J, Grau-Junyent Sanchez-Valle R, Molinuevo JL. Cere- W. White and Gray Matter Abnormali- JM, Morales M, Valls-Sole J. On the brospinal Fluid Biomarkers and Mem- ties in Idiopathic Rapid Eye Movement relationship between nociceptive ory Present Distinct Associations Sleep Behavior Disorder: A Diffusion- evoked potentials and intraepidermal along the Continuum from Healthy Tensor Imaging and Voxel-Based nerve fiber density in painful sensory Subjects to AD Patients. J ALZHEIM- Morphometry Study. ANN NEUROL. polyneuropathies. PAIN. 152:410-418. ERS DIS. 23:1-8. I.F.: 4.26. 69:400-407. I.F.: 10.75. I.F.: 5.36.

4 Antonell A, Fortea J, Rami L, 9 Schestatsky P, Callejas MA, Valls- 16 Casanova-Molla J, Leon L, Castillo Bosch B, Balasa M, Sanchez-Valle R, Sole J. Abnormal modulation of elec- CD, Valls-Sole J. Reinnervation by the Iranzo A, Molinuevo JL, Llado A. Dif- trodermal activity by thermoalgesic contralateral facial nerve in patients ferent profiles of Alzheimer’s disease stimuli in patients with primary palmar with peripheral facial palsy. MUSCLE cerebrospinal fluid biomarkers in hyperhidrosis. J NEUROL NEUROSUR NERVE. 44:923-929. I.F.: 2.30. controls and subjects with subjec- PS. 82:92-96. I.F.: 4.79. tive memory complaints. J NEURAL 17 Perez-Diaz H, Iranzo A, Rye DB, TRANSM. 118:259-262. I.F.: 2.60. 10 Casanova-Molla J, Morales M, Sola- Santamaria J. Restless abdomen A Valls N, Bosch A, Calvo M, Grau-Junyent phenotypic variant of restless legs syn- 5 Moreno-Lopez C, Santamaria J, JM, Valls-Sole J. Axonal fluorescence drome. NEUROLOGY. 77:1283-1286. Salamero M, DelSorbo F, Albanese A, quantitation provides a new approach to I.F.: 8.02. Pellecchia MT, Barone P, Overeem S, assess cutaneous innervation. J NEURO- Bloem B, Aarden W, Canesi M, Anto- SCI METH. 200:190-198. I.F.: 2.10. 18 Carreno M, Becerra JL, Castillo nini A, Duerr S, Wenning GK, Poewe J, Maestro I, Donaire A, Fernandez S, W, Rubino A, Meco G, Schneider 11 Murillo N, Kumru H, Vidal-Samso Bargallo N, Setoain X, Pintor L, Bailles E, SA, Bhatia KP, Djaldetti R, Coelho J, Benito J, Medina J, Navarro X, Valls- Rumia J, Boget T, Vernet O, Fumanal S. M, Sampaio C, Cochen V, Hellriegel Sole J. Decrease of spasticity with Seizure frequency and social outcome in H, Deuschl G, Colosimo C, Marsili L, muscle vibration in patients with spinal drug resistant epilepsy patients who do Gasser T, Tolosa E. Excessive Day- cord injury. CLIN NEUROPHYSIOL. not undergo epilepsy surgery. SEIZURE- time Sleepiness in Multiple System 122:1183-1189. I.F.: 2.79. EUR J EPILEP. 20:580-582. I.F.: 1.65.

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original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 67.12 19 11 3 19 Marinas A, Elices E, Gil-Nagel 26 Castany M, Jordi I, Catala J, Gual A, Salas-Puig J, Sanchez JC, Carreno A, Morales M, Gasull X, Pintor J. Glau- 2010 107.69 20 10 6 M, Villanueva V, Rosendo J, Porcel J, coma patients present increased levels 2011 128.70 26 12 7 Serratosa JM. Socio-occupational and of diadenosine tetraphosphate, Ap(4)A, employment profile of patients with in the aqueous humour. EXP EYE RES. epilepsy. EPILEPSY BEHAV. 21:223- 92(3):221-6. I.F.: 2.82 227. I.F.: 1.99. Sponsored by: Generalitat de Catalunya, 20 Cortes M, Thickbroom GW, ReViewS SGR09_869. Duration: 01/01/2009- Valls-Sole J, Pascual-Leone A, Ed- i.f.: 4.96 31/12/2013. wards DJ. Spinal associative stimulation: A non-invasive stimulation 1 Valls-Sole J, Castillo CD, Casanova- Valls J. Intervencions sobre els com- paradigm to modulate spinal excitabil- Molla J, Costa J. Clinical conse- ponents sensorial i emocional de ity. CLIN NEUROPHYSIOL. 122:2254- quences of reinnervation disorders les respostes a estímuls de dolor en 2259. I.F.: 2.79. after focal peripheral nerve lesions. pacients amb dolor neuropàtic crònic CLIN NEUROPHYSIOL. 122:219-228. (Interventions on emotional responses 21 Leon L, Casanova-Molla J, Lau- I.F.: 2.79. to pain stimuli in patients with chronic ria G, Valls-Sole J. The somatosen- neuropathic pain). Sponsored by: Funda- sory blink reflex in upper and lower 2 Iranzo A. Sleep-wake changes in ció La Marató de TV3, 071930. Duration: brainstem lesions. MUSCLE NERVE. the premotor stage of Parkinson dis- 25/02/2008-24/05/2011. 43:196-202. I.F.: 2.30. ease. J NEUROL SCI. 310:283-285. I.F.: 2.17. Gasull X. Desarrollo de un proyecto 22 Rubi S, Setoain X, Donaire A, Bar- llamado “Soluciones innovadoras para gallo N, Sanmarti F, Carreno M, Rumia acelerar la identificación y desarrollo de J, Calvo A, Aparicio J, Campistol J, Pons GRAntS foR ReSeARcH fármacos para patologías del Sistema F. Validation of FDG-PET/MRI coregistra- in pRoGReSS Nervioso. Sponsored by: Ministerio tion in nonlesional refractory childhood de Economía y Competitividad, CE- epilepsy. EPILEPSIA. 52:2216-2224. Valls J. Mecanismos fisiopatológicos NIT10 10/158. Duration: 01/01/2011- I.F.: 3.96. en la cronificación del dolor neuropático 31/12/2012. y en el origen del síndrome regional 23 Tulleuda A, Cokic B, Callejo G, complejo. Sponsored by: Instituto de Gasull X. Inflamación y dolor ocular: Saiani B, Serra J, Gasull X. TRESK chan- Salud Carlos III, PI080266. Duration: implicación de los canales ASIC nel contribution to nociceptive sensory 31/12/2008-30/12/2011. (acid-sensing ion channels) como neurons excitability: modulation by dianas farmacológicas. Sponsored by: nerve injury. MOL PAIN. 7:30. I.F.: 4.15. Gual A. Patologia ocular del envejeci- Ministerio de Ciencia e Innovación, miento, calidad visual y calidad de vida. PI11/01601. Duration: 31/12/2011- 24 Deval E, Noël J, Gasull X, De- Redes temáticas de centros (RETIC). 31/12/2014. launay A, Alloui A, Friend V, Eschalier Sponsored by: Ministerio de Sanidad y A, Lazdunski M, Lingueglia E. Acid- Consumo, RD07/0062/0006. Duration: Gasull X. Nous compostos pel trac- sensing ion channels in postoperative 01/01/2007-31/12/2012. tament de Glaucoma. Sponsored pain. J NEUROSCI. 31(16):6059-66. by: Generalitat de Catalunya (Centre I.F.: 7.27 Gasull X. El canal de leak TRESK en d’Innovació i Desenvolupament Em- la excitabilidad neuronal nociceptiva: presarial CIDEM), VALTEC09-1-0008. 25 Cuesto G, Enriquez-Barreto L, implicaciones en el dolor neuropático. Duration: 01/01/2009-31/12/2011. Caramés C, Cantarero M, Gasull X, Sponsored by: FIS, Ministerio de Sani- Sandi C, Ferrús A, Acebes Á, Morales dad y Consumo, PI080014. Duration: Valls J. Neurofisiologia del dolor, epi- M. Phosphoinositide-3-kinase activa- 01/01/2009-31/12/2011. lèpsia, son i control motor (NEDESC). tion controls synaptogenesis and Sponsored by: Generalitat de Catalu- spinogenesis in hippocampal neurons. Gual A. Lab. Neurofisiologia. Grup nya - AGAUR, SGR09_1253. Duration: J NEUROSCI. 31(8):2721-33. I.F.: 7.27 consolidat Generalitat de Catalunya. 15/09/2009-31/12/2013.

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Team involved in: Clinical and experimental neuroscience & Secondary lesions due to chronic alcohol ingestion, muscle pathology gROUP MeMBeRS StrateGic oBjectiveS

1. Study of the pathological mecha- teAM leADeR nisms of alcohol upon the organ cells Álvaro urbano Márquez and its pathological effects at neuro- (Hospital clínic) logical and cardiocirculatory level. tel.: 93 227 55 39 2. Importance of alcohol in intracyto- fax: 93 227 55 39 solic calcium transport. e-mail: [email protected] 3. Effect of food upon the prevention of chronic diseases and cancer. iDiBApS MeMBeRS: Marco Alba (Hospital clinic) 4. Prognosis of alcoholic myocardio- francesc cardellach (Hospital clínic) itziar tavera (Hospital clinic) pathy and its best management Ramón estruch (Hospital clínic) Sarai córdoba (MSc) options. Joaquin fernández (Hospital clínic) Marc catalán (fundació cellex) 5. Study of muscle and myocardial Josep M. Grau (Hospital clínic) francesc Borrisser (MSc) apoptosis in subjects presenting ferran Masanes (Hospital clínic) Maria Boto (fpu-Micinn) chronic alcohol abuse. José Maria nicolás (Hospital clínic) Ana lucia castillo 6. Study of the physiopathology of emilio Sacanella (Hospital clínic) (fellows from Mexico) muscle diseases, particularly as re- irene Roth (MSc) gards the muscle immunohistoche- poStDoctoRAl fellowS: mical, immunogenetic and angioge- Glòria Garrabou (ciBeReR) tecHniciAnS: nic changes (prognostic factors) in Mireia urpí (Sara Borrell-Micinn) esther tobias (pAS uB) inflammatory myopathies. Sara Arranz (Sara Borrell-Micinn) Mireia nicolàs (ciBeReR) 7. Study of metabolic myopathic Mercedes Morales (Marató tV3) disorders, particularly relating to ReSeARcH fellowS: glycogenosis and myoadenylate Rosas casas (pReDiMeD) nuRSinG StAff: deaminase deficiency. Ana García Martínez (SAf08) laia de lama (pReDiMeD) 8. Study of myocardial regeneration in constanza Morén (ciBeReR-fipSe) alcoholic myocardiopathy. Georgina espígol (postMiR iSciii) DietiStS: 9. Clinical and functional repercus- Marc corbera (Marató tV3) concha Viñas (pReDiMeD) sions of chronic fatigue syndrome. Sergio prieto (SAf08) 10. Study of the moderate consump- ester planas (SAf08) collABoRAtoRS: tion of wine and the Mediterranean Anna Sandra Hernàndez (Hospital clínic) emilia Antunez (facultat de diet in the prevention of cardiovas- Jordi casanova (postMiR iSciii) Medicina) cular diseases. Gemma chiva (MSc) Xavier Bosch (Hospital clínic) 11. Study of primary mitochondrial palmira Valderas (Apif - uB) edwin Saúl Romero (cnic) myopathic disorders in the adult and of secondary mitochondrial involvement in different pathological and toxic situations. 12. Study of the physiopathological mechanisms involved in the development of systemic vasculitis.

our future challenges are: 1. Furthering of knowledge of the action of alcohol upon signals translation and the appearance of apoptosis at muscle and myocardial level, and of the impact that alterations

216 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience SeconDARy leSionS Due to cHRonic AlcoHol inGeStion, MuScle pAtHoloGy

in mitochondrial DNA and in the mitochondrial respiratory chain may have upon degenerative diseases such as Alzheimer’s disease, inflammatory myopathy and inclusion body diseases. 2. Furthering of knowledge of the prognostic factors in dermatomyositis, with a view to allowing early identification of those cases requiring stronger treatment measures (anti-TNF agents, gammaglobulins). 3. Characterization of the clinical and Gomori trichromic staining of a muscle fibre in a patient with HIV infection morphological aspects of metabolic showing mitochondrial toxicity due to antiretroviral treatment with zidovudine (AZT). The white arrows indicate the presence of so-called ragged-red fibres, muscle diseases (glycogenosis and suggestive of toxic myopathy. MDA deficiency). 4. Study of sarcopenia in the geriatric population. drial disorders of genetic (primary) 3. Development of a questionnaire for 5. In-depth investigation of the mito- or toxic (secondary) origin. evaluating quality of life in patients chondrial toxicity of antiretroviral 3. Study of mitochondrial diseases, with giant cell arteritis (international drugs and carbon monoxide (CO). with special emphasis on bioche- study). 6. Evaluation of the involvement of mical and genetic investigations in 4. Expression of angiogenic and an- mitochondrias in disorders such as different cell substrates. tiangiogenic factors as prognostic Parkinson’s disease, reduced intrau- 4. Analysis of mitochondrial respira- data in dermatomyositis. terine fetal growth or sepsis. tion and DNA in muscle, adipose 7. Proteomic studies to clarify the tissue and lymphocytes of HIV- III Prevention and treatment of car- mechanisms of skeletal and cardiac infected patients subjected to anti- diovascular diseases: muscle damage secondary to alco- retroviral therapy. 1. Research is being carried out into hol exposure. 5. Effect of smoking, carbon mo- the relationship between alcohol and 8. Study of myocardial cell regenera- noxide, neuroleptic drugs and arterial hypertension; the evolution tion from stem cells in the myocar- antibiotics upon the mitochondrial of alcoholic myocardiopathy, the role dium of chronic alcoholic patients. function. of phenolic derivatives in wine, beer 9. Study of serum and urine biomarkers 6. Mitochondrial dysfunction in and alcohol as influencing factors in in relation to food consumption and Parkinson’s disease, reduced intrau- the development of atherosclerosis; changes in cardiovascular disease terine fetal growth and sepsis. the effect of nicotine and aging risk factors. upon mitochondrial respiration; and 10. In-depth study of the mechanisms II Vascular inflammation: the presence of growth factors and involved in the development of sys- 1. Expressions of cytokines and adhesion molecules in angiogenesis, temic vasculitis. growth factors in vascular inflam- apoptosis, myocardiopathy and alco- matory lesions and their relation- holic myopathy. main lineS ship with phenotypic expression, 2. Study of the effects of moderate wine of reSearcH complications and the prognosis of consumption, the Mediterranean diet systemic vasculitis. and other polyphenol-rich products I Research Group in Muscle and Mi- 2. Study of the interactions among such as tomatoes in the primary pre- tochondrial Function: lymphocytes, endothelium and vention of cardiovascular disease and 1. Histological, histochemical and im- extracellular matrix in the develop- other degenerative disorders. munohistochemical study of mus- ment and perpetuation of vascular 3. Proteomic studies of skeletal and cle diseases. inflammation and in the mecha- cardiac muscle in relation to the 2. Study of mitochondrial function in nisms that participate in vascular pathogenesis of tissue damage se- patients susceptible to mitochon- occlusion and regeneration. condary to alcohol exposure.

217 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Secondary lesions due to chronic alcohol ingestion, muscle pathology PUBLICATIONS

oRiGinAlS E, Lahoz C, Serra-Majem L, Pinto X, 11 Salas-Salvado J, Bullo M, Babio i.f.: 111.22 Ruiz-Gutierrez V, Covas MI. A Short N, Martinez-Gonzalez MA, Ibarrola-Ju- Screener Is Valid for Assessing Me- rado N, Basora J, Estruch R, Covas MI, 1 Prieto-Gonzalez S, Cardellach F, diterranean Diet Adherence among Corella D, Aros F, Ruiz-Gutierrez V, Ros Estruch R, Miguel R, Grau JM, Cid Older Spanish Men and Women. J E. Reduction in the Incidence of Type MC. Type 1 autoimmune hepatitis in NUTR. 141:1140-1145. I.F.: 4.30. 2 Diabetes With the Mediterranean a patient with microscopic polyan- Diet Results of the PREDIMED-Reus giitis: challenges in diagnosis and 7 Bullo M, Garcia-Aloy M, Martinez- nutrition intervention randomized trial. treatment. MED CLIN-BARCELONA. Gonzalez MA, Corella D, Fernandez- DIABETES CARE. 34:14-19. I.F.: 7.14. 136:345-348. I.F.: 1.41. Ballart JD, Fiol M, Gomez-Gracia E, Estruch R, Ortega-Calvo M, Francisco 12 Medina-Remon A, Zamora-Ros 2 Garrabou G, Lopez S, Moren C, S, Flores-Mateo G, Serra-Majem L, R, Rotches-Ribalta M, Andres-Lacueva Martinez E, Fontdevila J, Cardellach Pinto X, Covas MI, Ros E, Lamuela- C, Martinez-Gonzalez MA, Covas MI, F, Gatell JM, Miro O. Mitochondrial Raventos R, Salas-Salvado J. Associa- Corella D, Salas-Salvado J, Gomez- damage in adipose tissue of untrea- tion between a healthy lifestyle and Gracia E, Ruiz-Gutierrez V, DeLaCorte ted HIV-infected patients. AIDS. general obesity and abdominal obesity FJG, Fiol M, Pena MA, Saez GT, Ros 25:165-170. I.F.: 6.35. in an elderly population at high cardio- E, Serra-Majem L, Pinto X, Warnberg vascular risk. PREV MED. 53:155-161. J, Estruch R, Lamuela-Raventos RM. 3 Moren C, Noguera-Julian A, I.F.: 3.30. Total polyphenol excretion and blood Rovira N, Garrabou G, Nicolas M, pressure in subjects at high cardiovas- Cardellach F, Martinez E, Sanchez 8 Murie-Fernandez M, Irimia P, Tole- cular risk. NUTR METAB CARDIOVAS. E, Miro O, Fortuny C. Mitochon- do E, Martinez-Vila E, Buil-Cosiales P, 21:323-331. I.F.: 3.44. drial assessment in asymptomatic Serrano-Martinez M, Ruiz-Gutierrez V, HIV-infected paediatric patients on Ros E, Estruch R, Martinez-Gonzalez 13 Estruch R, Sacanella E, Mota F, HAART. ANTIVIR THER. 16:719-724. MA. Carotid intima-media thickness Chiva-Blanch G, Antuneza E, Casals E, I.F.: 3.77. changes with Mediterranean diet: A Deulofeu R, Rotilio D, Andres-Lacueva randomized trial (PREDIMED-Navarra). C, Lamuela-Raventos RM, DeGaeta- 4 Moren C, Noguera-Julian A, ATHEROSCLEROSIS. 219:158-162. no G, Urbano-Marquez A. Moderate Rovira N, Corrales E, Garrabou G, I.F.: 4.09. consumption of red wine, but not gin, Hernandez S, Nicolas M, Tobias E, decreases erythrocyte superoxide dis- Cardellach F, Miro O, Fortuny C. Mi- 9 Sala-Vila A, Harris WS, Cofan M, mutase activity: A randomised cross- tochondrial impact of human imnu- Perez-Heras AM, Pinto X, Lamuela- over trial. NUTR METAB CARDIOVAS. nodeficiency virus and antiretrovirals Raventos RM, Covas MI, Estruch R, 21:46-53. I.F.: 3.44. on infected pediatric patients with or Ros E. Determinants of the omega-3 without lipodystrophy. PEDIATR IN- index in a Mediterranean population at 14 Lluis M, Fernandez-Sola J, FECT DIS J. 30:992-995. I.F.: 3.06. increased risk for CHD. BRIT J NUTR. Castellvi-Bel S, Sacanella E, Estruch 106:425-431. I.F.: 3.07. R, Urbano-Marquez A. Evaluation of 5 Garrabou G, Inoriza JM, Moren C, Myocyte Proliferation in Alcoholic Oliu G, Miro O, Marti MJ, Cardellach 10 Sola R, Fito M, Estruch R, Salas- Cardiomyopathy: Telomerase Enzyme F. Mitochondrial Injury in Human Salvado J, Corella D, DeLaTorre R, Activity (TERT) Compared with Ki-67 Acute Carbon Monoxide Poisoning: Munoz MA, Lopez-Sabater MD, Marti- Expression. ALCOHOL ALCOHOLISM. The Effect of Oxygen Treatment. J nez-Gonzalez MA, Aros F, Ruiz-Gutie- 46:534-541. I.F.: 2.60. ENVIRON SCI HEAL C. 29:32-51. rrez V, Fiol M, Casals E, Warnberg J, I.F.: 4.84. Buil-Cosiales P, Ros E, Konstantinidou 15 Villegas E, Estruch R, Mengod G, V, Lapetra J, Serra-Majem L, Covas MI. Cortes R. NMDA receptors in frontal 6 Schroder H, Fito M, Estruch R, Effect of a traditional Mediterranean cortex and hippocampus of alcohol Martinez-Gonzalez MA, Corella D, diet on apolipoproteins B, A-I, and their consumers. ADDICT BIOL. 16:163- Salas-Salvado J, Lamuela-Raventos ratio: A randomized, controlled trial. 165. I.F.: 4.15. R, Ros E, Salaverria I, Fiol M, La- ATHEROSCLEROSIS. 218:174-180. petra J, Vinyoles E, Gomez-Gracia I.F.: 4.09.

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original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 119.15 23 16 6 16 Casanova-Molla J, Morales M, 22 Cobo E, Cortes J, Ribera JM, Sola-Valls N, Bosch A, Calvo M, Grau- Cardellach F, Selva-O’callaghan A, 2010 65.52 17 9 6 Junyent JM, Valls-Sole J. Axonal fluo- Kostov B, Garcia L, Cirugeda L, Altman 2011 111.22 27 9 6 rescence quantitation provides a new DG, Gonzalez JA, Sanchez JA, Miras F, approach to assess cutaneous inner- Urrutia A, Fonollosa V, Rey-Joly C, Vi- vation. J NEUROSCI METH. 200:190- lardell M. Effect of using reporting gui- 198. I.F.: 2.10. delines during peer review on quality of final manuscripts submitted to a bio- 17 Casanova-Molla J, Grau-Junyent medical journal: masked randomised JM, Morales M, Valls-Sole J. On the trial. BRIT MED J. 343:-. I.F.: 13.47. 27 Sanchez-Villegas A, Galbete C, relationship between nociceptive Martinez-Gonzalez MA, Martinez JA, evoked potentials and intraepidermal 23 Sacanella E, Perez-Castejon JM, Razquin C, Salas-Salvado J, Estruch R, nerve fiber density in painful sensory Nicolas JM, Masanes F, Navarro M, Buil-Cosiales P, Marti A. The effect of polyneuropathies. PAIN. 152:410-418. Castro P, Lopez-Soto A. Functional the Mediterranean diet on plasma bra- I.F.: 5.36. status and quality of life 12 months in-derived neurotrophic factor (BDNF) after discharge from a medical ICU in levels: The PREDIMED-NAVARRA 18 Prieto-Gonzalez S, Escoda R, Co- healthy elderly patients: a prospective randomized trial. NUTR NEUROSCI. loma E, Grau JM. Amoxicillin-induced observational study. CRIT CARE. 15:-. 14:195-201. I.F.: 1.30. acute aseptic meningitis. J CLIN NEU- I.F.: 4.60. ROSCI. 18:443-444. I.F.: 1.17. 24 Nunez M, Fernandez-Sola J, Nu- eDitoRiAlS 19 Corella D, Tai ES, Sorli JV, Chew nez E, Fernandez-Huerta JM, Godas- i.f.: 0.76 SK, Coltell O, Sotos-Prieto M, Garcia- Sieso T, Gomez-Gil E. Health-related Rios A, Estruch R, Ordovas JM. Asso- quality of life in patients with chronic 1 Fernandez-Sola J. Chronic fatigue ciation between the APOA2 promoter fatigue syndrome: group cognitive be- syndrome: current situation. REV CLIN polymorphism and body weight in havioural therapy and graded exercise ESP. 211:407-409. I.F.:0.76. Mediterranean and Asian populations: versus usual treatment. A randomised replication of a gene-saturated fat in- controlled trial with 1 year of follow- teraction. INT J OBESITY. 35:666-675. up. CLIN RHEUMATOL. 30:381-389. clinicAl GuiDelineS I.F.: 5.13. I.F.: 1.69. i.f.: 1.41

20 Chiva-Blanch G, Urpi-Sarda M, 25 Fernandez-Sola J, Lluis M, 1 Alobid I, Alonso JR, Barrot C, Beni- Rotches-Ribalta M, Zamora-Ros R, Sacanella E, Estruch R, Antunez E, tez P, Canizares S, Castanyer T, Cente- Llorach R, Lamuela-Raventos RM, Es- Urbano-Marquez A. Increased Myos- llas S, Civeira E, Climent B, Duenas A, truch R, Andres-Lacueva C. Determi- tatin Activity and Decreased Myocyte Fernandez-Sola J, Ferrer A, Gene M, nation of resveratrol and piceid in beer Proliferation in Chronic Alcoholic Car- Godas T, Gomez E, Montori E, Munne matrices by solid-phase extraction and diomyopathy. ALCOHOL CLIN EXP P, Nogue S, Picado C, Rovira E, Sanz P, liquid chromatography-tandem mass RES. 35:1220-1229. I.F.: 3.47. Valero A. Multiple chemical sensitivity. spectrometry. J CHROMATOGR A. MED CLIN-BARCELONA. 136:683-687. 1218:698-705. I.F.: 4.19. 26 Nordmann AJ, Suter-Zimmer- I.F.: 1.41. mann K, Bucher HC, Shai I, Tuttle KR, 21 Bullo M, Estruch R, Salas- Estruch R, Briel M. Meta-Analysis Salvado J. Dietary vitamin K intake Comparing Mediterranean to Low-Fat is associated with bone quantitative Diets for Modification of Cardiovascu- ultrasound measurements but not with lar Risk Factors. AM J MED. 124:841- bone peripheral biochemical markers U100. I.F.: 5.12. in elderly men and women. BONE. 48:1313-1318. I.F.: 4.60.

219 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Secondary lesions due to chronic alcohol ingestion, muscle pathology

GRAntS foR ReSeARcH Grau J. Grup de Recerca Muscular. in pRoGReSS Sponsored by: Generalitat de Catalun- ya - AGAUR, 2009_SGR_1158. Dura- Urbano A. Identification and Vali- tion: 23/09/2009-31/12/2013. dation of Alcohol Biomarker Sig- natures by Proteomics. (Subaward Sacanella E. Evaluación del efecto nº 080-04000-R82301). Sponsored antihipertensivo y antiinflamatorio de by: Thomas Jefferson University, los polifenoles, carotenos y vitamina NIH06 5 R01 AA016210. Duration: C del tomate, según la ración dietética 15/05/2006-30/04/2011. ingerida. Sponsored by: Ministerio de Ciencia e Innovación, AGL2010- Estruch R. Alimentación saludable 22319-C03-02. Duration: 01/01/2011- en la prevención primaria de enfer- 31/12/2013. medades crónicas: la Red PREDI- MED. Sponsored by: Instituto de Estruch R. Efectos de la dieta medite- Salud Carlos III, RD06/0045/1003. rránea sobre la carga arteriosclerótica Duration: 29/02/2008-31/12/2011. medida mediante técnicas de imagen y biomarcadores vasculares. Sponsored Estruch R. Effects of a medite- by: MAPFRE, MAPFRE10_004. Dura- rranean diet intervention on athe- tion: 16/02/2011-13/04/2012. rosclerotic burden measured by imaging techniques and systemic biomarkers. PREDIMED. (Effects of DoctoRAl tHeSeS a 2-year Mediterranean diet intervention on 3T MRI-monitored carotid Fernandez-Sola J. Estudi de la regene- plaque progression and vulnerabili- ració miocàrdica en la miocardiopatia ty). Sponsored by: Centro Nacional alcohòlica i la seva relació amb el dany de Investigaciones Cardiovasculares funcional i estructural miocàrdic, acti- (CNIC), 06-2007-S01. Duration: vació d’apoptosi i activitat miostatina. 01/01/2008-31/12/2011. PhD student: Meritxell Lluis Padierna.

Cardellach F, Coll JO, Hernandez AS, Garrabou G, Morén C. Toxicidad mitocondrial inducida por el consumo de tabaco en gestantes y sus recién nacidos. Sponsored by: FIS ISCIII, PI080229. Duration: 01/01/2009- 31/12/2011.

Estruch R, Sacanella E, Masa- nes F, Chiva G, Casas R, Urpi M. Desarrollo de biomarcadores de consumo y de efecto de un patrón de alimentación Mediterranea en la prevención de la enfermedad cardiovascular. Una aproximación metabolómica. Sponsored by: Mi- nisterio de Ciencia e Innovación, AGL2009-13906-C02-02. Duration: 01/01/2010-31/12/2012.

220 AReA 4

Clinical and experimental neuroscience Team involved in: & Cellular biology of pathological processes gROUP MeMBeRS

teAM leADeR Jordi Alberch (universitat de Barcelona) tel.: 93 403 52 85 fax: 93 402 19 07 e-mail: [email protected]

iDiBApS MeMBeRS: Adrià Sicart (uB) Josep M. canals (uB) Marta Anglada (fpi, uB) Gustavo egea (uB) Andreas Mezger (ple2009, uB) esther pérez (uB) Mónica pardo (ple2009, uB) Silvia Ginés (uB) carla Serra (fpi, uB) Marta cherubini (ciBeRneD) poStDoctoRAl fellowS: Gerardo García (uB) Albert Giralt (uB) Shiraz tyebji (fpi, uB) Miriam esgleas (ReticS, iDiBApS) Ana Saavedra (Juan de la cierva, uB) tecHniciAnS: Verónica Brito (cHDi foundation) cristina Herranz (ReticS, iDiBApS) Javier Selva (uB) Ana lópez (ciBeRneD) Maite Muñoz (uB) ReSeARcH fellowS: Josep Barrachina (uB) olga carretón (uB) laura Rué (uB) collABoRAtoRS: laia Salcedo (fpi, uB) Raquel Martín-ibáñez (ciBeRneD-uB) enrique Gutiérrez (fpu, uB) Bet Sarri (uB) Mar puigdellívol (cHDi foundation) Xavier Xifro (uG)

221 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Cellular biology of pathological processes

StrateGic main lineS oBjectiveS of reSearcH

1. Study of the cellular and mole- 1. Study of the implication of neuro- cular bases involved in neuronal trophic factors in the physiopatho- dysfunction and death associated logy and treatment of neurode- with basal ganglia neurodegenerative diseases of the basal generative disorders, mainly ganglia. Huntington’s disease. Our aim is 2. Study of the intracellular signa- to identify intracellular pathways – ling cascades implicated in the both neuroprotective and apopto- degeneration of striatal and hippo- tic – that are selectively altered in campal neurons in Huntington’s the affected neuron populations, disease. with the ultimate purpose of iden- 3. Study of the mechanisms un- tifying new therapeutic targets in derlying the differentiation of stem the management of these neuro- cells into neurons, for application Diolistic labeling (red) of hipocampal neuronal cells from HD mouse models. Nucleus are shown by DAPI staining (blue). degenerative diseases. to cellular therapy in neurode- Author: Verónica Brito. 2. Identification of the mechanisms generative diseases such as participating in the cognitive Huntington’s chorea. defects seen in Huntington’s di- 4. Characterization of extrinsic fac- sease. Knowledge of these me- tors and new transcription factors vesicles and in the structural organi- chanisms will make it possible of the development of human and zation of the Golgi apparatus. to develop new treatments for mouse nucleus striatum. 7. Study of the signaling pathways avoiding the cognitive disorders 5. Molecular bases of the interaction that regulate the cytoskeleton and induced by the mutated hunting- of actin dynamics with the Golgi actin dynamics, altered by ethanol tin gene. apparatus and secretory traffic. and other toxic agents. 3. Characterization of the mecha- 6. Role of diacylglycerol and phosphati- 8. Intracellular traffic and cytokine nisms of neuron differentiation dic acid in the formation of transport receptor signaling (TGF-beta). of stem cells from different organs. Our aim is to identify different extrinsic and intrinsic factors contributing to neuron differentiation, with the aim ReSeARCh gROUP of employing stem cells in cell memBrane traffic substitution therapies against neurodegenerative diseases. Group Leader: Gustavo Egea (UB) 4. Exploration of the molecular mechanisms involved in the interac- The objective of this group is to understand the principles that tion of the cytoskeleton with the control and regulate transport of the membrane components cell endomembrane system as (lipids and proteins) within the cell. In particular, we are investi- structural and functional support gating the interaction of the transport intermediaries (vesicles in secretory and endocytic mem- and tubules) with the actin cytoskeleton and its associated proteins and regula- brane traffic. Studies are also tors (myosins and Rho GTPases). We are also exploring the way in which lipid made of the way in which this homeostasis (particularly referred to diacylglycerol) participates in the organiza- interaction is altered in certain tion and traffic of membranes and in the formation of transport intermediaries. diseases such as alcoholism and Lastly, we wish to establish the physiopathological bases whereby ethanol alters other conditions with a strong nerve cell function and the mechanism underlying internalization of the receptors cardiovascular base such as Mar- of cytokines such as TGF-beta in the smooth muscle cells of the coronary ves- fan syndrome and Loeys-Dietz sels in cardiovascular patients. syndrome.

222 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience cellulAR BioloGy of pAtHoloGicAl pRoceSSeS

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 24.17 5 3 2 oRiGinAlS Marsicano G, Monory K, Lutz B, Romero i.f.: 74.18 J, Alberch J, Gines S, Kraus J, Fernandez- 2010 65.35 11 10 1 Ruiz J, Galve-Roperh I, Guzman M. Loss 2011 74.18 12 9 0 1 Rocha RA, Gimeno-Alcaniz JV, of striatal type 1 cannabinoid receptors is Martin-Ibanez R, Canals JM, Velez D, a key pathogenic factor in Huntington›s Devesa V. Arsenic and fluoride induce disease. BRAIN. 134:119-136. I.F.: 9.23. neural progenitor cell apoptosis. TOXI- COL LETT. 203:237-244. I.F.: 3.58. 8 Almajano MP, Vila I, Gines S. GRAntS foR ReSeARcH Neuroprotective Effects of White Tea in pRoGReSS 2 Sanchez-Gomez MV, Alberdi E, Against Oxidative Stress-Induced Toxi- Perez-Navarro E, Alberch J, Matute C. city in Striatal Cells. NEUROTOX RES. Canals JM. Red de Terapia Celular. Spon- Bax and calpain mediate excitotoxic 20:372-378. I.F.: 3.02. sored by: Ministerio Sanidad y Consumo, oligodendrocyte death induced by RD06/0010/0006. Duration: 01/01/2007- activation of both AMPA and kainate 9 Sarri E, Sicart A, Lazaro-Dieguez F, 31/12/2012. receptors. J NEUROSCI. 31:2996- Egea G. Phospholipid synthesis partici- 2300. I.F.: 7.27. pates in the regulation of diacylglycerol Alberch J. Generación de nuevos modelos required for membrane trafficking at the de enfermedad de Huntington para valorar 3 Giralt A, Carreton O, Lao-Peregrin Golgi complex. J BIOL CHEM. 286:28632- el papel del BDNF en los mecanismos C, Martin ED, Alberch J. Conditional 28643. I.F.: 5.33. patogénicos y en nuevas perspectivas BDNF release under pathological con- terapéuticas. Sponsored by: Ministerio de ditions improves Huntington’s disease 10 Saavedra A, Giralt A, Ruee L, Ciencia e Innovación (MICINN), SAF2008- pathology by delaying neuronal dys- Xifro X, Xu J, Ortega Z, Lucas JJ, Lom- 04360. Duration: 01/01/2009-31/12/2011. function. MOL NEURODEGENER. 6:-. broso PJ, Alberch J, Perez-Navarro I.F.: 5.36. E. Striatal-enriched protein tyrosine Alberch J. Habilitación de salas GMP para phosphatase expression and activity el programa de terapia celular de la Fa- 4 Selva J, Egea G. Ethanol increases in Huntington’s disease: a STEP in the cultat de Medicina. Sponsored by: Minis- p190RhoGAP activity, leading to actin resistance to excitotoxicity. J NEU- terio de Ciencia e Innovación (MICINN), cytoskeleton rearrangements. J NEU- ROSCI. 31:8150-8162. I.F.: 7.27. PLE2009-0128. Duration: 01/11/2009- ROCHEM. 119:1306-1316. I.F.: 4.34. 31/10/2012. 11 Bosch M, Mari M, Herms A, 5 Xifro X, Anglada-Huguet M, Rue L, Fernandez A, Fajardo A, Kassan A, Canals JM. Mejora de la supervivencia Saavedra A, Perez-Navarro E, Alberch J. Giralt A, Colell A, Balgoma D, Barbero y diferenciación de células madre neu- Increased 90-kDa ribosomal S6 kinase E, Gonzalez-Moreno E, Matias N, rales humanas para terapia celular de la (Rsk) activity is protective against mu- Tebar F, Balsinde J, Camps M, Enrich enfermedad de Huntington. Sponsored tant huntingtin toxicity. MOL NEURO- C, Gross SP, Garcia-Ruiz C, Perez- by: Ministerio de Ciencia e Innovación DEGENER. 6:-. I.F.: 5.36. Navarro E, Fernandez-Checa JC, Pol (MICINN), PLE2009-0089. Duration: A. Caveolin-1 Deficiency Causes 01/11/2009-31/10/2012. 6 Giralt A, Saavedra A, Carreton O, Cholesterol-Dependent Mitochondrial Xifro X, Alberch J, Perez-Navarro E. Dysfunction and Apoptotic Gines S. Role of p75 Neurotrophin Increased PKA signaling disrupts re- Susceptibility. CURR BIOL. 21:681- Receptor in Huntington’s Disease. Spon- cognition memory and spatial memory: 686. I.F.: 10.03. sored by: HIGH Q FOUNDATION - INC role in Huntington’s disease. HUM -OFICIAL, A-3468. Duration: 01/05/2010- MOL GENET. 20:4232-4247. I.F.: 8.06. 30/04/2012. 12 Smith SE, Granell S, Salcedo- 7 Blazquez C, Chiarlone A, Sagredo Sicilia L, Baldini G, Egea G, Teckman JH Gines S. Role of Cdk5 in Striatal and O, Aguado T, Pazos MR, Resel E, Pa- and Baldini G. ATF6 limits intracellular Hippocamapl Pathology in Hunting- lazuelos J, Julien B, Salazar M, Borner accumulation of mutant alpha-1-anti- tons Disease. Sponsored by: HIGH C, Benito C, Carrasco C, Diez-Zaera M, trypsin Z and mitochondrial damage Q FOUNDATION - INC -OFICIAL, Paoletti P, Diaz-Hernandez M, Ruiz C, in hepatoma cells. J BIOL CHEM. A-3880. Duration: 01/11/2010- Sendtner M, Lucas JJ, DeYebenes JG, 286:41563-41577. I.F.: 5.33 31/10/2012.

223 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Cellular biology of pathological processes

Egea G. Red Nacional sobre In- Alberch J. Fisiopatología de las enfer- tegración funcional del tráfico medades neurodegenerativas. Spon- de membranas, la señalización sored by: Generalitat de Catalunya, intracelular y la dinámica del citoes- SGR2009-00326. Duration: 01/01/2009- queleto. Sponsored by: Ministerio 31/12/2013. de Ciencia e Innovación (MICINN), BFU2008-03958-E/BMC. Duration: Canals JM. Terapia Celular: Implicación 01/11/2009-30/12/2012. de células madre adultas. Sponsored by: CMRB-Generalitat de Catalunya, Egea G. La dinámica de la actina y PROMT-0901. Duration: 01/01/2010- la homeostasis del diacilglicerol en 31/12/2012. la organización del aparato de Golgi. Sponsored by: Ministerio de Ciencia Perez E. Regulación de la vía PKA como e Innovación (MICINN), BFU2009- estrategia terapéutica para la enfermedad 07186(BMC). Duration: 01/01/2009- de Huntington. Sponsored by: Fondo 31/12/2012. de Investigaciones Sanitarias, Instituto de Salud Carlos III, Ministerio de Cien- Egea G. Nanotecnologías en Bio- cia e Innovación, PI10/0172. Duration: medicina (NanoBiomed). Sponsored 10/12/2010-10/12/2013. by: Ministerio de Ciencia e Innova- ción (MICINN), Programa Conso- lider, CSD2006-00012 . Duration: DoctoRAl tHeSeS 01/01/2006-14/09/2011. Alberch J. Estudio de la alteración de Gines S. Estudio de las cascadas de las vias de señalización implicadas en la señalización asociadas a la activación disfunción neuronal en la enfermedad de dopaminérgica y glutamatérgica Huntington: Evaluación de su aplicación como estrategia terapéutica en mo- como terapia preventiva de las deficien- delos murinos de la enfermedad de cias cognitivas. PhD student: Olga Carre- Huntington: Papel de la vía de Cdk5. tón Gómez. Sponsored by: Ministerio de Ciencia e Innovación, SAF2009-07077. Duration: Egea G. Vías de señalización y potencia- 01/01/2009-31/12/2012. les agentes terapéuticos en un modelo in vitro de síndrome alcohólico fetal. PhD Canals JM. Caracterización de nuevos student: Javier Selva Sánchez. factores de transcripción para la dife- renciación neuronal de células madre para la enfermedad neurodegenerativa de Huntington. Sponsored by: Ministe- rio de Ciencia e Innovación (MICINN), SAF2009-07774. Duration: 01/01/2010- 31/12/2012.

224 AReA 4 Team involved in: Clinical and experimental neuroscience Biological bases of psychiatric disorders and nuclear psychiatry gROUP MeMBeRS

teAM leADeR Miguel Bernardo (Hospital clínic) tel.: 93 227 54 00 (ext 3142) fax: 93 227 55 48 e-mail: [email protected]

iDiBApS MeMBeRS: Josefina castro (Hospital clínic) Rosa catalán (Hospital clínic) cristobal Gastó (Hospital clínic) Antoni Gual (Hospital clínic) fernando Gutierrez (Hospital clínic) Amalia lafuente (tu) luisa lázaro (Hospital clínic) francisco J. lomeña (Hospital clínic) Anabel Martínez-Arán (Hospital clínic) Guillem Masana (Hospital clínic) eduard parellada (Hospital clínic) luis pintor (Hospital clínic) Mercè torra (Hospital clínic) Alicia Valiente (Hospital clínic) collABoRAtoRS: Manuel Valdés (Hospital clínic) claudia cullell (ciBeRSAM) Jordi Blanch (Hospital clínic) eduard Vieta (Hospital clínic) esther Jimenez (iDiBApS) Mercè comes (Hospital clínic) Antonio Benabarre (Hospital clínic) Alessandra nivoli (fundació clínic) Jose Manuel Goikolea Rocío Martín-Santos (Hospital clínic) núria cruz (ciBeRSAM) (Hospital clínic) francesc colom (fundació clínic) Javier Goti (Hospital clínic) ester Gómez (Hospital clínic) lluïsa Garcia (Hospital clínic) Maria teresa plana (Hospital clínic) Joana Guarch (Hospital clínic) inmaculada Baeza (Hospital clínic) Vanessa Sánchez (Hospital clínic) teodoro Marcos (Hospital clínic) Astrid Morer liñán (Hospital clínic) Soledad Romero (Hospital clínic) Sergi Mas Herrero (Associat) Susana Andrés (Hospital clínic) Bibiana cabrera (fundació clínic) Victor navarro (Hospital clínic) Rafel penadés (Hospital clínic) nuria pujol (iDiBApS) Joan de pablo (Hospital clínic) olga puig (Hospital clínic) Maria Reinares (ciBeRSAM) poStDoctoRAl fellowS: M luisa imaz (Hospital clínic) Jose toro (Hospital clínic) patricia Gasso (fundació clínic) Anna torres (Hospital clínic) carla torrent (ciBeRSAM) Rosa calvo (Hospital clinic) Juan undurraga (Hospital clínic) piero castro loli iria Grande (Hospital clínic) (fundació clinic) ReSeARcH fellowS: carolina franco (Hospital clinic) elena de la Serna (ciBeRSAM) tecHniciAnS: Adriane R. Rosa (iDiBApS) caterina del Mar Bonnin (iDiBApS) M Alicia Durán (fundació clínic) cristina V. oliveira José Sánchez-Moreno (ciBeRSAM) Rosa Maria palaus (fundació clínic) (fundació clínic) isabella pachiarotti (ciBeRSAM) pere castellví (ciBeRSAM) Marc Valentí (iDiBApS) nuRSinG StAff: Rosa Díaz (Hospital clínic) clemente Garcia-Rizo (Hospital clínic) Ana Meseguer (ciBeRSAM) enric Buisan (forumclinic) Andrea Murru (fundació clinic) Brisa Solé (iDiBApS) ADMiniStRAtiVe StAff: Miquel Bioque (ciBeRSAM) Anna folch (ciBeRSAM)

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StrateGic relapse in a prospective longitudinal work (Xarxa Catalana de Drogodepen- oBjectiveS follow-up and treatment response dències); Screening instruments and study. We have examined the role of techniques for early detection and short Our group studies serious psychiatric schizophrenia in the development of counselling in alcohol-consumers at risk disorders from the neurobiological and cardiovascular and metabolic diseases, in the hospital setting and in primary therapeutic perspectives, based on and secondarily also the role of antipsy- care; Evaluation and prognosis of alco- the following 6 research lines: bipolar chotic drugs. The pharmacogenetics of holic patients candidates for liver trans- disorders, schizophrenia and depres- antipsychotic drugs has been studied plantation; treatment of smoking in sion-anxiety, pediatric psychiatry and to assess the efficacy and safety of alcoholic patients; and Evaluation of the psychology, psychiatric intervention in these drugs on the basis of the indi- European alcohol policies and their pu- medical pathology and alcoholism. vidual patient genetic characteristics. blic health impact. In 2011 we started Specifically, we have analyzed the phar- a new European project that expands main lineS macogenetics of the extrapyramidal the scope of the Unit towards other of reSearcH effects caused by antipsychotic drug addictive behaviors, keeping the focus therapy, the polymorphisms associa- on public health from an interdiscipli- The bipolar disorders program mainly ted with the risk of schizophrenia, and nary perspective. The project is called investigates the neurobiological and new pharmacogenetic techniques for Alcie Rap (www.alicerap.eu). Finally, anatomofunctional mechanisms im- implantation at healthcare and hospital we must also mention the research on plicated in the development of the level. A psychoeducational program is anticraving drugs, because we have al- disease (genetics, neuromodulators, adopting new knowledge transmission ready completed a trial with Nalmefene hormone factors and neuroimaging) and exchange formulas, with the appli- and about to undergo anorther one with and its relapses, the clinical course and cation of new technologies and offering oxibat with Sodium Oxibate. neuropsychological consequences, rigorous and communicatively ade- the efficacy of drug treatments and quate contents. The FòrumClínic web The line relating to depression aims to novel therapies, and psychological in- (www.forumclinic.org) is an interactive implement new psychopathological and terventions for the early detection and program designed to increase patient biological endophenotypic methods in prevention of recurrences – increasing autonomy in relation to personal health. application to major depression, with treatment compliance and improving A program has been developed for the development of mechanisms for the efficacy of the therapeutic strate- characterizing and preventing second the analysis of the mechanism of action gies applied to bipolar disorder. The psychotic episodes, in order to design of antidepressant drugs based on the strategic objectives are to investigate preventive strategies allowing us to in- platelet model of depression (developed the causes and mechanisms involved fluence the course of the disease. together with the hemostasis group led in the etiopathogenesis of bipolar disor- by Prof. Ginés-Escolar); the investigation der, and to investigate new treatments The Alcohol Unit is the reference in of neurotrophic factors (BDNF) in de- with a view to improving the prognosis Catalonia for the treatment of alcohol pressive patients; and the exploration of of the disease. dependency. We are one of the main factors conditioning the residual symp- research groups in Spain and consoli- toms of major depression. The schizophrenia program focuses dating our European leadership position research on the first schizophrenic in the setting of short interventions The main research lines of the pedia- episodes and on resistant and comor- designed to reduce consumption tric psychiatry and psychology re- bid schizophrenia, through functional among alcohol consumers at risk. This search group of the Hospital Clínic are neuroimaging (brain perfusion and leadership allowed us to coordinate the following: receptors SPECT, PET and functional two FP7 european projects: Amphora • Schizophrenia and bipolar disorder: magnetic resonance imaging). Sensory (www.amphoraproject.net) i Odhin Study and follow-up of the first and cognitive neuroactivation studies (www.odhinproject.eu). A number of psychotic episodes, cognitive reha- have been made with frontal activation research lines are being conducted in bilitation of adolescent patients with neuropsychological tests and dopami- the context of the Alcohol Unit. The schizophrenia, study of children and nergic receptor occupation studies, as main lines are the following: Pros- adolescents with a high genetic risk well as studies of the presynaptic do- pective longitudinal study of alcoholic of developing schizophrenia and bi- paminergic function. Likewise, plasma disease; Follow-up of a cohort of 850 polar disorder (offspring of patients metabolites of dopamine have been patients starting treatment in 1987 in with such disorders), study of the investigated as biological indicators of the Catalan Drug Dependencies Net- prodromic manifestations of psycho-

226 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience BioloGicAl BASeS of pSycHiAtRic DiSoRDeRS AnD nucleAR pSycHiAtRy

tic disorders in children and adolescents, and study of the tolerance and safety of antidepressants in children and adolescents. • Anorexia and bulimia nervosa, and obsessive-compulsive disorder: Study of the common and differential alterations (genetic, neuropsychological and neuroimaging) of anorexia nervosa and obsessive-compulsive disorder, study of new management approaches (psychological and pharmacological) in bulimia and anorexia nervosa, and study of autoimmune alterations in obsessive behavior and in anorexia. • Others: mention should be made of the investigation of addictive behaviors, analyzing the percentages of patients seen in the Department of Pediatric Psychiatry with different disorders and who moreover consu- MRI image of a healthy control of the study; genotype-phenotype me, abuse of or show dependency and environment interaction. Application of a predictive model in first psychotic episodes. of toxic substances – exploring the efficacy of new multimodal management modalities for addictive behavior in adolescents. In addition, the study line of the efficacy and safety of psychoactive drugs in children and attention deficit. Lastly, the research Investigations likewise have been con- adolescents focuses on the evalua- line in autoimmune/Tourette syndro- ducted into personality disorders: the tion and follow-up of the side effects me explores the inflammatory and structure of the diagnostic systems, of these drugs in children and adoles- autoimmune processes, and their their relationship to adjustment to the cents, as well as on the identification relation to serious psychiatric patho- environment and the validation of new of pharmacogenetic predictors of logy, in children and adolescents. models and instruments. drug response in such patients. The study line in autistic spectrum di- The line of psychiatric intervention sorders explores the efficacy of new in clinical pathology has focused re- For further information: psychological and pharmacological search on knowledge of the psychiatric Fòrumclínic treatments in these disorders, with alterations seen in the main neurologi- www.forumclinic.org examination of the neuropsycholo- cal diseases: dementia, multiple scle- centro de Investigación Biomédica gical profile of children with high- rosis, epilepsy, Parkinson’s disease and En Red de Salud Mental (cIBERSAM) function autistic spectrum disorders Huntington’s disease. The study of psy- www.cibersam.es and the correlation to clinical varia- chiatric disease and psychological as- bles. Mention also should be made pects associated with medical-surgical of the line for the development and hospital processes in turn addresses: validation of scales in application to transplantation, delirium, psychiatric different pathologies or symptoms. problems in clinical patients admitted In turn, the line referred to attention to a general hospital, the evaluation of deficit hyperactivity disorder (ADHA) predictive variables and factors associa- involves the neuropsychological, cli- ted with suicide in a general hospital. nical and neuroimaging assessment Studies are also made of the biological of predominantly inattentive children markers and therapeutic aspects of ma- versus children with combined-type jor depression.

227 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Biological bases of psychiatric disorders and nuclear psychiatry

ReSeARCh gROUP Bipolar diSorderS

Group Leader: Eduard Vieta (hospital clínic)

The bipolar disorder program has been recognized as gists, pharmacologists, biologists, nurses, social workers and person- a consolidated research group (2009 SGR 1022) by nel in training. Our group has pioneered effort in the characterization the Agency for the Management of University and of associated neurocognitive dysfunction, in the development of new Research Aids (Agència de Gestió d’Ajuts Univer- drug treatments, and in the implementation of psychoeducational sitaris i de Recerca, AGAUR). The bipolar disorders techniques targeted at both patients and their relatives. As a result of program fundamentally investigates the neurobiological and anatomo- such research and innovation, the main international diagnostic and functional mechanisms involved in the development of the disease treatment guides document these contributions and recommend their and its clinical course, comorbidity with other diseases, the implicated application in clinical practice. Our program is carried out in active neurocognitive mechanisms, and the search for new pharmacologi- collaboration with other groups of the IDIBAPS, with other groups of cal, biophysical and psychosocial treatments designed to improve the the CIBERSAM, and with European and other international research prognosis and quality of life of the patients. The program is character- centers, with a view to conducting multicenter studies with a special ized by a multidiscipline approach and includes psychiatrists, psycholo- dedication to translational and innovative investigation.

ReSeARCh gROUP eMeRgeNT gROUP ScHizopHrenia clinical depreSSion Group

Group Leader: Miquel Bernardo (hospital clínic) Group Leader: cristobal Gasto (hospital clínic) The Clinical Schizophrenia Group (GEC) has been recognized as a consolidated research group (2005SGR00223; 2009SGR1295) by Our group is specialized in the in- the Agency for the Management of University and Research Aids vestigation of the neurobiological (Agència de Gestió d’Ajuts Universitaris i de Recerca, AGAUR) since bases and clinical indicators of the year 2005. In 2011 we received the National Health System depression associated with treat- Best in Class Prize, to the Best Schizophrenia Unit in the Patient Care Expertise in ment response and the course of this disease. It Schizophrenia category. This grant is awarded by Gaceta Médica and the Cátedra de has been estimated that depression affects 10% Innovación y Gestión Sanitaria of the Universidad Rey Juan Carlos. This is an interdis- of all people at some point in their lives. Depres- ciplinary group composed of psychiatrists, psychologists, neuropsychologists, nurses, sion is currently one of the most important health physicians specialized in nuclear medicine, physicists, pharmacologists, toxicologists problems, particularly considering its slow and and biochemists linked to the Clinic Hospital and the University of Barcelona. sometimes incomplete resolution. This disorder Ours is a group of investigators forming part of the Clinical Schizophrenia Program significantly interferes with the normal functions (PEC) and working in disorders related to schizophrenia. This is a clinical care, re- of the patients and their relatives, and implies search and teaching program at both hospital and outpatient level that includes dif- a suicide risk in more than 10% of cases. The ferent management and research protocols designed to address problems raised by project of the World Health Organization (WHO) schizophrenia and which integrates the different resources of the Barcelona Clinic for the year 2020 considers that depression will Hospital. In the year 2007, the group became a constituting member of the Network be the second cause of disability after cardiovas- of Mental Diseases and Affective and Psychotic Disorders (REMTAP), and in 2008 cular disease. In Europe it has been estimated we likewise became a constituting member of the Center of Biomedical Research in that about 30 million people suffer some form of Mental Health Network (CIBERSAM) (www.cibersam.es). depression, generating an annual cost of approxi- The Clinical Schizophrenia Group centers its research on the study of the first schizo- mately 100 billion euros. Our group is actively phrenic episodes, schizophrenia starting in childhood/adolescence, and resistant and involved in the early detection and treatment of comorbid schizophrenia. The main research lines are physical health, neuroimaging, this disease, and its comorbidities (medical and psychoeducation and psychometric evaluation, genetics, neurobiology and neuropsychiatric). The genetic and neuroendocrine psychopharmacology in schizophrenia, with a supervisor for each of them, under the markers we are investigating have contributed coordination of Dr. Miguel Bernardo. Another research line focuses on childhood- better understanding of the physiopathological and adolescent-onset schizophrenia – these representing a high risk population for mechanisms of depression. Likewise, a number schizophrenia. This line is conducted in close collaboration with the Department of of investigators in our group are actively working Childhood and Adolescent Psychiatry of the Clinic Hospital, directed by Dr. Castro, on the design of new individual- and group-based together with Drs. Baeza, Lázaro and Sánchez-Gistau (Study of high genetic risk for pharmacological and psychotherapeutic manage- schizophrenia and early onset schizophrenia). ment strategies.

228 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience BioloGicAl BASeS of pSycHiAtRic DiSoRDeRS AnD nucleAR pSycHiAtRy

ReSeARCh gROUP reSearcH Group in pediatric PUBLICATIONS original publications pSycHiatry and pSycHoloGy from 2009 to 2011

Group Leader: oRiGinAlS Year IF Total Q 1 Q 2 Josefina castro (hospital clínic) i.f.: 286.57 2009 281.89 75 49 12 The research group in childhood 2010 271.16 75 50 12 psychology and psychiatry of the 1 Fortea J, Llado A, Clarimon J, 2011 286.57 68 46 10 Clinic Hospital forms part of the Lleo A, Oliva R, Peri J, Pintor L, Department of Childhood and Yague J, Blesa R, Molinuevo JL, Adolescent Psychiatry, which has developed three Sanchez-Valle R. PICOGEN: Five fields: healthcare, teaching and research. These years experience with a genetic 6 Carreno M, Becerra JL, Castillo fields are all clearly interrelated with a view to afford- counselling program for demen- J, Maestro I, Donaire A, Fernandez ing better healthcare, with standardized protocols tia. NEUROLOGIA. 26:143-149. S, Bargallo N, Setoain X, Pintor L, and evaluation and teaching at pre- and post- I.F.: 0.59. Bailles E, Rumia J, Boget T, Vernet graduate level. Our aim is to facilitate both clinical O, Fumanal S. Seizure frequency research and collaboration with groups specialized in 2 Mane A, Gallego J, Lomena F, and social outcome in drug resistant genetics, neuroimaging and neurobiology. The group Mateos JJ, Fernandez-Egea E, Horga epilepsy patients who do not under- is predominantly composed of members of the De- G, Cot A, Pavia J, Bernardo M, Parel- go epilepsy surgery. SEIZURE-EUR partment of Childhood Psychology and Psychiatry, lada E. A 4-year dopamine transporter J EPILEP. 20:580-582. I.F.: 1.65. and is integrated within the Biological Bases of Psy- (DAT) imaging study in neuroleptic- chiatric Disorders group (coordinated by Dr. M. Ber- naive first episode schizophrenia 7 Cobo E, Cortes J, Ribera JM, nardo). It also forms part of the CIBERSAM (Centro patients. PSYCHIAT RES-NEUROIM. Cardellach F, Selva-O›callaghan A, de Investigación Biomédica en Red de Salud Mental) 194:79-84. I.F.: 2.06. Kostov B, Garcia L, Cirugeda L, Alt- of the Carlos III Healthcare Institute. In addition, it man DG, Gonzalez JA, Sanchez JA, has established important collaboration agreements 3 Horga G, Parellada E, Lomena F, Miras F, Urrutia A, Fonollosa V, Rey- with the Department of Adult Psychiatry of the Fernandez-Egea E, Mane A, Font Joly C, Vilardell M. Effect of using Clinic Hospital (especially as refers to schizophrenia, M, Falcon C, Konova AB, Pavia J, reporting guidelines during peer re- bipolar disorder and addictive behavior), as well as Ros D, Bernardo M. Differential view on quality of final manuscripts with other centers at international level, such as the brain glucose metabolic patterns submitted to a biomedical journal: Childhood Psychiatry Group of the ECNP (European in antipsychotic-naive first-episode masked randomised trial. BRIT College of Neuopsychopharmacology), with which schizophrenia with and without au- MED J. 343:-. I.F.: 13.47. relevant aspects of childhood psychopharmacology ditory verbal hallucinations. J PSY- are investigated in the context of different projects, CHIATR NEUROSCI. 36:312-321. 8 Haro JM, Reed C, Gonzalez-Pinto the University of Pittsburgh Medical Center, Neuro- I.F.: 4.89. A, Novick D, Bertsch J, Vieta E. imaging Laboratory, Western Psychiatric Institute 2-year course of bipolar disorder type and Clinic, Pittsburgh (United States), with which 4 Roca A, Garcia-Esteve L, Imaz I patients in outpatient care: Factors studies are made in relation to bipolar disorder, and ML, Torres A, Hernandez S, Botet associated with remission and func- the Child and Adolescent Psychiatry Yale Child Study F, Gelabert E, Subira S, Plaza A, Val- tional recovery. EUR NEUROPSY- Center, New Haven (United States), with which as- des M, Martin-Santos R. Obstetrical CHOPHARM. 21:287-293. I.F.: 4.20. pects relating to autoimmunity are studied. and neonatal outcomes after prena- Our research objectives are the study of the mani- tal exposure to selective serotonin 9 Lazaro L, Castro-Fornieles J, festations, causes and treatment of the most seri- reuptake inhibitors: The relevance Cullell C, Andres S, Falcon C, Calvo ous and/or prevalent disorders found in these age of dose. J AFFECT DISORDERS. R, Bargallo N. A voxel-based mor- groups: schizophrenia and bipolar disorder, anorexia 135:208-215. I.F.: 3.74. phometric MRI study of stabilized and bulimia nervosa, obsessive-compulsive behav- obsessive-compulsive adolescent ior, autistic disorders, attention deficit disorders, 5 Peris P, Torra M, Olivares V, patients. PROG NEURO-PSY- and addictive behaviors. In parallel, other lines have Reyes R, Monegal A, Martinez- CHOPH. 35:1863-1869. I.F.: 2.88. been developed related to the efficacy and safety of Ferrer A, Guanabens N. Prolonged psychoactive drugs in children and adolescents, the bisphosphonate release after treat- 10 Albacar G, Sans T, Martin- development and validation of assessment scales, ment in women with osteoporosis. Santos R, Garcia-Esteve L, Guil- and the investigation of autoimmunity and psychiat- Relationship with bone turnover. lamat R, Sanjuan J, Canellas F, ric disease such as Tourette syndrome. BONE. 49:706-709. I.F.: 4.60. Gratacos M, Cavalle P, Arija V,

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Gaviria A, Gutierrez-Zotes A, Vilella Public Speaking in Treatment-Naive 20 Allamani A, Voller F, Decarli A, E. An association between plasma Social Phobia Patients. NEUROPSY- Casotto V, Pantzer K, Anderson P, ferritin concentrations measured CHOPHARMACOL. 36:1219-1226. Gual A, Matrai S, Elekes Z, Eisen- 48 h after delivery and postpartum I.F.: 6.69. bach-Stangl I, Schmied G, Knibbe depression. J AFFECT DISOR- RA, Nordlund S, Skjaelaaen O, Ols- DERS. 131:136-142. I.F.: 3.74. 15 Gonzalez-Pinto A, Alberich S, son B, Ornberg JC, Osterberg E, Barbeito S, Gutierrez M, Vega P, Karlsson T, Plant M, Miller P, Coghill 11 Valenti M, Pacchiarotti I, Rosa Ibanez B, Haidar MK, Vieta E, Aran- N, Swiatkiewicz G, Wieczorek L, AR, Bonnin CM, Popovic D, Nivoli go C. Cannabis and first-episode Annaheim B, Gmel G. Contextual AMA, Murru A, Grande I, Colom psychosis: different long-term out- Determinants of Alcohol Consump- F, Vieta E. Bipolar mixed episodes comes depending on continued or tion Changes and Preventive Alcohol and antidepressants: a cohort discontinued use. SCHIZOPHRE- Policies: A 12-Country European study of bipolar I disorder patients. NIA BULL. 37:631-639. I.F.: 8.27. Study in Progress. SUBST USE MIS- BIPOLAR DISORD. 13:145-154. USE. 46:1288-1303. I.F.: 1.06. I.F.: 5.22. 16 Serra-Millas M, Lopez-Vilchez I, Navarro V, Galan AM, Escolar 21 Mendoza L, Navines R, Crippa 12 Cuesta MJ, Pino O, Guilera G, G, Penades R, Catalan R, Fananas JA, Fagundo AB, Gutierrez F, Nardi Rojo JE, Gomez-Benito J, Purdon L, Arias B, Gasto C. Changes in AE, Bulbena A, Valdes M, Martin- SE, Franco M, Martinez-Aran A, plasma and platelet BDNF levels Santos R. Depersonalization and per- Segarra N, Tabares-Seisdedos R, induced by S-citalopram in major sonality in panic disorder. COMPR Vieta E, Bernardo M, Crespo-Facor- depression. PSYCHOPHARMA- PSYCHIAT. 52:413-419. I.F.: 2.38. ro B, Mesa F, Rejas J. Brief cogni- COLOGY. 216:1-8. I.F.: 3.82. tive assessment instruments in 22 Pacchiarotti I, Valenti M, Co- schizophrenia and bipolar patients, 17 Alemany S, Arias B, Aguilera lom F, Rosa AR, Nivoli AMA, Murru and healthy control subjects: A M, Villa H, Moya J, Ibanez MI, Vos- A, Sanchez-Moreno J, Vieta E. Dif- comparison study between the sen H, Gasto C, Ortet G, Fananas ferential outcome of bipolar patients Brief Cognitive Assessment Tool L. Childhood abuse, the BDNF- receiving antidepressant monothera- for Schizophrenia (B-CATS) and the Val66Met polymorphism and adult py versus combination with an anti- Screen for Cognitive Impairment in psychotic-like experiences. BRIT J manic drug. J AFFECT DISORDERS. Psychiatry (SC. SCHIZOPHR RES. PSYCHIAT. 199:38-42. I.F.: 5.95. 129:321-326. I.F.: 3.74. 130:137-142. I.F.: 4.37. 18 Andres-Perpina S, Lozano- 23 Fatjo-Vilas M, Papiol S, Es- 13 Gonzalez-Pinto A, DeAzua SR, Serra E, Puig O, Lera-Miguel trada G, Bombin I, Peralta V, Rosa Ibanez B, Otero-Cuesta S, Castro- S, Lazaro L, Castro-Fornieles J. A, Parellada M, Miret S, Martin M, Fornieles J, Graell-Berna M, Ugarte Clinical and biological correlates of Lazaro L, Campanera S, Munoz MJ, A, Parellada M, Moreno D, Soutullo adolescent anorexia nervosa with Lera-Miguel S, Arias B, Navarro ME, C, Baeza I, Arango C. Can positive impaired cognitive profile. EUR Castro-Fornieles J, Cuesta MJ, Aran- family factors be protective against CHILD ADOLES PSY. 20:541-549. go C, Fananas L. Dysbindin-1 Gene the development of psychosis?. I.F.: 1.62. Contributes Differentially to Early- PSYCHIAT RES. 186:28-33. and Adult-Onset Forms of Functional I.F.: 2.80. 19 DeLaSerna E, Baeza I, An- Psychosis. AM J MED GENET B. dres S, Puig O, Sanchez-Guistau 156B:322-333. I.F.: 4.16. 14 Bergamaschi MM, Queiroz V, Romero S, Bernardo M, Moreno RHC, Chagas MHN, DeOliveira D, Noguera A, Castro-Fornieles 24 Lera-Miguel S, Andres-Perpina DCG, DeMartinis BS, Kapczinski J. Comparison between young S, Calvo R, Fatjo-Vilas M, Lourdes F, Quevedo J, Roesler R, Schro- siblings and offspring of subjects F, Lazaro L. Early-onset bipolar der N, Nardi AE, Martin-Santos with schizophrenia: Clinical and disorder: how about visual-spatial R, Hallak JEC, Zuardi AW, Crippa neuropsychological characteris- skills and executive functions?. EUR JAS. Cannabidiol Reduces the tics. SCHIZOPHR RES. 131:35-42. ARCH PSY CLIN N. 261:195-203. Anxiety Induced by Simulated I.F.: 4.37. I.F.: 3.64.

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25 Gonzalez-Pinto A, Vieta E, Reed Bonnin CM, Grande I, Sanchez- paroxetine in nonresponders: a ran- C, Novick D, Barraco A, Aguado J, Moreno J, Vieta E, Colom F. Gender domized, placebo-controlled trial with Haro JM. Effectiveness of olanzapine differences in a cohort study of 604 a novel design. BIPOLAR DISORD. monotherapy and olanzapine combi- bipolar patients: The role of predomi- 13:111-117. I.F.: 5.22. nation treatment in the long term fol- nant polarity. J AFFECT DISORDERS. lowing acute mania - Results of a two 133:443-449. I.F.: 3.74. 37 Pacchiarotti I, Mazzarini L, Kot- year observational study in bipolar zalidis GD, Valenti M, Nivoli AMA, disorder (EMBLEM). J AFFECT DIS- 32 Miquel L, Usall J, Reed C, Sani G, Torrent C, Murru A, Sanchez- ORDERS. 131:320-329. I.F.: 3.74. Bertsch J, Vieta E, Gonzalez-Pinto Moreno J, Patrizi B, Girardi P, Vieta A, Angst J, Nolen W, VanRossum I, E, Colom F. Mania and depression. 26 Vieta E, Gunther O, Locklear J, Haro JM. Gender differences in out- Mixed, not stirred. J AFFECT DISOR- Ekman M, Miltenburger C, Chatterton comes of acute mania: a 12-month DERS. 133:105-113. I.F.: 3.74. ML, Astrom M, Paulsson B. Effective- follow-up study. ARCH WOMEN ness of psychotropic medications in MENT HLTH. 14:107-113. I.F.: 1.81. 38 Salvatore P, Baldessarini RJ, the maintenance phase of bipolar dis- Tohen M, Khalsa HMK, Sanchez- order: a meta-analysis of randomized 33 Muinos-Gimeno M, Espinosa- Toledo JP, Zarate CA, Vieta E, Mag- controlled trials. INT J NEUROPSY- Parrilla Y, Guidi M, Kagerbauer B, gini C. McLean-Harvard International CHOPH. 14:1029-1049. I.F.: 4.70. Sipila T, Maron E, Pettai K, Kananen First-Episode Project: Two-Year Sta- L, Navines R, Martin-Santos R, Grata- bility of ICD-10 Diagnoses in 500 27 Torrent C, Martinez-Aran A, Da- cos M, Metspalu A, Hovatta I, Estivill First-Episode Psychotic Disorder ban C, Amann B, Balanza-Martinez V, X. Human microRNAs miR-22, miR- Patients. J CLIN PSYCHIAT. 72:183- Bonnin CD, Cruz N, Franco C, Tabares- 138-2, miR-148a, and miR-488 are 193. I.F.: 5.02. Seisdedos R, Vieta E. Effects of atypi- associated with panic disorder and cal antipsychotics on neurocognition regulate several anxiety candidate 39 Fernandez-Egea E, Miller B, in euthymic bipolar patients. COMPR genes and related pathways. BIOL Garcia-Rizo C, Bernardo M, Kirk- PSYCHIAT. 52:613-622. I.F.: 2.38. PSYCHIAT. 69:526-533. I.F.: 8.67. patrick B. Metabolic Effects of Olanzapine in Patients With Newly 28 Yildiz A, Vieta E, Leucht S, 34 Vieta E, Pappadopulos E, Diagnosed Psychosis. J CLIN PSY- Baldessarini RJ. Efficacy of Antimanic Mandel FS, Lombardo I. Impact of CHOPHARM. 31:154-159. I.F.: 4.86. Treatments: Meta-analysis of Ran- geographical and cultural factors on domized, Controlled Trials. NEURO- clinical trials in acute mania: lessons 40 Filho AS, Maciel BC, Romano PSYCHOPHARMACOL. 36:375-389. from a ziprasidone and haloperidol MMD, Lascala TF, Trzesniak C, Freitas- I.F.: 6.69. placebo-controlled study. INT J Ferrari MC, Nardi AE, Martin-Santos NEUROPSYCHOPH. 14:1017-1027. R, Zuardi AW, Crippa JAS. Mitral valve 29 Yildiz A, Vieta E, Tohen M, I.F.: 4.70. prolapse and anxiety disorders. BRIT J Baldessarini RJ. Factors modifying drug PSYCHIAT. 199:247-248. I.F.: 5.95. and placebo responses in randomized 35 Gual A, Sabadini MBD. Imple- trials for bipolar mania. INT J NEURO- menting alcohol disorders treatment 41 Winton-Brown TT, Allen P, PSYCHOPH. 14:863-875. I.F.: 4.70. throughout the community. CURR Bhattacharyya S, Borgwardt SJ, OPIN PSYCHIATR. 24:203-207. Fusar-Poli P, Crippa JA, Seal ML, 30 Salavert J, Gasol M, Vieta E, I.F.: 3.00. Martin-Santos R, Ffytche D, Zuardi Cervantes A, Trampal C, Gispert JD. AW, Atakan Z, Mcguire PK. Modula- Fronto-limbic dysfunction in border- 36 VanDerLoos MLM, Mulder tion of auditory and visual processing line personality disorder: a 18F-FDG P, Hartong EGTM, Blom MBJ, by delta-9-tetrahydrocannabinol and positron emission tomography study. Vergouwen AC, VanNoorden MS, cannabidiol: an FMRI study. NEU- J AFFECT DISORDERS. 131:260-267. Timmermans MA, Vieta E, Nolen ROPSYCHOPHARMACOL. 36:1340- I.F.: 3.74. WA. Long-term outcome of bipolar 1348. I.F.: 6.69. depressed patients receiving la- 31 Nivoli AMA, Pacchiarotti I, Rosa motrigine as add-on to lithium with 42 Reig S, Parellada M, Castro- AR, Popovic D, Murru A, Valenti M, the possibility of the addition of Fornieles J, Janssen J, Moreno D,

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59 Cuyas E, Verdejo-Garcia A, Fa- month follow-up of family com- S, Rubenstein JL. No paradox, no gundo AB, Khymenets O, Rodriguez munication and psychopathology progress: inverse cancer comorbid- J, Cuenca A, Llopis SD, Langohr in children and adolescents with ity in people with other complex K, Pena-Casanova J, Torrens M, a first psychotic episode (CAFEPS diseases. LANCET ONCOL. 12:604- Martin-Santos R, Farre M, DeLaTorre study). PSYCHIAT RES. 185:72-77. 608. I.F.: 17.76. R. The Influence of Genetic and En- I.F.: 2.80. vironmental Factors among MDMA 2 Sole B, Martinez-Aran A, Tor- Users in Cognitive Performance. 65 Castro-Fornieles J, Baeza I, rent C, Bonnin CM, Reinares M, PLOS ONE. 6:-. I.F.: 4.41. DeLaSerna E, Gonzalez-Pinto A, Popovic D, Sanchez-Moreno J, Vieta Parellada M, Graell M, Moreno D, E. Are bipolar II patients cognitively 60 Almansa J, Ayuso-Mateos JL, Otero S, Arango C. Two-year diag- impaired? A systematic review. PSY- Garin O, Chatterji S, Kostanjsek N, nostic stability in early-onset first-ep- CHOL MED. 41:1791-1803. I.F.: 5.20. Alonso J, Valderas JM, Cieza A, isode psychosis. J CHILD PSYCHOL Raggi A, Svestkova O, Burger H, PSYC. 52:1089-1098. I.F.: 4.36. 3 Goodwin GM, Abbar M, Schlaep- Racca V, Vieta E, Leonardi M, Ferrer fer TE, Grunze H, Licht RW, Bellivier M. The International Classification of 66 DeLaSerna E, Flamarique I, F, Fountoulakis KN, Altamura AC, Functioning, Disability and Health: Castro-Fornieles J, Pons A, Puig O, Pitchot W, Agren H, Holsboer- development of capacity and perfor- Andres-Perpina S, Lazaro L, Garrido Trachsler E, Vieta E. Aripiprazole mance scales. J CLIN EPIDEMIOL. JM, Bernardo M, Baeza I. Two-Year in patients with bipolar mania and 64:1400-1411. I.F.: 3.75. Follow-Up of Cognitive Functions in beyond: an update of practical Schizophrenia Spectrum Disorders guidance. CURR MED RES OPIN. 61 Gelabert E, Subira S, Plaza A, of Adolescent Patients Treated with 27:2285-2299. I.F.: 2.61. Torres A, Navarro P, Imaz ML, Valdes Electroconvulsive Therapy. J CHILD M, Garcia-Esteve L, Martin-Santos ADOL PSYCHOP. 21:611-619. 4 Fountoulakis KN, Vieta E, R. The Vulnerable Personality Style I.F.: 2.48. Schmidt F. Aripiprazole monotherapy Questionnaire: psychometric proper- in the treatment of bipolar disorder: ties in Spanish postpartum women. 67 Garcia-Esteve L, Torres A, A meta-analysis. J AFFECT DISOR- ARCH WOMEN MENT HLTH. Navarro P, Ascaso C, Imaz ML, Her- DERS. 133:361-370. I.F.: 3.74. 14:115-124. I.F.: 1.81. reras Z, Valdes M. Validation and comparison of four instruments to 5 Rosa AR, Fountoulakis K, Sia- 62 Vieta E, Colom F. Therapeutic detect partner violence in health- mouli M, Gonda X, Vieta E. Is an- options in treatment-resistant de- care setting. MED CLIN-BARCELO- ticonvulsant treatment of mania a pression. ANN MED. 43:512-530. NA. 137:390-397. I.F.: 1.41. class effect? Data from random- I.F.: 4.32. ized clinical trials. CNS NEUROSCI 68 Plaza A, Torres A, Martin-Santos THER. 17:167-177. I.F.: 3.49. 63 Parellada M, Boada L, Fraguas R, Gelabert E, Imaz ML, Navarro P, D, Reig S, Castro-Fornieles J, More- Bremner JD, Valdes M, Garcia-Esteve 6 Montoya A, Colom S, Ferrin M. no D, Gonzalez-Pinto A, Otero S, L. Validation and Test-Retest Reli- Is psychoeducation for parents and Rapado-Castro M, Graell M, Baeza I, ability of Early Trauma Inventory in teachers of children and adoles- Arango C. Trait and State Attributes Spanish Postpartum Women. J NERV cents with ADHD efficacious? A of Insight in First Episodes of Early- MENT DIS. 199:280-285. I.F.: 1.80. systematic literature review. EUR Onset Schizophrenia and Other Psy- PSYCHIAT. 26:166-175. I.F.: 3.37. choses: A 2-Year Longitudinal Study. SCHIZOPHRENIA BULL. 37:38-51. ReViewS 7 Popovic D, Reinares M, Amann I.F.: 8.27. i.f.: 47.56 B, Salamero M, Vieta E. Number needed to treat analyses of drugs 64 Otero S, Moreno-Iniguez M, 1 Tabares-Seisdedos R, Dumont N, used for maintenance treatment Pay B, Castro-Fornieles J, Gonza- Baudot A, Valderas JM, Climent J, of bipolar disorder. PSYCHO- lez-Pinto A, Baeza I, Mayoral M, Valencia A, Crespo-Facorro B, Vieta PHARMACOLOGY. 213:657-667. Graell M, Arango-Lopez C. Twelve- E, Gomez-Beneyto M, Martinez I.F.: 3.82.

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8 Murru A, Pacchiarotti I, Nivoli GRAntS foR ReSeARcH Catalan R. Identificación de predictores AMA, Grande I, Colom F, Vieta E. What in pRoGReSS clínicos, neurohormonales, farmaco- we know and what we don’t know genéticos en la respuesta terapéutica a about the treatment of schizoaffec- Gasto C. Estrategias terapeuticas en clozapina en pacientes diagnosticados tive disorder. EUR NEUROPSYCHO- trastorno depresivo mayor resistente a de Esquizofrenia Refractaria. Sponsored PHARM. 21:680-690. I.F.: 4.20. tratamiento con inhibidores selectivos by: FIS (ISCIII), EC08/00184. Duration: de la recaptación de serotonina. Ensayo 01/01/2009-31/12/2012. 9 Rosa AR, Fountoulakis K, Siamouli clínico pragmático, paralelo. Aleatorizado M, Gonda X, Vieta E. When should con evaluación enmascarada. Sponsored Bernardo M. Reconocimiento como Gru- mood stabilizers be withdrawn due to by: Ministerio Sanidad y Consumo, po Consolidado de Investigación. Spon- lack of efficacy? Some methodologi- EC07/90825. Duration: 29/10/2007- sored by: Agència de Gestió d’Ajuts cal considerations. EUR PSYCHIAT. 30/11/2011. Universitaris i de Recerca, Generalitat 26:183-186. I.F.: 3.37. de Catalunya, 2009SGR1295. Duration: Lazaro L. Estudio de la relación clínica y 01/01/2009-31/12/2014. genética entre un subgrupo de pacientes eDitoRiAlS con anorexia nerviosa y pacientes con Vieta E. Grup de Recerca Consolidat i.f.: 20.68 trastorno obsesivo compulsivo en niños de la Generalitat de Catalunya. Spon- y adolescentes. Sponsored by: Ministerio sored by: Generalitat de Catalunya, 1 Gual A, Anderson P. A new AMPHO- Sanidad y Consumo, PI070350. Duration: 2009_SGR_1022. Duration: 01/01/2009- RA: an introduction to the project Alcohol 26/11/2007-30/06/2011. 31/12/2013. Measures for Public Health Research Alliance. ADDICTION. 106:1-3. I.F.: 4.15. Lazaro L. Anàlisi dels polimorfismes en Vieta E. European Network of Bipolar gens candidats en el trastorn obsessiu- Research Expert Centres (ENBREC). 2 Vieta E. Bipolar units and pro- compulsiu d’inici primerenc. Relació Sponsored by: European Union, 223102. grammes: are they really needed. amb alteracions cerebrals i dimen- Duration: 01/07/2009-30/06/2011. WORLD PSYCHIATRY. 10:152-152. sions simptomàtiques. Sponsored by: I.F.: 5.56. Fundació Marató TV3, 91710. Duration: Martinez A. Discapacidad en el trastorno 29/01/2010-28/07/2013. bipolar e impacto funcional de una es- 3 Frye MA, Ha K, Kanba S, Kato T, trategia de intervención neurocognitiva. Mcelroy SL, Ozerdem A, Vazquez G, Gutierrez F. Eficacia comparada de cu- Sponsored by: FIS, PI080180. Duration: Vieta E. International Consensus Group atro modelos diagnósticos de Trastor- 01/01/2009-31/12/2011. on Depression Prevention in Bipolar no de la Personalidad. Sponsored by: Disorder. J CLIN PSYCHIAT. 72:1295- Instituto de Salud Carlos III (ISCIII), Martin-Santos R, Garcia L, Gutierrez 1310. I.F.: 5.02. PI08/90434. Duration: 01/01/2009- F, Navines R, Imaz ML. Grup de Re- 31/01/2011. cerca en “Vulnerabilitat, psicopatologia 4 Colom F. Keeping therapies simple: i gènere” Modalitat Grup de recerca psychoeducation in the prevention of Bernardo M. Interacción genotipo- emergent. Sponsored by: Generalitat de relapse in affective disorders. BRIT J fenotipo y ambiente. Aplicación a Catalunya, SGR 2009/1435. Duration: PSYCHIAT. 198:338-340. I.F.: 5.95. un modelo predictivo en primeros 01/01/2009-31/12/2013. episodios psicóticos. Sponsored by: FIS (ISCIII), PI080208. Duration: Garcia L, Imaz ML, Botet F, Ascaso C, clinicAl GuiDelineS 01/01/2009-31/12/2011. Salamero M. Estudio farmacogenético y i.f.: 3.74 de seguridad clínica en niños de madres Parellada E. Apoptosis y cambios es- tratadas con inhibidores selectivos de 1 Nivoli AMA, Colom F, Murru A, tructurales progresivos en pacientes la recaptación de serotonina durante el Pacchiarotti I, Castro-Loli P, Gonzalez- con un primer episodio de esquizofre- embarazo: evaluación del funcionamien- Pinto A, Fountoulakis KN, Vieta E. New nia: estudio longitudinal y multimodal to cognitivo conductual a los 5 años de treatment guidelines for acute bipolar de neuroimagen y biología molecular. edad. Sponsored by: European Comis- depression: A systematic review. J AF- Sponsored by: FIS (ISCIII), PI080055. sion, EC08/00170. Duration: 01/01/2009- FECT DISORDERS. 129:14-26. I.F.: 3.74. Duration: 01/01/2009-31/12/2011. 31/12/2011.

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Pintor L. Análisis de los indicadores Castro J. Two year follow-up study of Lazaro L. Identificación de predictores far- clínicos que diferencian entre crisis epi- children and adolescent offspring of sub- macogenéticos en la respuesta terapéuti- lépticas y crisis no epilépticas psicógenas jects with schizophrenia or bipolar disor- ca a fluoxetina en pacientes diagnostica- (CNEP): Hacia un mejor diagnóstico ders. Sponsored by: Fundació La Marató dos de trastorno obsesivo-compulsivo en diferencial a través de un cuestionario de TV3, 091630. Duration: 29/01/2010- la infancia y la adolescencia. Sponsored de sospecha diagnóstica. Sponsored 28/01/2013. by: Fundación Alicia Koplowitz. Duration: by: Fondo de Investigaciones Sanitarias 26/05/2011-26/05/2013. (FIS), PI080111. Duration: 01/01/2009- Andres S. Trastornos de la Conducta 31/12/2011. Alimentaria, veinte años después. Es- Masana G. Ensayo doble ciego con- tudio de estado psicopatológico y físico trolado con placebo de la eficacia Gual A. Alcohol Public Health Research y su relación con el funcionamiento de reboxetina y citalopram como Alliance (AMPHORA). Sponsored by: general. Sponsored by: Instituto de la tratamiento coadyuvante de los an- Comissió Europea, 223059. Duration: Mujer, 234/09. Duration: 03/02/2010- tipsicóticos de segunda generación 01/01/2009-31/12/2013. 02/02/2012. en el tratamiento de los síntomas negativos de la esquizofrenia. Spon- Benabarre A. Identificación de variables Castro J. Suicidality: Treatment Oc- sored by: Instituto de Salud Carlos clínicas, sociológicas y genéticas pre- curring in Paediatrics. Sponsored by: III (ISCIII), EC07/90553. Duration: dictoras de la respuesta al tratamiento University College London UCL, 261411. 01/01/2008-31/12/2011. eutimizante en el Trastorno Bipolar. Duration: 01/11/2010-30/04/2014. Sponsored by: Instituto de Salud Carlos Castro J. Caracterísitcas psicopato- III, PI080247. Duration: 01/01/2009- Garcia L. Violencia sexual, estrés agudo y lógicas, neuropsicológicas y de neu- 31/12/2011. calidad de vida: estudio de los factores de roimagen comunes y diferenciales en riesgo en las mujeres atendidas en urgen- niños y adolescentes hijos de pacien- Colom F. Factores neurobiológicos, cog- cias tras una agresión sexual. Sponsored tes con esquizofrenia o con trastorno nitivos y clínicos asociados al pronóstico by: Instituto de la Mujer, 235/09. Duration: bipolar. Sponsored by: Instituto de clínico y funcional a un año de segui- 03/02/2010-02/02/2013. Salud Carlos III (ISCIII), PI 07/0066. miento de la psicoeducación en el Duration: 26/11/2007-30/12/2011. trastorno bipolar. Sponsored by: Instituto Bernardo M. Antipsicóticos típicos vs. de Salud Carlos III, PI09/1044. Duration: atípicos; impacto de la farmacogenética Castro J. Reconocimiento como 01/01/2010-31/12/2012. en la farmacocinética, la ocupación de grupo consolidado de investigación. receptores estriatales y la aparición se Sponsored by: Generalitat de Cata- Morer A. Inflamación, autoinmunidad y sintomatología extrapiramidal. Spon- lunya, AGAUR, 2009SGR1119. Dura- psicopatología: estudio en niños y adoles- sored by: Ministerio de Sanidad, Política tion: 03/07/2009-31/12/2013. centes con patología psiquiátrica aguda Social e Igualdad, TRA-065. Duration: y en hijos de madres afectadas de lupus 01/01/2010-31/12/2011. Morer A. Collaborative Genomic Stud- eritematoso sistémico. Sponsored by: ies of Tourette Disorders. Sponsored Instituto de Salud Carlos III, PI09/1347. Martin-Santos R. Estudio farmacogené- by: NIMH, RO1 MH092293. Duration: Duration: 01/01/2010-31/12/2012. tico y de predicción de la depresión indu- 01/01/2011-31/12/2012. cida por el tratamiento de la hepatitis C Vieta E. The neural correlates of eu- crónica con interferón alfa pegilado y riva- Morer A. European multicentre tics in thymic cognitive impairment in bipolar birina. Estudio psigen-vhc. subproyecto children studies (EMTICS). Sponsored by: disorder. Sponsored by: Instituto de coordinado I. Sponsored by: IInstituto de European Commission, 278367. Duration: Salud Carlos III, PI09/1893. Duration: Salud Carlos III, EC08/00201. Duration: 01/12/2011-30/05/2017. 01/01/2010-31/12/2012. 01/01/2009-31/05/2011. Colom F. Development and evaluation Castro J. Paediatric European Risperi- Vieta E. Metilfenidato en el tra- of a multidisciplinary service for people done Studies. Sponsored by: European tamiento inicial de mania aguda.. with bipolar disorder. Sponsored by: Comission, CE-FP7-HEALTH-1ST-09, Sponsored by: Ministerio de Sanidad, NIHR, Programme Grants for Applied 241959. Duration: 01/05/2010- Política Social e Igualdad, EC10-064. Research, RP-PG-0108-10087. Dura- 30/04/2015. Duration: 01/01/2011-31/12/2011. tion: 01/01/2009-31/12/2013.

235 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Biological bases of psychiatric disorders and nuclear psychiatry

Colom F. Enseñanza y desarrollo de un Martin-Santos R. Repercusión del inicio Bernardo M. Metabolism and inflam- programa psicoeducativo basado en la precoz del consumo continuado (cró- mation in first episode psychosis. PhD evidencia en primeros episodios psicó- nico) de substancias de abuso sobre student: Clemente García Rizo. ticos. Sponsored by: Instituto de Salud la red atencional: estudio de conecti- Carlos III (ISCIII), PI10/02209. Duration: vidad funcional cerebral y modulación Castro J. Prevalence, clinical correlates 01/01/2011-31/12/2013. genética. Sponsored by: Ministerio and factors associated with course and de Sanidad, política Social e Igualdad, outcome of anxiety disorders in youth Gual T. Optimizing delivery of health MSPSI_PNSD11 2011/050. Duration: with bipolar disorder. PhD student: Re- care interventions (Odhin). Spon- 08/11/2011-07/11/2014. gina Sala Cassola. sored by: European Commission, 259268. Duration: 01/01/2011- Martin-Santos R. Bases neurobioló- Bernardo M, Parellada E. Transportador 31/12/2014. gicas de la depresión inducida por de la Dopamina (DAT) y pronóstico de interferón en la hepatitis C crónica. la esquizofrenia: Estudio prospectivo de Gual T. Addictions and Lifestyles in Estudio PSICOCIT. Sponsored by: Ins- una cohorte evaluado mediante DATS- Contemporary Europe: Reframing ad- tituto de Salud Carlos III (ISCIII), FIS10 CAN, RM volumétrica y el polimorfismo dictions Project (Alice Rap). Sponsored PI10/02206. Duration: 01/01/2011- -67 A/T del gen DAT. PhD student: Anna by: European Commission, 266813. 31/12/2013. Mané Santacana. Duration: 01/01/2011-31/12/2016. Vieta E. Contratos Bases biológicas del Martin R. Early-onset of chronic can- Vieta E. Trastorn bipolar. Sponsored trastorno psíquico y psiquiatría nuclear. nabis use: effects on cognitive function by: Generalitat de Catalunya, AGAUR, Trastornos afectivos unipolares. Colabo- and brain activity. PhD student: Ana AGAUR_SGR09 2009_SGR_1022. ración con los grupos de investigación Beatriz Fagundo. Duration: 15/09/2009-31/12/2013. en trasplantes. Líneas de investigación en el programa de trastornos bipolares. Gasto C. Análisis de perfiles de Ministerio de Educación y Ciencia, metilación en genes involucrados JCI-2009-04329 Duration: 01/12/2009- en la respuesta al estrés y su corre- 30/11/2012. lación con morfología cerebral (MRI) en trastornos afectivos severos. Sponsored by: Ministerio de Econo- DoctoRAl tHeSeS mía y Competitividad, MEC_PN08 SAF2008-05674-C03-03. Duration: Castro J, Baeza I. Característiques 01/01/2009-31/12/2012. clíniques i neuropsicològiques en nens i adolescents d’alt risc per esquizofrè- Lazaro L. Identificación de predic- nia. PhD student: Elena de la Serna tores farmacogenéticos en la res- Gómez. puesta terapéutica a Fluoxetina en niños y adolescentes. Sponsored by: Vieta E, Colom F. Treatment outcomes Instituto de Salud Carlos III (ISCIII), of antidepressant use in bipolar disor- PI10/01965. Duration: 01/01/2011- der. PhD student: Isabella Pacchiarotti. 31/12/2013. Vieta E, Martinez A. Funcionament psi- Gual T. European Workplace and cosocial en el trastorn bipolar: Factors Alcohol. Sponsored by: Euro- implicats i seguiment als 4 anys. PhD pean Commission, CE_SANCO_09 student: Caterina del Mar Bonnin Roig. CE_SANCO_09_01. Duration: 01/01/2011-30/06/2013.

236 AReA 4

Clinical and experimental neuroscience

Neuropsychology gROUP MeMBeRS StrateGic oBjectiveS

Study of the consequences of cerebral teAM leADeR lesions and dysfunctions in relation to carme Junqué behavior and cognition. The technique (universitat de Barcelona) preferentially used in our studies is tel.: 93 403 92 98 magnetic resonance imaging in its fax: 93 403 52 94 structural and functional applications. e-mail: [email protected] We are equipped with a neuroimaging laboratory with different high-perfor- iDiBApS MeMBeRS: ReSeARcH fellowS: mance workstations. núria Bargalló (Hospital clínic) Davinia fernández (Mec) David Bartrés-faz (uB) Joana B. pereira (Micinn) main lineS teresa Boget (Hospital clínic) leire Zubiaurre (Micinn) of reSearcH teodor Marcos (Hospital clínic) eider Martinez de Arenaza (DGR) José M. Mercader (Hospital clínic) eva palacios (iDiBApS) 1. Neuropsychology and neu- Manuel Salamero (Hospital clínic) Roser Sala (Micinn) roimaging in normal aging and Josep M. Serra (uB) Didac Vidal (DGR) in degenerative diseases: Neu- pere Vendrell (uB) nuria pujol (Rio Hortega) roanatomical and neurofunctional Hugo cesar Baggio (DGR) bases of cognitive impairment in poStDoctoRAl fellowS: normal aging, Pakinson’s disease naroa ibarretxe (Mec) tecHniciAnS: and Alzheimer’s disease. This line Bárbara Segura (uB) Silvia Juanes (uB) makes use of combined structural and functional magnetic resonance imaging to detect early alterations in brain connectivity prior to clear cerebral atrophy caused by neuron death. Identification of the symptoms prior to actual clinical manifestations in degenerative diseases is a challenge for treatment intervention aiming to slow the neurodegenerative processes. As a subline, mention should be made of the study of the contribution of the cognitive reserve variables in the degree of cognitive deterioration associated with age and dementia, as well as of the neuroanatomical and neurophysiological bases of this phenomenon.

2. cerebral plasticity: Long-term consequences of brain damage. In the field of cerebral plasticity we investigate the changes in brain structure and function detectable by magnetic resonance imaging that are induced by transcranial electric stimulation.

237 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Neuropsychology

PUBLICATIONS

This technique can be used to 3. Development of imaging techni- oRiGinAlS simulate reversible lesions or to ques to study the areas of the brain i.f.: 125.07 investigate the changes in brain con- implicated in the higher function nectivity in normal subjects and also alterations in epileptic patients, 1 Iranzo A, Valldeoriola F, Lomena F, in degenerative processes. Another based on functional magnetic reso- Molinuevo JL, Serradell M, Salamero line of interest in which work is nance imaging. The aim of this line M, Cot A, Ros D, Pavia J, Santamaria being done is the study of cerebral of research is to develop cognitive J, Tolosa E. Serial dopamine transpor- language response in patients who paradigms such as those relating ter imaging of nigrostriatal function as a result of head injuries are in a to speech, perception or memory, in patients with idiopathic rapid-eye- chronic vegetative state or minimally based on functional magnetic reso- movement sleep behaviour disorder: a responsive state. Brain response nance imaging techniques - valida- prospective study. LANCET NEUROL. in the absence of motor response ting and applying them to clinical 10:797-805. I.F.: 21.66. can have clear consequences in the practice with a view to predicting differential diagnosis of these two neuropsychological sequelae and 2 Padilla N, Falcon C, Sanz-Cortes M, conditions. Likewise in head injury investigating cerebral plasticity me- Figueras F, Bargallo N, Crispi F, Eixarch patients, we study the relationship chanisms. E, Arranz A, Botet F, Gratacos E. Diffe- between the long-term cognitive rential effects of intrauterine growth sequelae and the white matter alte- restriction on brain structure and deve- rations identified by diffusion tensor lopment in preterm infants: A magnetic imaging (DTI), and also analyze the resonance imaging study. BRAIN RES. changes in the cortical layer related 1382:98-108. I.F.: 2.62. to alterations attributable to diffuse axonal damage. 3 Sole-Padulles C, Llado A, Bartres- Faz D, Fortea J, Sanchez-Valle R, Bosch B, Antonell A, Molinuevo JL, Rami L. Association between cerebrospinal fluid tau and brain atrophy is not related to clinical severity in the Alzheimer’s disease continuum. PSYCHIAT RES- NEUROIM. 192:140-146. I.F.: 2.06.

4 Ibarretxe-Bilbao N, Junque C, Marti MJ, Tolosa E. Brain structural MRI correlates of cognitive dysfunctions in Parkinson’s disease. J NEUROL SCI. 310:70-74. I.F.: 2.17.

5 Ibarretxe-Bilbao N, Junque C, Marti MJ, Tolosa E. Cerebral basis of visual hallucinations in Parkinson’s disease: Structural and functional MRI studies. J NEUROL SCI. 310:79-81. I.F.: 2.17.

6 Rami L, Valls-Pedret C, Bartres-Faz D, Differences between Parkinson’s disease (PD) patients and healthy controls in a fMRI task of Caprile C, Sole-Padulles C, Castellvi M, recognition memory. In yelow areas with decreased activation during the task and in blue areas Olives J, Bosch B, Molinuevo JL. Cogni- with decreased deactivation . (Ibarretxe-Bilbao et al. Neuroimage 2011). tive reserve questionnaire. Scores obtained in a healthy elderly population and in one with Alzheimer›s disease. REV NEUROLOGIA. 52:195-201. I.F.: 1.22.

238 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience neuRopSycHoloGy

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 109.29 33 21 8 7 Fortea J, Sala-Llonch R, Bartres-Faz D, 12 Fernandez S, Donaire A, Maes- Llado A, Sole-Padulles C, Bosch B, An- tro I, Seres E, Setoain X, Bargallo N, 2010 100.84 23 15 5 tonell A, Olives J, Sanchez-Valle R, Moli- Rumia J, Boget T, Falcon C, Carreno 2011 125.07 29 17 4 nuevo JL, Rami L. Cognitively Preserved M. Functional neuroimaging in start- Subjects with Transitional Cerebrospinal le epilepsy: Involvement of a mesial Fluid beta-Amyloid 1-42 Values Have frontoparietal network. EPILEPSIA. Thicker Cortex in Alzheimer’s Disease 52:1725-1732. I.F.: 3.96. Vulnerable Areas. BIOL PSYCHIAT. polar disorder cohort in the context of 70:183-190. I.F.: 8.67. 13 Carreno M, Becerra JL, Castillo a specialized-care program. BIPOLAR J, Maestro I, Donaire A, Fernandez S, DISORD. 13:679-686. I.F.: 5.22. 8 Ibarretxe-Bilbao N, Zarei M, Junque C, Bargallo N, Setoain X, Pintor L, Bailles Marti MJ, Segura B, Vendrell P, Valldeo- E, Rumia J, Boget T, Vernet O, Fumanal 18 Segarra N, Bernardo M, Gutierrez riola F, Bargallo N, Tolosa E. Dysfunctions S. Seizure frequency and social outco- F, Justicia A, Fernadez-Egea E, Allas of cerebral networks precede recognition me in drug resistant epilepsy patients M, Safont G, Contreras F, Gascon J, memory deficits in early Parkinson›s who do not undergo epilepsy surgery. Soler-Insa PA, Menchon JM, Junque disease. NEUROIMAGE. 57:589-597. SEIZURE-EUR J EPILEP. 20:580-582. C, Keefe RSE. Spanish validation of the I.F.: 5.94. I.F.: 1.65. Brief Assessment in Cognition in Schi- zophrenia (BACS) in patients with schi- 9 Moreno-Lopez C, Santamaria J, Sala- 14 Rubi S, Setoain X, Donaire zophrenia and healthy controls. EUR mero M, DelSorbo F, Albanese A, Pellec- A, Bargallo N, Sanmarti F, Carreno PSYCHIAT. 26:69-73. I.F.: 3.37. chia MT, Barone P, Overeem S, Bloem B, M, Rumia J, Calvo A, Aparicio J, Aarden W, Canesi M, Antonini A, Duerr Campistol J, Pons F. Validation of 19 Palacios EM, Fernandez-Espejo S, Wenning GK, Poewe W, Rubino A, FDG-PET/MRI coregistration in D, Junque C, Sanchez-Carrion R, Meco G, Schneider SA, Bhatia KP, Djal- nonlesional refractory childhood Roig T, Tormos JM, Bargallo N, detti R, Coelho M, Sampaio C, Cochen epilepsy. EPILEPSIA. 52:2216-2224. Vendrell P. Diffusion tensor imaging V, Hellriegel H, Deuschl G, Colosimo C, I.F.: 3.96. differences relate to memory deficits Marsili L, Gasser T, Tolosa E. Excessive in diffuse traumatic brain injury. BMC Daytime Sleepiness in Multiple System 15 Lazaro L, Castro-Fornieles J, NEUROL. 11:-. I.F.: 2.80. Atrophy (SLEEMSA Study). ARCH NEU- Cullell C, Andres S, Falcon C, Calvo ROL-CHICAGO. 68:223-230. I.F.: 7.11. R, Bargallo N. A voxel-based mor- 20 Fernandez-Espejo D, Bekinschtein phometric MRI study of stabilized T, Monti MM, Pickard JD, Junque C, 10 Arenaza-Urquijo EM, Bosch B, obsessive-compulsive adolescent Coleman MR, Owen AM. Diffusion Sala-Llonch R, Sole-Padulles C, Junque patients. PROG NEURO-PSYCHOPH. weighted imaging distinguishes the C, Fernandez-Espejo D, Bargallo N, Rami 35:1863-1869. I.F.: 2.88. vegetative state from the minimally L, Molinuevo JL, Bartres-Faz D. Specific conscious state. NEUROIMAGE. Anatomic Associations Between White 16 Reig S, Parellada M, Castro-For- 54:103-112. I.F.: 5.94. Matter Integrity and Cognitive Reserve nieles J, Janssen J, Moreno D, Baeza in Normal and Cognitively Impaired El- I, Bargallo N, Gonzalez-Pinto A, Graell 21 Verger E, Valduvieco I, Caral L, Pu- ders. AM J GERIAT PSYCHIAT. 19:33-42. M, Ortuno F, Otero S, Arango C, jol T, Ribalta T, Vinolas N, Boget T, Olea- I.F.: 3.57. Desco M. Multicenter Study of Brain ga L, Blanco Y, Graus F. Does gender Volume Abnormalities in Children and matter in glioblastoma?. CLIN TRANSL 11 Iranzo A, Frauscher B, Santos H, Adolescent-Onset Psychosis. SCHI- ONCOL. 13:737-741. I.F.: 1.25. Gschliesser V, Ratti L, Falkenstetter T, ZOPHRENIA BULL. 37:1270-1280. Sturner C, Salamero M, Tolosa E, Poewe I.F.: 8.27. 22 Lima FPS, Lima MO, Leon D, W, Santamaria J, Hogl B. Usefulness of Lucareli PRG, Falcon C, Cogo JC, Bar- the SINBAR electromyographic montage 17 Rosa AR, Reinares M, Amann gallo N, Vidal J, Bernabeu M, Junque to detect the motor and vocal manifes- B, Popovic D, Franco C, Comes M, C. fMRI of the sensorimotor cortex in tations occurring in REM sleep behavior Torrent C, Bonnin CM, Sole B, Valenti patients with traumatic brain injury after disorder. SLEEP MED. 12:284-288. M, Salamero M, Kapczinski F, Vieta E. intensive rehabilitation. NEUROL SCI. I.F.: 3.43. Six-month functional outcome of a bi- 32:633-639. I.F.: 1.22.

239 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Neuropsychology

23 Zubiaurre-Elorza L, Soria-Pastor 29 Rametti G, Carrillo B, Gomez-Gil Marcos T. Estudio de la eficacia de S, Junque C, Segarra D, Bargallo N, E, Junque C, Segovia S, Gomez A, Gui- la rehabilitación cognitiva en el tras- Mayolas N, Romano-Berindoague llamon A. White matter microstructure torno depresivo mayor refractario al C, Macaya A. Gray matter volume in female to male transsexuals before tratamiento farmacológico. Sponso- decrements in preterm children with cross-sex hormonal treatment. A diffu- red by: Instituto de Salud Carlos III, periventricular leukomalacia. PEDIATR sion tensor imaging study. J PSYCHIATR PI09/90126. Duration: 01/01/2010- RES. 69:554-560. I.F.: 2.80. RES. 45:199-204. I.F.: 3.83. 31/12/2011.

24 Pardo BM, Garolera M, Ariza Bartres D. Relación entre variables de M, Pareto D, Salamero M, Valles V, ReViewS reserva cerebral de tipo ambientales Delgado L, Alberni J. Improvement i.f.: 3.82 y genéticas y la función y estructura of cognitive flexibility and cingulate cerebrales en el envejecimiento sano blood flow correlates after atypical 1 Popovic D, Reinares M, Amann B, y patológico. Sponsored by: Ministerio antipsychotic treatment in drug- Salamero M, Vieta E. Number needed de Ciencia e Innovación, 052296. Dura- naive patients with first-episode to treat analyses of drugs used for main- tion: 01/01/2010-31/12/2013. schizophrenia. PSYCHIAT RES-NEU- tenance treatment of bipolar disorder. ROIM. 194:205-211. I.F.: 2.06. PSYCHOPHARMACOLOGY. 213:657-667. Bartres D. Prediction of cognitive I.F.: 3.82. properties of new drug candidates for 25 Salazar F, Donate M, Boget T, neurodegenerative diseases in early Bogdanovich A, Basora M, Torres F, clinical development. Sponsored by: Fabregas N. Intraoperative warming eDitoRiAlS European Commission, IMI/115009. and post-operative cognitive dys- i.f.: 15.47 Duration: 01/01/2010-31/12/2015. function after total knee replacement. ACTA ANAESTH SCAND. 55:216-222. 1 Valenzuela M, Bartres-Faz D, Beg F, Junqué C. Alteraciones en la conecti- I.F.: 2.20. Fornito A, Merlo-Pich E, Muller U, Ongur vidad cerebral estructural y funcional D, Toga AW, Yucel M. Neuroimaging as relacionadas con el deterioro cognitivo 26 Ortiz-Gil J, Pomarol-Clotet E, endpoints in clinical trials: Are we there leve en la enfermedad de Parkinson. Salvador R, Canales-Rodriguez EJ, yet? Perspective from the first Provence Sponsored by: Ministerio de Ciencia e Sarro S, Gomar JJ, Guerrero A, workshop. MOL PSYCHIATR. 16:1064- Innovación, PSI2010-16174. Duration: Sans-Sansa B, Capdevila A, Junque 1066. I.F.: 15.47. 01/01/2011-31/12/2013. C, Mckenna PJ. Neural correlates of cognitive impairment in schizophrenia. BRIT J PSYCHIAT. 199:202-210. GRAntS foR ReSeARcH DoctoRAl tHeSeS I.F.: 5.95. in pRoGReSS Bartres-Faz D. Estudios miltimodales de 27 Bartres-Faz D, Arenaza-Urquijo Salamero M. Desarrollo y validación reesonancia magnética y de líquido cefa- EM. Structural and Functional Imaging en una nueva escala de somnolen- lorraquídeo en la enfermedad de Alzhei- Correlates of Cognitive and Brain cia de aplicación clínica. Sponsored mer preclínica familiar y esporádica. PhD Reserve Hypotheses in Healthy and by: Ministerio Sanidad y Consumo, student: Juan Fortea Ormaechea. Pathological Aging. BRAIN TOPOGR. PI070318. Duration: 26/11/2007- 24:340-357. I.F.: 3.29. 31/12/2012.

28 Rametti G, Carrillo B, Gomez- Junqué C. Ajuts de Suport als grups Gil E, Junque C, Zubiarre-Elorza L, de Recerca. Sponsored by: DAGAUR, Segovia S, Gomez A, Guillamon A. 2009SGR941. Duration: 01/01/2009- The microstructure of white matter in 31/12/2013. male to female transsexuals before cross-sex hormonal treatment. A DTI study. J PSYCHIATR RES. 45:949-954. I.F.: 3.83.

240 AReA 4

Clinical and experimental neuroscience

Systems neuroscience gROUP MeMBeRS

teAM leADeR Maria Victoria Sánchez Vives (icReA-iDiBApS) tel.: 93 227 5400 (ext. 4301) fax: 93 227 1890 e-mail: [email protected]

iDiBApS MeMBeRS: tecHniciAnS: Albert compte (iDiBApS) carolina Sales carbonell David Robbe (iDiBApS) perla kaliman (iDiBApS) collABoRAtoRS: Jaime de la Rocha (iDiBApS) Vanessa fernandez Descalzo ( iDiBApS) enrique pérez-Garci (iDiBApS) lorena pérez Méndez laura ciria poStDoctoRAl fellowS: luis Zapata (iDiBApS) Daniel perez Marcos (iDiBApS) Marcelina párrizas (iDiBApS) David Borland (iDiBApS) Mercè pallàs (ciBeRneD - uB) ilias Bergstrom (iDiBApS) Julita de la Vega (la caixa, iDiBApS) pavel Rueda-orozco (iDiBApS) thomas Gener (cRG) Alexander Roxin (iDiBApS) Guillermo uriretagoyena (iDiBApS) Rita Almeida (iDiBApS) klaus wimmer (iDiBApS) ViSitinG ScientiStS: lucila kargieman (iDiBApS) Maurizio Mattia francesca Barbieri (istituto Superiore di Sanità, Roma) Juan Abolafia (iDiBApS) Duane Q. nykamp Matteo Martini (iDiBApS) (univ. Minnesota, uSA) Gabriela Mochol

ReSeARcH fellowS: Maria cano colino Daniel Jercog Diego lópez pigozzi (iDiBApS) Maria pérez Zabalza (iDiBApS) Marcel Ruiz Mejias (iDiBApS) María Jesús Álvarez lópez (fi -AGAuR) Marco castro (iDiBApS) Juan pablo Ramírez Mahaluf Marta cosín-tomás (iDiBApS) Sofia Seinfeld (iDiBApS) nuria tort (iDiBApS) Beatriz Rebollo (iDiBApS) Ainhoa Hermoso Mendizabal

241 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Systems neuroscience

StrateGic 1. cortical networks and EVENt Lab oBjectiveS (Virtual Environments in Neuroscien- ce and technology). headed by Dr. Recently, the growing knowledge of Maria Victòria Sánchez (IDIBAPS) synaptic physiology and brain circuits, Neuronal connectivity and cellular and together with the development of synaptic properties determine and give new instruments with which to regis- shape to the emergent population acti- tools. We work in parallel at two levels: ter, analyze and model the activity of vity (spontaneous or invoked) generated on one hand, we model the activity of a large number of neurons has made by the neuronal networks. At the same the cortical microcircuit in order to unit possible to address one of the great time, such activity has effects upon the derstand and quantify the mechanisms pending challenges in neuroscien- network, with the regulation of relevant underlying the generation of population ce: to understand the relationship mechanisms such as synaptic plasticity. activity in the circuit, and on the other between the activity of the neuron We are interested in different aspects we study the physiological bases of population and behavioral perfor- of the activity generated: the mecha- cognitive capacities such as working me- mance. The objective of the systems nisms that regulate it, the information it mory and selective attention, and their neuroscience group is to address this encodes, and the consequences of this dysfunction in psychiatric disorders. challenge combining experimental activity upon the network. studies in basal ganglia, hippocampal The impact which the different cellular For further information: and cortical networks with a theoreti- processes (e.g., ion channels activation) http://complab.fcrb.es cal approach. have upon the resultant network activity tends to be non-intuitive and unpredicta- main lineS of ble – thus making it necessary to adopt 3. Physiology and basal ganglia net- reSearcH a not only theoretical but also experi- works and regulation with cannabi- mental approach. noids. headed by Dr. David Robbe • Electrical activity generation and As regards the information encoded by (IDIBAPS) control mechanisms in neuronal the network activity, we have worked The principal objective of the laboratory networks – specifically, in the brain with different sensory modalities (visual, is to understand the processing of cortex. tactile, auditory), and are presently espe- cognitive and motor-sensory (cortical) • Hippocampal and subicular mecha- cially interested in the spatial processing information in the basal ganglia - a group nisms of spatial processing. that occurs in the hippocampal complex. of subcortical nuclei that are essential • Neuronal activity synchronization me- Lastly, integration of the cortical informa- for motor coordination and the forma- chanisms in cortical networks. tion giving rise to bodily representation tion of habits, and which are implicated • Distributed cortical network mecha- and the combination of brain-computer in Parkinson’s disease and in addictions. nisms implicated in selective atten- interfaces and virtual reality for unders- Surprisingly, the excellent description tion, working memory and executive tanding these processes, is another of the anatomical characteristics of the control. research line of our group, as part of the basal ganglia (BG) has given rise to two • Simple motor coding (head move- EVENT Lab (http://www.event-lab.org). opposed reference models of proces- ment, lever activation) based on stria- sing carried out in the BG. In the first tal clustering. For further information: model, the BG have been modelled as • Mechanism of information transfer http://www.sanchez-vives.org independent information processing between networks. channels, while the other model postu- • Effect of cannabinoids on high-volta- lates that the ganglia act as cortical input ge axes. 2. theoretical neurobiology of the cor- integrators. In order to address this • Use of virtual reality in neuroscien- tical networks.headed by Dr. Albert controversy, we use large-scale electro- ce, in the context of theEVENT Lab compte (IDIBAPS) physiological recording techniques (silica (Virtual Environments in Neuros- Our research is aimed at clarifying the catheters, tetrodes) in the course of cience and Technology), in collabo- mechanisms that operate in the cortical specific motor activities, in combination ration with Mel Slater (University of microcircuit, with a view to conducting with advanced analytical tools and phar- Barcelona). computations of relevance to behavior. macological perturbation (cannabinoids). • Effect of behavioral interventions on The tools we use are computer-imple- the epigenetic regulation of proces- mented cortical network models seeking For further information: ses implicated in chronic diseases biological plausibility at all times, and http://neuro.fcrb.es/BasalGangLab/Ro- and related to aging. technically sophisticated data-analyzing bbeLab/Welcome.html

242 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience SySteMS neuRoScience

PUBLICATIONS original publications from 2009 to 2011 4. Neuroepigenetics lab. headed by Year IF Total Q 1 Q 2 Perla kaliman (IDIBAPS) 2009 29.99 6 3 0 It is now accepted that brain net- oRiGinAlS works and genetic information in i.f.: 16.04 2010 51.07 11 4 5 adults are both sensitive and respon- 2011 16.04 4 3 1 sive to experience. An increasing 1 Abolafia JM, Vergara R, Arnold number of studies in animal models MM, Reig R, Sanchez-Vives MV. are starting to show that behavioral Cortical Auditory Adaptation in the interventions can induce changes in Awake Rat and the Role of Potas- Commission, 230976. Duration: epigenetic codes in the nervous sys- sium Currents. CEREB CORTEX. 01/09/2008-31/08/2012. tem that may be critical for synaptic 21:977-990. I.F.: 6.84. plasticity and complex processes Sanchez-Vives MV. Dinámica such as memory, learning and stress 2 Szczepanski J, Arnold M, cortical en los diferentes estados resistance. In this context, our re- Wajnryb E, Amigo JM, Sanchez- de activación de la red. Sponso- search is aimed at identifying beha- Vives MV. Mutual information red by: Ministerio de Ciencia y vioral-induced molecular biomarkers and redundancy in spontaneous Tecnologia (MICINN), BFU2008- associated with adaptive psycholo- communication between cortical 01371/BFI. Duration: 01/01/2009- gical and physiological changes. Ac- neurons. BIOL CYBERN. 104:161- 31/12/2011. cordingly, we investigate the effect 174. I.F.: 1.67. of behavioral interventions (e.g. Robbe D. Entendiendo los efectos voluntary exercise and enriched en- 3 Ruiz-Mejias M, Ciria-Suarez L, de los canabinoides en los episo- vironment in rodents and meditation- Mattia M, Sanchez-Vives MV. Slow dios epilepticos en la red talamo- based trainings in humans) on the and fast rhythms generated in the cortical. Sponsored by: Ministerio epigenetic regulation of processes cerebral cortex of the anestheti- de Educación y Ciencia, BFU2008- such as oxidative stress and inflam- zed mouse. J NEUROPHYSIOL. 03946/BFI. Duration: 01/01/2009- mation, which are at the root of most 106:2910-2921. I.F.: 3.11. 31/12/2011. chronic and aging-related diseases. 3 Ledberg A, Robbe D. Locomo- Sanchez-Vives MV. Grups Conso- 5. cortical circuit Dynamics Group. tion-related oscillatory body mo- lidats de Recerca “Neurociencias headed by Dr. Jaime de la Rocha vements at 6-12 Hz modulate the de Sistemas”. Sponsored by: (IDIBAPS) hippocampal theta rhythm. PLoS AGAUR, 2009 SGR1363. Duration: The main focus of our research is One. 6(11):e27575. I.F.: 4.41 01/01/2009-31/12/2013. the study of the circuit mechanisms underlying perception and decision Compte A. Mecanismos de re- making. In particular we are interes- ReViewS des distribuidas en memoria ted in the neural basis of auditory re- i.f.: 9.00 de trabajo y atención selectiva. presentation and its dependence on Sponsored by: Ministerio de Edu- brain state and other contextual varia- 1 Kaliman P, Parrizas M, Lalanza cación, BFU2009_09537. Duration: bles. We investigate the generation JF, Camins A, Escorihuela RM, 01/01/2010-31/12/2012. of ongoing cortical activity, its impact Pallas M. Neurophysiological and on perception and guiding decisions. epigenetic effects of physical Sanchez-Vives MV. BEAMING: We are particularly interested in the exercise on the aging process. Being through augmented media variability and co-variability observed AGEING RES REV. 10:475-486. for natural networked gatherings. in the sensory-evoked responses of I.F.:9.00. Sponsored by: European Commis- cortical neurons, the mechanisms sion, 248620. Duration: 01/01/2010- which generate them and their role in 31/12/2013. a neural code. We combine popula- GRAntS foR ReSeARcH tion cortical recordings in rats, quanti- in pRoGReSS Sanchez-Vives MV. VERE: Virtual tative analysis and computational mo- Embodiment and Robotic Re-Em- deling to address these questions. Robbe D. Dynamic of neuronal bodiment. Sponsored by: European network interactions in the basal Commission, 257695. Duration: For further information: ganglia. Sponsored by: European 01/06/2010-31/05/2015. http://neuro.fcrb.es/delaRochaLab

243 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Systems neuroscience

Robbe D. Basal Ganglia and the Compte A. Investigating the neural control of locomotion. Sponso- mechanisms of feature-based and red by: European Commission, spatial attention. Sponsored by: 253873. Duration: 01/10/2010- European Commission, CE-FP7- 30/09/2012. PEOPLE-IEF-10 275800. Duration: 01/06/2011-31/05/2013. De La Rocha J. Network dynamics of auditory cortex and the impact Perez E. Propiedades computacio- of correlations on the encoding of nales de las dendritas durante la sensory information. Sponsored actividad cortical lenta (< 1 Hz) y su by: European Commission, FP7- modulación por los sistemas activa- PEOPLE-IRG-10_01. Duration: dores colinérgicos. Sponsored by: 01/09/2010-31/08/2014. Ministerio de Ciencia e Innovación, MICINN_PN10 SAF2010-18884. Du- Sanchez-Vives MV. MELOMICS: ration: 01/01/2011-31/12/2013. Optimización de la respuesta terapéutica a la modulación de es- tímulos auditivos. Sponsored by: DoctoRAl tHeSeS Ministerio Ciencia e Innovación, INNPACTO IPT-300000-2010-0010. Sanchez-Vives MV. Neuronal basis Duration: 22/06/2010-31/12/2013. of auditory adaptation and temporal discrimination in the auditory cortex Kaliman P. Physical exercise and of the awake freely moving rat. aging: transcriptional and epige- PhD student: Juan Manuel Abolafia netic effects in and accelerated Moya. aging mouse model. Sponsored by: Ministerio de Ciencia y Tecno- Sanchez-Vives MV. Modulation of logía, SAF2010-15050. Duration: spatial processing by somatosen- 01/01/2010-31/12/2013. sory inputs in the rat. PhD student: Thomas Gener. Kaliman P. Wisconsin Center for the Neuroscience and Psycho- physiology of Meditation. Spon- sored by: University of Wisconsin Madison, Office of Research and Sponsored Programs, U.WISC_ KALIMAN. Duration: 01/01/2011- 30/06/2012.

De La Rocha J. Dinámica esto- cástica de los circuitos corticales y representación sensorial. Spon- sored by: Ministerio de Educación y Ciencia (MICINN), SAF2010- 15730. Duration: 01/01/2011- 31/12/2013.

244 AReA 4

Team involved in: Clinical and experimental neuroscience

Clinical and experimental neuroimmunology gROUP MeMBeRS

teAM leADeR francesc Graus (Hospital clínic) tel.: 93 227 57 85 fax: 93 227 57 83 e-mail: [email protected]

iDiBApS MeMBeRS: ion Agirrezabal (fiS) nuRSinG StAff: pablo Villoslada (iDiBApS) Anna Boronat (fiS) Montserrat Artola (ReeM, Beatriz Moreno (iDiBApS) Sara llufriu (iDiBApS) Red española esclerosis Múltiple) núria de la iglesia (iDiBApS) francesco Mannara (fundació clínic) lidia Sabater (fundació clínic) Marta Moreno (fpi) ADMiniStRAtiVe StAff: Albert Saiz (Hospital clínic) iñigo Gabilondo (iDiBApS) Gemma castillo (fundació clínic) yolanda Blanco (Hospital clínic) Sara Martínez (iDiBApS) eva Valero (ReeM) Josep Dalmau (icReA-iDiBApS) laura planas (ReeM) tecHniciAnS: Maria Rodés (iDiBApS) poStDoctoRAl fellowS: Begoña fernández (iDiBApS) Begonya otal (iDiBApS) Alice taubes (iDiBApS) collABoRAtoRS: Valeria colafrancesco (iDiBApS) nagore escala (iDiBApS) Myrna Rosenfeld (iDiBApS) nuria Gresa (iDiBApS) Mercè Albà (fundació clínic) Santiago ortiz (Hospital clínic) eva caballero (fundació clínic) Ana catafau (iDiBApS) ReSeARcH fellowS: esther Aguilar (iDiBApS) Bernardo Sanchez-Dalmau inna pertsovskaya (iDiBApS) elena fraga (iDiBApS) (Hospital clínic) oihana errea (iDiBApS) Alice Abernathy (iDiBApS)

245 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Clinical and experimental neuroimmunology

StrateGic oBjectiveS

1. The principal objective of the neuroimmunology group is the study of inflammation of the central nervous system, and of the mechanisms that are involved in this inflammatory response, and their implication in neurological disorders - fundamentally multiple sclerosis, autoimmune encephalitis and paraneoplastic neurological disorders. 2. Identification and characterization of factors implicated in the pathogenesis of gliomas, based on the study of proteins that control the maintenance, differentiation and migration Automatic segmentation of the corpus callosum through diffusion tensor imaging and 3D-T1 imaging using FSL software. In this way it is possible of normal neural stem cells. to determine the volumetric characteristics of this structure, which is frequently altered in multiple sclerosis. Accepted for the 17th Annual Mee- ting of the Organization for Human Brain Mapping (Quebec, June 2011). main lineS of reSearcH

1. Study of autoimmune mechanisms 4. Functional imaging in in paraneoplastic neurological di- neuroimmunology. sorders. 5. Study of the molecular bases of 2. Synaptic autoimmunity study in glioma pathogenesis: Identificati- encephalitis and other autoimmune on and functional characterization diseases of the central nervous of new factors implicated in the system. maintenance, differentiation and/ 3. Development of biomarkers and or migration of neural stem cells, new therapies in application to mul- and study of the role of these fac- tiple sclerosis and other neurological tors in the initiation and invasion diseases. of gliomas.

246 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience clinicAl AnD eXpeRiMentAl neuRoiMMunoloGy

ReSeARCh gROUP ReSeARCh gROUP patHoGeneSiS and new treatmentS autoimmunity aGainSt Synaptic antiGenS in multiple ScleroSiS Group Leader: Josep Dalmau (IDIBAPS) Group Leader: Pablo Villoslada (IDIBAPS)

Our research is focused on a group of di- The great challenge for our research team is to sorders at the intersection of autoimmunity, apply our discoveries to the clinical management cancer and synaptic proteins. This includes the of patients with multiple sclerosis. By late 2010 description of novel syndromes and associated we plan to enter the clinical phase of the study of methylthio- immune-mechanisms, isolation of the target antigens and de- adenosine as treatment in cases of multiple sclerosis. velopment of diagnostic tests and treatment strategies. These As the coordinating team of the RETICS REEM (Spanish Multi- studies have identified 17 auto-antigens and have generated a ple Sclerosis Network - www.reem.es), another of our strategic number of diagnostic tests, some of which are used worldwide. objectives is the transverse diffusion of knowledge and opti- In the last 5 years, we have discovered a new category of mum use of synergies, with a view to transferring the advances autoimmune disorders which affect memory, behavioural and in research to the clinical practice setting and to patients. cognitive functions and can cause psychosis. These disorders Lastly, the group has a constant commitment to innovation, are associated with autoimmune responses characterised by both in terms of the generation of patents and as regards the antibodies against synaptic receptors and proteins, such as the creation of spin-off companies to cover the gap in financing glutamate receptors (NMDA, AMPA) or GABA(B) receptors, or existing between basic research and the clinical phase devel- against synaptic proteins related to epilepsy (LGI1, Caspr2). opment of new drugs on the part of the biopharmaceutical Once the antigens are identified, our studies focus on identi- industry. fying the cellular and molecular mechanisms by which the antibodies alter the function of the synaptic receptors and proteins, thereby causing symptoms. The results of these studies have had an impact on many different medical and neuroscience dis- eMeRgeNT gROUP ciplines, providing a link between immunological processes and Glioma and neural Stem cell Group neuronal functions involved in memory, behaviour, psychosis, epilepsy and neuronal degeneration. Group Leader: Nuria De La Iglesia (IDIBAPS)

Our research group is devoted to applying developmental neurobiology knowledge to ReSeARCh gROUP the study of gliomas, some of the most ag- immunopatHoGeneSiS of paraneoplaStic gressive human tumors. Gliomas arise from neuroloGical diSorderS a rare subpopulation of cells which have stem-like properties Group Leader: Francesc Graus such as self-renewal, multipotency and the ability to initiate (hospital clínic) a tumor upon serial transplantation. These so-called glioma initiating cells (GIC) share specific properties with neural stem cells (NSC), including the localization to specialized microenvi- Paraneoplastic neurological disorders manifest in ronments within the brain that support their maintenance. This cancer patients generally in very early stages, and suggests that factors involved in either NSC maintenance or their correct diagnosis is essential for detecting the tumor and for differentiation are likely to contribute to the pathogenesis of preventing progression of the neurological disease. Our group has gliomas. made a fundamental contribution to confirmation of the immuno- Our main lines of research are: logical cause of these disorders, and is an international reference • Identification and characterization of new factors involved center for the evaluation of antineuronal antibodies associated to in NSC maintenance and differentiation, with a special paraneoplastic neurological disorders. The group is interested in emphasis on factors that mediate the localization of NSC to the characterization of antineuronal antibodies and corresponding their niches. antigens of potential diagnostic or pathogenic relevance in relation • Functional characterization of the factors identified above in to these diseases. Some of the antibodies identified by our group, the initiation, maintenance and invasiveness of gliomas. such as anti-Hu, anti-Tr or anti-SOX1, are currently used on a rou- • Design of new, alternative therapies for gliomas. tine basis as predictors of paraneoplastic neurological disorders.

247 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Clinical and experimental neuroimmunology PUBLICATIONS

oRiGinAlS Kornblum C, Bien CG, Honnorat J, 11 Blanco Y, Ercilla-Gonzalez i.f.: 139.97 Wong S, Xu J, Contractor A, Balice- G, Llufriu S, Casanova-Estruch B, Gordon R, Dalmau J. Antibodies to Magraner MJ, Ramio-Torrenta L, 1Abraira V, Alvarez-Cermeno JC, metabotropic glutamate receptor 5 in Mendibe-Bilbao MD, Ucles-Sanchez Arroyo R, Camara C, Casanova B, the Ophelia syndrome. NEUROLOGY. AJ, Casado-Chocan JL, DeMunain Cubillo S, DeAndres C, Espejo C, 77:1698-1701. I.F.: 8.02. AL, Ramo-Tello C, Santos-Lasaosa S, Fernandez O, Ferrer J, Figueredo Porras RFB, Segura-Bruna N, Sepul- MA, Garcia-Merino A, Garcia- 6 Mas N, Saiz A, Leite MI, Waters P, veda-Gazguez M, Villoslada P, Graus Sanchez MI, Garcia-Trujillo JA, Baron M, Castano D, Sabater L, Vin- F, Saiz A. HLA-DRB1 typing in Cau- Gomez M, Gonzalez-Oria C, Gosis cent A, Graus F. Antiglycine-receptor casians patients with neuromyelitis A, Izquierdo G, Jimenez J, Lopez- encephalomyelitis with rigidity. J optica. REV NEUROLOGIA. 53:146- Trascasa M, Montalban X, Moreno NEUROL NEUROSUR PS. 82:1399- 152. I.F.: 1.22. MJ, Munoz D, Nunez V, Muriel A, 1401. I.F.: 4.79. Navarro J, Olascoaga J, Oreja-Gue- 12 Brell M, Castaner S, Pujol-Farre vara C, Prada A, Ramil E, Ramo- 7 Vigliani MC, Honnorat J, Antoine T, Boluda S, Ribalta T, Bruna J, Mar- Tello C, Rodriguez C, Rodriguez E, JC, Vitaliani R, Giometto B, Psimaras tinez M, Verger E, Villa S, Vinolas N, Rodriguez-Frias F, Rodriguez-An- D, Franchino F, Rossi C, Graus F. Cho- Gil M, Graus F, Tortosa-Moreno A. tiguedad A, Rodriguez-Molina JJ, rea and related movement disorders Implication of radiological pattern Ruiz E, Saiz A, Sarasola E, Simo M, of paraneoplastic origin: the PNS in the prognosis of oligodendroglial Yague J, Villar LM. Utility of oligo- EuroNetwork experience. J NEUROL. tumors: correlation with genetic pro- clonal IgG band detection for MS 258:2058-2068. I.F.: 3.85. file. REV NEUROLOGIA. 52:465-471. diagnosis in daily clinical practice. I.F.: 1.22. J IMMUNOL METHODS. 371:170- 8 Boronat A, Sabater L, Saiz A, Dal- 173. I.F.: 2.34. mau J, Graus F. GABA(B) receptor 13 Lancaster E, Huijbers MGM, antibodies in limbic encephalitis and Bar V, Boronat A, Wong A, Martinez- 2 Gaig C, Valldeoriola F, Gelpi E, anti-GAD-associated neurologic di- Hernandez E, Wilson C, Jacobs D, Ezquerra M, Llufriu S, Buongiorno sorders. NEUROLOGY. 76:795-800. Lai M, Walker RW, Graus F, Bataller M, Rey MJ, Marti MJ, Graus F, To- I.F.: 8.02. L, Illa I, Markx S, Strauss KA, Peles losa E. Rapidly Progressive Diffuse E, Scherer SS, Dalmau J. Investi- Lewy Body Disease. MOVEMENT 9 Oyanguren-Desez O, Rodriguez- gations of Caspr2, an Autoantigen DISORD. 26:1316-1323. I.F.: 4.48. Antiguedad A, Villoslada P, Domercq of Encephalitis and Neuromyoto- M, Alberdi E, Matute C. Gain-of- nia. ANN NEUROL. 69:303-311. 3 Verger E, Valduvieco I, Caral L, function of P2X7 receptor gene I.F.: 10.75. Pujol T, Ribalta T, Vinolas N, Boget variants in multiple sclerosis. CELL T, Oleaga L, Blanco Y, Graus F. CALCIUM. 50:468-472. I.F.: 3.55. 14 Sepulcre J, Peraita H, Goni J, Does gender matter in glioblas- Arrondo G, Martincorena I, Duque toma?. CLIN TRANSL ONCOL. 10 Sawcer S, Hellenthal G, Pirinen B, DeMendizabal NV, Masdeu JC, 13:737-741. I.F.: 1.25. M, Spencer CCA, Patsopoulos NA, Villoslada P. Lexical access chan- Moutsianas L, Dilthey A, Su Z, Free- ges in patients with multiple scle- 4 Gabilondo I, Saiz A, Galan L, man C, Hunt SE, Edkins S, Gray E, rosis: A two-year follow-up study. Gonzalez V, Jadraque R, Sabater L, Booth DR, Potter SC, Goris A, Band J CLIN EXP NEUROPSYC. 33:169- Sans A, Sempere A, Vela A, Villalo- G, Oturai AB, Strange A, Saarela J, 175. I.F.: 1.81. bos F, Vinals M, Villoslada P, Graus Bellenguez C, Fontaine B, Gillman F. Analysis of relapses in anti-NM- M, Hemmer B, Gwilliam R, Zipp F, 15 DeMendizabal NV, Carneiro J, DAR encephalitis. NEUROLOGY. Jayakumar A, Martin R, Leslie S, Sole RV, Goni J, Bragard J, Marti- 77:996-999. I.F.: 8.02. Hawkins S, et al. (Villoslada P) Ge- nez-Forero I, Martinez-Pasamar S, netic risk and a primary role for cell- Sepulcre J, Torrealdea J, Bagnato 5 Lancaster E, Martinez-Her- mediated immune mechanisms in F, Garcia-Ojalvo J, Villoslada P. nandez E, Titulaer MJ, Boulos M, multiple sclerosis. NATURE. 476:214- Modeling the effector - regulatory Weaver S, Antoine JC, Liebers E, 219. I.F.: 36.10. T cell cross-regulation reveals the

248 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience clinicAl AnD eXpeRiMentAl neuRoiMMunoloGy

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 31.12 6 5 1 intrinsic character of relapses in 22 DeMiras JR, Navas J, Villos- Multiple Sclerosis. BMC SYST lada P, Esteban FJ. UJA-3DFD: 2010 98.76 19 11 4 BIOL. 5:-. I.F.: 3.57. A program to compute the 3D 2011 139.97 24 12 5 fractal dimension from MRI data. 16 Panzer J, Dalmau J. Movement COMPUT METH PROG BIO. disorders in paraneoplastic and 104:452-460. I.F.: 1.24. autoimmune disease. CURR OPIN NEUROL. 24:346-353. I.F.: 5.02. 23 Villa S, Weber DC, Moreto- nes C, Manes A, Combescure C, GRAntS foR ReSeARcH 17 Titulaer MJ, Soffietti R, Dal- Jove J, Puyalto P, Cuadras P, Bru- in pRoGReSS mau J, Gilhus NE, Giometto B, na J, Verger E, Balana C, Graus Graus F, Grisold W, Honnorat J, F. Validation of the new graded Villoslada P. Análisis de la respuesta Smitt PAES, Tanasescu R, Vedeler prognostic assessment scale for al tratamiento con interferon beta CA, Voltz R, Verschuuren JJGM. brain metastases: a multicenter en la esclerosis múltiple mediante Screening for tumours in paraneo- prospective study. RADIAT ON- biología de sistemas. Sponsored by: plastic syndromes: report of an COL. 6:-. I.F.: 2.41. Fundación de Investigación Médica EFNS Task Force. EUR J NEUROL. Mutua Madrileña, 08/458. Duration: 18:19-E3. I.F.: 3.77. 24 Cavanillas ML, Fernández 05/12/2008-04/12/2011. O, Comabella M, Alcina A, Fedetz 18 Briani C, Vitaliani R, Grisold W, M, Izquierdo G, Lucas M, Cenit Villoslada P. Red Española de Esclero- Honnorat J, Graus F, Antoine JC, MC, Arroyo R, Vandenbroeck K, sis Múltiple. Sponsored by: Instituto Bertolini G, Giometto B. Spectrum Alloza I, Garcia-Barcina M, Anti- de Salud Carlos III - Fondo de Investi- of paraneoplastic disease associa- guedad A, Leyva L, Gomes CL, gaciones Sanitarias, RD07/0060/0000. ted with lymphoma. NEUROLOGY. Olascoaga J, Otaegui D, Blanco Duration: 10/02/2009-31/12/2012. 76:705-710. I.F.: 8.02. Y, Saiz A, Montalban X, Matesanz F, Urcelay E. Replication of top Villoslada P. United europeans for the 19 Moreno B, Jukes JP, Vergara- markers of a genome-wide asso- development of pharmacogenomics Irigaray N, Errea O, Villoslada P, Perry ciation study in multiple sclerosis in multiple sclerosis. Sponsored by: VH, Newman TA. Systemic inflam- in Spain. GENES INMUN. 12:110- European Comisión. Marie Curie mation induces axon injury during 115. I.F.: 4.37. Training Network ,PITN-GA- 212877. brain inflammation. ANN NEUROL. Duration: 15/09/2008-15/09/2011. 70:932-942. I.F.: 10.75. ReViewS Villoslada P. Estudio del daño axonal 20 Colafrancesco V, Villoslada P. i.f.: 6.51 en esclerosis múltiple mediante Targeting NGF-pathway for develo- estudios de neuroimagen de la vía ping neuroprotective therapies for 1 Bosch X, Saiz A, Ramos-Casals óptica. Sponsored by: Instituto de Sa- multiple sclerosis and other neuro- M. Monoclonal antibody therapy-as- lud Carlos III, PS09/00259. Duration: logical diseases. ARCH ITAL BIOL. sociated neurological disorders. NAT 01/01/2010-31/12/2012. 149:183-192. I.F.: 0.78. REV NEUROL. 7;165-172. I.F.: 6.51 Graus F. Anticuerpos contra de an- 21 D’intino G, Lorenzini L, Fernan- tígenos de membrana neuronal en dez M, Taglioni A, Perretta G, DelVec- MulticentRicS síndormes neurológicos paraneoplá- chio G, Villoslada P, Giardino L, Calza i.f.: 10.75 sicos del sistema nervioso central. L. Triiodothyronine Administration Sponsored by: Instituto de Salud Ameliorates the Demyelination/Re- 1 Comi G, Cohen JA, Arnold DL, Carlos III (ISCIII), PI09/0193. Duration: myelination Ratio in a Non-Human Wynn D, Filippi M, ForteStudy 01/01/2010-31/12/2012. Primate Model of Multiple Sclerosis GROUP. Phase III dose-comparison by Correcting Tissue Hypothyroidism. study of glatiramer acetate for Villoslada P. Studying the relapsing dyna- J NEUROENDOCRINOL. 23:778-790. multiple sclerosis. ANN NEUROL. mics of major depression through net- I.F.: 4.65. 69:75-82. I.F.: 10.75. work analysis of fMRI connectivity maps:

249 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Clinical and experimental neuroimmunology

inplications for therapy. Sponsored by: Saiz A. Trasplante autólogo de Villoslada P. Desarrollo de terapias neu- Fundació La Marató de TV3, 091430. células madre mesenquimales en roprotectoras para Esclerosis Múltiple. Duration: 29/01/2010-28/01/2013. esclerosis múltiple: ensayo clínico Sponsored by: MICINN_INNPACTO11, fase II aleatorizado, doble-ciego y IPT-2011-1312-900000. Duration: De La Iglesia N. Factores de man- cruzado con placebo. Sponsored by: 04/05/2011-31/12/2013. tenimiento y diferenciación de cé- Ministerio de Sanidad, Política So- lulas madre neurales como actores cial e Igualdad, TRA-066. Duration: Villoslada P. STOP-ELA: Aproximación principales en la patogénesis de los 01/01/2010-31/12/2011. multi-tecnológica para el desarrollo de gliomas. Sponsored by: Ministerio nuevas terapias y sistemas. Sponsored de Educación, BFU2009_14616. Dalmau J. Paraneoplasic Disorders by: MICINN_INNPACTO11, IPT-2011- Duration: 01/01/2010-31/12/2012. of CNS: Autoantigen. Sponsored by: 1091-900000. Duration: 20/09/2008- National Institutes of Health (NIH), 31/12/2012. Villoslada P. Terapia neuroprotectora NINDS 9RO1NS077851-05A2 (pre- para EM mediante agonistas del viously RO1CA107192). Duration: Villoslada P. Congreso Internacional de Factor de Crecimiento Nervioso 01/04/2004-31/07/2016. Neuroinmunología. Sponsored by: MI- (NGF). Sponsored by: Ministerio CINN_AccCompl10 SAF2010-09238-E. de Educación, INC-0059. Duration: Dalmau J. Caspr2, lgi-1 and novel an- Duration: 1/6/2010-30/4/14. 01/01/2010-31/12/2011. tigen autoimmunity in neuropsychiatric dysfunction. Sponsored by: NIMH, Dalmau J, Nath A. Treatment of anti- Villoslada P. Congreso Internacional Eureka, 1RO1MH094741. Duration: NMDA receptor encephalitis. Sponso- de Neuroinmunología. Sponsored 01/08/2011-30/04/2015. red by: NIH Beside to Brench Program. by: Ministerio de Ciencia e Innova- Duration: 1/5/12-30/4/14. ción, SAF2010-09238-E. Duration: Dalmau J. Cellular, synaptic, and 01/06/2010-31/05/2011. circuit mechanisms of autoimmune anti-glutamate receptor disorders of Graus F, Dalmau J. Clinical spec- memory and cognition. Sponsored trum and cellular and synaptic me- by: MCKNIGHT FOUNDATION. Du- chanisms of autoimmune synaptic ration: 01/02/2010-31/01/2013. encephalitides. Sponsored by: Fun- dació La Marató de TV3, 101530. Dalmau J. Immunity to brain Ma Duration: 10/12/2010-09/12/2013. proteins: A remote effect of cancer. Sponsored by: National Institutes of Saiz A. Analysis of new antigens Health (NIH), NCI, 2RO1CA89054- in seronegative (NMO-IgG/AQP4) 06A2. Duration: 01/12/2000- neuromyelitis optica (Devic disea- 31/05/2013. se). Sponsored by: Fundació La Marató de TV3, 101610. Duration: Dalmau J. Synaptic autoimmunity in 10/12/2010-09/12/2013. disorders of memory behavior, cognition and psychosis. Sponsored by: Mahy N, Villoslada P. Nuevas NINDS/NIH ARRA Challenge Award, aproximaciones terapéuticas para IRCINS068204. Duration: 30/09/2009- la Esclerosis Múltiple y la Escle- 31/08/2012. rosis Lateral Amiotrófica: efectos modificadores de la enfermedad Villoslada P. Congress of the Interna- y neuroprotección. Sponsored by: tional Society of Neuroimmunology Ministerio de Ciencia e Innovación (ISNI). Sponsored by: Generalitat de - ADVANCELL -Advanced in vitro Catalunya, AGAUR, AGAUR_ARCS10 celltechno. IPT-010000-2010-0035. 2010 ARCS1 00329. Duration: Duration: 25/06/2010-31/12/2012. 26/10/2010-04/05/2012.

250 AReA 4

Team involved in: Clinical and experimental neuroscience

Neurobiology Unit gROUP MeMBeRS

teAM leADeR Ramon trullàs (iiBB-cSic) tel.: 93 363 83 03 fax: 93 363 83 01 e-mail: [email protected]

iDiBApS MeMBeRS: tecHniciAnS: nicole Mahy (uB) carmen Andrade (uB) Manuel Rodríguez (uB) nuria Serra (iiBB-cSic)

ReSeARcH fellowS: collABoRAtoRS: Javier ortega (uB) Marco pugliese (uB) Joana figueiro-Silva (iiBB-cSic) petar podlesniy (iDiBApS) Margot Martínez (iDiBApS) José Manuel Vidal-taboada (uB) Alan lópez (iDiBApS) Anna Gieryng (iDiBApS) iván cester (iDiBpAS)

251 CLINICAL AND exPeRIMeNTAL NeUROSCIeNCe Neurobiology Unit

StrateGic 3. Study of the mechanism by which support the hypothesis that regulation oBjectiveS the KATP channel modulates micro- of NP1 expression could be a target glial activation, thereby allowing the for therapeutic intervention, since it The Neurobiology Unit investigates in vivo and in vitro characterization effectively halts the neurodegeneration molecular mechanisms of excitotoxic of the neuroprotective and neuro- in Alzheimer’s Disease. Additionally, and apoptotic neuron death with the toxic effect of microglia in various we have developed a new differential objective of identifying new thera- neurological disorders, through proteomic analysis method by which we peutic targets for the management of the activation and blockade of this analysed samples of cerebrospinal fluid neurodegenerative diseases. Another channel. from subjects in the preclinical stage objective is to gain knowledge of the 4. Investigation of the role of the glia of Alzheimer’s Disease and from pre- mechanisms regulating neurogenesis in in the neurogenesis mechanisms symptomatic carriers of pathogenic mu- the adult brain. associated with chronic neurodege- tations on PSEN1, and compared them neration in the hippocampus of the with samples from patients diagnosed main lineS adult brain. with Alzheimer’s Disease. The aim of of reSearcH 5. Investigation of the efficacy and sa- these studies is to establish a specific fety of anti-A beta immunotherapy as profile for protein levels in cerebrospinal 1. Identify new biomarkers for early treatment for Alzheimer’s disease. fluid which would enable the preclinical detection of Alzheimer’s disease in diagnosis of Alzheimer’s Disease. the preclinical phase, using a new Results from the first two lines of In our studies into the role of the KATP method of differential proteomic research obtained in the last year channel in the modulation of microglia analysis. demonstrate that the mitochondrial activity, using a murine model of multiple 2. Investigation of the function of fragmentation occurring during the sclerosis and a rat model of excitotoxic neuronal pentraxin 1 (NP1) during neurodegenerative process is caused hippocampal damage, we found that programmed neuron death, with by NP1. We have also confirmed that chronic activation of the microglial KATP the hypothesis that inhibition of the NP1 regulates the transport of mito- channel reduces the pro-inflammatory expression of this protein may cons- chondria to the synaptic terminals and activity of the microglia, with significant titute a new treatment for chronic that this effect is independent of the general inhibition of the release of inflam- neurodegenerative disorders. pro-apoptotic protein BAX. These results matory factors, such as TNF-alpha and interleukin-1 beta and NO. This ultimately means a reduction in neuronal damage and a slowing down of the neurodegenerative process started in both models. We have also demonstrated that the KATP channel plays a central role in the control of the microglial reaction which follows ischaemia in tMCAO rats and we identified the microglia as a potent regulator of neuron survival in the first phases of cerebral stroke.

Confocal microscopic image of a hippocampal neuron isolated in culture showing the neuronal pentraxin 1 (green) and the KCNQ2 potassium channel (red) in the growth cone. Joana Figueiró-Silva, Petar Podlesniy and Ramón Trullas.

252 AReA 4 clinicAl AnD eXpeRiMentAl neuRoScience neuRoBioloGy unit

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 oRiGinAlS GRAntS foR ReSeARcH 2009 6.61 2 1 1 i.f.: 11.11 in pRoGReSS 2010 16.78 4 2 2 2011 11.11 2 1 0 1 Virgili N, Espinosa-Parrilla JF, Mahy N. Grup de Neuroquímica FM. Mancera P, Pasten-Zamorano A, Gi- Sponsored by: AGAUR (Generalitat de meno-Bayon J, Rodriguez MJ, Mahy Catalunya), 2009SGR1380. Duration: N, Pugliese M. Oral administration of 01/01/2009-31/12/2012. the K-ATP channel opener diazoxide ameliorates disease progression in a Mahy N, Villoslada P. Nuevas murine model of multiple sclerosis. J aproximaciones terapéuticas para NEUROINFLAMM. 8:-. I.F.: 5.79. la Esclerosis Múltiple y la Escle- rosis Lateral Amiotrófica: efectos 2 Minano-Molina AJ, Espana J, modificadores de la enfermedad Martin E, Barneda-Zahonero B, y neuroprotección. Sponsored by: Fado R, Sole M, Trullas R, Saura Ministerio de Ciencia e Innovación - CA, Rodriguez-Alvarez J. Soluble ADVANCELL -Advanced in vitro cell Oligomers of Amyloid-beta Peptide techno. IPT-010000-2010-0035. Du- Disrupt Membrane Trafficking of ration: 25/06/2010-31/12/2012. alpha-Amino-3-hydroxy-5-methyli- soxazole-4-propionic Acid Receptor Trullas R. Potenciación de la neuro- Contributing to Early Synapse Dys- génesis mediante la modulación de function. J BIOL CHEM. 286:27311- la actividad microglial. Sponsored by: 27321. I.F.: 5.33. Ministerio de Ciencia e Innovación, SAF2008-01902. Duration: 01/01/2009- 31/12/2011.

Mahy N. STOP-ELA: aproximación multi-tecnológica para el desarrollo de nuevas terapias y sistemas avanza- dos de administración farmacológica para la esclerosis lateral amiotrófica. Sponsored by: Ministerio de Ciencia e Innovación, IPT-2011-1091-900000. Du- ration: 25/06/2011-31/12/2013.

253

AReA 5

Oncology and haematology

Biological markers in oncology StrateGic oBjectiveS gROUP MeMBeRS The group focuses mainly on applied clinical research and works in collaboration with different clinical groups both within and outside Hospital Clínic de Barcelona. teAM leADeR Rafael Molina main lineS of (Hospital clínic - uB) reSearcH tel.: 93.227.54.00 e-mail: [email protected] 1. circulating tumor markers. Deve- lopment of new techniques for the xxxxxx iDiBApS MeMBeRS: study of biological markers, which Xavier filella (Hospital clínic) are the peripheral expression of the presence of malignant tumors. ReSeARcH fellowS: Study of the usefulness of proPSA José María Auge fradera in the diagnosis of prostate cancer. (fundació clínic) Evaluation of new tumor markers such as: epididymal protein HE4, of tecHniciAnS: great interest in ovarian cancer; and Alba Roset (fundació clínic) PCA3 in urine in prostate cancers.

collABoRAtoRS: 2. consolidation of diagnostic guides f. coca (Hospital clínic) to the clinical use of tumor mar- Amàlia lafuente (uB) kers. Collaboration with European M. portas (Hospital clínic) and North American groups for es- S. Román (Hospital clínic) tablishing consensus and publishing M. Sasot (Hospital clínic) clinical guides. Diffusion of these gui- Jose M. escudero (Hospital clínic) des at national level through the Can- cer Biological Markers Commission, created by members of the group, within the scientific committee of the Spanish Society of Biochemistry and Molecular Pathology.

3. Introduction of a technique for the detection of the PcA3 antigen by detection of mRNA in urine. Evaluation of the clinical interest in this methodology and its application in the diagnosis of prostate cancer and in the reduction in the number of unnecessary prostate biopsies.

4. collaboration in the colon and rectal cancer population screening program through the detection of occult blood in stools. During the last year over 15,000 asymptomatic individuals have been analyzed.

256 AReA 5 oncoloGy AnD HAeMAtoloGy BioloGicAl MARkeRS in oncoloGy

PUBLICATIONS original publications from 2009 to 2011 5. Evaluation and confirmation Year IF Total Q 1 Q 2 of the efficacy of a computer 2009 38.51 8 6 1 program for establishing risk oRiGinAlS 20.19 4 2 1 in patients with symptoms su- i.f.: 26.71 2010 ggestive of lung cancer which 2011 26.71 6 4 2 assesses risk on the basis of 6 1 DeLarrea CF, Tovar N, Cibeira MT, tumour markers and points to Arostegui JI, Rosinol L, Elena M, Fi- the histological type (small cell lella X, Yague J, Blade J. Emergence or non-small-cell). An added fea- of oligoclonal bands in patients with 6 Molina R, Alvarez E, Aniel-Quiroga ture has been introduced to enable multiple myeloma in complete remis- A, Borque M, Candas B, Leon A, Po- sub-classification of non-small-cell sion after induction chemotherapy: yatos RM, Gelabert M. Evaluation of carcinomas into adenocarcinomas association with the use of novel chromogranin A determined by three and squamous-cell carcinomas. The agents. HAEMATOL-HEMATOL J. different procedures in patients with process of obtaining a licence for 96:171-173. I.F.: 6.53. benign diseases, neuroendocrine tu- distribution of the program is pre- mors and other malignancies. TUMOR sently underway. 2 Martinez R, Menendez R, Reyes BIOL. 32:13-22. I.F.: 2.03. S, Polverino E, Cilloniz C, Martinez 6. Evaluation of a computer pro- A, Esquinas C, Filella X, Ramirez P, gram for establishing risk in Torres A. Factors associated with ReViewS patients with symptoms sugges- inflammatory cytokine patterns in i.f.: 4.10 tive of cancer (paraneoplastic syn- community-acquired pneumonia. dromes), which assesses risk on EUR RESPIR J. 37:393-399. I.F.: 5.92. 1 Filella X, Alcover J, Molina R. Acti- the basis of 9 tumour markers and ve surveillance in prostate cancer: the points to the origin. 3 Escudero JM, Auge JM, Filella X, need to standardize. TUMOR BIOL. Torne A, Pahisa J, Molina R. Compa- 32:839-843. I.F.: 2.03. 7. Evaluation and study of a po- rison of Serum Human Epididymis pulation screening programme Protein 4 with Cancer Antigen 125 as 2 Trape J, Filella X, Alsina-Donadeu for ovarian cancer through the a Tumor Marker in Patients with Ma- M, Juan-Pereira L, Bosch-Ferrer A, determination of HE-4 and CA125 in lignant and Nonmalignant Diseases. Rigo-Bonnin R. Increased plasma high-risk women: BRCA-1, BRCA-2 CLIN CHEM. 57:1534-1544. I.F.: 6.89. concentrations of tumour markers in mutations, previous medical history the absence of neoplasia. CLIN CHEM of breast and/or ovarian cancer. 4 Molina R, Escudero JM, Auge LAB MED. 49:1605-1620. I.F.: 2.07. JM, Filella X, Foj L, Torne A, Lejarce- 8. Investigation of cytokine invol- gui J, Pahisa J. HE4 a novel tumour vement in cancer development marker for ovarian cancer: compa- GRAntS foR ReSeARcH and progression. We are conso- rison with CA 125 and ROMA algo- in pRoGReSS lidating research into the clinical rithm in patients with gynaecological usefulness of cytokines in cancer diseases. TUMOR BIOL. 32:1087- Molina R. STREP - Multiparame- patients. This line is preferentially 1095. I.F.: 2.03. tric Quantum Dot Bioassay for developed in hematological and Point of Care Diagnosis. Sponso- urological neoplasms. 5 Cobo T, Palacio M, Martinez- red by: European Commission, Terron M, Navarro-Sastre A, Bosch J, LSHB-CT-2007-037933. Duration: 9. Markers used in pharmaco- Filella X, Gratacos E. Clinical and in- 01/01/2007-30/06/2011. genetics. Study of the genetic flammatory markers in amniotic fluid polymorphisms implicated in as predictors of adverse outcomes in metabolism and pharmacological preterm premature rupture of mem- targets. This line is particularly branes. AM J OBSTET GYNECOL. focused on predicting the safety 205:-. I.F.: 3.31. and efficacy of antineoplastic drugs. During the last year we have developed high performance genotyping techniques, such as minisequencing-SBE.

257 AReA 5

Team involved in: Oncology and haematology

Human and experimental functional oncomorphology

gROUP MeMBeRS StrateGic oBjectiveS

Identification of genetic and molecular mechanisms implicated in the deve- teAM leADeR lopment and progression of human elías campo Güerri (Hospital clínic) neoplasms. tel.: 93 227 54 50 Development of strategies for transfe- fax: 93 227 57 17 rring to clinical practice the knowled- e-mail: [email protected] ge generated by basic research on human tumors. Identification of para- xxxxxx iDiBApS MeMBeRS: eva fernández lópez meters allowing the improved diagnosis llúcia Alós (Hospital clínic) (fundació clínic - Hospital clínic) and prognosis of neoplastic disease, Virginia Amador (iDiBApS) laura Gelabert Blesa (iDiBApS) and the identification of possible thera- Silvia M. Beà (fundació clínic) cristina capdevilla (fundació clinic) peutic targets Josep Antoni Bombí (Hospital clínic) Mónica Marín (Hospital clínic - XBtc) pedro luis fernández (Hospital clínic) noelia García Martínez (fundació clínic) lluis Hernández pous (iDiBApS) Silvia Martín (fundació clínic) main lineS of pedro Jares (Hospital clínic) reSearcH carme Mallofré (Hospital clínic) nuRSinG StAff: Alfons nadal (Hospital clinic) Judith Safont (fundació clínic) Lymphoid neoplasms Antonio palacín (Hospital clínic) a) Study of the alterations of the mo- Antonio postigo (icReA - iDiBApS) ADMiniStRAtiVe StAff: lecular mechanisms related to the José francisco Ramírez (Hospital clínic) carmen Muro (fundació clínic) cell cycle, genomic instability and teresa María Ribalta (Hospital clínic) nathalie Villahoz (fundació clínic) the transcriptional expression pro- Manel Solé (Hospital clínic) files involved in the development Antonio Martínez pozo (Hospital clínic) StAtiSticiAn: and progression of these tumors lluis colomo (Hospital clínic) Guillem clot Razquin (fundació clínic) as biomarkers of clinicopathological esther Bladé (fundació clínic) relevance. poStDoctoRAl fellowS: b) Functional study of molecular fac- Ana enjuanes Guardiola (iDiBApS) collABoRAtoRS: tors that may contribute to tumor Rosa Miquel Morera (Hospital clínic) pathogenesis, and which therefore ReSeARcH fellowS: laura conde del campo (fundació clínic) may be candidates for the develo- Julia calvo castillo (fundació clínic) ester Sánchez tilló (iDiBApS) pment of novel guided treatment Alba navarro lópez (Mcyt) Magdalena pinyol Martínez (iDiBApS) strategies. cristina Royo Moreno (Mcyt) Roberto Alonso Gil (fundació clínic) Raquel Bermudo Gascón (iDiBApS) Maria carmela Vegliante (fundació clínic) Adriana García Herrera (Hospital clínic) lourdes Sánchez cid (iDiBApS) Jara palomero Gorrindo (Mcyt) Marta kulis (fundació clínic)

tecHniciAnS: laura pla Rodríguez (iDiBApS) Miriam prieto Beato (iDiBApS) Montse Sánchez Reina (iDiBApS) Sara Guijarro Gallardo (fundació clínic) concepción Muñoz lozano (iDiBApS)

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Solid neoplasms a) Study of the molecular mechanisms of invasion and metastasis, transcriptional expression profiles implicated in the development and progression of different human tumors in relation to development, biological aggressivity (adhesion molecules) and therapeutic options. We focus mainly on breast and prostate tumors as neoplasms under hormone influence, and urological tumors and airway neoplasms – including head and neck tumors. b) Study of the possible criteria of treatment response and prognosis in neurological tumors.

Microarray platforms allow the massive-scale analysis of genic expression profiles. In our group we use this technique in translation research of human lymphomas, as can be seen in the image, where cluster analysis allows us to detect new types of lymphomas at molecular level that also exhibit different clinical behaviors.

ReSeARCh gROUP ReSeARCh gROUP molecular patHoloGy of Solid tumorS tranScriptional reGulation of Genic expreSSion Group Leader: Pedro Luis Fernández (hospital clínic) Group Leader: Antonio Postigo (IDIBAPS) Our group has continued with the analysis of different types of solid tumours, in particular, urological, breast, nervous Regulation of Gene Expression During Cell Differentia- system and head and neck tumours. tion and in Cancer Research Group. The laboratory is An important part of the research into prostate cancer is the investigating the molecular mechanisms involved in the study of practical applications of its genetic signature through analysis of mate- regulation of gene expression during cell differentiation rial left over from biopsies which has been shown to be clinically viable (ref. 2). and in cancer. Out research is focusing on ZEB1/deltaEF1 We are in contact with various possible partners in the biomedical industry in and ZEB2/SIP1, which are key modulating factors in cell order to develop a commercial kit. Our collaboration with Dr Thomson’s group differentiation, maintenance of “stemness” in normal at the IBM-CSIC in Barcelona has made it possible to analyse prostate cancer and cancerous stem cells, oncogenic transformation and cell models with different degrees of aggressiveness, demonstrating the impor- tumour invasion and metastasis. tance of the mesenchymal and metastatic phenotypes, in development phase The group uses in vitro and in vivo models in two main in mouse models. lines of research: In breast cancer, analysis of the microRNA profiles of primary infiltrating ductal Study of the mechanisms by which ZEB1 and ZEB2 regu- carcinomas and their lymph node metastases has enabled us to define signa- late tumorigenesis and epithelial-mesenchymal transition tures of progression. (EMT) during the progression of the cancer. In nervous system cancers, studies continue in the area of confirmation and The role of ZEB1 and ZEB2 in the regulation of normal validation of the candidate genes EPHB1, BNIP3 and STAT1 obtained by analy- haematopoietic differentiation and its malignant transfor- sis of glioblastoma expression in patients with unusually long survival times. mation. These genes are involved in signalling pathways and intercellular interaction, The sources of funding for group’s research include sub- development and function of the nervous system, cell movement and cancer. sidies from the Spanish Ministry of Economy and Com- The research into head and neck tumours includes analysis of the genetic petitiveness (formerly Science and Innovation), the Euro- abnormalities in premalignant lesions in the mouth, with a particular focus on pean Union, the Associación Española Contra el Cáncer those that might be predictive of the development of carcinoma, and the mo- (AECC) [Spanish Cancer Association], Fundació La Caixa, lecular changes that occur in carcinoma of the larynx. Fundació Olga Torres and Avon Cosmetics SAU.

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Human and experimental functional oncomorphology

PUBLICATIONS

oRiGinAlS 6 Puente XS, Pinyol M, Quesada V, CD4+cell counts and HIV-RNA levels i.f.: 322.81 Conde L, Ordonez GR, Villamor N, Esca- do not predict outcomes of community- ramis G, Jares P, Bea S, Gonzalez-Diaz acquired pneumonia in hospitalized HIV- 1 Canete JD, Albaladejo C, Hernan- M, Bassaganyas L, Baumann T, Juan infected patients. INT J INFECT DIS. dez MV, Lainez B, Pinto JA, Ramirez M, Lopez-Guerra M, Colomer D, Tubio 15:E822-E827. I.F.: 2.53. J, Lopez-Armada MJ, Rodriguez-Cros JMC, Lopez C, Navarro A, Tornador C, JR, Engel P, Blanco FJ, Sanmarti R. Aymerich M, Rozman M, Hernandez 11 Riquelme R, Jimenez P, Videla AJ, Clinical significance of high levels of JM, Puente DA, Freije JMP, Velasco G, Lopez H, Chalmers J, Singanayagam soluble tumour necrosis factor-alpha Gutierrez-Fernandez A, Costa D, Carrio A, Riquelme M, Peyrani P, Wiemken receptor-2 produced by alternative A, Guijarro S, Enjuanes A, Hernandez T, Arbo G, Benchetrit G, Rioseco ML, splicing in rheumatoid arthritis: a L, Yague J, Nicolas P, Romeo-Casabona Ayesu K, Klotchko A, Marzoratti L, Raya longitudinal prospective cohort stu- CM, Himmelbauer H, Castillo E, Dohm M, Figueroa S, Saavedra F, Pryluka D, dy. RHEUMATOLOGY. 50:721-728. JC, DeSanjose S, Piris MA, DeAlava E, Inzunza C, Torres A, Alvare P, Fernan- I.F.: 4.17. Miguel JS, Royo R, Gelpi JL, Torrents dez P, Barros M, Gomez Y, Contreras C, D, Orozco M, Pisano DG, Valencia A, Rello J, Bordon J, Feldman C, Arnold F, 2 Silvarino R, Sant F, Espinosa G, Guigo R, Bayes M, Heath S, Gut M, Nakamatsu R, Riquelme J, Blasi F, Ali- Pons-Estel G, Sole M, Cervera R, Klatt P, Marshall J, Raine K, Stebbings berti S, Cosentini R, Lopardo G, Gnoni Arrizabalaga P. Nephropathy associa- LA, Futreal PA, Stratton MR, Campbell M, Welte T, Saad M, Guardiola J, Rami- ted with antiphospholipid antibodies PJ, Gut I, Lopez-Guillermo A, Estivill X, rez J. Predicting mortality in hospitali- in patients with systemic lupus Montserrat E, Lopez-Otin C, Campo E. zed patients with 2009 H1N1 influenza erythematosus. LUPUS. 20:721-729. Whole-genome sequencing identifies pneumonia. INT J TUBERC LUNG D. I.F.: 2.60. recurrent mutations in chronic lympho- 15:542-546. I.F.: 2.56. cytic leukaemia. NATURE. 475:101-105. 3 Gil C, Garcia MT, Garcia F, Miro I.F.: 36.10. 12 Campayo M, Navarro A, Vinolas JM, Aguero F, Alos L, Zamora L, N, Tejero R, Munoz C, Diaz T, Marrades Capon A, Costa J, Pumarola T, Gatell 7 Martina MN, Sole M, Masso E, R, Cabanas ML, Gimferrer JM, Gascon JM. Evaluation of the Roche COBAS Perez N, Campistol JM, Quintana LF. P, Ramirez J, Monzo M. A Dual Role (R) TaqMan (R) HIV-1 test for quanti- Mixed cryoglobulinaemia not related to for KRT81: A miR-SNP Associated with fying HIV-1 RNA in infected cells and hepatitis C virus, mesangiocapillary glo- Recurrence in Non-Small-Cell Lung Can- lymphoid tissue. J VIROL METHODS. merulonephritis and lymphoplasmocytic cer and a Novel Marker of Squamous 174:69-76. I.F.: 2.14. lymphoma. NEFROLOGIA. 31:743-746. Cell Lung Carcinoma. PLOS ONE. 6:-. I.F.: 0.74. I.F.: 4.41. 4 Bori G, Munoz-Mahamud E, Gar- cia S, Mallofre C, Gallart X, Bosch J, 8 Cagido VR, Zin WA, Ramirez J, Na- 13 Navarro A, Diaz T, Gallardo E, Vi- Garcia E, Riba J, Mensa J, Soriano vajas D, Farre R. Alternating ventilation nolas N, Marrades RM, Gel B, Campayo A. Interface membrane is the best in a rat model of increased abdominal M, Quera A, Bandres E, Garcia-Foncillas sample for histological study to pressure. RESP PHYSIOL NEUROBI. J, Ramirez J, Monzo M. Prognostic diagnose prosthetic joint infection. 175:310-315. I.F.: 2.38. Implications of miR-16 Expression Le- MODERN PATHOL. 24:579-584. vels in Resected Non-Small-Cell Lung I.F.: 4.18. 9 Almendros I, Farre R, Torres M, Cancer. J SURG ONCOL. 103:411-415. Bonsignore MR, Dalmases M, Ramirez I.F.: 2.43. 5 Diaz A, Garcia F, Mozos A, Caba- J, Navajas D, Montserrat JM. Early and llero M, Leon A, Martinez A, Gil C, mid-term effects of obstructive apneas 14 Campayo M, Vinolas N, Navarro Plana M, Gallart T, Gatell JM, Alos L. in myocardial injury and inflammation. A, Carcereny E, Casas F, Gel B, Diaz T, Lymphoid Tissue Collagen Deposition SLEEP MED. 12:1037-1040. I.F.: 3.43. Gimferrer JM, Marrades RM, Ramirez in HIV-Infected Patients Correlates J, Monzo M. Single Nucleotide Poly- With the Imbalance Between Matrix 10 Bordon J, Kapoor R, Martinez C, morphisms in Tobacco Metabolism and Metalloproteinases and Their Inhi- Portela D, Duvvuri P, Klochko A, Ayesu DNA Repair Genes and Prognosis in bitors. J INFECT DIS. 203:810-813. K, Peyrani P, Cilloniz C, Wiemken T, Resected Non-Small-Cell Lung Cancer. I.F.: 6.29. Parra A, Torres A, Rello J, Ramirez J. J SURG RES. 167:E5-E12. I.F.: 2.24.

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original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 241.60 45 31 8 15 Bermudo R, Abia D, Mozos A, 20 Sanchez-Tillo E, DeBarrios O, Garcia-Cruz E, Alcaraz A, Ortiz AR, Siles L, Cuatrecasas M, Castells A, 2010 317.65 34 20 8 Thomson TM, Fernandez PL. Highly Postigo A. beta-catenin/TCF4 complex 2011 322.81 50 31 9 sensitive molecular diagnosis of pros- induces the epithelial-to-mesenchymal tate cancer using surplus material was- transition (EMT)-activator ZEB1 to hed off from biopsy needles. BRIT J regulate tumor invasiveness. P NATL CANCER. 105:1600-1607. I.F.: 4.83. ACAD SCI USA. 108:19204-19209. ffin-Embedded Tissues. CLIN CANCER I.F.: 9.77. RES. 17:3727-3732. I.F.: 7.34. 16 Gutierrez-Garcia G, Cardesa-Salz- mann T, Climent F, Gonzalez-Barca E, 21 Soty M, Visa M, Soriano S, 26 Iqbal J, Meyer PN, Smith LM, Mercadal S, Mate JL, Sancho JM, Are- Carmona MD, Nadal A, Novials A. In- Johnson NA, Vose JM, Greiner TC, Con- nillas L, Serrano S, Escoda L, Martinez volvement of ATP-sensitive Potassium nors JM, Staudt LM, Rimsza L, Jaffe E, S, Valera A, Martinez A, Jares P, Pinyol (K-ATP) Channels in the Loss of Beta- Rosenwald A, Ott G, Delabie J, Campo M, Garcia-Herrera A, Martinez-Trillos A, cell Function Induced by Human Islet E, Braziel RM, Cook JR, Tubbs RR, Gas- Gine E, Villamor N, Campo E, Colomo Amyloid Polypeptide. J BIOL CHEM. coyne RD, Armitage JO, Weisenburger L, Lopez-Guillermo A. Gene-expression 286:40857-40866. I.F.: 5.33. DD, Chan WC. BCL2 Predicts Survival in profiling and not immunophenotypic Germinal Center B-cell-like Diffuse Large algorithms predicts prognosis in pa- 22 Verger E, Valduvieco I, Caral L, B-cell Lymphoma Treated with CHOP- tients with diffuse large B-cell lympho- Pujol T, Ribalta T, Vinolas N, Boget like Therapy and Rituximab. CLIN CAN- ma treated with immunochemotherapy. T, Oleaga L, Blanco Y, Graus F. Does CER RES. 17:7785-7795. I.F.: 7.34. BLOOD. 117:4836-4843. I.F.: 10.56. gender matter in glioblastoma?. CLIN TRANSL ONCOL. 13:737-741. I.F.: 1.25. 27 Gutierrez-Garcia G, Garcia-Herrera 17 Cardesa-Salzmann TM, Colomo L, A, Cardesa T, Martinez A, Villamor N, Gutierrez G, Chan WC, Weisenburger D, 23 Brell M, Castaner S, Pujol-Farre T, Ghita G, Martinez-Trillos A, Colomo L, Climent F, Gonzalez-Barca E, Mercadal Boluda S, Ribalta T, Bruna J, Martinez Setoain X, Rodriguez S, Gine E, Campo S, Arenillas L, Serrano S, Tubbs R, Dela- M, Verger E, Villa S, Vinolas N, Gil M, E, Lopez-Guillermo A. Comparison of bie J, Gascoyne RD, Connors JM, Mate Graus F, Tortosa-Moreno A. Implication four prognostic scores in peripheral JL, Rimsza L, Braziel R, Rosenwald A, of radiological pattern in the prognosis T-cell lymphoma. ANN ONCOL. 22:397- Lenz G, Wright G, Jaffe ES, Staudt L, of oligodendroglial tumors: correlation 404. I.F.: 6.45. Jares P, Lopez-Guillermo A, Campo E. with genetic profile. REV NEUROLO- High microvessel density determines a GIA. 52:465-471. I.F.: 1.22. 28 Zidar N, Bostjancic E, Gale N, poor outcome in patients with diffuse Kojc N, Poljak M, Glavac D, Cardesa A. large B-cell lymphoma treated with ritu- 24 Martin-Guerrero I, Enjuanes A, Down-regulation of microRNAs of the ximab plus chemotherapy. HAEMATOL- Richter J, Ammerpohl O, Colomer D, miR-200 family and miR-205, and an HEMATOL J. 96:996-1001. I.F.: 6.53. Ardanaz M, Marco F, Salas A, Campo altered expression of classic and des- E, Siebert R, Garcia-Orad A. A Pu- mosomal cadherins in spindle cell car- 18 Nicolau C, Bunesch L, Peri L, Sal- tative «hepitype» in the ATM Gene cinoma of the head and neck-hallmark vador R, Corral JM, Mallofre C, Sebastia Associated with Chronic Lymphocytic of epithelial-mesenchymal transition. C. Accuracy of contrast-enhanced ultra- Leukemia Risk. GENE CHROMOSOME HUM PATHOL. 42:482-488. I.F.: 3.00. sound in the detection of bladder cancer. CANC. 50:887-895. I.F.: 3.99. BRIT J RADIOL. 84:1091-1099. I.F.: 2.06. 29 Carrera C, Palou J, Malvehy J, 25 Rimsza LM, Wright G, Schwartz Segura S, Aguilera P, Salerni G, Lo- 19 Caldelari ACA, Miquel R, Bombi M, Chan WC, Jaffe ES, Gascoyne RD, vatto L, Puig-Butille JA, Alos L, Puig JA, Gines A, Fernandez-Esparrach G, Campo E, Rosenwald A, Ott G, Cook S. Early Stages of Melanoma on the Ayuso JR, Maurel J, Feu F, Castells A, JR, Tubbs RR, Braziel RM, Delabie J, Limbs of High-risk Patients: Clinical, Fernandez-Cruz L, Navarro S. Malig- Miller TP, Staudt LM. Accurate Classifi- Dermoscopic, Reflectance Confocal nancy predictive factors in pancreatic cation of Diffuse Large B-Cell Lympho- Microscopy and Histopathological Cha- intraductal papillary mucinous neoplasm. ma into Germinal Center and Activated racterization for Improved Recognition. MED CLIN-BARCELONA. 137:631-636. B-Cell Subtypes Using a Nuclease Pro- ACTA DERM-VENEREOL. 91:137-146. I.F.: 1.41. tection Assay on Formalin-Fixed, Para- I.F.: 2.78.

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30 Vegliante MC, Royo C, Palo- tion of Methylated Genes Associated t(14;18)-negative follicular lymphoma mero J, Salaverria I, Balint B, Martin- with Aggressive Clinicopathological support a late germinal center B-cell Guerrero I, Agirre X, Lujambio A, Features in Mantle Cell Lymphoma. phenotype. BLOOD. 118:5550-5558. Richter J, Xargay-Torrent S, Bea S, PLOS ONE. 6:-. I.F.: 4.41. I.F.: 10.56. Hernandez L, Enjuanes A, Calasanz MJ, Rosenwald A, Ott G, Roman- 35 Meyer PN, Fu K, Greiner TC, 39 Visco C, Hoeller S, Malik JT, Gomez J, Prosper F, Esteller M, Jares Smith LM, Delabie J, Gascoyne RD, Ott Xu-Monette ZY, Wiggins ML, Liu JS, P, Siebert R, Campo E, Martin-Subero G, Rosenwald A, Braziel RM, Campo Sanger WG, Liu ZF, Chang JL, Ranheim JI, Amador V. Epigenetic Activation E, Vose JM, Lenz G, Staudt LM, Chan EA, Gradowski JF, Serrano S, Wang HY, of SOX11 in Lymphoid Neoplasms by WC, Weisenburger DD. Immunohisto- Liu QQ, Dave S, Olsen B, Gascoyne Histone Modifications. PLOS ONE. chemical Methods for Predicting Cell RD, Campo E, Swerdlow SH, Chan 6:-. I.F.: 4.41. of Origin and Survival in Patients With WC, Tzankov A, Young KH. Molecular Diffuse Large B-Cell Lymphoma Trea- Characteristics of Mantle Cell Lym- 31 Sanz-Pamplona R, Aragues R, ted With Rituximab. J CLIN ONCOL. phoma Presenting With Clonal Plasma Driouch K, Martin B, Oliva B, Gil M, 29:200-207. I.F.: 18.97. Cell Component. AM J SURG PATHOL. Boluda S, Fernandez PL, Martinez A, 35:177-189. I.F.: 4.11. Moreno V, Acebes JJ, Lidereau R, 36 DeLarrea CF, Martinez-Pozo Reyal F, VanDeVijver MJ, Sierra A. A, Mercadal S, Garcia A, Gutierrez- 40 Navarro A, Royo C, Hernandez L, Expression of Endoplasmic Reticulum Garcia G, Valera A, Ghita G, Colomo Jares P, Campo E. Molecular Pathoge- Stress Proteins Is a Candidate Mar- L, Gainza E, Villamor N, Nomdedeu nesis of Mantle Cell Lymphoma: New ker of Brain Metastasis in both ErbB- B, Estrach T, Montserrat E, Campo Perspectives and Challenges With Cli- 2(+) and ErbB-2(-) Primary Breast E, Lopez-Guillermo A. Initial features nical Implications. SEMIN HEMATOL. Tumors. AM J PATHOL. 179:564-579. and outcome of cutaneous and non- 48:155-165. I.F.: 3.04. I.F.: 5.22. cutaneous primary extranodal follicular lymphoma. BRIT J HAEMATOL. 41 Garcia-Herrera A, Song JY, 32 Darwich E, Vicente A, Bolling 153:334-340. I.F.: 4.94. Chuang SS, Villamor N, Colomo L, Pitta- MC, Gonzalez-Ensenat MA, Cusi V, luga S, Alvaro T, Rozman M, Gonzalez Fortuny C, Bombi JA, Jonkman MF, 37 Hadzidimitriou A, Agathangelidis JD, Arrunategui AM, Fernandez E, Mascaro JM. Extensive acantholysis A, Darzentas N, Murray F, Delfau-Larue Gonzalvo E, Estrach T, Colomer D, Ra- as the major histological feature of MH, Pedersen LB, Lopez AN, Dagklis ffeld M, Gaulard P, Campo E, Jaffe ES, a severe case of Dowling Meara- A, Rombout P, Beldjord K, Kolstad A, Martinez A. Nonhepatosplenic gamma epidermolysis bullosa simplex: a Dreyling MH, Anagnostopoulos A, Tsaf- delta T-cell Lymphomas Represent a reappraisal of acantholysis in the taris A, Mavragani-Tsipidou P, Rosen- Spectrum of Aggressive Cytotoxic T-cell newborn. EUR J DERMATOL. wald A, Ponzoni M, Groenen P, Ghia P, Lymphomas With a Mainly Extranodal 21:966-971. I.F.: 2.42. Sander B, Papadaki T, Campo E, Geisler Presentation. AM J SURG PATHOL. C, Rosenquist R, Davi F, Pott C, Stama- 35:1214-1225. I.F.: 4.11. 33 Espinet B, Garcia-Herrera A, topoulos K. Is there a role for antigen Gallardo F, Baro C, Salgado R, Servitje selection in mantle cell lymphoma? 42 Ngo VN, Young RM, Schmitz R, O, Estrach T, Colomo L, Romagosa Immunogenetic support from a series Jhavar S, Xiao WM, Lim KH, Kohlham- V, Barranco C, Serrano S, Campo E, of 807 cases. BLOOD. 118:3088-3095. mer H, Xu WH, Yang YD, Zhao H, Sha- Pujol RM, Sole F. FOXP1 molecular I.F.: 10.56. ffer AL, Romesser P, Wright G, Powell cytogenetics and protein expression J, Rosenwald A, Muller-Hermelink HK, analyses in primary cutaneous large 38 Leich E, Zamo A, Horn H, Ha- Ott G, Gascoyne RD, Connors JM, Rim- B cell lymphoma, leg-type. HISTOL ralambieva E, Puppe B, Gascoyne sza LM, Campo E, Jaffe ES, Delabie HISTOPATHOL. 26:213-221. I.F.: 2.50. RD, Chan WC, Braziel RM, Rimsza J, Smeland EB, Fisher RI, Braziel RM, LM, Weisenburger DD, Delabie J, Tubbs RR, Cook JR, Weisenburger DD, 34 Enjuanes A, Fernandez V, Her- Jaffe ES, Fitzgibbon J, Staudt LM, Chan WC, Staudt LM. Oncogenically nandez L, Navarro A, Bea S, Pinyol Mueller-Hermelink HK, Calaminici active MYD88 mutations in human M, Lopez-Guillermo A, Rosenwald A, M, Campo E, Ott G, Hernandez L, lymphoma. NATURE. 470:115-U133. Ott G, Campo E, Jares P. Identifica- Rosenwald A. MicroRNA profiles of I.F.: 36.10.

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43 Weisenburger DD, Savage KJ, Ha- 48 Roue G, Perez-Galan P, Mozos J, Ribrag V, Unterhalt M, Hermine O, rris NL, Gascoyne RD, Jaffe ES, Maclen- A, Lopez-Guerra M, Xargay-Torrent S, Hoster E. Update on the molecular nan KA, Rudiger T, Pileri S, Nakamura S, Rosich L, Saborit-Villarroya I, Normant pathogenesis and clinical treatment Nathwani B, Campo E, Berger F, Coiffier B, E, Campo E, Colomer D. The Hsp90 of mantle cell lymphoma: report of Kim WS, Holte H, Federico M, Au WY, To- inhibitor IPI-504 overcomes bortezomib the 10th annual conference of the binai K, Armitage JO, Vose JM. Peripheral resistance in mantle cell lymphoma in European Mantle Cell Lymphoma T-cell lymphoma, not otherwise specified: vitro and in vivo by down-regulation Network. LEUKEMIA LYMPHOMA. a report of 340 cases from the Internatio- of the prosurvival ER chaperone BiP/ 52:2226-2236. I.F.: 2.49. nal Peripheral T-cell Lymphoma Project. Grp78. BLOOD. 117:1270-1279. BLOOD. 117:3402-3408. I.F.: 10.56. I.F.: 10.56. eDitoRiAlS 44 Diaz A, Valera A, Carrera C, Hakim 49 Meyer PN, Fu K, Greiner T, Smith i.f.: 12.27 S, Aguilera P, Garcia A, Palou J, Puig S, L, Delabie J, Gascoyne R, Ott G, Ro- Malvehy J, Alos L. Pigmented Spindle senwald A, Braziel R, Campo E, Vose 1 Arigita M, Martinez D, Nadal A, Cell Nevus: Clues for Differentiating It J, Lenz G, Staudt L, Chan W, Weisen- Borrell A. Spina bifida in a 13-week From Spindle Cell Malignant Melano- burger DD. The Stromal Cell Marker fetus with a normal intracranial trans- ma. A Comprehensive Survey Including SPARC Predicts for Survival in Patients lucency. PRENATAL DIAG. 31:1104- Clinicopathologic, Immunohistoche- With Diffuse Large B-Cell Lymphoma 1105. I.F.: 2.15. mical, and FISH Studies. AM J SURG Treated With Rituximab. AM J CLIN PATHOL. 35:1733-1742. I.F.: 4.11. PATHOL. 135:54-61. I.F.: 2.51. 2 Salerni G, Lovatto L, Carrera C, Palou J, Alos L, Puig-Butille JA, Bade- 45 Salles G, DeJong D, Xie WL, 50 Xargay-Torrent S, Lopez-Guerra M, nas C, Malvehy J, Puig S. Correlation Rosenwald A, Chhanabhai M, Gaulard Saborit-Villarroya I, Rosich L, Campo E, among Dermoscopy, Confocal Re- P, Klapper W, Calaminici M, Sander B, Roue G, Colomer D. Vorinostat-Induced flectance Microscopy, and Histologic Thorns C, Campo E, Molina T, Lee A, Apoptosis in Mantle Cell Lymphoma Is Features of Melanoma and Basal Cell Pfreundschuh M, Horning S, Lister A, Mediated by Acetylation of Proapoptotic Carcinoma Collision Tumor. DERMA- Sehn LH, Raemaekers J, Hagenbeek BH3-Only Gene Promoters. CLIN CAN- TOL SURG. 37:275-279. I.F.: 2.26. A, Gascoyne RD, Weller E. Prognostic CER RES. 17:3956-3968. I.F.: 7.34. significance of immunohistochemical 3 Navarro A, Campo E. New pers- biomarkers in diffuse large B-cell lym- pectives and challenges in the un- phoma: a study from the Lunenburg ReViewS derstanding of mantle cell lymphoma. Lymphoma Biomarker Consortium. i.f.: 13.82 ANN ONCOL. 22:32-35. I.F.: 6.45. BLOOD. 117:7070-7078. I.F.: 10.56. 1 Franchi A, Palomba A, Cardesa 4 Molina M, Sanchez M, Ramirez 46 Campo E, Swerdlow SH, Harris A. Current diagnostic strategies for J. Recurrent respiratory infections, NL, Pileri S, Stein H, Jaffe ES. The undifferentiated tumours of the nasal pneumonia and pulmonary interstitial 2008 WHO classification of lymphoid cavities and paranasal sinuses. HISTO- infiltrates in a 81 year old man. MED neoplasms and beyond: evolving PATHOLOGY. 59:1034-1045. I.F.: 3.57. CLIN-BARCELONA. 137:311-316. concepts and practical applications. I.F.: 1.41. BLOOD. 117:5019-5032. I.F.: 10.56. 2 Royo C, Salaverria I, Hartmann EM, Rosenwald A, Campo E, Bea S. The 47 Mozos A, Roue G, Lopez-Gui- complex landscape of genetic altera- GRAntS foR ReSeARcH llermo A, Jares P, Campo E, Colomer tions in mantle cell lymphoma. SEMIN in pRoGReSS D, Martinez A. The Expression of the CANCER BIOL. 21:322-334. I.F.: 7.76. Endoplasmic Reticulum Stress Sensor Jares P. Identification of Tumor Su- BiP/GRP78 Predicts Response to Che- 3 Dreyling M, Kluin-Nelemans HC, pressor Genes, Epigenetic Portrait, motherapy and Determines the Efficacy Bea S, Hartmann E, Salaverria I, Hutter and Genotyping of Mantle Cell Lym- of Proteasome Inhibitors in Diffuse Lar- G, Perez-Galan P, Roue G, Pott C, Le- phomas. Sponsored by: Lymphoma ge B-Cell Lymphoma. AM J PATHOL. Gouill S, Cortelazzo S, Rule S, Hess G, Research Foundation, 07/168. Dura- 179:2601-2610. I.F.: 5.22. Zaja F, Vitolo U, Szymczyk M, Walewski tion: 01/05/2007-31/12/2012.

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Human and experimental functional oncomorphology

Campo E. Red temática de investi- y progresión de estas neoplasias. Postigo A. Regulación de la diferencia- gación cooperativa de cáncer. Spon- Sponsored by: Asociación Española ción hematopoyetica y de su transfor- sored by: Ministerio Sanidad y Con- contra el cáncer, AECC_CAT_PI08 mación maligna por la familia ZEB de sumo, RD06/0020/0039. Duration: 08/004. Duration: 22/01/2009- factores de transcripción. Sponsored 01/01/2007-31/12/2012. 21/01/2011. by: Ministerio de Economía y Compe- titividad, BFU-2010-15163. Duration: Martinez A. Estudio de la activación Fernandez PL. Análisis de los fenotipos 01/01/2011-31/12/2013. de las vías de supervivencia y apop- CSC y EMT y su potencial modula- tosis en respuesta al estrés secretor ción por miRNA en la progresión de Postigo A. Validación del bucle ZEB1- dependiente del retículo endoplasmí- los tumores mamarios y próstáticos. ZEB2/microRNA como factor pronósti- tico en linfomas de células grandes Sponsored by: Ministerio de Ciencia co y diana terapéutica en la capacidad como una nueva diana terapéutica. e Innovación FIS, PI080274. Duration: invasiva/metastásica y la respuesta al Sponsored by: Ministerio Sanidad 01/01/2009-31/12/2011. tratamiento de carcinomas colorecta- y Consumo, PI080095. Duration: les. Sponsored by: Asociación Española 01/01/2008-01/12/2012. Amador V. Papel de los factores de contra el Cáncer. Duration: 01/04/2011- transcripción High-Mobility Group 31/03/2013. Bea S. Estudio de las Alteraciones (HMG) en los Linformas Malignos Genómicas y los Perfiles de Expre- Agresivos. Sponsored by: Ministerio Alos L. Identificación de las altera- sión de Neoplasias Linfoides. Iden- de Educación, BFU2009_09235. Du- ciones genéticas en la mucosa oral tificación de genes diana implicados ration: 01/01/2010-31/12/2012. predictivas del desarrollo del carcinoma en el desarrollo y progresión de estas escamoso. Sponsored by: Fundación de neoplasias y definición de su impacto Postigo A. Regulación transcrip- Investigación Médica Mutua Madrileña, clínico. Sponsored by: Instituto de cional de la cadherina E y de la FundMM_11 AP94722011. Duration: Salud Carlos III, PI080077. Duration: capacidad invasiva y metastática de 03/08/2011-02/08/2014. 31/12/2008-30/12/2011. tumores de colon. Sponsored by: Fundació Privada Olga Torres (FOT), Campo E. A BLUEPRINT of Haema- Campo E. Caracterización Genética FOT_09_002. Duration: 01/01/2010- topoietic Epigenomes. Sponsored y Molecular de Alta Resolución de 31/12/2012. by: European Commission, CE-FP7- Neoplasias Linfoides. Implicaciones HEALTH-1ST-11 282510. Duration: patogenéticas y clínicas. Sponsored Campo E. Procurem t of 40 paired 01/10/2011-31/03/2016. by: Ministerio de Ciencia e Inno- pre- and post-chemotherapy sam- vación, SAF2008-03630. Duration: ples of DNA derived from peripheral 01/01/2009-31/12/2013. blood for TCGA analysis. Sponsored DoctoRAl tHeSeS by: National Institutes of Health, Campo E. Estudio de la Genómica HHSN261201000076I. Duration: Alos L, Cardesa A. Expresion de mu- de la Leucemia Linfocítica Crónica. 08/09/2010-07/09/2012. cinas y moléculas relacionadas en los Sponsored by: Instituto de Salud Car- carcinomas mucoepidermoides de glán- los III, 0000. Duration: 27/03/2009- Campo E. SPECS II - Strategic Part- dulas salivales: Implicaciones diagnósti- 31/12/2012. nering to Evaluate Cancer Signatures. cas y pronósticas. PhD student: Blanca Sponsored by: National Institutes of Noemi Luján. Campo E. Ajuts per donar suport a Health, USA, University of Arizona, les activitats dels grups de recerca. SPECS II. Duration: 01/08/2011- Fernandez PL, Thomson T. Alteraciones Sponsored by: Generalitat de Ca- 31/07/2016. moleculares en la transición metastá- talunya, 2009, SGR_992. Duration: sica del carcinoma mamario. PhD stu- 30/06/2009-31/12/2013. Campo E. Identification of somatic mu- dent: Júlia Calvo Castillo. tations in mantle cell lymphoma using Jares P. Identificación de potencia- next generation sequencing. Sponso- les genes supresores de tumores red by: Lymphoma Research Foun- en neoplasias linfoides y análisis dation, USA. Duration: 30/09/2011- de su implicación en el desarrollo 29/11/2013.

264 AReA 5

Team involved in: Oncology and haematology & Diagnosis and therapy in oncology gROUP MeMBeRS StrateGic effectiveness of gold nanoparticles oBjectiveS and cisplatin is also studied. 3. Breast cancer imaging diagnosis. teAM leADeR • Development of techniques for im- Two types of studies are carried out. francesca pons proving the diagnosis, prognostic One type of study uses 10G needle (Hospital clínic) evaluation and treatment response biopsies to improve the presurgical tel.: 93 227 54 82 assessment in oncological patients. diagnosis of breast tumors, particularly fax: 93 451 81 37 • Development and application of new in application to those with microcal- e-mail: therapies in oncology. cifications. The aim is to minimize the [email protected] number of surgical biopsies required for establishing the diagnosis. The iDiBApS MeMBeRS: main lineS of other type of study assesses the res- Albert Biete (Hospital clínic) reSearcH ponse to neoadjuvant chemotherapy carles conill (Hospital clínic) in breast cancer based on breast MRI David fuster (Hospital clínic) 1. Molecular studies in embryonic evaluation. Xavier Setoain (Hospital clínic) and tumor cells: applications to 4. Gammagraphic (scintigraphic) de- Martín Velasco (Hospital clínic) pharmacogenomics. Two types of tection of the sentinel node. Lym- Sergi Vidal-Sicart (Hospital clínic) studies are carried out: one type analy- phogammagraphy and posterior use of Marià Monzó (uB) zes and compares microRNA patterns an external detection probe during sur- laura oleaga (Hospital clínic) in embryonic and tumor tissues, and gery serves to identify and remove the Maria Africa Muxí the other uses allelic discrimination to sentinel node. This technique makes it analyze polymorphic profiles (SNPs) possible to avoid 75% of all unneces- collABoRAtoRS: in oncological patients, with a view to sary lymphadenectomies. The use of a Sebastián capurro (Hospital clínic) selecting more specific treatments. portable gammacamera during surgery francesc casas (Hospital clínic) 2. Effects of synchrotron radiation offers additional advantages. lluís Donoso Bach (Hospital clínic) upon the neoplastic cell. In this 5. Application of positron emission Blanca farrús (Hospital clínic) study, which is carried out jointly with tomography (PEt-ct) in oncology. Mario pagés (Hospital clínic) Barcelona Autonomous University PET studies are made for the staging teresa pujol (Hospital clínic) (UAB), comparison is made of the bio- and control of treatment response in Sonia Rodríguez (Hospital clínic) logical action of synchrotron radiation different types of tumors, including Angels Rovirosa (Hospital clínic) (currently the Grenoble system until lymphomas, breast cancer and diges- Marcelo Sánchez (Hospital clínic) the UAB Alba unit comes into operative tract lesions. We plan to use an Gorane Santamaría (Hospital clínic) tion) with conventional X-rays used intraoperative PET probe to improve eugènia Verger (Hospital clínic) in radiotherapy. The cell-sensitizing the detection of tumor lesions. pilar paredes (Hospital clínic) francisco lomeña (Hospital clínic) Javier pavía (Hospital clínic) francisco campos (Hospital clínic)

Coronal Positron Emission Tomography (PET) images of a patient with diffuse large cell lymphoma (DLCL). A) Initial staging showing pathological uptake of 18F-FDG in the spleen and celiac, mesenteric and retroperitoneal lymph nodes. B) The PET performed at the end of the chemotherapy shows a normal uptake of 18F-FDG in the abdomen, without pathological uptake, suggesting a complete response to treatment.

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Diagnosis and therapy in oncology

PUBLICATIONS

oRiGinAlS 6 Campayo M, Vinolas N, Navarro A, with LRRK2 mutations. J NEUROL. i.f.: 81.69 Carcereny E, Casas F, Gel B, Diaz T, 258:1126-1132. I.F.: 3.85. Gimferrer JM, Marrades RM, Ramirez 1 Garcia AI, Milinkovic A, Tomas X, J, Monzo M. Single Nucleotide Poly- 12 Fernandez S, Donaire A, Maes- Rios J, Perez I, Vidal-Sicart S, Pomes morphisms in Tobacco Metabolism and tro I, Seres E, Setoain X, Bargallo N, J, DelAmo M, Mallolas J. MRI signal DNA Repair Genes and Prognosis in Rumia J, Boget T, Falcon C, Carreno changes of the bone marrow in HIV- Resected Non-Small-Cell Lung Cancer. M. Functional neuroimaging in start- infected patients with lipodystrophy: J SURG RES. 167:E5-E12. I.F.: 2.24. le epilepsy: Involvement of a mesial correlation with clinical parameters. frontoparietal network. EPILEPSIA. SKELETAL RADIOL. 40:1295-1301. 7 Torregrosa JV, Fuster D, Monegal 52:1725-1732. I.F.: 3.96. I.F.: 1.39. A, Gentil MA, Bravo J, Guirado L, Muxi A, Cubero J. Efficacy of low doses of 13 Carreno M, Becerra JL, Castillo 2 Fuster D, Soriano A, Garcia S, pamidronate in osteopenic patients J, Maestro I, Donaire A, Fernandez S, Piera C, Suades J, Rodriguez D, administered in the early post-renal Bargallo N, Setoain X, Pintor L, Bailles Martinez JC, Mensa J, Campos F, transplant. OSTEOPOROSIS INT. E, Rumia J, Boget T, Vernet O, Fumanal Pons F. Usefulness of Tc-99m-ci- 22:281-287. I.F.: 4.86. S. Seizure frequency and social outco- profloxacin scintigraphy in the diag- me in drug resistant epilepsy patients nosis of prosthetic joint infections. 8 Fuster D, Ayuso JR, Poveda A, Cu- who do not undergo epilepsy surgery. NUCL MED COMMUN. 32:44-51. bedo R, Casado A, Martinez-Trufero J, SEIZURE-EUR J EPILEP. 20:580-582. I.F.: 1.37. Lopez-Pousa A, DelMuro XG, Lomena I.F.: 1.65. F, Maurel J, Pons F. Value of FDG-PET 3 Bosch X, Esteve J, Sitges M, for monitoring treatment response in 14 Rubi S, Setoain X, Donaire A, DeCaralt TM, Domenech A, Ortiz patients with advanced GIST refractory Bargallo N, Sanmarti F, Carreno M, JT, Monzo M, Morales-Ruiz M, to high-dose imatinib. A multicenter Rumia J, Calvo A, Aparicio J, Campistol Perea RJ, Rovira M. Prevention of GEIS study. Q J NUCL MED MOL IM. J, Pons F. Validation of FDG-PET/MRI Chemotherapy-Induced Left Ventri- 55:680-687. I.F.: 2.54. coregistration in nonlesional refrac- cular Dysfunction With Enalapril and tory childhood epilepsy. EPILEPSIA. Carvedilol: Rationale and Design of 9 Obach V, Oleaga L, Urra X, Macho J, 52:2216-2224. I.F.: 3.96. the OVERCOME Trial. J CARD FAIL. Amaro S, Capurro S, Gomez-Choco M, 17:643-648. I.F.: 3.36. SanRoman L, Cervera A, Blasco J, Var- 15 Verger E, Valduvieco I, Caral L, gas M, Torres F, Chamorro A. Multimo- Pujol T, Ribalta T, Vinolas N, Boget 4 Campayo M, Navarro A, Vinolas dal CT-Assisted Thrombolysis in Patients T, Oleaga L, Blanco Y, Graus F. Does N, Tejero R, Munoz C, Diaz T, Ma- With Acute Stroke A Cohort Study. gender matter in glioblastoma?. CLIN rrades R, Cabanas ML, Gimferrer STROKE. 42:1129-1131. I.F.: 5.76. TRANSL ONCOL. 13:737-741. I.F.: 1.25. JM, Gascon P, Ramirez J, Monzo M. A Dual Role for KRT81: A miR- 10 Muxi A, Paredes P, Navales I, 16 Gutierrez-Garcia G, Garcia-Herrera SNP Associated with Recurrence Valldeoriola F, Gaig C, Lomena F, DeLa- A, Cardesa T, Martinez A, Villamor N, in Non-Small-Cell Lung Cancer and Cerda A, Sola O, Domenech B, Tolosa Ghita G, Martinez-Trillos A, Colomo L, a Novel Marker of Squamous Cell E, Pons F. Diagnostic cutoff points for Setoain X, Rodriguez S, Gine E, Campo Lung Carcinoma. PLOS ONE. 6:-. I-123-MIBG myocardial scintigraphy in a E, Lopez-Guillermo A. Comparison of I.F.: 4.41. Caucasian population with Parkinson’s four prognostic scores in peripheral disease. EUR J NUCL MED MOL I. T-cell lymphoma. ANN ONCOL. 22:397- 5 Navarro A, Diaz T, Gallardo E, 38:1139-1146. I.F.: 5.04. 404. I.F.: 6.45. Vinolas N, Marrades RM, Gel B, Campayo M, Quera A, Bandres E, 11 Valldeoriola F, Gaig C, Muxi A, 17 Artells R, Navarro A, Diaz T, Garcia-Foncillas J, Ramirez J, Monzo Navales I, Paredes P, Lomena F, De- Monzo M. Ultrastructural and Immu- M. Prognostic Implications of miR- LaCerda A, Buongiorno M, Ezquerra nohistochemical Analysis of Intestinal 16 Expression Levels in Resected M, Santacruz P, Marti MJ, Tolosa E. Myofibroblasts During the Early Orga- Non-Small-Cell Lung Cancer. J SURG I-123-MIBG cardiac uptake and smell nogenesis of the Human Small Intesti- ONCOL. 103:411-415. I.F.: 2.43. identification in parkinsonian patients ne. ANAT REC. 294:462-471. I.F.: 1.40.

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original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 67.93 21 8 4 18 Vidal-Sicart S, Brouwer OR, Valdes- 24 Gil S, Fernandez M, Prezado Y, Olmos RA. Evaluation of the sentinel Biete A, Bravin A, Sabes M. Synchro- 2010 67.05 22 6 7 lymph node combining SPECT/CT with tron radiation in cancer treatments and 2011 81.69 26 9 7 the planar image and its importance for diagnostics: an overview. CLIN TRANSL the surgical act. REV ESP MED NUCL. ONCOL. 13:715-720. I.F.: 1.25. 30:331-337. I.F.: 0.77. 25 Vidal-Sicart S, Vermeeren L, 19 Cibeira MT, DeLarrea CF, Navarro Sola O, Paredes P, Valdes-Olmos RA. de microarrays de microRNAs en A, Diaz T, Fuster D, Tovar N, Rosinol L, The use of a portable gamma camera sangre periférica de pacientes con Monzo M, Blade J. Impact on response for preoperative lymphatic mapping: a cáncer colorrectal. Sponsored by: and survival of DNA repair single nu- comparison with a conventional gam- Ministerio de Sanidad y Consumo, cleotide polymorphisms in relapsed or ma camera. EUR J NUCL MED MOL PS09/00547. Duration: 01/01/2009- refractory multiple myeloma patients I. 38:636-641. I.F.: 5.04. 31/12/2012. treated with thalidomide. LEUKEMIA RES. 35:1178-1183. I.F.: 2.56. 26 Rovirosa A, Ascaso C, Sanchez- Vidal S. Utilidad clínica del SPECT-CT Reyes A, Herreros A, Abellana R, y una gammacamara portátil para la 20 Diaz T, Navarro A, Ferrer G, Gel B, Pahisa J, Lejarcegui JA, Biete A. detección del ganglio centinela en Gaya A, Artells R, Bellosillo B, Garcia- Three or four fractions of 4-5 GY per el cáncer de cérvix y endometrio. Garcia M, Serrano S, Martinez A, Monzo week in postoperative High-Dose- Sponsored by: Instituto de Salud M. Lestaurtinib Inhibition of the JAK/STAT Rate brachytherapy for endometrial Carlos III (ISCIII), PI09/1108. Duration: Signaling Pathway in Hodgkin Lymphoma carcinoma. INT J RADIAT ONCOL. 01/01/2010-31/12/2012. Inhibits Proliferation and Induces Apopto- 81:418-423. I.F.: 4.50. sis. PLOS ONE. 6:-. I.F.: 4.41. Pons F. Imatge Molecular en Medici- na Nuclear. Sponsored by: Generalitat 21 SamperOts PM, Munoz J, Biete A, eDitoRiAlS de Catalunya, 2009_SGR_1049. Dura- Ortiz MJ, Acuna M, Cabrera J, LopezCa- i.f.: 2.18 tion: 15/09/2009-31/12/2013. rrizosa C, Bayo E, Herruzo I, Perez MM, Dominguez MA, MorilloMacias V, Mira M, 1 Fuertes J, Mestre-Fusco A, Sua- Monzó M. Oncologia i embriologia PerezCasas AM, Sevillano MM, GarciaRios I, rez M, Plancarte F, Munne-Collado J, molecular. Sponsored by: AGAUR_ Andreu F, Sotoca A, Alvarez A, Lopez E, Pe- Vidal-Sicart S. False positive of intra- SGR09, 2009_SGR_1339. Duration: rezEscutia MA, LoayzaVillaroel A. PITASOR mammary sentinel node. REV ESP 23/09/2009-31/12/2013. epidemiological study: prevalence, incidence MED NUCL. 30:112-113. I.F.: 0.77. and treatment of anaemia in radiation the- Oleaga L. Gestión del remodelado rapy oncology departments in Spain. CLIN 2 Setoain X, Lopez-Guillermo A. cardiovascular mediante integración TRANSL ONCOL. 13:322-327. I.F.: 1.25. Non-Hodgkin’s lymphoma staging de tecnologías de monitorización with PET-CT scan. MED CLIN-BARCE- ubicua y conceptos del humano 22 Balleyguier C, Sala E, DaCunha T, LONA. 137:402-404. I.F.: 1.41. fisiológico virtual. Sponsored by: CE- Bergman A, Brkljacic B, Danza F, Forstner NIT09 09/397. Duration: 15/9/2009- R, Hamm B, Kubik-Huch R, Lopez C, Man- 31/12/2012. fredi R, Mchugo J, Oleaga L, Togashi K, GRAntS foR ReSeARcH Kinkel K. Staging of uterine cervical can- in pRoGReSS cer with MRI: guidelines of the European DoctoRAl tHeSeS Society of Urogenital Radiology. EUR RA- Pons F. Red temática de investigación DIOL. 21:1102-1110. I.F.: 3.59. cooperativa de cáncer. Sponsored Oleaga L. Estudio del sistema muscu- by: Ministerio Sanidad y Consu- loesquelético mediamnte resonancia 23 Gil S, Sarun S, Biete A, Prezado Y, mo, RD06/0020/0038. Duration: magnética en la valoración del Sín- Sabes M. Survival analysis of F98 glioma 01/01/2007-31/12/2012. drome de Lipodistrofia en pacientes rat cells following minibeam or broad- infectados por el virus de la inmu- beam synchrotron radiation therapy. RA- Monzó M. Utilidad clínica de biomar- nodeficiencia humana. PhD student: DIAT ONCOL. 6:37-37. I.F.: 2.41. cadores tumorales mediante análisis García Díez Ana Isabel.

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Molecular genetics StrateGic function (Mateo et al., 2011; Oliva and oBjectiveS Castillo, 2011). We have also contribu- gROUP MeMBeRS ted to the identification of alterations The research group comprises the in the ratio of protamines in the sperm laboratories of Gene Expression and nucleus, which predict assisted repro- teAM leADeR Cancer (www.fisiologia.net) and Hu- duction outcomes and are associated cristóbal Mezquita man Genetics (www.ub.edu/human- with alterations in sperm DNA integrity (universitat de gen). Our research work is set within in infertile patients (Mateo et al., 2011; Barcelona) the paradigm of current physiology: Castillo et al., 2011). In another line of tel.: 93 402 45 18 the study of genic expression mecha- research, we completed a study on fax: 93 403 52 79 nisms as a new approach to the study mutations of the genes of protamines e-mail: of the functions of the body. On one 1 and 2 in infertile patients, identifying [email protected] hand, our work is presently directed several new mutations, polymorphisms towards the proteomic and molecular and haplotypes (Jodar et al. 2011). One xxxxxx iDiBApS MeMBeRS: characterization of spermatozoa in of the important challenges is to eluci- Jovita Mezquita (uB) infertile patients and controls, while date the basic mechanisms that opera- Rafael oliva (Hospital clínic i uB) on the other, studies are made of the te in nucleus-histone nucleus-protamine Josep oriola (Hospital clínic i uB) mechanisms involved in angiogenesis transition during spermatogenesis and and in tumor cell invasion. how alterations may lead to alterations poStDoctoRAl fellowS: in the sperm’s epigenetic information. Alexandra Amaral (uB) main lineS of Another challenge will be the transla- reSearcH tion of important basic observations to ReSeARcH fellowS: the clinical setting. Sara de Mateo (fundació clínic) The group has traditionally worked on VEGFR1 expression in different tumour Meritxell Jodar (fundació clinic) gene expression mechanisms and the cells is essential for the invasion and Rubén Azpiazu (fundació clinic) differentiation of the spermatogenic formation of metastases. VEGFR1 Judit castillo (fundació clinic) germinal line, and more recently on the expression in tissue stromal cells is mechanisms involved in angiogenesis also important in the formation of me- tecHniciAnS: and in tumour cell invasion. tastases. Not all invasive tumour cells Montserrat pau (uB) One relevant aspect is the identifi- express VEGFR1, due to the hyper- cation of numerous new proteins of methylation of the gene promoter. In collABoRAtoRS: the sperm nucleus and the approach highly invasive breast carcinoma cells, Betlem Mezquita (uB) regarding potential transmission to with the hypermethylated VEGFR1 Josep lluís Ballescà (Hospital clínic) the oocyte and potential epigenetic gene promoter, we have discovered the existence of truncated intracellular forms of VEGFR1 transcribed from intronic promoters. One of these forms is preferentially expressed in invasive breast carcinoma cells and promotes tumour invasion by activating the Src tyrosine kinase. We recently observed that this truncated form, which promotes invasion independently of VEGF and other ligands, is positively regulated by the Notch signalling pathway and negatively regulated by retinoic acid through the miR-200 microRNA family.

268 AReA 5 oncoloGy AnD HAeMAtoloGy MoleculAR GeneticS

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 12.97 4 3 0 oRiGinAlS 7 Jodar M, Oriola J, Mestre G, i.f.: 32.90 Castillo J, Giwercman A, Vidal- 2010 2.94 1 0 1 Taboada JM, Ballesca JL, Oliva R. 2011 32.90 11 5 1 1 Fortea J, Llado A, Clarimon J, Polymorphisms, haplotypes and Lleo A, Oliva R, Peri J, Pintor L, Ya- mutations in the protamine 1 and 2 gue J, Blesa R, Molinuevo JL, San- genes. INT J ANDROL. 34:470-485. chez-Valle R. PICOGEN: Five years I.F.: 3.60. experience with a genetic counse- GRAntS foR ReSeARcH lling program for dementia. NEURO- 8 DeMateo S, Ramos L, DeBoer in pRoGReSS LOGIA. 26:143-149. I.F.: 0.59. P, Meistrich M, Oliva R. Protamine 2 Precursors and Processing. PRO- Oliva R. Caracterización proteómica y 2 Wen L, Green EA, Stratmann T, TEIN PEPTIDE LETT. 18:778-785. genómica del núcleo del espermatozoi- Panosa A, Gomis R, Eynon EE, Flavell I.F.: 1.85. de humano normal y de sus alteracio- RA, Mezquita JA, Mora C. In vivo dianes en pacientes infértiles. Sponsored betogenic action of CD4(+) T lympho- 9 Castillo J, Simon L, DeMateo S, by: Ministerio de Ciencia e Innovación, cytes requires Fas expression and is Lewis S, Oliva R. Protamine/DNA Ra- BFU2009-07118. Duration: 31/12/2009- independent of IL-1 and IL-18. EUR J tios and DNA Damage in Native and 30/12/2012. IMMUNOL. 41:1344-1351. I.F.: 4.94. Density Gradient Centrifuged Sperm From Infertile Patients. J ANDROL. Oliva R. Grup de Genètica Humana. 3 Antonell A, Balasa M, Oliva R, 32:324-332. I.F.: 3.14. Sponsored by: Generalitat de Catalun- Llado A, Bosch B, Fabregat N, Fortea ya, AGAUR_SGR09, 2009_SGR_1440. J, Molinuevo JL, Sanchez-Valle R. A 10 DeMateo S, Castillo J, Estanyol Duration: 29/07/2009-31/12/2013. novel PSEN1 gene mutation (L235R) JM, Ballesca JL, Oliva R. Proteomic associated with familial early-onset characterization of the human sperm Alzheimer’s disease. NEUROSCI nucleus. PROTEOMICS. 11:2714- LETT. 496:40-42. I.F.: 2.06. 2726. I.F.: 4.82.

4 Fortea J, Llado A, Bosch B, 11 Simon L, Castillo J, Oliva R, Antonell A, Oliva R, Molinuevo JL, Lewis SEM. Relationships between Sanchez-Valle R. Cerebrospinal Fluid human sperm protamines, DNA Biomarkers in Alzheimer’s Disease damage and assisted reproduction Families with PSEN1 Mutations. outcomes. REPROD BIOMED ONLI- NEURODEGENER DIS. 8:202-207. NE. 23:724-734. I.F.: 2.29. I.F.: 3.79.

5 Mora M, Perales MJ, Serra-Prat M, ReViewS Palomera E, Buquet X, Oriola J, Puig- i.f.: 2.96 Domingo M. Aging phenotype and its relationship with IGF-I gene promoter 1 Oliva R, Badenas C, Claria J, polymorphisms in elderly people living Coll MJ. Molecular genetic reports in Catalonia. GROWTH HORM IGF in clinical practice: Content and RES. 21:174-180. I.F.: 2.23. nomenclature of mutations. MED CLIN-BARCELONA. 136:356-361. 6 DeMateo S, Ramos L, VanDerVlag I.F.: 1.41. J, DeBoer P, Oliva R. Improvement in chromatin maturity of human sperma- 2 Oliva R, Castillo J. Proteomics and tozoa selected through density gra- the genetics of sperm chromatin con- dient centrifugation. INT J ANDROL. densation. ASIAN J ANDROL. 13:24- 34:256-267. I.F.: 3.60. 30. I.F.: 1.55.

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Oncology and haematology Team involved in:

Genetics

gROUP MeMBeRS StrateGic main lineS of oBjectiveS reSearcH teAM leADeR Montserrat Milà Characterization of rare hereditary di- 1. Identification of thegenetic bases (Hospital clínic) seases in the clinical, cytogenetic and of intellectual disability (ID) of tel.: 93 227 54 00 molecular contexts. genetic origin, both syndromic (ext.2784) There are four main lines of research. and non-syndromic, using the new fax: 93 227 56 97 Each line has the strategic objectives NSG technologies. e-mail: defined by the supporting research Application of massive sequen- [email protected] projects. In this context, the study of cing to different groups of clinica- mental retardation (MR) and identifi- lly well characterized ID will allow xxxxxx iDiBApS MeMBeRS: cation of the causal genetic factors us to identify new genes and Anna carrió (Hospital clínic) are fundamented upon the applica- establish new molecular bases in carmen Herrero (Hospital clínic) tion of high performance array CGH ID. Application is also planned to Mario lecha (Hospital clínic) and Next Sequencing Generation the study of familial mental retar- ester Margarit (Hospital clínic) (NSG) technologies. On the other dation and to sporadic cases of Aurora Sánchez (Hospital clínic) hand, the study of fragile X–associa- non-syndromic ID. Anna Soler (Hospital clínic) ted tremor/ataxia syndrome (FXTAS) Jordi to-figueras (Hospital clínic) aims to identify a biological marker 2. Fragile x syndrome: Study of the allowing us to establish a presympto- pathologies associated with pre- collABoRAtoRS: matic diagnosis of FXTAS in carriers mutation of the FMR1 gene: FXPOI cèlia Badenas (Hospital clínic) of the premutation in the FMR1 (Premature ovarian insufficienciy), irene Mademont gene, based on study of the miRNA FXTAS (Fragile X Tremor Ataxia Syn- irene Madrigal (Hospital clínic) profile. Regarding the porphyrias, the drome), and fibromyalgia associated carmen Morales strategic objective is to advance in with the FMR1 gene. Study of the laia Rodriguez Revenga (ciBeReR) our knowledge of the correlation ge- microRNA and ASFMR1 gene ex- Maria isabel Alvarez (ciBeReR) notype – phenotype: biochemical and pression profiles as possible suscep- francisca Silva clinical expression. tibility factors for FXTAS.

c.2013delG mutation detected through Next Generation Sequencing in a family suffering an intellectual disability. The mutation was confirmed with Sanger sequencing, proven to be pathogenic with Poliphen2 software and analyzed in a family segregation study.

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PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 oRiGinAlS 2009 49.78 13 5 5 78.70 22 10 4 3. Detection of cryptic chromosomal i.f.: 128.51 2010 imbalances and the identification of 2011 128.51 14 7 4 new phenotypes, based on cyto- 1 Puente XS, Pinyol M, Quesada genetic - molecular techniques. One V, Conde L, Ordonez GR, Villamor N, is conducted in the prenatal and Escaramis G, Jares P, Bea S, Gonza- postnatal diagnostic setting. The aim lez-Diaz M, Bassaganyas L, Baumann Beaumont C, Ferreira GC, Deybach is to characterize chromosomal im- T, Juan M, Lopez-Guerra M, Colomer JC, Herrero C, Puy H. ALAS2 acts balances in fetuses with congenital D, Tubio JMC, Lopez C, Navarro A, as a modifier gene in patients with anomalies and a normal karyotype, Tornador C, Aymerich M, Rozman congenital erythropoietic porphyria. based on the use of CGH arrays. M, Hernandez JM, Puente DA, Freije BLOOD. 118:1443-1451. I.F.: 10.56. JMP, Velasco G, Gutierrez-Fernandez 4. Study of the genotype-phenotype A, Costa D, Carrio A, Guijarro S, 5 Aarsand AK, Villanger JH, Stole E, correlation and expression mecha- Enjuanes A, Hernandez L, Yague J, Deybach JC, Marsden J, To-Figueras nisms of porphyria. The research Nicolas P, Romeo-Casabona CM, J, Badminton M, Elder GH, Sandberg lines aim to establish the following: Himmelbauer H, Castillo E, Dohm JC, S. European Specialist Porphyria • Advance in the study of the alte- DeSanjose S, Piris MA, DeAlava E, Laboratories: Diagnostic Strategies, rations in iron regulation and me- Miguel JS, Royo R, Gelpi JL, Torrents Analytical Quality, Clinical Interpretation, tabolism in skin and erythropoietic D, Orozco M, Pisano DG, Valencia and Reporting As Assessed by an porphyria. A, Guigo R, Bayes M, Heath S, Gut External Quality Assurance Program. • Investigate the role of modifier M, Klatt P, Marshall J, Raine K, Ste- CLIN CHEM. 57:1514-1523. I.F.: 6.89. genes that modulate the clinical bbings LA, Futreal PA, Stratton MR, expression of erythropoietic por- Campbell PJ, Gut I, Lopez-Guillermo 6 Barrett JH, Iles MM, Harland M, phyria. A, Estivill X, Montserrat E, Lopez-Otin Taylor JC, Aitken JF, Andresen PA, • Study of new serum and urine C, Campo E. Whole-genome sequen- Akslen LA, Armstrong BK, Avril MF, biomarkers of acute porphyria se- cing identifies recurrent mutations in Azizi E, Bakker B, Bergman W, Bianchi- verity of use in clinical practice. chronic lymphocytic leukaemia. NA- Scarra G, Bressac-DePaillerets B, TURE. 475:101-105. I.F.: 36.10. Calista D, Cannon-Albright LA, Corda E, The group will remain a member of Cust AE, Debniak T, Duffy D, Dunning the “European Porphyria Initiative” 2 Arigita M, Borrell A, Mula R, AM, Easton DF, Friedman E, Galan network as a reference center for the Sanchez A, Mila M, Gratacos E. P, Ghiorzo P, Giles GG, Hansson J, diagnosis, investigation and treatment Use of fetal nuchal translucency in Hocevar M, Hoiom V, Hopper JL, Ingvar of porphyria the first trimester to predict single- C, Janssen B, Jenkins MA, Jonsson gene disorders. PRENATAL DIAG. G, Kefford RF, Landi G, Landi MT, Lang 31:1164-1168. I.F.: 2.15. J, Lubinski J, Mackie R, Malvehy J, Martin NG, Molven A, Montgomery 3 Alonso-Espinaco V, Giraldez MD, GW, VanNieuwpoort FA, Novakovic Trujillo C, VanDerKlift H, Munoz J, S, Olsson H, Pastorino L, Puig S, Balaguer F, Ocana T, Madrigal I, Puig-Butille JA, Randerson-Moor J, Jones AM, Echeverry MM, Velez Snowden H, Tuominen R, Vanbelle P, A, Tomlinson I, Mila M, Wijnen VanDerStoep N, Whiteman DC, Zelenika J, Carvajal-Carmona L, Castells D, Han JL, Fang SY, Lee JE, Wei QY, A, Castellvi-Bel S. Novel MLH1 Lathrop GM, Gillanders EM, Brown duplication identified in Colombian KM, Goldstein AM, Kanetsky PA, Mann families with Lynch syndrome. GJ, Macgregor S, Elder DE, Amos CI, GENET MED. 13:155-160. I.F.: 5.28. Hayward NK, Gruis NA, Demenais F, Bishop JAN, Bishop DT. Genome-wide 4 To-Figueras J, Ducamp S, Clayton association study identifies three new J, Badenas C, Delaby C, Ged C, melanoma susceptibility loci. NAT GEN- Lyoumi S, Gouya L, DeVerneuil H, ET. 43:1108-U98. I.F.: 36.38.

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7 To-Figueras J, Phillips JD, fluid samples during the last decade. 2 Schoof N, Iles MM, Bishop DT, Gonzalez-Lopez JM, Badenas C, EUR J OBSTET GYN R B. 157:156- Newton-Bishop JA, Barrett JH. Path- Madrigal I, Gonzalez-Romaris EM, 160. I.F.: 1.76. way-Based Analysis of a Melanoma Ramos C, Aguirre JM, Herrero C. Genome-Wide Association Study: Hepatoerythropoietic porphyria 13 Munoz-Santos C, Guilabert A, Analysis of Genes Related to Tumour- due to a novel mutation in the Moreno N, Gimenez M, Darwich E, To- Immunosuppression. PLOS ONE. 6:-. uroporphyrinogen decarboxylase Figueras J, Herrero C. The association I.F.: 4.41. gene. BRIT J DERMATOL. 165:499- between porphyria cutanea tarda and 505. I.F.: 4.35. diabetes mellitus: analysis of a long- term follow-up cohort. BRIT J DERMA- GRAntS foR ReSeARcH 8 Madrigal I, Xuncla M, Tejada TOL. 165:486-491. I.F.: 4.35. in pRoGReSS MI, Martinez F, Fernandez-Carvajal I, Perez-Jurado LA, Rodriguez- 14 Pereira A, Nomdedeu M, Aguilar Mila M. Estudio de los perfiles de Revenga L, Mila M. Intermediate JL, Belkaid M, Carrio A, Cobo F, Costa expresión de microRNAS y del gen FMR1 alleles and cognitive and/ D, Rozman M, Sanz C, Nomdedeu B. ASFMR1 como factores de sus- or behavioural phenotypes. EUR J Transfusion intensity, not the cumulative ceptibilidad para el desarrollo del HUM GENET. 19:921-923. I.F.: 4.38. red blood cell transfusion burden, síndrome FXTAS. Sponsored by: determines the prognosis of patients INSTITUTO DE SALUD CARLOS III, 9 Nakabayashi K, Trujillo AM, with myelodysplastic syndrome on PIO9/0413. Duration: 01/01/2010- Tayama C, Camprubi C, Yoshida W, chronic transfusion support. AM J HE- 31/12/2012. Lapunzina P, Sanchez A, Soejima H, MATOL. 86:245-250. I.F.: 3.58. Aburatani H, Nagae G, Ogata T, Hata Mila M. European Sequencing and K, Monk D. Methylation screening Genotyping Infrastructure (ESGI). of reciprocal genome-wide UPDs ReViewS Whole Exome Sequencing in Intelec- identifies novel human-specific i.f.: 1.41 tual Disability (WESID). Sponsored by: imprinted genes. HUM MOL GENET. European Commission, 7th Frame- 20:3188-3197. I.F.: 8.06. 1 Oliva R, Badenas C, Claria J, Coll work Programme, 262055. Duration: MJ. Molecular genetic reports in clinical 01/01/2011-31/12/2012. 10 Bennassar A, Mas A, practice: Content and nomenclature of Guilabert A, Julia M, Mascaro- mutations. MED CLIN-BARCELONA. Mila M. Grupo de excelencia reco- Galy JM, Herrero C. Multicentric 136:356-361. I.F.: 1.41. nocido y financiado. Sponsored by: reticulohistiocytosis with elevated Generalitat de Catalunya, AGAUR, cytokine serum levels. J DERMA- SGR1337. Duration: 01/01/2009- TOL. 38:905-910. I.F.: 1.36. MulticentRicS 31/12/2013. i.f.: 12.47 11 Segura S, Puig S, Carrera C, Lecha M, Borges V, Malvehy 1 Amos CI, Wang LE, Lee JE, DoctoRAl tHeSeS J. Non-invasive management of Gershenwald JE, Chen WV, Fang non-melanoma skin cancer in SY, Kosoy R, Zhang MF, Qureshi AA, Sanchez A. Evolució del diagnòstic patients with cancer predisposition Vattathil S, Schacherer CW, Gardner citogenètic prenatal i postnatal amb genodermatosis: a role for confocal JM, Wang YL, Bishop DT, Barrett JH, la implementació de noves tècniques microscopy and photodynamic Macgregor S, Hayward NK, Martin NG, de biologia molecular i la seva reper- therapy. J EUR ACAD DERMATOL. Duffy DL, Mann GJ, Cust A, Hopper cussió en el consell genètic. PhD stu- 25:819-827. I.F.: 3.31. J, Brown KM, Grimm EA, Xu YJ, Han dent: Mª Carme Morales Peydró. YH, Jing KY, Mchugh C, Laurie CC, 12 Mademont-Soler I, Morales Doheny KF, Pugh EW, Seldin MF, Han Herrero C. Porfiria cutánea tarda espo- C, Clusellas N, Soler A, Sanchez A. JL, Wei QY. Genome-wide association rádica y familiar: Estudio observacional Prenatal cytogenetic diagnosis in study identifies novel loci predisposing de las características clínicas, bioquí- Spain: analysis and evaluation of to cutaneous melanoma. HUM MOL micas y de los factores de riesgo. PhD the results obtained from amniotic GENET. 20:5012-5023. I.F.:8.06. student: Carlos Muñoz Santos.

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Oncology and haematology

Melanoma: imaging, genetics and immunology gROUP MeMBeRS

StrateGic oBjectiveS

1. Development of noninvasive ima- teAM leADeR ging techniques for the diagnosis of Susana puig (Hospital clínic) melanoma. tel.: 93 2275400 (ext 2891) 2. Study of the genetic bases implica- fax: 93 227 54 38 ted in susceptibility to melanoma e-mail: [email protected] and photocarcinogenesis. 3. Development of treatment study iDiBApS MeMBeRS: collABoRAtoRS: strategies in melanoma and skin Ramón Vilella (Hospital clínic) paula Aguilera (Hospital clínic) cancer: target-specific molecular, Josep Malvehy (Hospital clínic) pedro Arguís (Hospital clínic) immunological and photoprotection cristina carrera (Hospital clínic) therapies. ReSeARcH fellowS: Antonio campo (Hospital clínic) 4. Application of artificial intelligence Zighe ogbah (fundació clínic) carlos conill (Hospital clínic) systems for evaluating complex data Joan Anton puig (ciBeReR) Ramon Rull (Hospital clínic) in melanoma, combining imaging, Gabriel Salerni (fundació clínic) Sergi Vidal (Hospital clínic) epidemiological, clinical and molecu- Ramón Vilana (Hospital clínic) lar information. tecHniciAnS: teresa castel (Hospital clínic) 5. Development of models of humanized Remedios cervera (fundació clínic) Antoni Vilalta (Hospital clínic) mouse skin for the study of photopro- Dani Gabriel (fundació clínic) José palou (Hospital clínic) tection and photocarcinogenesis. pablo iglesias (fundació clínic) Melania Vargas (fundació clínic) Jordi Milà (Hospital clínic) celia Badenas (Hospital clínic) main lineS of luchi Millan (Hospital clínic) reSearcH laura Martín (fundació clínic) Our main lines of research, and some of the most relevant results obtained to date, are the following: 1. Dermatoscopy and digital dermatoscopy. In dermatoscopy studies are being made of the diagnostic criteria of different disorders that have still not been well characterized, the correlations with other imaging techniques, the impact upon the management of patients at risk, and the relationship between dermatoscopy and the genetic profile of the patients. In digital dermatoscopy we are examining the use of full body maps and digital dermatoscopy in the follow-up of patients at risk. 1.1 Definition of new dermatoscopic criteria in different dermatologi- cal processes (dermatofibromas, angiokeratomas, botryomycosis, blue nevus, xanthogranuloma,

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Melanoma: imaging, genetics and immunology

leishmaniasis, lichenoid keratosis, collision tumors). 1.2 Development of dermatoscopy for introduction in primary care, in pathology and dermatology (development of combined clinical dermatoscopic algorithms for the identification of melanomas that are difficult to diagnose). 1.3 Combined dermatoscopic and ultrasound protocol of the primary tumor for preoperative Breslow score estimation.

2. confocal microscopy in vivo. Des- cription of new algorithms, study of the evolution of lesions, new classifi- cations and the use of telemedicine. 2.1 Definition of criteria in nodular melanoma. ce gene in relation to melanoma 4.4 Expression studies (MAGE and 2.2 Creation of a differential diag- risk, and in reference to the cli- others) in melanoma. nostic algorithm for melanocytic nical and dermatoscopic aspects 4.5 Development of experimental and non-melanocytic lesions. of melanomas. models of gene/gene, gene/ 2.3 Characterization of pigmented 3.3 Identification of new melanoma environment interactions bet- basal cell carcinomas, squamous and nevogenicity susceptibility ween CDKN2A and MC1R. carcinomas and actinic keratosis. genes based on the study of Expression studies in kera- 2.4 Study of the use of confocal homozygous genome regions. tinocytes, melanocytes and microscopy for the correct 3.4 Susceptibility genes involved in fibroblasts according to their treatment of achromatic or melanoma prognosis genetic profile. poorly delimited lesions (deli- 4.6 DNA repair mechanisms and mitation of surgical margins or 4. Study of the mechanisms invol- their therapeutic implications. control of relapses). ved in carcinogenesis and photo- 2.5 Use of ex vivo confocal micros- carcinogenesis. 5. Development of new treatment copy for application to Mohs 4.1 Analysis of oral photoprotec- strategies for melanoma and surgery. tion. Study of genetic (CDK- other skin tumors. N2A, MC1R)/environmental 5.1 Hyperthermal perfusion of extre- 3. Genetic epidemiology. Study of interaction (UVR) in melanoma mities melanoma susceptibility genes in risk. Study of the influence of 5.2 Vaccines and new therapeutic familial melanoma and in sporadic ultraviolet radiation (UVR) (UVA; targets in melanoma. melanoma. Study of nevogenicity UVB; UVA/UVB) in the derma- 5.3 Electrochemotherapy in mela- and risk genes in melanoma. Study toscopic, histological and immu- noma. of pigmentation and risk genes in nohistochemical characteristics 5.4 Inhibition of the Hedgehog melanoma. Identification of new of melanocytic nevi. pathway for the treatment of genes and new mechanisms of me- 4.2 Dermatoscopic and genetic basal cell carcinomas. lanoma susceptibility using Genome characterization of the different 5.5 Specific immunotherapy in Mer- Wide Scan. Clark nevi in dysplastic nevus kel carcinoma. 3.1 Penetrance and phenotypic ex- syndrome, in relation to genetic pression studies in patients and polymorphisms. 6. Evaluation of immune response in families carrying known CDK- 4.3 Investigation of somatic muta- melanoma. N2A and p14arf mutations. tions of NRAS, BRAF, cKIT, ge- 6.1 Genetic expression arrays and 3.2 Study of the effect of polymor- nomic amplifications of different studies of SNPs associated phisms of the MC1R gene as oncogenes, and genomic losses with prognosis and treatment modifier gene and low penetran- of 9p21 (MLPA) in melanoma response.

274 AReA 5 oncoloGy AnD HAeMAtoloGy MelAnoMA: iMAGinG, GeneticS AnD iMMunoloGy

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 57.94 11 6 2 oRiGinAlS S, Elder DE, Amos CI, Hayward NK, i.f.: 133.79 Gruis NA, Demenais F, Bishop JAN, 2010 62.31 15 9 2 Bishop DT. Genome-wide association 2011 133.79 9 7 2 1 Carrera C, Palou J, Malvehy J, study identifies three new melano- Segura S, Aguilera P, Salerni G, Lo- ma susceptibility loci. NAT GENET. vatto L, Puig-Butille JA, Alos L, Puig 43:1108-U98. I.F.: 36.38. S. Early Stages of Melanoma on the Limbs of High-risk Patients: Clinical, 4 Segura S, Puig S, Carrera C, Lecha 7 Goulart JM, Malvehy J, Puig S, Dermoscopic, Reflectance Confocal M, Borges V, Malvehy J. Non-invasive Martin G, Marghoob AA. Dermoscopy Microscopy and Histopathological management of non-melanoma skin in Skin Self-examination A Useful Tool Characterization for Improved Re- cancer in patients with cancer predis- for Select Patients. ARCH DERMATOL. cognition. ACTA DERM-VENEREOL. position genodermatosis: a role for 147:53-58. I.F.: 4.23. 91:137-146. I.F.: 2.78. confocal microscopy and photodynamic therapy. J EUR ACAD DERMA- 8 Macgregor S, Montgomery GW, Liu 2 Diaz A, Valera A, Carrera C, TOL. 25:819-827. I.F.: 3.31. JZ, Zhao ZZ, Henders AK, Stark M, Schmid Hakim S, Aguilera P, Garcia A, H, Holland EA, Duffy DL, Zhang M, Painter Palou J, Puig S, Malvehy J, Alos 5 Lang JM, Shennan M, Njauw JN, Nyholt DR, Maskiell JA, Jetann J, L. Pigmented Spindle Cell Nevus: JCN, Luo S, Bishop JN, Harland M, Ferguson M, Cust AE, Jenkins MA, White- Clues for Differentiating It From Hayward NK, Tucker MA, Golds- man DC, Olsson H, Puig S, Bianchi-Scarra Spindle Cell Malignant Melanoma. tein AM, Landi MT, Puig S, Gruis G, Hansson J, Demenais F, Landi MT, Deb- A Comprehensive Survey Including NA, Bergman W, Bianchi-Scarra G, niak T, Mackie R, Azizi E, Bressac-DePaille- Clinicopathologic, Immunohisto- Ghiorzo P, Hogg D, Tsao H. A Flexi- rets B, Goldstein AM, Kanetsky PA, Gruis chemical, and FISH Studies. AM ble Multiplex Bead-Based Assay for NA, Elder DE, Newton-Bishop JA, Bishop J SURG PATHOL. 35:1733-1742. Detecting Germline CDKN2A and DT, Iles MM, Helsing P, Amos CI, Wei QY, I.F.: 4.11. CDK4 Variants in Melanoma-Prone Wang LE, Lee JE, Qureshi AA, Kefford RF, Kindreds. J INVEST DERMATOL. Giles GG, Armstrong BK, Aitken JF, Han 3 Barrett JH, Iles MM, Harland 131:480-486. I.F.: 6.27. JL, Hopper JL, Trent JM, Brown KM, Mar- M, Taylor JC, Aitken JF, Andresen tin NG, Mann GJ, Hayward NK. Genome- PA, Akslen LA, Armstrong BK, Avril 6 Bertolotto C, Lesueur F, Giulia- wide association study identifies a new MF, Azizi E, Bakker B, Bergman W, no S, Strub T, DeLichy M, Bille K, melanoma susceptibility locus at 1q21.3. Bianchi-Scarra G, Bressac-DePaille- Dessen P, D’hayer B, Mohamdi H, NAT GENET. 43:1114-U104. I.F.: 36.38. rets B, Calista D, Cannon-Albright Remenieras A, Maubec E, DeLaFou- LA, Corda E, Cust AE, Debniak chardiere A, Molinie V, Vabres P, Da- 9 Salerni G, Lovatto L, Carrera C, Puig T, Duffy D, Dunning AM, Easton lle S, Poulalhon N, Martin-Denavit T, S, Malvehy J. Melanomas Detected in a DF, Friedman E, Galan P, Ghiorzo Thomas L, Andry-Benzaquen P, Dupin Follow-up Program Compared With Me- P, Giles GG, Hansson J, Hocevar N, Boitier F, Rossi A, Perrot JL, Labei- lanomas Referred to a Melanoma Unit. M, Hoiom V, Hopper JL, Ingvar C, lle B, Robert C, Escudier B, Caron O, ARCH DERMATOL. 147:-. I.F.: 4.23. Janssen B, Jenkins MA, Jonsson G, Brugieres L, Saule S, Gardie B, Gad Kefford RF, Landi G, Landi MT, Lang S, Richard S, Couturier J, Teh BT, J, Lubinski J, Mackie R, Malvehy J, Ghiorzo P, Pastorino L, Puig S, Bade- eDitoRiAlS Martin NG, Molven A, Montgomery nas C, Olsson H, Ingvar C, Rouleau i.f.: 2.26 GW, VanNieuwpoort FA, Novakovic E, Lidereau R, Bahadoran P, Vielh P, S, Olsson H, Pastorino L, Puig S, Corda E, Blanche H, Zelenika D, Ga- 1 Salerni G, Lovatto L, Carrera C, Puig-Butille JA, Randerson-Moor J, lan P, Chaudru V, Lenoir GM, Lathrop Palou J, Alos L, Puig-Butille JA, Bade- Snowden H, Tuominen R, Vanbelle M, Davidson I, Avril MF, Demenais nas C, Malvehy J, Puig S. Correlation P, VanDerStoep N, Whiteman DC, F, Ballotti R, Bressac-DePaillerets B. among Dermoscopy, Confocal Re- Zelenika D, Han JL, Fang SY, Lee A SUMOylation-defective MITF ger- flectance Microscopy, and Histologic JE, Wei QY, Lathrop GM, Gillanders mline mutation predisposes to mela- Features of Melanoma and Basal Cell EM, Brown KM, Goldstein AM, noma and renal carcinoma. NATURE. Carcinoma Collision Tumor. DERMATOL Kanetsky PA, Mann GJ, Macgregor 480:94-U259. I.F.: 36.10. SURG. 37:275-279. I.F.: 2.26.

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MulticentRicS Vilella R. Estudio fase II aleatorizado i.f.: 12.47 en pacientes con cáncer colorectal en estadio IV progresivo a dos líneas de 1 Amos CI, Wang LE, Lee JE, quimioterapia, comparando el mejor Gershenwald JE, Chen WV, Fang tratamiento de soporte frente a trata- SY, Kosoy R, Zhang MF, Qureshi miento con células dendríticas y mejor AA, Vattathil S, Schacherer CW, tratamiento de soporte. Sponsored Gardner JM, Wang YL, Bishop DT, by: Ministerio de Sanidad, Política Barrett JH, Macgregor S, Hayward Social e Igualdad, TRA-082. Duration: NK, Martin NG, Duffy DL, Mann 01/01/2010-30/12/2011. GJ, Cust A, Hopper J, Brown KM, Grimm EA, Xu YJ, Han YH, Jing KY, Mchugh C, Laurie CC, Doheny KF, DoctoRAl tHeSeS Pugh EW, Seldin MF, Han JL, Wei QY. Genome-wide association study Puig S. Microscopía confocal de reflec- identifies novel loci predisposing to tancia in vivo en dermatología: Aplica- cutaneous melanoma. HUM MOL ción en el diagnóstico de tumores cutá- GENET. 20:5012-5023. I.F.: 8.06. neos. PhD student: Reyes Gamo.

2 Schoof N, Iles MM, Bishop DT, Puig S. Características dermatoscópi- Newton-Bishop JA, Barrett JH. cas de las lesiones melanocíticas en Pathway-Based Analysis of a Me- el síndrome del nevus con atipia en lanoma Genome-Wide Association diferentes áreas antómcas y de los Study: Analysis of Genes Related to melanomas en tronco y extremidades Tumour-Immunosuppression. PLOS inferiores. PhD student: Sonia Segura. ONE. 6:-. I.F.: 4.41. Puig S, Malvehy J. Descripción y eva- luación de los parámetros y patrones GRAntS foR ReSeARcH dermatoscópicos de las lesiones cutá- in pRoGReSS neas no melanocíticas y su diagnóstico diferencial con el melanoma. PhD stu- Puig S. NoE - Genetic and environ- dent: Pedro Zaballos Diego. mental risk factors for melanoma: translation into behavioural change. Puig S. Microscopía confocal de reflec- Sponsored by: European Commis- tancia in vivo en dermatología: Aplica- sion, LSHM-CT-2006-018702. Dura- ción en el diagnóstico de tumores cutá- tion: 01/12/2005-31/05/2011. neos. PhD student: Sonia Segura Tigell.

Puig S. Identificación de genes implicados en desarrollo y progresión de melanoma mediante la caracte- rización de regiones homozigotas. Sponsored by: Instituto de Salud Carlos III (ISCIII), PI09/1393. Dura- tion: 01/01/2010-31/12/2012.

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Oncology and haematology Team involved in:

Hematopoietic progenitor cell transplantation gROUP MeMBeRS

StrateGic oBjectiveS

In the last few years our group has developed basic and translational re- teAM leADeR search lines, thanks to collaboration Álvaro urbano-ispizúa (Hospital clínic) with other research groups of the Cli- tel.: 93 227 54 75 nic Hospital (Department of Immuno- e-mail: [email protected] logy, Department of Hemostasis) and of the Medical School (Department of iDiBApS MeMBeRS: nuRSinG StAff: Human Anatomy). Very recently, we enric carreras (Hospital clínic) Ariadna Domènech (fundació clínic) have established research space of our francesc fernández-Avilés (Hospital clínic) own in the CEK, and have expanded pedro Marín (Hospital clínic) collABoRAtoRS: our collaboration with other research carmen Martínez Muñoz (Hospital clínic) Josep Mensa (Hospital clínic) groups – particularly in reference to Montserrat Rovira (Hospital clínic) Alfons navarro (uB) cell therapy. Likewise, we have started Marià Monzó (uB) the expansion of hematopoietic precur- poStDoctoRAl fellowS: Maribel Díaz Ricart (Hospital clínic) sors from umbilical cord blood based Beatriz Martin Antonio (iDiBApS) Maria Suarez lledó (Hospital clinic) on co-cultures of mesenchymal cells and research lines in antitumor cell tecHniciAnS: therapy, anti-infectious treatment and Anna Mantecon (fundació clínic) cell immune modulation. Functional nuria Montfort (Hospital clínic) studies of genic polymorphisms have lucia Amleto (iDiBApS) also been started. Lastly, we plan to develop an important line of research in the field of the pharmacokinetics, pharmacodynamics and pharmacogenomics of immune modulators, as well as in the development of in vitro predictive models of graft-versus-host disease.

main lineS of reSearcH

cLINIcAL RESEARch LINES

1. Assessment of new hematopoietic precursor transplantation (hPt) indications. Treatment of diseases such as amyloidosis, POEMS syndrome, scleromyxede- ma, autoimmune disorders (multiple sclerosis, Crohn’s disease, lupus erythematosus), primary myelofibrosis or paroxysmal nocturnal he- moglobinuria – these being diseases in which our group has the most extensive experience in the country.

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Hematopoietic progenitor cell transplantation

2. Evaluation of new progenitor sources (high-complexity hematopoietic precursor transplantation). The lack of compatible siblings for all patients amenable to hematopoietic precursor transplantation is leading to the development of transplants from non-consanguineous donors or umbilical cord blood. We are the most active group in the country in relation to these high complexity procedures, which represent 30% of

our activity. A. Sphere obtained after one week of bone marrow B. Sphere expansion after four weeks of culture. isolated nestin-positive mesenchymal cell culture. 3. Evaluation of new transplant modalities. • Domiciliary autogenic HPT (the only such program in Europe, awarded on several occasions by the scientific and healthcare dysfunction. Our project aims to 4. Study of new techniques for societies) – a modality which we characterize such dysfunction and the early diagnosis of infections aim to extend to domiciliary allo- then to seek effective preventive in hPt. Following the advances genic HPT. and treatment options. This research made in the early diagnosis of • Umbilical cord blood cell trans- line is supported by two FIS grants fungal diseases (galactomannan plantation administered via the and an aid from the German José antigen, high-resolution CAT) and intraosseous route – an innovating Carreras Foundation. viral infections (CMV antigenemia modality which we and another and PCR applied to all herpes viru- European center are analyzing. 2. Study of immune reconstitution ses and other pathogens), which following hPt. Following charac- have facilitated our healthcare 4. Studies addressing the preven- terization of immune reconstitu- activities, we plan to continue tion and treatment of the main tion in HPT from bone marrow, evaluating new diagnostic tech- complications of hPt. peripheral blood and in reduced niques (quantitative PCR for EBV, • Prevention and treatment of intensity regimens, we plan to as- the application of PCR to tissue graft-versus-host disease with sess immune reconstitution in the samples, biological markers in new agents (anti-IL-2 receptor transplantation of umbilical cord bronchoalveolar lavage, and PET antibodies, new anti-thymocyte blood – this not ever having been scan assessment of infections). globulins, alemtuzumab and cell achieved to date. therapy using mesenchymal cells). Participation in different multicen- 3. Study of the impact of genic ter studies. polymorphisms upon the complications and outcomes of hPt. BASIc AND tRANSLAtIoNAL Following demonstration of the im- RESEARch LINES pact of the mannose-binding lectin variants upon the incidence of fun- 1. Study of the post-hPt complica- gal infections, of the NOD2/CARD15 tions originating from endothelial gene variants upon survival and the dysfunction. Different early compli- incidence of bronchiolitis obliterans cations appearing after HPT, such as and, more recently, of the impact of veno-occlusive syndrome, capillary the NLRP2 and NLRP3 gene variants rupture syndrome, thrombotic mi- upon HPT survival, we plan to conti- croangiopathy, graft syndrome, and nue this line of research, assessing idiopathic pneumonia syndrome, new polymorphisms that may affect appear to originate from endothelial the evolution of HPT.

278 AReA 5 oncoloGy AnD HAeMAtoloGy HeMAtopoietic pRoGenitoR cell tRAnSplAntAtion

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 55.38 8 7 0 oRiGinAlS 5 Palomo M, Diaz-Ricart M, i.f.: 82.13 Rovira M, Escolar G, Carreras E. 2010 43.66 12 6 3 Defibrotide Prevents the Activation 2011 82.13 15 11 4 1 Cervera C, Fernandez-Aviles of Macrovascular and Microvascular F, DeLaCalle-Martin O, Bosch X, Endothelia Caused by Soluble Rovira M, Plana M, Moreno A, Gar- Factors Released to Blood by cia F, Miro JM, Martinez A, Gallart Autologous Hematopoietic Stem T, Carreras E, Blade J, Gatell JM. Cell Transplantation. BIOL BLOOD 9 Aguilar-Guisado M, Jimenez- Non-myeloablative hematopoi- MARROW TR. 17:497-506. I.F.: 3.28. Jambrina M, Espigado I, Rovira M, etic stem cell transplantation in Martino R, Oriol A, Borrell N, Ruiz the treatment of severe idiopathic 6 Martin-Antonio B, Carmona M, I, Martin-Davila P, DeLaCamara R, CD4+lymphocytopenia. EUR J HAE- Falantes J, Gil E, Baez A, Suarez Salavert M, DeLaTorre J, Cisneros MATOL. 87:87-91. I.F.: 2.79. M, Marin P, Espigado I, Urbano- JM. Pneumonia in allogeneic stem Ispizua A. Impact of constitutional cell transplantation recipients: a 2 DeLarrea CF, Tovar N, Rozman M, polymorphisms in VCAM1 and CD44 multicenter prospective study. Rosinol L, Arostegui JI, Cibeira MT, on CD34(+) cell collection yield after CLIN TRANSPLANT. 25:E629-E638. Rovira M, Yague J, Blade J. Multiple administration of granulocyte colony- I.F.: 1.75. Myeloma in Serologic Complete stimulating factor to healthy donors. Remission after Autologous Stem HAEMATOL-HEMATOL J. 96:102-109. 10 Barba P, Pinana JL, Cell Transplantation: Impact of Bone I.F.: 6.53. Fernandez-Aviles F, Perez-Simon Marrow Plasma Cell Assessment JA, Martino R, Lopez-Guerrero E, by Conventional Morphology on 7 Perez-Simon JA, Lopez-Villar Valcarcel D, Rovira M, Novelli S, Disease Progression. BIOL BLOOD O, Andreu EJ, Rifon J, Muntion S, Campos-Varela I, Lopez-Anglada MARROW TR. 17:1084-1087. Campelo MD, Sanchez-Guijo FM, L, Vidal X, Corral LL, Carreras E, I.F.: 3.28. Martinez C, Valcarcel D, DelCanizo Sierra J. Pretransplantation Liver C. Mesenchymal stem cells Function Impacts on the Outcome 3 Bosch X, Esteve J, Sitges M, expanded in vitro with human serum of Allogeneic Hematopoietic Stem DeCaralt TM, Domenech A, Ortiz for the treatment of acute and Cell Transplantation: A Study of 455 JT, Monzo M, Morales-Ruiz M, chronic graft-versus-host disease: Patients. BIOL BLOOD MARROW Perea RJ, Rovira M. Prevention results of a phase I/II clinical trial. TR. 17:1653-1661. I.F.: 3.28. of Chemotherapy-Induced Left HAEMATOL-HEMATOL J. 96:1072- Ventricular Dysfunction With 1076. I.F.: 6.53. 11 Jacobsohn DA, Arora M, Enalapril and Carvedilol: Rationale Klein JP, Hassebroek A, Flowers and Design of the OVERCOME Trial. 8 Duarte RF, Shaw BE, Marin P, ME, Cutler CS, Urbano-Ispizua A, J CARD FAIL. 17:643-648. I.F.: 3.36. Kottaridis P, Ortiz M, Morante C, Bolwell BJ, Antin JH, Boyiadzis Delgado J, Gayoso J, Goterriz R, M, Cahn JY, Cairo MS, Herzig 4 Arora M, Klein JP, Weisdorf Martinez-Chamorro C, Mateos- RH, Isola LM, Klumpp TR, Lee DJ, Hassebroek A, Flowers MED, Mazon JJ, Ramirez C, DeLaRubia SJ, Petersdorf EW, Santarone S, Cutler CS, Urbano-Ispizua A, Antin J, Achtereekte H, Gandhi PJ, Gale RP, Schouten HC, Spellman JH, Bolwell BJ, Boyiadzis M, Cahn Douglas KW, Russell NH. Plerixafor SR, Weisdorf DJ, Wingard JR, JY, Cairo MS, Isola L, Jacobsohn plus granulocyte CSF can mobilize Horowitz MM, Pavletic SZ. Risk DA, Jagasia M, Klumpp TR, Lee hematopoietic stem cells from factors associated with increased SJ, Petersdorf EW, Santarone S, multiple myeloma and lymphoma nonrelapse mortality and with poor Gale RP, Schouten HC, Spellman S, patients failing previous mobilization overall survival in children with Wingard JR, Horowitz MM, Pavletic attempts: EU compassionate use chronic graft-versus-host disease. SZ. Chronic GVHD risk score: a data. BONE MARROW TRANSPL. BLOOD. 118:4472-4479. I.F.: 10.56. Center for International Blood and 46:52-58. I.F.: 3.66. Marrow Transplant Research analysis. BLOOD. 117:6714-6720. I.F.: 10.56.

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12 Daikeler T, Labopin M, DiGioia 15 Ruiz-Camps I, Len O, clinicAl GuiDelineS M, Abinun M, Alexander T, Miniati DeLaCamara R, Gurgui M, Martino i.f.: 0.67 I, Gualandi F, Fassas A, Martin T, R, Jarque I, Barrenetxea C, Schwarze CP, Wulffraat N, Buch DeHeredia CD, Batlle M, Rovira M, 1 Barberan J, Mensa J, Llamas M, Sampol A, Carreras E, Dubois DeLaTorre J, Torres A, Aguilar M, JCV, Ramos IJ, Ruiz JCG, Marin JRC, B, Gruhn B, Gungor T, Pohlreich D, Espigado I, Martin-Davila P, Bou G, Tello PB, Massana MB, Vidal JB, Schuerwegh A, Snarski E, Snowden Borrell N, Aguado JM, Pahissa A. Vinas JMC, Huelva FJC, Pons EC, J, Veys P, Fasth A, Lenhoff S, Valganciclovir as pre-emptive therapy Mediavilla JD, Morfa MLD, Barrigon Messina C, Voswinkel J, Badoglio for cytomegalovirus infection in FE, Avellan PF, Lopez SG, Garcia M, Henes J, Launay D, Tyndall A, allogeneic haematopoietic stem cell CG, Maraver DH, DeLaGuia AL, Gluckman E, Farge D. Secondary transplant recipients. ANTIVIR THER. Jimenez JL, Chacon EM, Rubio MO, autoimmune diseases occurring 16:951-957. I.F.: 3.77. DeOteyza JP, Ramirez GR, Contreras after HSCT for an autoimmune RR, Barbero AR, Tarrats MR, Felix disease: a retrospective study of DR, Godoy PS, Salinas AS, Alonso the EBMT Autoimmune Disease ReViewS MA, Torroba JD, Ferreiras DV, Lopez Working Party. BLOOD. 118:1693- i.f.: 3.66 LV, Garcia JMA, Perea JRA, Moreno 1698. I.F.: 10.56. RC, Cancer RC, Abete JF, Rodriguez 1 Carreras E, Diaz-Ricart M. The role of JG, Gomez JG, DeLaPedrosa EGG, 13 Carreras E, Diaz-Beya M, the endothelium in the short-term com- Baranda JMM, Garcia FJP, Camps Rosinol L, Martinez C, Fernandez- plications of hematopoietic SCT. BONE IR, Lleti MS, Cisneros JD. Recom- Aviles F, Rovira M. The Incidence MARROW TRANSPL. 46:1495-1502. mendations for the treatment of of Veno-Occlusive Disease Fol- I.F.: 3.66. invasive fungal infection caused by lowing Allogeneic Hematopoietic filamentous fungi in the hematologi- Stem Cell Transplantation Has cal patient. REV ESP QUIM. 24:263- Diminished and the Outcome Im- eDitoRiAlS 270. I.F.: 0.67. proved over the Last Decade. BIOL i.f.: 7.20 BLOOD MARROW TR. 17:1713- 1720. I.F.: 3.28. 1 Martinez C, Urbano-Ispizua MulticentRicS A. Graft-versus-host disease i.f.: 4.94 14 Robin M, Sanz GF, Ionescu therapy: something else beyond I, Rio B, Sirvent A, Renaud M, glucocorticoids?. HAEMATOL-HEMA- 1 Marks DI, Pagliuca A, Kibbler Carreras E, Milpied N, Mohty M, TOL J. 96:1249-1251. I.F.: 6.53. CC, Glasmacher A, Heussel CP, Beguin Y, Bordigoni P, DeWitte T, Kantecki M, Miller PJS, Ribaud P, Picardi A, Purtill D, Gluckman E, 2 Novo A, Llorente A, Cladera A, Schlamm HT, Solano C, Cook G. Kroger N, Rocha V. Unrelated cord Rubio D, Valcarcel D, Amutio E, Voriconazole versus itraconazole blood transplantation in adults with Conde E, Martin E, Diaz-Mediavilla J, for antifungal prophylaxis following myelodysplasia or secondary acute Rifon JJ, Diez JL, Cabrera JR, Serrano allogeneic haematopoietic stem-cell myeloblastic leukemia: a survey J, Besalduch J, Ruiz JCG, Zueco transplantation. BRIT J HAEMATOL. on behalf of Eurocord and CLWP JCG, Vallejo JC, Vazquez L, Cuesta 155:318-327. I.F.: 4.94. of EBMT. LEUKEMIA. 25:75-81. MA, Diaz ML, Batlle M, Rovira M, I.F.: 8.97. Abellan PF, Rojas R, Tabares S, Olave T, Gomez V. Invasive fungal infections in onco-haematology: a Spanish perspective. REV ESP QUIM. 24:168- 172. I.F.: 0.67.

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GRAntS foR ReSeARcH in pRoGReSS

Carreras E. Disfunción endotelial post- trasplante hematopoyético. Impacto de los agentes empleados en el régi- men de acondicionamiento y análisis de posibles agentes protectores. Sponsored by: Ministerio de Sanidad y Consumo, PI080156. Duration: 01/01/2009-31/12/2011.

Martinez Munoz C. Estudio de la farmacogenómica y la farmacodiná- mica de los inmunosupresores en el trasplante alogénico de progenitores hemopoyéticos y su implicación en las reacciones injerto contra huésped e injerto-contra-tumor. Sponsored by: Instituto de Salud Carlos III (ISCIII), PI09/1043. Duration: 01/01/2010- 31/12/2012.

Urbano A. Papel de los factores in- ducidos por hipoxia (HIFs), Notch, Oct4 y de microRNAs en la patogenia y transformación de los síndromes mielodisplásicos a leucemia aguda. Sponsored by: Instituto de Salud Car- los III (ISCIII), PI08/1137. Duration: 29/07/2010-30/12/2011.

Urbano A. Trasplante de progenitores hemopoyéticos en neoplasias hema- tológicas. Sponsored by: Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, RD06/0020/0012. Duration: 01/01/2007-31/12/2012.

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Team involved in: Oncology and haematology

Hematological oncology

gROUP MeMBeRS StrateGic oBjectiveS

The main strategic objectives of our team are clinical, applied and basic teAM leADeR research in hematological oncology. francisco cervantes (Hospital clínic) The team is structured into three tel.: 93 227 54 28 study groups of three major disease fax: 93 227 54 84 categories. e-mail: [email protected] xxxxxx main lineS of iDiBApS MeMBeRS: nuRSinG StAff: reSearcH prof. emili Montserrat (Hospital clínic) Sonia chaves (Hospital clínic) Joan Bladé (Hospital clínic) eva carrera (Hospital clínic) 1. Study of lymphoid neoplasms. Jordi esteve (Hospital clínic) Mónica Blanco (Hospital clínic) 2. Multiple myeloma and other Armando lópez-Guillermo (Hospital clínic) monoclonal gammapathies. Julio Delgado (Hospital clínic) ADMiniStRAtiVe StAff: 3. Study of myeloid neoplasms. eva Giné (Hospital clínic) Maria José Sánchez Melero laura Rosiñol (Hospital clínic) (Hospital clínic) cristina cerrato (Hospital clínic) poStDoctoRAl fellowS: Marta Bistagne (Hospital clínic) Gonzalo Gutierrez (fundació clínic) Maria teresa cibeira (fundació clínic) StAtiSticiAn: carlos fernández de larrea Antonio de la Riva (fundació clínic) (fundació clínic) Mª carmen pastor (fundació clínic) Montserrat pérez (fundació clínic) ReSeARcH fellowS: llúcia Sanz (fundació clínic) Anna Gaya (Hospital clínic) Marta pratcorona (iDiBApS) collABoRAtoRS: Marina Díaz Beyá (fundació clínic) Benet nomdedeu (Hospital clínic) Alejandra Martínez trillos (fundació clínic) Arturo pereira (Hospital clínic) Raquel Jiménez (fundació clínic) eduardo Arellano (Hospital clínic) Gerardo ferrer (fundació clínic) Alfons navarro (uB) Xavier calvo (Hospital clínic) Dolors costa ( Hospital clínic) Daniel esteban (fundació clínic) Ana carrió (Hospital clínic) cristina Motlló (fundació clínic) Ruth Muñoz Risueño (institut de Recerca natalia tovar (Hospital clínic) Josep carreras)

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ReSeARCh gROUP ReSeARCh gROUP lympHoid neoplaSmS myeloid neoplaSmS

Group Leader: Armando López (hospital clínic) Group Leader: Francisco cervantes (hospital clínic) 1. Lymphomas • Investigation of the progression mechanisms of the disease. 1. chronic myeloid leukaemia: Up- • Study of minimum residual disease and its clinical significance. dating of the Spanish protocol for • Genomic profile of the diffuse large cell lymphoma and its the treatment of chronic myeloid clinical significance (in collaboration with the National Cancer Institute (USA) leukaemia with escalating doses of imatinib versus and the Leukemia Lymphoma Molecular Profiling Project (LLMPP)). imatinib in combination with interferon (CML/PETHE- • New prognostic models in T cell lymphomas (collaboration in international MA). Participation in the European Chronic Myeloid studies, particularly the International T-cell Lymphomas Project. University Leukaemia Registry. Drawing up of new criteria for of Nebraska) and follicular lymphoma. response of CML to treatment with tyrosine kinase • Utility of PET in evaluating the response of lymphomas and chronic inhibitors, within the European LeukemiaNet expert lymphocytic leukemia (CLL). panel. Clinical trials for treatment of CML with new • Genic profile of Hodgkin lymphoma. tyrosine kinase inhibitors. • Phase I-II clinical trials with new drugs (bortezomib, anti-CD40, anti-CD22, aplidin, GA101, etc.), and international phase III trials to establish new 2. Philadelphia chromosome-negative chronic mye- indications in lymphomas (PRIMA and ZAR studies). loproliferative disease: Study of the thrombosis mechanisms. Leadership of the international study 2. chronic lymphocytic leukemia into predictive factors for the progression of primary • Mechanisms of progression of the disease. myelofibrosis to acute leukaemia, in collaboration with • Biology of ZAP-70 in relation to BCR the main groups in Europe and the United States. • Analysis of transforming CLL. Analysis of the relationship between mutational sta- • Influence of the cellular microenvironment upon the disease. tus and JAK2 and MPL allele burden, haplotype 46/1 • Study of the immunological alterations and immune reconstitution in of the JAK2 gene and the initial characteristics, the chronic lymphocytic leukemia (CLL Global Research Foundation project). progression pattern and the prognosis of myelofibro- • Evaluation of cellular proliferation in CLL. sis. Clinical trials for the treatment of myelofibrosis • Study of autoimmune phenomena. with JAK2 inhibitors and other new drugs. • Multiparametric analysis of prognostic factors in CLL. • Phase I/II and III clinical trials. 3. Acute myeloid leukaemia: Study of the biological • Project for the Chronic Lymphocytic Leukemia (CLL) Genome, in prognostic factors in AML of intermediate cytogenic collaboration with the Hematopatology Unit risk: genetic mutations, gene expression profile, microRNA expression pattern. Analysis of the microRNA expression pattern in AML with trans- ReSeARCh gROUP location (8;16)/MYST3-CREBBP, AML with t(6;9)/ myeloma and otHer monoclonal GammapatHieS DEK-NUP214 and AML with multilineage dysplasia. Prognostic value of molecular markers of AML in Group Leader: Joan Blade (hospital clínic) the results of haematopoietic stem cell transplantation (within the Acute Leukemia Working Party for 1. Study of molecular cytogenics, gene-expression profile of the European Group for Blood and Bone Marrow cytokines related to angiogenesis and the tumour micro- Transplantation, EBMT). Design of AML treatment environment and analysis of genes differentially expressed protocols for the Grupo Cooperativo para el Estudio y in bone marrow and in extramedullary plasmacytomas in Tratamiento de las Leucemias Agudas y Mielodispla- patients with multiple myoma. sias (CETLAM) [Cooperative Group for the Study and 2. Evaluation of immune reconstitution in patients in complete remission after Treatment of Acute Leukaemia and Myelodysplasia] autologous transplant and after chemotherapy and the possible relationship with (sequential protocol, AML-2012). Phase II and III cli- disease progression, compared to patients with partial response and monoclonal nical trials with new drugs for the treatment of AML gammopathies of undetermined significance (leucocyte subpopulations in and ALL: FLT3 inhibitors, azacitidine, blinatumomab. peripheral blood and bone marrow, minimal residual disease measured by cytometry, levels of free light chains and heavy chains, miRNA in serum and 4. Myelodysplastic Syndromes: Natural history bone marrow, functional analysis of the innate response by TLR and NK cell and prognosis. Participation in the Spanish MDS repertoire, mRNA microarrays in the bone marrow microenvironment, PET/CT). Registry. Prognostic importance of transfusion re- 3. Impact of individual genetic variability on the response to treatment in multiple quirements. Study of sensitisation to transfusion. myoma through the analysis of single nucleotide polymorphisms (SNPs). Cytogenetic and molecular abnormalities in MDS 4. Characterisation of cardiac involvement in AL amyloidosis based on clinical and the implications for prognosis. Study of microR- presentation, cardiac biomarker levels and imaging techniques, and the NA in MDS. Clinical trials with new drugs for the influence of genetics in the predilection of the light amyloidogenic chains for treatment of MDS. the heart and the severity of the cardiac involvement. 5. Clinical trials for the treatment of multiple myoma and primary amyloidosis. Phases I, II and III. Sponsored by PETHEMA and by the industry. 283 ONCOLOgy AND hAeMATOLOgy

Hematological oncology

PUBLICATIONS

oRiGinAlS 5 Puente XS, Pinyol M, Quesada 8 Cardesa-Salzmann TM, Colomo L, i.f.: 356.47 V, Conde L, Ordonez GR, Villamor N, Gutierrez G, Chan WC, Weisenburger Escaramis G, Jares P, Bea S, Gonzalez- D, Climent F, Gonzalez-Barca E, 1 Cervera C, Fernandez-Aviles Diaz M, Bassaganyas L, Baumann T, Mercadal S, Arenillas L, Serrano S, F, DeLaCalle-Martin O, Bosch X, Juan M, Lopez-Guerra M, Colomer Tubbs R, Delabie J, Gascoyne RD, Rovira M, Plana M, Moreno A, Gar- D, Tubio JMC, Lopez C, Navarro A, Connors JM, Mate JL, Rimsza L, cia F, Miro JM, Martinez A, Gallart Tornador C, Aymerich M, Rozman M, Braziel R, Rosenwald A, Lenz G, T, Carreras E, Blade J, Gatell JM. Hernandez JM, Puente DA, Freije JMP, Wright G, Jaffe ES, Staudt L, Jares Non-myeloablative hematopoietic Velasco G, Gutierrez-Fernandez A, P, Lopez-Guillermo A, Campo E. High stem cell transplantation in the Costa D, Carrio A, Guijarro S, Enjuanes microvessel density determines a treatment of severe idiopathic A, Hernandez L, Yague J, Nicolas P, poor outcome in patients with diffuse CD4+lymphocytopenia. EUR J Romeo-Casabona CM, Himmelbauer large B-cell lymphoma treated with HAEMATOL. 87:87-91. I.F.: 2.79. H, Castillo E, Dohm JC, DeSanjose rituximab plus chemotherapy. HAE- S, Piris MA, DeAlava E, Miguel JS, MATOL-HEMATOL J. 96:996-1001. 2 Ferrer G, Hodgson K, Pereira Royo R, Gelpi JL, Torrents D, Orozco I.F.: 6.53. A, Juan M, Elena M, Colomer D, M, Pisano DG, Valencia A, Guigo R, Roue G, Aymerich M, Baumann Bayes M, Heath S, Gut M, Klatt P, 9 Gutierrez-Garcia G, Garcia-Herrera T, Montserrat E, Moreno C. Marshall J, Raine K, Stebbings LA, A, Cardesa T, Martinez A, Villamor N, Combined analysis of levels of Futreal PA, Stratton MR, Campbell PJ, Ghita G, Martinez-Trillos A, Colomo L, serum B-cell activating factor and Gut I, Lopez-Guillermo A, Estivill X, Setoain X, Rodriguez S, Gine E, Cam- a proliferation-inducing ligand as Montserrat E, Lopez-Otin C, Campo E. po E, Lopez-Guillermo A. Comparison predictor of disease progression Whole-genome sequencing identifies of four prognostic scores in periphe- in patients with chronic recurrent mutations in chronic ral T-cell lymphoma. ANN ONCOL. lymphocytic leukemia. LEUKE- lymphocytic leukaemia. NATURE. 22:397-404. I.F.: 6.45. MIA LYMPHOMA. 52:2064-2068. 475:101-105. I.F.: 36.10. I.F.: 2.49. 10 Enjuanes A, Fernandez V, 6 Bosch X, Esteve J, Sitges M, Hernandez L, Navarro A, Bea S, Pinyol 3 DeLarrea CF, Tovar N, Cibeira DeCaralt TM, Domenech A, Ortiz M, Lopez-Guillermo A, Rosenwald A, MT, Arostegui JI, Rosinol L, JT, Monzo M, Morales-Ruiz M, Ott G, Campo E, Jares P. Identification Elena M, Filella X, Yague J, Blade Perea RJ, Rovira M. Prevention of Methylated Genes Associated J. Emergence of oligoclonal of Chemotherapy-Induced Left with Aggressive Clinicopathological bands in patients with multiple Ventricular Dysfunction With Enalapril Features in Mantle Cell Lymphoma. myeloma in complete remission and Carvedilol: Rationale and Design PLOS ONE. 6:-. I.F.: 4.41. after induction chemotherapy: of the OVERCOME Trial. J CARD association with the use of novel FAIL. 17:643-648. I.F.: 3.36. 11 DeLarrea CF, Martinez-Pozo agents. HAEMATOL-HEMATOL J. A, Mercadal S, Garcia A, Gutierrez- 96:171-173. I.F.: 6.53. 7 Gutierrez-Garcia G, Cardesa- Garcia G, Valera A, Ghita G, Colomo Salzmann T, Climent F, Gonzalez- L, Gainza E, Villamor N, Nomdedeu 4 DeLarrea CF, Tovar N, Rozman Barca E, Mercadal S, Mate JL, Sancho B, Estrach T, Montserrat E, Campo M, Rosinol L, Arostegui JI, JM, Arenillas L, Serrano S, Escoda E, Lopez-Guillermo A. Initial features Cibeira MT, Rovira M, Yague J, L, Martinez S, Valera A, Martinez A, and outcome of cutaneous and Blade J. Multiple Myeloma in Jares P, Pinyol M, Garcia-Herrera A, non-cutaneous primary extranodal Serologic Complete Remission Martinez-Trillos A, Gine E, Villamor N, follicular lymphoma. BRIT J HAEMA- after Autologous Stem Cell Campo E, Colomo L, Lopez-Guillermo TOL. 153:334-340. I.F.: 4.94. Transplantation: Impact of Bone A. Gene-expression profiling and Marrow Plasma Cell Assessment not immunophenotypic algorithms 12 Mozos A, Roue G, Lopez- by Conventional Morphology on predicts prognosis in patients with Guillermo A, Jares P, Campo Disease Progression. BIOL BLOOD diffuse large B-cell lymphoma treated E, Colomer D, Martinez A. The MARROW TR. 17:1084-1087. with immunochemotherapy. BLOOD. Expression of the Endoplasmic I.F.: 3.28. 117:4836-4843. I.F.: 10.56. Reticulum Stress Sensor BiP/GRP78

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original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 191.76 24 18 3 Predicts Response to Chemotherapy 17 Dubrey SW, Reece DE, and Determines the Efficacy of Sanchorawala V, Hegenbart U, Merlini 2010 243.89 26 19 1 Proteasome Inhibitors in Diffuse G, Palladini G, Fermand JP, Vescio RA, 2011 356.47 41 29 4 Large B-Cell Lymphoma. AM J Blade J, Heffner LT, Hassoun H, Liu PATHOL. 179:2601-2610. I.F.: 5.22. X, Enny C, Ramaswami P, Elsayed Y, VanDeVelde H, Mortimer S, Cakana A, 13 Cibeira MT, DeLarrea CF, Nava- Comenzo RL. Bortezomib in a phase rro A, Diaz T, Fuster D, Tovar N, Rosi- 1 trial for patients with relapsed AL with acute promyelocytic leukemia nol L, Monzo M, Blade J. Impact on amyloidosis: cardiac responses and treated with all-trans retinoic acid response and survival of DNA repair overall effects. QJM-INT J MED. and anthracycline-based regimens. single nucleotide polymorphisms in 104:957-970. I.F.: 2.15. BLOOD. 117:1799-1805. I.F.: 10.56. relapsed or refractory multiple myeloma patients treated with thalidomi- 18 Pfreundschuh M, Kuhnt E, 21 Paiva B, Martinez-Lopez J, Vi- de. LEUKEMIA RES. 35:1178-1183. Trumper L, Osterborg A, Trneny driales MB, Mateos MV, Montalban I.F.: 2.56. M, Shepherd L, Gill DS, Walewski MA, Fernandez-Redondo E, Alonso J, Pettengell R, Jaeger U, Zinzani L, Oriol A, Teruel AI, DePaz R, Larana 14 Diaz T, Navarro A, Ferrer G, PL, Shpilberg O, Kvaloy S, Brown JG, Bengoechea E, Martin A, Me- Gel B, Gaya A, Artells R, Bellosillo B, PD, Stahel R, Milpied N, Lopez- diavilla JD, Palomera L, DeArriba F, Garcia-Garcia M, Serrano S, Martinez Guillermo A, Poeschel V, Grass S, Blade J, Orfao A, Lahuerta JJ, Miguel A, Monzo M. Lestaurtinib Inhibition Loeffler M, Murawski N. CHOP- JF. Comparison of Immunofixation, of the JAK/STAT Signaling Pathway in like chemotherapy with or without Serum Free Light Chain, and Immuno- Hodgkin Lymphoma Inhibits Prolife- rituximab in young patients with phenotyping for Response Evaluation ration and Induces Apoptosis. PLOS good-prognosis diffuse large-B-cell and Prognostication in Multiple My- ONE. 6:-. I.F.: 4.41. lymphoma: 6-year results of an eloma. J CLIN ONCOL. 29:1627-1633. open-label randomised study of the I.F.: 18.97. 15 Pereira A, Nomdedeu M, Aguilar MabThera International Trial (MInT) JL, Belkaid M, Carrio A, Cobo F, Costa Group. LANCET ONCOL. 12:1013- 22 Paiva B, Perez-Andres M, D, Rozman M, Sanz C, Nomdedeu 1022. I.F.: 17.76. Vidriales MB, Almeida J, DeLasHeras B. Transfusion intensity, not the N, Mateos MV, Lopez-Corral L, cumulative red blood cell transfusion 19 Conconi A, Martinelli G, Lopez- Gutierrez NC, Blanco J, Oriol A, burden, determines the prognosis Guillermo A, Zinzani PL, Ferreri Hernandez MT, DeArriba F, DeCoca of patients with myelodysplastic AJM, Rigacci L, Devizzi L, Vitolo U, AG, Terol MJ, DeLaRubia J, Gonzalez syndrome on chronic transfusion Luminari S, Cavalli F, Zucca E. Clinical Y, Martin A, Sureda A, Schmidt-Hieber support. AM J HEMATOL. 86:245- activity of bortezomib in relapsed/ M, Schmitz A, Johnsen HE, Lahuerta 250. I.F.: 3.58. refractory MALT lymphomas: JJ, Blade J, San-Miguel JF, Orfao A. results of a phase II study of the Competition between clonal plasma 16 Nomdedeu J, Bussaglia E, International Extranodal Lymphoma cells and normal cells for potentially Villamor N, Martinez C, Esteve J, Study Group (IELSG). ANN ONCOL. overlapping bone marrow niches Tormo M, Estivill C, Queipo MP, 22:689-695. I.F.: 6.45. is associated with a progressively Guardia R, Carricondo M, Hoyos altered cellular distribution in MGUS M, Llorente A, Junca J, Gallart M, 20 Montesinos P, Rayon C, vs myeloma. LEUKEMIA. 25:697-706. Domingo A, Bargay J, Mascaro M, Vellenga E, Brunet S, Gonzalez J, I.F.: 8.97. Moraleda JM, Florensa L, Ribera Gonzalez M, Holowiecka A, Esteve JM, Gallardo D, Brunet S, Aventin J, Bergua J, Gonzalez JD, Rivas 23 Maffioli M, Camos M, Gaya A, A, Sierra J. Immunophenotype of C, Tormo M, Rubio V, Bueno J, Hernandez-Boluda JC, Alvarez-Larran acute myeloid leukemia with NPM Manso F, Milone G, DeLaSerna J, A, Domingo A, Granell M, Guillem mutations: Prognostic impact of Perez I, Perez-Encinas M, Krsnik I, V, Vallansot R, Costa D, Bellosillo B, the leukemic compartment size. Ribera JM, Escoda L, Lowenberg Colomer D, Cervantes F. Correlation LEUKEMIA RES. 35:163-168. B, Sanz MA. Clinical significance between genetic polymorphisms of I.F.: 2.56. of CD56 expression in patients the hOCT1 and MDR1 genes and the

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Hematological oncology

response to imatinib in patients 1/2 study. BLOOD. 118:865-873. CHOP, CNS Prophylaxis, and newly diagnosed with chronic- I.F.: 10.56. Contralateral Testis Irradiation: Final phase chronic myeloid leukemia. Results of an International Phase LEUKEMIA RES. 35:1014-1019. 28 Blade J, Sonneveld P, II Trial. J CLIN ONCOL. 29:2766- I.F.: 2.56. SanMiguel JF, Sutherland HJ, Hajek 2772. I.F.: 18.97. R, Nagler A, Spencer A, Robak T, 24 Such E, Cervera J, Costa D, Lantz KC, Zhuang SH, Harousseau 32 Mian M, Gaidano G, Conconi Sole F, Vallespi T, Luno E, Collado R, JL, Orlowski RZ. Efficacy and Safety A, Tsang R, Gospodarowicz MK, Calasanz MJ, Hernandez-Rivas JM, of Pegylated Liposomal Doxorubicin Rambaldi A, Rossi A, Oldani E, Cigudosa JC, Nomdedeu B, Mallo in Combination With Bortezomib for Federico M, Luminari S, Bellei M, M, Carbonell F, Bueno J, Ardanaz Multiple Myeloma: Effects of Adverse Pogliani EM, Rossini F, Cabrera MT, Ramos F, Tormo M, Sancho- Prognostic Factors on Outcome. CL ME, Martelli M, Lopez-Guillermo Tello R, DelCanizo C, Gomez V, LYMPH MYELOM LEUK. 11:44-49. A, Busetto M, Cavalli F, Zucca E, Marco V, Xicoy B, Bonanad S, Pedro I.F.: 1.99. Cortelazzo S. High response rate and C, Bernal T, Sanz GF. Cytogenetic improvement of long-term survival risk stratification in chronic myelo- 29 Delabie J, Holte H, Vose with combined treatment modalities monocytic leukemia. HAEMATOL- JM, Ullrich F, Jaffe ES, Savage KJ, in patients with poor-risk primary HEMATOL J. 96:375-383. I.F.: 6.53. Connors JM, Rimsza L, Harris NL, thyroid diffuse large B-cell lymphoma: Muller-Hermelink K, Rudiger T, an International Extranodal Lymphoma 25 Merino A, DeLarrea CF, Coiffier B, Gascoyne RD, Berger F, Study Group and Intergruppo Italiano Blade J. Cytoplasmic inclusions Tobinai K, Au WY, Liang R, Montserrat Linfomi study. LEUKEMIA LYMPHO- in leukocytes associated to E, Hochberg EP, Pileri S, Federico MA. 52:823-832. I.F.: 2.49. cryoglobulinemia and IgG-kappa M, Nathwani B, Armitage JO, monoclonal gammapathy of Weisenburger DD. Enteropathy- 33 Martinez-Lopez J, Blade J, undetermined significance. EUR J associated T-cell lymphoma: clinical Mateos MV, Grande C, Alegre HAEMATOL. 86:550-550. I.F.: 2.79. and histological findings from A, Garcia-Larana J, Sureda A, the International Peripheral T-Cell DeLaRubia J, Conde E, Martinez R, 26 Gangat N, Caramazza D, Lymphoma Project. BLOOD. 118:148- DeArriba F, Viguria MC, Besalduch Vaidya R, George G, Begna K, 155. I.F.: 10.56. J, Cabrera R, Gonzalez-SanMiguel Schwager S, VanDyke D, Hanson C, JD, Guzman-Zamudio JL, DelCastillo Wu WT, Pardanani A, Cervantes F, 30 Guglielmelli P, Biamonte F, MCG, Moraleda JM, Garcia-Ruiz JC, Passamonti F, Tefferi A. DIPSS Plus: Score J, Hidalgo-Curtis C, Cervantes SanMiguel J, Lahuerta JJ. Long-term A Refined Dynamic International F, Maffioli M, Fanelli T, Ernst T, prognostic significance of response Prognostic Scoring System Winkelman N, Jones AV, Zoi K, Reiter in multiple myeloma after stem cell for Primary Myelofibrosis That A, Duncombe A, Villani L, Bosi A, transplantation. BLOOD. 118:529-534. Incorporates Prognostic Information Barosi G, Cross NCP, Vannucchi AM. I.F.: 10.56. From Karyotype, Platelet Count, and EZH2 mutational status predicts poor Transfusion Status. J CLIN ONCOL. survival in myelofibrosis. BLOOD. 34 Ludwig H, Beksac M, Blade 29:392-397. I.F.: 18.97. 118:5227-5234. I.F.: 10.56. J, Cavenagh J, Cavo M, Delforge M, Dimopoulos M, Drach J, 27 Reece DE, Hegenbart U, 31 Vitolo U, Chiappella A, Ferreri Einsele H, Facon T, Goldschmidt H, Sanchorawala V, Merlini G, Palladini AJM, Martelli M, Baldi I, Balzarotti Harousseau JL, Hess U, Kropff M, G, Blade J, Fermand JP, Hassoun M, Bottelli C, Conconi A, Gomez DaCosta FL, Louw V, Magen-Nativ H, Heffner L, Vescio RA, Liu K, H, Lopez-Guillermo A, Martinelli H, Mendeleeva L, Nahi H, Plesner T, Enny C, Esseltine DL, VanDeVelde G, Merli F, Novero D, Orsucci San-Miguel J, Sonneveld P, Udvardy H, Cakana A, Comenzo RL. L, Pavone V, Ricardi U, Storti S, M, Sondergeld P, Palumbo A. Multiple Efficacy and safety of once-weekly Gospodarowicz MK, Cavalli F, Sarris Myeloma Treatment Strategies with and twice-weekly bortezomib in AH, Zucca E. First-Line Treatment Novel Agents in 2011: A European patients with relapsed systemic for Primary Testicular Diffuse Large Perspective. ONCOLOGIST. 16:388- AL amyloidosis: results of a phase B-Cell Lymphoma With Rituximab- 403. I.F.: 5.83.

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35 Mateos MV, Gutierrez NC, Mar- 39 Shah J, Blade J, Sonneveld P, 3 Hodgson K, Ferrer G, Montserrat tin-Ramos ML, Paiva B, Montalban Harousseau JL, Lantz K, Londhe A, E, Moreno C. Chronic lymphocytic MA, Oriol A, Martinez-Lopez J, Teruel Lowery C, Orlowski RZ. Rapid Early leukemia and autoimmunity: a AI, Bengoechea E, Martin A, Diaz- Monoclonal Protein Reduction After systematic review. HAEMATOL- Mediavilla J, DeArriba F, Palomera L, Therapy With Bortezomib or Bortezomib HEMATOL J. 96:752-761. I.F.: 6.53. Hernandez JM, Sureda A, Bargay J, and Pegylated Liposomal Doxorubicin Penalver FJ, Ribera JM, Martin-Ma- in Relapsed/Refractory Myeloma Is 4 Rajkumar SV, Harousseau JL, Durie teos ML, Fernandez M, Garcia-Sanz Associated With a Longer Time to B, Anderson KC, Dimopoulos M, Kyle R, Vidriales MB, Blade J, Lahuerta Progression. CANCER-AM CANCER R, Blade J, Richardson P, Orlowski JJ, SanMiguel JF. Outcome accord- SOC. 117:3758-3762. I.F.: 5.13. R, Siegel D, Jagannath S, Facon T, ing to cytogenetic abnormalities and Avet-Loiseau H, Lonial S, Palumbo A, DNA ploidy in myeloma patients 40 Salles G, Seymour JF, Offner Zonder J, Ludwig H, Vesole D, Sezer O, receiving short induction with weekly F, Lopez-Guillermo A, Belada D, Xerri Munshi NC, SanMiguel J. Consensus bortezomib followed by maintenance. L, Feugier P, Bouabdallah R, Catalano recommendations for the uniform BLOOD. 118:4547-4553. I.F.: 10.56. JV, Brice P, Caballero D, Haioun C, reporting of clinical trials: report of Pedersen LM, Delmer A, Simpson D, the International Myeloma Workshop 36 Cibeira MT, Sanchorawala Leppa S, Soubeyran P, Hagenbeek Consensus Panel 1. BLOOD. 117:4691- V, Seldin DC, Quillen K, Berk JL, A, Casasnovas O, Intragumtornchai 4695. I.F.: 10.56. Dember LM, Segal A, Ruberg F, T, Ferme C, DaSilva MG, Sebban C, Meier-Ewert H, Andrea NT, Sloan JM, Lister A, Estell JA, Milone G, Sonet A, 5 Pardanani A, Vannucchi AM, Finn KT, Doros G, Blade J, Skinner Mendila M, Coiffier B, Tilly H. Rituximab Passamonti F, Cervantes F, Barbui T, M. Outcome of AL amyloidosis after maintenance for 2 years in patients Tefferi A. JAK inhibitor therapy for high-dose melphalan and autologous with high tumour burden follicular myelofibrosis: critical assessment stem cell transplantation: long-term lymphoma responding to rituximab of value and limitations. LEUKEMIA. results in a series of 421 patients. plus chemotherapy (PRIMA): a phase 25:218-225. I.F.: 8.97. BLOOD. 118:4346-4352. I.F.: 10.56. 3, randomised controlled trial. LANCET. 377:42-51. I.F.: 33.63. 6 Palumbo A, Bringhen S, Ludwig 37 Ammatuna E, Montesinos P, H, Dimopoulos MA, Blade J, Mateos Hasan SK, Ramadan SM, Esteve J, 41 Calpe E, Codony C, Baptista MV, Rosinol L, Boccadoro M, Hubmann M, Pagoni M, Grimwade MJ, Abrisqueta P, Carpio C, Purroy N, Cavo M, Lokhorst H, Zweegman D, Sanz MA, Lo-Coco F. Presenting Bosch F, Crespo M. ZAP-70 enhances S, Terpos E, Davies F, Driessen C, features and treatment outcome of migration of malignant B lymphocytes Gimsing P, Gramatzki M, Hajek R, acute promyelocytic leukemia arising toward CCL21 by inducing CCR7 Johnsen HE, DaCosta FL, Sezer O, after multiple sclerosis. HAEMATOL- expression via IgM-ERK1/2 activation. Spencer A, Beksac M, Morgan G, HEMATOL J. 96:621-625. I.F.: 6.53. BLOOD. 118:4401-4410. I.F.: 10.56. Einsele H, Miguel JFS, Sonneveld P. Personalized therapy in multiple 38 Barragan E, Montesinos P, Ca- myeloma according to patient age and mos M, Gonzalez M, Calasanz MJ, ReViewS vulnerability: a report of the European Roman-Gomez J, Gomez-Casares i.f.: 95.83 Myeloma Network (EMN). BLOOD. MT, Ayala R, Lopez J, Fuster O, 118:4519-4529. I.F.: 10.56. Colomer D, Chillon C, Larrayoz MJ, 1 Cervantes F, Pereira A. Advances Sanchez-Godoy P, Gonzalez-Campos in the understanding and management 7 Barbui T, Barosi G, Birgegard G, J, Manso F, Amador ML, Vellenga E, of primary myelofibrosis. CURR OPIN Cervantes F, Finazzi G, Griesshammer Lowenberg B, Sanz MA. Prognostic ONCOL. 23:665-671. I.F.: 4.39. M, Harrison C, Hasselbalch HC, value of FLT3 mutations in patients Hehlmann R, Hoffman R, Kiladjian with acute promyelocytic leukemia 2 Hodgson K, Ferrer G, Pereira A, JJ, Kroger N, Mesa R, Mcmullin MF, treated with all-trans retinoic acid and Moreno C, Montserrat E. Autoimmune Pardanani A, Passamonti F, Vannucchi anthracycline monochemotherapy. cytopenia in chronic lymphocytic leu- AM, Reiter A, Silver RT, Verstovsek HAEMATOL-HEMATOL J. 96:1470- kaemia: diagnosis and treatment. BRIT S, Tefferi A. Philadelphia-Negative 1477. I.F.: 6.53. J HAEMATOL. 154:14-22. I.F.: 4.94. Classical Myeloproliferative Neoplasms:

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Critical Concepts and Management myelodysplastic syndrome with 2 Dimopoulos M, Kyle R, Fermand Recommendations From European isolated del(5q) and JAK2(V617F) JP, Rajkumar SV, SanMiguel J, Chanan- LeukemiaNet. J CLIN ONCOL. mutation. LEUKEMIA RES. 35:1276- Khan A, Ludwig H, Joshua D, Mehta 29:761-770. I.F.: 18.97. 1278. I.F.: 2.56. J, Gertz M, Avet-Loiseau H, Beksac M, Anderson KC, Moreau P, Singhal S, 8 Cervantes F, Mauro M. Practical 4 Blade J, DeLarrea CF. Toward deeper Goldschmidt H, Boccadoro M, Kumar Management of Patients With response in MM. BLOOD. 117:2986-+. S, Giralt S, Munshi NC, Jagannath Chronic Myeloid Leukemia. CAN- I.F.: 10.56. S. Consensus recommendations for CER-AM CANCER SOC. 117:4343- standard investigative workup: report 4354. I.F.: 5.13. 5 Gale RP, Barosi G, Barbui T, Cervantes of the International Myeloma Workshop F, Dohner K, Dupriez B, Gupta V, Harrison Consensus Panel 3. BLOOD. 117:4701- 9 Blade J, DeLarrea CF, Rosinol C, Hoffman R, Kiladjian JJ, Mesa R, 4705. I.F.: 10.56. L, Cibeira MT, Jimenez R, Powles McMullin MF, Passamonti F, Ribrag R. Soft-Tissue Plasmacytomas V, Roboz G, Saglio G, Vannucchi A, in Multiple Myeloma: Incidence, Verstovsek S. What are RBC-transfusion- GRAntS foR ReSeARcH Mechanisms of Extramedullary dependence and -independence?. LEU- in pRoGReSS Spread, and Treatment Approach. KEMIA RES. 35:8-11. I.F.: 2.56. J CLIN ONCOL. 29:3805-3812. Cervantes F. Red temática de investiga- I.F.: 18.97. ción cooperativa de cáncer. Sponsored clinicAl GuiDelineS by: Ministerio Sanidad y Consumo, 10 VanDeDonk NWCJ, Lokhorst i.f.: 10.56 RD06/0020/0004. Duration: 01/01/2007- HM, Dimopoulos M, Cavo M, 31/12/2012. Morgan G, Einsele H, Kropff M, 1 Cavo M, Rajkumar SV, Palumbo A, Schey S, Avet-Loiseau H, Ludwig Moreau P, Orlowski R, Blade J, Sezer Montserrat E. Diseño de un sistema H, Goldschmidt H, Sonneveld P, Jo- O, Ludwig H, Dimopoulos MA, Attal M, clínico-biológico para el pronóstico de hnsen HE, Blade J, San-Miguel JF, Sonneveld P, Boccadoro M, Anderson los pacientes con leucemia linfática Palumbo A. Treatment of relapsed KC, Richardson PG, Bensinger W, crónica (LLC). Sponsored by: Insti- and refractory multiple myeloma in Johnsen HE, Kroeger N, Gahrton G, tuto Carlos III- Ministerio de Ciencia the era of novel agents. CANCER Bergsagel PL, Vesole DH, Einsele H, e Innovación, PI080304. Duration: TREAT REV. 37:266-283. I.F.: 6.81. Jagannath S, Niesvizky R, Durie BGM, 01/01/2009-31/12/2011. SanMiguel J, Lonial S. International Myeloma Working Group consensus Montserrat E. Grup de Recerca Con- eDitoRiAlS approach to the treatment of multiple solidat: Unitat Clínico-Biològica per i.f.: 17.09 myeloma patients who are candidates a l’estudi de limfomes i síndromes for autologous stem cell transplantation. limproliferatives. Sponsored by: Gene- 1 Setoain X, Lopez-Guillermo A. BLOOD. 117:6063-6073. I.F.: 10.56. ralitat de Catalunya, 2009_SGR_1008. Non-Hodgkin’s lymphoma staging Duration: 23/09/2009-31/12/2013. with PET-CT scan. MED CLIN-BAR- CELONA. 137:402-404. I.F.: 1.41. MulticentRicS Blade J. Impacto de la variabilidad ge- i.f.: 15.69 nética individual mediante el análisis 2 Montserrat E, Gribben JG. Au- de single neucleotide polymorphisms tografting CLL: the game is over!. 1 Gonzalez-Porras JR, Cordoba I, Such (SNPS) en la respuesta al tratamiento BLOOD. 117:6057-6058. I.F.: 10.56. E, Nomdedeu B, Vallespi T, Carbonell en el mieloma múltiple. Sponsored by: F, Luno E, Ardanaz M, Ramos F, Pedro Instituto Carlos III- Ministerio de Cien- 3 Nomdedeu M, Maffioli M, Calvo C, Gomez V, DePaz R, Sanchez-Barba cia e Innovación, PI080147. Duration: X, Martinez-Trillos A, Baumann T, M, Sanz GF, DelCanizo C. Prognostic 01/01/2009-31/12/2011. Diaz-Beya M, Aguilar JL, Rozman impact of severe thrombocytopenia in M, Costa D, Esteve J, Cervantes F, low-risk myelodysplastic syndrome. Esteve J. Generación de un índice pro- Colomer D, Nomdedeu B. Efficacy CANCER-AM CANCER SOC. 117:5529- nóstico molecular en los enfermos con of lenalidomide in a patient with 5537. I.F.: 5.13. LMA de riego citogenético intermedio:

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análisis de mutaciones, nivel de expre- Montserrat E. NoE-Strengthen and sión génico y patrón de expresión mi- develop scientific and technological croRNA. Sponsored by: Instituto Carlos excellence in research and therapy of III- Ministerio de Ciencia e Innovación, leukemia (CML, AML, ALL, CLL, MDS, PI080158. Duration: 01/01/2009- CMPD) by integration of the leading 31/12/2011. national leukemia networks and their interdisciplinary partner groups in Eu- Lopez A. Estudio de la expresión de las rope. Sponsored by: European Commis- citoquinas y receptores de citoquinas en sion, LSHC-CT-2004-503216. Duration: los diferentes tipos de linfomas T peri- 01/01/2004-31/05/2012. féricos. Correlación con los perfiles ge- notípicos y significado clínico-biológico. Sponsored by: Instituto Carlos III. Minis- DoctoRAl tHeSeS terio de Ciencia e Innovación, PI070409. Duration: 01/01/2008-30/09/2011. Blade J. Remisión completa en el mieloma múltiple: Impacto pronóstico de Montserrat E. Estudio de las caracterís- las bandas oligoclonales, cociente de ticas biológicas (alteraciones genéticas, cadenas ligeras libres en suero y célu- inmunofeno-típicas y moleculares) y las plasmáticas residuales en médula su impacto clínico en los síndromes ósea. PhD student: Carlos José Fernán- linfoproliferativos crónicos. Sponsored dez de Larrea Rodríguez. by: Red temática de investigación cooperativa de cáncer. Ministerio Sanidad y Lopez-Guillermo A. Caracterización Consumo, RD06/0020/0051. Duration: biológica y pronóstica del linfoma di- 01/01/2007-31/12/2011. fuso de células grandes en la era de la immunoquimioterapia. PhD student: Blade J. Gammapatías monoclonales: Gonzalo Gutiérrez García. de la génesis a la terapéutica. Sponso- red by: Red Temática de Investigación Cooperativa Sanitaria (RTICS). Instituto de Salud Carlos III, RD06/0020/0005. Duration: 01/01/2007-31/12/2012.

Cervantes F. Estudio de la relación entre el estado mutacional y la carga alélica de JAK2 y MPL, el haplotipo 46/1 del gen JAK2 y las características iniciales, el patrón evolutivo y el pronóstico de los pacientes con mielofibrosis. Sponsored by: Instituto de Salud Carlos III (ISCIII), Minis- terio de Ciencia e Innovación, PI10/00236. Duration: 01/01/2011-31/12/2013.

Cervantes F. An European network for myelofibrosis. Consensus on definition of disease improvement and study of tyrosine kinase inhibitors. Sponsored by: European Commission, QLG1- CT-2002-01123. Duration: 28/10/2002- 28/11/2020.

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Team involved in: Oncology and haematology

Physiopathology and molecular bases in hematology

gROUP MeMBeRS

StrateGic oBjectiveS

Epidemiological, genetic, molecular and teAM leADeR physiopathological study of malignant Dolors colomer (Hospital clínic) hematological diseases and erythrocyte tel.: 93 227 55 72 pathology. fax: 93 227 55 72 e-mail: [email protected] main lineS of reSearcH iDiBApS MeMBeRS: ReSeARcH fellowS: Josep lluís Aguilar (Hospital clínic) laia Rosich (iDiBApS) 1. Molecular bases of apoptosis Marta Aymerich (Hospital clínic) Silvia Xargay regulation induced by drugs in teresa estrach (Hospital clínic) (Ministerio ciencia e innovacion) lymphoid neoplasms. Evaluation of Gael Roue (fundació clínic) Arnau Montraveta (fpi, Micinn) new strategies for the treatment Maria Rozman (Hospital clínic) laura olaya (eneRcA) of these disorders. Search for neus Villamor (Hospital clínic) Sandra Moros (iDiBApS) selective therapies against disre- Joan lluís Vives corrons Alba Matas (fundacio clínic) gulated signaling pathways in lym- (Hospital clínic) phoid malignancies. Mechanisms patricia pérez Galán (iDiBApS) tecHniciAnS: of action and awareness-raising Sandra cabezas (fundació clínic) strategies. poStDoctoRAl fellowS: laura Jimenez (fundació clínic) 2. Cytological, immunophenotypic and Mónica lopez (iDiBApS, Rticc) Jocabed Roldan (iDiBApS, Rticc) molecular study of malignant hema- ifigènia Saborit (iDiBApS) tological diseases. Development of Maria del Mar Mañu (eneRcA) new technologies for the diagnosis and follow-up of minimum residual disease. 3. Promotion of cooperative strategies in the molecular diagnostic setting of leukemias and lymphomas. 4. Design and implementation of internal and external quality control programs. 5. Cutaneous T and B cell lymphomas. Clinical, histopathological and immunophenotypic study. Prognostic factors and epidemiology. 6. Molecular study of the congenital alterations of erythrocytes and of the physiopathological mechanisms intervening in the production and destruction of erythrocytes as a cause of anemia or erythrocytosis. 7. Genetic and epidemiological study of hemoglobin diseases and thalas- semias.

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PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 101.35 15 10 3 oRiGinAlS identifies recurrent mutations in chronic i.f.: 142.13 lymphocytic leukaemia. NATURE. 2010 78.59 14 10 1 475:101-105. I.F.: 36.10. 2011 142.13 20 12 6 1 Ferrer G, Hodgson K, Pereira A, Juan M, Elena M, Colomer D, 4 Ramirez-Bajo MJ, Repiso A, Roue G, Aymerich M, Baumann T, DeLaOssa PP, Banon-Maneus E, Montserrat E, Moreno C. Combined DeAtauri P, Climent F, Corrons JLV, analysis of levels of serum B-cell Cascante M, Carreras J. Enzymatic Risk. GENE CHROMOSOME CANC. activating factor and a proliferation- and metabolic characterization of the 50:887-895. I.F.: 3.99. inducing ligand as predictor of di- phosphoglycerate kinase deficiency sease progression in patients with associated with chronic hemolytic 8 Gutierrez-Garcia G, Garcia-Herrera A, chronic lymphocytic leukemia. LEU- anemia caused by the PGK-Barcelona Cardesa T, Martinez A, Villamor N, Ghita KEMIA LYMPHOMA. 52:2064-2068. mutation. BLOOD CELL MOL DIS. G, Martinez-Trillos A, Colomo L, Setoain I.F.: 2.49. 46:206-211. I.F.: 2.72. X, Rodriguez S, Gine E, Campo E, Lopez- Guillermo A. Comparison of four prognos- 2 DeLarrea CF, Tovar N, Rozman M, 5 Gutierrez-Garcia G, Cardesa- tic scores in peripheral T-cell lymphoma. Rosinol L, Arostegui JI, Cibeira MT, Salzmann T, Climent F, Gonzalez-Barca ANN ONCOL. 22:397-404. I.F.: 6.45. Rovira M, Yague J, Blade J. Multiple E, Mercadal S, Mate JL, Sancho Myeloma in Serologic Complete JM, Arenillas L, Serrano S, Escoda 9 Espinet B, Garcia-Herrera A, Ga- Remission after Autologous Stem L, Martinez S, Valera A, Martinez A, llardo F, Baro C, Salgado R, Servitje Cell Transplantation: Impact of Bone Jares P, Pinyol M, Garcia-Herrera A, O, Estrach T, Colomo L, Romagosa V, Marrow Plasma Cell Assessment Martinez-Trillos A, Gine E, Villamor N, Barranco C, Serrano S, Campo E, Pujol by Conventional Morphology on Campo E, Colomo L, Lopez-Guillermo RM, Sole F. FOXP1 molecular cytogene- Disease Progression. BIOL BLOOD A. Gene-expression profiling and tics and protein expression analyses in MARROW TR. 17:1084-1087. not immunophenotypic algorithms primary cutaneous large B cell lympho- I.F.: 3.28. predicts prognosis in patients with ma, leg-type. HISTOL HISTOPATHOL. diffuse large B-cell lymphoma treated 26:213-221. I.F.: 2.50. 3 Puente XS, Pinyol M, Quesada with immunochemotherapy. BLOOD. V, Conde L, Ordonez GR, Villamor 117:4836-4843. I.F.: 10.56. 10 DeLarrea CF, Martinez-Pozo A, N, Escaramis G, Jares P, Bea S, Mercadal S, Garcia A, Gutierrez-Garcia Gonzalez-Diaz M, Bassaganyas L, 6 Sanchez-Schmidt JM, Salgado R, G, Valera A, Ghita G, Colomo L, Gainza Baumann T, Juan M, Lopez-Guerra Servitje O, Gallardo F, Ortiz-Romero E, Villamor N, Nomdedeu B, Estrach T, M, Colomer D, Tubio JMC, Lopez C, PL, Karpova MB, Zipser MC, Garcia- Montserrat E, Campo E, Lopez-Guiller- Navarro A, Tornador C, Aymerich M, Muret MP, Estrach T, Rodriguez-Pinilla mo A. Initial features and outcome of Rozman M, Hernandez JM, Puente SM, Climent F, Suela J, Ferreira BI, cutaneous and non-cutaneous primary DA, Freije JMP, Velasco G, Gutierrez- Cigudosa JC, Salido M, Barranco C, extranodal follicular lymphoma. BRIT J Fernandez A, Costa D, Carrio A, Serrano S, Dummer R, Sole F, Pujol HAEMATOL. 153:334-340. I.F.: 4.94. Guijarro S, Enjuanes A, Hernandez L, RM, Espinet B. Primary Cutaneous Yague J, Nicolas P, Romeo-Casabona CD30+ Anaplastic Large-Cell 11 Garcia-Herrera A, Song JY, CM, Himmelbauer H, Castillo E, Lymphomas Show a Heterogeneous Chuang SS, Villamor N, Colomo L, Pitta- Dohm JC, DeSanjose S, Piris MA, Genomic Profile: An Oligonucleotide luga S, Alvaro T, Rozman M, Gonzalez DeAlava E, Miguel JS, Royo R, Gelpi ArrayCGH Approach. J INVEST DERMA- JD, Arrunategui AM, Fernandez E, JL, Torrents D, Orozco M, Pisano TOL. 131:269-271. I.F.: 6.27. Gonzalvo E, Estrach T, Colomer D, Ra- DG, Valencia A, Guigo R, Bayes M, ffeld M, Gaulard P, Campo E, Jaffe ES, Heath S, Gut M, Klatt P, Marshall 7 Martin-Guerrero I, Enjuanes A, Martinez A. Nonhepatosplenic gamma J, Raine K, Stebbings LA, Futreal Richter J, Ammerpohl O, Colomer D, delta T-cell Lymphomas Represent a PA, Stratton MR, Campbell PJ, Gut Ardanaz M, Marco F, Salas A, Campo Spectrum of Aggressive Cytotoxic T-cell I, Lopez-Guillermo A, Estivill X, E, Siebert R, Garcia-Orad A. A Putative Lymphomas With a Mainly Extranodal Montserrat E, Lopez-Otin C, Campo «hepitype» in the ATM Gene Associat- Presentation. AM J SURG PATHOL. E. Whole-genome sequencing ed with Chronic Lymphocytic Leukemia 35:1214-1225. I.F.: 4.11.

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Physiopathology and molecular bases in hematology

12 Mozos A, Roue G, Lopez- Sierra J. Immunophenotype of acute 20 Florensa L, Navarro JT, Vila MEP, Guillermo A, Jares P, Campo myeloid leukemia with NPM mutations: Domingo A, DeLaBanda E, Rozman M, E, Colomer D, Martinez A. The Prognostic impact of the leukemic Camos M, Milla F, Perea G, Alonso E, Expression of the Endoplasmic compartment size. LEUKEMIA RES. Ayats R, Aventin A, Cabezudo E, Espi- Reticulum Stress Sensor BiP/GRP78 35:163-168. I.F.: 2.56. net B, Merino A, Romero P, Sanchez C, Predicts Response to Chemotherapy Tuset E, Sole F, Feliu E, Fernandez C, and Determines the Efficacy of 17 Maffioli M, Camos M, Gaya A, Gallart M, Vallespi T, Woessner S. Per- Proteasome Inhibitors in Diffuse Hernandez-Boluda JC, Alvarez-Larran sistent polyclonal B-cell lymphocytosis: Large B-Cell Lymphoma. AM J A, Domingo A, Granell M, Guillem study of 35 cases. MED CLIN-BARCE- PATHOL. 179:2601-2610. I.F.: 5.22. V, Vallansot R, Costa D, Bellosillo B, LONA. 136:565-573. I.F.: 1.41. Colomer D, Cervantes F. Correlation 13 Roue G, Perez-Galan P, Mozos between genetic polymorphisms of A, Lopez-Guerra M, Xargay-Torrent the hOCT1 and MDR1 genes and the ReViewS S, Rosich L, Saborit-Villarroya I, response to imatinib in patients newly i.f.: 14.18 Normant E, Campo E, Colomer diagnosed with chronic-phase chronic D. The Hsp90 inhibitor IPI-504 myeloid leukemia. LEUKEMIA RES. 1 Dreyling M, Kluin-Nelemans HC, Bea overcomes bortezomib resistance 35:1014-1019. I.F.: 2.56. S, Hartmann E, Salaverria I, Hutter G, in mantle cell lymphoma in vitro and Perez-Galan P, Roue G, Pott C, LeGouill in vivo by down-regulation of the 18 Barragan E, Montesinos P, Camos S, Cortelazzo S, Rule S, Hess G, Zaja prosurvival ER chaperone BiP/Grp78. M, Gonzalez M, Calasanz MJ, Roman- F, Vitolo U, Szymczyk M, Walewski BLOOD. 117:1270-1279. I.F.: 10.56. Gomez J, Gomez-Casares MT, Ayala R, J, Ribrag V, Unterhalt M, Hermine O, Lopez J, Fuster O, Colomer D, Chillon C, Hoster E. Update on the molecular patho- 14 Xargay-Torrent S, Lopez-Guerra Larrayoz MJ, Sanchez-Godoy P, Gonzalez- genesis and clinical treatment of mantle M, Saborit-Villarroya I, Rosich L, Cam- Campos J, Manso F, Amador ML, Vellen- cell lymphoma: report of the 10th annual po E, Roue G, Colomer D. Vorinostat- ga E, Lowenberg B, Sanz MA. Prognostic conference of the European Mantle Cell Induced Apoptosis in Mantle Cell value of FLT3 mutations in patients with Lymphoma Network. LEUKEMIA LYM- Lymphoma Is Mediated by Acetylation acute promyelocytic leukemia treated PHOMA. 52:2226-2236. I.F.: 2.49. of Proapoptotic BH3-Only Gene Pro- with all-trans retinoic acid and anthracy- moters. CLIN CANCER RES. 17:3956- cline monochemotherapy. HAEMATOL- 2 Kempf W, Pfaltz K, Vermeer MH, 3968. I.F.: 7.34. HEMATOL J. 96:1470-1477. I.F.: 6.53. Cozzio A, Ortiz-Romero PL, Bagot M, Olsen E, Kim YH, Dummer R, Pimpinelli 15 Pereira A, Nomdedeu M, 19 Olsen EA, Whittaker S, Kim YH, N, Whittaker S, Hodak E, Cerroni L, Aguilar JL, Belkaid M, Carrio A, Duvic M, Prince HM, Lessin SR, Wood Berti E, Horwitz S, Prince HM, Guitart J, Cobo F, Costa D, Rozman M, Sanz C, GS, Willemze R, Demierre MF, Pimpinelli Estrach T, Sanches JA, Duvic M, Ranki A, Nomdedeu B. Transfusion intensity, N, Bernengo MG, Ortiz-Romero PL, Dreno B, Ostheeren-Michaelis S, Knobler not the cumulative red blood cell Bagot M, Estrach T, Guitart J, Knobler R, Wood G, Willemze R. EORTC, ISCL, transfusion burden, determines the R, Sanches JA, Iwatsuki K, Sugaya M, and USCLC consensus recommendations prognosis of patients with myelodys- Dummer R, Pittelkow M, Hoppe R, for the treatment of primary cutaneous plastic syndrome on chronic trans- Parker S, Geskin L, Pinter-Brown L, CD30-positive lymphoproliferative fusion support. AM J HEMATOL. Girardi M, Burg G, Ranki A, Vermeer M, disorders: lymphomatoid papulosis and 86:245-250. I.F.: 3.58. Horwitz S, Heald P, Rosen S, Cerroni primary cutaneous anaplastic large-cell L, Dreno B, Vonderheid EC. Clinical lymphoma. BLOOD. 118:4024-4035. 16 Nomdedeu J, Bussaglia E, End Points and Response Criteria I.F.: 10.56. Villamor N, Martinez C, Esteve J, in Mycosis Fungoides and Sezary Tormo M, Estivill C, Queipo MP, Syndrome: A Consensus Statement of 3 Fernandez-Calotti PX, Colomer Guardia R, Carricondo M, Hoyos the International Society for Cutaneous D, Pastor-Anglada M. Translocation M, Llorente A, Junca J, Gallart M, Lymphomas, the United States of nucleoside analogs across the Domingo A, Bargay J, Mascaro M, Cutaneous Lymphoma Consortium, and plasma membrane in hematologic Moraleda JM, Florensa L, Ribera the Cutaneous Lymphoma Task Force. J malignancies. NUCLEOS NUCLEOT JM, Gallardo D, Brunet S, Aventin A, CLIN ONCOL. 29:2598-2560. I.F.: 18.97. NUCL. 30:1324-1340. I.F.: 1.13.

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eDitoRiAlS Vives J. Creation of a catalan network i.f.: 2.56 for the diagnosis and clinical management of rare anemias due to major 1 Nomdedeu M, Maffioli M, Calvo X, haemoglobinopathies. Sponsored by: Martinez-Trillos A, Baumann T, Diaz- Fundació la Marató de TV3, 101730. Beya M, Aguilar JL, Rozman M, Costa Duration: 14/12/2010-13/12/2013. D, Esteve J, Cervantes F, Colomer D, Nomdedeu B. Efficacy of lenalidomide Vives J. Déficit congénito de piru- in a patient with myelodysplastic vato cinasa. Influencia del equilibrio syndrome with isolated del(5q) and entre eritropoyesis y apoptosis en la JAK2(V617F) mutation. LEUKEMIA intensidad del síndrome hemolítico. RES. 35:1276-1278. I.F.: 2.56. Sponsored by: Instituto de Salud Car- los III (ISCIII), PI10/01460. Duration: 01/01/2011-31/12/2013. GRAntS foR ReSeARcH in pRoGReSS DoctoRAl tHeSeS Colomer D. Red temática de investiga- ción cooperativa de cáncer. Sponsored Estrach MT. Descripción y evaluación by: Ministerio Sanidad y Consumo, de los parámetros y patrones derma- RD06/0020/0014. Duration: 01/01/2007- toscópicos ede las lesiones cutáneas 31/12/2012. no melanocíticas y su diagnóstico diferencial con el melanoma. PhD student: Vives J. European Reference Network Pedro Zaballos Diego. of Expert Centres in Rare Anaemias. Sponsored by: European Commis- sion- Executive Agency for Health and Consumers, 2008 12 10. Duration: 01/06/2009-04/07/2012.

Colomer D. Dianes terapèutiques i noves tècniques diagnòstiques en neo- plasies limfoides. Sponsored by: Ge- neralitat de Catalunya, 2009_SGR_967. Duration: 15/09/2009-31/12/2013.

Roue G. Identificación de nuevas dianas terapéuticas para mejorar la actividad del velcade en el linfoma de células del manto. Sponsored by: Instituto de Salud Carlos III (ISCIII), PI09/0060. Du- ration: 01/01/2010-31/12/2012.

Colomer D. Utilización de terapias selectivas contra rutas de señalización desreguladas en neoplasias linfoides. Mecanismos de acción y estrategias de sensibilización. Sponsored by: Min- isterio de Educación, SAF2009_09503. Duration: 01/01/2010-31/12/2012.

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Hemotherapy - hemostasis

gROUP MeMBeRS StrateGic oBjectiveS

1. Study of the basic mechanisms regulating blood cell function and of teAM leADeR the interactions between such cells, Ginés escolar (Hospital clínic) with the vascular wall, and with tel.: 93 227 54 48 other cells. fax: 93 227 98 89 2. Evaluation of congenital and acqui- e-mail: [email protected] red defects in hemostasis and their pharmacological and/or transfusional xxxxxx iDiBApS MeMBeRS: tecHniciAnS: correction. Maribel Díaz-Ricart (Hospital clínic) Marc pino (Hospital clínic) 3. Laboratory characterization of blee- Ana M. Galán (iDiBApS) patricia Molina Moreno ding and thrombotic phenotypes and pablo García de frutos (cSic) (fundació clínic) genotypes. Miquel lozano (Hospital clínic) Verónica Sanz (fundació clínic) 4. Analysis of the efficacy and safety Anna M. Merino (Hospital clínic) Anhara Menéndez (cSic) of new strategies for sparing blood Joan Monteagudo (Hospital clínic) component transfusions. Antonio ordinas (Hospital clínic) collABoRAtoRS: 5. Development and evaluation of the Arturo pereira (Hospital clínic) Rosa Brugués (Hospital clínic) efficacy of synthetic platelet substi- Juan carles Reverter (Hospital clínic) Gabriela Gutiérrez (Hospital clínic) tutes. cristina ch. Sanz (Hospital clínic) M.Rosa Hernández (fundació clínic) 6. Characterization of animal models of M. Dolors tàssies (Hospital clínic) Josep M. Jou (Hospital clínic) hemostasis, preferentially in mice. Joan cid Vidal (Hospital clínic) Begoña Hurtado Villarejo (JAeDoc-cSic) poStDoctoRAl fellowS: cristina Aresté (JAeDoc-cSic) irene lópez-Vilchez (iDiBApS) eduardo Arellano Rodrigo (Hospital clínic) ReSeARcH fellowS: Marta palomo de udaeta (fundació clínic) carolina caballo Gordillo (fundació clínic)

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PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 oRiGinAlS 2009 84.32 20 10 4 main lineS of i.f.: 94.11 2010 93.91 22 8 6 reSearcH 2011 94.11 22 9 10 1 Cid J, Carbasse G, Pereira A, 1. Study of the mechanisms involved Sanz C, Mazzara R, Escolar G, in the development of bleeding and Lozano M. Platelet transfusions from thrombotic disorders. Proteomic D+ donors to D-patients: a 10-year study for determining the changes follow-up study of 1014 patients. in the vascular system and in the TRANSFUSION. 51:1163-1169. 6 Gimenez M, Gilabert R, different blood cells in thrombotic I.F.: 3.30. Monteagudo J, Alonso A, Casamitjana and bleeding disorders. R, Pare C, Conget I. Repeated Episodes 2. Evaluation of the physiological and 2 Sanchez-Palomino S, Massanella of Hypoglycemia as a Potential pathological implications of circula- M, Carrillo J, Garcia A, Garcia F, Aggravating Factor for Preclinical ting and/or intraplatelet tissue factor Gonzalez N, Merino A, Alcami J, Atherosclerosis in Subjects With Type in atherothrombosis. Bofill M, Yuste E, Gatell JM, Clotet 1 Diabetes. DIABETES CARE. 34:198- 3. Characterization of endothelial B, Blanco J. A cell-to-cell HIV 203. I.F.: 7.14. dysfunction as a common factor in transfer assay identifies humoral the development of complications responses with broad neutralization 7 Guasch E, Sionis A, Reverter JC, associated with multiple diseases. A activity. VACCINE. 29:5250-5259. Andrea R, Loma-Osorio P, Freixa X, physiological, biochemical and pro- I.F.: 3.57. Heras M. Safety issues of adjunctive teomic approach. clopidogrel in patients discharged after 4. New strategies for the treatment of 3 Ferrer G, Hodgson K, Pereira percutaneous coronary intervention combined humoral immunity in the- A, Juan M, Elena M, Colomer D, with stent placement and requiring rapeutic apheresis. Roue G, Aymerich M, Baumann T, oral anticoagulation. INT J CARDIOL. 5. Evaluation of the participation of Montserrat E, Moreno C. Combined 146:E1-E4. I.F.: 6.80. serotoninergic and purinergic me- analysis of levels of serum B-cell chanisms in platelet function. Study activating factor and a proliferation- 8 Martinez-Zamora MA, Creus M, of the antithrombotic potential of inducing ligand as predictor of Tassies D, Reverter JC, Civico S, pharmacological inhibitors. disease progression in patients with Carmona F, Balasch J. Reduced plasma 6. Role of the phenotype/genotype of chronic lymphocytic leukemia. LEU- fibrinolytic potential in patients with fibrinolysis and its repercussions KEMIA LYMPHOMA. 52:2064-2068. recurrent implantation failure after IVF upon global or specific functional I.F.: 2.49. and embryo transfer. HUM REPROD. tests in hemorrhagic and thrombotic 26:510-516. I.F.: 4.36. pathology. 4 Roque M, Sitges M, Sala J, 7. Study of the GAS6 vitamin K-depen- Delgado V, Morales M, Marrugat J, 9 LaMura V, Reverter JC, Flores- dent protein in hemostasis and the Vila J, Subirana I, Tassies D, Reverter Arroyo A, Raffa S, Reverter E, Seijo S, vascular wall, using knockout mice JC, Castro M, Duran M. Effects of Abraldes JG, Bosch J, Garcia-Pagan for this gene. Raloxifene on Endothelial Function JC. Von Willebrand factor levels predict 8. Evaluation of clotting factor con- and Hemostasis in Women With clinical outcome in patients with cir- centrates potential to reverse the Ischemic Heart Disease. REV ESP rhosis and portal hypertension. GUT. anticoagulant action of the new oral CARDIOL. 64:572-578. I.F.: 2.16. 60:1133-1138. I.F.: 10.61. antithrombotic agents 5 Freixa X, Masotti M, Palomo M, 10 Hanzu FA, Palomo M, Kalko Diaz-Ricart M, Escolar G, Guasch SG, Parrizas M, Garaulet M, E, Regueiro A, Jimenez M, Betriu Escolar G, Gomis R, Diaz-Ricart M. A, Heras M. Endothelin-1 levels Translational evidence of endothelial predict endothelial progenitor cell damage in obese individuals: mobilization after acute myocardial inflammatory and prothrombotic infarction. MICROVASC RES. 82:177- responses. J THROMB HAEMOST. 181. I.F.: 2.39. 9:1236-1245. I.F.: 5.44.

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11 Serra-Millas M, Lopez-Vilchez 16 Heddle NM, Wu C, Vassallo R, 22 Bosch MA, Contreras E, Madoz I, Navarro V, Galan AM, Escolar G, Carey P, Arnold D, Lozano M, Paven- P, Ortiz P, Pereira A, Pujol MM. The epi- Penades R, Catalan R, Fananas L, ski K, Sweeney J, Stanworth S, Liu Y, demiology of blood component transfu- Arias B, Gasto C. Changes in plasma Traore A, Barty R, Tinmouth A. Adju- sion in Catalonia, Northeastern Spain. and platelet BDNF levels induced by dicating bleeding events in a platelet TRANSFUSION. 51:105-116. I.F.: 3.30. S-citalopram in major depression. dose study: impact on outcome re- PSYCHOPHARMACOLOGY. 216:1-8. sults and challenges. TRANSFUSION. I.F.: 3.82. 51:2304-2310. I.F.: 3.30. ReViewS i.f.: 26.11 12 Pereira A, Nomdedeu M, 17 Hurtado B, Munoz X, Recarte- Aguilar JL, Belkaid M, Carrio A, Pelz P, Garcia N, Luque A, Krupinski J, 1 Font C, Vidal L, Espinosa G, Tassies Cobo F, Costa D, Rozman M, Sala N, DeFrutos PG. Expression of the D, Monteagudo J, Farrus B, Visa L, Sanz C, Nomdedeu B. Transfusion vitamin K-dependent proteins GAS6 Cervera R, Gascon P, Reverter JC. Solid intensity, not the cumulative red and protein S and the TAM receptor ty- cancer, antiphospholipid antibodies, and blood cell transfusion burden, rosine kinases in human atherosclerotic venous thromboembolism. AUTOIM- determines the prognosis of carotid plaques. THROMB HAEMOSTA- MUN REV. 10:222-227. I.F.: 6.56. patients with myelodysplastic SIS. 105:873-882. I.F.: 4.70. syndrome on chronic transfusion 2 Pons-Estel GJ, Salerni GE, Serrano support. AM J HEMATOL. 86:245- 18 Pinazo MJ, Tassies D, Munoz RM, Gomez-Puerta JA, Plasin MA, 250. I.F.: 3.58. J, Fisa R, Posada ED, Monteagudo J, Aldasoro E, Lozano M, Cid J, Cervera Ayala E, Gallego M, Reverter JC, Gas- R, Espinosa G. Therapeutic plasma 13 Palomo M, Diaz-Ricart M, con J. Hypercoagulability biomarkers exchange for the management of Rovira M, Escolar G, Carreras E. in Trypanosoma cruzi-infected patients. refractory systemic autoimmune dis- Defibrotide Prevents the Activation THROMB HAEMOSTASIS. 106:617- eases: Report of 31 cases and review of Macrovascular and Microvascular 623. I.F.: 4.70. of the literature. AUTOIMMUN REV. Endothelia Caused by Soluble 10:679-684. I.F.: 6.56. Factors Released to Blood by 19 Galan A, Lozano M, Molina P, Autologous Hematopoietic Stem Navalon F, Marschner S, Goodrich 3 Carreras E, Diaz-Ricart M. The role Cell Transplantation. BIOL BLOOD R, Escolar G. Impact of pathogen of the endothelium in the short-term MARROW TR. 17:497-506. I.F.: 3.28. reduction technology and storage in complications of hematopoietic SCT. platelet additive solutions on platelet BONE MARROW TRANSPL. 46:1495- 14 Merino A, DeLarrea CF, function. TRANSFUSION. 51:808- 1502. I.F.: 3.66. Blade J. Cytoplasmic inclusions 815. I.F.: 3.30. in leukocytes associated to 4 Cervantes F, Pereira A. Advances cryoglobulinemia and IgG-kappa 20 Font C, Farrus B, Vidal L, Caralt in the understanding and management monoclonal gammapathy of TM, Visa L, Mellado B, Tassies D, of primary myelofibrosis. CURR OPIN undetermined significance. EUR J Monteagudo J, Reverter JC, Gascon P. ONCOL. 23:665-671. I.F.: 4.39. HAEMATOL. 86:550-550. I.F.: 2.79. Incidental versus symptomatic venous thrombosis in cancer: a prospective 5 Hodgson K, Ferrer G, Pereira A, 15 Florensa L, Navarro JT, Vila observational study of 340 consecutive Moreno C, Montserrat E. Autoimmune MEP, Domingo A, DeLaBanda E, Roz- patients. ANN ONCOL. 22:2101-2106. cytopenia in chronic lymphocytic leu- man M, Camos M, Milla F, Perea G, I.F.: 6.45. kaemia: diagnosis and treatment. BRIT Alonso E, Ayats R, Aventin A, Cabe- J HAEMATOL. 154:14-22. I.F.: 4.94. zudo E, Espinet B, Merino A, Romero 21 Lopez-Vilchez I, Hedner U, P, Sanchez C, Tuset E, Sole F, Feliu Altisent C, Diaz-Ricart M, Escolar G, E, Fernandez C, Gallart M, Vallespi Galan AM. Redistribution and Hemos- T, Woessner S. Persistent polyclonal tatic Action of Recombinant Activated B-cell lymphocytosis: study of 35 Factor VII Associated with Platelets. cases. MED CLIN-BARCELONA. AM J PATHOL. 178:2938-2948. 136:565-573. I.F.: 1.41. I.F.: 5.22.

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GRAntS foR ReSeARcH Escolar G. Papel de Los receptores liga- in pRoGReSS dos a proteína G y los mecanismos de señalización mediados por kinasas en Reverter JC. Cáncer y Tromboembolis- la internalización y expresión del factor mo: Importancia de la generación de tisular por plaquetas: Implicaciones en trombina relacionada con las micropar- la trombogénesis. Sponsored by: Minis- tículas procoagulantes circulantes y los terio de Educación, SAF2009_10365. polimorfirmos de las mismas en el de- Duration: 01/01/2010-31/12/2012. sarrollo de trombosis en los pacientes de cáncer. Sponsored by: Ministerio Sa- García P. Papel regulador del sistema nidad y Consumo, PI070387. Duration: GAS6-PROS/TAM en la respuesta a 26/11/2007-31/10/2011. la inflamación de linfocitos y plaquetas. Sponsored by: Plan Nacional, Galan A. Desarrollo de preparaciones BFU2010-22185. Duration: 01/01/2011- con actividad hemostática como alter- 30/06/2012. nativa a la transfusión plaquetaria y al tratamiento procoagulante. Sponsored by: Ministerio de Educación y Ciencia, DoctoRAl tHeSeS PET2007-0169. Duration: 12/09/2008- 28/02/2011. Diaz-Ricart M. Molecular determinants of adipose tissue crosstalks. PhD stu- Escolar G. Red HERACLES: Deter- dent: Felicia Alexandra Hanzu. minantes genéticos y ambientales de la disfunción vascular. Sponso- Diaz-Ricart M, Escolar G. Biomarca- red by: Instituto de Salud Carlos III, dores precoces de la hiperactividad RD06/0009/1003. Duration: 29/02/2008- plaquetaria: particularidades de los me- 31/12/2012. canismos de contracción y secreción en équidos. PhD student: Lucas Brunso Escolar G. Desarrollo de modelos de Welker. coagulopatía dilucional y evaluación comparativa de eficacia correctora con distintos concentrados de factores de la coagulación. Sponsored by: Ministerio de Ciencia e Innovación, PET2008-0231. Duration: 01/03/2009- 28/02/2011.

García P. Thrombus stabilization as therapeutic target: from in vitro studies to animal models. Sponsored by: Fundació Marató de TV3. Duration: 01/01/2009- 31/12/2011.

Galan A. El sistema serotoninérgico: una conexión entre los mecanismos de la depresión mayor, la inflamación y el riesgo cardiovascular. Sponsored by: Instituto de Salud Carlos III (ISCIII), PI09/0664. Duration: 01/01/2010- 31/12/2012.

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Molecular and translational oncology

gROUP MeMBeRS StrateGic oBjectiveS

The strategic objectives of the labora- teAM leADeR tory are centered in three fields: pere Gascón Vilaplana 1. A purely scientific area correspon- (Hospital clínic) ding to the consolidation of the tel.: 93 227 54 02 investigational lines and groups fax: 93 454 65 20 that work in each of them. e-mail: [email protected] 2. A second area corresponding to the obtainment of aids and funding xxxxxx iDiBApS MeMBeRS: ADMiniStRAtiVe StAff: for research, in order to ensure the Juan José Grau (Hospital clínic) Marta Digón (Hospital clínic) good functioning of the laboratory. Joan Maurel (Hospital clínic) 3. A third objective is to formalize and Begoña Mellado (Hospital clínic) collABoRAtoRS: strengthen existing international núria Viñolas (Hospital clínic) elisabet Ametller (fundació clínic) partnerships with institutions from cristina nadal (Hospital clínic) Susana Garcia Recio (fundació clínic) Boston, Manchester and Oslo. noemí Reguart (Hospital clínic) Mercedes Marin (fundació clínic) Montserrat Muñoz (Hospital clínic) laura Vidal (Hospital clínic) The first of the mentioned areas (scien- Vanessa Almendro (iDiBApS) laura Visa (Hospital clínic, emili letang) tific) comprises a qualitative and quanti- estela pineda tative increase in scientific production. poStDoctoRAl fellowS: (Hospital clínic, emili letang) In particular, the colorectal and breast Anna Vidal (fundació clínic) Jordi Alcaraz cancer stem cell lines. (unitat Biofísica i Bioenginyeria, uB) Both the subject and the quality of tecHniciAnS: Ana Arance (Hospital clínic) research can attract investigators inter- eva Maria pastor (fundació clínic) patricia fernandez nogueira (uB) ested in a stay, in preparing a doctoral estel enreig (fundació clínic) Mario Mancino (fundació clínic) thesis, or in becoming part of the labo- Gemma fuster (fundació clínic) ratory personnel. In this sense in 2011 nuRSinG StAff: Arantzazu Zubeldia (fundació clínic) we have incorporated two new biolo- Àngels olivera (Hospital clínic) gists into the group. As regards the second area (funding of research), we must continue with the same criterion established years ago in order to ensure the continuity of all the research lines and facilitate the recruitment/ contracting of new personnel members. At present, the laboratory has one FISS grant (2012), one Networks funding from the Carlos III Institute, one grant from the Spanish Association Against Cancer (2009), and several research grants from the CELLEX Foundation.

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main lineS of gies for the reversal of chemore- 2.3. Role of the PPT-I gene in the reSearcH sistance (IDIBAPS: Joan Maurel; metastatic process (Pere Gas- Mercedes Marín. Germans Trias cón; Vanessa Almendro; Elisabet 1. tumor chemoresistance mecha- i Pujol Hospital: Albert Abad; Eva Ametller). nisms: Martínez; Anna Martínez). 2.4. Pre-angiogenic micrometastases 1.1. Resistance mechanisms in 1.7. Characterization of the role of of circulating cells (Cristina Nadal). colorectal cancer linked to the MMP-7 in resistance to beva- 2.5. Mechanisms of liver metastasis in extrinsic apoptotic pathway, in cizumab in colon cancer (Joan colorectal cancer (Cristina Nadal). vitro and in vivo (Joan Maurel). Maurel; Estela Pineda; Mercedes 2.6. Neuronal influence in breast can- 1.2. Mechanisms of epigenetic Marín; Cristobal Mezquita; Jovita cer progession of the phenotypy adaptation and cellular plasticity Mezquita; Betlem Mezquita). of the tumoral stem cell (Gemma during the adquisition of che- 1.8. Platform in orthotopic murine plat- Fuster, Vanessa Almendro). moresistance (Vanessa Almen- forms characterized by the study 3. Pharmacodynamic studies and pre- dros, Elisabet Ametller). of new drugs in pancreatic cancer diction of therapeutic response 1.3. Epithelial-mesenchymal tran- (IDIBAPS: Joan Maurel; Pere 3.1. Predictive and pharmacodynamic sition and resistance to che- Gascón; Salvador Navarro; David study of the response to neoad- motherapy (Elisabet Ametller; Fuster; Rosa Miquel. University juvant chemotherapy in prostate Vanessa Almendro). of Barcelona: Adela Mazo. CETIR: cancer. (Begoña Mellado). 1.4. Resistance to antitumor drugs in Yolanda González; Ignasi Carrió). 3.2. Mechanisms and markers of che- head and neck cancer (Principal 1.9. Mechanisms of tumor progression moresistance in prostate cancer. investigator: Juan J. Grau. Co- in breast cancer HER2+ induced Therapeutic strategies for the llaborators: Carmen Muñoz; Mi- by the adquisition of resistance to reversal of chemoresistance. (Be- guel Caballero; Mariano Monzó). Trastuzumab and Lapatinib (Patricia goña Mellado; Mercedes Marín). 1.5. Electrochemotherapy in solid Fernández, Vanessa Almendro). 4. Study on the determination and tumors. Study of electropora- 2. Stem cells, microenvironment and characterization of circulating tion. (Principal investigator: Juan mechanisms of metastasis. tumor cells J. Grau. Collaborators: Carmen 2.1. Neural control of breast cancer 4.1. In prostate cancer (Begoña Muñoz; Miguel Caballero. progression (Dra. Vanessa Al- Mellado). 1.6. Implication of IGF-1R and mendro, Mario Manzino, Elisabet 4.2. In breast cancer (Montse Muñoz; MMP-7 in the mechanisms of Ametller, Pere Gascón). Xavier González). resistance to chemotherapy and 2.2. Interaction between GPCRs and 5. Micro-RNAs in the development antibodies against tyrosine kina- RTKs (Vanessa Almendro; Elisa- and prognosis of non-small cell lung se receptors. Therapeutic strate- bet Ametller; Susana Garcia). cancer. (Nuria Viñolas). 6. Study of the tumor and stroma interactions in non-small cell lung cancer (NScLc): role of fibroblasts associated with cancer in NScLc (N. Reguart; J. Alcaraz; Marta Puig). 7. Effect of anomalous hardening of tumor tissue in NScLc (J. Alcaraz; N. Reguart; Marta Puig). 8. Study of sensitivity to trastuzumab in relation to the expression of to- poisomerase I (Xavi González; Montse Muñoz; Ana Arance). 9. characterization of the metastatic profile of malignant melanoma in circulating cells and primary tumors (Ana Arance; Laura Visa).

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PUBLICATIONS

oRiGinAlS Tobacco Metabolism and DNA Repair 10 Garcia-Albeniz X, Pericay C, i.f.: 263.85 Genes and Prognosis in Resected Non- Alonso-Espinaco V, Alonso V, Escudero Small-Cell Lung Cancer. J SURG RES. P, Fernandez-Martos C, Gallego R, Gas- 1 Casas F, Vinolas N, Ferrer F, 167:E5-E12. I.F.: 2.24. con P, Castellvi-Bel S, Maurel J. Serum Agusti C, Sanchez M, Gimferrer JM, matrilysin correlates with poor survival Lomena F, Campayo M, Jeremic B. 6 Fernandez-Esparrach G, Ayuso- independently of KRAS and BRAF sta- Long-Term Results of a Phase II Trial Colella JR, Sendino O, Pages M, tus in refractory advanced colorectal of Induction Paclitaxel-Carboplatin Cuatrecasas M, Pellise M, Maurel cancer patients treated with irinotecan Followed by Concurrent Radiation J, Ayuso-Colella C, Gonzalez-Suarez plus cetuximab. TUMOR BIOL. 32:417- Therapy and Weekly Paclitaxel and B, Llach J, Castells A, Gines A. EUS 424. I.F.: 2.03. Consolidation Paclitaxel-Carboplatin and magnetic resonance imaging in Stage III Non-small Cell Lung in the staging of rectal cancer: a 11 Fuster D, Ayuso JR, Poveda Cancer. J THORAC ONCOL. 6:79-85. prospective and comparative study. A, Cubedo R, Casado A, Martinez- I.F.: 4.04. GASTROINTEST ENDOSC. 74:347-354. Trufero J, Lopez-Pousa A, DelMuro I.F.: 5.65. XG, Lomena F, Maurel J, Pons F. Value 2 Campayo M, Navarro A, Vinolas of FDG-PET for monitoring treatment N, Tejero R, Munoz C, Diaz T, Mar- 7 Caldelari ACA, Miquel R, Bombi response in patients with advanced rades R, Cabanas ML, Gimferrer JA, Gines A, Fernandez-Esparrach G, GIST refractory to high-dose imatinib. JM, Gascon P, Ramirez J, Monzo M. Ayuso JR, Maurel J, Feu F, Castells A multicenter GEIS study. Q J NUCL A Dual Role for KRT81: A miR-SNP A, Fernandez-Cruz L, Navarro S. MED MOL IM. 55:680-687. I.F.: 2.54. Associated with Recurrence in Non- Malignancy predictive factors in Small-Cell Lung Cancer and a Novel pancreatic intraductal papillary 12 Verger E, Valduvieco I, Caral L, Marker of Squamous Cell Lung Carci- mucinous neoplasm. MED CLIN-BAR- Pujol T, Ribalta T, Vinolas N, Boget noma. PLOS ONE. 6:-. I.F.: 4.41. CELONA. 137:631-636. I.F.: 1.41. T, Oleaga L, Blanco Y, Graus F. Does gender matter in glioblastoma?. CLIN 3 Gomez-Caro A, Garcia S, Reguart 8 Perez-Torras S, Vidal-Pla A, Miquel TRANSL ONCOL. 13:737-741. I.F.: 1.25. N, Cladellas E, Arguis P, Sanchez M, R, Almendro V, Fernandez-Cruz L, Gimferrer JM. Determining the ap- Navarro S, Maurel J, Carbo N, Gascon 13 Brell M, Castaner S, Pujol- propriate sleeve lobectomy versus P, Mazo A. Characterization of human Farre T, Boluda S, Ribalta T, Bruna J, pneumonectomy ratio in central pancreatic orthotopic tumor xenografts Martinez M, Verger E, Villa S, Vinolas non-small cell lung cancer patients: suitable for drug screening. CELL ON- N, Gil M, Graus F, Tortosa-Moreno A. an audit of an aggressive policy of COL. 34:511-521. I.F.: 3.18. Implication of radiological pattern in the pneumonectomy avoidance. EUR prognosis of oligodendroglial tumors: J CARDIO-THORAC. 39:352-359. 9 Horndler C, Gallego R, Garcia- correlation with genetic profile. REV I.F.: 2.29. Albeniz X, Alonso-Espinaco V, Alonso NEUROLOGIA. 52:465-471. I.F.: 1.22. V, Escudero P, Jimeno M, Ortego J, 4 Navarro A, Diaz T, Gallardo E, Codony-Servat J, Fernandez-Martos C, 14 Barrett JH, Iles MM, Harland Vinolas N, Marrades RM, Gel B, Calatrava A, Marin-Aguilera M, Munoz M, Taylor JC, Aitken JF, Andresen Campayo M, Quera A, Bandres E, J, Castellvi-Bel S, Castells A, Rubini PA, Akslen LA, Armstrong BK, Avril Garcia-Foncillas J, Ramirez J, Monzo M, Gascon P, Maurel J. Co-expression MF, Azizi E, Bakker B, Bergman W, M. Prognostic Implications of miR- of matrix metalloproteinase-7 (MMP- Bianchi-Scarra G, Bressac-DePaillerets 16 Expression Levels in Resected 7) and phosphorylated insulin growth B, Calista D, Cannon-Albright LA, Non-Small-Cell Lung Cancer. J SURG factor receptor I (pIGF-1R) correlates Corda E, Cust AE, Debniak T, Duffy D, ONCOL. 103:411-415. I.F.: 2.43. with poor prognosis in patients with Dunning AM, Easton DF, Friedman E, wild-type KRAS treated with cetuximab Galan P, Ghiorzo P, Giles GG, Hansson 5 Campayo M, Vinolas N, Navarro or panitumumab A GEMCAD study. J, Hocevar M, Hoiom V, Hopper JL, A, Carcereny E, Casas F, Gel B, CANCER BIOL THER. 11:177-183. Ingvar C, Janssen B, Jenkins MA, Diaz T, Gimferrer JM, Marrades I.F.: 2.91. Jonsson G, Kefford RF, Landi G, Landi RM, Ramirez J, Monzo M. Single MT, Lang J, Lubinski J, Mackie R, Nucleotide Polymorphisms in Malvehy J, Martin NG, Molven A,

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original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 190.89 27 18 6 Montgomery GW, VanNieuwpoort FA, 18 VanCutsem E, Kohne CH, Lang I, Novakovic S, Olsson H, Pastorino L, Folprecht G, Nowacki MP, Cascinu S, 2010 131.60 15 10 2 Puig S, Puig-Butille JA, Randerson- Shchepotin I, Maurel J, Cunningham D, 2011 236.85 31 19 6 Moor J, Snowden H, Tuominen R, Tejpar S, Schlichting M, Zubel A, Celik I, Vanbelle P, VanDerStoep N, Whiteman Rougier P, Ciardiello F. Cetuximab Plus DC, Zelenika D, Han JL, Fang SY, Lee Irinotecan, Fluorouracil, and Leucovorin JE, Wei QY, Lathrop GM, Gillanders As First-Line Treatment for Metastatic Almel S, Rolski J, Munoz M, Moroose EM, Brown KM, Goldstein AM, Colorectal Cancer: Updated Analysis R, Hurvitz S, Banos A, Adewoye H, Hei Kanetsky PA, Mann GJ, Macgregor of Overall Survival According to Tumor YJ, Lindsay MA, Rupin M, Cabaribere S, Elder DE, Amos CI, Hayward NK, KRAS and BRAF Mutation Status. J D, Lemmerick Y, Mackey JR. Gruis NA, Demenais F, Bishop JAN, CLIN ONCOL. 29:2011-2019. I.F.: 18.97. Motesanib, or open-label bevacizumab, Bishop DT. Genome-wide association in combination with paclitaxel, as first- study identifies three new melanoma 19 Ametller E, Garcia-Recio S, line treatment for HER2-negative locally susceptibility loci. NAT GENET. Pastor-Arroyo EM, Callejo G, Carbo recurrent or metastatic breast cancer: 43:1108-U98. I.F.: 36.38. N, Gascon P, Almendro V. Differential a phase 2, randomised, double-blind, regulation of MMP7 in colon cancer placebo-controlled study. LANCET ON- 15 Font C, Farrus B, Vidal L, Caralt cells resistant and sensitive to COL. 12:369-376. I.F.: 17.76. TM, Visa L, Mellado B, Tassies D, oxaliplatin-induced cell death. CANCER Monteagudo J, Reverter JC, Gascon P. BIOL THER. 11:4-13. I.F.: 2.91. 24 Martin M, Sanchez-Rovira P, Munoz Incidental versus symptomatic venous M, Baena-Canada JM, Mel JR, Margeli thrombosis in cancer: a prospective 20 Almendro V, Fuster G. M, Ramos M, Martinez E, Garcia-Saenz observational study of 340 consecutive Heterogeneity of breast cancer: JA, Casado A, Jaen AM, Gonzalez-Farre patients. ANN ONCOL. 22:2101-2106. etiology and clinical relevance. CLIN X, Escudero MJ, Rodriguez-Martin I.F.: 6.45. TRANSL ONCOL. 13:767-773. I.F.: 1.25. C, Carrasco E. Pegylated liposomal doxorubicin in combination with 16 Casado E, Garcia VM, San- 21 Robert C, Thomas L, Bondarenko cyclophosphamide and trastuzumab in chez JJ, Blanco M, Maurel J, Feliu I, O’day S, Weber J, Garbe C, Lebbe HER2-positive metastatic breast cancer J, Fernandez-Martos C, DeCastro J, C, Baurain JF, Testori A, Grob JJ, patients: efficacy and cardiac safety from Castelo B, Belda-Iniesta C, Sereno M, Davidson N, Richards J, Maio M, the GEICAM/2004-05 study. ANN ON- Sanchez-Llamas B, Burgos E, Garcia- Hauschild A, Miller WH, Gascon P, COL. 22:2591-2596. I.F.: 6.45. Cabezas MA, Mancenido N, Miquel Lotem M, Harmankaya K, Ibrahim R, R, Garcia-Olmo D, Gonzalez-Baron Francis S, Chen TT, Humphrey R, Hoos 25 Bellmunt J, Gonzalez-Larriba JL, M, Cejas P. A Combined Strategy of A, Wolchok JD. Ipilimumab plus Dacar- Prior C, Maroto P, Carles J, Castellano D, SAGE and Quantitative PCR Provides bazine for Previously Untreated Meta- Mellado B, Gallardo E, Perez-Gracia JL, a 13-Gene Signature that Predicts static Melanoma. NEW ENGL J MED. Aguilar G, Villanueva X, Albanell J, Calvo Preoperative Chemoradiotherapy Res- 364:2517-2526. I.F.: 53.49. A. Phase II study of sunitinib as first-line ponse and Outcome in Rectal Cancer. treatment of urothelial cancer patients CLIN CANCER RES. 17:4145-4154. 22 Gascon P, Almenarez J, Artal A, ineligible to receive cisplatin-based I.F.: 7.34. Camps C, Firvida JL, Garrido P, Larriba chemotherapy: baseline interleukin-8 JLG, Montalar J. Management of lung and tumor contrast enhancement as 17 Porta R, Sanchez-Torres JM, cancer-associated anaemia: the Spanish potential predictive factors of activity. Paz-Ares L, Massuti B, Reguart N, Lung Cancer Anaemia Survey (SLCAS). ANN ONCOL. 22:2646-2653. I.F.: 6.45. Mayo C, Lianes P, Queralt C, Guillem CLIN TRANSL ONCOL. 13:328-334. V, Salinas P, Catot S, Isla D, Pradas I.F.: 1.25. 26 Rosell R, Molina MA, Costa C, A, Gurpide A, DeCastro J, Polo E, Simonetti S, Gimenez-Capitan A, Bertran- Puig T, Taron M, Colomer R, Rosell R. 23 Martin M, Roche H, Pinter T, Alamillo J, Mayo C, Moran T, Mendez Brain metastases from lung cancer Crown J, Kennedy MJ, Provencher L, P, Cardenal F, Isla D, Provencio M, Cobo responding to erlotinib: the importan- Priou F, Eiermann W, Adrover E, Lang I, M, Insa A, Garcia-Campelo R, Reguart N, ce of EGFR mutation. EUR RESPIR J. Ramos M, Latreille J, Jagiello-Gruszfeld Majem M, Viteri S, Carcereny E, Porta R, 37:624-631. I.F.: 5.92. A, Pienkowski T, Alba E, Snyder R, Massuti B, Queralt C, DeAguirre I, Sanchez

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Molecular and translational oncology

JM, Sanchez-Ronco M, Mate JL, Ariza Lopez-Brea M, Marquez A, Sanchez-Ronco 4 Gascon P, Aapro M, Ludwig H, A, Benlloch S, Sanchez JJ, Bivona TG, M, Taron M, Santarpia MC, Rosell R. Rosencher N, Boccadoro M, Turner M, Sawyers CL, Taron M. Pretreatment Single nucleotide polymorphisms in MDR1 Macdonald K, Muenzberg M, Abraham EGFR T790M Mutation and BRCA1 gen correlates with outcome in advanced I. Update on the MONITOR-GCSF mRNA Expression in Erlotinib-Treated non-small-cell lung cancer patients treated study of biosimilar filgrastim to reduce Advanced Non-Small-Cell Lung Cancer with cisplatin plus vinorelbine. LUNG CAN- the incidence of chemotherapy- Patients with EGFR Mutations. CLIN CER. 71:191-198. I.F.: 3.36. induced febrile neutropenia in cancer CANCER RES. 17:1160-1168. I.F.: 7.34. patients: Protocol amendments. CRIT 31 Marotta LLC, Almendro V, Marusyk REV ONCOL HEMAT. 77:198-200. 27 Baro E, Carulla J, Cassinello A, Shipitsin M, Schemme J, Walker SR, I.F.: 4.69. J, Colomer R, Mata JG, Gascon P, Bloushtain-Qimron N, Kim JJ, Choudhury Gasquet JA, Rodriguez CA, Valentin SA, Maruyama R, Wu Z, Gonen M, V. Psychometric properties of the Mulvey LA, Bessarabova MO, Huh SJ, eDitoRiAlS Perform Questionnaire: a brief scale Silver SJ, Kim SY, Park SY, Lee HE, i.f.: 1.41 for assessing patient perceptions of Anderson KS, Richardson AL, Nikolskaya fatigue in cancer. SUPPORT CARE T, Nikolsky Y, Liu XS, Root DE, Hahn WC, 1 Grau JJ, Caballero M, Tagliapetra CANCER. 19:657-666. I.F.: 2.06. Frank DA, Polyak K. The JAK2/STAT3 A. New antitarget antineoplastic drugs. signaling pathway is required for growth Clinical indications in the treatment 28 Garcia-Del-Muro X, Lopez-Pousa of CD44(+)CD24(-) stem cell-like breast of cancer. MED CLIN-BARCELONA. A, Maurel J, Martin J, Martinez-Trufe- cancer cells in human tumors. J CLIN IN- 137:370-376. I.F.: 1.41. ro J, Casado A, Gomez-Espana A, Fra VEST. 121:2723-2735. I.F.: 14.15. J, Cruz J, Poveda A, Meana A, Pericay C, Cubedo R, Rubio J, DeJuan A, Lai- clinicAl GuiDelineS nez N, Carrasco JA, DeAndres R, Bue- ReViewS i.f.: 5.16 sa JM. Randomized Phase II Study i.f.: 25.83 Comparing Gemcitabine Plus Dacar- 1 Maurel J, Fernandez-Martos bazine Versus Dacarbazine Alone in 1 Font C, Vidal L, Espinosa G, Tassies C, Feliu J, Isla D. SEOM clinical Patients With Previously Treated Soft D, Monteagudo J, Farrus B, Visa L, guidelines for the treatment of anal Tissue Sarcoma: A Spanish Group for Cervera R, Gascon P, Reverter JC. Solid cancer. CLIN TRANSL ONCOL. Research on Sarcomas Study. J CLIN cancer, antiphospholipid antibodies, and 13:525-527. I.F.: 1.25. ONCOL. 29:2528-2533. I.F.: 18.97. venous thromboembolism. AUTOIM- MUN REV. 10:222-227. I.F.: 6.56. 2 Feliu J, Sastre J, Maurel J, Isla D. 29 Garcia-Donas J, Esteban E, Hepatocellular and biliary tract carcinomas: Leandro-Garcia LJ, Castellano DE, 2 Gascon P, Aapro M, Ludwig H, SEOM clinical guidelines. CLIN TRANSL DelAlba AG, Climent MA, Arranz Rosencher N, Turner M, Song MK, ONCOL. 13:536-544. I.F.: 1.25. JA, Gallardo E, Puente J, Bellmunt Macdonald K, Lee C, Muenzberg J, Mellado B, Martinez E, Moreno F, M, Abraham I. Background and 3 Munoz AJ, Vinolas N, Cubedo R, Font A, Robledo M, Rodriguez-Antona methodology of MONITOR-GCSF, a Isla D. SEOM guidelines on thrombosis C. Single nucleotide polymorphism pharmaco-epidemiological study of the in cancer patients. CLIN TRANSL ON- associations with response and toxic multi-level determinants, predictors, and COL. 13:592-596. I.F.: 1.25. effects in patients with advanced renal- clinical outcomes of febrile neutropenia cell carcinoma treated with first-line prophylaxis with biosimilar granulocyte- 4 GarciaDelMuro X, Martin J, Mau- sunitinib: a multicentre, observational, colony stimulating factor filgrastim. rel J, Cubedo R, Bague S, DeAlava prospective study. LANCET ONCOL. CRIT REV ONCOL HEMAT. 77:184-197. E, Pousa AL, Narvaez JA, Ortiz E, 12:1143-1150. I.F.: 17.76. I.F.: 4.69. Pomes J, Poveda A, Romasanta LP, Tendero O, Viñals JM, GrupoEspañol- 30 Vinolas N, Provencio M, Reguart 3 Mancino M, Ametller E, Gascon P, DeInvestigacionEnSarcomas (GEIS). N, Cardenal F, Alberola V, Sanchez- Almendro V. The neuronal influence on Soft tissue sarcomas: clinical practice Torres JM, Baron FJ, Cobo M, Maestu I, tumor progression. BBA-REV CANCER. guidelines. MED CLIN-BARCELO- Moreno I, Mesia C, Izquierdo A, Felip E, 1816:105-118. I.F.: 9.89. NA:-. I.F.: 1.41.

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MulticentRicS Reguart N. Papel de los fibroblastos i.f.: 12.10 asociados a tumores (CAFS) en el carcinoma broncogénico de pulmón: 1 Arrieta O, Cardona AF, Bramuglia mecanismos de interacción de modelos GF, Gallo A, Campos-Parra AD, Serrano de cultivo celular 3D. Sponsored by: S, Castro M, Aviles A, Amorin E, Kir- Instituto de Salud Carlos III (ISCIII), chuk R, Cuello M, Borbolla J, Riemers- PI09/1377. Duration: 01/01/2010- ma O, Becerra H, Rosell R. Genotyping 31/12/2012. Non-small Cell Lung Cancer (NSCLC) in Latin America. J THORAC ONCOL. Reguart N. Contribución de los fibro- 6:1955-1959. I.F.: 4.04. blastos asociados a tumores (CAFs) al cáncer de pulmón estudiado con mode- 2 Amos CI, Wang LE, Lee JE, Gers- los de cultivo celular tridimensionales. henwald JE, Chen WV, Fang SY, Kosoy Sponsored by: Asociación Española R, Zhang MF, Qureshi AA, Vattathil S, Contra el Cáncer, 10/103. Duration: Schacherer CW, Gardner JM, Wang YL, 22/02/2010-21/02/2012. Bishop DT, Barrett JH, Macgregor S, Hayward NK, Martin NG, Duffy DL, Mann Maurel J. Papel de MMP-7 en la GJ, Cust A, Hopper J, Brown KM, Grimm transactivación IGF-1R-EGFR y la re- EA, Xu YJ, Han YH, Jing KY, Mchugh C, sistencia intrínseca a los inhibidores Laurie CC, Doheny KF, Pugh EW, Seldin de Epidermal Growth Factor Receptor MF, Han JL, Wei QY. Genome-wide as- (EGFR) en cáncer colorectal. Sponsored sociation study identifies novel loci pre- by: Fundación de Investigación Médica disposing to cutaneous melanoma. HUM Mútua Madrileña, AP75002010. Dura- MOL GENET. 20:5012-5023. I.F.: 8.06. tion: 17/09/2010-16/09/2011.

GRAntS foR ReSeARcH DoctoRAl tHeSeS in pRoGReSS Vinolas N. Anàlisi de polimorfismes Gascon P. Mecanismos de transacti- d’una sola base (SNPs) com a factors vación de los miembros de la familia predictius de recaiguda en pacients amb ERB-B en cáncer de mama: importancia càncer de pulmó de cèl·lula no petita de las neuroquininas y la neurogénesis. quirúrgic. PhD student: Marc Campayo. Sponsored by: Fondo de Investigacio- nes Sanitarias de la Seguridad Social Vinolas N. Importancia clínica de los mi- (FISS), PI080022. Duration: 01/01/2009- croRNAs de la vía de p53 en cáncer de 31/12/2011. pulmón no microcítico: miR-34ª y miR- 16. PhD student: Elena Gallardo Martín. Gascon P. Red temática de investi- gación cooperativa de Cáncer. Spon- sored by: Instituto de Salud Carlos III, RED07/0020/2014. Duration: 23/02/2009-31/12/2012.

Grau JJ. Efectividad y seguridad de la electroquimioterapia en el tratamiento de tumores sólidos. Sponsored by: Instituto de Salud Carlos III (ISCIII), PI09/90664. Duration: 01/01/2010-31/12/2011.

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Team involved in: Oncology and haematology

Cell proliferation and signaling

gROUP MeMBeRS

teAM leADeR oriol Bachs (universitat de Barcelona) tel.: 93 403 52 86 fax: 93 402 19 07 e-mail: [email protected] xxxxxx iDiBApS MeMBeRS: Meritxell Reverter (uB) tecHniciAnS: neus Agell (uB) Adam kassan (iDiBApS) Sonia Brun (uB) Rosa Aligué (uB) Alba llopis (uB) Alba fajardo (uB) carles enrich (uB) carles Barceló (uB) María Molinos (uB) Albert pol (icReA-iDiBApS) natalia de olano (uB) eulalia Rius (uB) francesc tebar (uB) Anna Alvarez-Guaita (uB) David Gimenez (uB) Montserrat Jaumot (uB) Atilla Biçer (uB) Maria Jesús pujol (uB) eugenia cisneros (uB) collABoRAtoRS: Amaia ercilla (uB) Marta Bosch (iDiBApS) ReSeARcH fellowS: Mariona Gelabert (uB) teresa Royo (iDiBApS) María pérez (uB) Alba Gómez (uB) edurne Gallastegui (uB) Raffaella pippa (uB) noelia paco (uB) carles Rentero (iDiBApS) Sandra Vilà de Muga (uB) Anna perearnau (uB) Marta Sanchez (uB) David Soriano (uB) Serena orlando (iDiBApS) Maite Vidal-Quadras (uB) Albert Herms (iDiBApS) Gemma Ventura (iDiBApS)

304 AReA 5 oncoloGy AnD HAeMAtoloGy cell pRolifeRAtion AnD SiGnAlinG

StrateGic oBjectiveS

The general goal of the group is the analysis of the mechanisms involved in cell cycle progression and signaling in health and disease. Co-localitzation of p27 (green) and PCAF (red) during apoptosis. main lineS of reSearcH regulated is one of the most crucial 1. cell proliferation and cancer: The objectives in biomedical research.The objective of this line of research is aim of this research focuses on iden- the analysis of the mechanisms in- tifying the molecular mechanisms volved in cell cycle regulation and its by which cell cycle is regulated by alterations during tumorigenesis: stress-activated protein kinases. • Role of the CKI p27(Kip1) on the regulation of transcription, splicing 4. Endocytosis, membrane traffic- and translation of genes involved king and signaling: This line of in tumorigenesis. research includes the following acti- • Cell cycle regulation by protein vities: acetylation. • Study of endocytosis and mem- • Role of calmodulin in nuclear brane trafficking in polarized cells, functions. such as hepatocytes and in non- polarized cells. 2. cell cycle: signal transduction and • Study the role of calmodulin in the checkpoints: The main topics in this regulation of trafficking and signa- research line are the analysis of: lling of EGFR. the regulation of the functionality of • Study the role of Annexin A6 in the K-Ras by Calmodulin-binding and by transport of caveolin, the forma- phosphorylation; the regulation of tion of caveolae, homeostasis of p21CIP1 localization and the relevan- cholesterol and signaling of Ras/ ce of its binding to calmodulin and its MAPK. phosphorylation; and, the DNA replication checkpoint in not transformed 5. Lipid trafficking and storage: The versus transformed cell lines. aim of our project is to characterize in health and disease, the cellular 3. Signaling and regulation of the cell processes regulated or deregulated cycle: In eukaryotic organisms, the by the accumulation of lipids within response to stress insults is through cells. With a special attention to the activation of the MAP kinases the cellular cost of accumulation of pathway, Progression through the cholesterol in the organelles and the cell cycle is dependent on external role of the caveolin protein in the stimuli and failure to correctly inte- regulation of these mechanisms. grate the induced signals can lead to accumulation of genetic damage contributing to cancer development. For further information: Understanding how signaling net- www.celltrafficbcn.cat works and the cellular responses are

305 ONCOLOgy AND hAeMATOLOgy

Cell proliferation and signaling

PUBLICATIONS

oRiGinAlS 6 Aranda JF, Reglero-Real N, Kremer L, 2 Enrich C, Rentero C, DeMuga SV, i.f.: 50.95 Marcos-Ramiro B, Ruiz-Saenz A, Calvo Reverter M, Mulay V, Wood P, Koese M, Enrich C, Correas I, Millan J, Alonso M, Grewal T. Annexin A6-Linking Ca2+ 1 Bosch M, Mari M, Herms A, MA. MYADM regulates Rac1 targeting signaling with cholesterol transport. Fernandez A, Fajardo A, Kassan A, to ordered membranes required for cell BBA-MOL CELL RES. 1813:935-947. Giralt A, Colell A, Balgoma D, Barbero spreading and migration. MOL BIOL I.F.: 4.73. E, Gonzalez-Moreno E, Matias N, CELL. 22:1252-1262. I.F.: 5.86. Tebar F, Balsinde J, Camps M, Enrich C, Gross SP, Garcia-Ruiz C, Perez- 7 Custodio L, Escapa AL, Fernandes E, GRAntS foR ReSeARcH Navarro E, Fernandez-Checa JC, Pol Fajardo A, Aligue R, Albericio F, Neng N, in pRoGReSS A. Caveolin-1 Deficiency Causes Nogueira JMF, Romano A. Phytochemical Cholesterol-Dependent Mitochondrial Profile, Antioxidant and Cytotoxic Bachs O. Red temática de investiga- Dysfunction and Apoptotic Activities of the Carob Tree (Ceratonia ción cooperativa de cáncer. Sponsored Susceptibility. CURR BIOL. 21:681- siliqua L.) Germ Flour Extracts. PLANT by: Ministerio Sanidad y Consumo, 686. I.F.: 10.03. FOOD HUM NUTR. 66:78-84. I.F.: 2.46. RD06/0020/0010. Duration: 01/01/2006- 31/12/2011. 2 Bosch M, Mari M, Gross 8 Matito C, Agell N, Sanchez-Tena SP, Fernandez-Checa JC, Pol S, Torres JL, Cascante M. Protective Agell N. Relevancia de la fosforilación A. Mitochondrial Cholesterol: A Effect of Structurally Diverse Grape de K-Ras y de las alteraciones en el Connection Between Caveolin, Procyanidin Fractions against UV- Checkpoint de replicación del DNA en Metabolism, and Disease. TRAFFIC. Induced Cell Damage and Death. J AGR la oncogénesis. Sponsored by: Minis- 12:1483-1489. I.F.: 5.28. FOOD CHEM. 59:4489-4495. I.F.: 2.82. terio de Educación, SAF2010-20712. Duration: 01/01/2011-31/12/2013. 3 Custodio L, Fernandes E, Escapa 9 Vidal-Quadras M, Gelabert-Baldrich AL, Fajardo A, Aligue R, Albericio F, M, Soriano-Castell D, Llado A, Rentero Aligué R. La MAP quinasa p38 y la MA- Neng NR, Nogueira JMF, Romano A. C, Calvo M, Pol A, Enrich C, Tebar PKAP en la señalización de respuesta Antioxidant and Cytotoxic Activities F. Rac1 and Calmodulin Interactions a estrés y el control del ciclo celular. of Carob Tree Fruit Pulps Are Strongly Modulate Dynamics of ARF6- Sponsored by: Ministerio de Educa- Influenced by Gender and Cultivar. J Dependent Endocytosis. TRAFFIC. ción, BFU-2009-10778/BMC. Duration: AGR FOOD CHEM. 59:7005-7012. 12:1879-1896. I.F.: 5.28. 01/01/2009-31/12/2011. I.F.: 2.82. 10 Wood P, Mulay V, Darabi M, Chan Bachs O. Papel del regulador del ciclo 4 Millour J, DeOlano N, Horimoto KC, Heeren J, Pol A, Lambert G, Rye celular p27Kip1 en la oncogénesis. Y, Monteiro LJ, Langer JK, Aligue KA, Enrich C, Grewal T. Ras/Mitogen- Sponsored by: Ministerio de Educa- R, Hajji N, Lam EWF. ATM and p53 activated Protein Kinase (MAPK) ción, SAF2009- 07769 (GEN). Duration: Regulate FOXM1 Expression via Signaling Modulates Protein Stability 01/01/2009-31/12/2012. E2F in Breast Cancer Epirubicin and Cell Surface Expression of Sca- Treatment and Resistance. MOL venger Receptor SR-BI. J BIOL CHEM. Bachs O. Proteored. Sponsored by: Ge- CANCER THER. 10:1046-1058. 286:23077-23092. I.F.: 5.33. noma España, SAF2009- 07769 (GEN). I.F.: 5.23. Duration: 01/01/2005-31/12/2011.

5 Reverter M, Rentero C, DeMuga ReViewS Bachs O. Proliferació Cel·lular. Sponso- SV, Alvarez-Guaita A, Mulay V, Cairns i.f.: 8.98 red by: Grups de Recerca de la Gene- R, Wood P, Monastyrskaya K, Pol ralitat de Catalunya, 2009 SGR 1382. A, Tebar F, Blasi J, Grewal T, Enrich 1 Cornely R, Rentero C, Enrich C, Duration: 01/01/2009-31/12/2013. C. Cholesterol transport from late Grewal T, Gaus K. Annexin A6 is an endosomes to the Golgi regulates Organizer of Membrane Microdomains Enrich C. Ras/MAPK signaling regulates t-SNARE trafficking, assembly, and to Regulate Receptor Localization and cholesterol efflux. Sponsored by: Fun- function. MOL BIOL CELL. 22:4108- Signalling. IUBMB LIFE. 63:1009-1017. dació la Marató de TV3 ,81110. Dura- 4123. I.F.: 5.86. I.F.: 4.25. tion: 01/01/2009-31/12/2011.

306 AReA 5 oncoloGy AnD HAeMAtoloGy cell pRolifeRAtion AnD SiGnAlinG

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 56.36 10 8 1 Enrich C. Endocitosi, tràfic i senyalització. Sponsored by: MICINN, BFU2006- Sponsored by: Grups de Recerca de 26075-E/BMC. Duration: 01/01/2009- 2010 41.72 7 7 0 la Generalitat de Catalunya, 2009 SGR 31/12/2011. 2011 50.95 10 9 0 1526. Duration: 01/01/2009-31/12/2013. Enrich C. Creación de la Red Española Enrich C. Estudio de l tráfico intra- de Microscopia óptica (REMOA). Spon- celular de la caveolina, formación de sored by: Ministerio de Ciencia e In- caveolas y la señalización: papel de la novación, BIO2010-12435-E. Duration: annexin A6. Sponsored by: MCINN, 01/01/2011-31/12/2012. Bachs O. P27kip1 regula la transcrip- BFU2009-10335. Duration: 01/01/2010- ción de genes implicados en la tumori- 31/12/2012. Enrich C. Ras signalling and cholesterol génesis. PhD student: Raffaella Pippa. efflux from late endosomes. Sponsored Enrich C. Ayuda para la organización by: National Health Medical Research Agell N. SAPKs en el checkpoint de re- de la Conferencia Internacional so- Council of Australia (NHMRC), Project plicación del DNA. PhD student: Noelia bre Annexinas. Sponsored by: MI- Grant 510294. Duration: 01/01/2008- Salvador Marcos. CINN, BFU2010-11196-E. Duration: 31/12/2011. 01/01/2011-31/12/2011. Pol A. Biogénesis de los cuerpos Li- Enrich C. Regulation of EGF receptor pídicos. PhD student: Elena González Pol A. Hepatic and brain mitochondrial signalling. Sponsored by: National Moreno. cholesterol/glycosphingolipids and Health Medical Research Council of altered metabolism contribute to the Australia (NHMRC), Project Grant Tebar F. Funcionalidad de la unión de pathology of Niemann Pick type C dis- 510293. Duration: 01/01/2008- calmodulina a RAC 1: Implicaciones ease and caveolinopathies. Sponsored 31/12/2011. en la endocitosis independiente de by: Fundació Marató de TV3, PI041315. clatrina. PhD student: Mª Teresa Vidal- Duration: 01/01/2010-31/12/2014. Enrich C. Mechanism of protein secre- Quadras de Soto. tion and compartment organization. Pol A. Mechanism of Lipid Droplet Sponsored by: Consolider -INGENIO formation. Sponsored by: MICINN, 2010, CSD2009-00016. Investigador CONSOLIDER-INGENIO 2010, coordinador: Dr. Vivek Malhotra. Inves- CSD2009.00016. Duration: 01/01/2009- tigador principal Grupo 7: Carlos Enrich. 31/12/2014. Duration 01/01/2009- 31/12/2013.

Pol A. Intracellular accumulation of lipids: Role of CAV1, molecular DoctoRAl tHeSeS mechanisms and implications on cell proliferation. Sponsored by: MICINN, Bachs O. Evolució del diagnòstic ci- BFU2008-00345. Duration: 01/01/2008- togenètic prenatal i postnatal amb la 31/12/2011. implementació de noves tècniques de biologia molecular i la seva repercussió Tebar F. Función de PKCdelta y calmo- en el consell genètic. PhD student: Mª dulina en la regulación de la dinámica Carme Morales Peydró. del citoesqueleto de actina y del tráfico intracelular del factor de crecimiento Bachs O. Implicación de proteinas G y epidérmico. Sponsored by: MICINN, de PKA en la regulación local de la vía BFU2009-13526/BMC. Duration: de sonic hedgehog en el cilio promario. 01/01/2010-31/12/2012. PhD student: María de las Mercedes Barzi Diéguez. Tebar F. Integración funcional del tráfico de membranas, la señalización intra- Pol A. The study of lipid droplets bio- celular y la dinámica del citoesqueleto. genesis. PhD student: Adam Kassan

307

Transversal research groups

Transversal group for research in primary care

gROUP MeMBeRS StrateGic oBjectiveS

Primary care is the point of patient entry to the healthcare system, and teAM leADeR the primary care centers are where Antoni Sisó Almirall (GeSclÍnic) most of the population health prob- tel.: 93 227 99 24 lems are dealt with. It is in this set- fax: 93 227 55 97 ting where the relationship between e-mail: [email protected] the patient and reference primary care physician and nurse is a key iDiBApS MeMBeRS: ReSeARcH fellowS: factor in preventing and healing dis- lluisa Benito Serrano (GeSclinic) emma Marianela Morales espinoza eases, and in promoting healthy hab- Marta catalán Adell (cApSe) (GeSclinic) its. In the research context, the mul- Zoe Herreras pérez (cApSe) norma nely nardi (Hospital clínic) tidisciplinary and transverse nature imma Garrell lluís (cApSe) of the activities of the primary care Joan Gené Badia (cApSe) nuRSinG StAff: professional favors a biological, psy- imma Grau corral (Hospital clínic) narly Benachi Sandoval (cApSe) chological and social approach to the pilar navarrete Duran (cApSe) noemí García (cApSe) patients and their illnesses, in both Marta navarro González (cApSe) Rosa Segarra (cApSe) the consulting office and in the home. Jacinto ortiz Molina (GeSclinic) esther Blat (GeSclinic) The integral approach to the indi- ignacio Menacho (GeSclinic) elena Mañes (cApSe) vidual and longitudinal care over the Antoni Salvà Riquer (cApSe) full course of the life of the patient núria Sánchez Ruano (cApSe) StAticiAnS: makes it possible to conduct pro- laura Sebastián Montal (GeSclinic) Belchin Adriyanov kostov prietary and/or collaborative studies ethel Sequeira Aymar (cApSe) (fundació clínic) targeted at knowledge of the char- Josep Miquel Sotoca (Hospital clínic) acteristics of the population, people Marina Rovira (cApSe) collABoRAtoRS: and their illnesses. Primary care aims lluís González de paz (GeSclinic) Sílvia canivell fusté (iDiBApS) to carry out research inherent to its elisenda Sant Arderiu (cApSe) Jaume Benavent Àreu (institut català de la Salut)

310 tRAnSVeRSAl ReSeARcH GRoupS tRAnSVeRSAl GRoup foR ReSeARcH in pRiMARy cARe

PUBLICATIONS

original publications from 2009 to 2011

Year IF Total Q 1 Q 2 nature, integrating within the existing main lineS of 2009 6.41 2 0 1 investigational networks and groups, reSearcH 2010 49.85 7 4 2 and working in a coordinated man- 2011 23.06 5 2 3 ner with other consolidated research • Healthcare continuity and mana- teams from different perspectives: gement of chronic diseases. • Conduction of population-based • Use of healthcare services. studies (both descriptive and evalu- • The fragility – geriatrics – depen- oRiGinAlS ating interventions and follow-up), dency – home care axis. i.f.: 23.06 in an accessible and well defined • Use of medicines. population of subjects, taking ad- • Primary care and autoimmunity. 1 Benito L, Hoyo J, Montroig A, vantage of the computer-based fil- • Atherogenesis, risk factors and Fornes B, Fluxa G, Marti D, Pedros ing of clinical data. cardiovascular diseases. M, Siso A, Mont L, Miro O, Coll- • Conduction of research into health- • Chronic pain. Vinent B. Adverse effects of antiar- care results or outcomes. • Mental health, smoking and other rhythmic drugs in patients with atrial • Description of the natural history addictions. fibrillation in Primary Care. MED of the patient and disease from a • Respiratory diseases. CLIN-BARCELONA. 137:241-246. biological, psychological and social • Digestive and liver diseases. I.F.: 1.41. perspective. • HIV infection – AIDS and other • Conduction of studies of risk factors infectious diseases. 2 Riesgo A, Sant E, Benito L, Hoyo and preventive medicine. • 2.0. Health. J, Miro O, Mont L, Bragulat E, Coll- • Analysis of the morbidity and mortal- Vinent B. Sex Differences in the ity of the most prevalent disorders. Treatment of Patients With Atrial • Development of collaborative studies Fibrillation: Population-Based Study with the administration and research in a Local Health District. REV ESP entities or groups allowing the imple- CARDIOL. 64:233-236. I.F.: 2.16. mentation of translation research. 3 Falces C, Andrea R, Heras M, In the year 2011, Research in Primary Vehi C, Sorribes M, Sanchis L, Care has been organized around the Cevallos J, Menacho I, Porcar S, Font CAPSE-GESCLINIC Research Unit, inte- D, Sabate M, Brugada J. Integration grated by Dr. Antoni Sisó (Director of the Between Cardiology and Primary CAPSE_GESCLINIC Unit), Dr. Laura Se- Care: Impact on Clinical Practice. REV bastián (Manager of CAPSE-GESCLIN- ESP CARDIOL. 64:564-571. I.F.: 2.16. IC), Lluís González (DUE-GESCLINIC), Elena Mañes (DUE-CAPSE), and Narly 4 Cobo E, Cortes J, Ribera JM, Benachi (DUE-Clinical Trials-CAPSE). Cardellach F, Selva-O’callaghan A, Kostov B, Garcia L, Cirugeda L, Altman DG, Gonzalez JA, Sanchez JA, Miras F, Urrutia A, Fonollosa V, Rey-Joly C, Vilardell M. Effect of using reporting guidelines during peer review on quality of final manuscripts submitted to a biomedical journal: masked randomised trial. BRIT MED J. 343:-. I.F.: 13.47.

311 TRANSveRSAL ReSeARCh gROUPS

Transversal group for research in primary care

5 Mas S, Gasso P, Alvarez S, Ortiz DoctoRAl tHeSeS J, Sotoca JM, Francino A, Carne X, Lafuente A. Pharmacogenetic Siso A, Ramos-Casals M. Significado predictors of angiotensin-converting clínico de la presencia de autoanticuer- enzyme inhibitor-induced cough: pos en el síndrome de Sjögren prima- the role of ACE, ABO, and BDKRB2 rio: implicaciones en la práctica diaria. genes. PHARMACOGENET GENOM. PhD student: Norma Nardi, Universitat 21:531-538. I.F.: 3.87. de Barcelona.

Siso A. Anàlisis de les comunitats GRAntS foR ReSeARcH virtuals en els fòrums del portal Forum- in pRoGReSS Clinic. PhD student: Immaculada Grau Corral. Grau I. Desarrollo y coorganización del proyecto ForumClinic. Programa interactiu per a pacients adreçat a què aquests augmentin el seu grau d’autonomia respecte a la seva salut utilitzant les oportunitats de les noves tecnologies. Sponsored by: Fundación BBVA. Duration: 01/01/2009-31/12/2012.

Siso A. Multilingual OrganiK Infor- mation management in the medical domain (Projecte MORMED). Spon- sored by: Comission Europea, 250534. Duration: 01/03/2010- 31/08/2012.

Ortega E, Catalan M, Herreras Z. Riesgo cardiovascular en sujetos con diabetes tipo 2 (DM2) de re- ciente diagnóstico: grosor de intima media (GIMC) y presencia de placa carotídea (PC) como discriminador de riesgo cardiovascular al diagnóstico y tras tratamiento de la enfermedad. Sponsored by: Instituto de Salud Car- los III (ISCIII), PI11/01723. Duration: 01/01/2011-31/12/2012.

312

Transversal research groups

Research in nursing StrateGic oBjectiveS gROUP MeMBeRS Research in nursing is essential for responding to the healing demands of the current healthcare system. Its complexity in the hospital setting is derived from the associ- teAM leADeR ated increase in patient severity Adelaida Zabalegui (Hospital clínic) upon admission, the reduction in tel.: 93 227 54 24 hospital stay, the incorporation of fax: 93 227 17 77 new technologies, the aging of the e-mail: [email protected] population, patient requests for information, social change, and the collABoRAtoRS: global crisis. Mercè piazuelo i pont (Hospital clínic) Amèlia pérez González (Hospital clínic) main lineS of Miquel Sanz Moncosi (Hospital clínic) reSearcH Mª teresa Hospital Vidal (Hospital clínic) Mercè comes forastero (Hospital clínic) Internationally, research activity in felip Burgos Rincón (Hospital clínic) nursing is improving thanks to the Dolors Robles Antúnez (Hospital clínic) definition of priorities, the identifi- Montserrat Amigó tandin (Hospital clínic) cation of groups and the focusing luis González de paz (Gesclínic) of their research lines, increased funding, and integration of the results obtained in the clinical practice setting. Accordingly, an increase is being observed in the number of publications in international journals, documented in the Cumulative Index to Nursing and Allied Health Literature (CINAH) and the Medline database, affording credibility and acknowledgement to our research activities. This improved scientific production has been achieved through the competitive funding of projects and the development of research training programs on the part of the professional and government organizations, and the gener- alized application of anonymous and rigorous peer review of the results of the investigations made.

Research in nursing presents differential paradigmatic elements with respect to other types of research in the health sciences, such as its particular patient focus (rather than disease-based focus), and the study of physiological, psychological, so- ciocultural and/or spiritual aspects

313 TRANSveRSAL ReSeARCh gROUPS

Research in nursing

PUBLICATIONS

of the individual, with a view to im- We are aware of the enormous task proving healing. The effort to secure awaiting us. In this context, we are oRiGinAlS this unique approach has resulted in inspired by the brilliant trajectory i.f.: 33.91 the definition of priority research ar- of research in nursing in the United eas in nursing, which in this country States or Europe (United kingdom, 1 Nunez M, Lozano L, Nunez E, comprise the following: evaluation of Sweden, Finland, the Netherlands, Sastre S, DelVal JL, Suso S. Good the efficacy of nursing interventions; etc.) – countries where nursing has Quality of Life in Severely Obese the promotion of health and the been capable of attracting financial Total Knee Replacement Patients: A development of strategies designed support, gaining access to mentors, Case-Control Study. OBES SURG. to implicate patients in their own and consolidating its lines of re- 21:1203-1208. I.F.: 3.08. healing; healing based on evidence; search. Nursing in the Clinic Hospital the implementation and evaluation can lead the process of incorporating 2 Moize V, Deulofeu R, Torres F, of results in clinical practice; and research to clinical practice, based on DeOsaba JM, Vidal J. Nutritional measurement of the quality of nurs- a solid institutional reference and a Intake and Prevalence of Nutritional ing care. strongly-rooted scientific culture. The Deficiencies Prior to Surgery in a recent creation of the Nursing Re- Spanish Morbidly Obese Population. In Spain, research in nursing is still search Committee aims to visualize OBES SURG. 21:1382-1388. an emergent activity. Its consolida- and reinforce this activity. We already I.F.: 3.08. tion will be facilitated by the recent have competitive projects financed introduction of degree programs, by national and European agencies, 3 Compta Y, Ezquerra M, Munoz masters and doctorate courses and have ambitious plans for im- E, Tolosa E, Valldeoriola F, Rios J, specifically targeted at nursing, with provement that should result in an Camara A, Fernandez M, Buongiorno the participation of professionals increase in the number and relevance MT, Marti MJ. High cerebrospinal accredited for teaching in research. of our publications. In sum, our hos- tau levels are associated with the For the first time, nurses following a pital has the motivation and scientific rs242557 tau gene variant and low doctorate program will be able to ac- leadership needed to face the chal- cerebrospinal beta-amyloid in Par- cess extensive and rigorous training lenge of research in nursing. kinson disease. NEUROSCI LETT. in the scientific method, to ensure 487:169-173. I.F.: 2.06. the quality of their scientific production in the field of nursing care. Our 4 Valldeoriola F, Coronell C, Pont present challenge is application to C, Buongiorno MT, Camara A, Gaig the healthcare setting: nurses should C, Compta Y. Socio-demographic understand research as a driving and clinical factors influencing force in their professional develop- the adherence to treatment in ment and in the improvement of their Parkinson’s disease: the ADHESON care of patients and their families – study. EUR J NEUROL. 18:980-987. incorporating it into their daily clinical I.F.: 3.77. practice. 5 Nunez M, Fernandez-Sola J, Nunez E, Fernandez-Huerta JM, Godas-Sieso T, Gomez-Gil E. Health- related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up. CLIN RHEUMATOL. 30:381-389. I.F.: 1.69.

314 tRAnSVeRSAl ReSeARcH GRoupS ReSeARcH in nuRSinG

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 2009 10.27 6 1 1 6 Rosa AR, Reinares M, Amann Zabalegui A. Grup de recerca recon- 2010 22.63 9 3 3 B, Popovic D, Franco C, Comes M, egut com consolidat de Catalunya al 2011 33.91 9 5 2 Torrent C, Bonnin CM, Sole B, Valenti “Grup de Cures a la Gent Gran De- M, Salamero M, Kapczinski F, Vieta pendent”. Sponsored by: Agència de E. Six-month functional outcome of a Gestió d’Ajuts Universitaris i de Recer- bipolar disorder cohort in the context of ca (AGAUR), 2009 SGR 916. Duration: a specialized-care program. BIPOLAR 03/07/2009-31/12/2012. DISORD. 13:679-686. I.F.: 5.22. Rodriguez E. Disseny d’un instrument Zabalegui A. Estudio experimental d’avaluació de competencias per al 7 Vizcaya D, Mirabelli MC, Anto JM, sobre la eficacia de una intervención laboratorio de simulación d’infermeria. Orriols R, Burgos F, Arjona L, Zock JP. A innovadora de información, formación Sponsored by: Colegio Oficial de workforce-based study of occupational y apoyo social “INFOSA” a cuidadores Enfermería de Barcelona. Duration: exposures and asthma symptoms in principales de personas mayores de- 01/01/2011-31/12/2011. cleaning workers. OCCUP ENVIRON pendientes. Sponsored by: Instituto MED. 68:914-919. I.F.: 3.49. de Salud Carlos III (ISCIII), PI09/0111. Zabalegui A. Reflection. projecte Duration: 17/02/2010-31/12/2012. europeu en intervencions complexes 8 Guiral E, Mendez-Arancibia E, Soto d’infermeria. Sponsored by: European SM, Salvador P, Fabrega A, Gascon J, Comes M. Impacte d’un programa Science Foundation - European Union. Vila J. CTX-M-15-producing Enteroag- d’intervenció multidisciplinari sobre Duration: 01/01/2011-31/12/2014. gregative Escherichia coli as Cause of l’estil de vida en la millora del funcion- Travelers’ Diarrhea. EMERG INFECT ament psicosocial i la qualitat de vida DIS. 17:1950-1953. I.F.: 6.86. dels pacients bipolars d’inici precoç. Sponsored by: COIB, PR-5385-11. Du- 9 Sole M, Pitart C, Roca I, Fabrega A, ration: 01/01/2011-31/12/2011. Salvador P, Munoz L, Oliveira I, Gascon J, Marco F, Vila J. First Description of Nuñez M. Programa educatiu per a an Escherichia coli Strain Producing pacients amb artrosi de genoll i obe- NDM-1 Carbapenemase in Spain. ANTI- sitat tipus I i tipus II, un estudi aleato- MICROB AGENTS CH. 55:4402-4404. ritzat i d’aplicació pràctica. Sponsored I.F.: 4.67. by: COIB, PR- 5383-11. Duration: 01/01/2011-31/12/2011.

GRAntS foR ReSeARcH Ocaña T. Avaluació de l’impacte de la in pRoGReSS realització de reunions informatives a famílies amb síndrome de Lynch en la Burgos F. Estudio Europeo de Salud prevenció del càncer colorectal. Spon- Respiratoria: Seguimiento de la po- sored by: COIB, PR- 5382-11. Dura- blación española a los 18 años de su tion: 01/01/2011-31/12/2011. inicio. Sponsored by: FIS, 2009 ECRHS III. Duration: 01/01/2009-31/12/2011. Moreno C. Empowerment del paciente a través de la información-educació Zabalegui A. Improving health services dels pacients programats a interven- for European citizens with dementia: ción quirúrgicas de prótesis de maluc Development of best practice strate- o de genoll. Sponsored by: Colegio gies for the transition from ambulatory Oficial de Enfermería de Barcelona. to institutional long-trem care facilities Duration: 01/01/2010-31/12/2013. (RightTimePlaceCare). Sponsored by: European Commission, 2421153. Dura- tion: 01/01/2010-30/06/2013.

315

Team involved in: Transversal research groups

Clinical pharmacology

gROUP MeMBeRS StrateGic oBjectiveS

The team carries out clinical research support activities with different De- teAM leADeR partments: Xavier carné (Hospital clínic) 1. The clinical trials Agency, to- tel.: 93 227 91 68 gether with the Department of fax: 93 227 98 77 Pharmacy, provides support of all e-mail: [email protected] technical and administrative aspects related to clinical trials carried out in xxxxxx iDiBApS MeMBeRS: the Clinic Hospital - IDIBAPS. The Joan Albert Arnaiz (Hospital clínic) Agency serves as a single window Gonzalo calvo (Hospital clínic) for sponsors and investigators, and José Ríos (iDiBApS) as secretary to the CREC of the Clin- ferran torres (iDiBApS) ic Hospital (Clinical Research Ethics Committee). collABoRAtoRS: Begoña Gómez (Hospital clínic) 2. The ctU (Clinical Trials Unit), Amalia lafuente (uB) provides support for the conduction neus Riba (Hospital clínic) of clinical trials on the part of the Josep Ribas (Hospital clínic) investigators of the institution that Ana cruceta (fundació clínic) act as sponsors, in aspects related Judit pich (fundació clínic) to study design, implementation and Sara Varea (fundació clínic) monitorization. núria Sanz (fundació clínic) carles codina (Hospital clínic) 3. The Statistical and Methodologi- cal Support Unit (USEM) offers counselling in trial data analysis and planning.

4. The Pharmacoepidemiology and therapeutic Evaluation Unit, offers support of activities in pharmacovigilance, epidemiology and the evaluation of drugs in our setting.

316 tRAnSVeRSAl ReSeARcH GRoupS clinicAl pHARMAcoloGy

PUBLICATIONS original publications from 2009 to 2011

Year IF Total Q 1 Q 2 oRiGinAlS 2009 41.47 15 7 6 78.15 23 9 8 5. The team collaborates with Dr. i.f.: 76.89 2010 Amàlia Lafuente (UB) of the Phar- 2011 76.89 29 10 4 macology Unit of the University 1 Canovas M, Torres F, Domenech of Barcelona, who conducts studies G, Cebrecos J, Pelagio P, Manriquez relating genetics to drug substance M, Martinez G, Arcabell M, Cabre activity and response. F. Bioequivalence evaluation of two dosage forms of olanzapine 10 mg of quetiapine fumarate in healthy 6. Lastly, the team participates in the formulations in healthy volunteers. volunteers. ARZNEIMITTEL-FORSCH. trial follow-up committees known ARZNEIMITTEL-FORSCH. 61:75-79. 61:489-493. I.F.: 0.63. as DSMB (Data and Safety I.F.: 0.63. Monitoring Boards), in charge of 7 Matt P, VanZwieten-Boot B, external supervision of the course 2 Ohmann C, Kuchinke W, CalvoRojas G, TerHofstede H, Garcia- of the clinical trials, and of deciding Canham S, Lauritsen J, Salas N, Carbonero R, Camarero J, Abadie E, the pertinence of their continuity Schade-Brittinger C, Wittenberg M, Pignatti F. The European Medicines over time. Mcpherson G, Mccourt J, Gueyffier Agency review of Tegafur/Gimeracil/ F, Lorimer A, Torres F. Standard Oteracil (Teysuno™) for the treatment main lineS of requirements for GCP-compliant data of advanced gastric cancer when given reSearcH management in multinational clinical in combination with cisplatin: summary trials. TRIALS. 12:-. I.F.: 2.08. of the Scientific Assessment of the • Ethics in clinical research Committee for medicinal products for • Clinical trials, design and methodo- 3 Lopez CC, Marti T, Catala V, human use. ONCOLOGIST. 16:1451- logy. Torres F, Mateu S, Castan JB, Balcells 1457. I.F.: 5.83. • Statistical support of clinical rese- RT. Effects of rapamycin on angio- arch. myolipomas in patients with tuberous 8 Description of sexual assaults • Pharmacovigilance and pharmacoepi- sclerosis. NEFROLOGIA. 31:292-298. treated in the emergency department demiology. I.F.: 0.74. of a referral hospital. GAC SANIT. • Pharmacogenetics and pharmacoge- 25:166-169. I.F.: 1.11. nomics. 4 Domingo P, Cabeza MC, Pruvost A, Torres F, Salazar J, Gutierrez MD, 9 Obach V, Oleaga L, Urra X, Macho Mateo MG, Fontanet A, Fernandez J, Amaro S, Capurro S, Gomez-Choco I, Domingo JC, Villarroya F, Vidal F, M, SanRoman L, Cervera A, Blasco Baiget M. Association of Thymidylate J, Vargas M, Torres F, Chamorro A. Synthase Gene Polymorphisms with Multimodal CT-assisted thrombolysis Stavudine Triphosphate Intracellular in patients with acute stroke: a cohort Levels and Lipodystrophy. ANTIMI- study. STROKE. 42:1129-1131. CROB AGENTS CH. 55:1428-1435. I.F.: 5.76. I.F.: 4.67. 10 Ribera T, Monreal L, Armengou 5 Masclans JR, Roca O, Munoz X, L, Rios J, Prades M. Synovial fluid D- Pallisa E, Torres F, Rello J, Morell F. dimer concentration in foals with septic Quality of Life, Pulmonary Function, joint disease. J VET INTERN MED. and Tomographic Scan Abnormalities 25:1113-1117. I.F.: 2.28. After ARDS. CHEST. 139:1340-1346. I.F.: 6.52. 11 Leon A, Caceres C, Fernandez E, Chausa P, Martin M, Codina C, 6 Canovas M, Torres F, Domenech Rousaud A, Blanch J, Mallolas J, G, Cebrecos J, Pelagio P, Martinez Martinez E, Blanco JL, Laguno M, G, Polonio F, Cabre F. Bioequivalence Larrousse M, Milinkovic A, Zamora L, evaluation of two oral formulations Canal N, Miro JM, Gatell JM, Gomez

317 TRANSveRSAL ReSeARCh gROUPS

Clinical pharmacology

EJ, Garcia F. A New Multidisciplinary JM, Plana M, Esteban M. Safety 22 Compta Y, Ezquerra M, Munoz Home Care Telemedicine System and immunogenicity of a modified E, Tolosa E, Valldeoriola F, Rios J, to Monitor Stable Chronic Human pox vector-based HIV/AIDS vaccine Camara A, Fernandez M, Buongiorno Immunodeficiency Virus-Infected candidate expressing Env, Gag, Pot MT, Marti MJ. High cerebrospinal Patients: A Randomized Study. PLOS and Nef proteins of HIV-1 subtype B tau levels are associated with the ONE. 6:-. I.F.: 4.41. (MVA-B) in healthy HIV-1-uninfected rs242557 tau gene variant and low volunteers: A phase I clinical trial cerebrospinal beta-amyloid in Par- 12 Tomas X, Bori G, Garcia S, (RISVAC02). VACCINE. 29:8309- kinson disease. NEUROSCI LETT. Garcia-Diez AI, Pomes J, Soriano A, 8316. I.F.: 3.57. 487:169-173. I.F.: 2.06. Rios J, Almela M, Mensa J, Gallart X, Martinez JC, Riba J. Accuracy of 17 Morina D, Puig P, Rios J, Vilella 23 Botta-Orfila T, Ezquerra M, CT-guided joint aspiration in patients A, Trilla A. A statistical model for Rios J, Fernandez-Santiago R, with suspected infection status post- hospital admissions caused by seasonal Cervantes S, Samaranch L, Pastor total hip arthroplasty. SKELETAL RA- diseases. STAT MED. 30:3125-3136. P, Marti MJ, Munoz E, Valldeoriola DIOL. 40:57-64. I.F.: 1.39. I.F.: 2.33. F, Aguilar M, Calopa M, Hernandez- Vara J, Tolosa E. Lack of interaction 13 Carcelero E, Tuset M, Martin 18 Guitian PP, Xarau SN, of SNCA and MAPT genotypes in M, DeLazzari E, Codina C, Miro J, Guillermo JR, Tejero IN, Viladot JRA. Parkinson’s disease. EUR J NEUROL. Gatell JM. Evaluation of antiretroviral- Evaluation of acute poisonings due 18:E32-E32. I.F.: 3.77. related errors and interventions by to chemical agents treated in an the clinical pharmacist in hospitalized Emergency Department. MED CLIN- 24 Mas S, Gasso P, Alvarez S, HIV-infected patients. HIV MED. BARCELONA. 136:149-152. I.F.: 1.41. Ortiz J, Sotoca JM, Francino A, Carne 12:494-499. I.F.: 3.58. X, Lafuente A. Pharmacogenetic 19 Tamborero D, Vidal B, Tolosana predictors of angiotensin-converting 14 Garcia AI, Milinkovic A, Tomas JM, Sitges M, Berruezo A, Silva E, enzyme inhibitor-induced cough: X, Rios J, Perez I, Vidal-Sicart S, Castel M, Matas M, Arbelo E, Rios the role of ACE, ABO, and BDKRB2 Pomes J, DelAmo M, Mallolas J. J, Villacastin J, Brugada J, Mont genes. PHARMACOGENET GENOM. MRI signal changes of the bone L. Electrocardiographic versus 21:531-538. I.F.: 3.87. marrow in HIV-infected patients with Echocardiographic Optimization of lipodystrophy: correlation with clinical the Interventricular Pacing Delay 25 Salazar F, Donate M, Boget T, parameters. SKELETAL RADIOL. in Patients Undergoing Cardiac Bogdanovich A, Basora M, Torres 40:1295-1301. I.F.: 1.39. Resynchronization Therapy. J CAR- F, Fabregas N. Intraoperative DIOVASC ELECTR. 22:1129-1134. warming and post-operative 15 Font-Vizcarra L, Lozano L, Rios I.F.: 3.29. cognitive dysfunction after total knee J, Forga MT, Soriano A. Preoperative replacement. ACTA ANAESTH SCAND. nutritional status and post-operative 20 Alonso I, Fuste V, DelPino M, 55:216-222. I.F.: 2.20. infection in total knee replacements: Castillo P, Torne A, Fuste P, Rios J, A prospective study of 213 patients. Pahisa J, Balasch J, Ordi J. Does 26 Sanz G, Fuster V, Guzman L, INT J ARTIF ORGANS. 34:876-881. human papillomavirus infection Guglietta A, Arnaiz JA, Martinez F, I.F.: 1.50. imply a different prognosis in vulvar Sarria A, Roncaglioni MC, Taubert K. squamous cell carcinoma?. GYNE- The Fixed-dose Combination Drug 16 Garcia F, DeQuiros JCLB, COL ONCOL. 122:509-514. I.F.: 3.76. for Secondary Cardiovascular Pre- Gomez CE, Perdiguero B, Najera vention project: Improving equitable JL, Jimenez V, Garcia-Arriaza J, 21 Moize V, Deulofeu R, Torres access and adherence to secondary Guardo AC, Perez I, Diaz-Brito V, F, DeOsaba JM, Vidal J. Nutritional cardiovascular prevention with a fixed- Conde MS, Gonzalez N, Alvarez Intake and Prevalence of Nutritional dose combination drug. Study design A, Alcami J, Jimenez JL, Pich J, Deficiencies Prior to Surgery in a and objectives. AM HEART J. 162:-. Arnaiz JA, Maleno MJ, Leon A, Spanish Morbidly Obese Population. I.F.: 5.05. Munoz-Fernandez MA, Liljestrom OBES SURG. 21:1382-1388. P, Weber J, Pantaleo G, Gatell I.F.: 3.08.

318 tRAnSVeRSAl ReSeARcH GRoupS clinicAl pHARMAcoloGy

eDitoRiAlS Arnaiz JA. Fixed Dose Combination i.f.: 15.62 drugs for Secondary Cardiovascular Prevention. Sponsored by: CNIC- 1 Dal-Re R, Moher D, Gluud C, Treweek Centro Nacional de Investigaciones S, Demotes-Mainard J, Carne X. Disclo- Cardiovasculares Carlos III, 241559. sure of Investigators’ Recruitment Perfor- Duration: 01/07/2010-30/06/2013. mance in Multicenter Clinical Trials: A Further Step for Research Transpar- Calvo G. Estudio de cohortes para ency. PLOS MED. 8:-. I.F.: 15.62. evaluar la seguridad y la efectividad del programa de vacunación frente a la gripe A (H1N1) en el área de MulticentRicS cobertura sanitaria de un hospital i.f.: 15.74 de tercer nivel. Sponsored by: Min- isterio de Sanidad, Politica Social 1 Petoumenos K, Worm S, Reiss P, e Igualdad, TRA-063. Duration: DeWit S, Monforte AD, Sabin C, Friis- 01/01/2010-31/12/2011. Moller N, Weber R, Mercie P, Pradier C, El-Sadr W, Kirk O, Lundgren J, Law MG. Calvo G. Estudio prospectivo multi- Rates of cardiovascular disease following céntrico de la incidencia, relevancia smoking cessation in patients with HIV clínica, factores de riesgo y preven- infection: results from the D:A:D study. tibilidad del ingreso hospitalario por HIV MED. 12:412-421. I.F.: 3.58. fracaso renal agudo asociado al uso de fármacos inhibidores del sistema 2 Kowalska JD, Friis-Moller N, Kirk renina-angiotensina. Sponsored O, Bannister W, Mocroft A, Sabin C, by: Instituto de Salud Carlos III, Reiss P, Gill J, Lewden C, Phillips A, EC08/00173. Duration: 01/01/2009- Monforte AD, Law M, Sterne J, DeWit 30/12/2011. S, Lundgren JD. The Coding Causes of Death in HIV (CoDe) Project Initial Calvo G. Evaluación de la utilidad clínica Results and Evaluation of Methodology. de un protocolo estandarizado de dis- EPIDEMIOLOGY. 22:516-523. I.F.: 5.87. minución de dosis en pacientes con espondilartritis axiales (EA) en remisión 3 DataCollectionOnAdverseEvents clínica persistente en tratamiento con OfAnti-HivDrugs(d:a:d) STUDY. The terapia anti-TNFalfa. Sponsored by: In- impact of fasting on the interpreta- stituto de Salud Carlos III (ISCIII) ,Inves- tion of triglyceride levels for predicting tigación independiente FIS. Duration: myocardial infarction risk in HIV-positive 01/01/2011-31/12/2012. individuals: the D:A:D study. J INFECT DIS. 204:521-525. I.F.: 6.29. DoctoRAl tHeSeS

GRAntS foR ReSeARcH Carne X. Evaluation of the efficacy in pRoGReSS of acupuncture in the prevention of migraine attacks. PhD student: Jerusa Carne X. European Clinical Research Alecrim Andrade. Infrastructures Network and biotherapy facilities: Preparation Phase for the Infrastructure: INSERM. Sponsored by: IEuropean Commission, FP7. Duration: 01/03/2008-28/02/2011.

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a M Àlvar Agustí ...... 135 Guadalupe Mengod ...... 198 Jordi Alberch ...... 221 Cristóbal Mezquita ...... 268 Antonio Alcaraz ...... 138 Montserrat Milà ...... 270 Vicente Arroyo ...... 156 Oscar Miró ...... 90 Rafael Molina ...... 256 b Oriol Bachs ...... 304 P Juan Balasch ...... 142 Julián Panés ...... 168 Joan Albert Barberà ...... 126 Albert Parés ...... 172 Miguel Bernardo ...... 225 César Picado ...... 130 Jaume Bosch ...... 163 Anna M. Planas ...... 203 Josep Brugada ...... 103 Francesca Pons ...... 265 Jordi Bruix ...... 160 Susana Puig...... 273

c r Josep Mª Campistol ...... 109 Antonia Ribes ...... 188 Elías Campo ...... 258 Antoni Rimola ...... 178 Xavier Carné ...... 316 Emili Ros ...... 113 Antoni Castells ...... 182 Francisco Cervantes ...... 282 s Ricard Cervera ...... 60 Manel Sabaté ...... 98 Daniel Closa ...... 94 Maria Victoria Sánchez ...... 241 Dolors Colomer ...... 290 Raimon Sanmartí ...... 58 Antoni Sisó ...... 310 E Ginés Escolar ...... 294 t Eduardo Tolosa ...... 206 F Antoni Torres ...... 120 Ramon Farré ...... 117 Ramon Trullàs ...... 251 José Carlos Fernández-Checa .. 175 Jorge Ferrer ...... 190 U Joaquim Forés ...... 84 Álvaro Urbano-Ispizúa ...... 277 Xavier Forns ...... 152 Álvaro Urbano Márquez ...... 216

G V Pere Gascón ...... 298 Josep Valls ...... 212 Josep M. Gatell ...... 67 Josep Vidal ...... 192 Eduard Gratacós ...... 146 Francesc Graus ...... 245 y Núria Guañabens ...... 172 Jordi Yagüe ...... 88

j Z Carme Junqué ...... 237 Adelaida Zabalegui ...... 313

L Francisco Lozano ...... 80

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