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  • 101. Wickbom, Anna
    et al.
    Lindqvist, Magnus
    Bohr, Johan
    Ung, Kjell-Arne
    Bergman, Jan
    Eriksson, Sune
    Tysk, Curt
    Örebro University, Department of Clinical Medicine.
    Colonic mucosal tears in collagenous colitis2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 6, p. 726-729Article in journal (Refereed)
    Abstract [en]

    In general, the colonic mucosa is macroscopically normal in collagenous colitis, although minor, non-specific abnormalities may be found. Significant endoscopic abnormalities, "mucosal tears" representing longitudinal mucosal lacerations, have been reported in a few patients with collagenous colitis. We report the cases of three women with collagenous colitis and mucosal tears detected at the index colonoscopy in order to illustrate the endoscopic characteristics and review the literature. Including the present cases, a total of 12 patients with mucosal tears and collagenous colitis have been reported. In 10 patients, the mucosal lacerations involved the ascending or the transverse colon. Three of the 12 patients had a colonic perforation immediately after the colonoscopy. The colonoscopist should be aware that the risk of perforation is likely to be increased when mucosal tears are present.

  • 102.
    Wickbom, Anna
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden; Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Bohr, Johan
    Örebro University Hospital. School of Medical Sciences, Örebro University, Örebro, Sweden; Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Tysk, Curt
    Örebro University Hospital. School of Medical Sciences, Örebro University, Örebro, Sweden; Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Family history, comorbidity, smoking and other risk factors in microscopic colitis: a case-control study2017In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 29, no 5, p. 587-594Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Data on heredity, risk factors and comorbidity in microscopic colitis, encompassing collagenous colitis (CC) and lymphocytic colitis (LC), are limited.

    AIM: The aim was to carry out a case-control study of family history, childhood circumstances, educational level, marital status, smoking and comorbidity in microscopic colitis.

    METHODS: A postal questionnaire was sent in 2008-2009 to microscopic colitis patients resident in Sweden and three population-based controls per patient, matched for age, sex and municipality.

    RESULTS: Some 212 patients and 627 controls participated in the study. There was an association with a family history of microscopic colitis in both CC [odds ratio (OR): 10.3; 95% confidence interval (CI): 2.1-50.4, P=0.004] and LC (OR not estimated, P=0.008). Current smoking was associated with CC [OR: 4.7; 95% CI: 2.4-9.2, P<0.001) and LC (OR: 3.2; 95% CI: 1.6-6.7, P=0.002). The median age at diagnosis was around 10 years earlier in ever-smokers compared with never-smokers.CC was associated with a history of ulcerative colitis (UC) (OR: 8.7, 95% CI: 2.2-33.7, P=0.002), thyroid disease (OR: 2.3; 95% CI: 1.1-4.5, P=0.02), coeliac disease (OR: 13.1; 95% CI: 2.7-62.7, P=0.001), rheumatic disease (OR 1.9; 95% CI: 1.0-3.5, P=0.042) and previous appendicectomy (OR: 2.2; 95% CI: 1.3-3.8, P=0.003), and LC with UC (OR: 6.8; 95% CI: 1.7-28.0, P=0.008), thyroid disease (OR: 2.4; 95% CI: 1.1-5.4, P=0.037) and coeliac disease (OR: 8.7; 95% CI: 2.8-26.7, P<0.001).

    CONCLUSION: Association with a family history of microscopic colitis indicates that familial factors may be important. The association with a history of UC should be studied further as it may present new insights into the pathogenesis of microscopic colitis and UC.

  • 103. Willing, B.
    et al.
    Halfvarson, Jonas
    Dicksved, J.
    Rosenquist, M.
    Järnerot, G.
    Engstrand, L.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Jansson, J. K.
    Studying discordant monozygotic twins reveals differences in mucosa-associated microbiota depending on Crohn's disease phenotype2008Conference paper (Other (popular science, discussion, etc.))
  • 104. Willing, Ben
    et al.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences.
    Dicksved, Johan
    Rosenquist, Magnus
    Järnerot, Gunnar
    Örebro University, School of Health and Medical Sciences.
    Engstrand, Lars
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Jansson, Janet K.
    Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 5, p. 653-660Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Large interindividual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease (CD).

    METHODS: To reduce variations in exposure during establishment of the gut flora and the influence of genotype, we studied the mucosa-associated microbiota of monozygotic twin pairs that were discordant (n = 6) or concordant (n = 4) for CD. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing, and quantitative real-time polymerase chain reaction (PCR).

    RESULTS: The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal CD had a dramatically lower abundance (P < 0.001) of Faecalibacterium prausnitzii and increased abundance (P < 0.03) of Escherichia coli compared to healthy co-twins and those with CD localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype.

    CONCLUSIONS: The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal CD phenotype, distinct from colonic CD, and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of CD and eventually customized treatment.

  • 105.
    Willing, Ben P.
    et al.
    Dept Microbiol, Swedish Univ Agr Sci, Uppsala, Sweden .
    Dicksved, Johan
    Dept Microbiol, Swedish Univ Agr Sci, Uppsala, Sweden .
    Halfvarson, Jonas
    Dept Med, Div Gastroenterol, Örebro Univ Hosp, Örebro, Sweden .
    Andersson, Anders F.
    Dept Bacteriol, Swedish Inst Infect Dis Control, Solna, Sweden.
    Lucio, Marianna
    Res Ctr Environ, Inst Ecol Chem, Helmholtz Zentrum Muenchen, Neuherberg, Germany .
    Zheng, Zongli
    Dept Med Epidemiol & Biostat, Karolinska Inst, Solna, Sweden.
    Järnerot, Gunnar
    Dept Med, Div Gastroenterol, Örebro Univ Hosp, Örebro, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Jansson, Janet K.
    Lawrence Berkeley Lab, Div Earth Sci, Univ Calif Berkeley, Berkeley CA, USA.
    Engstrand, Lars
    Dept Bacteriol, Swedish Inst Infect Dis Control, Solna, Sweden.
    A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes2010In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 139, no 6, p. 1844-1854.e1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: The composition of the gastrointestinal microbiota is thought to have an important role in the etiology of inflammatory bowel diseases (IBDs) such as Crohn's disease (CD) and ulcerative colitis (UC). Interindividual variation and an inability to detect less abundant bacteria have made it difficult to correlate specific bacteria with disease.

    METHODS: We used 454 pyrotag sequencing to determine the compositions of microbial communities in feces samples collected from a cohort of 40 twin pairs who were concordant or discordant for CD or UC, and in mucosal samples from a subset of the cohort. The cohort primarily comprised patients who were in remission, but also some with active disease.

    RESULTS: The profiles of the microbial community differed with disease phenotypes; relative amounts of bacterial populations correlated with IBD phenotypes. The microbial compositions of individuals with CD differed from those of healthy individuals, but were similar between healthy individuals and individuals with UC. Profiles from individuals with CD that predominantly involved the ileum differed from those with CD that predominantly involved the colon; several bacterial populations increased or decreased with disease type. Changes specific to patients with ileal CD included the disappearance of core bacteria, such as Faecalibacterium and Roseburia, and increased amounts of Enterobacteriaceae and Ruminococcus gnavus.

    CONCLUSIONS: Bacterial populations differ in abundance among individuals with different phenotypes of CD. Specific species of bacteria are associated with ileal CD; further studies should investigate their role in pathogenesis.

  • 106. Zhulina, Yaroslava
    et al.
    Carlson, M.
    Peterson, C.
    Gustavsson, A.
    Bohr, J.
    Bodin, L.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Halfvarson, Jonas
    Fekalt calprotectin hos tvillingar med inflammatorisk tarmsjukdom2011In: Gastrokuriren, ISSN 1651-0453, Vol. 16, no 29, p. PO-09-PO-09Article in journal (Other academic)
  • 107.
    Zhulina, Yaroslava
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Carlson, Marie
    Peterson, Christer G.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Gustavsson, Anders
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bodin, Lennart
    Örebro University, Örebro University School of Business.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden.
    Subclinical inflammation due to environmental exposure in health co-twins to twins with inflammatory bowel disease2009In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 136, no 5, p. A20-A20Article in journal (Other academic)
  • 108. 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)
  • 109. Zhulina, Yaroslava
    et al.
    Hahn Strömberg, Victoria
    Shamikh, A.
    Gustavsson, A.
    Bohr, J.
    Nyhlin, Nils
    Wickbom, A.
    Bodin, L.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Carlson, M.
    Halfvarson, Jonas
    Aktiverad NFkB i colonbiopsier hos tvillingar med inflammatorisk tarmsjukdom2012In: Gastrokuriren, ISSN 1651-0453, Vol. 17, no 37, p. PO-27-PO-27Article in journal (Other academic)
  • 110.
    Zhulina, Yaroslava
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Hahn-Strömberg, Victoria
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Pathology, Örebro University Hospital, Örebro, Sweden; Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Shamikh, Alia
    Department of Pathology, Örebro University Hospital, Örebro, Sweden; Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Peterson, Christer G. B.
    Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
    Gustavsson, Anders
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Bodin, Lennart
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institute, Stockholm, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Carlson, Marie
    Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Subclinical Inflammation with Increased Neutrophil Activity in Healthy Twin Siblings Reflect Environmental Influence in the Pathogenesis of Inflammatory Bowel Disease2013In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 19, no 8, p. 1725-1731Article in journal (Refereed)
    Abstract [en]

    Background: The mechanisms behind increased fecal calprotectin (FC) in healthy relatives of patients with inflammatory bowel disease (IBD) are unknown. Our aims were to explore if there is a subclinical inflammation with increased neutrophil activity in healthy twin siblings in discordant twin pairs with IBD and to assess the influence of genetics in this context.

    Methods: Nuclear factor kappa B (NF-B) and neutrophil activity, based on myeloperoxidase (MPO) and FC, were analyzed in healthy twin siblings in discordant twin pairs with IBD and compared with healthy controls. NF-B and MPO were assessed by immunohistochemistry and FC by enzyme-linked immunosorbent assay.

    Results: In total, 33 of 34 healthy twin siblings were histologically normal. Increased NF-B was more often observed in healthy twin siblings in discordant twin pairs with Crohn's disease (13/18 [73%]) and with ulcerative colitis (12/16 [75%]) than in healthy controls (8/45 [18%]). MPO was more often increased in healthy twin siblings in discordant pairs with Crohn's disease (12/18 [67%]) than in healthy controls (11/45 [24%]) and FC more often in healthy twin siblings in discordant pairs with ulcerative colitis (14/21 [67%]) than in healthy controls (6/31 [19%]). Interestingly, the observed differences remained when healthy monozygotic and dizygotic twin siblings were analyzed separately.

    Conclusions:We observed increased NF-B, MPO, and FC in healthy twins in both monozygotic and dizygotic discordant pairs with IBD. These novel findings speak for an ongoing subclinical inflammation with increased neutrophil activity in healthy first-degree relatives.

  • 111. Zhulina, Yaroslava
    et al.
    Lindberg, E.
    Sjöberg, Mats
    Nyhlin, Nils
    Wickbom, Anna
    Eriksson, C
    Johansson, I.
    van Nieuwenhoven, Michiel A.
    Salén, E.
    Curman, B.
    Yimam, Y.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, J.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Halfvarson, Jonas
    Inflammatorisk tarmsjukdom i Örebro 2010: en epidemiologisk uppdatering2011In: Gastrokuriren, ISSN 1651-0453, Vol. 16, no 29, p. PO-10-PO-10Article in journal (Other academic)
  • 112.
    Zhulina, Yaroslava
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Henriksson, Ida
    Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden .
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Temporal trends in non-stricturing and non-penetrating behaviour at diagnosis of Crohn's disease in Örebro, Sweden: a population-based retrospective study2014In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 8, no 12, p. 1653-1660Article in journal (Refereed)
    Abstract [en]

    Background and aim: The incidence of Crohn's disease (CD) is continuing to rise in several countries and in others it appears to have already levelled off after a period of increase. We updated our previous population-based study, by re-extraction of all information on patients diagnosed with CD between 1963 and 2010. Our aim was to assess temporal trends in incidence, prevalence and disease phenotype at diagnosis.

    Methods: Patients of all ages with a potential diagnosis of CD were identified retrospectively by evaluation of medical notes of all current and previous patients at the colitis clinic, Örebro University Hospital amended by computerised search in the inpatient, outpatient, primary care and histopathological records. Diagnosis was confirmed by subsequent evaluation of medical notes. Disease phenotype was defined according to the Montreal classification.

    Results: The incidence increased over time, especially among Crohn's disease, A1 and A3. SaTScan model revealed a statistically significant high incidence during 1991-2010 (p=0.0001). The median age at diagnosis increased from 28 (3-79) years to 37 (5-87) years (p=0.0002). The point prevalence increased from 21/10(5) (14-32) in 1965 to 267/10(5) (244-291) in 2010. Non-stricturing and non-penetrating disease at diagnosis increased from 12.5% in 1963-1965 to 82.3% in 2006-2010 (p<0.0001).

    Conclusion: The incidence of CD increased over time, although it seemed to be plateauing during the most recent decades. A striking increase in non-stricturing, non-penetrating disease at diagnosis was observed, suggesting earlier diagnosis or phenotypic change. The observed point prevalence in 2010 is among the highest reported.

  • 113.
    Zhulina, Yaroslava
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Gastroenterology, , Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Gastroenterology, , Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    The changing face of Crohn’s disease: a population-based study of the natural history of Crohn’s disease in Örebro, Sweden 1963-20052016In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 3, p. 304-313Article in journal (Refereed)
    Abstract [en]

    Objective: Changes in medical therapy and surgery might have influenced the natural history Crohn’s disease (CD). Our aim was to explore the short-term outcome of CD and to specifically assess trends in disease phenotype, medications and surgery in the first five years from diagnosis.

    Material and Methods: A population-based cohort comprising 472 CD patients diagnosed within the primary catchment area of Örebro University Hospital 1963-2005 were identified retrospectively and described. Data on medication, surgery, progression in disease location and behaviour, were extracted from the medical records. Patients were divided into three cohorts based on year of diagnosis.

    Results: The proportion of patients with complicated disease behaviour 5 years after diagnosis decreased from 54.4% (95%CI, 43.9-65.6) to 33.3% (27.4-40.0) in patients diagnosed 1963-1975 and 1991-2005, respectively (p=0.002), whereas the proportion of patients progressing to complicated disease behaviour was stable among those with non-stricturing, non-penetrating disease at diagnosis (p=0.435). The proportion of patients undergoing surgery decreased from 65.8% (55.4-76.0) to 34.6% (28.6-41.5) in patients diagnosed 1963-1975 and 1991-2005, respectively (p<0.001). The reduction in surgery preceded an increased use of immunomodulators and was explained by a decrease in surgery within three months from diagnosis (p=0.001).

    Conclusions: We observed a striking decrease in complicated disease behaviour and surgery five years after CD diagnosis, the latter largely due to a decrease in early surgery. Our findings suggest that the introduction of new treatments alone does not explain the reduction in surgery rates, the increasing proportion of patients with inflammatory disease at diagnosis also play an important role.

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