Selskab for Medicinsk Studenterforskning KONGRES FOR MEDICINSK STUDENTERFORSKNING ABSTRACTS
Sandbjerg Gods, Sønderborg 5. ‒ 8. marts 2020
c 2020 Selskab for Medicinsk Studenterforskning
ISBN-13: 978-87-995206-8-8
Typografi: pdfLATEX og memoir-klassen, 9pt Indhold
Velkomst 4
Program 5
Paneldebat 8
Taksigelser 9
Arrangører 10
Chairmen 11
List of Talks 14
Poster sessioner 17 P.1 Intern Medicin ...... 17 P.2 Epidemiologi ...... 26 P.3 Grundforskning ...... 36 P.4 Kardiologi ...... 46
Orale sessioner 55 O.1 Mor & Barn ...... 55 O.2 Kardiologi ...... 62 O.3 Grundforskning ...... 68 O.4 Psykiatri & Neuroscience ...... 76 O.5 Epidemiologi ...... 83 O.6 Intern Medicin ...... 90
3 Velkomst
På vegne af Selskab for Medicinsk Studenterforskning ønskes I hermed hjertelig velkommen til Kongres for Medicinsk Studenterforskning 2020.
Igennem det sidste år har vi I Selskab for Medicinsk Studenterforskning arbejdet for at skabe de bedste rammer for denne weekend – og det er med stor spænding, at vi nu begynder denne weekends rejse sammen med jer.
Weekenden vil byde på oplæg fra inviterede talere, en samfundsrelevant paneldebat med fokus på evidensens rolle i nutidens sundhedssystem – og sidst, men ikke mindst – alle Jeres spændende præsentationer.
Alle deltagere er studenterforskere på samme niveau og alle kan bidrage på lige fod. Dette understøtter studenterkongressens helt særlige læringsmiljø: Et “beskyttet værksted”, hvor alle tør udfordre sig selv og hvor vi griber hinanden når vi “falder”. Jeg håber, at du vil være med til at understøtte dette trygge læringsmiljø igennem hele weekenden.
For at fremme det trygge miljø har vi sørget for en masse sjove og spændende sociale aktiviteter, så du kan lære din sidemand og -kvinde bedre at kende.
Jeg håber, at denne weekend vil ruste dig til at deltage i internationale kongresser i fremtiden samt fremme dit netværk af ligesindede yngre forskere.
Afslutningsvis vil jeg takke alle vores bidragsydere samt alle de SMS’er, som har lagt tid og engagement i at forberede kongressen. Uden dette kunne KMS2020 ikke lade sig gøre.
Vi håber at alle får en fremragende kongres!
Kasper Munch Lauridsen
Formand, Selskab for Medicinsk Studenterforskning
4 Program
Program torsdag d. 5.
16.45 Ankomst 16.45 – 17.30 Indkvartering 17.40 – 17.45 Velkomstdrink 17.45 – 18.00 Velkomst Kasper Munch Lauridsen Formand, Selskab for Medicinsk Studenterforskning 18.00 – 19.00 Middag 19.10 – 20.00 Foredrag Niels Holmark Andersen Den svære kunst at præsentere Lektor, Odense Universitetshospital forskning 20.00 – 22.00 Teambuilding
5 Program fredag d. 6.
07.00 – 08.00 Morgenløb eller yoga 08.00 – 09.00 Morgenmad 09.00 – 10.10 Session O.1 Chairmen: Mor & Barn Cecilie Ramlau-Hansen Dorthe Maria Vittrup
10.10 – 10.20 Kaffe, vand & frugt 10.20 – 11.20 Session O.2 Chairmen: Kardiologi Henning Rud Andersen Ida Albertsen
11.20 – 11.30 Kaffe, vand & frugt 11.30 – 12.30 Foredrag Ulrik Wilbek Motivation i medgang og modgang Borgmester, Viborg Kommune 12.30 – 13.30 Frokostbuffet 13.30 – 15.00 Paneldebat Debatdeltagere: Det evidensbaserede Ida Donkin sundhedsvæsen Jesper Fisker Jonas Dahl Leif Vestergaard Pedersen Marlene Øhrberg Krag Moderator: Charlotte Strøm
15.00 – 15.20 Kaffe & kage 15.20 – 16.45 Poster sessioner Chairmen: P.1 Intern Medicin Allan Flyvbjerg Stine Karlsen P.2 Epidemiologi Daniel Kjær Helene Mathilde Larsen
16.45 – 17.00 Kaffe & kage 17.00 – 18.30 Session O.3 Chairmen: Grundforskning Anne-Mette Hvas Sofie Bech Andersen 18.45 – 19.45 Middag 20.00 – 22.00 Pubquiz
6 Program lørdag d. 7.
07.00 – 08.00 Morgenløb eller morgenbadning & fællessang 08.00 – 09.00 Morgenmad 09.00 – 10.30 Session O.4 Chairmen: Psykiatri & Neuroscience Carsten Reidies Bjarkam Nanna Romar Pagsberg
10.30 – 10.50 Kaffe, vand & frugt 10.50 – 12.30 Poster sessioner Chairmen: P.3 Grundforskning Malene Hvid Klara Rasmussen Lanng P.4 Kardiologi Emil Nielsen Holck Nanna Junker Udesen 12.30 – 13.30 Frokostbuffet 13.30 – 14.45 Session O.5 Chairmen: Epidemiologi Mette Nørgaard Morten Schmidt 14.45 – 15.30 Gåtur
15.30 – 15.45 Kaffe & kage 15.45 – 17.15 Session O.6 Chairmen: Intern Medicin Janne Ladefoged Fassov Zheer Husain 18.45 – 19.00 Velkomstdrink 19.00 Gallamiddag Festtaler: Jesper Højager Fabech Bille 03.00 Natmad
Program søndag d. 8.
09.30 – 10.30 Morgenmad 10.30 – 11.00 Udtjekning 11.00 – 11.45 Foredrag: Klaus Larsen Medicinens historie – fra vrøvl til Journalist, Ugeskrift for Læger videnskab
11.45 – 12.00 Kaffe, frugt & sandwich
12.00 Afslutning & afrejse
7 Paneldebat – Det evidensbaserede sundhedsvæsen Paneldebatten ved Kongres for Medicinsk Studenterforskning 2020 stiller spørgsmålstegn ved vores evidensbaserede sundhedsvæsen. Har vi et evidensbaseret sundhedsvæsen? Er evidens vigtigt? Og i så fald hvorfor? Bør der altid foreligge evidens bag nye tiltag? Hvad gør vi, når forskningen skrider for langsomt frem til at imødekomme befolkningens ønsker? Eller til at afværge en epidemi? Hvornår kan vi gå på kompromis med evidensen? Bør vi nogensinde?
Emnet er højaktuelt i det danske samfund. Medicinsk cannabis har for alvor rejst debatten om ibrugtagning af lægemidler med ringe evidens og Lægeforeningen har krævet skrappere kontrol med alternativ behandling. Almindelige borgere og patientforeninger stiller krav til politikere, til læger og forskere og til sundhedsvæsenet.
Til at belyse disse og en række andre problemstillinger har Selskab for Medicinsk Studenterforskning inviteret årets debattører: Ida Donkin fra Læger Formidler, Leif Vestergaard Pedersen fra Medicinrådet og Det Etiske Råd, Jesper Fisker fra Kræftens Bekæmpelse, Jonas Dahl fra Regionshospitalet Randers og Marlene Øhrberg Kragh fra Sundhedsstyrelsen. Charlotte Strøm vil lede debatten med sikker hånd, og vi håber, at alle på KMS vil deltage aktivt og spørgende. Forståelse for andre dele af vores sundhedsvæsen kan højne vort fremtidige samarbejde – og måske vi alle går klogere herfra.
Panelet Debattører Ida Donkin Læge, Ph.d., sundhedsformidler for Læger Formidler Jesper Fisker Cand.scient.pol., Ph.d., administrerende direktør for Kræftens Bekæmpelse Jonas Dahl Cand.mag., hospitalsdirektør på Regionshospitalet Randers Leif Vestergaard Pedersen Cand.oecon., medlem af Medicinrådet og af Det Etiske Råd Marlene Øhrberg Krag Læge, centerchef for Evidens, Uddannelse og Beredskab ved Sundhedsstyrelsen Moderator Charlotte Strøm Læge, journalist, underviser i forskningskommunikation på KU
8 Taksigelser
Selskab for Medicinsk Studenterforskning vil gerne takke alle sponsorerne for deres flotte bidrag, uden hvilke Kongres for Medicinsk Studenterforskning 2020 ikke var mulig.
Aarhus Universitets Forskningsfond
Brødrene Hartmanns Fond
Institut for Klinisk Medicin, Aarhus Universitet
Institut for Biomedicin, Aarhus Universitet
Rigshospitalet
Aarhus Universitetshospital
Health, Aarhus Universitet
Det Sundhedsfaglige Fakultet, Aalborg Universitet
Det Sundhedsfaglige Fakultet, Syddansk Universitet
Institut for Folkesundhedsvidenskab, Aarhus Universitet
Forskningens Hus, Aalborg Universitetshospital
Familien Hede Nielsens Fond
Regionshospitalet Randers
9 Arrangører
Aimi Hamilton Marie-Louise Beier Guldfeldt
Alexander Emil Kaspersen Martin Thomsen
Anne Sofie Borg Hammer Mette Vestergård Pedersen
Casper Homilius Omeed Neghabat
Christina Shen-Zhuang Nielsen Pernille Tilma Tonnesen
Ditte Kamille Rasmussen Peter Carøe Lind
Dung Thuy Nguyen Simone Buchardt Brandt
Henrik Bjerre Simone Juel Dragsbæk
Jonathan Yde Thomas Weiss
Kasper Munch Lauridsen Tobias Stemann Lau
Mads Andersen
10 Chairmen
Poster session 1 Allan Flyvbjerg Centerdirektør, Steno Diabetes Center Copenhagen Stine Karlsen Ph.d.-studerende, Aarhus Universitetshospital
Poster session 2 Daniel Willy Kjær Klinisk lektor, Aarhus Universitetshospital Helene Mathilde Larsen Ph.d.-studerende, Aarhus Universitetshospital
Poster session 3 Malene Hvid Lektor, Aarhus Universitet Klara Rasmussen Lanng Ph.d.-studerende, Psykiatrisk Center Ballerup
Poster session 4 Emil Nielsen Holck Ph.d.-studerende, Aarhus Universitetshospital Nanna Junker Udesen Ph.d.-studerende, Odense Universitetshospital
11 Oral session 1 Cecilie Ramlau-Hansen Professor, Aarhus Universitet Dorthe Maria Vittrup Ph.d.-studerende, Herlev og Gentofte Hospital
Oral session 2 Henning Rud Andersen Professor, Aarhus Universitetshospital Ida Albertsen Ph.d.-studerende, Aalborg Universitetshospital
Oral session 3 Anne-Mette Hvas Viceinstitutleder, Aarhus Universitet Sofie Bech Andersen Ph.d.-studerende, Rigshospitalet
Oral session 4 Carsten Reidies Bjarkam Klinisk professor, Aalborg Universitetshospital Nanna Romar Pagsberg Ph.d.-studerende, Psykiatrisk Center Ballerup
Oral session 5 Mette Nørgaard Professor, Aarhus Universitetshospital Morten Schmidt Lektor, Aarhus Universitetshospital
Oral session 6 Janne Ladefoged Fassov Afdelingslæge, Aarhus Universitetshospital Zheer Husain Ph.d.-studerende, Aarhus Universitetshospital
12 INDHOLD
Oversigt over sessioner
P.1 Intern Medicin ...... 17
P.2 Epidemiologi ...... 26
P.3 Grundforskning ...... 36
P.4 Kardiologi ...... 46
O.1 Mor & Barn ...... 55
O.2 Kardiologi ...... 62
O.3 Grundforskning ...... 68
O.4 Psykiatri & Neuroscience ...... 76
O.5 Epidemiologi ...... 83
O.6 Intern Medicin ...... 90
13 List of Talks
List of Talks
P.1 Intern Medicin 17 Shathmigha Ketheeswaran Kumarasamy ...... 17 Frederik Brix ...... 18 Magnus Møller ...... 19 Jacob Venborg ...... 19 Christian Møller Jensen ...... 20 Alex Thomsen ...... 21 Janne Meisner Madsen ...... 22 Mette Freytag ...... 23 Jonatan Bundgaard Troldborg ...... 23 Signe Risbøl Vils ...... 24 Jelena Stankovic ...... 25
P.2 Epidemiologi 26 Ann-Katrine Roswalld Andersen ...... 26 Anne Emilie Secher ...... 27 Adam Flensborg Safikhany ...... 28 Elsa Rán Kristjánsdóttir ...... 28 Simone Haastrup ...... 29 Wafie Hussein Chahrour ...... 30 Marte Holmen ...... 31 Sibel Yilmaz ...... 32 Nanna Juanita Lund Sørensen ...... 33 Julie Ravn ...... 34 Anders Lehmann Dahl Pedersen ...... 35
P.3 Grundforskning 36 Lærke Hjøllund Hansen ...... 36 Nanna Steengaard Mikkelsen ...... 36 Amalie Dyrelund Broksø ...... 37 Henriette Mathiesen ...... 38 Trine Rerup ...... 39 Camilla Wibrand ...... 39 Elisabeth Larsen ...... 40 Benedikte Niemann ...... 41 Yoanna Vladimirova ...... 42
14 Dorthe Dahmke ...... 43 Silke Dahlbom Nielsen ...... 43 Kathrine Friis ...... 44 Julie Bjerrelund ...... 45
P.4 Kardiologi 46 Mette Vold Hansen ...... 46 Trine Trab ...... 47 Cecilie Budolfsen ...... 48 Salma Raghad Karim ...... 48 André Shamoun ...... 49 Natascha Gaster ...... 50 Naja Stausholm Winther ...... 50 Jacob Valentin Hansen ...... 51 Simone Juel Dragsbæk ...... 52 Pernille Tonnesen ...... 53 Dung Thuy Nguyen ...... 54
O.1 Mor & Barn 55 Louise Gunhard Nielsen ...... 55 Emma Sofie Høgsted ...... 56 Gülizar Saritas ...... 57 Sofie Elmqvist Bendixen ...... 58 Louise Ruby Høj Illum ...... 59 Laura Louise Fosgrau Hergel ...... 60 Aimi Hamilton ...... 61
O.2 Kardiologi 62 Harman Yonis ...... 62 Jacob Seefeldt ...... 63 Henrik Bjerre ...... 64 Casper Homilius ...... 65 Martin Sejr-Hansen ...... 66 Lucas Malta Westergaard ...... 67
O.3 Grundforskning 68 Xabier Sørtvedt ...... 68 Katrine Bønnerup ...... 69 Nanna Johnsen ...... 69 Kristian Antonsen ...... 70 Ditte Rasmussen ...... 71 Ann-Sophie Bech ...... 72 Frederik Duch ...... 73 Julie Hessellund ...... 74 Mie Wolff Kristensen ...... 75
O.4 Psykiatri & Neuroscience 76 Albin Arvidsson ...... 76 Line Amalie Hellemose ...... 77 Theis Mariager ...... 78
15 Navid Noory ...... 79 Kjeld Mohr ...... 79 Stine Uhrenholt Jensen ...... 80 Casper Skjærbæk ...... 81 Linda Eriksen ...... 82
O.5 Epidemiologi 83 Henriette Vendelbo Graversen ...... 83 Kamilla Lanng ...... 84 Mads Albrecht Andersen ...... 85 Marwan Othman ...... 86 Elizabeth Vlk ...... 87 Thomas Aamand ...... 88 Philip Munch ...... 89
O.6 Intern Medicin 90 Lotte Lindgreen Eriksen ...... 90 Sofie Amalie Gehrcke Bisholm ...... 91 Søren Klingenberg ...... 92 Rasmus Bastkjær ...... 93 Cecilie Mæng ...... 94 Daniella Rahim ...... 95 Line Elise Møller Hansen ...... 96 Camilla Ann Fjelsted ...... 97 Marie Øbo ...... 98
16 P.1. INTERN MEDICIN
Poster sessioner
Session P.1: Intern Medicin
P-1.01 Shathmigha The effect of protein supplement on the Ketheeswaran reproductive health of male mice Kumarasamy S Ketheeswaran1, 2 SE Pors3 L Zuniga3 CE Lemser3 P Christensen4 P Humaidan1, 2 SG Kristensen3 1Faculty of Health, Aarhus University 2The Fertility Clinic, Skive Regional Hospital 3Laboratory of Reproductive Biology, Rigshospitalet 4SPZ Lab A/S
Background: Protein supplements are becoming prominent nutritional supplements among young men. However, they remain unregulated as they do not identify as medical drugs, and concerns have been raised about potential contaminants possibly affecting reproductive health. A recent pilot study by our group reported a negative effect of protein supplement intake on semen parameters among 20 infertile males. The current study in male mice, investigated if protein supplement affected their reproductive health.
Methods: A total of 24 mice was fed protein supplement and 24 controls were included. Over two time periods of 3 months the mice were fed protein supplement (Whey100 from BodyLab) 5 days a week, in order to ensure that the murine spermatogenetic cycle was covered. To standardize semen parameters and obtain reproductive outcomes, the males were housed with 2 females for 5 days at the end of the experiment. Two days after mating, the animals were euthanized and reproductive parameters were assessed.
Results: There was no significant effect of protein supplement, between controls and the protein supplement group, on the following parameters: sperm concentration, total and progressive motility, DNA fragmentation index, oxidation-reduction potential in seminal plasma, body and testicular weight, serum testosterone, litter size and impregnation rate. However, all mice in the protein supplement group, impregnated at least one female, whereas 13% of the controls did not impregnate any.
17 P.1. INTERN MEDICIN
Conclusion: The particular protein supplement investigated in the current study does not seem to affect the reproductive health of male mice when exposed at human levels.
Acknowledgements: Frimodt Heineke Foundation and A.P. Møller Foundation (Fonden til Lægevidenskabens fremme, 18-L-0347) are thanked for having funded this study. We would also like to thank Ida Marie Boisen for her help with the sperm retrieval protocols.
P-1.02 Frederik Brix Role of lymphocyte-activation gene-3 and fibrinogen like protein-1 in alcoholic hepatitis. FH Brix1 BW. Deleuran2 TD Sandahl1 S Støy1 1Department of Hepatology and Gastroenterology, Aarhus University Hospital 2Department of Biomedicine, Aarhus University
Background: Alcoholic hepatitis (AH) is characterized by destructive hepatic inflammation and a primed, but ineffective, immune system. Lymphocyte-activation gene (LAG)-3 is an inhibitory receptor linked to T-cell exhaustion. Fibrinogen like-protein (FGL)-1 was recently shown to potentiate the inhibitory properties of LAG-3. FGL-1 is a liver-derived protein, which is upregulated in response to liver inflammation. We therefore want to investigate if LAG-3 and FGL-1 are involved in the immune paralysis in AH.
Methods: The study population consists of 40 patients with AH. Samples were collected at diagnosis and at days 7 and 90 following diagnosis. Controls were stable, alcohol-related cirrhosis patients and healthy subjects. Liver LAG-3 and FGL-1 was measured by RNA-sequencing. Soluble LAG-3 and FGL-1 was measured by ELISA and T cell expression of LAG-3 and the effect of FGL-1 stimulation will be carried out by flow cytometry.
Results: Patients with AH have decreased mRNA expression of LAG-3 in the liver at diagnosis compared with healthy controls (P < 0.001). Similarly, at diagnosis plasma sLAG-3 is significantly decreased compared to their individual steady state levels at day 90 (P < 0.05). The expression of FGL-1 in liver tissue is significantly increased in patients with AH compared to healthy control as is plasma FGL-1 (P < 0.05, both)
Conclusion: Preliminary results. Our current working hypothesis is that low sLAG3 reflects high surface expression LAG-3 on peripheral T cells, which via elevated FGL-1 contributed to the depressed T cell functions involved in the immune paralysis.
Acknowledgements: This project is funded by Novo Nordisk Fonden.
18 P.1. INTERN MEDICIN
P-1.03 Magnus Møller Transplacental transport and foetal accumulation of artificial sweeteners M Møller1, 2 M Pedersen2 E Greibe3 E Hoffman-Lücke3 PG Ovesen1 1Department of Obstetrics and Gynecology, Aarhus University Hospital 2Comparative Medicine Lab, Aarhus University 3Department of Clinical Biochemistry, Aarhus University Hospital
Background: Obesity is increasing and evidence points towards obesity being rooted in childhood and is even programmed in-utero. Currently overweight women are advised to substitute sugar-sweetened beverages with diet drinks containing artificial sweeteners (AS). Recent evidence suggests that consumption of AS during pregnancy increases the risk of obesity in the child, putting already exposed children at further risk. We hypothesize a transport of AS across placenta into the foetal circulation.
Methods: We will conduct a clinical trial in which 30 pregnant women are given an oral dose of artificial sweeteners before planned caesarean section. 10 controls will refrain from intake of AS. The amount of AS is then measured via high-performance liquid chromatography in maternal blood and urine and in foetal blood, amniotic fluid and placental tissue.
Results: Inclusion of patients is ongoing. The ratio between plasma concentrations of AS in maternal and foetal blood is considered the primary outcome. Maternal urinary concentration of AS and a possible accumulation of AS in amniotic fluid and placental tissue are secondary outcomes. Preliminary results will be presented at KMS 2020 if available.
Conclusion: To our knowledge we are the first to investigate if artificial sweeteners can cross the placenta and enter foetal circulation. The results have the potential to change the current dietary guidelines for pregnant women. A conclusion is expected in spring 2020.
Acknowledgements: The project has received funding from P. Carl Petersen Foundation. No conflict of interest to declare.
P-1.04 Jacob Venborg The Effect of Transcutaneous Vagus Nerve Stimulation in Patients with Polymyalgia Rheumatica J Venborg1 C Brock2 AL Wegeberg2 M Pfeiffer-Jensen1 1Department of Rheumatology, Aarhus University Hospital 2Aalborg University Hospital
Background: Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease characterised by proximal muscle pain and stiffness. The main treatment is systemically
19 P.1. INTERN MEDICIN administered prednisolone, a treatment linked to numerous adverse effects. In recent years, studies have shown that stimulation of the vagus nerve can reduce the inflammatory response. This study investigates the effect of transcutaneous vagal nerve stimulation (tVNS) in prednisolone-naïve patients with PMR.
Methods: 20 prednisolone-naïve patients diagnosed with PMR underwent a 5-day tVNS intervention, stimulating themselves thrice a day using a handheld vagus nerve stimulator. Patient visits were conducted on baseline, day 2 and 5. Blood samples were drawn, vagus nerve activity was assessed and health assessment questionnaires were completed during visits. Vagal tone was measured as cardiac vagal tone (CVT) assessed as heart rate variability (HRV) using an ECG-device.
Results: The project is currently ongoing. Thus, no results nor conclusion can be made at this point. If available, preliminary results and conclusions will be presented at the congress. CVT, CRP and serum levels of IL-6 will be compared between baseline, day 2 and 5. Statistical analyzes will be performed in STATA.
Conclusion: Above.
Acknowledgements: This project was funded by The Danish Rheumatism Association.
P-1.05 Christian Comorbidities in patients with head and neck Møller Jensen cancer treated with curative intent radiotherapy and their effect on radiotherapy interruptions, and infectious complications CM Jensen1 C Terrones-Campos1 B Ledergerber1 IR Vogelius2 M Helleberg1 L Specht2 JD Lundgren1 1Centre of Excellence for Health, Immunity and Infections, Rigshospitalet 2Department of Oncology, Rigshospitalet
Background: Patients with cancer and comorbidities require a careful assessment of their treatment and follow-up. Little is known about comorbidities in the setting of cancer diagnoses and their effect on treatment outcomes. The hypothesis of this study is that comorbidities affect patient response and expose them to infectious complications. The purpose of the study is to evaluate how chronic comorbidities influence cancer treatment outcomes in patients undergoing radiotherapy, using registry data.
Methods: Patients with head and neck cancer treated with curative intent radiotherapy at Rigshospitalet from 2009 to 2016 are included. Type, duration, severity and specific treatment of comorbidities will be described according to cancer diagnoses. The number of radiotherapy interruptions, the duration of the treatment interruption, whether the interruption was due to an infectious complication or related to the chronic condition, and if the interruption required a hospital admission will be determined.
Results: None yet.
20 P.1. INTERN MEDICIN
Conclusion: No conclusions have been made yet.
Acknowledgements: This study has not received any funding thus far, but an application to Rigshospitalets Forskningsfond is being reviewed. No conflicts of interest
P-1.06 Alex Thomsen A mechanistic evaluation of the effect induced by repeated administration of local anesthetic EMLA-cream on itch AB Thomsen1 SL Vecchio2 L Arendt-Nielsen1, 2, 3, 4 1Department of Health Science and Technology, Aalborg University 2Center for Sensory-Motor Interaction, Aalborg University 3Center for Neuroplasticity and Pain, Aalborg University 4Department of Translational Pain Biomarkers, Aalborg University
Background: Itch is a common symptom in many diseases, primarily in the skin and is often disregarded. Chronic itch, however, is a debilitating condition seriously affecting quality of life. As of now, there exist several treatments on itch but they all show low effect and some with serious side effects in prolonged use. This study aims to see if repeated application of a topical anesthetic mixture of lidocaine and prilocaine (EMLA) is an effective treatment of histaminergic and non-histaminergic itch
Methods: 26 healthy participants will be enrolled on three consecutive days. At all days a 2x3 hours application of EMLA and placebo on the forearms are made with measurements at the end of each application. Measurements consist of laser perfusion image and sensibility tests including mechanical pain sensitivity and threshold, heat detection and pain thresholds, supra-threshold pain, and alloknesis. On day 3, a 9-minute VAS-test of itch and pain is recorded in each area, provoked by histamine or cowhage
Results: The study is ongoing and results will be presented at KMS 2020
Conclusion: Will be presented at KMS 2020
Acknowledgements: The study is sponsored by Center for neuroplasticity and pain (CNAP) and Center of Sensory-Motor Interaction, Aalborg University.
21 P.1. INTERN MEDICIN
P-1.07 Janne Meisner Bioimpedance: An objective measure for fluid Madsen balance in patients with septic shock in the ICU? JM Madsen1, 2 TS Itenov1 M Bestle1, 2 1Department of anaesthesiology, ICU, Nordsjællands hospital Hillerød 2University of Copenhagen
Background: Initial fluid resuscitation is vital when treating septic shock. It can lead to overhydration, organ dysfunction, and higher mortality. Treatment target is to infuse just the correct amount of water, but no clinical objective method is available to guide this. Bioimpedance measures body fluid volume. It is non-invasive, safe, fast and low-cost. The aim of this study is to determine if bioimpedance is a precise and reproducible method to measure fluids in patients with septic shock in the ICU.
Methods: A prospective observational proof-of-concept study situated in one ICU in Denmark and one in Belgium. We aim to include 45 patients. Adult patients are included within 24 hours of diagnosing septic shock according to the Sepsis-3 criteria. The patient must, therefore, have an infection, need for vasopressors and S-Lactate above 2 mmol/L. Bioimpedance measures will be made with two different devices on ICU days 1, 2, 3, 10 and 11. Inclusion is expected to start December 2019 and end in May 2020.
Results: The hypothesis is that there is an agreement between bioimpedance measured with two different devices on the right and the left side of the patient and with 1 hour between measurements. This agreements should be independent of whether the patient is in septic shock or not and whether the measurements are done in the early (day 1-3) or late (day 10-11) phase. We expect an agreement between bioimpedance and clinical methods such as weighing, fluid balance, edema, and the physician’s assessment.
Conclusion: The validation of bioimpedance in patients with septic shock may have a clinical impact in both guiding fluid resuscitation in the acute phase and in the deresuscitation phase, where fluids are removed. It is also a possible research tool for already planned studies in the ICU.
Acknowledgements: Affiliation: M.D. and Ph.D. Theis Skovsgaard Itenov and Senior consultant, associate professor of research Morten H. Bestle
Funding: Nordsjællands hospital, Hillerød.
Investigation site: department of anaesthesiology, ICU, Nordsjællands hospital Hillerød.
For free lend of Bioimpedance apparatus and service support: Fresenius Medical Care Maltron
22 P.1. INTERN MEDICIN
P-1.08 Mette Freytag Identification of Novel Innate Immunodeficiencies in Patients with Varicella-Zoster Virus Encephalitis M Freytag1, 2 MM Thomsen1, 2 SE Jørgensen1, 2 ME Carter-Timofte1, 2 SR Paludan2 TH Mogensen1, 2, 3 1Department of Infectious Diseases, Aarhus University Hospital 2Department of Biomedicine, Aarhus University 3Department of Clinical Medicine, Aarhus University
Background: Varicella-Zoster virus (VZV) causes varicella during primary infection and zoster upon reactivation. A rare but serious complication is the virus spreading to the central nervous system (CNS) and the subsequent development of encephalitis. Host genetics is believed to be the determining factor of disease manifestations and here we aim to identify and functionally characterize novel single inborn errors of immunity associated with increased susceptibility to VZV infections in the CNS.
Methods: We will perform Whole Exome Sequencing on patient DNA to identify potential disease causing mutations, particularly in genes encoding innate immune molecules involved in type 1 Interferon production. Subsequently, we will study antiviral responses in patient peripheral blood mononuclear cells (PBMCs) compared to healthy controls. Finally, the molecular basis for altered function of the immune molecules will be evaluated as well as viral replication in different experimental neuronal cell models.
Results: Preliminary results will be presented at KMS20
Conclusion: The study will provide greater insight into VZV neuropathogenesis and host immunity to VZV. This knowledge may enable us to identify individuals with increased risk of severe CNS infection by VZV, and will furthermore be valuable in future development of improved diagnosis, prevention and treatment.
Acknowledgements: The project is financially supported by the Lundbeck Foundation. The authors have no conflicts of interest to declare.
P-1.09 Jonatan A case-control study on quantifying levels of Bundgaard physical activity in the adult Nepalese Troldborg population living with type 2 diabetes in Pokhara, Nepal JB Troldborg1 RØ Nielsen1 P Kallestrup1 D Neupane2 1Department of Public Health, Aarhus University, Denmark 2Nepal Development Society (NEDS), Pokhara, Nepal
Background: Type 2 diabetes is a growing health problem in developing countries such as Nepal. In Nepalese literature there is a paucity on physical activity data, and just a single study has investigated the association between physical inactivity and type
23 P.1. INTERN MEDICIN
2 diabetes based on self-reported data. This study will improve the understanding of the growing incidence of type 2 diabetes among adults in Nepal by quantifying levels of physical activity in the study population.
Methods: This is a case-control study with estimated 2 000 samples. Study population will be randomly selected from the COBIN-D trial and the ongoing World Diabetes Foundation project. Measurement of physical activity will be collected via a Garmin wearable device during a 14 days period. Time spent in physical activity will be assessed and categorized into four groups. Furthermore, participants will provide information on comorbidity that can affect their level of physical activity.
Results: As of December 2019, no results have been obtained yet
Conclusion: As of December 2019, no conclusions have been drawn.
Acknowledgements: I would like to thank my main supervisor lector Rasmus Østergaard Nielsen, Department of Public Health, Aarhus University as well as supervisors Per Kallestrup, Department of Epidemology, Aarhus University and Dinesh Neupane, Nepal Development Society NEDS, Pokhara, Nepal.
P-1.10 Signe Risbøl Thromboembolic risk in Systemic Lupus Vils Erythematosus and Antiphosholipid Syndrome SR Vils1 A Troldborg1, 2 AM Hvas3 S Thiel1 1Department of Biomedicine, Aarhus University 2Department of Rheumatology, Aarhus University Hospital 3Center for Haemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital
Background: Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are chronic autoimmune diseases, which often overlap, where about 40% of SLE patients also suffer from APS. The significant reduction in life expectancy seen in these patients is mainly caused by thromboembolic events. SLE and APS patients have increased activation of the complement system and increased platelet-activation, which could contribute to the patients’ pro-thrombotic phenotype.
Methods: 60 patients, divided into 3 groups based on their diagnosis (SLE, SLE and APS, APS) will be included in the project. 60 gender-matched controls will be included concurrently. Upon inclusion, blood- and plasma-samples will be collected, as well as information about patient and disease status. Proteins of the complement system will be characterized using the time-resolved immune-fluorometric method. Platelets will be characterized using light transmission aggregometry and flow cytometry.
Results: At the time of application, patient inclusion has begun, but no results have been produced. Our hypothesis is that concentrations of complement-proteins, as well as the degree of platelet activation, will be altered in all 3 patient-groups compared to the healthy controls, and that the degree of complement activation is correlated to increased platelet activity.
24 P.1. INTERN MEDICIN
Conclusion: With this study, we will explore the interplay between the complement system and platelets in patients with SLE, APS or SLE combined with APS. Through these studies, we will expand the knowledge about complement-platelet interactions and the mechanisms behind immune-mediated blood clot formation.
Acknowledgements: The project is financed by Gigtforeningen.
P-1.11 Jelena Food Neophobia among Danish adolescents Stankovic diagnosed with ADHD J Stankovic1 PH Thomsen2 T Ovesen1 1Department of Oto-rhino-laryngology, Regional Hospital in Holstebro 2Department of Child- and Youth Psychiatry, Aarhus University Hospital
Background: A high level of Food Neophobia (avoidance of novel foods) is associated with deficiencies in nutrients. The same spectrum of nutrients has been established to be deficient among adolescents with ADHD. This nutritional deficiency is associated with pronounced symptoms of ADHD. If there is an association between food neophobia and the eating habits of adolescents diagnosed with ADHD based on an altered olfaction/gustation it will create a new target for intervention/treatment of ADHD.
Methods: Danish adolescents in the age of 13–16 years will be enrolled. 100 without and 100 with an ADHD-diagnosis. The participants will answer two questionnaires concerning their dietary pattern and potential food neophobic behavior. Their olfactory function will be quantified using Sniffin’ Sticks and their gustatory level will be quantified using Taste Spray. Participants showing the most food neophobic pattern will be invited to perform a behavioral test and quality-of-life questionnaire.
Results: Data is pending. Preliminary results will be presented at KMS2020.
Conclusion: Conclusions are yet to be made.
Acknowledgements: Nothing to declare.
25 P.2. EPIDEMIOLOGI
Session P.2: Epidemiologi
P-2.01 Ann-Katrine Differentiating between Fatigue and Sleepiness Roswalld in Patients with Multiple Sclerosis and Efficacy Andersen of Modafinil as Treatment in these Symptoms AK Roswalld Andersen1, 2 KB Svendsen1, 2 T Petersen1, 2 M Otto1, 2, 3 1Department of Neurology, Aarhus University Hospital 2Department of Clinical Medicine, Aarhus University 3Department of Clinical Neurophysiology, Aarhus University Hospital
Background: Fatigue is a common symptom in Multiple Sclerosis (MS) patients, and previous studies show they frequently suffer from sleep problems as well as sleepiness. Modafinil has a wake-promoting effect in particularly narcolepsy patients, but more studies are needed to assess the effect on sleepiness and fatigue in MS patients. We aim to contribute to the understanding of correlations between sleep and sleepiness/fatique in MS patients, and to better identify who will benefit from modafinil treatment.
Methods: This study will include 30 MS patients, who experience daytime tiredness. The project is an open-label study, which investigates the effects of 3 weeks of modafinil treatment on sleepiness and fatigue in MS patients. The study will examine sleep quality and efficacy, quality of life, sleepiness and fatigue through 7 questionnaires, daily sleep diaries and a wrist-worn actigraph. All participants will undergo neurological examinations as well as electrocardiography, and blood tests will be taken.
Results: The study is ongoing, and results are yet to be produced. Preliminary results will be presented at KMS 2020 if available.
Conclusion: Conclusions are yet to be made.
Acknowledgements: This project is supported by a scholarship from the Danish Society for Neuroscience.
26 P.2. EPIDEMIOLOGI
P-2.02 Anne Emilie Health in offspring of mothers with Secher Inflammatory Arthritis treated with Tumor Necrosis Factor inhibitors in pregnancy: a collaborative NordForsk cohort study from four Nordic countries AE Secher1 K Hellgren2, 3 B Glintborg1, 4 AL Rom5 B Michelsen6, 7 B Gudbjornsson8 F Granath3 ML Hetland1, 4 1COPECARE, Center for Rheumatology and Spine Diseases, Rigshospitalet, Denmark 2Rheumatology Unit, Dept of Medicine, Karolinska Institutet, Sweden 3Clinical Epidemiology Division, Dept. of Medicine, Karolinska Institutet, Sweden 4Dept of Clin Med, Fac of Health and Med Sciences, University of Copenhagen, Denmark 5Research Unit Women’s and Children’s Health, Rigshospitalet, Denmark 6Dept of Rheumatology, Diakonhjemmet Hospital, Norway 7Division of Rheumatology, Hospital of Southern Norway Trust, Norway 8Centre for Rheumatology Research, University Hospital and Faculty of Medicine, University of Iceland, Iceland Background: Maternal inflammatory arthritis (IA) is associated with increased risk of adverse pregnancy outcomes. Tumor Necrosis Factor inhibitors (TNFi) are used to treat women with IA and have in recent years, increasingly, been continued into pregnancy. Few studies have explored consequences of intra-uterine TNFi in IA on offsprings. Although the results are reassuring, follow-up has been short and with few included patients. We aim to explore health status of the children in the first 10 years of life.
Methods: Children (born 2006–2015) of mothers with IA in Denmark, Sweden, Norway and Iceland will be included based on data from health and population registries. Exposure of interest will be TNFi any time during pregnancy. Outcomes are infections in children <1 year of age, and epilepsy, diabetes mellitus, juvenile arthritis, asthma and neoplasms <10 years of age. Cox proportional hazards models will be used to calculate HRs and 95% CIs for risks of outcomes among TNFi exposed vs unexposed offsprings.
Results: The project is a collaboration between four Nordic countries that all have unique possibilities to link between complete and prospective patient registers. We are in the process of assembling datasets from all countries at Statistics Denmark. Since collaborating beyond national borders in a time of increasing data protection regulations is a difficult task, the different aspects of these challenges will be presented at KMS 2020.
Conclusion: Our ambition is that the results of this project will have a direct impact on patient counselling, which is at this point insufficient, regarding potential short- and long-term effects in the offsprings of TNFi vs no-TNFi exposure during pregnancy.
Acknowledgements: The project was partly funded the Danish Rheumatoid Association, NordForsk and FOREUM. Anne Emilie Secher has received a pre-graduate research scholarship from Rigshospitalets Forskningspuljer.
27 P.2. EPIDEMIOLOGI
P-2.03 Adam Developing a mid-upper arm Flensborg circumference-for-age growth curve for school Safikhany children aged 8–16 years in Nepal. AF Safikhany1 P Kallestrup1 CB Patsche1 D Neupane2 1Department of Global Health, Aarhus University, Denmark 2Nepal Development Society (NEDS), Pokhara, Nepal
Background: Children and young adolescents in low-income countries suffer from a high prevalence of malnutrition. Measuring mid-upper arm circumference (MUAC), compared to Body mass index (BMI), is a faster, easier, cheaper, and more sensitive anthropometric measure to give information about the nutritional status. Today there is no internationally accepted reference for MUAC-for-age curve among school-aged children. This study aims to develop a MUAC-for-age curve among school children in Nepal.
Methods: This is a cross-sectional study with an estimated 18 000 samples. The participants will be school children aged 8–16 years from schools in the city and rural areas of Pokhara. This study will measure the children’s MUAC (cm), height (cm), weight (kg), and waist circumference (cm) and provide information on biological sex, date of birth, and ethnicity of the children through a handed questionnaire.
Results: As of November 2019, no results have been obtained yet.
Conclusion: As of November 2019, no conclusions have been drawn.
Acknowledgements: I would like to thank my main supervisor lector Per Kallestrup, Department of Epidemology, Aarhus University as well as supervisors Cecilie Blenstrup Patsche and Dinesh Neupane, Nepal Development Society NEDS, Pokhara, Nepal.
P-2.04 Elsa Rán Adherence and compliance during maintenance Kristjánsdóttir treatment of adult patients with acute lymphoblastic leukemia. ER Kristjánsdóttir1, 2 CU Rank1, 3 LN Toksvang1, 2 K Schmiegelow1, 2, 4 1Pediatric Oncology Research Laboratory, Rigshospitalet, University of Copenhagen 2Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen 3Department of Hematology, Rigshospitalet, University of Copenhagen 4Insitute of Clinical Medicine, The Faculty of Medicine, University of Copenhagen
Background: The prognosis of adults diagnosed with acute lymphoblastic leukemia (ALL) decreases with increasing age, and their survival is inferior when compared with children with ALL. Patient adherence and physician compliance to protocol guidelines are essential for survival, especially during the 2-year long maintenance treatment
28 P.2. EPIDEMIOLOGI consisting of oral 6-mercaptopurine and methotrexate. We hypothesize that the inferior survival of adults is affected by poor adherence and compliance.
Methods: This retrospective study includes adult (aged 18–45 years) ALL patients (N = 65), who have been treated in Denmark, according to the Nordic/Baltic NOPHO ALL2008 protocol and have received maintenance treatment. Collected patient data regarding maintenance treatment (e.g. prescribed doses of methotrexate and 6-mercaptopurine, adverse events and blood sample results including metabolites of methotrexate and 6-mercaptopurine) will be compared and analyzed to explore the adherence and compliance.
Results: Results are preliminary and will be presented at KMS 2020.
Conclusion: Investigating the adherence and compliance during maintenance treatment will add to the knowledge regarding adult ALL. This can be a step towards a more efficient treatment strategy, and thus an increase in the survival rate of adult ALL patients.
Acknowledgements: This project was funded by the Danish Cancer Society.
P-2.05 Simone Reversal of dabigatran in acute situations: Haastrup Real-world use of idarucizumab from introduction in 2015 to 2019 S Haastrup1 M Hellfritzsch2 AM Hvas1, 3, 4 E Lerkevang Grove1, 3 1Department of Clinical Medicine, Faculty of Health, Aarhus University 2Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark 3Department of Cardiology, Aarhus University Hospital 4Department of Clinical Biochemistry, Aarhus University Hospital
Background: Idarucizumab was introduced in Denmark in December 2015 as an antidote for dabigatran. Within recent years there has been a substantial increase in the use of dabigatran and other DOACs. Bleeding is an important side effect of all anticoagulants. Therefore, the lack of a reversal agent has been of concern for both patients and physicians. The actual clinical use and significance of this new drug has not been explored.
Methods: The study is to be conducted as observational case series describing the use of idarucizumab in acute clinical situations, exploring details in individual cases and patterns across the entire region. We will identify all patients who have received idarucizumab in the Central Denmark Region since market introduction and obtain all data from these patients medical records.
Results: Results are pending.
29 P.2. EPIDEMIOLOGI
Conclusion: Pending.
Acknowledgements: None.
P-2.06 Wafie Hussein Assessing the impact of supplementary training Chahrour on the spiritual conversations between employees and patients at hospice W H Chahrour1 N C Hvidt1 E A Hvidt1 D T Viftrup1 1Forskningsenheden for Almen Praksis
Background: Patients at the end of life don’t experience their existential and spiritual needs being sufficiently met by health care professionals. Studies have found that, according to health care professionals, this inadequacy is a result of insufficient education and knowledge. Professional shyness in the face of spiritual conversation and limited understanding of the existential needs of patients is also found to influence the inadequacy.
Methods: Methods for obtaining both qualitative and quantitative data were applied: focus group interviews, individual interviews and questionnaires with both qualitative and quantitative questions. Qualitative data were analyzed through interpretative phenomenological analysis (IPA). We included quantitative metrics to the questionnaire to better asses the impact and significance of the course for the participants.
Results: Preliminary results indicate that existential self-reflection and practicing communicational skill in safe environments increase staff’s experience of being competent in providing care for patients’ spiritual and existential needs.
Conclusion: A supplementary educational course for hospice staff with focus on existential self-reflection, the vulnerable encounter and developing shared professional language for spiritual care can make hospice staff better equipped to care for patients’ spiritual and existential needs.
Acknowledgements: Lundeckfondens Scholarstipendier i Almen Medicin
30 P.2. EPIDEMIOLOGI
P-2.07 Marte Holmen Thromboembolic risk among patients with elevated homocysteine levels M Holmen1 JF Arendt2 A-M Hvas1, 3 1Center for Haemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital 2Department of Clinical Biochemistry, Aarhus University Hospital 3Department of Clinical Medicine, Aarhus University
Background: Homocysteine (Hcy) is a sulhydryl-containing amino acid, metabolism of Hcy requires vitamin B12, folic acid and B6. An elevated level of plasma homocysteine is suggested to induce an increased risk of thromboembolism. Treatment with vitamin B12, folic acid and/or B6 have been shown to reduce Hcy with over 25%. It is, however, persistently controversial whether treating hyperhomocysteinemia with vitamin B12, folic acid and/or B6 improves vascular disease-associated morbidity and mortality.
Methods: We have identified 170 230 patients from Northern and Central Denmark in this population-based cohort study. All patients had a registered Hcy-measurement in the study period, 01.01.2000 to 31.12.2017. The diagnosis- and prescription history were collected, including thromboembolic events and prescription of homocysteine-lowering vitamin treatment in the study population.
Results: The study is ongoing, with expected analysis of data during spring 2020. We want to compare thromboembolic risk and treatment effect in patients with normal and elevated Hcy, and aim to clarify treatment practice in patients with elevated tHcy and their subsequent risk of arterial and/or venous thromboembolism.
Conclusion: Decisions on treatment as well as strategies for follow-up in patients with elevated Hcy have previously not been standardized. A clarification on which patients will benefit from vitamin treatment may lead to a more personalized treatment regime and a better prognosis for patients with elevated Hcy
Acknowledgements: The research project has received financial support from Orphan Europe Pharmaceutical Company.
31 P.2. EPIDEMIOLOGI
P-2.08 Sibel Yilmaz Clinical repeatability of radiostereometry using the EOS Imaging System for asessing hip prosthesis S Yilmaz1 K Kjaergaard1 J Jensen4 TR Savarimuthu2 S Overgaard1 H Malchau3 C Bragdon3 M Ding1 1Orthopaedic Research Laboratory, Department of Orthopaedic Surgery and Traumatology, Odense University Hospital, Department of Clinical Research, University of Southern Denmark, Denmark 2SDU Robotics, The Maersk Mc-Kinney Moller Institute, University of Southern Denmark, Denmark 3Harris Orthopaedic Laboratory, Massachusetts General Hospital, Boston, United States 4Research and Innovation Unit of Radiology, University of Southern Denmark Department of Radiology, Odense University Hospital, Denmark
Background: With the numbers of primary total hip arthroplasty (THA) increasing in Denmark, there is a need to precisely assess the longevity of these evolving prostheses. While radiostereometric analysis (RSA) is the current gold standard for wear measurement in THA, EOS-based biplanar RSA is a new, promising method. The aim of this study is to assess measurement-to-measurement variability of radiostereometry using the EOS Imaging System.
Methods: The study includes 30 patients, each of whom is scanned twice in the EOS Imaging System, consecutively. Images are analyzed, the 3D positions of the hip prosthesis cup and head are reconstructed, and the difference in distance from head center to cup center between first and second scan is assessed. Primary outcome will be standard deviation (s.d.) with corresponding standard errors (s.e.) and 95% confidence intervals for each position. P values 0.05 is considered significant. ≤ Results: Data collection and analysis will take place from January 2020 to March 2020. Preliminary results will be presented if available.
Conclusion: If there is no significant variation between repeated measurements, this method could replace conventional RSA. We will be able to measure wear and placement of the prosthesis with high resolution pictures and this can be done much faster with lower radiation doses than with conventional RSA.
Acknowledgements: Nothing to declare.
32 P.2. EPIDEMIOLOGI
P-2.09 Nanna Juanita Anti androgenous agents’ effect on Bone mass, a Lund Sørensen systematic review NJL Sørensen1 FD Højsager1 TK Jensen1 1Department of Environmental Medicine, Odense University Hospital
Background: Per- and polyfluoroalkyl substances (PFAS), phthalates and bisphenol-A (BPA) are substances used in the production of nonstick coatings, softening of plastic and production of plastic respectively, and have been suspected to have an inhibitory effect on androgens. Androgens play a central role in bone formation, and it is therefore relevant to explore the relationship between the blood and/or urine content of these substances and bone mass density (BMD).
Methods: A systematic review was conducted based on 6 articles exploring this connection in adult men and women as well as children. Studies focused on postmenopausal women were excluded. All articles were found on PubMed on march 29th 2019.
Results: The studies found that a significant correlation between high PFAS-levels and reduced BMD existed.
Conclusion: As little research has been done on this topic, and due to the variation in test populations, methodology as well as results, more research on this topic is needed.
Acknowledgements: Nothing to declare
33 P.2. EPIDEMIOLOGI
P-2.10 Julie Ravn First trimester screening for late-onset preeclampsia: Evaluation of novel predictive biomarker MMP-7 in combination with the FMF algorithm JD Ravn1 I Riishede Christiansen3 CK Ekelund3 A Tabor4 M Overgaard2 L Sperling1 1Department of Gynecology and Obstetrics, Odense University Hospital 2Department of Clinical Biochemistry and Pharmacology, Odense University Hospital 3Center of Fetal Medicine and Pregnancy, Rigshospitalet 4Department of Clinical Biochemistry, Rigshospitalet
Background: Preeclampsia (PE) affects 2–8% of pregnancies and is a leading cause of maternal mortality worldwide. Although 75–90% of PE cases result in delivery after 34 weeks of pregnancy, useful biomarkers for late-onset PE (LO-PE) have yet to be identified. This study evaluates matrix metalloproteinase 7 (MMP-7) as a biomarker for LO-PE at 11-14 weeks of pregnancy, alone and in combination with maternal characteristics, mean arterial pressure (MAP), and uterine artery pulsatility index (UA PI).
Methods: This is a nested case-control study, the cohort of which consists of pregnant women assigned to Odense University Hospital for their first trimester scan. MAP, UA PI, maternal characteristics, and blood samples are obtained on the day of the visit. All data and samples are then stored and analyzed only after participants have delivered and upon formation of case and control groups. Primary outcome is LO-PE. Secondary outcomes include method of delivery, birthweight, and Apgar score.
Results: Data processing is expected to begin in March 2020 and results will hence not be available for presentation at the congress.
Conclusion: If MMP-7 shows to be useful in predicting LO-PE, it could offer new insight into its etiology as well as pave the way for research on prophylaxis treatments.
Acknowledgements: This pre-graduate research project is carried out as a sub-study of the multicenter validation study PRESIDE (Preeclampsia Screening In Denmark). The PRESIDE study has received grants for a total of 3.201 million DKK, including 0.5 million DKK from the RH-OUH research foundation. The running costs of a pre-graduate project are covered by this budget. Additionally, the pre-graduate project has received a grant of 67 950 DKK from the OUH research foundation for blood sample analyses.
34 P.2. EPIDEMIOLOGI
P-2.11 Anders Prevalence and prognostic implications of apical Lehmann Dahl basal strain ratio in aortic stenosis undergoing Pedersen transcatheter aortic valve replacement ALD Pedersen1 JA Povlsen1 AM Dybro1 TS Clemmensen1 B Ladefoged1 SH Poulsen1 1Department of Cardiology, Aarhus University Hospital
Background: Overlapping conditions are common in aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR). Coexisting transthyretin cardiac amyloidosis (ATTR-CA) in AS is common but underdiagnosed. The aim of the present study was to investigate the preoperative prevalence and prognostic value of apical basal strain ratio (ABr), a marker of ATTR-CA, in a cohort of consecutive patients with severe symptomatic AS undergoing TAVR.
Methods: This study is a single center, retrospective, observational, cohort study of symptomatic and significant AS patients who underwent TAVR at Aarhus University Hospital in the study period from 2016 to 2018. A total of 610 patients were treated with TAVR during the time period. Preoperative echocardiograms were reexamined for speckle tracking analysis of 17 segment global longitudinal strain (GLS). The ABr was calculated by dividing the average of apical segments by the average of basal segments.
Results: Our main results include: 1) A prevalence of increased ABr >2.9 and 4 were found in 25% and 16%, respectively. 2) Patients with ABr 4 had significantly≥ increased preoperative NYHA-class and serum NT-proBNP≥ compared to ABr 0-2. A decrease in NYHA-class and serum NT-proBNP were seen across ABr subgroups after TAVR but remained significantly increased for ABr ?4 as compared to ABr 0-2. 3) Our study demonstrates that an ABr ?4 is related to significant adverse outcome compared to ABr <4.
Conclusion: The prevalence of increased ABr 3 and 4 is 25% and 16% in severe symptomatic AS patients undergoing TAVR. Furthermore,≥ ≥ pre- and postoperative NYHA class, serum NT-proBNP and mortality are significantly increased for ABr 4. ≥ Acknowledgements: This project is funded by the Independent Research Fund Denmark.
35 P.3. GRUNDFORSKNING
Session P.3: Grundforskning
P-3.01 Lærke Neuroprotective effect of remote ischemic Hjøllund postconditioning and therapeutic hypothermia Hansen in a piglet model of moderate to severe hypoxic ischemic encephalopathy L Hansen1 TCK Andelius1 M Andersen1 H Brogård1 KJ Kyng1 TB Henriksen1 1Department of Pediatrics, Aarhus University Hospital
Background: Therapeutic hypothermia (TH) is an efficient treatment of neonates with hypoxic ischemic encephalopathy (HIE). However, TH only reduces part of the acquired brain damage. Remote ischemic postconditioning (RIPC) has been shown to be neuroprotective in rats and piglets. It is unknown whether there is any additional neuroprotective effect when combining RIPC with TH. The aim of this study is to investigate the effect of RIPC combined with TH in a piglet model of moderate to severe HIE.
Methods: A total of 24 piglets will be anesthetised. A hypoxic-ischemic insult will be induced by reducing the fraction of inspired oxygen during a 45-minute period. Animals will be randomized to TH+RIPC or TH. RIPC will be induced by occluding blood flow to both hind limbs for five minutes followed by five minutes of reperfusion in four cycles. Outcome will be thalamic lactate/n-acetylaspartate-ratio measured by magnetic resonance spectroscopy performed 24 and 48 hours after the insult.
Results: Data will be collected during 2020.
Conclusion: A conclusion is expected in August 2021.
Acknowledgements: Nothing to declare
P-3.02 Nanna Therapeutic enrichment of CRISPR/Cas-edited Steengaard cells for treatment of monogenic diseases Mikkelsen NS Mikkelsen1 Z Gao1 TI Jensen1 RO Bak1 1Department of Biomedicine, Aarhus University
Background: CRISPR/Cas-mediated targeted integration of DNA via homology-directed repair (HDR) has revolutionized gene therapy research and has the potential to cure most monogenic diseases. However, cells that have undergone HDR cannot be detected and sorted unless a reporter gene is present. Permanent integration of a reporter gene is not desired due to potential side effects. Therefore, reporter gene-independent enrichment of cells that have undergone HDR is highly desirable.
36 P.3. GRUNDFORSKNING
Methods: We will evaluate the efficacy of the CRISPR/Cas system to induce stable integration of the HBB gene along with the reporter gene tNGFR. We will then deliver the HBB gene by an AAV-based vector and evaluate the HDR efficiency, and lastly design and analyze enrichment of CRISPR/Cas edited cells both reporter gene dependently and independently.
Results: We have showed that the CRISPR/Cas system can create intended double-strand DNA breaks and stably integrate the HBB gene along with the tNGFR reporter gene. We have showed a further increase in HDR efficiency with AAV-based vector delivery of the template HBB gene. And successful construction of a CRISPRa activatable HDR cassette will result in the design of reporter gene dependent and independent constructs to enrich and sort CRISPR/Cas edited cells.
Conclusion: The CRISPR/Cas system has the potential to cure several monogenic diseases but is limited by the unfavorable enrichment of edited cells using reporter genes. This project will develop novel methods to ensure reporter gene-independent selection of edited cells to supply highly efficient gene therapy.
Acknowledgements: This project is performed at the Department of Biomedicine at Aarhus University with guidance from Rasmus O. Bak. No grants are awarded, and the researchers have no conflicts of interest to declare.
P-3.03 Amalie Exploring the anti-inflammatory properties of Dyrelund Glucagon-like peptide 1 in rheumatoid arthritis Broksø using disease associated synovial fluid cells as in vitro model AD Broksø1 U Simmonsen1 TW Kragstrup1 1Department of Biomedicine, Aarhus University
Background: Inflammation is the hallmark pathological phenomenon of inflammatory arthritis such as rheumatoid arthritis (RA). These patients have an increased cardiovascular mortality. Recent studies have identified that GLP-1 mimetics, used for the treatment of type 2 diabetes, exerts cardio protective effects (CPEs). We hypothesize that these CPEs could be mediated via anti-inflammatory mechanisms. This study will therefore try to examine the anti-inflammatory effects of GLP-1 in the pathogenesis of RA.
Methods: We stimulate healthy PBMCs and SFMCs from both RA and spondyloarhtritis (SpA) patients with respectively LPS and CD3/CD28 to initiate an immune response. We then test whether liraglutide, in concentrations that are therapeutic relevant, reduce the induced immune reactions. The cytokine profile will be analysed by ELISA. Additionally, we will measure the expression of GLP-1 and GLP-1 receptors in both plasma and synovial fluid from RA and SpA patients in København University (KU).
37 P.3. GRUNDFORSKNING
Results: The experimental work is still in progress but is expected to be completed primo February and ready for presentation at KMS 2020.
Conclusion: The results of this study aim to describe whether liraglutide exhibits anti-inflammatory effects on disease associated SFMCs and PBMC controls upon stimulation.
Acknowledgements: A thank to Tue W. Kragstrup and the rest of the Bent Deleuran lab, Department of Biomedicine, Aarhus University for the support and guidance needed to perform this project. Also a thank to Ulf Simmonsen and his group for providing pharmaceutical products.
P-3.04 Henriette STAT3 inhibition specifically in CD163+ TAMs Mathiesen as a therapeutic approach in cancer H Mathiesen1 MW Kristensen1 T Vorup-Jensen1 M Hokland1 A Etzerodt1 MN Andersen1, 2 1Department of Biomedicine, Faculty of Health, Aarhus University 2Department of Hematology, Aarhus University Hospital
Background: Tumor-associated macrophages (TAMs) play important roles in cancer-related immune suppression, and tumor infiltration by CD163+ TAMs is associated with worse prognosis in several human cancers, making TAMs a potential target for anti-cancer therapy. The transcription factor STAT3 is overactivated in many cancers and STAT3 inhibition has been shown to have anti-tumor effects. Importantly, STAT3 inhibition specifically within TAMs may overcome tumor immune suppression with minimal side effects.
Methods: We produced liposomes containing the STAT3-inhibitor NSC74859 (by extrusion method). These liposomes were targeted specifically to CD163+ cells by modification with anti-CD163 monoclonal antibodies. HEK-Blue IL-6-STAT3 reporter cell lines ( CD163-transfection) were used to measure STAT3 inhibition by our drug. Since the fluorescent± intensity in this assay reflects STAT3 activation level, we used this system as an in vitro model for testing our STAT3-inhibitory CD163-targeted drug.
Results: Results are expected before the conference.
Conclusion: Results are expected before the conference.
Acknowledgements: The work was supported by The Department of Biomedicine, Aarhus University.
38 P.3. GRUNDFORSKNING
P-3.05 Trine Rerup Establishment of a Primary Monolayer Culture of Mouse Distal Colon Epithelia – a Model to Investigate P-glycoprotein Expression in Mouse Intestines T Rerup1 J Yde1 HB Møller1 1Department for Biomedicine, Aarhus University
Background: The membrane protein P-glycoprotein (P-gp) plays a major role in bioavailability of drugs as it is responsible for the efflux of broad range of pharmaceuticals into the intestinal lumen. As a long-term aim, I wish to investigate a potential downregulation of P-gp expression in the colon under the condition of obesity. In this project, I sought to establish a 2D primary monolayer cell culture from epithelia of distal mouse colon representing the physiological polarization and expression of P-gp.
Methods: Immunostained segments of mouse intestines were evaluated by microscopy to assess the P-gp expression. Ca2+ chelation was used to isolate epithelia from various intestinal segments of the mouse. Efficacy of the Ca2+ chelation was evaluated by microscopy of PAS-stained sections after the Ca2+ chelation. Isolated epithelial cells were cultured in transwells enabling the cells to polarize. Cultures were fixated and immunostained for P-gp and polarization markers.
Results: P-gp was expressed throughout the intestinal tract with an apical location. The Ca2+ chelation was proven to be effective with only minimal crypt epithelia still present in intestinal tissue after chelation. Two of four cultures were successful, and immunostaining revealed polarized cells with apical and basolateral differentiation and apical P-gp expression as seen on the control sections.
Conclusion: Establishment of this 2D monolayer culture is still work in progress. However, the initial results showed the great potential of this model as it resembles the physiological differentiation of intestinal epithelia on several markers and has the strength of an easily accessible apical side.
Acknowledgements: The project is financed by Novo Nordisk-stipendium, Agnes og Poul Friis Fond, and Bønnelyckes Fond. Supervised by Hanne B. Møller and co-supervisor Agnete Larsen.
P-3.06 Camilla Phenotypic differences among MHC-haplotypes Wibrand in a mouse model of the autoimmune disease systemic lupus erythematosus (SLE) C Wibrand1 T Wittenborn1 SE Degn1 1Institute of Biomedicine, Aarhus University
Background: SLE is an autoimmune disease characterized by the presence of affinity-matured autoantibodies. After a B cell has endocytosed antigen, it presents
39 P.3. GRUNDFORSKNING antigen-derived peptides on MHCII to CD4 T-cells, which further activate the B cell and stimulate the production of affinity-matured antibodies. Numerous MHC-haplotypes exists and are thought to support e.g. the presentation of self-peptides to different degrees. This study investigates the MHC-haplotypes H2b/b, H2d/b and H2d/b.
Methods: The project uses the 564-Igi mouse model which is generated by recombinant insertion of a B cell receptor (BCR) recognizing double-stranded DNA. Mice, that are hetero- or homozygous for this BCR make anti-dsDNA-antibodies, which induce an autoimmune response. The phenotypic differences are investigated with flow cytometry, calcium-flux-analyses, analyses of tissue samples by confocal microscopy and serum analyses for anti-dsDNA-antibodies with TRIFMA and cytokine assessments.
Results: Preliminary data from flow cytometry show a significant increase in the amount of germinal center (GC) B cells in spleens from H2b/ compared to H2d/d littermates. Also, the frequency of cells carrying the knock-in receptor was significantly higher in blood of H2B/d mice, compared to H2d/d littermates. Due to a low number of H2b/b mice (n = 1), this phenotype has not been included in the analysis yet.
Conclusion: The observed differences in GC B cells could indicate that the H2b/d background is less able to control the autoimmune response than the H2d/d background. The higher levels of circulating knock-in cells in the H2d/b mouse further support this notion.
Acknowledgements: This research is performed in the Degn Lab with supervision of Søren Degn and Thomas Wittenborn. The project is financed by the Novo Nordisk Foundation.
P-3.07 Elisabeth The role of SorCS2 in neuropathic pain and its Larsen implications as a possible target for treatment. E Larsen1 M Richner1 1Department of Biomedicine, Aarhus University
Background: Injuries or disease to the peripheral nervous system can lead to neuropathic pain (NP), which is a chronic and strongly disabling pain condition. Current treatment is pharmaceutical with limited effect and a lot of side effects. The mechanisms underlying NP are incompletely understood, but it is established that neurotrophic factors are involved in both development and sustainment of NP, where downregulation of the potassium-chloride-cotransporter KCC2 in the spinal cord is critical.
Methods: Wild type and SorCS2-deficient mice were subjected to the spared nerve injury (SNI) paradigm of peripheral nerve injury. Subsequent mechanical allodynia levels, a symptom of NP, have been assessed up to 14 days post SNI by von Frey testing. Furthermore, injured and non-injured mice of both genotypes have been used for tissue harvest (spinal cord at the lumbar area L3–5) at 5 days and 14 days post injury for subsequent analysis by Western blotting (WB).
40 P.3. GRUNDFORSKNING
Results: SorCS2 has been shown to be involved in NP development: Using SorCS2-deficient mice we have demonstrated that absence of SorCS2 completely protects against developing NP following SNI, while normal mice developed significant NP. Preliminary data show, the influence of SorCS2 on BDNF levels as well as on KCC2, a downstream molecule of the BDNF/TrkB pathway. By protein analysis in spinal cord tissue, we aim at examining these mechanisms further.
Conclusion: Preliminary data show that SorCS2-deficient mice are protected against NP development. We hypothesize that this may be due to an effect of SorCS2 on spinal BDNF levels and KCC2. Our goal is to unveil the role of SorCS2 in mechanisms leading to NP development for the purpose of targeted treatment.
Acknowledgements: I would like to thank my supervisor Assistant Professor Mette Richner and group leader Associate Professor Christian B. Vægter as well as Aase og Ejner Danielsens Fond for financial support.
P-3.08 Benedikte Analysis of potentially pathogenic proteins in Niemann the peripheral nervous system in diabetic mice with peripheral neuropathy B Niemann1 C Bjerggaard Vægter2 NP Gonçalves3 1Department of Biomedicine, Aarhus University
Background: The most common complication of diabetes is diabetic neuropathy (DN), affecting as many as 50% of patients. DN is characterized by damage to the peripheral nerves resulting in neurodegeneration, senso-ry disruption and pain. A still incomplete understanding of the pathogenesis behind underlie the lack of efficient therapeutics. Therefore, the goal of this study is to analyze proteins that may be involved in the pathogenesis of DN, aiming at finding a disease biomarker or new targets for therapy.
Methods: For this project, I will analyze dorsal root ganglia and sciatic nerves from mice fed with a high fat diet (60% fat from lard) or a control diet with 10% fat. After 24 weeks of special feeding, and previously to my bachelor program, sciatic nerves were analyzed with RNA sequencing with several genes found up and downregulated. Thus, in my project I will study protein levels and tissue localization of selected candidates by western blot analysis (WB), immunohistochemistry and confocal microscopy.
Results: Preliminary data and the protocol will be presented at KMS 2020.
Conclusion: By better understanding the pathogenic mechanisms linked to DN, we hope to find a potential biomarker for the diagnosis of this disease associated complication or ultimately, discover a novel target for therapy.
Acknowledgements: I would like to thank my supervisor Nádia Pereira Gonçalves and lector Christian Bjerggaard Vægter, Department of Biomedicine, Aarhus University for providing materials, equipment, guiding and sparring for this project. I would also like to thank the Danish Research Council (grant number 8020-00118B), Dagmar
41 P.3. GRUNDFORSKNING
Marshalls Fund and Novo Nordisk Foundation (NNF14OC0011633) for financial support for the completion of the study.
P-3.09 Yoanna Soluble SIRPα: Establishing a robust ELISA Vladimirova and investigating expression by different macrophage subpopulations YV Vladimirova1 KW Antonsen1 HJ Møller1 1Department of Clinical Biochemistry, Aarhus University Hospital
Background: Signal regulatory protein alpha (SIRPa) on macrophages functions as a phagocytosis checkpoint by binding to the CD47-receptor on tumor cells and inhibiting their phagocytosis. Trials using CD47 blockade for cancer therapy are ongoing. SIRPa exists as a soluble variant (sSIRPa) which may function as a biomarker to e.g. predict better survival in cancer. Enzyme-linked immunosorbent assays (ELISA’s) for sSIRPa are available commercially, but lack specificity or have not been properly validated.
Methods: Commercial SIRPa antibodies and recombinant proteins will be used in an in-house ELISA. Purity and identity of calibrators will be verified by Western blotting and mass spectrometry. THP-1 cells will be differentiated into M0-macrophages and further polarized into macrophage subtypes (M1 and M2 types). Expression of SIRPa will be monitored by qPCR and flow cytometry, and sSIRPa measured in culture supernatants. Human blood samples will be obtained from blood donors at Aarhus University Hospital.
Results: The study starts February 1, 2020. We will establish a robust ELISA for measuring sSIRPa in cell culture media and human serum. The assay will be validated with respect to precision, detection limit, linearity, specificity (e.g. SIRP beta) and trueness. Moreover, we will investigate sample stability and range of levels in healthy individuals. We will also investigate the expression of sSIRPa in macrophage subpopulations in vitro by stimulation of cells with pro- and anti-inflammatory cytokines.
Conclusion: The establishment of a robust, well-validated assay for soluble SIRPa may pave the way for establishing SIRPa as a useful biomarker in cancer. Knowledge of factors upregulating sSIRPa may direct future macrophage targeted immunotherapy in cancer.
Acknowledgements: The project is supported by the Department of Clinical Biochemistry, Aarhus University Hospital. The participants have nothing to disclose.
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P-3.10 Dorthe The role of the BK γ-subunit LRRC26 in colonic Dahmke K+-secretion D Dahmke1 MV Sørensen1 J Leipziger1 1Department of Biomedicine, Aarhus University
Background: Colonic potassium secretion follows the pump-leak mechanism, in which 2+ + the large conductance Ca -activated K channel (KCa1.1) has a highly regulated apical K+ conductance. The physiological importance of auxiliary β and γ subunits of the pore forming α-subunit of the KCa1.1 channel is not yet fully elucidated. The γ-subunit LRRC26 of the KCa1.1 channel is markedly expressed in the epithelium of the distal colon.
Methods: This project studies the role of LRRC26 protein in colonic potassium secretion after ATP stimulation. We will compare mice with and without the gene and will activate the channel through purinergic stimulation via the P2Y2 and the P2Y4 receptors. The Ussing chamber will be used to quantify the secretory K+-current that indicates colonic potassium secretion.
Results: All knockout mice showed a lower depolarization than the wildtypes, and the results where statistically significant. Therefore, a nonfunctioning LRRC26 protein might influence the transport of potassium through the BK-channel.
Conclusion: A lack of the LRRC26 protein in mice might inhibit the BK-channel from working properly, at least to some extent. Therefore, a nonfunctioning LRRC26 protein might influence the transport of potassium through the BK-channel.
Acknowledgements: This project could not have been made without Mads Vaarby Sørensen, Jens Leipziger, Samuel Svendsen and Karen from the Laboratory.
P-3.11 Silke Dahlbom Elucidating mechanism of a defective STING Nielsen pathway in non-small cell lung cancer SD Nielsen1 SH Godsk1 KR Gammelgaard1 MR Jakobsen1 1Department of Biomedicine, Aarhus University
Background: Within recent years, researchers have become aware that the innate immune system plays a central role in tumorigenesis. In particularly, the cGAS-STING pathway seems to be essential. cGAS, a cytosolic DNA-sensor, produces the natural STING ligands cGAMP upon detection of cytoplasmic accumulated self-DNA. Upon cGAMP binding to STING, the cell induces inflammatory cytokines and interferons. It is generally believed that such reaction in the tumor can lead to a systemic antitumoral immune response.
Methods: This study focus on cancer cell lines obtained from non-small cell lung cancer patients (NSCLC). Cell lines with knockout of cGAS are produced using CRISPR/Cas9 editing. The innate immune response is investigated in the cell lines
43 P.3. GRUNDFORSKNING upon stimulation with dsDNA and cGAMP. Expression and phosphorylation of proteins in the STING-pathway is detected using immunoblotting. Production of inflammatory cytokines are detected using ELISA and type I IFN cell reporter assay.
Results: Numerous of cell lines tested expressed key proteins involved in the STING pathway. Upon dsDNA stimulation, all cell lines were able to induce an inflammatory IL6 response. Interestingly, only a fraction of cell lines produced a type I IFN response, even though all showed activation of the STING-pathway signaling compounds, TBK1 and IRF3. To determine whether this response was cGAS-dependent, knockout cell lines were produced. These data are pending but expected to be presented at the conference
Conclusion: Our data indicate that in NSCLC an impaired STING-pathway may be related to a tumorigenic phenotype where specific pro-tumoral cytokines but not anti-tumoral cytokines are selectively secreted upon innate immune activation. Further conclusions will be drawn when more data are collected.
Acknowledgements: Nothing to declare.
P-3.12 Kathrine Friis In vitro investigation of the role of NCBE in inflammation induced cerebrospinal fluid hypersecretion of the choroid plexus KA Friis1 LØ Johnsen1 J Praetorius1 HH Damkier1 1Intstitute of Biomedicine Background: Hydrocephalus is a known complication to subarachnoid hemorrhage (SAH) and caused by an increased volume of cerebrospinal fluid (CSF). CSF is produced by choroid plexus (CP) in the blood CSF barrier. SAH leads to inflammation + of the CP that increases secretion of CSF. In rats the abundance of the Na :HCO3− exchanger in CPE increases after SAH causing increased CSF production. This increased expression of NCBE may be mediated by the NF-Kβ pathway that increases CSF-secretion after hemorrhage.
Methods: In an in vitro model of the BCSFB we will imitate an SAH inflammatory response using proinflammatory cytokines, IL-1, IL-6 and TNFα. The expression of NCBE will be evaluated by qPCR, western blot and immunocytochemistry. The therapeutic effect of an NCBE- and NF-Kβ inhibitor is tested using siRNA targeting NCBE and Triptolide. To investigate if the NF-Kβ pathway mediates the expression of NCBE, the NF-Kβ pathway is inhibited followed by stimulating NCBE with TNFα.
Results: Pending.
Conclusion: No conclusion yet to be made.
Acknowledgements: Research year funded by Novo Nordisk Fonden
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P-3.13 Julie Clinical and genetic findings in patients with Bjerrelund familial multiple lipomatosis (FML) J Bjerrelund1, 2 LB Ousager1, 3 M Larsen1, 3 AL Frederiksen4, 5 1Department of Clinical Genetics, Odense University Hospital 2University of Southern Denmark 3Clinical Institute, University of Southern Denmark 4Department of Clinical Genetics, Aalborg University Hospital 5Clinical Institute, Aalborg University
Background: Familial multiple lipomatosis (FML) is a rare dominant inherited condition characterized by multiple, usually painless, subcutaneous lipomas, located on the trunk and extremities. There may be reduced penetrance and a variable expression of the disorder. The genetic cause(s) for the condition gene(s) have however, not yet been identified. We aim to screen for a monogenetic cause of the disease and describe details if the phenotype.
Methods: Next generation sequencing performed on six patients diagnosed with FML and two healthy family members. Cell- and gene expressions studies for identifying the function of the gene(s) and the effect on involved pathways. Clinical assessment including assessment of the lipid metabolism. In-vitro cultures of human bone marrow skeletal (mesenchymal) stem cells to address the details of cell phenotype of bone forming cells, osteoblasts and adipocytes.
Results: Five families with the clinical diagnosis FML including (n = 18) have been identified including (M = 12) and (F = 6). Age of onset: 20–35 years. The patients have no other comorbidities. The number and location of the lipomas has a greater diversity, even within the families. Six of the patients have accepted to participate, and genetic analyses are ongoing.
Conclusion: Five families with the clinical diagnosis FML have been identified. Genetic cause(s) will be studied using whole genome sequencing. Cellular and clinical phenotypes will be detailed.
Acknowledgements: This study was supported by A.P. Møller Fonden, Overlægerådets Forskningsfond and OUHs prægraduat pulje.
45 P.4. KARDIOLOGI
Session P.4: Kardiologi
P-4.01 Mette Vold Identifying the Most Effective Method to Hansen Activate the Pediatric Mode in Automated External Defibrillators – A Randomized Controlled Study MV Hansen1, 2 KG Lauridsen1, 2 B Løfgren1, 2 1Department of Medicine, Randers Regional Hospital 2Research Center for Emergency Medicine, Aarhus University Hospital
Background: Each year thousands of children suffer from an out-of-hospital cardiac arrest in Europe. Early defibrillation with use of an Automated External Defibrillator (AED) is essential to improve survival but AED usage remains low. When using an AED for children, it is recommended to use a lower energy setting by switching to a pediatric mode. This study aims to investigate the fastest way to activate pediatric mode when using an AED for pediatric cardiac arrest.
Methods: This is a randomized, controlled simulation study including 90 teachers and student teachers (exclusion criteria: life support instructors, healthcare education) randomized (1:1:1) to use one of three AEDs with different ways to activate the pediatric mode. Primary endpoint: time to first shock. Secondary endpoints: Number of participants able to deliver shock in pediatric mode, time to activation of pediatric mode, time to electrode attachment, and correct electrode placement.
Results: Data will be collected from November 2019 through January 2020 and will be presented at KMS 2020.
Conclusion: This study may guide future recommendations on how to design AEDs and change guidelines for pediatric cardiopulmonary resuscitation. Reducing time to defibrillation when using the pediatric mode may increase defibrillation success and survival rates following pediatric cardiac arrest.
Acknowledgements: Research Center for Emergency Medicine (AUH), Children’s Hospital of Philadelphia, Department of Internal Medicine (Randers Regional Hospital), Cardiocare Scandinavia and Laerdal Medical Copenhagen.
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P-4.02 Trine Trab Coronary artery calcification in patients with schizophrenia T Trab1 RE Nielsen1 JB Frøkjær3 SE Jensen2 1Department of Psychiatry, Aalborg University Hospital 2Department of Cardiology, Aalborg University Hospital 3Department of Radiology, Aalborg University Hospital
Background: Coronary artery disease (CAD) is one of the major causes of premature mortality in patients with schizophrenia. Coronary artery calcification (CAC) is an independent predictor of cardiac mortality and coronary artery disease. However, it has not yet been investigated in patients with schizophrenia. The aim of the present study is to compare CAC quantified by cardiac computed tomography (CT) in patients with schizophrenia to the general population.
Methods: This cross-sectional study includes 200 patients with chronic (at least 10 years living with diagnosis) and 86 patients with debut (two years living with diagnosis) schizophrenia. Patients with debut schizophrenia are matched 1:1 on age, gender and smoking status with psychiatrically healthy controls (PHC). All participants undergo cardiac CT and CAC is quantified using Agatston Score. Mean CAC in the chronic group is compared to reference CAC scores and mean CAC in debut is compared to PHC.
Results: Data is currently being analyzed and preliminary results will be presented at KMS 2020.
Conclusion: If the CAC quantified by CT in patients with schizophrenia differs from the general population, it might be used for early detection of CAD in these patients. Thus, the findings of this study might contribute to preventive strategies in order to decrease cardiovascular mortality.
Acknowledgements: The Obel Family Foundation and The Lundbeck Foundation.
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P-4.03 Cecilie NT-proBNP Measurements to Rule Out Heart Budolfsen Failure among Atrial Fibrillation Patients: A Prospective Clinical Study C Budolfsen1, 2, 3 AS Schmidt, KG Lauridsen1, 2, 3 DT Nguyen1, 2 C Bang1, 2, 3 CB Poulsen4 F Waziri3, 4 H Rickers3 B Løfgren1, 3, 4, 5 1Research Center for Emergency Medicine, Aarhus University 2Clinical Research Unit, Randers Regional Hospital 3Department of Internal Medicine, Randers Regional Hospital 4Department of Clinical Medicine, Aarhus University 5Department of Cardiology, Aarhus University Hospital
Background: Heart failure (HF) and atrial fibrillation (AF) often co-exist and HF is important to identify. Performing an echocardiography is considered gold-standard for diagnosing HF, but may not always be readily available. The biomarker N-terminal pro brain natriuretic peptide (NT-proBNP) can be used to rule out HF in patients with sinus rhythm, however, AF affects the level of NT-proBNP. The aim of the study is to investigate if NT-proBNP can rule out heart failure in atrial fibrillation patients.
Methods: This is an observational clinical study including a total of 403 patients admitted to hospital with AF. Project examinations will include blood-sampling for quantification of NT-proBNP levels, an echocardiography, and a chest X-ray. Lastly, patients will be asked to answer a questionnaire regarding their symptoms. The primary endpoint is the NT-proBNP cut-off level that rules out heart failure among AF patients.
Results: Results are pending and the study design will be presented at KMS 2020.
Conclusion: This study will evaluate if the use of NT-proBNP may be feasible to rule-out heart failure in patients admitted to hospital with atrial fibrillation.
Acknowledgements: We thank patients and staff at Randers Regional Hospital for supporting the project.
P-4.04 Salma Raghad Evaluation of coronary pressure, flow and Karim resistance in chronic total occlusions (CTO) SR Karim1 A Eftekhari1 EH Christiansen1 1Deaprtment of Cardiologi, Aarhus University Hospital
Background: Studies have mentioned short-term changes in fractional flow reserve in chronic total occluded coronary artery post PCI, however there’s no data beyond 4 months post-PCI. And the microcirculatory system has not been considered in earlier studies which is crucially important in regulating blood flow of the occluded vessel. The aim of this study is evaluation of FFR, coronary flow reserve and index of microvascular resistance in the donor vessel and the CTO artery following PCI.
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Methods: Patients randomized to PCI will undergo assessment of coronary physiology in the donor vessel prior and following PCI of the non-CTO lesion. The CTO-vessel is assessed physiologically post CTO-PCI. This is done through thermodilution using a combined coronary pressure and flow wire. Symptomatic patients with 5% of myocardial ischemia will undergo a follow-up invasive CAG 1 year after≥ CTO-PCI. Physiological measurements of the donor-vessel and the CTO-vessel will be performed once again
Results: The inclusion is ongoing and continues to primo 2023. We are hoping to contribute to the knowledge on CTO treatment and in time change clinical practise in treating and guiding patient with CTO.
Conclusion: .
Acknowledgements: Nothing to declare.
P-4.05 André The impact of dysglycemia on plaque burden Shamoun and plaque morphology in coronary arteries in asymptomatic Danish men aged 65-75 years. A Coronary CT-angiography (CCTA) study A Shamoun1 J Larsion1 L Heinsen1 J Lambrechtsen1 K Egstrup1 1Kardiologisk forskningsenhed, Svendborg Sygehus, OUH
Background: This study investigates the precursors of blood cloths (plaque) in the coronary vessels. To evaluate the coronary plaque volume we are using Coronary CT angiography. We aim to investigate the correlation between coronary plaque volume and glycemic status, which has been evaluated by an oral glucose tolerance test. Glycemic status will be viewed upon in two ways. As continues data (HbA1c) and as ordinal data (p-glucose) with 3 subpopulations: Normal, dysglycemia and type 2 diabetes mellitus.
Methods: We made a descriptive cross-sectional study with blinded comparison of glycemic status and coronary atherosclerosis (probe design) with 489 patients. State-of-the-art cardiac CT scanner is used to make CT-imaging and dedicated software (QAngioCT) will be used to assess the plaque analysis. Multiple linear regression prediction models are used to assess the importance of glycemic status. Directed acyclic graphs are used to map confounders and cross-validation used to generalize the model.
Results: Non
Conclusion: Non
Acknowledgements: Non
49 P.4. KARDIOLOGI
P-4.06 Natascha Cardiovascular risks associated with non-aspirin Gaster NSAID use in patients with nonobstructive coronary artery disease verified with coronary computed tomography angiography (CCTA) N Gaster1 M Scmidt1 H Sørensen1 L Pedersen1 V Ehrenstein1 1Department of Clinical Epidemiology, Aarhus University Hospital
Background: Patients with non-obstructive coronary artery disease account for around 12% of all patients examined with CCTA on suspicion of angina. 20% will redeem at least one NSAID prescription within one year of CCTA. NSAID use is associated with increased cardiovascular risks. It is unknown whether NSAIDs confer particular risk in these patients. No recommendations exist. We aim to examine whether NSAID-associated cardiovascular risks differ according to CCTA-verified degree of coronary atherosclerosis.
Methods: We will conduct a population-based cohort study in Western Denmark from 2008–2017. We will identify all individuals undergoing CCTA on angina pectoris indication and their subsequent NSAID use, by accessing the Danish medical registries. Primary outcomes include incident myocardial infarction (MI), heart failure, atrial fibrillation, ischemic stroke, venous thromboembolism, coronary intervention, and cardiac death.
Results: The project will commence in February 2020. Preliminary results will be presented at KMS2020 if available.
Conclusion: Pending study results it might be possible to gain a better understanding of the cardiac risks associated with non-aspirin use in non-obstructive coronary artery disease and thereby a better foundation for future recommendations.
Acknowledgements: The study is supported by the Novo Nordisk Foundation grant NNF19OC0054908. The founding source had no influence in the conduct of the study.
P-4.07 Naja Survival after successful versus unsuccessful Stausholm recanalization of chronic total occluded coronary Winther arteries N Winther1 E Holck1 S Karim1 A Eftekari1 EH Christiansen1 1Department of Cardiology, Aarhus University Hospital
Background: Patients with coronary artery disease (CAD) who has chronic total coronary occlusion (CTO) have a higher mortality. Studies indicate that revascularization with percutaneous coronary intervention (PCI) have beneficial effects
50 P.4. KARDIOLOGI on CTO-patients, despite the complexity the procedures. The aim of the present study is to compare clinical outcomes of patients who underwent successful versus unsuccessful revascularization for a CTO.
Methods: 650 patients who have had CTO-PCI performed at Aarhus University Hospital between 2009–2019 are enrolled in this retrospective register-based case-control study. Patients stratified on successful versus unsuccessful PCI procedure. Primary endpoint is all-cause-mortality and is tested after a median of 5 years follow-up. Secondary endpoints include difference in major adverse cardiovascular events.
Results: Protocol and preliminary results are presented at KMS2020.
Conclusion: The present study will investigate the difference in all-cause mortality after treatment of CTO lesions stratified on unsuccessful or successful revascularization. Protocol and preliminary results are presented at KMS2020.
Acknowledgements: The project is financed by Department of Cardiology, Aarhus University Hospital
P-4.08 Jacob Valentin Lung perfusion changes after balloon pulmonary Hansen angioplasty in patients with chronic thromboembolic pulmonary hypertension JV Hansen1 MD Lyhne1 SJ Dragsbæk1 A Andersen1 JE Nielsen-Kudsk1 1Department of Cardiology, Aarhus University Hospital
Background: Around 5% of pulmonary embolism survivors develop chronic thromboembolic pulmonary hypertension (CTEPH). It is an overlooked and serious disease with a 3-year survival rate of only 10% untreated. The treatment is removal of the obstructive lesions either through surgery or balloon pulmonary angioplasty (BPA). CTEPH diagnosis and treatment monitoring require both anatomical images and functional measurements of lung perfusion. Dual-Energy CT shows great promise and delivers both in one scan.
Methods: Patients (n = 17) will undergo 4 DECT scans in total. The 1st scan will be before the BPA procedure (baseline DECT). The 2nd DECT scan is done the day after the procedure (early DECT), and the 3rd scan is performed 4 weeks later (late DECT). The final scan (end DECT) is performed 4 weeks after the last BPA. The primary endpoint is the pulmonary perfusion defect score (P-score) and/or pulmonary blood volume/pulmonary artery enhancement (PBV/PAenh)-ratio.
Results: Preliminary results will be presented at KMS2020.
Conclusion: If we gain a greater understanding of lung perfusion changes over time after BPA, we may lower the number of procedures needed, reducing both periprocedural risks and complications from pulmonary hyperperfusion.
51 P.4. KARDIOLOGI
Acknowledgements: None.
P-4.09 Simone Juel Long-term Cardiopulmonary Responses to Dragsbæk Pulmonary Embolism in an in Vivo Animal Model SJ Dragsbæk1 MD Lyhne1 JV Hansen1 CCE Pederesen2 FSH De-Man3 JE Kudsk-Nielsen1 A Andersen1 1Department of Cardiology, Aarhus University Hospital, Denmark 2Department of Forensic Medicine, Aarhus University Hospital, Denmark 3Department of Pulmonary Medicine, Amsterdam University Medical Centers, the Netherlands Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication to pulmonary embolism (PE). CTEPH is due to incomplete resolution of material from an acute PE with persistent increased pulmonary arterial pressure (PAP) that may develop into a decompensated state of right heart failure. To understand the pathophysiology and improve it is key to have an animal model that resembles the disease as closely as possible.
Methods: 60 kg pigs are anesthetized and ventilated and autologous blood clots created ex vivo will be introduced en-bloc. 12 pigs will be randomized to an intervention group or a sham group. The pigs will be evaluated at baseline, after the acute embolization and 30 days later. Evaluation consists of: hemodynamic measurements, bi-ventricular pressure-volume loop recordings, blood samples, and Computed Tomography. After euthanisation, tissue samples are saved for further analyses.
Results: Results pending. Preliminary results will be presented at the kongres.
Conclusion: We will describe the long-term cardiopulmonary changes in a porcine model of PE aiming to give insights into the transition from acute PE into CTEPH. It has the potential to lead to the development of an animal model of CTEPH and serve as a platform for testing interventions in CTEPH.
Acknowledgements: Hjerteforeningen.
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P-4.10 Pernille The role of mitochondria in the protection Tonnesen against myocardial ischemia-reperfusion injury in the states of pre-diabetes, onset of and late diabetes PT Tonnesen1, 2 NR Jespersen1, 2 MV Hjortbak1, 2 TR Lassen1, 2 J Seefeldt1, 2 NB Støttrup1 J Johnsen1 HE Bøtker1 1Department of Cardiology, Aarhus University Hospital 2Department of Clinical Medicine, Aarhus University
Background: Attenuation of cardiac ischemia-reperfusion (IR) injury can be achieved through manipulation of the mitochondrial metabolism by dimethyl malonate (DiMal). DiMal reduce detrimental ROS production in IR-injury by inhibition of succinate dehydrogenase (SDH). However, it is unknown whether presence of type 2 diabetes mellitus influence the cardioprotective properties of DiMal. This study aims to investigate the effect of DiMal treatment in hearts from diabetic and non-diabetic rats.
Methods: Zucker Diabetic Fatty (ZDF) rats (fa/fa) and their lean controls (fa/+) were investigated at 6, 12 and 24 weeks corresponding to the states of pre-diabetes, onset of and late diabetes. Rat hearts were mounted in an isolated perfused heart model and subjected to global ischemia and reperfusion. The hearts were randomised to Sham, IR-injury or pre-ischemic co-perfusion with either 0.1 mM or 0.6 mM DiMal. Mitochondrial respiratory capacity was evaluated post-ischemic.
Results: Results will be presented at KMS 2020.
Conclusion: This study will provide valuable insight into the mitochondrial function of three temporal diabetes stages and age-matched non-diabetic rat hearts after subjection to ischemia and reperfusion. It enables us to evaluate the possible efficacy of DiMal treatment modulating the mitochondrial function.
Acknowledgements: We sincerely thank Casper Elkjær for the technical support. No conflicts of interest to declare.
53 P.4. KARDIOLOGI
P-4.11 Dung Thuy Dual Operator CPR Compared to Single Nguyen Operator CPR for Laypersons: A Randomized Simulation Trial DT Nguyen1, 2 KG Lauridsen1, 2, 3 C Budolfsen1, 2 K Krogh2, 4 B Løfgren2, 5, 6, 7 1Clinical Research Unit, Randers Regional Hospital, Denmark 2Research Center for Emergency Medicine, Aarhus University Hospital, Denmark 3Center for Simulation, Advanced Education and Innovation, The Children’s Hospital of Philadelphia, USA 4Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Denmark 5Department of Internal Medicine, Randers Regional Hospital, Denmark 6Department of Clinical Medicine, Aarhus University Hospital, Denmark 7Department of Cardiology, Aarhus University Hospital, Denmark
Background: Each year, more than 5 000 Danes suffer an out-of-hospital cardiac arrest. In the presence of multiple rescuers, international guidelines recommend that laypersons perform cardiopulmonary resuscitation (CPR) alternately every two minutes. However, this strategy may induce prolonged pauses in chest compressions for rescue breaths. This study aims to investigate whether CPR performed collaboratively in pairs by laypersons can reduce chest compression pauses compared to performing CPR alternately.
Methods: This randomized, controlled, simulation study will allocate 160 laypersons 1:1 to basic life support training with performance of CPR individually or collaboratively in pairs. Participants will be tested immediately after training in a simulated CPR scenario with two rescuers present and again after three months. Primary outcome: no-flow time during rescue breaths.
Results: The data analysis is ongoing, and results will be presented at KMS2020.
Conclusion: The results of this study may change future international resuscitation guidelines and training in resuscitation worldwide. This may increase survival for thousands of people suffering an out-of-hospital cardiac arrest each year.
Acknowledgements: We thank the voluntary participants from companies in Denmark. Furthermore, we thank Augustinus Fonden, Henry og Astrid Møllers Fond, Frimodt-Heineke Fonden, Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond, and Broderloge nr. 73 Svend Fældings humanitære fond for supporting the project.
54 O.1. MOR & BARN
Orale sessioner
Session O.1: Mor & Barn
O-1.01 Louise Precursors of hypomania in Adolescence in the Gunhard General population Nielsen LG Nielsen1, 2 MK Rimvall1 EM Olsen3, 4 AM Skovgaard4, 5 CU Rask6, 7 J Van Os8 F Verhulst1, 2 P Jeppesen1, 2 1Child and Adolescent Mental Health Centre, Mental Health Services, Capital Region of Denmark, Gentofte Hospital 2Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen 3Center for Clinical Research and Prevention, Frederiksberg Hospital 4Department of Public Health, Faculty of Health and Medical sciences, University of Copenhagen 5National Institute of Public Health, Faculty of Health Sciences, University of Southern Denmark 6Research Unit, Department of Child and Adolescent Psychiatry, Psychiatry Aarhus University Hospital 7Department of Clinical Medicine, Aarhus University 8Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Centre Utrecht
Background: Bipolar disorder (BD) has an estimated lifetime prevalence of 1–2%, and typically has its onset in early adulthood, being characterized by depressive and manic episodes. However, precursors and risk factors in childhood and adolescence are poorly described and might include low-grade hypomanic symptoms. We aim to explore the prevalence of hypomania symptoms at age 11 years and examine other potential risk-factors at age 11 of hypomania symptoms at age 16.
Methods: The study population comprised 893 adolescents from the Copenhagen Child Cohort 2000. At age 11, the participants were assessed by clinician interview regarding hypomania, depressive symptoms, psychotic experiences and sleep. Furthermore, they were diagnostically assessed using the Development and Well Being Assessment. At age 16, outcome of hypomania was measured by self-report using the Hypomania Checklist 32 (HCL-32). We used the 10th percentile score on the HCL as our hypomania outcome.
55 O.1. MOR & BARN
Results: Initial results showed that hypomanic symptoms at age 11 increased the risk of reporting hypomanic symptoms at age 16 (RR = 2.02 [95% CI: 1.09–3.76]), whereas the association between age 11 depressive symptoms and hypomanic symptoms at age 16 was statistically insignificant (RR = 1.35 [95% CI: 0.84–2.17]). Further analyses of potential risk factors of age 16 hypomania are still in process and the results will be presented at the KMS2020.
Conclusion: The current study contributes with new knowledge of hypomania patterns in childhood, and risk-factors of hypomania in adolescence. The preliminary results show that hypomanic symptoms at age 11 predicts hypomanic symptoms at age 16, which might be a future target of early detection and intervention.
Acknowledgements: The project is funded by the Lundbeck foundation.
O-1.02 Emma Sofie Women who use oral contraceptives have Høgsted blunted cortisol dynamics ES Høgsted1 DS Stenbæk1 A Nasser1 CB Larsen1 VG Frøkjær1 1Neurobiology Research Unit, Copenhagen University Hospital
Background: Estradiol may affect hippocampal function, i.e., working memory (WM) and stress regulation. A dynamic cortisol response is critical for a healthy adaption to stress. Cortisol dynamics, such as cortisol awakening response (CAR), may be affected by oral contraceptives (OC) containing synthetic analogues of estradiol and progesterone. We hypothesize that use of OC affects WM (hippocampal function), measured with the Letter-Number-Sequencing task, and that this is associated with a blunted CAR.
Methods: Data from 95 healthy women were available from the Cimbi database (27 OC-users, 68 non-users). We used a linear regression model adjusted for age and education to determine if WM was associated with OC-use (OC-user vs non-user) in interaction with plasma estradiol. Further, we assessed if CAR differed between OC-users and non-users, in a linear regression model adjusted for age, BMI, CRP and 5-HTTLPR genotype. Group differences in cortisol levels were assessed with Welch’s two-sample t-test.
Results: OC-users displayed a blunted CAR compared to non-users (β = -2.43 [95% CI: -92.2 – -394.2], P = 0.003) and had higher baseline cortisol levels at awakening (Mean = 13.99 [SD: 6.31]) compared to non-users (Mean = 9.49 [SD: 4.17], P = 0.003), whereas they did not differ in diurnal cortisol levels. We observed no effect of OC-use, estradiol or an estradiol BY OC-use interaction effect on WM (All P-values > 0.15).
Conclusion: OC-use seems to affect stress hormone dynamics, but not working memory in healthy women. It is unclear from the present data to which extent hippocampus is affected. Analyses of structural brain images may advance the results.
Acknowledgements: The Lundbeck Foundation is acknowledged for financial support.
56 O.1. MOR & BARN
O-1.03 Gülizar Saritas Signaling in human oocytes from primordial and primary follicles creates a basic platform for a potential fertility treatment G Saritas1 E Bruun1 M Amoushahi1 S Attaee1, 2 M Kok1 K Lykke-Hartmann1, 3, 4 1Department of Biomedicine, Aarhus University, Denmark 2Department of Animal Sciences University of Tehran, Iran 3Department of Clinical Genetics, Aarhus University Hospital, Denmark 4Department of Clinical Medicine, Aarhus University, Denmark
Background: Fertility treatment today is limited by the lack of insights into signaling pathways that could drive activation of dormant (primordial) follicles. Primordial follicles can maintain dormancy for decades however, once the intraovarian environment becomes activating, the primordial follicles transit to primary follicles. Todays, we know that PI3K/AKT, mTOR and IGF signaling pathways are involved in the shift of the intraovarian environment to activate or maintain dormancy of primordial follicles.
Methods: Human oocytes from primordial (n = 436) and primary (n = 182) follicles from cryopreserved ovarian tissue donated by three women was isolated by Laser Capture Microdissection. Total RNA was extracted, submitted to HiSeq Illumina platform, and data analysis was performed using different bioinformatic tools. Ingeuity R Pathways Analysis (IPA) software was used to model complex biological systems creating a comparison study between oocytes from primordial and primary follicles.
Results: The transcriptomic study revealed 223 and 268 down- and up-regulated pathways, respectively, in the oocytes from the primordial-to-primary follicle transition. The oocytes showed enrichment in pathways ‘mTOR signaling, PI3K/AKT signaling’ and ‘PTEN signaling’ revealed by IPA. Many signaling pathways not previously associated with primordial follicle activation are being tested and we functionally address this using a pharmacological in vitro approach using mouse as our experimental system.
Conclusion: Global transcriptomic profiling of human oocytes from primordial and primary follicles revealed new molecular clues for future pharmacological manipulation to increase clinical interventions of fertility in women.
Acknowledgements: Transcriptomic study was performed in the laboratory (Ernst et al, 2017, Ernst et al, 2018) and pathway analysis has been performed (Steffensen et al, 2018, Ernst et al, 2018, Ernst et al, 2018). Further analysis and other potential signaling pathways are currently being part of the team research at Aarhus University (Saritas et al, Nielsen et al and Amoushahi et al). We are grateful to the Novo Nordisk Foundation and the Carlsberg Fondet for their support towards this study.
57 O.1. MOR & BARN
O-1.04 Sofie Elmqvist Abdominal complications during treatment for Bendixen pediatric acute myeloid leukemia SE Bendixen1 DJA Løhmann1 H Hasle1 1Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital
Background: Acute myeloid leukemia (AML) accounts for 15-20% of all childhood leukemias. Due to highly intensive therapy, up to 5% of patients suffer from treatment-related mortality (TRM). Abdominal complications are often seen, however the literature on this subject is sparse. We aimed to characterize abdominal pain (AP) and hyperbilirubinemia (HBR) World Health Organization grade 3 to 4 experienced by pediatric patients treated for AML.
Methods: All patients treated according to NOPHO-AML 2004 protocol were included (n = 313). Information on toxicity was collected prospectively and additional information was requested retrospectively through questionnaires sent to the treating center. Results were analyzed using descriptive statistics and the Aalen-Johansen estimator for cumulative incidence of toxicity.
Results: The median age was 6 years (range 0–17), 57% were male and 18% were overweight. Sixteen episodes of HBR and 107 episodes of AP were reported. Infection was the most frequently reported cause (HBR 44% and AP 30%). Six patients developed appendicitis. They were older (median age 14) and more overweight (50%) compared to the entire cohort. The combination of AP and sepsis were associated with TRM in 36%. Eighty percent of episodes with HBR fulfilled the criteria for veno-occlusive disease (VOD).
Conclusion: Abdominal complications were frequent with infection being the predominate cause. Most patients with HBR fulfilled criteria for VOD. AML treatment might be associated with appendicitis. Patients suffering from AP and sepsis showed high risk of TRM, suggesting need of close monitoring.
Acknowledgements: The Danish Cancer Society founded the project.
58 O.1. MOR & BARN
O-1.05 Louise Ruby Regional differences in endometriosis in Høj Illum Denmark: Who gets the diagnosis? LRH Illum1 A Forman2 D Rytter1 1Department of Public Health, Aarhus University 2Department of Obstetrics and Gynecology, Aarhus University Hospital
Background: Endometriosis (endo) is a highly underdiagnosed disease, partly due to the lack of awareness among both patients and physicians. Geographical residence could potentially influence the risk of getting an endo-diagnosis, because of regional differences in awareness and differences in the referral process to specialized endometriosis centers. Hence, the objective of this study is to investigate, whether living in different regions of DK influences the probability of getting an endo-diagnosis.
Methods: A register based cohort study was conducted using data from Statistics Denmark and the Danish National Patient Registry. The study population consisted of all women aged 15–55 living in DK at some point from 1990–2017. Incidence rates of endo-diagnosis was calculated for each municipality, stratified by age group and calendar time. Finally, a cox regression analysis was performed to estimate the association between residence and risk of diagnosis, adjusting for socioeconomic covariates.
Results: We included 2 188 720 women, and during the follow-up period, 26 539 cases of endo were identified. The geographical distribution of incidence rates showed a clear pattern, with higher incidence rates in the eastern and northern part of Jutland compared to the rest of the country. Similar patterns were found when stratifying on age and calendar time, except for the period 1990–1999. The regression model, considering socioeconomic position, also indicated higher incidence in the same areas.
Conclusion: The results indicate considerable regional differences in the incidence rates of endometrioses in DK, suggesting that some areas of the country might have a higher rate of underdiagnosing endometriosis.
Acknowledgements: This research was funded by the Graduate School of Health Aarhus University, Endometriose Foreningen, Fonden af 1870 and Ellen Pedersens Legat.
59 O.1. MOR & BARN
O-1.06 Laura Louise Elevated macrophage activation markers CD163 Fosgrau Hergel and mannose receptor are associated with occurrence of aGVHD and SOS after pediatric allogeneic hematopoietic stem cell transplantation (HSCT). LLF Hergel1, 2 K Kielsen2, 3 SW Weiscendorff1, 2 M Segelcke Rosenkrantz Ifversen1 C Nielsen2 H Grønbæk4 K Müller1, 2 1Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet 2Institute for Inflammation Research, Copenhagen University Hospital Rigshospitalet 3Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet 4Department of Hepatology & Gastroenterology, Aarhus University Hospital
Background: Acute graft-versus-host disease (aGVHD) and sinusoidal obstruction syndrome (SOS) are potentially severe complications after HSCT. The complications are thought to be propagated by inflammation involving macrophage activation. CD163 and the mannose receptor are expressed on macrophages and are shed into the circulation upon inflammatory activation. We investigated the role of macrophages in aGVHD and SOS by measuring plasma levels of soluble CD163 (sCD163) and mannose receptor (sMR).
Methods: We included 93 Danish children and adolescents undergoing HSCT between 2010-2018. Diagnoses included AML, ALL, other malignancies and benign disorders. All patients received myeloablative conditioning based on either Total Body Irradiation or high dose chemotherapy. Plasma levels of sCD163 and sMR were measured before start of conditioning, at the day of HSCT and at day +7, +14, +21, +30, +90 and +180 after HSCT. Controls included 56 healthy children.
Results: Patients with aGVHD grade 2–4 had significantly higher levels of sCD163 and sMR between day +14 and +28 post-HSCT compared to patients with aGVHD grade 0–1(sCD163 day +14: median: 3.7 mg/L [IQR: 2.46-3.09] vs median 2.2 mg/L [IQR: 5 1.64–2.95] P = 7.425 10− . sMR day +21: median: 0.48 [IQR: 0.37–0.60] vs 0.36 [IQR: 0.30–0.45] P < 0.01).· sCD163 levels were increased in patients fulfilling selected criteria for SOS at day +21 (median: 4.82 mg/L [IQR: 3.17–5.77] vs 2.85 mg/L [IQR: 2.20–3.80] P < 0.05)
Conclusion: Plasma levels of sCD163 and sMR were elevated in children undergoing HSCT and this was associated with aGVHD and liver dysfunction. This suggest that macrophages play a key role in the immune response involved in induction of SOS and aGVHD and may be useful as predictors of these complications.
Acknowledgements: Danish Cancer Society
60 O.1. MOR & BARN
O-1.07 Aimi Hamilton Escherichia coli growth is dependent on urine concentration both in vitro and in vivo AD Munk Hamilton1 H Prætorius Øhrwald1 1Department of Biomedicine, Aarhus University
Background: Urinary tract infections (UTIs) are very common and often caused by Escherichia coli. The E. coli that successfully ascend to the kidney and cause pyelonephritis produce different virulence factors including alpha-haemolysin (HlyA). Preliminary data on in vitro growth of E. coli in human urine has shown a reduction in bacterial growth when diluting the urine, leading us to hypothesise that a sufficient dilution of urine will increase resistance against development of an ascending UTI in vivo.
Methods: We used the HlyA-producing E. coli strain ARD6 and female Balb /c mice, which were subcutaneously anaesthetized, and bacteria or vehicle was injected directly into the bladder. The mice were randomized to receive volume loaded food or not and left for 24 hours before they were put down. Urine and kidney were removed beforehand and plated overnight. The number of colony forming units (CFUs) were counted the following day.
Results: 15 out of 17 mice given volume loaded food presented with pyelonephritis compared to only 9 out of 18 mice given regular food. This was despite the mice given volume loaded food having significantly diluted urine with a mean osmolarity of 671 mmol/kg compared to 1427 mmol/kg of the control group. Investigating the effect of osmolarity on number of CFU’s in the kidney lead us to find an optimum of infection seemingly between 500 and 1300 mmol/kg.
Conclusion: Dilution of human urine in vitro lead to a decrease in E. coli growth, whereas dilution of mouse urine in vivo lead to an increase. This may be caused by a higher osmolarity in mouse urine than human. We plan to test whether further decrease of osmolarity has a protective effect against UTI.
Acknowledgements: Helle Jakobsen Aarhus University, Denmark and Prof. Rodney Welch University of Wisconsin, WI, USA.
61 O.2. KARDIOLOGI
Session O.2: Kardiologi
O-2.01 Harman Yonis 1-year follow-up of mortality, anoxic brain damage, nursing home admission and in-home care among 30-day survivors of in-hospital cardiac arrest H Yonis1 K Bundgaard2 M Wissenberg3 G Gislason3 L Koeber4 C Torp Pedersen5 JM Larsen2 K Hay Kragholm1, 6 1Unit of Clinical Biostatistics, Aalborg University Hospital 2Department of Cardiology, Aalborg University Hospital 3Department of Cardiology, Gentofte University Hospital 4Department of Cardiology, Rigshospitalet, Copenhagen University Hospital 5Department of Clinical Research and Cardiology, Nordsjællands Hospital 6Department of Cardiology, North Denmark Regional Hospital
Background: Survivors of in-hospital cardiac arrest are at risk of anoxic brain damage that can lead to admission to nursing home or need of in-home care. This study aimed to investigate the composite endpoint of nursing home admission or anoxic brain damage among 30-day survivors of in-hospital cardiac arrest within the first-year post-arrest. As a sub analysis, we also investigated the additional need of in-home care.
Methods: All in-hospital cardiac arrests in 13 Danish hospitals during 2013-2015 were identified from the DANARREST register. Inclusion criteria were indication for a resuscitation attempt and survival to day 30. Patients who, prior to arrest, already lived in a nursing home, and/or had anoxic brain damage were excluded. In the sub analysis patients who received in-home care prior to arrest were also excluded. The DANARREST data was linked to nationwide registries.
Results: The primary study population comprised of 454 (26.3%) 30 day-survivors. The 1-year risk of anoxic brain damage or nursing home admission was 4.6% (95% CI: 2.7%–6.6%) with a competing risk of death of 15.6% (95% CI: 12.3%–19.0%). The sub study population comprised of 343 30-day survivors with a 1-year risk of anoxic brain damage, nursing home admission or need of in-home care of 23.6% (95% CI: 19.1%–28.1%). The competing risk of death was 7.6% (95% CI: 4.8%–10.4%).
Conclusion: The majority of 30-day survivors of in-hospital cardiac arrest were alive at one-year follow-up without being diagnosed with anoxic brain damage, admitted to nursing home or without need of in-home care.
Acknowledgements: Nothing to declare.
62 O.2. KARDIOLOGI
O-2.02 Jacob Seefeldt The SGLT-2 inhibitor, empagliflozin, protects against ischemia-reperfusion injury, enhances mitochondrial respiratory capacity and restores systolic function in heart failure JM Seefeldt1 TR Lassen1 NR Jespersen1 MV Hjortbak1 J Hansen2 HE Botker1 1Kardiologisk afdeling, Aarhus Universitetshospital 2Institut for Retsmedicin, Aarhus Universitetshospital
Background: The sodium glucose co-transporter 2 inhibitor (SGLT2i), empagliflozin, reduces mortality and hospitalisation due to heart failure in patients following myocardial infarction, regardless of diabetes status. Interestingly, the risk of myocardial infarction per se is unchanged, indicating an innate cardioprotective effect of SGLT2i. However, the cardioprotective mechanism of SGLT2i is unclear. Mitochondrial performance determines ischemia-reperfusion (IR) injury after myocardial infarction.
Methods: We examined the effects of empagliflozin on infarct size in vivo (series I), ex vivo (series II), mitochondrial respiration in early reperfusion (series III) and in post-ischemic heart failure (series IV) in male Sprague Dawley rats undergoing 30 minutes left anterior descending coronary artery ligation. Furthermore, in series IV hemodynamic variables were assessed by transthoracic echocardiography at day 27 post IR. Empagliflozin (30mg/kg/day) was administered by oral gavage.
Results: Treatment with empagliflozin prior to IR significantly reduced infarct size in vivo but not ex vivo, and improved mitochondrial glucose and fatty acid state 3 respiration in early reperfusion. Empagliflozin improved left ventricular ejection fraction in both pre-IR treated, and post-IR treated animals with heart failure. The effect was attributed to restoration of systolic function and mitochondrial respiration. Intriguingly, the mitochondrial respiration was enhanced in the healthy myocardium.
Conclusion: Empagliflozin yields cardioprotection against acute IR injury in vivo. The protection perseveres in the failing rat heart with restored systolic function. The effect extends beyond that caused by reduction of acute IR injury alone and is associated with enhanced mitochondrial respiratory capacity.
Acknowledgements: Nothing to declare.
63 O.2. KARDIOLOGI
O-2.03 Henrik Bjerre Effect of pencil beam proton therapy on cardiac implantable electronic devices – an in vitro study HL Bjerre1, 2 MB Kronborg1 CJS Kronborg2 E Almhagen MF Jensen3 JC Nielsen1 1Department of Cardiology, Aarhus University Hospital, Denmark 2Danish Centre for Particle Therapy, Aarhus University Hospital, Denmark 3The Scandion Clinic, Sweden
Background: Cancer patients who undergo radiotherapy, and who also have a cardiac implantable electronic device (CIED), present a complex challenge, because CIEDs are sensitive to ionizing radiation and therefore risk malfunctioning during radiotherapy. Proton beam therapy has only recently become available as cancer treatment in Denmark, and only little research has been devoted to investigating this issue. This means many proton facilities exclude CIED patients from this otherwise beneficial treatment.
Methods: Therefore, this experimental in vitro study aims to investigate CIED malfunctioning risk during modern pencil beam proton therapy. A total of 20 CIEDs (10 pacemakers and 10 ICDs) will be irradiated in a Pleksiglas-phantom while located outside the direct radiation field, to simulate clinical conditions. All CIEDs will undergo four clinical-like scenarios mimicking lung-, breast-, brain- and prostate cancer, with increasing distance between the CIED and the radiation field.
Results: We successfully conducted two pilot trials. The first saw irradiation of one pacemaker and one ICD with protons, while located inside the direct radiation field. Both reported a reset-to-back-upmalfunction, after 5Gy and 2Gy respectively. The second pilot also had one pacemaker and one ICD irridiated with protons, this time located outside the direct radiation field. The pacemaker reset to backup mode after 47Gy and the ICD reset to backup mode after 27 Gy.
Conclusion: The two succesful pilot trials confirms that CIEDs are indeed sensitive to proton therapy, and that our experimental setup is well suited to investigate CIED malfunction risk during pencil beam proton therapy. We expect to present preliminary results at KMS 2020.
Acknowledgements: The investigator is grateful of the all important support and supervison of Professor Jens Cosedis Nielsen, Mads Brix Kronborg, Camilla Jensenius Skovhus Kronborg, Maria Fuglsang Jensen, Morten Høyer, Christian Søndergaard, Erik Almhagen and Håkan Nyström, as well as the assistance from the staff at the Department of Cardiology and the Danish Centre for Proton Therapy. This Project is funded by the Danish Heart Association (Hjerteforeningen).
64 O.2. KARDIOLOGI
O-2.04 + Casper Smelly gas plays an essential role in K -induced Homilius coronary artery relaxation C Homilius1 S Kim1 V Matchkov1 E Bødtkjer1 1Institut for Biomedicin, Aarhus Universitet
Background: Regulation of coronary artery (CA) tone plays essential (patho-)physiological roles by matching local blood flow to metabolic demand. Increased cardiac activity or ischemia elevates the extracellular (o) [K+], and even moderate + increases in [K ]o relax CAs. However, the mechanistic background remains poorly understood. We investigated the involvement of the endothelium and the hypothesis that decreases in smooth muscle Ca2+-sensitivity contribute to K+-induced vasorelaxation.
Methods: Vasorelaxations were studied in isolated rat CAs (coronary septal arteries) mounted in wire myographs. Fluorescence-based recordings of intracellular (i) [Ca2+] were performed in CAs loaded with the Ca2+-sensitive fluorophores. Membrane potentials of smooth muscle cells were measured using sharp electrodes. Changes in phosphorylation of the myosin phosphatase targeting subunit (MYPT, regulatory subunit of the myosin phosphatase) were determined by immunoblotting.
+ Results: Moderate [K ]o elevation cause potent CA vasorelaxation involving inward + rectifier K -channel (KIR) activation. However, relaxation is not fully accounted for by 2+ + decreased [Ca ]i. Elevated [K ]o reduces MYPT phosphorylation by 20%. Removing the endothelium, blocking H2S synthesis or putative downstream H2S targets attenuate + [K ]-induced relaxation. Consistently, inhibiting H2S production abolishes the [K+]-induced reduction in [Ca2+]-sensitivity.
+ Conclusion: Moderate elevations in [K ]o relax CAs. This occurs partly through classical KIR-dependent smooth muscle hyperpolarization but also depends on a novel + 2+ K -induced mechanism that is H2S-dependent and lowers the [Ca ]-sensitivity of the smooth muscle contractile machinery.
Acknowledgements: The project is funded by MEMBRANES, Aarhus University.
65 O.2. KARDIOLOGI
O-2.05 Martin Comparison of quantitative flow ratio and Sejr-Hansen fractional flow reserve with myocardial perfusion scintigraphy and cardiovascular magnetic resonance as reference standard. A Dan-NICAD substudy M Sejr-Hansen1 J Westra1 S Winther1 S Tu2 L Nissen3 L Gormsen1 EH Christiansen1 NR Holm1 1Department of cardiology, Aarhus Univeristy Hospital, Aarhus, Denmark 2School of Biochemical Engineering, Shanghai Jiao Tong University, Shanghai, China 3Department of Cardiology, Hospital Unit West Jutland, Herning, Denmark
Background: Quantitative flow ratio (QFR) and fractional flow reserve (FFR) have not yet been compared head to head with perfusion imaging as reference for myocardial ischemia. We aimed to compare the diagnostic accuracy of QFR and FFR with myocardial perfusion scintigraphy (MPS) or cardiovascular magnetic resonance (CMR) as reference. This study is a predefined post hoc analysis of the Dan-NICAD study (NCT02264717).
Methods: Patients with suspected coronary artery disease by coronary computed tomography angiography (CCTA) were randomized 1:1 to MPS or CMR and were referred to invasive coronary angiography with FFR and predefined QFR assessment. Paired data with FFR, QFR and MPS or CMR were available for 232 vessels with stenosis in 176 patients.
Results: Perfusion defects were detected in 57 vessel territories (25%). For QFR and FFR the diagnostic accuracy was 61% and 57% (P = 0.18) and area under the receiver operating curve was 0.64 vs. 0.58 (P = 0.22). Stenoses with absolute indication for stenting due to diameter stenosis > 90% by visual estimate were not classified as significant by either QFR or MPS/CMR in 21% (7 of 34) of cases.
Conclusion: The diagnostic performance of QFR and FFR was similar but modest with MPS or CMR as reference. Comparable performance levels for QFR and FFR are encouraging for this pressure wire-free diagnostic method
Acknowledgements: Funding The Dan-NICAD study was funded by Acarix. Software for QFR analysis was provided free of charge by Medis Medical Imaging B.V.
66 O.2. KARDIOLOGI
O-2.06 Lucas Malta Rate control management and cardiovascular Westergaard outcomes among patients with atrial fibrillation: a Danish cohort study LM Westergaard, MB1 C Lee, MD, PhD2 EL Fosbøl, MD, PhD1 SL Kristiensen, MD, PhD1 GH Gislason MD, PhD1, 2 L Køber MD, DSc2, 3, 4, 5 C Torp-Pedersen, MD, DSc1 PE Weeke, MD, PhD1 1Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen Health Science Partners 2Department of Cardiology, Herlev-Gentofte Hospital, University Hospital Copenhagen 3National Institute of Public Health, University of Southern Denmark, Copenhagen 4Department of Cardiology, University of Southern Denmark 5The Danish Heart Foundation Background: Clinical trials have shown that rate control is an effective treatment strategy for management of patients with atrial fibrillation (AF). However, less is known regarding the effects of heart rate among patients with AF and a rate control strategy on the risk of developing heart failure (HF) and mortality. We aimed to investigate one-year risk of developing HF and all-cause mortality in a cohort of patients presenting with AF on an electrocardiogram (ECG) in rate controlling pharmacotherapy.
Methods: The Copenhagen General Practitioners’ Laboratory’s ECG register was used to identify patients with AF based on ECG findings (2001–2015). Index was defined as date of first ECG presenting AF. Concomitant and rate controlling pharmacotherapy and comorbidities were identified using nationwide Danish registers. One-year risk of developing HF and/or mortality was estimated using adjusted Cox proportional hazards analyses.
Results: We identified 7 225 patients with AF (median age = 78 years [interquartile range (IQR) = 71–85 years], 45.2% males, median ventricular rate [VR] = 83bpm [IQR = 71–101bpm]). During one-year, 652 (9.0%) patients developed HF and 836 (11.6%) patients died. Patients with a high VR (110–200bpm) <75 years (HR = 3.82 [95% CI: 2.56–5.70], P < 0.001) and 75 years (HR = 1.86 [95% CI: 1.43–2.43], P < 0.001) had a higher risk of developing≥ HF compared to patients with a normal VR (60–79bpm).
Conclusion: Patients with AF and rapid VR were at greater risk of developing HF compared to AF patients with normal ventricular response, although the effects were greater among patients <75 years. Among patients <75 years, a very slow VR rate was associated with increased risk of mortality.
Acknowledgements: Nothing to declare.
67 O.3. GRUNDFORSKNING
Session O.3: Grundforskning
O-3.01 Xabier The localization of β-catenin and E-cadherin Sørtvedt changes in the kidney inner medulla of rats with lithium-induced Nephrogenic Diabetes Insipidus X Sørtvedt1 BM Christensen1 1Department of Biomedicine, Aarhus University
Background: Nephrogenic Diabetes Insipidus (NDI) is a side-effect in around 40% of psychiatric patients receiving lithium treatment. NDI is characterized by the inability of the kidney to concentrate urine. The disease is associated with dysregulation of the water channel AQP2 and changes in the cellular composition of the kidney collecting duct. We aimed to investigate if cellular adhesion complexes have a role in the morphological remodeling of the collecting duct.
Methods: Immunolabeling of different cell-contact proteins was performed on rat kidney sections used in previously published studies. Kidney sections were from rats treated for 4, 10 or 15 days of lithium. Additionally, rats from a recovery protocol including 0, 6 and 12 days of recovery following 4 weeks of lithium treatment was used as well.
Results: Immunohistochemistry showed labeling of the adherens junction proteins, E-cadherin and β-catenin predominantly in the basal membrane of inner medullary collecting duct cells from control rats. Both proteins disappeared from the basal membrane of many collecting duct cells after 4, 10 and 15 days of lithium treatment and reappeared again after 4 weeks of lithium. After 12 days of recovery from lithium a similar disappearance of basal labeling was observed.
Conclusion: Lithium induces changes in the localization of E-cadherin and β-catenin in kidney collecting duct cells. These changes may be involved in the cellular remodeling during lithium treatment and recovery.
Acknowledgements: We thank Inger Merete S Paulsen for introduction to immunohistochemistry. The project was funded by Department of Biomedicine, Aarhus University.
68 O.3. GRUNDFORSKNING
O-3.02 Katrine Therapeutic correction of mutations in CD40L Bønnerup causing immunodeficiency by CRISPR delivery to hematopoietic stem cells using nucleofection K Bønnerup1 JG Mikkelsen1 D Haslund1 1Department of Biomedicine, Aarhus University
Background: Immunodeficiencies can be treated by gene delivery and integration in stem cells, but this comes with risk of insertional mutagenesis and cancer. Genome editing based on the CRISPR technology is more precise and potentially safer. Hyper IgM syndrome is an immunodeficiency caused by a variation in the CD40L gene. Defective class-switch recombination and somatic hypermutation causes numerous severe infections and a high mortality even after treatment with allogenic stem cell transplantation.
Methods: Recombinant Cas9 protein complexed with single guide RNA (sgRNA) are delivered as ribonucleoprotein (RNP)-complexes with nucleofection to K562 erythroleukemia cells and cord blood-derived hematopoietic stem cells (HSCs) to induce double stranded breaks targeted to the CD40L gene. Adeno-associated virus (AAV) will be used for delivery of donor DNA, which will serve as the template for DNA repair and correction of the disease-causing CD40L variation.
Results: Five different sgRNAs targeting five different sites in the CD40L gene have been designed as the most likely to induce cuts in the genome. By nucleofection, we demonstrated efficient targeting of and DNA cleavage within the CD40L resulting in indel rates (percentage of CD40L alleles in the cell population harboring an insertion or a deletion) ranging from 5% to 95% in K562 cells for the five sgRNAs. In cord blood-derived HSCs, we obtained indel rates ranging from 0% to 82%.
Conclusion: My findings demonstrate that several of the designed sgRNAs effectively induced targeted DNA cleavage in the CD40L gene in K562 cells and HSCs. AAV-based donor vectors are being produced in ongoing work, allowing studies of CD40L gene editing in HSCs and injection into mice to test engraftment.
Acknowledgements: The project is kindly funded by a scholarship from Novo Nordisk Foundation.
O-3.03 Nanna Hlya Cause Platelet Activation During Urosepsis Johnsen N Johnsen1 MG Christensen1 A Hamilton1 M Skals1 AM Hvas1, 2 H Prætorius1 1Department of Biomedicine, Aarhus University 2Department of Clinical Medicine, Aarhus University
Background: The urinary tract is frequently the primary infection site in patients with severe sepsis. UTI’s are often caused by E.coli producing the virulence factors HlyA. HlyA is known to trigger ATP release from cells and thus, acts as an aggressive
69 O.3. GRUNDFORSKNING activator of immune cells and platelets. Our previous data support that HlyA is largely responsible for the septic symptoms observed in response to bacteraemia with uropathogenic E.coli, and thus, a prime candidate for promoting intravascular coagulation.
Methods: The effect of antagonising platelet P2Y receptors (P2Y12 and P2Y1) was tested during sepsis with uropathogenic E.coli (ARD6, O6:K13:H1) by infusion of cangrelor (8.6 or 86µg/hour) or MRS2500 (624µg/hour) in anaesthetised mice. Parametre tested was: survival timeover 6 hours thrombocyte count, TAT complex levels, intravascular haemolysis, bacteria load and cytokine levels (TNF-α, IL-1β, IL-6 and KC) after 2.5h sepsis.
Results: In aggreement with the literature, infusion of the P2Y12 antagonist cangrelor did not change survival or any tested sepsis parameters except a reduction in platelets. In vivo, infusion of MRS2500 increased the survival in mice exposed to uropathogenic E. coli. Moreover, infusion of MRS2500 partially prevented the 60% fall in platelet count otherwise seen in response to sepsis in control mice. However the remaining tested parameters was not affected when MRS2500 is adminstred.
Conclusion: Inhibtion of thrombocyte activation through P2Y12 did not alter the survival of sepsis. However, an inhibition of P2Y1 result in decreased mortality of sepsis induced by HlyA-producing E. coli most likely by preventing the sepsis-associated drop in circulating thrombocytes.
Acknowledgements: Funded by the Independent Research Fund- Denmark
O-3.04 Kristian Is the soluble PD-1 variant (sPD-1) expressed Antonsen by human macrophages? KW Antonsen1 CVB Hviid1 MK Hagensen1 HJ Møller1 1Department of Clinical Biochemistry, Aarhus University Hospital
Background: Soluble PD-1 (sPD-1) is the free circulating form of the PD-1 receptor. PD-1 is expressed on various cells of the immune system and is a treatment target for immunotherapy. sPD-1 can originate from alternative splicing of PD-1 mRNA and could compete with PD-1 for ligand binding. Tumour associated macrophages influence survival in cancer, and the PD-1/PD-L1 axis has been suggested to play a role in their regulation. This study investigated PD-1 and sPD-1 expression in macrophages.
Methods: Human monocytes (THP-1 cells and CD14+ monocytes from healthy blood donors) were differentiated into macrophages with either PMA or M-CSF and GM-CSF respectively. Macrophages were polarized to either an M1 (IFN-γ and LPS) or M2 (IL-4 and IL-13) phenotype. Phenotype markers (CD14, CD11b, CD163, TLR-2, CD206 & CD80) and PD-1 was assessed by flow cytometry. Expression of PD-1 and sPD-1 mRNA will be assessed by droplet digital PCR. Secretion of sPD-1 protein was assessed by ELISA.
70 O.3. GRUNDFORSKNING
Results: Compared to control cells, M1 cells expressed significantly more CD80 and TLR-2 while M2 cells expressed significantly more CD11b and CD206. No PD-1+ population was induced. sPD-1 was secreted by M1 THP-1 cells after 72 hours of stimulation. In monocyte-derived macrophages, sPD-1 was secreted by both M2 (1/4 donors) and M1 (2/4 donors) cells, but results were inconsistent between donors. No unstimulated macrophages secreted sPD-1. Gene expression results are still awaited.
Conclusion: IFN-γ and LPS induces secretion of sPD-1 in THP-1 macrophages. In monocyte-derived macrophages, secretion of sPD-1 in response to stimuli is inconsistent between donors. Stimulation with IFN-γ and LPS or IL-4 and IL-13 does not induce a PD-1+ macrophage phenotype in vitro.
Acknowledgements: This study was supported by The Danish Cancer Society with a pre-graduate scholarship.
O-3.05 Ditte New culture method for the ARPE-19 cell line Rasmussen is suitable for studying endocytosis in the retinal pigment epithelium (RPE) in vitro DK Rasmussen1 T Storm2 R Nielsen1 1Department of Biomedicine, Aarhus University 2Nuffield Department of Clinical Neurosciences, Robert E. MacLaren Laboratory of Ophtalmology, Oxford University
Background: The investigation of endocytosis in the RPE is difficult, as no suitable cell line exist. Animal studies are expensive, and the only well-differentiated in vitro models are low-passage RPE-cells from human donors. Recent studies at University College London indicate that a new culture method for ARPE-19 cells allows them to differentiate further than old culture methods. We tested this new culture method to see, if the cell line is suitable for endocytosis experiments.
Methods: The ARPE-19 cell line was grown in X-VIVO10 medium with 10% penicillin/streptomycin in 6, 48 and 96 well plates at a density of 90 000 cells/cm2. Cells were differentiated for 1 week, 6 weeks, 8 weeks and 9 weeks. q-RT-PCR, western blotting and immunocytochemistry was performed to characterize the cells. Cells were then incubated with a fluorescent retinoic acid (RA) to test if this is endocytosed in the cells.
Results: q-RT-PCR showed a high level of differentiation markers as expected. Western blotting showed expression of proteins involved in the visual cycle and the uptake of retinol (Stra6). This was confirmed by immunocytochemistry. It was hereby confirmed, that the cell line expressed the relevant enzymes. The cells were then incubated with the fluorescent RA, which showed uptake in the well-differentiated cells. The uptake was significantly larger when cells were not incubated with fecal calf serum.
Conclusion: The ARPE-19 cell line is suitable for studying endocytosis of retinoic acid in the retinal pigment epithelium in vivo. More experiments are needed to study the endocytosis of other compounds.
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Acknowledgements: Thanks to the Velux Foundation, Helga og Peter Kornings Fond and A.P. Møllers Fond for sponsoring this study. A further thanks to Nuffield Department of Clinical Neurosciences, Robert E. Maclaren Laboratory of Ophthalmology, Oxford University for the use of laboratory facilities necessary for these studies.
O-3.06 Ann-Sophie Peptidoglycan Recognition Peptide 2 Aggravates Bech Weight Loss in a Murine Model of Chemotherapy-induced Gastrointestinal Toxicity A Bech1, 3 AB Nexøe1 JB Møller1 GL Sørensen1 U Holmskov1 GI Madsen2 M Rathe3 S Husby3 1Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark. 2Department of Pathology, Odense University Hospital, Denmark 3HCA Research, H.C. Andersen Children’s Hospital, Odense University Hospital
Background: Chemotherapy-induced gastrointestinal mucositis (CGIM) is a frequent, severe and dose-limiting side effect and it increases the risk of infections. CIGM is characterized by activation of NF-κβ which leads to upregulation of proinflammatory cytokines. The innate immune protein Peptidoglycan recognition peptide 2 (PGLYRP2) binds to microorganisms and expression of PGLYRP2 is upregulated in the intestine of chemotherapy treated piglets. We investigated the role of PGLYRP2 in CGIM.
Methods: PGLYRP2 wildtype (WT) and PGLYRP2 knockout (KO) mice received an intraperitoneal injection of chemotherapy (Doxorubicin 20 mg/kg). Weight was monitored daily, and animals were euthanized after 2 or 7 days. Expression of proinflammatory cytokines in the jejunum were measured by real-time polymerase-chain reaction (RT-PCR). Villus height, crypt depth, and histologic inflammation were evaluated on H&E stained tissue.
Results: Chemotherapeutic treatment induced weight loss, shortening of the small intestine, elongation of villus height, increased crypt depth, and elevated mRNA levels of Il1β, Il6, and Tnf at day 2. WT mice had a more pronounced weight loss compared to KO mice from day 3 to day 7 (P < 0.01). No other phenotypic differences were detected.
Conclusion: PGLYRP2 aggravates chemotherapy-induced weight loss but does not induce a specific pattern of inflammation and morphological changes in the small intestines. PGLYRP2-antagonists could potentially be a new treatment pathway for ameliorating chemotherapy-induced weight loss.
Acknowledgements: The project was supported financially by the Novo Nordisk Foundations Pre-graduate Scholarship and A.P Møller’s Foundation for the Advancement of Medical Science. We declare no conflicts of interest.
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O-3.07 Frederik Duch The effect of intermittent hypoxia on bone in disuse osteopenic mice FU Duch1 MB Brent1 M Pedersen2 JS Thomsen1 A Brüel1 C Foldager3 1Department of Biomedicine, Aarhus University 2Comparative Medicine Lab, Aarhus University Hospital 3Orthopedic Research Lab, Aarhus University Hospital
Background: Treatment with intermittent hypoxia (IH) has been shown to affect both intracellular pathways and migration of cells important to bone formation. Recently, it has been shown that IH has a positive effect on endochondral bone formation in young mice. However, it remains unexplored whether IH influences disuse induced loss of bone in mature mice. The aim of the present study was to examine whether IH treatment can counteract Botox (BTX)-induced osteopenia in mice.
Methods: Thirty female mice were stratified to four groups: 1) Control, 2) BTX, 3) Control+IH, 4) BTX+IH. At study start BTX was injected into the quadriceps and calf muscles of the right hindlimb of the animals. This led to paralysis of the muscles followed by loss of bone mass. IH animals were placed in a normobaric hypoxia-chamber (10% oxygen) for 1 hour twice daily 5 days/week. Animals were sacrificed after 21 days and DEXA, µCT, and mechanical testing was performed on the femora.
Results: BTX resulted in a significant decrease of bone mass, density and strength compared to ambulating mice. IH treatment did not counteract the disuse-induced deterioration of trabecular microarchitecture, loss of bone mass, density, or strength. Interestingly, hypoxia had no negative effects on the bone properties in either BTX or control mice. This indicates that IH treatment did not have any detrimental effects on trabecular or cortical bone.
Conclusion: The study confirmed that BTX led to loss of bone mass, deterioration of trabecular microstructure and loss of bone strength. These changes were not influenced by IH. Notably, IH had no detrimental effect on bone. This indicates that IH treatment can be administered without causing harm to the bone.
Acknowledgements: Nothing to declare.
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O-3.08 Julie Acidosis inhibits contractions of rat thoracic Hessellund duct JD Hessellund1 DMB Bødtkjer1 E Bødtkjer1 1Department of Biomedicine, Aarhus University
Background: The lymphatic system is responsible for transporting excess fluid from the tissue back to the vascular system. Therefore, a malfunctioning lymphatic system often results in lymphedema; an invalidating condition. In the human thoracic duct, acidosis inhibits basal phasic activity and force development in response to noradrenaline and serotonin. We aim to investigate the mechanism behind inhibition of contractile responses of rat thoracic duct.
Methods: Male Wistar rats are euthanized, and the thoracic duct is isolated and cleaned. To investigate force development at different extracellular pH conditions, we cut the thoracic duct in 2 mm long segments, which we mount in a 4-channel wire myograph. The vessels are randomized to a pH of 7.4, 7.1 or 6.8, and the force development in response to noradrenaline and serotonin (5-HT) is tested in each segment at both control pH (7.4) and the randomized pH.
Results: We find significant inhibition of force development at pH 6.8 compared to pH 7.4 in response to NA (P < 0.0001) and 5-HT (P < 0.0001). At pH 7.1 the response to 5-HT (P = 0.0073) is also attenuated compared to pH 7.4. The difference in contraction between pH 7.4 and pH 6.8 remained when endothelium-dependent vasorelaxation was blocked with indomethacin and L-NAME.
Conclusion: Our results demonstrate that acidosis inhibits force development of the rat thoracic duct in response to both NA and 5-HT and support that effects on endothelium-dependent vasorelaxation are not responsible for the inhibition. The exact mechanism behind the inhibition remains to be investigated.
Acknowledgements: Thanks to Ebbe Bødtkjer and Donna Bødtkjer for being my supervisors. Thanks to Anders Lerche Møller for teaching me the dissection and mounting methods. Thanks to the Novo Nordisk foundation for founding my research year.
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O-3.09 Mie Wolff Prognostic Value of PD-1 Expression on Kristensen Peripheral Blood Lymphocyte Subsets in Metastatic Renal Cell Carcinoma MW Kristensen1 KM Lauridsen1 S Al-Karradi1 F Donskov2 M Hokland1 MN Andersen1, 3 1Department of Biomedicine, Aarhus University 2Department of Oncology, Aarhus University Hospital 3Department of Hematology, Aarhus University Hospital
Background: Interleukin (IL)-2 based immune therapy is curative in a subgroup of metastatic renal cell carcinoma (mRCC) patients, and bevacizumab (Avastin) has been associated with improved survival in some patients. However, there is still a need for biomarkers to guide treatment decisions and to improve prognostication. Programmed Cell Death Protein 1 (PD-1) expression in tumor has shown prognostic potential in other cancers, however, in mRCC the prognostic value of PD-1 in peripheral blood is unknown.
Methods: The present study includes 89 mRCC patients from the DaRenCa 1 study, where patients were randomized to IL-2 and interferon-α Avastin. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples± collected at baseline and during treatment at 5 weeks, 9 months, and/or progression. Using flow cytometry, we examined PD-1 expression on lymphocyte subsets. Primary endpoints were progression free and overall survival (PFS and OS).
Results: There was a significant longer OS in MSKCC (Memorial Sloan-Kettering Cancer Center) intermediate prognostic group when Tc and Th cell PD-1 median fluorescence intensity (MFI) decreased from baseline to week 5. Interestingly, patients with progressive disease, who had a decrease in Tc and Th cell PD-1 MFI from baseline to week 5, had a significantly longer survival than those who did not.
Conclusion: A decrease in Tc and Th cell PD-1 expression from baseline to week 5 was associated with longer OS, especially for patients in the intermediate MSKCC prognostic group.
Acknowledgements: All experiments were performed using the LSRFortessa flow cytometer (BD Biosciences) at the FACS core facility, Aarhus University, Denmark. The authors thank Anni Skovbo for excellent technical assistance. The project was financially supported by the Danish Cancer Society.
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Session O.4: Psykiatri & Neuroscience
O-4.01 Albin Associations between risk factors for depression Arvidsson and serotonin 2A receptor binding in healthy humans: a PET molecular brain imaging study A Arvidsson1 MK Madsen1 PMF Fisher1 GM Knudsen1, 2 VG Frokjaer1, 2 1Neurobiology Research Unit, Rigshospitalet 2Faculty of Health and Medical Sciences, University of Copenhagen
Background: Depression is a leading cause of disability worldwide. Personality trait neuroticism and stressful life events (SLEs) are strong risk factors for major depressive disorder (MDD). The serotonin system is a key component in the pathophysiology and treatment of MDD. Although animal studies suggest an important role for the serotonin 2A receptor (5-HT2AR) in stress and anxiety-related behavior, the relationship between 5-HT2AR levels, stressful life events, and neuroticism in humans is not known.
Methods: In this study, we make use of a large dataset (n = 172) containing 5-HT2AR PET brain scans coupled with neuropsychological data and personality assessments. Statistical analysis will be performed using multiple linear regression, adjusting for possible confounding variables. We hypothesize that SLEs are positively correlated with cerebral 5-HT2AR levels, and that neuroticism moderates this association such that high neuroticism individuals display a more pronounced positive association.
Results: Analyses are ongoing. The results from this study on the cerebral 5-HT2AR architecture and known risk factors for MDD will be available for presentation at KMS20.
Conclusion: Much is still unknown about the role and function of the serotonergic system in the brain. This project will advance our understanding of how it relates to personality, psychosocial adversity, and mood disorders.
Acknowledgements: This study is funded by a scholarship stipend granted by the Lundbeck Foundation through the Danish Psychiatric Society.
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O-4.02 Line Amalie Life with chronic pain: Patients’ stories about Hellemose the impact of pain in their lives. A narrative study LA Hellemose1 LK Gormsen1 JE Møller2 1Center of Functional Disorders, Aarhus University Hospital 2Center for Health Sciences Education (CESU), Clinal Institute, Health, Aarhus University
Background: Chronic pain is a very frequent condition that is extremely disabling for the individual patient, in addition to being a burden to the community. Chronic pain is a condition that is difficult to treat, both in general practice and in specialized pain clinics. The aim of this study was to examine which stories do patients with chronic pain tell about how pain influence their lives, and how does these narratives relate to their pain treatment.
Methods: This study was made on the basis of semi-structured interviews of three chronic pain patients who were treated in general practice. The interviews were subsequently analyzed by qualitative narratological approach according to Rita Charon principles of narrative medicine.
Results: The informants have several general narratives in the interviews, which together can be reduced to the lack of a language of their pain. It leads to miscommunication with both relatives and therapists, and gives patients a feeling of isolation and hopelessness, in addition to frustrations and conflicts around their pain. Furthermore, there is a tendency to informants describe their pain in a biomedical context.
Conclusion: This study shows that patients need to be met with a curiosity and recognition of their pain symptoms, although there is no good biomedical explanation for them. Patients need that clinicians meets them in a holistic way, to get a good treatment relation and a greater chance of successful treatment.
Acknowledgements: none
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O-4.03 Theis Mariager Induction of brain abscess in a porcine model by stereotaxic injection T. Mariager1 J. Bodilsen2 H. Nielsen3 C. Bjarkam4 1Department of Neurosurgery, Aalborg University Hospital 2Department of Infectious Diseases, Aalborg University Hospital 3Department of Clinical Microbiology, Aarhus University Hospital 4Department of Biochemistry, Aalborg University Hospital 5Department of Pathology, Aalborg University Hospital
Background: Brain abscess (BA) is a rare but serious infection with high fatality and serious sequelae in 20–70% of survivors. The aetiology consists primarily of oral cavity bacteria or S. aureus. Treatment entails neurosurgical intervention and i.v. antibiotics. Current knowledge of BA is limited to models in small animals. However, pigs may prove a superior model due to anatomical and physiological similarities with humans. In the present study, we aimed to establish an in vivo model of BA in pigs.
Methods: A 500µL bacterial solution of oral cavity bacteria (Aggregatibacter aphrophilus, Fusobacterium nucleatum and Streptococcus intermedius) is injected into the temporal lobe of two domestic landrace pigs. The neurosurgical procedure will be carried out by MRI guided stereotaxic technique. 14 days post inoculation MRI-scans, blood and CSF samples are obtained before euthanization and fixation of brain tissue. Infected brain tissue is saved for microbiological and histological examination.
Results: The project will commence in November 2019. Series of experiments will be carried out in November, December, and January including advanced cranial imaging as well as state-of-the-art microbiological and histopathological analyses. Results will be presented at KMS 2020 if available.
Conclusion: We aim to develop a robust model of BA with bacteria, anatomy and physiology reflecting those seen in humans. If successful, the BA pig model will be pivotal for further studies into the pathogenesis of BA and pharmaco-kinetic studies of antibiotic treatment of this devastating disease.
Acknowledgements: Nothing to declare.
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O-4.04 Navid Noory Clinical characteristics and neuroanatomical findings in 74 patients with secondary trigeminal neuralgia attributed to multiple sclerosis N Noory1 E Andonov Smilkov2 JL Frederiksen3 TB Heinskou1 AS Schott Andersen1 S Maarbjerg1 L Bendtsen1 1Danish Headache Center, Rigshospitalet Glostrup 2Department of Diagnostic Radiology, Rigshospitalet Glostrup 3Department of Neurology, Rigshospitalet Glostrup
Background: Trigeminal neuralgia (TN) is a painful neurological disease, which affects the extra-and intraoral territory of the fifth cranial nerve and is 20-fold more prevalent in patients with multiple sclerosis (MS). A neurovascular contact (NVC) at the root entry zone (REZ) is a major contributor to the etiology of primary TN. Considering the etiology in secondary TN attributed to MS, it was recently proposed that it is rather a dual concurrent mechanism by both NVC and demyelating plaques.
Methods: We prospectively enrolled consecutive TN-MS patients from the Danish Headache Center from October 2012 – December 2019. All patients underwent neurological examination by experienced neurologists, who filled semi-structured interviews. MRi scans where done using a 3.0 Tesla imager, and the axial, coronal and sagittal planes where evaluated by the same experienced neuroradiologist, who was blinded to the side of symptoms.
Results: A total of 74 consecutive TN-MS patients were included in this cross-sectional study. Eight patients did not have a protocolized MRi scan. A total of 66 MRi scans were evaluated for neuroanatomical abnormalities. All data has been collected and are currently analyzed. Results will be presented at KMS 2020.
Conclusion: This study is to our knowledge the largest study to evaluate the clinical characteristics and MRi neuroabnormalities in TN-MS patients. It has the potential to improve clinical diagnosis of TN-MS and to shed light on the underlying etiology of TN-MS. Conclusion will be presented at KMS 2020
Acknowledgements: Nothing to declare
O-4.05 Kjeld Mohr Comparison of GFAP expression as marker for activated satellite glial cells in mice and rats K Mohr1 LT Pallesen1 M Richner1 CB Vægter1 1Department of Biomedicine, Aarhus University
Background: Satellite glial cells (SGC) surround neuronal somas in the dorsal root ganglia (DRG). They are activated and undergo molecular and structural changes, following nerve injury that contribute to the development of neuropathic pain. This makes SGCs potential target for therapy of neuropathic pain. There has been disagreement about specific markers for SGCs, especially the protein glial fibrillary
79 O.4. PSYKIATRI & NEUROSCIENCE acidic protein (GFAP) has been used in different animal models though its expression is controversial.
Methods: C57BL/6J mice and Sprague Dawley rats were used for 3 models of neuropathic pain and inflammation. In the 1. model animals underwent a full ligation of the sciatic nerve. In the 2., animals were injected with lipopolysaccharide (LPS) to stimulate a systemic inflammation. In both models DRGs were dissected after 3 and 14 days for immunohistochemistry. In the 3. model primary cultures of DRGs were stimulated with LPS and stained by immunocytochemistry. Stimulated SGCs were compared to naive.
Results: Experimental results are expected before the conference.
Conclusion: The results may contribute to a generalised understanding of the characteristics of SGCs leading to a better comparability of other studies, and thereby facilitate further research of the functions of SGCs and possible treatment options of neuropathic pain.
Acknowledgements: This project has been founded by the Lundbeck Foundation. No conflicts of interest are declared by the authors.
O-4.06 Stine Autonomic Sympathetic Nervous Function and Uhrenholt Delirium in the ICU Study Jensen S. Uhrenholt1, 3 J. Stokholm2 T. Chistensen2, 3 M. Bestle1, 3 1Dept. of Anesthesiology and Intensive Care, Nordsjællands Hospital 2Dept. of Neurology, Nordsjællands Hospital 3Dept. of Clinical Medicine, University of Copenhagen
Background: Delirium is often underdiagnosed and causes higher morbidity, mortality and longer hospitalization, making early recognition and treatment essential. The ICU screening tool CAM-ICU has a low specificity. The pathology behind delirium is not fully understood but increased autonomic drive is hypothesized to be a part of it. This study tests measuring modalities as surrogate markers for increased sympathetic activity in delirious patients.
Methods: A prospective, observational study at the ICU at Nordsjællands Hospital. In order to examine the sympathetic drive three non-invasive measures are done daily: facial thermography, pupillary light reflex, and palm electrical skin conductance level. A daily blood sample of catecholamines are taken and all patients are screened daily with the CAM-ICU.
Results: Inclusions are ongoing. At the time of the hand-in of this abstract 65 patients have been included. The aim is that 100 patients should be included by the end of January 2020. Preliminary results of the first 40 patients show no significant connection between delirium and the degree of autonomic activation in the ICU patient.
80 O.4. PSYKIATRI & NEUROSCIENCE
Conclusion: The sample size of the preliminary results is too small to conclude anything significant. The conclusions of this project will be published at the end of summer 2020.
Acknowledgements: Forskningspuljen at Nordsjællands Hospital: Undergraduate research year scholarship for the first author and catecholamine analyses.
O-4.07 Casper Does Parkinson’s Disease start in the gut – an Skjærbæk esophageal transit and intestinal dysfunction study C Skjaerbaek1 K Knudsen1 P Borghammer1 1Department of Nuclear Medicine and PET, Aarhus University Hospital
Background: Parkinson’s Disease (PD) is a neurodegenerative disease clinically characterized by bradykinesia, tremor and rigidity. Yet, non-motor symptoms including constipation and dysphagia are common. According to the body-first hypothesis PD may originate in the gastrointestinal tract and spread to the brainstem. Predilection sites for PD-related histopathology include the vagal nerve and the lower third of the esophagus. However, most structures innervated by the autonomic nervous system are affected.
Methods: We aim to validate esophageal scintigraphy as a method for detecting esophageal dysfunction in PD. Furthermore, we will study potential correlations among objective and subjective measures of gastrointestinal dysfunction. 30 early-to-moderate PD patients and 28 healthy, matched controls (HC) are included. In addition colonic transit and volume are determined by CT-scanning after radio opaque marker ingestion. Olfaction tests, motor symptom evaluation and several questionnaires are carried out.
Results: Preliminary results of an explorative part (14 PD and 14 HC) indicate prolonged transit time in the lower part of the esophagus as well as prolonged intestinal transit time in PD patients. Prior to analysis of the validation part (16 PD, 14 HC) a semiautomated, script-based method for evaluation of esophageal transit will be developed. By February 1st, we expect to have analysed 30 PD patients and 28 control subjects.
Conclusion: The preliminary results suggest that gastrointestinal dysfunction occurs early in PD thus supporting the body-first hypothesis. The importance of the gastrointestinal tract in PD is underlined if an ongoing imaging study of de novo PD confirms the widespread involvement of the gastrointestinal tract
Acknowledgements: Funding was provided by the Independent Research Fund Denmark, the Novo Nordisk Foundation and the Lundbeck Foundation. No conflicts of interests to declare.
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O-4.08 Linda Eriksen Spinal Cord Stimulation in Severe Cases of Complex Regional Pain Syndrome (CRPS) LE Eriksen1, 2, 4 AJ Terkelsen1, 4 JCH Sørensen2, 4 K Meier2, 3, 4 1Department of Neurology and Danish Pain Research Center, Aarhus University Hospital 2Department of Neurosurgery, Aarhus University Hospital 3Department of Anesthesiology, Aarhus University Hospital 4Institute of Clinical Medicine, Aarhus University
Background: Complex regional pain syndrome (CRPS) is an often debilitating pain condition preceded by trauma to an extremity. The acute phase is characterized by inflammation and peripheral sensitization, whereas the chronic phase is mainly due to central mechanisms. Standard treatment is often inadequate, and spinal cord stimulation (SCS) may therefore be an option. We here assess the effect of SCS for CRPS and elucidate whether symptom duration preceding implantation is a predictor of treatment efficacy.
Methods: We aim to offer a comprehensive statement of the effect of SCS as a treatment of CRPS. The study includes CRPS patients implanted with an SCS system at the University Hospital in Aarhus, Odense or Aalborg, Denmark. Data for the analysis are recorded in the Neurizon Neuromodulation Database. Pain intensity (numeric rating scale, NRS 0–10) is considered the primary outcome of treatment. As a secondary outcome, we assess whether the effect varies in relation to preoperative symptom duration.
Results: Data are currently being prepared for analysis. Preliminary results will be presented at KMS 2020. A significant effect of the SCS treatment in patients with CRPS is expected to be verified.
Conclusion: As of November 2019, no final conclusions have been drawn.
Acknowledgements: The project is funded by The Lundbeck Foundation granted by the Danish Neurological Society.
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Session O.5: Epidemiologi
O-5.01 Henriette Does chronic kidney disease increase the risk of Vendelbo acute kidney injury in patients with a first-time Graversen diagnosis of acute pyelonephritis? HV Graversen1 CF Christiansen1 M Nørgaard1 1Department of Clinical Epidemiology, Aarhus University Hospital
Background: Pyelonephritis is reported to increase the risk of acute kidney injury (AKI). This critical condition is associated with increased mortality and morbidity. Therefore, it is of importance to examine underlying causes of AKI in patients with pyelonephritis. Research has revealed that AKI and chronic kidney disease (CKD) are closely connected. This cohort study examines if pre-existing CKD is a risk factor for development of AKI among patients with a first-time diagnosis of pyelonephritis.
Methods: We will conduct a large population-based cohort study of patients with a first-time diagnosis of pyelonephritis from 2000 to 2017. We will obtain data using ICD-codes and laboratory data. Cumulative incidence of AKI according to pre-existing CKD status will be assessed and compared by hazard ratios (HRs). HRs will be computed using cox regression adjusted for age, sex, malformation of the urinary tract, hypertension, heart failure, acute myocardial infarction and diabetes.
Results: We expect to include about 40 000 patients with a first-time inpatient or outpatient primary or secondary diagnosis of acute pyelonephritis recorded in the Danish National Patient Registry. Analysis of data is ongoing and results will be presented at the conference.
Conclusion: It is of importance to examine if pre-existing CKD increases the risk of AKI in patients with pyelonephritis, because such knowledge could direct more attention to prevention of AKI in patients with pyelonephritis and co-morbid CKD.
Acknowledgements: Nothing to declare.
83 O.5. EPIDEMIOLOGI
O-5.02 Kamilla Lanng Eosinophilia and elevated IgE in screenings of newly arrived refugees, neglected biomarkers of underlying disease? K Lanng1 C Wejse1, 2 P Kallestrup1, 3 AM Floe Hvass2 1Section for Global Health, Department of Public Health, Aarhus University 2Department of Infectious Diseases, Aarhus University Hospital 3Section of General Practice, Department of Public Health, Aarhus University
Background: Previous studies show that eosinophilia is common in refugees and that the most frequent cause of eosinophilia in migrants are helminthic infections. Health screenings at arrival are a common tool used to monitor disease in refugees, and in this study, our aim is to evaluate the diagnostic value of eosinophil and IgE count in screening of refugees. The study intends to describe the prevalence, characterise the refugees with elevated count and find the underlying cause.
Methods: In Aarhus municipality systematic health assessments (HA) have been offered to all refugees that obtained a residence permit since June 2013. Eosinophil count became a part of the HA in January 2016 and IgE in November 2016. In this study we included all participants who had eosinophilia and/or elevated IgE at the HA, and are doing follow-up at General Practitioners(GP’s) to find later diagnosed, underlying causes of the elevations.
Results: 86% out of 1325 invited between 2015–2016, participated the HA. 788 were examined for eosinophilia and 407 of those were also examined for IgE. 7% (95% CI: 0.05–0.09) had eosinophilia, 32% (95% CI: 0.27–0.37)had elevated IgE and 4% (95% CI: 0.02–0.06) had both elevated IgE and eosinophilia. The majority did not have a diagnosis that could explain the elevations, and if elevated a family member was likely to have elevated counts as well. The follow-up at GPs is still ongoing.
Conclusion: Our study shows that eosinophilia and especially elevated IgE is prevalent in refugees and is most frequent without a known cause. The follow-up with GPs, should contribute to information about and understanding of underlying cause, data we hope to present at KMS 2020.
Acknowledgements: the project is funded by Novo Nordisk Foundation Pre-graduate Scholarships.
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O-5.03 Mads Albrecht Late-onset multiple sclerosis is associated with Andersen an increased rate of reaching disability milestones MA Andersen1, 2 M Magyari1, 2 1Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet 2Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet
Background: Most patients with multiple sclerosis (MS) have clinical onset between ages 20 and 40 years. However, an increasing proportion of patients are presenting with late-onset multiple sclerosis (LOMS), commonly defined as disease onset after the age 50 years. Evidence on the presenting characteristics and the prognosis for these patients is scarce.
Methods: The nationwide population-based Danish Multiple Sclerosis Registry served as data source including all patients with available demographic and clinical features. We conducted a cohort study and applied descriptive statistics to present demographic and clinical characteristics. The Expanded Disability Status Scale (EDSS) score was used to assess patient disability. Rates of reaching EDSS milestones were analyzed using Cox regression models stratified on baseline EDSS.
Results: We identified 27 615 MS patients with known year of clinical onset, of which 4 678 had LOMS. Comparing the non-LOMS cohort with the LOMS cohorts we found 63.7% vs. 60.7% female patients and mean EDSS score at diagnosis to be 2.1 vs. 2.8. Patients with LOMS had an increased rate of reaching EDSS milestones of 4 (Hazard ratio (HR) = 1.4 [95% CI: 1.1–1.8]), 6 (HR = 1.6 [95% CI: 1.2–2.2]) and 7 (HR = 1.8 [95% CI: 1.0–3.0]) when compared to the non-LOMS patients.
Conclusion: Onset of clinical symptoms after the age of 50 years is associated with a lower female to male ratio, a higher EDSS score at diagnosis and an increased rate of reaching disability milestones.
Acknowledgements: The authors acknowledge the Danish MS Society for funding and assisting the DMSR and all MS clinics in Denmark in providing data to the DMSR.
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O-5.04 Marwan Public opinion and legislations on brain death, Othman circulatory death and organ donation M Othman1 A Dutta2 D Kondziella1, 3 1Departments of Neurology, Rigshospitalet, Copenhagen University Hospital, Denmark 2Department of Biomedical Engineering, University of Buffalo, State University of New York, NY, United States 3Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Background: Organ donation is possible after brain death (BD) and sometimes circulatory death (CD), but it is poorly understood how the public perceives the difference between BD and CD and how this may influence attitudes towards organ donation. We investigated the public opinion on BD versus CD and documented inconsistencies in the legislations of countries with different cultural and socioeconomic backgrounds.
Methods: Using a crowdsourcing approach, we randomized 1 072 participants from 30 countries to either a case report of organ donation after BD or to one following CD. Further, we reviewed the scientific literature and sampled guidelines from 24 countries and 5 continents.
Results: Exposure to “BD” was not associated with a lesser likelihood of participants agreeing with organ donation (82.1%) compared to “CD” (81.9%, RR 1.02 [95% CI: 0.99–1.03], P = 0.11). Participants exposed to “CD” were more certain that the patient was truly dead (87.9% 19.7%) than participants exposed to “BD” (84.1% 22.7%, Cohen’s d 0.18, P = 0.004).± Guidelines and literature review revealed large differences± between countries regarding procedures required to confirm BD and CD.
Conclusion: Implementation of organ donation after CD is unlikely to negatively influence the willingness to donate organs. However, legislation is still BD-based in most countries. The time may be ripe to adjust legislations and increase the rate of CD-based organ donation.
Acknowledgements: The authors declare no conflict of interests.
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O-5.05 Elizabeth Vlk Survival outcomes after adrenalectomy due to metastatic disease – a Danish nation-wide study E Harregaard Vlk1 AL Ebbehøj2 F Donskov3 P Løgstrup Poulsen2, 4 L Rolighed1, 5 1Department of Surgery, Aarhus University Hospital 2Department of Endocrinology, Aarhus University Hospital 3Department of Oncology, Aarhus University Hospital 4Department of Internal medicine, Aarhus University Hospital 5Department of Otorhinolaryngology, Aarhus University Hospital
Background: Adrenal metastases are common in patients with cancer. Current treatment guidelines supports adrenalectomy in patients with solitary adrenal metastases. Although surgical resection of adrenal metastases may prolong survival in selected patients, it is a clinical challenge to identify which patients may or may not benefit from this approach.
Methods: We conducted a nation-wide retrospective cohort study. We identified patients registered in the Danish National Pathology Registry with tissue codes for “metastasis” and “adrenal gland”. All pathology reports from 2000–2018 were reviewed to determine primary cancer, tumor stage and size of metastasis. Kaplan-Meier survival analysis was used to calculate survival, while the Log-rank test and Cox regression was applied to compare survival between groups.
Results: We identified 472 patients who underwent adrenalectomy due to metastases. Most common primary cancer origin was renal (48%), lung (24%), and colorectal (10%). The median postoperative survival was 20 months (IQR 9, 41 months). Overall survival at 1, 5, and 10 years was 70%, 30%, and 14%. Lung cancer patients had worse survival outcomes (HR = 1.44, P = 0.007). Clear tumor margins predicted prolonged survival (HR = 1.73, P < 0.001). Survival decreased with increasing tumor size (P < 0.05).
Conclusion: The use of adrenalectomy in cancer patients is increasing. We identified a significant proportion of patients with long-term survival after adrenalectomy due to metastatic disease. Longest survival was in patients with small metastatic lesions, clear margins, and renal or colorectal cancer origin.
Acknowledgements: We received funding from Augustinus Fonden, Dagmar Marshall Fonden, and Andersen-Isted fonden. The authors declare no conflict of interest.
87 O.5. EPIDEMIOLOGI
O-5.06 Thomas Do Pentavalent vaccines have sex-differential Aamand non-specific effects? T Aamand1, 2 AB Fisker1, 3 SM Thysen1, 2, 3 1Bandim Health Project, INDEPTH Network, Bissau, Guinea-Bissau 2GloHAU, Department of Public Health, University of Aarhus, Aarhus, Denmark 3Department of Clinical Research, OPEN, University of Southern Denmark, Odense, Denmark
Background: Vaccines may alter the ability to combat infections unrelated to the target disease i.e. have “non-specific effects” (NSE). Live vaccines tend to decrease and non-live to increase susceptibility. The Diphtheria-Tetanus-Pertussis vaccine (DTP) has been associated with increased child mortality, especially for girls. In 2008, the DTP-containing Pentavalent vaccine replaced DTP in Guinea Bissau. The aim of this study is to investigate female relative to male mortality after Penta-vaccination.
Methods: Bandim Health Project (BHP) runs a rural Health and Demographic Surveillance System in Guinea-Bissau, West Africa. Vaccination and vital status were registered for children at biannual visits. At all visits between September 1, 2008 and January 1, 2018, vaccines were provided according to the recommended schedule. Children aged 6 weeks to 8 months at Penta-vaccination by BHP were followed for survival until a subsequent visit where a vaccine was given/registered or for a maximum of 6 months.
Results: Will be presented at the congress.
Conclusion: Will be presented at the congress.
Acknowledgements: This study was supported by Danmarks Frie Forskningsfond, Else og Mogens Wedell-Wedellsborgs Fond, Aase og Ejnar Danielsens Fond, Handelsgartner Ove William Buhl Olesen og ægtefælle fru Edith Buhl Olesens Mindelegat, Kong Christian IX og Dronning Louises Jubilæumslegat, Fonden til Lægevidenskabens Fremme. We would like to thank the local assistants at BHP and children and mothers of Guinea-Bissau participating in the data collection, without whom this study would not be possible.
88 O.5. EPIDEMIOLOGI
O-5.07 Philip Munch Is the risk of cardiovascular disease increased after living kidney donation? P Munch1 H Birn2 CF Christiansen2 C Erikstrup3 M Nørgaard1 1Department of Clinical Epidemiology, Aarhus University Hospital 2Department of Renal Medicine, Aarhus University Hospital 3Department of Clinical Immunology, Aarhus University Hospital
Background: Living kidney transplantation is considered the best treatment of end stage renal disease. However, it involves removal of a kidney from an otherwise healthy individual. Donor nephrectomy inevitably leads to a reduction in renal function. Since reduced renal function is a well-known risk factor for cardiovascular disease (CVD) and hypertension (HT), we examined the risk of ischemic cardiovascular disease, atrial fibrillation and hypertension after living kidney donation.
Methods: In this nationwide cohort study, we included individuals who underwent living donor nephrectomy in the period 1996–2018 and followed them for cardiovascular diagnoses through medical registries. We compared the risks of CVD and HT in kidney donors with those in healthy sex and age-matched individuals from the general population using Cox-regression. Additionally, we compared the risks in kidney donors and blood donors using standardization.
Results: Compared with the general population, kidney donors had a lower risk of both ischemic cardiovascular disease and atrial fibrillation, while the risk of HT was similar. Compared with blood donors, kidney donors had a similar risk of ischemic cardiovascular disease (standardized incidence ratio (SIR) = 1.08 [95% CI: 0.82–1.43]), a slightly decreased risk of atrial fibrillation (SIR = 0.84 [95% CI: 0.53–1.34]) and a 31% increased risk of HT (SIR = 1.31 [95% CI: 1.11–1.56]).
Conclusion: We did not find a clearly higher risk of CVD after living kidney donation. This supports the practice of living kidney donation among carefully selected donors. The potential increased risk of HT found in this study emphasize the importance of subsequent regular follow-up care of kidney donors.
Acknowledgements: The study is funded by the Independent Research Fund Denmark
89 O.6. INTERN MEDICIN
Session O.6: Intern Medicin
O-6.01 Lotte Reduced T cell 4-1BB expression is associated Lindgreen with infection in alcoholic hepatitis Eriksen LL Eriksen1 MA Nielsen2 TL Laursen1 B Deleuran2 H Vilstrup1 S Støy1 1Department of Hepatology and Gastroenterology, Aarhus University Hospital 2Department of Biomedicine, Aarhus University
Background: Alcoholic hepatitis (AAH) has a high mortality and dysfunctional T cells are thought to be involved in the high susceptibility to infection. T cell activation is governed by the balance between co-stimulatory receptors such as 4-1BB and inhibitory receptors such as Programmed Death receptor 1 (PD-1).We characterised the expression of 4-1BB on T cells and its inhibitory soluble (s) form s4-1BB in relation to expression of PD-1 and the presence of infection.
Methods: Blood from 35 patients with AAH (diagnosis, day 7 and 90) was compared with healthy abstinent controls (HC). T cell receptor expression was quantified by flow cytometry and plasma s4-1BB by ELISA.
Results: The frequency of 4-1BB+ CD4 and CD8 (both P < 0.05) T cells were higher in AAH compared with HC. In patients with AAH, the frequency of 4-1BB+ relative to PD-1+ T cells was decreased (P < 0.05). Also, the frequency of T cells expressing both 4-1BB and PD-1 and only PD-1 (both P < 0.05) was increased. s4-1BB tended to be elevated in AAH compared with HC (P = 0.07). Patients infected at day 7 had a decrease in 4-1BB+ T cells and an increase in s4-1BB within the first week compared to those uninfected.
Conclusion: In patients with AAH, the balance between 4-1BB and PD-1 is skewed towards T cell inhibition and associated with infection.
Acknowledgements: This project was funded by Novo Nordisk Foundation and Aase and Ejnar Danielsens Foundation. The parties involved declare no conflicts of interest.
90 O.6. INTERN MEDICIN
O-6.02 Sofie Amalie Soluble α4β7 as a prognostic marker of the Gehrcke clinical response to the integrin-blocking Bisholm antibody, vedolizumab, in Crohn’s patients. SAG Bisholm1 T Vorup-Jensen1 TW Kragstrup1 AK Dige2 1Department of Biomedicine, Aarhus University 2Department of Clinical Medicine, Aarhus University Hospital
Background: The integrin α4β7 expressed on gut-homing T-lymphocytes is important for the increased intestinal extravasation of lymphocytes characteristic of Crohn’s disease. Treatment with the α4β7-blocking antibody vedolizumab has proven to be correlated with remission of symptoms in some but not all patients. There is an unmet need for a prognostic marker of response to vedolizumab which could subdivide Chron’s patients into vedolizumab responders and non-responders.
Methods: A time-resolved immunofluorometry assay (TRIFMA) was used to measure soluble α4β7 concentrations with therapeutic antibodies vedolizumab and natalizumab for capture and detection. Measurements were made on EDTA-plasma from healthy volunteers, Crohn’s patients pre- and post-treatment with the TNF-α inhibitor adalimumab, and rheumatoid arthritis (RA) patients. Further measurements were conducted on synovial fluid from RA patients and on LPS-stimulated PBMCs.
Results: Multiple experiments were conducted to establish the α4β7 assay with an acceptable sensitivity and signal-to-noise ratio. In these proof-of-concept studies the lower detection limit of recombinant α4β7 was approximately 1 ng/mL with the highest sensitivity being achieved with vedolizumab as the capture antibody and natalizumab as the detection antibody. This antibody combination also enabled detection of soluble α4β7 in plasma from healthy volunteers.
Conclusion: A TRIFMA assay for detection of recombinant and soluble α4β7 in human plasma has been established. Future research will aim to investigate potential correlations between Crohn’s patients’ response to vedolizumab and soluble α4β7 concentrations.
Acknowledgements: The authors want to thank Bettina Grumsen for great technical support. Furthermore, we want to thank Annette Gudmann Hansen and professor Steffen Thiel for kindly letting us use their technical apparatus. Finally, we wish to thank Morten Leif Munding Stilund for advice on therapeutic antibodies.
91 O.6. INTERN MEDICIN
O-6.03 Søren RNA-sequencing of formalin-fixed, Klingenberg paraffin-embedded primary prostate cancer tissue: Transcriptomic profiling to distinguish metastatic potential at diagnosis S Klingenberg1, 2, 5 J Fredsøe1, 5 BP Ulhøi3 MR Jochumsen2, 5 M Borre4, 5 K Bouchelouche2, 5 KD Sørensen1, 5 1Department of Molecular Medicine, Aarhus University Hospital 2Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital 3Department of Pathology, Aarhus University Hospital 4Department of Urology, Aarhus University Hospital 5Department of Clinical Medicine, Aarhus University
Background: The inability to accurately predict whether primary prostate cancer (PC) will progress to metastatic disease (MD) leads to overtreatment of indolent cases and delayed or suboptimal treatment of aggressive cases. Thus, we aimed to use RNA-Seq to identify novel gene expression profiles that can predict metastatic potential at diagnosis in primary PC tumors.
Methods: From 113 PET/CT prostate-specific membrane antigen (PSMA)-positive, newly diagnosed high-risk PC patients, we used formalin-fixed, paraffin-embedded (FFPE) tissue samples from transrectal ultrasound- or MRI-guided biopsies or radical prostatectomy (RP) specimens. Based on primary staging results from 68Ga-PSMA PET/CT, patients represented three distinct subgroups: a) 41 with localized disease (LD), b) 35 with lymph node metastases only (LNM), and c) 37 with bone metastases (BM).
Results: We achieved a mean 3.2 million reads in each sample with 48.65% of reads successfully mapped to target genes. Differential expression analysis revealed vast differences in transcriptomic profiles between patients with LD and patients with MD (LNM and BM). Dissimilarities between patients with LND and BM were present at a lesser extent. Gene set enrichment analysis showed increased interferon signaling and epithelial to mesenchymal transition in patients with MD compared to patients with LD.
Conclusion: These findings suggest that primary PC tumors exhibit altered transcriptomic profiles observed in patients with evident MD. Lastly, we have shown that archival FFPE tissue is useful for whole-transcriptomic profiling using a standard 3’ mRNA-Seq protocol within at least two years after fixation.
Acknowledgements: We would like to thank The Danish Cancer Society for financial support regarding both the research year scholarship and operating expenses. The authors have nothing to declare.
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O-6.04 Rasmus The Frequency of Localized and Systemic Bastkjær Amyloidosis in Patients Receiving Carpal Tunnel Release R Bastkjær1, 2 F Grønnehave1, 2 A Petersen3 H Møller1, 4 N Marcussen1, 4 S Overgaard5 N Abildgaard1, 6 J Mogensen1, 2 1Odense Amyloidosis Centre, Odense University Hospital 2Department of Cardiology, Odense University Hospital 3Department of Orthopaedic Surgery, Kolding Hospital 4Department of Pathology, Odense University Hospital 5Department of Orthopaedic Surgery, Odense University Hospital 6Department of Hematology, Odense University Hospital
Background: Retrospective observations have established that as many as 50% of patients with cardiac amyloidosis caused by transthyretin (ATTR) have been diagnosed with carpal tunnel syndrome (CTS) 5–10 years prior to diagnosis of their cardiac condition. However, only few studies have investigated the presence of localized and systemic amyloidosis in patients undergoing carpal tunnel release (CTR). The aim of this study was to investigate the prevalence of amyloidosis among patients undergoing CTR.
Methods: 100 consecutive patients eligible for CTR without a recognised cause of their nerval compression were investigated. Biopsies of tenosynovial and fatty tissue were stained with Congo Red. Amyloid positive biopsies were subtyped by immunoelectron microscopy and mass spectrometry. Patients with amyloid positive biopsies underwent thorough investigations for cardiac and systemic amyloidosis.
Results: 17 patients had amyloid positive biopsies. Amyloid positive patients were significantly older (73 years vs 55 years, P < 0.001) and the prevalence of males was significantly higher in the amyloid positive group (47% vs 22%, P = 0.038). The subtype of amyloid was: ATTR in 13 patients, light-chain in 1 patient, and fibrinogen alpha in 1 patient. For 2 patients the amyloid subtype was undetermined. Interestingly, none of the amyloid positive patients were identified with organ involvement.
Conclusion: 17% of CTR patients had amyloidosis confined to the carpal tunnel, with no signs of organ involvement. The proportion of these patients who may develop systemic disease is unknown. Long-term follow-up of these patients is needed before routine tests for amyloidosis in CTR patients may be considered.
Acknowledgements: The authors would like to thank the participating patients and physicians who made the study possible. The work was supported by Alnylam Pharmaceuticals, Inc. No conflicts of interests to declare.
93 O.6. INTERN MEDICIN
O-6.05 Cecilie Mæng Changes in intensive care unit admission rates, organ support, and mortality in patients with acute myeloid leukemia over a 12-year period CV Mæng1, 3 LSG Østgård1 CF Christiansen2 K Dori Liu3 1Afdeling for blodsygdomme, Aarhus Universitetshospital 2Klinisk Epidemiologisk Afdeling, Aarhus Universitetshospital 3Department of Nephrology, University of California San Francisco (UCSF)
Background: The mortality in non-promyelocytic acute myeloid leukemia (AML) has decreased as a result of improved supportive care, allowing for more aggressive curative treatment, including increased use of stem cell transplantation. We evaluated trends in ICU admission rates, use of organ support, 1-year mortality overall, and after ICU admission in all Danish AML patients from 2005 to 2016.
Methods: The study included all adult Danish AML patients registered in the Danish Acute Leukemia Registry diagnosed between 2005 and 2016. ICU admission details was obtained from the Danish Intensive Care Database. We examined the rate of ICU admitted AML patients. We examined the proportion receiving organ supportive treatment in the ICU. The trends were examined using linear regression analysis and presented as predicted yearly percent point difference (pp/year) with 95% CI.
Results: ICU admission rate did not change over time, nor did available SAPSII score. Use of mechanical ventilation (MV) dropped (pp/year = -2.0 [95% CI: -3.5 – -0.5]), with a parallel increase in use of non-invasive ventilation (NIV) (pp/year = 2.6 [95% CI: 1.1 – 4.0]). Use of dialysis decreased (pp/year = -1.7 [95% CI: -3.0 – -0.4]). The overall 1-year mortality decreased (pp/year = -1.0 [95% CI: -1.7 – -0.25]). In the ICU admitted cohort, the mortality decreased (pp/year = -1.4 [95% CI: -2.8 – -0.07]).
Conclusion: Over a 12-year period, the ICU treatment pattern changed. Concurrently, the mortality for AML patients declined overall and in the subset of patients admitted to an ICU. Importantly, the decreasing mortality after ICU admission could not be explained by a change in ICU admission rate or SAPS score.
Acknowledgements: We wish to thank all the individuals who carefully report the relevant clinical data to the Danish National Acute Leukemia Registry and the Danish Intensive Care Datebase. The study was supported by the Danish-American Research Exchange (DARE) Program funded by the Lundbeck Foundation. Additionally, the study was funded by Tømrermester Jørgen Holm & Hustru Elisa F. Hansens Mindelegat, Slagtermester Max Wørzner & Hustru Inger Wørzners Mindelegat, and Raimond & Dagmar Ringgård-Bohns Fond.
94 O.6. INTERN MEDICIN
O-6.06 Daniella Acute intensive blood pressure control in acute Rahim ischemic stroke patients treated with thrombolysis: A retrospective quality control study D Rahim1 B Modrau2 1D Rahim, BSc. Med., Aalborg University Hospital. 2B Modrau Dep of Neurology, Aalborg University Hospital
Background: Acute ischemic stroke (AIS) is treated with thrombolysis with intravenous recombinant tissue plasminogen activator and/or endovascular treatment of large vessel occlusions. High blood pressure (BP) >185/110 is a contraindication for thrombolysis, whereas acute BP lowering is applied. Aim of this study was to assess the frequency and sufficiency of acute BP lowering during the first 24 hours after thrombolysis, and the risk of intracranial hemorrhage (ICH), poor functional outcome and mortality.
Methods: BP-course, Labetalol administration, Clinical and imaging data were collected for patients with magnetic resonance image verified AIS treated with thrombolysis at Aalborg University Hospital in 2016–2018. Exclusion criteria were missing baseline characteristics, BP course, medical record data or missing imaging at 24-hours follow-up. ICH within 24-hours follow-up was defined as primary endpoint and functional outcome at 24-hours and at 3 months follow-up was defined as secondary endpoint
Results: Out of the 471 patients included, high BP was present in 205 (43%) patients and 141 (69%) of these received Labetalol. Patients receiving Labetalol had increased risk (P < 0.05) of ICH (OR = 2.69 [95% CI 1.34–5.4]), death at 3 months (OR 2.69 [95% CI 1.34–5.4]) death related to thrombolysis (OR = 9.6 [95% CI 1.06–86]) compared to patients without increased BP not receiving Labetalol. Patients treated with Labetalol tend to have worse functional outcome at three months (OR = 0.18 [95% CI -0.2–0.5]).
Conclusion: Acute intensive BP control in AIS patients treated with thrombolysis was associated with increased risk of ICH, death at 3 months and death caused by thrombolysis, compared to patients without increased BP and without acute BP lowering.
Acknowledgements: This study is not funded.
95 O.6. INTERN MEDICIN
O-6.07 Line Elise People with diabetes have decreased pain Møller Hansen perception in the tibial bone LEM Hansen1 CA Fjelsted1 AM Drewes2, 3 SS Olesen2, 3 AL Wegeberg2, 3 C Brock2, 3 1Aalborg University, Department of Health Science and Technology 2Mech-Sense, Aalborg Universityhospital 3Clinical Institute, Aalborg University Hospital
Background: Diabetes is a prevalent disease and the incidence is expected to rise in the future. There is two major types, Type 1 and Type 2, which differs through pathogenesis. Neuropathy is the most common cause of long-term diabetes, with the most prevalent type affecting the peripheral nerves. The pain perception of the peripheral nervous system can be evaluated with quantitative sensory testing. Thus, the aim was to investigate if people with diabetes had hypoalgesia compared to healthy controls.
Methods: Pain perception was investigated in 56 people with type 1 diabetes, 64 people with type 2 diabetes and 122 healthy controls using pressure algometry to perform muscle- and bone pressure stimulation. Pressure pain detection and pressure pain threshold was measured at dermatomes of TH10 ventral and dorsum, C5 by midline of clavicle, L1 at spina iliaca anterior superior, and L4 at rectus femoralis and the middle of the tibia bone.
Results: Pressure pain detection was significant decreased at the tibial bone (L4) in people with Type 1 and Type 2 diabetes compared to healthy (P 0.05). ≤ Conclusion: The results show hypoalgesia at the tibial bone, which indicates a decreased in the pain perception in people with diabetes compared to healthy controls.
Acknowledgements: The study is financial supported from Knowledge for the World Talent Program, Aalborg University.
96 O.6. INTERN MEDICIN
O-6.08 Camilla Ann Decreased Inhibitory Pathway Effect of the Pain Fjelsted System in People with Type 1 Diabetes CA Fjelsted1 LEM Hansen1 AM Drewes2, 3 SS Olesen2, 3 AL Wegeberg2, 3 C Brock2, 3 1Department of Health Science and Technology, Aalborg University 2Mech-Sense, Aalborg University Hospital 3Clinical Institute, Aalborg University Hospital
Background: The incidence of diabetes is expected to increase notably in the coming years. A serious complication to this disease is neuropathy, which can lead to pain. However, it is still unknown whether the central nervous system, regarding pain perception, is affected. The aim in this study was to explore if people with type 1 or type 2 diabetes had a higher pain sensitivity compared to healthy controls.
Methods: 56 participants with type 1, 64 participants with type 2 diabetes and 122 healthy controls were included in the study. Maximum pain tolerance was investigated by immersing the dominant hand into 2◦C cold water for as long as tolerable but for maximum 120 seconds. Immediately before and after the cold pressure test (CPT) pressure pain threshold (PPT) was obtained on the participants thigh. Pain was rated on a numeric rating scale every 10 seconds during the CPT.
Results: People with type 1 diabetes reached their maximum pain tolerance both before (P = 0.02) and after CPT (P < 0.01) compared to healthy controls. No significant difference was found for people with type 2 diabetes. People with type 1 (P < 0.000) and type 2 (P = 0.005) diabetes had a higher pain rating compared to the healthy controls during the CPT.
Conclusion: This study found that people with type 1 diabetes had a lower pain threshold and higher pain score. This could indicate a central sensitization of the pain pathways in the central nervous system, where the inhibitory pain processing is affected.
Acknowledgements: This study has received financial support from Knowledge for the World Talent Programme, Aalborg University.
97 O.6. INTERN MEDICIN
O-6.09 Marie Øbo Nonspecific Lung Nodules in Colorectal Cancer – Diagnostic Value of Circulating Tumor DNA M Øbo1 LMS Petersen2 IH Jakobsen1 FV Mortensen1 CL Andersen2 AR Knudsen1 1Department of Gastroenterological Surgery, Aarhus University Hospital 2Department of Molecular Medicine, Aarhus University Hospital
Background: Most patients with colorectal cancer (CRC) present with local disease, but despite treatment up to 50% experience relapse. During CT follow-up, non-specific lung nodules are common and present a major clinical challenge, since the nodules are too small for biopsy. However, inn patients with CRC, circulating tumor-DNA (ctDNA) can be found in blood. The aim of this study was to investigate whether ctDNA could be used to distinguish between CRC patients with benign and malignant lung nodules.
Methods: Curatively intended liver surgery was performed at the Department of Surgery, Aarhus University Hospital. Patient specific mutation analysis was performed on fresh frozen tumor samples. The mutation was used as target for liquid biopsy analysis in sequential blood samples in a 3-year follow-up period. Patient records were reviewed and compared with ctDNA levels. Measures of sensitivity, specificity, positive and negative predictive value were calculated using Wilson-Brown’s test.
Results: 19 patients were included. Multiple entries were allowed given no residual disease between relapses. Of 3 entries with positive ctDNA samples, all had clinical relapse (PPV = 100% [95% CI: 0.44–1]). Of 20 entries with negative ctDNA samples, 13 had clinical relapse (NPV = 35% [95% CI: 0.18–0.57]). Statistical analyses showed the ctDNA test to have a specificity and a positive predictive value of 100%. Sensitivity and negative predictive value were unsatisfactorily low at 19% and 35%, respectively.
Conclusion: In managing metastatic CRC, ctDNA cannot yet be used to discriminate between benign and malignant lung nodules due to low NPV and sensitivity. Results are limited by a small cohort and more studies are needed to investigate the potential of ctDNA which may still hold promise as a specific biomarker.
Acknowledgements: Novo Nordisk Fonden, Kræftens Bekæmpelse, Danmarks Frie Forskningsfond, The Danish Council for Strategic Research
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