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  • 1.
    Berglund, Martin
    et al.
    Dept Microbiol & Immunol, Inst Biomed, Sahlgrenska Acad, Univ Gothenburg, Gothenburg, Sweden.
    Melgar, Silvia
    Alimentary Pharmabiot Ctr, Univ Coll Cork, Cork, Ireland; Immunoinflammat CEDD GlaxoSmithKline, Stevenage Herts, England.
    Kobayashi, Koichi S.
    Harvard Univ, Boston MA, USA.
    Flavell, Richard A.
    Yale Univ, New Haven CT, USA.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Health and Medical Sciences.
    Hultgren, Olof H.
    Department of Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Örebro University Hospital, Örebro, Sweden.
    IL-1 receptor-associated kinase M downregulates DSS-induced colitis2010In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 16, no 10, p. 1778-1786Article in journal (Refereed)
    Abstract [en]

    Background: Ulcerative colitis is associated with increased colon permeability resulting in bacterial translocation into the lamina propria. We investigate the importance of the Toll-like receptor (TLR) regulating protein IL-1 receptor-associated kinase M (IRAK-M) using the erosive dextran sulfate sodium (DSS)-induced model of colitis. Methods: IRAK-M-competent and -incompetent mice were treated with 3% DSS for 5 days followed by 2 days of regular drinking water. Clinical signs of disease were followed for 7 days. At day 7 the mice were sacrificed and plasma and tissue were collected for histopathological examination and analyses of the production of cytokines and chemokines as well as expression of T-cell transcription factors. Results: At day 7 IRAK-M-deficient mice display a reduced total body weight (77.1 +/- 2.1 versus 88.5 +/- 2.0, *P=0.002) and an increased macroscopical (2.7 +/- 0.2 versus 1.6 +/- 0.1, *P 0.002) and histopathological (6.0 +/- 0 versus 3.3 +/- 60.5, *P < 0.001) colon score compared to wildtype mice. Furthermore, IRAK-M-deficient mice have increased colon mRNA expression of proinflammatory cytokines and increased tumor necrosis factor concentrations (41.1 +/- 13.5 versus 12.8 +/- 2.0 pg/mL, *P = 0.010) in plasma. Conclusions: This is the first report examining the role of IRAK-M in colitis. We find that IRAK-M is of critical importance in downregulating induction and progression of DSS colitis, and thereby suggesting that IRAK-M might be a target for future interventional therapies. (Inflamm Bowel Dis 2010; 16: 1778-1786)

  • 2.
    Burisch, Johan
    et al.
    Med Sect, Ctr Digest Dis, Herlev Univ Hosp, Copenhagen, Denmark.
    Pedersen, Natalia
    Med Sect, Ctr Digest Dis, Herlev Univ Hosp, Copenhagen, Denmark.
    Cukovic-Cavka, Silvja
    Univ Hosp Ctr Zagreb, Div Gastroenterol & Hepatol, Univ Zagreb School of Medicine, Zagreb, Croatia.
    Turk, Niksa
    Univ Hosp Ctr Zagreb, Div Gastroenterol & Hepatol, Univ Zagreb School of Medicine, Zagreb, Croatia.
    Kaimakliotis, Ioannis
    Nicosia Private Practice, Nicosia, Cyprus.
    Duricova, Dana
    IBD Ctr ISCARE, Charles Univ Prague, Prague, Czech Republic.
    Shonova, Olga
    Dept Gastroenterol, Hosp Ceske Budejovice, Ceske Budejovice, Czech Republic.
    Vind, Ida
    Dept Med, Amager Hosp, Amager, Denmark.
    Avnstrom, Soren
    Dept Med, Amager Hosp, Amager, Denmark.
    Thorsgaard, Niels
    Dept Med, Herning Cent Hosp, Herning, Denmark.
    Krabbe, Susanne
    Dept Med, Viborg Reg Hosp, Viborg, Denmark.
    Andersen, Vibeke
    Medical Department, Viborg Regional Hospital, Viborg, Denmark; Medical Department, Hospital of Southern Jutland, Aabenraa, Denmark; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
    Jens, Frederik Dahlerup
    Dept Med Hepatol & Gastroenterol 5, Aarhus Univ Hosp, Aarhus, Denmark.
    Kjeldsen, Jens
    Dept Med Gastroenterol, Odense Univ Hosp, Odense, Denmark.
    Salupere, Riina
    Div Gastroenterol & Endocrinol, Tartu Univ Hosp, Tartu, Estonia.
    Olsen, Jongero
    Dept Med, Natl Hosp Faroe Islands, Torshavn, Denmark.
    Nielsen, Kari Rubek
    Dept Med, Natl Hosp Faroe Islands, Torshavn, Denmark.
    Manninen, Pia
    Dept Gastroenterol & Alimentary Tract Surg, Tampere Univ Hosp, Tampere, Finland.
    Collin, Pekka
    Dept Gastroenterol & Alimentary Tract Surg, Tampere Univ Hosp, Tampere, Finland.
    Katsanos, Konstantinnos H.
    Div Internal Med 1, Univ Hosp, Ioannina, Greece ; Hepatogastroenterol Unit, Univ Hosp, Ioannina, Greece.
    Tsianos, Epameinondas V.
    Div Internal Med 1, Univ Hosp, Ioannina, Greece ; Hepatogastroenterol Unit, Univ Hosp, Ioannina, Greece.
    Ladefoged, Karin
    Dept Med, Dronning Ingrids Hosp, Nuuk, Greenland.
    Lakatos, Laszlo
    Dept Med, Csolnoky F Prov Hosp, Veszprem, Hungary.
    Bailey, Yvonne
    Adelaide & Meath Hosp, Dept Gastroenterol, Trinity Coll Dublin, Dublin, Ireland.
    O'Morain, Colm
    Dept Gastroenterol, Adelaide & Meath Hosp, Dublin, Ireland.
    Schwartz, Doron
    Dept Gastroenterol & Hepatol, Soroka Med Ctr, Beer Sheva, Israel; Ben Gurion Univ of the Negev, Beer Sheva, Israel .
    Odes, Selwyn
    Dept Gastroenterol & Hepatol, Soroka Med Ctr, Beer Sheva, Israel; Ben Gurion Univ of the Negev, Beer Sheva, Israel .
    Martinato, Matteo
    U.O. Gastroenterologia, Azienda Ospedaliera, Università di Padova, Padova, Italy.
    Lombardini, Silvia
    UO Medicina 38 e Gastroenterologia, Azienda Ospedaliera Arcispedale S Maria Nuova, Reggio Emilia, Italy.
    Jonaitis, Laimas
    Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
    Kupcinskas, Limas
    Department of Gastroenterology, State University of Medicine and Pharmacy of the Republic of Moldova, Chisinau, Moldova.
    Turcan, Svetlana
    Dept Gastroenterol, State Univ Med & Pharm Republ Moldova, Kishinev, Moldova.
    Barros, Louisa
    Dept Med, Hosp Vale de Sousa, Oporto, Portugal.
    Magro, Fernando
    Dept Gastroenterol, Hosp Sao Joao, Oporto, Portugal ; Inst Pharmacol & Therapeut, Oporto Med Sch, Oporto, Portugal ; Inst Mol & Cell Biol, Univ Porto, Oporto, Portugal .
    Lazar, Daniela
    Gastroenterol Clin, Univ Med 'Victor Babes', Timisoara, Romania.
    Goldis, Adrian
    Gastroenterol Clin, Univ Med 'Victor Babes', Timisoara, Romania.
    Nikulina, Inna
    Department of Gastroenterology, Moscow Regional Research Clinical Institute, Moscow, Russian Federation.
    Belousova, Elena
    Dept Gastroenterol, Moscow Reg Res Clin Inst, Moscow, Russia.
    Fernandez, Alberto
    Dept Gastroenterol, POVISA Hosp, Vigo, Spain.
    Hernandez, Vicent
    Dept Gastroenterol, Complexo Hospitalario Univ Vigo, Vigo, Spain.
    Almer, Sven
    Div Gastroenterol & Hepatol, Karolinska Instutue, Stockholm, Sweden ; Dept Gastroenterol UHL, Cty Council Östergötland,Linköping, Sweden .
    Zhulina, Yaroslava
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Div Gastroenterol, Dept Med, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Div Gastroenterol, Dept Med, Örebro University Hospital, Örebro, Sweden.
    Tsai, Her-Hsin
    Hull and East Yorkshire NHS Trust, Kingston-Upon-Hull, UK; Hull and York Medical School, Kingston-Upon-Hull, UK; Hull Royal Infirmary, Kingston-Upon-Hull, UK.
    Sebastian, Shaji
    Hull and East Yorkshire NHS Trust, Kingston-Upon-Hull, UK; Hull and York Medical School, Kingston-Upon-Hull, UK; Hull Royal Infirmary, Kingston-Upon-Hull, UK.
    Lakatos, Peter Laszlo
    Dept Med 1, Semmelweis Univ, Budapest, Hungary.
    Langholz, Ebbe
    Dept Med Gastroenterol, Gentofte Univ Hosp, Copenhagen, Denmark.
    Munkholm, Pia
    Med Sect, Ctr Digest Dis, Herlev Univ Hosp, Copenhagen, Denmark.
    EpiCom Northern Italy Centre Based in Crema and Cremona, Padova and Reggio Emilia, Italy (Lombardini & Martinato, on behalf of ), Group author
    Initial Disease Course and Treatment in an Inflammatory Bowel Disease Inception Cohort in Europe: The ECCO-EpiCom Cohort2014In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 20, no 1, p. 36-46Article in journal (Refereed)
    Abstract [en]

    Background:The EpiCom cohort is a prospective, population-based, inception cohort of inflammatory bowel disease (IBD) patients from 31 European centers covering a background population of 10.1 million. The aim of this study was to assess the 1-year outcome in the EpiCom cohort.

    Methods:Patients were followed-up every third month during the first 12 (3) months, and clinical data, demographics, disease activity, medical therapy, surgery, cancers, and deaths were collected and entered in a Web-based database (www.epicom-ecco.eu).

    Results:In total, 1367 patients were included in the 1-year follow-up. In western Europe, 65 Crohn's disease (CD) (16%), 20 ulcerative colitis (UC) (4%), and 4 IBD unclassified (4%) patients underwent surgery, and in eastern Europe, 12 CD (12%) and 2 UC (1%) patients underwent surgery. Eighty-one CD (20%), 80 UC (14%), and 13 (9%) IBD unclassified patients were hospitalized in western Europe compared with 17 CD (16%) and 12 UC (8%) patients in eastern Europe. The cumulative probability of receiving immunomodulators was 57% for CD in western (median time to treatment 2 months) and 44% (1 month) in eastern Europe, and 21% (5 months) and 5% (6 months) for biological therapy, respectively. For UC patients, the cumulative probability was 22% (4 months) and 15% (3 months) for immunomodulators and 6% (3 months) and 1% (12 months) for biological therapy, respectively in the western and eastern Europe.

    Discussion:In this cohort, immunological therapy was initiated within the first months of disease. Surgery and hospitalization rates did not differ between patients from eastern and western Europe, although more western European patients received biological agents and were comparable to previous population-based inception cohorts.

  • 3.
    Burisch, Johan
    et al.
    Digestive Disease Centre, Medical Section, Herlev University Hospital, Copenhagen, Denmark.
    Vardi, Hillel
    Department of Public Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
    Pedersen, Natalia
    Digestive Disease Centre, Medical Section, Herlev University Hospital, Copenhagen, Denmark.
    Brinar, Marko
    Division of Gastroenterology and Hepatology, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
    Cukovic-Cavka, Silvja
    Division of Gastroenterology and Hepatology, University Hospital Center Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
    Kaimakliotis, Ioannis
    Private Practice, Nicosia, Cyprus.
    Duricova, Dana
    IBD Center ISCARE, Charles University, Prague, Czech Republic.
    Bortlik, Martin
    IBD Center ISCARE, Charles University, Prague, Czech Republic.
    Shonová, Olga
    Department of Gastroenterology, Hospital Ceske Budejovice, Ceske Budejovice, Czech Republic.
    Vind, Ida
    Department of Medicine, Amager Hospital, Amager, Denmark.
    Avnstrøm, Søren
    Department of Medicine, Amager Hospital, Amager, Denmark.
    Thorsgaard, Niels
    Department of Medicine, Herning Central Hospital, Herning, Denmark.
    Krabbe, Susanne
    Medical Department, Viborg Regional Hospital, Viborg, Denmark.
    Andersen, Vibeke
    Medical Department, Viborg Regional Hospital, Viborg, Denmark; Organ Center, Hospital of Southern Jutland, Aabenraa, Denmark; Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
    Dahlerup, Jens F
    Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Arhus, Denmark.
    Kjeldsen, Jens
    Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark.
    Salupere, Riina
    Division of Endocrinology and Gastroenterology, Tartu University Hospital, Tartu, Estonia.
    Olsen, Jónger
    Medical Department, The National Hospital of the Faroe Islands, Torshavn, Faroe Islands.
    Nielsen, Kári R
    Medical Department, The National Hospital of the Faroe Islands, Torshavn, Faroe Islands.
    Manninen, Pia
    Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.
    Collin, Pekka
    Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.
    Katsanos, Konstantinnos H
    First Division of Internal Medicine and Hepato-Gastroenterology Unit, University Hospital, Ioannina, Greece.
    Tsianos, Epameinondas V
    First Division of Internal Medicine and Hepato-Gastroenterology Unit, University Hospital, Ioannina, Greece.
    Ladefoged, Karin
    Medical Department, Dronning Ingrids Hospital, Nuuk, Greenland.
    Lakatos, Laszlo
    First Department of Medicine, Semmelweis University, Budapest, Hungary.
    Bailey, Yvonne
    Department of Gastroenterology, Adelaide and Meath Hospital, TCD, Dublin, Ireland.
    OʼMorain, Colm
    Department of Gastroenterology, Adelaide and Meath Hospital, TCD, Dublin, Ireland.
    Schwartz, Doron
    Department of Gastroenterology and Hepatology, Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
    Lupinacci, Guido
    U.O. di Gastroenterologia e Endoscopia Digestiva, Az.Ospedaliera Ospedale Maggiore di Crema, Crema, Italy; EpiCom Northern Italy centre based in Crema and Cremona, Firenze, Forli, Padova and Reggio Emilia, Italy.
    De Padova, Angelo
    EpiCom Northern Italy centre based in Crema and Cremona, Firenze, Forli, Padova and Reggio Emilia, Italy; U.O. Gastroenterologia ed Endoscopia Digestiva, Ospedale Morgagni, Pierantoni, Forli, Italy.
    Jonaitis, Laimas
    Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
    Kupcinskas, Limas
    Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
    Turcan, Svetlana
    Department of Gastroenterology, State University of Medicine and Pharmacy of the Republic of Moldova, Chisinau, Republic of Moldova.
    Barros, Louisa
    Department of Medicine, Hospital de Vale de Sousa, Porto, Portugal.
    Magro, Fernando
    Department of Gastroenterology, Hospital de Sao Joao, Porto, Portugal; Institute of Pharmacology and Therapeutics, Oporto Medical School, Porto, Portugal; Institute for molecular and cell biology, University of Porto, Porto, Portugal.
    Lazar, Daniela
    Clinic of Gastroenterology, University of Medicine "Victor Babes," Timisoara, Romania.
    Goldis, Adrian
    Clinic of Gastroenterology, University of Medicine "Victor Babes," Timisoara, Romania.
    Nikulina, Inna
    Department of Gastroenterology, Moscow Regional Research Clinical Institute, Moscow, Russia.
    Belousova, Elena
    Department of Gastroenterology, Moscow Regional Research Clinical Institute, Moscow, Russia.
    Fernandez, Alberto
    Gastroenterology Department, POVISA Hospital, Vigo, Spain.
    Pineda, Juan R
    Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain.
    Almer, Sven
    GastroCentrum, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Solna, Karolinska University Hospital, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Tsai, Her-Hsin
    Hull and East Yorkshire NHS Trust and Hull and York Medical School, Hull Royal Infirmary, Hull, United Kingdom.
    Sebastian, Shaji
    Hull and East Yorkshire NHS Trust and Hull and York Medical School, Hull Royal Infirmary, Hull, United Kingdom.
    Friger, Michael
    Department of Public Health, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
    Greenberg, Dan
    Department of Health Systems Management, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel; Guilford Glazer Faculty of Business and Management, Ben Gurion University of the Negev, Beer Sheva, Israel.
    Lakatos, Peter L
    First Department of Medicine, Semmelweis University, Budapest, Hungary.
    Langholz, Ebbe
    Department of Medical Gastroenterology, Gentofte Hospital, Copenhagen, Denmark.
    Odes, Selwyn
    Department of Gastroenterology and Hepatology, Soroka Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel.
    Munkholm, Pia
    Digestive Disease Centre, Medical Section, Herlev University Hospital, Copenhagen, Denmark.
    Costs and resource utilization for diagnosis and treatment during the initial year in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom Study2015In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 21, no 1, p. 121-131Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: No direct comparison of health care cost in patients with inflammatory bowel disease across the European continent exists. The aim of this study was to assess the costs of investigations and treatment for diagnostics and during the first year after diagnosis in Europe.

    METHODS: The EpiCom cohort is a prospective population-based inception cohort of unselected inflammatory bowel disease patients from 31 Western and Eastern European centers. Patients were followed every third month from diagnosis, and clinical data regarding treatment and investigations were collected. Costs were calculated in euros (&OV0556;) using the Danish Health Costs Register.

    RESULTS: One thousand three hundred sixty-seven patients were followed, 710 with ulcerative colitis, 509 with Crohn's disease, and 148 with inflammatory bowel disease unclassified. Total expenditure for the cohort was &OV0556;5,408,174 (investigations: &OV0556;2,042,990 [38%], surgery: &OV0556;1,427,648 [26%], biologicals: &OV0556;781,089 [14%], and standard treatment: &OV0556;1,156,520 [22%)]). Mean crude expenditure per patient in Western Europe (Eastern Europe) with Crohn's disease: investigations &OV0556;1803 (&OV0556;2160) (P = 0.44), surgery &OV0556;11,489 (&OV0556;13,973) (P = 0.14), standard treatment &OV0556;1027 (&OV0556;824) (P = 0.51), and biologicals &OV0556;7376 (&OV0556;8307) (P = 0.31). Mean crude expenditure per patient in Western Europe (Eastern Europe) with ulcerative colitis: investigations &OV0556;1189 (&OV0556;1518) (P < 0.01), surgery &OV0556;18,414 (&OV0556;12,395) (P = 0.18), standard treatment &OV0556;896 (&OV0556;798) (P < 0.05), and biologicals &OV0556;5681 (&OV0556;72) (P = 0.51).

    CONCLUSIONS: In this population-based unselected cohort, costs during the first year of disease were mainly incurred by investigative procedures and surgeries. However, biologicals accounted for >15% of costs. Long-term follow-up of the cohort is needed to assess the cost-effectiveness of biological agents.

  • 4.
    Canova, Cristina
    et al.
    Department of Molecular Medicine, University of Padua, Padua, Italy.
    Pitter, Gisella
    Department of Molecular Medicine, University of Padua, Padua, Italy; School of Specialization in Hygiene and Preventive Medicine, University of Padua, Padua, Italy.
    Zanier, Loris
    Epidemiological Service, Udine, Italy.
    Zanotti, Renzo
    Department of Molecular Medicine, University of Padua, Padua, Italy.
    Simonato, Lorenzo
    Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, Italy.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, College of Physicians and Surgeons, Columbia University, New York NY, USA.
    Inflammatory Bowel Diseases in Children and Young Adults with Celiac Disease: A Multigroup Matched Comparison2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 11, p. 1996-2000Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Celiac disease (CD) has been linked to inflammatory bowel disease (IBD) but previous reports have been inconsistent and may have been affected by surveillance bias.

    METHODS: Matched birth cohort study in Friuli-Venezia Giulia Region, Italy. We identified 1294 individuals with CD aged 0 to 23 years at diagnosis using pathology reports, hospital discharge records, or copayment exemptions. Each CD individual was matched with up to 5 general population reference individuals from the regional Medical Birth Register in Friuli-Venezia Giulia (n = 5681). As secondary comparison groups, we used individuals undergoing small intestinal biopsy but not having villous atrophy (either Marsh 0-1-2 or exclusively Marsh 0). Individuals with IBD were identified through hospital discharge records or copayment exemptions. Conditional logistic regression was used to estimate odds ratios (ORs) for having IBD among CD individuals (before or after CD diagnosis) compared with their matched references.

    RESULTS: Overall 35 individuals with IBD were identified (29 with CD and 6 general population controls). This corresponded to an increased risk of IBD in CD (OR = 24.17; 95% CI, 10.03-58.21). However, compared with individuals with Marsh 0-1-2 the OR decreased to 1.41 (95% CI, 0.91-2.18) and restricting our comparison group to individuals with Marsh 0, the OR was 1.28 (95% CI, 0.61-2.70).

    CONCLUSIONS: In conclusion, this article found a highly increased risk of IBD in individuals with CD when comparing with the general population. Bias is the likely explanation for the very high risk increase for IBD in CD because the excess risk was substantially lower when we used individuals with a small intestinal biopsy without villous atrophy as our reference.

  • 5.
    Drobin, Kimi
    et al.
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Assadi, Ghazaleh
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Hong, Mun-Gwan
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Andersson, Eni
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Fredolini, Claudia
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Forsström, Björn
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Reznichenko, Anna
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Akhter, Tahmina
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Ek, Weronica E.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; Department of Gastrointestinal and Liver Diseases, Biodonostia Health Research Institute, San Sebastián, Spain.
    Hansen, Mark Berner
    AstraZeneca R&D Mölndal, Innovative and Global Medicines, Mölndal, Sweden; Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
    Sandberg, Kristian
    Science for Life Laboratory, Drug Discovery & Development Platform & Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Greco, Dario
    Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Schwenk, Jochen M.
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    D'Amato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioDonostia Health Research Institute, San Sebastian, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci2019In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 2, p. 306-316Article in journal (Refereed)
    Abstract [en]

    Background: Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential.

    Methods: Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohn's disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping.

    Results: By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity.

    Conclusions: Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.

  • 6.
    Everhov, Åsa H.
    et al.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Khalili, Hamed
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Gastroenterology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Masschusetts, USA.
    Askling, Johan
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Myrelid, Pär
    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, Linköping, Sweden.
    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 University, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Nordenvall, Caroline
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Center for Digestive Disease, Division of Coloproctology, Karolinska University Hospital, Stockholm, Sweden.
    Neovius, Martin
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Söderling, Jonas
    Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Olén, Ola
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Pediatric Gastroenterology and Nutrition, Sachs' Children and Youth Hospital, Stockholm, Sweden.
    Work Loss Before and After Diagnosis of Crohn's Disease2019In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 7, p. 1237-1247Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to examine work loss in patients with Crohn's disease.

    Methods: Using nationwide registers, we identified incident patients with Crohn's disease (2007-2010) and population comparator subjects without inflammatory bowel disease, matched by age, sex, calendar year, health care region, and education level. We assessed the number of lost workdays due to sick leave and disability pension from 5 years before to 5 years after first diagnosis of Crohn's disease or end of follow-up (September 30, 2015).

    Results: Among the 2015 incident Crohn's disease patients (median age, 35 years; 50% women), both the proportion with work loss and the mean annual number of lost workdays were larger 5 years before diagnosis (25%; mean, 45 days) than in the 10,067 comparators (17%; mean, 29 days). Increased work loss was seen during the year of diagnosis, after which it declined to levels similar to before diagnosis. Of all patients, 75% had no work loss 24-12 months before diagnosis. Of them, 84% had full work ability also 12-24 months after diagnosis. In patients with total work loss (8.3% of all) before diagnosis, 83% did not work after. Among those with full work ability before diagnosis, the absolute risk of having total work loss after diagnosis was 1.4% (0.43% in the comparators). Our results were consistent across several sensitivity analyses using alternative definitions for date of diagnosis.

    Conclusions: Patients with Crohn's disease had increased work loss several years before diagnosis, possibly explained by comorbidity or by diagnostic delay.

  • 7.
    Fritsch Fredin, Maria
    et al.
    Astra-Zeneca, Mölndal.
    Hultin, Leif
    Astra-Zeneca, Mölndal.
    Hyberg, Gina
    Astra-Zeneca, Mölndal.
    Rehnström, Erika
    Astra-Zeneca, Mölndal.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Health and Medical Sciences.
    Melgar, Silvia
    Astra-Zeneca, Mölndal.
    Jansson, Liselotte
    Astra-Zeneca, Mölndal.
    Predicting and monitoring colitis development in mice by micro-computed tomography2008In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 14, no 4, p. 491-499Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Computed tomography (CT) has been developed as a tool for monitoring human inflammatory bowel disease (IBD). The aim of this study was to evaluate colon wall thickness as a noninvasive marker in the dextran sodium sulfate (DSS) mouse model of colitis using micro-CT. METHODS: Mice were examined by micro-CT 1, 2, or 4 times between day 0 (d0) and d26 after induction of colitis to document the kinetics of changes in colon wall thickness and its relation to colitis development. RESULTS: DSS-treated mice displayed a significantly thicker colon wall at all timepoints (days 5, 8, 12, 19, and 26) investigated compared to healthy controls. Colon wall thickness showed a good correlation to the macroscopic grading of colitis (r = 0.81). The increase in colon wall thickness occurred mainly during the acute phase of colitis (between days 5 and 12) and did not progress much further in the chronic phase of colitis (d26). Colon wall thickness at d26 was thereby predicted by measurements at d12. All mice did not respond equally to DSS and this difference was manifest during the first 2 weeks of colitis, providing an important tool in stratifying responders from nonresponders. CONCLUSIONS: While the potential impact of handling and anesthesia should be considered on repeated micro-CT, irradiation exposure during repeated micro-CT did not affect the development of colitis. Thus, the results suggest that micro-CT can be used for monitoring and prediction of the inflammatory response in mouse colitis in future therapeutic studies.

  • 8.
    Ganda Mall, John-Peter
    et al.
    Örebro University, School of Medical Sciences.
    Casado-Bedmar, Maite
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Winberg, Martin E.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Brummer, Robert Jan
    Örebro University, School of Medical Sciences.
    Schoultz, Ida
    Örebro University, School of Medical Sciences.
    Keita, Åsa V.
    A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, no 1, p. 166-178Article in journal (Refereed)
    Abstract [en]

    Background: Administration of β-glucan has shown immune-enhancing effects. Our aim was to investigate whether β-glucan could attenuate mast cell (MC)-induced hyperpermeability in follicle-associated epithelium (FAE) and villus epithelium (VE) of patients with Crohn's disease (CD) and in noninflammatory bowel disease (IBD)-controls. Further, we studied mechanisms of β-glucan uptake and effects on MCs in vitro.

    Methods: Segments of FAE and VE from 8 CD patients and 9 controls were mounted in Ussing chambers. Effects of the MC-degranulator compound 48/80 (C48/80) and yeast-derived β-1,3/1,6 glucan on hyperpermeability were investigated. Translocation of β-glucan and colocalization with immune cells were studied by immunofluorescence. Caco-2-cl1- and FAE-cultures were used to investigate β-glucan-uptake using endocytosis inhibitors and HMC-1.1 to study effects on MCs.

    Results: β-glucan significantly attenuated MC-induced paracellular hyperpermeability in CD and controls. Transcellular hyperpermeability was only significantly attenuated in VE. Baseline paracellular permeability was higher in FAE than VE in both groups, P<0.05, and exhibited a more pronounced effect by C48/80 and β-glucan P<0.05. No difference was observed between CD and controls. In vitro studies showed increased passage, P<0.05, of β-glucan through FAE-culture compared to Caco-2-cl1. Passage was mildly attenuated by the inhibitor methyl-β-cyclodextrin. HMC-1.1 experiments showed a trend to decreasing MC-degranulation and levels of TNF-α but not IL-6 by β-glucan. Immunofluorescence revealed more β-glucan-uptake and higher percentage of macrophages and dendritic cells close to β-glucan in VE of CD compared to controls.

    Conclusions: We demonstrated beneficial effects of β-glucan on intestinal barrier function and increased β-glucan-passage through FAE model. Our results provide important and novel knowledge on possible applications of β-glucan in health disorders and diseases characterized by intestinal barrier dysfunction.

  • 9.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medicine, Div. of Gastroenterol., Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Department of Medicine, Div of Gastroenterol, Örebro Univ Hosp, Örebro, Sweden; Fac of Med and Hlth, Örebro Univ, Örebro, Sweden.
    Hultgren, Olof
    Örebro University, School of Medical Sciences. Department of Microbiology and Immunology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 6, p. 932-945Article in journal (Refereed)
    Abstract [en]

    Background: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.

    Methods: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCR beta) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with non-inflamed colons using next-generation sequencing.

    Results: Compared with controls and patients with CC, patients with LC had significantly lower diversity with significantly lower evenness and richness in TCRVb-Jb gene segments. Similarly, patients with LC-HR had lower diversity because of significantly lower TCRVb-Jb clone richness. Patients with UC and UC-R showed significantly higher diversity and richness. Univariate and multivariate analyses were performed to identify TCRVb-Jb gene segments differentiating disease types from controls or their remission counterparts. Patients with LC were discriminated from controls by 12 clones and from patients with CC by 8 clones. Neither univariate nor multivariate analyses showed significance for patients with CC or CC-HR compared with controls. Patients with UC and UC-R had 16 and 14 discriminating clones, respectively, compared with controls.

    Conclusions: Altogether, patients with MC and UC showed an oligoclonal TCRb distribution. TCRVb-Jb clone types and their diversity were distinctive between patients with CC and LC, as well as for patients with UC, suggesting different pathophysiological mechanisms according to disease type and stage. This study suggests that CC and LC are different entities because of differences in immunoregulatory responses, as mirrored by their T-cell repertoire.

  • 10.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences. Department of Internal Medicine, Division of Gastroenterology.
    Genetics in twins with Crohn's disease: less pronounced than previously believed?2011In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 17, no 1, p. 6-12Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The influence of genetics in inflammatory bowel disease is emphasized by twin concordance. Previous studies have methodological limitations. The aims were to establish reliable concordance rates and compare phenotypic characteristics in concordant and discordant monozygotic pairs, anticipating the former reflects a genetically determined subgroup.

    METHODS: By re-running the Swedish twin registry with the Swedish hospital discharge register, observation time was extended. Diagnoses and phenotype were based on medical notes. Pairs with unknown zygosity and where both twins were not alive or not responding to the questionnaire were excluded. In all, 149 new twin pairs of the same sex, born 1909-1980 were identified.

    RESULTS: Of new pairs, 4/29 monozygotic, 0/38 dizygotic, and 0/1 twin pairs with unknown zygosity were concordant for Crohn's disease (CD). In ulcerative colitis (UC), 4/31 monozygotic, 4/48 dizygotic, and 0/1 twin pairs with unknown zygosity were concordant. New pairs were added to the original cohort. Restricting analyses to pairs born 1886-1958, the time period used in the original cohort, 9/33 monozygotic and 1/50 dizygotic pairs were concordant for CD (P = 0.008), 6/41 and 3/49, correspondingly, for UC (P = 0.29). There was a trend for concordant twins to have less colonic CD than discordant twins, 15% versus 35% (P = 0.09) in twins born 1886-1980.

    CONCLUSIONS: Previous twin studies have overestimated the influence of genetics in CD. A trend for phenotypic difference between concordant and discordant pairs was observed, suggesting that the clinical entity represents diseases with different pathophysiological backgrounds.

  • 11.
    Halfvarson, Jonas
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden.
    Jess, Tine
    Bodin, Lennart
    Örebro University, Örebro University School of Business.
    Järnerot, Gunnar
    Munkholm, Pia
    Binder, Vibeke
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Longitudinal concordance for clinical characteristics in a Swedish-Danish twin population with inflammatory bowel disease2007In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 13, no 12, p. 1536-1544Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The genetic influence on disease course in inflammatory bowel disease (IBD) remains unknown. We therefore aimed to study longitudinal concordance for clinical characteristics and longitudinal stability using the Montreal Classification in an IBD twin population. METHODS: A total of 158 twins with ulcerative colitis (UC) (18 belonging to 9 concordant monozygotic pairs) and 141 twins with Crohn's disease (CD) (34 belonging to 17 concordant monozygotic pairs) were enrolled. Medical notes were scrutinized for clinical characteristics at diagnosis and after 10 years. Using the binominal distribution, we tested the hypothesis that clinical characteristics were independent within individuals in disease concordant monozygotic pairs. RESULTS: In CD, location was identical in 11/17 monozygotic concordant pairs at diagnosis (P = 0.008) and in 11/16 pairs after 10 years (P = 0.02). Behavior at diagnosis was identical in 13/17 pairs (P = 0.03) and in 11/16 pairs after 10 years (P = 0.01). Monozygotic UC twins were concordant (within 5 years) for age at diagnosis (6/9 pairs; P < 0.001) and symptomatic onset (4/9 pairs; P = 0.02) but not for extent of disease at diagnosis or after 10 years. The Montreal Classification did not demonstrate longitudinal stability, either regarding location or behavior of CD or extent of UC. CONCLUSIONS: The high phenotypic concordance, both at diagnosis and longitudinally, in monozygotic twins with CD supports a genetic influence not only on disease occurrence but also on disease course. This contrasts with UC, where the genetic impact appears less. Montreal Classification characteristics changed over time and should be used cautiously.

  • 12. Halfvarson, Jonas
    et al.
    Jess, Tine
    Magnuson, Anders
    Montgomery, Scott M.
    Örebro University, Department of Clinical Medicine.
    Orholm, Marianne
    Tysk, Curt
    Örebro University, Department of Clinical Medicine.
    Binder, Vibeke
    Järnerot, Gunnar
    Environmental factors in inflammatory bowel disease: a co-twin control study of a Swedish-Danish twin population2006In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 12, no 10, p. 925-933Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Genetics and environmental factors are implicated in the etiology of inflammatory bowel disease (IBD). We studied environmental factors in a population-based Swedish-Danish twin cohort using the co-twin control method.

    SUBJECTS AND METHODS:

    A questionnaire was sent to 317 twin pairs regarding markers of exposures in the following areas: infections/colonization and diet as well as smoking, appendectomy, and oral contraceptives. Odds ratios (OR) were calculated by conditional logistic regression. When confounding appeared plausible, multivariate conditional logistic regression was added. The questions were also divided into topic groups, and adjustment was made for multiple testing within each of the groups.

    RESULTS:

    The response rate to the questionnaire was 83%. In consideration of the study design, only discordant pairs were included (Crohn's disease [CD], n = 102; ulcerative colitis [UC], n = 125). Recurrent gastrointestinal infections were associated with both UC (OR, 8.0; 95% confidence interval [CI], 1.0-64) and CD (OR, 5.5; 95% CI, 1.2-25). Hospitalization for gastrointestinal infections was associated with CD (OR, 12; 95% CI, 1.6-92). Smoking was inversely associated with UC (OR, 0.4; 95% CI, 0.2-0.9) and associated with CD (OR, 2.9; 95% CI, 1.2-7.1).

    CONCLUSIONS:

    The observed associations indicate that markers of possible infectious events may influence the risk of IBD. Some of these effects might be mediated by long-term changes in gut flora or alterations in reactivity to the flora. The influence of smoking in IBD was confirmed.

  • 13.
    Halfvarson, Jonas
    et al.
    Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Sweden.
    Järnerot, Gunnar
    Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Sweden.
    Treatment of choice for acute severe steroid-refractory ulcerative colitis is remicade2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 1, p. 143-145Article in journal (Refereed)
  • 14. Hjortswang, Henrik
    et al.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Bohr, Johan
    Benoni, Cecilia
    Kilander, Anders
    Larsson, Lasse
    Vigren, Lina
    Ström, Magnus
    Defining clinical criteria for clinical remission and disease activity in collagenous colitis2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 12, p. 1875-1881Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Collagenous colitis is a chronic inflammatory bowel disease accompanied mainly by nonbloody diarrhea. The objectives of treatment are to alleviate the symptoms and minimize the deleterious effects on health-related quality of life (HRQOL). There is still no generally accepted clinical definition of remission or relapse. The purpose of this study was to analyze the impact of bowel symptoms on HRQOL and accordingly suggest criteria for remission and disease activity based on impact of patient symptoms on HRQOL.

    METHODS: The design was a cross-sectional postal survey of 116 patients with collagenous colitis. The main outcome measures were 4 HRQOL questionnaires: the Short Health Scale, the Inflammatory Bowel Disease Questionnaire, the Rating Form of IBD Patient Concerns, and the Psychological General Well-Being Index, and a 1-week symptom diary recording number of stools/day and number of watery stools/day.

    RESULTS: Severity of bowel symptoms had a deleterious impact on patients' HRQOL. Patients with a mean of >/=3 stools/day or a mean of >/=1 watery stool/day had a significantly impaired HRQOL compared to those with <3 stools/day and <1 watery stool/day.

    CONCLUSIONS: We propose that clinical remission in collagenous colitis is defined as a mean of <3 stools/day and a mean of <1 watery stool per day and disease activity to be a daily mean of >/=3 stools or a mean of >/=1 watery stool.

  • 15.
    Jansson, A.
    et al.
    School of Life Sciences, Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
    Pernestig, A.-K.
    School of Life Sciences, Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
    Nilsson, P.
    School of Life Sciences, Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
    Jirstrand, M.
    Fraunhofer-Chalmers Research Centre for Industrial Mathematics, Gothenburg, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Biomedicine.
    Toward quantifying the thymic dysfunction state in mouse models of inflammatory bowel disease2013In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 19, no 4, p. 881-888Article, review/survey (Refereed)
    Abstract [en]

    Inflammatory bowel disease is characterized by a number of immunological alterations, not the least in the T-cell compartment. Numerous animal models of colitis have revealed aberrant thymocyte dynamics associated with skewed thymocyte development. The recent advancements in quantitative methods have proposed critical kinetic alterations in the thymocyte development during the progression of colitis. This review focuses on the aberrant thymocyte dynamics in Gαi2-deficient mice as this mouse model provides most quantitative data of the thymocyte development associated with colitis. Herein, we discuss several dynamic changes during the progression of colitis and propose a hypothesis for the underlying causes for the skewed proportions of the thymocyte populations seen in the Gαi2-deficient mice and in other mouse models of colitis.

  • 16.
    Malmborg, Petter
    et al.
    Department of Women and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Bahmanyar, Shahram
    Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.
    Grahnquist, Lena
    Department of Women and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Hildebrand, Hans
    Department of Women and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Primary Care and Public Health, Charing Cross Hospital, Imperial College, London, UK.
    Cesarean section and the risk of pediatric Crohn's disease2012In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 18, no 4, p. 703-708Article in journal (Refereed)
    Abstract [en]

    Background: Crohn's disease (CD) could involve an inappropriate immune response against normal bowel flora. Disrupted or atypical patterns of microbial bowel colonization may impair development of homeostasis between gut flora and the immune system. Perinatal microbial exposures may be particularly important in stimulating intestinal immune recognition. As birth by cesarean section is thought to represent an atypical pattern of early bowel colonization, we examined its association with pediatric CD. Methods: Some 1536 patients diagnosed with pediatric CD and 15,439 controls matched by delivery unit, week of birth, sex, and born between 1973 and 2006 were identified through Swedish registers. The association of birth by cesarean section with pediatric CD was examined using conditional logistic regression, with stratification by sex and adjustment for parental socioeconomic index and maternal infections during pregnancy. Results: Birth by cesarean section is associated with a modestly increased risk for pediatric CD among boys (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.01-1.54) but not girls, (OR = 0.99, 95% CI 0.76-1.29) and elective cesarean section is associated with a modest increased risk for the entire population (OR = 1.36, 95% CI 1.02-1.80). Conclusions: This study does not suggest that the delivery procedure should be altered, but the findings may be of etiological significance in CD, indicating a potential role for perinatal exposures associated with delivery mode. Although the sex difference may have arisen by chance, the modestly increased CD risk for boys delivered by cesarean section is consistent with sex-specific differences in susceptibility to some exposures.

  • 17.
    Malmborg, Petter
    et al.
    Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
    Grahnquist, Lena
    Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
    Ideström, Maja
    Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
    Lindholm, Johan
    Departments of Oncology-Pathology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Befrits, Ragnar
    Departments of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden .
    Björk, Jan
    Departments of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden .
    Montgomery, Scott
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom .
    Hildebrand, Hans
    Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
    Presentation and progression of childhood-onset inflammatory bowel disease in northern Stockholm County2015In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 21, no 5, p. 1098-1108Article in journal (Refereed)
    Abstract [en]

    Background: Some studies have suggested that childhood-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid progression to complications. Here, we report the presentation and progression of patients diagnosed with IBD during childhood in a population-based cohort from northern Stockholm County.

    Methods: Medical records for all 280 patients diagnosed in the period 1990-2007 with childhood-onset IBD in northern Stockholm County were followed until 2011 (median follow-up time, 8.8 yr). Disease phenotypes were classified according to the Paris pediatric IBD classification.

    Results: Among the 74 patients with ulcerative colitis, 72% presented with pancolitis. Among the 200 patients with Crohn's disease (CD), 75% presented with colitis. Complicated disease behavior was observed in 18% of patients with CD by end of follow-up. Extension of the disease territory was observed in 22% of patients with ulcerative colitis and 15% of patients with CD. The cumulative risk of intra-abdominal surgery after 10 years was 8% (95% confidence interval, 4%-20%) for ulcerative colitis and 22% (95% confidence interval, 15%-28%) for patients with CD. Nonmucosal healing at 1 year was associated with a complicated disease course in patients with CD (hazard ratio = 14.56; 95% confidence interval, 1.79-118.68; P = 0.01).

    Conclusions: Patients with childhood-onset IBD were characterized by extensive colitis that was relatively stable over time and associated with a relatively low risk of complications and abdominal surgery. Our findings confirm the more extensive disease location in pediatric IBD but did not identify the proposed dynamic and aggressive nature of the childhood-onset phenotype. The association of nonmucosal healing with a complicated disease course suggests that endoscopy should guide treatment intensity in childhood-onset CD.

  • 18.
    Malmborg, Petter
    et al.
    Sach’ Children and Youth Hospital, South General Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Mouratidou, Natalia
    Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Sachs, Michael C.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Hammar, Ulf
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Khalili, Hamed
    Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston Massachusetts, USA.
    Neovius, Martin
    Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Hjern, Anders
    Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre for Health Equity Studies, Stockholm University/Karolinska Institutet, Stockholm, Sweden.
    Smedby, Karin E.
    Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Ekbom, Anders
    Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Askling, Johan
    Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    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.
    Olén, Ola
    Sach’ Children and Youth Hospital, South General Hospital, Stockholm, Sweden; Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
    Effects of Childhood-onset Inflammatory Bowel Disease on School Performance: A Nationwide Population-based Cohort Study Using Swedish Health and Educational Registers2019In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 10, p. 1663-1673Article in journal (Refereed)
    Abstract [en]

    Background: Childhood-onset inflammatory bowel disease (IBD) might negatively impact academic school performance. We conducted a nationwide study to examine the association between childhood-onset IBD and school results.

    Methods: Our study population was selected from Swedish health registers. In the National Patient Register (1990 to 2013), we identified 2827 children with IBD: Crohn's disease (CD), n = 1207, and ulcerative colitis (UC), n = 1370. Patients were matched with 10 reference individuals by age, sex, birth year, and place of residence (n = 28,235). Final compulsory school grades (0 to 320 grade points) and qualification for high school (yes or no) were obtained through the National School Register. Regression models controlling for socioeconomic factors were used to analyze the association of IBD with school performance.

    Results: Children with IBD had a lower final grade point average (adjusted mean grade difference [AMGD] -4.9, 95% confidence interval [CI] -7.1 to -2.6) but not a significantly higher risk to not qualify for high school (odds ratio [OR] 1.14, CI 0.99-1.31). The results were similar in children with UC (AMGD -5.5, CI -8.7 to -2.3) and CD (AMGD -4.7, CI -8.2 to -1.2). Underperformance was more common in subsets of IBD children characterized by markers associated with long-standing active disease (eg, >30 inpatient days [AMGD-18.1, CI -25.8 to -10.4]).

    Conclusion: Most children with IBD achieve comparable results in the final year of compulsory school as their healthy peers. Care should be improved for the subgroup of children for which IBD has a stronger negative impact on school performance.

  • 19. Schepens, Marloes A. A.
    et al.
    Vink, Carolien
    Schonewille, Arjan J.
    Roelofs, Hennie M. J.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences.
    van der Meer, Roelof
    Bovee-Oudenhoven, Ingeborg M. J.
    Supplemental antioxidants do not ameliorate colitis development in HLA-B27 transgenic rats despite extremely low glutathione levels in colonic mucosa2011In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 17, no 10, p. 2065-2075Article in journal (Refereed)
    Abstract [en]

    Background: Oxidative stress is presumed to play an important role in inflammatory bowel disease (IBD). Accordingly, antioxidant supplementation might be protective. Dietary calcium inhibited colitis development in HLA-B27 transgenic rats, an animal model mimicking IBD. As antioxidants might act at mucosa level and calcium predominantly in the gut lumen, we hypothesize that the combination has additive protective effects on colitis development. Methods: HLA-B27 rats were fed a control diet or the same diet supplemented with the antioxidants glutathione, vitamin C, and vitamin E, or supplemented with both antioxidants and calcium. Oxidative stress in colonic mucosa, colonic inflammation, intestinal permeability, and diarrhea were quantified. Results: Intestinal permeability, diarrhea, myeloperoxidase, and interleukin-1 beta levels were significantly lower in rats fed both antioxidants and calcium compared to rats supplemented with antioxidants only. No beneficial effects were observed in rats fed the diet supplemented with antioxidants only. Strikingly, despite extremely low colonic mucosal glutathione levels in HLA-B27 rats, there was no oxidative stress-related damage. Subsequent analyses showed no defect in expression of glutathione synthesis genes. Additional experiments, comparing young and older HLA-B27 rats, showed that glutathione levels and also reactive oxygen species production decreased with progression of intestinal inflammation. Conclusions: Antioxidant supplementation was ineffective in HLA-B27 rats despite low mucosal glutathione levels, because colitis development did not coincide with oxidative stress in this model. This indicates that the neutrophilic respiratory burst, and thus innate immune defense, is compromised in HLA-B27 rats. As supplementation with both calcium and antioxidants attenuated colitis development, we speculate that this protective effect is attributed to calcium only.

  • 20.
    Schoultz, Ida
    et al.
    Department of Physiology and Pharmacology, Calvin, Phoebe and Joan Snyder Institute of Infection Immunity and Inflammation, University of Calgary, Calgary, Canada .
    Söderholm, Johan D.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    McKay, Derek M.
    Department of Physiology and Pharmacology, Calvin, Phoebe and Joan Snyder Institute of Infection Immunity and Inflammation, University of Calgary, Calgary, Canada .
    Is metabolic stress a common denominator in inflammatory bowel disease?2011In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 17, no 9, p. 2008-18Article, review/survey (Refereed)
    Abstract [en]

    The enteric epithelium represents the major boundary between the outside world and the body, and in the colon it is the interface between the host and a vast and diverse microbiota. A common feature of inflammatory bowel disease (IBD) is decreased epithelial barrier function, and while a cause-and-effect relationship can be debated, prolonged loss of epithelial barrier function (whether this means the ability to sense bacteria or exclude them) would contribute to inflammation. While there are undoubtedly individual nuances in IBD, we review data in support of metabolic stress--that is, perturbed mitochondrial function--in the enterocyte as a contributing factor to the initiation of inflammation and relapses in IBD. The postulate is presented that metabolic stress, which can arise as a consequence of a variety of stimuli (e.g., infection, bacterial dysbiosis, and inflammation also), will reduce epithelial barrier function and perturb the enterocyte-commensal flora relationship and suggest that means to negate enterocytic metabolic stress should be considered as a prophylactic or adjuvant therapy in IBD.

  • 21.
    Sjöberg, Mats
    et al.
    Department of Medicine, Skaraborgs hospital, Lidköping, Sweden.
    Walch, Andrea
    Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria.
    Meshkat, Mina
    Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria.
    Gustavsson, Anders
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Järnerot, Gunnar
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Vogelsang, Harald
    Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria.
    Hertervig, Erik
    Department of Gastroenterology, Skåne University Hospital, Lund University, Lund, Sweden.
    Novacek, Gottfried
    Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria.
    Friis-Liby, Ingalill
    Department of Medicine, Division of Gastroenterology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Blomquist, Lars
    Department of Gastroenterology and Hepatology, Karolinska University Hospital Solna, Stockholm, Sweden.
    Angelberger, Sieglinde
    Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria.
    Karlén, Per
    Department of Medicine, Division of Gastroenterology, South Hospital, Stockholm, Sweden.
    Granno, Christer
    Department of Medicine, Division of Gastroenterology, Ryhov Hospital, Jönköping, Sweden.
    Vilien, Mogens
    Division of Gastroenterology, Hilleroed Hospital, Hilleroed, Denmark.
    Ström, Magnus
    Division of Gastroenterology and Hepatology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Verbaan, Hans
    Department of Gastroenterology, Skåne University Hospital, Malmö, Sweden.
    Hellström, Per M.
    Department of Gastroenterology and Hepatology, Karolinska University Hospital Solna, Stockholm, Sweden.
    Dejaco, Clemens
    Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria.
    Magnuson, Anders
    Clinical epidemiology and biostatistic unit, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Reinisch, Walter
    Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis: a retrospective observational study2012In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 18, no 2, p. 212-218Article in journal (Refereed)
    Abstract [en]

    Background: Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives. Methods: Outcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid-refractory moderate to severe UC: 1) a Swedish-Danish cohort (n 49) treated with a single infusion of IFX; 2) an Austrian cohort (n 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy-free survival at 3 and 12 months. Kaplan-Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy. Results: At 15 days, colectomy-free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX-treated patients of 11.2 (95% confidence interval [CI] 2.4-53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1-8.2, P = 0.030) at 12 months in comparison with CsA-treated patients. There were no opportunistic infections or mortality. Conclusions: Colectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months' follow-up. The superiority of CsA was seen principally during the first 15 days.

  • 22. Stjernman, Henrik
    et al.
    Grännö, Christer
    Järnerot, Gunnar
    Ockander, Leif
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Blomberg, Björn
    Ström, Magnus
    Hjortswang, Henrik
    Short health scale: a valid, reliable, and responsive instrument for subjective health assessment in Crohn's disease.2008In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 14, no 1, p. 47-52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Health-related quality of life (HRQoL) is an essential part of inflammatory bowel disease (IBD) assessment. The Short Health Scale (SHS), an HRQoL questionnaire in which the patients rate the disease impact on 4 important aspects of subjective health (symptoms, function, worry, and general well-being) was demonstrated in a previous study to be valid, reliable, and responsive in patients with ulcerative colitis. The present study evaluates the SHS in patients with Crohn's disease (CD). METHODS: In all, 367 CD patients completed the SHS and 4 other HRQoL questionnaires (IBDQ, SF-36, RFIPC, and PGWB) at their regular outpatient visits. Then 330 patients completed the questionnaires at a second visit 6 months later. In addition, reliability data were obtained from repeat measurements 4 weeks after the first visit in 40 patients stable in remission. RESULTS: Patients in remission scored better on all 4 questions than those with active disease (P < 0.001). All 4 questions were strongly correlated with the corresponding dimensions of the other HRQoL questionnaires (r(s) = 0.74-0.83). Reliability was confirmed with strong test-retest correlations (r(s) = 0.69-0.82) and intraclass correlation coefficients (0.66-0.77). Patients who changed from remission to active disease or vice versa showed a significant change in all 4 SHS scores (P < 0.005). CONCLUSIONS: SHS is a valid, reliable and responsive HRQoL instrument also in patients with CD. It is easily completed by the patient and requires no further calculation by the investigator. SHS gives a comprehensive overview of the main aspects of the patient's subjective health perception and is a useful tool in both clinical practice and clinical studies.

  • 23. Stjernman, Henrik
    et al.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Almer, Sven
    Ström, Magnus
    Hjortswang, Henrik
    Factors predicting the outcome of disease activity assessment in Crohn's disease2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 12, p. 1859-1866Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Crohn's Disease Activity Index (CDAI) has become the gold standard for assessment of disease activity in CD. This study investigated the relationship between CDAI and the physicians' global assessment of disease activity (PGA) and whether different demographic and disease-related factors predict the outcome.

    METHODS: Multiple linear regression analysis was used to investigate the relationship between CDAI and PGA obtained from 405 CD patients. Predictors of the CDAI and the PGA outcome were identified.

    RESULTS: The correlation between CDAI and PGA was moderate. In patients with CDAI >150, 72% of the total score were derived from the subjective variables. The regression coefficients were not significant for 3 of the CDAI variables. In regression analysis, C-reactive protein (CRP), stenosis, smoking, bowel resection, concomitant disease, and gender predicted the CDAI outcome. The PGA outcome was predicted only by CRP, stenosis, and fistula.

    CONCLUSIONS: The correlation between CDAI and PGA was moderate and the subjective variables had a high impact on CDAI. Factors with no obvious relation to inflammatory activity predicted the outcome of CDAI, but not PGA. In trials of CD therapies, separation of subjective (symptoms, well-being) from objective (endoscopy, inflammatory markers) variables should be considered in the assessment of disease activity.

  • 24.
    Théibaut, R.
    et al.
    UMR843, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique Hopitaux, Paris Université, Paris, France.
    Douchin, V.
    UMR843, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique Hopitaux, Paris Université, Paris, France.
    Jung, C.
    UMR843, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique Hopitaux, Paris Université, Paris, France.
    Merlin, F.
    UMR843, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique Hopitaux, Paris Université, Paris, France.
    Colombel, J. F.
    Registre EPIMAD, Serv Epidemiol & Sante Publ, Hop Calmette, Lille, France.
    Lemann, M.
    GETAID, Serv Gastroenterol, Hop St Louis, Paris, France.
    Almer, Sven
    Inst Klin Expt Med IKE, EM Kliniken, Univ Sjukhuset, Linköping Univ, Linköping, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    O'Morain, C.
    Fac Hlth Sci, Trinity Coll Dublin, Dublin, Ireland.
    Gassull, M.
    Hosp Badalona Germans Trias & Pujol, Badalona, Spain.
    Finkel, Y.
    Dept Clin Sci & Educ, Karolinska Inst, Stockholm, Sweden.
    Zouali, H.
    Centre d'Etude du Polymorphisme Humain (CEPH), Fondation Jean Dausset, Paris, France.
    Pascoe, L.
    Centre d'Etude du Polymorphisme Humain (CEPH), Fondation Jean Dausset, Paris, France.
    Hugot, J. P.
    UMR843, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique Hopitaux, Paris Université, Paris, France.
    RIP2 polymorphisms in inflammatory bowel diseases2011In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 17, no 4, p. 1055-1055Article in journal (Refereed)
  • 25. Törkvist, Leif
    et al.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ong, Rick T H
    Lördal, Mikael
    Sjöqvist, Urban
    Bresso, Francesca
    Björk, Jan
    Befrits, Ragnar
    Löfberg, Robert
    Blom, Johannes
    Carlson, Marie
    Padyukov, Leonid
    D'Amato, Mauro
    Seielstad, Mark
    Pettersson, Sven
    Analysis of 39 Crohn's disease risk loci in Swedish inflammatory bowel disease patients2010In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 16, no 6, p. 907-909Article in journal (Refereed)
  • 26.
    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, Stockholm, Sweden.
    Saunders-Pullman, Rachel
    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
    Ludvigsson, Jonas F.
    Department Medical Epidemiology and Biostatistics, 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, New York, USA.
    Burisch, Johan
    Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark.
    Olén, Ola
    Clinical Epidemiology Unit, Department of Medicine Solna, 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.
    Inflammatory Bowel Disease and Parkinson's Disease: A Nationwide Swedish Cohort Study2019In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 1, p. 111-123Article in journal (Refereed)
    Abstract [en]

    Background: Few studies have examined the association between inflammatory bowel disease (IBD) and Parkinson's disease (PD).

    Methods: To estimate the incidence and relative risk of PD development in a cohort of adult IBD, we included all incident IBD patients (n = 39,652) in the Swedish National Patient Register (NPR) between 2002 and 2014 (ulcerative colitis [UC]: n = 24,422; Crohn's disease [CD]: n = 11,418; IBD-unclassified [IBD-U]: n = 3812). Each IBD patient was matched for sex, age, year, and place of residence with up to 10 reference individuals (n = 396,520). In a cohort design, all incident PD occurring after the index date was included from the NPR. In a case-control design, all incident PD occurring before the index date was included. The association between IBD and PD and vice versa was investigated by multivariable Cox and logistic regression.

    Results: In IBD, there were 103 cases of incident PD, resulting in hazard ratios (HRs) for PD of 1.3 (95% confidence interval [CI], 1.0-1.7; P = 0.04) in UC, 1.1 (95% CI, 0.7-1.7) in CD, and 1.7 (95% CI, 0.8-3.0) in IBD-U. However, these effects disappeared when adjusting for number of medical visits during follow-up to minimize potential surveillance bias. In a case-control analysis, IBD patients were more likely to have prevalent PD at the time of IBD diagnosis than matched controls, with odds ratios of 1.4 (95% CI, 1.2-1.8) in all IBD patients, 1.4 (95% CI, 1.1-1.9) for UC, and 1.6 (95% CI, 1.1-2.3) for CD patients alone.

    Conclusions: IBD is associated with an increased risk of PD, but some of this association might be explained by surveillance bias. 10.1093/ibd/izy190_video1izy190.video15785623138001.

  • 27.
    Weimers, Petra
    et al.
    Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Saunders-Pullman, Rachel
    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department 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, NY, USA.
    Olén, Ola
    Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark; Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Pediatric Gastroenterology and Nutrition, Sachs' Children and Youth Hospital, Stockholm, Sweden.
    Burisch, Johan
    Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Inflammatory Bowel Disease and Parkinson's Disease: A Reply to Letter to the Editor of Shih-Wei Lai2019In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 10, p. E127-E127Article in journal (Refereed)
  • 28.
    Wickbom, Anna
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Eriksson, Sune
    Dept Pathology, Örebro Univ Hosp, Örebro, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clin Epidemiol & Biostat Unit, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences. Dept Gastroenterol, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Stable Incidence of Collagenous Colitis and Lymphocytic Colitis in Orebro, Sweden, 1999-2008: A Continuous Epidemiologic Study2013In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 19, no 11, p. 2387-2393Article in journal (Refereed)
    Abstract [en]

    Background: The incidence of microscopic colitis (MC) has increased in several centers, but long-term epidemiologic data are missing. We report an epidemiologic study of collagenous colitis (CC) and lymphocytic colitis (LC) during 1999-2008, as a follow-up of our previous studies 1984-1998. Methods: Population-based study of residents of the catchment area of the hospital, with a new diagnosis of MC between 1999 and 2008. Patients were identified by diagnosis registers of the Departments of Medicine and Pathology. Medical files were reviewed, and colonic biopsies were reevaluated. Results: Collagenous colitis was diagnosed in 96 patients (75 females) and LC in 90 patients (74 females). The mean annual age-standardized incidence (per 100,000 inhabitants) was MC 10.2 (95% confidence interval: 8.7-11.7), CC 5.2 (4.2-6.3), and LC 5.0 (4.0-6.0). Age-specific incidence showed a peak in females older than 70 years. Prevalence (per 100,000 inhabitants) on December 31, 2008, was MC 123 (107.6-140.0), CC 67.7 (56.4-80.6), and LC 55.3 (45.2-67.1). A comparison of current study period with 1993-1998 showed unchanged mean incidence of MC, but a 2-fold increase in women older than 60 years with LC (standardized rate ratios 2.2, [1.2-3.7]) and increased female to male ratio (4.6:1 versus 2.1:1; P = 0.02) in LC. Conclusions: After an initial rise during 1980s and early 1990s, annual incidence of CC and LC has been stable during the last 15 years around 5/100,000 inhabitants for each disorder. The increasing incidence in older women with LC may be related to an increasing proportion of older individuals in the background population and increased colonoscopy frequency in elderly.

  • 29. 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.

  • 30.
    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.

  • 31. Zucchelli, M
    et al.
    Torkvist, L
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Söderhäll, C
    Lee, Y-A
    Löfberg, R
    Kere, J
    D ´Amato, M
    No association between the eczema genes COL29A1 and IL31 and inflammatory bowel disease2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 7, p. 961-962Article in journal (Refereed)
  • 32. Zucchelli, Marco
    et al.
    Torkvist, Leif
    Bresso, Francesca
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hellquist, Anna
    Anedda, Francesca
    Assadi, Ghazaleh
    Lindgren, Gunnar B
    Svanfeldt, Monika
    Janson, Martin
    Noble, Colin L
    Pettersson, Sven
    Lappalainen, Maarit
    Paavola-Sakki, Paulina
    Halme, Leena
    Färkkilä, Martti
    Turunen, Ulla
    Satsangi, Jack
    Kontula, Kimmo
    Löfberg, Robert
    Kere, Juha
    D'Amato, Mauro
    PepT1 oligopeptide transporter (SLC15A1) gene polymorphism in inflammatory bowel disease2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 10, p. 1562-1569Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Human polymorphisms affecting gut epithelial barrier and interactions with bacteria predispose to the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC). The intestinal transporter PepT1, encoded by the SLC15A1 gene, mediates intracellular uptake of bacterial products that can induce inflammation and NF-kappaB activation upon binding to NOD2, a protein often mutated in CD. Hence, we tested SLC15A1 polymorphisms for association with IBD.

    METHODS: Twelve SLC15A1 single nucleotide polymorphisms (SNPs) were genotyped in 1783 individuals from 2 cohorts of Swedish and Finnish IBD patients and controls. An in vitro system was set up to evaluate the potential impact of SLC15A1 polymorphism on PepT1 transporter function by quantification of NOD2-mediated activation of NF-kappaB.

    RESULTS: The common allele (C) of a coding polymorphism (rs2297322, Ser117Asn) was associated with CD susceptibility both in Sweden and in Finland, but with genetic effects in opposite directions (risk and protection, respectively). The best evidence of association was found in both populations when the analysis was performed on individuals not carrying NOD2 common risk alleles (Sweden allelic P = 0.0007, OR 1.97, 95% confidence interval [CI] 1.34-2.92; Finland genotype P = 0.0013, OR 0.63, 95% CI 0.44-0.90). The PepT1 variant encoded by the C allele (PepT1-Ser117) was associated with reduced signaling downstream of NOD2 (P < 0.0001 compared to Pept1-Asn117).

    CONCLUSIONS: A functional polymorphism in the SLC15A1 gene might be of relevance to inflammation and antibacterial responses in IBD. Whether this polymorphism truly contributes to disease susceptibility needs to be further addressed, and should stimulate additional studies in other populations.

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