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  • 1. Chan, Simon S. M.
    et al.
    Luben, Robert
    Olsen, Anja
    Tjonneland, Anne
    Kaaks, Rudolf
    Teucher, Birgit
    Lindgren, Stefan
    Grip, Olof
    Key, Timothy
    Crowe, Francesca L.
    Bergmann, Manuela M.
    Boeing, Heiner
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Overvad, Kim
    Palli, Domenico
    Masala, Giovanna
    Kennedy, Hugh
    vanSchaik, Fiona
    Bueno-de-Mesquita, Bas
    Oldenburg, Bas
    Khaw, Kay-Tee
    Riboli, Elio
    Hart, Andrew R.
    Body Mass Index and the Risk for Crohn's Disease and Ulcerative Colitis: Data From a European Prospective Cohort Study (The IBD in EPIC Study)2013Inngår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 108, nr 4, s. 575-582Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Obesity is associated with a proinflammatory state that may be involved in the etiology of inflammatory bowel disease (IBD), for which there are plausible biological mechanisms. Our aim was to perform the first prospective cohort study investigating if there is an association between obesity and the development of incident IBD. METHODS: A total of 300,724 participants were recruited into the European Prospective Investigation into Cancer and Nutrition study. At recruitment, anthropometric measurements of height and weight plus physical activity and total energy intake from validated questionnaires were recorded. The cohort was monitored identifying participants who developed either Crohn's disease (CD) or ulcerative colitis (UC). Each case was matched with four controls and conditional logistic regression used to calculate odds ratios (ORs) for body mass index (BMI) adjusted for smoking, energy intake, and physical activity. RESULTS: In the cohort, 177 participants developed incident UC and 75 participants developed incident CD. There were no associations with the four higher categories of BMI compared with a normal BMI for UC (P-trend = 0.36) or CD (P-trend = 0.83). The lack of associations was consistent when BMI was analyzed as a continuous or binary variable (BMI 18.5 <25.0 vs. >= 25 kg/m(2)). Physical activity and total energy intake, factors that influence BMI, did not show any association with UC (physical activity, P-trend = 0.79; total energy intake, P-trend = 0.18) or CD (physical activity, P-trend = 0.42; total energy, P-trend = 0.11). CONCLUSIONS: Obesity as measured by BMI is not associated with the development of incident UC or CD. Alternative measures of obesity are required to further investigate the role of obesity in the development of incident IBD.

  • 2. Efe, Cumali
    et al.
    Tascilar, Koray
    Henriksson, Ida
    Lytvyak, Ellina
    Alalkim, Fatema
    Trivedi, Hirsh
    Eren, Fatih
    Eliasson, Johanna
    Beretta-Piccoli, Benedetta Terziroli
    Fischer, Janett
    Caliskan, Ali Riza
    Chayanupatkul, Maneerat
    Coppo, Claudia
    Ytting, Henriette
    Purnak, Tugrul
    Muratori, Luigi
    Werner, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Muratori, Paolo
    Rorsman, Fredrik
    Onnerhag, Kristina
    Gunsar, Fulya
    Nilsson, Emma
    Heurgue-Berlot, Alexandra
    Guzelbulut, Fatih
    Demir, Nurhan
    Gonen, Can
    Semela, David
    Aladag, Murat
    Kiyici, Murat
    Schiano, Thomas
    Montano-Loza, Aldo
    Berg, Thomas
    Ozaslan, Ersan
    Yoshida, Eric
    Bonder, Alan
    Marschall, Hanns-Ulrich
    Wahlin, Staffan
    Validation of Risk Scoring Systems in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cholangitis2019Inngår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 114, nr 7, s. 1101-1108Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: Risk stratification based on biochemical variables is a useful tool for monitoring ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC). Several UDCA response criteria and scoring systems have been proposed for risk prediction in PBC, but these have not been validated in large external cohorts. METHODS: We performed a study on data of 1746 UDCA-treated patients with PBC from 25 centers in Europe, United States, and Canada. The prognostic performance of the risk scoring systems (GLOBE and UK-PBC) and the UDCA response criteria (Barcelona, Paris I, Paris II, Rotterdam, and Toronto) were evaluated. We regarded cirrhosis-related complications (ascites, variceal bleeding, and/or hepatic encephalopathy) as clinical end points. RESULTS: A total of 171 patients reached a clinical end point during a median 7 years (range 1-16 years) of follow-up. The 5-, 10- and 15-year adverse outcome-free survivals were 95%, 85%, and 77%. The GLOBE and UK-PBC scores predicted cirrhosis-related complications better than the UDCA response criteria. The hazard ratio (HR) for a 1 standard deviation increase was HR 5.05 (95% confidence interval (CI): 4.43-5.74, P < 0.001) for the GLOBE score and HR 3.39 (95% CI: 3.10-3.72, P < 0.001) for the UK-PBC score. Overall, the GLOBE and UK-PBC risk scores showed similar and excellent prognostic performance (C-statistic, 0.93; 95% CI: 0.91%-95% vs 0.94; 95% CI: 0.91%-0.96%). DISCUSSION: In our international, multicenter PBC cohort, the GLOBE and UK-PBC risk scoring systems were good predictors of future cirrhosis-related complications.

  • 3.
    Forsberg, Göte
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Fahlgren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hörstedt, Per
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Hammarström, Sten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hammarström, Marie-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Presence of bacteria and innate immunity of intestinal epithelium in childhood celiac disease2004Inngår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 99, nr 5, s. 894-904Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Exposure to gliadin and related prolamins and appropriate HLA-DQ haplotype are necessary but not sufficient for contracting celiac disease (CD). Aberrant innate immune reactions could be contributing risk factors. Therefore, jejunal biopsies were screened for bacteria and the innate immune status of the epithelium investigated.

    METHODS: Children with untreated, treated, challenged CD, and controls were analyzed. Bacteria were identified by scanning electron microscopy. Glycocalyx composition and mucin and antimicrobial peptide production were studied by quantitative RT-PCR, antibody and lectin immunohistochemistry.

    RESULTS: Rod-shaped bacteria were frequently associated with the mucosa of CD patients, with both active and inactive disease, but not with controls. The lectin Ulex europaeus agglutinin I (UEAI) stained goblet cells in the mucosa of all CD patients but not of controls. The lectin peanut agglutinin (PNA) stained glycocalyx of controls but not of CD patients. mRNA levels of mucin-2 (MUC2), alpha-defensins HD-5 and HD-6, and lysozyme were significantly increased in active CD and returned to normal in treated CD. Their expression levels correlated to the interferon-gamma mRNA levels in intraepithelial lymphocytes. MUC2, HD-5, and lysozyme proteins were seen in absorptive epithelial cells. beta-defensins hBD-1 and hBD-2, carcinoembryonic antigen (CEA), CEA cell adhesion molecule-1a (CEACAM1a), and MUC3 were not affected.

    CONCLUSIONS: Unique carbohydrate structures of the glycocalyx/mucous layer are likely discriminating features of CD patients. These glycosylation differences could facilitate bacterial adhesion. Ectopic production of MUC2, HD-5, and lysozyme in active CD is compatible with goblet and Paneth cell metaplasia induced by high interferon-gamma production by intraepithelial lymphocytes.

  • 4.
    Ou, Gangwei
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hedberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hörstedt, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Baranov, Vladimir
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Forsberg, Göte
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Drobni, Mirva
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Sandström, Olof
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Hammarström, Marie-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hammarström, Sten
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Proximal small intestinal microbiota and identification of rod-shaped bacteria associated with childhood celiac disease2009Inngår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 104, nr 12, s. 3058-3067Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Alterations in the composition of the microbiota in the intestine may promote development of celiac disease (CD). Using scanning electron microscopy (SEM) we previously demonstrated that rod-shaped bacteria were present on the epithelium of proximal small intestine in children with CD but not in controls. In this study we characterize the microbiota of proximal small intestine in children with CD and controls and identify CD-associated rod-shaped bacteria. METHODS: Proximal small intestine biopsies from 45 children with CD and 18 clinical controls were studied. Bacteria were identified by 16S rDNA sequencing in DNA extracted from biopsies washed with buffer containing dithiothreitol to enrich bacteria adhering to the epithelial lining, by culture-based methods and by SEM and transmission electron microscopy. RESULTS: The normal, mucosa-associated microbiota of proximal small intestine was limited. It was dominated by the genera Streptococcus and Neisseria, and also contained Veillonella, Gemella, Actinomyces, Rothia, and Haemophilus. The proximal small intestine microbiota in biopsies from CD patients collected during 2004-2007 differed only marginally from that of controls, and only one biopsy (4%) had rod-shaped bacteria by SEM (SEM+). In nine frozen SEM+ CD biopsies from the previous study, microbiotas were significantly enriched in Clostridium, Prevotella, and Actinomyces compared with SEM- biopsies. Bacteria of all three genera were isolated from children born during the Swedish CD epidemic. New Clostridium and Prevotella species and Actinomyces graevenitzii were tentatively identified. CONCLUSIONS: Rod-shaped bacteria, probably of the indicated species, constituted a significant fraction of the proximal small intestine microbiota in children born during the Swedish CD epidemic and may have been an important risk factor for CD contributing to the fourfold increase in disease incidence in children below 2 years of age during that time.

  • 5. Swahn, Fredrik
    et al.
    Nilsson, Magnus
    Arnelo, Urban
    Löhr, Matthias
    Persson, Gunnar
    Enochsson, Lars
    Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Department of Surgical Gastroenterology, Karolinska University Hospital, Stockholm, Sweden.
    Rendezvous cannulation technique reduces post-ERCP pancreatitis: a prospective nationwide study of 12,718 ERCP procedures2013Inngår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 108, nr 4, s. 552-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: The aim of this study was to investigate if intraoperative rendezvous cannulation reduces the risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) because there is no universal consensus on the optimal treatment of common bile duct stones.

    METHODS: We performed a nationwide case-control study, nested within the cohort of ERCP procedures reported to the Swedish Registry for Gallstone Surgery and ERCP (GallRiks), between 2007 and 2009. Data were collected prospectively from a web-based registry of ERCP procedures that includes variables such as patient characteristics, indication, cannulation technique, diagnostic findings, therapeutic measures, and complications. The primary outcome was PEP.

    RESULTS: The registry included 12,718 ERCP procedures performed on patients without a history of previous ERCP. The risk of PEP when using the rendezvous technique compared with those who were cannulated by conventional means was reduced from 3.6 to 2.2% (odds ratio (OR) 0.5, 95% confidence interval 0.2-0.9, P=0.02). Although a significant reduction there are overall relatively few cases with PEP and the calculated numbers needed to treat to avoid one case of PEP is as high as 71. Other factors associated with increased risk of PEP were young age, prolonged procedure time, and elective ERCP.

    CONCLUSIONS: Rendezvous bile duct cannulation during ERCP reduces the risk of PEP from 3.6 to 2.2% compared with conventional biliary cannulation.

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