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  • 1.
    Adams, A.
    et al.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Kalla, R.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Vatn, S.
    Institute of Clinical Medicine, EpiGen, University of Oslo, Oslo, Norway.
    Bonfiglio, F.
    BioCruces Health Research Institue, Bilbao, Spain.
    Nimmo, E.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Kennedy, N.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Ventham, N.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Vatn, M.
    Institute of Clinical Medicine, EpiGen, University of Oslo, Oslo, Norway.
    Ricanek, P.
    Department of Gastroenterology, Akershus University, Akershus, Norway.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Söderholm, J.
    Department of Surgery, Linköping University Hospital, Linköping, Sweden;.
    Pierik, M.
    Department of Gastroenterology and Hepatology, Maastricht University Medical Center (MUMC), Maastricht, Netherlands.
    Törkvist, L.
    Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.
    Gomollon, F.
    University Hospital Clinic Lozano Blesa, Zaragoza, Spain.
    Gut, I.
    CNAG-CRG Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.
    Jahnsen, J.
    Institute of Clinical Medicine, EpiGen, University of Oslo, Oslo, Norway.
    Satsangi, J.
    Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Epigenetic alterations at diagnosis predict susceptibility, prognosis and treatment escalation in inflammatory bowel disease - IBD Character2017In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no Suppl. 1, p. S108-S108Article in journal (Refereed)
  • 2. Almer, Sven
    et al.
    Befrits, Ragnar
    Eriksson, Anders S
    Halfvarson, Jonas
    Hindorf, Ulf
    Löfberg, Robert
    Modern läkemedelsterapi vid Crohn  [Current drug therapy in Crohn disease]: nationella riktlinjer [national guidelines]2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 45, p. 2988-2993Article in journal (Refereed)
  • 3. Amcoff, K.
    et al.
    Joossens, M.
    Pierik, M. J.
    Jonkers, D.
    Bohr, J.
    Joossens, S
    Romberg-Camp, M.
    Nyhlin, Nils
    Wickbom, A.
    Rutgeerts, P. J.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bodin, L.
    Colombel, J. F.
    Vermeire, S.
    Halfvarson, Jonas
    Arvets inverkan på serologiska markörer hos tvillingar med IBD2012In: Gastrokuriren, ISSN 1651-0453, Vol. 17, no 26, p. MP-06-MP-06Article in journal (Other academic)
  • 4.
    Amcoff, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Bergenmalm, Daniel
    University Hospital Maastricht, Maastricht, The Netherlands.
    Pierik, Marie J.
    University Hospital Maastricht, Maastricht, The Netherlands.
    Colombel, Jean-Frederic
    University Hospital Gasthuisberg, Leuven, Belgium.
    Vermeire, Severine
    Karolinska Institute, Stockholm, Sweden.
    Bodin, Lennart
    Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Environmental and genetic factors in the development of perinuclear-antineutrophil cytoplasmic antibody (pANCA) positive ulcerative colitis: a European twin studyManuscript (preprint) (Other academic)
  • 5.
    Amcoff, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Zhulina, Yaroslava
    Örebro University Hospital. Örebro University, School of Medical Sciences.
    Lampinen, M.
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Carlson, M.
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Prognostic significance of eosinophil granule proteins in inflammatory bowel disease2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S181-S182Article in journal (Other academic)
  • 6.
    Amcoff, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Cao, Yang
    Örebro University, School of Medical Sciences. Karolinska Institutet, Stockholm, Sweden.
    Zhulina, Yaroslava
    Örebro University, School of Medical Sciences.
    Lampinen, Maria
    Uppsala University, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Carlson, Marie
    Uppsala University, Uppsala, Sweden.
    Prognostic significance of eosinophile granule proteins in inflammatory bowel diseaseManuscript (preprint) (Other academic)
  • 7.
    Amcoff, Karin
    et al.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Zhulina, Yaroslava
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Lampinen, Maria
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Carlson, Marie
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Prognostic significance of faecal eosinophil granule proteins in inflammatory bowel disease2019In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 10, p. 1237-1244Article in journal (Refereed)
    Abstract [en]

    Background: Non-invasive markers for predicting relapse would be a useful tool for the management of patients with inflammatory bowel disease. Eosinophil granulocytes and their granule proteins eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) have previously been shown to reflect disease activity in Crohn's disease and ulcerative colitis.

    Aim: To examine the capacity of faecal ECP and EDN to predict relapse in ulcerative colitis and Crohn's disease, and to compare these proteins with faecal calprotectin.

    Methods: Patients with Crohn's disease (n=49) and ulcerative colitis (n=55) were followed prospectively until relapse or end of the two-year study period. Faecal samples were obtained every third month. The predictive value of ECP and EDN was assessed in Cox regression models.

    Results: In ulcerative colitis, a doubled EDN or ECP concentration was associated with a 31% and 27% increased risk of relapse, respectively. EDN levels were increased both at relapse and three months prior. By contrast, in Crohn's disease, the concentration of EDN was higher among patients in remission than in those who relapsed. Correlations between faecal calprotectin, ECP and EDN were observed in both diseases.

    Conclusions: We demonstrate that the risk of relapse in ulcerative colitis can be predicted by consecutively measuring faecal EDN every third month, and suggest EDN as a complementary faecal marker to calprotectin to predict future relapse in ulcerative colitis. Our finding of higher EDN in Crohn's disease-patients staying in remission than in those who relapsed indicates different functions of the protein in ulcerative colitis and Crohn's disease.

  • 8. Amcoff, Karin
    et al.
    Joossens, Marie
    Pierik, Marie J.
    Jonkers, Daisy
    Bohr, Johan
    Joossens, Sofie
    Romberg-Camps, Marielle
    Nyhlin, Nils
    Wickbom, Anna K.
    Rutgeerts, Paul J.
    Tysk, Curt
    Bodin, Lennart
    Colombel, Jean-Frederic
    Vermeire, Severine
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden.
    Influence of genetics in the expression of serological markers in twins with IBD2012In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 142, no 5, p. S881-S881Article in journal (Other academic)
  • 9.
    Amcoff, Karin
    et al.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Joossens, Marie
    Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit, Leuven,Belgium; VIB Center for the Biology of Disease, Leuven, Belgium; Microbiology Unit, Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit, Brussels, Belgium.
    Pierik, Marie J.
    Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
    Jonkers, Daisy
    Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
    Bohr, Johan
    Örebro University, School of Health Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Joossens, Sofie
    Gastroenterology, Catholic University of Leuven (KUL), Leuven, Belgium.
    Romberg-Camps, Mariëlle
    Department of Gastroenterology-Hepatology, Zuyderland Medical Center, Sittard, Netherlands.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Rutgeerts, Paul J.
    Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
    Tysk, Curt
    Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bodin, Lennart
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institute, Stockholm, Sweden.
    Colombel, Jean-Frederic
    Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY, USA.
    Vermeire, Severine
    Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 6, p. 695-702Article in journal (Refereed)
    Abstract [en]

    Background and Aims: An adaptive immunological response to microbial antigens has been observed in Crohn's disease (CD). Intriguingly, this serological response precedes the diagnosis in some patients and has also been observed in healthy relatives. We aimed to determine whether genetic factors are implicated in this response in a CD twin cohort.

    Methods: In total, 82 twin pairs (Leuven n = 13, Maastricht n = 8, Örebro n = 61) took part: 81 pairs with CD (concordant monozygotic n = 16, discordant monozygotic n = 22, concordant dizygotic n = 3, discordant dizygotic n = 40) and 1 monozygotic pair with both CD and ulcerative colitis. Serology for Pseudomonas fluorescens-related protein (anti-I2), Escherichia coli outer membrane porin C (anti-OmpC), CBir1flagellin (anti-CBir1) and antibodies to oligomannan (anti-Saccharomyces cerevisiae antibody [ASCA]) was determined by standardized enzyme-linked immunoassay.

    Results: All markers were more often present in CD twins than in their healthy twin siblings. Using the intraclass correlation coefficient (ICC), agreements in concentrations of anti-OmpC and anti-I2 were observed in discordant monozygotic but not in discordant dizygotic twin pairs with CD (anti-OmpC, ICC 0.80 and -0.02, respectively) and (anti-I2, ICC 0.56 and 0.05, respectively). In contrast, no agreements were found in anti-CBir, immunoglobulin (Ig) G ASCA and ASCA IgA.

    Conclusions: We show that anti-I2 and anti-CBir1 statuses have specificity for CD and confirm previous reported specificities for anti-OmpC and ASCA. Based on quantitative analyses and observed ICCs, genetics seems to predispose to the anti-OmpC and anti-I2 response but less to ASCA and anti-CBir1 responses.

  • 10.
    Amcoff, Karin
    et al.
    Department of Gastroenterology, Örebro University Hospital, Örebro, sweden.
    Stridsberg, Mats
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Lampinen, Maria
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Magnuson, Anders
    linical EpiSchool of Medical Sciences, Örebro University, Örebro, Sweden.
    Carlson, Marie
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 344-350Article in journal (Refereed)
    Abstract [en]

    Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.

    Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Bühlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).

    Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Bühlmann 845 (1061-226) μg/g versus 62 (224-39) μg/g, Phadia 369 (975-122) μg/g versus 11 (52-11) μg/g, and Immundiagnostik 135 (302-69) μg/g versus 8 (56-4) μg/g. The Bühlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Bühlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50 μg/g was used, whereas the differences in sensitivity were less pronounced.

    Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.

  • 11.
    Andersen, Vibeke
    et al.
    Medical Department, Sygehus Sønderjylland Aabenraa, Aabenraa, Denmark; Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Örebro University Hospital, Örebro University, Örebro, Sweden.
    Vogel, Ulla
    National Research Centre for the Working Environment, Copenhagen, Denmark.
    Colorectal cancer in patients with inflammatory bowel disease: can we predict risk?2012In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 18, no 31, p. 4091-4094Article in journal (Refereed)
    Abstract [en]

    The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), may be complicated by colorectal cancer (CRC). In a recent population-based cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC during 30 years of observation. The overall risk of CRC among patients with UC and CD was comparable with that of the general population. However, patients diagnosed with UC during childhood or as adolescents, patients with long duration of disease and those with concomitant primary sclerosing cholangitis were at increased risk. In this commentary, we discuss the mechanisms underlying carcinogenesis in IBD and current investigations of genetic susceptibility in IBD patients. Further advances will depend on the cooperative work by epidemiologist and molecular geneticists in order to identify genetic polymorphisms involved in IBD-associated CRC. The ultimate goal is to incorporate genotypes and clinical parameters into a predictive model that will refine the prediction of risk for CRC in colonic IBD. The challenge will be to translate these new findings into clinical practice and to determine appropriate preventive strategies in order to avoid CRC in IBD patients. The achieved knowledge may also be relevant for other inflammation-associated cancers.

  • 12.
    Anderson, Carl A.
    et al.
    Wellcome Trust Genome Campus Hinxton, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences.
    Rioux, John D.
    Inflammatory Bowel Diseases, Queensland Institute of Medical Research, Brisbane, Australia.
    Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 472011In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 43, no 3, p. 246-252Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

  • 13.
    Andersson, Erik
    et al.
    Örebro University, School of Medical Sciences.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    D'Amato, M.
    Department of Medicine, Karolinska Institutet Solna, Stockholm, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Inflammatory biomarkers in serum discriminate Crohn's disease and ulcerative colitis from healthy controls2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no Suppl. 1, p. S86-S87Article in journal (Other academic)
  • 14.
    Andersson, Erik
    et al.
    Örebro University, School of Medical Sciences.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    Neumann, Gunter
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    D'Amato, Mauro
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; BioDonostia Health Research Institute, San Sebastian, Spain; IKERBASQUE Basque Foundation for Science, Bilbao, Spain.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Subphenotypes of inflammatory bowel disease are characterized by specific serum protein profiles2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 10, article id e0186142Article in journal (Refereed)
    Abstract [en]

    Objective: Genetic and immunological data indicate that inflammatory bowel disease (IBD) are characterized by specific inflammatory protein profiles. However, the serum proteome of IBD is still to be defined. We aimed to characterize the inflammatory serum protein profiles of Crohn's disease (CD) and ulcerative colitis (UC), using the novel proximity extension assay.

    Methods: A panel of 91 inflammatory proteins were quantified in a discovery cohort of CD (n = 54), UC patients (n = 54), and healthy controls (HCs; n = 54). We performed univariate analyses by t-test, with false discovery rate correction. A sparse partial least-squares (sPLS) approach was used to identify additional discriminative proteins. The results were validated in a replication cohort.

    Results: By univariate analysis, 17 proteins were identified with significantly different abundances in CD and HCs, and 12 when comparing UC and HCs. Additionally, 64 and 45 discriminant candidate proteins, respectively, were identified with the multivariate approach. Correspondingly, significant cross-validation error rates of 0.12 and 0.19 were observed in the discovery cohort. Only FGF-19 was identified from univariate comparisons of CD and UC, but 37 additional discriminant candidates were identified using the multivariate approach. The observed cross-validation error rate for CD vs. UC remained significant when restricting the analyses to patients in clinical remission. Using univariate comparisons, 16 of 17 CD-associated proteins and 8 of 12 UC-associated proteins were validated in the replication cohort. The area under the curve for CD and UC was 0.96 and 0.92, respectively, when the sPLS model from the discovery cohort was applied to the replication cohort.

    Conclusions: By using the novel PEA method and a panel of inflammatory proteins, we identified proteins with significantly different quantities in CD patients and UC patients compared to HCs. Our data highlight the potential of the serum IBD proteome as a source for identification of future diagnostic biomarkers.

  • 15. Anedda, Francesca
    et al.
    Zucchelli, Marco
    Schepis, Danika
    Hellquist, Anna
    Corrado, Lucia
    D'Alfonso, Sandra
    Achour, Adnane
    McInerney, Gerald
    Bertorello, Alejandro
    Lordal, Mikael
    Befrits, Ragnar
    Bjork, Jan
    Bresso, Francesca
    Torkvist, Leif
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences.
    Kere, Juha
    D'Amato, Mauro
    Multiple polymorphisms affect expression and function of the neuropeptide S receptor (NPSR1)2011In: PLOS ONE, E-ISSN 1932-6203, Vol. 6, no 12, p. e29523-Article in journal (Refereed)
    Abstract [en]

    Background: neuropeptide S (NPS) and its receptor NPSR1 act along the hypothalamic-pituitary-adrenal axis to modulate anxiety, fear responses, nociception and inflammation. The importance of the NPS-NPSR1 signaling pathway is highlighted by the observation that, in humans, NPSR1 polymorphism associates with asthma, inflammatory bowel disease, rheumatoid arthritis, panic disorders, and intermediate phenotypes of functional gastrointestinal disorders. Because of the genetic complexity at the NPSR1 locus, however, true causative variations remain to be identified, together with their specific effects on receptor expression or function. To gain insight into the mechanisms leading to NPSR1 disease-predisposing effects, we performed a thorough functional characterization of all NPSR1 promoter and coding SNPs commonly occurring in Caucasians (minor allele frequency >0.02). Principal Findings: we identified one promoter SNP (rs2530547 [-103]) that significantly affects luciferase expression in gene reporter assays and NPSR1 mRNA levels in human leukocytes. We also detected quantitative differences in NPS-induced genome-wide transcriptional profiles and CRE-dependent luciferase activities associated with three NPSR1 non-synonymous SNPs (rs324981 [Ile107Asn], rs34705969 [Cys197Phe], rs727162 [Arg241Ser]), with a coding variant exhibiting a loss-of-function phenotype (197Phe). Potential mechanistic explanations were sought with molecular modelling and bioinformatics, and a pilot study of 2230 IBD cases and controls provided initial support to the hypothesis that different cis-combinations of these functional SNPs variably affect disease risk. Significance: these findings represent a first step to decipher NPSR1 locus complexity and its impact on several human conditions NPS antagonists have been recently described, and our results are of potential pharmacogenetic relevance.

  • 16.
    Angelison, L.
    et al.
    Helsingborg, Sweden.
    Almer, S.
    Stockholm, Sweden.
    Eriksson, A.
    Gothenburg, Sweden.
    Karling, P.
    Umeå, Sweden.
    Fagerberg, U.
    Västeras, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Thörn, M.
    Uppsala, Sweden.
    Björk, J.
    Stockholm, Sweden.
    Hindorf, U.
    Lund, Sweden.
    Löfberg, R.
    Stockholm, Sweden.
    Bajor, A.
    Gothenburg, Sweden.
    Hjortswang, H.
    Linköping, Sweden.
    Hammarlund, P.
    Ängelholm, Sweden.
    Grip, O.
    Malmö, Sweden.
    Torp, J.
    Kristianstad, Sweden.
    Marsal, J.
    Lund, Sweden.
    Hertervig, E.
    Lund, Sweden.
    Long-term outcome of infliximab treatment in chronic active ulcerative colitis: a Swedish multicentre study of 250 patients2017In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 45, no 4, p. 519-532Article in journal (Refereed)
    Abstract [en]

    Background: Real-life long-term data on infliximab treatment in ulcerative colitis are limited.

    Aim: To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined.

    Methods: A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant.

    Results: Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy.

    Conclusions: Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.

  • 17.
    Assadi, G.
    et al.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Saleh, R.
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Hadizadeh, F.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Vesterlund, L.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Bonfiglio, F.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Törkvist, L.
    Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden.
    Eriksson, A. S.
    Gatroenterology Unit, Department of Internal Medicine, Sahlgren's University Hospital/Östra, Göteborg, Sweden.
    Harris, H. E.
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Sundberg, E.
    Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    D'Amato, M.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
    LACC1 polymorphisms in inflammatory bowel disease and juvenile idiopathic arthritis2016In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 17, no 4, p. 261-264Article in journal (Refereed)
    Abstract [en]

    The function of the Laccase domain-containing 1 (LACC1) gene is unknown, but genetic variation at this locus has been reported to consistently affect the risk of Crohn's disease (CD) and leprosy. Recently, a LACC1 missense mutation was found in patients suffering from monogenic forms of CD, but also systemic juvenile idiopathic arthritis. We tested the hypothesis that LACC1 single nucleotide polymorphisms (SNPs), in addition to CD, are associated with juvenile idiopathic arthritis (JIA, non-systemic), and another major form of inflammatory bowel disease, ulcerative colitis (UC). We selected 11 LACC1 tagging SNPs, and tested their effect on disease risk in 3855 Swedish individuals from three case-control cohorts of CD, UC and JIA. We detected false discovery rate corrected significant associations with individual markers in all three cohorts, thereby expanding previous results for CD also to UC and JIA. LACC1's link to several inflammatory diseases suggests a key role in the human immune system and justifies further characterization of its function(s).

  • 18.
    Assadi, Ghazaleh
    et al.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden .
    Vesterlund, Liselotte
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Mazzurana, Luca
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Cordeddu, Lina
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Schepis, Danika
    Rheumatology unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden .
    Mjösberg, Jenny
    Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden .
    Ruhrmann, Sabrina
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Fabbri, Alessia
    Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy .
    Vukojevic, Vladana
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden .
    Percipalle, Piergiorgio
    Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
    Salomons, Florian A.
    Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
    Laurencikiene, Jurga
    Lipid laboratory, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Törkvist, Leif
    Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden .
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    D'Amato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioDonostia Health Research Institute, San Sebastian and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain .
    Functional Analyses of the Crohn's Disease Risk Gene LACC12016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 12, article id e0168276Article in journal (Refereed)
    Abstract [en]

    Background: Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression.

    Methods: We implemented Western blot, quantitative real-time PCR, immunofluorescence microscopy, and flow cytometry analyses to investigate fatty acid metabolism-immune nexus (FAMIN; the LACC1 encoded protein) expression in subcellular compartments, cell lines and relevant human tissues. Gene-set enrichment analyses were performed to initially investigate modulatory mechanisms of LACC1 expression. A small-interference RNA knockdown in vitro model system was used to study the effect of FAMIN depletion on peroxisome function.

    Results: FAMIN expression was detected in macrophage-differentiated THP-1 cells and several human tissues, being highest in neutrophils, monocytes/macrophages, myeloid and plasmacytoid dendritic cells among peripheral blood cells. Subcellular co-localization was exclusively confined to peroxisomes, with some additional positivity for organelle endomembrane structures. LACC1 co-expression signatures were enriched for genes involved in peroxisome proliferator-activated receptors (PPAR) signaling pathways, and PPAR ligands downregulated FAMIN expression in in vitro model systems.

    Conclusion: FAMIN is a peroxisome-associated protein with primary role(s) in macrophages and other immune cells, where its metabolic functions may be modulated by PPAR signaling events. However, the precise molecular mechanisms through which FAMIN exerts its biological effects in immune cells remain to be elucidated.

  • 19.
    Axelrad, J.
    et al.
    Department of Gastroenterology, New York University School of Medicine, New York, NY, USA.
    Olén, O.
    Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Sachs, M.
    Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Erichsen, R.
    Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
    Pedersen, L.
    Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Askling, J.
    Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Ekbom, A.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Sørensen, H. T.
    Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics.
    Inflammatory bowel disease and risk of small bowel cancer: A binational population-based cohort study from Denmark and Sweden2020In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 14, no Suppl. 1, p. S007-S009Article in journal (Other academic)
  • 20.
    Axelrad, Jordan E.
    et al.
    Inflammatory Bowel Disease Center at NYU Langone Health, Division of Gastroenterology, Department of Medicine, New York University School of Medicine, New York, New York, USA .
    Olén, Ola
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Sachs, Michael C.
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Erichsen, Rune
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; Department of Surgery, Randers Regional Hospital, Randers, Denmark.
    Pedersen, Lars
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Askling, Johan
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Ekbom, Anders
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Sørensen, Henrik Toft
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Orebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, United States.
    Inflammatory bowel disease and risk of small bowel cancer: a binational population-based cohort study from Denmark and Sweden2021In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 70, no 2, p. 297-308Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD).

    DESIGN: In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs).

    RESULTS: We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32).

    CONCLUSION: SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.

  • 21.
    Axelrad, Jordan E.
    et al.
    Inflammatory Bowel Disease Center at NYU Langone Health, Division of Gastroenterology, Department of Medicine, New York University School of Medicine, New York, New York, USA.
    Olén, Ola
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Sachs, Michael C.
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Erichsen, Rune
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; Department of Surgery, Randers Regional Hospital, Randers, Denmark.
    Pedersen, Lars
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Askling, Johan
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Ekbom, Anders
    Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Sørensen, Henrik Toft
    Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, United States.
    Reply: Survival in Crohn's disease-associated small bowel adenocarcinoma2021In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 70, no 5, p. 998-998Article in journal (Refereed)
  • 22.
    Axelrad, Jordan
    et al.
    Inflammatory Bowel Disease Center at NYU Langone Health, Division of Gastroenterology, Department of Medicine, NYU School of Medicine, New York, New York, USA.
    Olén, Ola
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Söderling, Jonas
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Roelstraete, Bjorn
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Khalili, Hamed
    Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
    Song, Mingyang
    Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
    Faye, Adam
    Inflammatory Bowel Disease Center at NYU Langone Health, Division of Gastroenterology, Department of Medicine, NYU School of Medicine, New York, New York, USA.
    Eberhardson, Michael
    Department of Gastroenterology and Hepatology, Linköping University Hospital, Linköping University, Linköping, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
    Inflammatory Bowel Disease and Risk of Colorectal Polyps: A nationwide population-based cohort study from Sweden2023In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no 9, p. 1395-1409Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Inflammatory bowel disease (IBD) has been linked to an increased risk of colorectal neoplasia. However, the types and risks of specific polyp types in IBD are less clear.

    METHODS: We identified 41,880 individuals with IBD [Crohn's disease (CD: n=12,850); Ulcerative colitis (UC): n=29,030)] from Sweden matched with 41,880 reference individuals. Using Cox regression, we calculated adjusted hazard ratios (aHRs) for neoplastic colorectal polyps (Tubular, Serrated/Sessile, Advanced and Villous) defined by histopathology codes.

    RESULTS: During follow-up, 1648 (3.9%) IBD patients and 1143 (2.7%) reference individuals had an incident neoplastic colorectal polyp, corresponding to an incidence rate of 46.1 and 34.2 per 10,000 person-years, respectively. This correlated to an aHR of 1.23 (95% CI 1.12-1.35) with the highest HRs seen for sessile serrated polyps (8.50, 95% CI 1.10-65.90) and traditional serrated adenomas (1.72, 95% CI 1.02-2.91). aHRs for colorectal polyps were particularly elevated in those diagnosed with IBD at a young age and after 10 years after diagnosis. Both absolute and relative risks of colorectal polyps were higher in UC than in CD (aHRs 1.31 vs. 1.06, respectively), with a 20-year cumulative risk differences of 4.4% in UC and 1.5% in CD, corresponding to one extra polyp in 23 patients with UC and one in 67 CD patients during the first 20 years after IBD diagnosis.

    CONCLUSIONS: In this nationwide population-based study, there was an increased risk of neoplastic colorectal polyps in IBD patients. Colonoscopic surveillance in IBD appears important, especially in UC and after 10 years of disease.

  • 23.
    Bazov, Igor
    et al.
    Örebro University, School of Medical Sciences.
    Kruse, Robert
    Örebro University, School of Medical Sciences.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Hedin, C. R.
    Karolinska Institutet, Department of Medicine, Solna, Stockholm, Sweden; Karolinska University Hospital, Gastroenterology unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden.
    Carlson, M.
    Uppsala University, Department of Medical Sciences, Uppsala, Sweden.
    van Nieuwenhoven, Michiel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Keita, Å. V.
    Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden.
    Magnusson, M. K.
    University of Gothenburg, Sahlgrenska Academy, Department of Microbiology and Immunology, Institute of Biomedicine, Gothenburg, Sweden.
    Almer, S.
    Karolinska Institutet, Department of Medicine, Solna, Stockholm, Sweden; Karolinska university hospital, Gastroenterology unit, Department of Gastroenterology, Dermatovenereology and Rheumatology, Stockholm, Sweden.
    Strid, H.
    Södra Älvsborgs Hospital, Department of Internal Medicine, Borås, Sweden.
    Mathisen, C. Bache-Wiig
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
    Bengtsson, M. B.
    Vestfold Hospital Trust, Department of Gastroenterology, Tønsberg, Norway.
    Aabrekk, T. Bergene
    University of Oslo, Institute of Clinical Medicine, Oslo, Norway; Vestfold Hospital Trust, Department of Gastroenterology, Tønsberg, Norway.
    Medhus, A. W.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
    Detlie, T. E.
    Akershus University Hospital, Department of Gastroenterology, Lørenskog, Norway; University of Oslo, Insititute of Clinical Medicine, Oslo, Norway.
    Frigstad, S. O.
    Vestre Viken Hospital Trust- Bærum Hospital, Department of Internal Medicine, Bærum, Norway.
    Huppertz-Hauss, G.
    Telemark Hospital Trust, Skien, Department of Gastroenterology, Skien, Norway.
    Opheim, R.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Health and Society, Oslo, Norway.
    Ricanek, P.
    Akershus University Hospital, Department of Gastroenterology, Lørenskog, Norway; Lovisenberg Diaconal Hospital, Department of Gastroenterology, Oslo, Norway.
    Kristensen, V. A.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; Lovisenberg Diaconal Hospital, Unger-Vetlesen Institute, Oslo, Norway .
    Salihovic, Samira
    Örebro University, School of Medical Sciences.
    D'Amato, M.
    Karolinska Institutet, Clinical Epidemiology Division, Department of Medicine Solna, Stockholm, Sweden; IKERBASQUE, Basque Foundation for Science, Bilbao, Gastrointestinal Genetics Lab, CIC bioGUNE - BRTA, Bilbao, Spain.
    Öhman, L.
    University of Gothenburg, Sahlgrenska Academy, Department of Microbiology and Immunology, Institute of Biomedicine, Gothenburg, Sweden.
    Söderholm, J. D.
    Linköping University, Department of Biomedical and Clinical Sciences, Linköping, Sweden.
    Lindqvist, C. M.
    Örebro University, School of Medical Sciences, Faculty of Medicine and Health, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Høivik, M. L.
    Oslo University Hospital, Department of Gastroenterology, Oslo, Norway; University of Oslo, Institute of Clinical Medicine, Oslo, Norway.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    A novel serum protein signature as biomarker for Inflammatory Bowel Disease: A diagnostic performance and prediction modelling study using data from two independent inception cohorts2023In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 17, no Suppl. 1, p. I314-I315, article id P154Article in journal (Other academic)
  • 24.
    Beaudoin, Melissa
    et al.
    Research Center, Montreal Heart Institute, Montreal QC, Canada.
    Goyette, Philippe
    Research Center, Montreal Heart Institute, Montreal QC, Canada.
    Boucher, Gabrielle
    Research Center, Montreal Heart Institute, Montreal QC, Canada.
    Lo, Ken Sin
    Research Center, Montreal Heart Institute, Montreal QC, Canada.
    Rivas, Manuel A.
    Center for the Study of IBD (CSIBD) Genetics, The Broad Institute, Cambridge MA, United States.
    Stevens, Christine
    Center for the Study of IBD (CSIBD) Genetics, The Broad Institute, Cambridge MA, United States.
    Alikashani, Azadeh
    Research Center, Montreal Heart Institute, Montreal QC, Canada.
    Ladouceur, Martin
    Research Center, Montreal Heart Institute, Montreal QC, Canada.
    Ellinghaus, David
    Christian-Albrechts-University, Kiel, Germany.
    Törkvist, Leif
    Karolinska Institutet, Stockholm, Sweden.
    Goel, Gautam
    Harvard School of Medicine, Boston MA, USA.
    Lagace, Caroline
    Research Center, Montreal Heart Institute, Montreal QC, Canada.
    Annese, Vito
    Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Unit of Gastroenterology SOD2, Azienda Ospedaliero Universitaria (AOU) Careggi, Florence, Italy.
    Bitton, Alain
    McGill University Health Centre, Royal Victoria Hospital, Montreal QC, Canada.
    Begun, Jakob
    Harvard School of Medicine, Boston MA, USA.
    Brant, Steve R.
    Johns Hopkins University, Baltimore MD, USA.
    Bresso, Francesca
    Karolinska University Hospital, Solna, Sweden.
    Cho, Judy H.
    Yale University, New Haven CT, USA.
    Duerr, Richard H.
    Graduate School of Public Health, University of Pittsburgh, Pittsburgh PA, USA.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    McGovern, Dermot P. B.
    Cedars-Sinai Medical Center, Los Angeles CA, USA.
    Radford-Smith, Graham
    University of Queensland, Brisbane, Australia.
    Schreiber, Stefan
    Christian-Albrechts-University, Kiel, Germany.
    Schumm, Philip L.
    University of Chicago, Chicago ILL, USA.
    Sharma, Yashoda
    Yale University, New Haven CT, USA.
    Silverberg, Mark S.
    University of Toronto, Toronto ON, Canada.
    Weersma, Rinse K.
    University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
    D'Amato, Mauro
    Karolinska Institutet, Stockholm, Sweden.
    Vermeire, Severine
    University Hospital Gasthuisberg, Leuven, Belgium.
    Franke, Andre
    Christian-Albrechts-University, Kiel, Germany.
    Lettre, Guillaume
    Research Center, Montreal Heart Institute, Montreal QC, Canada; Universite de Montreal, Montreal QC, Canada .
    Xavier, Ramnik J.
    Harvard School of Medicine, Boston MA, USA; Broad Institute of MIT and Harvard University, Cambridge MA, USA .
    Daly, Mark J.
    Massachusetts General Hospital, Harvard Medical School, Boston MA, USA.
    Rioux, John D.
    Research Center, Montreal Heart Institute, Montreal QC, Canada; Universite de Montreal, Montreal QC, Canada.
    Deep Resequencing of GWAS Loci Identifies Rare Variants in CARD9, IL23R and RNF186 That Are Associated with Ulcerative Colitis2013In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, no 9, article id e1003723Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (similar to 14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci.

  • 25.
    Bergemalm, Daniel
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Andersson, Erik
    Örebro University, School of Medical Sciences. Department of Gastroenterolog.
    Hultdin, Johan
    Department of Medical Biosciences, Division of Clinical Chemistry, Umeå University, Umeå, Sweden.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Rush, Stephen T.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Kalla, Rahul
    MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
    Adams, Alex T.
    Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
    Keita, Åsa V.
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    D'Amato, Mauro
    CIC bioGUNE Basque Research and Technology Alliance, BRTA and IKERBASQUE, Basque Science Foundation, Bilbao, Spain; Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Gomollon, Fernando
    HCU "Lozano Blesa," IIS Aragón, Zaragoza, Spain.
    Jahnsen, Jorgen
    Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Ricanek, Petr
    Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
    Satsangi, Jack
    Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Karling, Pontus
    Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Systemic Inflammation in Preclinical Ulcerative Colitis2021In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 161, no 5, p. 1526-1539.e9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Pre-clinical ulcerative colitis is poorly defined. We aimed to characterize the pre-clinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.

    METHODS: We obtained plasma samples, biobanked from individuals who later in life developed ulcerative colitis (n=72), and matched healthy controls (n=140), within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biological relevance of these findings were validated in an inception cohort of ulcerative colitis patients (n=101), and healthy controls (n=50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of ulcerative colitis patients (n=41) and matched healthy controls (n=37) were explored.

    RESULTS: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP1) were upregulated (p<0.05) in pre-clinical ulcerative colitis compared to controls based on both univariate and mulativariable models. Ingenuity Pathway Analyses identified several potential key regulators, including IL-1b, TNF, IFN-gamma, OSM, NFĸB, IL-6 and IL-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve ulcerative colitis patients from controls with leave-one-out cross-validation (AUC=0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly upregulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.

    CONCLUSIONS: A set of inflammatory proteins are upregulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be upregulated already at exposure to genetic and environmental risk factors.

  • 26.
    Bergemalm, Daniel
    et al.
    Örebro University, School of Medical Sciences.
    Andersson, Erik
    Örebro University, School of Medical Sciences.
    Karling, Pontus
    Department of Public Health and Clinical Medicine, Division of Medicine, Umea University, Umeå, Sweden.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Hultdin, Johan
    Medical Biosciences, Clinical Chemistry, Umea University, Umeå, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    IBD Character Consortium,
    Markers of systemic inflammation in preclinical ulcerative colitis2019In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 7, no 8_suppl, p. 111-111Article in journal (Refereed)
    Abstract [en]

    Introduction: Data on the preclinical stage of ulcerative colitis (UC) are sparse. At diagnosis, UC often shows a modest increase in systemic inflammatory markers like C-reactive protein (CRP). However, a subclinical inflammation with elevated levels of CRP and interleukin-6 (IL6) in serum have been observed several years before diagnosis [1]. First-degree relatives, including healthy twin siblings, also display elevated levels of some inflammatory markers as a consequence of shared genetic and environmental risk factors [2]. It is reasonable to believe that the preclinical inflammation, reflecting early pathogenic mechanisms, ultimately leads to a diagnosis of UC.

    Aim and Method: We aimed to deeper examine the systemic preclinical inflammation in UC using a comprehensive set of protein markers. Cases with UC were identified at clinical follow-up of a prospectively collected population-based cohort of healthy individuals from northern Sweden. Plasma samples from cases and controls were subjected to proximity extension assay for relative quantification of 92 protein markers of inflammation. Results were validated in an inception cohort of treatment naïve, newly diagnosed patients with UC (n=101) vs. healthy controls (n=50). In addition, to examine the impact of shared genetic and environmental factors, a cohort of healthy mono- and dizygotic twin siblings of twins with UC (n=41) and matched healthy controls (n=37) were explored.

    Results: Pre-diagnostic plasma samples from 72 cases who later in life developed UC and 140 controls, matched for gender, age, year of health survey and area of residence, were identified (table 1). Six proteins were significantly upregulated (p<0.05) in pre-diagnostic UC compared to matched healthy controls. A receiver-operating curve based prediction model using the six protein markers combined with sex, age, smoking status and time to diagnose was set up for validation. The model discriminated newly diagnosed, treatment naïve UC cases from healthy controls (AUC=0.96; CI 0.93-0.98). An AUC of 0.73 (CI 0.62-0.84) was observed when the model was applied to healthy twin siblings vs. healthy controls and four out of six proteins were upregulated similarly as in the pre-diagnostic samples. The relative levels of the six proteins showed an intermediate upregulation in pre-diagnostic samples and samples from healthy twin siblings compared to samples at diagnosis of UC. Only one protein showed a significant correlation with time to diagnosis in the pre-diagnostic samples. Using pathway analysis, the six protein upregulations pointed towards subclinical inflammation in UC being caused by dysregulation of four immune pathways.

    Conclusions: This is the first comprehensive characterisation of preclinical systemic inflammation in UC. Inflammatory proteins were upregulated several years prior to diagnosis of UC and to some extent these alterations were also seen in healthy twin siblings of UC patients. Characterisation of the preclinical stage of UC could pave the way for identification of predictive biomarkers and preventive strategies.

  • 27.
    Bergemalm, Daniel
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Kruse, Robert
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Sapnara, Maria
    Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden; Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Elevated fecal peptidase D at onset of colitis in Galphai2(-/-) mice, a mouse model of IBD2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174275Article in journal (Refereed)
    Abstract [en]

    Background: The identification of novel fecal biomarkers in inflammatory bowel disease (IBD) is hampered by the complexity of the human fecal proteome. On the other hand, in experimental mouse models there is probably less variation. We investigated the fecal protein content in mice to identify possible biomarkers and pathogenic mechanisms.

    Methods: Fecal samples were collected at onset of inflammation in Galphai2(-/-) mice, a well-described spontaneous model of chronic colitis, and from healthy littermates. The fecal proteome was analyzed by two-dimensional electrophoresis and quantitative mass spectrometry and results were then validated in a new cohort of mice.

    Results: As a potential top marker of disease, peptidase D was found at a higher ratio in Galphai24mouse feces relative to controls (fold change 27; p = 0.019). Other proteins found to be enriched in Gai2(-/-) mice were mainly pancreatic proteases, and proteins from plasma and blood cells. A tendency of increased calprotectin, subunit S100-A8, was also observed (fold change 21; p = 0.058). Proteases are potential activators of inflammation in the gastrointestinal tract through their interaction with the proteinase-activated receptor 2 (PAR2). Accordingly, the level of PAR2 was found to be elevated in both the colon and the pancreas of Galphai24- mice at different stages of disease.

    Conclusions: These findings identify peptidase D, an ubiquitously expressed intracellular peptidase, as a potential novel marker of colitis. The elevated levels of fecal proteases may be involved in the pathogenesis of colitis and contribute to the clinical phenotype, possibly by activation of intestinal PAR2.

  • 28.
    Björkqvist, Olle
    et al.
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Serrander, Lena
    Division of Clinical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Magnusson, Cecilia
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Infectious Diseases, Region Jönköping County, Jönköping, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Norén, Torbjörn
    Örebro University, School of Medical Sciences. Faculty of Medicine and Health, Department of Laboratory Medicine, National Reference Laboratory for Clostridioides Difficile, Clinical Microbiology.
    Bergman-Jungeström, Malin
    Division of Clinical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Faecalibacterium prausnitzii increases following fecal microbiota transplantation in recurrent Clostridioides difficile infection2021In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 4, article id e0249861Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective treatment for Clostridioides difficile infection (CDI). However, the fecal transplant's causal components translating into clearance of the CDI are yet to be identified. The commensal bacteria Faecalibacterium prausnitzii may be of great interest in this context, since it is one of the most common species of the healthy gut microbiota and produces metabolites with anti-inflammatory properties. Although there is mounting evidence that F. prausnitzii is an important regulator of intestinal homeostasis, data about its role in CDI and FMT are relatively scarce.

    METHODS: Stool samples from patients with recurrent CDI were collected to investigate the relative abundance of F. prausnitzii before and after FMT. Twenty-one patients provided fecal samples before the FMT procedure, at 2 weeks post-FMT, and at 2-4 months post-FMT. The relative abundance of F. prausnitzii was determined using quantitative polymerase chain reaction.

    RESULTS: The abundance of F. prausnitzii was elevated in samples (N = 9) from donors compared to pre-FMT samples (N = 15) from patients (adjusted P<0.001). No significant difference in the abundance of F. prausnitzii between responders (N = 11) and non-responders (N = 4) was found before FMT (P = 0.85). In patients with CDI, the abundance of F. prausnitzii significantly increased in the 2 weeks post-FMT samples (N = 14) compared to the pre-FMT samples (N = 15, adjusted P<0.001). The increase persisted 2-4 months post-FMT (N = 15) compared to pre-FMT samples (N = 15) (adjusted P<0.001).

    CONCLUSIONS: FMT increases the relative abundance of F. prausnitzii in patients with recurrent CDI, and this microbial shift remains several months later. The baseline abundance of F. prausnitzii in donors or recipients was not associated with future treatment response, although a true predictive capacity cannot be excluded because of the limited sample size. Further studies are needed to discern whether F. prausnitzii plays an active role in the resolution of CDI.

  • 29.
    Björkqvist, Olle
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Seifert, M.
    Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Engstrand, L.
    Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Increasing abundance of faecalibacterium prausnitzii is associated with decreased intestinal inflammation in Crohn's disease: A longitudinal study2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S468-S469Article in journal (Other academic)
  • 30.
    Björkqvist, Olle
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Orebro Univ, Sch Med Sci, Orebro, Sweden..
    Seifert, Maike
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Brislawn, Colin
    Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland WA, USA.
    Jansson, Janet
    Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland WA, USA.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Rangel, Ignacio
    Örebro University, School of Medical Sciences.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Alterations in the relative abundance of Faecalibacterium prausnitzii correlate with changes in fecal calprotectin in patients with ileal Crohn's disease: a longitudinal study2019In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 4, p. 577-585Article in journal (Refereed)
    Abstract [en]

    Objectives: Crohn's disease is characterized by a gut dysbiosis with decreased abundance of butyrate producers such as Faecalibacterium prausnitzii. Although F. prausnitzii secretes anti-inflammatory molecules, few studies have addressed the importance of F. prausnitzii in a longitudinal setting. We aimed to examine the relationship between temporal profiles of F. prausnitzii, the C. leptum group, overall butyrate production, and inflammatory activity.

    Material and methods: Fecal samples (n = 59) were collected every third month from nine patients with ileal Crohn's disease. The abundance of F. prausnitzii and C. leptum was quantified relative to the total amount of bacteria using quantitative-PCR. To assess butyrate production of gut microbiota, gene copy numbers of the butyryl-CoA:acetate-CoA transferase (BCoAT) gene were quantified by qPCR. The inflammatory activity was defined by fecal (f)-calprotectin.

    Results: No correlation between the relative abundance of F. prausnitzii, the C. leptum group, or copy numbers of the BCoAT gene, and f-calprotectin was observed in the total sample set. By analyzing alterations between consecutive samples, a negative correlation between changes in the relative abundance of F. prausnitzii and f-calprotectin was observed (R = -0.39; p = .009). Changes in C. leptum (R = -0.18, p = .23) and number of copies of the BCoAT gene (R = -0.12; p = .42) did not correlate with f-calprotectin.

    Conclusions: There was an inverse correlation between temporal changes in the relative abundance of F. prausnitzii, but not overall butyrate producing capacity, and changes in inflammatory activity in ileal Crohn's disease. These findings indicate that F. prausnitzii may play a role in gut homeostasis, even though causality is still to be demonstrated.

  • 31. Blom, Kristin
    et al.
    Rubin, Jenny
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Intestinal Medicine, Örebro University Hospital, Örebro, Sweden.
    Törkvist, Leif
    Rönnblom, Anders
    Sangfelt, Per
    Lördal, Mikael
    Jönsson, Ulla-Britt
    Sjöqvist, Urban
    Håkansson, Lena Douhan
    Venge, Per
    Carlson, Marie
    Eosinophil associated genes in the inflammatory bowel disease 4 region: correlation to inflammatory bowel disease revealed2012In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 18, no 44, p. 6409-6419Article in journal (Refereed)
    Abstract [en]

    AIM: To study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP).

    METHODS: DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn's disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5'-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP(®) system as described by the manufacturer. Statistical tests for calculations of results were χ(2) test, Fisher's exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant.

    RESULTS: The genotype frequency for males with UC and with an age of disease onset of ≥ 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject's genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29%,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of ≥ 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in μg/10(6) eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes.

    CONCLUSION: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.

  • 32.
    Bodea, Corneliu A.
    et al.
    Department of Statistics, Carnegie Mellon University, Pittsburgh PA, USA; Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge MA, USA.
    Neale, Benjamin M.
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge MA, USA; Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge MA, USA.
    Ripke, Stephan
    Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge MA, USA; Department of Psychiatry and Psychotherapy, Charite, Campus Mitte, Berlin, Germany.
    International IBD Genetics Consortium, Group author
    Daly, Mark J.
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge MA, USA; Analytical and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge MA, USA.
    Devlin, Bernie
    Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh PA, USA.
    Roeder, Kathryn
    Department of Statistics, Carnegie Mellon University, Pittsburgh PA, USA; Computational Biology Department, Carnegie Mellon University, Pittsburgh PA, USA.
    A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies2016In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 98, no 5, p. 857-868Article in journal (Refereed)
    Abstract [en]

    One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data.

  • 33. Bodger, K.
    et al.
    Halfvarson, Jonas
    Dodson, A. R.
    Campbell, F.
    Wilson, S.
    Lee, R.
    Lindberg, E.
    Järnerot, G.
    Tysk, Curt
    Örebro University, Department of Clinical Medicine.
    Rhodes, J. M.
    Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients2006In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, no 7, p. 973-977Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Previous chromatographic analysis of colonic mucins from monozygotic twins with inflammatory bowel disease (IBD) suggested a genetic mucin alteration in ulcerative colitis (UC). This study explores this further by assessing mucosal expression of the oncofetal carbohydrate antigen TF (galactose beta1, 3 N-acetylgalactosamine alpha-), among the same IBD twins. MATERIALS AND METHODS: Formalin fixed paraffin embedded rectal biopsies were studied from 22 monozygotic twin pairs with IBD. These included eight UC twin pairs and 14 Crohn's disease (CD) twin pairs, with six pairs concordant for disease and 16 unaffected twin siblings. Closely adjacent sections were assessed by peanut lectin histochemistry for TF expression and immunohistochemically for nuclear factor kappaB (NFkappaB) activation with investigators blinded to the diagnosis. RESULTS: Unaffected twins were almost all TF positive (15/16) compared with 5/29 histologically normal controls (p<0.0001). Unaffected UC (7/8) and CD twins (8/8) were similarly TF positive. TF positivity was confined mainly to the superficial epithelium and absent from the stem cell compartment of the lower crypts, suggesting that glycosylation changes are acquired rather than genetically determined. Activated NFkappaB was present in the surface epithelium of mucosal biopsies from 13/14 unaffected IBD twins but in only 6/22 histologically normal controls (p=0.0004). All 22 affected IBD twins were TF positive and 18 were positive for activated NFkappaB. CONCLUSIONS: Altered mucosal glycosylation in unaffected identical twins of IBD patients was confirmed in this study. This occurred in both UC and CD twins. The changes are probably acquired rather than congenital and may reflect "preinflammatory" NFkappaB activation.

  • 34.
    Bröms, Gabriella
    et al.
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Internal Medicine, Danderyds Hospital, Stockholm, Sweden.
    Söderling, Jonas
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Sachs, Michael C.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Myrelid, Par
    Department of Surgery, Linköping University Hospital, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Everhov, Åsa H.
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden.
    Olén, Ola
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Capturing biologic treatment for IBD in the Swedish Prescribed Drug Register and the Swedish National Patient Register: a validation study2021In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 56, no 4, p. 410-421Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR).

    METHODS: A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/- one year and within +/- three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005-2008, 2009-2012, and 2013-2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes.

    RESULTS: Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4-81.7) were ever captured in the PDR/NPR in. A time window of +/- one year or +/- three months reduced the sensitivity to 63.3% (95% CI: 61.3-65.3) and 52.6% (95% CI: 50.5-54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab.

    CONCLUSIONS: The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG.

  • 35.
    Burisch, J.
    et al.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark.
    Andersen, V.
    Dept Med, Viborg Reg Hosp, Viborg, Denmark; Dept Med, Hosp Southern Jutland, Aabenraa, Denmark.
    Cukovic-Cavka, S.
    Sch Med, Div Gastroenterol & Hepatol, Univ Hosp Ctr Zagreb, Univ Zagreb, Zagreb, Croatia.
    Lakatos, P. L.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    D'Inca, R.
    Dept Surg Oncol & Gastroenterol, Azienda Osped Padova, Padua, Italy.
    Magro, F.
    Inst Mol & Cell Biol, Univ Porto, Porto, Portugal; Dept Gastroenterol, Hosp Sao Joao, Porto, Portugal.; Inst Pharmacol & Therapeut, Oporto Med Sch, Porto, Portugal.
    Arebi, N.
    Gastroenterol, St Marks Hosp, London, England.
    Kievit, L.
    Dept Med, Herning Cent Hosp, Herning, Denmark.
    Kaimakliotis, I.
    Nicosia Private Practice, Nicosia, Cyprus.
    Valpiani, D.
    Dept Gastroenterol & Digest Endoscopy, Morgagni Hosp, Forli, Italy.
    Katsanos, K. H.
    Div Internal Med 1, Univ Hosp, Ioannina, Greece; Gastroenterol Unit, Ioannina, Greece.
    Vegh, Z.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Dahlerup, J. F.
    Dept Gastroenterol & Hepatol, Aarhus Univ Hosp, Aarhus, Denmark.
    Fumery, M.
    Epimad Registry, Gastroenterol Unit, Amiens Univ & Hosp, Amiens, France.
    Pedersen, N.
    Dept Gastroenterol, Slagelse Hosp, Slagelse, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Belousova, E.
    Dept Gastroenterol, Moscow Reg Res Clin Inst, Moscow, Russia.
    Nielsen, K. R.
    Dept Med, Natl Hosp Faroe Isl, Torshavn, Denmark.
    Turcan, S.
    Dept Gastroenterol, State Univ Med & Pharm Republ Moldova, Kishinev, Moldova.
    Ellul, P.
    Div Gastroenterol, Mater Hosp, L Imsida, Malta.
    Kupcinskas, L.
    Inst Digest Res, Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Oksanen, P.
    Dept Gastroenterol & Alimentary Tract Surg, Tampere Univ Hosp, Tampere, Finland.
    Duricova, D.
    IBD Ctr ISCARE, Charles Univ, Prague, Czech Republic.
    Giannotta, M.
    Dept Gastroenterol, AOU Careggi Reg Referral Ctr Inflammatory Bowel D, Florence, Italy.
    Goldis, A.
    Gastroenterol Clin, Univ Med Victor Babes, Timisoara, Romania.
    Hernandez, V.
    Dept Gastroenterol, Complexo Hosp Univ Vigo, Vigo, Spain.
    Salupere, R.
    Div Gastroenterol & Endocrinol, Tartu Univ Hosp, Tartu, Estonia.
    Odes, S.
    Soroka Med Ctr, Beer Sheva, Israel; Dept Gastroenterol & Hepatol, Ben Gurion Univ Negev, Beer Sheva, Israel.
    Langholz, E.
    Dept Med Gastroenterol, Gentofte Univ Hosp, Copenhagen, Denmark.
    Munkholm, P.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark.
    Immunomodulators reduce the risk of surgery and hospitalisation in Crohn's disease in a prospective European population-based inception cohort: the Epi-IBD cohort2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S42-S43Article in journal (Other academic)
  • 36.
    Burisch, J.
    et al.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark.
    Ellul, P.
    Div Gastroenterol, Mater Dei Hosp, L Imsida, Malta.
    Arebi, N.
    Gastroenterol, St Marks Hosp, London, England.
    Kaimakliotis, I.
    D'Inca, R.
    Dept Surg Oncol & Gastroenterol, Azienda Osped Padova, Padua, Italy.
    Andersen, V.
    Med Dept, Viborg Reg Hosp, Viborg, Denmark; Med Dept, Hosp Southern Jutland, Aabenraa, Denmark.
    Belousova, E.
    Dept Gastroenterol, Moscow Reg Res Clin Inst, Moscow, Russia.
    Hernandez, V.
    Gastroenterol Dept, Complexo Hosp Univ Vigo, Vigo, Spain.
    Vegh, Z.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Turcan, S.
    Dept Gastroenterol, State Univ Med & Pharm Republ Moldova, Kishinev, Moldova.
    Magro, F.
    Inst Mol & Cell Biol, Univ Porto, Porto, Portugal; Dept Gastroenterol, Hosp Sao Joao, Porto, Portugal; Inst Pharmacol & Therapeut, Oporto Med Sch, Porto, Portugal.
    Kupcinskas, L.
    Inst Digest Res, Lithuanian Univ of Hlth Sci, Kaunas, Lithuania.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Lakatos, P. L.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Duricova, D.
    IBD Ctr ISCARE, Charles Univ, Prague, Czech Republic.
    Kievit, L.
    Dept Med, Herning Cent Hosp, Herning, Denmark.
    Goldis, A.
    Clin Gastroenterol, Univ Med Victor Babes, Timisoara, Romania.
    Dahlerup, J. F.
    Dept Hepatol & Gastroenterol, Aarhus Univ Hosp, Aarhus, Denmark.
    Oksanen, P.
    Dept Gastroenterol & Alimentary Tract Surg, Tampere Univ Hosp, Tampere, Finland.
    Cukovic-Cavka, S.
    Div Gastroenterol & Hepatol, Sch Med, Univ Hosp Ctr Zagreb, Univ Zagreb, Zagreb, Croatia.
    Fumery, M.
    Gastroenterol Unit, Epimad Registry, Amiens Hosp & Univ, Amiens, France.
    Odes, S.
    Soroka Med Ctr, Beer Sheva, Israel; Dept Gastroenterol & Hepatol, Ben Gurion Univ Negev, Beer Sheva, Israel.
    Nielsen, K. R.
    Med Dept, Natl Hosp Faroe Isl, Torshavn, Denmark.
    Valpiani, D.
    Dept Gastroenterol & Digest Endoscopy, Morgagni Hosp, Forli, Italy.
    Pedersen, N.
    Dept Gastroenterol, Slagelse Hosp, Slagelse, Denmark.
    Giannotta, M.
    Reg Referral Ctr Inflammatory Bowel D, Dept Gastroenterol, AOU Careggi Florence, Italy.
    Salupere, R.
    Div Endocrinol & Gastroenterol, Tartu Univ Hosp, Tartu, Estonia.
    Katsanos, K. H.
    Div Internal Med 1, Univ Hosp Ioannina, Ioannina, Greece; Hepatogastroenterol Unit, Univ Hosp Ioannina, Ioannina, Greece.
    Langholz, E.
    Dept Med Gastroenterol, Gentofte Univ Hosp, Copenhagen, Denmark.
    Munkholm, P.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark.
    Natural disease course of inflammatory bowel disease unclassified in a prospective European population-based inception cohort-the Epi-IBD cohort2018In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, no Suppl. 1, p. S523-S524Article in journal (Other academic)
  • 37.
    Burisch, J.
    et al.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark.
    Gerdes, U.
    Ctr Qual, Region Southern Denmark, Middelfart, Denmark; Inst Reg Hlth Res, Univ Southern Denmark, Odense, Denmark.
    Almer, S.
    Dept Gastroenterol, University Hospital Linköping, County Council Östergötland, Linköping, Sweden.
    Cukovic-Cavka, S.
    Sch Med, Div Gastroenterol & Hepatol, Univ Hosp Ctr Zagreb, Univ Zagreb, Zagreb, Croatia.
    Sebastian, S.
    Hull Royal Infirm, Hull & East Yorkshire NHS Trust, Kingston Upon Hull, England; Hull & York Med Sch, Kingston Upon Hull, England.
    Kaimakliotis, I.
    Duricova, D.
    IBD Ctr ISCARE, Charles Univ, Prague, Czech Republic.
    Pedersen, N.
    Dept Gastroenterol, Slagelse Hosp, Slagelse, Denmark.
    Salupere, R.
    Div Gastroenterol & Endocrinol, Tartu Univ Hosp, Tartu, Estonia.
    Nielsen, K. R.
    Dept Med, Natl Hosp Faroe Isl, Torshavn, Denmark; Genet Biobank, Torshavn, Faroe Islands, Danmark.
    Manninen, P.
    Dept Gastroenterol & Alimentary Tract Surg, Tampere Univ Hosp, Tampere, Finland.
    Katsanos, K. H.
    Div Internal Med 1, Univ Hosp, Ioannina, Greece; Hepatogastroenterol Unit, Univ Hosp, Ioannina, Greece.
    Odes, S.
    Soroka Med Ctr, Beer Sheva, Israel; Dept Gastroenterol & Hepatol, Ben Gurion Univ Negev, Beer Sheva, Israel.
    Andersen, V.
    Dept Med, Viborg Reg Hosp, Viborg, Denmark; Dept Med, Hosp Southern Jutland, Aabenraa, Denmark.
    D'Inca, R.
    Kupcinskas, L.
    Inst Digest Res, Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Turcan, S.
    Dept Gastroenterol, State Univ Med & Pharm Republ Moldova, Kishinev, Moldova.
    Magro, F.
    Inst Mol & Cell Biol, Univ Porto, Oporto, Portugal; Dept Gastroenterol, Hosp Sao Joao, Oporto, Portugal; Inst Pharmacol & Therapeut, Oporto Med Sch, Oporto, Portugal.
    Goldis, A.
    Gastroenterol Clin, Univ Med Victor Babes, Timisoara, Romania.
    Vinding, K. Kofod
    Dept Med, Amager Hosp, Amager, Denmark.
    Belousova, E.
    Dept Gastroenterol, Moscow Reg Res Clin Inst, Moscow, Russia.
    Ladefoged, K.
    Dept Med, Dronning Ingrids Hosp, Nuuk, Greenland.
    Bailey, Y.
    Dept Gastroenterol, Adelaide & Meath Hosp, Trinity College Dublin, Dublin, Ireland.
    Hernandez, V.
    Dept Gastroenterol, Complexo Hosp Univ Vigo, Vigo, Spain.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Arebi, N.
    Gastroenterol, St Marks Hosp, London, England.
    Shonova, O.
    Dept Gastroenterol, Nemocnice Ceske Budejovice, Ceske Budejovice, Czech Republic.
    Hoivik, M. L.
    Dept Gastroenterol, Oslo Univ Hosp, Oslo, Norway.
    Moum, B.
    Dept Gastroenterol, Oslo Univ Hosp, Oslo, Norway.
    Langholz, E.
    Dept Med Gastroenterol, Gentofte Univ Hosp, Copenhagen, Denmark.
    Lakatos, P. L.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Munkholm, P.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark.
    Dahlerup, J. F.
    Dept Gastroenterol & Hepatol, Aarhus Univ Hosp, Aarhus, Denmark.
    Frequency of anaemia and anaemia subtypes in east-west European inception cohort: an ECCO-EpiCom cohort study2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no Suppl. 1, p. S453-S454Article in journal (Other academic)
  • 38.
    Burisch, J.
    et al.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark..
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastronterology, Örebro University Hospital, Örebro, Sweden.
    Kupcinskas, L.
    Inst Digest Res, Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Hernandez, V.
    Dept Gastroenterol, Complexo Hosp Univ Vigo, Vigo, Spain.
    Kaimakliotis, I.
    Nicosia Private Practice, Nicosia, Cyprus..
    Valpiani, D.
    Dept Gastroenterol & Digest Endoscopy, Morgagni Hosp, Forli, Italy.
    Pedersen, N.
    Dept Gastroenterol, Slagelse Hosp, Slagelse, Denmark.
    Duricova, D.
    IBD Ctr ISCARE, Charles Univ Prague, Prague, Czech Republic.
    Kievit, L.
    Dept Med, Herning Cent Hosp, Herning, Denmark.
    Dahlerup, J. F.
    Dept Gastroenterol & Hepatol, Aarhus Univ Hosp, Aarhus, Denmark.
    Fumery, M.
    Gastroenterol Unit, Epimad Registry, Amiens Univ & Hosp, Amiens, France.
    Salupere, R.
    Div Gastroenterol & Endocrinol, Tartu Univ Hosp, Tartu, Estonia.
    Arebi, N.
    Gastroenterol, St Marks Hosp, London, England.
    Nielsen, K. R.
    Dept Med, Natl Hosp Faroe Isl, Torshavn, Denmark.
    Giannotta, M.
    Dept Gastroenterol, AOU Careggi, Regional Referral Centre of Inflammatory Bowel, Florence, Italy.
    Oksanen, P.
    Dept Gastroenterol & Alimentary Tract Surg, Tampere Univ Hosp, Tampere, Finland.
    Katsanos, K. H.
    Div Internal Med 1, Univ Hosp, Ioannina, Greece; Hepatogastroenterol Unit, Univ Hosp, Ioannina, Greece.
    Vegh, Z.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Ellul, P.
    Div Gastroenterol, Mater Dei Hosp, LImsida, Malta.
    Schwartz, D.
    Soroka Med Ctr, Beer Sheva, Israel; Dept Gastroenterol & Hepatol, Ben Gurion Univ Negev, Beer Sheva, Israel.
    Cukovic-Cavka, S.
    Sch Med, Div Gastroenterol & Hepatol, Univ Hosp Ctr , Univ Zagreb, Zagreb, Croatia.
    D'Inca, R.
    Dept Surg Oncol & Gastroenterol, Azienda Osped Padova, Padua, Italy.
    Turcan, S.
    Dept Gastroenterol, State Univ Med Pharm, Kishinev, Moldova.
    Magro, F.
    Inst Mol & Cell Biol, Univ Porto, Oporto, Portugal; Dept Gastroenterol, Hosp Sao Joao, Oporto, Portugal; Inst Pharmacol & Therapeut, Oporto Med Sch, Oporto, Portugal.
    Goldis, A.
    Gastroenterol Clin, Univ Med Victor Babes, Timisoara, Romania.
    Langholz, E.
    Dept Med Gastroenterol, Gentofte Univ Hosp, Copenhagen, Denmark..
    Lakatos, P. L.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Munkholm, P.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark.
    Change in Crohn's disease behavior in a prospective European population-based inception cohort - the ECCO-EpiCom cohort2017In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no Suppl. 1, p. S452-S453Article in journal (Refereed)
  • 39.
    Burisch, J.
    et al.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Kupcinskas, L.
    Inst Digest Res, Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Hernandez, V.
    Dept Gastroenterol, Complexo Hosp Univ Vigo, Vigo, Spain.
    Kaimakliotis, I.
    Nicosia Private Practice, Nicosia, Cyprus.
    Valpiani, D.
    Dept Gastroenterol & Digest Endoscopy, Morgagni Hosp, Forli, Italy.
    Pedersen, N.
    Dept Gastroenterol, Slagelse Hosp, Slagelse, Denmark.
    Duricova, D.
    IBD Ctr ISCARE, Prague, Charles Univ Prague, Czech Republic.
    Kievit, L.
    Dept Med, Herning Cent Hosp, Herning, Denmark.
    Dahlerup, J. F.
    Dept Gastroenterol & Hepatol, Aarhus Univ Hosp, Aarhus, Denmark.
    Fumery, M.
    Epimad Registry, Gastroenterol Unit, Amiens Univ & Hosp, Amiens, France.
    Salupere, R.
    Div Gastroenterol & Endocrinol, Tartu Univ Hosp, Tartu, Estonia.
    Arebi, N.
    Gastroenterol, St Marks Hosp, London, England.
    Nielsen, K. R.
    Dept Med, Natl Hosp Faroe Islands, Torshavn, Denmark..
    Giannotta, M.
    Inflammatory Bowel D, Dept Gastroenterol, AOU Careggi Regional Referral Centre, Florence, Italy.
    Oksanen, P.
    Dept Gastroenterol & Alimentary Tract Surg, Tampere Univ Hosp, Tampere, Finland.
    Katsanos, K. H.
    Div Internal Med 1, Univ Hosp Ioannina, Ioannina, Greece; Hepatogastroenterol Unit, Univ Hosp Ioannina, Ioannina, Greece.
    Vegh, Z.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Ellul, P.
    Div Gastroenterol, Mater Dei Hosp, Limsida, Malta.
    Schwartz, D.
    Soroka Med Ctr, Beer Sheva, Israel; Dept Gastroenterol & Hepatol, Ben Gurion Univ Negev, Beer Sheva, Israel.
    Cukovic-Cavka, S.
    Sch Med, Div Gastroenterol & Hepatol, Univ Hosp Ctr Zagreb, Univ Zagreb, Zagreb, Croatia.
    D'Inca, R.
    Dept Surg Oncol & Gastroenterol, Azienda Osped Padova, Padua, Italy.
    Turcan, S.
    Dept Gastroenterol, State Univ Med & Pharm, Kishinev, Moldova..
    Magro, F.
    Inst Mol & Cell Biol, Univ Porto, Oporto, Portugal; Dept Gastroenterol, Hosp Sao Joao, Oporto, Portugal; Inst Pharmacol & Therapeut, Oporto Med Sch, Oporto, Portugal.
    Goldis, A.
    Gastroenterol Clin, Univ Med Victor Babes, Timisoara, Romania.
    Langholz, E.
    Dept Med Gastroenterol, Gentofte Univ Hosp, Copenhagen, Denmark.
    Lakatos, P. L.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Munkholm, P.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark.
    Disease course during the first five years following diagnosis in a prospective European population-based inception cohort - the ECCO-EpiCom cohort2017In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no Suppl. 1, p. S435-S436Article in journal (Refereed)
  • 40.
    Burisch, J.
    et al.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastronterology, Örebro University Hospital, Örebro, Sweden.
    Kupcinskas, L.
    Inst Digest Res, Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Hernandez, V.
    Dept Gastroenterol, Complexo Hosp Univ Vigo, Vigo, Spain.
    Kaimakliotis, I.
    Nicosia Private Practice, Nicosia, Cyprus.
    Valpiani, D.
    Dept Gastroenterol & Digest Endoscopy, Morgagni Hosp, Forli, Italy.
    Pedersen, N.
    Dept Gastroenterol, Slagelse Hosp, Slagelse, Denmark.
    Duricova, D.
    IBD Ctr ISCARE, Charles Univ Prague, Prague, Czech Republic.
    Kievit, L.
    Dept Med, Herning Cent Hosp, Herning, Denmark.
    Dahlerup, J. F.
    Dept Gastroenterol & Hepatol, Aarhus Univ Hosp, Aarhus, Denmark.
    Fumery, M.
    Epimad Registry, Gastroenterol Unit, Amiens Univ & Hosp, Amiens, France.
    Salupere, R.
    Div Gastroenterol & Endocrinol, Tartu Univ Hosp, Tartu, Estonia.
    Arebi, N.
    Gastroenterol, St Marks Hosp, London, England.
    Nielsen, K. R.
    Dept Med, Natl Hosp Faroe Islands, Torshavn, Denmark.
    Giannotta, M.
    Dept Gastroenterol, AOU Careggi, Regional Referral Centre of Inflammatory Bowel Disease, Florence, Italy.
    Oksanen, P.
    Dept Gastroenterol & Alimentary Tract Surg, Tampere Univ Hosp, Tampere, Finland.
    Katsanos, K. H.
    Div Internal Med 1, Univ Hosp Ioannina, Ioannina, Greece; Hepatogastroenterol Unit, Univ Hosp, Ioannina, Greece.
    Vegh, Z.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Ellul, P.
    Div Gastroenterol, Mater Dei Hosp, Limsida, Malta.
    Schwartz, D.
    Soroka Med Ctr, Beer Sheva, Israel; Dept Gastroenterol & Hepatol, Ben Gurion Univ Negev,Beer Sheva, Israel.
    Cukovic-Cavka, S.
    Sch Med, Div Gastroenterol & Hepatol, Univ Hosp Ctr Zagreb, Univ Zagreb, Zagreb, Croatia.
    D'Inca, R.
    Dept Surg Oncol & Gastroenterol, Azienda Osped Padova, Padua, Italy.
    Turcan, S.
    Dept Gastroenterol, State Univ Med & Pharm Republ Moldova, Kishinev, Moldova.
    Magro, F.
    Inst Mol & Cell Biol, Univ Porto, Oporto, Portugal; Dept Gastroenterol, Hosp Sao Joao, Oporto, Portugal; Inst Pharmacol & Therapeut, Oporto Med Sch, Oporto, Portugal.
    Goldis, A.
    Gastroenterol Clin, Univ Med Victor Babes, Timisoara, Romania.
    Langholz, E.
    Dept Med Gastroenterol, Gentofte Univ Hosp, Copenhagen, Denmark.
    Lakatos, P. L.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Munkholm, P.
    Dept Gastroenterol, North Zealand Univ Hosp, Frederikssund, Denmark.
    The risk of proximal disease extension in patients with limited ulcerative colitis in a prospective European population-based inception cohort - the ECCO-EpiCom cohort2017In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, no Suppl. 1, p. S436-S436Article in journal (Refereed)
  • 41.
    Burisch, J.
    et al.
    Gastrounit, Medical section, Hvidovre University Hospital, Hvidovre, Denmark.
    Kaimakliotis, I.
    Nicosia Private practice, Nicosia, Cyprus.
    Duricova, D.
    IBD Center ISCARE, Charles University, Prague, Czech Republic.
    Kievit, L.
    Department of medicine, Herning Central Hospital, Herning, Denmark.
    Dahlerup, J. F.
    Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
    Salupere, R.
    Division of Endocrinology and Gastroenterology, Tartu University Hospital, Tartu, Estonia.
    Nielsen, K. R.
    Medical Department, The National Hospital of the Faroe Islands, Thorshavn, Denmark.
    Manninen, P.
    Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.
    Tsianos, E. V.
    1st Division of Internal Medicine and Hepato-Gastroenterology Unit, University Hospital, Ioannina, Greece.
    Vegh, Z.
    1st Department of Medicine, Semmelweis University, Budapest, Hungary.
    Odes, S.
    Department of Gastroenterology and Hepatology, Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
    D'Inca, R.
    EpiCom Northern Italy, Florence, Forlì and Padova, Italy.
    Kupcinskas, L.
    Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
    Turcan, S.
    Department of Gastroenterology, Chisinau, State University of Medicine and Pharmacy of the Republic of Moldova, Moldova, Republic of Moldova.
    Magro, F.
    Institute for molecular and cell biology, University of Porto, Porto, Portugal; Department of Gastroenterology, Hospital de São João, Porto, Portugal; Institute of Pharmacology and Therapeutics, Oporto Medical School, Porto, Portugal.
    Goldis, A.
    Clinic of Gastroenterology, University of Medicine Victor Babes, Timisoara, Romania.
    Hernandez, V.
    Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden.
    Arebi, N.
    Gastroenterology, St Mark's Hospital, London, United Kingdom.
    Langholz, E.
    Department of Medical Gastroenterology, Gentofte Hospital, Copenhagen, Denmark.
    Lakatos, P. L.
    1st Department of Medicine, Semmelweis University, Budapest, Hungary.
    Munkholm, P.
    Department of gastroenterology, Herlev University Hospital, Herlev, Denmark.
    EpiCom Northern Italy, Group author
    Unchanged surgery and hospitalization rates in an East-West European inception cohort despite differences in use of biologicals-3-year follow-up of the ECCO-EpiCom cohort2015In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 9, p. S5-S6Article in journal (Other academic)
  • 42.
    Burisch, J.
    et al.
    Dept Gastroenterol, Herlev Univ Hosp, Herlev, Denmark.
    Kaimakliotis, I.
    Nicosia Private Practice, Nicosia, Cyprus.
    Duricova, D.
    IBD Ctr ISCARE, Charles Univ, Prague, Czech Republic.
    Thorsgaard, N.
    Dept Med, Herning Cent Hosp, Herning, Denmark.
    Andersen, V.
    Dept Med, Viborg Reg Hosp, Viborg, Denmark; Inst Reg Hlth Res, Univ Southern Denmark, Odense, Denmark; Dept Med, Hosp Southern Jutland, Aabenraa, Denmark.
    Nielsen, K. R.
    Dept Med, Natl Hosp Faroe Islands, Torshavn, Denmark.
    Tsianos, E. V.
    Div Internal Med 1, Univ Hosp, Ioannina, Greece; Hepatogastroenterol Unit, Ioannina, Greece.
    Ladefoged, K.
    Dept Med, Dronning Ingrids Hosp, Nuuk, Greenland.
    Bailey, Y.
    Dept Gastroenterol, Adelaide & Meath Hosp, Trinity College, Dublin, Ireland.
    D'Inca, R.
    UO Gastroenterol, Azienda Osped, Univ Padua, Padua, Italy; EpiCom Northern Italy Ctr Based Crema & Cremona, Forli, Italy; EpiCom Northern Italy Ctr Based Crema & Cremona, Reggio Emilia, Italy.
    Kupcinskas, L.
    Inst Digest Res, Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Turcan, S.
    Dept Gastroenterol, State University of Medicine and Pharmacy "Nicolae Testemitanu", Kishinev, Moldova.
    Magro, F.
    Inst Pharmacol & Therapeut, Oporto Med Sch, Oporto, Portugal; Dept Gastroenterol, Hosp Sao Joao, Oporto, Portugal; Inst Mol & Cell Biol, Univ Porto, Oporto, Portugal.
    Goldis, A.
    Gastroenterol Clin, Univ Med Victor Babes, Timisoara, Romania.
    Belousova, E.
    Dept Gastroenterol, Moscow Reg Res Clin Inst, Moscow, Russia.
    Hernandez, V.
    Gastroenterol, Complejo Hosp Univ Vigo, Vigo, Spain.
    Almer, S.
    Dept Gastroenterol, Uiveraity Hospital, Cty Council Östergötland, Linköping, Sweden; Div Gastroenterol & Hepatol, Karolinska Inst, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Dept Med 24, Div Gastroenterol, Örebro Univ Hosp, Örebro, Sweden .
    Sebastian, S.
    Hull Royal Infirm, Hull & East Yorkshire NHS Trust, Kingston Upon Hull, England; Hull & York Med Sch, Kingston Upon Hull, England.
    Langholz, E.
    Dept Med Gastroenterol, Gentofte Univ Hosp, Copenhagen, Denmark.
    Odes, S.
    Soroka Med Ctr, Beer Sheva, Israel; Dept Gastroenterol & Hepatol, Ben Gurion Univ Negev, Beer Sheva, Israel.
    Munkholm, P.
    Dept Gastroenterol, Herlev Univ Hosp, Herlev, Denmark.
    The cost of investigations and medical treatment including biological therapy in a European inception cohort from the biological era: An ECCO-EpiCom study2014In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, no Suppl. 1, p. S5-S6Article in journal (Refereed)
  • 43.
    Burisch, J.
    et al.
    Digestive Disease Centre, Medical Section, Herlev University Hospital, Copenhagen, Denmark.
    Pedersen, N.
    Digestive Disease Centre, Medical Section, Herlev University Hospital, Copenhagen, Denmark.
    Cukovic-Cavka, S.
    Division of Gastroenterology and Hepatology, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
    Brinar, M.
    Division of Gastroenterology and Hepatology, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
    Kaimakliotis, I.
    Nicosia private practice, Nicosia, Cyprus.
    Duricova, D.
    IBD Centre ISCARE, Charles University, Prague, Czech Republic.
    Shonova, O.
    Gastroenterology Department, Hospital České Budějovice, České Budějovice, Czech Republic.
    Vind, I.
    Department of Medicine, Amager Hospital, Amager, Denmark.
    Avnstrom, S.
    Department of Medicine, Amager Hospital, Amager, Denmark.
    Thorsgaard, N.
    Department of Medicine, Herning Central Hospital, Herning, Denmark.
    Andersen, V.
    Medical Department, Viborg Regional Hospital, Viborg, Denmark; Medical Department, Hospital of Southern Jutland, Aabenraa, Denmark; University of Southern Denmark, Odense, Denmark.
    Krabbe, S.
    Medical Department, Viborg Regional Hospital, Viborg, Denmark.
    Dahlerup, J. F.
    Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Arhus, Denmark.
    Salupere, R.
    Division of Endocrinology and Gastroenterology, Tartu University Hospital, Tartu, Estonia.
    Nielsen, K. R.
    Medical Department, The National Hospital of the Faroe Islands, Torshavn, Faroe Islands.
    Olsen, J.
    Medical Department, The National Hospital of the Faroe Islands, Torshavn, Faroe Islands.
    Manninen, P.
    Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.
    Collin, P.
    Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.
    Tsianos, E. V.
    1st Division of Internal Medicine and Hepato-Gastroenterology Unit, University Hospital, Ioannina, Greece.
    Katsanos, K. H.
    1st Division of Internal Medicine and Hepato-Gastroenterology Unit, University Hospital, Ioannina, Greece.
    Ladefoged, K.
    Medical Department, Dronning Ingrids Hospital, Nuuk, Greenland.
    Lakatos, L.
    1st Department of Medicine, Semmelweis University, Budapest, Hungary.
    Bjornsson, E.
    Department of Internal Medicine, Section of Gastroenterology and Hepatology, The National University Hospital, Reykjavik, Iceland.
    Ragnarsson, G.
    Department of Internal Medicine, Section of Gastroenterology and Hepatology, The National University Hospital, Reykjavik, Iceland.
    Bailey, Y.
    Department of Gastroenterology, Adelaide and Meath Hospital, TCD, Dublin, Ireland.
    Odes, S.
    Department of Gastroenterology and Hepatology, Soroka Medical Centre and Ben Gurion University of the Negev, Beer Sheva, Israel.
    Schwartz, D.
    Department of Gastroenterology and Hepatology, Soroka Medical Centre and Ben Gurion University of the Negev, Beer Sheva, Israel.
    Martinato, M.
    UO Gastroenterologia, Azienda Ospedaliera—Università di Padova, Padova, Italy.
    Lupinacci, G.
    UO di Medicina e Gastroenterologia, Az Ospedaliera Ospedale di Cremona, Cremona, Italy; UO di Gastroenterologia e Endoscopia Digestiva, Az Ospedaliera Ospedale Maggiore di Crema, Crema, Italy.
    Milla, M.
    Gastroenterology Unit, Careggi Hospital, Florence, Italy.
    De Padova, A.
    UO Gastroenterologia ed Endoscopia Digestiva, Ospedale Morgagni-Pierantoni, Forlì, Italy.
    D'lnca, R.
    UO Gastroenterologia, Azienda Ospedaliera-Università di Padova, Padova, Italy.
    Beltrami, M.
    UO Gastroenterologia ed Endoscopia Digestiva, Ospedale Morgagni-Pierantoni, Forlì, Italy.
    Kupcinskas, L.
    Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
    Kiudelis, G.
    Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
    Turcan, S.
    Department of Gastroenterology, State University of Medicine and Pharmacy of the Republic of Moldova, Chisinau, Republic of Moldova.
    Tighineanu, O.
    Department of Paediatric Gastroenterology, Centre of Mother and Child, Chisinau, Republic of Moldova.
    Mihu, I.
    Department of Paediatric Gastroenterology, Centre of Mother and Child, Chisinau, Republic of Moldova.
    Magro, F.
    Department of Gastroenterology, Hospital de São João, Porto, Portugal; Institute of Pharmacology and Therapeutics, Oporto Medical School, Porto, Portugal; Hospital de Vale de Sousa, Porto, Portugal.
    Barros, L. F.
    Hospital de Vale de Sousa, Porto, Portugal.
    Goldis, A.
    Clinic of Gastroenterology, University of Medicine ‘Victor Babes’, Timisoara, Romania.
    Lazar, D.
    Clinic of Gastroenterology, University of Medicine ‘Victor Babes’, Timisoara, Romania.
    Belousova, E.
    Department of Gastroenterology, Moscow Regional Research Clinical Institute, Moscow, Russia.
    Nikulina, I.
    Department of Gastroenterology, Moscow Regional Research Clinical Institute, Moscow, Russia.
    Hernandez, V.
    Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain.
    Martinez-Ares, D.
    Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain.
    Almer, S.
    Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Gastroenterology/UHL, County Council of Östergötland, Linköping, Sweden.
    Zhulina, Yaroslava
    Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Arebi, N.
    Sir Alan Park's Physiology Unit, St Mark's Hospital, Imperial College London, London, UK.
    Sebastian, S.
    Hull and East Yorkshire NHS Trust and Hull and York Medical School, Hull Royal Infirmary, Hull, UK.
    Lakatos, P. L.
    1st Department of Medicine, Semmelweis University, Budapest, Hungary.
    Langholz, E.
    Department of Medical Gastroenterology, Gentofte Hospital, Copenhagen, Denmark.
    Munkholm, P.
    Digestive Disease Centre, Medical Section, Herlev University Hospital, Copenhagen, Denmark.
    East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort2014In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 4, p. 588-597Article in journal (Refereed)
    Abstract [en]

    Objective: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East–West gradient in the incidence of IBD in Europe exists.

    Design: A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience.

    Results: 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn’s disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100 000 in 2010 for CD were 6.5 (range 0–10.7) in Western European centres and 3.1 (range 0.4–11.5) in Eastern European centres, for UC 10.8 (range 2.9–31.5) and 4.1 (range 2.4–10.3), respectively, and for IBDU 1.9 (range 0–39.4) and 0 (range 0–1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy.

    Conclusions: An East–West gradient in IBD incidence exists in Europe. Among this inception cohort—including indolent and aggressive cases—international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

  • 44.
    Burisch, J.
    et al.
    Med Sect, Ctr Digest Dis, Herlev Univ Hosp, Copenhagen, Denmark.
    Pedersen, N.
    Med Sect, Ctr Digest Dis, Herlev Univ Hosp, Copenhagen, Denmark.
    Cukovic-Cavka, S.
    Div Gastroenterol & Hepatol, Sch Med, Univ Hosp Ctr Zagreb, Univ Zagreb, Zagreb, Croatia.
    Turk, N.
    Div Gastroenterol & Hepatol, Sch Med, Univ Hosp Ctr Zagreb, Univ Zagreb, Zagreb, Croatia.
    Kaimakliotis, I.
    Nicosia Private Practice, Nicosia, Cyprus.
    Duricova, D.
    IBD Ctr ISCARE, Charles Univ, Prague, Czech Republic.
    Bortlik, M.
    IBD Ctr ISCARE, Charles Univ, Prague, Czech Republic.
    Shonova, O.
    Dept Gastroenterol, Hosp Ceske Budejovice, Ceske Budejovice, Czech Republic.
    Vind, I.
    Dept Med, Amager Hosp, Amager, Denmark.
    Avnstrom, S.
    Dept Med, Amager Hosp, Amager, Denmark.
    Thorsgaard, N.
    Dept Med, Herning Cent Hosp, Herning, Denmark.
    Krabbe, S.
    Dept Med, Viborg Reg Hosp, Viborg, Denmark.
    Andersen, V.
    Dept Med, Viborg Reg Hosp, Viborg, Denmark; Organ Ctr, Hosp Southern Jutland, Aabenraa, Denmark; Inst Reg Hlth Res, Univ Southern Denmark, Odense, Denmark.
    Dahlerup, J. F.
    Dept Med Hepatol & Gastroenterol, Aarhus Univ Hosp, Aarhus, Denmark.
    Kjeldsen, J.
    Dept Med Gastroenterol, Odense Univ Hosp, Odense, Denmark.
    Salupere, R.
    Olsen, J.
    Div Gastroenterol & Endocrinol, Tartu Univ Hosp, Tartu, Estonia; , Dept Med, Natl Hosp Faroe Islands, Torshavn, Denmark.
    Nielsen, K. R.
    Dept Med, Natl Hosp Faroe Islands, Torshavn, Denmark.
    Manninen, P.
    Dept Gastroenterol & Alimentary Tract Surg, Tampere Univ Hosp, Tampere, Finland.
    Collin, P.
    Dept Gastroenterol & Alimentary Tract Surg, Tampere Univ Hosp, Tampere, Finland.
    Katsanos, K. H.
    Div Internal Med, Univ Hosp, Ioannina, Greece; Hepatogastroenterol Unit, Univ Hosp, Ioannina, Greece.
    Tsianos, E. V.
    Div Internal Med, Univ Hosp, Ioannina, Greece; Hepatogastroenterol Unit, Univ Hosp, Ioannina, Greece.
    Ladefoged, K.
    Dept Med, Dronning Ingrids Hosp, Nuuk, Greenland.
    Lakatos, L.
    Dept Med, Semmelweis Univ, Budapest, Hungary.
    Ragnarsson, G.
    Sect Gastroenterol & Hepatol, Dept Internal Med, Natl Univ Hosp Reykjavik, Reykjavik, Iceland.
    Björnsson, E.
    Sect Gastroenterol & Hepatol, Dept Internal Med, Natl Univ Hosp Reykjavik, Reykjavik, Iceland.
    Bailey, Y.
    Dept Gastroenterol, TCD, Adelaide & Meath Hosp, Dublin, Ireland.
    O'Morain, C.
    Dept Gastroenterol, TCD, Adelaide & Meath Hosp, Dublin, Ireland.
    Schwartz, D.
    Dept Gastroenterol & Hepatol, Soroka Med Ctr, Beer Sheva, Israel; Ben Gurion Univ Negev, Beer Sheva, Israel.
    Odes, S.
    Dept Gastroenterol & Hepatol, Soroka Med Ctr, Beer Sheva, Israel; Ben Gurion Univ Negev, Beer Sheva, Israel.
    Giannotta, M.
    Gastroenterol Unit, Careggi Hosp, Florence, Italy.
    Girardin, G.
    UO Gastroenterol, Azienda Osped Univ Padova, Padua, Italy.
    Kiudelis, G.
    Inst Digest Res, Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Kupcinskas, L.
    Inst Digest Res, Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Turcan, S.
    Dept Gastroenterol, State Univ Med & Pharm Republ Moldova, Kishinev, Moldova.
    Barros, L.
    Hosp de Vale de Sousa, Oporto, Portugal.
    Magro, F.
    Dept Gastroenterol, Hosp Sao Joao, Oporto, Portugal; Inst Pharmacol & Therapeut, Oporto Med Sch, Oporto, Portugal; Inst Mol & Cell Biol, Univ Porto, Oporto, Portugal.
    Lazar, D.
    Gastroenterol Clin, Univ Med Victor Babes, Timisoara, Romania.
    Goldis, A.
    Gastroenterol Clin, Univ Med Victor Babes, Timisoara, Romania.
    Nikulina, I.
    Dept Gastroenterol, Moscow Reg Res Clin Inst, Moscow, Russia.
    Belousova, E.
    Dept Gastroenterol, Moscow Reg Res Clin Inst, Moscow, Russia.
    Martinez-Ares, D.
    Dept Gastroenterol, Complexo Hosp Univ Vigo, Vigo, Spain.
    Hernandez, V.
    Dept Gastroenterol, Complexo Hosp Univ Vigo, Vigo, Spain.
    Almer, S.
    Div Gastroenterol & Hepatol, Karolinska Inst, Stockholm, Sweden; Dept Gastroenterol UHL, Cty Council Östergötland, Linköping, Sweden.
    Zhulina, Yaroslava
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Div Gastroenterol, Dept Med.
    Halfvarson, Jonas
    Örebro University Hospital. Div Gastroenterol, Dept Med.
    Arebi, N.
    St Marks Hosp, Univ London Imperial Coll Sci Technol & Med, London, England.
    Tsai, H. H.
    Hull Royal Infirm, Hull & York Med Sch, Hull & East Yorkshire NHS Trust, Kingston Upon Hull, N Humberside, England.
    Sebastian, S.
    Hull Royal Infirm, Hull & York Med Sch, Hull & East Yorkshire NHS Trust, Kingston Upon Hull, N Humberside, England.
    Lakatos, P. L.
    Dept Med, Semmelweis Univ, Budapest, Hungary.
    Langholz, E.
    Dept Med Gastroenterol, Gentofte Univ Hosp, Copenhagen, Denmark.
    Munkholm, P.
    Med Sect, Ctr Digest Dis, Herlev Univ Hosp, Copenhagen, Denmark.
    Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe: An ECCO-EpiCom study2014In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, no 7, p. 607-616Article in journal (Refereed)
    Abstract [en]

    Background and Aims: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of Living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients.

    Methods: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors.

    Results: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p < 0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p < 0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p < 0.01).

    Conclusions: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle. (C) 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  • 45.
    Burisch, J.
    et al.
    North Zealand University Hospital, Frederikssund, Denmark.
    Vardi, H.
    Ben Gurion University of the Negev, Beer Sheva, Israel.
    Schwartz, D.
    Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel.
    Krznaric, Z.
    University Hospital Center Zagreb, Zagreb, Croatia.
    Lakatos, P. L.
    Semmelweis University, Budapest, Hungary.
    Fumery, M.
    Amiens University and Hospital, Amiens, France.
    Kupcinskas, L.
    Lithuanian University of Health Sciences, Kaunas, Lithuania.
    Magro, F.
    Hospital de São João, Porto, Portugal.
    Belousova, E.
    Moscow Regional Research Clinical Institute, Moscow, Russian Federation.
    Oksanen, P.
    Tampere University Hospital, Tampere, Finland.
    Arebi, N.
    Imperial College London, London, UK.
    Langholz, E.
    Herlev University Hospital, Herlev, Denmark.
    Turcan, S.
    State University of Medicine and Pharmacy of the Republic of Moldova, Chisinau, Republic of Moldova.
    D'Inca, R.
    Azienda Ospedaliera di Padova, Padova, Italy.
    Hernandez, V.
    Complexo Hospitalario Universitario de Vigo, Vigo, Spain.
    Valpiani, D.
    Morgagni Hospital, Forli, Italy.
    Vegh, Z.
    Semmelweis University, Budapest, Hungary.
    Giannotta, M.
    Careggi Regional Referral Center for Inflammatory Bowel Disease, Florence, Italy.
    Katsanos, K. H.
    University Hospital, Ioannina, Greece.
    Duricova, D.
    Charles University, Prague, Czech Republic.
    Nielsen, K. R.
    National Hospital of the Faroe Islands, Torshavn, Faroe Islands.
    Kievit, H. A. L.
    Herning Hospital, Herning, Denmark.
    Ellul, P.
    Mater Dei Hospital, Msida, Malta.
    Salupere, R.
    Tartu University Hospital, Tartu, Estonia.
    Goldis, A.
    University of Medicine ‘Victor Babes’, Timisoara, Romania.
    Kaimakliotis, I.
    American Gastroenterology center, Nicosia, Cyprus.
    Pedersen, N.
    Slagelse Hospital, Department of medicine, Denmark.
    Andersen, V.
    Regional Hospital of Viborg, Viborg, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Sebastian, S.
    Hull and East Yorkshire NHS Trust, Hull, UK.
    Dahlerup, J. F.
    Aarhus University Hospital, Aarhus, Denmark.
    Munkholm, P.
    North Zealand University Hospital, Frederikssund, Denmark.
    Odes, S.
    Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel.
    Cost analysis in a prospective European population-based inception cohort: is there a cost-saving effect of biological therapy?2019In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, no Suppl. 1, p. S9-S10Article in journal (Other academic)
  • 46.
    Burisch, J.
    et al.
    Med Sect, Ctr Digest Dis, Herlev Univ Hosp, Copenhagen, Denmark.
    Vegh, Z.
    Med Sect, Ctr Digest Dis, Herlev Univ Hosp, Copenhagen, Denmark; Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Pedersen, N.
    Med Sect, Ctr Digest Dis, Herlev Univ Hosp, Copenhagen, Denmark.
    Cukovic-Cavka, S.
    Univ Hosp Ctr Zagreb, Div Gastroenterol & Hepatol, Univ Zagreb Sch Med, Zagreb, Croatia.
    Turk, N.
    Univ Hosp Ctr Zagreb, Div Gastroenterol & Hepatol, Univ Zagreb Sch Med, Zagreb, Croatia.
    Kaimakliotis, I.
    Duricova, D.
    IBD Ctr ISCARE, Charles Univ, Prague, Czech Republic.
    Bortlik, M.
    IBD Ctr ISCARE, Charles Univ, Prague, Czech Republic.
    Shonova, O.
    Dept Gastroenterol, Hosp Ceske Budejovice, Ceske Budejovice, Czech Republic.
    Thorsgaard, N.
    Dept Med, Cent Hosp, Herning, Denmark.
    Krabbe, S.
    Dept Med, Reg Hosp, Viborg, Denmark.
    Andersen, V.
    Dept Med, Reg Hosp, Viborg, Denmark; Dept Med, Hosp Southern Jutland, Aabenraa, Denmark; Inst Reg Hlth Res, Univ Southern Denmark, Odense, Denmark.
    Dahlerup, J. F.
    Dept Med Hepatol & Gastroenterol 5, Aarhus Univ Hosp, Aarhus, Denmark.
    Kjeldsen, J.
    Dept Med Gastroenterol, Univ Hosp, Odense, Denmark.
    Salupere, R.
    Div Gastroenterol & Endocrinol, Univ Hosp, Tartu, Estonia.
    Olsen, J.
    Dept Med, Natl Hosp Faroe Isl, Torshavn, Denmark.
    Nielsen, K. R.
    Dept Med, Natl Hosp Faroe Isl, Torshavn, Denmark.
    Manninen, P.
    Dept Gastroenterol & Alimentary Tract Surg, Univ Hosp, Tampere, Finland.
    Collin, P.
    Dept Gastroenterol & Alimentary Tract Surg, Univ Hosp, Tampere, Finland.
    Katsanos, K. H.
    Sch Med, Div Internal Med 1, Univ Ioannina, Ioannina, Greece; Sch Med, Div Gastroenterol, Univ Ioannina, Ioannina, Greece.
    Tsianos, E. V.
    Sch Med, Div Internal Med 1, Univ Ioannina, Ioannina, Greece; Sch Med, Div Gastroenterol, Univ Ioannina, Ioannina, Greece.
    Ladefoged, K.
    Dept Med, Dronning Ingrids Hosp, Nuuk, Greenland.
    Ragnarsson, G.
    Sect Gastroenterol & Hepatol, Dept Internal Med, Natl Univ Hosp, Reykjavik, Iceland.
    Björnsson, E.
    Sect Gastroenterol & Hepatol, Dept Internal Med, Natl Univ Hosp, Reykjavik, Iceland.
    Bailey, Y.
    Dept Gastroenterol, Adelaide & Meath Hosp, Trinity College Dublin, Dublin, Ireland.
    O'Morain, C.
    Dept Gastroenterol, Adelaide & Meath Hosp, Trinity College Dublin, Dublin, Ireland.
    Schwartz, D.
    Odes, S.
    Dept Gastroenterol & Hepatol, Soroka Med Ctr, Beer Sheva, Israel; Ben Gurion Univ Negev, Beer Sheva, Israel .
    Politi, S. P.
    UO Med Interna & Gastroenterol, Azienda Osped Istituti Ospitalieri Cremona, Cremona, Italy; EpiCom Northern Italy Ctr, Crema Cremona, Italy; EpiCom Northern Italy Ctr, Florence, Italy; EpiCom Northern Italy Ctr, Forli, Italy; EpiCom Northern Italy Ctr, Padua, Italy; EpiCom Northern Italy Ctr, Reggio Emilia, Italy .
    Santini, A.
    Gastroenterol Unit, Careggi Hosp, Florence, Italy; EpiCom Northern Italy Ctr, Crema Cremona, Italy; EpiCom Northern Italy Ctr, Florence, Italy; EpiCom Northern Italy Ctr, Forli, Italy; EpiCom Northern Italy Ctr, Padua, Italy; EpiCom Northern Italy Ctr, Reggio Emilia, Italy .
    Kiudelis, G.
    Inst Digest Res, Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Kupcinskas, L.
    Inst Digest Res, Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Turcan, S.
    State Univ Med & Pharm Republ Moldova, Dept Gastroenterol, Kishinev, Moldova.
    Magro, F.
    Hosp Sao Joao, Dept Gastroenterol, Oporto, Portugal; Inst Pharmacol & Therapeut, Oporto Med Sch, Oporto, Portugal; Inst Mol & Cell Biol, Univ Porto, Oporto, Portugal.
    Barros, L.
    Hosp Vale Sousa, Oporto, Portugal.
    Lazar, D.
    Gastroenterol Clin, Univ Med Victor Babes, Timisoara, Romania.
    Goldis, A.
    Gastroenterol Clin, Univ Med Victor Babes, Timisoara, Romania.
    Nikulina, I.
    Dept Gastroenterol, Moscow Reg Res Clin Inst, Moscow, Russia.
    Belousova, E.
    Moscow Reg Res Clin Inst, Dept Gastroenterol, Moscow, Russia.
    Sanroman, L.
    Dept Gastroenterol, Complexo Hosp Univ Vigo, Vigo, Spain.
    Martinez-Ares, D.
    Dept Gastroenterol, Complexo Hosp Univ Vigo, Vigo, Spain.
    Almer, S.
    Dept Med, Div Gastroenterol & Hepatol, Karolinska Inst, Stockholm, Sweden; Dept Gastroenterol UHL, Cty Council Ostergötland, Linköping, Sweden .
    Zhulina, Yaroslava
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Div Gastroenterol, Dept Med, Örebro Univ Hosp, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden. Div Gastroenterol, Dept Med, Örebro Univ Hosp, Örebro, Sweden.
    Arebi, N.
    St Marks Hosp, Sir Alan Parks Physiol Unit, Univ London Imperial Coll Sci Technol & Med, London, England.
    Houston, Y.
    Hull & East Yorkshire HNS Trust, Dept Gastroenterol, Kingston Upon Hull, N Humberside, England.
    Sebastian, S.
    Hull & East Yorkshire NHS Trust, Hull Royal Infirm, Kingston Upon Hull, England; Hull & York Med Sch, Hull Royal Infirm, Kingston Upon Hull, England.
    Langholz, E.
    Dept Med Gastroenterol, Gentofte Univ Hosp, Copenhagen, Denmark.
    Lakatos, P. L.
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Munkholm, P.
    Med Sect, Ctr Digest Dis, Herlev Univ Hosp, Copenhagen, Denmark.
    Health care and patients' education in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom study2014In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, no 8, p. 811-818Article in journal (Refereed)
    Abstract [en]

    Background and Aims: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1 million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD).

    Methods: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers.

    Results: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p < 0.05), the main source was the Internet (92% vs. 88% p = 0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p < 0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p < 0.05).

    Conclusion: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management. (c) 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  • 47.
    Burisch, J.
    et al.
    Digestive Disease Centre, Medical Section, Herlev University Hospital, Copenhagen, Denmark .
    Weimers, P.
    Digestive Disease Centre, Medical Section, Herlev University Hospital, Copenhagen, Denmark .
    Pedersen, N.
    Digestive Disease Centre, Medical Section, Herlev University Hospital, Copenhagen, Denmark .
    Cukovic-Cavka, S.
    Division of Gastroenterology and Hepatology, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia .
    Vucelic, B.
    Division of Gastroenterology and Hepatology, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia .
    Kaimakliotis, I.
    Nicosia Private Practice, Nicosia, Cyprus.
    Duricova, D.
    IBD Center ISCARE, Charles University, Prague, Czech Republic.
    Bortlik, M.
    IBD Center ISCARE, Charles University, Prague, Czech Republic.
    Shonová, O.
    Gastroenterology Department, Hospital České Budějovice, České Budějovice, Czech Republic.
    Vind, I.
    Department of Medicine, Amager Hospital, Amager, Denmark .
    Avnstrøm, S.
    Department of Medicine, Amager Hospital, Amager, Denmark .
    Thorsgaard, N.
    Department of Medicine, Herning Central Hospital, Herning, Denmark .
    Krabbe, S.
    Medical Department, Viborg Regional Hospital, Viborg, Denmark .
    Andersen, V.
    Medical Department, Viborg Regional Hospital, Viborg, Denmark ; Medical Department, Hospital of Southern Jutland, Aabenraa, Denmark; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark .
    Dahlerup, J. F.
    Department of Medicine V, Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark .
    Kjeldsen, J.
    Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark .
    Salupere, R.
    Division of Endocrinology and Gastroenterology, Tartu University Hospital, Tartu, Estonia .
    Olsen, J.
    Medical Department, The National Hospital of the Faroe Islands, Torshavn, Denmark.
    Nielsen, K. R.
    Medical Department, The National Hospital of the Faroe Islands, Torshavn, Denmark.
    Manninen, P.
    Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland .
    Collin, P.
    Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland .
    Katsanos, K. H.
    1st Division of Internal Medicine and Division of Gastroenterology, Medical School, University of Ioannina, Ioannina, Greece .
    Tsianos, E. V.
    1st Division of Internal Medicine and Division of Gastroenterology, Medical School, University of Ioannina, Ioannina, Greece .
    Ladefoged, K.
    Medical Department, Dronning Ingrids Hospital, Nuuk, Greenland .
    Lakatos, L.
    Department of Medicine, Csolnoky F. Province Hospital, Veszprem, Hungary .
    Ragnarsson, G.
    Department of Internal Medicine, Section of Gastroenterology and Hepatology, The National University Hospital, Reykjavik, Iceland .
    Björnsson, E.
    Department of Internal Medicine, Section of Gastroenterology and Hepatology, The National University Hospital, Reykjavik, Iceland .
    Bailey, Y.
    Department of Gastroenterology, Adelaide and Meath Hospital, Trinity College Dublin, Dublin, Ireland .
    O'Morain, C.
    Department of Gastroenterology, Adelaide and Meath Hospital, Trinity College Dublin, Dublin, Ireland .
    Schwartz, D.
    Department of Gastroenterology and Hepatology, Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel ; Department of Gastroenterology and Hepatology, Ben Gurion University of the Negev, Beer Sheva, Israel.
    Odes, S.
    Department of Gastroenterology and Hepatology, Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel ; Department of Gastroenterology and Hepatology, Ben Gurion University of the Negev, Beer Sheva, Israel.
    Valpiani, D.
    U.O. Gastroenterologia ed Endoscopia Digestiva, Ospedale Morgagni - Pierantoni, Forlì, Italy.
    Boni, M. C.
    U.O. Medicina 3 e Gastroenterologia, Azienda Ospedaliera Arcispedale S. Maria Nuova, Reggio Emilia, Italy .
    Jonaitis, L.
    Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania .
    Kupcinskas, L.
    Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania .
    Turcan, S.
    Department of Gastroenterology, State University of Medicine and Pharmacy of the Republic of Moldova, Chisinau, Moldova.
    Barros, L.
    Hospital de Vale de Sousa, Porto, Portugal .
    Magro, F.
    Department of Gastroenterology, Hospital São João, Porto, Portugal; Institute of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal; IBMC - Institute for Molecular and Cell Biology, University of Porto, Porto, Portugal.
    Lazar, D.
    Clinic of Gastroenterology, University of Medicine 'Victor Babes', Timisoara, Romania .
    Goldis, A.
    Clinic of Gastroenterology, University of Medicine 'Victor Babes', Timisoara, Romania .
    Nikulina, I.
    Department of Gastroenterology, Moscow Regional Research Clinical Institute, Moscow, Russian Federation .
    Belousova, E.
    Department of Gastroenterology, Moscow Regional Research Clinical Institute, Moscow, Russian Federation .
    Fernandez, A.
    Gastroenterology Department, POVISA Hospital, Vigo, Spain .
    Sanroman, L.
    Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain .
    Almér, S.
    Division of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;Department of Gastroenterology/UHL, County Council of Östergötland, Linköping, Sweden.
    Zhulina, Yaroslava
    Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Arebi, N.
    St. Mark's Hospital, Imperial College London, London, United Kingdom.
    Diggory, T.
    Hull and East Yorkshire NHS Trust, Hull and York Medical School, Hull Royal Infirmary, Hull, United Kingdom; Hull and York Medical School, Hull Royal Infirmary, Hull, United Kingdom .
    Sebastian, S.
    Hull and East Yorkshire NHS Trust, Hull and York Medical School, Hull Royal Infirmary, Hull, United Kingdom; Hull and York Medical School, Hull Royal Infirmary, Hull, United Kingdom .
    Lakatos, P. L.
    1st Department of Medicine, Semmelweis University, Budapest, Hungary .
    Langholz, E.
    Department of Medical Gastroenterology, Gentofte Hospital, Copenhagen, Denmark .
    Munkholm, P.
    Digestive Disease Centre, Medical Section, Herlev University Hospital, Copenhagen, Denmark .
    Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with Inflammatory Bowel Disease: An ECCO-EpiCom study2014In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, no 9, p. 1030-1042Article in journal (Refereed)
    Abstract [en]

    Background & Aims: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe.

    Methods: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up.

    Results: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population.

    Conclusion: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

  • 48.
    Burisch, Johan
    et al.
    Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Munkholm, Pia
    Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark.
    The use of 5-aminosalicylate for patients with Crohn's disease in a prospective European inception cohort with 5 years follow-up - an Epi-IBD study2020In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 8, no 8, p. 949-960Article in journal (Refereed)
    Abstract [en]

    Background: The lack of scientific evidence regarding the effectiveness of 5-aminosalicylate in patients with Crohn's disease is in sharp contrast to its widespread use in clinical practice.

    Aims: The aim of the study was to investigate the use of 5-aminosalicylate in patients with Crohn's disease as well as the disease course of a subgroup of patients who were treated with 5-aminosalicylate as maintenance monotherapy during the first year of disease.

    Methods: In a European community-based inception cohort, 488 patients with Crohn's disease were followed from the time of their diagnosis. Information on clinical data, demographics, disease activity, medical therapy and rates of surgery, cancers and deaths was collected prospectively. Patient management was left to the discretion of the treating gastroenterologists.

    Results: Overall, 292 (60%) patients with Crohn's disease received 5-aminosalicylate period during follow-up for a median duration of 28 months (interquartile range 6-60). Of these, 78 (16%) patients received 5-aminosalicylate monotherapy during the first year following diagnosis. Patients who received monotherapy with 5-aminosalicylate experienced a mild disease course with only nine (12%) who required hospitalization, surgery, or developed stricturing or penetrating disease, and most never needed more intensive therapy. The remaining 214 patients were treated with 5-aminosalicylate as the first maintenance drug although most eventually needed to step up to other treatments including immunomodulators (75 (35%)), biological therapy (49 (23%)) or surgery (38 (18%)).

    Conclusion: In this European community-based inception cohort of unselected Crohn's disease patients, 5-aminosalicylate was commonly used. A substantial group of these patients experienced a quiescent disease course without need of additional treatment during follow-up. Therefore, despite the controversy regarding the efficacy of 5-aminosalicylate in Crohn's disease, its use seems to result in a satisfying disease course for both patients and physicians.

  • 49.
    Burisch, Johan
    et al.
    Department of gastroenterology, North Zealand Hospital, University of Copenhagen, Denmark.
    Chetcuti Zammit, Stefania
    Division of Gastroenterology, Mater Dei Hospital, Msida, Malta.
    Ellul, Pierre
    Division of Gastroenterology, Mater Dei Hospital, Msida, Malta.
    Turcan, Svetlana
    Department of Gastroenterology, State University of Medicine and Pharmacy of the Republic of Moldova, Chisinau, Republic of Moldova.
    Duricova, Dana
    IBD clinical and research centre, ISCARE., Prague, Czech Republic.
    Bortlik, Martin
    IBD clinical and research centre, ISCARE., Prague, Czech Republic; Institute of Pharmacology, 1st Faculty of Medicine, Charles University in Prague, Prague.
    Winther Andersen, Karina
    Medical Department, Regional Hospital of Viborg, Viborg, Denmark.
    Andersen, Vibeke
    Medical Department, Regional Hospital of Viborg, Viborg, Denmark; Focused research unit for Molecular Diagnostic and Clinical Research (MOK), IRS-Center Sonderjylland, Hospital of Southern Jutland, Aabenraa, Denmark; Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
    Kaimakliotis, Ioannis P.
    Nicosia private practice, Nicosia, Cyprus.
    Fumery, Mathurin
    Gastroenterology Unit, Epimad Registry, CHU Amiens Sud, Avenue Laennec-Salouel, Amiens University Hospital, Amiens, France.
    Gower-Rousseau, Corinne
    Public Health, Epidemiology and Economic Health, Registre Epimad, Lille University and Hospital, Lille, France; Lille Inflammation Research International Center LIRIC, Lille University, Lille, France.
    Girardin, Giulia
    Department of Surgical, Oncological and gastroenterological Sciences, Azienda, University of Padua, Padua, Italy.
    Valpiani, Daniela
    U.O. Gastroenterologia ed Endoscopia digestiva, Hospital Morgagni Pierantoni, Forlì, Italy.
    Goldis, Adrian
    Clinic of Gastroenterology, University of Medicine 'Victor Babes', Timisoara, Romania.
    Brinar, Marko
    Division of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia.
    Čuković-Čavka, Silvija
    Division of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia.
    Oksanen, Pia
    Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland; University of Tampere, Tampere, Finland.
    Collin, Pekka
    Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland; University of Tampere, Tampere, Finland.
    Barros, Luisa
    Department of Gastroenterology, Centro Hospitalar de São João EPE, Porto, Portugal.
    Magro, Fernando
    Department of Gastroenterology, Centro Hospitalar de São João EPE, Porto, Portugal; Department of Biomedicine, Institute of Pharmacology, Faculty of Medicine of Porto University, Porto, Portugal.
    Misra, Ravi
    IBD Department, St Marks Hospital, Imperial College London, London, UK.
    Arebi, Naila
    IBD Department, St Marks Hospital, Imperial College London, London, UK.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Gastroenterology.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Kievit, Hendrika Adriana Linda
    Department of Medicine, Herning Central Hospital, Herning, Denmark.
    Pedersen, Natalia
    Gastroenterology Department, Slagelse Hospital, Slagelse, Denmark.
    Kjeldsen, Jens
    Gastroenterology Department, Odense University Hospital, Odense, Denmark.
    Myers, Sally
    IBD Unit, Hull & East Yorkshire NHS Trust, Hull, UK.
    Sebastian, Shaji
    IBD Unit, Hull & East Yorkshire NHS Trust, Hull, UK.
    Katsanos, Konstantinos H.
    Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece.
    Christodoulou, Dimitrios K.
    Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece.
    Midjord, Jóngerð
    Medical Department, The National Hospital of the Faroe Islands, Torshavn, Faroe Islands.
    Nielsen, Kári Rubek
    Medical Department, The National Hospital of the Faroe Islands, Torshavn, Faroe Islands.
    Kiudelis, Gediminas
    Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
    Kupcinskas, Limas
    Institute for Digestive Research, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania; Department of Gastroenterology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
    Nikulina, Inna
    Department of Gastroenterology, Moscow Regional Research Clinical Institute, Moscow, Russian Federation.
    Belousova, Elena
    Department of Gastroenterology, Moscow Regional Research Clinical Institute, Moscow, Russian Federation.
    Schwartz, Doron
    Department of Gastroenterology and Hepatology, Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel.
    Odes, Selwyn
    Department of Gastroenterology and Hepatology, Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel.
    Salupere, Riina
    Department of Gastroenterology and Hepatology, Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel.
    Carmona, Amalia
    Department of Gastroenterology. Hospital POVISA, Vigo, Spain.
    Pineda, Juan R.
    Department of Gastroenterology. Hospital Alvaro Cunqueiro, Instituto Investigación Sanitaria Galicia Sur, EOXI de Vigo, Vigo, Spain.
    Vegh, Zsuzsanna
    1st Department of Medicine, Semmelweis University, Budapest, Hungary.
    Lakatos, Peter L.
    1st Department of Medicine, Semmelweis University, Budapest, Hungary; Division of Gastroenterology, McGill University Health Center, Montreal, Canada.
    Langholz, Ebbe
    Department of Gastroenterology, Herlev and Gentofte Hospital, University of Copenhagen, Denmark.
    Munkholm, Pia
    Department of gastroenterology, North Zealand Hospital, University of Copenhagen, Denmark.
    Epi-IBD, group
    Disease course of inflammatory bowel disease unclassified in a European population-based inception cohort: an Epi-IBD study2019In: Journal of Gastroenterology and Hepatology, ISSN 0815-9319, E-ISSN 1440-1746, Vol. 34, no 6, p. 996-1003Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A definitive diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) is not always possible and a proportion of patients will be diagnosed as inflammatory bowel disease unclassified (IBDU). The aim of the study was to investigate the prognosis of patients initially diagnosed with IBDU and the disease course during the following five years.

    METHODS: The Epi-IBD study is a prospective population-based cohort of 1,289 IBD patients diagnosed in centres across Europe. Clinical data were captured prospectively throughout the follow-up period.

    RESULTS: Overall, 476 (37%) patients were initially diagnosed with CD, 701 (54%) with UC, and 112 (9%) with IBDU. During follow-up, 28 (25%) IBDU patients were changed diagnoses to either UC (n=20, 71%) or CD (n=8, 29%) after a median of six months (IQR: 4-12), while 84 (7% of the total cohort) remained IBDU. A total of 17 (15%) IBDU patients were hospitalized for their IBD during follow-up, while 8 (7%) patients underwent surgery. Most surgeries (n=6, 75%) were performed on patients whose diagnosis was later changed to UC; three of these colectomies led to a definitive diagnosis of UC. Most patients (n=107, 96%) received 5-aminosalicylic acid, while 11 (10%) patients received biologicals, of whom five remained classified as IBDU.

    CONCLUSIONS: In a population-based inception cohort, 7% of IBD patients were not given a definitive diagnosis of IBD after five years of follow-up. One in four patients with IBDU eventually were classified as CD or UC. Overall, the disease course and medication burden in IBDU patients were mild.

  • 50. Burisch, Johan
    et al.
    Cukovic-Cavka, Silvija
    Kaimakliotis, Ioannis
    Shonová, Olga
    Andersen, Vibeke
    Dahlerup, Jens F
    Elkjaer, Margarita
    Langholz, Ebbe
    Pedersen, Natalia
    Salupere, Riina
    Kolho, Kaija-Leena
    Manninen, Pia
    Lakatos, Peter Laszlo
    Shuhaibar, Mary
    Odes, Selwyn
    Martinato, Matteo
    Mihu, Ion
    Magro, Fernando
    Belousova, Elena
    Fernandez, Alberto
    Almer, Sven
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences.
    Hart, Ailsa
    Munkholm, Pia
    Construction and validation of a web-based epidemiological database for inflammatory bowel diseases in Europe an EpiCom study2011In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 5, no 4, p. 342-349Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The EpiCom-study investigates a possible East-West-gradient in Europe in the incidence of IBD and the association with environmental factors. A secured web-based database is used to facilitate and centralize data registration.

    AIM: To construct and validate a web-based inception cohort database available in both English and Russian language.

    METHOD: The EpiCom database has been constructed in collaboration with all 34 participating centers. The database was translated into Russian using forward translation, patient questionnaires were translated by simplified forward-backward translation. Data insertion implies fulfillment of international diagnostic criteria, disease activity, medical therapy, quality of life, work productivity and activity impairment, outcome of pregnancy, surgery, cancer and death. Data is secured by the WinLog3 System, developed in cooperation with the Danish Data Protection Agency. Validation of the database has been performed in two consecutive rounds, each followed by corrections in accordance with comments.

    RESULTS: The EpiCom database fulfills the requirements of the participating countries' local data security agencies by being stored at a single location. The database was found overall to be "good" or "very good" by 81% of the participants after the second validation round and the general applicability of the database was evaluated as "good" or "very good" by 77%. In the inclusion period January 1st -December 31st 2010 1336 IBD patients have been included in the database.

    CONCLUSION: A user-friendly, tailor-made and secure web-based inception cohort database has been successfully constructed, facilitating remote data input. The incidence of IBD in 23 European countries can be found at www.epicom-ecco.eu.

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