Activity Report

Edita: IDIVAL Depósito Legal: SA 525-2015

Valdecilla Biomedical Research Institute Avda. Cardenal Herrera Oria s/n 39011 Santander – Spain 05

Contents

07 Prologue 13 Valdecilla, IDIVAL 17 Organisational Structure 25 Researcher Support Services. 41 Training 55 Some milestones 2016 61 IDIVAL R&D Activity 93 Research Areas 95 Transplantation 119 Neuroscience 139 Cancer 173 Cross-Disciplinary 181 Infection and Immunity 207 Metabolism

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Prologue

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healthcare areas, whether in hospitals or in primary care, and researchers in biomedical and technological fields and other disciplines in our Autonomous Community, can and must be present in the projects designed to improve The Marqués de Valdecilla Research Institute (IDIVAL) healthcare in Cantabria. We believe that IDIVAL, like is established as a key actor in the generation of applied Valdecilla, must be both integrated and open, and have knowledge in our region. Its core engine, the Marqués the best among its personnel, in order to maintain a top- de Valdecilla University Hospital, one of Spain’s leading level healthcare system and continue to earn the support hospitals, in partnership with the University of Cantabria, of all Cantabria’s society. promotes new solutions for patients’ health problems thanks to the research and innovation of its excellent Similarly, we must continue working to ensure that the professionals. It is for this reason that we have the public-private partnership model, based on transparency, optimal elements to continue leading in certain fields of provides greater benefits. We must see the annual knowledge: expert personnel, next-generation technology expenditure of the healthcare sector in Cantabria as and magnificent facilities, which we are committed to an investment, an opportunity, and make the most of making the best possible use of. our partnerships with business, understanding that we can add value to its products, acquiring them, but Every day, the world’s best healthcare centres generate also evaluating, improving and designing them. The wealth and solutions for patients through research and experience and expertise of our professionals must be innovation. Spain as a whole hopes to move forward given the maximum value. in this value model based on knowledge, a value that includes the application of the generated knowledge and Talent is one of the main keys to success. Training a socioeconomic benefit. Cantabria is no exception, and new generations, facilitating their professional growth, has some elements that make it possible and almost especially in research and innovation, and attracting necessary: its size, an important Hospital and University, expert professionals to help this ongoing regeneration and a high level of scientific expertise. Knowledge in process, are essential goals for ensuring that the high the healthcare field generates wealth in itself, as IDIVAL quality healthcare system we want continues to be demonstrates, insofar as it creates jobs and improves one of the distinguishing features of our Autonomous the approach to health problems. However, we still have Community. To do this, we must create mechanisms to a long way to go. The modern globalised world gives us overcome barriers, whether geographical, administrative, unique opportunities that stem from interdisciplinary, or sometimes cultural, requiring the collaboration of multinational partnerships, and taking advantage of them patients, healthcare professionals, managers, and society is a key part of developing projects with real impact. in general.

IDIVAL, as a Healthcare Research Institute accredited by the Carlos III Health Institute, encouraging translational research and innovation as a foundation for improving patient care, must have an international outlook. This cross-border vision must coexist with a integrating vision that lets the different areas that could add value María Luisa Real González to healthcare research in Cantabria contribute to IDIVAL. Minister of Health of the Government of Cantabria Patients, nurses, doctors, and personnel from other President of the Board of IDIVAL

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necessary tool for our researchers, and to restore our library to the place its history deserves. Finally, I would like to welcome the research groups who passed a tough he Marqués de Valdecilla Research Institute (IDIVAL) evaluation and have now joined IDIVAL. We all hope is responsible for promoting and managing our they settle in quickly. As an example of our commitment biomedical research. IDIVAL has been recognised by to inclusiveness, let me highlight the research groups the Carlos III Health Institute as a benchmark centre for in Nursing and Primary Care. In a small Autonomous research in Spain. Its main distinguishing features include Community like ours, it is only by working together the search for excellence and innovation, always focused (hospitals, primary care, university and private enterprise) on improving the health of our citizens. that we can continue moving forwards to attract resources and scientific talent. 2016 was a productive year for IDIVAL. Among its achievements, in 2016 IDIVAL produced nearly 500 indexed publications, with a very high average impact factor (3.89), and 30 articles published in journals with an impact factor higher than 10. It continued to attract external resources, with 80 competitive research projects and 175 open clinical trials. This is an important point, because it shows we are competitive and contributes to our sustainability, for example enabling us to increase the number of post-MIR contracts and grants to research groups. A significant figure was the record number of competitive research projects granted by the Carlos III Health Institute in the 2016 campaign. However, in an increasingly competitive environment, we must be aware that IDIVAL can only be sustainable and continue to expand if we consolidate repeated access to European projects. This must be one of our main challenges in the coming years.

To conclude, I will comment on some of the initiatives developed specifically in IDIVAL in 2016 that we are particularly proud of. We launched the COLABORA campaign, designed to attract altruistic, transparent donations for research, something our region was clearly lacking. The “Santander Biomedical Lectures” were a success in lecturers and attendees, and I am sure they Julio Pascual have contributed to creating a vocation for research Managing Director of the Marqués de Valdecilla University among some of the many young people who enjoyed Hospital, member of the Board of Governors, and Chairman of them. During 2016 the new website of the Marquesa the Executive Committee of the IDIVAL Board of Governors de Pelayo library was finalised. An extraordinary and

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Valdecilla

The innovative spirit of the Valdecilla Foundation and evolved following the mark is particularly evident in IDIVAL, model of health research institutes conceived with the goal of promoting and in line with the points set out R&D in the field of biomedical in Royal Decree 339/2004 of 27 Valdecilla is the unifying mark sciences at the Marqués de February. Therefore, the constitution that Ramón Pelayo de la Torriente, Valdecilla University Hospital with of IDIVAL implies strong support Marquis de Valdecilla left on the the contribution of the University of its founding institutions, the institutions that came to be during of Cantabria, placing it at a level of University of Cantabria and the his marquessate: the Marqués de national and international excellence. Government of Cantabria for health Valdecilla University Hospital, the research in the Valdecilla setting. de la Torriente, Marquis de Valdecilla IDIVAL was conceived at the end of left on the institutions that came to 2013 through an agreement between Taking over from IFIMAV, IDIVAL was be during his marquessate: the Government of Cantabria and the launched in 2014 to harmoniously the Marqués de Valdecilla University University of Cantabria, as the heir of integrate basic, clinical and public Hospital, the Marqués de Valdecilla the Marqués de Valdecilla Training health research, encouraging Research Institute (IDIVAL), and Research Institute (IFIMAV). translational research and promoting and the Valdecilla Virtual Hospital, a better transfer of the which today maintains the innovative, IFIMAV was established in 2002 scientific progress obtained in cross-disciplinary and philanthropic as a research management unit addressing the most prevalent health spirit with which it was created. within the Marqués de Valdecilla problems.

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IDIVAL

are also contributing to scientific IDIVAL seeks to improve translational production. research and promote progress in Cantabria. Its goals include IDIVAL promotes and manages the IDIVAL pursues excellence. In 2016, the development of knowledge, biomedical research of the Marqués IDIVAL’s researchers published high- technological progress, and de Valdecilla University Hospital impact works in collaboration with innovation in healthcare. IDIVAL’s and the University of Cantabria. some of the world’s best research current challenge is to maximise the It is financed by the Government groups in various biomedical application of research results to of Cantabria and the University of disciplines. Our impact factor was improve healthcare. Cantabria. over 1915 points in 2016. We have accumulated over 100,000 citations In partnership with prestigious IDIVAL encourages the development in international literature. institutions such as the Botín of knowledge. IDIVAL promotes Foundation, IDIVAL has launched an activities for the development of IDIVAL supports researchers. ambitious innovation programme. excellent scientific production, and In 2016, we launched several has established 15 high-impact programmes to support innovation IDIVAL is a leading institution. research groups in six areas of and research. IDIVAL issued grants IDIVAL was recognised by the Carlos research: Cancer, Neuroscience, for healthcare research worth over a III Health Institute in 2015 as one Transplants, Infection, Metabolism, million euros in 2016. of Spain’s accredited healthcare and Transversal. Another 14 groups IDIVAL is committed to society. research institutes.

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Organisational Structure BOARD January 2014), by a Board, an DELEGATED COMMITTEE Executive Committee,a Management Director, a Scientific Director and its MANAGEMENT SCIENTIFIC own consulting bodies: Internal DIRECTOR DIRECTOR Scientific Council and External Governance Scientific Council, appointed by the CENTRAL UNIT RESEARCH and Advisory Board. SUPPORT AREAS External Scientific Bodies It is also advised by the Clinical Council Research Ethics Committee of Cantabria and the Bioethics Clinical Research Committee at the University of Ethic Committee IDIVAL is governed in accordance Cantabria in compliance with the Bioethics with its by-laws in the Official Gazette requirements of clinical research and Committee of Cantabria (BOC No. 7 of 13 animal research, respectively Internal Scientific Council

Senior Management Operations Consulting bodies Organisational Structure Governance and Advisory Bodies

The board of IDIVAL

In accordance with the IDIVAL by- laws published in the Official Gazette of Cantabria of 13 January 2014, the board is the highest governing body of IDIVAL and has the highest level of representation. Among its functions are approving the budget, the action plan and the annual report of the Institute as well as appointing the directors and members of advisory bodies. In 2015, the Board was made up of the following individuals:

President: D. Julio Pascual Gómez. Marqués de Valdecilla University Managing Director of the Marqués de Hospital. Tenured Professor in the Valdecilla University Hospital. Department of Molecular Biology. Dª. María Luisa Real González. University of Cantabria Minister of Health and Social Services D. Piero Crespo Baraja. of the Government of Cantabria. Profesor del CSIC. Director del Instituto D. José Antonio Amado Señarís. de Biomedicina y Biotecnología de Section Head of the Endocrinology Cantabria. Department. Professor in the Department of Medicine and Vice-president: D. Manuel Gómez Fleitas. Psychiatry. University of Cantabria. Department Head. General Surgery Department. Marqués de Valdecilla D. Ángel Pazos Carro. University Hospital. Professor in the Dean of the University of Cantabria. Department of Medicine and Surgery. Secretary, non-board: University of Cantabria.

D. Pedro José Prada Gómez. D. Joaquín Cayón de las Cuevas. Department Head. Radiation Oncology Head of the Legal Counsel Office of Department. Marqués de Valdecilla the Ministry of Health Chairs: University Hospital. D. José Antonio Riancho Moral. D. Javier León Serrano. Section Head. Internal Medicine Assistant Dean of Research and Department. Marqués de Valdecilla Knowledge Transfer. University of University Hospital.Professor in the Cantabria. Department of Medicine and Dª. María de la Cruz Reguera Psychiatry. University of Cantabria Andrés. D. Javier Crespo García. General Secretary. Ministry of Health. Professor in the Department of Molecular Biology. University of D. María Antonia Mora González. Cantabria Director of the Institute of General Director of Planning and The IDIVAL Board met twice in 2016. Biomedicine and Biotechnology of Healthcare Ministry of Health. Cantabria. At these meetings, the audited accounts and annual report for 2016 D. Julián Pérez Gil. D. Luis Martínez Martínez. Manager director of the Cantabrian and action plans and budget for 2017 Head of the Microbiology Department. Health Service. were approved. 19

Chairs: Department. Marqués de Valdecilla Delegated University Hospital. Representative of the University of Cantabria. Professor D. Javier León Serrano. in the Department of Medicine and Committee Assistant Dean of Investigation and Psychiatry. University of Cantabria. Knowledge Transfer. University of Cantabria Representative of the University of Cantabria. D. Luis Martínez Martínez. Head of the Microbiology Department. Dª. Mª de la Cruz Reguera Andrés. Marqués de Valdecilla University General Secretary. Ministry of Health. Hospital. Tenured Professor in the President: Department of Molecular Biology. D. María Antonia Mora González. University of Cantabria Representative General Director of Planning and of the Healthcare Administration. D. Julio Pascual Gómez. Healthcare Ministry of Health. President according to the by-laws as Managing Director of the Marqués de D. José Antonio Riancho Moral. Valdecilla University Hospital. Section Head. Internal Medicine Organisational Structure Governance and Advisory Bodies

IDIVAL’s senior management body Marqués de Valdecilla University consists of a Scientific Director and Hospital (he resigned as scientific Governance a Managing Director, both appointed director in February 2017). by the Board of Governors.

Scientific Director: Managing Director: The Scientific Director is the senior The Managing Director acts as the representative and spokesperson for representative and spokesperson the Foundation on scientific matters. for the Foundation in its dealings He directs, plans and leads the Foundation’s scientific policy, draws with other institutions in relation to up the scientific plan for the Institute, management activities, and manages and coordinates its execution. The the Institute’s internal organisation scientific director of IDIVAL in 2016 and research infrastructure. The was Miguel Angel Piris, Head of the Managing Director of IDIVAL in 2016 Pathological Anatomy Department, was Galo Peralta Fernández. 21

President: Miguel López-Botet Arbona. Consejo científico Professor of Immunology, Pompeu Ángel Carracedo Álvarez. Fabra University. externo Professor of Legal Medicine. University of Santiago de Compostela. Josep M. Grinyó. Senior Clinic. University of Bellvitge. University of Barcelona. The External Scientific Council contributes as a scientific advisor in Juan Bernal Carrasco. achieving the scientific excellence Professor of Research of the Superior pursued by IDIVAL. The External Council of Scientific Researchers Scientific Council offers opinions (CSIC), Director of the Department at the request of the Board or the Chairs: of Endocrine and Nervous System Directorate of IDIVAL and advises Pathophysiology. Alberto Sols Institute on the evaluation of the Institute’s of Biomedical Research. activity. Ana María Zubiaga Elordieta. Professor of Genetics at the University Miguel Delgado Rodríguez. The current Council was appointed of Basque Country, Faculty of Science Professor of Preventative Medicine and in 2009 as the advising body of the and Technology. Department Head of Public Health. University of Jaén. now defunct IFIMAV. Since then, Genomics of the UPV/EHU. some changes to its roster have Rafael Cantón Moreno. been made. The appointment of Francesc Graus Ribas. Head of the Microbiology Department its members was endorsed by the Head of the Neurology Department. of the Ramón y Cajal Hospital. IDIVAL Board in its meeting on 25 Hospital Clinic of Barcelona. University Associate Professor of the Department February 2014, through a proposal of Barcelona. IDIBAPS. of Microbiology, Faculty of Pharmacy. from the management at IDIVAL. Complutense University Madrid. Francisco Mora Teruel. It is made up of the following Professor of Human Physiology in the Xosé Ramón Bustelo. individuals: Faculty of Medicine at the Complutense Director of the Genomics and University of Madrid. Professor of Proteomics Unit. Centre of Cancer Molecular Physiology and Biophysics Investigation. CSIC-University of in the Faculty of Medicine at the Salamanca. University of Iowa. José Carlos Flórez. Jordi Vila Estapé. Chief, Diabetes Unit. Investigator, Head of the Bacteriology Department. Center for Genomic Medicine; Hospital Clinic of Barcelona. Professor Massachusetts General Hospital. of Microbiology. Autonomous Associate Professor; Harvard Medical University of Barcelona. CRESIB. School. Institute Member; Broad Institute. Organisational Structure Governance and Advisory Bodies

Internal Scientific Council

EL Consejo Científico Interno está presidido por el Director Científico de IDIVAL y está integrado por investigadores nombrados por el Patronato. El Consejo Científico Interno de IDIVAL ha sido nombrado, a propuesta del Director Científico, por el Patronato en reunión de 25 de Febrero de 2014.

Su composición en 2016 ha sido la siguiente:

President: de Valdecilla University Hospital. María Amor Hurlé González. Universitario Marqués de Valdecilla. Representative of the University of Miguel Ángel Piris. Cantabria. Professor of Pharmacology. Scientific Director of IDIVAL. Head of Javier Llorca Díaz. University of Cantabria. the Pathological Anatomy Department. Coordinator of the Cross-Disciplinary Marqués de Valdecilla University Area. Professor of Preventative Hospital. (He ceases in February 2017). Javier Crespo García. Medicine and Public Health. Head of the Iidestive Disease Service. University of Cantabria. Jefe del Servicio de Digestivo. Professor of the Department of Medicine and María Carmen Fariñas Álvarez. Psychiatry. University of Cantabria. Chairs: Coordinator of the Infectious Diseases and Immune System Area. Head of the Infectious Diseases Service. Marqués de Valdecilla University Marcos López Hoyos. Hospital. Tenured Professor of the Coordinator of the Organ and Tissue Department of Molecular Biology. The Internal Scientific Council of Transplant and New Therapies Area. University of Cantabria. IDIVAL met in 2016 on 10 occasions, Head of the Immunology Department. and among other aspects it has Marqués de Valdecilla University monitored the Strategic Plan 2011- Hospital. Professor of the Department José Antonio Riancho Moral. Coordinator of the Metabolism, 2016, participated in the design of of Medicine and Psychiatry. University the new Strategic Plan 2017-2020, Diseases of Ageing and Lifestyle of Cantabria. revised the program of grants of Habits Area. Section Head. Internal IDIVAL , The annual report and Medicine Department. Marqués the projects presented to the Benedicto Crespo Facorro. de Valdecilla University Hospital. Convocation of the Strategic Action Coordinator of the Neuroscience Area. Professor of the Department of in Health. Section Head. Psychiatry Department. Medicine and Psychiatry. University Marqués de Valdecilla University of Cantabria. Hospital. Professor of the Department The IDIVAL Board of Trustees has of Medicine and Psychiatry. University approved the incorporation of two Miguel Ángel Lafarga of Cantabria. new members, Dr. Javier Crespo Coscojuela. García, Fernando Rivera Herrero, Representative of the University of and the renewal of the Coordinators Fernando Rivera Herrero. Cantabria. Professor of Anatomy of the Transplant and Infection and Coordinator of the Cancer Area. Head and Cellular Biology. University of Immunity Areas to IDIVAL’s Internal of the Oncology Service. Marqués Cantabria. Scientific Council. 23 Estructura Organizativa Órganos de Gobierno y Asesoramiento 25

Support for CENTRAL SUPPORT researchers UNIT

PROJECTS TRAINING CLINICAL TECHNOLOGICAL INNOVATION AREA AREA TRIALS SERVICES AREA

Valdecilla, and in a broader sense, the entire biomedical environment COORDINATION Regional of Cantabria, is able to develop its funds work with elements to support the Biobank National research that unites IDIVAL’s Central funds Support Research Unit. This Unit is Microscopy organised into six areas: International funds Agencia Cytometry Projects Area,Training and TTO Methodological Support Area, Private Library Unidad de funds ensayos Sequencing Clinical Trial Area, Technological Innovation Support Area, Innovation Area and Lab. support unit General Services Area. Neuroimaging

GENERAL SERVICES

COORDINATION Support for researchers Central Support Unit

IDIVAL Building

IDIVAL has its own facilities, located within the physical setting of the Marqués de Valdecilla University Hospital. The IDIVAL building measures 3,000 m2. Located inside the building are most services of the Central Support Research Unit, as well as laboratory spaces for IDIVAL the management of its patents groups and meeting rooms. In 2015 Projects and business creation. It carries the laboratory area was extended to out actions for the promotion of house the Neuroimaging Laboratory. Area innovative culture, research and

evaluation of technological solutions, preparation and drafting of R&D The Projects Area at IDIVAL projects and the search for funding, brings together the resources as well as all activities needed to needed to manage the grants ensure that the R&D results from promoted by IDIVAL itself as well IDIVAL research groups and General as the application, execution and researchers from the Cantabria justification of both public and private Health Services reach society Services Area funds at the disposal of the IDIVAL through public-private partnerships. research groups.

The General Services Area of IDIVAL brings together the resources needed Technology Transfer Office: for the cross-cutting management Technicians and support of the other areas at Beatriz García González. (IDIVAL) Patricia Zorrilla de la Fuente. IDIVAL. (IDIVAL) Raquel Leal García. (IDIVAL) Charo González Cabria. (IDIVAL) Coordinator: Lorena Agüero Cobo. (IDIVAL)

Julio Muela Carriles. (IDIVAL) Innovation Unit

Laura Herrero Urigüen. (IDIVAL) Technicians: Innovation Paloma Glez Álvarez. (IDIVAL) Ana Temperán Galbán. (IDIVAL) Accounting: Area Health technology assessment Javier Arce Saiz. (IDIVAL) (Evaltec®) RRHH: Marina Cano Iglesias. (IDIVAL) Aroa Sanz Carreira. (IDIVAL) IDIVAL has an Innovation Area, which forms part of the ITEMAS Platform of the Carlos III Health Institute (ISCIII). It also includes a Administrative staff: Results Transfer Office (OTRI), which is part of the Spanish OTRI network. Billing: Laura del Río Celis. (IDIVAL) This area aims to promote, enhance RRHH: and disseminate research results María José San Emeterio. (IDIVAL) amongst society, encouraging the Registry: interaction of researchers with the Elena Calvo Llano. (IDIVAL) corporate and social environment, 27

in Spain, designed to become a National Library of Medicine, on the initiative of Dr Wenceslao López Albo, the first Managing Director of Casa de Salud Valdecilla, under the patronage of María Luisa Gómez de Pelayo, Marquesa de Pelayo, the niece of Ramón Pelayo de la Torriente, Marqués de Valdecilla. Since then, it has been considered one of Spain’s leading specialist libraries.

In 2016 the library introduced a new Cantabria. The library facilities, platform providing access to its consisting of a Great Hall, electronic resources, as part of the Training and classroom, copy services room, IDIVAL website, notably improving Methodology study room, periodicals library, its accessibility. video library, depositories of less Support Area used and antique holdings, two storerooms, and an administration and management area, are located Librarian: in the Marqués de Valdecilla IDIVAL, as part of its goal University Hospital. The electronic Mario Corral García. (IDIVAL) to strengthen and facilitate library, Biblioteca Virtual Marquesa scientific training associated with de Pelayo, offers all its services research, provides library support (inter-library loans, reference, etc.) to researchers and promotes, and online resources (organised coordinates and performs training according to the Haynes Pyramid) activities in this area throughout the via the IDIVAL website. The Administrative staff: year. catalogue can be accessed directly at s-hmv.c17.es Rafael Lavín Fuentes. (HUMV) Mª del Carmen Fuente San The Library was first opened in Bartolomé. (HUMV) 1929, the second oldest and the first fully modern library of its kind Marquesa de Pelayo Library

The Marquesa de Pelayo Library is an active centre of biomedical information resources. Its mission is to contribute to raising the level of innovation and excellence in three fundamental areas of Cantabria’s public healthcare system: clinical care, teaching, and research, by an intensive use of information and communication technologies.

The Library is governed by IDIVAL and provides support for the public healthcare system throughout Support for researchers Central Support Unit

Trial Unit. The Agency provides Platform for Clinical Research and support for the management of Clinical Trial Units (SCREN, Spanish Clinical clinical trials, and the Unit supports Clinical Research Network) of the their execution. Both bodies are Carlos III Health Institute. Trials involved in advising, designing, evaluating, managing, implementing In 2016, Cantabria introduced a new Area and executing clinical trials, form of contract for clinical trials, including technical support for the in line with national regulations Clinical Research Ethics Committee and providing greater transparency, of Cantabria. substantially improving the The Clinical Trials Area includes a management of clinical trials within Clinical Trial Agency and a Clinical The Clinical Trials Area is part of the IDIVAL.

Clinical Trial Agency

The agency offers its organisation Technician: and resources to researchers to promote reliable clinical trials María Rodríguez Rodríguez. that can guarantee the quality of (IDIVAL) the study, patient safety and data reliability. It also provides support Administrative staff: to the Clinical Research Ethics Committee of Cantabria. Blanca del Pozo Fernández. (IDIVAL) Lorena Martín Guerra. (IDIVAL)

Clinical Trials Unit

The IDIVAL Clinical Trial Unit, Equipment: under the Clinical Pharmacology Department, located in the Mª Blanca Sánchez Santiago. Marqués de Valdecilla University (Clinical Pharmacology Department, Hospital, has 250 m2 of facilities HUMV) equipped to care for nine patients Mª Ángeles de Cos. simultaneously. It began operations (Clinical Pharmacology Department, in 2013, partially financed with HUMV) funds from the Farmaindustria R&D Javier Adín Ibarra. programme. It provides support for (Clinical Pharmacology Department, highly complex clinical trials in the HUMV) Valdecilla environment. Nuria Sánchez Avelló. (HUMV) Amaya Riaño Laguillo. (IDIVAL) 29

The Technology Support Services Technology Services are Coordinator: Technology Area consists of six units: Biobank, Laser Microscopy Unit, Electron Mª José Marín Vidalled. Support Services Microscopy Unit, Flow Cytometry (IDIVAL). and Cell Separation Unit and Area Neuroimaging Unit.

Valdecilla Biobank

Scientific Director:

Pascual Sánchez Juan. (Neurology Service, HUMV)

DNA AND FLUIDS NODE

Coordinator:

Mª José Marín Vidalled. (IDIVAL)

Technicians:

Inés Santiuste Torcida. (IDIVAL) The Biobank VALDECILLA is a Biobank Valdecilla is one of David Ramos Melendro. (IDIVAL) hospital biobank that manages the units that form part of the human biological samples with the Hospital Biobanks Platform of the purpose of supporting biomedical Carlos III Health Institute, which TISSUES NODE research through the collection, has four programs: promotion of storage and transfer of samples and strategic collections, promotion Coordinator: associated clinical data, all in the of network services, R & D in strictest conditions of quality and biobanks and ethical aspects, Santiago Montes Moreno. confidentiality. Legal and social. (Pathology Service, HUMV)

It is functionally organized in In December of 2015 the biobank three Nodes: the DNA and Fluid renewed the authorization of Technicians: Node, located on floor 0 of the the Ministry of Health of the IDIVAL building and the Solid Government of Cantabria to José Bernardo Revert Arce. Sample Nodes, and neurological function as a biobank. This (IDIVAL) tissues located in the Pathology authorization implies compliance Department of the Marqués de with the requirements established Valdecilla Hospital. The biobank NEUROLOGICAL TISSUES NODE has a large catalog of collections in Royal Decree 1716/2011 of samples of various pathologies of November 18 and its Coordinador: of high scientific interest and incorporation in the National also provides a variety of services Registry of Biobanks of the Carlos Nuria Terán Villagrá. derived from the use of its III Health Institute. (Pathology Service, HUMV) equipment, offering comprehensive support to researchers whose In November 2015, Biobank projects involve the use of human Valdecilla has achieved ISO9001: biological samples. 2015 quality management. Support for researchers Central Support Unit

Laser Microscopy Unit

The IDIVAL Laser Microscopy epifluorescence module, incubation Unit offers a high-end and micro-injection systems and microscopy service to its own an optical system that allow the and external research groups tracking of fast processes in living with the fundamental objective cells. of obtaining a full performance in their fluorescence studies in the shortest possible time. For Scientific coordinator: this purpose, it has the latest generation equipment consisting Mónica López Fanarraga. of two imaging systems, a specular (UC) confocal laser microscope (LSM) and fully automated Nikon A1R combined TIRF, which allows high- quality confocal image capture of Superior Technician: cells and molecular events at high speed and sensitivity, And a live Fidel Madrazo Toca. cell device with a motorized NIKON (IDIVAL) Ti microscope equipped with an

Electronic Microscopy Unit

The Electronic Microscopy Unit began its activity in early 2012. It Scientific coordinator: has a transmission microscope JEOL, Model JEM-1011 equipped Miguel Lafarga Coscojuela. with a Gatan digital camera, mod. (UC) SC1000 Orius high resolution solution that provides excellent image quality. This microscope allows the analysis of ultrafine Technician: sections of cells and tissues, as well as observation of microorganism Fidel Madrazo Toca. preparations and macromolecular (IDIVAL) complexes contrasted with negative staining.

Each year, both laser microscopy and electron microscopy units organize a microscopy and sample preparation course for researchers and support staff. 31

Cytometry and Cell Separation Unit

both to researchers at the centre and any external group that needs Scientific Coordinator: it. It has an upgraded FACSAria II (BD Biosciences) cytometer/sorter Marcos López Hoyos. updated in 2013, a FACSCanto (Immunology Service, HUMV) cytometer (BD Biosciences) and an Auto-MACS Pro Separator (Miltenyi Biotec) magnetic bead The Flow Cytometry and Cell cell separator, which allows for Technical coordinator: Separation Unit was created the separation of cell populations in 2005 as a support unit to in infertility. David San Segundo Arribas. IDIVAL research and operates (Immunology Service, HUMV) in the IDIVAL building within The Unit organises an annual the Laboratory of the Research course on flow cytometry in Group of Transplantation and collaboration with the Inbiomed Autoimmunity. The aim of this Cytometry Unit intended for both Laboratory coordinator: unit is to provide technical and researchers and health workers. methodological support regarding David Merino Fernández. the use of flow cytometry and cell (IDIVAL) separation; this service is offered

Genomics Unit

The Genomics Unit works under the Molecular Genetics Unit Scientific Coordinator: of the Marqués de Valdecilla University Hospital, located José Luis Fernández Luna. on the first floor of the IDIVAL (Molecular Genetics Unit, HUMV) building. It has functioned as such since 2002, performing Technicians: care-related genetic studies for hospitals and health centres in Ana Fontalba Romero. Cantabria and other regions and (HUMV) providing primarily sequencing Olga Gutiérrez Saiz. services. (IDIVAL) Support for researchers Central Support Unit

Neuroimaging Unit

This laboratory has implemented severe mental illness, constituting a and developed a wide range of fundamental tool in brain research. techniques for quantitative image analysis of the human brain obtained by magnetic resonance imaging (MRI), which is now at the Scientific coordinatori: service of IDIVAL researchers and external groups in order to provide Benedicto Crespo Facorro. technical and methodological (Psychiatry Service, HUMV) support in the design and execution of scientific studies.

The analysis techniques employed Technicians: can obtain quantitative data on important cerebral variables Diana Tordesillas Gutiérrez. of interest (volume of cerebral (IDIVAL) structures or areas, cortical Roberto Roiz Santibáñez. thickness, gyrification patterns, (CIBERSAM) white matter structure, activity Víctor Ortiz de la Foz. patterns, etc.) for the advancement (IDIVAL) of in vivo knowledge of the brain, and therefore, possible alterations in

Units Supported by the University of Cantabria

IDIVAL has a number of facilities Animal housing and that the University of Cantabria experimentation services. offers its researchers, such (SEEA) as materials characterisation, Materials characterisation chromatography, and animal service. (SERCAMAT) housing and experimentation. Optical transmission microscopy service. (SERMET) Supercomputing service Hydrobiology laboratory. (I. Hidráulica) Chromotography service.

Advanced microscopy. (IBBTEC)

Mass sequencing service. (IBBTEC) 33

> Inn-Val Grants. Awarded to Marqués de Valdecilla University Innovation projects. Hospital.

IDIVAL > Next-Val Grants. Awarded to > Post-MIR Wenceslao López Albo Research projects for young researchers. contracts programme (described in the training section of the report). Grants > Ges-Val Grants. A research training scholarship. > Complementary personnel for projects from the National Plan. > Int-Val Grants. For research intensification. > National call for “Enfermería Valdecilla” research projects. > Ment-Val Grants. Mentoring programme for resident doctors. > Scholarship for training in spine IDIVAL has a line of research grants Production grants (support surgery for traumatology and focusing on fostering talent. Each programme). orthopaedic specialists, and in of these programmes has a clear neurosurgery. > Summer internships. educational focus and the description of their activity is featured in the > Pre-doctorate contracts. training section of this report. In > Innplant programme. Programme 2016, IDIVAL launched the following to implant clinical researchers The total amount of IDIVAL grants grants: as Heads of Department at the awarded in 2016 was as follows:

Grants Programme Amount awarded (€)

Inn-Val grants 105.000 (7 projects)

Next-Val grants 100.000 (9 projects)

Ges-Val grants 57.960 (one grant lasting three years)

Int-Val grants 60.000 (2 intensification programmes over 6 months)

Ment-Val grants 8.000 (1 project)

Production grants 401.546 (one grant per group, 30 groups)

Summer internships 2.800 (4 internships of 2 months)

Predoctoral contracts 329.600 (4 contracts for 4 years)

Post-MIR Valdecilla contract programme 262.962 (3 contracts for 2 years)

Complementary personnel for 46.875 (cofunding 5 contracts) National Plan projects

National call for 7.000 (2 projects) “Enfermería Valdecilla” research projects

Scholarship for training in spine surgery for 19.089 (1 scholarship) traumatology and orthopaedic specialists, and in neurosurgery Total awarded 1.400.832 € Support for researchers Central Support Unit

INN-VAL Grants

Main researcher: common mental disorders in a Conde Portilla, Olga María. Healthcare Centre (PsicAPCantabria): Diagnosis of tendinous chordae a randomised controlled clinical trial. of the human mitral valve using Amount awarded: €15,000. multiple approaches in analysis: optical, mechanical, micro-structural, Main researcher: and anatomical (DICUTEN). Riancho Zarrabeitia, Javier. Amount awarded: €15,000. New RXR agonists as a treatment of ALS. Main researcher: Amount awarded: €15,000. Crespo Facorro, Benedicto. Technological solution to prevent Main researcher: relapses and for rehabilitation in Villegas Sordo, Juan Carlos. schizophrenia. Design of bio-synthetic nano- Amount awarded: €15,000. dispensers to transport treatments to In 2015, IDIVAL implemented the motor neuron cytoplasm. the Inn-Val grant programme, Main researcher: Amount awarded: €15,000. in collaboration with the Botín Delgado Alvarado, Manuel. Foundation, which acted as Augmented reality device combined co-financier, focusing on the with subsensory mechanical development of innovative feedback in the treatment of motor technological and healthcare blocks in Parkinson’s disease. projects. The programme seeks to Amount awarded: €15,000. promote the transfer of knowledge Main researcher: Gómez Ruiz, Marcos. to society and the market, and Development of hardware and to integrate local agents in the software applicable to stereotactic Valdecilla environment. In 2016, navigation of the pelvic organs. the grants announced in 2015 were Amount awarded: €15,000. awarded, and a second round of grants was announced, which will Main researcher: be awarded in 2017. The following González-Blanch Bosch, César. projects were awarded grants in Cost-effectiveness of transdiagnostic 2016: psychological group therapy for 35

NEXT-VAL Grants

In 2016 IDIVAL announced the Main researcher: implantation compared to aortic second round of NEXT-VAL (NEXT San Segundo Arribas, David. valve replacement surgery. generation VALdecilla) grants for Project: Myeloid-derived suppressor Amount: €10,000. the development of one- or two- cells (MDSC) and immune year research projects led by novice regulation in kidney transplants: Main researcher: researchers, in order to encourage differential effect between Collado Garrido, Luisa. the recruitment of new researchers calcineurin and mTOR inhibitors and Project: Effectiveness of resistance in the Valdecilla environment. This evaluation as post-transplantation therapy on the motion, quality of life call for NEXT-VAL research projects biomarkers. and safety of acute stroke patients: is intended for translational research Amount: € 20,000. Randomised controlled trial. projects led by Main researchers Amount: € 5,000 who have never received this type Main researcher: Riancho Zarrabeitia, Javier. of competitive access grant in such Main researcher: Project: Alzheimer’s disease and Campos Juanatey, Felix. a role. The five projects selected in Down syndrome: a clinical and Project: Etiological diagnosis and 2016 were: experimental approach. treatment of complex urinary probes Amount: €15,000. using portable urethrocystoscopy. Amount: €10,000 Main researcher: Mondejar Garcia, Rufino Main researcher: Marceliano. Arias Loste, María Teresa. Project: Directed therapy guided Project: Effects of chronic by molecular markers in patients hypercapnia, with or without with cutaneous T-cell lymphoma. hypoxia, on the hepatic level. Amount: €10,000. Hepatocyte culture study and validation in a cohort of patients Main researcher: with fatty liver disease from normal Martín Rodríguez, Rosa. clinical practice. Project: Development of Amount: €10,000 multifunctional nanoparticles for cancer diagnosis and treatment. Main researcher: Amount: €10,000. Alonso González, Carolina. Project: Study of the sensitising Main researcher: effects of melatonin on neoadjuvant Fradejas Sastre, Victor. chemotherapy in breast cancer Project: Impact on quality of treatment. life and functionality of patients Amount: €10,000 with percutaneous aortic valve Support for researchers Central Support Unit

GES-VAL Grants

In 2015, IDIVAL launched a grant research management to be carried promotes the training of technicians programme for the development out at IDIVAL over a period of two in this field, as they learn different of a plan for training activities in to three years, with a second round aspects of management, monitoring science and health technology announced in 2016. This programme and evaluation of research projects.

INT-VAL Grants

In 2016, IDIVAL introduced the IDIVAL funds the part-time or Benedicto Crespo Facorro. Int-Val programme (Intensification full-time substitution of doctors Duration: 6 months of research - Valdecilla) to release or nurses involved in research or clinical practitioners with heavy innovation projects. Miguel Ángel González Gay research and/or innovation The two researchers receiving Mantecón. workloads from their other duties. intensification grants in 2016 were: Duration: 6 months

MENT-VAL Grants

In 2016, IDIVAL launched a with drive seeking excellence, Teresa Borderías Villarroel, who mentoring programme for and also as a way to provide in 2016 chose the Cardiology resident doctors at Valdecilla, personalised specialist Department at Marqués de intended to attract new healthcare training and an Valdecilla University Hospital medical professionals finalising introduction to research. for her residency. their training, young people The selected candidate was 37

Production Grants

In 2016, IDIVAL allocated funds group is first or last, differentiating and the responsibility of any for the operating costs of groups, them from the impact factor of group members to any IDIVAL based on their production in projects where authors from the platform were also considered. The 2015. This grant was calculated group are neither the first nor following production grants were considering the impact factor of last. The funds obtained by the allocated to IDIVAL groups in 2016: each IDIVAL research group in group, the patents generated, projects in which an author in the RETIC or CIBER membership,

Group Total €

Pathological anatomy and molecular pathology 19.188 Apoptosis 4.018 Nuclear cell biology 6.641 Cell cycle, stem cells and cancer 4.489 Cytokines and growth factors in pathological tissue plasticity phenomena 11.760 Clinic and genetics of headaches 13.541 Diagnosis and treatment by image 8.224 Neurodegenerative diseases 20.569 Genetic epidemiology and atherosclerosis in systemic inflammatory diseases 49.945 Epidemiology and pathogenic mechanisms of infectious diseases 9.553 Epidemiology and public health 19.185 Genomics of cancer 34.782 Nanovaccines and cellular vaccines based on listeria monocytogenes and their applications in biomedicine 4.512 Study Group on Hereditary Hemorrhagic Telangiectasia (Rendu Osler Weber) 3.213 Cardiovascular research group 6.436 Molecular image 6.488 Infection and immunity and digestive pathology 34.966 Immunopathology of rheumatic diseases 3.157 Melatonin and breast cancer 5.456 Mineral and lipid metabolism 22.201 Clinical and molecular microbiology 19.448 Advanced microscopy and folding of proteins and cytoskeleton 2.479 Nanomedicine 8.412 Hematologic Neoplasms and Hematopoietic Progenitor Transplantation 10.405 Neurophysiology in epilepsy and neurointensive 2.834 New techniques in abdominal surgery 6.025 Psychiatry 14.135 Cell signaling and therapeutic targets in cancer 19.288 Transplantation and autoimmunity 20.322 Unit for clinical trials and medical oncology 9.874 Support for researchers Central Support Unit

Addition of Complementary Personnel for Projects in the National R&D+I Plan

IDIVAL has co-financed personnel following projects, started in recruited through this line of expenses for projects submitted previous years, were co-financed co-financing in 2016 have been to the National Plan call by by IDIVAL for the hiring of offered their third and fourth researchers at the Institute. The complementary personnel. Staff contract years:

Principal investigator Title Funding

José Ramos Vivas. Key host-pathogen interactions of clinical 9.375€ relevance in Acinetobacter species (PI 13/01310).

Carmen Fariñas Álvarez. Intestinal colonisation by multiresistant 9.375€ enterobacteriaceae in patients with renal and liver transplants: multicentre cohort study and randomised, controlled, open clinical trial (PI 13/01191).

José Luís Fernandez-Luna. Prognostic and therapeutic relevance 9.375€ in ODZ 1 glioblastoma, a new target in cancer (PI 13/01760).

Mónica Lopez-Fanarraga. Antineoplastic development based on 9.375€ nanomaterials (PI 13/01074).

José Antonio Riancho Moral. DNA Methylation: pathogenic and 9.375€ biomarker factors in bone formation disorders (PI 12/00615). 39

Pre-Doctorate Contracts

In 2016, IDIVAL partnered with the University of Cantabria to Pre-doctoral contract holder: Pre-doctoral contract holder: launch the second pre-doctorate Lourdes María Valdivia María Iglesias Escudero. contract programme, in which Fernández. Director: seven candidates were selected Director: Marcos López Hoyos. (HUMV) (four funded by IDIVAL and three Mónica López Fanarraga. (UC) by the University of Cantabria) Pre-doctoral contract holder: for a contract of up to four years Pre-doctoral contract holder: Lorenzo Joaquín Gutiérrez with the goal of completing their Carmen Lage Martinez. Avilés. doctoral theses. Director: Director: Pascual Jesús Sánchez Juan. José Carlos Rodríguez Rey. (UC) The selected candidates and their (HUMV) thesis directors were:

Summer internships

IDIVAL, in collaboration with The students selected to work in the Institute of Biomedicine the IDIVAL Group laboratories in Fernando Andrés García. and Biotechnology of Cantabria 2016 were: Internship at the Transplantation and (IBBTEC), funds summer Autoimmunity Group. internships for students in the PI: Marcos López Hoyos. biomedical and biotechnological Estefanía Esteban Rodríguez. fields at the IDIVAL research group Internship in Clinical and Molecular Sonia Aracil Gisbert. laboratories. The grant funds an Microbiology. Internship at the Cancer Genomics eight-week stay during the months PI: Jose Ramos Vivas. Study Group. of July, August and September PI: Nerea Martínez for students in their last year of Adriana Solís Angulo. Magunecelaya. undergraduate or master’s degree Internship at the Nanovaccines Group and cellular vaccines based on Listeria studies in a biomedical subject monocytogenes and their applications (biology, biotechnology, nursing, in biomedicine. pharmacy, medicine, dentistry, PI: Carmen Álvarez Domínguez. etc.) during the internship period.

41

Training

IDIVAL considers research and a wide range of activities including innovation training and dissemination ten different lines of training and to be among the cornerstones of its dissemination. activity. Therefore, it participates in Training Hospital Sessions

10: Budget management at HUMV. 16: Genetics: Strategies for Juan Carlos Dueñas, Deputy Director Translating Genetic Findings into of Financial Management, Marqués de Clinical Care. Dr David C. Glahn Hospital Valdecilla University Hospital. – Professor of Psychiatry and Psychology, University of Yale (USA) Sessions 17: New CPR guidelines? Dr Rodriguez Borregán. Intensive 23: Presentation of the results of Care Dept., Marqués de Valdecilla the HUMV’s Clinical Commissions. This dissemination activity includes University Hospital. Dr Concepción Fariñas – Quality monthly scientific sessions with Coordinator. Marqués de Valdecilla the participation of internationally University Hospital. renowned guests and IDIVAL researchers, who lead sessions in APRIL: 30: IDIVAL - Multiple Sclerosis in the environment of the Marques Cantabria: Advances and future 14: Multiresistant germs: the current challenges. Dr Vicente González de Valdecilla University Hospital situation at HUMV. Multiresistant Quintanilla; Post-MIR Valdecilla Lopez (HUMV). workgroup, Marqués de Valdecilla Albo contract. University Hospital: Dr L. Martínez, Dr These sessions are interspersed R Wallmann, Dr C. Fariñas. with weekly hospital sessions at the OCTOBER: HUMV. The 2016 sessions were the 21: Erectile dysfunction: A marker following: 6: Heart transplant with asystolic of health and quality of life. Dr J. donors. Peter McDonald. Heart and A. Portillo Martín. Urology Dept., Lung Transplant Unit. St. Vincent’s JANUARY: Marqués de Valdecilla University Hospital. Sydney. Australia Hospital. 21: Commitment to quality at HUMV: 13: Clinical-pathological session: Best in Class awards. Dr Julio Pascual 28: IDIVAL - Medical doctorate neuropathology. Dr Nuria Terán. Gómez, Managing Director. Marqués programmes. Current regulatory Anatomical Pathology Department, de Valdecilla University Hospital. and operational aspects. Alberto Marqués de Valdecilla University Ruiz Jimeno, Dr B. Crespo and Dr D. Hospital. 28: Challenges in molecular Delgado. University of Cantabria. diagnostics in sarcomas. Dr Javier 20: Workplace Risk Prevention Plan. Crespo, Head of Department, Marqués Marco Antonio Gandarillas González, de Valdecilla University Hospital. S. Occupational Medicine, Marqués de MAY: Valdecilla University Hospital.

5: Major Outpatient Surgery: a FEBRUARY: commitment to the future Dr José NOVEMBER: María Capitán Vallvey, Head of 4: Contrast-induced acute renal the Surgery Dept., Jaén Hospital, 3: The Marquesa de Pelayo Library: failure. Dr A. L. Martin de Francisco. National Coordinator of the National tools for new challenges. Mario Nephrology Department. Marqués de Association of Surgeons. Corral García. Head Librarian of the Valdecilla University Hospital. Marquesa de Pelayo Library, IDIVAL. 12: 1816-2016. The rise and fall of 11: Presentation of the Chronic the art of auscultation. Dr J. Ramón 10: Homage to Dr Arias. Kidney Disease Strategy for Cantabria. Dr Berrazueta, Cardiology Dept., Marqués transplants: history and new I. Lapuente Heppe – SCS / Dr C. de Valdecilla University Hospital. breakthroughs. Dr Federico Fernández Viadero – Minister for Oppenheimer. – Hospital Clinic of Health. 19: Phlebitis Zero project. Multimodal strategy. Jose Luis Cobo Sánchez Barcelona. 18: The current value of the clinical (Quality, Training and Research). autopsy. Dr Félix Arce Mateos, Marqués de Valdecilla University Pathological Anatomy Dept., Marqués Hospital. DECEMBER: de Valdecilla University Hospital. 26: Intraoperative neurophysiological 1: Homage to Dr Castrillo. Emergency 25: Training leaders in brain health. monitoring: new horizons, new medicine: an unfinished business? Dr Bruce Miller, Aging and Memory challenges. Dr Veldran Deletis / St. Tomás Toranzo, former President of Center UCSF (USA) Luke’s Hospital, N. York the Spanish Society of Emergency Medicine.

15: Stratified treatment in MARCH: JUNE: schizophrenia: integrating results of 3: Clinical anatomy session: On the human and cellular transcriptome 9: The artificial heart at HUMV: various cases of sudden death. in antipsychotic treatment strategies. seven years saving lives. Dr Virginia Dr Marta Mayorga Fernández, Dr Benedicto Crespo, Psychiatry Burgos, Cardiology Dept., Marqués de Pathological Anatomy Dept., Marqués Department, Marqués de Valdecilla Valdecilla University Hospital. de Valdecilla University Hospital. University Hospital. 43

4TH INNOVATION AND INTRODUCTORY BIOMEDICAL DEVELOPMENT SEMINARS. RESEARCH WORKSHOP.

Training Related For a third year, the IDIVAL With the participation of IDIVAL. introductory programme to to Support Unit Lecture and workshop: Introduction Biomedicine “Long Live Science! An to Design Thinking and People- introduction to biomedical research” Departments Centred Innovation, by Asier was held in collaboration with the Pérez, Director of Research and Ministry of Education, Culture and Creativity at Dowayo Foresight. In Sport of the Government of Cantabria. partnership with the Nursing Quality, There were a total of 7 classroom- Training, and R&D area at HUMV, based workshops in November, this lecture and workshop were with the participation of 80 students Includes activities for researchers organised in November to introduce from schools in Cantabria. The workshops were designed, directed provided by Institute departments. the Design Thinking methodology and its application to healthcare. and developed by IDIVAL with the In 2016, the following dissemination “Generating ideas, introducing main goal of encouraging the region’s activities were provided under this solutions” with the lecture “How to students to consider a career in line: protect innovation”. science, in the field of biomedicine.

III Flow Cytometry Course. RESEARCHERS’ NIGHT. Techniques and applications in clinical practice and research, This European science project forms SCIENCE WEEK. 30/05/2016 - 02/06/2016 part of the PEOPLE Programme in the 7th EU Framework Programme, Science Week was held in November promoted by the Ministry of Education 2015, an initiative coordinated by and Employment of the Government the University of Cantabria in which of Cantabria and coordinated by IDIVAL participated by opening its the Research Institutes of Physics doors to five primary and secondary (IFCA) and Environmental Hydraulics schools, with more than 100 (IH Cantabria) of the University of students participating. Students Cantabria and the International Institute of Prehistoric Research (IIIPC). got to see the IDIVAL facilities, with Dissemination IDIVAL, IBBTEC and Smart Santander brief presentations by researchers also participate in this initiative. Activities including José Ramos Vivas, David San Segundo Arribas and Fidel Madrazo Toca, with whom they could talk about the research professional STUDENT VISITS. in the context of clinical research and The IDIVAL Innovation Area learn about the tools used in their During 2016 there were seven visits disseminates and promotes the daily work, such as the Microscopy by students from various Cantabrian culture of innovation. In 2016, there Unit, Cytometry Unit, the research schools. The visits included the were several dissemination events in laboratories, etc. Microscopy and Flow Cytometry units and the Molecular Microbiology this field: laboratory. Training Collaborations with Universities

MASTER’S DEGREE: MANAGEMENT Introduction to biomedical OF HEALTHCARE AND SOCIAL information for Primary Care. Collaborations SERVICES. with Universities Dates: 22 - 23 November. Director: David Cantarero Prieto Duration: 6 hours / seminar. (University Professor in the Area of Primary Care medical students. Applied Economics, Area of Public Tax Location: Library Classroom. Authority, Department of Economics Teacher: Mario Corral, Librarian. of the University of Cantabria). University of Cantabria.

Library immersion course for MASTER’S DEGREE: THE STUDY AND HUMV Residents. TREATMENT OF PAIN. Date: 2 July. Duration: 1 hour. Rey Juan Carlos University and University of Cantabria. Students: HUMV Residents-1. Teacher: Mario Corral, Librarian.

MASTER’S DEGREE: INTRODUCTION Basic reference search using TO MENTAL HEALTH RESEARCH the Marquesa de Pelayo Library University of Cantabria; Complutense for midwives. University of Madrid; Autonomous Dates: 18, 19 and 20 October. University of Barcelona; University of Duration: 9h. Barcelona and University of Cádiz) in collaboration with CIBERSAM. Location: Library classroom. Teacher: Mario Corral, Librarian.

UIMP MEETING. THE SOCIOECONOMIC Reference searches in EVALUATION OF HEALTHCARE MEDLINE via PUBMED. RESEARCH. IDIVAL’s research groups include Date: 25 - 26 October. 40 of the 132 associate professors Directors: Alfonso Beltrán (Deputy Duration: 8 hours. working in the Marqués de Valdecilla General Director for International Location: Sierrallana Hospital - University Hospital. Of the 26 Research Programmes and Tres Mares. professors from the University of Institutional Relations, Carlos III Health Teacher: Mario Corral, Librarian. Cantabria working at the Marqués Institute), Pedro Cortegoso (General de Valdecilla University Hospital, 23 Secretary, Carlos III Health Institute), belong to IDIVAL groups. Galo Peralta Fernández (Director of Web of Science advanced level. Management at IDIVAL). 29 June to 1 In terms of training in the various July 2016. Annual landmark meeting Date: 13 October. fields related to research, IDIVAL in which IDIVAL collaborates with the Location: Library classroom. Carlos III Health Institute. researchers have collaborated on Duration: 1h. the organisation and implementation Teacher: Rachel Mangan of training within different master’s (FECYT). degree programmes:

Research Methodology MASTER’S DEGREE: MOLECULAR BIOLOGY AND BIOMEDICINE. This section includes in-house University of Cantabria and University training activities and programmes of the Basque Country Director: organised and financed directly by Dolores Delgado (Professor of IDIVAL. In 2016, the activities of this Immunology. Department of Molecular section directed at training on using Biology. University of Cantabria). library resources were the following: 45

residents, internal pharmaceutical for the Santander Area, a specialist residents, internal biology residents, in Occupational Medicine, and 10 Specialist internal chemistry residents and nurses specialising in Obstetrics and internal midwifery nursing residents. Gynaecology. Training In 2016, the Marqués de Valdecilla University Hospital offered 82 places The medical specialisations in 39 specialisations. The Marqués accredited in the Marqués de The Marqués de Valdecilla University de Valdecilla University Hospital also Valdecilla University Hospital and Hospital is accredited to train participated in the training of the the number of places offered in internal medical residents in various 20 places offered for specialisation the last call for specialised health specialisations, internal psychology in Family and Community Medicine training were:

Especialidad Nº Especialidad Nº

Allergology 1 Intensive Medicine 3 Clinical Analysis 1 Internal Medicine 4 Pathological Anatomy 3 Nuclear Medicine 2 Anaesthesiology and Reanimation 6 Microbiology and Parasitology 1 Gastroenterologist 2 Nephrology 2 Clinical Biochemistry 3 Pneumology 2 Cardiology 3 Neurosurgery 1 Cardiovascular Surgery 1 Clinical Neurophysiology 2 General and Digestive Surgery 2 Neurology 2 Oral and Maxillofacial Surgery 1 Obstetrics and Gynaecology 3 Orthopaedic Surgery and Traumatology 2 Ophthalmology 1 Thoracic Surgery 1 Medical Oncology 1 Medical-Surgical Dermatology 1 Radiotherapeutic Oncology 1 Endocrinology and Nutrition 1 Otorhinolaryngology 1 Hospital Pharmacy 2 Paediatrics and Specific Areas 5 Clinical Pharmacology 2 Clinical Psychology 1 Haematology and Haemotherapy 3 Psychiatry 3 Immunology 2 Radiodiagnostics 4 Occupational Medicine 1 Hospital Radiophysics 1 Family and Community Medicine 20 Rheumatology 2 Physical Medicine and Rehabilitation 1 Urology 1 Training Training of New Clinical Researchers

innovation, known as Post-MIR programme supervised by the Wenceslao López Albo contracts, is Marqués de Valdecilla University Training of specifically for residents who have Hospital of up to three years in completed their specialisation. It duration that should include a New Clinical has been active since 2003 as a way stay at one or various renowned to promote training, attracting and international centres. Researchers consolidating talent in the Marqués de Valdecilla University Hospital In 2016, IDIVAL offered grants environment. for an 18-month contract to four specialists; the Post-MIR Valdecilla This nationwide call invites recently- contracts of a further five specialists IDIVAL’s training programme in trained specialists from any centre were active at some point during healthcare-related research and in the country to develop a research 2016.

Call 2016

ONAINDIA PÉREZ, ARANTZA. Institute of Neurology (London), Stay: Brigham and Women’s Hospital Specialist in Pathological Anatomy Johns Hopkins Hospital (Baltimore), (Boston, USA) formed in the HUMV. Imaging interventionnelle oncologique Duration: 18 months. Tutor: Miguel Ángel Piris. et viscérale - NHC (Strasbourg). Project: Application of new molecular Project: Innovation project in techniques to the routine diagnosis of Neuromusculoskeletal Radiology. FABREGAT BORRÁS, ROSA. cancer patients. Duration: 18 months. Specialist in Radiation Oncology Stay: MD Anderson Cancer Center, trained in the HUMV. The University of Texas. Tutor: Pedro Prada. LAS VECILLAS SÁNCHEZ, Duration: 18 months. Project: Intraoperative radiotherapy LETICIA. as a treatment of care innovation Specialist in allergology trained at the in the Public Health System of DRAKE PÉREZ, MARTA. HUMV. Cantabria. Technical and clinical Specialist in Radiodiagnóstico formed Project: Creation of a unit of characteristics, methodology, in the HUMV. desensitization to chemotherapeutic dosimetry and quality control. Tutor: Gerardo Lopez Rasines. and biological drugs. Prospective Stays: Gregorio Marañón University Stays: Geneva University Hospital, study of the risk factors in the Hospital (Madrid) European Institute Department of Neuroradiology population of patients desensitized of Oncology (Milan). National Hospital for Neurology, to chemotherapy, antibiotics and Duration: 18 months. Neurosurgery and Psychiatry UCL biologicals. 47

Call 2015

RIANCHO ZARRABEITIA, KISLÍKOVÁ, MÁRIA. RIAÑO MOLLEDA, MARÍA. JAVIER. Specialist in Nephrology trained in the Specialist in General Surgery trained Specialist in Neurology trained in the HUMV. at the HUMV. HUMV. Tutor: Ángel Martín de Francisco. Tutor: Manuel Fleitas. Tutor: Jon Infante. Project: Epigenetic Regulation of Project: Training in hepatobiliary Project: Epigenetics and new Arterial Smooth Muscle Phenotype surgery and liver transplantation and technologies in dementias: a in CKD-Associated Vascular Disease. study and application of solutions and translational approach and assistance External stay: Dr. David Wheeler. The machines for the preservation of solid innovation. UCL Center for Nephrology, University abdominal organs for transplantation. External stay: Dr. Bruce Miller. College of London. External stay: Professeur René Memory Aging Center, in San Duration: 2 years. ADAM, Paul Brousse Hospital in Francisco, University of California Paris and Hammersmith Hospital in (UCSF MAC). London. Duration 2 years. Duration: 2 years.

Call 2014

IRUZUBIETA COZ, PAULA. intestinal microbiota in liver disease Hospital and Institute of Cellular Specialist in Digestive System formed by non-alcoholic fatty deposit in Medicine at Newcastle University for in the HUMV. obesity. 12 months. Tutor: Javier Crespo García (Head of External stay: Cooperative Research Duration: 3 years. the Digestive S., HUMV). Center on Biosciences (CIC bioGUNE Project: Role of immunity and 6 months), and Newcastle Freeman

Call 2013

GONZÁLEZ QUINTANILLA, markers of inflammation and cerebral Dr. Alan Thompson, National Hospital VICENTE. atrophy in patients with multiple for Neurology and Neurosurgery, Specialist in Neurology trained in the sclerosis in Cantabria. London. HUMV. External stay: Dr. Pozzilli, Sant Duration: 2 years. Tutor: Agustín Oterino Durán. Andrea Hospital in Rome and Dr. Project: Evolutionary study of Salvetti, University of Sapienza and Training Doctoral Thesis. Doctorate Programs

Faculty of Medicine of the The formative activity of IDIVAL University of Cantabria has assets: has been reflected in the doctoral Doctoral Thesis. theses. > Doctorate in molecular biology Doctorate and biomedicine (coordinated by In 2016 the IDIVAL groups have Dolores Delgado, with mention participated in a total of 57 Programs of quality). doctoral theses, either through its management or its authorship. > Doctorate in health sciences The list of theses read or directed (currently coordinated by a IDIVAL researchers participate in by IDIVAL staff is shown in the researcher at the institute, attached table. the two doctoral programs that the Benedict Crespo-Facorro).

AUTHOR AND DIRECTOR (S) TITLE UNIVERSITY

Sara Rodríguez Prado, Ocular involvement in Rendu-Osler-Weber University of Cantabria Inés Gómez Acebo disease: characteristics and associations

Inmaculada Hernández Bejarano, Ana Isabel Analysis of the evolution of renal University of Salamanca. Morales Martín, Marta Prieto Vicente, Mª transplantation through the identification of risk Ángeles Ramos Barrón, Carlos Gómez Alamillo. biomarkers in the donor and in the recipient

Rubén Gonzalo González, Analysis of factors predicting remission of Universidad de Cantabria. Manuel Gómez Fleitas. type 2 diabetes mellitus in morbidly obese patients after Roux-en-Y gastric bypass

Ana Machín Mave, Joaquín Cañal Villanueva, Epidemiological and evolutionary analysis of University of Cantabria Pedro Muñoz Cacho. open eye trauma in Cantabria

Marcos Pajarón Guerrero, María Del Carmen Self-management of endovenous (atade) University of Cantabria Fariñas Álvarez, José Ramón De Berrazueta domiciliary antimicrobial treatment in Fernández. infective endocarditis: a safe and efficient care model

Mª Elena Arnáiz García, Aortic root replacement surgery with valvular University of Cantabria Juan Francisco Nistal Herrera. preservation: analysis of early and long-term surgical outcomes, and study of predictors of survival, valvular function stability, and reoperation

Francisco Ortiz Sanjuan, Ricardo Blanco Classification of cutaneous vasculitis University of Cantabria Alonso, Miguel Ángel González-Gay Mantecón, María Del Carmen González Vela.

Ruth Gonzalez Sanchez, José Javier Gómez Development of a diagnostic method for University of Cantabria Román, Francisco Javier Freire Salinas. gastrointestinal stromal tumors (GIST)

Leyre Riancho Zarrabeitia, Miguel Ángel Detection of risk factors for subclinical University of Cantabria González-Gay Mantecón, Ricardo Blanco atherosclerotic disease and cardiovascular Alonso. events in patients with systemic lupus erythematosus

Diana Tordesillas Gutiérrez, Benedicto Crespo Differences in gray matter volume in University of Cantabria Facorro. patients with a first psychotic episode and age-onset effects using voxel-based morphometry 49

Autor y directores Título Universidad

Javier Vázquez Bourgon, Benedicto Crespo Disc 1 and non-affective psychosis: University of Cantabria Facorro. variations in endophenotypes and clinical characteristics in first episodes of psychosis

José Ignacio Martín Parra, Manuel Gómez Design of a training program for residents University of Cantabria Fleitas, Robert Simon, José Mª Maestre of general surgery and digestive system Alonso. based on competences: integration of clinical simulation and practice of care

Ana Esteban Herrera, Javier Ayesta Ayesta, Effectiveness in the management of University of Cantabria Javier Llorca Díaz. smoking cessation

Jorge Duerto Alvarez, Eduardo Miñambres Long-term effect in renal grafts of an University of Cantabria García, María De Los Ángeles Ballesteros intensive management protocol of the Sanz. multiorganic donor

Jaime Lucas Carbonero, José Antonio Vázquez Efficacy and safety of corticosteroid University of Cantabria De Prada Tiffe. withdrawal after cardiac transplantation

María Ruiz Soto, Miguel Ángel Lafarga Oxidative stress in satellite glia of the University of Cantabria Coscojuela, María Teresa Berciano Blanco. spinal ganglia induces sensory alterations in the murine HSOD1G93A model of amyotrophic lateral sclerosis (ALS)

Francisco José Amo Setien, Maria Jesús Dura The study of social support and quality of Autonomous University Ros. life from personal networks: the case of of Barcelona chronic pain

Marcos Gómez Ruiz, Manuel Gómez Fleitas, Comparative study of laparoscopic surgery University of Cantabria José Fernández-Escalante Moreno. versus robotic surgery in the treatment of rectal cancer

Jana González Gómez, Controlled study of risk factors and clinical University of Cantabria Andrés Gómez Del Barrio. variables associated with the development of a eating disorder in the community of Cantabria

María Toriello Suárez, Agustín Oterino Durán, Genetic association study of genes University of Cantabria Jesús Castillo Obeso. encoding the GABA receptor in migraine

José Javier Gómez Román, Francisco Javier Study of markers of mesenchymal University of Cantabria Freire Salinas. epithelium transition in renal neoplasms

José Helmut Ramírez Cuentas, Isabel De Las Study of parents’ satisfaction in a University of Cantabria Cuevas Terán, Luis Gaite Pindado. neonatology unit

Jose Ignacio Fortea Ormaechea, Cristina Ripoll Study of the effect of enoxaparin Universidad Noiseux, Rafael Bañares Cañizares. on cirrhosis and experimental portal Complutense de Madrid hypertension

Javier Pérez López, Study of the role of mir-148a in the University of Cantabria José Carlos Rodríguez Rey. regulation of genes of lipid metabolism and adipogenesis

Ana De Juan Ferré, José Manuel López Vega, Phase II intramural study of neoadjuvant University of Cantabria Marta Mayorga Fernández. chemotherapy with platinum, doxorubicin and taxane salts in operable breast cancer

José Javier Gómez Román, Francisco Javier Evaluation of biomarkers predicting University of Cantabria Freire Salinas. peritoneal carcinomatosis in colon carcinoma Training Doctoral Thesis. Doctorate Programs

Autor y directores Título Universidad

Javier Rueda Gotor, Miguel Ángel González- Evaluation of cardiovascular risk in patients University of Cantabria Gay Mantecón, Javier Llorca Díaz. with predominantly axial spondyloarthritis

Rosalía Demetrio Pablo, Pedro Muñoz Cacho, Thrombotic risk assessment University of Cantabria Víctor Manuel Martínez Taboada. in asymptomatic patients with antiphospholipid antibodies

Amador Priede Diaz, César González-Blanch Cognitive factors associated with the University of Cantabria Bosch. development of anxiety-depressive symptoms in newly diagnosed cancer patients

Carlos López López, José Manuel López Vega, Clinical-molecular prognostic factors University of Cantabria Jaime Sanz Ortíz. and predictive models in glioblastoma multiforme from an intramural experience: service of medical oncology of Hospital Universitario Marqués de Valdecilla (2000- 2010)

Yhivian Peñasco Martín, Alejandro González Prognostic factors of severe thoracic University of Cantabria Castro, Javier Llorca Díaz. trauma in the population aged over 65, 1991 - 2012

Beatriz Payá González, Jesús Ángel Artal Premorbid functioning in early-onset University of Cantabria Simón, Celso Arango López. psychotic disorders: differences between people diagnosed with schizophrenia, bipolar disorder and healthy population

Rosana García Díaz, Cesar Baldomero Madrazo Impact of the implementation of the University of Cantabria Leal, Manuel Gómez Fleitas. checklist on a general surgery service

Javier Gonzalo Ocejo Viñals, María Del Carmen Immunogenetics of pulmonary University of Cantabria Fariñas Álvarez. tuberculosis: influence of major histocompatibility complex polymorphisms, repertoire of KIR genes and other genes of the immune system

Arantza Onaindia Pérez, Peripheral T-lymphomas: study of University of Cantabria Miguel Ángel Piris Pinilla. histological, immunophenotypic and molecular markers, and selection of targeted therapy

Ana Mª Arnaiz García, José Manuel Bernal Morbidity and mortality in deferred sternal University of Cantabria Marco, Mª Concepcion Fariñas Álvarez, María closure Del Carmen Fariñas Álvarez.

María Isabel González Aramburu, Jon Infante Serum levels of uric acid and progranulin, University of Cantabria Ceberio, Onofre Combarros Pascual. genetic factors that regulate them and Parkinson’s disease

Javier Aragón Valverde, Manuel Gómez Fleitas, Role of metalloproteinase-11 and tissue University of Cantabria Francisco José Vizoso Piñeiro. inhibitor of metalloproteinase-2 (TIMP-2) as factors of the inflammatory process and tumor invasion in non-small cell lung carcinoma

Paula Ruiz Martín, Marta Martín Millán, Jesús Role of the WNT canonical pathway in University of Cantabria González Macías, Maria Ángeles Ros Lasierra. osteoclast resorptive function

Marta Fernández Hernandez, José Antonio Guidelines for immunosuppression in heart University of Cantabria Vázquez De Prada Tiffe, Francisco Jesús transplantation in the medium and long González Vílchez term 51

Autor y directores Título Universidad

José Quintanar Lartuno, Manuel Antonio Arias Peritonitis in peritoneal dialysis University of Cantabria Rodríguez, Luis Martínez Martínez

Soraya Curiel Del Olmo, José Pedro Vaqué Precision medicine in Merkel cell University of Cantabria Díez, Miguel Ángel Piris Pinilla carcinoma and advanced cutaneous melanoma

José Alberto Sanchez Ortega, Javier Llorca Prevalence of tobacco, alcohol and drug University of Cantabria Díaz, Mª Concepción Fariñas Álvarez use among university students in Cantabria

José María Castillo Oti, Joaquín Cañal Prevalence and risk factors associated with University of Cantabria Villanueva, Pedro Muñoz Cacho diabetic retinopathy in Cantabria

José Gabriel Calcedo Giraldo, Andrés Gómez Prevention in eating disorders in high University of Cantabria Del Barrio school students in Cantabria

Alicia Márquez López, Luis Martínez Quinolone resistance and hemolysin University of Cantabria Martínez production in clinical isolates

Felipe Rodríguez Entem, José Antonio Vázquez Follow-up of the cardiac transplantation University of Cantabria De Prada Tiffe, José Manuel Revuelta Soba with echocardiographic rejection monitoring strategy

Laura Carral Fernández, Andrés Gómez Del Cognitive Bias in Eating Disorders: A Case- University of Cantabria Barrio Control Study

Liébana Maria Piedra Antón, Luis Ansorena Emergency information systems University of Cantabria Pool, María Del Carmen Fariñas Álvarez

Sandra Properzi, Pierpaolo Vittorini, Carmen Sviluppo of a system of formazione per Università Degli Studi María Sarabia Cobo sustentere the cognitive capacità of the Dell’aquila, Italia persone anziane affette of the cognitive deterioration lieve

Lorena García Hevia, Mónica López Fanarraga Cancer therapy based on the biomimetics University of Cantabria of carbon nanotubes with cell filaments

Gabriela Saravia Campelli, María Del Carmen A randomized intervention program to University of Cantabria Fariñas Álvarez, Mª Concepcion Fariñas Álvarez optimize the quality of hospital use of antibiotics

Araceli Prieto Santa-Cruz, José Javier Gómez Utility of a process-based management University of Cantabria Román system in the care and perceived quality of lung cancer

Juan Carlos Albarracin Castillo, Juan Carlos Value of endoscopic ultrasonography University of Cantabria Rodríguez Sanjuan, Manuel Gómez Fleitas and magnetic cholangioresonance in the diagnosis of choledocholithiasis

Montserrat Robustillo Villarino, Javier Llorca Evaluation of cardiovascular risk using University of Cantabria Díaz, Miguel Ángel González-Gay Mantecón non-invasive techniques in patients with rheumatoid arthritis

Jacqueline Maria Mayoral Van Son, Benedicto A three-year longitudinal study of clinical University of Cantabria Crespo Facorro evolution in patients who, after a single episode of non-affective psychosis, have achieved a complete recovery and decided to withdraw antipsychotic medication. Training Progress Reports

1. Undergraduate Studies in Wednesday 16/11/2016: Medicine at the University Progress of Cantabria. Courses at the Speaker: Marqués de Valdecilla University Reports Ana V. Villar. Hospital cover students of the Associate Professor of the Faculty of Medicine in their Physiology and Pharmacology third, fourth, fifth and sixth year department in the Faculty of medical studies The number of students enrolled in these of Medicine, University of This programme began as a courses whose training involves Cantabria. joint initiative by the Biomedical the Marqués de Valdecilla Heat shock protein 90 Research Forum of Cantabria, Title: University Hospital (in the consisting of researchers from participates in myocardial last five academic years) is as IDIVAL, the University of Cantabria fibrogenic response. The follows: 4th year of Medical and the Institute of Biology and potential of designed Studies: 132, 5th year of Medical Biomedicine of Cantabria, that was biosynthetic inhibitors. Studies: 157, 6th year of Medical organised in 2016 as a continuation Studies: 100. of the programme of research seminars presented by young researchers, in collaboration with 2. Summer internship clinical and basic researchers. programme. In 2013, IDIVAL Wednesday 21/12/2016: launched a grant programme The 2016 programme consisted for five students studying for an undergraduate of the following seminars, held Speaker: degree or diploma in any in the Faculty of Medicine of the Paula Iruzubieta Coz. biomedical discipline (biology, University of Cantabria, in the Specialist in the Digestive biotechnology, nursing, Marqués de Valdecilla University System at Marqués de pharmacy, medicine, dentistry, Hospital and the IDIVAL facilities. Valdecilla University Hospital. etc.) to spend a summer working Post-MIR Wenceslao López in the laboratories of IDIVAL Albo contract holder. groups, a programme that has Title: The liver-specific deletion been continued into 2014, 2015 of the respiratory chain inhibitor and 2016. The students awarded MCJ attenuates NAFLD the grant and the research group progression by enhancing in which they worked during the hepatic beta-oxidativo summer of 2016 appear in the IDIVAL grants section.

3. Spanish for Health Programme with the Comillas Foundation. IDIVAL, in collaboration with the Comillas Foundation, hosts four medical students from New Wednesday 02/11/2016: Student York University Langone for Training six weeks so they can study Speaker: Spanish for Health. Ana Lara Pelayo Negro. Specialist in the Neurology Department of Marqués de IDIVAL’s research groups include Valdecilla University Hospital, 40 of the 132 associate professors former holder of a Post-MIR working in the Marqués de Wenceslao López Albo contract. Valdecilla University Hospital. Of Title: Evolution of Charcot– the 10 tenured professors and 10 Marie–Tooth disease type 1a other professors from the University duplication: a 2-year clinical- of Cantabria working with the electrophysiological and lower- Marqués de Valdecilla University limb muscle MRI longitudinal Hospital, 18 belong to IDIVAL study. groups. 53

Oncology Santander Biomedical Lectures

The Biomedical Research Forum of Cantabria, consisting of Cantabria Healthcare Services, the Marqués de Valdecilla Research Institute (IDIVAL), the University of Cantabria and the Institute of Biomedicine and Biotechnology of Cantabria have launched the SANTANDER BIOMEDICAL LECTURES programme, a series of lectures intended to advance worldwide Biomedical knowledge.

Prestigious researchers at the top of the field worldwide are invited to lecture on subjects such as Oncology, Neurology, Immunology, Regenerative Medicine, and Microbiology.

These lectures were an initiative of scientists at the different research centres of Cantabria to create a forum for discussing current advances in biomedicine, in which some of our region’s research groups play a leading role. department at Ramón y Cajal Thursday 17/11/2016: They will also be a discussion University Hospital. forum for young researchers Title: Current and future Speaker: and healthcare personnel in our challenges in lung cancer. hospitals, and for the general public, Jesús San Miguel. and an opportunity to establish Medical Director of the partnerships. The lectures in this University Clinic of Navarre. programme in 2016 were: Specialist in Haematology and Haemotherapy. Title:Multiple myeloma, from Thursday 27/10/2016: biology to therapy.

Speaker: Francesc Artigas. Thursday 24/11/2016: Director of the Neurochemistry and Neuropharmacology Department of the Insitut Ponente: Thursday 29/09/2016: d’Investigacions Biomèdiques Giuseppe Del Giudice. Translational Science Leader at de Barcelona. GSK Vaccines Srl, Siena, Italy. Speaker: Title: Fast-acting Título: The quest of early Pilar Garrido. antidepressants: Are they biomarkers of vaccine safety Section Head of the Medical possible? and long-term immunity.

55

Some milestones 2016 Some milestones 2016 Organigram

APPROVAL OF NEW STRATEGIC PLAN 2017-2021

CERTIFICATION 166002-2014

LAUNCH RESOLUCION HRS4R CONVOCATION LAUNCHING NEXTVAL PROGRAM IMPLANT NEW CONTRACT FOR FIRST CLINICAL CLINICAL TRIALS VALDECILLA MEETING OF TRIAL PHASE 90.000 LAUNCH BOARD OF TRUSTEES I WITH QUOTES IN THE INNOVATION INCOME LITERATURE BULLETIN

1-ene 1-feb 1-mar 1-abr 1-may 1-jun 1-jul 1-ago 1-sep 1-oct 1-nov 1-dic

REINFORCEMENT MEETING UNITY UIMP SANTANDER PROJECTS FIRST RESIDENT ISCIII BIOMEDICAL EUROPEAN MENTORING LECTURES PROGRAM INTERNAL OPENING CALL COUNCIL FOR THE INN- UPDATE OPENING VAL ANNOUNCEMENT CAMPAIGN POSTMIR COLLABORATES GETTING STARTED CONCESSION PROGRESS HELP BY NEW LIBRARY REPORTS PRODUCTION WEBSITE MARQUESA DE PELAYO PREDOCTORAL CALL FOR PROPOSALS IDIVAL-UC

MEETING OF BOARD OF TRUSTEES 57

without), the largest genetic be reclassified, and that studies study of schizophrenia to date of the magnetic resonance News Stories was able to isolate the rare imaging of the leg muscles can genetic variants that increase be used to detect minimal signs from 2016 the risk of this illness. of the disease. Meanwhile, a The work, recently published in transcriptomic analysis of the Nature Genetics, was led by the cells of several patients enabled University of San Diego (USA) the identification of new factors and the Psychiatric Genomic associated with LRSAM1 Valdecilla launches the COLABORA Consortium (PGC) with data dysfunction, which offer new campaign from over 43 research groups, therapeutic targets shared with including the CIBERSAM amyotrophic lateral sclerosis and The biomedical research of the research group coordinated by Alzheimer’s disease. Valdecilla environment is only Benedicto Crespo-Facorro at possible thanks to the help of UC-IDIVAL. everyone involved. Patients, nurses, researchers, doctors, citizens, companies, patients’ Robotic surgery to treat colorectal associations, all work together Very good results for IDIVAL in the cancer to defeat more diseases Strategic Action for Health 2016 thanks to breakthroughs in the understanding of their causes, In the Colorectal Surgery Unit at symptoms and behaviour, The strategic action is a set Marqués de Valdecilla University and the emergence of new of annual programmes to Hospital, robotics has been the treatments. For this reason encourage biomedical research, preferred approach since 2010 IDIVAL is launching a campaign promoted by the Carlos III for treating rectal cancer in all to inform society about the Health Institute, which are patients who can benefit from research projects in the Valdecilla essential for research in it, and has been used on over environment that seek solutions Spain’s healthcare system. As 500 colorectal cancer patients for health problems, and that a healthcare research institute so far. This is the longest series anyone can support. accredited by the Carlos III in Spain and one of the longest Health Institute, IDIVAL’s experiments in Europe; this researchers at the University of Unit is one of just a few groups Cantabria and the Marqués de teaching other teams at the Valdecilla University Hospital national and international levels. attend these annual aid programmes every year. The Recently, this team published results in 2016 were excellent. its short-term and medium-term The total grants awarded in results in the European Journal the 2016 round were worth of Surgical Oncólogy. This €2,307,508. The success rate publication revealed that very of the projects was notably high satisfactory results had been at 50%. obtained overall. Using the da Vinci robot, there is much less need for large incisions, and there are far fewer serious post- surgical complications.

Charcot-Marie-Tooth disease type 2G redefined by a new mutation in LRSAM1

IDIVAL’s Neurodegenerative IDIVAL participates in the largest Diseases Group participated ever genetic study of schizophrenia and made key contributions to this multinational work, which After analysing over 41,000 has concluded that this sub- people (21,000 individuals type of the disease, based on with schizophrenia and 20,000 the mutation causing it, should Some milestones 2016 News Stories from 2016

Stratification of patients with diffuse that this proposed intensive Deconstructing schizophrenia: new large B-cell lymphoma treated with treatment of the donor does discoveries reveal altered cerebral chemoimmunotherapy: GCB/non- not affect the availability of the physiological processes GCB by immunohistochemistry is other donated organs (heart, still a robust and feasible marker liver, pancreas, and kidneys); in The article published recently fact, it increases the availability in the journal Nature by IDIVAL’s Cancer Genomics of cardiac inserts. Sekar et al. is an outstanding Group coordinates an genetic and neurobiological international multicentre study representing a major study that validates the breakthrough, demonstrating effectiveness of a method based that genetic anomalies (gen on immunohistochemistry. C4) and functional anomalies The work is a retrospective in immunological processes international multicentre A Valdecilla study concludes that (major histocompatibility study coordinated by the teenage binge drinking alters complex) could be causing Pathological Anatomy and cognitive functions alterations in normal brain Haematology departments development. Professor Crespo- of Marqués de Valdecilla The Cognitive Deterioration Facorro’s group (University of University Hospital/IDIVAL. Unit at Hospital Valdecilla, Cantabria-IDIVAL-CIBERSAM) It confirms the prognostic directed by Pascual Sánchez- collaborated in this international validity of this method based Juan, neurologist at Marqués research project. “Changes on the immunohistochemical de Valdecilla University in the structure of a gene study of tumoral samples from Hospital and IDIVAL researcher, associated with schizophrenia patients diagnosed with diffuse carried out a study to assess could lead to excessive loss large B-cell lymphoma. It also the effects of the “botellón” of inter-neuron connections in demonstrates the utility of a custom on some cognitive adolescence. Synaptic pruning diagnostic approach combining functions. The results obtained is a normal physiological immunohistochemical and show that young people process during brain fluorescent in situ hybridisation with a pattern of binge development, in which surplus techniques to assign the drinking at the weekends connections are eliminated in biological risk of each tumour present poorer performance order to optimise brain function. more precisely. in neuropsychological tests But excessive paring during this that assess attention span period alters mental functions.” and mental agility. The deficit observed is more marked in Based on powerful genome- women and in subjects who wide analyses, a zone in began consuming alcohol at an chromosome 6 had been earlier age. identified that includes various genes relating to the This study, the largest of this immune function, which is type performed to date, was very significantly related to Valdecilla researchers develop new published in the journal Plos schizophrenia. “This research treatment strategies to preserve One and studied 206 university is a step forward, not just for donor organs students at the Gimbernat- its discoveries, but also for Cantabria School, a centre the research model, working This prospective study led attached to the University of from genetic finds and gene by Eduardo Miñambres, Cantabria. expressions to the altered transplant coordinator at biological process.” “Having Hospital Valdecilla and IDIVAL Doctor Sánchez-Juan a specific variant of the C4 researcher, demonstrates highlighted that “these results gene apparently facilitates an the benefits of a triple are an alarm call on the immunological trigger that therapy to conserve donated effects of binge drinking on would lead to a faulty synaptic tissues, based on protective the immature brain, which is pruning, eliminating too many connections in the patients.” mechanical ventilation, invasive particularly significant given the haemodynamic monitoring high prevalence of this habit with water restriction, and the among young Spaniards” use of hormone therapy. The study included 618 multi-organ donors, and it demonstrated 59

The Valdecilla brand has over IDIVAL launches the innovation Valdecilla Research Institute 90,000 citations in international newsletter (IDIVAL), the University of Cantabria and the Institute of literature On 5 May IDIVAL launched a Biomedicine and Biotechnology R&D newsletter for biomedical of Cantabria have launched professionals in Cantabria. The The Valdecilla brand, created the SANTANDER BIOMEDICAL weekly newsletter covers the in 1929, has been cited over LECTURES programme, a main news in the field, with 90,000 times in the international series of lectures intended to information on R&D conferences biomedical literature, according advance worldwide Biomedical and funding opportunities to data from the Web of Science knowledge. The lectures bring in national and international to Santander prestigious platform. The Valdecilla is not grant announcements. It also international researchers just a consolidated brand in gathers the latest high-impact in fields such as Oncology, our region and in Spain, having publications in national and Neurology, Immunology, earned the respect and affection international journals. The weekly Regenerative Medicine, and of the people of Cantabria, and newsletter is designed and Microbiology. These lectures regarded as a benchmark in published by IDIVAL’s Innovation were an initiative of scientists certain medical fields by Spanish department and emailed to at the different research centres doctors. It is also well-known professionals on request. It is of Cantabria to create a forum internationally, as attested by also available on the IDIVAL for discussing current advances data from the scientific literature. website. in biomedicine, in which some The citations were calculated of our region’s research groups using the search term play a leading role. They will “Valdecilla” in the “address” field also be a discussion forum of the Web of Science (WOS) for young researchers and search engine. Remarkably, healthcare personnel in our hospitals, and for the general the first article by Valdecilla IDIVAL, in partnership with the public. researchers was cited in 1930 University of Cantabria and and 1941. This was the paper IBBTEC, launches the Santander published by Dr González Biomedical Lectures Aguilar: González-Aguilar, J. Contribution to the pathogeny The Biomedical Research of tendon tumours of giant Forum of Cantabria, consisting cells. Journal of Bone and Joint of Cantabria Healthcare Surgery, 1930; 12: 280-288. Services, the Marqués de

Annual citations in the period 1998-2016 of works identified with the descriptor “Valdecilla” in filiation

14000

12000

10000

8000

6000

4000

2000

0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 (fuente: WOS)

61

R&D activity IDIVAL R&D activity IDIVAL IDIVAL Funding in 2016

IDIVAL FUNDING IN 2016

Revenue

IDIVAL recorded total revenue of representing 31.2% of total at national and international levels €6.98 million in 2016. The revenue revenue. The remaining revenue (€2.53 million) and to the private pertaining to the Government (68.8%) pertains to the public and agreements and contracts signed of Cantabria was €2.18 million, private competitive programmes during the year (€2.25 million)

ORIGIN OF REVENUES 2016 IDIVAL 2016

Government of Cantabria 2.178.554,00 Competitive calls 2.526.390,63 Regional programs 22.586,49 National R & D & I Plan 2.306.428,24 Programs European Commission 16.648,79 Private Competitive Aid 180.727,11 Private contracts and agreements 2.249.767,36 Clinical Trials 583.914,86 Service Contracts 584.655,10 Collaboration Agreements 356.652,80 Donations 724.544,60 Provision of services 20.521,49 Total income 6.975.233,48 €

31,2% 32,2%

Competitive funding

36,2% Private funding Cantabria government 63

Expenditure

IDIVAL’s expenditure is essentially In 2016, it allocated a total of €2.84 The IDIVAL grant programme allocated to developing self-funded million to developing projects with represented expenditure of research projects, to the IDIVAL specific funding, €1.93 million to €760,000 (Post-MIR Valdecilla research grant programme and to structural, costs and €230,000 to López Albo contracts, pre-doctoral structural costs (support personnel, investments. contracts, co-financing of projects in-house research personnel and and contracts, etc.). operational costs)

Personnel

In 2016, IDIVAL had 29 Research Researcher Programmes Number Groups, consisting of researchers, collaborators and technical Miguel Servet Programme (ISCIII) 2 personnel, all belonging to the IDIVAL Researchers 6 Marqués de Valdecilla University Hospital and the University of Research Training Programme Number Cantabria. Of these research Rio Hortega Programme (ISCIII) 1 groups, 16 are consolidated, 2 emerging, 8 clinical, 1 newly Sara Borell Programme (ISCIII) 2 created and 2 cross-disciplinary. Wenceslao López Albo Programme (IDIVAL) 9 Of these, 20 are directed by head researchers involved with clinical IDIVAL Predoctoral programme 5 activity, 7 by researchers of the MINECO Predoctoral programme 1 University of Cantabria and 2 by Institute researchers. Contracts for Research Projects Number IDIVAL-funded contracts 21 In 2016, these groups had a ISCIII contracts 20 total of 650 members, of which 59 were Main researchers on MICINN contracts 3 projects developed through Privately-funded contracts 45 competitive funding in active national or international calls over Support Services Number the last five years (2011-2015). Scren Programme (ISCIII) 2 Personnel contracted by IDIVAL Biobank network (ISCIII) 1 during 2016 belong to the ITEMAS Platform (ISCIII) 3 following programmes: Infrastructure technicians (ISCIII) 1 IDIVAL support personnel 12 ISCIII Healthcare Research Manager 1 Research Management Training Programme Number IDIVAL Healthcare Research Manager 2 R&D activity IDIVAL Scientific output in 2016

Publications

In terms of production activity, in 2016 (excluding conference last author belongs to IDIVAL. IDIVAL researchers have papers published in journals). In published 493 indexed papers 246 papers (49.9%), the first or

Impact factor

In 2016. the cumulative impact factor publications with an impact factor impact factor in the first decile of the of IDIVAL group publications was in the first quartile was 40%, and subject category.. 1915 (JCR 2015), the percentage of 70 papers published in 2016 had an

Citations

The first article by Valdecilla Joint Surgery, 1930; 12: 280-288. affiliation field). Thus, in 2016 researchers was cited in 1930 the Valdecilla brand exceeded an and 1941. This was the paper Throughout 2016, the Valdecilla accumulated 101,000 citations, and published by Dr González Aguilar: brand obtained 12,711 citations, more than 150 works exceeded González-Aguilar J. Contribution to according to data from the ISI 100 citations, with the number the pathogeny of tendon tumours Web of Knowledge platform (using of citations obtained annually of giant cells. Journal of Bone and the descriptor “Valdecilla” in the continuing to increase.

2016 IDIVAL PUBLICATIONS, DISTRIBUTED BY QUARTILE

200 199 175

150

125 140 100

75

80 50 72

25

0 Q1 Q2 Q3 Q4 65

EVOLUTION OF THE TOTAL IMPACT FACTOR AND THE AVERAGE IMPACT FACTOR

2000

1750 1.949 1.915 1.788 1.795 1500 1.549 1250

1000

750

500

250

0 2012 2013 2014 2015 2016

EVOLUTION OF THE DISTRIBUTION BY QUARTERS OF THE IMPACT FACTOR. DISTRIBUTION BY CUARTILES

Year Q1 Q2 Q3 Q4 Total

N % N % N % N %

2012 188 51,6% 69 19,0% 64 17,6% 43 11,81% 364 2013 170 44,2% 98 25,5% 63 16,4% 54 14,0% 385 2014 171 52,1% 73 22,3% 56 17,1% 28 8,5% 328 2015 207 49,1% 99 23,5% 72 17,1% 44 10,4% 422 2016 199 40,4% 142 28,8% 80 16,2% 72 14,6% 493

200 207 199 188 175 170 171 150

125 142

100 98 99 75 80 73 72 72 69 65 50 63 56 54 43 44 25 28

0 Q1 Q2 Q3 Q4

2012 2013 2014 2015 2016 R&D activity IDIVAL Scientific output in 2016

IDIVAL PUBLICATIONS IN 2016 ACCORDING TO IMPACT FACTOR

(Excluding those derived from multicentre collaborations)

Journa IF (JCR 2015) Nº IF Suma Cuartil Decil

ACTA DIABETOL 3,074 1 3,074 2 5

ACTAS UROL 0,964 ESP 5 4,82 4 9

ADV HEALTHC MATER 5,76 1 5,76 1 1

ADV THER 2,503 1 2,503 2 5

AGING (ALBANY NY) 3,979 3 11,937 2 4

AIDS REV 2,068 1 2,068 4 8

ALLERGOL IMMUNOPATHOL (MADR) 1,689 1 1,689 4 8

ALLERGY 6,335 3 19,005 1 1

AM J CARDIOL 3,154 4 12,616 2 4

AM J CRIT CARE 2,053 1 2,053 3 7

AM J DERMATOPATHOL 1,396 1 1,396 3 7

AM J RESPIR CRIT CARE MED 13,118 4 52,472 1 1

AM J SURG PATHOL 4,951 2 9,902 1 2

AM J TRANSPLANT 5,669 3 17,007 1 1

AN PEDIATR (BARC) 0,773 3 2,319 4 9

ANN HEMATOL 3,022 2 6,044 2 5

ANN NEUROL 9,638 1 9,638 1 1

ANN ONCOL 9,269 1 9,269 1 1

ANN RHEUM 12,384 DIS 1 12,384 1 1

ANTICANCER 1,895 RES 1 1,895 3 8

ANTIMICROB AGENTS CHEMOTHER 4,415 3 13,245 1 2

APPL PHYSIOL NUTR METAB 1,91 1 1,91 3 7

ARCH BRONCONEUMOL 1,771 3 5,313 3 8

ARCH ESP UROL 0,307 2 0,614 4 10

ARTHRITIS CARE RES (HOBOKEN) 3,229 1 3,229 2 4

ARTHRITIS RES THER 3,979 1 3,979 1 3

ARTHRITIS RHEUMATOL 6,009 4 24,036 1 2

ATHEROSCLEROSIS 3,942 1 3,942 1 2

AUTOIMMUN 8,49 REV 1 8,49 1 1

BEST PRACT RES CLIN RHEUMATOL 3,267 2 6,534 2 4

BIOL BLOOD MARROW TRANSPLANT 3,98 1 3,98 1 2

BIOMED OPT EXPRESS 3,344 1 3,344 2 3 67

Journa IF (JCR 2015) Nº IF Suma Cuartil Decil

BLOOD 11,847 2 23,694 1 1

BMC CANCER 3,265 3 9,795 2 4

BMC MED 8,005 1 8,005 1 1

BMC NEUROL 1,961 1 1,961 3 6

BMC PULM 2,329MED 1 2,329 3 6

BMJ OPEN 2,562 1 2,562 1 3

BONE 3,736 1 3,736 2 3

BONE MARROW TRANSPLANT 3,636 2 7,272 2 3

BR J CANCER 5,569 1 5,569 1 2

BR J HAEMATOL 5,812 1 5,812 1 2

BR J NEUROSURG 1,063 1 1,063 4 9

BRAIN BEHAV IMMUN 5,874 1 5,874 1 2

BRAIN IMAGING BEHAV 3,667 1 3,667 2 3

BREAST CANCER RES 5,211 1 5,211 1 2

BREAST CARE (BASEL) 1,645 1 1,645 3 7

CALCIF TISSUE 3,052 INT 1 3,052 2 5

CANCER EPIDEMIOL 2,644 2 5,288 3 6

CANCER LETT 5,992 1 5,992 1 2

CANCER MED 2,915 1 2,915 3 6

CARDIOVASC DIABETOL 4,534 1 4,534 1 2

CARDIOVASC 5,465 RES 1 5,465 1 2

CATHETER CARDIOVASC INTERV 2,181 2 4,362 3 6

CELL SIGNAL 4,191 1 4,191 2 4

CELL TISSUE 2,948 RES 1 2,948 3 6

CEPHALALGIA 6,052 1 6,052 1 1

CEREBELLUM 2,429 1 2,429 3 6

CHEST 6,136 1 6,136 1 2

CIR 1 ESP 1 1 3 7

CIRC CARDIOVASC INTERV 5,706 1 5,706 1 2

CIRC 4,124 J 1 4,124 1 3

CIRCULATION 17,202 1 17,202 1 1

CLIMACTERIC 2,492 1 2,492 2 3

CLIN CANCER 8,738 RES 2 17,476 1 1

CLIN CARDIOL 2,431 1 2,431 2 5

CLIN CHEM LAB MED 3,017 1 3,017 1 2

CLIN CHIM ACTA2,799 1 2,799 1 3 R&D activity IDIVAL Scientific output in 2016

Journa IF (JCR 2015) Nº IF Suma Cuartil Decil

CLIN EXP IMMUNOL 3,148 1 3,148 2 5

CLIN EXP RHEUMATOL 2,495 25 62,375 2 5

CLIN GASTROENTEROL HEPATOL 7,68 2 15,36 1 1

CLIN IMMUNOL 4,034 1 4,034 2 3

CLIN MICROBIOL INFECT 4,575 2 9,15 1 2

CLIN NEUROPHYSIOL 3,426 1 3,426 2 3

CLIN NEUROPSYCHOL 1,556 1 1,556 3 8

CLIN NUCL MED4,278 1 4,278 1 2

CLIN PHYSIOL FUNCT IMAGING 1,869 1 1,869 3 7

CLIN SCI (LOND) 5,016 1 5,016 1 2

CLIN TRANSL ONCOL 2,075 3 6,225 3 8

CNS DRUGS 4,91 1 4,91 1 2

COLORECTAL 2,452 DIS 1 2,452 3 6

COMPUT BIOL MED 1,521 1 1,521 2 5

DERMATOLOGY 1,449 1 1,449 3 6

DIABETES CARE 8,934 1 8,934 1 1

DIAGN MICROBIOL INFECT DIS 2,45 3 7,35 3 6

DIS MODEL 4,316MECH 1 4,316 2 4

DRUG RESIST UPDAT 7,95 1 7,95 1 1

EARLY INTERV PSYCHIATRY 2,889 1 2,889 2 4

ELECTROPHORESIS 2,482 1 2,482 2 5

EMERG MICROBES INFECT 4,012 1 4,012 2 4

EMERGENCIAS 2,917 1 2,917 1 2

ENDOCRINOL NUTR 1,314 3 3,942 4 9

ENDOSCOPY 5,634 1 5,634 1 2

ENFERM INFECC MICROBIOL CLIN 1,53 3 4,59 3 8

ENVIRON. HEALTH PERSPECT. 8,443 2 16,886 1 1

EPIDEMIOL PSYCHIATR SCI 2,847 1 2,847 2 4

EUR ARCH PSYCHIATRY CLIN NEUROSCI 4,113 1 4,113 1 2

EUR EAT DISORD REV 2,912 1 2,912 2 4

EUR HEART 15,064J 5 75,32 1 1

EUR HEART J CARDIOVASC IMAGING 4,293 1 4,293 1 3

EUR J APPL PHYSIOL 2,328 1 2,328 2 5

EUR J CANCER 6,163 1 6,163 1 2

EUR J CARDIOTHORAC SURG 2,803 2 5,606 2 5

EUR J EPIDEMIOL 7,105 1 7,105 1 1 69

Journa IF (JCR 2015) Nº IF Suma Cuartil Decil

EUR J HAEMATOL 2,544 2 5,088 3 6

EUR J HUM 4,58GENET 1 4,58 1 3

EUR J INTERN MED 2,591 2 5,182 1 2

EUR J NUCL MED MOL IMAGING 5,537 3 16,611 1 1

EUR J SURG ONCOL 2,94 1 2,94 2 5

EUR UROL 14,976 1 14,976 1 1

EUROINTERVENTION 3,863 2 7,726 2 3

EUROPACE 4,021 1 4,021 2 3

EXP HEMATOL 2,303 1 2,303 3 6

EXP. OPIN. ORPHAN DRUGS 0,464 1 0,464 4 10

EXPERT OPIN DRUG METAB TOXICOL 2,598 2 5,196 3 6

EXPERT REV ANTICANCER THER 2,094 1 2,094 3 8

EXPERT REV CLIN IMMUNOL 2,596 1 2,596 3 6

FREE RADIC BIOL MED 5,784 1 5,784 1 2

FRONT AGING NEUROSCI 4,348 1 4,348 1 2

FRONT IMMUNOL 5,695 1 5,695 1 2

FRONT NEUROL 3,184 1 3,184 2 4

FRONT PSYCHOL 2,463 2 4,926 1 0

FUTURE MICROBIOL 3,637 1 3,637 2 3

GAC SANIT 1,509 1 1,509 3 7

GASTROENTEROL HEPATOL 0,8 1 0,8 4 9

GASTROINTEST ENDOSC 6,217 1 6,217 1 2

GENE 2,319 1 2,319 3 6

GENES CHROMOSOMES CANCER 3,96 1 3,96 1 3

GENES GENOM 0,692 1 0,692 4 10

HAEMATOLOGICA 6,671 1 6,671 1 1

HEADACHE 2,961 3 8,883 2 4

HEART 5,693 1 5,693 1 2

HEPATOL INT 1,125 1 1,125 4 9

HIPPOCAMPUS 4,074 1 4,074 1 3

HORM RES PAEDIAT 1,661 1 1,661 2 5

HUM IMMUNOL 2,127 1 2,127 3 8

IMMUNOBIOLOGY 2,781 1 2,781 3 6

IMMUNOLOGY 4,078 1 4,078 2 3

IMMUNOTHERAPY 2,083 1 2,083 3 8

INFLAMM BOWEL DIS 4,358 1 4,358 1 3 R&D activity IDIVAL Scientific output in 2016

Journa IF (JCR 2015) Nº IF Suma Cuartil Decil

INJURY 1,91 1 1,91 3 8

INT BRAZ J UROL0,871 2 1,742 4 9

INT IMMUNOL 3,031 1 3,031 2 5

INT J ANTIMICROB AGENTS 4,097 1 4,097 1 2

INT J CANCER 5,531 3 16,593 1 2

INT J CARDIOL 4,638 5 23,19 1 2

INT J COLORECTAL DIS 2,383 1 2,383 3 6

INT J INFECT 2,229 DIS 1 2,229 3 6

INT J MOL SCI 3,257 1 3,257 2 4

INT J NEUROPSYCHOPHARMACOL 4,333 1 4,333 1 2

INTENSIVE CARE MED 10,125 1 10,125 1 1

J ACAD NUTR 3,609 DIET 1 3,609 1 3

J ALZHEIMERS 3,92 DIS 1 3,92 1 3

J AM ACAD DERMATOL 5,621 1 5,621 1 1

J ANTIMICROB CHEMOTHER 4,919 4 19,676 1 2

J CARDIOVASC SURG (TORINO) 1,632 1 1,632 3 7

J CLIN GASTROENTEROL 3,163 1 3,163 2 4

J CLIN LIPIDOL 4,906 1 4,906 1 1

J CLIN NEUROPHYSIOL 1,337 1 1,337 4 8

J CLIN ONCOL 20,982 2 41,964 1 1

J CLIN PSYCHIATRY 5,408 1 5,408 1 2

J CLIN SLEEP 2,71 MED 1 2,71 2 4

J CLIN VIROL 2,647 2 5,294 2 5

J CRANIOFAC SURG 0,7 1 0,7 4 9

J CROHNS COLITIS 6,585 1 6,585 1 2

J CUTAN PATHOL 1,409 2 2,818 3 7

J DERMATOL 1,577 2 3,154 2 5

J EUR ACAD DERMATOL VENEREOL 3,029 2 6,058 1 2

J EXP MED 11,24 1 11,24 1 1

J GERONTOL A BIOL SCI MED SCI 5,476 1 5,476 1 1

J HEART LUNG TRANSPLANT 7,509 1 7,509 1 1

J HUM GENET 2,487 1 2,487 3 6

J IMMUNOL 2,812 RES 1 2,812 3 6

J INFECT 4,382 3 13,146 1 2

J INVEST DERMATOL 6,915 1 6,915 1 1

J LARYNGOL 0,736 OTOL 1 0,736 4 9 71

Journa IF (JCR 2015) Nº IF Suma Cuartil Decil

J LUMIN 2,693 1 2,693 1 2

J MATER CHEM C MATER OPT ELECTRON DEVICES 5,066 1 5,066 1 2

J NATL COMPR CANC NETW 4,262 1 4,262 1 3

J NEUROL 3,408 3 10,224 2 3

J NEUROL SCI 2,126 2 4,252 3 6

J NEUROONCOL 2,754 1 2,754 2 4

J NON-CRYST SOLIDS 1,825 1 1,825 1 2

J PHYS CHEM 4,509 C 1 4,509 1 3

J PINEAL RES 9,314 1 9,314 1 1

J PLAST RECONSTR AESTHET SURG 1,743 1 1,743 2 5

J PROTEOMICS 3,867 1 3,867 1 2

J RHEUMATOL 3,236 2 6,472 2 4

J THERM ANAL CALORIM 1,781 1 1,781 2 4

J THORAC CARDIOVASC SURG 3,494 2 6,988 2 3

J TRANSL MED 3,694 1 3,694 1 3

J VASC SURG VENOUS LYMPHAT DISORD 0,882 1 0,882 3 8

J. NEUROL. NEUROSURG. PSYCHIATRY 6,431 2 12,862 1 1

JACC CARDIOVASC INTERV 7,63 2 15,26 1 1

JAMA PSYCHIATRY 14,417 1 14,417 1 1

LANCET NEUROL 23,468 1 23,468 1 1

LANGENBECKS ARCH SURG 2,149 1 2,149 2 4

LEUK LYMPHOMA 3,093 2 6,186 2 4

LEUK RES 2,606 1 2,606 3 6

LEUKEMIA 12,104 2 24,208 1 1

LIFE 2,685 SCI 1 2,685 2 5

LIVER TRANSPL 3,951 1 3,951 1 3

MATURITAS 3,12 1 3,12 2 4

MED CLIN (BARC) 1,267 12 15,204 2 5

MED INTENSIVA 1,193 5 5,965 4 10

MEDIATORS INFLAMM 3,418 1 3,418 2 4

MEDICINE (BALTIMORE) 2,133 4 8,532 2 3

MICROBES INFECT2,291 1 2,291 3 7

MOL NEUROBIOL 5,397 1 5,397 1 2

MOL PSYCHIATRY 13,314 1 13,314 1 1

MOV DISORD 6,01 1 6,01 1 1 R&D activity IDIVAL Scientific output in 2016

Journa IF (JCR 2015) Nº IF Suma Cuartil Decil

NANO LETT 13,779 1 13,779 1 1

NANOMATERIALS (BASEL) 2,69 1 2,69 1 3

NANOSCALE 7,76 1 7,76 1 2

NAT COMMUN 11,329 1 11,329 1 1

NAT NEUROSCI 16,724 2 33,448 1 1

NAT REV GASTROENTEROL HEPATOL 14,435 1 14,435 1 1

NAT REV RHEUMATOL 10,531 1 10,531 1 1

NEFROLOGIA 1,207 7 8,449 4 8

NEPHROL DIAL TRANSPLANT 4,085 1 4,085 1 2

NEUROBIOL AGING 5,153 2 10,306 1 2

NEUROCHEM 2,472 RES 1 2,472 3 6

NEURODEGENER DIS 2,937 1 2,937 2 4

NEUROENDOCRINOLOGY 2,583 6 15,498 3 6

NEUROIMAGING CLIN N AM 1,557 1 1,557 3 7

NEUROL SCI 1,783 1 1,783 3 7

NEUROLOGY 8,166 1 8,166 1 1

NEUROMUSCUL DISORD 3,107 1 3,107 2 4

NEUROPATHOL APPL NEUROBIOL 4,483 1 4,483 1 2

NEUROSCI BIOBEHAV REV 8,58 1 8,58 1 1

NEUROSURGERY 3,78 1 3,78 1 3

NEUROTOX RES3,14 1 3,14 2 4

NPJ PRIM CARE RESPIR MED 1,447 1 1,447 3 6

NUCL MED COMMUN 1,453 1 1,453 3 8

NUTR HOSP 1,497 1 1,497 3 8

OCCUP ENVIRON MED 3,745 1 3,745 1 2

OCUL IMMUNOL INFLAMM 2,481 2 4,962 2 4

ONCOGENE 7,932 1 7,932 1 1

ONCOL. RES. TREAT. 1,333 2 2,666 4 9

ONCOTARGET 5,008 6 30,048 1 3

OPT LASER TECHNOL 1,879 1 1,879 2 4

OSTEOPOROS 3,445 INT 1 3,445 2 4

PATHOL RES PRACT 1,388 4 5,552 3 7

PATIENT EDUC COUNS 2,232 1 2,232 2 4

PHYS CHEM CHEM PHYS 4,449 1 4,449 1 3

PLOS ONE 3,057 11 33,627 1 2

POLYMERS-BASEL 2,944 1 2,944 1 3 73

Journa IF (JCR 2015) Nº IF Suma Cuartil Decil

PROG NEUROBIOL 13,177 1 13,177 1 1

PSYCHOPHARMACOLOGY (BERL) 3,54 1 3,54 2 4

QJM 2,824 2 5,648 1 2

RADIOTHER ONCOL 4,817 1 4,817 1 2

RESPIR MED 3,036 1 3,036 2 4

REV ESP ENFERM DIG 1,455 2 2,91 4 9

REV ESP MED NUCL IMAGEN MOL 0,983 3 2,949 4 9

REV ESP QUIMIOTER 1,014 5 5,07 4 9

REV NEUROL 0,684 11 7,524 4 10

REV PSIQUIATR SALUD MENT 1,65 1 1,65 3 7

RHEUMATOL 1,702 INT 1 1,702 3 8

RHEUMATOLOGY (OXFORD) 4,524 3 13,572 1 2

ROM J MORPHOL EMBRYOL 0,811 1 0,811 4 10

SCAND J GASTROENTEROL 2,199 1 2,199 3 7

SCI 5,228 REP 8 41,824 1 2

SEIZURE 2,109 2 4,218 3 6

SEMIN ARTHRITIS RHEUM 3,946 3 11,838 2 3

SIMUL HEALTHC 1,685 1 1,685 3 6

SKELETAL RADIOL 1,527 1 1,527 2 5

SLEEP BREATH 2,332 1 2,332 2 5

SOL ENERGY MATER SOL CELLS 4,732 1 4,732 1 2

THER DRUG MONIT 2,094 3 6,282 2 4

THORAX 8,121 1 8,121 1 1

THROMB HAEMOST 5,255 3 15,765 1 2

THROMB RES 2,32 2 4,64 3 7

TRANSPL IMMUNOL 1,317 1 1,317 4 10

TRANSPL INT 2,835 2 5,67 1 2

TRANSPLANT PROC 0,867 10 8,67 4 10

TRANSPLANT REV (ORLANDO) 3,915 1 3,915 2 4

TRANSPLANTATION 3,69 2 7,38 2 4

UROLOGY 2,187 1 2,187 2 4

WOMEN HEALTH 1,294 1 1,294 1 2

WORLD J GASTROENTEROL 2,787 2 5,574 2 5

WORLD J UROL 2,397 1 2,397 2 4

WORLD NEUROSURG 2,685 3 8,055 2 4

Total general 493 1915,369 R&D activity IDIVAL Scientific output in 2016

Impact Factor The number of works by IDIVAL factors are shown in the following of Research research groups and their impact table: Groups

GROUP Nº of works IF Total

Pathological anatomy and molecular pathology 18 36,4555 Apoptosis 3 12,492 Nuclear Cell Biology 7 24,839 Cell cycle, stem cells and cancer 4 21,835 Cytokines and growth factors in pathological tissue plasticity phenomena 11 47,704 Clinic and genetics of headaches 11 43,673 Diagnosis and treatment by image 8 32,138 Neurodegenerative diseases 33 123,897 Genetic epidemiology and atherosclerosis in systemic inflammatory diseases 72 264,243 Epidemiology and pathogenic mechanisms of infectious diseases 30 98,636 Epidemiology and public health 36 145,435 Transplantation hemopathology 37 164,141 Nanovaccines and cellular vaccines based on listeria monocytogenes and its applications in biomedicine 6 25,070 Group of cardiovascular investigation 21 140,623 Molecular image 21 61,852 Infection and immunity and digestive pathology 26 116,186 Immunopathology of rheumatic diseases 13 56,390 Melatonin and breast cancer 3 9,331 Mineral and lipid metabolism 36 103,717 Clinical and molecular microbiology 31 94,143 Advanced microscopy and folding of proteins and cytoskeleton 1 4,348 Nanomedicine 13 58,565 Hematological neoplasms and hematopoietic progenitors transplantation 14 51,393 Neurophysiology in epilepsy and neurointensive 5 18,524 New techniques in abdominal surgery 11 21,292 Psychiatry 23 130,588 Cellular signaling and therapeutic targets in cancer 11 30,862 Transplantation and autoimmunity 48 118,768 Unit of clinical trials and medical oncology and palliative medicine 29 104,217 75

Chinarro B, Orosa-Bertol B, Martinez- 8. Orta-Mascaró M, Consuegra- Garcia MA. Fernández M, Carreras E, Roncagalli R, Some of the most Spanish Sleep Network. Continuous Carreras-Sureda A, Alvarez P, Girard L, Positive Airway Pressure Improves Simões I, Martínez-Florensa M, Aranda Representative Quality of Life in Women with F, Merino R, Martínez VG, Vicente R, Obstructive Sleep Apnea. A Merino J, Sarukhan A, Malissen M, Articles Randomized Controlled Trial. Malissen B, Lozano F. Am J Respir Crit Care Med 2016. 194: CD6 modulates thymocyte selection 1286-1294. FI: 13,118(Q1) and peripheral T cell homeostasis. J Exp Med 2016. 213: 1387-1397. 1. Adams HH, Hibar DP, Chouraki FI: 11,240(Q1) V, Stein JL, Nyquist PA, Rentería 5. García-Hevia L, Valiente R, Martín- ME, Trompet S, Arias-Vasquez A, Rodríguez R, Renero-Lecuna C, Seshadri S, Desrivières S, Beecham González J, Rodríguez-Fernández L, 9. Peeters K, Palaima P, Pelayo- AH, Jahanshad N, Wittfeld K, Van der Aguado F, Villegas JC, Fanarraga ML. Negro AL, García A, Gallardo E, Lee SJ, Abramovic L, Alhusaini S, Nano-ZnO leads to tubulin García-Barredo R, Mateiu L, Baets J, Amin N, Andersson M, Arfanakis K, macrotube assembly and actin Menten B, De Vriendt E, De Jonghe P, Aribisala BS, Armstrong NJ, Athanasiu bundling, triggering cytoskeletal Timmerman V, Infante J, Berciano J, L, Axelsson T, Beiser A, Bernard M, Bis catastrophe and cell necrosis. Jordanova A. JC, Blanken LM, Blanton SH, Bohlken NANOSCALE 2016. 8: 10963-10973. Charcot-Marie-Tooth disease type MM, ..., Thompson PM. FI: 7,760(Q1) 2G redefined by a novel mutation in Novel genetic loci underlying LRSAM1. human intracranial volume identified Ann Neurol 2016. 80: 823-833. through genome-wide association. 6. Márquez A, Vidal-Bralo L, FI: 9,638(Q1) Nat Neurosci 2016. 19: 1569-1582. Rodríguez-Rodríguez L, González- FI: 16,724(Q1) Gay MA, Balsa A, González-Álvaro I, Carreira P, Ortego-Centeno N, 10. Perelló CS, Fernández-Carrillo C, Ayala-Gutiérrez MM, García-Hernández Londoño MC, Arias-Loste T, Hernández- 2. Berciano J, Gallardo E, Orizaola P, FJ, González-Escribano MF, Sabio Conde M, Llerena S, Crespo J, Forns X, Marco de Lucas E, García A, Pelayo- JM, Tolosa C, Suárez A, González A, Calleja JL. Negro AL, Sedano MJ. Padyukov L, Worthington J, Vyse T, Reactivation of Herpesvirus in Early axonal Guillain-Barré syndrome Alarcón-Riquelme ME, Martín J. Patients With Hepatitis C Treated with normal peripheral conduction: A combined large-scale meta- With Direct-Acting Antiviral Agents. imaging evidence for changes in analysis identifies COG6 as a novel Clin Gastroenterol Hepatol 2016. proximal nerve segments. shared risk locus for rheumatoid FI: 7,680(Q1) J Neurol Neurosurg Psychiatry 2016. arthritis and systemic lupus 87: 563-565. FI: 6,431(Q1) erythematosus. Ann Rheum Dis 2017. 76: 286-294. 11. Robles EF, Mena-Varas M, Barrio FI: 12,384(Q1) L, Merino-Cortes SV, Balogh P, Du MQ, 3. Cabezas J, Sampedro B, Hernández Akasaka T, Parker A, Roa S, Panizo C, C, Crespo J. Martin-Guerrero I, Siebert R, Segura Computerized Physician Order Entry- 7. Masa JF, Corral J, Caballero C, V, Agirre X, Macri-Pellizeri L, Aldaz B, Based System Improves Hepatitis Barrot E, Terán-Santos J, Alonso- Vilas-Zornoza A, Zhang S, Moody S, B Virus Screening in Patients Álvarez ML, Gomez-Garcia T, González Calasanz MJ, Tousseyn T, Broccardo Undergoing Chemotherapy. M, López-Martín S, De Lucas P, C, Brousset P, Campos-Sanchez J Clin Oncol 2016. 34: 290-0. Marin JM, Marti S, Díaz-Cambriles E, Cobaleda C, Sanchez-Garcia I, FI: 20,982(Q1) T, Chiner E, Egea C, Miranda E, Fernandez-Luna JL, Garcia-Muñoz Mokhlesi B, Spanish Sleep Network, R, Pena E, ..., Martinez-Climent JA. García-Ledesma E, Sánchez-Quiroga Homeobox NKX2-3 promotes 4. Campos-Rodriguez F, Queipo- MÁ, Ordax E, González-Mangado marginal-zone lymphomagenesis by Corona C, Carmona-Bernal C, N, Troncoso MF, Martinez-Martinez activating B-cell receptor signalling Jurado-Gamez B, Cordero-Guevara J, MÁ, Cantalejo O, Ojeda E, Carrizo SJ, and shaping lymphocyte dynamics. Reyes-Nuñez N, Troncoso-Acevedo Gallego B, Pallero M, ..., Bengoa M. Nat Commun 2016. 7: 11889-0. F, Abad-Fernandez A, Teran-Santos J, Non-invasive ventilation in obesity FI: 11,329(Q1) Caballero-Rodriguez J, Martin-Romero hypoventilation syndrome without M, Encabo-Motiño A, Sacristan-Bou L, severe obstructive sleep apnoea. Navarro-Esteva J, Somoza-Gonzalez M, Thorax 2016. 71: 899-906. 12. Roncero AM, López-Nieva P, Masa JF, Sanchez-Quiroga MA, Jara- FI: 8,121(Q1) Cobos-Fernández MA, Villa-Morales M, R&D activity IDIVAL Some of the most Representative Articles

González-Sánchez L, López-Lorenzo Fontano E, Sjoberg DD, Russo P, 18. Setién-Suero E, Suárez-Pinilla M, JL, Llamas P, Ayuso C, Rodríguez- Coleman JA, Akin O, Touijer KA. Suárez-Pinilla P, Crespo-Facorro B, Pinilla SM, María Del CA, Piris M, An Arterial Based Complexity Ayesa-Arriola R. Fernández-Navarro P, Fernández (ABC) Scoring System to Assess Homocysteine and cognition: A AF, Fraga MF, Santos J, Fernández- the Morbidity Profile of Partial systematic review of 111 studies. Piqueras J. Nephrectomy. Eur Urol 2016. 69: 72- Neurosci Biobehav Rev 2016. 69: Contribution of JAK2 mutations 79. FI: 14,976(Q1) 280-298. FI: 8,580(Q1) to T-cell lymphoblastic lymphoma development. Leukemia 2016. 30: 94-103. 16. van Erp TG, Hibar DP, 19. López-Mejías R, Castañeda S, FI: 12,104(Q1) Rasmussen JM, Glahn DC, Pearlson González-Juanatey C, Corrales A, GD, Andreassen OA, Agartz I, Ferraz-Amaro I, Genre F, Remuzgo- Westlye LT, Haukvik UK, Dale AM, Martínez S, Rodriguez-Rodriguez 13. Sanchez-Barcelo EJ, Mediavilla Melle I, Hartberg CB, Gruber O, L, Blanco R, Llorca J, Martín J, MD, Vriend J, Reiter RJ. González-Gay MA. Kraemer B, Zilles D, Donohoe G, Kelly Constitutive photomorphogenesis Cardiovascular risk assessment in S, McDonald C, Morris DW, Cannon protein 1 (COP1) and COP9 patients with rheumatoid arthritis: DM, Corvin A, Machielsen MW, signalosome, evolutionarily The relevance of clinical, genetic Koenders L, de Haan L, Veltman DJ, conserved photomorphogenic and serological markers. Satterthwaite TD, Wolf DH, Gur RC, proteins as possible targets of Autoimmun Rev 2016. 15: 1013- Gur RE, ..., melatonin. 1030. FI: 8,490(Q1) Turner JA. Subcortical brain J Pineal Res 2016. 61: 41-51. volume abnormalities in 2028 FI: 9,314(Q1) individuals with schizophrenia 20. Remuzgo-Martínez S, Genre F, and 2540 healthy controls via the López-Mejías R, Ubilla B, Mijares 14. Sanz B, Calatayud MP, Torres TE, ENIGMA consortium. V, Pina T, Corrales A, Blanco R, Fanarraga ML, Ibarra MR, Goya GF. Mol Psychiatry 2016. 21: 547-553. Martín J, Llorca J, González-Gay MA. Magnetic hyperthermia enhances FI: 13,314(Q1) Expression of osteoprotegerin and cell toxicity with respect to its ligands, RANKL and TRAIL, in exogenous heating. rheumatoid arthritis. BIOMATERIALS 2017. 114: 62-70. 17. Zufiría M, Gil-Bea FJ, Fernández- Sci Rep 2016. 6: 29713-0. FI: 8,387(Q1) Torrón R, Poza JJ, Muñoz-Blanco FI: 5,228(Q1) JL, Rojas-García R, Riancho J, de Munain AL.ALS: A bucket of genes, 15. Spaliviero M, Poon BY, Karlo environment, metabolism and CA, Guglielmetti GB, Di Paolo PL, unknown ingredients. Beluco Corradi R, Martin-Malburet Prog Neurobiol 2016. 142: 104-129. AG, Campos-Juanatey F, Escudero- FI: 13,177(Q1) 77

Research Projects

R&D+I NATIONAL PLAN PROJECTS ACTIVE OR GRANTED IN 2016

Active Grants

Throughout 2016, IDIVAL groups PI12/00999 molecular biomarkers and targeted maintained 34 active projects in the Juan Francisco Nistal Herrera. therapies. MINECO. 2014-2016.. R&D+i National Plan, 7 research Role of adiponectin and its contracts, and two European relationship with TGF beta in PI13/01008 projects. myocardial remodelling induced by Eloy Manuel Rodríguez pressure overload in aortic stenosis Rodríguez. and its post-surgical regression. Alzheimer’s disease biomarkers Projects CARLOS III HEALTH INSTITUTE. as prognostic factors in idiopathic 2013-2016. normal pressure hydrocephalus. PI12/02605 CARLOS III HEALTH INSTITUTE. María Victoria Mier Ruiz. PI12/00615. 2014-2016. Epidemiological aspects, variability José Antonio Riancho Moral. and survival in cardiac arrest care DNA Methylation: The pathogenic PI13/01310. outside hospital by emergency and biomarker factor in bone José Ramos Vivas. services in Spain (sub-project formation disorders. CARLOS III Clinically relevant host-pathogen Cantabria). CARLOS III HEALTH HEALTH INSTITUTE. 2013-2017. key interaction in Acinetobacter INSTITUTE. 2013-2016. species. CARLOS III HEALTH SAF2013-46292-R INSTITUTE. 2014-2016. PI12/02288 Benedicto Crespo Facorro. New Juan Pascual Sánchez. candidate genes for the response PI13/01760. Multimodal study of Alzheimer’s to antipsychotic treatment in José Luis Fernández Luna. disease biomarkers in postoperative schizophrenia: evidence from gene Prognostic and therapeutic cognitive decline. CARLOS III expression studies. MINECO. 2014- relevance in ODZ 1 glioblastoma, HEALTH INSTITUTE. 2013-2016. 2017. a new target in cancer. CARLOS III HEALTH INSTITUTE. 2014-2016. PI12/00060 SAF2013-47416-R Miguel Ángel González-Gay Miguel Ángel Piris Pinilla. PI13/01884. Mantecón. Aggressive lymphomas: treatment Eugenio Carrasco Marín. Study of genetic markers of guided by molecular diagnosis. Defects in innate immunity and cardiovascular disease and MINECO. 2014-2016. coinfection with respiratory viruses: subclinical atherosclerosis in the perfect storm to develop invasive rheumatoid arthritis patients. SAF2013-42012-P. pneumococcal disease in children? CARLOS III HEALTH INSTITUTE. Samuel Cos Corral. CARLOS III HEALTH INSTITUTE. 2013-2016. Sensitising effects of melatonin for 2014-2016. chemotherapy and radiotherapy: a PI12/01405 study of the molecular changes that PI13/01249. Jesús González Macías. modulate this process. MINECO. Juan Martino González. The canonical WNT pathway in 2014-2016. Preservation of areas involved in the osteoclast: study of its intervention verbal working memory to prevent in the regulation of bone mass. SAF2013-47434-R. sequelae in glioma surgery in CARLOS III HEALTH INSTITUTE. María amor Hurle González. eloquent areas. CARLOS III HEALTH 2013-2016. MicroRNAs in neuropathic pain: INSTITUTE. 2014-2016. R&D activity IDIVAL Research Projects

PI13/01191. Heteroresistance and Persistence migraines: case-control study. María del Carmen Fariñas in carbapenem-resistant Klebsiella Murine experimental model Álvarez. pneumoniae. CARLOS III HEALTH creation. CARLOS III HEALTH Intestinal colonisation by INSTITUTE. 2015-2017. INSTITUTE. 2016-2018. multiresistant enterobacteriaceae in patients with renal and liver PI15/00009. PI15/00069. transplants: multicentre cohort Alain Antonio Ocampo Sosa. Javier Llorca Díaz. study and randomised, controlled, Functional identification Integration of genetic big data and open clinical trial CARLOS III and characterisation of new clinical data: survival with breast HEALTH INSTITUTE. 2014-2016. components of type VI secretion cancer in the MCC-Spain study. systems and the molecular basis CARLOS III HEALTH INSTITUTE. BFU2014-54754-P. of their regulation in clinical strains 2016-2018. Mª Teresa Berciano Blanco, of Pseudomonas aeruginosa. Miguel Ángel Lafarga CARLOS III HEALTH INSTITUTE. PIE15/00079. Coscojuela. 2016-2018. Javier Crespo García. Acetylation regulation of the Personalized Medicine in HCV survival factor of motoneurons: its PI15/00521. infection: understanding and importance in snRNP biogenesis José Manuel Olmos Martínez. predicting hepatic and systemic and the assembly of CAJAL Study of bone and mineral responses in the era of the nuclear bodies. MINECO. 2015- metabolism of the post- new antiviral drugs. CARLOS III 2017. menopausal female and male HEALTH INSTITUTE. 2016-2018. population aged 50 and over BFU2014-54026-P. receiving care from a health centre PIE15/00081. Juan Hurle González. in Cantabria. CARLOS III HEALTH Miguel Ángel Piris Pinilla. Biological mechanism and new INSTITUTE. 2016-2018. Discovery, Validation and significance of the interdigital Implementation of Biomarkers for cell death responsible for the PI15/00525. Precision Oncology. CARLOS III separation of the fingers during Miguel Ángel González-Gay HEALTH INSTITUTE. 2016-2019. limb development. MINECO. 2015- Mantecón. RTC-2015-3786-1. 2017. Genetic markers of atherosclerotic disease in Rheumatoid Arthritis. Javier Gómez Román. PI14/00378. CARLOS III HEALTH INSTITUTE. Development of anti-CCR9 Manuel Antonio Árias Rodríguez. 2016-2018. therapeutic antibodies for the Study of serological factors and personalised treatment of tumours- cellular activation as potential PI15/01224. TERPERAN. CARLOS III HEALTH early markers of chronic antibody- Juan Francisco Nistal Herrera. INSTITUTE. 2016-2018. mediated rejection in renal Bone morphogenetic protein 7 DTS15/00238 transplants. CARLOS III HEALTH (BMP7): Potential therapeutic Olga María Conde Portilla. INSTITUTE. 2015-2017. target in the pathological remodelling of the cardiovascular Fusioderm, fusion of photonic PI14/00900. system. CARLOS III HEALTH technologies for dermatological Alberto Gandarillas Solinis. INSTITUTE. 2016-2018. diagnosis. CARLOS III HEALTH New Routes and Strategies INSTITUTE 2016-2017. Towards Squamous Cell Cancer. PI15/02138. CARLOS III HEALTH INSTITUTE. Javier Crespo García. 2015-2017. Endothelial dysfunction, subclinical atheromatous disease and PI14/00918. cardiomyopathy in patients with Rosa Ayesa Arriola. HCV infection. Characterisation PAFIP neurocognition: Long-term and potential reversibility with longitudinal study (10 years) of direct antiviral agents. CARLOS III cognitive functioning in patients HEALTH INSTITUTE. 2016-2018.. with schizophrenia spectrum psychosis. CARLOS III HEALTH PI15/01285. INSTITUTE. 2015-2017. Agustín Oterino Durán. Epigenetic modifications induced PI14/01911. by adverse childhood experiences Luis Martínez Martínez. and endothelial damage in chronic 79

Research and Mobility 2015-2017. BA15/00053 Contracts Santiago Montes Moreno. BES-2014-070615 CARLOS III HEALTH INSTITUTE CP12/03149 Fulgencio Ruso Julve. 2016. Alain Antonio Ocampo Sosa. Grants for pre-doctorate contracts. OprD analysis in clinical strains MINECO 2015-2019. of Pseudomonas aeruginosa with GIS15/00017 different carbapenem sensitivity Aroa Sanz Carreira. levels and study of the molecular Active European Projects Healthcare Research Management bases of OprD regulation Contracts in IIS. CARLOS III HEALTH in 2016 mechanisms. CARLOS III HEALTH INSTITUTE 2016-2018. INSTITUTE. 2013-2016. EU12/01- PSYSCAN. CD15/00095 MS12/03149 Benedicto Crespo Facorro. Fernanda Genre. Alain Antonio Ocampo Sosa. Translating neuroimaging findings Sara Borrell contracts. CARLOS III Miguel Servet Type I contracts, from research into clinical practice. HEALTH INSTITUTE 2016-2019. CARLOS III HEALTH INSTITUTE. 7PM. European Commission. 2013-2017. CM15/00186 EU13/01- Precisesads. Rufino Mondejar García. CD13/00088 Miguel Ángel González-Gay. Rio Hortega contracts. CARLOS III Cristina Pérez Menéndez. Sara Molecular Reclassification to Find HEALTH INSTITUTE 2016-2018. Borrell contracts. CARLOS III Clinically Useful Biomarkers for Systemic Autoimmune Diseases. HEALTH INSTITUTE. 2014-2017. INT15/00096 FP7, Innovative Medicines Benedicto Crespo Facorro. CPII14/00016 Contracts for intensification Initiative. European Commission. José Ramos Vivas. of research activity in the SNS Miguel Servet Type II contracts. CARLOS III HEALTH INSTITUTE CARLOS III HEALTH INSTITUTE. 2016.

Grants awarded

In 2016, IDIVAL researchers PI16/00915 PI16/01294 received a positive response on 13 José Antonio Riancho Moral. Miguel ángel Piris Pinilla. projects in the National Plan: Study of mesenchymal stem Aggressive lymphomas: Interaction cells in osteoporosis: Role of long between the tumour genome non-coding RNAs (lncRNAs) and and the microenvironment as a regenerative potential. CARLOS III determinant of progression and Proyectos HEALTH INSTITUTE. 2017-2019. response to therapy. CARLOS III HEALTH INSTITUTE. 2017-2019. PI16/00156 José Pedro Vaque Díez. PI16/01103 PI16/01397 New mechanisms in aggressive José Ramos Vivas. Santiago Montes Moreno. skin cancers: Applications to the Integrated biology of infection Targeted exonic next generation diagnosis, prognosis and treatment and antimicrobial resistance of sequencing for the molecular of therapy-resistant melanoma and Acinetobacter baumannii and diagnosis and cell free tumor DNA Merkel-cell carcinoma. CARLOS III A. pittii. CARLOS III HEALTH analysis as a screening method for HEALTH INSTITUTE. 2017-2019. INSTITUTE. 2017-2019. patients with DLBCL. CARLOS III HEALTH INSTITUTE. 2017-2019. R&D activity IDIVAL Research Projects

PI16/01415 regulator of TGF beta signalling, as There were also positive resolutions María del Carmen Fariñas Álvarez. a pathogenic factor and prognostic of the following programmes in Impact of intestinal colonisation by marker in rheumatoid arthritis. 2016: multiresistant enterobacteriaceae CARLOS III HEALTH INSTITUTE. in systemic infections, graft-versus- 2017-2019. host disease (GVHD), and mortality Ciber in patients receiving transplants of CP16/00033 allogeneic hematopoietic progenitor Raquel López Mejías. CB16/12/00291 cells (Alo-HCT). CARLOS III HEALTH Cardiovascular risk assessment in Miguel Ángel Piris Pinilla. INSTITUTE. 2017-2019. patients with rheumatoid arthritis: Cancer subject area, CARLOS III the relevance of genetic markers. HEALTH INSTITUTE 2017-2021. CARLOS III HEALTH INSTITUTE PI16/01535 2017-2019. María Victoria Francia Gil. Induction of conjugative Human Resources PI16-00496 pheromone-induced plasmid Mónica López Fanarraga. transfer. CARLOS III HEALTH MS16/00033 Design and evaluation of multi- Raquel López Mejías. INSTITUTE. 2017-2019. therapeutic nano-dispensers based Miguel Servet Type I contract. on carbon nanotubes to treat CARLOS III HEALTH INSTITUTE PI16/01585 tumours. CARLOS III HEALTH 2017-2021. Marcos López Hoyos. INSTITUTE. 2017-2019. Utility of the study of Myeloid- CM16/00051 Derived Suppressor Cells (MDSC) SAF2016-76046-R Javier Riancho Zarrabeitia. when monitoring kidney transplants. Benedicto Crespo Facorro. Rio Hortega contract. CARLOS III CARLOS III HEALTH INSTITUTE. Stratified treatment in schizophrenia: HEALTH INSTITUTE 2017-2018. 2017-2019. integrating results of the human and cellular transcriptome in CM16/00034 PI16/01652 antipsychotic treatment strategies. Manuel Delgado Alvarado. Juan Pascual Sánchez. MINECO. 2017-2019. Rio Hortega contract. CARLOS III Study of rare variant genes associated HEALTH INSTITUTE 2017-2018.. with Alzheimer’s disease in the SAF2016-75195-R Spanish population. CARLOS III Jesús Merino Pérez. INT16/00133 HEALTH INSTITUTE. 2017-2019. BAMBI, a regulator of TGF Miguel Ángel González-gay beta signalling, in cutaneous Mantecón. PI16/01656 inflammation and differentiation of CARLOS III HEALTH INSTITUTE Julio Francisco Jimenez Bonilla. Human CD4 T Lymphocytes. 2017. 5-Year study of a population with Mild Cognitive Impairment (MCI) PTA2015-11501-I previously evaluated with 11C-PIB Saray Pereda Marcos. Mobility and 18F-FDG PET/TAC. CARLOS III Research Technical Support Contract MINECO 2017-2019. HEALTH INSTITUTE. 2017-2019. BA16/00021 Jose María De la Torre Hernández. CARLOS III HEALTH INSTITUTE PI16/01717 2017. Víctor Manuel Martínez Taboada. Study of the role of BAMBI, a 81

During 2016, IDIVAL authorised shown in the attached table. a total of 57 clinical trials and 49 Clinical post-authorisation studies to be Notably, in 2016 a Phase I clinical performed in the Marqués de trial was begun for the first time Trials Valdecilla University Hospital and its with an admission to the Valdecilla area of influence. The list of major Clinical Trial Unit. clinical trials approved in 2016 is

List of clinical trials whose contracts were signed in 2016

Clinical trial Leader researcher

EECC for the suspension of valganciclovir prophylaxis in CMV-seropositive kidney María del Carmen Fariñas Álvarez. transplant recipients who develop CMV-specific CD8 + cellular immunity after receiving thymoglobulin.

Telavancin open-label multicenter, open-label clinical trial in comparison to María del Carmen Fariñas Álvarez. conventional intravenous therapy in the treatment of patients with Staphylococcus aureus bacteremia, including endocarditis.

A randomized, double-blind, placebo-controlled, active-controlled (fluoxetine) and Beatriz Payá González. fixed-dose vortioxetine trial in pediatric patients 7 to 11 years of age with major depressive disorder (MDD).

A multicenter, randomized, placebo-controlled, double-blind study to evaluate the Julio Jose Castillo Diego. efficacy and tolerability of 2% diltiazem hydrochloride in the treatment of chronic anal fissure, and a 24-week follow-up period.

A 24-week randomized, double-blind, phase IIIb study comparing “closed” triple Juan García Rivero. therapy (ff / umec / vi) with “open” triple therapy (ff / vi + umec) in subjects with pulmonary disease Chronic obstructive pulmonary disease (COPD).

A randomized, multicenter, open-label, parallel-group Phase III study to evaluate María del Carmen Fariñas Álvarez. the efficacy, safety, and tolerability of a long-acting intramuscular regimen of cabotegravir and rilpivirine in maintenance of virologic suppression following induction with Single-blocker with an integrase inhibitor in a randomized, multicenter, open-label, parallel-group study to assess the efficacy, safety, and tolerability of a long-acting intramuscular regimen with cabotegravir and rilpivirine in maintenance of suppression After induction with a single tablet treatment with an integrase inhibitor in HIV-1 infected adult patients who have not received prior antiretroviral therapy

Osmo study: multicenter, open-label study with a treatment arm of 32 weeks in Juan García Rivero. subjects with severe eosinophilic asthma not optimally controlled with their current treatment with omalizumab, who are switched from omalizumab to mepolizumab 100 mg subcutaneously.

A 29-day, double-blind, placebo-controlled, multicenter, parallel-group study to Ángel Luis Martín De Francisco evaluate the efficacy, safety, and pharmacokinetics of three-weekly GSK1278863 Hernández. administration in hemodialysis-dependent subjects with anemia associated with chronic nephropathy Who received a stable dose of an erythropoiesis-stimulating drug.

Phase II, multicenter, randomized, double-blind (non-blind to the promoter), placebo- Fernando Rodríguez Fernández. controlled, parallel-group study to evaluate the efficacy and safety of sirukumab in subjects with poorly controlled severe asthma. R&D activity IDIVAL Clinical Trials

Ensayo Investigador principal

Active, parallel group, double-blind, phase III study to compare the efficacy, safety, Fernando Rodríguez Fernández. and tolerability of the FF / UMEC / VI fixed dose combination versus the fixed dose dual FF / VI combination administered Once daily with dry powder inhaler, in subjects with inadequately controlled asthma

Study of the efficacy and safety of bardoxolone methyl in patients with pulmonary José Manuel Cifrián Martínez. arterial hypertension associated with connective tissue disease.

Protocol for the use of open treatment for daratumumab in subjects with multiple Andrés Insunza Gaminde. myeloma who have received at least 3 previous treatment lines (including a proteasome inhibitor and an immunomodulatory drug) or have double resistance to a proteasome inhibitor and an immunomodulatory drug.

First-administration, double-blind, randomized, placebo-controlled, phase I Javier Crespo García. study of jnj-56136379 administered orally to examine safety, tolerability and pharmacokinetics after ascending single doses and a multiple dose regimen in healthy volunteers (part i) , And after multiple multiple dose regimens in subjects with chronic hepatitis b (part ii).

Phase 3b, double-blind, randomized, placebo-controlled, multicenter study Javier Crespo García. evaluating the effect of obeticolic acid on clinical outcomes in patients with primary biliary cirrhosis.

Phase 3 multicenter, randomized, double masked, long-term, placebo-controlled Javier Crespo García. study to evaluate the safety and efficacy of obeticolic acid in subjects with non- alcoholic steatohepatitis.

Multivessel, prospective, non-safety-related, clinical efficacy and pharmacokinetic Marcos López Hoyos. properties of normal human immunoglobulin for intravenous administration of bts95 as a restitution treatment in patients with primary immunodeficiency (ip).

Phase 3, randomized, double-blind, placebo-controlled, multicenter study of the Cristina Martínez Dubois. safety and efficacy of analgesic subcutaneous administration of Tanezumab in subjects with osteoarthritis of the hip or knee.

Obinutuzumab in combination with Clorambucilo, ACP 196 in combination with Lucrecia Yáñez San Segundo. Obinutuzumab and ACP 196 in monotherapy, in subjects with chronic non-treated lymphocytic leukemia.

A Randomized, Multicenter, Open-Label, Phase 3 Study of Acalabrutinib (ACP-196) Lucrecia Yáñez San Segundo. Versus Investigator Choice of Either Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Subjects with Relapsed or Refractory Chronic Lymphocytic Leukemia.

Randomized controlled trial of maintenance therapy with S-1 in metastatic Fernando Rivera Herrero. esophageal-gastric cancer. Randomized clinical trial to compare the efficacy of the Angiolite stent versus a Jose Javier Zueco Gil. second-generation drug-eluting stent such as Xience in patients with indication for percutaneous coronary intervention.

Phase II study of plitidepsin in patients with relapsed or refractory T cell Isabel Fernández González de angioinmunoblastic lymphoma. Villambrosia.

Phase III prospective, randomized, double-blind, multicentre study of the efficacy Carlos López López. and safety of lanreotide autogel / depot 120 mg plus the best supportive treatment (mts) versus placebo plus the best supportive treatment for tumor control in subjects with Well differentiated metastatic and / or unresectable, typical or atypical lung neuroendocrine tumors.

A randomized controlled study on the safety and efficacy of low molecular weight Ángela María Puente Sánchez. heparins in the prevention of thrombotic events in hospitalized cirrhotic patients. 83

Ensayo Investigador principal

Open, multicenter clinical trial with subcutaneous immunotherapy at depot Fernando Rodríguez Fernández. presentation in patients with allergic rhinoconjunctivitis sensitized to domestic mites.

Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group Eloy Manuel Rodríguez Rodríguez. study to evaluate the efficacy and safety of crenezumab in patients with mild to prodromal Alzheimer’s disease.

A multicenter, randomized, double-blind, placebo-controlled study to evaluate Ricardo Blanco Alonso. the safety, tolerability and efficacy of secukinumab in patients with active non- radiographic axial spondyloarthritis over a 2-year period.

Comparison between the absorbable bioreabsorbable framework and the xience José María De La Torre Hernández. metal stent in the prevention of restenosis following percutaneous coronary intervention in patients at high risk of restenosis.

Phase II clinical trial demonstrating viability to evaluate the efficacy and safety of Borja Suberviola Cañas. MEDI3902 in the prevention of nosocomial pneumonia caused by Pseudomonas aeruginosa in patients undergoing mechanical ventilation.

A randomized, double-blind, double-simulated, 24-week, parallel-group, multicenter Juan García Rivero. clinical trial to evaluate the efficacy and safety of the fixed-dose combination of aclidinium bromide 400 mcg / formoterol fumarate 12 mcg twice a Day as compared to each active ingredient in monotherapy (aclidinium bromide 400 mcg twice daily and formoterol fumarate 12 mcg twice daily) and with tiotropium 18 mcg once daily in its administration to patients with chronic obstructive pulmonary disease.

A randomized, double-blind, placebo-controlled phase II study of neoadjuvant Ana De Juan Ferré. chemotherapy with carboplatin and paclitaxel with or without debio 1143 in patients with newly diagnosed advanced ovarian epithelial cancer.

Dexmedetomidine versus usual clinical practice during non-invasive mechanical Mª Isabel Rubio Lopez. ventilation: Randomized clinical trial.

Closure of mucosal defects with clips after endoscopic mucosal resection of large Joaquin De La Peña García. colorectal lesions as prophylaxis of delayed hemorrhage.

Double-blind, randomized, placebo-controlled phase II / III study to evaluate the Montserrat Rivero Tirado. safety and efficacy of induction and maintenance therapy with GS-5745 in patients with moderate to severe active ulcerative colitis.

A randomized, multicenter, open-label Phase II study to evaluate the efficacy Javier Crespo García. and safety of the fixed-dose combination (cdf) of sofosbuvir / velpatasvir and the sofosbuvir / velpatasvir cdf plus ribavirin in patients with chronic HCV genotype 3 infection cirrhosis.

Phase II, randomized, double-blind, placebo-controlled trial of the combination of the Borja Suberviola Cañas. monoclonal antibody MHAA4549A with oseltamivir versus oseltamivir alone for the treatment of influenza-to-severe infection.

A 36-week open-label multicentre phase III study followed by a double-blind, Ricardo Blanco Alonso. randomized withdrawal period from week 36 to week 104 to assess the long-term efficacy and safety of ixekizumab (LY2439821) 80 mg Every 2 weeks in patients with active psoriatic arthritis who have never received a disease-modifying biological antirheumatic drug.

Phase II randomized trial evaluating alternative doses of ramucirumab in Rivera Herrero, Fernando. combination with paclitaxel as second line treatment in patients with gastric or locally advanced or metastatic and unresectable gastroesophageal adenocarcinoma.

Phase III, randomized, double-blind, placebo-controlled study evaluating LY2951742 Agustín Oterino Durán. in patients with episodic migraine - EVOLVE-2 study. R&D activity IDIVAL Clinical Trials

Ensayo Investigador principal

Phase III, randomized, double-blind, placebo-controlled study evaluating LY2951742 Agustín Oterino Durán. in patients with chronic migraine - REGAIN study.

A multicenter, randomized, double-blind, placebo-controlled trial to evaluate Javier Crespo García. emsartan (idn 6556), an oral caspase inhibitor, in subjects with nonalcoholic steatohepatitis (ehna) fibrosis).

A multicenter, randomized, double-blind, placebo-controlled trial to evaluate Javier Crespo García. emsartan, an oral caspase inhibitor, in subjects with non-alcoholic steatohepatitis (NASH) cirrhosis and severe portal hypertension.

“TWILIGHT-Ticagrelor Study with Aspirin or Alone in High-Risk Patients After José María De La Torre Hernández. Coronary Intervention”

A 12-week parallel-group, randomized, double-blind, placebo-controlled, phase-II José Estévez Tesouro. clinical trial to evaluate the efficacy and safety of three ultra-low estriol vaginal gel formulations (estriol vaginal gel 0.005%, 0.27% estriol vaginal gel, 0.0008% estriol vaginal gel) in the treatment of vaginal dryness in postmenopausal women with vaginal atrophy.

Phase III, randomized, double-blind study comparing abt-494 with placebo in stable Ricardo Blanco Alonso. treatment with conventional synthetic disease modifying antirheumatic drugs (farmesc) in subjects with moderate to severe rheumatoid arthritis with insufficient response or intolerance to biological farms (Farmeb).

Phase III, randomized, double-blind study comparing ABT-494 15 mg once daily in Ricardo Blanco Alonso. monotherapy and ABT-494 30 mg once daily in monotherapy versus methotrexate (MTX) monotherapy in subjects not previously treated with MTX with arthritis Moderate to severe active rheumatoid.

ABT 493 / ABT 530 in adults with chronic hepatitis C virus genotype 1, 2, 4, 5 or 6 and Javier Crespo García. compensated cirrhosis (EXPEDITION- 1).

A randomized, double-blind phase III study comparing ABT-494 with placebo and with Ricardo Blanco Alonso. adalimumab in subjects with moderate to severe active rheumatoid arthritis treated with methotrexate (MTX) in stable doses and who did not respond adequately to MTX (MTX- GO).

Multicenter clinical trial of maintenance treatment based on biomarkers for first line Fernando Rivera Herrero. metastatic colorectal cancer (Modul).

A multicenter, randomized, phase 2b study to evaluate the efficacy, safety, and Javier Crespo García. tolerability of ocr-002 (ornithine phenylacetate) in hospitalized patients with cirrhosis and hyperamoniaemia associated with an episode of hepatic encephalopathy. Studio stop-he.

Ib / 2 phase study of combined treatment with Ibrutinib in selected gastrointestinal Fernando Rivera Herrero. and genitourinary tumors.

Phase III, randomized, double-blind, placebo-controlled trial to evaluate the efficacy Emilio Rodrigo Calabia. and safety of qpi-1002 in preventing delayed graft function in recipients of a kidney transplant of elderly donors with brain death.

A randomized, multicenter, open-label, controlled, Phase III trial to demonstrate María Del Carmen Fariñas Álvarez. non-inferiority of targeted narrow-spectrum antibiotic treatment versus broad- spectrum anti-pseudomonal beta-lactam treatment in the treatment of patients with Enterobacteriaceae bacteremia.

Phase 2 randomized study comparing different dose-induction treatment regimens Fernando Rivera Herrero. (first cycle) regorafenib in patients with metastatic colorectal cancer (mcrc).

Phase II study to evaluate the efficacy of FOLFIRI + aflibercept in patients with Fernando Rivera Herrero. metastatic colorectal cancer previously treated with oxaliplatin with or without ACE polymorphisms. 85

Hoyos M, Barten MJ, Bergan S, J, Bermejo F, Bujanda L, Calvet X, Picard N, Millán López O, Marquet P, Castro-Fernández M, Cuadrado-Lavín Clinical Hesselink DA, Noceti O, Pawinski T, A, Elizalde JI, Gene E, Gomollón Wallemacq P, Oellerich M. Barcelona F, Lanas Á, Martín de Argila C, Practice Consensus on Biomarker-Based Mearin F, Montoro M, Pérez-Aisa Immunosuppressive Drugs Á, Pérez-Trallero E, McNicholl AG. Guidelines Management in Solid Organ IV Spanish Consensus Conference Transplantation. on Helicobacter pylori infection Ther Drug Monit 2016;38 Suppl treatment. 1:S1-20. Gastroenterol Hepatol 2016;39:697- 721. IDIVAL researchers have Del Pino-Montes J, Blanch J, Nogués participated in 2016 in the following X, Moro MJ, Valero Mdel C, Canals L, Lopez de Munain L, Juan-Garcia clinical practice guidelines and Lizán L. FJ, Duarte E, Martin-Mourelle R, consensus documents. The Expert Consensus on the Rodriguez S, Moraleda-Perez S. relevance of these guidelines is Management of Patients with [Early pharmacologic treatment with undoubtedly as systematically Postmenopausal Osteoporosis in the botulinum toxin A in post-stroke developed recommendations to Spanish Healthcare System. spasticity: consensus evidence- help professionals and patients Adv Ther 2016;33:658-69. based recommendations]. make the most appropriate health Rev Neurol 2016; 16;63:363-369. care decisions and to select the most appropriate diagnostic Fernández Castro M, Andreu JL, or therapeutic options when Sánchez-Piedra C, Martínez Taboada V, Martínez López JA, García Vivar addressing a health problem. Olivé A, Rosas J, Sánchez-Alonso F; ML, Cáliz R, Freire M, Galindo M, En representación del Grupo Hernández MV, López Longo FJ, de trabajo en Enfermedade Martínez Taboada V, Pego Reigosa Autoinmunes Sistémicas de la JM, Rubio E, Trujillo E, Vela- Sociedad Española de Reumatología Casasempere P. (EAS-SER) y de la Unidad de Recommendations for the evaluation Anguita Sánchez M, Lambert Investigación de la Sociedad and management of patients Rodríguez JL, Bover Freire R, Comín Española de Reumatología (UI-SER).. with rheumatic autoimmune and Colet J, Crespo Leiro MG, González Sjögren SER: National registry of the inflammatory diseases during the Vílchez F, Manito Lorite N, Segovia Spanish Society of Rheumatology reproductive age, pregnancy, Cubero J, Ruiz Mateas F, Elola Somoza of patients with primary Sjögren postpartum and breastfeeding. FJ, Íñiguez Romo A. syndrome: Objectives and Reumatol Clin 2016: S1699. Classification and Quality Standards methodology. of Heart Failure Units: Scientific Reumatol Clin 2016;12(4):184-9. Consensus of the Spanish Society of Martín-Richard M, Díaz Beveridge R, Cardiology. Arrazubi V, Alsina M, Galan Guzmán Rev Esp Cardiol (Engl Ed). García-Vicuña R, Martín-Martínez MA, M, Custodio AB, Gómez C, Muñoz FL, 2016;69:940-950. Gonzalez-Crespo MR, Tornero-Molina Pazo R, Rivera F. J, Fernández-Nebro A, Blanco-García SEOM Clinical Guideline for FJ, Blanco-Alonso R, Marsal-Barril S; the diagnosis and treatment of Apostolo J, Holland C, O’Connell En representación del Comité esophageal cancer (2016). MD, Feeney J, Tabares-Seisdedos Científico del trabajo de Clin Transl Oncol 2016;18:1179-1186. R, Tadros G, Campos E, Santos Recomendaciones de la Sociedad N, Robertson DA, Marcucci M, Española de Reumatología para Varela-Nieto I, Crespo-Facorro B, Mingot-Castellano ME, Álvarez- el manejo clínico del paciente Vieta E, Navarro-Pardo E, Selva-Vera Román MT, López-Fernández MF, con artritis reumatoide que no G, Balanzá-Martínez V, Cano A. . A Altisent-Roca C, Canaro-Hirnyk MI, puede utilizar metotrexato.. position statement of the Cognitive Jiménez-Yuste V, Cid-Haro AR, Pérez- Recommendations by the Decline Group of the European Garrido R, Sedano-Balbas C. Spanish Rheumatology Society Innovation Partnership for Active Spanish consensus guidelines for the management of patients and Healthy Ageing (EIPAHA). on prophylaxis with bypassing diagnosed with rheumatoid arthritis Maturitas 2016;83:83-93. agents for surgery in patients with who cannot be treated with haemophilia and inhibitors. methotrexate. Eur J Haematol. 2016 May;96(5):461- Brunet M, Shipkova M, van Gelder Reumatol Clin. 2016; 5. S1699. 74. T, Wieland E, Sommerer C, Budde K, Haufroid V, Christians U, López- Gisbert JP, Molina-Infante J, Amador R&D activity IDIVAL Clinical Practice Guidelines

Montejo ÁL, Arango C, Bernardo [Consensus-based approach for Diseases and Clinica Microbiology M, Carrasco JL, Crespo-Facorro B, severe paediatric asthma in routine (GESITRA-SEIMC).; Spanish Cruz JJ, Del Pino J, García Escudero clinical practice]. Network for Research in Infectious MA, García Rizo C, González-Pinto An Pediatr (Barc). 2016 Feb;84(2):122. Diseases (REIPI).. Management A, Hernández AI, Martín Carrasco M, e1-122.e11. of cytomegalovirus infection in Mayoral Cleries F, Mayoral van Son solid organ transplant recipients: J, Mories MT, Pachiarotti I, Ros S, SET/GESITRA-SEIMC/REIPI Sevilla I, Segura Á, Capdevila J, López Vieta E. recommendations. C, García-Carbonero R, Grande E; Spanish consensus on the risks and Transplant Rev (Orlando) GETNE (Spanish Group of detection of antipsychotic drug- 2016;30:119-43. NeuroEndocrine Tumors).. related hyperprolactinaemia. Management of controversial Rev Psiquiatr Salud Ment 2016; 9:158- gastroenteropancreatic Vera R, Dotor E, Feliu J, González E, 73. neuroendocrine tumour clinical Laquente B, Macarulla T, Martínez E, situations with somatostatin Maurel J, Salgado M, Manzano JL. Müller-Arteaga C, Arlandis Guzmán analogues: results of a Delphi SEOM Clinical Guideline for the S, Lorenzo Gómez MF, Errando-Smet questionnaire panel from the treatment of pancreatic cancer C, González López R, Cambronero NETPraxis program. (2016). Santos J, Gutiérrez Baños JL, BMC Cancer 2016 7;16:858. Clin Transl Oncol 2016;18:1172-1178. Sánchez Marcos M, Ortiz Gamiz A, Merino Salas S, Martínez Rodriguez Torre-Cisneros J, Aguado JM, Caston Villar-Del-Moral J, Capela-Costa R, Olano Grasa I. JJ, Almenar L, Alonso A, Cantisán J, Jiménez-García A, Sitges-Serra [Expert opinion about the use of S, Carratalá J, Cervera C, Cordero E, A, Casanova-Rituerto D, Rocha J, transdermic oxybutynin in Spain for Fariñas MC, Fernández-Ruiz M, Fortún Martos-Martínez JM, de la Quintana- the treatment of adult overactive J, Frauca E, Gavaldá J, Hernández D, Basarrate A, Rosa-Santos J, Guirao- bladder.]. Herrero I, Len O, Lopez-Medrano F, Garriga X, Bravo-de-Lifante JM, Vidal- Arch Esp Urol 2016;:613-620. Manito N, Marcos MA, Martín-Dávila Pérez Ó, Moral-Duarte A, Polónia J; P, Monforte V, Montejo M, Moreno A, Iberpara Study Group.. Compliance Plaza AM, Ibáñez MD, Sánchez-Solís Muñoz P, Navarro D, Pérez-Romero with recommendations on surgery M, Bosque-García M, Cabero MJ, P, Rodriguez-Bernot A, Rumbao J, for primary hyperparathyroidism- Corzo JL, García-Hernández G, de San Juan R, Vaquero JM, Vidal E; from guidelines to real practice: la Hoz B, Korta-Murua J, Sánchez- Spanish Society of Transplantation results from an Iberian survey. Salguero C, Torres-Borrego J, (SET).; Group for Study of Langenbecks Arch Surg. 2016; Tortajada-Girbés M, Valverde-Molina J, Infection in Transplantation of 401:953-963. Zapatero L, Nieto A. the Spanish Society of Infectious 87

Networks for Cooperative Research in a context of more restricted (RETIC) Platforms and Biomedical execution. Retics and Research Centre Networks (CIBER) in which IDIVAL groups Ciber with the participate. These organisational IDIVAL participates in three CIBERs, structures formed by a variable set seven RETICS and three other Participation of of multidisciplinary centres and platforms Three of the RETICs in IDIVAL research groups in biomedicine aim which IDIVAL participates (ITEMAS to conduct cooperative research Platform, the Biobank Platform projects of general interest, centred and the Scren Platform) have a on a common specific area for the supportive and cross-disciplinary The Carlos III Health Institute achievement of scientific objectives nature, making up part of the has promoted various Thematic that would be difficult to achieve researcher support services.

CIBER/RETIC/Platform IDIVAL Group IP

CIBER of Mental Health (CIBERSAM) Psychiatry Benedicto Crespo Facorro

CIBER of Neurodegenerative Diseases Neurodegenerative José Ángel Berciano Blanco (CIBERNED) Diseases

CIBER of Epidemiology and Public Health Epidemiology and Javier Llorca Díaz (CIBERESP) Public Spanish Infectious Pathology Research Network Clinical Microbiology and Luis Martínez Martínez (REIPI) Molecule

Maternal and Child Health and Development Network University Hospital Marqués Maria Jesús Cabero (SAMID NETWORK) de Valdecilla

Thematic Network of Cooperative Research in Aging Mineral and Lipid Jesús González Macías and Fragility (RETICEF) Metabolism

Renal Research Network (REDinREN) Transplantation and autoimmunity Manuel Arias Rodríguez

Red Temática de Investigación Cooperativa de Cáncer Cell Signaling and Therapeutic José Luis Fernández Luna (RTICC) Targets in Cancer

Research Network Cooperative Cancer Research Hematologic Neoplasms and Eulogio Conde García (RTICC) Hematopoietic Progenitor Transplantation

Thematic Network of Cooperative Cancer Research Genomic Cancer Miguel Ángel Piris Pinilla (RTICC)

Cardiovascular Research Network (RIC) Cytokines and growth Juan Francisco Nistal factors in pathological tissue plasticity phenomena

Research Network on Inflammation and Rheumatic Genetic epidemiology and Miguel Angel Glez Gay Diseases (RIER) atherosclerosis in systemic inflammatory diseases

Biobanks Platform IDIVAL Pascual Sánchez Juan

Platform for Innovation in Health Technologies IDIVAL Galo Peralta Fernández (ITEMAS)

Platform of Clinical Research Units and Clinical Trials IDIVAL Galo Peralta Fernández (Scren) R&D activity IDIVAL Innovation

Innovation

Introduction

IDIVAL has an Innovation Area At IDIVAL, we believe that that includes a Research Results innovation and knowledge Fostering Transfer Office (OTRI) and an transfer can become drivers of Innovation Innovation Unit, which forms part the economy in the region of

of the ITEMAS network. Cantabria, and therefore we are Public-private Fostering committed to the activities of the Collaboration Innovation The current context of market Innovation Unit. globalisation is guiding European countries towards innovation as a major driver of continued growth. Transfer

ITEMAS Platform

health technology as a crucial tool National Healthcare System. to make the National Healthcare System more sustainable, IDIVAL participates in the ITEMAS supporting development of the platform through the IDIVAL Innovation Unit, which throughout IDIVAL is the node of the Platform innovative culture needed to for Innovation in Medical and 2016 worked on related activities integrate scientific and industrial Health Technologies (ITEMAS) linked to its participation in systems in the field of medical promoted by the Carlos III Health different work groups and its technology. The core of ITEMAS Institute (ISCIII). Assembly. Specifically, it leads the currently comprises the innovation Alliances working group within the ITEMAS promotes innovation in units of large hospitals in the Platform.

Innovative Culture

To promote the culture of that encourage creativity and The Innovation Unit has innovation in the Valdecilla teamwork, issues reports, and participated in various activities environment, IDIVAL organises a provides training on specific aspects presented in the training section. series of courses and workshops of the innovation process, etc. 89

Transfer

At present, innovation is relation to this, IDIVAL adheres to considered to be a fundamental Industrial Property Regulations, One European patent factor for growth and which govern the management application to the European competitiveness in the economic and use of intellectual and Patent Office (EPO). and business sphere. From industrial property rights and the point of view of society, transfers to the market within A utility model application to innovation in the healthcare sector the area of responsibility of the the Spanish Office of Patents means continuous improvement Healthcare Administration of and Brands (OEPM). of the efficiency and productivity Cantabria. of national health systems, A Community Design significantly improving patients’ Since the establishment of the application to the Office for quality of life. OTRI, the following have been Harmonization in the Internal presented: Market (OHIM). Nineteen patent applications Three Spanish trademark For the transfer of research results to the Spanish Office of Patents and Brands (OEPM). applications to the Spanish from our environment to the Office of Patents and Brands market to be effective and have an (OEPM). impact on society, an economic Twelve international patent and legal environment conducive applications through the to innovation and economic Patent Cooperation Treaty (PCT). Of these, the following were development must be created. In processed in 2016:

Nº Solicitud Título Solicitantes Inventor

National patent- “Uso de un complejo IDIVAL-SCS Carmen Álvarez Domínguez P201600160 GNP-LLO91-99 para el tratamiento Ricardo Calderón González y la prevención del cáncer” Elisabet Frande Cabanes Eva Ferrández Fernández Sonsoles Yáñez Díaz Soledad Penadés Ullate Marco Marradi Isabel García Martín

National patent- “Método para predecir la respuesta IDIVAL-UC-SCS- José Luis Fernández Luna P201600636 clínica a un tratamiento con VHIR-IdiPAZ Víctor Manuel Martínez Taboada agentes antiinflamatorios” Silvia Torices del Val Marcos López Hoyos Pedro Muñoz Cacho Ignacio Varela Egocheaga Alejandro Balsa Criado Sara Marsal Barril Antonio Julià Cano

European Patent – “Device and method for the SCS-IDIVAL- José Luis Fernández Luna 14721426.6 detection of biomarkers” UC-TEKNIKER- Ana Talamillo Cancelo CELLBIOCAN Fernando Moreno García Francisco González Fernández Ruth Díez Ahedo Santos Merino Álvarez Deitze Otaduy del Paso R&D activity IDIVAL Innovation

Nº Solicitud Título Solicitantes Inventor

National Utility Model “Dispositivo de tracción dinámica SCS Federico Castillo Suescun -U201600872 de pared para abdomen abierto”

National patent “Uso del gen PRKACA para IDIVAL-SCS Carlos Pipaón González -P201601099 predecir la respuesta de un sujeto Lucrecia Yáñez San Segundo al tratamiento con un análogo de purina”

Para todas ellas se han llevado, o se realizan en la actualidad, labores de transferencia y contacto con posibles licenciatarios.

Innovation Funnel

In 2016, 12 new ideas were market research, patentability 5. Market. analysed. The projects were reports, or product value or cases where innovation is found in classified into FIVE phases, as technical feasibility reports are one of the following situations: defined below: being carried out are considered. a) Licensed to industry 1. Capturing ideas. 3. Development. In this phase, the ideas that This includes the development of b) Generated a spin-off Innovation Areas captured in 2016 prototypes, approvals and testing. are considered, as well as those c) Forms part of an exclusive captured in previous years that did 4. Transfer. agreement with a company not advance to a later stage. Ideas that have generated some type of commercial activity, d) Implemented in a healthcare 2. Analysis. e.g., contact with companies or centre (in the case of healthcare In this phase, proposals for which potential licensees. and organisational innovations).

5 3 IDEAS VALUATION DEVELOPMENT TRANSFER MARKET

healthcare IT Materials and Devices Image Pharmaceuticals Biotechnology and Innovation in care Molecular Diagnosis or Organisation 91

In 2016, the Innovation Area among the five stages as follows: managed 32 ideas, distributed

0 5 10 15 20 25 30 35

Catchment Evaluation Development Transfer Market

Research Areas

95

Organ Transplants and Tissue and Marcos López Hoyos. Coordinator of the Transplant Area of Organs New Therapies and Tissues and New Therapies. Head of Immunology Service. Area University Hospital Marqués de Valdecilla. Research Areas Organ Transplants and Tissue and New Therapies Area

Group Leader Juan Francisco Cytokines and Growth Factors Nistal Herrera Cardiovascular inÁreas Pathological de Tissue Plasticity Surgery Service University Hospital Phenomena Marqués de Valdecilla investigación University of Cantabria

[email protected]

Contributors ManuelCobo Belaustegui Víctor García Expósito García Raquel López Aritz Gil Ongay Carlos Juárez Crespo Miguel Fernando Llano Cardenal Rafael Martín Durán Luis Javier Ruiz Guerrero Valentín Tascón Quevedo Mónica Tramullas Fernández Verónica Vidal Sánchez

Nurses Elena Martín Delgado Roberto Moreta Sánchez

Predoctoral María Carcelen Labrador Raquel Frances Romero Consolidated group Sara Lantigua Romero

Technicians Ana María Cayón Gómez Researchers María de las Nieves García Iglesias María Amor Hurlé González María Eva García Iglesias Carmen Martínez-Cue Pesini María Navarro Rego

97

phenotypic characteristics. We Chronic neuropathic pain is are studying the involvement highly resistant to conventional Research of the TGF-ß family in cardiac drug treatment. We have Lines development variations found in demonstrated the involvement of this model. the TGF-ß family in processing the physiological nociceptive signal. We intend to study: a) 2. Pathological plasticity of the Molecular mechanisms involving aortic wall. 1. Pathological plasticity of TGF-ß in neuropathic pain, and myocardium. We are analysing the involvement experimental inflammatory pain; b) The interaction between TGF- We are analysing the involvement of transforming growth factors beta ßs and the endogenous opioid of transforming growth factors in the molecular pathophysiology system; c) The involvement of beta (TGF-Ðs, activin and BMPs) in of the remodelling of the aortic wall TGF-ßs in adaptive processes in the molecular pathophysiology of in relation to aneurysm formation. chronic opioid therapy; d) The myocardial remodelling secondary Progressive dilation of the aorta involvement of TGF-ßs in the to haemodynamic stress and in carries high rates of morbidity and hypoesthesia of experimental altered development. mortality. We are studying the role of TGF-ßs in the molecular Down syndrome. pathophysiology of the pathological 1. 1. Pathological plasticity 3.2. Pathological neuronal remodelling of the aortic wall in of myocardium subjected to plasticity in learning and memory aneurysm formation. pressure overload. circuits. We are analysing the Aortic stenosis is the most mechanisms that connect the We intend to: 1) Establish frequent cause of surgery in TGF-ß family with cognitive signalling pathways involved in our setting, and it associates a variations and neurodegenerative the vascular chronic inflammatory left ventricular hypertrophy that disease in Down syndrome. is a response of pathological process responsible for progressive significance in these patients. aortic dilatation; 2) Identify Down syndrome causes more We studied the molecular biomarkers to assess the risk cases of mental retardation mechanisms of myocardial of rupture and assist in surgery and all patients develop an remodeling in this context using indication; and 3) Establish new Alzheimer-type neuropathology myocardial samples from patients therapeutic targets. early on. Deficits in the synthesis with aortic stenosis, a murine and transport of trophic factors experimental model of said 3. Pathological plasticity in the could mediate these variations. pathology central nervous system. Furthermore, the TGF-ß family is involved in the pathophysiology 1.2. Alteraciones del desarrollo y 3.1 Pathological neuronal of experimental Alzheimer’s plasticidad miocárdica patológica plasticity of the nociceptive disease. We intend to evaluate en el síndrome de Down. system. The mechanisms linking the role of TGF-ß in the cognitive The Ts65Dn mouse (trisomy TGF- ßs and modulation of pain variations found in the Ts65Dn of an area of chromosome 16 transmission, basally and in mouse and evaluate different homologous to the human 21) is pathological plasticity models of therapeutic strategies. an experimental model of Down the nociceptive system, are being syndrome that reproduces its analysed. Research Areas Organ Transplants and Tissue and New Therapies Area

PUBLICATIONS: EUROPACE. 2016;18:1203-1210. Herrera, Juan Francisco. F.I.:4,021. [doi:10.1093/europace/ Infestation of a diabetic foot by euv337] Wohlfahrtia Magnifica. IMPACT FACTOR | 47,704 J Vasc Surg Venous Lymphat Disord. 5. Tramullas M, Finger BC, Dinan TG, 2016;2:119-122.F.I.:0,882. Cryan JF. Obesity Takes Its Toll on Visceral Pain: High-Fat Diet Induces Toll-Like Receptor 4-Dependent Visceral Original articles Hypersensitivity. Reviews PLoS One. 2016;11:F.I.:3,057. [doi:10.1371/journal.pone.0155367] 1. García R, Merino D, Gómez JM, 1. Ballantyne MD, Pinel K, Dakin Nistal JF, Hurlé MA, Cortajarena AL, R, Vesey AT, Diver L, Mackenzie R, Villar AV. Garcia R, Welsh P, Sattar N, Hamilton 6. Parisotto EB, Vidal V, García- Extracellular heat shock protein G, Joshi N, Dweck MR, Miano JM, Cerro S, Lantigua S, Wilhelm Filho D, 90 binding to TGFß receptor I McBride MW, Newby DE, McDonald Sanchez-Barceló EJ, Martínez-Cué C, participates in TGFß-mediated RA, Baker AH. Rueda N. collagen production in myocardial Smooth Muscle Enriched Chronic Melatonin Administration fibroblasts. Long Noncoding RNA (SMILR) Reduced Oxidative Damage Cell Signal. 2016;28:1563-1579. Regulates Cell Proliferation. and Cellular Senescence in the F.I.:4,191. [doi:10.1016/j. Circulation. 2016;133:2050-2065. Hippocampus of a Mouse Model of cellsig.2016.07.003] F.I.:17,202. [doi:10.1161/ Down Syndrome. CIRCULATIONAHA.115.021019] Neurochem Res. 2016;41:2904-2913. F.I.:2,472. [doi:10.1007/s11064-016- 2008-8] 2. Merino D, Villar AV, García R, Tramullas M, Nistal JF, Hurlé MA. Doctoral thesis BMP-7 attenuates left ventricular 7. Expósito V, Rodríguez-Entem F, remodelling under pressure González-Enríquez S, Veiga G, Olavarri 1. Mª Elena Arnáiz García. overload and facilitates reverse I, Olalla JJ. Aortic root replacement surgery remodelling and functional Stroke and Systemic Embolism with valvular preservation: analysis recovery. After Successful Ablation of Typical of early and long-term surgical Cardiovasc Res. 2016;110:331-345. Atrial Flutter. outcomes, and study of predictors F.I.:5,465. [doi:10.1093/cvr/cvw076] Clin Cardiol. 2016;39:347-351. of survival, valvular function F.I.:2,431. [doi:10.1002/clc.22538] stability, and reoperation. Director/a: Juan Francisco Nistal 3. Gradari S, Pérez-Domper P, Butler Herrera. University of Cantabria. RG, Martínez-Cué C, de Polavieja GG, 8. Santurtún A, Villar A, López- Trejo JL. Delgado L, Riancho J. The relationship between behavior Amyotrophic lateral sclerosis and acquisition and persistence abilities: richness: A correlation study across Involvement of adult hippocampal Spain. neurogenesis. J Neurol Sci. 2016;367:380-381. HIPPOCAMPUS. 2016;26:857-874. F.I.:2,126. [doi:10.1016/j. F.I.:4,074. [doi:10.1002/hipo.22568] jns.2016.06.050]

PROJECTS

4. Expósito V, Rodríguez-Mañero 9. Santurtún A, Villar A, Delgado- M, González-Enríquez S, Arias MA, Alvarado M, Riancho J. Trends in Sánchez-Gómez JM, Andrés La Huerta motor neuron disease: association A, Bertomeu-González V, Arce-León Á, with latitude and air lead levels in Projects Barrio-López MT, Arguedas-Jiménez Spain. H, Seara JG, Rodriguez-Entem F. Neurol Sci. 2016;37:1271-1275. Primary prevention implantable F.I.:1,783. [doi:10.1007/s10072-016- 1. María Amor Hurlé González. cardioverter-defibrillator and 2581-2] MicroRNAs in neuropathic pain: cardiac resynchronization therapy- molecular biomarkers and targeted defibrillator in elderly patients: therapies. results of a Spanish multicentre 10. Angulo López, Itziar, Nistal SAF2013-47434-R. study. 99

2. Juan Francisco Nistal Herrera. CARLOS III. MINISTERIO DE in Cardiovascular Diseases. Bone morphogenetic protein 7 ECONOMÍA Y COMPETITIVIDAD. RD12/0042/0018. INSTITUTO DE (BMP7): possible therapeutic target SALUD CARLOS III. MINISTERIO DE in the pathological remodeling of ECONOMÍA Y COMPETITIVIDAD. the cardiovascular system. 3. Juan Francisco Nistal Herrera. PI15/01224. INSTITUTO DE SALUD Thematic Network for Research Research Areas Organ Transplants and Tissue and New Therapies Area

Group Leader José Antonio Vázquez de Prada Tiffe Cardiology Service CardiovascularÁreas de Marqués de Valdecilla University of Cantabria Researchinvestigación Group

[email protected]

Contributors Iván Olavarri de Miguel José María de la Torre Hernández Mónica Fernández-Valls Gómez Francisco Jesús González Vílchez Dae Hyun Lee Hwang Javier Ruano Calvo Cristina Ruisánchez Villar Fermín Sainz Laso Manuel Jesús Zarauza Navarro José Javier Zueco Gil

Technicians María Cristina Obregón Rodríguez Clinic group

clinical implementation of new b. Vasculopathy with intravascular immunosuppressive approaches ultrasonography (IVUS), optical with proliferation signal inhibitors coherence and virtual histology. Research (mTOR inhibitors). c. Transesophageal three- lines b. Drug eluting stents, especially in dimensional echocardiography the setting of left main disease. in atrial septal defects and mitral valve prolapse. Percutaneous Structural Heart The Cardiovascular Research Disease Interventions d. Three-dimensional Group is actively working in the echocardiography evaluation of fields of Heart Failure and Heart c. Atrial septal defects closure the mitral annulus. Transplantation, Interventional Cardiology and the different d. Transcatheter aortic valve e. Strain and strain-rate in diabetic modalities of Cardiac Imaging (2D implantations (TAVI) and oncologic cardiomyopathy. and 3D echocardiography, coronary angiography -including IVUS e. Prosthetic leaks closure -Left f. Genetic study of prolapse and optical coherence-, coronary atrial appendage closure Mitral valve. CT angiography and Magnetic Resonance Imaging). Our main f. Preconditioning in acute g. Evaluation of response to areas of research are: coronary syndromes. Ischemic preconditioning. During myocardial infarction with 1. Cardiovascular Therapy: 2. Multimodality Cardiac Imaging: magnetic resonance. a.Immunosuppression in Heart a. Diagnosis and characterization Transplantation, specifically the of Cardiac Allograft 101

Figure. Three-dimensional echocardiogram demonstrating mitral valve prolapse

N, Jiménez-Quevedo P, Cárdenas A, Napp LC, Chandran S, de la Torre PUBLICATIONS: Fernández C. Hernández JM, Chen SL, Varbella F, Under the auspices of the Omedè P, Taha S, Meliga E, Kawamoto IMPACT FACTOR | 80,367 Interventional Cardiology Working H, Montefusco A, Mervyn C, Garot Group of the Spanish. Everolimus- P, Sin L, Gasparetto V, Abdirashid M, Eluting Stents in Patients With Bare- Cerrato E, Biondi-Zoccai G, Gaita F, Metal and Drug-Eluting In-Stent Escaned J, Hiddick Smith D, Lefèvre Restenosis: Results From a Patient- T, Colombo A, Sheiban I, Moretti C. Level Pooled Analysis of the RIBS IV Provisional vs. two-stent technique Original articles and V Trials. for unprotected left main coronary Circ Cardiovasc Interv. 2016;9: artery disease after ten years follow 1. Crespo-Leiro MG, Muñiz J, F.I.:5,706. [doi:10.1161/ up: A propensity matched analysis. Gonzalez-Vilchez F. CIRCINTERVENTIONS.115.003479] Int J Cardiol. 2016;211:37-42.F.I.:4,638. Spanish Post-Heart Transplant [doi:10.1016/j.ijcard.2016.02.136] Tumor Registry Investigators. Comment on: Post-transplant 3. Delgado JF, Alonso-Pulpón L, lymphoproliferative disease in heart Mirabet S, Almenar L, Pérez Villa F, 5. Parra JA, Cuesta JM, Zarrabeitia R, and lung transplantation: Defining González-Vílchez F, Palomo J, Blasco Fariñas-Álvarez C, Bueno J, Marqués S, risk and prognostic factors. T, García-Cosio MD, González-Costello Parra-Fariñas C, Botella ML, Bernabéu J Heart Lung Transplant. 2016;35:693- J, de la Fuente L, Rábago G, Lage E, C, Zarauza J. 694.F.I.:7,509. [doi:10.1016/j. Pascual D, Díaz Molina B, Arizón JM, Screening pulmonary arteriovenous healun.2016.01.006] Muñiz J, Crespo-Leiro MG. malformations in a large cohort of Cancer Incidence in Heart Spanish patients with hemorrhagic Transplant Recipients With Previous hereditary telangiectasia. 2. Alfonso F, Pérez-Vizcayno MJ, Neoplasia History. Am J Transplant. Int J Cardiol. 2016;218:240-245. García Del Blanco B, García-Touchard 2016;16:1569-1578. F.I.:4,638. [doi:10.1016/j. A, López-Mínguez JR, Masotti M, F.I.:5,669. [doi:10.1111/ajt.13637] ijcard.2016.05.065] Zueco J, Melgares R, Mainar V, Moreno R, Domínguez A, Sanchís J, Bethencourt A, Moreu J, Cequier A, 4. D’Ascenzo F, Iannaccone M, 6. Sambola, Antonia, Mutuberria, Martí V, Otaegui I, Bastante T, Gonzalo Giordana F, Chieffo A, Connor SO, Maria, del Blanco, Bruno Garcia, Research Areas Organ Transplants and Tissue and New Therapies Area

Alonso, Albert, Barrabes, Jose A., Moris C, Urbano-Carrillo C, Bastante Patients with Atrial Fibrillation Alfonso, Fernando, Bueno, Hector, T, Rivero F, Cárdenas A, Gonzalo N, Undergoing Percutaneous Cequier, Angel, Zueco, Javier, Jiménez-Quevedo P, Fernández C. Coronary Intervention. PLoS One. Rodriguez-Leor, Oriol, Bosch, Eduard, Restenosis Intra-Stent: Drug-Eluting 2016;11:F.I.:3,057. [doi:10.1371/ Tornos, Pilar, Garcia-Dorado, David. Balloon vs Everolimus-Eluting Stent journal.pone.0147245] Effects of Triple Therapy in Patients (RIBS-I. Comparison of the Efficacy With Non-Valvular Atrial Fibrillation of Everolimus-Eluting Stents Versus Undergoing Percutaneous Drug-Eluting Balloons in Patients 13. De la Torre Hernández JM, Tejedor Coronary Intervention Regarding With In-Stent Restenosis (from the P, Camarero TG, Duran JM, Lee DH, Thromboembolic Risk Stratification. RIBS IV and V Randomized Clinical Monedero J, Laso FS, Calderón MA, CIRC J. 2016;80:354-362. Trials). Veiga G, Zueco J. F.I.:4,124. [doi:10.1253/circj.CJ-15- Am J Cardiol. 2016;117:546-554. Early healing assessment with 0923] F.I.:3,154. [doi:10.1016/j. optical coherence tomography amjcard.2015.11.042] of everolimus-eluting stents with bioabsorbable polymer (synergy™) 7. Leone, Antonio Maria, Martin- at 3 and 6 months after Reyes, Roberto, Baptista, Sergio B., 10. Sheiban I, Moretti C, D’Ascenzo implantation. Amabile, Nicolas, Raposos, Luis, F, Chieffo A, Taha S, Connor SO, Catheter Cardiovasc Interv. 2016;88:67- Franco Pelaez, Juan Antonio, Trani, Chandran S, de la Torre Hernández 73.F.I.:2,181. [doi:10.1002/ccd.26299] Carlo, Cialdella, Pio, Basile, Eloisa, JM, Chen S, Varbella F, Omedè P, Zimbardo, Giuseppe, Burzotta, Iannaccone M, Meliga E, Kawamoto Francesco, Porto, Italo, Aurigemma, H, Montefusco A, Mervyn C, Garot 14. Martin-Reyes R, de la Torre Cristina, Rebuzzi, Antonio G., Faustino, P, Sin L, Gasparetto V, Abdirashid M, Hernandez JM, Franco-Pelaez J, Mariana, Niccoli, Giampaolo, Abreu, Cerrato E, Biondi Zoccai G, Gaita F, Lopez-Palop R, Telleria Arrieta M, Amat Pedro F., Slama, Michel S., Spagnoli, Escaned J, Hiddick Smith D, Lefèvre Santos IJ, Carrillo Saez P, Sanchez- Vincent, Telleria Arrieta, Miren, T, Colombo A. Long-Term (=10 Years) Recalde A, Sanmartin Pena JC, Garcia Amat Santos, Ignacio J., de la Tone Safety of Percutaneous Treatment Camarero T, Brugaletta S, Gimeno de Hernandez, Jose M., Lopez Palop, of Unprotected Left Main Stenosis Carlos F, Pinero A, Sorto Sanchez DC, Ramon, Crea, Filippo. With Drug-Eluting Stents. Am J Frutos A, Lasa Larraya G, Navarro F, The Multi-center Evaluation of the Cardiol. 2016;118:32-39.F.I.:3,154. Farre J. Accuracy of the Contrast MEdium [doi:10.1016/j.amjcard.2016.04.007] The use of the acute Pd/Pa drop INduced Pd/Pa RaTiO in Predicting after intracoronary nitroglycerin FFR (MEMENTO-FFR) Study. infusion to rule out significant EuroIntervention. 2016;12:708-715. 11. Hernández-Enriquez M, Andrea FFR: CANICA (Can intracoronary F.I.:3,863. R, Brugaletta S, Jiménez-Quevedo P, nitroglycerin predict fractional Hernández-García JM, Trillo R, Larman flow reserve without adenosine?) M, Fernández-Avilés F, Vázquez- multicenter study. 8. Lozano I, Sanchez-Insa E, de Leiras González N, Iñiguez A, Zueco J, Catheter Cardiovasc Interv. SR, Carrillo P, Ruiz-Quevedo V, Pinar Ruiz-Salmerón R, Del Valle R, Molina 2016;87:262-269. E, Gopar-Gopar S, Bayon J, Mañas P, E, García Del Blanco B, Berenguer A, F.I.:2,181. [doi:10.1002/ccd.25983] Lasa G, CruzGonzalez I, Hernandez Valdés M, Moreno R, Urbano-Carrillo F, Fernandez-Portales J, Fernandez- C, Hernández-Antolín R, Gimeno F, Fernandez J, Pérez-Serradilla A, de la Cequier Á, Cruz I, López-Mínguez JR, 15. Dominguez F, Ramos A, Bouza Torre Hernandez JM, Gomez-Jaume A. Aramendi JI, Sánchez Á, Goicolea E, Muñoz P, Valerio MC, Fariñas MC, Acute Coronary Syndromes, J, Albarrán A, Díaz JF, ..., Sabaté M. de Berrazueta JR, Zarauza J, Pericás Gastrointestinal Protection, and Puncture Versus Surgical Cutdown Pulido JM, Paré JC, de Alarcón A, Recommendations Regarding Complications of Transfemoral Sousa D, Rodriguez Bailón I, Montejo- Concomitant Administration of Aortic Valve Implantation (from the Baranda M, Noureddine M, García Proton-Pump Inhibitors (Omeprazol/ Spanish TAVI Registry). Vázquez E, Garcia-Pavia P. Esomeprazole) and Clopidogrel. Am J Cardiol. 2016;118:578-584. Infective endocarditis in Am J Cardiol. 2016;117:366-368. F.I.:3,154. [doi:10.1016/j. hypertrophic cardiomyopathy: A F.I.:3,154. [doi:10.1016/j. amjcard.2016.05.054] multicenter, prospective, cohort amjcard.2015.11.007] study. Medicine (Baltimore). 2016;95: 12. Sambola A, Mutuberría M, García F.I.:2,133. [doi:10.1097/ 9. Alfonso F, Pérez-Vizcayno MJ, Del Blanco B, Alonso A, Barrabés JA, MD.0000000000004008] García Del Blanco B, García-Touchard Bueno H, Alfonso F, Cequier A, Zueco A, Masotti M, López-Minguez JR, J, Rodríguez-Leor O, Tornos P, García- Iñiguez A, Zueco J, Velazquez M, Dorado D. 16. De la Torre Hernández JM, Moreno Cequier A, Lázaro-García R, Martí V, Impact of Triple Therapy in Elderly R, Lee DH, Garcia Del Blanco B, San 103

Martin JC, Serra Garcia V, Gaviria K, 2. Jaime Lucas Carbonero. Garcia Blas S, Garcia I, Zueco J. Editorials Efficacy and safety of The routine use of surgical corticosteroid withdrawal after exposure approach for trans- 1. Alfonso F, De la Torre Hernández JM. cardiac transplantation. femoral implantation of the balloon Vasa vasorum and coronary artery Director: José Antonio Vázquez De expandable aortic prosthesis is disease progression: optical Prada Tiffe. associated to a low rate of vascular coherence tomography findings. University of Cantabria. complications. Eur Heart J Cardiovasc Imaging. J Cardiovasc Surg (Torino). 2016;17:280-282.F.I.:4,293. 2016;57:615-619.F.I.:1,632. [doi:10.1093/ehjci/jev318] 3. Felipe Rodríguez Entem. Follow-up of the cardiac transplantation with a echocardiography-based rejection 17. Díaz-Molina B, Lambert JL, Doctoral Thesis monitoring strategy. Vílchez FG, Cadenas F, Bernardo MJ, Directors: José Antonio Vázquez De Velasco E, Martín M, Morís C. 1. Marta Fernández Hernández. Prada Tiffe, José Manuel Revuelta Quality of Life According to Dosing schedule for immunosuppression in heart Soba. Urgency Status in De Novo Heart transplantation in the medium and University of Cantabria. Transplant Recipients. Transplant long term. Proc. 2016;48:3024-3026. Directors: José Antonio Vázquez de F.I.:0,867. [doi:10.1016/j. Prada, Francisco Jesús González transproceed.2016.09.011] Vilchez. University of Cantabria Research Areas Organ Transplants and Tissue and New Therapies Area

Group Leader Javier Crespo García Digestive Service Infection,Áreas Immunity de and Marqués de Valdecilla Digestiveinvestigación Diseases University of Cantabria

[email protected]

Ainhoa Díaz Pérez Emilio Fábrega García Tatiana Fernández Lanas Pedro Luis Fernández Gil José Ignacio Fortea Ormaechea María José García García Paula Iruzubieta Coz Susana Llerena Santiago Luis Martín Ramos Susana Menéndez Secades Helena Pisonero Fraga Ángela María Puente Sánchez Montserrat Rivero Tirado Carlos Rodríguez De Lope López Álvaro Terán Lantarón

Nurses Emerging group Lidia Amigo Cabria María Rita Millor Rojo

Technicians Researchers Joaquín Cabezas González Fernando Casafont Morencos Lorena Cayón Estrada José Pedro Vaqué Díez Beatriz Castro Senosiain Ángel Estebanez Gallo Marta Cobo Martín Laura García Laso Contributors Antonio Cuadrado Lavín Agustín García Blanco María Teresa Arias Loste Joaquin de La Peña García María Elena Pérez García 105

carcinoma and cutaneous T-cell The partial deficiency of the lymphoma. lysosomal acid lipase (LAL) enzyme Research is an inherited, autosomal recessive pathology of lipid metabolism 3. Fatty Liver Disease (EHDG). Lines characterized by accumulation in Obesity and insulin resistance lysosomes, especially in the liver are associated with a chronic of cholesterol and triglyceride inflammatory state. Current esters, which may erroneously be diagnosed in the adult as HDSH. 1. Hepatitis C. evidence indicates that the activation of the signal transduced This pathology is due to mutations To know the real epidemiology at the level of the innate immune of the LAL gene (LIPA), of which of hepatitis C virus infection in system by receptors such as TLRs more than 40 mutations have been our country. To evaluate the role and NLRs plays a decisive role in described. We intend to evaluate of the innate immune system in the genesis of this inflammatory whether the active screening by the spontaneous clearance of state. Both receptor families, mass sequencing of the LIPA gene C virus infection, as well as the together with RLRs, make up what in adults with a diagnosis of GDHD evolution towards chronicity and we know as pattern recognition could be relevant from a clinical its implication in response / failure receptors (PRRs). However, the role point of view. to treatment with new direct played by PRRs in the pathogenesis acting antiviral agents (ADIs). of HDD is largely unknown. It is 4. Alcoholic liver disease. Regarding the therapeutic failure, possible that differences in the the viral variants associated with gene and protein expression of To study the pathophysiological resistance will also be studied. In these peripheral, hepatic and fatty mechanisms of acute alcoholic addition, we will study whether receptors between obese and hepatitis and the search for the hepatitis C virus is capable of non-obese subjects translate into molecular targets. Analysis of the producing endothelial dysfunction, a different susceptibility to the hepatic transcriptome in patients subclinical atheromatosis, disorder development of fatty liver disease. with alcoholic liver disease for of mineral and bone metabolism or neurocognitive manifestations the development of molecular signatures of gene expression. and its potential reversibility after On the other hand, the severity curing the infection with the new of the histological lesion of GHTD ADD agents. Finally, we intend to has been associated with the 5. Liver cirrhosis and portal study whether regression occurs in concomitant presence of hypopnea hypertension. liver fibrosis after the response to sleep apnea syndrome. The role DDA and the pathogenic role of the that intermittent hypoxia plays in To characterize the natural history enzyme Lisil-oxidase like 2 (LOXL2) the development of liver injury has of hepatic cirrhosis and factors that in this process. been studied previously. However, may influence the portal pressure there are no studies aimed at gradient. To evaluate the long-term 2. Molecular characterization of evaluating the effect of hypercapnia role of new oral anticoagulants specific cases of human cancer. maintained at the hepatic level. For in the survival and development this reason, we intend to analyze of complications of portal Potential implications in diagnosis the effect of chronic hypercapnia, hypertension in patients with liver and therapy. Oncogenic signaling with or without added hypoxemia, cirrhosis. mechanisms that control initiation, at the liver level with ex vivo models progression and response to of primary culture of immortalized 6. Liver transplantation. therapy. Study from a personalized hepatocytes, by analysis of gene point of view, advanced cases expression associated with glucose To study non-invasive blood of human cancer that at present and lipid metabolism and regulatory biomarkers of clinical events related lack effective therapies. Currently genes of the immune response, as to liver transplantation (rejection, we have research projects in liver well as assessing the inflammatory infection, vascular pathology, biliary cancer as well as some types of response induced in these cells by disease, and short- and long-term aggressive skin cancers such as the infusion of lipopolysaccharide. survival of the graft). advanced melanoma, Merkel cell Research Areas Organ Transplants and Tissue and New Therapies Area

Cadilla J, Calvo M, Chaparro M, Ginard Inflamm Bowel Dis. 2016;22:894-901. PUBLICATIONS: D, Guerra I, Maroto N, Calvet X, F.I.:4,358. [doi:10.1097/ Fernández-Salgado E, Gordillo J, Rojas MIB.0000000000000757] Feria M, GETECCU. IMPACT FACTOR | 116,186 Tuberculosis in Anti-Tumour Necrosis 10. Fortún J, Muriel A, Martín-Dávila Factor-treated Inflammatory P, Montejo M, Len O, Torre-Cisneros Bowel Disease Patients After the J, Carratalá J, Muñoz P, Fariñas C, Implementation of Preventive Moreno A, Fresco G, Goikoetxea J, Measures: Compliance With Gavaldá J, Pozo JC, Bodro M, Vena Original articles Recommendations and Safety of A, Casafont F, Cervera C, Silva JT, Retreatment. Aguado JM, GESITRA/GEMICOMED J CROHNS COLITIS. 2016;10:1186- (SEIMC), and REIPI (a).. 1. Cabezas J, Sampedro B, Hernández 1193.F.I.:6,585. 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Cubiella J, Carballo F, Portillo I, Crespo-Facorro B. enough to give up boozing?. Cruzado Quevedo J, Salas D, Binefa Incidence of non-alcoholic fatty Nat Rev Gastroenterol Hepatol. G, Milà N, Hernández C, Andreu liver disease and metabolic 2016;13:191-192.F.I.:14,435. M, Terán Á, Arana-Arri E, Ono A, dysfunction in first episode [doi:10.1038/nrgastro.2016.39] Valverde MJ, Bujanda L, Hernández schizophrenia and related psychotic V, Morillas JD, Jover R, Castells A. disorders: a 3-year prospective 3. Albéniz E, Fraile M, Ibáñez B, Alonso- Incidence of advanced neoplasia randomized interventional study. Aguirre P, Martínez-Ares D, Soto S, during surveillance in high- and Psychopharmacology (Berl). Gargallo CJ, Ramos Zabala F, Álvarez intermediate-risk groups of the 2016;233:3947-3952.F.I.:3,540. MA, Rodríguez-Sánchez J, Múgica F, European colorectal cancer screening [doi:10.1007/s00213-016-4422-7] Nogales Ó, de Tejada AH, Redondo E, guidelines. Guarner-Argente C, Pin N, León-Brito H, Endoscopy. 2016;48:995-1002.F.I.:5,634. 12. Arias-Loste MT, Iruzubieta P, Pardeiro R, López-Roses L, Rodríguez- [doi:10.1055/s-0042-112571] Puente Á, Ramos D, Santa Cruz C, Téllez M, Jiménez A, Martínez-Alcalá F, Estébanez Á, Llerena S, Alonso-Martín 8. Gallego-Durán R, Cerro-Salido P, García O, de la Peña J, Ono A, Alberca C, San Segundo D, Álvarez L, López Gomez-Gonzalez E, Pareja MJ, Ampuero de Las Parras F, Pellisé M, Rivero L, Useros A, Fábrega E, López-Hoyos J, Rico MC, Aznar R, Vilar-Gomez Saperas E, ..., M, Crespo J. Increased Expression E, Bugianesi E, Crespo J, González- Endoscopic Mucosal Resection Profile and Functionality of TLR6 in Sánchez FJ, Aparcero R, Moreno I, Soto Endoscopic Spanish Society Group. A Peripheral Blood Mononuclear Cells S, Arias-Loste MT, Abad J, Ranchal I, Scoring System to Determine Risk of and Hepatocytes of Morbidly Obese Andrade RJ, Calleja JL, Pastrana M, Delayed Bleeding After Endoscopic Patients with Non-Alcoholic Fatty Iacono OL, Romero-Gómez M. Mucosal Resection of Large Liver Disease. Imaging biomarkers for Colorectal Lesions. INT J MOL SCI. 2016;17: steatohepatitis and fibrosis detection Clin Gastroenterol Hepatol. F.I.:3,257. [doi:10.3390/ijms17111878] 2016;14:1140-1147.F.I.:7,680. in non-alcoholic fatty liver disease. [doi:10.1016/j.cgh.2016.03.021] Sci Rep. 2016;6:31421-31421. 13. Rodríguez-Nóvoa S, García- F.I.:5,228. [doi:10.1038/srep31421] Samaniego J, Prieto M, Calleja JL, 4. Perelló CS, Fernández-Carrillo C, Pascasio JM, Delgado Blanco M, Londoño MC, Arias-Loste T, Hernández- 9. Guerra I, Pérez-Jeldres T, Iborra Crespo J, Buti M, Bonet Vidal ML, Conde M, Llerena S, Crespo J, Forns X, M, Algaba A, Monfort D, Calvet X, Arenas Ruiz Tapiador J, Fernández- Calleja JL. Chaparro M, Mañosa M, Hinojosa E, Rodríguez C, Solá R, Fraga E, Reactivation of Herpesvirus in Minguez M, Ortiz de Zarate J, Márquez González Diéguez L, Núñez O, Praga Patients With Hepatitis C Treated L, Prieto V, García-Sánchez V, Guardiola M, Del Pino-Montes J, Romero- With Direct-Acting Antiviral Agents. J, Rodriguez GE, Martín-Arranz MD, Gómez M, Morillas R, Diago M, Clin Gastroenterol Hepatol. García-Tercero I, Sicilia B, Masedo Á, Castro Á, MENTE Study Group. 2016;14:1662.F.I.:7,680. [doi:10.1016/j. Lorente R, Rivero M, Fernández-Salazar Altered Underlying Renal Tubular cgh.2016.05.016] L, Gutiérrez A, Van Domselaar M, López-SanRomán A, Ber Y, García- Function in Patients With Chronic Hepatitis B Receiving Nucleos(t)ide 5. Carpio D, Jauregui-Amezaga A, de Sepulcre M, Ramos L, ..., Gisbert JP. Analogs in a Real-World Setting: Francisco R, de Castro L, Barreiro-de Incidence, Clinical Characteristics, The MENTE Study. Acosta M, Mendoza JL, Mañosa M, and Management of Psoriasis J Clin Gastroenterol. 2016;50:779- Ollero V, Castro B, González-Conde Induced by Anti-TNF Therapy in 789.F.I.:3,163. [doi:10.1097/ B, Hervías D, Sierra Ausin M, Sancho Patients with Inflammatory Bowel MCG.0000000000000569] Del Val L, Botella-Mateu B, Martínez- Disease: A Nationwide Cohort Study. 107

14. Santibáñez M, Garrastazu R, Crespo, Javier. Ruiz-Nuñez M, Helguera JM, Arenal S, Causes of treatment failure for Editorials Bonnardeux C, León C, García-Rivero hepatitis C in the era of direct-acting JL. antiviral therapy. Predictors of Hospitalized Rev Esp Enferm Dig. 2016;108:421- 1. Cabezas J, Bataller R. Exacerbations and Mortality in 430.F.I.:1,455. Alcoholic hepatitis: should we Chronic Obstructive Pulmonary combine old drugs for better results?. Disease. 20. Díaz-González Á, Forner A, HEPATOL INT. 2016;10:851-853. PLoS One. 2016;11:F.I.:3,057. Rodríguez de Lope C, Varela M. F.I.:1,125. [doi:10.1007/s12072-016- [doi:10.1371/journal.pone.0158727] New challenges in clinical research 9768-8] on hepatocellular carcinoma. Rev Esp Enferm Dig. 2016;108:485-493. 15. Boix-Giner F, Millan O, San F.I.:1,455. [doi:10.17235/ Segundo D, Muñoz-Cacho P, Mancebo reed.2015.4012/2015] E, Llorente S, Rafael-Valdivia L, Rimola A, Fábrega E, Mrowiec A, Allende L, 21. San Segundo D, Alonso C, Ruiz P, Minguela A, Bolarín JM, Paz-Artal E, Roman I, Arias-Loste MT, Cuadrado A, López-Hoyos M, Brunet M, Muro M. Puente A, Casafont F, López-Hoyos M, Tesis doctorales High frequency of central memory Crespo J, Fábrega E. regulatory T cells allows detection of De Novo Donor-Specific Anti- liver recipients at risk of early acute Human Leukocyte Antigen Antibody 1. Jose Ignacio Fortea Ormaechea. rejection within the first month after Detection in Long-Term Adult Liver Study of the effect of enoxaparin transplantation. Transplantation. on cirrhosis and experimental portal Int Immunol. 2016;28:55-64.F.I.:3,031. Transplant Proc. 2016;48:2980-2982. hypertension. [doi:10.1093/intimm/dxv048] F.I.:0,867. [doi:10.1016/j. Directors: Cristina Ripoll Noiseux, transproceed.2016.08.037] Rafael Bañares Cañizares. 16. Boix F, Millan O, Segundo DS, Complutense University of Madrid. Mancebo E, Rimola A, Fabrega E, 22. San Segundo D, Ruiz P, Irure J, Fortuna V, Mrowiec A, Castro-Panete Arias-Loste MT, Cuadrado A, Puente A, MJ, Peña J, Llorente S, Minguela A, Casafont F, López-Hoyos M, Crespo J, Bolarin JM, Paz-Artal E, Lopez-Hoyos Fábrega E. M, Brunet M, Muro M. Serum Levels of Interleukin-34 High expression of CD38, CD69, During Acute Rejection in Liver

CD95 and CD154 biomarkers in Transplantation. PROJECTS Transplant Proc. 2016;48:2977-2979. cultured peripheral T lymphocytes F.I.:0,867. [doi:10.1016/j. correlates with an increased risk transproceed.2016.08.038] of acute rejection in liver allograft recipients. 23. Gisbert JP, Molina-Infante J, Projects IMMUNOBIOLOGY. 2016;221:595- Amador J, Bermejo F, Bujanda L, Calvet 603.F.I.:2,781. [doi:10.1016/j. X, Castro-Fernández M, Cuadrado-Lavín imbio.2016.01.008] A, Elizalde JI, Gene E, Gomollón F, 1. Javier Crespo García. Lanas Á, Martín de Argila C, Mearin F, Endothelial dysfunction, subclinical 17. Calleja JL, Delgado S, Del Val A, Montoro M, Pérez-Aisa Á, Pérez-Trallero atheromatosis and cardiomyopathy Hervás A, Larraona JL, Terán Á, Cucala E, McNicholl AG. in patients with HCV infection. M, Mearin F. IV Spanish Consensus Conference Characterization and potential Colon Cancer Study Group. Ferric on Helicobacter pylori infection reversibility with direct antiviral carboxymaltose reduces transfusions treatment. agents. and hospital stay in patients with Gastroenterol Hepatol. 2016;39:697- Instituto de Salud Carlos III. Ministerio colon cancer and anemia. 721.F.I.:0,800. [doi:10.1016/j. de Economía y Competitividad. INT J COLORECTAL DIS. 2016;31:543- gastrohep.2016.05.003] 551.F.I.:2,383. [doi:10.1007/s00384-015- 2. Javier Crespo García. 2461-x] Personalized Medicine in HCV infection: understanding and 18. Fernández-Salazar L, Muñoz F, Reviews predicting hepatic and systemic Barrio J, Muñoz C, Pajares R, Rivero M, responses in the era of the new Prieto V, Legido J, Bouhmidi A, Herranz antiviral drugs. 1. Calleja JL, Llerena S, Perelló C, M, Fernández N, Sánchez-Ocaña R, PIE15/00079. Instituto de Salud Crespo J. Joao D, Santos F. Carlos III. Ministerio de Economía y NS5A Resistance: Clinical Infliximab in ulcerative colitis: real- Competitividad. Implications and Treatment life analysis of factors predicting Possibilities. treatment discontinuation due to AIDS REV. 2016;18:15-22.F.I.:2,068. 3. José Pedro Vaqué Díez. lack of response or colectomy: ECIA New mechanisms in aggressive (ACAD Colitis and Infliximab Study). 2. Val-Bernal JF, Mayorga M, Cagigal skin cancers: applications to the Scand J Gastroenterol. 2016;51:186- ML, Cabezas-González J. diagnosis, prognosis and therapy of 195.F.I.:2,199. [doi:10.3109/00365521.2 Gastric pyogenic granuloma: melanoma resistant to Merkel cell 015.1070900] Report of two cases and review therapy and carcinoma. of the literature. Pathol Res PI16/00156. Instituto de Salud 19. Cabezas, Joaquin, Llerena, Susana, Pract. 2016;212:68-71.F.I.:1,388. Carlos III. Ministerio de Economía y Puente, Angela, Fabrega, Emilio, [doi:10.1016/j.prp.2015.11.001] Competitividad. Research Areas Organ Transplants and Tissue and New Therapies Area

Group Leader Eulogio Haematologic Neoplasms Conde García Hematology Service andÁreas Haematopoietic de Stem Marqués de Valdecilla Cellsinvestigación Transplantation University Hospital

[email protected]

Sonia González de Villambrosía Pellón Andrés Insunza Gaminde Mónica López Duarte Carmen Montes Gaisán Javier Núñez Céspedes Carlos Richard Espiga Consolidated group Iñigo Romón Alonso Lucrecia Yáñez San Segundo

Nurses Researchers José Luis Arroyo Rodríguez María Ana Batlle López María del Carmen García Casquero Carlos Pipaón González Mª Aránzazu Bermúdez Rodríguez Sara Bravo Navas Contributors Mª De Las Mercedes Colorado Technicians Cristina Amunárriz Águeda Araujo María Pilar González Echezarreta 109

regimens including proteasome Iruin, Gemma, Herrero, Sonia, Soto, inhibitors, monoclonal antibodies Inmaculada, de Rueda, Beatriz, Research and liposomal formulations in Jimenez-Yuste, Victor, Alonso, Nieves, lymphoid pathology. Vilarino, Dolores, Arija, Olga, Campos, Rosa, Jose Paloma, Maria, Bermejo, Lines Nuria, Toll, Teresa, Mateo, Jose, ..., LINE 3. TRANSPLANTATION OF Vidal, Francisco. HEMATOPOYETIC PROGENITORS. Molecular and clinical profile of von Willebrand disease in Spain LINE 1. CELLULAR BIOLOGY OF Clinical results of allo-TPH in (PCM-EVW-ES): Proposal for a new HEMOPATHIES. patients with different neoplastic diagnostic paradigm. pathologies Thromb Haemost. 2016;115:40-50. Prognostic significance of BCL6 F.I.:5,255. [doi:10.1160/TH15-04-0282] and MYC expression in lymphomas. Extracorporeal phototherapy as The expression of MYC and BCL6 treatment of acute or chronic seems to have a prognostic and 2. Ramos F, Robledo C, Izquierdo- steroid-resistant CHF. García FM, Suárez-Vilela D, Benito therapeutic importance in NHL. R, Fuertes M, Insunza A, Barragán This line is being developed in Investigate the usefulness of E, Del Rey M, de Morales JM, collaboration with the group of the CMN infusion of the patient Tormo M, Salido E, Zamora L, Pathological Anatomy and group treated with metopsipsoralen Pedro C, Sánchez-Del-Real J, Díez- of Molecular Biology of Faculty of and submitted to extracorporeal Campelo M, Del Cañizo C, Sanz GF, Medicine of UC of Cantabria. phototherapy. Hernández-Rivas JM, Spanish Group for Myelodysplastic Syndromes Cooperative clinical research on (GESMD). Bone marrow fibrosis Chronic lymphatic leukemia: TCPH. Our casuistry is incorporated in myelodysplastic syndromes: a Analysis of post-transduction into national and international prospective evaluation including modifications, prognostic value databases, allowing a large number mutational analysis. study and therapeutic applications. of cases to be accumulated for Oncotarget. 2016;7:30492-30503. F.I.:5,008. [doi:10.18632/ Study of resistance to purine retrospective studies. analogs mediated by kinases. oncotarget.9026] Investigation on the application of specific anti-CMV vaccine Molecular biology and genetics 3. Batlle-López A, González in patients with hematopoietic of SMD: prospective tracking de Villambrosía S, Mazorra F, allograft to reduce complications of alterations in the FA-BRACA Malatxeberria S, Sáez A, Montalban associated with it. Phase III trial. C, Sánchez L, Garcia JF, González- pathway. Barca E, López A, Ruiz-Marcellan MC, Study of different modalities of Mollejo M, Grande C, Richards KL, Hsi LINE 2. DIAGNOSTIC AND immunosuppression, including ED, Tzankov A, Visco C, Xu-Monette THERAPEUTIC INNOVATION post-transplant cyclophosphamide ZY, Cao X, Young KH, Angel Piris M, in high-risk allogeneic Conde E, Montes-Moreno S. Research on the application of transplantation. Stratifying diffuse large B-cell lymphoma patients treated with new drugs in relapsed / refractory . chemoimmunotherapy: GCB/non- chronic lymphatic leukemia or with GCB by immunohistochemistry is high-risk cytogenetic alterations PUBLICATIONS: still a robust and feasible marker. (17p13 and / or 11q23). Phase II Oncotarget. 2016;7:18036-18049. and Phase III trials. F.I.:5,008. [doi:10.18632/ IMPACT FACTOR | 51,393 oncotarget.7495] Research on treatment regimens in patients with newly diagnosed 4. Bermudez G, González de myeloma as well as application of Original articles Villambrosía S, Martínez-López A, new drugs in multiple myeloma in Batlle A, Revert-Arce JB, Cereceda refractory relapse. Phase III trials Company L, Ortega Bezanilla C, Piris 1. Batlle, Javier, Perez-Rodriguez, MA, Montes-Moreno S. Almudena, Corrales, Irene, Fernanda Incidental and Isolated Follicular Application of new treatment Lopez-Fernandez, Maria, Rodriguez- Lymphoma In Situ and Mantle Cell regimens in patients with elderly Trillo, Angela, Loures, Esther, Rosa Lymphoma In Situ Lack Clinical myeloblastic leukemia. Phase III Cid, Ana, Bonanad, Santiago, Cabrera, Significance. trials Noelia, Moret, Andres, Parra, Rafael, Am J Surg Pathol. 2016;40:943-949. Eva Mingot-Castellano, Maria, Balda, F.I.:4,951. [doi:10.1097/ Ignacia, Altisent, Carmen, Perez- PAS.0000000000000628] Application of new treatment Montes, Rocio, Maria Fisac, Rosa, Research Areas Organ Transplants and Tissue and New Therapies Area

5. Orti G, Sanz J, Bermudez A, Bone Marrow Transplant. Ana, Escudero, Antonio, Villegas, Ana, Caballero D, Martinez C, Sierra 2016;51:1259-1261.F.I.:3,636. Gonzalez-Fernandez, Fernando A., J, Cabrera Marin JR, Espigado I, [doi:10.1038/bmt.2016.97] Ropero, Paloma. Solano C, Ferrà C, García-Noblejas HB Puerta del Sol [HBA1:c.148A>C], A, Jimenez S, Sampol A, Yañez L, HB Valdecilla [HBA2:c.3G>T], HB García-Gutiérrez V, Pascual MJ, 8. De La Serna J, Sanz J, Bermúdez Gran Vía [HBA2:c.98T>G], HB Jurado M, Moraleda JM, Valcarcel A, Cabrero M, Serrano D, Vallejo C, Macarena [HBA2:c.358C>T] and HB D, Sanz MA, Carreras E, Duarte RF. Gómez V, Moraleda JM, Perez SG, El Retiro [HBA2:c.364_366dupGTG]: Outcome of Second Allogeneic Caballero MD, Conde E. description of five new Hematopoietic Cell Transplantation Lahuerta JJ, Sanz G. Toxicity and hemoglobinopathies. after Relapse of Myeloid efficacy of busulfan and fludarabine Clin Chem Lab Med. 2016;54:553-560. Malignancies following Allogeneic myeloablative conditioning for F.I.:3,017. [doi:10.1515/cclm-2015- Hematopoietic Cell Transplantation: HLA-identical sibling allogeneic 0649] A Retrospective Cohort on Behalf hematopoietic cell transplantation in of the Grupo Español de Trasplante AML and MDS. Hematopoyetico. Bone Marrow Transplant. 2016;51:961- 13. Ribera JM, García O, Oriol A, Gil Biol Blood Marrow Transplant. 966.F.I.:3,636. [doi:10.1038/ C, Montesinos P, Bernal T, González- 2016;22:584-588.F.I.:3,980. bmt.2016.42] Campos J, Lavilla E, Ribera J, Brunet [doi:10.1016/j.bbmt.2015.11.012] S, Martínez MP, Tormo M, Genescà E, Barba P, Sarrà J, Monteserín MC, 9. Kelleher N, Gallardo D, González- Soria B, Colorado M, Cladera A, 6. Nomdedeu M, Calvo X, Pereira A, Campos J, Hernández-Rivas JM, García-Guiñón A, Calbacho M, Serrano Carrió A, Solé F, Luño E, Cervera J, Montesinos P, Sarrá J, Gil C, Barba A, Ortín X, Pedreño M, Amigo ML, Vallespí T, Muñoz C, Gómez C, Arias P, Guàrdia R, Brunet S, Bernal T, Escoda L, Feliu E. A, Such E, Sanz G, Grau J, Insunza A, Martínez MP, Abella E, Bermúdez PETHEMA Group, Spanish Society Calasanz MJ, Ardanaz MT, Hernández- A, Sánchez-Delgado M, Antònia C, of Hematology. Feasibility and Rivas JM, Azaceta G, Álvarez S, Gayoso J, Calbacho M, Ribera JM, results of subtype-oriented protocols Sánchez J, Martín ML, Bargay J, Pethema Group, Spanish Society in older adults and fit elderly Gómez V, Cervero CJ, Allegue MJ, of Hematology. Incidence, clinical patients with acute lymphoblastic Collado R, Campo E, Esteve J, ..., and biological characteristics leukemia: Results of three Spanish Group of Myelodysplastic and outcome of secondary acute prospective parallel trials from the Syndromes. Prognostic impact lymphoblastic leukemia after solid PETHEMA group. of chromosomal translocations organ or hematologic malignancy. Leuk Res. 2016;41:12-20.F.I.:2,606. in myelodysplastic syndromes Leuk Lymphoma. 2016;57:86-91. [doi:10.1016/j.leukres.2015.11.012] and chronic myelomonocytic F.I.:3,093. [doi:10.3109/10428194.201 leukemia patients. A study by the 5.1040013] spanish group of myelodysplastic 14. Romòn I, Montes C, Ligeiro D, syndromes. Trindade H, Sanchez-Mazas A, Nunes Genes Chromosomes Cancer. 10. Gratwohl A, Iacobelli S, Bootsman JM, Buhler S. 2016;55:322-327.F.I.:3,960. N, van Biezen A, Baldomero H, Arcese Mapping the HLA diversity of the [doi:10.1002/gcc.22333] W, Arnold R, Bron D, Cordonnier Iberian Peninsula. C, Ernst P, Ferrant A, Frassoni F, Hum Immunol. 2016;77:832-840. Gahrton G, Richard C, Kolb HJ, Link H, F.I.:2,127. [doi:10.1016/j. 7. Koenecke, C., Heim, D., van Biezen, Niederwieser D, Ruutu T, Schattenberg humimm.2016.06.023] A., Heuser, M., Aljurf, M., Kyrcz- A, Schmitz N, Torres-Gomez A, Zwaan Krzemien, S., Volin, L., de Souza, C. A., F, Apperley J, Olavarria E, Kröger N. Gedde-Dahl, T., Sengeloev, H., Schanz, Chronic Malignancies Working Party U., Komarnicki, M., Arroyo, C. H., of the European Society for Blood Tholouli, E., Gluckman, E., Esquirol, A., and Marrow. Splenic irradiation Reviews Yakoub-Agha, I., Gurman, G., Olavarria, before hematopoietic stem cell E., Kroeger, N., Rovira, M., Kahls, P., transplantation for chronic myeloid Alegre, A., Nemet, D., Stamatovic, D., leukemia: long-term follow-up of a 1. Piris MÁ, Battle-Lopez A, Nuñez J, Vitek, A., Hamladji, R., Hellmann, A., prospective randomized study. Cagigal ML, Montes-Moreno S, Conde Chybicka, A., ..., Finke, J.. Ann Hematol. 2016;95:967-972. E. Outcome of patients with chronic F.I.:3,022. [doi:10.1007/s00277-016- Epstein-Barr virus-associated diffuse myeloid leukemia and a low-risk 2638-6] large B-cell lymphoma: diagnosis, score: allogeneic hematopoietic difficulties and therapeutic options. stem cell transplantation in the era Expert Rev Anticancer Ther. of targeted therapy. A report from 12. De la Fuente-Gonzalo, Felix, Nieto, 2016;16:411-421.F.I.:2,094. [doi:10.158 the EBMT Chronic Malignancies Jorge M., Velasco, Diego, Cela, Elena, 6/14737140.2016.1149065] Working Party. Perez, German, Fernandez-Teijeiro, 111 Research Areas Organ Transplants and Tissue and New Therapies Area

Group Leader Marcos López Hoyos Immunology Service Áreas de Marqués de Valdecilla Transplantation and University Hospital Autoimmunityinvestigación

[email protected]

Carmen Pérez Robles Vicente Celestino Piñera Haces Mª Ángeles Ramos Barrón Juan Carlos Ruíz San Millán David San Segundo Arribas Jorge Alberto Suárez Rodríguez Silvia Torices Del Val Rosalia Valero San Cecilio Ana Victoria Villar Ramos Consolidated group Nurses Mª Consuelo Agüeros Blanco Montserrat González García María José Novo Fernández María Del Camino Villa Llamazares

Researchers Predoctoral Mª De Los Ángeles Ballesteros Sanz María Iglesias Escudero Manuel Antonio Arias Rodríguez Adalberto Benito Hernández Victor Manuel Martínez Taboada Gema Fernández Fresnedo Eduardo Miñambres García Carlos Gómez Alamillo Technicians Emilio Rodrigo Calabia Luis Martin Penagos Ángel Luis Martín De Francisco Paloma Barreda Monteoliva Contributors Hernández José Óscar García Ruíz Lorena Álvarez Rodríguez Rosa Palomar Fontanet Sandra Raso Torres 113

2. Immunoregulation in kidney LINE 2: INFLAMMATION AND and lung transplantation. AUTOIMMUNE DISEASES Research To evaluate the effect that changes in blood and tissues 1. Inflammatory diseases Lines of cellular populations with associated with aging (giant cell immunoregulatory capacity may arteritis, polymyalgia rheumatica have on the long-term evolution and rheumatoid arthritis of onset of the transplant in general and in the elderly). These syndromes, of the renal in particular. In the which are very prevalent in the LINE 1: TRANSPLANTATION OF case of renal transplantation, elderly population, are mainly SOLID ORGANS we have found a clear influence treated with corticosteroids, of the level of pharmacological which are accompanied by a 1. Non-invasive blood and immunosuppression on the high toxicity. Studies investigate urine biomarkers of clinical number and function of the role of cytokines, regulatory events related to solid organ regulatory T cells. In addition, cells and alterations of innate transplantation (rejection, in lung transplantation we have immunity, with the ultimate goal infection, immunosuppression verified how a certain number of developing less toxic and more conversion, short-term and of regulatory T cells in blood effective therapies. We used long-term graft survival). prior to transplantation plays a cellular markers (phenotypic This line focuses on soluble prognostic role in the incidence of and functional), serological and and cellular markers related rejection. This line together with genetic (expression and genetic to the immune response in the previous one receives regular polymorphisms). More recently allotransplantation and more competitive financing from the we have started a line of work on recently. In addition, we included ISCIII. arthritis in connection with FIS- the study of molecular profiles funded FG-beta signaling. predictive of failure of renal 3. Intensive treatment of 2. Antiphospholipid syndrome. function and increase of fibrosis donors to increase the The role that the innate in initial stages. Together with number of grafts suitable immune response (specifically our own studies, we participated for transplantation. Intensive the TLR) and the different in REDINREN (Research treatment of multiorgan donors immunoregulatory populations Network on Renal Diseases: based on specific ventilatory may play in the pathogenesis of RD16 / 0009/027). At the same therapy, extrapulmonary water- this disease is studied. We also time, we have transferred the guided hemodynamic goals, analyzed the clinical results of the study of biomarkers to lung and hormone therapy increases Unit of Autoimmune Gravidarum transplantation since it is a very the number of transplant-able Pathology and performed a potent clinical activity in our pulmonary grafts. This increase beta study to evaluate new center, which has already allowed in the number of available methods of measurement of us to obtain results quickly, which pulmonary grafts is due to the diagnostic antibodies in this have demonstrated specific improvement in oxygenation of pathology. In particular, we are differences between kidney and the lungs in the period between validating the usefulness of new lung transplantation. Soluble death and organ harvesting. This immunoglobulin isotypes (IgA) markers of humoral rejection. specific treatment is associated against phospholipids as well This line of research has made with an increase in the rest of as the value of other antibodies it possible to transfer to the organs to improve the perfusion against other phospholipids not clinic the monitoring of anti-HLA and oxygenation of all of them. included in the diagnostic criteria antibodies in desensitization so far. treatments in renal transplants The use of regional normothermic of patients hypersensitized with perfusion to deceased donors by 3. Biomarkers. The group has live donors. Thanks to this line, circulatory criteria has allowed to a large library associated with our center attracts patients from reduce the ischemic damage of clinical data collected since other regions and has allowed us the grafts due to the deleterious 1997. This library allows the to be part of the national cross- effect of the cardiac arrest, and study and validation of new renal donation program. This line to simultaneously extract and markers involved in the diagnosis, of work is also included in the successfully transplant all types of prognosis and response to REDINREN program and we lead grafts (lungs, liver, Pancreas and the treatment of autoimmune within the network. We consider kidneys). Both lines of research pathology. In addition, we have this line one of the greatest have developed multicentric all the type of tests necessary for potential of clinical transference. studies with funding from the the development and serological Mutua Madrileña Foundation. studies of autoimmunity. As a Research Areas Organ Transplants and Tissue and New Therapies Area

result of the exploitation of this Martínez-Taboada V, Erra A, Sánchez- Taboada V, Fernández-Luna JL. library we have defined new Fernández S, Alonso A, Lopez-Lasanta A functional variant of TLR10 diagnostic uses of antibodies not M, Tortosa R, Codó L, Gelpi JL, modifies the activity of NFkB and explored until now (anti-PR3) in García-Montero AC, Bertranpetit J, may help predict a worse prognosis Absher D, Bridges SL, Myers RM, in patients with rheumatoid arthritis. pathologies such as inflammatory Tornero J, Marsal S. A genome-wide Arthritis Res Ther. 2016;18:221-221. bowel disease with IDIVAL’s association study identifies SLC8A3 F.I.:3,979. [doi:10.1186/s13075-016- group of digestive pathology. as a susceptibility locus for ACPA- 1113-z] positive rheumatoid arthritis. Rheumatology (Oxford). 2016;55:1106- 10. Pippias M, Stel VS, Aresté-Fosalba 1111.F.I.:4,524. [doi:10.1093/ N, Couchoud C, Fernandez-Fresnedo rheumatology/kew035] G, Finne P, Heaf JG, Hoitsma A, De Meester J, Pálsson R, Ravani P, PUBLICATIONS: 5. López-Hoyos M, Álvarez-Rodríguez L, Segelmark M, Traynor JP, Reisæter AV, Mahler M, Torices S, Calvo-Alén J, Villa Caskey FJ, Jager KJ. Long-term Kidney Transplant IMPACT FACTOR | 118,768 I, Seaman A, Yee A, Martínez-Taboada V. Anti-carbamylated protein antibodies Outcomes in Primary in patients with ageing associated Glomerulonephritis: Analysis inflammatory chronic disorders. From the ERA-EDTA Registry. Rheumatology (Oxford). 2016;55:764- Transplantation. 2016;100:1955-1962. Original articles 766.F.I.:4,524. [doi:10.1093/ F.I.:3,690. [doi:10.1097/ rheumatology/kev391] TP.0000000000000962]

11. Rodrigo E, Segundo DS, Fernández- 1. Julià A, Blanco F, Fernández- 6. Porrini EL, Díaz JM, Moreso F, Fresnedo G, López-Hoyos M, Benito A, Gutierrez B, González A, Cañete JD, Delgado Mallén PI, Silva Torres I, Ruiz JC, de Cos MA, Arias M. Maymó J, Alperi-López M, Olivè A, Ibernon M, Bayés-Genís B, Benitez- Within-Patient Variability in Corominas H, Martínez-Taboada V, Ruiz R, Lampreabe I, Lauzurrica R, Tacrolimus Blood Levels Predicts González I, Fernandez-Nebro A, Erra Osorio JM, Osuna A, Domínguez- Kidney Graft Loss and Donor- A, Sánchez-Fernández S, Alonso A, Rollán R, Ruiz JC, Jiménez-Sosa A, Specific Antibody Development. López-Lasanta M, Tortosa R, Codó González-Rinne A, Marrero-Miranda D, Transplantation. 2016;100:2479-2485. L, Lluis Gelpi J, García-Montero AC, Macía M, García J, Torres A. F.I.:3,690. [doi:10.1097/ Bertranpetit J, Absher D, Myers RM, Clinical evolution of post-transplant TP.0000000000001040] Tornero J, Marsal S. diabetes mellitus. Identification of IRX1 as a Risk Nephrol Dial Transplant. 2016;31:495- 12. Arias-Loste MT, Iruzubieta P, Locus for Rheumatoid Factor 505.F.I.:4,085. [doi:10.1093/ndt/gfv368] Puente Á, Ramos D, Santa Cruz C, Positivity in Rheumatoid Arthritis in Estébanez Á, Llerena S, Alonso-Martín a Genome-Wide Association Study. 7. Merino D, San Segundo D, Medina C, San Segundo D, Álvarez L, López Arthritis Rheumatol. 2016;68:1384-1391. JM, Rodrigo E, Asensio E, Irure J, Useros A, Fábrega E, López-Hoyos M, F.I.:6,009. [doi:10.1002/art.39591] Fernández-Fresnedo G, Arias MA, Crespo J. López-Hoyos M. 2. Merino D, Villar AV, García R, Increased Expression Profile and Different in vitro proliferation and Tramullas M, Nistal JF, Hurlé MA. Functionality of TLR6 in Peripheral cytokine-production inhibition BMP-7 attenuates left ventricular Blood Mononuclear Cells and of memory T-cell subsets after remodelling under pressure overload Hepatocytes of Morbidly Obese calcineurin and mammalian target and facilitates reverse remodelling Patients with Non-Alcoholic Fatty of rapamycin inhibitors treatment. and functional recovery. Liver Disease. Immunology. 2016;148:206-215. Cardiovasc Res. 2016;110:331-345. INT J MOL SCI. 2016;17: F.I.:4,078. [doi:10.1111/imm.12603] F.I.:5,465. [doi:10.1093/cvr/cvw076] F.I.:3,257. [doi:10.3390/ijms17111878]

13. Boix-Giner F, Millan O, San 3. Calero L, Martin-Lorenzo M, 8. López Hoyos, Marcos. Segundo D, Muñoz-Cacho P, Mancebo Ramos-Barron A, Ruiz-Criado J, Multicenter study for the evaluation E, Llorente S, Rafael-Valdivia L, Rimola Maroto AS, Ortiz A, Gomez-Alamillo of the antibody response against A, Fábrega E, Mrowiec A, Allende L, C, Arias M, Vivanco F, Alvarez-Llamas salmonella typhi Vi vaccination Minguela A, Bolarín JM, Paz-Artal E, G. Urinary Kininogen-1 and Retinol (EMPATHY) for the diagnosis of Anti- López-Hoyos M, Brunet M, Muro M. binding protein-4 respond to Acute polysaccharide antibody production High frequency of central memory Kidney Injury: predictors of patient deficiency in patients with primary regulatory T cells allows detection of prognosis?. immunodeficiency. liver recipients at risk of early acute Sci Rep. 2016;6:19667-19667. CLIN IMMUNOL. 2016;169:80-84. rejection within the first month after F.I.:5,228. [doi:10.1038/srep19667] F.I.:4,034. [doi:10.1016/j. transplantation. clim.2016.05.006] Int Immunol. 2016;28:55-64. 4. Julià A, González I, Fernández- F.I.:3,031. [doi:10.1093/intimm/dxv048] Nebro A, Blanco F, Rodriguez L, 9. Torices S, Julia A, Muñoz P, Varela I, González A, Cañete JD, Maymó J, Balsa A, Marsal S, Fernández-Nebro A, 14. Díaz-Angulo S, López-Hoyos M, Alperi-López M, Olivé A, Corominas H, Blanco F, López-Hoyos M, Martinez- Muñoz Cacho P, Fernández M, López- 115

Escobar M, Rodríguez F, González- 19. Boix F, Millan O, Segundo DS, 23. Demetrio Pablo, R., Munoz, P., López MA. Mancebo E, Rimola A, Fabrega E, Riancho-Zarrabeiti, L., Calvo-Rio, V., Prevalence of thyroid autoimmunity Fortuna V, Mrowiec A, Castro-Panete Lopez-Hoyos, M., Martinez-Taboada, in spanish patients with chronic MJ, Peña J, Llorente S, Minguela A, V.. RISK FACTORS FOR PREGNANCY idiopathic urticaria: a case-control Bolarin JM, Paz-Artal E, Lopez-Hoyos MORBIDITY IN PATIENTS WITH study involving 343 subjects. M, Brunet M, Muro M. ANTIPHOSPHOLIPID ANTIBODIES J Eur Acad Dermatol Venereol. High expression of CD38, CD69, WITHOUT A DEFINED CLINICAL 2016;30:692-693. CD95 and CD154 biomarkers in ANTIPHOSPHOLIPID SYNDROME. F.I.:3,029. [doi:10.1111/jdv.12979] cultured peripheral T lymphocytes Clin Exp Rheumatol. 2016;34:49-49. correlates with an increased risk F.I.:2,495. 15. Krämer BK, Montagnino G, Krüger of acute rejection in liver allograft B, Margreiter R, Olbricht CJ, Marcen recipients. 24. Riancho Zarrabeitia, L., Daroca, R, Sester U, Kunzendorf U, Dietl KH, IMMUNOBIOLOGY. 2016;221:595-603. G., Lopez-Hoyos, M., Munoz, Rigotti P, Ronco C, Hörsch S, Banas B, F.I.:2,781. [doi:10.1016/j. P., Haya, A., Gonzalez, M., Del Mühlbacher F, Arias M. imbio.2016.01.008] Barrio, R., Martinez-Taboada, V.. European Tacrolimus vs. SEROLOGICAL EVOLUTION IN Ciclosporin Microemulsion Renal 20. Demetrio-Pablo, R., Munoz, P., FERTILE WOMEN WITH POSITIVE Transplantation Study Gr. Efficacy Calvo-Rio, V., Riancho-Zarrabeitia, L., ANTIPHOSPHOLIPID ANTIBODIES. and safety of tacrolimus compared Lopez-Hoyos, M., Martinez-Taboada, V. Clin Exp Rheumatol. 2016;34:44-44. with ciclosporin-A in renal EVALUATION OF THROMBOTIC F.I.:2,495. transplantation: 7-year observational RISK IN PATIENTS WITH POSITIVE results. ANTIPHOSPHOLIPID ANTIBODIES 25. Galindo-Izquierdo M, Rodriguez- Transpl Int. 2016;29:307-314. WITHOUT CLINICAL CRITERIA FOR Almaraz E, Pego-Reigosa JM, F.I.:2,835. [doi:10.1111/tri.12716] THE DISEASE. López-Longo FJ, Calvo-Alén J, Olivé A, Clin Exp Rheumatol. 2016;34:97-97. Fernández-Nebro A, Martinez-Taboada 16. Carbone, J., Cifrian, J., Lopez- F.I.:2,495. V, Vela-Casasempere P, Freire M, Hoyos, M., Bravo, C., Lopez, S., Narváez FJ, Rosas J, Ibáñez-Barceló M, Ussetti, P., Laporta, R., De Pablos, A., 21. Torrente-Segarra V, Salman-Monte Uriarte E, Tomero E, Zea A, Horcada Pleguezuelo, D., Sole, A., Jaramillo, TC, Rúa-Figueroa Í, Pérez-Vicente S, L, Torrente V, Castellvi I, Calvet J, M., Navarro, J., Rodriguez-Molina, J., López-Longo FJ, Galindo-Izquierdo Menor-Almagro R, Zamorano MA, Sarmiento, E.. M, Calvo-Alén J, Olivé-Marqués A, Raya E, Díez-Álvarez E, Vázquez- PRE-TRANSPLANT HUMORAL Ibañez-Ruán J, Horcada L, Sánchez- Rodríguez T, García de la Peña P, IMMUNITY RISK FACTORS Atrio A, Montilla C, Rodríguez-Gómez Movasat A, Andreu JL, Richi P, ..., OF INFECTION IN LUNG M, Díez-Álvarez E, Martinez-Taboada RELESSER Group, from the Spanish TRANSPLANTATION: RESULTS OF A V, Andreu JL, Fernández-Berrizbeitia Society of Rheumatology Systemic MULTICENTER STUDY. O, Hernández-Beriain JA, Gantes M, Autoimmune Dis. Characterization Transpl Int. 2016;29:5-5. Hernández-Cruz B, Pecondón-Español of Patients With Lupus Nephritis F.I.:2,835. Á, Marras C, Bonilla G, Pego-Reigosa Included in a Large Cohort From the JM. Spanish Society of Rheumatology 17. Sánchez-Fructuoso AI, Pérez- RELESSER Study Group of the Registry of Patients With Systemic Flores I, Valero R, Moreno MA, Spanish Society of Rheumatology Lupus Erythematosus (RELESSER). Fernandez-Arquero M, Urcelay E, (SER) and the Study. Fibromyalgia Medicine (Baltimore). 2016;95: Fernández-Pérez C, Santiago JL. prevalence and related factors in F.I.:2,133. [doi:10.1097/ The Polymorphism -308G/A of Tumor a large registry of patients with MD.0000000000002891] Necrosis Factor-a Gene Modulates systemic lupus erythematosus. the Effect of Immunosuppressive Clin Exp Rheumatol. 2016;34:40-47. 26. Llompart-Pou JA, Chico- Treatment in First Kidney Transplant F.I.:2,495. Fernández M, Sánchez-Casado M, Subjects Who Suffer an Acute Alberdi-Odriozola F, Guerrero-López F, Rejection. 22. Rua-Figueroa, I., Castro, M. Mayor-García MD, González-Robledo J, J Immunol Res. 2016;2016:2197595- Fernandez, Pego-Reigosa, J. M., Ballesteros-Sanz MÁ, Herrán-Monge R, 2197595. Sanchez-Piedra, C., Lopez-Longo, León-López R, López-Amor L, Bueno- F.I.:2,812. [doi:10.1155/2016/2197595] J., Taboada, V. Martinez, Calvo-Alen, González A. J., Olive, A., Galindo, M., Blanco, R., Trauma Neurointensive Care 18. Miñambres E, Pérez-Villares JM, Alonso, F., Erausquin, C., Andreu, J. L. Working Group of the Spanish Terceros-Almanza L, Dueñas-Jurado PREVALENCE OF COMORBIDITIES Society of Intensive Car. Age-related JM, Zabalegui A, Misis M, Bouza MT, IN PATIENTS WITH PRIMARY injury patterns in Spanish trauma Ballesteros MA, Coll E. SJOGREN’S SYNDROME ICU patients. Results from the An intensive lung donor treatment AND SYSTEMIC LUPUS RETRAUCI. protocol does not have negative ERYTHEMATOSUS: A Injury. 2016;47 Suppl 3:61-65. influence on other grafts: a COMPARATIVE, REGISTER-BASED F.I.:1,910. [doi:10.1016/S0020- multicentre study. STUDY WITH EMPHASIS IN 1383(16)30608-8] Eur J Cardiothorac Surg. CARDIOVASCULAR DISEASE. 2016;49:1719-1724. Clin Exp Rheumatol. 2016;34:98-99. F.I.:2,803. [doi:10.1093/ejcts/ezv454] F.I.:2,495. 27. Mancebo E, Castro MJ, Allende LM, Talayero P, Brunet M, Millán Research Areas Organ Transplants and Tissue and New Therapies Area

O, Guirado L, López-Hoyos M, San 33. Torres A, Torregrosa V, Marcen R, San Segundo D. Segundo D, Rodrigo E, Muñoz P, Campistol JM, Arias M, Hernández D, Antibody-Mediated Rejection in Boix Giner F, Llorente Viñas S, Muro- Fernández C, Esforzado N, Paschoalin Kidney Transplantation Without Amador M, Paz-Artal E. R, Pérez N, García AI, Del Amo M, Evidence of Anti-HLA Antibodies?. High proportion of CD95(+) and Pomés J, González Rinne A, Marrero D, Transplant Proc. 2016;48:2888-2890. CD38(+) in cultured CD8(+) T Pérez E, Henríquez F, Díaz JM, Silva I, F.I.:0,867. [doi:10.1016/j. cells predicts acute rejection and López V, Perello M, Ramos D, Beneyto transproceed.2016.09.025] infection, respectively, in kidney I, Cruzado JM, Martínez Castelao A, recipients. Bravo J, Rodríguez M, Díaz C, Crespo 38. Ramos-Barron MA, Hernandez Transpl Immunol. 2016;34:33-41. J, ..., Gómez Alamillo C. Bejarano I, Rodrigo E, Cruz Iglesias E, F.I.:1,317. [doi:10.1016/j. 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D, Rodrigo E, Lopez-Hoyos M, Benito 29. Monfá E, Rodrigo E, Belmar L, Nefrologia. 2016;36:446-448.F.I.:1,207. A, Ángeles Ramos M, Gómez-Román Sango C, Moussa F, Ruiz San Millán [doi:10.1016/j.nefro.2016.02.007] J, Arias M. JC, Piñera C, Fernández-Fresnedo G, B-Cell-Activating Factor Levels Are Arias M. 35. Chico-Fernández M, Llompart-Pou Associated With Antibody-Mediated A high sodium intake reduces JA, Guerrero-López F, Sánchez-Casado Histological Damage in Kidney antiproteinuric response to renin- M, García-Sáez I, Mayor-García MD, Transplantation. angiotensin-aldosterone system Egea-Guerrero J, Fernández-Ortega Transplant Proc. 2016;48:2910-2912. blockade in kidney transplant JF, Bueno-González A, González- F.I.:0,867. [doi:10.1016/j. recipients. Robledo J, Servià-Goixart L, Roldán- transproceed.2016.09.019] Nefrologia. 2016;36:545-551.F.I.:1,207. Ramírez J, Ballesteros-Sanz MÁ, [doi:10.1016/j.nefro.2016.01.018] Tejerina-Alvarez E, García-Fuentes C, 40. San Segundo D, Alonso C, Ruiz P, Alberdi-Odriozola F, en representación Roman I, Arias-Loste MT, Cuadrado A, 30. De Francisco AL, Gillespie IA, del Grupo de Trabajo de Trauma Puente A, Casafont F, López-Hoyos M, Gioni I, Floege J, Kronenberg F, y Neurointensivismo SEMICYUC. Crespo J, Fábrega E. Marcelli D, Wheeler DC, Froissart M, Epidemiology of severe trauma in De Novo Donor-Specific Anti- Drueke TB. Spain. Registry of trauma in the ICU Human Leukocyte Antigen Antibody ARO Steering Committee (RETRAUCI). Pilot phase. Detection in Long-Term Adult Liver Cllaborators. Anti-parathyroid Med Intensiva. 2016;40:327-347. Transplantation. treatment effectiveness F.I.:1,193. [doi:10.1016/j. Transplant Proc. 2016;48:2980-2982. and persistence in incident medin.2015.07.011] F.I.:0,867. [doi:10.1016/j. haemodialysis patients with transproceed.2016.08.037] secondary hyperparathyroidism. 36. Chico-Fernández M, Llompart- Nefrologia. 2016;36:164-175.F.I.:1,207. Pou JA, Sánchez-Casado M, Alberdi- 41. Valentin MO, Ruiz JC, Vega R, [doi:10.1016/j.nefro.2015.10.006] Odriozola F, Guerrero-López F, Martín C, Matesanz R. Mayor-García MD, Egea-Guerrero working group PATHI. 31. Seras M, Martín de Francisco ÁL. JJ, Fernández-Ortega JF, Bueno- Implementation of a National Haemodialysis session: The perfect González A, González-Robledo J, Priority Allocation System for storm for vascular calcification. Servià-Goixart L, Roldán-Ramírez J, Hypersensitized Patients in Spain, Nefrologia. 2016;36:442-443.F.I.:1,207. Ballesteros-Sanz MÁ, Tejerina-Alvarez Based on Virtual Crossmatch: Initial [doi:10.1016/j.nefro.2016.02.001] E, Pino-Sánchez FI, Homar-Ramírez Results. J, in representation of the Trauma Transplant Proc. 2016;48:2871-2875. 32. Belmar Vega L, de Francisco A, and Neurointensive Care Working F.I.:0,867. [doi:10.1016/j. Albines Fiestas Z, Serrano Soto M, Group of the SEM. 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Transplant Proc. 2016;48:2950-2952. 4. Mercè B, Olga M, Marcos LH. microbiological profile, antimicrobial F.I.:0,867. [doi:10.1016/j. T-Cell Cytokines as Predictive sensitivity and differences according transproceed.2016.09.012] Markers of the Risk of Allograft to age. Rejection. Directors: Manuel Antonio Arias 43. San Segundo D, Ruiz P, Irure J, Ther Drug Monit. 2016;38 Suppl 1:21-28. Rodríguez, Luis Martínez Martínez. Arias-Loste MT, Cuadrado A, Puente A, F.I.:2,094. [doi:10.1097/ University of Cantabria. Casafont F, López-Hoyos M, Crespo J, FTD.0000000000000253] Fábrega E. Serum Levels of Interleukin-34 During Acute Rejection in Liver Transplantation. Transplant Proc. 2016;48:2977-2979. PROYECTOS F.I.:0,867. [doi:10.1016/j. transproceed.2016.08.038] Editorials

1. Cuervas-Mons V, López-Hoyos M. Proyectos Preface. Transplant Proc. 2016;48:2855-2855. F.I.:0,867. [doi:10.1016/j. 1. Manuel Antonio Arias Rodríguez. transproceed.2016.10.004] Reviews Research Network on Kidney Diseases. RD12/0021/0007. INSTITUTO DE SALUD CARLOS III. MINISTERIO DE ECONOMÍA Y 1. García R, Merino D, Gómez JM, COMPETITIVIDAD. Nistal JF, Hurlé MA, Cortajarena AL, Doctoral thesis Villar AV. 2. Manuel Antonio Arias Rodríguez. Extracellular heat shock protein Study of serological and cell 90 binding to TGFß receptor I 1. Jorge Duerto Alvarez. activation factors as possible early participates in TGFß-mediated Long-term effect in renal grafts of markers of chronic kidney-mediated collagen production in myocardial an intensive management protocol rejection in renal transplantation. fibroblasts. of the multiorganic donor. Directors: PI14/00378. INSTITUTO DE SALUD Cell Signal. 2016;28:1563-1579. Eduardo Miñambres García, María CARLOS III. MINISTERIO DE F.I.:4,191. [doi:10.1016/j. De Los Ángeles Ballesteros Sanz. ECONOMÍA Y COMPETITIVIDAD. cellsig.2016.07.003] University of Cantabria. 3. Marcos López Hoyos. 2. Brunet M, Shipkova M, van Gelder Usefulness of the study of T, Wieland E, Sommerer C, Budde K, 2. Rosalía Demetrio Pablo. suppressor myeloid cells (MDSC) in Haufroid V, Christians U, López-Hoyos Evaluation of thrombotic risk renal transplant monitoring. M, Barten MJ, Bergan S, Picard N, in asymptomatic patients with PI16/01585. INSTITUTO DE SALUD Millán López O, Marquet P, Hesselink antiphospholipid antibodies. CARLOS III. MINISTERIO DE DA, Noceti O, Pawinski T, Wallemacq P, Directors: Pedro Muñoz Cacho, Victor ECONOMÍA Y COMPETITIVIDAD. Oellerich M. Manuel Martínez Taboada. University Barcelona Consensus on Biomarker- of Cantabria. Based Immunosuppressive Drugs 4. Víctor Manuel Martínez Taboada. Management in Solid Organ Study of the role BAMBI, a 3. Inmaculada Hernandez Bejarano. Transplantation. regulator of TGF beta signaling, as Analysis of the evolution of renal Ther Drug Monit. 2016;38 Suppl 1:1-20. a pathogenic factor and prognostic transplantation by identifying F.I.:2,094. [doi:10.1097/ marker in rheumatoid arthritis. risk biomarkers in the donor and FTD.0000000000000287] PI16/01717. INSTITUTO DE SALUD recipient. Directors: Ana Isabel CARLOS III. MINISTERIO DE Morales Martin, Marta Prieto 3. López-Hoyos M, San Segundo ECONOMÍA Y COMPETITIVIDAD. Vicente, Mª Ángeles Ramos Barrón, D, Brunet M. Regulatory T Cells Carlos Gómez Alamillo. as Biomarkers for Rejection and 5. Marcos López Hoyos. University of Salamanca. Immunosuppression Tailoring in Research Network for Kidney Solid Organ Transplantation. Diseases. RD16/0009/0027. Ther Drug Monit. 2016;38 Suppl 1:36-42. 4. José Quintanar Lartuno. INSTITUTO DE SALUD CARLOS F.I.:2,094. [doi:10.1097/ Peritonitis in peritoneal dialysis. III. MINISTERIO DE ECONOMÍA Y FTD.0000000000000265] Experience over a decade: evolution, COMPETITIVIDAD.

119

Neuroscience Area Benedicto Crespo Facorro Coordinator of the Neuroscience Area.

Section Chief, Psychiatry. University Hospital Marqués de Valdecilla. Professor of the Department of Medicine and Psychiatry. University of Cantabria Research Areas Neuroscience Area

Group Leader Miguel Ángel Lafarga Coscojuela Department of Anatomy Áreas de and Cell Biology School of Medicine Nuclearinvestigación Cell Biology University of Cantabria

[email protected]

Co-leader María Teresa Berciano Blanco

Contributors Jorge Mata Garrido Josep Oriol Narcis Majos

Predoctoral Jorge Mata Garrido Josep Oriol Narcis Majos Consolidated group

responsible for spinal muscular demonstrates that acetylation atrophy (SMA), which causes motor modifies the interactions of the SMN neuron degeneration and is the main with its target proteins, affecting the Research cause of genetic-based mortality cellular localization of the protein and Lines in the childhood. In addition to its ability to nuclear CBs. SMNs and snRNPs and snoRNPs, another essential component of CB is the coilin nucleating protein. The Line 2. Importance of dysfunction Line 1. Role of motor neuron fundamental objective of this line is to of nuclear compartments of spinal survival factor (SMN) acetylation analyze the mechanisms that regulate motor neurons in the cellular and in the Cajal nuclear body assembly the molecular assembly of the CB molecular pathophysiology of (Cajal body, CB): and its importance in the SMA. We spinal muscular atrophy (SMA) in have recently shown that the SMN murine model SMNd7. importance in spinal muscular protein is a substrate of SUMO1 As discussed above, mutation or atrophy (SMA). The core of Cajal (CB, and that its conjugation with SUMO deletion of the SMN1 gene in SMA Fig. 1) is the nuclear power plant is another factor regulating the produces a severe deficiency of the that directs the final assembly and formation of CBs. We are currently functional SMN protein, leading to quality control of the snRNPs and studying the impact of another degeneration and death of spinal snoRNPs (small nuclear nucleolar post-translational modification of neurons. In the pathophysiology of ribonucleoproteins) involved in SMN, acetylation, on the assembly SMA, three essential mechanisms the splicing of pre-mRNAs and in of snRNPs and snoRNPs and the exist at the level of spinal the maturation of pre-rRNAs. The formation of CBs. Our preliminary motoneurons: splicing dysfunction mutation in the gene encoding experiments indicate that SMN is of pre-mRNAs, axonal transport one of its essential proteins, acetylated by acetyltranferase and alterations and dysfunction of the SMN (Survival Motor Neuron), is CBP analysis with mass spectrometry 121

neuromuscular synapse. All of them 3). In addition we are characterizing MXD1 localizes in the nucleolus, contribute to neurodegeneration with ChIP-seq techniques DNA binds UBF and impairs rRNA and, consequently, to atrophy and sequences enriched in the “persistent synthesis. muscular paralysis. Our research foci” of cortical neurons. We have Oncotarget. 2016;7:69536-69548. focuses on deepening the nuclear identified 17 sequences associated F.I.:5,008. [doi:10.18632/ oncotarget.11766] mechanisms affected by the disease, with genes essential for neuronal which results in an alteration of the homeostasis whose dysfunction 4. Riancho J, Berciano MT, Berciano J, nuclear metabolism of the RNAs in is related to pictures of human Lafarga M. the motoneurons (Fig. 2). SMA has neuropathology. This line opens a Relaunching an old drug: the reported a deficit in the assembly new horizon that should allow to potential role of bexarotene in of snRNPs for the spliceosome, the identify neural genes very vulnerable neurodegenerative diseases. molecular machinery that governs to DNA damage or difficult to repair, J Neurol. 2016;263:177-178.F.I.:3,408. the splicing of pre-mRNAs. The Cajal whose accumulation of lesions may [doi:10.1007/s00415-015-8004-0] nuclear body (CB) is a nuclear power be involved in neurodegenerative 5. Romero AM, Palanca A, Ruiz-Soto plant that governs the assembly and diseases. M, Llorca J, Marín MP, Renau-Piqueras nuclear trafficking of snRNPs and J, Berciano MT, Lafarga M. snoRNPs to the spliceosome and Chronic Alcohol Exposure Decreases nucleolus, respectively. 53BP1 Protein Levels Leading to a Defective DNA Repair in Cultured In this context, we consider that the Primary Cortical Neurons. loss of CBs and their interactions Neurotox Res. 2016;29:69-79. F.I.:3,140. [doi:10.1007/s12640-015- with the nucleolus, required for the 9554-8] transport of snoRNPs involved in nucleolar processing of rRNAs, are responsible for the severe disruption of splicing and biogenesis of Reviews ribosomes in the motoneurons of The SMA. To investigate these nuclear 1. Riancho J, Berciano MT, Ruiz-Soto mechanisms we used the transgenic M, Berciano J, Landreth G, Lafarga M. Retinoids and motor neuron disease: mouse SMNd7 as a model of SMA PUBLICATIONS: Potential role in amyotrophic lateral type I, the most severe that causes sclerosis. the degeneration of motor neurons IMPACT FACTOR | 24,839 J Neurol Sci. 2016;360:115-120. and death of animals between F.I.:2,126. [doi:10.1016/j. postnatal days 13 and 16. jns.2015.11.058] Original articles Line 3. Neuronal response to Doctoral thesis DNA damage: importance in neurodegeneration. 1. García-Hevia L, Villegas JC, 1. Maria Ruiz Soto. Fernández F, Casafont Í, González J, El estrés oxidativo en la glia satélite There is growing evidence in the Valiente R, Fanarraga ML. de los ganglios raquídeos induce literature that defects in DNA repair Multiwalled Carbon Nanotubes alteraciones sensitivas en el modelo and the consequent accumulation of Inhibit Tumor Progression in a murino HSOD1g93a de esclerosis DNA lesions play an important role Mouse Model. lateral amiotrófica (ELA). in the molecular pathophysiology Adv Healthc Mater. 2016;5:1080-1087. Director/es: Miguel Ángel Lafarga of multiple neurodegenerative F.I.:5,760. [doi:10.1002/ Coscojuela, María Teresa Berciano processes. Our goal is to analyze adhm.201500753] Blanco. UNIVERSIDAD DE the nuclear processing of DNA CANTABRIA. 2. Casafont I, Palanca A, Lafarga V, damage in normal, ganglionic and Mata-Garrido J, Berciano MT, Lafarga M. cerebral cortex neurons irradiated Dynamic Behavior of the RNA with X-rays (4 Gy) to induce DNA Polymerase II and the Ubiquitin Projects double-strand breaks. In this model Proteasome System During the we have observed that most of the Neuronal DNA Damage Response to 1. María Teresa Berciano Blanco. neuronal DNA breaks are repaired Ionizing Radiation. Regulación por acetilación del in the first 24 hours, but there Mol Neurobiol. 2016;53:6799-6808. factor de supervivencia de las are persistent foci of unrepaired F.I.:5,397. [doi:10.1007/s12035-015- neuronas motoras: su importancia DNA that remain for months in a 9565-8] en la biogénesis de snrnps y en el specific nuclear compartment. We ensamblaje de cuerpos nucleares have characterized the structural, 3. Lafita-Navarro MC, Blanco R, de cajal. BFU2014-54754-P. MINISTERIO DE molecular and spatial organization Mata-Garrido J, Liaño-Pons J, Tapia ECONOMIA Y COMPETITIVIDAD. of this nuclear compartment as well O, García-Gutiérrez L, García-Alegría as its transcriptional repression (Fig. E, Berciano MT, Lafarga M, León J. Research Areas Neuroscience Area

Group Leader Agustín Oterino Durán Neurología Service Áreas de University Hospital Cephalea Clinic Marqués de Valdecilla andinvestigación Genetics

[email protected]

Researchers Julio Pascual Gómez

Contributors Jesús Castillo Obeso Vicente González Quintanilla Rosa María Martínez Nieto Silvia Montes Gómez Enrique Jesús Palacio Portilla Estrella Quintela Obregón

Nurses Silvia Gutiérrez González

Technicians María Toriello Suárez Clinic group

of new neuromodulators (topiramate we demonstrated that there are and zonisamide) in the treatment variants of certain subunits of GABA of refractory chronic migraines. In associated with migraines in general. Research the field of genetics, the epistatic interaction of genes related to Lines 2. Clinical and Genetic Research in estrogen metabolism in migraines Multiple Sclerosis. (estrogen receptor ESR2) has been described in 594 subjects grouped In this line of research, we are in 132 families, confirming the developing sub-programmes which existence of a genetic factor in include: 1. Genetics of migraines. the pathogenesis of migraines as related to sex hormones; we further > HLA haplotype study regarding The group has maintained its researched the association of genes the origin within the region. epidemiological-clinical and of the folate metabolic pathway and Influence of HLA on multiple basic research activity (mainly in migraines, confirming the association sclerosis. genetic association studies) in the of migraines with aura and high field of cephalalgias. Within this homocysteine levels. We have > Study of vascular damage first aspect, we should highlight recently demonstrated that there associated with Multiple Sclerosis the demonstration of the dose- is significant endothelial activation by analysing circulating endothelial dependent association between in migraine sufferers and that this cells: the correlation of endothelial migraines and tobacco, and studies activation is more pronounced in activation with the severity and focusing on proving the usefulness chronic migraines. Furthermore, stage of the disease. 123

PUBLICACIONES: 6. Oterino, Agustin, Uria, Dionisio F., Editorials Pena, Joaquin, Solar, Dulce, Villafani, IMPACT FACTOR | 42,989 Javier, Oliva-Nacarino, Pedro, 1. Purdy AR, Pascual J. Suarez-Moro, Roberto, Quintanilla, Don’t Bring Me Down--Too Fast!. Vicente G. Fingolimod: efectividad Headache. 2016;56:223-224. y seguridad en la practica clinica F.I.:2,961. [doi:10.1111/head.12761] habitual. Estudio observacional, Original articles retrospectivo y multicentrico en Asturias y Cantabria. 1. Ramos ML, Pascual J. Rev Neurol. 2016;63:19-26. AMG 334 CGRP antibody for F.I.:0,684. migraine: time to celebrate?. Lancet Neurol. 2016;15:347-349. Doctoral thesis F.I.:23,468. [doi:10.1016/S1474- 7. Palacio E, Viadero-Cervera R, Revilla 4422(16)00040-5] M, Larrosa-Campo D, Acha-Salazar O, Novo-Robledo F, Oterino A. 1. María Toriello Suárez. Utilidad del tratamiento con Genetic association study of genes 2. González-Quintanilla V, Toriello atorvastatina 40 mg más ezetimiba encoding the GABA-A receptor in M, Palacio E, González-Gay MA, 10 mg frente a atorvastatina 80 migraine. Castillo J, Montes S, Martínez-Nieto mg en la reducción de los niveles Un estudio de asociación familiar. R, Fernandez J, Rojo A, Gutiérrez S, de colesterol LDL en pacientes Director/es: Agustín Oterino Durán, Pons E, Oterino A. con ictus isquémico o ataque Jesús Castillo Obeso. Systemic and cerebral endothelial isquémico transitorio. University of Cantabria. dysfunction in chronic migraine. A Rev Neurol. 2016;62:203-210. case-control study with an active F.I.:0,684. comparator. Cephalalgia. 2016;36:552-560. F.I.:6,052. 8. Palacio, Enrique, Viadero-Cervera, [doi:10.1177/0333102415607857] Raquel, Revilla, Marian, Larrosa- Campo, Davinia, Acha-Salazar, Olga, Novo-Robledo, Francisco, Oterino, 3. Cernuda-Morollón E, Riesco N, Agustin. PROJECTS Martínez-Camblor P, Serrano-Pertierra Utility of treatment with E, García-Cabo C, Pascual J. atorvastatin 40 mg plus ezetimibe No Change in Interictal PACAP 10 mg versus atorvastatin 80 Levels in Peripheral Blood in mg in reducing the levels of Women With Chronic Migraine. LDL cholesterol in patients with Projects Headache. 2016;56:1448-1454. ischaemic stroke or transient F.I.:2,961. [doi:10.1111/head.12949] ischaemic attack. 1. Agustín Oterino Durán. Rev Neurol. 2016;62:203-210. Epigenetic modifications induced F.I.:0,684. by childhood adverse experiences 4. Larrosa D, Ramón C, Alvarez R, and endothelial damage in chronic Martínez-Camblor P, Cernuda E, migraine. Pascual J. a case-control study. Creation of No Relationship Between Patent murine experimental model. Foramen Ovale and Migraine PI15/01285. INSTITUTO DE SALUD Frequency. CARLOS III. MINISTERIO DE Headache. 2016;56:1466-1473. ECONOMÍA Y COMPETITIVIDAD. F.I.:2,961. [doi:10.1111/head.12945] Reviews 2. Agustín Oterino Durán. 5. Martínez-Rodríguez L, Pascual Thematic Network of Multiple J. Negligencia de afeitado en la 1. Riesco N, García-Cabo C, Pascual J. Sclerosis. hemicara izquierda por isquemia Migraña. RD16/0015/0023. INSTITUTO DE parietal. Med Clin (Barc). 2016;146:35-39. SALUD CARLOS III. MINISTERIO DE Med Clin (Barc). 2016;147:93-93. F.I.:1,267. [doi:10.1016/j. ECONOMÍA Y COMPETITIVIDAD. F.I.:1,267. [doi:10.1016/j. medcli.2015.07.003] medcli.2015.11.035] Research Areas Neuroscience Area

Group Leader Jon Infante Ceberio Neurology Service Áreas de University Hospital Neurodegenerative Marqués de Valdecilla Diseasesinvestigación

[email protected]

Ana Lara Pelayo Negro Ana Pozueta Cantudo Javier Riancho Zarrabeitia Consolidated group María José Sedano Tous María Sierra Peña José Luis Vázquez Higuera

Researchers Elena Carmen Gallardo Agromayor Antonio García García José Ángel Berciano Blanco Nurses Eloy Manuel Rodríguez Rodríguez María García Martínez Martha Kazimierczak Pascual Jesús Sánchez Juan Andrea Gonzalez Suarez Maria Isabel González Aramburu Andrés González Mandly Contributors Carmen Lage Martínez Technicians Manuel Delgado Alvarado José Ignacio Mateo Fernández Mª del Coro Sánchez Quintana 125

This notion is applicable to both method, particularly useful for at- demyelinating and axonal forms risk children. In collaboration with Research of the syndrome (figure 1). Our Dr Albena Jordanova (Department contributions to GBS nosology have of Genetics, University of Antwerp, Lines been compiled in a monographic Belgium), we have continue textbook (see publications 2015). evaluating a large CMT2 pedigree, categorized as CMT2G by linkage In two pedigrees of Charcot-Marie- analysis. Using next-generation Tooth disease (CMT) harboring sequencing technology, we have NEFL mutations, either E397K found a pathogenic LRSAM1 or N98S, we have re-defined 1. Peripheral neuropathy. missense mutation indicating the corresponding phenotypes, that the syndrome should be which should be classified in the In a prospective study of six early reclassified as a novel CMT2P category of dominant intermediate Guillain-Barre syndrome (GBS) phenotype. In two review papers, CMT. We have reported the first patients, we have demonstrated we have addressed the role of electrophysiological recording of T the pathogenic relevance of imaging techniques in the diagnosis reflex in CMT1A duplication, which inflammatory oedema in proximal of inflammatory and inherited is a simple and painless diagnostic nerves, particularly in spinal nerves. neuropathies.

Figure 1. Picture taken from the paper by Berciano et al (JNNP 2016; 87: 563-5. Epub 2015 May 13) showing electrophysiological and imaging findings in a patient with the paraparetic and axonal form of GBS. (A) Tibial nerve motor conduction velocity (MCV) study on day 4 after onset showing normal compound muscle action potential (CMAP) morphology, both on distal (ankle to abductor hallucis [AH] muscle) and proximal stimulation (popliteal fossa [PF] to AH); proximal CMAP amplitude is 14.4 mV, and distal CMAP amplitude is 18.9 mV (normal, = 3); MCV is 47 m/s (normal, = 41). (B) On day 12, note severe CMAP amplitude reduction to 1.7 mV, both on distal and proximal stimulation. Comparatively with the previous study, at this stage there was a mild slowing of MCV (passing from 47 m/s to 39.4 m/s) and prolongation of F-wave latency (55.5 ms; normal, = 55), which seems to be proportional to the observed CMAP reduction. Post contrast sagittal (C) and coronal (D) T1-weighted, fat-saturation MR images of the lower thoracic and lumbosacral spine, performed on day 4, showing diffusely thickened cauda equine (arrowheads), which in the axial image (L1 level) selectively involves the anterior roots (E, arrows); CM indicates conus medullaris. (F) Sagittal sonogram of the right ventral rami of C6-C7 cervical nerves (callipers) performed on day 3; note their characteristic homogeneous hypoechoic texture with partial loss of the surrounding perineural hyperechoic rims. (G) Short-axis sonogram the right ventral ramus of the C7 spinal nerve showing the cross-sectional area (dotted green tracing) measuring 27.47 mm2 (control, 12.29 ± 5.3 mm2)2. Note blurred margins and the absence of the physiologic hyperechoic rim. Asterisks indicate the posterior tubercle of the seventh transverse vertebral process. Research Areas Neuroscience Area

2. Hereditary Ataxias. biomarkers, we are carrying out PET-PIB and PET-FDG studies to: 1) Timmerman V, Infante J, Berciano J, We have continued with the patients with AD,2) patients with Jordanova A. SCANatural History Study within the mild cognitive impairment and 3) Charcot-Marie-Tooth disease type EUROSCA project (for more details healthy controls. We are preparing 2G redefined by a novel mutation http:// www.ataxia-study-group.net/ an article describing our clinical in LRSAM1. html/studies/eurosca). Also, within experience in the use of amyloid- Ann Neurol. 2016;80:823-833. the EUROSCA group we have PET and we have collaborated F.I.:9,638. [doi:10.1002/ana.24775] continued with the prospective with our data in international follow-up of patients with dominant consortiums producing a double 2. Sailer A, Scholz SW, Nalls MA, ataxia included in the RISCA project publication in JAMA describing Schulte C, Federoff M, Price TR, we have participated in a follow-up the prevalence of brain amyloid Lees A, Ross OA, Dickson DW, Mok study of a longitudinal cohort of deposits in healthy subjects and K, Mencacci NE, Schottlaender L, patients with SCA1, 2, 3 and 6 (see subjects with mild cognitive Chelban V, Ling H, O’Sullivan SS, references of our group published impairment. in 2005). Wood NW, Traynor BJ, Ferrucci L, Federoff HJ, Mhyre TR, Morris HR, 5. Prionopathies. Deuschl G, Quinn N, Widner H, 3. Parkinson’s disease. We have Albanese A, Infante J, Bhatia KP, demonstrated that serum uric acid In 2015, we have published a Poewe W, Oertel W. levels are not associated with the genome wide association study European Multiple System Atrophy risk of dementia in Parkinson’s (GWAs) with the largest sample Study Group and the UK Multiple disease. We have participated in of patients recruited so far (1543 System Atrophy. A genome-wide two international collaborative samples from patients with association study in multiple studies analyzing the temporal sporadic Creutzfeldt Jakob disease, system atrophy. profile of non-motor symptoms coming from 7 European countries Neurology. 2016;87:1591-1598. in idiopathic and LRRK2G2019S and Australia, and 4203 controls). F.I.:8,166. [doi:10.1212/ associated Parkinson’s disease (PD). This study has been carried out in WNL.0000000000003221] Through a blood transcriptomic the framework of a collaborative analysis, we have identified 13 European project, JPND DEMTEST. candidate genes for PD in sporadic 3. Carr AS, Pelayo-Negro AL, Evans cases, asymptomatic carriers of the MR, Laurà M, Blake J, Stancanelli C, G2019S mutation and controls. Iodice V, Wechalekar AD, Whelan CJ, Gilmore JD, Hawkins PN, Reilly MM. As member of the EMSA-SG group A study of the neuropathy (www.emsa-sg. org/), we have associated with transthyretin participated in a study that discards amyloidosis (ATTR) in the UK. J. the pathogenic role of mutations in Neurol. Neurosurg. COQ2 in MSA Psychiatry. 2016;87:620-627. F.I.:6,431. [doi:10.1136/jnnp-2015- In collaboration with the Neurology 310907] Department of Toulouse Purpam Hospital (INSERM), we are participating in an ongoing project 4. Berciano J, Gallardo E, Orizaola P, to identify clinical and preclinical Marco de Lucas E, García A, Pelayo- (multimodal MRI) biomarkers in Negro AL, Sedano MJ. LRRK2- PD 4.Alzheimer’s disease. PUBLICATIONS: Early axonal Guillain-Barré syndrome with normal peripheral conduction: imaging evidence 4. Alzheimer’s disease. Our IMPACT FACTOR | 42,989 for changes in proximal nerve group is a founder member of the segments. J. Neurol. Neurosurg. Spanish consortium of dementia Psychiatry. 2016;87:563-565. (DEGESCO). As a consequence of F.I.:6,431. [doi:10.1136/jnnp-2015- this collaboration, in the framework Original articles 310601] of CIBERNED, we have published in 2015 an association between MAPT gene variants and different 1. Peeters K, Palaima P, Pelayo-Negro 5. Barbagallo G, Sierra-Peña M, neurodegenerative conditions in AL, García A, Gallardo E, García- Nemmi F, Traon AP, Meissner WG, a sample of 11572 subjects. In Barredo R, Mateiu L, Baets J, Menten Rascol O, Péran P. the line of Alzheimer’s disease B, De Vriendt E, De Jonghe P, Multimodal MRI assessment of 127

nigro-striatal pathway in multiple F.I.:5,153. [doi:10.1016/j. A, López-Alburquerque T, Gallardo system atrophy and Parkinson neurobiolaging.2015.10.026] E, Hernández-Fabián A, Pelayo- disease. Negro AL, De Vriendt E, Infante J, Mov Disord. 2016;31:325-334. Jordanova A. F.I.:6,010. [doi:10.1002/mds.26471] 10. Sierra M, Gelpi E, Martí MJ, NEFL N98S mutation: another Compta Y. cause of dominant intermediate Lewy- and Alzheimer-type Charcot-Marie-Tooth disease 6. Riancho J. pathologies in midbrain and with heterogeneous early-onset Retinoids and PPAR agonists: cerebellum across the Lewy body phenotype. Promising partners in disorders spectrum. J Neurol. 2016;263:361-369. neurodegenerative diseases?. Neuropathol Appl Neurobiol. F.I.:3,408. [doi:10.1007/s00415-015- Free Radic Biol Med. 2016;97:616- 2016;42:451-462. 7985-z] 617. F.I.:5,784. [doi:10.1016/j. freeradbiomed.2016.07.024] F.I.:4,483. [doi:10.1111/nan.12308] 15. Riancho J, Berciano MT, 11. Jiménez-Bonilla JF, Banzo I, Berciano J, Lafarga M. De Arcocha-Torres M, Quirce R, Relaunching an old drug: the 7. Jimenez-Bonilla, J. F., Quirce, R., Martínez-Rodríguez I, Sánchez-Juan potential role of bexarotene in De Arcocha-Torres, M., Martinez- P, Carril JM. Amyloid Imaging With neurodegenerative diseases. Rodriguez, I., Carril, J. M., Jimenez- 11C-PIB in Patients With Cognitive J Neurol. 2016;263:177-178. Alonso, M., Banzo, I., Pozueta, Impairment in a Clinical Setting: F.I.:3,408. [doi:10.1007/s00415-015- A., Martin-Laez, R., Rodriguez- A Visual and Semiquantitative 8004-0] Rodriguez, E. Analysis. Amyloid brain deposition in Clin Nucl Med. 2016;41:18-23. idiopathic normal pressure F.I.:4,278. [doi:10.1097/ 16. Riancho J, Delgado-Alvarado M, hydrocephalus assessed by RLU.0000000000000934] Fernández-Torre JL, Sánchez-Juan P, 11C-PIB PET/CT. Polo JM. Eur J Nucl Med Mol Imaging. Subacute progressive aphasia: a 2016;43:134-134. 12. Pastor P, Moreno F, Clarimón rare presentation of Creutzfeldt- F.I.:5,537. J, Ruiz A, Combarros O, Calero M, Jakob disease. López de Munain A, Bullido MJ, de J Neurol. 2016;263:600-602. Pancorbo MM, Carro E, Antonell A, F.I.:3,408. [doi:10.1007/s00415-016- 8. Dols-Icardo O, Iborra O, Valdivia Coto E, Ortega-Cubero S, Hernandez 8054-y] J, Pastor P, Ruiz A, de Munain AL, I, Tárraga L, Boada M, Lleó A, Dols- Sánchez-Valle R, Álvarez V, Sánchez- Icardo O, Kulisevsky J, Vázquez- Juan P, Lleó A, Fortea J, Blesa R, Higuera JL, Infante J, Rábano A, 17. Salas-Gomez D, Fernandez- Cardona F, Baquero M, Alonso MD, Fernández-Blázquez MÁ, Valentí Gorgojo M, Pozueta A, Diaz-Ceballos I, Ortega-Cubero S, Pastor MA, Razquin M, Indakoetxea B, Barandiarán M, Lamarain M, Perez C, Sanchez-Juan P. C, Boada M, Hernández I, Gorostidi Gorostidi A, Frank-García A, Sastre I, Binge Drinking in Young University A, Moreno F, Zulaika M, Lladó A, ..., Sánchez-Juan P. Students Is Associated with Coto E, Combarros O, Pérez-Tur J, MAPT H1 Haplotype is Associated Alterations in Executive Functions Clarimón J. with Late-Onset Alzheimer’s Related to Their Starting Age. Dementia Genetics Spanish Disease Risk in APOE?4 PLoS One. 2016;11: Consortium (DEGESCO). Assessing Noncarriers: Results from the F.I.:3,057. [doi:10.1371/journal. the role of TUBA4A gene in Dementia Genetics Spanish pone.0166834] frontotemporal degeneration. Consortium. Neurobiol Aging. 2016;38: J Alzheimers Dis. 2016;49:343-352. 18. Riancho J, Lozano-Cuesta P, F.I.:5,153. [doi:10.1016/j. F.I.:3,920. [doi:10.3233/JAD-150555] Santurtún A, Sánchez-Juan P, López- neurobiolaging.2015.10.030] Vega JM, Berciano J, Polo JM. 13. Berciano J, García A. Amyotrophic Lateral Sclerosis in 9. Infante J, Prieto C, Sierra M, Sural-sparing in Guillain-Barré Northern Spain 40 Years Later: Sánchez-Juan P, González-Aramburu syndrome: Does it mean lack of What Has Changed?. I, Sánchez-Quintana C, Berciano J, histopathological changes?. Neurodegener Dis. 2016;16:337-341. Combarros O, Sainz J. Comparative Clin Neurophysiol. 2016;127:969-970. F.I.:2,937. [doi:10.1159/000445750] blood transcriptome analysis in F.I.:3,426. [doi:10.1016/j. idiopathic and LRRK2 G2019S- clinph.2015.03.023] 19. Linnemann C, Tezenas du associated Parkinson’s disease. Montcel S, Rakowicz M, Schmitz- Neurobiol Aging. 2016;38: Hübsch T, Szymanski S, Berciano J, 14. Berciano J, Peeters K, García Research Areas Neuroscience Area

van de Warrenburg BP, Pedersen K, Trends in motor neuron disease: 28. Velasquez, Carlos, Caballero, Depondt C, Rola R, Klockgether T, association with latitude and air Hugo, Bucheli, Carlos, Berciano, García A, Mutlu G, Schöls L. lead levels in Spain. Jose, Vazquez-Barquero, Alfonso, Peripheral Neuropathy in Neurol Sci. 2016;37:1271-1275. Martino, Juan. Spinocerebellar Ataxia Type 1, 2, F.I.:1,783. [doi:10.1007/s10072-016- A very slow-growing exophytic 3, and 6. 2581-2] hemisphere glioma: a case report. Cerebellum. 2016;15:165-173. Rev Neurol. 2016;62:23-27. F.I.:2,429. [doi:10.1007/s12311-015- F.I.:0,684. 0684-6] 24. Jiménez-Bonilla JF, Banzo I, De Arcocha-Torres M, Quirce R, Martínez-Rodríguez I, Lavado-Pérez 29. Fernandez-Fernandez J, Real- 20. Santurtún A, Villar A, López- C, Bravo-Ferrer Z, Rodríguez- Noval H, Rodriguez-Rodriguez E. Delgado L, Riancho J. Rodríguez E, Sánchez-Juan P, Carril Embolia aerea cerebral masiva tras Amyotrophic lateral sclerosis JM. colangiopancreatografia retrograda and richness: A correlation study Diagnostic role of 11C-Pittsburgh endoscopica. Presentacion de un across Spain. compound B retention patterns and caso y revision de la bibliografia. J Neurol Sci. 2016;367:380-381. glucose metabolism by fluorine-18- Rev Neurol. 2016;63:497-500. F.I.:2,126. [doi:10.1016/j. fluorodeoxyglucose PET/CT in F.I.:0,684. jns.2016.06.050] amnestic and nonamnestic mild cognitive impairment patients. 30. Velasquez C, Caballero H, Nucl Med Commun. 2016;37:1189- Bucheli C, Berciano J, Vazquez- 21. Santos-García D, Mir P, Cubo E, 1196. Barquero A, Martino J. Vela L, Rodríguez-Oroz MC, Martí F.I.:1,453. [doi:10.1097/ Glioma exofítico hemisférico de MJ, Arbelo JM, Infante J, Kulisevsky MNM.0000000000000569] muy lento crecimiento: a propósito J, Martínez-Martín P. de un caso. COPPADIS Study Group. Rev Neurol. 2016;62:23-27. COPPADIS-2015 (COhort of 25. Riancho J, Navasa JM, Sedano- F.I.:0,684. Patients with PArkinson’s DIsease Tous MJ, Polo JM. in Spain, 2015), a global--clinical Fístula carótido-cavernosa tratada evaluations, serum biomarkers, con compresiones carotídeas. 31. Fernandez-Fernandez, genetic studies and neuroimaging- Med Clin (Barc). 2016;146:48-48. Jennifer, Real-Noval, Hector, -prospective, multicenter, non- F.I.:1,267. [doi:10.1016/j. Rodriguez-Rodriguez, Eloy. interventional, long-term study on medcli.2015.04.022] Massive cerebral air embolism Parkinson’s disease progression. following endoscopic retrograde BMC Neurol. 2016;16:26-26. cholangiopancreatography, A case F.I.:1,961. [doi:10.1186/s12883-016- 26. Santurtún A, Delgado-Alvarado report and review of the literature. 0548-9] M, Villar A, Riancho J. Rev Neurol. 2016;63:497-500. Patrón geográfico de la mortalidad F.I.:0,684. por enfermedad de Parkinson en 22. Santos-García D, Mir P, Cubo España y su asociación con los E, Vela L, Rodríguez-Oroz MC, niveles de plomo en el aire. Martí MJ, Arbelo JM, Infante J, Med Clin (Barc). 2016;147:481-487. Reviews Kulisevsky J, Martínez-Martín P, F.I.:1,267. [doi:10.1016/j. COPPADIS Study Group. Erratum medcli.2016.07.022] to: COPPADIS-2015 (COhort of Patients with PArkinson’s DIsease 1. Zufiría M, Gil-Bea FJ, Fernández- in Spain, 2015), a global--clinical 27. Banzo I, Jiménez-Bonilla JF, Torrón R, Poza JJ, Muñoz-Blanco JL, evaluations, serum biomarkers, Martínez-Rodríguez I, Quirce R, de Rojas-García R, Riancho J, de Munain genetic studies and neuroimaging- Arcocha-Torres M, Bravo-Ferrer Z, AL. -prospective, multicenter, non- Lavado-Pérez C, Sánchez-Juan P, ALS: A bucket of genes, interventional, long-term study on Rodríguez E, Jiménez-Alonso M, environment, metabolism and Parkinson’s disease progression. López-Defilló J, Carril JM. unknown ingredients. BMC Neurol. 2016;16:44-44. Patterns of 11C-PIB cerebral PROG NEUROBIOL. 2016;142:104- F.I.:1,961. [doi:10.1186/s12883-016- retention in mild cognitive 129.F.I.:13,177. [doi:10.1016/j. 0567-6] impairment patients. pneurobio.2016.05.004] Rev Esp Med Nucl Imagen Mol. 2016;35:171-174. 23. Santurtún A, Villar A, Delgado- F.I.:0,983. [doi:10.1016/j. 2. Riancho J, Berciano MT, Ruiz-Soto Alvarado M, Riancho J. remn.2015.09.008] M, Berciano J, Landreth G, Lafarga M. 129

Retinoids and motor neuron Projects 2. Pascual Jesús Sánchez Juan. disease: Potential role in Biobanks Platform. amyotrophic lateral sclerosis. PT13/0010/0024. INSTITUTO DE J Neurol Sci. 2016;360:115-120. 1. Eloy Manuel Rodríguez Rodríguez. SALUD CARLOS III. MINISTERIO DE F.I.:2,126. [doi:10.1016/j. Alzheimer’s disease biomarkers ECONOMÍA Y COMPETITIVIDAD. jns.2015.11.058] as prognostic factors in idiopathic normal pressure hydrocephalus. 3. Pascual jesús sánchez juan. PI13/01008. INSTITUTO DE SALUD Study of rare variants in genes CARLOS III. MINISTERIO DE associated with Alzheimer’s ECONOMÍA Y COMPETITIVIDAD, disease in Spanish population. INSTITUTO DE SALUD CARLOS PI16/01652. INSTITUTO DE SALUD III. MINISTERIO DE ECONOMÍA Y CARLOS III. MINISTERIO DE PROJECTS COMPETITIVIDAD. CONOMÍA Y COMPETITIVIDAD. Research Areas Neuroscience Area

Group Leader José Luis Fernández Torre Neurophisiology Service Áreas de University Hospital Neurophysiology in Epilepsy Marqués de Valdecilla andinvestigación Neurointensive Care

[email protected]

Researchers Mª Blanca Sánchez Santiago

Contributors Francisco Javier Adin Ibarra Miguel Ángel Hernández Hernández Ana María Ruiz Ruiz

Technicians María Paz Polo Sobrón

Clinic group

> Super-refractory or malignant > Utility of EEG in the diagnosis of nonconvulsive status epilepticus. brain death.

Research > Multimodal neuromonitoring > Toxic encephalopathy in Lines including intracortical electrodes in neurocritical patients. acute brain injury patients. > The use of bilateral bispectral index (BIS) in the diagnosis of > EEG patterns and prognosis in nonconvulsive status epilepticus in hipoxic-ischemic encephalopathy. comatose patients.

> Post-anoxic myoclonic status > Experimental models of status > Refractory nonconvulsive status epilepticus. Stimulus-induced epilepticus. EEG phases of status epilepticus postanoxic myoclonus. epilepticus in humans. 131

Subacute progressive aphasia: a color del BIS bilateral en estado PUBLICATIONS: rare presentation of Creutzfeldt- epiléptico. Jakob disease. An Pediatr (Barc). 2016;85:44-47. IMPACT FACTOR | 18,524 J Neurol. 2016;263:600-602. F.I.:0,773. [doi:10.1016/j. F.I.:3,408. [doi:10.1007/s00415-016- anpedi.2015.09.021]. 8054-y].

Original articles 3. Hernández-Hernández MA, Fernández-Torre JL. Color density spectral array of 1. Hernández-Hernández MA, bilateral bispectral index system: Fernández-Torre JL, Holanda-Peña MS, Electroencephalographic correlate Cabello M. in comatose patients with Central venous catheter malposition Reviews nonconvulsive status epilepticus. into pulmonary vein: an unusual Seizure. 2016;34:18-25. cause of epileptic seizures. F.I.:2,109. [doi:10.1016/j. 1. Drake-Pérez M, Marco de Lucas Intensive Care Med. 2016;42:113-114. seizure.2015.11.001]. E, Lyo J, Fernández-Torre JL. F.I.:10,125. [doi:10.1007/s00134-015- Neuroimaging features in subacute 3940-9]. encephalopathy with seizures 4. Hernández-Hernández MA, Iglesias- in alcoholics (SESA syndrome). 2. Riancho J, Delgado-Alvarado M, Posadilla D, Ruiz-Ruiz A, Gómez- Seizure. 2016;40:102-107. Fernández-Torre JL, Sánchez-Juan P, Marcos V, Fernández-Torre JL. F.I.:2,109. [doi:10.1016/j. Polo JM. Matriz de densidad espectral de seizure.2016.06.009]. Research Areas Neuroscience Area

Group Leader Benedicto Crespo Facorro Psichiatry Service Áreas de University Hospital Marqués de Valdecilla Psychiatryinvestigación University of Cantabria

[email protected]

Beatriz Payá González Mª Luz Ramírez Bonilla Roberto Miguel Roiz Santiáñez Paula Suárez Pinilla Javier Vázquez Bourgon Consolidated group Nurses Obdulia Martínez García Researchers Andrés Gómez Del Barrio Predoctoral María Rosa Ayesa Arriola Elsa Gómez Ruíz Jana González Gómez Fulgencio Ruso Julve César González-Blanch Bosch Contributors José Andrés Herrán Gómez Technicians Manuel Delgado Alvarado Sara Herrera Castanedo Noemí de la Fuente González Jesús Ángel Artal Simón Jacqueline Maria Mayoral Van Son José Antonio Jorrín Moreno Laura Carral Fernández María Soraya Otero Cuesta Víctor Ortíz García De La Foz Luis Gaite Pindado Gema Pardo García Diana Tordesillas Gutiérrez 133

techniques to assess neuronal a. To study new short- and long- processes genesis. term therapeutic, pharmacological, Research psychotherapeutic interventions in the treatment of non-affective Lines 2- Genomic of non-affective psychosis. Special interest in psychosis). treating metabolic side effects associated with antipsychotic Responsible: Dr. B. Crespo treatments. 1- Brain Neuroimaging in Non- Facorro. In this field, our group Affective Psychosis (NAP). has focused its work on two main lines of activity. Firstly, in the field 4. Cognition in non-affective Responsible: R. Roiz Santiáñez of Pharmacogenetics, we work psychosis. y D. Tordesillas Gutiérrez. The on the study of single nucleotide techniques of brain imaging, such polymorphisms (SNPs) of candidate Responsible: Dra. R. Ayesa Arriola. as magnetic resonance imaging genes, specifically the genes involved The main objectives of this research (MRI), allow exploring the presence in dopaminergic neurotransmission, are: of structural alterations from the serotonergic and candidate genes first clinical phases of the disease in linking regions. The aim is to a. To evaluate the course of early (neurodevelopmental anomalies) and determine whether single nucleotide cognitive function in a sample also study the onset of morphological polymorphisms are associated with of first episodes of psychosis changes during the course of psychotic symptomatology, evolution individuals. the disease (neurodegeneration and response to treatment. Also, b. To examine the relationship processes). Our work in this area we work in the field of “imaging between cognitive functions and aims to: genetics” genetic variations clinical variables. associated with brain alterations; In a. To compare the volume of gray particular, gene expression studies c. To evaluate the influence of and white matter in the cortex are being carried out to identify cognitive function in the outcome between patients and controls genes whose expression is different and prognosis of the disease. b. To determine the existence of in people with a first psychotic differences in volume of the basal episode with respect to people not ganglia between patients and affected by the disease and also 5. Research and Intervention controls in possible differences in gene program focused on the early expression in people with a first phases of eating disorders. c. study to detect structural Psychotic episode before starting changes over time in people with treatment and after one year of Responsible: Dr. J.A. Gómez schizophrenia, and pharmacological treatment. del Barrio. It consists of a bio- d. To study the relationship psychosocial line of research and between variables related to brain a therapeutic intervention and structure and other clinical and / or 3- Epidemiology and Clinical prevention focused on early phases genetic variables. characteristics of non-affective of eating disorders: psychosis. a. Implement an early, multi- Responsible: Dr. B. Crespo Facorro. disciplined and multi-factorial Entre los objetivos de esta línea evaluation and intervention desarrollada por nuestro grupo, se protocol for all patients that encuentran: develop an eating disorder in the area referenced by the Psychiatric a. To investigate the incidence of Service of University Hospital psychosis in Cantabria and likely Marqués de Valdecilla. related factors. b. Research the early phases of a. To identify the profile of the disease— the psychological, symptoms during early phases of biological, and social components the illness. of eating disorders. a. To describe predictors of c. Identify and define the risk outcome. factors of developing eating disorders, as well as the nature At present, we are developing a. To advance in the knowledge of and characteristics of prodromal research by DTI to explore alterations biological markers (neuroimaging, symptoms and earliest clinical in the integrity of white matter tracts. biochemical, genetic) of manifestations. Another line of recent research is Schizophrenia. the development of spectroscopy d. Evaluate the response to Research Areas Neuroscience Area

interventions, as well as the of Psychosis in children and mononuclear cells). Our work in this evolutionary course of the disease, adolescents. area aims to: researching bio-psycho-social factors that condition them. a. Detect blood biomarkers and altered cellular signaling pathways e. Evaluate the costs derived from 7. Strategies of assessment in mental health. leading to diagnose patients with treatment, as well as the level of a first episode of psychosis from patient and family satisfaction. Responsible: Dr. L. Gaite Pindado healthy controls, combined with The line of investigation incorporates y Dra. S. Herrera Castanedo. Since clinical practice. the following studies: the inception of the UIPC, one of the b. Determine peripheral differences areas of greatest interest has been Intervention study focused on between patients with an episode the development and dissemination cognitive processes in eating of non-affective psychosis and of the evaluation methodology disorders. Responsible: Laura Carral healthy controls, from the onset in mental health, along with the Fernandez y J.A. Gomez del Barrio. and over time. adaptation to our environment of This study is framed under an tools and strategies for the evaluation c. Conduct a longitudinal study of investigation contract Rio Hortega the change in biomarkers over time (CM10/0017). of mental health services. In this sense, the Unit has collaborated with in people with schizophrenia. This program focuses on intervention the European Network for Mental d. Study the relationship between and therapeutic strategies based on Health Evaluation Service (ENMESH), changes in peripheral molecules new technology for early phases of which integrates European experts and correlate with longitudinal eating disorders. Responsible: Dra. in the field of evaluation of mental severity scores. Jana Gonzalez Gomez and Dr. J.A. health services and has as main Gomez del Barrio. This program objectives: e. Detect biomarkers to predict integrates DETECTA (DEtecion treatment response. TEmprana en Cantabria de Trasornos a. To develop and consolidate a Alimentarios) and is framed under network of health professionals a research scholarship, financed by interested in investigating mental 9. Classification and assessment of IDIVAL (Lopez Albo WLA 02/11). health services and needs. disability in mental health.

b. To promote the development Responsible: Dra. S. Herrera and dissemination of investigations 6. Research and Pharmacological Castanedo y Dr. L. Gaite Pindado. on instruments of assessment and Interventions Program for Early Since 1993, our research group has indicators of outcome (including Phases of Psychoses in children been involved in the development, economic indicators). and adolescents’ population. publication and dissemination of the International classification Responsible: Dra. S. Otero Cuesta of Functionality (ICF) and related y Dra. B. Payá González. This is a 8. Molecular basis of non-affective instruments of assessment research program focused on mental psychosis. (i.e., World Health Organization health problems of young people. Disability Assessment Schedule The main areas of interest are: Responsible: Dra. P. Suárez Pinilla 11 (WHO-DAS 11). In addition, in y Dr. B Crespo Facorro. The 2011, the Development Project for a. Clinical trials on effectiveness range of clinical features shows the Spanish version of the WHO and safety of new drugs for that schizophrenia affects multiple International Standard Classification children and adolescents’ brain circuits, and also peripheral of Functioning, Disability and Health- psychiatric disorders. pathways. Recently, we have been Children and Youth Version has developing the research in this been culminated with its definitive b. Research on Prevention field through the study of serum publication and the beginning of the Strategies and Bio-psycho-social and PBMCs (peripheral blood dissemination work Same. Interventions for Early Phases 135

F.I.:14,417. [doi:10.1001/ AK, Bishop JR, Ikeda M, Molero P, PUBLICATIONS: jamapsychiatry.2016.0129] Ortuno F, Porcelli S, Samochowiec J, Mierzejewski P, Gao S, Crespo-Facorro IMPACT FACTOR | 130,588 4. van Erp TG, Hibar DP, Rasmussen B, Pelayo-Terán JM, Kaur H, Kukreti R, JM, Glahn DC, Pearlson GD, Meltzer HY, Lieberman JA, Potkin SG, Andreassen OA, Agartz I, Westlye Müller DJ, Kennedy JL. LT, Haukvik UK, Dale AM, Melle I, Catechol-O-Methyltransferase Hartberg CB, Gruber O, Kraemer Val158Met Polymorphism and Original articles B, Zilles D, Donohoe G, Kelly S, Clinical Response to Antipsychotic McDonald C, Morris DW, Cannon DM, Treatment in Schizophrenia and Corvin A, Machielsen MW, Koenders L, Schizo-Affective Disorder Patients: a 1. Franke B, Stein JL, Ripke S, Anttila de Haan L, Veltman DJ, Satterthwaite Meta-Analysis. V, Hibar DP, van Hulzen KJ, Arias- TD, Wolf DH, Gur RC, Gur RE, ..., Int J Neuropsychopharmacol. 2016;19: Vasquez A, Smoller JW, Nichols Turner JA. F.I.:4,333. [doi:10.1093/ijnp/pyv132] TE, Neale MC, McIntosh AM, Lee Subcortical brain volume P, McMahon FJ, Meyer-Lindenberg abnormalities in 2028 individuals A, Mattheisen M, Andreassen OA, with schizophrenia and 2540 9. Ayesa-Arriola R, Rodríguez- Gruber O, Sachdev PS, Roiz-Santiañez healthy controls via the ENIGMA Sánchez JM, Suero ES, Reeves LE, R, Saykin AJ, Ehrlich S, Mather KA, consortium. Tabarés-Seisdedos R, Crespo-Facorro Turner JA, Schwarz E, Thalamuthu A, Mol Psychiatry. 2016;21:547-553. B. Diagnosis and neurocognitive Yao Y, Ho YY, Martin NG, Wright MJ, F.I.:13,314. [doi:10.1038/mp.2015.63] profiles in first-episode non-affective ..., Sullivan PF. psychosis patients. Genetic influences on schizophrenia Eur Arch Psychiatry Clin Neurosci. and subcortical brain volumes: large- 5. Haenisch F, Cooper JD, Reif 2016;266:619-628. scale proof of concept. A, Kittel-Schneider S, Steiner J, F.I.:4,113. [doi:10.1007/s00406-015- NAT NEUROSCI. 2016;19:420-431. Markus Leweke F, Rothermundt M, 0667-0] F.I.:16,724. [doi:10.1038/nn.4228] van Beveren NJ, Crespo-Facorro B, Niebuhr DW, Cowan DN, Weber NS, 10. Vázquez-Bourgon J, Roiz- Yolken RH, Penninx BW, Bahn S. Santiañez R, Papiol S, Ferro A, Varela- 2. Adams HH, Hibar DP, Chouraki Towards a blood-based diagnostic Gómez N, Fañanás L, Crespo-Facorro V, Stein JL, Nyquist PA, Rentería panel for bipolar disorder. B. ME, Trompet S, Arias-Vasquez A, BRAIN BEHAV IMMUN. 2016;52:49- Variations in Disrupted-in- Seshadri S, Desrivières S, Beecham 57. Schizophrenia 1 gene modulate AH, Jahanshad N, Wittfeld K, Van der F.I.:5,874. [doi:10.1016/j. long-term longitudinal differences in Lee SJ, Abramovic L, Alhusaini S, bbi.2015.10.001] cortical thickness in patients with a Amin N, Andersson M, Arfanakis K, first-episode of psychosis. Aribisala BS, Armstrong NJ, Athanasiu BRAIN IMAGING BEHAV. 2016;10:629- L, Axelsson T, Beiser A, Bernard M, Bis 6. Mayoral-van Son J, Ortiz-Garcia de 635. JC, Blanken LM, Blanton SH, Bohlken la Foz V, Martinez-Garcia O, Moreno F.I.:3,667. [doi:10.1007/s11682-015- MM, ..., Thompson PM. T, Parrilla-Escobar M, Valdizan EM, 9433-1] Novel genetic loci underlying Crespo-Facorro B. human intracranial volume identified Clinical outcome after antipsychotic through genome-wide association. treatment discontinuation in 11. Morlán-Coarasa MJ, Arias-Loste NAT NEUROSCI. 2016;19:1569-1582. functionally recovered first-episode MT, Ortiz-García de la Foz V, Martínez- F.I.:16,724. [doi:10.1038/nn.4398] nonaffective psychosis individuals: a García O, Alonso-Martín C, Crespo J, 3-year naturalistic follow-up study. Romero-Gómez M, Fábrega E, Crespo- J Clin Psychiatry. 2016;77:492- Facorro B. 3. Mehta D, Tropf FC, Gratten 500.F.I.:5,408. [doi:10.4088/ Incidence of non-alcoholic fatty J, Bakshi A, Zhu Z, Bacanu SA, JCP.14m09540] liver disease and metabolic Hemani G, Magnusson PK, Barban dysfunction in first episode N, Esko T, Metspalu A, Snieder H, schizophrenia and related psychotic Mowry BJ, Kendler KS, Yang J, 7. Córdova-Palomera A, Tornador disorders: a 3-year prospective Visscher PM, McGrath JJ, Mills MC, C, Falcón C, Bargalló N, Brambilla P, randomized interventional study. Wray NR, Lee SH, Schizophrenia Crespo-Facorro B, Deco G, Fañanás L. Psychopharmacology (Berl). Working Group of the Psychiatric Environmental factors linked 2016;233:3947-3952. Genomics Consortium, LifeLines to depression vulnerability are F.I.:3,540. [doi:10.1007/s00213-016- Co, Andreassen OA, Bramon E, associated with altered cerebellar 4422-7] Bruggeman R, Buxbaum JD, Cairns resting-state synchronization. MJ, Cantor RM, Cloninger CR, Cohen Sci Rep. 2016;6:37384-37384. D, ..., Wu JQ. F.I.:5,228. [doi:10.1038/srep37384] 12. Las Hayas C, Padilla P, Del Barrio Evidence for Genetic Overlap AG, Beato-Fernandez L, Muñoz P, Between Schizophrenia and Age at Gámez-Guadix M. First Birth in Women. 8. Huang E, Zai CC, Lisoway A, Individualised Versus Standardised JAMA Psychiatry. 2016;73:497-505. Maciukiewicz M, Felsky D, Tiwari Assessment of Quality of Life in Research Areas Neuroscience Area

Eating Disorders. 18. Montejo ÁL, Arango C, Bernardo CNS Drugs. 2016;30:357-368. EUR EAT DISORD REV. 2016;24:147- M, Carrasco JL, Crespo-Facorro B, F.I.:4,910. [doi:10.1007/s40263-016- 156. Cruz JJ, Del Pino J, García Escudero 0331-x] F.I.:2,912. [doi:10.1002/erv.2411] MA, García Rizo C, González-Pinto A, Hernández AI, Martín Carrasco M, 3. Apostolo J, Holland C, O’Connell Mayoral Cleries F, Mayoral van Son J, MD, Feeney J, Tabares-Seisdedos 13. Crespo-Facorro, Benedicto. Mories MT, Pachiarotti I, Ros S, Vieta E. R, Tadros G, Campos E, Santos N, What We Talk About When We Talk Spanish consensus on the risks and Robertson DA, Marcucci M, Varela- About Specialized Early Intervention detection of antipsychotic drug- Nieto I, Crespo-Facorro B, Vieta Programs: 15 Years of PAFIP related hyperprolactinaemia. E, Navarro-Pardo E, Selva-Vera G, (Cantabria, Spain). Rev Psiquiatr Salud Ment. 2016;9:158- Balanzá-Martínez V, Cano A. Early Interv Psychiatry. 2016;10:45-45. 173. Mild cognitive decline. A position F.I.:2,889. F.I.:1,650. [doi:10.1016/j. statement of the Cognitive Decline rpsm.2015.11.003] Group of the European Innovation Partnership for Active and Healthy 14. Alvarez-Jimenez M, Gleeson JF, Ageing (EIPAHA). Rice S, Gonzalez-Blanch C, Bendall S. 19. Carral-Fernández L, González- Maturitas. 2016;83:83-93. Online peer-to-peer support in Blanch C, Goddard E, González-Gómez F.I.:3,120. [doi:10.1016/j. youth mental health: seizing the J, Benito-González P, Bustamante-Cruz maturitas.2015.10.008] opportunity. E, Gómez Del Barrio A. Epidemiol Psychiatr Sci. 2016;25:123- Planning Abilities in Patients with 126. Anorexia Nervosa Compared with F.I.:2,847. [doi:10.1017/ Healthy Controls. S2045796015001092] CLIN NEUROPSYCHOL. 2016;30:228- Doctoral thesis 242. F.I.:1,556. [doi:10.1080/13854046.201 15. Lopez-Morinigo JD, Ayesa-Arriola 6.1147603] 1. Amador Priede Diaz. R, Torres-Romano B, Fernandes AC, Cognitive factors associated Shetty H, Broadbent M, Dominguez- with the development of anxiety- Ballesteros ME, Stewart R, David AS, 20. Las Hayas C, Padierna JA, Muñoz depressive symptoms in newly Dutta R. P, Agirre M, Gómez Del Barrio A, diagnosed cancer patients. Risk assessment and suicide by Beato-Fernandez L, Calvete E. Director: César González-Blanch patients with schizophrenia in Resilience in eating disorders: A Bosch. secondary mental healthcare: a qualitative study. University of Cantabria. case-control study. WOMEN HEALTH. 2016;56:576-594. BMJ Open. 2016;6: F.I.:1,294. [doi:10.1080/03630242.201 F.I.:2,562. [doi:10.1136/ 5.1101744] 2. Beatriz Payá González. Predicted bmjopen-2016-011929] functioning in psychotic disorders of early onset: differences between people diagnosed with 16. Albacete, Auria, Contreras, schizophrenia, bipolar disorder and Fernando, Bosque, Clara, Gilabert, healthy population. Ester, Albiach, Angela, Menchon, Jose Directors: Jesús Ángel Artal Simón, M., Crespo-Facorro, Benedicto, Ayesa- Reviews Celso Arango Lopez. Arriola, Rosa. University of Cantabria. Counterfactual Reasoning in Non- psychotic First-Degree Relatives of 1. Setién-Suero E, Suárez-Pinilla M, People with Schizophrenia. Suárez-Pinilla P, Crespo-Facorro B, 3. Diana Tordesillas Gutiérrez. Front Psychol. 2016;7:665-665. Ayesa-Arriola R. Differences in gray matter volume F.I.:2,463. [doi:10.3389/ Homocysteine and cognition: A in patients with a first psychotic fpsyg.2016.00665] systematic review of 111 studies. episode and age-onset effects using Neurosci Biobehav Rev. 2016;69:280- voxel-based morphometry. 298. Director: Benedicto Crespo Facorro. 17. Ayesa-Arriola R, Setién-Suero E, F.I.:8,580. [doi:10.1016/j. University of Cantabria. Neergaard KD, Ferro A, Fatjó-Vilas neubiorev.2016.08.014] M, Ríos-Lago M, Otero S, Rodríguez- Sánchez JM, Crespo-Facorro B. 2. Alvarez-Jimenez M, O’Donoghue 4. Jacqueline Maria Mayoral Van Son. Evidence for Trait Related Theory B, Thompson A, Gleeson JF, Bendall A three-year longitudinal study of of Mind Impairment in First S, Gonzalez-Blanch C, Killackey clinical evolution in patients who, Episode Psychosis Patients and Its E, Wunderink L, McGorry PD. after a single episode of non- Relationship with Processing Speed: Beyond Clinical Remission in First affective psychosis, have achieved A 3 Year Follow-up Study. Episode Psychosis: Thoughts on a complete recovery and decided to Front Psychol. 2016;7:592-592. Antipsychotic Maintenance vs. withdraw antipsychotic medication. F.I.:2,463. [doi:10.3389/ Guided Discontinuation in the Directoa: Benedicto Crespo Facorro. fpsyg.2016.00592] Functional Recovery Era. University of Cantabria. 137

5. Jana González Gómez. 9. Laura Carral Fernández. longitudinal study (10 years) of Controlled study of risk factors and Cognitive bias in eating disorders: a cognitive functioning in patients clinical variables associated with the case-control study. with schizophrenia spectrum development of a eating disorder Director/a: Andrés Gómez Del Barrio. psychosis. in the community of Cantabria. University of Cantabria. PI14/00918. INSTITUTO DE SALUD Director: Andrés Gómez Del Barrio. CARLOS III. MINISTERIO DE University of Cantabria. ECONOMÍA Y COMPETITIVIDAD.

4. Benedicto Crespo Facorro. 6. Javier Vázquez Bourgon. PROJECTS Aid for predoctoral contracts for the DISC1 and non-affective psychosis: training of doctors. variations in endophenotypes and BES-2014-070615. clinical characteristics in the first MINISTERIO DE ECONOMIA Y episodes of psychosis. Projects COMPETITIVIDAD. Director: Benedicto Crespo Facorro. University of Cantabria. 5. Benedicto Crespo Facorro. 1. Benedicto Crespo Facorro. Contracts for the intensification of Center for Biomedical Research in the research activity in the SNS. 7. José Gabriel Calcedo Giraldo. Mental Health Network. CIBERSAM. INT15/00096. Prevention in eating disorders in CIBERSAM. INSTITUTO DE SALUD INSTITUTO DE SALUD CARLOS high school students in cantabria. CARLOS III. MINISTERIO DE III. MINISTERIO DE ECONOMÍA Y Director: Andrés Gómez Del Barrio. ECONOMÍA Y COMPETITIVIDAD. COMPETITIVIDAD. University of Cantabria. 2. Benedicto Crespo Facorro. 6. Benedicto Crespo Facorro. Translating neuroimaging findings Stratified treatment in 8. Jose Helmut Ramirez Cuentas. from research into clinical practice. schizophrenia: integrating human Study of parents’ satisfaction in a EU12/01- PSYSCAN. and cellular transcriptome results in neonatal unit. COMISIÓN EUROPEA. antipsychotic treatment strategies. Directors: Isabel De Las Cuevas SAF2016-76046-R. Terán, Luis Gaite Pindado. 3. Diana Tordesillas Gutiérrez. MINISTERIO DE ECONOMIA Y University of Cantabria.. 10PAFIP neurocognition: long-term COMPETITIVIDAD.

139

Cancer Area

Fernando Rivera Herrero Coordinator of the Cancer Area.

Head of the Oncology Service. University Hospital Marqués de Valdecilla. Research Areas Cancer Area

Group Leader José Javier Gómez Román Pathology Service Áreas de University Hospital Anatomical and Marqués de Valdecilla Molecularinvestigación Pathology University of Cantabria

[email protected]

Contributors Ainara Azueta Etxebarría Clara Isabel Caballero Escudero Clara Isabel Esparza Del Valle Francisco Javier Freire Salinas Maria Pilar Garcia-Berbel Molina Javier Martín López Marta Mayorga Fernández Steliana Florina Racean

Nurses Montserrat Fernández Álvarez Maria Montserrat Nicolas Martínez

Technicians María Dolores Herrera Cisneros Servando Lazuen Fernández Consolidated group Maria Sierra Rumoroso

1. Diagnostic and predictive response value (Mamacan project). biomarkers in solid tumors. This project is designed to find Research stromal based biomarkers capable Our main task remains to establish to be transformed in therapeutic Lines a model of translational medicine, targets in breast carcinomas. The which is to be the bridge between same methodology is being applied basics and applied investigation. to urinary bladder carcinomas, lung We are basically implied in all the carcinomas, renal cell carcinomas Research on cancer is one of new biomarkers that are necessary and gastrointestinal stromal tumors the most important and we can to obtain a correct diagnosis at the (GIST). distinguish the following lines: right time with a strong predictive 141

clinical establishment and in new models of anti-PD1-L1 antibodies SP142, SP263, 22C3 and 28-8. The availability of all antibodies allows the participation in clinical trials of new development in new tumor models. The research line in non- tumoral pathology is reflected by the existence of several doctoral theses in development that explore the detection of viral infectious agents in Immunosuppressed patients in the tissue and its relation to graft failures in the case of organ transplantation. We collaborate actively with Nephrology groups (gene expression project in transplant patients’ biopsies) in this sense. Our collaboration extends to the University of Cantabria with active projects in relation to Legal Medicine (utility of DNA extraction methods in ancient samples) and IBBTEC in Genomics (Dr Ignacio Varela with several projects underway using mass sequencing procedures). The collaboration with 2. We have developed systems Thus, we use the EGFR and ALK national research groups is mainly to diagnose hereditary cancer and ROS1 rearrangements in with the CIMA of the University of in clinical routine based in Next non-small cell lung carcinomas, Navarra in its line of oncology led generation sequencing and we the KRAS and NRAS mutations in by Professor Luis Montuenga in the have incorporated the epithelial- colon adenocarcinomas by several field of lung cancer and with the mesenchymal transition program to techniques, including liquid biopsy, University of Oviedo and various our biomarker’s discovery plan. and several other biomarkers that hospitals of the national network in are the key to precision medicine the Role of epithelial-mesenchymal establishment. transition in breast cancer We received rotating professionals from 3. Our most important role as different hospitals of the national pathologists is to incorporate our 4. Development of network to deepen teaching. The results to clinical routine, mainly Immunotherapy in cancer. collaboration extends to European in oncology. countries as with the group of Dr Immunotherapy is one of the most Julian Downward of the London We believe the basic investigation promising fields in new cancer Research Institute investigating results are very difficult to use therapies. The use of so-called factors of resistance to drugs in our day-to-day work. We try “companion tests” are mandatory inhibiting the tyrosine kinase to streamline the process to according to the regulatory activity in lung cancer. We also give the oncologist the data he agencies for prescription. Our collaborated with MD Anderson needs to treat the patient with interest is to develop all of the Hospital on a neuroendocrine the biomarkers that have been markers associated with specific evaluation project and its new accepted by the international therapies anti PD1 and anti PD-L1. classification (Dr César Morán). community and the agencies. To do this we are involved in the Research Areas Cancer Area

Elisabet, Ferrandez-Fernandez, Eva, 12. Velilla G, Carrión CJ, Portillo JA, PUBLICATIONS: Freire, Javier, Penades, Soledad, Truán D, Azueta A, Fuentes J, Herrero Marradi, Marco, Garcia, Isabel, Gomez- E, Gala L. Roman, Javier, Yanez-Diaz, Sonsoles, Microcytic carcinoma of the urinary IMPACT FACTOR | 33,960 Alvarez-Dominguez, Carmen. bladder: Experience over 22 years. Pregnancy Vaccination with Gold Actas Urol Esp. 2016;40:195-200. Glyco-Nanoparticles Carrying F.I.:0,964. [doi:10.1016/j. Listeria monocytogenes Peptides acuro.2015.11.008] Artículos originales Protects against Listeriosis and Brain- and Cutaneous-Associated 13. Irure J, López-Hoyos M, Rodrigo Morbidities. E, Gómez-Román J, Ruiz JC, Arias M, 1. Villalba M, Diaz-Lagares A, Redrado Nanomaterials (Basel). 2016;6: San Segundo D. M, de Aberasturi AL, Segura V, F.I.:2,690. [doi:10.3390/nano6080151] Antibody-Mediated Rejection in Bodegas ME, Pajares MJ, Pio R, Freire Kidney Transplantation Without J, Gomez-Roman J, Montuenga LM, Evidence of Anti-HLA Antibodies?. Esteller M, Sandoval J, Calvo A. 6. Loricera J, González-Vela C, Transplant Proc. 2016;48:2888-2890. Epigenetic alterations leading Blanco R, Hernández JL, Armesto S, F.I.:0,867. [doi:10.1016/j. to TMPRSS4 promoter González-López MA, Calvo-Río V, Ortiz- transproceed.2016.09.025] hypomethylation and protein Sanjuán F, Val-Bernal JF, Hermana S, overexpression predict poor Onaindia-Pérez A, González-Gay MA. prognosis in squamous lung cancer Histopathologic differences between 14. Sango C, Merino D, San Segundo patients. cutaneous vasculitis associated D, Rodrigo E, Lopez-Hoyos M, Benito Oncotarget. 2016;7:22752-22769. with severe bacterial infection and A, Ángeles Ramos M, Gómez-Román F.I.:5,008. [doi:10.18632/ cutaneous vasculitis secondary to J, Arias M. oncotarget.8045] other causes: study of 52 patients. B-Cell-Activating Factor Levels Are Clin Exp Rheumatol. 2016;34:93-97. Associated With Antibody-Mediated F.I.:2,495. Histological Damage in Kidney 2. Calderon-Gonzalez R, Bronchalo- Transplantation. Transplant Proc. Vicente L, Freire J, Frande-Cabanes 2016;48:2910-2912. 7. Val-Bernal JF, Mayorga M, Val D. E, Alaez-Alvarez L, Gomez-Roman J, F.I.:0,867. [doi:10.1016/j. Incidental Melanocytic Nevi in Yañez-Diaz S, Alvarez-Dominguez C. transproceed.2016.09.019] Exceptional antineoplastic activity Hemorrhoidectomy Specimens. of a dendritic-cell-targeted vaccine Am J Dermatopathol. 2016;38:278- loaded with a Listeria peptide 282.F.I.:1,396. [doi:10.1097/ 15. Belmar Vega L, Rodrigo Calabia E, proposed against metastatic DAD.0000000000000419] Gómez Román JJ, Ruiz San Millán JC, melanoma. Martín Penagos L, Arias Rodríguez M. Oncotarget. 2016;7:16855-16865. Relationship Between Albuminuria F.I.:5,008. [doi:10.18632/ 8. Val-Bernal JF, Hermana S. During the First Year and Antibody- oncotarget.7806] Arteriovenous malformation of the Mediated Rejection in Protocol uterine cervix. Biopsies in Kidney Transplant Pathol Res Pract. 2016;212:226-228. Recipients. 3. Real, Eusebio, Fernando Val-Bernal, F.I.:1,388. [doi:10.1016/j. Transplant Proc. 2016;48:2950-2952. Jose, Revuelta, Jose M., Ponton, prp.2015.08.010] F.I.:0,867. [doi:10.1016/j. Alejandro, Calvo Diez, Marta, Mayorga, transproceed.2016.09.012] Marta, Lopez-Higuera, Jose M., Conde, Olga M. 9. Val-Bernal JF, Mayorga M, Terán- 16. Val-Bernal JF, Hermana S. Hessian analysis for the delineation Villagrá N. Dermal plexiform spindle cell of amorphous anomalies in optical Extracutaneous intravascular lipoma. coherence tomography images of histiocytosis of the aortic valve: Rom J Morphol Embryol. 2016;57:875- the aortic wall. Report of two cases. 878.F.I.:0,811. BIOMED OPT EXPRESS. 2016;7:1415- Pathol Res Pract. 2016;212:258-263. 1429.F.I.:3,344. [doi:10.1364/ F.I.:1,388. [doi:10.1016/j. BOE.7.001415] prp.2015.12.016]

10. Val-Bernal JF, Mayorga M. Reviews 4. Córdoba A, Lisa M, Gómez-Román Incidental vaginal müllerianosis. JJ, Hernández JL. Pathol Res Pract. 2016;212:568-572. Pulmonary pseudo-tumour, aortitis 1. Val-Bernal JF, Mayorga M, Cagigal F.I.:1,388. [doi:10.1016/j. and IgG4 disease. ML, Cabezas-González J. prp.2016.02.023] QJM. 2016;109:345-346. Gastric pyogenic granuloma: Report F.I.:2,824. [doi:10.1093/qjmed/hcw008] of two cases and review of the 11. Val-Bernal JF. Respuesta. literature. Med Clin (Barc). 2016;146:186-187. Pathol Res Pract. 2016;212:68-71. 5. Calderon-Gonzalez, Ricardo, Teran- F.I.:1,267. [doi:10.1016/j. F.I.:1,388. [doi:10.1016/j. Navarro, Hector, Frande-Cabanes, medcli.2015.09.001] prp.2015.11.001] 143

Evaluation of biomarker predictors Marqués de Valdecilla. Doctoral thesis of peritoneal carcinomatosis in colon Directors: José Manuel López Vega, carcinoma. Marta Mayorga Fernández. Directors: José Javier Gómez Román, University of Cantabria. 1. Ruth Gonzalez Sanchez. Francisco Javier Freire Salinas. Development of a diagnostic University of Cantabria. method for gastrointestinal stromal tumors (GIST). 4. Nuria E. Cadenas González. Directors: José Javier Gómez Román, Study of mesenchymal epithelial PROYECTS Francisco Javier Freire Salinas. transition markers in renal University of Cantabria. neoplasms. Directors: José Javier Gómez Román, Francisco Javier Freire Salinas. Proyects 2. Araceli Prieto Santacruz. University of Cantabria. Utility of a process-based 1. José Javier Gómez Román. management system in the care and Development of anti-CCR9 perceived quality of lung cancer. 5. Ana De Juan Ferré. therapeutic antibodies for the Director: José Javier Gómez Román. Phase II intramural study of personalized treatment of University of Cantabria. neoadjuvant chemotherapy with platinum, doxorubicin and taxane tumors-TERPERAN. salts in operable breast cancer. RTC-2015-3786-1. MINISTERIO DE ECONOMIA Y 3. Víctor Jacinto Ovejero Gómez. Experience of the medical oncology service of the University Hospital COMPETITIVIDAD. Research Areas Cancer Area

Group Leader Juan M. Hurlé Gonzalez Department of Molecular Áreas de Biology School of Medicine Apoptosisinvestigación University of Cantabria

[email protected]

Researchers Juan Antonio Montero Simón

Contributors Juan Antonio García-Porrero Pérez Carlos Ignacio Lordá Díez

Predoctoral Beatriz García-Riart Monzón Cristina Sánchez Fernández

Consolidated group

of skeletal progenitors and also of the embryonic limb bud follow two to provide information about limb alternative fates: in the future digit morphogenesis. Gens identified regions, mesodermal cells aggregate Research by different molecular strategies and differentiate into cartilage, joints Lines are functionally analyzed through and fibrous tissues such as tendons gain-of- and lossof-function or ligaments; in the interdigital experiments. Gain-of-function regions, cells do not condense experiments are performed through and instead undergo massive cell the overexpression of the selected death. The goal of these studies is genes employing viral infections or to obtain information of relevance We are interested in the development plasmid electroporation. Loss-of- in regenerative medicine to direct of the vertebrate limb using avian function experiments are made with the differentiation of stem cells into and mouse embryos as experimental short hairpin RNAi or CRISPR-Cas9 skeletal tissues and to provide basic models. The aim of our research approaches. Our major research field information about the mechanisms is to uncover molecular signals is the formation of the digits. During accounting for programmed cell which regulate the differentiation this process, mesodermal progenitors death. 145

PUBLICATIONS: 2. Arroba AI, Rosa LR, Murillo-Cuesta PROYECTOS S, Vaquero-Villanueva L, Hurlé JM, Varela-Nieto I, Valverde ÁM. IMPACT FACTOR | 12,492 Autophagy resolves early retinal inflammation in Igf1-deficient mice. Proyectos Dis Model Mech. 2016;9:965-974. F.I.:4,316. [doi:10.1242/dmm.026344] Original articles 1. Juan M. Hurlé Gonzalez. Mechanism and new biological significance of interdigital cell death 3. Lorda-Diez CI, Montero JA, Garcia- 1. Montero, Juan A., Sanchez- responsible for the separation of the Porrero JA, Hurle JM. The tumor Fernandez, Cristina, Lorda-Diez, fingers during the development of suppressor BTG1 is expressed in Carlos I., Garcia-Porrero, Juan A., the extremities. BFU2014-54026-P. the developing digits and regulates Hurle, Juan M. MINISTERIO DE ECONOMIA Y skeletogenic differentiation of limb DNA damage precedes apoptosis COMPETITIVIDAD. mesodermal progenitors in high during the regression of the density cultures. interdigital tissue in vertebrate Cell Tissue Res. 2016;364:299-308. embryos. F.I.:2,948. [doi:10.1007/s00441-015- Sci Rep. 2016;6:35478-35478. 2331-4] F.I.:5,228. [doi:10.1038/srep35478] Research Areas Cancer Area

Group Leader Alberto Gandarillas Solinis Fundación Instituto de CellÁreas cycle, Determining de stem Investigación Marqués de Valdecilla Cellsinvestigación and Cancer IDIVAL

[email protected]

Ana Freije Leon Maria Teresa Gil Aguilar Carmelo Morales Angulo Sergio Obeso Aguera Juan Ramón Sanz Giménez-Rico Ana Tardaguila Calvo Sandra Patricia Vergara Pastrana

Consolidated group Predoctoral Rut Molinuevo Llaria Natalia Sanz Gómez Contributors Higinio Ayala Gutiérrez Ernesto de Diego García José Manuel Bernal Marco Isabel de Pedro González Technicians Natalia Castañeda Curto Inmaculada Fernández Jiménez Laura Ceballos Castillo

is the most common cancer. This Older Adolescents & Young Adults. stems from variations in DNA 2007. SEER AYA Monograph, pages caused primarily by ultraviolet 53–57). Research radiation (UV) from the sun and Lines the Human Papillomavirus (HPV). For these reasons, the skin needs It is also the cancer with the most powerful cellular and molecular increasing frequency within our mechanisms to protect itself societies, due to the aesthetic from continued mutagenic risk. tendencies that induce tanning, These mechanisms go through Among the many skin conditions which is making it the leading the proper control of Stem Cells that affect the health and life cause of cancer death in women and homoeostasis. The main goal expectancy of the population aged 20-30 years (*National Cancer of our group is to research these and that pose a growing problem Institute. Bethesda, MD, http:// mechanisms and their variations in in public health (psoriasis, seer.cancer.gov/csr/1975_2008/ hyperproliferative skin problems, xerodermas, keratosis), skin cancer index.html. Cancer Epidemiology in mainly those leading to cancer. The 147

objective is the reciprocal transfer of degenerative regurgitation between the laboratory (molecular Original articles with restrictive annuloplasty: A mechanisms of the cell cycle), the conundrum of knowledge. industry (exploitation of results) and J Thorac Cardiovasc Surg. 1. Stoll SW, Stuart PE, Swindell WR, the hospital (obtaining biopsies, 2016;151:110-111.F.I.:3,494. Tsoi LC, Li B, Gandarillas A, Lambert characterisation, monitoring, new [doi:10.1016/j.jtcvs.2015.10.055] S, Johnston A, Nair RP, Elder JT. diagnostics or therapies). The EGF receptor ligand amphiregulin controls cell division The main lines that are currently via FoxM1. PROJECTS active are: Oncogene. 2016;35:2075-2086. 1) Functional control F.I.:7,932. [doi:10.1038/onc.2015.269] mechanisms of mitosis and Projects differentiation in the skin. 2. Stoll SW, Stuart PE, Lambert S, Gandarillas A, Rittié L, Johnston A, 2) Epidermal protection and 1. Alberto Gandarillas Solinis. Elder JT. repair mechanisms against New Routes and Strategies for Membrane-Tethered Intracellular Squamous Cell Cancer. PI14/00900. genetic damage. Domain of Amphiregulin Promotes INSTITUTO DE SALUD CARLOS Keratinocyte Proliferation. 3) Variations in mitosis III. MINISTERIO DE ECONOMÍA Y J Invest Dermatol. 2016;136:444-452. control and differentiation in COMPETITIVIDAD. F.I.:6,915. [doi:10.1016/j. epidermoid cancer. jid.2015.10.061] 4) Stem Cell applications in the repair and regeneration of tissue. OTHER PUBLICATIONS Editorials Doctoral thesis 1. Bernal JM, Mestres CA. Epicardial adipose hypertrophy: The Phantom of the Opera. 1. Ana Mª Arnaiz García. J Thorac Cardiovasc Surg. Morbidity and mortality in deferred 2016;151:31-32.F.I.:3,494. sternal closure. [doi:10.1016/j.jtcvs.2015.10.050] Director/es: José Manuel Bernal PUBLICATIONS: Marco, Mª Concepcion Fariñas Álvarez, María Del Carmen Fariñas IMPACT FACTOR | 21,835 2. Bernal JM, Mestres CA. Álvarez. Mitral valve gradient after repair University of Cantabria. Research Areas Cancer Area

Group Leader Santiago Montes Moreno Pathology Service TranslationalÁreas de University Hospital Marqués de Valdecilla Hematopathologyinvestigación

[email protected]

Contributors Ruth Alonso Alonso Catuxa Celeiro Muñoz Sandra Hermana Ramirez Alicia León Del Castillo Arantza Onaindia Pérez

Predoctoral Nuria García Díaz

Technicians Laura Cereceda Company Soraya Curiel Del Olmo Ainara González Pereña Consolidated group

The field of hematopathology is in molecular diagnostic tools useful continuous development regarding in the area of hematolymphoid the identification of new molecular pathology. He has participated Research markers of clinical utility. The in the validation of monoclonal Lines use of phenotyping techniques, antibodies useful in the diagnosis new technologies such as mass (ie GCET1, SPI-B), validation and sequencing, high sensitivity standardization of the protocols expression analysis techniques of analysis and interpretation of (ie digital quantitative PCR), lymphoid B and T clonality of the detection of circulating plasma DNA European consortium Biomed2 (liquid biopsy) requires rigorous and recently generated a protocol 1. New technologies useful for the preclinical validation for use as Of clinical diagnosis of somatic molecular diagnosis of patients clinical diagnostic tools. Our group mutation MYD88L265P, useful for with hematolymphoid neoplasms. generates and validates clinical small cell B-cell lymphomas with 149

differentiation (lymphoplasma B 2013 (EudraCT No: 2013- 001065- lymphoma) for which standard lymphoplasmacytic / Waldestrom 17), LR-ESHAP (EudraCT No.: therapy is ineffective or inadequate disease) and diffuse large cell 2010-018463-41) This collaboration Recent studies using massive lymphoma of the ABC phenotype involves several clinical groups at genome and exome sequencing that is applied in the clinical the national level and other groups are identifying recurrent genetic diagnostic field. Currently a line specialized in laboratory diagnosis, alterations in the NFkB, BCR, JAK / of advance is the optimization of mainly at the Hospital Clínico STAT pathways, Histone-modifying a protocol for the identification Universitario de Salamanca and at genes and genes related to the of somatic mutations in free the Hospital The platform integrates immune response, among others circulating tumor DNA in plasma of clinical groups responsible for in LBDCG. In aggressive variants patients with LBDCG that serves as the development of clinical trials such as plasmablast lymphoma, a screening for the diagnosis of the with subjects and groups of relevant role of the MYC oncogene disease and clinical follow-up of translational research, responsible has been identified, with gene patients. for the study of the samples and translocation occurring in about the Laboratory development, more 60% of the cases. Recent data experimental. A small group of from our group demonstrate that 2. Clinical validation of pathologists who are experts in in this type of lymphomas there biomarkers in translational the area are also included, who is overexpression of the MYC research projects linked to validate the diagnoses of the protein in the majority of cases of multicenter clinical trials for patients included in the EECC and plasmablast lymphoma, associated patients with hematolymphoid process the samples appropriately with marked overexpression of the neoplasms. for the laboratory studies. The alpha isoform of PRDM1 / Blimp1, The clinical validation of molecular incorporation of Biobank Valdecilla a key tumor suppressor gene in markers is concretized by analyzing into the network facilitates and induction of the plasmocellular the impact of these biomarkers in normalizes the use of biological phenotype and inhibitor of MYC clinical trials designed to test their samples from patients. under physiological conditions. predictive value of response and Additionally, we have demonstrated a high frequency of recurrent point prognosis. The design of protocols 3. Identification of biomarkers mutations in PRDM1 / Blimp1 of biological study of the samples, of diagnostic, prognostic and regulatory domains, by targeted linked to clinical trials with new predictive usefulness of response sequencing of the PRDM1 / Blimp1 drugs is the method that allows to therapy in patients with large exome. These results reinforce the to accelerate the translation of cell B-cell lymphoma. results and to demonstrate its relevance of the MYC oncogene in potential clinical utility. In this Diffuse large cell lymphoma this type of neoplasia and describe, sense, our group, integrated with (LBDCG) is the most common form for the first time, somatic mutations the HUMV Pathology Service, of non-Hodgkin’s lymphoma in in PRDM1 / blimp1 in plasmablast leads a centralized anatomical and our country and accounts for 80% lymphoma, which would explain molecular diagnostic platform for of aggressive lymphomas, with the apparent paradox, biologically, the samples of patients included an upward trend of about 93,000 involving the coexpression of in clinical trials of the cooperative new cases per year in Europe MYC and PRDM1 / Blimp1. These national group GELTAMO (Spanish (BLOBOCAN (IARC)) The precise preliminary data confirm the Group of Lymphomas and Bone subclassification of the different intrinsic heterogeneity of LBDCG Marrow Transplant) , As responsible LBDCG entities is clinically relevant and lead to the need to specifically for the centralized diagnosis from a prognostic and therapeutic identify those functionally and generation of protocols of selection point of view, as there biologically relevant events and, molecular studies of the different are a number of aggressive clinical on the other hand, predictors of open-label clinical trials in large cell behavioral phenotypes (high grade response to specific therapies or lymphoma (GEL-BRCAP21 (EudraCT B lymphoma with “double / LBDCG prognoses in a specific therapeutic No: 2012-005138-12), GEL-RCOMP of ABC subtype, plasmablast context. Research Areas Cancer Area

Figura a. Image depicting recurrent mutated (Stratifying diffuse large B-cell lymphoma Figura d.The complete molecular genes in LBDCG. The new methods of patients treated with chemoimmunotherapy: characterization (genotype and phenotype) directed sequencing of the exoma allow GCB / Non-GCB by immunohistochemistry is of aggressive B-cell subtypes such as generating mapping of the cases in order still a robust and feasible marker. Oncotarget plasmablastic lymphoma allows explaining to identify profiles that guide the optimal 2016). the interaction between neoplastic driver therapy in each subject. . genes (MYC) and other regulatory genes Figura c. Clinical validation of new molecular (PRDM1 / Blimp1) revealing new molecular Figura b. The correlation of expression data diagnostic techniques (identification of mechanisms of disease (Plasmablastic with global survival and progression-free the mutation of MYD88L265P by AS-PCR Lymphoma phenotype is determined by survival in LBDCG allows the identification of and direct sequencing in large cell type B genetic alterations in MYC and PRDM1, patients who could benefit from inclusion in lymphoma is shown as an example) is useful Modern Pathology 2017). clinical trials with new, more selective drugs for proper subclassification of each case. 151

Papadopoulou E, Davis Z, Algara Increased prevalence of subclinical PUBLICATIONS: P, Kanellis G, Traverse-Glehen A, atherosclerosis in patients with Mollejo M, Anagnostopoulos A, hidradenitis suppurativa (HS). Ponzoni M, Gonzalez D, Pospisilova J Am Acad Dermatol. 2016;75:329- IMPACT FACTOR | 159,151 S, Matutes E, Piris MA, Papadaki 335.F.I.:5,621. [doi:10.1016/j. T, Ghia P, Rosenquist R, Oscier D, jaad.2016.03.025] Darzentas N, Tzovaras D, Belessi C, Hadzidimitriou A, Stamatopoulos K. 11. Ye Q, Xu-Monette ZY, Tzankov A, An Immunogenetic Signature of Deng L, Wang X, Manyam GC, Visco Original articles Ongoing Antigen Interactions in C, Montes-Moreno S, Zhang L, Dybkær Splenic Marginal Zone Lymphoma K, Chiu A, Orazi A, Zu Y, Bhagat G, Expressing IGHV1-2*04 Receptors. Richards KL, Hsi ED, Choi WW, van Clin Cancer Res. 2016;22:2032-2040. Krieken JH, Huh J, Ponzoni M, Ferreri 1. Roncero AM, López-Nieva P, F.I.:8,738. [doi:10.1158/1078-0432. AJ, Parsons BM, Møller MB, Piris MA, Cobos-Fernández MA, Villa-Morales M, CCR-15-1170] Winter JN, Medeiros LJ, Hu S, Young González-Sánchez L, López-Lorenzo KH. JL, Llamas P, Ayuso C, Rodríguez- 6. Xu-Monette Z, Deng Q, Manyam G, Prognostic impact of concurrent Pinilla SM, María Del CA, Piris M, Tzankov A, Li L, Xia Y, Wang XX, Zou MYC and BCL6 rearrangements and Fernández-Navarro P, Fernández D, Visco C, Dybkaer K, Li J, Zhang L, expression in de novo diffuse large AF, Fraga MF, Santos J, Fernández- Liang H, Montes-Moreno S, Chiu A, B-cell lymphoma. Piqueras J. Orazi A, Zu Y, Bhagat G, Richards KL, Oncotarget. 2016;7:2401-2416. Contribution of JAK2 mutations Hsi ED, Choi WW, van Krieken HJ, F.I.:5,008. [doi:10.18632/ to T-cell lymphoblastic lymphoma Huh J, Ponzoni M, Ferreri AJ, Parsons oncotarget.6262] development. B, Moller MB, Wang S, Miranda R, ..., Leukemia. 2016;30:94-103. Young KH. F.I.:12,104. [doi:10.1038/leu.2015.202] 12. Batlle-López A, González Clinical and Biologic Significance of de Villambrosía S, Mazorra F, MYC Genetic Mutations in De Novo Malatxeberria S, Sáez A, Montalban 2. Deng L, Xu-Monette ZY, Loghavi Diffuse Large B-cell Lymphoma. C, Sánchez L, Garcia JF, González- S, Manyam GC, Xia Y, Visco C, Huh Clin Cancer Res. 2016;22:3593-3605. Barca E, López A, Ruiz-Marcellan MC, J, Zhang L, Zhai Q, Wang Y, Qiu L, F.I.:8,738. [doi:10.1158/1078-0432. Mollejo M, Grande C, Richards KL, Hsi Dybkær K, Chiu A, Perry AM, Zhang S, CCR-15-2296] ED, Tzankov A, Visco C, Xu-Monette Tzankov A, Rao H, Abramson J, Sohani ZY, Cao X, Young KH, Angel Piris M, AR, Xu M, Hsi ED, Zhu J, Ponzoni 7. Manso R, Bellas C, Martin-Acosta Conde E, Montes-Moreno S. M, Wang S, Li L, Zhang M, Ferreri P, Mollejo M, Menárguez J, Rojo F, Stratifying diffuse large B-cell AJ, Parsons BM, Li Y, ..., Young KH. Llamas P, Piris MA, Rodríguez-Pinilla lymphoma patients treated with Primary testicular diffuse large B-cell SM. chemoimmunotherapy: GCB/non- lymphoma displays distinct clinical C-MYC is related to GATA3 GCB by immunohistochemistry is and biological features for treatment expression and associated with poor still a robust and feasible marker. failure in rituximab era: a report from prognosis in nodal peripheral T-cell Oncotarget. 2016;7:18036-18049. the International PTL Consortium. lymphomas. F.I.:5,008. [doi:10.18632/ Leukemia. 2016;30:361-372. Haematologica. 2016;101:336-338. oncotarget.7495] F.I.:12,104. [doi:10.1038/leu.2015.237] F.I.:6,671. [doi:10.3324/ haematol.2016.143768] 13. Onaindia A, Martínez N, Montes- 3. Xu-Monette ZY, Li L, Byrd JC, Moreno S, Almaraz C, Rodríguez-Pinilla Jabbar KJ, Manyam GC, Maria de 8. De las Vecillas, L., Montecchiani, V, SM, Cereceda L, Revert JB, Ortega C, Winde C, van den Brand M, Tzankov Morchon, E., Linares, E., Montes, S., Tardio A, González L, García S, Camacho A, Visco C, Wang J, Dybkaer K, Chiu Rodriguez, F. FI, González-Vela C, Piris MA. A, Orazi A, Zu Y, Bhagat G, Richards Granulomatous sarcoidal reaction CD30 Expression by B and T KL, Hsi ED, Choi WW, Huh J, Ponzoni due to palladium monosensitization Cells: A Frequent Finding in M, Ferreri AJ, Møller MB, Parsons BM, for dental prosthesis. Angioimmunoblastic T-Cell Winter JN, Wang M, Hagemeister FB, Allergy. 2016;71:550-551. Lymphoma and Peripheral T-Cell Piris MA, van Krieken JH, Medeiros LJ, F.I.:6,335. Lymphoma-Not Otherwise Specified. ..., Young KH. Am J Surg Pathol. 2016 Mar;40(3):378-85. Assessment of CD37 B-cell antigen and cell of origin significantly 9. Martín A, Redondo AM, Dlouhy I, 14. Bermudez G, González de improves risk prediction in diffuse Salar A, González-Barca E, Canales Villambrosía S, Martínez-López A, large B-cell lymphoma. M, Montes-Moreno S, Ocio EM, Batlle A, Revert-Arce JB, Cereceda Blood. 2016;128:3083-3100. López-Guillermo A, Caballero D. Company L, Ortega Bezanilla C, Piris F.I.:11,847. [doi:10.1182/ Lenalidomide in combination with MA, Montes-Moreno S. blood-2016-05-715094] R-ESHAP in patients with relapsed or refractory diffuse large B-cell Incidental and Isolated Follicular lymphoma: a phase 1b study from Lymphoma In Situ and Mantle Cell 4. Piris MA. GELTAMO group. Lymphoma In Situ Lack Clinical Nodal marginal zone mutational Br J Haematol. 2016;173:245-252. Significance. signature. F.I.:5,812. [doi:10.1111/bjh.13945] Am J Surg Pathol. 2016;40:943-949. Blood. 2016;128:1315-1316 F.I.:4,951. [doi:10.1097/ F.I.:11,847. [doi:10.1182 PAS.0000000000000628] blood-2016-07-724963] 10. González-López MA, Hernández JL, Lacalle M, Mata C, López- Escobar M, López-Mejías R, Portilla 15. Xu-Monette ZY, Zhang S, Li X, 5. Bikos V, Karypidou M, Stalika E, V, Fuentevilla P, Corrales A, González- Manyam GC, Wang XX, Xia Y, Visco Baliakas P, Xochelli A, Sutton LA, Vela MC, González-Gay MA, Blanco R. C, Tzankov A, Zhang3 L, Montes- Papadopoulos G, Agathangelidis A, Moreno S, Dybkaer K, Chiu A, Orazi Research Areas Cancer Area

A, Zu Y, Bhagat G, Richards KL, Hsi R, Armesto S, Ubilla B, Mijares V, 25. Pina T, Corrales A, Lopez-Mejias ED, Choi WW, van Krieken JH, Huh J, Dierssen-Sotos T, Corrales A, Gonzalez- R, Armesto S, Gonzalez-Lopez MA, Ponzoni M, Ferreri AJ, Zhao X, Møller Lopez MA, Gonzalez-Vela MC, Blanco Gómez-Acebo I, Ubilla B, Remuzgo- MB, Parsons BM, Winter JN, Piris MA, R, Llorca J, Gonzalez-Gay MA. Martínez S, Gonzalez-Vela MC, Blanco Medeiros LJ, Young KH. Anti-TNF-a therapy reduces retinol- R, Hernández JL, Llorca J, Gonzalez-Gay p63 expression confers significantly binding protein 4 serum levels in MA. better survival outcomes in high- non-diabetic patients with psoriasis: Anti-tumor necrosis factor-alpha risk diffuse large B-cell lymphoma a 6-month prospective study. therapy improves endothelial function and demonstrates p53-like and J Eur Acad Dermatol Venereol. and arterial stiffness in patients with p53-independent tumor suppressor 2016;30:92-95. moderate to severe psoriasis: A function. F.I.:3,029. [doi:10.1111/jdv.13005] 6-month prospective study. Aging (Albany NY). 2016;8:345-365. J Dermatol. 2016;43:1267-1272. F.I.:3,979. [doi:10.18632/aging.100898] 21. Sebastián E, Alcoceba M, Martín- F.I.:1,577. [doi:10.1111/1346- García D, Blanco Ó, Sanchez-Barba 8138.13398] 16. Zhang M, Xu-Monette ZY, Li L, M, Balanzategui A, Marín L, Montes- Manyam GC, Visco C, Tzankov A, Moreno S, González-Barca E, Pardal E, 26. Pina T, Genre F, Lopez-Mejias Wang J, Montes-Moreno S, Dybkaer Jiménez C, García-Álvarez M, Clot G, R, Armesto S, Ubilla B, Mijares K, Chiu A, Orazi A, Zu Y, Bhagat G, Carracedo Á, Gutiérrez NC, Sarasquete V, Dierssen-Sotos T, Corrales A, Richards KL, Hsi ED, Choi WW, Han ME, Chillón C, Corral R, Prieto-Conde Gonzalez-Lopez MA, Gonzalez- van Krieken J, Huh J, Ponzoni M, MI, Caballero MD, Salaverria I, García- Vela MC, Blanco R, Hernández Ferreri AJ, Møller MB, Parsons BM, Sanz R, González M. JL, Llorca J, Gonzalez-Gay MA. Winter JN, Piris MA, Medeiros LJ, High-resolution copy number Asymmetric dimethylarginine but Pham LV, Young KH. analysis of paired normal-tumor not osteoprotegerin correlates RelA NF-?B subunit activation as a samples from diffuse large B cell with disease severity in patients therapeutic target in diffuse large lymphoma. with moderate-to-severe psoriasis B-cell lymphoma. Ann Hematol. 2016;95:253-262. undergoing anti-tumor necrosis Aging (Albany NY). 2016;8:3321-3340. F.I.:3,022. [doi:10.1007/s00277-015- factor-a therapy. F.I.:3,979. [doi:10.18632/aging.101121] 2552-3] J Dermatol. 2016;43:389-394. F.I.:1,577. [doi:10.1111/1346- 17. Calvo-Río V, Blanco R, Santos- 22. Loricera J, González-Vela C, 8138.13094] Gómez M, Rubio-Romero E, Cordero- Blanco R, Hernández JL, Armesto S, Coma M, Gallego-Flores A, Veroz González-López MA, Calvo-Río V, Ortiz- 27. González-López MA, Blanco R, R, Torre I, Hernández FF, Atanes A, Sanjuán F, Val-Bernal JF, Hermana S, Mata C, López-Escobar M, Lacalle Loricera J, González-Vela MC, Palmou Onaindia-Pérez A, González-Gay MA. M, Consuegra G, González-Vela MC, N, Hernández JL, González-Gay MA. Histopathologic differences between González-Gay MA. Golimumab in refractory uveitis cutaneous vasculitis associated Coexistence of Hidradenitis related to spondyloarthritis. with severe bacterial infection and Suppurativa with Autoimmune Multicenter study of 15 patients. cutaneous vasculitis secondary to Thyroiditis: Report of Three Cases. Semin Arthritis Rheum. 2016;46:95- other causes: study of 52 patients. Dermatology. 2016;232:162-164. 101.F.I.:3,946. [doi:10.1016/j. Clin Exp Rheumatol. 2016;34:93-97. F.I.:1,449. [doi:10.1159/000439562] semarthrit.2016.03.002] F.I.:2,495. 28. Suárez AE, Artiga MJ, Santonja 18. Real, Eusebio, Fernando Val- 23. Santos-Gómez M, Calvo-Río V, C, Montes-Moreno S, De Pablo P, Bernal, Jose, Revuelta, Jose M., Blanco R, Beltrán E, Mesquida M, Requena L, Piris MA, Rodríguez- Ponton, Alejandro, Calvo Diez, Marta, Adán A, Cordero-Coma M, García- Pinilla SM. Mayorga, Marta, Lopez-Higuera, Jose Aparicio ÁM, Valls Pascual E, Martínez- Angioimmunoblastic T-cell M., Conde, Olga M. Costa L, Hernández MV, Hernandez lymphoma with a clonal plasma Hessian analysis for the delineation Garfella M, González-Vela MC, Pina cell proliferation that underwent of amorphous anomalies in optical T, Palmou-Fontana N, Loricera J, immunoglobulin isotype switch in coherence tomography images of Hernández JL, González-Gay MA. the skin, coinciding with cutaneous the aortic wall. The effect of biologic therapy disease progression. BIOMED OPT EXPRESS. 2016;7:1415- different from infliximab or J Cutan Pathol. 2016;43:1203-1210. 1429.F.I.:3,344. [doi:10.1364/ adalimumab in patients with F.I.:1,409. [doi:10.1111/cup.12814] BOE.7.001415] refractory uveitis due to Behçet’s disease: results of a multicentre 29. Santonja C, Soto C, Manso R, 19. Cordoba R, Sanchez-Beato M, open-label study. Requena L, Piris MA, Rodríguez-Pinilla Herreros B, Domenech E, Garcia- Clin Exp Rheumatol. 2016;34:34-40. SM. Marco J, Garcia JF, Martinez-Lopez J, F.I.:2,495. Primary cutaneous follicular helper Rodriguez A, Garcia-Raso A, Llamas P, T-cell lymphoma. Piris MA. 24. Calvo-Río V, Hernández JL, Ortiz- J Cutan Pathol. 2016;43:164-170. Two distinct molecular subtypes of Sanjuán F, Loricera J, Palmou-Fontana F.I.:1,409. [doi:10.1111/cup.12614] chronic lymphocytic leukemia give N, González-Vela MC, González- new insights on the pathogenesis Lamuño D, González-López MA, 30. Herráez Albendea MD, Jarilla of the disease and identify novel Armesto S, Blanco R, González-Gay Fernández MD, Jiménez Burgos F, therapeutic targets. MA. Montes Moreno S. Leuk Lymphoma. 2016;57:134-142. Relapses in patients with Henoch- Procesos linfoproliferativos múltiples F.I.:3,093. [doi:10.3109/10428194.201 Schönlein purpura: Analysis of 417 en un paciente. 5.1034706] patients from a single center. Med Clin (Barc). 2016;146:563-564. Medicine (Baltimore). 2016;95: F.I.:1,267. [doi:10.1016/j. 20. Pina T, Genre F, Lopez-Mejias F.I.:2,133. [doi:10.1097/ medcli.2015.12.004] MD.0000000000004217] 153

31. Mondejar, Rufino, Delgado, Epstein-Barr virus-associated diffuse Eur J Haematol. 2016;97:7-8. Mercedes, Solano, Francisca, large B-cell lymphoma: diagnosis, F.I.:2,544. [doi:10.1111/ejh.12704] Izquierdo, Guillermo, Martinez-Mir, difficulties and therapeutic options. Amalia, Lucas, Miguel. Expert Rev Anticancer Ther. Analysis of CCM1 expression 2016;16:411-421. uncovers novel minor-form exons F.I.:2,094. [doi:10.1586/14737140.201 PROJECTS and variable splicing patterns. 6.1149065] GENES GENOM. 2016;38:879-889. F.I.:0,692. [doi:10.1007/s13258-016- 0435-1] 3. Val-Bernal JF, Mayorga M, Cagigal ML, Cabezas-González J. Projects Gastric pyogenic granuloma: Report of two cases and review of the Reviews literature. 1. Santiago Montes Moreno. Pathol Res Pract. 2016;212:68-71. Thematic Network of Cooperative F.I.:1,388. [doi:10.1016/j. Cancer Research. 1. Loricera J, Blanco R, Hernández JL, prp.2015.11.001] RD12/0036/0060. Castañeda S, Humbría A, Ortego N, INSTITUTO DE SALUD CARLOS Bravo B, Freire M, Melchor S, Mínguez III. MINISTERIO DE ECONOMÍA Y M, Salvatierra J, González-Vela C, COMPETITIVIDAD. Calvo-Río V, Santos-Gómez M, Pina T, González-Gay MA. Editorials 2. Santiago Montes Moreno. Tocilizumab in patients with Targeted exonic next generation Takayasu arteritis: a retrospective sequencing for the molecular study and literature review. 1. Montes-Moreno S. diagnosis and cell free tumor DNA Clin Exp Rheumatol. 2016;34:44-53. Targeting CD30 expression in analysis as screening method for F.I.:2,495. diverse Large B-cell lymphoma patients with DLBCL. entities: Editorial comment to CD30 PI16/01397. 2. Piris MÁ, Battle-Lopez A, Nuñez Expression and Its Correlation with INSTITUTO DE SALUD CARLOS J, Cagigal ML, Montes-Moreno S, MYC Rearrangement in De Novo III. MINISTERIO DE ECONOMÍA Y Conde E. Diffuse Large B-Cell Lymphoma. COMPETITIVIDAD. Research Areas Cancer Area

Group Leader José Ignacio Banzo Marraco Nuclear Medicine Áreas de Service Hospital Universitario Molecularinvestigación Imaging Marqués de Valdecilla

[email protected]

Researchers José Antonio Amado Señaris J. Ramón de Berrazueta Fernández María Isabel Martínez Rodríguez

Contributors María De Arcocha Torres Iván García Martín María Teresa García Unzueta Julio Francisco Jimenez Bonilla Néstor Anibal Martínez Amador Pedro José Prada Gómez Remedios Quirce Pisano María Ángeles Revilla García Clinic group 155

18F-FNa PET/CT and 18F-FDG establish the optimum time for PET/CT in the management image acquisition of atherosclerosis in diabetic Research c. To identify the normal uptake patients. Lines patterns in different vascular a. To establish an acquisition territories protocol for 18F-FNa PET/CT and d. To quantify the arterial wall 18F-FDG PET/CT for the study activity in relation to the global of atherosclerosis in diabetic vascular activity patients e. To calculate the standard 1. Molecular Imaging and b. To identify uptake patterns in uptake values (SUV) in normal Glucose Metabolism in Oncology. different vascular territories of the subjects and in patients with body in diabetic patients a. Imaging Criteria for measuring arterial wall inflammation the Metabolic Response to c. To evaluate the correlation treatment in Oncology. between the arterial uptake of 18F-Fna and cardiovascular risk 6. Research and Development b. Assessment of the role of factor of diabetes. of new molecular imagen 18F-FDG PET/CT on the effect of radiotracers. biologic therapy in solid tumors. a. ETo study the application of c. Tissue characterization of 4. Molecular Imaging of the radiotracers for prostate cancer pulmonary lesions by 18F-FDG protein b-amyloid in the study recurrence PET/CT. of the cognitive impairment and assessment of its clinical impact. b. To assess the role of d. Assessment of the role of 11C-methionine in primary 18F-FDG PET/CT to the nodal a. Identification of patients with hyperparathyroidism staging of lung cancer. Alzheimer´s disease c. To evaluate the role of b. To establish an acquisition 11C-methionine in the suspicion 2. Molecular Imaging in the study protocol for b-amyloid imaging of brain tumor recurrence assessment of the mineralization using 11C-PIB PET/CT and inflammation of the carotid d. To carry out the synthesis and atheroma plaque. c. To determine the 11C-PIB clinical and to assess the clinical retention patterns in the brain contribution of 18F-FLT a. To define an acquisition d. To study the contribution of protocol of 18F-FDG PET/CT e. To carry out the synthesis and 11C-PIB PET/CT in the study of to study the carotid plaque develop cognitive impairment metabolism. e. To identify the patients with b b. To assess the inflammation amyloid deposit in the brain process of the carotid plaque by 18F-FDG PET/CT f. To assess the role of 11C-PIB in differential diagnose of dementias c. To assess the calcification process of the carotid plaque by g. To evaluate quantitatively the 18FNa PET/CT contribution of 11C-PIB d. To monitor the response to anti-inflammatory treatment by 5. Molecular Imaging in the 18F-FDG PET/CT early diagnosis and extension of e. To study the carotid plaque vasculitis. stability and to identify the vulnerable plaque by molecular a. ETo establish an acquisition imaging techniques. protocol for 18F-FDG in patients with suspicion of large vessel vasculitis. 3. Assessment and evaluation b. To determine the biokinetics of of the clinical impact of FDG in the large vessels was, to Research Areas Cancer Area

High-dose-rate interstitial symptomatic and asymptomatic PUBLICATIONS: brachytherapy as monotherapy in carotid plaques after recent CVA. one fraction for the treatment of Preliminary results. Clin Physiol Funct favorable stage prostate cancer: Imaging. 2016;36:499-503. IMPACT FACTOR | 60,981 Toxicity and long-term biochemical F.I.:1,869. [doi:10.1111/cpf.12254] results. RADIOTHER ONCOL. 2016;119:411- 416.F.I.:4,817. [doi:10.1016/j. 11. Moran Lopez, Jesus Manuel, radonc.2016.04.006] Luengo Perez, Luis Miguel, Beneitez Moralejo, Belen, Piedra Leon, Maria, Original articles Gonzalez Aguado, Rocio, Enclso 6. Jiménez-Bonilla JF, Banzo I, De Izquierdo, Fldel Jesus, Amado Senaris, Arcocha-Torres M, Quirce R, Martínez- Jose Antonio. 1. Dominguez Rodriguez, F., Ramos, Rodríguez I, Sánchez-Juan P, Carril JM. Impact of adequate coding of A., Bouza, E., Munoz, P., Valerio, M. Amyloid Imaging With 11C-PIB in undernutrition and nutritional C., Farinas, C., De Berrazueta, J. R., Patients With Cognitive Impairment procedures on case-mix index in Zarauza, J., Pericas Pulido, J. M., in a Clinical Setting: A Visual and medical and surgical pathologies. Pare, J. C., De Alarcon, A., Sousa, D., Semiquantitative Analysis. Nutr Hosp. 2016;33:64-69. Rodriguez Bailon, I., Montejo-Baranda, Clin Nucl Med. 2016;41:18-23. F.I.:1,497. M., Garcia-Pavia, P. F.I.:4,278. [doi:10.1097/ Infective endocarditis in RLU.0000000000000934] hypertrophic cardiomyopathy: 12. Jiménez-Bonilla JF, Banzo I, De should antibiotic prophylaxis be Arcocha-Torres M, Quirce R, Martínez- reconsidered?. 7. Riancho-Zarrabeitia L, García- Rodríguez I, Lavado-Pérez C, Bravo- Eur Heart J. 2016;37:1015-1015. Unzueta M, Tenorio JA, Gómez- Ferrer Z, Rodríguez-Rodríguez E, F.I.:15,064. Gerique JA, Ruiz Pérez VL, Heath KE, Sánchez-Juan P, Carril JM. Lapunzina P, Riancho JA. Diagnostic role of 11C-Pittsburgh Clinical, biochemical and compound B retention patterns and 2. Jimenez-Bonilla, J. F., Quirce, R., genetic spectrum of low alkaline glucose metabolism by fluorine- De Arcocha-Torres, M., Martinez- phosphatase levels in adults. 18-fluorodeoxyglucose PET/CT in Rodriguez, I., Carril, J. M., Jimenez- Eur J Intern Med. 2016;29:40-45. amnestic and nonamnestic mild Alonso, M., Banzo, I., Pozueta, F.I.:2,591. [doi:10.1016/j. cognitive impairment patients. Nucl A., Martin-Laez, R., Rodriguez- ejim.2015.12.019] Med Commun. 2016;37:1189-1196. Rodriguez, E. F.I.:1,453. [doi:10.1097/ Amyloid brain deposition in MNM.0000000000000569] idiopathic normal pressure 8. Amado CA, García-Unzueta MT, hydrocephalus assessed by 11C-PIB Fariñas MC, Santos F, Ortiz M, Muñoz- PET/CT. Cacho P, Amado JA. 13. Amado Diago CA, García-Unzueta Eur J Nucl Med Mol Imaging. Vitamin D nutritional status and MT, Fariñas MD, Amado JA. 2016;43:134-134.F.I.:5,537. vitamin D regulated antimicrobial Calcitriol-modulated human peptides in serum and pleural fluid antibiotics: New pathophysiological of patients with infectious and aspects of vitamin D. 3. Lopez-Defillo, J. L., Martinez- noninfectious pleural effusions. Endocrinol Nutr. 2016;63:87-94. Rodriguez, I., De Arcocha-Torres, BMC Pulm Med. 2016;16:99-99. F.I.:1,314. [doi:10.1016/j. M., Jimenez-Bonilla, J., Quirce, R., F.I.:2,329. [doi:10.1186/s12890-016- endonu.2015.09.005] Jimenez-Alonso, M., Gomez-De La 0259-4] Fuente, F., Lavado-Perez, C., Martinez- Amador, N., Banzo, I. 14. Morán López JM, Piedra León M, Contribution of 11C-Methionine PET/ 9. Dominguez F, Ramos A, Bouza E, Enciso Izquierdo FJ, Luengo Pérez LM, CT in the management of patients Muñoz P, Valerio MC, Fariñas MC, Amado Señaris JA. with brain tumors. de Berrazueta JR, Zarauza J, Pericás Differences in quality standards Eur J Nucl Med Mol Imaging. Pulido JM, Paré JC, de Alarcón A, when prescribing nutritional 2016;43:261-261.F.I.:5,537. Sousa D, Rodriguez Bailón I, Montejo- support: Differences between Baranda M, Noureddine M, García specialist and non-specialist Vázquez E, Garcia-Pavia P. physicians. 4. Jimenez-Alonso, M., Martinez- Infective endocarditis in Endocrinol Nutr. 2016;63:27-31. Rodriguez, I., Lavado-Perez, C., Lopez- hypertrophic cardiomyopathy: A F.I.:1,314. [doi:10.1016/j. Defillo, J., Quirce, R., Jimenez-Bonilla, multicenter, prospective, cohort endonu.2015.08.002] J., De Arcocha-Torres, M., Meza- study. Escobar, D., Loricera, J., Gonzalez-Gay, Medicine (Baltimore). 2016;95: M., Banzo, I. F.I.:2,133. [doi:10.1097/ 15. Belmar Vega L, de Francisco A, Semiquantitative analysis of MD.0000000000004008] Albines Fiestas Z, Serrano Soto M, 18F-FDG PET/CT in the follow-up of Kislikova M, Seras Mozas M, Unzueta large vessel vasculitis. MG, Arias Rodríguez M. Eur J Nucl Med Mol Imaging. 10. Quirce R, Martínez-Rodríguez I, Investigation of iron deficiency 2016;43:62-62.F.I.:5,537. Banzo I, Jiménez-Bonilla J, Martínez- in patients with congestive heart Amador N, Ibáñez-Bravo S, López- failure: A medical practice that Defilló J, Jiménez-Alonso M, Revilla requires greater attention. Nefrologia. 5. Prada PJ, Cardenal J, Blanco AG, MA, Carril JM. 2016;36:249-254. Anchuelo J, Ferri M, Fernández G, New insight of functional molecular F.I.:1,207. [doi:10.1016/j. Arrojo E, Vázquez A, Pacheco M, imaging into the atheroma nefro.2016.03.001] Fernández J. biology: 18F-NaF and 18F-FDG in 157

16. Banzo I, Jiménez-Bonilla JF, Low-dose-rate brachytherapy for Martínez-Rodríguez I, Quirce R, de patients with transurethral resection Doctoral thesis Arcocha-Torres M, Bravo-Ferrer Z, before implantation in prostate Lavado-Pérez C, Sánchez-Juan P, cancer. Longterm results. Rodríguez E, Jiménez-Alonso M, INT BRAZ J UROL. 2016;42:47-52. 1. Marcos Pajaron Guerrero. López-Defilló J, Carril JM. F.I.:0,871. Self-management of intravenous Patterns of 11C-PIB cerebral antimicrobial (a-tade) treatment in retention in mild cognitive infective endocarditis: a safe and efficient care model. impairment patients. 19. Palacio E, Viadero-Cervera R, Directors: María Del Carmen Fariñas Rev Esp Med Nucl Imagen Mol. Revilla M, Larrosa-Campo D, Acha- Álvarez, José Ramón De Berrazueta 2016;35:171-174. Salazar O, Novo-Robledo F, Oterino A. Fernández. Utilidad del tratamiento con F.I.:0,983. [doi:10.1016/j. University of Cantabria. remn.2015.09.008] atorvastatina 40 mg más ezetimiba 10 mg frente a atorvastatina 80 mg en la reducción de los niveles de 17. Ibáñez-Bravo S, Banzo I, Quirce R, colesterol LDL en pacientes con Martínez-Rodríguez I, Jiménez-Bonilla ictus isquémico o ataque isquémico J, Martínez-Amador N, Parra JA, transitorio. PROJECTS González-Macías J, Carril JM. Rev Neurol. 2016;62:203-210. Ventilation/Perfusion SPECT F.I.:0,684. lung scintigraphy and computed tomography pulmonary angiography Projects in patients with clinical suspicion of pulmonary embolism. 1. Julio Francisco Jiménez Bonilla. Rev Esp Med Nucl Imagen Mol. Editorials Five-year evolution study in a 2016;35:215-220. population with mild Cognitive F.I.:0,983. [doi:10.1016/j. Impairment (DCL) previously remn.2015.12.008] 1. Banzo I. evaluated with 11C-PIB and Un trabajo apasionante. 18F-FDG PET/ CT. Rev Esp Med Nucl Imagen Mol. PI16/01656. 18. Prada PJ, Anchuelo J, Blanco AG, 2016;35:1-2. INSTITUTO DE SALUD CARLOS Paya G, Cardenal J, Acuna E, Ferri M, F.I.:0,983. [doi:10.1016/j. III. MINISTERIO DE ECONOMÍA Y Vazquez A, Pacheco M, Sanchez J. remn.2015.10.008] COMPETITIVIDAD. Research Areas Cancer Area

Group Leader Samuel Cos Corral Department of Physiology MelatoninÁreas and de and Pharmacology School of Medicine Breastinvestigación Cancer University of Cantabria

[email protected]

Contributors Carolina Alonso González Andrea Corrales Pardo Alicia Verónica González Cabeza Carlos Manuel Martínez Campa Javier Menéndez Menéndez Noemí Rueda Revilla

Predoctoral Alicia González González

Technicians José Antonio Cos Cossio Gema Viar Ruiz Consolidated group

the incidence and development levels of gonadal estrogens, and b) of spontaneous mammary direct actions at the tumoral level Research tumors or chemically-induced interfering with the activation of Lines mammary tumors in rodents, while the estrogen receptor, therefore pinealectomy or experimental behaving as a SERM (selective conditions involving a reduction estrogen receptor modulator). in melatonin synthesis stimulate In last years, research activity mammary carcinogenesis. In vitro, in our group focuses on the melatonin inhibits proliferation description of a third mechanism Our group focuses its research and invasiveness of human breast by which melatonin may reduce on the actions of melatonin, the cancer cells. The antitumoral the development of estrogen- main hormone produced in the properties of melatonin are based dependent tumors, based on the pineal gland, on the genesis on its ability to interact with ability of melatonin to modulate and development of hormone- estrogen-signaling pathways. estrogen synthesis in both tumoral dependent mammary tumors. Two types of mechanisms have and peritumoral surrounding In vivo, either experimental been proposed to explain these tissues, behaving as a SEEM manipulations that activate the oncostatic actions of melatonin: a) (selective estrogen enzyme pineal gland or the exogenous downregulation of the circulating modulator). administration of melatonin, reduce 159

The research that we are currently with melatonin on cognitive and developing centers on: neuromorphological deficits in Transplantation. Transplant Proc. 2016;48:2980-2982. Ts65Dn mouse, a model of Down F.I.:0,867. [doi:10.1016/j. a. To study, on the one hand, syndrome. transproceed.2016.08.037] the ability of melatonin to modulate the activity of some enzymes (aromatase, PUBLICATIONS: sulfatase, 17Ð-dehydrogenase, Doctoral thesis sulfotransferase) involved in the IMPACT FACTOR | 9,331 synthesis of estrogens at tumor 1. Andrea Corrales Pardo. level, and, then, to analyze the EStudy of the protective effects of possible intracellular mediators chronic treatment with melatonin through which melatonin on the cognitive deficits of TS65DN Original articles mouse, a model of Down syndrome. regulates the activity and Director: Noemí Rueda Revilla. expression of these enzymes. University of Cantabria. 1. Alonso-González C, González

A, Martínez-Campa C, Menéndez- b. To study the ability of Menéndez J, Gómez-Arozamena J, 2. Susana García Cerro. García-Vidal A, Cos S. melatonin to modulate the Study of the effect of the reduction Melatonin enhancement of the angiogenesis and to antagonize of copy number of the dyrk1a radiosensitivity of human breast gene on different functional and the effects of estrogens on cancer cells is associated with the neuromorphological phenotypes new blood vessel formation modulation of proteins involved in found in a murine model of down estrogen biosynthesis. in hormone-dependent breast syndrome and in euploid mice. Cancer Lett. 2016;370:145-152. cancer. Directors: Carmen Martínez-Cue F.I.:5,992. [doi:10.1016/j. Pesini, Noemí Rueda Revilla. canlet.2015.10.015] c. To study the ability of University of Cantabria. melatonin to increase the sensibility of human breast cancer 2. Parisotto EB, Vidal V, García-Cerro S, Lantigua S, Wilhelm Filho D, Sanchez- cells to the action of radiotherapy Barceló EJ, Martínez-Cué C, Rueda N. in base to its actions modulating Chronic Melatonin Administration the enzymes that participate in Reduced Oxidative Damage the synthesis of estrogens and its and Cellular Senescence in the PROYECTS Hippocampus of a Mouse Model of antiestrogenic actions. Down Syndrome. Neurochem Res. 2016;41:2904-2913. d. To study the protective F.I.:2,472. [doi:10.1007/s11064-016- 2008-8] Proyects effects of melatonin on the molecular changes induced by chemotherapy used in the 3. San Segundo D, Alonso C, Ruiz P, 1. Samuel Cos Corral. treatment of breast cancer. Roman I, Arias-Loste MT, Cuadrado A, Sensitizing effects of melatonin to Puente A, Casafont F, López-Hoyos M, chemotherapy and radiotherapy: Crespo J, Fábrega E. study of the molecular changes that e. To study the protective De Novo Donor-Specific Anti- modulate this process. effects of chronic treatment Human Leukocyte Antigen Antibody SAF2013-42012-P. Detection in Long-Term Adult Liver Research Areas Cancer Area

Group Leader Mónica López Fanárraga Departamento de Áreas de Biología Molecular School of Medicine Nanomedicineinvestigación University of Cantabria

[email protected]

Jesús González Gómez Fernando González Martínez Rosa Martín Rodríguez Débora Muñoz Guerra Ana Carmen Perdigón Aller Carmen Pesquera González Ciro Luis Salcines Suárez Nuria Terán Villagra Juan Carlos Villegas Sordo

Predoctoral Group of new establishment Eloísa González Lavado Nerea Iturrioz Rodriguez Elena María Navarro Palomares Researchers Contributors Esperanza Padín González Rafael Valiente Barroso Fidel Angel Fernández Fernández Lourdes María Valdivia Fernández

offered by nanomaterials (Nano- or vinca derivatives) is its large drugs, injectable nanovectors, surface area of interaction with functional polymer nano-systems), the microtubule, which makes Research regenerative medicine, as contrast resistance quite unlikely. Lines agents for imaging techniques Our most immediate objectives and detection of tumor borders for are to provide a topical NTC-based surgery, nanobiocides, etc. treatment for cancer treatment, for Our studies demonstrate how example for use as an adjuvant or carbon nanotubes (NTC) can neoadjuvant treatment in cancers The group of Nanomedicine-IDIVAL penetrate cells, interfering with affecting the skin, head neck studies the biological response microtubule dynamics and behaving cancers or topically accessible to different nanomaterials. The like microtubule stabilizing drugs, or by injection ) in the zone. This main activity of our group focuses acting as mitotic spindle disrupters. development we already have a on the study of nanomaterials NTC interacts biomimetically with patent. Currently we work on the as treatments for cancer, microtubules causing aberrant or functionalisation of the surface of nanotoxicity and the development catastrophic mitosis, and triggering the NTC to preferentially target of fluorescent probes for in vivo cell death. The advantage of them to the target cells and imaging with up-conversion NTC versus traditional cytotoxic develop in the medium / long term particles, without stopping chemotherapy (taxol and its a parenteral treatment and in the to explore other possibilities derivatives, epothilones, colchicine biocompatibilization of the NTC so 161

that they are more biodegradable 3. García-Hevia L, Villegas JC, J., Trejo-Luna, R. through different treatments. Fernández F, Casafont Í, González J, Carbon implanted waveguides in Together with this line of Valiente R, Fanarraga ML. soda lime glass doped with Yb3+ Multiwalled Carbon Nanotubes and Er3+ for visible light emission. research we are investigating a Inhibit Tumor Progression in a OPT LASER TECHNOL. 2016;79:132- series of biological applications Mouse Model. 136.F.I.:1,879. [doi:10.1016/j. of upconversion luminescent Adv Healthc Mater. 2016;5:1080-1087. optlastec.2015.12.002] nanoparticles, synthesized by F.I.:5,760. [doi:10.1002/ the physicists and chemists of adhm.201500753] 10. Kaur, Amandeep, Khanna, Atul, Gonzalez, Fernando, Pesquera, the group, which we will try to 4. Gomez-Salces, Susana, Antonio Carmen, Chen, Banghao. adapt (modifying diameters and Barreda-Argueso, Jose, Valiente, Structural, optical, dielectric and composition) for use as intracellular Rafael, Rodrigueza, Fernando. thermal properties of molybdenum nano-thermometers and as contrast A study of Ce3+ to Mn2+ energy tellurite and borotellurite glasses. systems Based on the application of transfer in high transmission glasses J NON-CRYST SOLIDS. 2016;444:1-10. using time-resolved spectroscopy. F.I.:1,825. [doi:10.1016/j. infrared light (not harmful to living J Mater Chem C Mater Opt Electron jnoncrysol.2016.04.033] tissue) for diagnosis and tumor Devices. 2016;4:9021-9026. detection. F.I.:5,066. [doi:10.1039/c6tc01408a] 11. Fernandez, Josefa, Gonzalez, Fernando, Pesquera, Carmen, Neves, 5. Gomez-Salces, Susana, Barreda- Alex, Jr., Viana, Marcelo Mendes, Argueso, Jose A., Valiente, Rafael, Dweck, Jo. Rodriguez, Fernando. Qualitative and quantitative Solarization-induced redox characterization of a coal power reactions in doubly Ce3+/Mn2+- plant waste by TG/DSC/MS, XRF and doped highly transmission glasses XRD. studied by optical absorption and J THERM ANAL CALORIM. photoluminescence. 2016;125:703-710. Sol Energy Mater Sol Cells. F.I.:1,781. [doi:10.1007/s10973-016- 2016;157:42-47.F.I.:4,732. 5270-8] [doi:10.1016/j.solmat.2016.05.010] 12. Val-Bernal JF, Mayorga M, 6. Antonio Barreda-Argueso, J., Terán-Villagrá N. Extracutaneous Aguado, Fernando, Gonzalez, Jesus, intravascular histiocytosis of the Valiente, Rafael, Nataf, Lucie, Sanz- aortic valve: Report of two cases. Ortiz, Marta N., Rodriguez, Fernando. Pathol Res Pract. 2016;212:258-263. Crystal-Field Theory Validity Through F.I.:1,388. [doi:10.1016/j. Local (and Bulk) Compressibilities in prp.2015.12.016] CoF2 and KCoF3. J PHYS CHEM C. 2016;120:18788- PUBLICATIONS: 18793.F.I.:4,509. [doi:10.1021/acs. jpcc.6b06132] IMPACT FACTOR | 58,565 7. Villanueva-Delgado P, Krämer KW, Doctoral thesis Valiente R, de Jong M, Meijerink A. Modeling blue to UV upconversion in ß-NaYF4:Tm(3). PHYS CHEM CHEM PHYS. 1. Lorena García Hevia. Original articles 2016;18:27396-27404. Cancer therapy based on the F.I.:4,449. [doi:10.1039/c6cp04347j] biomimetics of carbon nanotubes with cell filaments. 8. Dikhtiarenko, Alla, Villanueva- Director: Mónica López Fanárraga. 1. Almonacid G, Martín-Rodríguez University of Cantabria. R, Renero-Lecuna C, Pellicer-Porres Delgado, Pedro, Valiente, Rafael, J, Agouram S, Valiente R, González Garcia, Jose R., Gimeno, Jose. J, Rodríguez F, Nataf L, Gamelin DR, Tris(bipyridine)Metal(II)-Templated Segura A. Assemblies of 3D Alkali-Ruthenium Structural Metastability and Oxalate Coordination Frameworks: Crystal Structures, Characterization Quantum Confinement in Zn1-xCoxO PROJECTS Nanoparticles. and Photocatalytic Activity in Water NANO LETT. 2016;16:5204-5212. Reduction. F.I.:13,779. [doi:10.1021/acs. POLYMERS-BASEL. 2016;8: nanolett.6b02230] F.I.:2,944. [doi:10.3390/polym8020048] Projects 2. García-Hevia L, Valiente R, Martín- 9. Valiente, Rafael, Renero-Lecuna, Rodríguez R, Renero-Lecuna C, Carlos, Rodriguez, Fernando, Gonzalez, Jesus. González J, Rodríguez-Fernández L, 1. Mónica López Fanárraga. Aguado F, Villegas JC, Fanarraga ML. Role of high pressure for understanding luminescent Development of antineoplastics Nano-ZnO leads to tubulin based on nanomaterials. macrotube assembly and actin phenomena. J LUMIN. 2016;169:410-414.F.I.:2,693. PI13/01074. bundling, triggering cytoskeletal INSTITUTO DE SALUD CARLOS catastrophe and cell necrosis. [doi:10.1016/j.jlumin.2014.11.043] Vazquez, G. V., Valiente, R., Gomez- III. MINISTERIO DE ECONOMÍA Y NANOSCALE. 2016;8:10963-10973. COMPETITIVIDAD. F.I.:7,760. [doi:10.1039/c6nr00391e] Salces, S., Flores-Romero, E., Rickards, Research Areas Cancer Area

Group Leader Manuel Gómez Fleitas Surgery Service Áreas de University Hospital New Techniques in Marqués de Valdecilla Abdominalinvestigación Surgery University of Cantabria

drgomezfl[email protected]

Julio José del Castillo Diego Ramón Agustín Domínguez Díez Maria Jose Fernandez Diaz Roberto Fernandez Santiago Elena García Somacarrera Marcos Gómez Ruiz Monica Gonzalez Noriega Gonzalo Gutiérrez Fernández Fernando Luis Hernanz de La Fuente Antonio López Useros Cesar Baldomero Madrazo Leal José Carlos Manuel Palazuelos José Ignacio Martín Parra Clinic group Dieter José Morales García Carlos Ortega Morales Rodrigo Perea Muñoz Maria Riaño Molleda Contributors Researchers Juan Carlos Rodríguez Sanjuan Luis Antonio Herrera Noreña Joaquín Alonso Martín Isabel Seco Olmedo Federico Castillo Suescun Mª Soledad Trugeda Carrera

c. Biliary tumor pathology and f. Breast cancer. Tumor excision non-neoplastic pathology. using image-guided techniques. Research Implementing new clinical Oncoplastic surgical techniques for surgical procedures (Laparoscopic breast cancer surgery. choledocholithotomy). Lines g. Research on new techniques d. Results in tumor for training surgeons. pathology. Thermal ablation of Development of simulators for hepatocellular carcinoma as a training in surgical and endoscopic bridge to transplantation and techniques. Impact of training with a. Liver tumor pathology. Staging, Xenotransplantation. simulation methods in the teaching new diagnosis and therapeutic of professionals. Development of techniques. e. Obesity surgery. Effects of simulation models for training in bariatric surgery on the morbidity b. Pancreatic tumor pathology. teamwork, communication skills factors of obesity in steatohepatitis Staging, new diagnosis and and critical situations. and ghrelin levels. Evaluation of therapeutic techniques. results. 163

PUBLICATIONS: 5. Hernanz F, Fidalgo M, Muñoz P, Noriega MG, Gómez-Fleitas M. Doctoral thesis Impact of reduction mammoplasty IMPACT FACTOR | 21,292 on the quality of life of obese 1. Javier Aragon Valverde. patients suffering from symptomatic Role of metalloproteinase-11 macromastia: A descriptive cohort and tissue inhibitor of study. metalloproteinase-2 (timp-2) J Plast Reconstr Aesthet Surg. as factors of the inflammatory Original articles 2016;69:168-173.F.I.:1,743. [doi:10.1016/j.bjps.2016.05.012] process and tumor invasion in non-small cell lung carcinoma. Directors: Manuel Gómez Fleitas, 1. Arias-Loste MT, Iruzubieta P, Puente 6. Arminanzas, Carlos, Antonio Francisco Jose Vizoso Piñeiro. Á, Ramos D, Santa Cruz C, Estébanez Herrera, Luis, Carmen Farinas, University of Cantabria. Á, Llerena S, Alonso-Martín C, San Maria. Bacteriobilia: a non-resolved Segundo D, Álvarez L, López Useros A, problem. Fábrega E, López-Hoyos M, Crespo J. Rev Esp Quimioter. 2016;29:113-118. 2. José Ignacio Martín Parra. Increased Expression Profile and F.I.:1,014. Design of a training program Functionality of TLR6 in Peripheral for residents of general surgery Blood Mononuclear Cells and and digestive system based on 7. Armiñanzas C, Tigera T, Ferrer Hepatocytes of Morbidly Obese competences: integration of D, Calvo J, Herrera LA, Pajarón M, Patients with Non-Alcoholic Fatty clinical simulation and practice of Liver Disease. Gómez-Fleitas M, Fariñas MC. care. INT J MOL SCI. 2016;17: Papel de la bacteriobilia en las Directors: Manuel Gómez Fleitas, F.I.:3,257. [doi:10.3390/ijms17111878] complicaciones postoperatorias. Rev Esp Quimioter. 2016;29:123- Robert Simon, José Mª Maestre 129.F.I.:1,014. Alonso. 2. Gómez-Acebo I, Dierssen-Sotos T, University of Cantabria. Palazuelos C, Pérez-Gómez B, Lope V, Tusquets I, Alonso MH, Moreno 8. Arminanzas, Carlos, Tigera, Teresa, V, Amiano P, Molina de la Torre AJ, Ferrer, Diego, Calvo, Jorge, Antonio 3. Juan Carlos Albarracin Castillo. Barricarte A, Tardon A, Camacho A, Herrera, Luis, Pajaron, Marcos, Gomez- Value of endoscopic Peiro-Perez R, Marcos-Gragera R, Fleitas, Manuel, Carmen Farinas, ultrasonography and magnetic Muñoz M, Michelena-Echeveste MJ, Maria. cholangioresonance in the Ortega Valin L, Guevara M, Castaño- Role of bacteriobilia in postoperative diagnosis of choledocholithiasis. Vinyals G, Aragonés N, Kogevinas M, complications. Directors: Juan Carlos Rodríguez Pollán M, Llorca J. Rev Esp Quimioter. 2016;29:123-129. Sanjuan, Manuel Gómez Fleitas. The Use of Antihypertensive F.I.:1,014. University of Cantabria. Medication and the Risk of Breast Cancer in a Case-Control Study in a 9. Colsa Gutiérrez P, Viadero Cervera Spanish Population: The MCC-Spain 4. Marcos Gómez Ruiz. R, Morales-García D, Ingelmo Setién A. Study. Comparative study of laparoscopic Intraoperative peripheral nerve injury PLoS One. 2016;11:F.I.:3,057. surgery versus robotic surgery in in colorectal surgery. [doi:10.1371/journal.pone.0159672] the treatment of rectal cancer. An update. Cir Esp. 2016;94:125-136. Directors: Manuel Gómez Fleitas, F.I.:1,000. [doi:10.1016/j. José Fernández-Escalante Moreno. 3. Gómez Ruiz M, Alonso Martin J, ciresp.2015.03.008]. University of Cantabria. Cagigas Fernández C, Martín Parra JI, Real Noval H, Martín Rivas B, Toledo Martínez E, Castillo Diego J, Gómez 5. Rosana García Díaz. Fleitas M. Reviews Impact of the implementation of Short- and mid-term outcomes of the checklist on a general surgery robotic-assisted total mesorectal service. excision for the treatment of rectal 1. Rodriguez-Sanjuan, Juan C., Directors: Cesar Baldomero cancer. Our experience after 198 Gomez-Ruiz, Marcos, Trugeda-Carrera, Madrazo Leal, Manuel Gómez consecutive cases. Soledad, Manuel-Palazuelos, Carlos, Fleitas. Eur J Surg Oncol. 2016;42:848-854. Lopez-Useros, Antonio, Gomez-Fleitas, F.I.:2,940. [doi:10.1016/j. University of Cantabria. Manuel. ejso.2016.03.006] Laparoscopic and robot-assisted laparoscopic digestive surgery: 6. Rubén Gonzalo Gonzalez. 4. Castillo J, Cristóbal L, Alonso J, Present and future directions. Analysis of factors predicting Martín R, Suárez D, Martínez MA, World J Gastroenterol. 2016;22:1975- remission of type 2 diabetes Cagigas C, Gómez-Ruiz M, Gomez- 2004.F.I.:2,787. [doi:10.3748/wjg.v22. mellitus in morbidly obese patients Fleitas M, Vazquez-Barquero A. i6.1975] after gastric bypass at Roux-en-Y. Sacral nerve stimulation lead Director: Manuel Gómez Fleitas. implantation in partial sacral University of Cantabria. 2. Armiñanzas C, Herrera LA, Fariñas MC. agenesis using intra-operative Bacteriobilia: un problema sin computerized tomography. resolver. COLORECTAL DIS. 2016;18:923-923. Rev Esp Quimioter. 2016;29:113-118. F.I.:2,452. [doi:10.1111/codi.13437] F.I.:1,014. Research Areas Cancer Area

Group Leader José Luis Fernández Luna Molecular Genetics Unit CellÁreas Signalling de and University Hospital Marqués de Valdecilla Therapeuticinvestigación Targets in Cancer

fl[email protected]

Researchers Juan Martino González

Contributors Ana María Fontalba Romero Ana Antonia Talamillo Cancelo Alfonso Vázquez Barquero

Predoctoral María del Pilar Mollinedo Sedano

Technicians Eva Ferrández Fernández Maria Olga Gutierrez Saiz Consolidated group Rebeca Madureira Rivero

parenchyma is one of the main problems for an efficient therapeutic strategy because it makes complete Research resection nearly impossible. Among Lines the GBM cells there is a small population (<5%) with the capacity to regenerate the tumor and with features similar to those found in adult stem cells. They are the 1. Study of the invasive capacity so-called cancer stem cells. If the of glioblastoma stem cells current hypothesis is right, this cell (GSCs). population is the proper target for new therapeutic strategies. We aim The capacity of glioblastoma (GBM) to identify molecular mediators of cells to invade the surrounding migration and invasion of GSCs. 165

2. Development of in vitro use cell cultures on 2D surfaces. lack of proof of concept still persist, models to study the response of There are many evidences which means that there are no drugs GBM cells to chemotherapy in about the role of the biophysical approved for this indication. This physiological environments. features of the microenvironment novel therapeutic area is open to in cellular processes studied in different experimental approaches vitro (differentiation, migration, including combinatorial chemistry, survival). In order to optimize re - profiling and virtual screening, more physiological in vitro models among others. In collaboration with of chemotherapy response, a start-up from the Bioinformatics closer to in vivo models, we are Unit at Centro de Biologia Molecular studying the behavior of GBM cells Severo Ochoa (CSIC), we have (GSCs and tumor parenchymal established a platform that joints cells) following exposure to computational screening of 5 million chemotherapeutic agents in compounds with the validation of different microenvironments. candidates in biological models in vitro and in vivo. Target cells are 3. Screening of novel compounds cancer stem cells from GBM and addressed to cancer stem cells by colon cancer. using computational and biologic platforms. 4. Development of a biosensor device to detect, quantify and Currently, there are different isolate circulating tumor cells undergoing clinical trials addressed Most in vitro studies to measure the from cancer patients: SENTIR to kill cancer stem cells. However, a cellular response to chemotherapy Project.

Figura. Esquema de trabajo que incluye los principales objetivos de esta línea de investigación. Research Areas Cancer Area

This device, based on optical principles and a microfluidic C, Brousset P, Campos-Sanchez WORLD NEUROSURG. 2016;87:200- system, is being developed jointly E, Cobaleda C, Sanchez-Garcia I, 206.F.I.:2,685. [doi:10.1016/j. by IDIVAL (group of cell signaling Fernandez-Luna JL, Garcia-Muñoz wneu.2015.12.035] R, Pena E, ..., Martinez-Climent JA. and therapeutic targets and group Homeobox NKX2-3 promotes of Medical Oncology), University marginal-zone lymphomagenesis 6. Castillo J, Cristóbal L, Alonso J, of Cantabria (optics group of the by activating B-cell receptor Martín R, Suárez D, Martínez MA, Faculty of Sciences), the center signalling and shaping lymphocyte Cagigas C, Gómez-Ruiz M, Gomez- Technological group IK4-TEKNIKER dynamics. Fleitas M, Vazquez-Barquero A. (micro-manufacturing group) and Nat Commun. 2016;7:11889-11889. Sacral nerve stimulation lead the Cantabrian biotech company F.I.:11,329. [doi:10.1038/ implantation in partial sacral ncomms11889] agenesis using intra-operative CELLBIOCAN. Currently, the computerized tomography. assembly of an experimental COLORECTAL DIS. 2016;18:923-923 prototype is being finalized, which 2. Torices S, Julia A, Muñoz P, Varela F.I.:2,452. [doi:10.1111/codi.13437] will be optimized until it reaches a I, Balsa A, Marsal S, Fernández- final product with which a clinical Nebro A, Blanco F, López-Hoyos M, validation will be performed with Martinez-Taboada V, Fernández-Luna 7. Molina D, Pérez-Beteta J, samples from cancer patients. The JL. Martínez-González A, Martino J, A functional variant of TLR10 Velásquez C, Arana E, Pérez-García objective is to quantify blood CTCs modifies the activity of NFkB VM. Influence of gray level and as a predictor, and to isolate them and may help predict a worse space discretization on brain tumor for further genetic analysis, which prognosis in patients with heterogeneity measures obtained rheumatoid arthritis. will allow a personalized selection from magnetic resonance images. Arthritis Res Ther. 2016;18:221-221. of the treatment. COMPUT BIOL MED. 2016;78:49-57. F.I.:3,979. [doi:10.1186/s13075-016- F.I.:1,521. [doi:10.1016/j. 1113-z] compbiomed.2016.09.011]

3. Vergani F, Martino J, Morris C, 8. Álvarez de Eulate-Beramendi S, Attems J, Ashkan K, Dell’Acqua F. Álvarez-Vega MA, Balbin M, Sanchez- Anatomic Connections of the Pitiot A, Vallina-Alvarez A, Martino- Subgenual Cingulate Region. González J. Neurosurgery. Prognostic factors and survival 2016;79:465-472. study in high-grade glioma in the F.I.:3,780. [doi:10.1227/ elderly. NEU.0000000000001315] Br J Neurosurg. 2016;30:330-336. F.I.:1,063. [doi:10.3109/02688697.20 16.1139049] 4. Martín-Láez R, Caballero-Arzapalo H, Valle-San Román N, López- Menéndez LÁ, Carlos Arango- PUBLICATIONS: 9. Velasquez, Carlos, Caballero, Lasprilla J, Vázquez-Barquero A. Hugo, Bucheli, Carlos, Berciano, Incidence of Idiopathic Normal- Jose, Vazquez-Barquero, Alfonso, IMPACT FACTOR | 30,862 Pressure Hydrocephalus in Martino, Juan. Northern Spain. A very slow-growing exophytic WORLD NEUROSURG. 2016;87:298- hemisphere glioma: a case report. 310. Rev Neurol. 2016;62:23-27. F.I.:2,685. [doi:10.1016/j. F.I.:0,684. Original articles wneu.2015.10.069]

10. Velasquez C, Caballero H, Bucheli 1. Robles EF, Mena-Varas M, Barrio L, 5. Velasquez C, Caballero H, C, Berciano J, Vazquez-Barquero A, Merino-Cortes SV, Balogh P, Du MQ, Vazquez-Barquero A, Vega M, Rial Martino J. Akasaka T, Parker A, Roa S, Panizo C, JC, Carcedo-Barrio MC, Martino J. Glioma exofítico hemisférico de Martin-Guerrero I, Siebert R, Segura Insular Gliomas with Exophytic muy lento crecimiento: a propósito V, Agirre X, Macri-Pellizeri L, Aldaz B, Extension to the Sylvian Cistern: de un caso. Vilas-Zornoza A, Zhang S, Moody S, A Glioma Growth Pattern That Has Rev Neurol. 2016;62:23-27. Calasanz MJ, Tousseyn T, Broccardo Gone Previously Unnoticed. F.I.:0,684. 167

Projects COMPETITIVIDAD. 3. Juan Martino González. Preservation of the areas involved 2. José Luis Fernández Luna. in verbal work memory to avoid Prognostic and therapeutic sequelae in gliomas surgery in eloquent areas. 1. José Luis Fernández Luna. relevance in glioblastoma of ODZ1, PI13/01249. Thematic Network of Cooperative a new target in cancer. INSTITUTO DE SALUD CARLOS Cancer Research. PI13/01760. RD12/0036/0022. INSTITUTO DE SALUD CARLOS III. MINISTERIO DE ECONOMÍA Y INSTITUTO DE SALUD CARLOS III. III. MINISTERIO DE ECONOMÍA Y COMPETITIVIDAD. MINISTERIO DE ECONOMÍA Y COMPETITIVIDAD. Research Areas Cancer Area

Group Leader Fernando Rivera Herrero Oncology Clinical Oncology Service Áreas de University Hospital trialsinvestigación Unit Marqués de Valdecilla

[email protected]

Contributors Ana de Juan Ferré Almudena García Castaño Carmen Hinojo González Carlos López López José Manuel López Vega Marta Francisca López-Brea Piqueras Eva Martínez De Castro

Clinic group

Clinical trials in solid tumors therapies, anti-VGF and anti-PD-L1. Nowadays our Unit starts around Research thirty new clinical trials every year, This line of research is well many of them in Phases II and III, established; it is the basis of the Lines becoming a leading center in Spain group’s publications and has an on development of some lines of intense activity. new drugs, particularly anti-EGFR 169

efficacy data from head-to-head Silvia, Ramos, Manuel, Munoz, PUBLICACIONES: first-line trials of epidermal growth Monserrat, Lluch, Ana, de Juan-Ferre, factor receptor inhibitors versus Ana, Jara, Carlos, Lope, Virginia, IMPACT FACTOR | 104,217 bevacizumab in patients with RAS Jimeno, Maria A., Arriola-Arellano, wild-type metastatic colorectal Esperanza, Diaz, Elena, Guillem, cancer. Vicente, Carrasco, Eva, Perez-Gomez, Eur J Cancer. 2016;67:11-20. Beatriz, Vioque, Jesus, Pollan, Marina. F.I.:6,163. [doi:10.1016/j. Evaluating the Applicability of Original articles ejca.2016.07.019] Data-Driven Dietary Patterns to Independent Samples with a Focus on Measurement Tools for Pattern 4. Fonseca PJ, Carmona-Bayonas 1. iMartin-Broto J, Pousa AL, de Las Similarity. A, García IM, Marcos R, Castañón E, Peñas R, García Del Muro X, Gutierrez J Acad Nutr Diet. 2016;116:1914. Antonio M, Font C, Biosca M, Blasco A, Martinez-Trufero J, Cruz J, Alvarez F.I.:3,609. [doi:10.1016/j. A, Lozano R, Ramchandani A, Beato C, R, Cubedo R, Redondo A, Maurel J, jand.2016.05.008] de Castro EM, Espinosa J, Martínez- Carrasco JA, López-Martin JA, Sala Á, García J, Ghanem I, Cubero JH, Meana JA, Ramos R, Martinez-Serra Manrique IA, Navalón FG, Sevillano 8. Lainez N, García-Donas J, Esteban J, Lopez-Guerrero JA, Sevilla I, Balaña E, Manzano A, Virizuela J, Garrido E, Puente J, Sáez MI, Gallardo E, C, Vaz Á, De Juan A, Alemany R, M, Mondéjar R, Arcusa MÁ, Bonilla Pinto-Marín Á, Vázquez-Estévez S, Poveda A. Y, Pérez Q, Gallardo E, Del Carmen León L, García-Carbonero I, Suárez- Randomized Phase II Study of Soriano M, ..., Ayala F. Rodríguez C, Molins C, Climent-Duran Trabectedin and Doxorubicin A nomogram for predicting MA, Lázaro-Quintela M, González Compared With Doxorubicin complications in patients with solid Del Alba A, Méndez-Vidal MJ, Alone as First-Line Treatment in tumours and seemingly stable Chirivella I, Afonso FJ, López-Brea Patients With Advanced Soft Tissue febrile neutropenia. M, Sala-González N, Domenech M, Sarcomas: A Spanish Group for Br J Cancer. 2016;114:1191-1198. Basterretxea L, Santander-Lobera C, Research on Sarcoma Study. F.I.:5,569. [doi:10.1038/bjc.2016.118] Gil-Arnáiz I, Fernández O, Caballero- J Clin Oncol. 2016;34:2294-2302. Díaz C, Mellado B, Marrupe D, García- F.I.:20,982. [doi:10.1200/ Sánchez J, ..., Castellano D. JCO.2015.65.3329] 5. Perez EA, López-Vega JM, Petit Impact on clinical practice of the T, Zamagni C, Easton V, Kamber J, implementation of guidelines for the Restuccia E, Andersson M. 2. Pérez-Valderrama B, Arranz Arija JA, toxicity management of targeted Safety and efficacy of vinorelbine in Rodríguez Sánchez A, Pinto Marín A, therapies in kidney cancer. combination with pertuzumab and Borrega García P, Castellano Gaunas The protect-2 study. BMC Cancer. trastuzumab for first-line treatment DE, Rubio Romero G, Maximiano 2016;16:135-135. of patients with HER2-positive Alonso C, Villa Guzmán JC, Puertas F.I.:3,265. [doi:10.1186/s12885-016- locally advanced or metastatic Álvarez JL, Chirivella González I, 2084-9] breast cancer: VELVET Cohort 1 final Méndez Vidal MJ, Juan Fita MJ, León- results. Mateos L, Lázaro Quintela M, García Breast Cancer Res. 2016;18:126-126. 9. Sevilla I, Segura Á, Capdevila Domínguez R, Jurado García JM, Vélez F.I.:5,211. [doi:10.1186/s13058-016- J, López C, García-Carbonero R, de Mendizábal E, Lambea Sorrosal 0773-6] Grande E, GETNE (Spanish Group JJ, García Carbonero I, González Del of NeuroEndocrine Tumors). Alba A, Suárez Rodríguez C, Jiménez Management of controversial Gallego P, Meana García JA, García 6. Carmona-Bayonas A, Jiménez- gastroenteropancreatic Marrero RD, Gajate Borau P, Santander Fonseca P, Lorenzo ML, Ramchandani neuroendocrine tumour clinical Lobera C, Molins Palau C, López Brea A, Martínez EA, Custodio A, Garrido situations with somatostatin M, ..., González Larriba JL. M, Echavarría I, Cano JM, Barreto JE, analogues: results of a Delphi Validation of the International García TG, Manceñido FÁ, Lacalle A, questionnaire panel from the Metastatic Renal-Cell Carcinoma Cardona MF, Mangas M, Visa L, Buxó NETPraxis program. Database Consortium (IMDC) E, Azkarate A, Díaz-Serrano A, Montes BMC Cancer. 2016;16:858-858. prognostic model for first-line AF, Rivera F. F.I.:3,265. [doi:10.1186/s12885-016- pazopanib in metastatic renal On the Effect of Triplet or Doublet 2901-1] carcinoma: the Spanish Oncologic Chemotherapy in Advanced Gastric Genitourinary Group (SOGUG) Cancer: Results From a National SPAZO study. Cancer Registry. 10. Riancho J, Lozano-Cuesta P, Ann Oncol. 2016;27:706-711. J Natl Compr Canc Netw. Santurtún A, Sánchez-Juan P, López- F.I.:9,269. [doi:10.1093/annonc/ 2016;14:1379-1388. Vega JM, Berciano J, Polo JM. mdv601] F.I.:4,262. Amyotrophic Lateral Sclerosis in Northern Spain 40 Years Later: What Has Changed?. 3. Heinemann V, Rivera F, O’Neil BH, 7. Castello, Adela, Buijsse, Brian, Neurodegener Dis. 2016;16:337-341. Stintzing S, Koukakis R, Terwey JH, Martin, Miguel, Ruiz, Amparo, Casas, F.I.:2,937. [doi:10.1159/000445750] Douillard JY. Ana M., Baena-Canada, Jose M., Balana C, De Las Penas R, Sepúlveda A study-level meta-analysis of Pastor-Barriuso, Roberto, Antolin, JM, Gil-Gil MJ, Luque R, Gallego O, Research Areas Cancer Area

Carrato C, Sanz C, Reynes G, Herrero Irrespective of Previous Therapies. 19. Martin-Richard M, Custodio A, A, Ramirez JL, Pérez-Segura P, Berrocal Neuroendocrinology. 2016;103:80-80. García-Girón C, Grávalos C, Gomez A, Vieitez JM, Garcia A, Vazquez- F.I.:2,583. C, Jimenez-Fonseca P, Manzano JL, Estevez S, Peralta S, Fernandez I, Pericay C, Rivera F, Carrato A. Henriquez I, Martinez-Garcia M, De la Erratum to: SEOM guidelines for the 15. Sevilla, I., Segura, A., Capdevila, Cruz JJ, Capellades J, Giner P, Villà S. treatment of gastric cancer 2015. J., Lopez, C., Carbonero R., Garcia, Bevacizumab and temozolomide Clin Transl Oncol. 2016;18:426-426. Grande, E. versus temozolomide alone as F.I.:2,075. [doi:10.1007/s12094-016- Management of Controversial neoadjuvant treatment in unresected 1491-3] Gastroenteropancreatic (GEP) glioblastoma: the GENOM 009 Neuroendocrine Tumour (NET) randomized phase II trial. Clinical Situations (CS) with 20. Pérez-Segura P, Manneh R, J Neurooncol. 2016;127:569-579. Somatostatin Analogues (SSAs): Ceballos I, García A, Benavides M, F.I.:2,754. [doi:10.1007/s11060-016- Results of a Delphi Questionnaire Fuster J, Vaz MA, Cano JM, Berros 2065-5] (Q) Panel from the NETPraxis JP, Covela M, Moreno V, Quintanar Program. Neuroendocrinology. T, García Bueno JM, Fernández I, 11. Crespo, G. H., Jimenez-Fonseca, 2016;103:75-75. Sepúlveda J. P., Custodio, A., Lopez, C., Carmona- F.I.:2,583. GEINOFOTE: efficacy and safety of Bayonas, A., Alonso, V, Navarro, M., fotemustine in patients with high- Aller, J., Sevilla, I, Gajate, P., Alonso, grade recurrent gliomas and poor 16. Nunez, B., Castano, A., Teule T., Matos, I, Capdevila, J., Nieto, B., performance status. Vega, A., Marazuela Azpiroz, M., Barriuso, J. Clin Transl Oncol. 2016;18:805-812. Medina, K., Segura, A., Villabona, Capecitabine and Temozolomide F.I.:2,075. [doi:10.1007/s12094-015- C., Benavent, M., Lopez, C., Alonso in NETs G1-2: The Experience 1444-2] Gordoa, T., Capdevila, J., Alonso of Various Hospitals in Spain. Orduna, V, Carmona-Bayonas, A., Neuroendocrinology. 2016;103:66-66. Garcia Carbonero, R., Jimenez- 21. Martin-Richard M, Díaz F.I.:2,583. Fonseca, P. Beveridge R, Arrazubi V, Alsina M, Therapeutic Strategies in Patients Galan Guzmán M, Custodio AB, 12. Crespo, G. H., Lopez, C., Jimenez- with Gastroenteropancreatic Gómez C, Muñoz FL, Pazo R, Rivera Fonseca, P., Matos, I, Capdevila, J., Neuroendocrine Neoplasms F. Custodio, A., Carmona-Bayonas, A., (GEP-NEN): Results from the SEOM Clinical Guideline for Alonso, T., Gajate, P., Aller, J., Navarro, National Neuroendocrine Cancer the diagnosis and treatment of M., Sevilla, I, Alonso, V, Nieto, B., Registry of Spain (R-GETNE). esophageal cancer (2016). Barriuso, J. Neuroendocrinology. 2016;103:89-89. Clin Transl Oncol. 2016;18:1179- Capecitabine-Temozolomide in F.I.:2,583. 1186. G3 Neuroendocrine Neoplasms. F.I.:2,075. [doi:10.1007/s12094-016- Neuroendocrinology. 2016;103:66-66. 1577-y] 17. Munoz Martin, A. J., Ziyatdinov, F.I.:2,583. A., Castellon Rubio, V., Pachon Olmos, V., Morejon Huerta, B., Calzas 22. Vera R, Dotor E, Feliu J, González 13. Carmona-Bayonas, A., Jimenez- Rodriguez, J., Salgado Fernandez, E, Laquente B, Macarulla T, Martínez Munarriz, B., Jimenez-Fonseca, P., M., Martinez de Castro, E., Luque E, Maurel J, Salgado M, Manzano Custodio, A., Alonso, V, Alonso, Caro, R., Soria Fernandez, J. M. JL. SEOM Clinical Guideline for T., Lopez, C., Matos, I, Crespo, G., A new genetic risk score for the treatment of pancreatic cancer Garcia-Paredes, B., Aller, J., Grande, E., predicting venous thromboembolic (2016). Capdevila, J., Sastre, J., Barriuso, J. events in cancer patients receiving Clin Transl Oncol. 2016;18:1172- Everolimus (EVE) Safety Profile chemotherapy. 1178. in Patients (pts) with Advanced Thromb Res. 2016;140:177-178. F.I.:2,075. [doi:10.1007/s12094-016- G1-G2 Neuroendocrine Tumours F.I.:2,320. 1586-x] (NETs) from Daily Clinical Practice. Neuroendocrinology. 2016;103:79-80. 18. Adrian, S. G., Martinez de Castro, 23. Martínez-Jañez N, Chacón I, de F.I.:2,583. E., Pachon Olmos, V., Navarro Martin, Juan A, Cruz-Merino L, Del Barco M., Martinez del Prado, P., Lobo S, Fernández I, García-Teijido P, 14. Custodio, A., Alonso, V, Jimenez- Mena, M., Rua Ramirez, O. Raziel, Gómez-Bernal A, Plazaola A, Ponce J, Fonseca, P., Lopez, C., Alonso, T., Cacho Lavin, D., Arango Arteaga, J. Servitja S, Zamora P. Crespo, G., Matos, I, Garcia-Paredes, F., Munoz Martin, A. J. Anti-HER2 Therapy Beyond B., Carmona-Bayonas, A., Alvarez- Incidence of venous Second-Line for HER2-Positive Escola, C., Capdevila, J., Grande, thromboembolism (VTE) in bile Metastatic Breast Cancer: A Short E., Barriuso, J., Feliu, J., Aller, J. duct tumors (BDT) treated with Review and Recommendations for Everolimus (EVE) Treatment for chemotherapy in ambulatory Several Clinical Scenarios from a Advanced G1-G2 Neuroendocrine setting. Spanish Expert Panel. Tumours (NETs) in the Community Thromb Res. 2016;140:178-178. Breast Care (Basel). 2016;11:133-138. Setting: Clinical Benefit F.I.:2,320. F.I.:1,645. [doi:10.1159/000443601] 171

24. Karthaus, M., Sobrero, A., Hospital Marqués de Valdecilla. Douillard, J. -Y, Rivera, F., Forget, F., Reviews Directors: José Manuel López Valladares-Ayerbes, M., Demonty, G., Vega, Marta Mayorga Fernández. Guan, X., Peeters, M. 1. Pericay C, Rivera F, Gomez-Martin University of Cantabria. An exploratory analysis evaluating C, Nuñez I, Cassinello A, Imedio ER. the effect of sequence of biologic Positioning of second-line 2. Carlos López López. therapies on overall survival (OS) treatment for advanced gastric Clinical-molecular prognostic in patients (pts) with RAS wild- and gastroesophageal junction factors and predictive models in type (WT) metastatic colorectal adenocarcinoma. glioblastoma multiforme from an carcinoma (mCRC). Cancer Med. 2016;5:3464-3474. intramural experience: service of Oncol. Res. Treat.2016;39:94-94. F.I.:2,915. [doi:10.1002/cam4.941] medical oncology at University F.I.:1,333. Hospital Marqués de Valdecilla (2000-2010). Directors: José Manuel López Vega, 25. Karthaus, M., Rivera, F., Jaime Sanz Ortíz. Valladares-Ayerbes, M., Gallego, J., University of Cantabria. Koukakis, R., Demonty, G., Douillard, J. -Y. Impact of early tumour Doctoral thesis shrinkage (ETS) on overall survival (OS) in patients with RAS wild- type (WT) metastatic colorectal 1. Ana De Juan Ferré. cancer (mCRC) receiving first-line Phase II intramural study of treatment in three randomised neoadjuvant chemotherapy panitumumab trials: An exploratory with platinum, doxorubicin and study-level meta-analysis. taxane salts in operable breast Oncol. Res. Treat.2016;39:93-94. cancer. Experience of the medical F.I.:1,333. oncology service of the University

173

Transversal Area

Javier Llorca Díez Coordinator of the Transversal Area.

Professor of Preventive Medicine and Public Health. University of Cantabria. Research Areas Transversal Area

Group Leader Javier Llorca Díaz Department of Preventive Áreas de Medicine and Public Health Epidemiology and School of Medicine Publicinvestigación Health University of Cantabria

[email protected]

Researchers Trinidad Dierssen Sotos Paz Rodríguez Cundín

Contributors Jessica Alonso Molero Inés Gómez Acebo

Predoctoral Camilo Palazuelos Calderón

Research Lines

1. Epidemiology of cancer:

Development of methods for estimating confidence intervals of the population attributable fraction (Stat Med) and its assignation when Figura. ROC Curves for the death day mortality and 0.8900 [95% CI 0.8311 risk factors are not additive (J Clin outcomes at: (a) 30 days after to 0.9488] for 90-day mortality). Dashed Epidemiol). Analysis of competing transplantation, and (b) 90 days after lines: artificial neural network (AUC is risks of death using Gompertzian transplantation. Solid lines: logistic 0.8806 [95% CI 0.7551 to 1.00] for 30-day models (Mech Ageing Develop; regression (area under ROC curve [AUC] is mortality and 0.8625 [95% CI 0.7865 to 0.7246 [95% CI 0.6080 to 0.8913] for 30- 0.9389] for 90-day mortality J Epidemiol Commun Health; Rev Esp Cardiol), Markov chains with conditional independence (Int J Epidemiol) and in lack of Line started in 2009 when entering the between cases (breast, prostate, independence (J Clin Epidemiol). MCC-Spain project. There have been colorectal, stomach and Chronic recruited 10000 participants lymphocytic leukemia) and controls in the different nodes of the project 175

(Asturias, Cantabria, León, Guipúzcoa, 4. Epidemiological method: Spanish population. Navarre, Gerona, Barcelona, Valencia, Eur J Epidemiol. 2016;31:867-878. Our old line of epidemiological method F.I.:7,105. [doi:10.1007/s10654-015- Murcia, Granada, Huelva and 0073-y] Madrid). The Cantabria node is the has been refocused towards the 4th in number of participants (after Of Research of new methods to study 5. Butt J, Romero-Hernández B, Pérez- Madrid, Barcelona and Leon). gene-gene and gene-environment Gómez B, Willhauck-Fleckenstein interaction; this includes regression M, Holzinger D, Martin V, Moreno V, with lasso and ridge penalty, artificial Linares C, Dierssen-Sotos T, Barricarte Our group has obtained three FIS A, Tardón A, Altzibar JM, Moreno- projects as IP for this project in 2009 (5 neural networks, and Bayesian Osset E, Franco F, Olmedo Requena R, Projects coordinated by the Cantabria networks. This refocus should begin to María Huerta J, Michel A, Waterboer T, node), 2012 (4 projects coordinated produce End of 2017. Castaño-Vinyals G, Kogevinas M, Pollán by The Madrid node) and 2015 (3 M, Boleij A, de Sanjosé S, Del Campo R, Tjalsma H, Aragonés N, Pawlita M. projects coordinated by the Cantabria Association of Streptococcus node), In addition to participating with gallolyticus subspecies gallolyticus collaborating researchers in projects PUBLICATIONS: with colorectal cancer: Serological of 2011 and 2014 Led by CREAL, the evidence. Int J Cancer. 2016;138:1670-1679. National Center for Epidemiology and F.I.:5,531. [doi:10.1002/ijc.29914] the ICO-Belvitge. IMPACT FACTOR | 140,445 6. Espejo-Herrera N, Gràcia-Lavedan MCC-Spain began publishing its E, Boldo E, Aragonés N, Pérez-Gómez results in mid-2015 and at the B, Pollán M, Molina AJ, Fernández T, Martín V, La Vecchia C, Bosetti moment has published 27 articles, Original articles C, Tavani A, Polesel J, Serraino D, of which the node of Cantabria has Gómez Acebo I, Altzibar JM, Ardanaz led 3 on Consumption of drugs and E, Burgui R, Pisa F, Fernández- 1. González-Gay MA, Llorca J. Tardón G, Tardón A, Peiró R, Navarro breast cancer (BMC Cancer, PlosOne Clinical guidelines: Best C, Castaño-Vinyals G, Moreno V, and Breast Cancer Research and practices and uncertainties in the Righi E, Aggazzotti G, Basagaña X, management of PMR. Treatment). Nieuwenhuijsen M, ..., Villanueva CM. Nat Rev Rheumatol. 2016;12:3-4. Colorectal cancer risk and nitrate F.I.:10,531. [doi:10.1038/ exposure through drinking water With the 2015 project, a turn in the nrrheum.2015.142] project is initiated to transform the and diet. Int J Cancer. 2016;139:334-346. cases into Cohorts for the study of 2. Espejo-Herrera N, Gracia-Lavedan F.I.:5,531. [doi:10.1002/ijc.30083] prognostic factors. To this end, the E, Pollan M, Aragonés N, Boldo E, Perez-Gomez B, Altzibar JM, Amiano Coordinating committee of MCC- 7. Costas L, Benavente Y, Olmedo- P, Zabala AJ, Ardanaz E, Guevara M, Requena R, Casabonne D, Robles Spain, including from November Molina AJ, Barrio JP, Gómez-Acebo I, C, Gonzalez-Barca EM, de la Banda 2016 to Javier Llorca as a follow-up Tardón A, Peiró R, Chirlaque MD, Palau E, Alonso E, Aymerich M, Tardón A, M, Muñoz M, Font-Ribera L, Castaño- coordinator. Marcos-Gragera R, Gimeno-Vázquez Vinyals G, Kogevinas M, Villanueva E, Gómez-Acebo I, Papantoniou K, CM. Castaño-Vinyals G, Aragonés N, Pollán Ingested Nitrate and Breast Cancer 2. Epidemiology of rheumatic M, Kogevinas M, de Sanjosé S. in the Spanish Multicase-Control diseases: Night shift work and chronic Study on Cancer (MCC-Spain). lymphocytic leukemia in the MCC- Environ. Health Spain case-control study. Line initiated in 2000 in collaboration Perspect.2016;124:1042-1049. Int J Cancer. 2016;139:1994-2000. with the group of Dr. González-Gay F.I.:8,443. [doi:10.1289/ehp.1510334] F.I.:5,531. [doi:10.1002/ijc.30272] (then, In the Hospital Xeral Calde 3. Pastor-Barriuso R, Fernández de Lugo). We have worked on 8. Remuzgo-Martínez S, Genre F, MF, Castaño-Vinyals G, Whelan D, rheumatoid arthritis, arteritis of giant López-Mejías R, Ubilla B, Mijares V, Perez-Gomez B, Llorca J, Villanueva Pina T, Corrales A, Blanco R, Martín J, cells, Schönlein-Henoch’s disease, CM, Guevara M, Molina JM, Artacho- Llorca J, González-Gay MA. ankylosing spondylitis, Psoriatic Cordon F, Barriuso-Lapresa L, Tusquets Expression of osteoprotegerin and I, Dierssen-Sotos T, Aragonés N, Olea arthropathy among others, giving its ligands, RANKL and TRAIL, in N, Kogevinas M, Pollan M. rise to a large number of articles rheumatoid arthritis. Total Effective Xenoestrogen Burden Sci Rep. 2016;6:29713-29713. in first Decile / quartile and to the in Serum Samples and Risk for F.I.:5,228. [doi:10.1038/srep29713] presentation of 7 doctoral theses. At Breast Cancer in a Population-Based this point, we continue Fundamentally Multicase-Control Study in Spain. 9. López-Mejías R, Genre F, Remuzgo- Environ. Health in two sub-lines: cardiovascular risk Martínez S, González-Juanatey C, Perspect.2016;124:1575-1582. in diseases Rheumatic and genetic Robustillo-Villarino M, Llorca J, F.I.:8,443. [doi:10.1289/EHP157] factors that influence this risk. Corrales A, Vicente E, Miranda-Filloy JA, Magro C, Tejera-Segura B, Ramírez 4. Papantoniou K, Castaño-Vinyals G, Huaranga MA, Pina T, Blanco R, Espinosa A, Aragonés N, Pérez-Gómez Alegre-Sancho JJ, Raya E, Mijares 3. Clinical Epidemiology: B, Ardanaz E, Altzibar JM, Sanchez V, Ubilla B, Mínguez Sánchez MD, VM, Gómez-Acebo I, Llorca J, Muñoz Gómez-Vaquero C, Balsa A, Pascual- D, Tardón A, Peiró R, Marcos-Gragera In these years, the line of clinical Salcedo D, López-Longo FJ, Carreira R, Pollan M, Kogevinas M. epidemiology has focused the P, González-Álvaro I, Rodríguez- Breast cancer risk and night shift transplant, especially the lung, giving Rodríguez L, Fernández-Gutiérrez work in a case-control study in a rise to 18 articles and 5 theses. B, Ferraz-Amaro I, Castañeda S, ..., Research Areas Transversal Area

González-Gay MA. Subclinical Atherosclerosis in Ortega Valin L, Guevara M, Castaño- Influence of elevated-CRP level- Patients with Rheumatoid Arthritis. Vinyals G, Aragonés N, Kogevinas M, related polymorphisms in non- J Rheumatol. 2016;43:486-494. Pollán M, Llorca J. rheumatic Caucasians on the F.I.:3,236. [doi:10.3899/jrheum.150510] The Use of Antihypertensive risk of subclinical atherosclerosis Medication and the Risk of Breast and cardiovascular disease in 15. González-Gay MA, Llorca J, Cancer in a Case-Control Study in a rheumatoid arthritis. González-Juanatey C, Martín-Martínez Spanish Population: The MCC-Spain Sci Rep. 2016;6:31979-31979. MA, Castañeda S. Study. F.I.:5,228. [doi:10.1038/srep31979] Why is Rheumatoid Arthritis PLoS One. 2016;11: Mortality Still High Despite the F.I.:3,057. [doi:10.1371/journal. 10. López-Mejías R, Genre F, Advent of New Therapies? Comment pone.0159672] Remuzgo-Martínez S, Robledo G, on the Article by Widdifield et al. Llorca J, Corrales A, González-Juanatey Arthritis Care Res (Hoboken). 21. Pina T, Genre F, Lopez-Mejias C, Ubilla B, Mijares V, Pina T, Blanco R, 2016;68:726-727. R, Armesto S, Ubilla B, Mijares V, Castañeda S, Martín J, González-Gay F.I.:3,229. [doi:10.1002/acr.22731] Dierssen-Sotos T, Corrales A, Gonzalez- MA. Lopez MA, Gonzalez-Vela MC, Blanco Vitamin D receptor GATG haplotype 16. Romero AM, Palanca A, Ruiz-Soto R, Llorca J, Gonzalez-Gay MA. association with atherosclerotic M, Llorca J, Marín MP, Renau-Piqueras Anti-TNF-a therapy reduces retinol- disease in patients with rheumatoid J, Berciano MT, Lafarga M. binding protein 4 serum levels in arthritis. Chronic Alcohol Exposure Decreases non-diabetic patients with psoriasis: Atherosclerosis. 2016;245:139-142. 53BP1 Protein Levels Leading to a a 6-month prospective study. F.I.:3,942. [doi:10.1016/j. Defective DNA Repair in Cultured J Eur Acad Dermatol Venereol. atherosclerosis.2015.12.011] Primary Cortical Neurons. 2016;30:92-95. Neurotox Res. 2016;29:69-79. F.I.:3,029. [doi:10.1111/jdv.13005] 11. Gyarmati G, Turner MC, Castaño- F.I.:3,140. [doi:10.1007/s12640-015- Vinyals G, Espinosa A, Papantoniou K, 9554-8] 22. Ríos A, López-Navas AI, López- Alguacil J, Costas L, Pérez-Gómez B, López AI, Gómez FJ, Iriarte J, Herruzo Martin Sanchez V, Ardanaz E, Moreno 17. García-Esquinas E, Guinó E, R, Blanco G, Llorca FJ, Asunsolo A, V, Gómez-Acebo I, Fernández-Tardon Castaño-Vinyals G, Pérez-Gómez B, Sánchez-Gallegos P, Gutiérrez PR, G, Villanueva Ballester V, Capelo R, Llorca J, Altzibar JM, Peiró-Pérez R, Fernández A, de Jesús MT, Martínez- Chirlaque MD, Santibáñez M, Pollán M, Martín V, Moreno-Iribas C, Tardón A, Alarcón L, Lana A, Fuentes L, Aragonés N, Kogevinas M. Caballero FJ, Puig-Vives M, Guevara M, Hernández JR, Virseda J, Yelamos J, Night shift work and stomach Villa TF, Salas D, Amiano P, Dierssen- Bondía JA, Hernández AM, Ayala MA, cancer risk in the MCC-Spain study. Sotos T, Pastor-Barriuso R, Sala M, Ramírez P, Parrilla P. Occup Environ Med. 2016;73:520-527. Kogevinas M, Aragonés N, Moreno V, Acceptance of living liver donation F.I.:3,745. [doi:10.1136/ Pollán M. among medical students: A oemed-2016-103597] Association of diabetes and diabetes multicenter stratified study from treatment with incidence of breast Spain. 12. Olmos JM, Hernández JL, cancer. World J Gastroenterol. 2016;22:5800- García-Velasco P, Martínez J, Llorca J, ACTA DIABETOL. 2016;53:99-107. 5813. González-Macías J. F.I.:3,074. [doi:10.1007/s00592-015- F.I.:2,787. [doi:10.3748/wjg.v22. Serum 25-hydroxyvitamin D, 0756-6] i25.5800] parathyroid hormone, calcium intake, and bone mineral density in 18. Lázaro-Díez M, Remuzgo-Martínez 23. Lope V, García-Esquinas E, Pérez- Spanish adults. S, Rodríguez-Mirones C, Acosta F, Icardo Gómez B, Altzibar JM, Gracia-Lavedan Osteoporos Int. 2016;27:105-113. JM, Martínez-Martínez L, Ramos-Vivas J. E, Ederra M, Molina de la Torre AJ, F.I.:3,445. [doi:10.1007/s00198-015- Effects of Subinhibitory LLorca FJ, Tardón A, Moreno V, Bayo 3219-6] Concentrations of Ceftaroline on J, Salas-Trejo D, Marcos-Gragera R, Methicillin-Resistant Staphylococcus Pumarega J, Dierssen-Sotos T, Lera 13. Dierssen-Sotos T, Gómez-Acebo I, aureus (MRSA) Biofilms. JP, de Miguel Medina MA, Tusquets de Pedro M, Pérez-Gómez B, Servitja PLoS One. 2016;11: I, Amiano P, Boldo E, Kogevinas M, S, Moreno V, Amiano P, Fernandez-Villa F.I.:3,057. [doi:10.1371/journal. Aragonés N, Castaño-Vinyals G, Pollán T, Barricarte A, Tardon A, Diaz-Santos pone.0147569] M. M, Peiro-Perez R, Marcos-Gragera R, Perinatal and childhood factors and Lope V, Gracia-Lavedan E, Alonso MH, 19. Lope V, Fernández de Larrea N, risk of breast cancer subtypes in Michelena-Echeveste MJ, Garcia- Pérez-Gómez B, Martín V, Moreno V, adulthood. Palomo A, Guevara M, Castaño-Vinyals Costas L, Longo F, Jiménez-Moleón Cancer Epidemiol. 2016;40:22-30. G, Aragonés N, Kogevinas M, Pollán JJ, Llorca J, Ascunce N, Peiró-Pérez F.I.:2,644. [doi:10.1016/j. M, Llorca J. R, Altzibar JM, Tardón A, Alguacil J, canep.2015.11.004] Use of non-steroidal anti- Navarro C, Sierra Á, Vega AB, Villafañe inflammatory drugs and risk of A, Castaño-Vinyals G, Kogevinas M, 24. Lope V, García-Esquinas E, Ruiz- breast cancer: The Spanish Multi- Pollán M, Aragonés N. Dominguez JM, LLorca J, Jiménez- Case-control (MCC) study. Menstrual and Reproductive Factors Moleón JJ, Ruiz-Cerdá JL, Alguacil J, BMC Cancer. 2016;16:660-660. and Risk of Gastric and Colorectal Tardón A, Dierssen-Sotos T, Tabernero F.I.:3,265. [doi:10.1186/s12885-016- Cancer in Spain. Á, Mengual L, Kogevinas M, Aragonés 2692-4] PLoS One. 2016;11: N, Castaño-Vinyals G, Pollán M, Pérez- F.I.:3,057. [doi:10.1371/journal. Gómez B. 14. Dessein PH, Corrales A, Lopez- pone.0164620] Perinatal and childhood factors and Mejias R, Solomon A, Woodiwiss AJ, risk of prostate cancer in adulthood: Llorca J, Norton GR, Genre F, Blanco R, 20. Gómez-Acebo I, Dierssen-Sotos MCC-Spain case-control study. Pina T, Gonzalez-Juanatey C, Tsang L, T, Palazuelos C, Pérez-Gómez B, Lope Cancer Epidemiol. 2016;43:49-55. Gonzalez-Gay MA. V, Tusquets I, Alonso MH, Moreno F.I.:2,644. [doi:10.1016/j. The Framingham Score and the V, Amiano P, Molina de la Torre AJ, canep.2016.06.012] Systematic Coronary Risk Evaluation Barricarte A, Tardon A, Camacho A, at Low Cutoff Values Are Useful Peiro-Perez R, Marcos-Gragera R, 25. Rueda-Gotor J, Llorca J, Corrales Surrogate Markers of High-risk Muñoz M, Michelena-Echeveste MJ, A, Blanco R, Fuentevilla P, Portilla V, 177

Expósito R, Mata C, Pina T, González- JL, Ruiz M, Helguera JM, Arenal Juanatey C, González-Gay M. S, Bonnardeux C, León C, Llorca Doctoral thesis Carotid ultrasound in the J, Santibañez M. Prevalence of cardiovascular risk stratification of Influenza Vaccination in Chronic patients with ankylosing spondylitis: Obstructive Pulmonary Disease 1. Javier Rueda Gotor. results of a population-based study. Patients and Impact on the Risk of Evaluation of cardiovascular risk in Clin Exp Rheumatol. 2016;34:885-892. Severe Exacerbations. patients with predominantly axial F.I.:2,495. Arch Bronconeumol. 2016;52:88-95. spondyloarthritis. F.I.:1,771. [doi:10.1016/j. Directors: Miguel Ángel González- 26. Remuzgo-Martínez S, Genre F, arbres.2015.09.001] Gay Mantecón, Javier Llorca Díaz. López-Mejías R, Ubilla B, Mijares V, University of Cantabria. Pina T, Corrales A, Blanco R, Martín 32. Pina T, Corrales A, Lopez-Mejias J, Llorca J, González-Gay MÁ. R, Armesto S, Gonzalez-Lopez MA, 2. Montserrat Robustillo Villarino. Decreased expression of methylene Gómez-Acebo I, Ubilla B, Remuzgo- Evaluation of cardiovascular risk tetrahydrofolate reductase (MTHFR) Martínez S, Gonzalez-Vela MC, Blanco using non-invasive techniques in gene in patients with rheumatoid R, Hernández JL, Llorca J, Gonzalez- patients with rheumatoid arthritis. arthritis. Gay MA. Directors: Javier Llorca Díaz, Miguel Clin Exp Rheumatol. 2016;34:106-110. Anti-tumor necrosis factor-alpha Ángel González-Gay Mantecón. F.I.:2,495. therapy improves endothelial University of Cantabria. function and arterial stiffness in 27. López-Mejías R, Genre F, patients with moderate to severe 3. Yhivian Peñasco Martín. Remuzgo-Martínez S, Sevilla Pérez psoriasis: A 6-month prospective Prognostic factors of severe thoracic B, Castañeda S, Llorca J, Ortego- study. trauma in the population aged over Centeno N, Ubilla B, Mijares V, Pina T, J Dermatol. 2016;43:1267-1272. 65, 1991-2012. Calvo-Río V, Miranda-Filloy JA, Navas F.I.:1,577. [doi:10.1111/1346- Directors: Alejandro González Castro, Parejo A, Argila D, Sánchez-Pérez J, 8138.13398] Javier Llorca Díaz. University of Rubio E, Luque ML, Blanco-Madrigal Cantabria. JM, Galíndez-Aguirregoikoa E, Martín 33. Pina T, Genre F, Lopez-Mejias J, Blanco R, González-Gay MA. R, Armesto S, Ubilla B, Mijares 4. Sara Rodríguez Prado. Interleukin 1 beta (IL1ß) rs16944 V, Dierssen-Sotos T, Corrales A, Ocular involvement in rendu-osler- genetic variant as a genetic marker Gonzalez-Lopez MA, Gonzalez- weber disease: characteristics and of severe renal manifestations and Vela MC, Blanco R, Hernández associations. renal sequelae in Henoch-Schönlein JL, Llorca J, Gonzalez-Gay MA. Director: Inés Gómez Acebo. purpura. Asymmetric dimethylarginine but University of Cantabria. Clin Exp Rheumatol. 2016;34:84-88. not osteoprotegerin correlates F.I.:2,495. with disease severity in patients 5. Ana Esteban Herrera. with moderate-to-severe psoriasis Effectiveness in the management 28. Ferraz-Amaro I, López-Mejías R, undergoing anti-tumor necrosis of smoking cessation. Cohort study Ubilla B, Genre F, Tejera-Segura B, de factor-a therapy. in a primary care context. Directors: Vera-González AM, González-Rivero J Dermatol. 2016;43:389-394. Javier Ayesta Ayesta, Javier Llorca AF, Olmos JM, Hernández JL, Llorca J, F.I.:1,577. [doi:10.1111/1346- Díaz. González-Gay MA. 8138.13094] University of Cantabria. Proprotein convertase subtilisin/ kexin type 9 in rheumatoid arthritis. 6. Jose Alberto Sanchez Ortega. Clin Exp Rheumatol. 2016;34:1013- Prevalence of tobacco, alcohol and 1019. drug use among university students F.I.:2,495. Reviews in Cantabria. Directors: Javier Llorca Díaz, Mª 29. Rueda-Gotor J, Llorca J, Corrales Concepcion Fariñas Álvarez. A, Blanco R, Fuentevilla P, Portilla V, 1. López-Mejías R, Castañeda S, University of Cantabria. Expósito R, Mata C, Pina T, González- González-Juanatey C, Corrales A, Juanatey C, González-Gay MA. Ferraz-Amaro I, Genre F, Remuzgo- Subclinical atherosclerosis is not Martínez S, Rodriguez-Rodriguez L, increased in patients with non- Blanco R, Llorca J, Martín J, González- radiographic axial spondyloarthritis. Gay MA. Clin Exp Rheumatol. 2016;34:159-160. Cardiovascular risk assessment in PROJECTS F.I.:2,495. patients with rheumatoid arthritis: The relevance of clinical, genetic and 30. Ríos A, López-Navas A, López- serological markers. López A, Gómez FJ, Iriarte J, Herruzo Autoimmun Rev. 2016;15:1013-1030. R, Blanco G, Llorca FJ, Asunsolo A, F.I.:8,490. [doi:10.1016/j. Projects Sánchez P, Gutiérrez PR, Fernández autrev.2016.07.026] A, de Jesús MT, Martínez-Alarcón L, Del Olivo M, Fuentes L, Hernández JR, Virseda J, Yelamos J, Bondía JA, 1. Javier Llorca Díaz. Hernández A, Ayala MA, Ramírez P, Integration of genetic big data and Parrilla P. clinical data: survival with breast Medical students faced with Editorials cancer in the MCC-Spain study. related and unrelated living PI15/00069. kidney donation: a stratified and INSTITUTO DE SALUD CARLOS III. multicentre study in Spain. 1. Gonzalez-Gay MA, Castañeda S, MINISTERIO DE ECONOMÍA Y WORLD J UROL. 2016;34:1673-1684. Llorca J. COMPETITIVIDAD. F.I.:2,397. [doi:10.1007/s00345-016- Giant Cell Arteritis: Visual Loss Is 1797-3] Our Major Concern. J Rheumatol. 2016;43:1458-1461. 31. Garrastazu R, García-Rivero F.I.:3,236. [doi:10.3899/jrheum.160466] Research Areas Transversal Area

Group Leader Juan Carlos Zabala Otaño Advanced Microscopy and Department of Áreas de Molecular Biology Protein Folding School of Medicine andinvestigación Citoesqueleto University of Cantabria

[email protected]

Researchers Jorge Alfonso Díaz Gómez 179

2. Study of the folding of proteins trying to characterize the molecular in organisms living between -1 mechanism leading to Kenny- Research and -2 ° C (Antarctic fish). Caffey syndrome in which the TBCE cofactor has a deletion of four Lines amino acids. The approach used is 3. Study of protein folding in multidisciplinary. organisms living between -1 and -2 ° C (Antarctic fish).

The research of our group, since PUBLICACIONES: 1. Study of tubulin folding its creation, has been articulated cofactors (TBCs). around the study of the Microtubule FACTOR DE IMPACTO | 4,348. Protease of tubulin. Development Cytoskeleton and specifically in the of biochemical and biophysical characterization of any activity of a techniques to study the interactions family of proteins intimately linked Artículos Originales of these proteins with others, to tubulins such as co-factors of identify their “partners” in the cell folding (TBCs) in addition to Other Avila J, Jiménez JS, Sayas CL, Bolós and dissect each and every one of chaperones involved in their folding 1. M, Zabala JC, Rivas G, Hernández F. their functions using, among others, as the cytosolic chaperonin CCT. Our studies have also focused Tau Structures. electron microscopy and confocal FRONT AGING NEUROSCI 2016. 8: on the role of these proteins in techniques. 262-0.FI: 4,348. different diseases but we are mainly

Anafase en célula humana. DNA en violeta, microtúbulos en Metafase aberrante en célula humana de 3 polos. DNA en amarillo y TBCB en verde. violeta, microtúbulos en amarillo y TBCB en verde.

181

Infectious Diseases and Immune System

Area María Carmen Fariñas Álvarez Coordinator of the Area of Infectious Diseases and Immune System.

Jefa del Servicio de Enfermedades Infecciosas. Head of the Infectious Service. University Hospital Marqués de Valdecilla. Professor of the Department of Medicine and Psychiatry. University of Cantabria. Research Areas Infectious Diseases and Immune System Area

Group Leader Epidemiología Genética y Miguel Ángel González-Gay Arterioesclerosis Mantecón enÁreas Enfermedades de Rheumatology Service University Hospital Inflamatoriasinvestigación Sistémicas Marqués de Valdecilla

[email protected]

Victor Manuel Mora Cuesta Natalia Palmou Fontana Mª Enriqueta Peiró Callizo José Luis Peña Sagredo Genma Pérez Paredes Trinitario Pina Murcia Consolidated group Federico Rehbergeer Bescos Sara Remuzgo Martínez Leyre Riancho Zarrabeitia Javier Rueda Gotor Researchers Lucia Cristina Dominguez Casas Begoña Ubilla García Ricardo Blanco Alonso Marta Drake Monfort Nuria Vegas Revenga Raquel López Mejías Carlos Fernández Diaz Iosune Vilanova Vadaniz Sonia Maria Fernández Rozas José Héctor Fernández Llaca Contributors Virginia Franco Gutierrez Nurses Pilar Alonso Lecue Lorien Garcia Cuello Patricia Fuentevilla Rodríguez Susana Armesto Alonso Fernanda Genre Virginia Portilla González Luis Miguel Blasco Mata Marcos Antonio González López Vanesa Calvo Del Río David Iturbe Fernandez Benigno Casanueva Fernandez Marina Lacalle Calderon Technicians Javier Loricera García Beatriz Castro Gutiérrez Javier García Fernández Maria Marcellán Fernández José Manuel Cifrián Martínez Jesús González Vela Cristina Martínez Dubois Germana Consuegra Romero Verónica Mijares Díaz María Cristina Mata Arnaiz Alfonso Fernando Corrales Martínez Enar Pons Sierra 183

biological agents in patients with for reporting, screening for and autoimmune diseases (mainly preventing selected comorbidities in chronic inflammatory rheumatic RA, EspA and psoriasis). Effect diseases in daily practice: a EULAR Research on clinical parameters of the initiative’ by Baillet et al. disease and the development of CV Ann Rheum Dis. 2016;75:55-55. Line disease. Based strictly on clinical F.I.:12,384. [doi:10.1136/ indication for lack of response to annrheumdis-2016-209836] conventional standard therapy, 3. González-Gay MA, Llorca J. 1. Epidemiology of autoimmune in those patients that due to the Clinical guidelines: Best diseases (mainly rheumatoid severity of the disease require practices and uncertainties in the arthritis (RA), giant cell arteritis, biological treatments, we analyze management of PMR. scleroderma, spondyloarthropathies the impact of these therapies on Nat Rev Rheumatol. 2016;12:3-4. F.I.:10,531. [doi:10.1038/ (EspA), systemic lupus the progression of atherosclerotic nrrheum.2015.142] erythematosus (SLE), psoriasis, disease, analyzing serum markers anti-synthetase syndrome, and clinical parameters Associated 4. Alonso A, Julià A, Vinaixa M, interstitial lung disease, Schönlein- with an increased risk of CV Domènech E, Fernández-Nebro A, Henoch purpura PSH), aortitis, mortality and the implication of Cañete JD, Ferrándiz C, Tornero J, Gisbert JP, Nos P, Casbas AG, Puig L, fibromyalgia and hidradenitis these drugs in their pathogenesis González-Álvaro I, Pinto-Tasende JA, suppurativa). We analyze incidence, as potentially “protective” therapies Blanco R, Rodríguez MA, Beltran A, clinical spectrum and evolutionary against the development of CV Correig X, Marsal S, IMID Consortium. course of these diseases. In many disease progression. Urine metabolome profiling of cases, these data are unknown immune-mediated inflammatory diseases. in the Spanish population, which BMC MED. 2016;14:133-133. puts our center as a reference for F.I.:8,005. [doi:10.1186/s12916-016- the knowledge of these diseases in 0681-8] southern European population. 5. González-Quintanilla V, Toriello M, Palacio E, González-Gay MA, 2. Cardiovascular risk (CV) and Castillo J, Montes S, Martínez-Nieto R, Fernandez J, Rojo A, Gutiérrez S, vascular disease in autoimmune Pons E, Oterino A. diseases (mainly RA, EspA, Systemic and cerebral endothelial SLE, psoriasis and hidradenitis dysfunction in chronic migraine. A suppurativa). Role of inflammation case-control study with an active and genetics in their development comparator. PUBLICACIONES: Cephalalgia. 2016;36:552-560. and clinical presentation. We F.I.:6,052. analyzed the markers (analytical, [doi:10.1177/0333102415607857] clinical and imaging) associated IMPACT FACTOR | 251,768 with inflammation that may be 6. López-Isac E, Martín JE, Assassi S, Simeón CP, Carreira P, Ortego- involved in the development of Centeno N, Freire M, Beltrán E, CV events and early mortality in Narváez J, Alegre-Sancho JJ, patients with chronic inflammatory Original articles Spanish Scleroderma Group, rheumatologic diseases. Fernández-Gutiérrez B, Balsa A, Ortiz AM, González-Gay MA, Beretta L, Santaniello A, Bellocchi C, Lunardi 1. Navas Tejedor, P., Tenorio Castano, C, Moroncini G, Gabrielli A, Witte 3. Genetic, serum and J., Quezada Loaiza, C. A., Moran T, Hunzelmann N, Distler JH, Fernandez, L. L., Palomino Doza, gene expression profiles of Riekemasten G, van der Helm-van Mil J., Rodriguez Reguero, J. J., Cifrian autoimmune diseases and their AH, de Vries-Bouwstra J, Magro-Checa Martinez, J., Ruiz Iturriaga, L. A., associated comorbidities (mainly C, Voskuyl AE, ..., Martín J. Martinez Menana, A., Arias, P., Gordo, Brief Report: IRF4 Newly Identified RA, giant cell arteritis, scleroderma, G., Lapunzina Abadia, P., Escribano as a Common Susceptibility EspA, SLE, psoriasis, anti- Subias, P. Locus for Systemic Sclerosis and The finding of a founder mutation synthetase syndrome, interstitial Rheumatoid Arthritis in a Cross- c.3344C > T(p.Pro1115Leu) in lung disease, aortitis and PSH). Disease Meta-Analysis of Genome- EIF2KA4 gene in iberian romani Wide Association Studies. Study of the genetic predisposition patients with pulmonary veno- Arthritis Rheumatol. 2016;68:2338- pattern of susceptibility as well occlusive disease: a family matter. 2344. as analysis of serum biomarkers Eur Heart J. 2016;37:1187-1187. F.I.:6,009. [doi:10.1002/art.39730] and gene expression profiles F.I.:15,064. in rheumatologic autoimmune 7. Rodríguez-Carrio J, López-Mejías 2. Castañeda S, Vicente EF, R, Alperi-López M, López P, Ballina- inflammatory diseases and their González-Gay MA. García FJ, González-Gay MÁ, Suárez A. associated comorbidities. Additional proposals to reduce Paraoxonase 1 Activity Is Modulated comorbidity in patients with chronic by the rs662 Polymorphism and inflammatory rheumatic diseases: IgG Anti-High-Density Lipoprotein 4. Therapeutic strategy with comment on ‘Points to consider Antibodies in Patients With Research Areas Infectious Diseases and Immune System Area

Rheumatoid Arthritis: Potential 13. Rodríguez-Carrio J, Alperi-López Remuzgo-Martínez S, Robledo G, Implications for Cardiovascular M, López-Mejías R, López P, Ballina- Llorca J, Corrales A, González- Disease. García FJ, Abal F, González-Gay MÁ, Juanatey C, Ubilla B, Mijares V, Pina Arthritis Rheumatol. 2016;68:1367- Suarez A. T, Blanco R, Castañeda S, Martín J, 1376.F.I.:6,009. [doi:10.1002/art.39609] Antibodies to paraoxonase 1 are González-Gay MA. associated with oxidant status and Vitamin D receptor GATG haplotype 8. González-López MA, Hernández endothelial activation in rheumatoid association with atherosclerotic JL, Lacalle M, Mata C, López- arthritis. disease in patients with rheumatoid Escobar M, López-Mejías R, Portilla Clin Sci (Lond). 2016;130:1889-1899. arthritis. V, Fuentevilla P, Corrales A, González- F.I.:5,016. [doi:10.1042/CS20160374] Atherosclerosis. 2016;245:139-142. Vela MC, González-Gay MA, Blanco R. F.I.:3,942. [doi:10.1016/j. Increased prevalence of subclinical 14. Lafita-Navarro MC, Blanco R, atherosclerosis.2015.12.011] atherosclerosis in patients with Mata-Garrido J, Liaño-Pons J, Tapia hidradenitis suppurativa (HS). O, García-Gutiérrez L, García-Alegría 19. Dessein PH, Corrales A, Lopez- J Am Acad Dermatol. 2016;75:329- E, Berciano MT, Lafarga M, León J. Mejias R, Solomon A, Woodiwiss AJ, 335. MXD1 localizes in the nucleolus, Llorca J, Norton GR, Genre F, Blanco R, F.I.:5,621. [doi:10.1016/j. binds UBF and impairs rRNA Pina T, Gonzalez-Juanatey C, Tsang L, jaad.2016.03.025] synthesis. Gonzalez-Gay MA. Oncotarget. 2016;7:69536-69548. The Framingham Score and the 9. Jimenez-Alonso, M., Martinez- F.I.:5,008. [doi:10.18632/ Systematic Coronary Risk Evaluation Rodriguez, I., Lavado-Perez, C., Lopez- oncotarget.11766] at Low Cutoff Values Are Useful Defillo, J., Quirce, R., Jimenez-Bonilla, Surrogate Markers of High-risk J., De Arcocha-Torres, M., Meza- 15. Pego-Reigosa JM, Lois-Iglesias A, Subclinical Atherosclerosis in Escobar, D., Loricera, J., Gonzalez-Gay, Rúa-Figueroa Í, Galindo M, Calvo-Alén Patients with Rheumatoid Arthritis. M., Banzo, I. J, de Uña-Álvarez J, Balboa-Barreiro J Rheumatol. 2016;43:486-494. Semiquantitative analysis of V, Ibáñez Ruan J, Olivé A, Rodríguez- F.I.:3,236. [doi:10.3899/jrheum.150510] 18F-FDG PET/CT in the follow-up of Gómez M, Fernández Nebro A, Andrés large vessel vasculitis. M, Erausquin C, Tomero E, Horcada 20. González-Gay MA, Llorca J, Eur J Nucl Med Mol Imaging. Rubio L, Uriarte Isacelaya E, Freire M, González-Juanatey C, Martín-Martínez 2016;43:62-62.F.I.:5,537. Montilla C, Sánchez-Atrio AI, Santos- MA, Castañeda S. Soler G, Zea A, Díez E, Narváez J, Why is Rheumatoid Arthritis 10. Remuzgo-Martínez S, Genre F, Blanco-Alonso R, Silva-Fernández L, Mortality Still High Despite the López-Mejías R, Ubilla B, Mijares V, Ruiz-Lucea ME, Fernández-Castro M, Advent of New Therapies? Comment Pina T, Corrales A, Blanco R, Martín J, Hernández-Beriain JÁ, Gantes-Mora M, on the Article by Widdifield et al. Llorca J, González-Gay MA. ..., López-Longo FJ. Arthritis Care Res (Hoboken). Expression of osteoprotegerin and Relationship between damage 2016;68:726-727. its ligands, RANKL and TRAIL, in clustering and mortality in systemic F.I.:3,229. [doi:10.1002/acr.22731] rheumatoid arthritis. lupus erythematosus in early and Sci Rep. 2016;6:29713-29713. late stages of the disease: cluster 21. Alvarez P, Genre F, Iglesias M, F.I.:5,228. [doi:10.1038/srep29713] analyses in a large cohort from the Augustin JJ, Tamayo E, Escolà-Gil Spanish Society of Rheumatology JC, Lavín B, Blanco-Vaca F, Merino R, 11. López-Mejías R, Genre F, Lupus Registry. Merino J. Remuzgo-Martínez S, González- Rheumatology (Oxford). 2016;55:1243- Modulation of autoimmune arthritis Juanatey C, Robustillo-Villarino 1250. severity in mice by apolipoprotein E M, Llorca J, Corrales A, Vicente E, F.I.:4,524. [doi:10.1093/rheumatology/ (ApoE) and cholesterol. Miranda-Filloy JA, Magro C, Tejera- kew049] CLIN EXP IMMUNOL. 2016;186:292- Segura B, Ramírez Huaranga MA, 303. Pina T, Blanco R, Alegre-Sancho JJ, 16. Charles-Schoeman C, Wicker P, F.I.:3,148. [doi:10.1111/cei.12857] Raya E, Mijares V, Ubilla B, Mínguez Gonzalez-Gay MA, Boy M, Zuckerman Sánchez MD, Gómez-Vaquero C, Balsa A, Soma K, Geier J, Kwok K, Riese R. 22. Ortiz-Fernández L, Carmona FD, A, Pascual-Salcedo D, López-Longo Cardiovascular safety findings in Montes-Cano MA, García-Lozano JR, FJ, Carreira P, González-Álvaro I, patients with rheumatoid arthritis Conde-Jaldón M, Ortego-Centeno N, Rodríguez-Rodríguez L, Fernández- treated with tofacitinib, an oral Castillo MJ, Espinosa G, Graña-Gil G, Gutiérrez B, Ferraz-Amaro I, Castañeda Janus kinase inhibitor. Sánchez-Bursón J, Juliá MR, Solans R, S, ..., González-Gay MA. Semin Arthritis Rheum. 2016;46:261- Blanco R, Barnosi-Marín AC, Gómez Influence of elevated-CRP level- 271. de la Torre R, Fanlo P, Rodríguez- related polymorphisms in non- F.I.:3,946. [doi:10.1016/j. Carballeira M, Rodríguez-Rodríguez L, rheumatic Caucasians on the semarthrit.2016.05.014] Camps T, Castañeda S, Alegre-Sancho risk of subclinical atherosclerosis JJ, Martín J, González-Escribano MF. and cardiovascular disease in 17. Calvo-Río V, Blanco R, Santos- Genetic Analysis with the rheumatoid arthritis. Gómez M, Rubio-Romero E, Cordero- Immunochip Platform in Behçet Sci Rep. 2016;6:31979-31979. Coma M, Gallego-Flores A, Veroz Disease. Identification of Residues F.I.:5,228. [doi:10.1038/srep31979] R, Torre I, Hernández FF, Atanes A, Associated in the HLA Class I Loricera J, González-Vela MC, Palmou Region and New Susceptibility Loci. 12. Abella V, Scotece M, Conde J, N, Hernández JL, González-Gay MA. PLoS One. 2016;11: López V, Pirozzi C, Pino J, Gómez R, Golimumab in refractory uveitis F.I.:3,057. [doi:10.1371/journal. Lago F, González-Gay MÁ, Gualillo O. related to spondyloarthritis. pone.0161305] The novel adipokine progranulin Multicenter study of 15 patients. counteracts IL-1 and TLR4-driven Semin Arthritis Rheum. 2016;46:95- 23. Pina T, Genre F, Lopez-Mejias inflammatory response in human 101. R, Armesto S, Ubilla B, Mijares V, and murine chondrocytes via F.I.:3,946. [doi:10.1016/j. Dierssen-Sotos T, Corrales A, Gonzalez- TNFR1. semarthrit.2016.03.002] Lopez MA, Gonzalez-Vela MC, Blanco Sci Rep. 2016;6:20356-20356. R, Llorca J, Gonzalez-Gay MA. F.I.:5,228. [doi:10.1038/srep20356] 18. López-Mejías R, Genre F, Anti-TNF-a therapy reduces retinol- 185

binding protein 4 serum levels in Clin Exp Rheumatol. 2016;34:625-633. erythematosus: a comparative, non-diabetic patients with psoriasis: F.I.:2,495. register-based study with emphasis a 6-month prospective study. in cardiovascular disease. J Eur Acad Dermatol Venereol. 30. Remuzgo-Martínez S, Genre F, Clin Exp Rheumatol. 2016;34:98-99. 2016;30:92-95. López-Mejías R, Ubilla B, Mijares V, F.I.:2,495. F.I.:3,029. [doi:10.1111/jdv.13005] Pina T, Corrales A, Blanco R, Martín J, Llorca J, González-Gay MÁ. 36. Ferraz-Amaro I, López-Mejías R, 24. Díaz-Angulo S, López-Hoyos M, Decreased expression of methylene Ubilla B, Genre F, Tejera-Segura B, de Muñoz Cacho P, Fernández M, López- tetrahydrofolate reductase (MTHFR) Vera-González AM, González-Rivero Escobar M, Rodríguez F, González- gene in patients with rheumatoid AF, Olmos JM, Hernández JL, Llorca J, López MA. arthritis. González-Gay MA. Prevalence of thyroid autoimmunity Clin Exp Rheumatol. 2016;34:106-110. Proprotein convertase subtilisin/ in spanish patients with chronic F.I.:2,495. kexin type 9 in rheumatoid arthritis. idiopathic urticaria: a case-control Clin Exp Rheumatol. 2016;34:1013- study involving 343 subjects. 31. Demetrio-Pablo, R., Munoz, P., 1019. J Eur Acad Dermatol Venereol. Calvo-Rio, V., Riancho-Zarrabeitia, L., F.I.:2,495. 2016;30:692-693. Lopez-Hoyos, M., Martinez-Taboada, V. F.I.:3,029. [doi:10.1111/jdv.12979] Evaluation of thrombotic 37. Ortiz-Fernandez, L., Montes- risk in patients with positive Cano, M. -A., Garcia-Lozano, J. -R., 25. Carbone, J., Cifrian, J., Lopez- antiphospholipid antibodies without Conde-Jaldon, M., Ortego-Centeno, Hoyos, M., Bravo, C., Lopez, S., clinical criteria for the disease. N., Gonzalez-Leon, R., Espinosa, Ussetti, P., Laporta, R., De Pablos, A., Clin Exp Rheumatol. 2016;34:97-97. G., Grana-Gil, G., Sanchez-Burson, Pleguezuelo, D., Sole, A., Jaramillo, F.I.:2,495. J., Julia, M. R., Solans, R., Blanco, M., Navarro, J., Rodriguez-Molina, J., R., Bamosi-Marin, A. -C., Fanlo, P., Sarmiento, E. 32. Loricera J, González-Vela C, Carballeira, M. Rodriguez, Camps, T., Pre-transplant humoral immunity Blanco R, Hernández JL, Armesto S, Castaneda, S., Martin, J., Gonzalez- risk factors of infection in lung González-López MA, Calvo-Río V, Ortiz- Escribano, M. F. transplantation: results of a Sanjuán F, Val-Bernal JF, Hermana S, PTPN22 is not associated with multicenter study. Onaindia-Pérez A, González-Gay MA. Behçet’s disease. Study spanning Transpl Int. 2016;29:5-5. Histopathologic differences between the complete gene region in the F.I.:2,835. cutaneous vasculitis associated Spanish population and meta- with severe bacterial infection and analysis of the functional variant 26. Abella V, Pérez T, Scotece M, cutaneous vasculitis secondary to R620W. Conde J, Pirozzi C, Pino J, Lago F, other causes: study of 52 patients. Clin Exp Rheumatol. 2016;34:41-45. González-Gay MÁ, Mera A, Gómez R, Clin Exp Rheumatol. 2016;34:93-97. F.I.:2,495. Gualillo O. F.I.:2,495. Pollutants make rheumatic diseases 38. Zarrabeitia, L. Riancho, Corrales, worse: Facts on polychlorinated 33. López-Mejías R, Genre F, A., Vegas-Revenga, N., Dominguez- biphenyls (PCBs) exposure and Remuzgo-Martínez S, Sevilla Pérez Casas, L., Portilla, V., Blanco, R., rheumatic diseases. B, Castañeda S, Llorca J, Ortego- Gonzalez-Gay, M. A. Life Sci. 2016;157:140-144. Centeno N, Ubilla B, Mijares V, Pina T, Rheumatoid arthritis and systemic F.I.:2,685. [doi:10.1016/j. Calvo-Río V, Miranda-Filloy JA, Navas lupus erythematosus exhibit similar lfs.2016.06.010] Parejo A, Argila D, Sánchez-Pérez J, degree of severity of subclinical Rubio E, Luque ML, Blanco-Madrigal atherosclerosis. Results from a 27. Riancho-Zarrabeitia L, García- JM, Galíndez-Aguirregoikoa E, Martín cross-sectional study in a population Unzueta M, Tenorio JA, Gómez- J, Blanco R, González-Gay MA. of northwestern Spain. Gerique JA, Ruiz Pérez VL, Heath KE, Interleukin 1 beta (IL1ß) rs16944 Clin Exp Rheumatol. 2016;34:97-98. Lapunzina P, Riancho JA. genetic variant as a genetic marker F.I.:2,495. Clinical, biochemical and of severe renal manifestations and genetic spectrum of low alkaline renal sequelae in Henoch-Schönlein 39. Demetrio Pablo, R., Munoz, P., phosphatase levels in adults. purpura. Riancho-Zarrabeiti, L., Calvo-Rio, V., Eur J Intern Med. 2016;29:40-45. Clin Exp Rheumatol. 2016;34:84-88. Lopez-Hoyos, M., Martinez-Taboada, V. F.I.:2,591. [doi:10.1016/j. F.I.:2,495. Risk factors for pregnancy morbidity ejim.2015.12.019] in patients with antiphospholipid 34. Márquez A, Fernández-Aranguren antibodies without a defined clinical 28. Rueda-Gotor J, Llorca J, Corrales T, Witte T, González-Gay MA, Martín antiphospholipid syndrome. A, Blanco R, Fuentevilla P, Portilla V, J, Spanish GCA Group, Spanish Clin Exp Rheumatol. 2016;34:49-49. Expósito R, Mata C, Pina T, González- Scleroderma Group. F.I.:2,495. Juanatey C, González-Gay M. LILRA3 deficiency is not involved in Carotid ultrasound in the the giant cell arteritis and systemic 40. Riancho Zarrabeitia, L., Daroca, G., cardiovascular risk stratification of sclerosis predisposition. Lopez-Hoyos, M., Munoz, P., Haya, A., patients with ankylosing spondylitis: Clin Exp Rheumatol. 2016;34 Suppl Gonzalez, M., Del Barrio, R., Martinez- results of a population-based study. 100:208-209. Taboada, V. Clin Exp Rheumatol. 2016;34:885-892. F.I.:2,495. Serological evolution in F.I.:2,495. fertile women with positive 35. Rua-Figueroa, I., Castro, M. antiphospholipid antibodies. 29. Kremer JM, Blanco R, Halland AM, Fernandez, Pego-Reigosa, J. M., Clin Exp Rheumatol. 2016;34:44-44. Brzosko M, Burgos-Vargas R, Mela Sanchez-Piedra, C., Lopez-Longo, F.I.:2,495. CM, Rowell L, Fleischmann RM. J., Taboada, V. Martinez, Calvo-Alen, Clinical efficacy and safety J., Olive, A., Galindo, M., Blanco, R., 41. Tejera-Segura B, de Vera-González maintained up to 5 years in patients Alonso, F., Erausquin, C., Andreu, J. L. AM, López-Mejías R, González-Gay with rheumatoid arthritis treated Prevalence of comorbidities in MA, Ferraz-Amaro I. with tocilizumab in a randomised patients with primary sjogren’s Serum cathepsin S and cystatin C: trial. syndrome and systemic lupus relationship to subclinical carotid Research Areas Infectious Diseases and Immune System Area

atherosclerosis in rheumatoid against Ocular Inflammation. factor-a therapy. arthritis. OCUL IMMUNOL INFLAMM. J Dermatol. 2016;43:389-394. Clin Exp Rheumatol. 2016;34:230-235. 2016;24:167-172. F.I.:1,577. [doi:10.1111/1346- F.I.:2,495. F.I.:2,481. [doi:10.3109/09273948.201 8138.13094] 4.967779] 42. Rueda-Gotor J, Llorca J, Corrales 52. González-López MA, Blanco R, A, Blanco R, Fuentevilla P, Portilla V, 47. Fonollosa A, Martinez-Indart Mata C, López-Escobar M, Lacalle Expósito R, Mata C, Pina T, González- L, Artaraz J, Martinez-Berriotxoa A, M, Consuegra G, González-Vela MC, Juanatey C, González-Gay MA. Agirrebengoa K, Garcia M, Lopez-Soria González-Gay MA. Subclinical atherosclerosis is not L, Sorribas M, Diaz-Valle D, Blanco Coexistence of Hidradenitis increased in patients with non- R, Rueda-Gotor J, Adan A, Llorenç V, Suppurativa with Autoimmune radiographic axial spondyloarthritis. Cordero-Coma M, Distefano L, Segura Thyroiditis: Report of Three Cases. Clin Exp Rheumatol. 2016;34:159-160. A, Blanco A. Dermatology. 2016;232:162-164. F.I.:2,495. Clinical Manifestations and F.I.:1,449. [doi:10.1159/000439562] Outcomes of Syphilis-associated 43. Raymond AR, Brooksbank RL, Uveitis in Northern Spain. 53. Castañeda S, Vicente EF, Millen AM, Norton GR, Solomon A, OCUL IMMUNOL INFLAMM. González-Gay MA. Woodiwiss AJ, Tsang L, Dessein PH, 2016;24:147-152. Enfermedad de Still del adulto. Gonzalez-Gay MA. F.I.:2,481. [doi:10.3109/09273948.201 Med Clin (Barc). 2016;147:217-222. Telomere length, endothelial 4.943349] F.I.:1,267. [doi:10.1016/j. activation and carotid medcli.2016.03.034] atherosclerosis in black and white 48. Lázaro-Díez M, Navascués-Lejarza African patients with rheumatoid T, Remuzgo-Martínez S, Navas J, 54. Gonzalez-Gay, Miguel A., arthritis. Icardo JM, Acosta F, Martínez-Martínez Castaneda, Santos. Clin Exp Rheumatol. 2016;34:864-871. L, Ramos-Vivas J. Managing of giant cell arteritis and F.I.:2,495. Acinetobacter baumannii and A. polymyalgia rheumatica. pittii clinical isolates lack adherence Exp. Opin. Orphan Drugs. 44. Santos-Gómez M, Calvo-Río V, and cytotoxicity to lung epithelial 2016;4:1133-1144. Blanco R, Beltrán E, Mesquida M, cells in vitro. F.I.:0,464. [doi:10.1080/21678707.201 Adán A, Cordero-Coma M, García- Microbes Infect. 2016;18:559-564. 6.1244480] Aparicio ÁM, Valls Pascual E, Martínez- F.I.:2,291. [doi:10.1016/j. Costa L, Hernández MV, Hernandez micinf.2016.05.002] Garfella M, González-Vela MC, Pina T, Palmou-Fontana N, Loricera J, 49. Calvo-Río V, Hernández JL, Reviews Hernández JL, González-Gay MA. Ortiz-Sanjuán F, Loricera J, Palmou- The effect of biologic therapy Fontana N, González-Vela MC, different from infliximab or González-Lamuño D, González-López 1. López-Mejías R, Castañeda S, adalimumab in patients with MA, Armesto S, Blanco R, González- González-Juanatey C, Corrales A, refractory uveitis due to Behçet’s Gay MA. Ferraz-Amaro I, Genre F, Remuzgo- disease: results of a multicentre Relapses in patients with Henoch- Martínez S, Rodriguez-Rodriguez L, open-label study. Schönlein purpura: Analysis of 417 Blanco R, Llorca J, Martín J, González- Clin Exp Rheumatol. 2016;34:34-40. patients from a single center. Gay MA. F.I.:2,495. Medicine (Baltimore). 2016;95: Cardiovascular risk assessment in F.I.:2,133. [doi:10.1097/ patients with rheumatoid arthritis: 45. Casanueva B, García-Fructuoso MD.0000000000004217] The relevance of clinical, genetic and F, Belenguer R, Alegre C, Moreno- serological markers. Muelas J, Hernández JL, Pina T, 50. Pina T, Corrales A, Lopez-Mejias Autoimmun Rev. 2016;15:1013-1030. González-Gay MÁ. R, Armesto S, Gonzalez-Lopez MA, F.I.:8,490. [doi:10.1016/j. The Spanish version of the 2010 Gómez-Acebo I, Ubilla B, Remuzgo- autrev.2016.07.026] American College of Rheumatology Martínez S, Gonzalez-Vela MC, Blanco Preliminary Diagnostic Criteria for R, Hernández JL, Llorca J, Gonzalez- 2. Mavrogeni, Sophie I., Kitas, fibromyalgia: reliability and validity Gay MA. George D., Dimitroulas, Theodoros, assessment. Anti-tumor necrosis factor-alpha Sfikakis, Petros P., Seo, Philip, Gabriel, Clin Exp Rheumatol. 2016;34:55-58. therapy improves endothelial Sherine, Patel, Amit R., Gargani, F.I.:2,495. function and arterial stiffness in Luna, Bombardieri, Stefano, Matucci- patients with moderate to severe Cerinic, Marco, Lombardi, Massimo, 46. Casanueva B, Belenguer R, psoriasis: A 6-month prospective Pepe, Alessia, Aletras, Anthony H., Moreno-Muelas JV, Urtiaga J, Urtiaga study. Kolovou, Genovefa, Miszalski, Tomasz, B, Hernández JL, Pina T, González- J Dermatol. 2016;43:1267-1272. van Riel, Piet, Semb, AnneGrete, Gay MA. F.I.:1,577. [doi:10.1111/1346- Angel Gonzalez-Gay, Miguel, Dessein, Validation of the Spanish version of 8138.13398] Patrick, Karpouzas, George, Puntmann, the fibromyalgia rapid screening tool Valentina, Nagel, Eike, Bratis, to detect fibromyalgia in primary 51. Pina T, Genre F, Lopez-Mejias Konstantinos, Karabela, Georgia, care health centres. R, Armesto S, Ubilla B, Mijares Stavropoulos, Efthymios, Katsifis, Clin Exp Rheumatol. 2016;34:125-128. V, Dierssen-Sotos T, Corrales A, Gikas, Koutsogeorgopoulou, Loukia, F.I.:2,495. Gonzalez-Lopez MA, Gonzalez- van Rossum, Albert, Rademakers, Vela MC, Blanco R, Hernández Frank, ..., Lima, Joao A. C. 46. Llorenç V, Mesquida M, Sainz de JL, Llorca J, Gonzalez-Gay MA. Cardiovascular magnetic resonance la Maza M, Blanco R, Calvo V, Maíz Asymmetric dimethylarginine but in rheumatology: Current status and O, Blanco A, de Dios-Jiménez de not osteoprotegerin correlates recommendations for use. Aberásturi JR, Adán A. with disease severity in patients Int J Cardiol. 2016;217:135-148. Certolizumab Pegol, a New Anti- with moderate-to-severe psoriasis F.I.:4,638. [doi:10.1016/j. TNF-a in the Armamentarium undergoing anti-tumor necrosis ijcard.2016.04.158] 187

3. Charles-Schoeman C, Gonzalez-Gay Gay Mantecón, Ricardo Blanco MA, Kaplan I, Boy M, Geier J, Luo Z, Editorials Alonso. Zuckerman A, Riese R. University of Cantabria. Effects of tofacitinib and other 1. González-Gay MA, González- DMARDs on lipid profiles in Juanatey C. 6. Montserrat Robustillo Villarino. rheumatoid arthritis: implications for Cardiovascular risk factor Evaluation of cardiovascular risk the rheumatologist. assessment: still an unmet need using non-invasive techniques in patients with rheumatoid arthritis. Semin Arthritis Rheum. 2016;46:71-80. in chronic inflammatory diseases. Directors: Javier Llorca Díaz, Miguel F.I.:3,946. [doi:10.1016/j. Heart. 2016;102:1937-1939. Ángel González-Gay Mantecón. semarthrit.2016.03.004] F.I.:5,693. [doi:10.1136/ heartjnl-2016-310292] University of Cantabria. 4. Castañeda S, Blanco R, González- 2. Gonzalez-Gay MA, Castañeda S, Gay MA. Adult-onset Still’s disease: Llorca J. Advances in the treatment. Giant Cell Arteritis: Visual Loss Is Best Pract Res Clin Rheumatol. Our Major Concern. PROJECTS 2016;30:222-238. J Rheumatol. 2016;43:1458-1461. F.I.:3,267. [doi:10.1016/j. F.I.:3,236. [doi:10.3899/jrheum.160466] berh.2016.08.003] 3. Castañeda S, López-Mejías R, Projects 5. Castañeda S, Nurmohamed MT, González-Gay MA. González-Gay MA. Gene polymorphisms and therapy in 1. Miguel Ángel González-Gay Cardiovascular disease in rheumatoid arthritis. Mantecón. inflammatory rheumatic diseases. Expert Opin Drug Metab Toxicol. 2016;12:225-229. Research Network on Inflammation Best Pract Res Clin Rheumatol. and Rheumatic Diseases. 2016;30:851-869. F.I.:2,598. [doi:10.1517/17425255.201 6.1141405] RD12/0009/0013. F.I.:3,267. [doi:10.1016/j. INSTITUTO DE SALUD CARLOS III. berh.2016.10.006] MINISTERIO DE ECONOMÍA Y COMPETITIVIDAD. 6. López-Delgado L, Riancho- Zarrabeitia L, Riancho JA. 2. Miguel Ángel González-Gay Genetic and acquired factors Doctoral thesis Mantecón. influencing the effectiveness Sara Borrell Contracts. and toxicity of drug therapy in CD15/00095. osteoporosis. 1. Ana Machin Mave. INSTITUTO DE SALUD CARLOS III. Expert Opin Drug Metab Toxicol. Epidemiological and evolutionary MINISTERIO DE ECONOMÍA Y COMPETITIVIDAD. 2016;12:389-398. analysis of open eye trauma in cantabria. 2007-2014. Directors: F.I.:2,598. [doi:10.1517/17425255.201 3. Miguel Ángel González-Gay 6.1154533] Joaquín Cañal Villanueva, Pedro Muñoz Cacho. Mantecón. University of Cantabria. Molecular Reclassification to Find 7. Carmona FD, Martín J, González- Clinically Useful Biomarkers for Gay MA. 2. Francisco Ortiz Sanjuan. Systemic Autoimmune Diseases. New insights into the pathogenesis Classification of cutaneous EU13/01- PRECISESADS. of giant cell arteritis and hopes for vasculitis. Cutaneous vasculitis by COMISIÓN EUROPEA, INNOVATIVE the clinic. drugs. MEDICINES INITIATIVE. Expert Rev Clin Immunol. 2016;12:57- Directors: Ricardo Blanco Alonso, 66 Miguel Ángel González-Gay 4. Miguel Ángel González-Gay F.I.:2,596. [doi:10.1586/174466 Mantecón, María Del Carmen Mantecón. 6X.2016.1089173] González Vela. Genetic markers of atherosclerotic University of Cantabria. disease in rheumatoid arthritis. PI15/00525. 8. Loricera J, Blanco R, Hernández JL, INSTITUTO DE SALUD CARLOS III. Castañeda S, Humbría A, Ortego N, 3. Javier Rueda Gotor. MINISTERIO DE ECONOMÍA Y Bravo B, Freire M, Melchor S, Mínguez Evaluation of cardiovascular risk in COMPETITIVIDAD. M, Salvatierra J, González-Vela C, patients with predominantly axial Calvo-Río V, Santos-Gómez M, Pina T, spondyloarthritis. 5. Miguel Ángel González-Gay González-Gay MA. Directors: Miguel Ángel González- Mantecón. Tocilizumab in patients with Gay Mantecón, Javier Llorca Díaz. Thematic Network in Inflammation Takayasu arteritis: a retrospective University of Cantabria. and Rheumatic Diseases. study and literature review. RD16/0012/0009. Clin Exp Rheumatol. 2016;34:44-53. 4. Jose Maria Castillo Oti. INSTITUTO DE SALUD CARLOS III. F.I.:2,495. Prevalence and risk factors MINISTERIO DE ECONOMÍA Y associated with diabetic retinopathy COMPETITIVIDAD. 9. Martin-Mola E, Balsa A, García- in Cantabria. Raquel López Mejías. Vicuna R, Gómez-Reino J, González- Directors: Joaquín Cañal Villanueva, 6. Project associated to the Miguel Gay MA, Sanmartí R, Loza E. Pedro Muñoz Cacho. University of Cantabria. Servet Posdoctoral Contract Type. Anti-citrullinated peptide antibodies CV risk assessment in patients with and their value for predicting 5. Leyre Riancho Zarrabeitia. rheumatoid arthritis: the relevance responses to biologic agents: a of genetic marker. review. Detection of risk factors for subclinical atherosclerotic disease CP16/00033. Rheumatol Int. 2016;36:1043-1063. and cardiovascular events in patients INSTITUTO DE SALUD CARLOS F.I.:1,702. [doi:10.1007/s00296-016- with systemic lupus erythematosus. III. MINISTERIO DE ECONOMÍA Y 3506-3] Directors: Miguel Ángel González- COMPETITIVIDAD. Research Areas Infectious Diseases and Immune System Area

Group Leader María Del Carmen Fariñas Álvarez Pathogenic Epidemiology and Infectious Diseases MechanismsÁreas de of Infectious Service University Hospital Diseases Marqués de Valdecilla investigación University of Cantabria

[email protected]

Contributors Carlos Armiñanzas Castillo Ana Mª Arnaiz García Francisco Arnaiz de Las Revillas Almajano Mª Concepcion Fariñas Álvarez Marta Fernández Sampedro Claudia González Rico Manuel Gutiérrez Cuadra Javier Gonzalo Ocejo Viñals Borja Suberviola Cañas Clinic group

2. The study of Articular extracellular traps). Prosthesis Infections. Research This line began in 2009 with the 3. Optimization of antimicrobial Lines execution of the Research Project: treatment and its impact of PI 08/0609 where the study of the antibiotic consumption on cost role of sonication in the diagnosis savings and bacterial resistance. of joint prosthesis infections was Initiated in 2006 with the granting introduced. The results have had as of two research projects (FIS: PI06 / a positive result the incorporation 90094 and API: 06/01). This project into the laboratory routine of has received the Valdecilla-Caja Microbiology of this technique. Cantabria Teaching Excellence 1. Infections in Transplanted Solid Then, and thanks to API 11/09, Award in 2013. Since then, the Organs. are there more accurate Systemic experience accumulated at the Markers in the diagnosis of Knee This line of research started in 2012 Marqués de Valdecilla Hospital is Prosthesis Infection (IPRC) prior to is being consolidated in our group being transferred to other hospitals Implant withdrawal? the study of mainly through the acquisition through the teaching of professional Systemic Markers is being carried of competitive funding research specialists of staff from National out in the diagnosis of Infection of projects (FIS - PI13 / 01191 - PI16 Hospitals that go to Diseases Knee Prosthesis or Hip (IPRC) prior / 01415 and Mutua Madrileña Infectious. to the withdrawal of the Implant FMM 14/01. Research in Infectious such as ILA6, Procalcitonin, VEGF Pathology (REIPI) and European The excessive and inadequate (Vascular Endothelial Growth Projects (Increment-SOT). use of antimicrobials is currently Factor) or NETs ( Neutrophils an important economic and 189

public health problem due to the consolidated with the obtaining Of Pardo JR, ..., Aguado JM. emergence of microorganisms an API1010 Grant. Currently still Clinical Presentation and Determinants of Mortality of that are increasingly resistant active. Likewise, the search for Invasive Pulmonary Aspergillosis to available antibiotics. This other genes for susceptibility or in Kidney Transplant Recipients: A study is part of an attempt to resistance to progression, from a Multinational Cohort Study. achieve these objectives through latent state of tuberculosis infection Am J Transplant. 2016;16:3220-3234. recommendations on the use of to disease, is another objective of F.I.:5,669. [doi:10.1111/ajt.13837] antimicrobials in a standardized way the group. 4. López-Medrano F, Silva JT, by a person with experience in this Fernández-Ruiz M, Carver PL, van area, the result of a multidisciplinary Delden C, Merino E, Pérez-Saez collaboration. MJ, Montero M, Coussement J, de Abreu Mazzolin M, Cervera C, Santos 4. Epidemiology of Infective L, Sabé N, Scemla A, Cordero E, Cruzado-Vega L, Martín PL, Len Ó, Endocarditis. Rudas E, Ponce de León A, Arriola M, Lazurica R, David M, González-Rico C, With the creation of the Henríquez-Palop F, Fortún J, Nucci M, Endocarditis Management Manuel O, Paño-Pardo JR, ..., Assistance Group in Spain (GAMES) Swiss Transplant Cohort Study (STCS). Risk Factors Associated in 2007, which comprises 35 With Early Invasive Pulmonary hospitals, a better knowledge of PUBLICACIONS: Aspergillosis in Kidney Transplant this disease is being achieved, Recipients: Results From a which is having an impact on a IMPACT FACTOR | 98,636 Multinational Matched Case-Control better diagnostic and therapeutic Study. Am J Transplant. 2016;16:2148-2157. approach. Our group manages F.I.:5,669. [doi:10.1111/ajt.13735] one of the 7 nodes in which the participating Hospitals have been Original articles 4. Merino I, Shaw E, Horcajada JP, divided and has contributed Cercenado E, Mirelis B, Pallarés MA, Gómez J, Xercavins M, Martínez- to the formation of the HUMV Martínez L, De Cueto M, Cantón R, Multidisciplinary Endocarditis 1. Dominguez Rodriguez, F., Ramos, A., Bouza, E., Munoz, P., Valerio, M. Ruiz-Garbajosa P, ITUBRAS-GEIH- Group, H. Sierrallana and H. de C., Farinas, C., De Berrazueta, J. R., SEIMC Group. Laredo, in which the Cardiology, Zarauza, J., Pericas Pulido, J. M., CTX-M-15-H30Rx-ST131 subclone Cardiovascular Surgery, Home Pare, J. C., De Alarcon, A., Sousa, D., is one of the main causes of healthcare-associated ESBL- Hospitalization, Internal Medicine Rodriguez Bailon, I., Montejo-Baranda, M., Garcia-Pavia, P. producing Escherichia coli and Microbiology. Infective endocarditis in bacteraemia of urinary origin in hypertrophic cardiomyopathy: Spain. should antibiotic prophylaxis be J Antimicrob Chemother. 5. Research in the field of sepsis. reconsidered?. 2016;71:2125-2130. Eur Heart J. 2016;37:1015-1015. F.I.:4,919. [doi:10.1093/jac/dkw133] Study of sepsis in a global way, F.I.:15,064. both from the point of view of 5. Díez-Villanueva P, Muñoz P, Marín M, Bermejo J, de Alarcón González predisposing factors and the 2. Calderon-Gonzalez R, Teran- Navarro H, Marimon JM, González- A, Fariñas MC, Gutiérrez-Cuadra M, optimization of its treatment and Rico C, Calvo-Montes J, Frande- Pericás-Pulido JM, Lepe JA, Castelo the identification of prognostic Cabanes E, Alkorta-Gurrutxaga M, L, Goenaga MÁ, Ruiz-Morales factors. This line of research Fariñas MC, Martínez-Martínez L, J, Tarabini P, Martínez-Sellés M, began with research projects with Perez-Trallero E, Alvarez-Dominguez C. GAMES (Spanish Collaboration on Endocarditis — Grupos de Apoyo al competitive funding: PI07 / 0723, Biomarker Tools to Design Clinical Vaccines Determined from a Study Manejo de la E. PI10 / 01497 and API11 / 35. of Annual Listeriosis Incidence in Infective endocarditis: Absence Northern Spain. of microbiological diagnosis is an Front Immunol. 2016;7:541-541. independent predictor of inhospital 6. Tuberculosis (Infection / F.I.:5,695. [doi:10.3389/ mortality. Disease) and Genetic Alterations. fimmu.2016.00541] Int J Cardiol. 2016;220:162-165. F.I.:4,638. [doi:10.1016/j. The study of alleles and haplotypes 3. López-Medrano F, Fernández-Ruiz ijcard.2016.06.129] of the major histocompatibility M, Silva JT, Carver PL, van Delden C, Merino E, Pérez-Saez MJ, Montero M, 6. Parra JA, Cuesta JM, Zarrabeitia complex between healthy controls, Coussement J, de Abreu Mazzolin M, R, Fariñas-Álvarez C, Bueno J, individuals with latent tuberculosis Cervera C, Santos L, Sabé N, Scemla Marqués S, Parra-Fariñas C, and individuals with active A, Cordero E, Cruzado-Vega L, Martín- Botella ML, Bernabéu C, Zarauza J. Moreno PL, Len Ó, Rudas E, Ponce de Screening pulmonary arteriovenous pulmonary tuberculosis in the malformations in a large cohort of population of Cantabria, is one of León A, Arriola M, Lauzurica R, David M, González-Rico C, Henríquez-Palop Spanish patients with hemorrhagic the lines initiated in 2008 and later F, Fortún J, Nucci M, Manuel O, Paño- hereditary telangiectasia. Research Areas Infectious Diseases and Immune System Area

Int J Cardiol. 2016;218:240-245. 316. multicenter, prospective, cohort F.I.:4,638. [doi:10.1016/j. F.I.:4,097. [doi:10.1016/j. study. ijcard.2016.05.065] ijantimicag.2016.05.021] Medicine (Baltimore). 2016;95: F.I.:2,133. [doi:10.1097/ 7. Benito N, Franco M, Ribera A, 11. Fortún J, Muriel A, Martín-Dávila MD.0000000000004008] Soriano A, Rodriguez-Pardo D, Sorlí P, Montejo M, Len O, Torre-Cisneros L, Fresco G, Fernández-Sampedro J, Carratalá J, Muñoz P, Fariñas C, 16. García-Álvarez L, Sanz MM, Marín M, Dolores Del Toro M, Guío L, Moreno A, Fresco G, Goikoetxea J, M, Fariñas M, Montejo M, Goikoetxea Sánchez-Rivas E, Bahamonde A, Riera Gavaldá J, Pozo JC, Bodro M, Vena J, Rodríguez García R, de Alarcón M, Esteban J, Baraia-Etxaburu JM, A, Casafont F, Cervera C, Silva JT, A, Almela M, Fernández-Hidalgo N, Martínez-Alvarez J, Jover-Sáenz A, Aguado JM, Alonso Socas MD, Goenaga MÁ, Dueñas C, Ramos A, Sobrino B, Euba GESITRA/GEMICOMED (SEIMC), Navas E, Vicioso L, Oteo JA, G, Morata L, Pigrau C, Coll P, Mur I, and REIPI (a).. Caspofungin versus Spanish Collaboration on Ariza J, fluconazole as prophylaxis of Endocarditis-Grupo de Apoyo REIPI (Spanish Network for invasive fungal infection in high-risk al Manejo de la Endocarditi. Research in Infectious Disease) liver transplantation recipients: A Tropheryma whipplei endocarditis Group for the Study o. Time trends propensity score analysis. in Spain: Case reports of 17 in the aetiology of prosthetic joint Liver Transpl. 2016;22:427-435. prospective cases. infections: a multicentre cohort F.I.:3,951. [doi:10.1002/lt.24391] Medicine (Baltimore). 2016;95: study. F.I.:2,133. [doi:10.1097/ Clin Microbiol Infect. 2016;22: 12. Martínez-Sellés M, Bouza E, MD.0000000000004058] F.I.:4,575. [doi:10.1016/j. Díez-Villanueva P, Valerio M, Fariñas cmi.2016.05.004] MC, Muñoz-García AJ, Ruiz-Morales 17. Suberviola B, Márquez-López J, Gálvez-Acebal J, Antorrena I, de la A, Castellanos-Ortega A, Fernández- 8. Cuervo G, Gasch O, Shaw E, Hera Galarza JM, Navas E, Muñoz P. Mazarrasa C, Santibáñez M, Martínez Camoez M, Domínguez MÁ, Padilla Incidence and clinical impact LM. B, Pintado V, Almirante B, Lepe JA, of infective endocarditis after Microbiological Diagnosis of Sepsis: López-Medrano F, Ruiz de Gopegui transcatheter aortic valve Polymerase Chain Reaction System E, Martínez JA, Montejo JM, Perez- implantation. Versus Blood Cultures. Nadales E, Arnáiz A, Goenaga MÁ, EuroIntervention. 2016;11:1180-1187. AM J CRIT CARE. 2016;25:68-75. Benito N, Horcajada JP, Rodríguez- F.I.:3,863. [doi:10.4244/ F.I.:2,053. [doi:10.4037/ajcc2016728] Baño J, Pujol M. EIJY15M02_05] REIPI/GEIH study group. Clinical 18. Amado Diago CA, García-Unzueta characteristics, treatment and 13. Ramos A, García-Montero C, MT, Fariñas MD, Amado JA. outcomes of MRSA bacteraemia in Moreno A, Muñoz P, Ruiz-Morales Calcitriol-modulated human the elderly. J, Sánchez-Espín G, Porras C, Sousa antibiotics: New pathophysiological J Infect. 2016;72:309-316. D, Castelo L, Del Carmen Fariñas aspects of vitamin D. F.I.:4,382. [doi:10.1016/j. M, Gutiérrez F, Reguera JM, Plata A, Endocrinol Nutr. 2016;63:87-94. jinf.2015.12.009] Bouza E, Antorrena I, de Alarcón A, F.I.:1,314. [doi:10.1016/j. Pericás JM, Gurguí M, Rodríguez- endonu.2015.09.005] 9. Rodríguez AH, Avilés-Jurado FX, Abella H, Ángel Goenaga M, Antonio Díaz E, Schuetz P, Trefler SI, Solé- Oteo J, García-Pavía P. 19. Arnáiz-García AM, Arnáiz-García Violán J, Cordero L, Vidaur L, Estella Endocarditis in patients with ME, González-Santos JM, Arnáiz J. Á, Pozo Laderas JC, Socias L, Vergara ascending aortic prosthetic graft: Cistitis enfisematosa. JC, Zaragoza R, Bonastre J, Guerrero a case series from a national Med Clin (Barc). 2016;147:184-184. JE, Suberviola B, Cilloniz C, Restrepo multicentre registry. F.I.:1,267. [doi:10.1016/j. MI, Martín-Loeches I, Eur J Cardiothorac Surg. medcli.2015.11.033] SEMICYUC/GETGAG Working 2016;50:1149-1157. Group. Procalcitonin (PCT) levels F.I.:2,803. [doi:10.1093/ejcts/ezw190] 20. Urbina Soto L, García Ávila S, for ruling-out bacterial coinfection Córdoba Alonso AI, Roiz Mesones in ICU patients with influenza: A 14. Amado CA, García-Unzueta MT, MP, Arnaiz García AM, Valero Díaz de CHAID decision-tree analysis. Fariñas MC, Santos F, Ortiz M, Muñoz- Lamadrid MC. J Infect. 2016;72:143-151. Cacho P, Amado JA. Clostridium difficile associated F.I.:4,382. [doi:10.1016/j. Vitamin D nutritional status and diarrhoea: An increased problem. jinf.2015.11.007] vitamin D regulated antimicrobial Med Clin (Barc). 2016;147:543-546. peptides in serum and pleural fluid F.I.:1,267. [doi:10.1016/j. 10. Lora-Tamayo J, Euba G, Cobo J, of patients with infectious and medcli.2016.09.026] Horcajada JP, Soriano A, Sandoval noninfectious pleural effusions. E, Pigrau C, Benito N, Falgueras L, BMC Pulm Med. 2016;16:99-99. 21. Rodrigo E, Suberviola B, Albines Palomino J, Del Toro MD, Jover-Sáenz F.I.:2,329. [doi:10.1186/s12890-016- Z, Castellanos Á, Heras M, Rodriguez- A, Iribarren JA, Sánchez-Somolinos 0259-4] Borregán JC, Piñera C, Serrano M, M, Ramos A, Fernández-Sampedro M, Arias M. Riera M, Baraia-Etxaburu JM, Ariza J, 15. Dominguez F, Ramos A, Bouza A comparison of acute kidney injury Prosthetic Joint Infection Group of E, Muñoz P, Valerio MC, Fariñas MC, classification systems in sepsis. the Spanish Network for Research in de Berrazueta JR, Zarauza J, Pericás Nefrologia. 2016;36:530-534. Infectio. Short- versus long-duration Pulido JM, Paré JC, de Alarcón A, F.I.:1,207. [doi:10.1016/j. levofloxacin plus rifampicin for Sousa D, Rodriguez Bailón I, Montejo- nefro.2016.03.021] acute staphylococcal prosthetic joint Baranda M, Noureddine M, García infection managed with implant Vázquez E, Garcia-Pavia P. 22. Capdevila, Josep A., Guembe, retention: a randomised clinical trial. Infective endocarditis in Maria, Barberan, Jose, de Alarcon, Int J Antimicrob Agents. 2016;48:310- hypertrophic cardiomyopathy: A Aristides, Bouza, Emilio, Carmen 191

Farinas, M., Galvez, Juan, Angel Goenaga, Miguel, Gutierrez, Reviews 5. Liebana Maria Piedra Anton. Francisco, Kestler, Martha, Llinares, Information systems of urgency Pedro, Miro, Jose M., Montejo, services. Application to the Miguel, Munoz, Patricia, Rodriguez- 1. Torre-Cisneros J, Aguado JM, Caston Sierrallana Hospital. Creixems, Marta, Sousa, Dolores, JJ, Almenar L, Alonso A, Cantisán Directors: Luis Ansorena Pool, Cuenca, Jose, Mestres, Carlos-A., S, Carratalá J, Cervera C, Cordero E, María Del Carmen Fariñas Álvarez. SEICAV Soc, SEMI Soc, SEQ Fariñas MC, Fernández-Ruiz M, Fortún University of Cantabria. Soc, SECTCV Soc. 2016 Expert J, Frauca E, Gavaldá J, Hernández D, consensus document on prevention, Herrero I, Len O, Lopez-Medrano F, diagnosis and treatment of short- Manito N, Marcos MA, Martín-Dávila 6. Marcos Pajaron Guerrero. term peripheral venous catheter- P, Monforte V, Montejo M, Moreno A, Self-management of intravenous related infections in adult. Muñoz P, Navarro D, Pérez-Romero antimicrobial treatment (a-tade) in Rev Esp Quimioter. 2016;29:230-238. P, Rodriguez-Bernot A, Rumbao J, infective endocarditis: a safe and F.I.:1,014. ..., Spanish Network for Research efficient care model. in Infectious Diseases (REIPI). Director/es: María Del Carmen 23. Arminanzas, Carlos, Antonio Management of cytomegalovirus Fariñas Álvarez, José Ramón De Herrera, Luis, Carmen Farinas, Maria. infection in solid organ transplant Berrazueta Fernández. Bacteriobilia: a non-resolved recipients: SET/GESITRA-SEIMC/ University of Cantabria. problem. REIPI recommendations. Rev Esp Quimioter. 2016;29:113-118. Transplant Rev (Orlando). 2016;30:119- F.I.:1,014. 143.F.I.:3,915. [doi:10.1016/j. trre.2016.04.001] 24. Armiñanzas C, Tigera T, Ferrer 2. Armiñanzas C, Herrera LA, D, Calvo J, Herrera LA, Pajarón PROJECTS M, Gómez-Fleitas M, Fariñas MC. Fariñas MC. Papel de la bacteriobilia en las Bacteriobilia: un problema sin complicaciones postoperatorias. resolver. Rev Esp Quimioter. 2016;29:123-129. Rev Esp Quimioter. 2016;29:113-118. F.I.:1,014. F.I.:1,014. Projects

25. Arminanzas, Carlos, Tigera, Teresa, Ferrer, Diego, Calvo, Jorge, 1. María del Carmen Fariñas Álvarez. Antonio Herrera, Luis, Pajaron, Doctoral thesis Spanish Network of Research Marcos, Gomez-Fleitas, Manuel, in Infectious Pathology. Carmen Farinas, Maria. RD12/0015/0019. Role of bacteriobilia in postoperative 1. Ana Mª Arnaiz García. INSTITUTO DE SALUD CARLOS III. complications. Morbidity and mortality in deferred MINISTERIO DE ECONOMÍA Y Rev Esp Quimioter. 2016;29:123-129. sternal closure. COMPETITIVIDAD. F.I.:1,014. Directors: José Manuel Bernal Marco, Mª Concepcion Fariñas 2. María del Carmen Fariñas 26. Planelles D, Vilches C, González- Álvarez, María Del Carmen Fariñas Álvarez. Intestinal colonization by Escribano F, Muro M, González- Álvarez. multiresistant enterobacteria in Fernández R, Sánchez F, Gonzalo University of Cantabria. patients with renal and hepatic Ocejo J, Eiras A, Caro JL, Palou E, transplantation: multicenter cohort Campillo JA, de Juan MD, Montes O, 2. Gabriela Saravia Campelli. study and randomized, controlled Balas A, Marín L, Torío A, Fernández- A randomized intervention program and open clinical trial. Arquero M, González-Roiz C, López- to optimize the quality of antibiotic PI13/01191. Vázquez A, Cisneros E, Abad-Molina use in the hospital. INSTITUTO DE SALUD CARLOS III. C, López R, Abad-Alastruey ML, Serra Directors: María Del Carmen Fariñas MINISTERIO DE ECONOMÍA Y C, García-Alonso AM, Vicario JL. Álvarez, Mª Concepcion Fariñas COMPETITIVIDAD. Report From the First and Second Álvarez. Spanish Killer Immunoglobulin-Like University of Cantabria. 3. María del Carmen Fariñas Álvarez. Receptor Genotyping Workshops: Impact of intestinal colonization External Quality Control for Natural 3. Javier Gonzalo Ocejo Viñals. by multiresistant enterobacteria on Killer Alloreactive Donor Selection Immunogenetics of pulmonary systemic infections, graft versus in Haploidentical Stem Cell tuberculosis: influence of major host disease (GVHD), and mortality Transplantation. histocompatibility complex of patients receiving allogeneic Transplant Proc. 2016;48:3043-3045. polymorphisms, repertoire of kir transplantation of haematopoietic F.I.:0,867. [doi:10.1016/j. genes and other genes of the progenitors (Alo-TPH). transproceed.2016.07.037] immune system. PI16/01415. Director: María Del Carmen Fariñas INSTITUTO DE SALUD CARLOS III. 27. Eza-Nuñez P, Fariñas-Alvarez C, Álvarez. MINISTERIO DE ECONOMÍA Y Fernandez NP. University of Cantabria. COMPETITIVIDAD. Comparison of three diagnostic tests in detecting vestibular 4. Jose Alberto Sanchez Ortega. 4. María del Carmen Fariñas Álvarez. deficit in patients with peripheral Prevalence of tobacco, alcohol and Thematic Network on Infectious vestibulopathy. drug use among university students Diseases. RD16/0016/0007. J Laryngol Otol. 2016;130:145-150. in Cantabria. INSTITUTO DE SALUD CARLOS III. F.I.:0,736. [doi:10.1017/ Directors: Javier Llorca Díaz, Mª MINISTERIO DE ECONOMÍA Y S0022215115003114] Concepcion Fariñas Álvarez. University of Cantabria. COMPETITIVIDAD. Research Areas Infectious Diseases and Immune System Area

Group Leader Nanovaccines and Cellular Carmen Álvarez Domínguez Vaccines Based on Listeria Valdecilla Biomedical MonocytogenesÁreas de and their Research Institute Marqués de Valdecilla Applicationsinvestigación in Biomedicine IDIVAL

[email protected]

Contributors Ricardo Calderón González Susana Gómez Salces Héctor Terán Navarro Sonsoles Yáñez Diaz

Technicians Milagros González Toca

Emerging group

08695, SAF2012-34203). To 2. Listeria based dendritic establish cerebral and neonatal vaccines loaded with peptides Research listeriosis models to analyze specific against infectious agents. virulence factors of the pathogen Lines targeted to microglia and design (PI: Dr. C. Alvarez Dominguez and Co-PI: Dra. S. Yañez Diaz/Grants: a cerebral listeriosis vaccine. This SAF2009-08695 y SAF2012-34203 study implies the characterization and Approved Clinical Study: of microglia phagosomes using 1.Cerebral listeriosis and neonatal CEIC-Acta 19/2014- 2014.228). A listeriosis models. differential proteomics (col. C. Gil. Listeria based dendritic vaccine UCM) and examine new adjuvants loaded with peptides from virulence (PI: Dr. C. Alvarez Domínguez/ for neonatal vaccines (col. M. factors specific of Listeria (LLO) Grants: SAF2006- 08968, SAF2009- Fresno, CBMSO). and common to Mycobacterium

Figura1. Listeriosis cerebral neonatal y papel de microglía 193

Figura 2. Vacuna dendrítica con un nuevo antígeno de Listeria monocytogenes: GAPDH.

smegmatis (GAPDH) will be used to group preparing AuGNP (cols. Dr. examine experimental prophylactic M. Marradi, Dr. I. Garcia and Dr. Devices. 2016;4:9021-9026. measures against both bacteria. S. Penades). We have performed F.I.:5,066. [doi:10.1039/c6tc01408a] Moreover, we are performing a studies with a prophylactic 3. Calderon-Gonzalez R, Bronchalo- clinical study with listeriosis patients experimental nanovaccine Vicente L, Freire J, Frande-Cabanes from a 2014 outbreak with Dr. C. against listeriosis and a non- E, Alaez-Alvarez L, Gomez-Roman J, Fariñas (Infectious Section-HUMV) pathogenic tuberculosis model. Yañez-Diaz S, Alvarez-Dominguez C. and Dr. Martinez (Microbiology Dpt- The efficiency of nanovaccine Exceptional antineoplastic activity HUMV) and Biodonostia Group of is based in their targeting to of a dendritic-cell-targeted vaccine Microbiologists (col. Dr. E. Trallero, dendritic cells, lack of toxicity, loaded with a Listeria peptide Dr. J. Marimon and Dr. CG. Cilla) biocompatibility and induction proposed against metastatic to elaborate a human vaccine for of a cytotoxic cellular immune melanoma. patients at high risk of listeriosis response. Other applications with Oncotarget. 2016;7:16855-16865. these Nanovaccines and their F.I.:5,008. [doi:10.18632/ oncotarget.7806]. modifications are tumor therapies. 3. Listeria based dendritic vaccines loaded with peptides 4. Gomez-Salces, Susana, Barreda- against melanoma. Argueso, Jose A., Valiente, Rafael, Rodriguez, Fernando. (IP: Dr. C. Alvarez Dominguez y Dra. Solarization-induced redox reactions in doubly Ce3+/Mn2+- S. Yañez Diaz/Proyects: SAF2009- doped highly transmission glasses 08695 y SAF2012-34203 y Estudio studied by optical absorption and Clínicos aprobado: CEIC-Acta photoluminescence. 30/2012). A Listeria-based DC PUBLICACIONS: Sol Energy Mater Sol Cells. vaccine loaded with the peptide 2016;157:42-47. LLO91-99 is used as anti-adhesive F.I.:4,732. [doi:10.1016/j. therapy for melanoma in murine IMPACT FACTOR | 25,070 solmat.2016.05.010]. models (Dr. J. Gomez-Roman, S. Anatomia Patologica) and to prepare 5. Calderon-Gonzalez, Ricardo, Teran- Navarro, Hector, Frande-Cabanes, in melanoma patients a vaccine Elisabet, Ferrandez-Fernandez, Eva, DC in combination with the HUMV Original articles Freire, Javier, Penades, Soledad, Oncology and Dermatology Services Marradi, Marco, Garcia, Isabel, Gomez- (metastatic melanoma) (Dr. H. Roman, Javier, Yanez-Diaz, Sonsoles, 1. Calderon-Gonzalez R, Teran-Navarro Fernandez-Llaca and Dr. A. Garcia) Alvarez-Dominguez, Carmen. H, Marimon JM, González-Rico C, Pregnancy Vaccination with Gold and the UPV Human Melanoma Calvo-Montes J, Frande-Cabanes E, Glyco-Nanoparticles Carrying Group (Dr. Boyano Lopez). Alkorta-Gurrutxaga M, Fariñas MC, Listeria monocytogenes Peptides Martínez-Martínez L, Perez-Trallero E, Protects against Listeriosis and Alvarez-Dominguez C. Brain- and Cutaneous-Associated 4. Listeria based Nanovaccines Biomarker Tools to Design Clinical Morbidities. and their applications. Vaccines Determined from a Study Nanomaterials (Basel). 2016;6: of Annual Listeriosis Incidence in F.I.:2,690. [doi:10.3390/nano6080151]. (PI: Dr. C. Alvarez Dominguez, Dr. Northern Spain. S. Gomez Salces and Dr. S. Yañez Front Immunol. 2016;7:541-541. 6. Vazquez, G. V., Valiente, R., Gomez- Diaz/Grants: SAF2012-34203, F.I.:5,695. [doi:10.3389/ Salces, S., Flores-Romero, E., Rickards, and Approved Clinical Study: fimmu.2016.00541]. J., Trejo-Luna, R. CEIC-Acta 1/2016-2015.177). In Carbon implanted waveguides in 2. Gomez-Salces, Susana, Antonio this study, we used as vaccine soda lime glass doped with Yb3+ Barreda-Argueso, Jose, Valiente, vectors gold glyconanoparticles and Er3+ for visible light emission. Rafael, Rodrigueza, Fernando. (AuGNP) of 2 nm size conjugated OPT LASER TECHNOL. 2016;79:132- A study of Ce3+ to Mn2+ energy to Listeria peptides, LLO91-99 and 136. transfer in high transmission glasses F.I.:1,879. [doi:10.1016/j. GAPDH1-22. The group of CIC- using time-resolved spectroscopy. J optlastec.2015.12.002]. biomaGUNE collaborates with our Mater Chem C Mater Opt Electron Research Areas Infectious Diseases and Immune System Area

Group Leader Jesús Merino Pérez Department of Molecular ImmunopathologyÁreas de of Biology School of Medicine Rheumaticinvestigación Diseases University of Cantabria

[email protected]

Contributors Elena Aurrecoechea Aguinaga Luis Buelta Carrillo Manuel Ignacio González Carreró Marcos Iglesias Lozano Marta Muñoz Ruiz Jorge Postigo Fernández Teresa Ruiz Jimeno Juan Ignacio Villa Blanco

Predoctoral Pilar Álvarez Sáinz de la Maza

Technicians María Aramburu Landeras Natalia Cobo Rosado Yordana Vega Miranda

Jointly Responsible Jaime Calvo Alén Consolidated group 195

the role in inflammation of the > Influence of treatment with immunomodulatory molecules, TNF inhibitors in the oxidative Research CD38 (Dr. Jaime Sancho, Granada), phenotype of HDL cholesterol CD5 and CD6 (Dr Francisco Lozano, and its influence on their anti- Lines Barcelona), the transcriptional atherogenic capacity in patients factors E2F1 and E2F2 (Dr. with rheumatoid arthritis. Ana Zubiaga, UPV) and GPBP > Lipoprotein profiles and HDL (Goodpasture antigen binding phenotypes in patients with The research activity of our group protein), a protein-kinase that forms systemic lupus erithematosus focuses on the study of the cellular quaternary protein structures (Dr (SLE) in correlation with and molecular mechanisms Juan Saus, Fibrostatin SL, Valencia). involved in rheumatic inflammatory inter-ethnic differences, in diseases. Our final aims are the Overall, this research activity collaboration with the University identification and characterization pretends to validate these of Puebla (Mexico). molecules as therapeutic targets of potential therapeutic targets for > Prospective evaluation of in inflammation and autoimmune the treatment of these diseases. individuals with high titers of diseases. For this purpose we use We undertake these tasks from a antinuclear antibodies (>1280) murine models of these diseases, basic approach, coordinated by Dr. without clinical symptoms of such as the collagen-II-induced Jesus Merino at the University of autoimmune diseases. Cantabria, and a clinical approach arthritis, adriamycin or bleomycin- coordinated by Dr. Jaime Calvo induced pulmonary fibrosis, the > Evaluation of new criteria for at the Hospital Sierrallana of colitis induced by sodium dextran clinical classification of SLE Torrelavega. Jesus Merino, in sulphate, or the psoriasis caused patients (SLICC criteria), in close collaboration with Dr. Ramon by local application of Imiquimod collaboration with Dr. Luis Ines Merino (IBBTEC), is studying or i.p. injection of Saccharomyces (University of Coimbra, Portugal). cerevisiae mannan. several molecules involved in the > Co-chairman in the RELESSER- control of inflammatory responses, PROS registration for the follow- such as BAMBI (BMP and activin > PImpact of gender on prognosis up of SLE patients. membrane bound inhibitor) and of rheumatoid arthritis, with > Phase 3 Clinical trials: two trials BCL2A1 (a cell death regulator). We particular emphasis on quality of in rheumatoid arthritis and one in maintain also collaborations with life. other Spanish groups to evaluate psoriatic arthritis. Research Areas Infectious Diseases and Immune System Area

PUBLICATIONS: Sánchez-Atrio AI, Santos-Soler G, Zea Merino R. A, Díez E, Narváez J, Blanco-Alonso Selective Impairment of TH17- R, Silva-Fernández L, Ruiz-Lucea ME, Differentiation and Protection IMPACT FACTOR | 56,390 Fernández-Castro M, Hernández- against Autoimmune Arthritis after Beriain JÁ, Gantes-Mora M, ..., Overexpression of BCL2A1 in T López-Longo FJ. Lymphocytes. Relationship between damage PLoS One. 2016;11: clustering and mortality in F.I.:3,057. [doi:10.1371/journal. Original articles systemic lupus erythematosus pone.0159714] in early and late stages of the disease: cluster analyses in a large 1. Orta-Mascaró M, Consuegra- cohort from the Spanish Society of 9. Torrente-Segarra V, Salman-Monte Fernández M, Carreras E, Roncagalli Rheumatology Lupus Registry. TC, Rúa-Figueroa Í, Pérez-Vicente S, R, Carreras-Sureda A, Alvarez P, Rheumatology (Oxford). López-Longo FJ, Galindo-Izquierdo Girard L, Simões I, Martínez-Florensa 2016;55:1243-1250. M, Calvo-Alén J, Olivé-Marqués A, M, Aranda F, Merino R, Martínez VG, F.I.:4,524. [doi:10.1093/ Ibañez-Ruán J, Horcada L, Sánchez- Vicente R, Merino J, Sarukhan A, rheumatology/kew049] Atrio A, Montilla C, Rodríguez-Gómez Malissen M, Malissen B, Lozano F. M, Díez-Álvarez E, Martinez-Taboada CD6 modulates thymocyte V, Andreu JL, Fernández-Berrizbeitia selection and peripheral T cell 5. Rosal-Vela A, Barroso A, Giménez O, Hernández-Beriain JA, Gantes M, homeostasis. E, García-Rodríguez S, Longobardo V, Hernández-Cruz B, Pecondón-Español J Exp Med. 2016;213:1387-1397. Postigo J, Iglesias M, Lario A, Merino Á, Marras C, Bonilla G, Pego-Reigosa F.I.:11,240. [doi:10.1084/ J, Merino R, Zubiaur M, Sanz-Nebot JM. jem.20151785] V, Sancho J. RELESSER Study Group of the Identification of multiple transferrin Spanish Society of Rheumatology species in the spleen and serum (SER) and the Study. Fibromyalgia 2. Postigo J, Iglesias M, Álvarez from mice with collagen-induced prevalence and related factors in P, Augustin JJ, Buelta L, Merino J, arthritis which may reflect changes a large registry of patients with Merino R. in transferrin glycosylation systemic lupus erythematosus. Bone Morphogenetic Protein and associated with disease activity: Clin Exp Rheumatol. 2016;34:40-47. Activin Membrane-Bound Inhibitor, The role of CD38. F.I.:2,495. a Transforming Growth Factor ß J PROTEOMICS. 2016;134:127-137. Rheostat That Controls Murine Treg F.I.:3,867. [doi:10.1016/j. Cell/Th17 Cell Differentiation and jprot.2015.11.023] 10. Rua-Figueroa, I., Castro, M. the Development of Autoimmune Fernandez, Pego-Reigosa, J. M., Arthritis by Reducing Interleukin-2 Sanchez-Piedra, C., Lopez-Longo, Signaling. 6. Alvarez P, Jensen LE. J., Taboada, V. Martinez, Calvo-Alen, Arthritis Rheumatol. 2016;68:1551- Imiquimod Treatment Causes J., Olive, A., Galindo, M., Blanco, R., 1562. Systemic Disease in Mice Alonso, F., Erausquin, C., Andreu, J. L. F.I.:6,009. [doi:10.1002/art.39557] Resembling Generalized Pustular Prevalence of comorbidities in Psoriasis in an IL-1 and IL-36 patients with primary sjogren’s Dependent Manner. syndrome and systemic lupus 3. López-Hoyos M, Álvarez- Mediators Inflamm. 2016;2016: erythematosus: a comparative, Rodríguez L, Mahler M, Torices S, 6756138-6756138. register-based study with emphasis Calvo-Alén J, Villa I, Seaman A, Yee F.I.:3,418. in cardiovascular disease. A, Martínez-Taboada V. [doi:10.1155/2016/6756138] Clin Exp Rheumatol. 2016;34:98-99. Anti-carbamylated protein F.I.:2,495. antibodies in patients with ageing associated inflammatory chronic 7. Alvarez P, Genre F, Iglesias M, disorders. Augustin JJ, Tamayo E, Escolà-Gil 11. Galindo-Izquierdo M, Rodriguez- Rheumatology (Oxford). 2016;55:764- JC, Lavín B, Blanco-Vaca F, Merino R, Almaraz E, Pego-Reigosa JM, 766. Merino J. López-Longo FJ, Calvo-Alén J, Olivé A, F.I.:4,524. [doi:10.1093/ Modulation of autoimmune Fernández-Nebro A, Martinez-Taboada rheumatology/kev391] arthritis severity in mice by V, Vela-Casasempere P, Freire M, apolipoprotein E (ApoE) and Narváez FJ, Rosas J, Ibáñez-Barceló M, cholesterol. 4. Pego-Reigosa JM, Lois-Iglesias A, Uriarte E, Tomero E, Zea A, Horcada L, CLIN EXP IMMUNOL. 2016;186:292- Rúa-Figueroa Í, Galindo M, Calvo- Torrente V, Castellvi I, Calvet J, Menor- 303. Alén J, de Uña-Álvarez J, Balboa- Almagro R, Zamorano MA, Raya E, F.I.:3,148. [doi:10.1111/cei.12857] Barreiro V, Ibáñez Ruan J, Olivé A, Díez-Álvarez E, Vázquez-Rodríguez Rodríguez-Gómez M, Fernández T, García de la Peña P, Movasat A, Nebro A, Andrés M, Erausquin C, Andreu JL, Richi P, ..., 8. Iglesias M, Augustin JJ, Alvarez P, Tomero E, Horcada Rubio L, Uriarte RELESSER Group, from the Santiuste I, Postigo J, Merino J, Isacelaya E, Freire M, Montilla C, Spanish Society of Rheumatology 197

Systemic Autoimmune Dis. 12. Canut-Blasco A, Calvo J, Reviews Characterization of Patients With Rodríguez Díaz JC, Martínez- Lupus Nephritis Included in a Martínez L. 1. Rodríguez-Martínez JM, Machuca Large Cohort From the Spanish Informes acumulados de J, Cano ME, Calvo J, Martínez- Society of Rheumatology Registry sensibilidad a los antimicrobianos. of Patients With Systemic Lupus Martínez L, Pascual A. Enferm Infecc Microbiol Clin. Plasmid-mediated quinolone Erythematosus (RELESSER). 2016;34:524-530. resistance: Two decades on. Medicine (Baltimore). 2016;95: F.I.:1,530. [doi:10.1016/j. Drug Resist Updat. 2016;29:13-29. F.I.:2,133. [doi:10.1097/ eimc.2015.03.019] F.I.:7,950. [doi:10.1016/j. MD.0000000000002891] drup.2016.09.001] Research Areas Infectious Diseases and Immune System Area

Group Leader Jorge Calvo Montes Microbiology Service Áreas de University Hospital Clinical and Molecular Marqués de Valdecilla Microbiologyinvestigación

[email protected]

Marina Fernández Torres Carlos Fernández Mazarrasa Maria Lázaro Diez Inmaculada Concepción Pérez del Molino Bernal Santiago Redondo Salvo María Asunción Rodríguez Feijoo Jesús Rodríguez Lozano Consolidated group María Pía Róiz Mesones Carlos Ruiz De Alegría Puig Ana Sáez López Carlos Salas Venero Researchers Contributors Jesús Agüero Balbín Amaia Aguirre Quiñonero María Victoria Francia Gil Itziar Angulo López Technicians Jesús Navas Méndez María Eliecer Cano García Alain Antonio Ocampo Sosa Itziar Chapartegui González Laura Álvarez Montes José Ramos Vivas Marta Fernández Martinez María Jesús Lecea Cuello

investigadora de nuestro grupo se entre otros. En relación con ello, centra en el estudio de aspectos los dos aspectos a los que se ha Líneas de genéticos y bioquímicos de los prestado particular atención son la mecanismos de resistencia a multirresistencia y el bajo nivel de investigación los antimicrobianos de mayor resistencia. El impacto clínico de interés clínico (fundamentalmente, los organismos multirresistentes beta-lactámicos, quinolonas y es profundo ya que existen pocos aminoglucósidos) en una gama de fármacos nuevos en desarrollo que 1. Resistencia a los bacterias resistentes, particularmente sean eficaces contra estas cepas. El antimicrobianos en bacterias los organismos Gramnegativos como grupo forma parte del Programa de Gram-negativas de interés médico. enterobacterias (Escherichia coli, Resistencia a los Antimicrobianos Klebsiella pneumoniae, Enterobacter de la Red de Investigación en La resistencia a los antimicrobianos spp.) y los no fermentadores Patología Infecciosa (REIPI, http:// es un problema importante desde como Pseudomonas aeruginosa, reipi.org/) financiada por el ISCIII. el punto de vista de la salud Actinetobacter baumannii y el Esta Red ha desarrollado y está pública. Gran parte de la actividad complejo de Burkholderia cepacia, desarrollando diversos estudios 199

multicéntricos sobre aspectos como es el caso de Pseudomonas evaluar la importancia de las bombas clínicos y microbiológicos putida y otras especies relacionadas de expulsión activa en la resistencia de infecciones causadas por taxonómicamente como P. monteilii, intrínseca de bacterias Gram- microorganismos resistentes de que constituyen reservorios de negativas a antibióticos utilizados interés clínico, un grave problema genes de multirresistencia, en en la clínica, como los mencionados sanitario en muchos hospitales particular MBL, de las cuales se han beta-lactámicos, quinolonas españoles. Nuestra colaboración en reportado infecciones nosocomiales y aminoglucósidos, así como el estudio de las bases moleculares causadas por estas cepas portando estudiar el papel de las porinas de de la resistencia ha permitido obtener VIM-2 en pacientes gravemente enterobacterias (fundamentalmente nueva información sobre aspectos enfermos o inmunocomprometidos K. pneumoniae, E. coli, Enterobacter clínicos de las infecciones causadas, con frecuencia hospitalizados en spp.) en la resistencia de bajo nivel entre otros, por Escherichia unidades de cuidados intensivos. Las a los antibióticos y el estudio de los coli, Klebsiella pneumoniae, fluoroquinolonas como ciprofloxacino mecanismos de regulación de la Pseudomonas aeruginosa y son antibióticos de amplio espectro porina OprD de P. aeruginosa en la Acinetobacter baumannii. El grupo de una gran utilidad para tratar resistencia a carbapenémicos. colabora también activamente en infecciones por varias especies de el otro programa, de infecciones en Gram-negativos y Gram-positivos. trasplantados, de la REIPI. Nuestros Debido a que estos son agentes 2. Mecanismos de patogenicidad objetivos incluyen la caracterización totalmente sintéticos se pensó que e interacciones patógeno/ de genes y elementos móviles la resistencia transferible era poco hospedador en bacterias gram- (plásmidos, transposones, integrones, probable, ya que no hay ningún negativas de interés clínico. casetes genéticos) implicados en la organismo ambiental productor Pseudomonas aeruginosa y resistencia a los antimicrobianos. que proporcionara una fuente de Burkholderia cepacia son capaces de Nuestros estudios han contribuido genes de resistencia. Sin embargo, liberar una gran variedad de enzimas también a descubrir y caracterizar numerosos genes qnr (resistencia hidrolíticas e inyectarlas dentro de nuevas beta-lactamasas, como es el a quinolonas) se han diseminado las células del hospedador mediante caso de la nueva oxacilinasa OXA- horizontalmente en todo el mundo complejos sistemas de secreción 207 en cepas de Acinetobacter pittii, en una extensa gama de patógenos (SST) que involucran diversos un microorganismo relacionado bacterianos (principalmente Gram- complejos de proteínas que están con A. baumannii, que también negativos). Por tanto, nuestro grupo parcialmente embebidas dentro está implicado en infecciones continúa con la línea de trabajo de la envoltura celular bacteriana. nosocomiales. Los beta-lactámicos sobre el estudio de los mecanismos Uno de estos sistemas es el SST6, siguen siendo la clase más prescrita plasmídicos de resistencia a recientemente descubierto, el de antibióticos. Dentro de estos, los quinolonas. cual secreta proteínas que están carbapenémicos, los más nuevos implicadas tanto en la interacción con y potentes beta-lactámicos, se La resistencia a los aminoglucósidos células eucariotas como procariotas. han convertido en los fármacos en Gram-negativos, principalmente La secreción de proteínas es de elección para el tratamiento de en enterobacterias, es otra de fundamental en muchos aspectos de infecciones por bacterias patógenas las líneas de trabajo del grupo, la patogénesis bacteriana. Muchas oportunistas Gram-negativas. Sin específicamente 1) la resistencia de las proteínas efectoras del SST6 embargo, la resistencia a estos debida a la presencia de enzimas se relacionan con las capacidades antimicrobianos ha surgido en modificadoras de aminoglucósidos de adhesión e invasión a la célula varias especies de Gram-negativos, del tipo N-acetiltransferasas hospedadora, así como la inducción fundamentalmente mediada por (AAC), Ofosfotransferasas (APH) de crecimiento y la supervivencia enzimas que contrarrestan la y O-nucleotidiltransferasas (ANT) intracelular en macrófagos. Nuestro acción de los carbapenémicos que provocan que su fijación al grupo se centra en la caracterización llamadas carbapenemasas. Entre ARN 16S se vea afectada y de de nuevos efectores de SST6 nuestros objetivos está el uso esta forma pierdan su actividad, y en Pseudomonas aeruginosa y métodos fenotípicos y genotípicos 2) a la presencia de metilasas de diferentes especies dentro del para estudiar y caracterizar y ARN 16S, que como su nombre complejo de Burkholderia cepacia. los mecanismos de resistencia lo indica metilan esta molécula en Por otro lado, se ha visto que los a carbapenémicos conferida determinadas posiciones confiriendo SST6 de P. aeruginosa también están por una gama de metalo-beta- resistencia de alto nivel a los relacionado con la producción de lactamasas (MBL) (incluyendo aminoglucósidos. Los genes que biofilms y la resistencia específica el IMP, VIM, SPM y tipos NDM) codifican dichas enzimas suelen de estos a ciertos antibióticos como y por serina-betalactamasas encontrarse en elementos genéticos los aminoglucósidos. Los biofilms de las clases A y D de Ambler. móviles llevados por plásmidos, lo o biopelículas son comunidades Nuestros intereses se extienden cual favorece en gran medida su microbianas formadas por una o también a la caracterización dispersión intra- e inter-especies. varias especies de microorganismos de dichas enzimas aisladas de asociadas a superficies vivas microorganismos ambientales, Otros de nuestros objetivos es o inertes. La mayoría de los Research Areas Infectious Diseases and Immune System Area

microorganismos existen en la naturaleza formando biopelículas, lo cual constituye un medio eficaz mediante el cual estos se mantienen en un nicho protegido. En el hombre, el establecimiento de las biopelículas puede conducir a una infección bacteriana crónica. Se ha demostrado que las biopelículas presentan una mayor resistencia al tratamiento con antibióticos y son resistentes a la erradicación por el sistema inmune. Nuestro grupo también está implicado en la identificación de los principales reguladores que intervienen en la percepción de las señales ambientales mediante “quórum sensing”, que inducen la formación de biopelículas y su dispersión. Y también en la caracterización de los determinantes moleculares que contribuyen a la virulencia y a la resistencia a los antibióticos en estos microorganismos. Para nuestros estudios, disponemos de un amplio abanico de herramientas de genómica y transcriptómica. Varias especies del género Acinetobacter se han vuelto muy importantes como patógenos asociados a infecciones hospitalarias, especialmente en las unidades de cuidados intensivos. hospedador y la resistencia a los 3. Mecanismos de resistencia en Estas bacterias pueden sobrevivir antimicrobianos, nuestro grupo bacterias Gram positivas. en el ambiente hospitalario durante desarrolla una investigación largos periodos de tiempo y tienen multidisciplinar sobre interacciones El grupo está interesado en la una gran propensión a desarrollar hospedador-patógeno en estas tres caracterización de los elementos resistencias a múltiples clases especies de Acinetobacter. genéticos implicados en la resistencia de antibióticos. Esta tendencia a antibióticos y en su diseminación al aumento de resistencias Los objetivos de nuestro grupo en en enterococos multirresistentes, se ha convertido en una gran este campo son: (1) Desarrollar principalmente Enterococcus faecalis preocupación, al reducir las opciones nuevas herramientas para el estudio y terapéuticas para combatir estas de interacciones hospedador- Enterococcus faecium. Ambos cepas multirresistentes. Mientras que patógeno en Acinetobacter. (2) son patógenos oportunistas la epidemiología y los mecanismos Estudiar el impacto de diferentes asociados a bacteriemia, de resistencia de Acinetobacter antibióticos a concentraciones endocarditis e infecciones urinarias baumannii han recibido especial sub-inhibitorias (sub-CMIs) y postoperatorias que normalmente atención durante los últimos años, sobre la producción de biocapas habitan en el intestino humano. Y las bases moleculares, genéticas en Acinetobacter, y sobre las son, además, uno de los organismos y fenotípicas de la virulencia de A. interacciones hospedador-patógeno más comunes implicados en baumannii, A. pittii, y A. nosocomialis in vitro. (3) infecciones nosocomiales a nivel son escasamente conocidas, y mundial. En concreto, estamos tampoco se ha incrementado de Desenmarañar la dinámica y el interesados en el mecanismo de manera importante la información papel de las vesículas extracelulares conjugación de diversos elementos sobre la respuesta del hospedador a producidas por las especies de genéticos móviles enterococales, estas bacterias. Acinetobacter. (4) Realizar un entre ellos, los plásmidos de análisis detallado de la respuesta respuesta a feromonas, que son de células inmunitarias y no plásmidos que se encuentran Respondiendo a la necesidad de inmunitarias humanas frente a cepas en casi un 95% de las cepas estudios sobre los mecanismos de de Acinetobacter de diferentes clínicas de E. faecalis asociadas a interacción con células del fenotipos. brotes hospitalarios y que pueden 201

transferirse con una frecuencia del Nuestro grupo también está de la polimerasa (PCR) se han vuelto 100%. estudiando la resistencia a indispensables para el diagnóstico antimicrobianos en distintas especies de las enfermedades infecciosas. En Enterococcus faecalis Se de corinebacterias. Estas bacterias En la última década, ha habido está analizando la regulación están ampliamente distribuidas en un incremento extraordinario de transcripcional del plásmido la naturaleza, encontrándose en el la utilización de test moleculares conjugativo pAD1, que codifica suelo, agua y también en la piel y para diagnosticar y controlar las múltiples resistencias a antibióticos y mucosas de hombres y animales. enfermedades infecciosas. Como se encuentra en el 90% de las cepas Algunas especies son patógenas resultado, nuestro laboratorio clínicas de E. faecalis asociadas a para el hombre. La especie más de Microbiología Clínica en el brotes hospitalarios. El promotor importante es C. diphteriae, pero Hospital Universitario Marqués de la relaxasa del plásmido se ha también estudiamos otras como, de Valdecilla ofrece un número caracterizado y se ha visto que C. amycolatum, C. xerosis, y C. creciente y consolidado de técnicas tanto la relaxasa como una proteína jeikeium, ya que buena parte de los de amplificación de ácidos nucleicos codificada por un gen adyacente aislados clínicos de estas especies para la detección e identificación regulan negativamente su propia son resistentes a varios antibióticos. de patógenos bacterianos, víricos expresión. Además se ha analizado y fúngicos. Un buen ejemplo de la regulación de la transferencia del En los últimos años hemos nuestra experiencia es laamplificación plásmido, de forma que una región realizado además, estudios sobre y secuenciación del 16S rDNA, de unos 25- 30 Kb se induce en las resistencias a antibióticos en genes de resistencia y mutaciones respuesta a la feromona específica cepas de las especies C. striatum relacionadas con la resistencia a cAD1. Para que esta inducción y C. urealyticum aisladas en el antibióticos. tenga lugar es clave TraE1, de forma hospital Marqués de Valdecilla y su que mutaciones dentro de este entorno cercano. Nos centramos Dada la complejidad del mundo gen impiden la transferencia del en los mecanismos de resistencia y microbiano y del aumento y plásmido. Nuestro objetivo inmediato propagación, y también realizamos sofisticación de las técnicas de es la caracterización del mecanismo estudios de su interacción con el amplificación de ácidos nucleicos, molecular por el que TraE1 regula la hospedador. hemos adquirido no solo experiencia expresión del resto de los genes de para desarrollar ensayos sino también conjugación. El grupo trabaja además en el para la rutina clínica, lo que mejora desarrollo y aplicación de nuevos la atención al paciente, reduce la Se están analizando tanto los métodos para diagnóstico en utilización de antibióticos, optimiza clones de E. faecium como los Microbiología Clínica basados la utilización de pruebas diagnósticas plásmidos que han diseminado en la genómica y la proteómica, y aumenta la eficiencia nuestro la resistencia a vancomicina en principalmente orientados a su laboratorio y del hospital. nuestro hospital durante el periodo aplicación a las actinobacterias. 2002-2012. Principalmente 3 clones Recientemente hemos incorporado (ST132, ST18 y ST192, todos E. un sistema de espectrometría faecium CC17) son responsables 4. Metodología diagnóstica y de masas automatizado para la de la transmisión de la resistencia a epidemiológica. identificación microbiana (Matrix glucopéptidos. Todos estos clones El diagnóstico molecular de las Assisted Laser Desorption Ionization llevan múltiples plásmidos que se enfermedades infecciosas se ha Time-of-Flight, MALDI-TOF) con una están caracterizando. La resistencia a vuelto una herramienta indispensable amplia base de datos de especies vancomicina se localiza en variantes en nuestro Servicio de Microbiología, clínicamente importantes, que del transposón Tn1546que contienen incluyendo la secuenciación y nos permite obtener resultados en principalmente ISEf1 e IS1216. la detección directa de genes minutos. Otra parte importante de nuestro relacionados con la taxonomía trabajo se centra en la identificación microbiana y los mecanismos de Por otra parte, es interesante analizar y caracterización de plásmidos en resistencia a antibióticos. Durante aislados múltiples pertenecientes cepas hospitalarias de E. faecium más de 100 años, los agentes a una especie para determinar multirresistentes, sobre todo en lo causantes de enfermedades si representan una cepa única o que respecta a plásmidos implicados infecciosas han sido identificados múltiples cepas. El proceso de en la aparición y diseminación directamente tras el aislamiento y diferenciar cepas basado en sus de la resistencia a vancomicina, crecimiento en cultivo gracias a su diferencias genotípicas y fenotípicas aunque sin olvidar otros genes de fenotipo. En la era de la biología se conoce como “tipificación”. Los resistencia a antibióticos importantes molecular, tenemos la oportunidad métodos de genotipificación implican en enterococos (resistencia a de detectar patógenos de forma más el estudio del ADN microbiano. aminoglucósidos y macrólidos, rápida y más precisa basándonos principalmente) y su asociación a en su huella genética. Los métodos El desarrollo de métodos de determinados elementos genéticos moleculares, esencialmente los genotipipificación molecular ha móviles. pasados en la reacción en cadena revolucionado la posibilidad de Research Areas Infectious Diseases and Immune System Area

clasificar los microorganismos multicéntricos de evaluación de a nivel de subespecie, lo que es nuevos antimicrobianos, consistentes Original articles crucial para descifrar la relación en medir la actividad in vitro de los molecular entre los aislados, para mismos frente a la amplia colección 1. Calderon-Gonzalez R, Teran- estudios epidemiológicos. Para de cepas de la que dispone nuestro Navarro H, Marimon JM, González- ello, los nuevos métodos de tipado grupo. Asimismo, participamos Rico C, Calvo-Montes J, Frande- basados en PCR han supuesto un en la evaluación con métodos Cabanes E, Alkorta-Gurrutxaga M, avance importante para determinar de referencia de los sistemas Fariñas MC, Martínez-Martínez L, la epidemiología molecular de los automatizados de antibiograma, Perez-Trallero E, Alvarez-Dominguez microorganismos. especialmente cuando estos sistemas C. incorporan antimicrobianos nuevos. Biomarker Tools to Design Clinical Las principales ventajas de estos En los últimos años hemos estudiado Vaccines Determined from a Study métodos son la flexibilidad, la la actividad de daptomicina, linezolid, of Annual Listeriosis Incidence in simplicidad técnica y el alto poder chelocardina y ceftarolina. Con Northern Spain. discriminatorio. Aunque la mayoría algunos de ellos, nuestro grupo Front Immunol. 2016;7:541-541. F.I.:5,695. [doi:10.3389/ de estos métodos basados en ha colaborado también en el fimmu.2016.00541] PCR son más rápidos, sencillos y establecimiento de puntos de corte de fácil interpretación, en algunos de sensibilidad para definir categorías casos (dependiendo de la especie clínicas. 2. Merino I, Shaw E, Horcajada JP, estudiada) se requieren otras Cercenado E, Mirelis B, Pallarés MA, aproximaciones para estudiar la Nuestro grupo ha colaborado Gómez J, Xercavins M, Martínez- relación clonal entre los aislados. además en el estudio de las variables Martínez L, De Cueto M, Cantón R, Estas incluyen la electroforesis en que influyen en la actividad in Ruiz-Garbajosa P, campo pulsado (PFGE) técnica vitro de una nueva cefalosporina ITUBRAS-GEIH-SEIMC Group. principal para el tipificación de la (ceftarolina) con actividad frente a CTX-M-15-H30Rx-ST131 subclone mayoría de bacterias y hongos, el Staphylococcus aureus resistente a is one of the main causes of tipado de secuencias multilocus meticilina (MRSA). Para este mismo healthcare-associated ESBL- producing Escherichia coli (MLST), y el tipificación VNRT. compuesto, hemos analizado la bacteraemia of urinary origin in Estos métodos de tipificación idoneidad de los puntos de corte para definir categorías clínicas. Spain. son realizados en las distintas J Antimicrob Chemother. Hemos contribuido al estudio in áreas de nuestro laboratorio y son 2016;71:2125-2130. vitro de un nuevo antimicrobiano, muy útiles para el control de las F.I.:4,919. [doi:10.1093/jac/dkw133] infecciones en el hospital, para chelocardina, cuya síntesis se ha estudios epidemiológicos y para la mejorado mediante ingeniería comprensión de la patogénesis y las genética y cuya actividad in vitro 3. Gutiérrez-Gutiérrez B, Bonomo RA, infecciones. frente a diversas especies de Carmeli Y, Paterson DL, Almirante B, bacterias multirresistentes resulta Martínez-Martínez L, Oliver A, Calbo Mediante la utilización de esta prometedora. Los estudios en este E, Peña C, Akova M, Pitout J, Origüen J, Pintado V, García-Vázquez E, Gasch metodología, los principales objetivos ámbito se han desarrollado en O, Hamprecht A, Prim N, Tumbarello de nuestro grupo incluyen: estudiar colaboración con miembros de la Universidad de Cantabria y de la M, Bou G, Viale P, Tacconelli E, la epidemiología molecular de las Almela M, Pérez F, Giamarellou H, Universidad de Lubljana (Eslovenia). bacterias resistentes, y en particular Cisneros JM, Schwaber MJ, Venditti Recientemente, hemos coordinado del problema de la multirresistencia M, Lowman W, Bermejo J, ..., en el entorno hospitalario, e y participado en la elaboración de Rodríguez-Baño J. implementar el uso de herramientas una guía sobre la preparación de Ertapenem for the treatment de secuenciación masiva para una datos acumulados de antibiograma. of bloodstream infections mejor integración de la información Esta guía ayudará al proceso de due to ESBL-producing sobre resistencia y virulencia. estandarización de los estudios Enterobacteriaceae: a multinational locales y nacionales de seguimiento pre-registered cohort study. y evaluación de la resistencia a los J Antimicrob Chemother. 5. Actividad in vitro de nuevos antimicrobianos. EL grupo está 2016;71:1672-1680. antimicrobianos. iniciando su colaboración con otros F.I.:4,919. [doi:10.1093/jac/dkv502] grupos de IDIVAL en la desarrollar Diversos organismos mundiales, las bases que permitan la aplicación 4. Delgado-Valverde M, Torres E, incluida la OMS, han alertado que de la nanomedicina en terapia Valiente-Mendez A, Almirante B, la resistencia a antimicrobianos antimicrobiana. constituye uno de los principales Gómez-Zorrilla S, Borrell N, Corzo JE, problemas de salud en todo el Gurgui M, Almela M, García-Álvarez L, Fontecoba-Sánchez MC, Martínez- mundo, y una de las estrategias PUBLICATIONS: prioritarias para afrontarlo es el Martínez L, Cantón R, Praena J, Causse desarrollo de nuevos antimicrobianos. M, Gutiérrez-Gutiérrez B, Roberts JA, Farkas A, Pascual Á, Rodríguez-Baño J, Nuestro grupo participa en proyectos IMPACT FACTOR | 94,143 203

REIPI/GEIH-SEIMC BACTERAEMIA- 2016;60:6407-6410. 12. Pérez Del Molino Bernal IC, MIC group. Impact of the MIC F.I.:4,415. [doi:10.1128/AAC.01282-16] Lillebaek T, Pedersen MK, Martinez- of piperacillin/tazobactam on the Martinez L, Folkvardsen DB, Agüero outcome for patients J, Rasmussen EM. 8. Cabot G, López-Causapé C, with bacteraemia due to Genomic Diversity of Ocampo-Sosa AA, Sommer LM, Enterobacteriaceae: the Mycobacterium tuberculosis Domínguez MÁ, Zamorano L, Juan C, Bacteraemia-MIC project. Complex Strains in Cantabria Tubau F, Rodríguez C, Moyà B, Peña C, J Antimicrob Chemother. (Spain), a Moderate TB Incidence Martínez-Martínez L, Plesiat P, Oliver A, 2016;71:521-530. Setting. Spanish Network for Research F.I.:4,919. [doi:10.1093/jac/dkv362] PLoS One. 2016;11: in Infectious Diseases (REIPI). F.I.:3,057. [doi:10.1371/journal. Deciphering the Resistome of pone.0157266] 5. Freitas AR, Tedim AP, Francia the Widespread Pseudomonas MV, Jensen LB, Novais C, Peixe L, aeruginosa Sequence Type Sánchez-Valenzuela A, Sundsfjord 175 International High-Risk 13. Navas J, Fernández-Martínez A, Hegstad K, Werner G, Sadowy E, Clone through Whole-Genome M, Salas C, Cano ME, Martínez- Hammerum AM, Garcia-Migura L, Sequencing. Martínez L. Susceptibility to Willems RJ, Baquero F, Coque TM. Antimicrob Agents Chemother. Aminoglycosides and Distribution Multilevel population genetic 2016;60:7415-7423. of aph and aac(3)-XI Genes among analysis of vanA and vanB F.I.:4,415. [doi:10.1128/AAC.01720-16] Corynebacterium striatum Clinical Enterococcus faecium causing Isolates. nosocomial outbreaks in 27 PLoS One. 2016;11: 9. Palacios-Baena ZR, Oteo J, Conejo countries (1986-2012). F.I.:3,057. [doi:10.1371/journal. C, Larrosa MN, Bou G, Fernández- J Antimicrob Chemother. pone.0167856] Martínez M, González-López JJ, 2016;71:3351-3366. Pintado V, Martínez-Martínez L, F.I.:4,919. [doi:10.1093/jac/dkw312] Merino M, Pomar V, Mora-Rillo M, 14. Gozalo-Marguello, M., Angulo- Rivera MA, Oliver A, Ruiz-Carrascoso Lopez, I., Aguirre-Quinonero, A., Ruiz 6. Gutiérrez-Gutiérrez B, Pérez- G, Ruiz-Garbajosa P, Zamorano L, de Alegria, C., Aguero-Balbin, J., Galera S, Salamanca E, de Cueto M, Bautista V, Ortega A, Morales I, Martinez-Martinez, L. Calbo E, Almirante B, Viale P, Oliver Pascual Á, Campos J, Rodríguez- Comparison of two multiplexed A, Pintado V, Gasch O, Martínez- Baño J, PCR assays for respiratory Martínez L, Pitout J, Akova M, Peña GEIH-GEMARA (SEIMC) and REIPI virus detection in ICU patients: C, Molina J, Hernández A, Venditti M, Group for CPE. Comprehensive FilmArray (R) respiratory panel and Prim N, Origüen J, Bou G, Tacconelli clinical and epidemiological Allplex (TM) respiratory full panel. E, Tumbarello M, Hamprecht A, assessment of colonisation and J Clin Virol. 2016;82:50-50. Giamarellou H, Almela M, Pérez F, infection due to carbapenemase- F.I.:2,647. [doi:10.1016/j. Schwaber MJ, Bermejo J, Lowman producing Enterobacteriaceae in jcv.2016.08.098] W, ..., Spain. Investigators from the REIPI/ J Infect. 2016;72:152-160. 15. Gozalo-Marguello, M., Angulo- ESGBIS/INCREMENT Group. F.I.:4,382. [doi:10.1016/j. Lopez, I., Martinez-Martinez, L., A Multinational, Preregistered jinf.2015.10.008] Aguero-Balbin, J. Cohort Study of ß-Lactam/ß- Monitoring of BK and JC Lactamase Inhibitor Combinations 10. Gamal D, Fernández-Martínez polyomavirus viruria and viremia in for Treatment of Bloodstream M, El-Defrawy I, Ocampo-Sosa AA, hematopoietic stem cell transplant Infections Due to Extended- Martínez-Martínez L. (HSCT) and renal transplant (RT) Spectrum-ß-Lactamase-Producing First identification of NDM-5 recipients. Enterobacteriaceae. associated with OXA-181 in J Clin Virol. 2016;82:102-103. Antimicrob Agents Chemother. Escherichia coli from Egypt. F.I.:2,647. [doi:10.1016/j. 2016;60:4159-4169. Emerg Microbes Infect. 2016;5: jcv.2016.08.205] F.I.:4,415. [doi:10.1128/AAC.00365-16] F.I.:4,012. [doi:10.1038/emi.2016.24]

16. López IA, Montes JC, Álvarez 7. Torrens G, Cabot G, Ocampo-Sosa 11. Lázaro-Díez M, Remuzgo-Martínez MJ, Mazarrasa CF, Martínez-Martínez AA, Conejo MC, Zamorano L, Navarro S, Rodríguez-Mirones C, Acosta F, L. F, Pascual Á, Martínez-Martínez L, Icardo JM, Martínez-Martínez L, Cephalothin is not a reliable Oliver A. Ramos-Vivas J. surrogate marker for oral Activity of Ceftazidime-Avibactam Effects of Subinhibitory cephalosporins in susceptibility against Clinical and Isogenic Concentrations of Ceftaroline on testing of Enterobacteriaceae Laboratory Pseudomonas Methicillin-Resistant Staphylococcus causing urinary tract infection. aeruginosa Isolates Expressing aureus (MRSA) Biofilms. Diagn Microbiol Infect Dis. Combinations of Most Relevant PLoS One. 2016;11: 2016;86:412-416. ß-Lactam Resistance Mechanisms. F.I.:3,057. [doi:10.1371/journal. F.I.:2,450. [doi:10.1016/j. Antimicrob Agents Chemother. pone.0147569] diagmicrobio.2016.08.017] Research Areas Infectious Diseases and Immune System Area

17. María DA, María-Isabel M, María- Herreros JM, Cano ME, Gato E, Ruiz Antonio Herrera, Luis, Pajaron, Carmen C, Álvaro P, Jorge C, Luis de Alegría C, Fernández-Cuenca F, Marcos, Gomez-Fleitas, Manuel, MM, Francesc M, Jordi V, Adriana O, Vila J, Martínez-Martínez L, Tomás- Carmen Farinas, Maria. Jesús O, Rafael C. Carmona MD, Pascual Á, Bou G, Role of bacteriobilia in Establishing the validity of different Pachón-Diaz J, Rodríguez-Baño J. postoperative complications. susceptibility testing methods to Acinetobacter baumannii in Rev Esp Quimioter. 2016;29:123-129. evaluate the in vitro activity of critically ill patients: Molecular F.I.:1,014. amoxicillin-clavulanate against epidemiology, clinical features and Escherichia coli. predictors of mortality. 28. Angulo López, Itziar, Nistal Diagn Microbiol Infect Dis. Enferm Infecc Microbiol Clin. Herrera, Juan Francisco. 2016;84:334-336. 2016;34:551-558. Infestation of a diabetic foot by F.I.:2,450. [doi:10.1016/j. F.I.:1,530. [doi:10.1016/j. Wohlfahrtia Magnifica. diagmicrobio.2015.12.012] eimc.2015.11.018] J Vasc Surg Venous Lymphat Disord. 2016;2:119-122. 18. Koeth LM, Apfalter P, Becker K, 23. Machuca J, Briales A, Díaz- F.I.:0,882. Gesu G, Martínez-Martínez L, Lahiri de-Alba P, Martínez-Martínez L, SD, Alm RA, Ambler J, Iaconis J. Rodríguez-Martínez JM, Pascual Á. Multi-center and multi-method Comparison of clinical categories evaluation of in vitro activities of for Escherichia coli harboring ceftaroline against S. aureus. specific qnr and chromosomal- Reviews Diagn Microbiol Infect Dis. mediated fluoroquinolone 2016;85:452-458. resistance determinants according F.I.:2,450. [doi:10.1016/j. to CLSI and EUCAST. 1. Rodríguez-Martínez JM, Machuca diagmicrobio.2016.05.003] Enferm Infecc Microbiol Clin. J, Cano ME, Calvo J, Martínez- 2016;34:188-190. Martínez L, Pascual A. F.I.:1,530. [doi:10.1016/j. Plasmid-mediated quinolone 19. Lázaro-Díez M, Navascués- eimc.2015.01.019] resistance: Two decades on. Lejarza T, Remuzgo-Martínez S, Drug Resist Updat. 2016;29:13-29. Navas J, Icardo JM, Acosta F, F.I.:7,950. [doi:10.1016/j. Martínez-Martínez L, Ramos-Vivas J. 24. Canut-Blasco A, Calvo J, Rodríguez- drup.2016.09.001] Acinetobacter baumannii and A. Díaz JC, Martínez-Martínez L. PITTII clinical isolates lack Informes acumulados de adherence and cytotoxicity to lung sensibilidad a los antimicrobianos. epithelial cells in vitro. Enferm Infecc Microbiol Clin. Microbes Infect. 2016;18:559-564. 2016;34:524-530.F.I.:1,530. F.I.:2,291. [doi:10.1016/j. [doi:10.1016/j.eimc.2015.03.019] Doctoral Thesis micinf.2016.05.002]

25. Urbina Soto L, García Ávila S, 20. Gamal D, Fernández-Martínez M, Córdoba Alonso AI, Roiz Mesones 1. Alicia Márquez López. Salem D, El-Defrawy I, Montes LÁ, MP, Arnaiz García AM, Valero Díaz de Resistance to quinolones and Ocampo-Sosa AA, Martínez-Martínez L. Lamadrid MC. production of hemolysins in clinical Carbapenem-resistant Klebsiella Clostridium difficile associated isolates of E. coli. pneumoniae isolates from Egypt diarrhoea: An increased problem. Director: Luis Martínez Martínez. containing blaNDM-1 on IncR Med Clin (Barc). 2016;147:543-546. University of Cantabria. plasmids and its association with F.I.:1,267. [doi:10.1016/j. RMTF. medcli.2016.09.026] 2. José Quintanar Lartuno. Peritonitis INT J INFECT DIS. 2016;43:17-20. en diálisis peritoneal. F.I.:2,229. [doi:10.1016/j. 26. Ruiz de Alegria-Puig, Carlos, Peritonitis in peritoneal dialysis. ijid.2015.12.003] Aguirre-Quinonero, Amaia, Aguero- Experience over a decade: Balbin, Jesus, Pia Roiz-Mesones, Ma, evolution, microbiological profile, 21. Suberviola B, Márquez-López Martinez-Martinez, Luis. antimicrobial sensitivity and A, Castellanos-Ortega A, Fernández- Correlation between MALDI- differences according to age. Mazarrasa C, Santibáñez M, Martínez LM. TOF Vitek-MS (TM) system Directors: Manuel Antonio Arias Microbiological Diagnosis of Sepsis: and conventional identification Rodríguez, Luis Martínez Martínez. Polymerase Chain Reaction System methods of gastrointestinal University of Cantabria. Versus Blood Cultures. infection causing bacteria. AM J CRIT CARE. 2016;25:68-75. Rev Esp Quimioter. 2016;29:265-268. F.I.:2,053. [doi:10.4037/ajcc2016728] F.I.:1,014.

22. Garnacho-Montero J, Gutiérrez- 27. Arminanzas, Carlos, Tigera, Pizarraya A, Díaz-Martín A, Cisneros- Teresa, Ferrer, Diego, Calvo, Jorge, PROJECTS 205

Projects characterization of new components PI16/01103. of type VI secretion systems and the INSTITUTO DE SALUD CARLOS III. molecular bases of their regulation MINISTERIO DE ECONOMÍA Y 1. José Ramos Vivas. in clinical strains of Pseudomonas COMPETITIVIDAD. Host-pathogen key interactions in aeruginosa. PI15/00009. Acinetobacter species of clinical INSTITUTO DE SALUD CARLOS III. 4. María Victoria Francia Gil. relevance. MINISTERIO DE ECONOMÍA Y Induction of the conjugative PI13/01310. COMPETITIVIDAD. transfer of the pheromone INSTITUTO DE SALUD CARLOS III. response plasmids. MINISTERIO DE ECONOMÍA Y 3. José Ramos Vivas. PI16/01535. COMPETITIVIDAD. Integrated biology of infection INSTITUTO DE SALUD CARLOS III. and antimicrobial resistance of MINISTERIO DE ECONOMÍA Y 2. Alain Antonio Ocampo Sosa. Acinetobacter baumannii and A. COMPETITIVIDAD. Identification and functional PITTII.

207

Metabolism, Diseases of Aging and Life

Habits Area José Antonio Riancho Moral Coordinator of the Area of Metabolism, Diseases of Aging and Habits of Life.

Head of Section of the Internal Medicine Service. University Hospital Marqués de Valdecilla. Professor of the Department of Medicine and Psychiatry. University of Cantabria. Research Areas Metabolism, Diseases of Aging and Life Habits Area

Group Leader José Antonio Parra Blanco Radiology Service Áreas de University Hospital Diagnosis and Treatment Marqués de Valdecilla Usinginvestigación Imaging (radiology) University of Cantabria

[email protected]

Pedro Lastra García-Barón Elena López Uzquiza Gerardo López Rasines Enrique Marco de Lucas Sarah Marqués Llano Paula Merino Rasillo Jose Maria Navasa Melado Estrella Ortega García Clinic group Luis Antonio Ortiz Rivas María Macarena Otero Fernández Marta Peláz Esteban Contributors Raúl Pellón Daben Rosa Fabregat Borrás María Elena Peña Gómez María Mercedes Acebo García Alejandro Fernández Flórez Mariano Rico Gutiérrez María Pilar Alonso Bartolomé Ana García Bolado Eva Ruiz Pérez Eva Alonso Fernández Mª Del Rosario García-Barredo Pérez Alba Salvador Errasti Gerardo Blanco Rodríguez Vanesa Gómez Dermit Sonia Sánchez Gómez Ana Canga Villegas Francisco José González Sánchez Elena Sánchez Salmón Juan Crespo Del Pozo Agustín Gutiérrez Gutiérrez Sergio Tapia Concha Alexandra de Diego Diez Amaya Iturralde Garriz Natalia Valle San Roman Javier Valentin de La Calle Lorenzo Carlos Jimenez Zapater Alfonso Vega Bolivar Maria Rosa de La Puente Formoso Juan Jordá Lope Héctor Vidal Trueba Maria Diez Blanco Angélica Lamagrande Obregón Cristina Villaespesa Diaz Marta Drake Perez Rosa Maria Landeras Álvaro Elena Yllera Contreras 209

Spanish patients with hemorrhagic PUBLICATIONS: hereditary telangiectasia. Int J Cardiol. 2016;218:240-245. F.I.:4,638. [doi:10.1016/j. Research IMPACT FACTOR | 32,138 ijcard.2016.05.065] Lines 5. Ibáñez-Bravo S, Banzo I, Quirce R, Martínez-Rodríguez I, Jiménez-Bonilla J, Martínez-Amador N, Parra JA, Active research lines: González-Macías J, Carril JM. Original articles Ventilation/Perfusion SPECT > Evaluation of new low lung scintigraphy and computed percutaneous breast biopsy devices tomography pulmonary Image control. angiography in patients with 1. Peeters K, Palaima P, Pelayo- clinical suspicion of pulmonary Negro AL, García A, Gallardo E, embolism. > Study of arteriovenous García-Barredo R, Mateiu L, Baets J, Rev Esp Med Nucl Imagen Mol. malformations in patients with Menten B, De Vriendt E, De Jonghe 2016;35:215-220. Telangiectasia Hemorrhagic P, Timmerman V, Infante J, Berciano F.I.:0,983. [doi:10.1016/j. J, Jordanova A. remn.2015.12.008] Hereditary (THH). Charcot-Marie-Tooth disease type 2G redefined by a novel mutation > Quantification of coronary in LRSAM1. calcium and carotid Ann Neurol. 2016;80:823-833. ultrasonography and as predictors F.I.:9,638. [doi:10.1002/ana.24775] of cardiovascular risk. 2. Berciano J, Gallardo E, Orizaola P, > Development of hybrid Marco de Lucas E, García A, Pelayo- Reviews techniques: surgical-radiological in Negro AL, Sedano MJ. the treatment of Vascular pathology. Early axonal Guillain-Barré syndrome with normal peripheral 1. Drake-Pérez M, Marco de Lucas E, > Evaluation of the usefulness and conduction: imaging evidence Lyo J, Fernández-Torre JL. for changes in proximal nerve complications of thermoablation Neuroimaging features in subacute segments. encephalopathy with seizures in treatments in patients with J. Neurol. Neurosurg. Psychiatry. alcoholics (SESA syndrome). neoplastic disease 2016;87:563-565. Seizure. 2016;40:102-107. F.I.:6,431. [doi:10.1136/jnnp-2015- F.I.:2,109. [doi:10.1016/j. > Ultrasonic contrasts in the study 310601] seizure.2016.06.009] of hepatic, renal and intestinal pathology. 3. Zarrabeitia, Roberto, Ojeda- Fernandez, Luisa, Recio, Lucia, 2. Drake-Pérez M, Smirniotopoulos JG. Bernabeu, Carmelo, Parra, Jose A., Extraparenchymal Lesions in > Study of cerebral connectivity Adults. with diffusion tensor MRI. Albinana, Virginia, Botella, Luisa M. Bazedoxifene, a new orphan drug Neuroimaging Clin N Am. for the treatment of bleeding 2016;26:621-646. > Anatomic-radiological correlation in hereditary haemorrhagic F.I.:1,557. [doi:10.1016/j. studies in cutaneous pathology. telangiectasia. nic.2016.06.009] Thromb Haemost. 2016;115:1167- > Ultrasound in the diagnosis 1177. and follow-up of hidradenitis F.I.:5,255. [doi:10.1160/TH15-03- 3. Hernando MF, Cerezal L, Pérez- 0239] Carro L, Canga A, González RP. suppurativa. Evaluation and management of ischiofemoral impingement: a > Anatomical-radiological (MR) 4. Parra JA, Cuesta JM, Zarrabeitia R, pathophysiologic, radiologic, and correlation in corpse. Fariñas-Álvarez C, Bueno J, Marqués therapeutic approach to a complex S, Parra-Fariñas C, Botella ML, diagnosis. > Contribution of multi-cut CT in Bernabéu C, Zarauza J. Skeletal Radiol. 2016;45:771-787. Screening pulmonary arteriovenous the evaluation of perforating arteries F.I.:1,527. [doi:10.1007/s00256-016- malformations in a large cohort of 2354-2] prior to Plastic reconstructive surgery. Research Areas Metabolism, Diseases of Aging and Life Habits Area

Group Leader Jesús González Macías Internal Medicine Service Áreas de University Hospital Mineral and Lipid Marqués de Valdecilla Metabolisminvestigación University of Cantabria

[email protected]

Daniel Narcis Nan Nan Flor María Pérez Campo Ana Santurtun Zarrabeitia Carmen Valero Díaz De Lamadrid María Teresa Zarrabeitia Cimiano Consolidated group Nurses Isabel Sierra Setién Researchers Contributors José Luís Hernández Hernández Alvaro del Real Bolt Technicians José Manuel Olmos Martínez Mª Carmen García Ibarbia Estefanía Escalante Lanza José Antonio Riancho Moral Marta Martín Millán Maria Luisa Junco Martin José Carlos Rodríguez Rey Josefina Micaela Martínez García Carolina Sañudo Campo

skeletal diseases like osteoarthritis in the modulation of the expression and osteoporosis. The following of genes which play a key role in Research issues are addressed: skeletal homeostasis. Lines Genetic polymorphisms that The possible role of the differential influence bone mass, the risk of expression of microRNAs in bone fractures and large joint osteoarthritis, changes that characterize these using candidate genes and genome- disorders. 1. Line of genetics/genomics. wide association studies.

It studies the genetic and epigenetic Molecular and functional study mechanisms involved in prevalent The role of DNA methylation in the of mesenchymal stem cells as differentiation of bone cells as well as precursors of bone-forming cells. 211

2. Clinical and epidemiological line. of the actuality of the topic, bone The Group of Molecular Biology and mineral metabolism changes (Prof. Rodriguez Rey) investigates Its objective is to study in Cantabria, in patients with hepatitis C virus on the molecular mechanisms as well as in the whole Spain (the infection will be tackled too. All these of mesenchymal stem cells latter by means of multicenter aspects will be approached by both differentiation into adipose tissue. studies), the prevalence and cross-sectional and longitudinal Firstly, the group studies the role of incidence of different aspects of studies. epigenetic regulation in the process mineral and bone metabolism of progenitor cell differentiation diseases, mainly (but not only) into adipocytes and its possible 3. Animal models (mainly mouse). osteoporosis. This includes the relationship with obesity, with prevalence of osteoporosis, the This line focuses on studying particular emphasis on the role of incidence of osteoporotic fractures the Wnt/b-catenin pathway in microRNAs (in collaboration with Dr (vertebral and hip fractures), and the osteoclasts, using models with Carlos Fernandez of Yale University). prevalence of low vitamin D levels conditional changes of the b-catenin Secondly, the group investigates and secondary hyperparathyroidism, gene in these cells. Animal models the role of other epigenetic as well as the analysis of those with gain or loss of function of mechanism, the methylation of factors influencing the response to b-catenin in cells of osteoclastic DNA, in the modulation of gene treatment. The relationship between lineage are generated by means expression during the process of osteoporosis and other disorders, of the CRE/loxP technology. The adipocyte differentiation. Besides such as dyslipidemias, diabetes, Cre recombinase is placed under that, and in collaboration with obesity, and metabolic syndrome the control of the promoter of should also be studied. Of particular the Group of Professor Carmen lysozyme M or cathepsin K, so that interest is the follow-up of the Évora (Pharmaceutical Technology the osteoclast can be analyzed at cohort of Camargo, which allows the Department, Universidad de la different evolutive moments. Studies analysis of the association between Laguna) and Dr. Gomez-Cimiano in other animal models assess the various manifestations of bone and (Orthopedics and trauma Service, effect of certain therapeutic agents mineral metabolism diseases with HUMV) it is developing an such as PTH and strontium ranelate their risk factors. Mortality rate will be experimental model consisting of considered in the study. Prominent on bone strength. using mesenchymal stem cells among the factors to be analyzed modified in the treatment of fractures of critical size. is the trabecular bone score (TBS), 4. Line of lipid metabolism a new tool to evaluate the risk of genomic. osteoporotic fractures. Because

Figura. Imágenes de hueso por micro TC de animales OVX y control. Research Areas Metabolism, Diseases of Aging and Life Habits Area

Férec C, Hardiman O, Zarrabeitia M, 10. Pérez-Campo FM, Santurtún A, PUBLICATIONS: Jiménez S, Pinheiro MF, Jarreta BM, García-Ibarbia C, Pascual MA, Valero Olofsson J, Morling N, de Pancorbo C, Garcés C, Sañudo C, Zarrabeitia IMPACT FACTOR | 98,727 MM. MT, Riancho JA. New clues to the evolutionary Osterix and RUNX2 are history of the main European Transcriptional Regulators of paternal lineage M269: dissection Sclerostin in Human Bone. of the Y-SNP S116 in Atlantic Calcif Tissue Int. 2016;99:302- Original articles Europe and Iberia. 309.F.I.:3,052. [doi:10.1007/s00223- Eur J Hum Genet. 2016;24:437-441. 016-0144-4] F.I.:4,580. [doi:10.1038/ 1. González-López MA, Hernández ejhg.2015.114] JL, Lacalle M, Mata C, López- 11. Riancho J, Lozano-Cuesta P, Escobar M, López-Mejías R, Santurtún A, Sánchez-Juan P, López- Portilla V, Fuentevilla P, Corrales A, 6. Vidal-Bralo L, Lopez-Golan Y, Vega JM, Berciano J, Polo JM. González-Vela MC, González-Gay Mera-Varela A, Rego-Perez I, Horvath Amyotrophic Lateral Sclerosis in MA, Blanco R. Increased prevalence S, Zhang Y, Del Real Á, Zhai G, Northern Spain 40 Years Later: of subclinical atherosclerosis Blanco FJ, Riancho JA, Gomez-Reino What Has Changed?. in patients with hidradenitis JJ, Gonzalez A. Neurodegener Dis. 2016;16:337-341. suppurativa (HS). Specific premature epigenetic F.I.:2,937. [doi:10.1159/000445750] J Am Acad Dermatol. 2016;75:329- aging of cartilage in osteoarthritis. 335. Aging (Albany NY). 2016;8:2222- F.I.:5,621. [doi:10.1016/j. 2231 12. Córdoba A, Lisa M, Gómez- F.I.:3,979. [doi:10.18632/ jaad.2016.03.025] Román JJ, Hernández JL. aging.101053] Pulmonary pseudo-tumour, aortitis and IgG4 disease. 2. Martin-Cano FE, Camello-Almaraz QJM. 2016;109:345-346. 7. Calvo-Río V, Blanco R, Santos- C, Macías JG, Pozo MJ, Camello PJ. F.I.:2,824. [doi:10.1093/qjmed/ Gómez M, Rubio-Romero E, Cordero- Propagation of Intracellular Ca2+ hcw008] Coma M, Gallego-Flores A, Veroz Signals in Aged Exocrine Cells. R, Torre I, Hernández FF, Atanes J Gerontol A Biol Sci Med Sci. A, Loricera J, González-Vela MC, 2016;71:145-152. 13. Napal JJ, Neila S, Pérez-Montes Palmou N, Hernández JL, González- F.I.:5,476. [doi:10.1093/gerona/ R, Sierra I, Ruiz S, Hernández JL. Gay MA. Golimumab in refractory glv018] The role of coagulation disorders in uveitis related to spondyloarthritis. patients with retinal vein occlusion. Multicenter study of 15 patients. QJM. 2016;109:97-102. 3. Ruiz P, Martin-Millan M, Gonzalez- Semin Arthritis Rheum. 2016;46:95- F.I.:2,824. [doi:10.1093/qjmed/ Martin MC, Almeida M, González- 101. hcv088] Macias J, Ros MA. F.I.:3,946. [doi:10.1016/j. CathepsinKCre mediated deletion semarthrit.2016.03.002] of ßcatenin results in dramatic loss 14. Riancho-Zarrabeitia L, García- Unzueta M, Tenorio JA, Gómez- of bone mass by targeting both 8. Toraño EG, Bayón GF, Del Real osteoclasts and osteoblastic cells. Gerique JA, Ruiz Pérez VL, Heath KE, Á, Sierra MI, García MG, Carella A, Lapunzina P, Riancho JA. Sci Rep. 2016;6:36201-36201. Belmonte T, Urdinguio RG, Cubillo Clinical, biochemical and F.I.:5,228. [doi:10.1038/srep36201] I, García-Castro J, Delgado-Calle J, genetic spectrum of low alkaline Pérez-Campo FM, Riancho JA, Fraga phosphatase levels in adults. MF, Fernández AF. 4. De Castro-Orós I, Civeira F, Pueyo Eur J Intern Med. 2016;29:40-45. Age-associated MJ, Mateo-Gallego R, Bolado- F.I.:2,591. [doi:10.1016/j. hydroxymethylation in human Carrancio A, Lamíquiz-Moneo I, ejim.2015.12.019] bone-marrow mesenchymal stem Álvarez-Sala L, Fabiani F, Cofán M, cells. Cenarro A, Rodríguez-Rey JC, Ros E, J TRANSL MED. 2016;14:207-207. Pocoví M. 15. Del Pino-Montes J, Blanch J, F.I.:3,694. [doi:10.1186/s12967-016- Rare genetic variants with Nogués X, Moro MJ, Valero MD, 0966-x] large effect on triglycerides in Canals L, Lizán L. subjects with a clinical diagnosis Expert Consensus on the Management of Patients with of familial vs nonfamilial 9. Olmos JM, Hernández JL, García- hypertriglyceridemia. Velasco P, Martínez J, Llorca J, Postmenopausal Osteoporosis in J CLIN LIPIDOL. 2016;10:790-797. González-Macías J. the Spanish Healthcare System. F.I.:4,906. [doi:10.1016/j. Serum 25-hydroxyvitamin D, Adv Ther. 2016;33:658-669. jacl.2016.02.010] parathyroid hormone, calcium F.I.:2,503. [doi:10.1007/s12325-016- intake, and bone mineral density in 0314-9] Spanish adults. 5. Valverde L, Illescas MJ, Villaescusa Osteoporos Int. 2016;27:105-113. 16. Loricera J, González-Vela C, P, Gotor AM, García A, Cardoso S, F.I.:3,445. [doi:10.1007/s00198-015- Algorta J, Catarino S, Rouault K, Blanco R, Hernández JL, Armesto 3219-6] S, González-López MA, Calvo-Río 213

V, Ortiz-Sanjuán F, Val-Bernal JF, Clin Exp Rheumatol. 2016;34:125-128. association with latitude and air Hermana S, Onaindia-Pérez A, F.I.:2,495. lead levels in Spain. González-Gay MA. Neurol Sci. 2016;37:1271-1275. Histopathologic differences F.I.:1,783. [doi:10.1007/s10072-016- 21. Prieto-Fernández E, Baeta M, between cutaneous vasculitis 2581-2] Núñez C, Zarrabeitia MT, Herrera RJ, associated with severe bacterial Builes JJ, de Pancorbo MM. infection and cutaneous vasculitis Development of a new highly 27. Pina T, Corrales A, Lopez-Mejias secondary to other causes: study efficient 17 X-STR multiplex for R, Armesto S, Gonzalez-Lopez MA, of 52 patients. forensic purposes. Gómez-Acebo I, Ubilla B, Remuzgo- Clin Exp Rheumatol. 2016;34:93-97. Electrophoresis. 2016;37:1651-1658. Martínez S, Gonzalez-Vela MC, F.I.:2,495. F.I.:2,482. [doi:10.1002/ Blanco R, Hernández JL, Llorca J, elps.201500546] Gonzalez-Gay MA. 17. Ferraz-Amaro I, López-Mejías R, Anti-tumor necrosis factor-alpha therapy improves endothelial Ubilla B, Genre F, Tejera-Segura B, de 22. Nelo-Bazán MA, Latorre P, function and arterial stiffness in Vera-González AM, González-Rivero Bolado-Carrancio A, Pérez-Campo patients with moderate to severe AF, Olmos JM, Hernández JL, Llorca FM, Echenique-Robba P, Rodríguez- psoriasis: A 6-month prospective J, González-Gay MA. Rey JC, Carrodeguas JA. study. Proprotein convertase subtilisin/ Early growth response 1 (EGR-1) J Dermatol. 2016;43:1267-1272. kexin type 9 in rheumatoid arthritis. is a transcriptional regulator of F.I.:1,577. [doi:10.1111/1346- Clin Exp Rheumatol. 2016;34:1013- mitochondrial carrier homolog 1 8138.13398] 1019. (MTCH 1)/presenilin 1-associated F.I.:2,495. protein (PSAP). Gene. 2016;578:52-62. 28. Pina T, Genre F, Lopez-Mejias F.I.:2,319. [doi:10.1016/j. R, Armesto S, Ubilla B, Mijares 18. Santos-Gómez M, Calvo-Río gene.2015.12.014] V, Dierssen-Sotos T, Corrales A, V, Blanco R, Beltrán E, Mesquida Gonzalez-Lopez MA, Gonzalez- M, Adán A, Cordero-Coma M, Vela MC, Blanco R, Hernández García-Aparicio ÁM, Valls Pascual 23. Largeot A, Perez-Campo FM, JL, Llorca J, Gonzalez-Gay MA. E, Martínez-Costa L, Hernández MV, Marinopoulou E, Lie-a-Ling M, Asymmetric dimethylarginine but Hernandez Garfella M, González- Kouskoff V, Lacaud G. not osteoprotegerin correlates Vela MC, Pina T, Palmou-Fontana N, Expression of the MOZ-TIF2 with disease severity in patients Loricera J, Hernández JL, González- oncoprotein in mice represses with moderate-to-severe psoriasis Gay MA. senescence. undergoing anti-tumor necrosis The effect of biologic therapy Exp Hematol. 2016;44: factor-a therapy. different from infliximab or F.I.:2,303. [doi:10.1016/j. J Dermatol. 2016;43:389-394. adalimumab in patients with exphem.2015.12.006] F.I.:1,577. [doi:10.1111/1346- refractory uveitis due to Behçet’s 8138.13094] disease: results of a multicentre 24. Calvo-Río V, Hernández JL, open-label study. Ortiz-Sanjuán F, Loricera J, Palmou- Clin Exp Rheumatol. 2016;34:34-40. 29. Urbina Soto L, García Ávila S, Fontana N, González-Vela MC, F.I.:2,495. Córdoba Alonso AI, Roiz Mesones González-Lamuño D, González-López MP, Arnaiz García AM, Valero Díaz de MA, Armesto S, Blanco R, González- Lamadrid MC. Gay MA. 19. Casanueva B, García-Fructuoso Clostridium difficile associated Relapses in patients with Henoch- F, Belenguer R, Alegre C, Moreno- diarrhoea: An increased problem. Schönlein purpura: Analysis of 417 Muelas J, Hernández JL, Pina T, Med Clin (Barc). 2016;147:543-546. patients from a single center. González-Gay MÁ. F.I.:1,267. [doi:10.1016/j. Medicine (Baltimore). 2016;95: The Spanish version of the 2010 medcli.2016.09.026] F.I.:2,133. [doi:10.1097/ American College of Rheumatology MD.0000000000004217] Preliminary Diagnostic Criteria for fibromyalgia: reliability and validity 30. Santurtún A, Delgado-Alvarado M, Villar A, Riancho J. assessment. 25. Santurtún A, Villar A, López- Patrón geográfico de la mortalidad Clin Exp Rheumatol. 2016;34:55-58. Delgado L, Riancho J. por enfermedad de Parkinson en F.I.:2,495. Amyotrophic lateral sclerosis España y su asociación con los and richness: A correlation study niveles de plomo en el aire. across Spain. Med Clin (Barc). 2016;147:481-487. 20. Casanueva B, Belenguer R, J Neurol Sci. 2016;367:380-381. F.I.:1,267. [doi:10.1016/j. Moreno-Muelas JV, Urtiaga J, Urtiaga F.I.:2,126. [doi:10.1016/j. medcli.2016.07.022] B, Hernández JL, Pina T, González- jns.2016.06.050] Gay MA. Validation of the Spanish version 31. Ibáñez-Bravo S, Banzo I, Quirce of the fibromyalgia rapid screening 26. Santurtún A, Villar A, Delgado- R, Martínez-Rodríguez I, Jiménez- tool to detect fibromyalgia in Alvarado M, Riancho J. Bonilla J, Martínez-Amador N, Parra primary care health centres. Trends in motor neuron disease: Research Areas Metabolism, Diseases of Aging and Life Habits Area

JA, González-Macías J, Carril JM. 2016;12:389-398. Ventilation/Perfusion SPECT F.I.:2,598. [doi:10.1517/17425255.20 PROJECTS lung scintigraphy and computed 16.1154533] tomography pulmonary angiography in patients with 3. Loricera J, Blanco R, Hernández clinical suspicion of pulmonary JL, Castañeda S, Humbría A, Ortego Projects embolism. N, Bravo B, Freire M, Melchor S, Rev Esp Med Nucl Imagen Mol. Mínguez M, Salvatierra J, González- 2016;35:215-220. Vela C, Calvo-Río V, Santos-Gómez F.I.:0,983. [doi:10.1016/j. M, Pina T, González-Gay MA. 1. Jesús González Macías. remn.2015.12.008] Tocilizumab in patients with Thematic Network of Cooperative Takayasu arteritis: a retrospective Research in Aging and Fragility. study and literature review. RD12/0043/0009. Clin Exp Rheumatol. 2016;34:44-53. INSTITUTO DE SALUD F.I.:2,495. Reviews 2. José Manuel Olmos Martínez. Study of the bone and mineral 1. Brennan-Olsen SL, Page RS, Berk metabolism of the postmenopausal M, Riancho JA, Leslie WD, Wilson Doctoral thesis and male female population SG, Saban KL, Janusek L, Pasco over 50 years of age attended JA, Hodge JM, Quirk SE, Hyde NK, by a Health Center in Cantabria. Hosking SM, Williams LJ. PI15/00521. DNA methylation and the social 1. Paula Ruiz Martin. INSTITUTO DE SALUD CARLOS III. gradient of osteoporotic fracture: A Role of the canonical pathway of MINISTERIO DE ECONOMÍA Y conceptual model. wnt in the osteoclast resorptive COMPETITIVIDAD. Bone. 2016;84:204-212. function. Directors: Marta Martín Millán, Jesús González Macías, F.I.:3,736. [doi:10.1016/j. 3. José Antonio Riancho Moral. Maria Angeles Ros Lasierra. bone.2015.12.015] Study of mesenchymal stem cells University of Cantabria. in osteoporosis: Role of long non-coding RNAs (lncRNAs) and 2. López-Delgado L, Riancho- 2. Javier Pérez López. regenerative potential. Zarrabeitia L, Riancho JA. Study of the role of mir-148a in PI16/00915. Genetic and acquired factors the regulation of genes of lipid INSTITUTO DE SALUD CARLOS III. influencing the effectiveness metabolism and adipogenesis. MINISTERIO DE ECONOMÍA Y and toxicity of drug therapy in Director: José Carlos Rodríguez COMPETITIVIDAD, INSTITUTO DE osteoporosis. Rey. SALUD CARLOS III. Expert Opin Drug Metab Toxicol. University of Cantabria.