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  • 1. 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.

  • 2.
    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.

  • 3.
    Burisch, Johan
    et al.
    Department of Gastroenterology, Nordsjællands Hospital, University of Copenhagen, Frederikssund, Denmark.
    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.
    Kievit, Hendrika Adriana Linda
    Department of Medicine, Herning Central Hospital, Herning, Denmark.
    Andersen, Karina Winther
    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.
    Salupere, Riina
    Division of Gastroenterology, Tartu University Hospital, University of Tartyu, Tartu, Estonia.
    Pedersen, Natalia
    Gastroenterology Department, Slagelse Hospital, Slagelse, Denmark.
    Kjeldsen, Jens
    Gastroenterology Department, Odense University Hospital, Odense, Denmark.
    D'Incà, Renata
    Department of Surgical, Oncological and Gastroenterological Sciences, Azienda, University of Padua, Padova, Italy.
    Valpiani, Daniela
    U.O. Gastroenterologia ed Endoscopia digestiva, Hospital Morgagni Pierantoni, Forlì, Italy.
    Schwartz, Doron
    Department of Gastroenterology and Hepatology, Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
    Odes, Selwyn
    Department of Gastroenterology and Hepatology, Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
    Olsen, Jóngerð
    Medical Department, The National Hospital of the Faroe Islands, Thorshavn, Denmark.
    Nielsen, Kári Rubek
    Medical Department, The National Hospital of the Faroe Islands, Thorshavn, Denmark.
    Vegh, Zsuzsanna
    1st Department of Medicine, Semmelweis University, Budapest, Hungary.
    Lakatos, Peter Laszlo
    1st Department of Medicine, Semmelweis University, Budapest, Hungary; Division of Gastroenterology, McGill University Health Center, Montreal, Canada.
    Toca, Alina
    Department of Gastroenterology, State University of Medicine and Pharmacy of the Republic of Moldova, Chisinau, Republic of Moldova.
    Turcan, Svetlana
    Department of Gastroenterology, State University of Medicine and Pharmacy of the Republic of Moldova, Chisinau, Republic of Moldova.
    Katsanos, Konstantinos H.
    Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece.
    Christodoulou, Dimitrios K
    Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece.
    Fumery, Mathurin
    Gastroenterology Unit, Epimad Registry, Centre hospitalier universitaire (CHU) Amiens Sud, Amiens University Hospital, Amiens, France.
    Gower-Rousseau, Corinne
    Public Health, Epidemiology and Economic Health, Registre Epimad, Lille Hospital, Lille University, Lille, France; Lille Inflammation Research International Center (LIRIC), Lille University, Lille, France.
    Zammit, Stefania Chetcuti
    Division of Gastroenterology, Mater Dei Hospital, Msida, Malta.
    Ellul, Pierre
    Division of Gastroenterology, Mater Dei Hospital, Msida, Malta.
    Eriksson, Carl
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Magro, Fernando Jose
    Department of Gastroenterology, Centro Hospitalar de São João EPE, Porto, Portugal; Department of Biomedicine, Institute of Pharmacology, Faculty of Medicine, Porto University, Porto, Portugal.
    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, Czech Republic.
    Fernandez, Alberto
    Department of Gastroenterology, Hospital POVISA, Vigo, Spain.
    Hernández, Vicent
    Department of Gastroenterology, Hospital Alvaro Cunqueiro. Instituto Investigación Sanitaria Galicia Sur. EOXI de Vigo, Vigo, Spain.
    Myers, Sally
    IBD Unit, Hull and East Yorkshire NHS Trust, Hull, UK.
    Sebastian, Shaji
    IBD Unit, Hull and East Yorkshire NHS Trust, Hull, UK.
    Oksanen, Pia
    Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland; University of Tampere, Tampere, Finland.
    Collin, Pekka
    University of Tampere, Tampere, Finland.
    Goldis, Adrian
    Clinic of Gastroenterology, University of Medicine 'Victor Babes', Timisoara, Romania.
    Misra, Ravi
    IBD Department, Imperial College London, London, UK.
    Arebi, Naila
    IBD Department, Imperial College London, London, UK.
    Kaimakliotis, Ioannis P.
    Nicosia private practice, Nicosia, Cyprus.
    Nikuina, 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.
    Brinar, Marko
    Division of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia.
    Cukovic-Cavka, Silvija
    Division of Gastroenterology and Hepatology, University Hospital Center Zagreb, Zagreb, Croatia.
    Langholz, Ebbe
    Department of Gastroenterology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
    Munkholm, Pia
    Department of Gastroenterology, Nordsjællands Hospital, University of Copenhagen, Frederikssund, Denmark.
    Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study2019In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 3, p. 423-433Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn's disease (CD).

    DESIGN: Patients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.

    RESULTS: In total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).

    CONCLUSION: Despite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

  • 4.
    Butwicka, Agnieszka
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland.
    Sariaslan, Amir
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Myrelid, Pär E.
    Division of Surgery, Department of Clinical and Experimental Medicine, Faulty of Health Sciences, Linköping University, Linköping, Sweden; Department of Surgery, County Council of Östergötland, Linköping, Sweden.
    Olén, Ola
    Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Frisen, Louise
    Child and Adolescent Psychiatry Research Center, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro University, Örebro, Sweden.
    No association between urbanisation, neighbourhood deprivation and IBD: a population-based study of 4 million individuals2019In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 5, p. 947-948Article in journal (Refereed)
  • 5.
    Eriksson, Carl
    et al.
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Rundquist, Sara
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis: a cohort study2019In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 4, p. 623-632Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Thiopurines are used as maintenance therapy in ulcerative colitis (UC), but whether these drugs influence the natural history of the disease is unknown. We aimed to assess the effect of thiopurines in terms of colectomy, hospital admission, progression in disease extent and anti-tumour necrosis factor (TNF) therapy within 10 years from initiation.

    DESIGN: Patients diagnosed with UC within the Örebro University Hospital catchment area, during 1963-2010, who initiated thiopurines (n=253) were included. To overcome the risk of confounding by indication, we compared patients who stopped treatment within 12 months because of an adverse reaction (n=76) with patients who continued therapy or discontinued due to other reasons (n=177) and assessed long-term outcomes using Cox regression with adjustment for potential confounding factors.

    RESULTS: The cumulative probability of colectomy within 10 years was 19.5% in tolerant patients compared with 29.0% in intolerant (adjusted HR 0.49; 95% CI 0.21 to 0.73). The probability of hospital admission was 34.0% in tolerant versus 56.2% in intolerant patients (adjusted HR 0.36; 95% CI 0.23 to 0.56). The risk for progression in disease extent was 20.4% in tolerant patients compared with 48.8% in intolerant (adjusted HR 0.47; 95% CI 0.21 to 1.06). Within 10 years, 16.1% of tolerant and 27.5% of intolerant patients received anti-TNF therapy (adjusted HR 0.49; 95% CI 0.26 to 0.92).

    CONCLUSION: Based on the novel approach of comparing patients tolerant and intolerant to thiopurines, we reveal that thiopurines have a profound beneficial impact of the natural history and long-term colectomy rates of UC.

  • 6.
    Fall, Katja
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
    Ye, W.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
    Nyrén, O.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, stockholm.
    Antibiotic treatment and risk of gastric cancer2006In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, no 6, p. 793-6Article in journal (Refereed)
    Abstract [en]

    Background/aims: Helicobacter pylori infection is undoubtedly an important risk factor for gastric cancer. It remains unclear however whether antibiotic treatment may prevent gastric cancer development. Our aim was to assess long term gastric cancer risks in historic cohorts of patients presumed to have been heavily exposed to antibiotics.

    Subjects: Using the Swedish Inpatient Register, we identified 501 757 individuals discharged with any one of 10 selected infectious disease diagnoses between 1970 and 2003.

    Methods: We counted person time and non-cardia gastric cancer occurrences through linkage to virtually complete population and health care registers. Standardised incidence ratios (SIRs) were calculated for comparisons with cancer incidence rates of the general population in Sweden.

    Results: No reduction in gastric cancer risk was observed in the infectious disease cohort in total (SIR 1.08 (95% confidence intervals 1.00-1.17) or for any of the presumed antibiotic regimens. There were no clear trends towards decreasing risk with time of follow up, but the risk tended to fall with increasing age at first hospitalisation for the infection (p<0.04).

    Conclusions: Our results do not confirm earlier observational findings of a reduced risk of gastric cancer following exposure to heavy antibiotic treatment among hip replacement patients. Suboptimal drug regimens, inadequate timing of H pylori eradication, or insufficient follow up time may possibly explain the lack of association in this setting. Although our findings do not rule out the cancer preventive potential of H pylori eradication, they emphasise that detection of such an effect, if any, may require considerable efforts.

  • 7. Gustavsson, A.
    et al.
    Halfvarson, Jonas
    Tysk, C.
    Järnerot, G.
    Long-term follow-up study of patients given an intensive intravenous corticosteroid therapy for severe attack of ulcerative colitis2005In: Gut, ISSN 0017-5749, E-ISSN 1468-3288Article in journal (Refereed)
  • 8. Gustavsson, A.
    et al.
    Järnerot, G.
    Hertervig, E.
    Friis-Liby, I.
    Blomquist, L.
    Karlen, P.
    Grännö, C.
    Vilien, M.
    Ström, M.
    Verbaan, H.
    Hellström, P. M.
    Halfvarson, Jonas
    Magnuson, A.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Colectomy after rescue therapy for intravenous-steroid resistant acute ulcerative colitis: a 3-year follow-up study of the Swedish-Danish infliximab/placebo trial2008In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57(Suppl 1), p. A79-A79Article in journal (Refereed)
  • 9. Halfvarson, Jonas
    et al.
    Jess, T.
    Bodin, L.
    Tysk, C.
    Binder, V.
    Järnerot, G.
    Concordance in phenotype in ulcerative colitis: a study in monozygotic twins2004In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 53, no Suppl VI, p. A145-A145Article in journal (Other academic)
  • 10. Halfvarson, Jonas
    et al.
    Jess, T.
    Jespersgaard, C.
    Riis, L.
    Tysk, C.
    Järnerot, G.
    Skytt Andersen, P.
    Munkholm, P.
    Prevalence of Toll-like receptor 2 and 4 polymorphisms in twins with inflammatory bowel disease: a population based Danish Swedish cohort study2005In: Gut, ISSN 0017-5749, E-ISSN 1468-3288Article in journal (Other academic)
  • 11. Halfvarson, Jonas
    et al.
    Standaert-Vitse, A
    Järnerot, G
    Sendid, B
    Jouault, T
    Bodin, L
    Duhamel, A
    Colombel, J F
    Tysk, C
    Poulain, D
    Anti-Saccharomyces cerevisiae antibodies in twins with inflammatory bowel disease2005In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 54, no 9, p. 1237-1243Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: An increased occurrence of anti-Saccharomyces cerevisiae antibodies (ASCA) is reported in unaffected members of families with Crohn's disease. Whether ASCA is a familial trait due to genetic factors or is caused by exposure to environmental factors is unknown. To assess the genetic influence of ASCA we studied its occurrence in a twin population.

    PATIENTS AND METHODS: ASCA were analysed in 98 twin pairs with inflammatory bowel disease and were related to clinical phenotype and CARD15/NOD2 genotype.

    RESULTS: ASCA were more common in Crohn's disease than in ulcerative colitis (40/70 (57%) twins v 5/43 (12%) twins). Associations with ileal Crohn's disease, stricturing/penetrating behaviour, and young age, but not CARD15/NOD2 were confirmed. ASCA were found in 1/20 (5%) healthy siblings in discordant monozygotic pairs with Crohn's disease compared with 7/27 (26%) in discordant dizygotic pairs. Using the intraclass correlation coefficient (ICC), no agreement in ASCA titres was observed in discordant twin pairs with Crohn's disease, in monozygotic (ICC = -0.02) or dizygotic (ICC = -0.26) pairs. In contrast, strong agreement was seen within concordant monozygotic twin pairs with Crohn's disease (ICC = 0.76).

    CONCLUSIONS: These findings question the concept of ASCA as a marker of genetic susceptibility for Crohn's disease. The agreement in ASCA titres within concordant monozygotic twin pairs with Crohn's disease, suggests that the level of increase is genetically determined. We propose that ASCA are a marker of a response to an environmental antigen and that a specific gene(s) other than CARD15/NOD2 determines the level of response and perhaps also specific phenotypic characteristics.

  • 12.
    Jakobsson, Hedvig E.
    et al.
    Dept Preparedness, Swedish Inst Communicable Dis Control, Solna, Sweden; Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Abrahamsson, Thomas R.
    Div Pediat, Dept Clin & Expt Med, Linköping Univ, Linköping, Sweden.
    Jenmalm, Maria C.
    Div Inflammat Med, Dept Clin & Expt Med, Linköping Univ, Linköping, Sweden.
    Harris, Keith
    School of Engineering, Univ Glasgow, Glasgow, UK.
    Quince, Christopher
    Sch Engn, Univ Glasgow, Glasgow, UK.
    Jernberg, Cecilia
    Dept Preparedness, Swedish Inst Communicable Dis Control, Solna, Sweden.
    Björkstén, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Inst Environm Med, Karolinska Inst, Stockholm, Sweden.
    Engstrand, Lars
    Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Andersson, Anders F.
    Sci Life Lab, Sch Biotechnol, Div Gene Technol, KTH Royal Inst Technol, Solna, Sweden.
    Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section2014In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 4, p. 559-566Article in journal (Refereed)
    Abstract [en]

    Objective The early intestinal microbiota exerts important stimuli for immune development, and a reduced microbial exposure as well as caesarean section (CS) has been associated with the development of allergic disease. Here we address how microbiota development in infants is affected by mode of delivery, and relate differences in colonisation patterns to the maturation of a balanced Th1/Th2 immune response.

    Design The postnatal intestinal colonisation pattern was investigated in 24 infants, born vaginally (15) or by CS (nine). The intestinal microbiota were characterised using pyrosequencing of 16S rRNA genes at 1 week and 1, 3, 6, 12 and 24 months after birth. Venous blood levels of Th1- and Th2-associated chemokines were measured at 6, 12 and 24 months.

    Results Infants born through CS had lower total microbiota diversity during the first 2 years of life. CS delivered infants also had a lower abundance and diversity of the Bacteroidetes phylum and were less often colonised with the Bacteroidetes phylum. Infants born through CS had significantly lower levels of the Th1-associated chemokines CXCL10 and CXCL11 in blood.

    Conclusions CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life.

  • 13. Jess, Tine
    et al.
    Halfvarson, Jonas
    Bodin, L.
    Tysk, C.
    Järnerot, G.
    Binder, V.
    Concordance for Vienna Classification Characteristics in monozygotic twins with Crohn’s disease: a Danish-Swedish cohort study of IBD twins2004In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 53, no Suppl VI, p. A140-A140Article in journal (Other academic)
  • 14. Joossens, S.
    et al.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden.
    Camps, M.
    Vermeire, S.
    Jarnerot, G.
    Stockbrugger, R.
    Bossuyt, X.
    Rutgeerts, P.
    Tysk, C.
    A panel of serologic markers in twins with inflammatory bowel disease2005In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, no Suppl.Article in journal (Refereed)
  • 15. Kalla, R.
    et al.
    Adams, A. T.
    Gastroenterology, University of Edinburgh, Edinburgh, UK.
    Vatn, S.
    Gastroenterology, Akershus University, Lorenskog, Norway.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Ricanek, P.
    Gastroenterology, Institute of Clinical Medicine, Oslo, Norway.
    Lindstrom, J. C.
    Gastroenterology, Akershus University, Lorenskog, Norway.
    Ocklind, A.
    Olink Proteomics, Uppsala, Sweden.
    Nordberg, N.
    Olink Proteomics, Uppsala, Sweden.
    Kennedy, N. A.
    Gastroenterology, University of Edinburgh, Edinburgh, UK.
    Ventham, N.
    Gastroenterology, University of Edinburgh, Edinburgh, UK.
    Vatn, M. H.
    Gastroenterology, Institute of Clinical Medicine, Oslo, Norway.
    Söderholm, J. D.
    Surgery, Linköping University, Linköping, Sweden.
    Pierik, M.
    Gastroenterology, Maastricht University Medical centre, Maastricht, Netherlands.
    Torkvist, L.
    Clinical Science, Karolinska Instituet, Karolinska, Sweden.
    Gomollon, F.
    Gastroenterology, HCU “Lozano Blesa” , Zaragosa, Spain.
    Jahnsen, J.
    Gastroenterology, Akershus University, Lorenskog, Norway.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Satsangi, J.
    Gastroenterology, University of Edinburgh, Edinburgh, UK.
    Proximity extension assay based proteins show immune cell specificity and can diagnose and predict outcomes in inflammatory bowel diseases: ibd character study2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no Suppl. 2, p. A202-A203, article id AODTH-008Article in journal (Other academic)
  • 16. Kalla, R.
    et al.
    Adams, A. T.
    Gastroenterology, University of Edinburgh, Edinburgh, UK.
    Vatn, S.
    Gastroenterology, Akershus University, Lorenskog, Norway.
    Bonfiglio, F.
    Gastroenterology, Biocruces Health Research Institute, Bilbao, Spain.
    Nimmo, E. R.
    Gastroenterology, University of Edinburgh, Edinburgh, UK.
    Kennedy, N. A.
    Gastroenterology, University of Edinburgh, Edinburgh, UK.
    Ventham, N.
    Gastroenterology, University of Edinburgh, Edinburgh, UK.
    Vatn, M. H.
    Gastroenterology, Institute of Clinical Medicine, Oslo, Norway.
    Ricanek, P.
    Gastroenterology, Institute of Clinical Medicine, Oslo, Norway.
    Bergemalm, Daniel
    Örebro University, School of Medical Sciences. Örebro University Hospital. Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Söderholm, J. D.
    Surgery, Linköping Univeristy, Linköping, Sweden.
    Pierik, M.
    Gastroenterology, Maastricht University Medical centre, Maastricht, Netherlands.
    Torkvist, L.
    Clinical Science, Karolinska Instituet, Karolinska, Sweden.
    Gomollon, F.
    Gastroenterology, HCU “Lozano Blesa”, Zaragosa, Spain.
    Gut, I.
    Centre for Genomic Regulation, CNAG-CRG, Barcelona, Spain.
    Jahnsen, J.
    Gastroenterology, Akershus University, Lorenskog, Norway.
    Satsangi, J.
    Gastroenterology, University of Edinburgh, Edinburgh, UK.
    Epigenetic alterations at diagnosis predict susceptibility, prognosis and treatment escalation in inflammatory bowel disease – ibd character2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no Suppl. 2, p. A24-A25, article id OC-047Article in journal (Other academic)
  • 17.
    Kantor, Elizabeth D.
    et al.
    Department of Epidemiology, Harvard School of Public Health, Boston, USA.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Signorello, Lisa B.
    Department of Epidemiology, Harvard School of Public Health, Boston, USA.
    Giovannucci, Edward L.
    Department of Epidemiology, Harvard School of Public Health, Boston, USA; Department of Nutrition, Harvard School of Public Health, Boston, USA; Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, USA.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Research Department of Epidemiology and Public Health, University College London, London, United Kingdom; Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Fall, Katja
    Örebro University, School of Medical Sciences. Department of Epidemiology, Harvard School of Public Health, Boston, USA; Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Adolescent body mass index and erythrocyte sedimentation rate in relation to colorectal cancer risk2016In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 65, no 8, p. 1289-1295Article in journal (Refereed)
    Abstract [en]

    Objective: Adult obesity and inflammation have been associated with risk of colorectal cancer (CRC); however, less is known about how adolescent body mass index (BMI) and inflammation, as measured by erythrocyte sedimentation rate (ESR), relate to CRC risk. We sought to evaluate these associations in a cohort of 239 658 Swedish men who underwent compulsory military enlistment examinations in late adolescence (ages 16-20 years).

    Design: At the time of the conscription assessment (1969-1976), height and weight were measured and ESR was assayed. By linkage to the national cancer registry, these conscripts were followed for CRC through 1 January 2010. Over an average of 35 years of follow-up, 885 cases of CRC occurred, including 501 colon cancers and 384 rectal cancers. Cox regression was used to estimate adjusted HRs and corresponding 95% CIs.

    Results: Compared with normal weight (BMI 18.5 to <25 kg/m(2)) in late adolescence, upper overweight (BMI 27.5 to <30 kg/m(2)) was associated with a 2.08-fold higher risk of CRC (95% CI 1.40 to 3.07) and obesity (BMI 30+ kg/m(2)) was associated with a 2.38-fold higher risk of CRC (95% CI 1.51 to 3.76) (p-trend: <0.001). Male adolescents with ESR (15+ mm/h) had a 63% higher risk of CRC (HR 1.63; 95% CI 1.08 to 2.45) than those with low ESR (<10 mm/h) (p-trend: 0.006). Associations did not significantly differ by anatomic site.

    Conclusions: Late-adolescent BMI and inflammation, as measured by ESR, may be independently associated with future CRC risk. Further research is needed to better understand how early-life exposures relate to CRC.

  • 18.
    Kuja-Halkola, Ralf
    et al.
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lebwohl, Benjamin
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Celiac Disease Center, Columbia University Medical Center, Columbia University, New York, USA.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wijmenga, Cisca
    Department of Genetics, University Medical Center, University of Groningen, Groningen, The Netherlands.
    Magnusson, Patrik K. E.
    Department Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Department 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, City Hospital, University of Nottingham, Nottingham, UK.
    Heritability of non-HLA genetics in coeliac disease: a population-based study in 107 000 twins2016In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 65, no 11, p. 1793-1798Article in journal (Refereed)
    Abstract [en]

    Background and objective: Almost 100% individuals with coeliac disease (CD) are carriers of the human leucocyte antigen (HLA) DQ2/DQ8 alleles. Earlier studies have, however, failed to consider the HLA system when estimating heritability in CD, thus violating an underlying assumption of heritability analysis. We examined the heritability of CD in a large population-based sample of twins, considering HLA.

    Design: In a population-representative sample of 107 912 twins, we identified individuals with CD (equal to villous atrophy) through biopsy reports from all Swedish pathology departments. We calculated concordance rates and tetrachoric correlations for monozygotic (MZ) and dizygotic (DZ) twin pairs. Further, we estimated heritability of CD, first strictly from observed data, and then the non-HLA heritability, representing the heritability of all genetic factors except the HLA locus, using an approach that circumvent the violation of underlying assumptions.

    Results: We identified 513 twins with a diagnosis of CD (prevalence 0.48%). Concordance rates were higher in MZ pairs (0.49) than in DZ pairs (0.10), as were tetrachoric correlations (0.89 in MZ vs 0.51 in DZ pairs). The heritability of CD was 75% (95% CI 55% to 96%). The non-HLA heritability was slightly attenuated, 68% (95% CI 40% to 96%), with shared (17%) and non-shared (15%) environmental factors explaining the remaining variability of CD.

    Conclusions: CD is characterised by a high heritability, but our study also suggests that non-shared environmental factors may be of importance to CD development. HLA seems to have only moderate impact on heritability estimates.

  • 19. Kumawat, Ashok Kumar
    et al.
    Strid, H.
    Elgbratt, K.
    Nyhlin, Nils
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Bohr, J.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Collagenous colitis patients demonstrate a Th1/CTL-associated gene expression profile with increased frequencies of Ki67+ proliferating and CD45RO+ activated/memory CD8+ and CD4+8+ mucosal T cells2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no Suppl. 3, p. A318-Article in journal (Refereed)
  • 20.
    Kurien, Matthew
    et al.
    Gastroenterol & Liver Unit, Royal Hallamshire Hosp, Sheffield, England; Univ Sheffield, Sheffield, England.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Sanders, David S.
    Gastroenterol & Liver Unit, Royal Hallamshire Hosp, Sheffield, England; Univ Sheffield, Sheffield, England.
    A no biopsy strategy for adult patients with suspected coeliac disease: making the world gluten-free2015In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 64, no 6, p. 1003-1004Article in journal (Refereed)
  • 21. Labus, J. S.
    et al.
    Mayer, E. A.
    Jarcho, J.
    Kilpatrick, L. A.
    Kilkens, T. O. C.
    Evers, E. A. T.
    Backes, W. H.
    Brummer, Robert Jan
    Örebro University, School of Health and Medical Sciences.
    van Nieuwenhoven, Michiel A
    Acute tryptophan depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy women2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no 9, p. 1196-1203Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Alterations in serotonin signalling within the brain-gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD.

    METHODS: 12 healthy females (19-25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24-50 years).

    RESULTS: In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C.

    CONCLUSIONS: The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced visceral hyperalgesia in healthy controls, and the near-identical effective connectivity pattern observed in patients with IBS-C, these findings suggest that dysregulation of this brain network may play a role in central pain amplification and IBS pathophysiology.

  • 22.
    Ludvigsson, Jonas F.
    et al.
    Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Bai, Julio C.
    Dept Med, Dr C Bonorino Udaondo Gastroenterol Hosp, Salvador Univ, Buenos Aires DF, Argentina.
    Biagi, Federico
    Dept Internal Med 1, Coeliac Ctr, IFdn IRCCS Policlin San Matteo, Univ Pavia, Pavia, Italy.
    Card, Timothy R.
    Dept Epidemiol & Publ Hlth, City Hosp Nottingham, Univ Nottingham, Nottingham, England..
    Ciacci, Carolina
    Dept Med & Surg, Univ Salerno, Salerno, Italy.
    Ciclitira, Paul J.
    Div Nutr Sci, Rayne Inst, St Thomas Hosp, Kings College, London, England.
    Green, Peter H. R.
    Coeliac Dis Ctr, Columbia Univ, New York NY, USA.
    Hadjivassiliou, Marios
    Royal Hallamshire Hosp, Dept Neurol, Royal Hallamshire Hosp, Sheffield, England.
    Holdoway, Anne
    British Dietet Assoc, Bath, England.
    van Heel, David A.
    Blizard Inst, Barts & London Sch Med & Dent, Queen Mary Univ, London, England.
    Kaukinen, Katri
    Sch Med, Univ Tampere, Tampere, Finland; Dept Gastroenterol & Alimentary Tract Surg, Tampere Univ Hosp, Tampere, Finland; Dept Med, Seinajoki Cent Hosp, Seinajoki, Finland.
    Leffler, Daniel A.
    Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Harvard Univ, Boston MA, USA.
    Leonard, Jonathan N.
    Dept Dermatol, St Marys Hosp, Imperial Coll NHS Healthcare Trust, London, England.
    Lundin, Knut E. A.
    Dept Gastroenterol,Ctr Immune Regulat, Oslo Univ Hosp, Univ Oslo, Oslo, Norway.
    McGough, Norma
    Apollo Ctr, Coeliac UK, London, England..
    Davidson, Mike
    Coeliac UK, Sheffield, England.
    Murray, Joseph A.
    Dept Immunol, Div Gastroenterol & Hepatol, Mayo Clin, Rochester MN, USA.
    Swift, Gillian L.
    Dept Gastroenterol, Univ Hosp, Llandough, UK.
    Walker, Marjorie M.
    Fac Hlth & Med, Sch Med & Publ Hlth, Univ Newcastle, Callaghan NSW, Australia.
    Zingone, Fabiana
    Dept Med & Surg, Univ Salerno, Salerno, Italy.
    Sanders, David S.
    Gastroenterol & Liver Unit, Royal Hallamshire Hosp, Sheffield, England; Univ Sheffield, Sheffield, England.
    Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology2014In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 8, p. 1210-1228Article in journal (Refereed)
    Abstract [en]

    A multidisciplinary panel of 18 physicians and 3 non-physicians from eight countries (Sweden, UK, Argentina, Australia, Italy, Finland, Norway and the USA) reviewed the literature on diagnosis and management of adult coeliac disease (CD). This paper presents the recommendations of the British Society of Gastroenterology. Areas of controversies were explored through phone meetings and web surveys. Nine working groups examined the following areas of CD diagnosis and management: classification of CD; genetics and immunology; diagnostics; serology and endoscopy; follow-up; gluten-free diet; refractory CD and malignancies; quality of life; novel treatments; patient support; and screening for CD.

  • 23.
    Ludvigsson, Jonas F.
    et al.
    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.
    Ciacci, Carolina
    Coeliac Center at Department of Medicine and Surgery, Scuola Medica Salernitana, University of Salerno, Salerno, Italy.
    Green, Peter H. R.
    Celiac Disease Center at Columbia University, New York, USA.
    Kaukinen, Katri
    Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; Department of Internal Medicine, Tampere University Hospital, Tampere, Finland.
    Korponay-Szabo, Ilma R.
    Coeliac Disease Centre, Heim Pál Children’s Hospital, Budapest, Hungary; Department of Paediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
    Kurppa, Kalle
    Celiac Disease Research Center, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland; Department of Paediatrics, Tampere University Hospital, Tampere, Finland.
    Murray, Joseph A.
    The Mayo Clinic, Rochester Minnesota, USA.
    Lundin, Knut Erik Aslaksen
    Institute of Clinical Medicine and K. G. Jebsen Coeliac Disease Research Centre, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterology, Oslo University Hospital, Oslo, Norway.
    Maki, Markku J.
    Science Center, Tampere University Hospital, Tampere, Finland; Tampere Centre for Child Health Research, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland.
    Popp, Alina
    Institute for Mother and Child Health Bucharest, University of Medicine and Pharmacy ’Carol Davila’, Bucharest, Romania; Tampere Centre for Child Health Research, University of Tampere, Tampere University Hospital, Tampere,Finland.
    Reilly, Norelle R.
    Division of Pediatric Gastroenterology, Columbia University Medical Center, New York, USA; Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, USA.
    Rodriguez-Herrera, Alfonso
    Gupo IHP Pediatria, Sevilla, Spain.
    Sanders, David S.
    Academic Unit of Gastroenterology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK.
    Schuppan, Detlef
    Celiac Center, University Medical Center, Johannes-Gutenberg University, Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
    Sleet, Sarah
    Coeliac UK, Buckinghamshire, UK.
    Taavela, Juha
    Tampere Centre for Child Health Research, University of Tampere, Tampere University Hospital, Tampere, Finland.
    Voorhees, Kristin
    Continuum Clinical, Northbrook, Illinois, USA.
    Walker, Marjorie M.
    Faculty of Health and Medicine, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
    Leffler, Daniel A.
    Celiac Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
    Outcome measures in coeliac disease trials: the Tampere recommendations2018In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 8, p. 1410-1424Article in journal (Refereed)
    Abstract [en]

    Objective: A gluten-free diet is the only treatment option of coeliac disease, but recently an increasing number of trials have begun to explore alternative treatment strategies. We aimed to review the literature on coeliac disease therapeutic trials and issue recommendations for outcome measures.

    Design: Based on a literature review of 10 062 references, we (17 researchers and 2 patient representatives from 10 countries) reviewed the use and suitability of both clinical and non-clinical outcome measures. We then made expert-based recommendations for use of these outcomes in coeliac disease trials and identified areas where research is needed.

    Results: We comment on the use of histology, serology, clinical outcome assessment (including patient-reported outcomes), quality of life and immunological tools including gluten immunogenic peptides for trials in coeliac disease.

    Conclusion: Careful evaluation and reporting of outcome measures will increase transparency and comparability of coeliac disease therapeutic trials, and will benefit patients, healthcare and the pharmaceutical industry.

  • 24.
    Ludvigsson, Jonas F.
    et al.
    Örebro University Hospital. Clin Epidemiol Unit, Dept Med, Karolinska Inst, Stockholm, Sweden; Dept Paediat, Örebro University Hospital, Örebro, Sweden.
    Leffler, Daniel A.
    Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Harvard Univ, Boston MA, USA.
    Bai, Julio C.
    Dept Med, Dr C Bonorino Udaondo Gastroenterol Hosp, Del Salvador Univ, Buenos Aires DF, Argentina.
    Biagi, Federico
    Dept Internal Med 1, Coeliac Ctr, Univ Pavia, Pavia, Italy.
    Fasano, Alessio
    Sch Med, Ctr Coeliac Res, Univ Maryland, Baltimore MD, USA.
    Green, Peter H. R.
    Coeliac Dis Ctr, Columbia Univ, New York NY, USA.
    Hadjivassiliou, Marios
    Dept Neurol, Royal Hallamshire Hosp, Sheffield, England.
    Kaukinen, Katri
    School of Medicine, University Tampere, Tampere, Finland.
    Kelly, Ciaran P.
    Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Harvard University, Boston MA, USA.
    Leonard, Jonathan N.
    Dept Dermatol, St Marys Hosp, Imperial Coll, NHS Healthcare Trust, London, England.
    Lundin, Knut Erik Aslaksen
    Dept Gastroenterol, Oslo University Hosp, Oslo, Norway; Center of Immune Regulation, Oslo University Hospital, Oslo, Norway.
    Murray, Joseph A.
    Dept Gastroenterol & Hepatol, Mayo Clinic, Rochester MN, USA.
    Sanders, David S.
    Gastroenterol & Liver Unit, Royal Hallamshire Hosp, University Sheffield, Sheffield, England; University of London Imperial Coll Sci Technol & Med, London, England; Fac Med, Ctr Pathol, St Marys Hosp, London, England.
    Walker, Marjorie M.
    Sci Technol & Med, St Marys Hosp, Fac Med, Ctr Pathol, Imperial College, London, England.
    Zingone, Fabiana
    Dept Clin & Expt Med, Univ Naples Federico II, Naples, Italy.
    Ciacci, Carolina
    Dept Gastroenterol, Univ Salerno, Salerno, Italy.
    The Oslo definitions for coeliac disease and related terms2013In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 62, no 1, p. 43-52Article in journal (Refereed)
    Abstract [en]

    Objective The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. Design A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to 'CD', the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. Results CD was defined as 'a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Classical CD was defined as 'CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.' 'Gluten-related disorders' is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. Conclusion This paper presents the Oslo definitions for CD-related terms.

  • 25.
    Ludvigsson, Jonas F.
    et al.
    Örebro University, School of Health and Medical Sciences.
    Olén, O.
    Bell, M.
    Ekbom, A.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Coeliac disease and risk of sepsis2008In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57, no 8, p. 1074-1080Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the risk of subsequent sepsis in individuals with coeliac disease.Design: We used Swedish national health registers to identify 15 325 individuals with a diagnosis of coeliac disease (1964–2003) and 14 494 inpatient reference individuals. Cox regression estimated the hazard ratios (HRs) for subsequent sepsis.Results: Compared with inpatient reference individuals, individuals with coeliac disease were at increased risk of sepsis (HR  = 1.6, 95% confidence interval (95% CI)  = 1.2 to 1.9, p<0.001). The highest risk estimates were seen for pneumococcal sepsis (HR  = 2.5, 95% CI  = 1.2 to 5.1, p = 0.014). Individuals with coeliac disease diagnosed in childhood were not at increased risk of subsequent sepsis (HR  = 1.0, 95% CI  = 0.6 to 1.9, p = 0.908). When individuals with coeliac disease were compared with reference individuals from the general population, coeliac disease was associated with an increased risk of sepsis (HR  = 2.6, 95% CI  = 2.1 to 3.0, p<0.001). The HR for pneumococcal sepsis was 3.9 (95% CI  = 2.2 to 7.0, p<0.001). In this comparison, children with coeliac disease were also at an increased risk of sepsis (HR  = 1.8, 95% CI  = 1.2 to 2.7, p = 0.003).Conclusion: This study showed a modestly increased risk of sepsis in patients with coeliac disease with the highest risk for pneumococcal sepsis. This risk increase was limited to those with coeliac disease diagnosed in adulthood. Potential explanations include hyposplenism, increased mucosal permeability and an altered composition of the intestinal glycocalyx in individuals with coeliac disease.

  • 26.
    Ludvigsson, Jonas F.
    et al.
    Örebro University Hospital. Örebro University, School of Medical Sciences. 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, City Hospital, University of Nottingham, Nottingham, UK; Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
    Sjölander, Arvid
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Murray, Joseph A.
    Division of Gastroenterology and Hepatology, Department of Immunology, Mayo Clinic, Rochester MN, USA.
    Hjalgrim, Henrik
    Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark; Department of Hematology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
    Edgren, Gustaf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
    Haemoglobin decline before coeliac disease diagnosis: a nationwide transfusion cohort study of 1.1 million blood donors2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 11, p. 2036-2037Article in journal (Refereed)
  • 27.
    Munch, Andreas
    et al.
    Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Bohr, Johan
    Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Miehlke, Stephan
    Centre for Digestive Disease, Hamburg, Germany.
    Benoni, Cecilia
    Department of Gastroenterology, University Hospital, Malmö, Sweden.
    Olesen, Martin
    Department of Pathology, University Hospital, Malmö, Sweden.
    Öst, Åke
    Department of Pathology and Cytology, Aleris Medilab, Täby, Sweden.
    Strandberg, Lars
    Regional Hospital, Falun, Sweden.
    Hellström, Per M.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Hertervig, Erik
    Department of Gastroenterology, University Hospital, Lund, Sweden.
    Armerding, Peter
    Gastroenterology, Private Practice, Berlin, Germany.
    Stehlik, Jiri
    Department of Gastroenterology, Regional Hospital, Usti nad Labem, Czech Republic.
    Lindberg, Greger
    Centre for Digestive Diseases, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Björk, Jan
    Centre for Digestive Diseases, Karolinska University Hospital Solna, Stockholm, Sweden.
    Lapidus, Annika
    Department of Gastroenterology, Ersta Hospital, Stockholm, Sweden.
    Löfberg, Robert
    IBD Unit, Department of Gastroenterology, Sophiahemmet, Stockholm, Sweden.
    Bonderup, Ole
    Department of Gastroenterology, Regional Hospital, Silkeborg, Denmark.
    Avnström, Sören
    Department of Gastroenterology, Amager Hospital, Copenhagen, Denmark.
    Rössle, Martin
    Gastroenterology, Private Practice, Freiburg, Germany.
    Dilger, Karin
    Dr Falk Pharma GmbH, Freiburg, Germany.
    Mueller, Ralph
    Dr Falk Pharma GmbH, Freiburg, Germany.
    Greinwald, Roland
    Dr Falk Pharma GmbH, Freiburg, Germany.
    Tysk, Curt
    Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Ström, Magnus
    Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial2016In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 65, no 1, p. 47-56Article in journal (Refereed)
    Abstract [en]

    Objective: This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis.

    Design: A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase.

    Results: Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious.

    Conclusions: Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation.

  • 28.
    Murphy, E. F.
    et al.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Alimentary Health Ltd, Cork, Ireland.
    Cotter, P. D.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Teagasc Moorepark Food Research Centre, Fermoy, Ireland.
    Healy, S.
    Alimentary Health Ltd, Cork, Ireland.
    Marques, Tatiana M.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Teagasc Moorepark Food Research Centre, Fermoy, Ireland.
    O'Sullivan, O.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Teagasc Moorepark Food Research Centre, Fermoy, Ireland.
    Fouhy, F.
    Teagasc Moorepark Food Research Centre, Fermoy, Ireland.
    Clarke, S. F.
    Teagasc Moorepark Food Research Centre, Fermoy, Ireland; Department of Microbiology, University College Cork, Cork, Ireland.
    O'Toole, P. W.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Microbiology, University College Cork, Cork, Ireland.
    Quigley, E. M.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
    Stanton, C.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Teagasc Moorepark Food Research Centre, Fermoy, Ireland.
    Ross, P. R.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Teagasc Moorepark Food Research Centre, Fermoy, Ireland.
    O'Doherty, R. M.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, USA.
    Shanahan, F.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
    Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models2010In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 59, no 12, p. 1635-42Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Increased efficiency of energy harvest, due to alterations in the gut microbiota (increased Firmicutes and decreased Bacteroidetes), has been implicated in obesity in mice and humans. However, a causal relationship is unproven and contributory variables include diet, genetics and age. Therefore, we explored the effect of a high-fat (HF) diet and genetically determined obesity (ob/ob) for changes in microbiota and energy harvesting capacity over time.

    METHODS: Seven-week-old male ob/ob mice were fed a low-fat diet and wild-type mice were fed either a low-fat diet or a HF-diet for 8 weeks (n=8/group). They were assessed at 7, 11 and 15 weeks of age for: fat and lean body mass (by NMR); faecal and caecal short-chain fatty acids (SCFA, by gas chromatography); faecal energy content (by bomb calorimetry) and microbial composition (by metagenomic pyrosequencing).

    RESULTS: A progressive increase in Firmicutes was confirmed in both HF-fed and ob/ob mice reaching statistical significance in the former, but this phylum was unchanged over time in the lean controls. Reductions in Bacteroidetes were also found in ob/ob mice. However, changes in the microbiota were dissociated from markers of energy harvest. Thus, although the faecal energy in the ob/ob mice was significantly decreased at 7 weeks, and caecal SCFA increased, these did not persist and faecal acetate diminished over time in both ob/ob and HF-fed mice, but not in lean controls. Furthermore, the proportion of the major phyla did not correlate with energy harvest markers.

    CONCLUSION: The relationship between the microbial composition and energy harvesting capacity is more complex than previously considered. While compositional changes in the faecal microbiota were confirmed, this was primarily a feature of high-fat feeding rather than genetically induced obesity. In addition, changes in the proportions of the major phyla were unrelated to markers of energy harvest which changed over time. The possibility of microbial adaptation to diet and time should be considered in future studies.

  • 29.
    Murphy, Eileen F.
    et al.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Alimentary Health Ltd., Cork, Ireland.
    Cotter, Paul D.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Fermoy, Ireland.
    Hogan, Aileen
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
    O'Sullivan, Orla
    Teagasc Food Research Centre, Fermoy, Ireland.
    Joyce, Andy
    Alimentary Health Ltd., Cork, Ireland.
    Fouhy, Fiona
    Teagasc Food Research Centre, Fermoy, Ireland; Department of Microbiology, University College Cork, Cork, Ireland.
    Clarke, Siobhan F.
    Teagasc Food Research Centre, Fermoy, Ireland; Department of Microbiology, University College Cork, Cork, Ireland.
    Marques, Tatiana M.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Fermoy, Ireland.
    O'Toole, Paul W.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Microbiology, University College Cork, Cork, Ireland.
    Stanton, Catherine
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Fermoy, Ireland.
    Quigley, Eamonn M. M.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Medicine, University College Cork, Cork, Ireland.
    Daly, Charlie
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
    Ross, Paul R.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Fermoy, Ireland.
    O'Doherty, Robert M.
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh PA, USA.
    Shanahan, Fergus
    Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Medicine, University College Cork, Cork, Ireland.
    Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity2013In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 62, no 2, p. 220-226Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The gut microbiota is an environmental regulator of fat storage and adiposity. Whether the microbiota represents a realistic therapeutic target for improving metabolic health is unclear. This study explored two antimicrobial strategies for their impact on metabolic abnormalities in murine diet-induced obesity: oral vancomycin and a bacteriocin-producing probiotic (Lactobacillus salivarius UCC118 Bac(+)).

    DESIGN: Male (7-week-old) C57BL/J6 mice (9-10/group) were fed a low-fat (lean) or a high-fat diet for 20 weeks with/without vancomycin by gavage at 2 mg/day, or with L. salivarius UCC118Bac(+) or the bacteriocin-negative derivative L. salivarius UCC118Bac(-) (each at a dose of 1×10(9) cfu/day by gavage). Compositional analysis of the microbiota was by 16S rDNA amplicon pyrosequencing.

    RESULTS: Analysis of the gut microbiota showed that vancomycin treatment led to significant reductions in the proportions of Firmicutes and Bacteroidetes and a dramatic increase in Proteobacteria, with no change in Actinobacteria. Vancomycin-treated high-fat-fed mice gained less weight over the intervention period despite similar caloric intake, and had lower fasting blood glucose, plasma TNFα and triglyceride levels compared with diet-induced obese controls. The bacteriocin-producing probiotic had no significant impact on the proportions of Firmicutes but resulted in a relative increase in Bacteroidetes and Proteobacteria and a decrease in Actinobacteria compared with the non-bacteriocin-producing control. No improvement in metabolic profiles was observed in probiotic-fed diet-induced obese mice.

    CONCLUSION: Both vancomycin and the bacteriocin-producing probiotic altered the gut microbiota in diet-induced obese mice, but in distinct ways. Only vancomycin treatment resulted in an improvement in the metabolic abnormalities associated with obesity thereby establishing that while the gut microbiota is a realistic therapeutic target, the specificity of the antimicrobial agent employed is critical.

  • 30. Münch, A.
    et al.
    Bohr, J.
    Vigren, L.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Ström, M.
    Methotrexate is not effective in budesonide-refractory collagenous colitis2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no Suppl 3, p. A406-A406Article in journal (Refereed)
  • 31.
    Ng, Siew C.
    et al.
    Li Ka Shing Inst Hlth Sci, Dept Med & Therapeut, Inst Digest Dis, Chinese Univ, Hong Kong, China.
    Bernstein, Charles N.
    Dept Internal Med, IBD Clin & Res Ctr, University Manitoba, Winnipeg MB, Canada.
    Vatn, Morten H.
    Dept Gastroenterol, Inst Clin Med, EpiGen, University of Oslo, Oslo, Norway.
    Lakatos, Peter Laszlo
    Dept Med 1, Semmelweis University, Budapest, Hungary.
    Loftus, Edward V., Jr.
    Div Gastroenterol & Hepatol, Mayo Clin, Rochester MN, USA.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Gastroenterol.
    O'Morain, Colm
    Dept Gastroenterol, Adelaide & Meath Hosp, Trinity Coll Dublin, Dublin, Ireland.
    Moum, Björn
    Dept Gastroenterol, University of Oslo Hosp, Oslo, Norway; Inst Clin Med, University of Oslo, Oslo, Norway.
    Colombel, Jean-Frederic
    Div Gastroenterol, Mt Sinai Sch Med, New York NY, USA.
    Geographical variability and environmental risk factors in inflammatory bowel disease2013In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 62, no 4, p. 630-649Article in journal (Refereed)
    Abstract [en]

    The changing epidemiology of inflammatory bowel disease (IBD) across time and geography suggests that environmental factors play a major role in modifying disease expression. Disease emergence in developing nations suggests that epidemiological evolution is related to westernisation of lifestyle and industrialisation. The strongest environmental associations identified are cigarette smoking and appendectomy, although neither alone explains the variation in incidence of IBD worldwide. Urbanisation of societies, associated with changes in diet, antibiotic use, hygiene status, microbial exposures and pollution have been implicated as potential environmental risk factors for IBD. Changes in socioeconomic status might occur differently in different geographical areas and populations and, consequently, it is important to consider the heterogeneity of risk factors applicable to the individual patient. Environmental risk factors of individual, familial, community-based, country-based and regionally based origin may all contribute to the pathogenesis of IBD. The geographical variation of IBD provides clues for researchers to investigate possible environmental aetiological factors. The present review aims to provide an update of the literature exploring geographical variability in IBD and to explore the environmental risk factors that may account for this variability.

  • 32. Nyhlin, Nils
    et al.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Wickbom, Anna
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Abdominal pain is common in microscopic colitis despite remission: a long-term follow-up of 203 patients2008In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57, no suppl IArticle in journal (Other academic)
  • 33. Oxelmark, L.
    et al.
    Lindberg, A.
    Löfberg, R.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Lapidus, A. B.
    Eriksson, A. S.
    Sternby, B.
    Benoni, C.
    Almer, S.
    Kilander, A.
    Danielsson, Å.
    SOIBD KAM, Study group
    Complementary and alternative medicine in patients with inflammatory bowel disease2010In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 59, no suppl 3, p. A409-A409Article in journal (Refereed)
  • 34.
    Reilly, Norelle R.
    et al.
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA; Division of Pediatric Gastroenterology, Department of Pediatrics, Columbia University Medical Center, New York NY, USA.
    Green, Peter H. R.
    Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    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.
    No difference in emergency department visits before and after transition for coeliac disease2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 11, p. 2039-2040Article in journal (Refereed)
  • 35.
    Siegel, Corey A.
    et al.
    Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon NH, USA.
    Whitman, Cynthia B.
    Department of Health Services, Cedars-Sinai Medical Center, Los Angeles CA, USA.
    Spiegel, Brennan M. R.
    Department of Health Services, Cedars-Sinai Medical Center, Los Angeles CA, USA.
    Feagan, Brian
    Department of Health Services, Cedars-Sinai Medical Center, Los Angeles California, USA.
    Sands, Bruce
    Icahn School of Medicine at Mount Sinai, New York, USA.
    Loftus, Edward V.
    Mayo Clinic, Rochester MN, USA.
    Panaccione, Remo
    University of Calgary, Calgary AB, Canada.
    D'Haens, Geert
    Academic Medical Center, Amsterdam, Netherlands.
    Bernstein, Charles N.
    University of Manitoba, Winnipeg MB, Canada.
    Gearry, Richard
    University of Otago, Christchurch, New Zealand.
    Ng, Siew C.
    Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
    Mantzaris, Gerassimos J.
    Evangelismos-PolyCliniki-Ophthalmiatreion Hospital, Athens, Greece.
    Sartor, Balfour
    University of North Carolina, Chapel Hill NC, USA.
    Silverberg, Mark S.
    Mount Sinai Hospital, Toronto ON, Canada.
    Riddell, Robert
    Mount Sinai Hospital, Toronto ON, Canada.
    Koutroubakis, Ioannis E.
    University Hospital Heraklion, Crete, Greece.
    O'Morain, Colm
    Faculty of Health Sciences Trinity College Dublin, Dublin, Ireland.
    Lakatos, Peter L.
    Semmelweis University, Budapest, Hungary.
    McGovern, Dermot P. B.
    Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai, Medical Center, Los Angeles CA, USA.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Reinisch, Walter
    McMaster University, Hamilton ON, Canada.
    Rogler, Gerhard
    University Hospital of Zuürich, Zurich, Switzerland.
    Kruis, Wolfgang
    University of Cologne, Koln, Germany.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Schreiber, Stefan
    University Hopital Schleswig Holstein, Kiel, Germany.
    Danese, Silvio
    Humanitas University, Milan, Italy.
    Sandborn, William
    UCSD, San Diego CA, USA.
    Griffiths, Anne
    Hospital for Sick Children, Toronto ON, Canada.
    Moum, Bjorn
    Oslo University Hospital and University Oslo, Oslo, Norway.
    Gasche, Christoph
    Medical University and General Hospital Vienna, Vienna, Austria.
    Pallone, Francesco
    University of Rome Tor Vergata, Rome, Italy.
    Travis, Simon
    Oxford University Hospital, Oxford, UK.
    Panes, Julian
    Hospital Clinic de Barcelona, Institut d'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
    Colombel, Jean-Frederic
    Icahn School of Medicine at Mount Sinai, New York, USA.
    Hanauer, Stephen
    Northwestern Feinberg School of Medicine, Chicago IL, USA.
    Peyrin-Biroulet, Laurent
    Inserm U954 and Centre Hospitaliers Régionaux et Universitaires (CHU) de Nancy, Lorraine University, Nancy, France.
    Development of an index to define overall disease severity in IBD2018In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 2, p. 244-254Article in journal (Refereed)
    Abstract [en]

    Background and aim: Disease activity for Crohn's disease (CD) and UC is typically defined based on symptoms at a moment in time, and ignores the long-term burden of disease. The aims of this study were to select the attributes determining overall disease severity, to rank the importance of and to score these individual attributes for both CD and UC.

    Methods: Using a modified Delphi panel, 14 members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) selected the most important attributes related to IBD. Eighteen IOIBD members then completed a statistical exercise (conjoint analysis) to create a relative ranking of these attributes. Adjusted utilities were developed by creating proportions for each level within an attribute.

    Results: For CD, 15.8% of overall disease severity was attributed to the presence of mucosal lesions, 10.9% to history of a fistula, 9.7% to history of abscess and 7.4% to history of intestinal resection. For UC, 18.1% of overall disease severity was attributed to mucosal lesions, followed by 14.0% for impact on daily activities, 11.2% C reactive protein and 10.1% for prior experience with biologics. Overall disease severity indices were created on a 100-point scale by applying each attribute's average importance to the adjusted utilities.

    Conclusions: Based on specialist opinion, overall CD severity was associated more with intestinal damage, in contrast to overall UC disease severity, which was more dependent on symptoms and impact on daily life. Once validated, disease severity indices may provide a useful tool for consistent assessment of overall disease severity in patients with IBD.

  • 36. Sjöberg, Mats
    et al.
    Almer, S.
    Befrits, R.
    Benoni, C.
    Carlson, M.
    Eriksson, A.
    Friis Liby, I.
    Halfvarson, Jonas
    Hertervig, E.
    Karlén, P.
    Lapidus, A.
    Magnusson, A.
    Midhagen, G.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Long-term efficacy of rescue therapy with infliximab in steroid-refractory acute attack of ulcerative colitis2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no Suppl 3, p. A48-A48Article in journal (Refereed)
  • 37.
    Stevens, Craig
    et al.
    University of Edinburgh, Edinburgh, UK .
    Henderson, Paul
    University of Edinburgh, Edinburgh, UK .
    Nimmo, Elaine R
    University of Edinburgh, Edinburgh, UK .
    Soares, Dinesh S.
    University of Edinburgh, Edinburgh, UK .
    Dogan, Belgin
    Cornell University, Ithaca NY, USA .
    Simpson, Kenneth W.
    Cornell University, Ithaca NY, USA .
    Barrett, Jefferey C.
    Wellcome Trust Sanger Institute, Cambridge, UK .
    Wilson, David C.
    University of Edinburgh, Edinburgh, UK .
    Satsangi, Jack
    University of Edinburgh, Edinburgh, UK .
    The intermediate filament protein vimentin is a regulator of NOD2 activity2013In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 62, no 5, p. 695-707Article in journal (Refereed)
    Abstract [en]

    Objective Mutations in the nucleotide-binding oligomerisation domain-containing protein 2 (NOD2) gene remain the strongest genetic determinants for Crohn's disease (CD). Having previously identified vimentin as a novel NOD2-interacting protein, the authors aimed to investigate the regulatory effects of vimentin on NOD2 function and the association of variants in Vim with CD susceptibility.

    Design Coimmunoprecipitation, fluorescent microscopy and fractionation were used to confirm the interaction between NOD2 and vimentin. HEK293 cells stably expressing wild-type NOD2 or a NOD2 frameshift variant (L1007fs) and SW480 colonic epithelial cells were used alongside the vimentin inhibitor, withaferin A (WFA), to assess effects on NOD2 function using the nuclear factor-kappaB (NF-κB) reporter gene, green fluorescent protein-LC3-based autophagy, and bacterial gentamicin protection assays. International genome-wide association meta-analysis data were used to test for associations of single-nucleotide polymorphisms in Vim with CD susceptibility.

    Results The leucine-rich repeat domain of NOD2 contained the elements required for vimentin binding; CD-associated polymorphisms disrupted this interaction. NOD2 and vimentin colocalised at the cell plasma membrane, and cytosolic mislocalisation of the L1007fs and R702W variants correlated with an inability to interact with vimentin. Use of WFA demonstrated that vimentin was required for NOD2-dependent NF-κB activation and muramyl dipeptide-induced autophagy induction, and that NOD2 and vimentin regulated the invasion and survival properties of a CD-associated adherent-invasive Escherichia coli strain. Genetic analysis revealed an association signal across the haplotype block containing Vim.

    Conclusion Vimentin is an important regulator of NOD2 function and a potential novel therapeutic target in the treatment of CD. In addition, Vim is a candidate susceptibility gene for CD, supporting the functional data.

  • 38. Strid, H.
    et al.
    Kumawat, Ashok Kumar
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, J.
    Altered gene expression of IL-6 and rennin in colonic biopsies from collagenous colitis and ulcerative colitis compared to healthy controls2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no Suppl. 3, article id A317Article in journal (Refereed)
  • 39. Tamboli, C.
    et al.
    Attaluri, A.
    Yan, J.
    Duke, A.
    Colombel, J. F.
    Silverberg, M.
    McLeod, R.
    Jewell, D.
    Goldthorpe, S.
    Vernier, G.
    Vermeire, S.
    Joossens, M.
    Chapman, J. O.
    Bernstein, C.
    Annese, V.
    Lombardi, G.
    Bengtson, M. B.
    Vatn, M.
    Halfvarson, Jonas
    Tysk, C.
    Jess, T.
    Riis, L.
    Timmer, A.
    Bauer, A.
    Korelitz, B.
    Sultan, K.
    Reinisch, W.
    Biancone, L.
    Pallone, F.
    Hibi, T.
    Phenotypic concordance and time clustering of diagnosis in multiply affected ibd families: the IOIBD Multiplex Family Collaborative Project, phases I & II2005In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. SupplArticle in journal (Other academic)
  • 40. Vigren, L.
    et al.
    Sjöberg, K.
    Benoni, C.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, J.
    Kilander, A.
    Larsson, L.
    Ström, M.
    Hjortswang, H.
    Smoking habits in patients with collagenous colitis2010In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 59, no suppl 3, p. A182-A182Article in journal (Other academic)
  • 41. Walch, A.
    et al.
    Sjöberg, Mats
    Meshkat, M.
    Gustavsson, A.
    Järnerot, G.
    Vogelsang, H.
    Hertervig, E.
    Novacek, G.
    Friis-Liby, I.
    Blomquist, L.
    Angelberger, S.
    Karlen, P.
    Grännö, C.
    Vilien, M.
    Ström, M.
    Verbaan, H.
    Hellström, P. M.
    Ngo, Y.
    Halfvarson, Jonas
    Reinisch, W.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Outcome of rescue therapy in steroid-resistant ulcerative colitis: a retrospective study comparing cyclosporine and infliximab2008In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57(Suppl II), p. A265-Article in journal (Refereed)
  • 42.
    Weimers, Petra
    et al.
    Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Sachs, Michael C.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Peter, Inga
    Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
    Olén, Ola
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Pediatric Gastroenterology and Nutrition, Sachs' Children and Youth Hospital, Stockholm, Sweden; Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Burisch, Johan
    Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark.
    Association between inflammatory bowel disease and Parkinson's disease: seek and you shall find?2019In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 1, p. 175-176Article in journal (Refereed)
  • 43.
    Welander, Adina
    et al.
    Clinical Epidemiology Unit, Department of Medicine, T2, Karolinska Institutet, Stockholm, Sweden.
    Prutz, Karl-Goran
    Department of Nephrology and Transplantation, Ska ne University Hospital, Malmö, Sweden.
    Fored, Michael
    Clinical Epidemiology Unit, Department of Medicine, T2, Karolinska Institutet, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Clinical Epidemiology Unit, Department of Medicine, T2, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Increased risk of end-stage renal disease in individuals with coeliac disease2012In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 61, no 1, p. 64-68Article in journal (Refereed)
    Abstract [en]

    Objective: The prevalence of end-stage renal disease (ESRD) is increasing worldwide. Although increased levels of coeliac disease (CD) autoantibodies are often seen in renal disease, the importance of biopsy-verified CD for the risk of future ESRD is unclear. The aim of this study was therefore to investigate the risk of future ESRD in individuals with CD.

    Methods: This was a population-based prospective cohort study. 29 050 individuals with CD (Marsh III) were identified through small-intestinal biopsy reports obtained between July 1969 and February 2008 in Sweden's 28 pathology departments. ESRD was defined as the need for renal dialysis or renal transplant in accordance with the international classification of disease and procedure codes in Swedish patient registers. Using Cox regression, the risk of ESRD in individuals with CD compared with age- and sex-matched reference individuals was estimated.

    Results: During follow-up, 90 individuals with CD developed ESRD (expected count 31). This corresponded to a HR for ESRD of 2.87 (95% CI 2.22 to 3.71, p<0.001). Adjusting for diabetes mellitus had only a marginal effect on the risk estimate (HR 2.52, 95% CI 1.92 to 3.31). Excluding individuals with any urinary/renal disorder before study entry, the HR for ESRD in CD was 2.47 (95% CI 1.80 to 3.40). When restricting the outcome measure to ESRD confirmed by independent data from the Swedish Renal Registry (SRR), the risk estimate increased to 3.20 (95% CI 2.39 to 4.28).

    Conclusion: This study indicates that individuals with biopsy-verified CD suffer increased risk of subsequent ESRD.

  • 44.
    Westerlind, Helga
    et al.
    Inst Environm Med, Karolinska Inst, Stockholm, Sweden; Dept Biosci & Nutr, Karolinska Inst, Stockholm, Sweden.
    Mellander, Marie-Rose
    Dept Med Solna, Karolinska Inst, Stockholm, Sweden; Gastroctr, Karolinska Univ Hosp, Stockholm, Sweden.
    Bresso, Francesca
    Dept Med Solna, Karolinska Inst, Stockholm, Sweden;Gastroctr, Karolinska Univ Hosp, Stockholm, Sweden.
    Munch, Andreas
    Dept Clin & Expt Med, Fac Hlth Sci, Linköpings Univ, Linköping, Sweden.
    Bonfiglio, Ferdinando
    Dept Biosci & Nutr, Karolinska Inst, Stockholm, Sweden.
    Assadi, Ghazaleh
    Dept Biosci & Nutr, Karolinska Inst, Stockholm, Sweden.
    Rafter, Joseph
    Dept Biosci & Nutr, Karolinska Inst, Stockholm, Sweden.
    Huebenthal, Matthias
    Inst Clin Mol Biol, Christian Albrechts Univ Kiel, Kiel, Germany.
    Lieb, Wolfgang
    Inst Epidemiol, Christian Albrechts Univ Kiel, Kiel, Germany; Biobank POPGEN, Christian Albrechts Univ Kiel, Kiel, Germany.
    Kallberg, Henrik
    Inst Environm Med, Karolinska Inst, Stockholm, Sweden.
    Brynedal, Boel
    Inst Environm Med, Karolinska Inst, Stockholm, Sweden.
    Padyukov, Leonid
    Dept Med Solna, Karolinska Inst, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Törkvist, Leif
    Gastroctr, Karolinska Univ Hosp, Stockholm, Sweden.
    Björk, Jan
    Gastroctr, Karolinska Univ Hosp, Stockholm, Sweden.
    Andreasson, Anna
    Dept Neurobiol Care Sci & Soc, Karolinska Inst, Stockholm, Sweden.
    Agreus, Lars
    Dept Neurobiol Care Sci & Soc, Karolinska Inst, Stockholm, Sweden.
    Almer, Sven
    Dept Med Solna, Karolinska Inst, Stockholm, Sweden; Gastroctr, Karolinska Univ Hosp, Stockholm, Sweden.
    Miehlke, Stephan
    Ctr Digest Dis, Internal Med Ctr Eppendorf, Hamburg, Germany.
    Madisch, Ahmed
    Clin Gastroenterol Endoscopy & Intervent Diabetol, Siloah Hosp, Hannover, Germany.
    Ohlsson, Bodil
    Dept Clin Sci, Skåne Univ Hosp, Lund Univ, Lund, Sweden.
    Löfberg, Robert
    Dept Med Solna, Karolinska Inst, Stockholm, Sweden; Sophiahemmet Hosp, Stockholm, Sweden.
    Hultcrantz, Rolf
    Dept Med Huddinge, Karolinska Inst, Stockholm, Sweden.
    Franke, Andre
    Inst Clin Mol Biol, Christian Albrechts Univ Kiel, Kiel, Germany.
    D'Amato, Mauro
    Dept Biosci & Nutr, Karolinska Inst, Stockholm, Sweden; Basque Fdn Sci, BioCruces Hlth Res Inst, Bilbao, Spain; Basque Fdn Sci (Ikerbasque), Bilbao, Spain.
    Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis2017In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 66, no 3, p. 421-428Article in journal (Refereed)
    Abstract [en]

    Objective: Collagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predisposed individuals, but the contribution of genetic factors to CC is underinvestigated. We systematically tested immune-related genes known to impact the risk of several autoimmune diseases for their potential CC-predisposing role.

    Design: Three independent cohorts of histologically confirmed CC cases (N=314) and controls (N=4299) from Sweden and Germany were included in a 2-step association analysis. Immunochip and targeted single nucleotide polymorphism (SNP) genotype data were produced, respectively, for discovery and replication purposes. Classical human leucocyte antigen (HLA) variants at 2-digit and 4-digit resolution were obtained via imputation from single marker genotypes. SNPs and HLA variants passing quality control filters were tested for association with CC with logistic regression adjusting for age, sex and country of origin.

    Results: Forty-two markers gave rise to genome-wide significant association signals, all contained within the HLA region on chromosome 6 (best p=4.2x10(-10) for SNP rs4143332). Among the HLA variants, most pronounced risk effects were observed for 8.1 haplotype alleles including DQ2.5, which was targeted and confirmed in the replication data set (p=2.3x10(-11); OR=2.06; 95% CI (1.67 to 2.55) in the combined analysis).

    Conclusions: HLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.

  • 45.
    Wouters, Mira M.
    et al.
    Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium.
    Lambrechts, Diether
    Vesalius Research Center, VIB, Leuven University, Leuven, Belgium; Laboratory for Translational Genetics, Department of Oncology, Leuven University, Leuven, Belgium .
    Knapp, Michael
    Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany .
    Cleynen, Isabelle
    Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium .
    Whorwell, Peter
    Department of Medicine, University of Manchester, Manchester, UK .
    Agreus, Lars
    Centre for Family Medicine, Karolinska Institutet, Stockholm, Sweden.
    Dlugosz, Aldona
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden .
    Schmidt, Peter Thelin
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden .
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Internal Medicine.
    Simren, Magnus
    Department of Internal Medicine, Gothenburg University, Gothenburg, Sweden .
    Ohlsson, Bodil
    Department of Clinical Sciences, Skånes University Hospital, Malmö, Sweden .
    Karling, Pontus
    Department of Medicine, Umeå University, Umeå, Sweden .
    Van Wanrooy, Sander
    Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium.
    Mondelaers, Stephanie
    Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium.
    Vermeire, Severine
    Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium.
    Lindberg, Greger
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Spiller, Robin
    Queen's Medical Centre, Nottingham, UK .
    Dukes, George
    Academic DPU, GlaxoSmithKline, Research Triangle Park, Durham NC, USA .
    D'Amato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Boeckxstaens, Guy
    Translational Research Center for Gastrointestinal Disorders, Leuven University, Leuven, Belgium .
    Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome2014In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 63, no 7, p. 1103-1111Article in journal (Refereed)
    Abstract [en]

    Objective: The complex genetic aetiology underlying irritable bowel syndrome (IBS) needs to be assessed in large-scale genetic studies. Two independent IBS cohorts were genotyped to assess whether genetic variability in immune, neuronal and barrier integrity genes is associated with IBS.

    Design: 384 single nucleotide polymorphisms (SNPs) covering 270 genes were genotyped in an exploratory cohort (935 IBS patients, 639 controls). 33 SNPs with P-uncorrected<0.05 were validated in an independent set of 497 patients and 887 controls. Genotype distributions of single SNPs were assessed using an additive genetic model in IBS and clinical subtypes, IBS-C and IBS-D, both in individual and combined cohorts. Trait anxiety (N=614 patients, 533 controls), lifetime depression (N=654 patients, 533 controls) and mRNA expression in rectal biopsies (N=22 patients, 29 controls) were correlated with SNP genotypes.

    Results: Two SNPs associated independently in the exploratory and validation cohort: rs17837965-CDC42 with IBS-C (ORexploratory=1.59 (1.05 to 1.76); ORvalidation=1.76 (1.03 to 3.01)) and rs2349775-NXPH1 with IBS-D (ORexploratory=1.28 (1.06 to 1.56); ORvalidation=1.42 (1.08 to 1.88)). When combining both cohorts, the association of rs2349775 withstood post hoc correction for multiple testing in the IBS-D subgroup. Additionally, three SNPs in immune-related genes (rs1464510-LPP, rs1881457-IL13, rs2104286-IL2RA), one SNP in a neuronal gene (rs2349775-NXPH1) and two SNPs in epithelial genes (rs245051-SLC26A2, rs17837965-CDC42) were weakly associated with total-IBS (P-uncorrected<0.05). At the functional level, rs1881457 increased IL13 mRNA levels, whereas anxiety and depression scores did not correlate with rs2349775-NXPH1.

    Conclusions: Rs2349775 (NXPH1) and rs17837965 (CDC42) were associated with IBS-D and IBS-C, respectively, in two independent cohorts. Further studies are warranted to validate our findings and to determine the mechanisms underlying IBS pathophysiology.

  • 46. Zhulina, Yaroslava
    et al.
    Hahn Strömberg, V.
    Shamikh, A.
    Gustavsson, A.
    Bohr, J.
    Nyhlin, N.
    Wickbom, Anna
    Bodin, L.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Carlson, M.
    Halfvarson, Jonas
    NFkB is activated in colonic mucosa of healthy co-twins to twins with inflammatory bowel disease2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no Suppl 3, p. A290-A290Article in journal (Refereed)
  • 47. Zucchelli, Marco
    et al.
    Camilleri, Michael
    Andreasson, Anna Nixon
    Bresso, Francesca
    Dlugosz, Aldona
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Törkvist, Leif
    Schmidt, Peter T
    Karling, Pontus
    Ohlsson, Bodil
    Duerr, Richard H
    Simren, Magnus
    Lindberg, Greger
    Agreus, Lars
    Carlson, Paula
    Zinsmeister, Alan R
    D'Amato, Mauro
    Association of TNFSF15 polymorphism with irritable bowel syndrome2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no 12, p. 1671-1677Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder, affecting more than 10% of the general population worldwide. Although a genetic component is suspected, unambiguous susceptibility genes have so far not been identified. This study tested the hypothesis that genes contributing to epithelial barrier integrity, control of mucosal immune responses and interactions with bacteria in the gut are associated with IBS.

    METHODS: Single nucleotide polymorphisms (SNPs) corresponding to top signals of association with Crohn's disease at 30 known susceptibility loci were tested for their effect on IBS risk in 1992 individuals from two independent case-control cohorts from Sweden and the USA. Association tests included a conservative Bonferroni correction for multiple comparisons, and were also performed on specific subgroups of patients characterised by constipation (IBS-C), diarrhoea (IBS-D) or alternating constipation and diarrhoea (IBS-A).

    RESULTS: The Crohn's disease risk allele rs4263839 G in the TNFSF15 gene was significantly associated with an increased risk of both IBS (p=2.2×10(-5); OR 1.37) and more pronouncedly, IBS-C (p=8.7×10(-7); OR 1.79) in the entire sample. Similar associations and risk effects of the same magnitude were observed in the two cohorts analysed separately. A correlation between rs4263839 genotype and TNFSF15 mRNA expression was detected both in peripheral blood and in rectal mucosal biopsies from healthy individuals (combined p=0.0033).

    CONCLUSIONS: TNFSF15 is a susceptibility gene for IBS and IBS constipation. As TL1A, the protein encoded by TNFSF15, contributes to the modulation of inflammatory responses, the results support a role of immune activation in IBS.

  • 48.
    Örtqvist, Anne K.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lundholm, Cecilia
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    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.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Fetal and early life antibiotics exposure and very early onset inflammatory bowel disease: a population-based study2019In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 68, no 2, p. 218-225Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Earlier studies on antibiotics exposure and development of IBD (Crohn's disease (CD) and ulcerative colitis (UC)) may have been biased by familial factors and gastroenteritis. We aimed to estimate the association between antibiotics during pregnancy or infantile age and very early onset (VEO) IBD.

    DESIGN: In this cohort study of 827 239 children born in Sweden between 2006 and 2013, we examined the link between exposure to systemic antibiotics and VEO-IBD (diagnosis <6 years of age), using Cox proportional hazard regression models. Information on antibiotics and IBD was retrieved from the nationwide population-based Swedish Prescribed Drug Register and the National Patient Register. We specifically examined potential confounding from parental IBD and gastroenteritis.

    RESULTS: Children exposed to antibiotics during pregnancy were at increased risk of IBD compared with general population controls (adjusted HR (aHR) 1.93; 95% CI 1.06 to 3.50). Corresponding aHRs were 2.48 (95% CI 1.01 to 6.08) for CD and 1.25 (95% CI 0.47 to 3.26) for UC, respectively. For antibiotics in infantile age, the aHR for IBD was 1.11 (95% CI 0.57 to 2.15); for CD 0.72 (95% CI 0.27 to 1.92) and 1.23 (95% CI 0.45 to 3.39) for UC. Excluding children with gastroenteritis 12 months prior to the first IBD diagnosis retained similar aHR for antibiotics during pregnancy and CD, while the association no longer remained significant for IBD.

    CONCLUSION: We found that exposure to antibiotics during pregnancy, but not in infantile age, is associated with an increased risk of VEO-IBD regardless of gastroenteritis. The risk increase for exposure in pregnancy may be due to changes in the microbiota.

1 - 48 of 48
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