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  • 1.
    Almer, Sven
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Granerus, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Olaison, Gunnar
    Bonnet, Joëlle
    Lémann, Marc
    Smedh, Kennet
    Franzén, Lennart
    Bertheau, Philippe
    Cattan, Pierre
    Rain, Jean-Didier
    Modigliani, Robert
    Leukocyte scintigraphy compared to intraoperative small bowel enteroscopy and laparotomy findings in Crohn's disease2007In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 13, no 2, p. 164-174Article in journal (Refereed)
    Abstract [en]

    Background: Leukocyte scintigraphy is a noninvasive investigation to assess inflammation. We evaluated the utility of labeled leukocytes to detect small bowel inflammation and disease complications in Crohn's disease and compared it to whole small bowel enteroscopy and laparotomy findings. Methods: Scintigraphy with technetium-99m exametazime-labeled leukocytes was prospectively performed in 48 patients with Crohn's disease a few days before laparotomy, 41 also had an intraoperative small bowel enteroscopy. The same procedures were performed in 8 control patients. Independent grading of scans was compared with the results of enteroscopy and with surgical, histopathologic, and clinical data. Results: In the 8 control patients leukocyte scan, endoscopy, and histopathology were all negative for the small bowel. In patients with Crohn's disease and small bowel inflammation seen at enteroscopy and/or laparotomy (n = 39) the scan was positive in 33. In 8 patients without macroscopic small bowel inflammation, the scan was positive for the small bowel in 3 patients, at histology, 2 of 3 had inflammation. When combining results for patients and controls, the sensitivity of leukocyte scan for macroscopically evident small bowel inflammation was 0.85, specificity 0.81, accuracy 0.84, positive predictive value 0.92, and negative predictive value 0.68. Scintigraphy detected inflammatory lesions not known before laparotomy in 16 of 47 (34%) Crohn's disease patients and showed uptake in 25 of 35 (71 %) bowel strictures. It was diagnostic regarding 4 of 8 abscesses and 9 of 15 fistulas. In 6 patients (13%) lesions first demonstrated by leukocyte scintigraphy were treated during the surgery performed. Conclusions: Leukocyte scintigraphy reliably detects small bowel inflammation in Crohn's disease. It gives additional information on the presence of inflammatory lesions in a fraction of patients planned for surgery. Copyright © 2006 Crohn's & Colitis Foundation of America, Inc.

  • 2.
    Da Silva, Stéphanie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Keita, Åsa V.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Mohlin, Sofie
    Translational Cancer Research, Cancer Center at Medicon Village, Lund University, Lund, Sweden.
    Påhlman, Sven
    Translational Cancer Research, Cancer Center at Medicon Village, Lund University, Lund, Sweden.
    Théodorou, Vassilia
    Toxalim UMR 1331 INRA/INP/UPS Neuro-Gastroenterology and Nutrition Unit, Toulouse, France.
    Påhlman, Ingrid
    Albireo AB, Arvid Wallgrens Backe, Gothenburg, Sweden.
    Mattson, Jan P.
    Albireo AB, Arvid Wallgrens Backe, Gothenburg, Sweden.
    Söderholm, Johan D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    A novel topical PPARγ agonist induces PPARγ-activity in ulcerative colitis mucosa and prevents and reverses inflammation in induced-colitis models2018In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, no 4, p. 792-805Article in journal (Refereed)
    Abstract [en]

    Background: Peroxisome proliferator-activated receptor-gamma (PPARγ) exerts anti-inflammatory effects and is therefore a potential target in ulcerative colitis (UC). A novel PPARγ agonist (AS002) developed for local action was evaluated ex vivo in biopsies from UC patients and in vivo in mice with low-grade dextran sodium sulfate (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis.Methods: Colonic biopsies from UC patients (n = 18) and healthy controls (n = 6) were incubated with AS002 or rosiglitazone (positive control) to measure mRNA expression of the PPARγ-responsive gene ADIPOPHILIN and protein levels of UC-related cytokines (enzyme-linked immunosorbent assay). AS002 absorption was determined in the colonic mucosa of UC patients. DSS-colitis mice received PPARγ agonists or vehicle daily by intrarectal administration starting 2 days before induction of colitis (preventive) or from days 3 to 8 (curative). Myeloperoxidase (MPO) and cytokine levels in colonic mucosa were determined. In addition, AS002 effects were studied in TNBS colitis.Results: AS002 displayed an absorption pattern of a lipophilic drug totally metabolized in the mucosa. AS002 and rosiglitazone increased ADIPOPHILIN mRNA expression (3-fold) and decreased TNF-α, IL-1β, and IL-13 levels in human UC biopsies. In DSS, in both preventive and curative treatment and in TNBS colitis, AS002 protected against macroscopic and histological damage and lowered MPO and TNF-α, IL-1β, and IL-13 levels.Conclusions: AS002 triggers anti-inflammatory PPARγ activity in the human colonic mucosa of UC patients and prevents and reverses colitis in mice. Our data suggest that AS002 has potential for topical maintenance treatment of UC, which warrants further studies in vivo in patients.

  • 3.
    Everhov, Asa H.
    et al.
    Karolinska Inst, Sweden.
    Khalili, Hamed
    Karolinska Inst, Sweden; Harvard Med Sch, MA 02115 USA.
    Askling, Johan
    Karolinska Inst, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Ludvigsson, Jonas F.
    Karolinska Inst, Sweden; Orebro Univ Hosp, Sweden.
    Halfvarson, Jonas
    Orebro Univ, Sweden.
    Nordenvall, Caroline
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Neovius, Martin
    Karolinska Inst, Sweden.
    Soderling, Jonas
    Karolinska Inst, Sweden.
    Olen, Ola
    Karolinska Inst, Sweden; Sachs Children and Youth Hosp, Sweden.
    Work Loss Before and After Diagnosis of Crohns 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 Crohns disease. Methods Using nationwide registers, we identified incident patients with Crohns 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 Crohns disease or end of follow-up (September 30, 2015). Results Among the 2015 incident Crohns 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 Crohns disease had increased work loss several years before diagnosis, possibly explained by comorbidity or by diagnostic delay.

  • 4.
    Ganda Mall, John-Peter
    et al.
    School of Medical Sciences, Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Casado-Bedmar, Maite
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Winberg, Martin E.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Brummer, Robert J.
    School of Medical Sciences, Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Schoultz, Ida
    School of Medical Sciences, Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. School of Medical Sciences, Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    A ß-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohns Disease and Control Subjects2018In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, no 1, p. 166-178Article in journal (Refereed)
    Abstract [en]

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

  • 5. Gasche, C
    et al.
    Berstad, A
    Befrits, R
    Beglinger, C
    Dignass, A
    Erichsen, K
    Gomollon, F
    Hjortswang, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Koutroubakis, I
    Kulnigg, S
    Oldenburg, B
    Rampton, D
    Schroeder, O
    Stein, J
    Travis, S
    Van Assche, G
    Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases2007In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 13, no 12, p. 1545-1553Article in journal (Refereed)
    Abstract [en]

    Anemia is a common complication of inflammatory bowel diseases. An international working party has formed and developed guidelines for evaluation and treatment of anemia and iron deficiency that should serve practicing gastroenterologists. Within a total of 16 statements, recommendations are made regarding diagnostic measures to screen for iron- and other anemia-related deficiencies regarding the triggers for medical intervention, treatment goals, and appropriate therapies. Anemia is a common cause of hospitalization, prevents physicians from discharging hospitalized patients, and is one of me most frequent comorbid conditions in patients with inflammatory bowel disease. It therefore needs appropriate attention and specific care. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

  • 6.
    Halfvarson, Jonas
    et al.
    Örebro University Hospital.
    Jess, T
    University of Copenhagen.
    Bodin, L
    Örebro University Hospital.
    Järnerot, Gunnar
    Örebro University Hospital.
    Munkholm, P
    University of Copenhagen.
    Binder, V
    University of Copenhagen.
    Tysk, Curt
    Örebro University Hospital.
    Longitudinal concordance for clinical characteristics in a Swedish-Danish twin population with inflammatory bowel disease.2007In: 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.

  • 7.
    Halfvarson, Jonas
    et al.
    Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden.
    Jess, Tine
    Department of Medical Gastroenterology C, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
    Magnusson, Andreas
    Statistical and Epidemiological Unit, Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott M.
    Statistical and Epidemiological Unit, Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Orholm, Marianne
    Department of Internal Medicine, Elsinore Hospital, Elsinore, Denmark.
    Tysk, Curt
    Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden and Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Binder, Vibeke
    Department of Medical Gastroenterology C, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
    Järnerot, Gunnar
    Division of Gastroenterology, Department of Internal Medicine, Örebro University Hospital, Örebro, Sweden.
    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.

  • 8.
    Hallert, Claes
    et al.
    Linköping University, Department of Welfare and Care (IVV). Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Björck, Inger
    Department of Applied Nutrition and Food Chemistry, Chemical Center, Lund University, Lund, Sweden.
    Nyman, Margareta
    Department of Applied Nutrition and Food Chemistry, Chemical Center, Lund University, Lund, Sweden.
    Pousette, Anneli
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Grännö, Christer
    Departments of Internal Medicine, Ryhov Hospital, Jönköping.
    Svensson, Hans
    Östergötlands Läns Landsting, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Increasing Fecal Butyrate in Ulcerative Colitis Patients by Diet: Controlled Pilot Study2003In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 9, no 2, p. 116-121Article in journal (Refereed)
    Abstract [en]

    Topical butyrate has been shown to be effective in the treatment of ulcerative colitis (UC). Butyrate is derived from colonic fermentation of dietary fiber, and our aim was to study whether UC patients could safely increase the fecal butyrate level by dietary means. We enrolled 22 patients with quiescent UC (mean age, 44 years; 45% women; median time from last relapse, 1 year) in a controlled pilot trial lasting 3 months. The patients were instructed to add 60 g oat bran (corresponding to 20 g dietary fiber) to the daily diet, mainly as bread slices. Fecal short-chain fatty acids (SCFAs) including butyrate, disease activity, and gastrointestinal symptoms were recorded every 4 weeks. During the oat bran intervention the fecal butyrate concentration increased by 36% at 4 weeks (from 11 +/- 2 (mean +/- SEM) to 15 +/- 2 mumol/g feces) (p < 0.01). The mean butyrate concentration over the entire test period was 14 +/-1 &mu;mol/g feces (p < 0.05). Remaining fecal SCFA levels were unchanged. No patient showed signs of colitis relapse. Unlike controls, the patients showed no increase in gastrointestinal complaints during the trial. Yet patients reporting abdominal pain and reflux complaints at entry showed significant improvement at 12 weeks that returned to baseline 3 months later. This pilot study shows that patients with quiescent UC can safely take a diet rich in oat bran specifically to increase the fecal butyrate level. This may have clinical implications and warrants studies of the long-term benefits of using oat bran in the maintenance therapy in UC.

  • 9.
    Hjortswang, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tysk, Curt
    Orebro Univ Hosp, Dept Med, Div Gastroenterol, Orebro, Sweden.
    Bohr, Johan
    Orebro Univ Hosp, Dept Med, Div Gastroenterol, Orebro, Sweden.
    Benoni, Cecilia
    MAS Univ Hosp, Dept Med, Div Gastroenterol, Malmo, Sweden.
    Kilander, Anders
    Sahlgrenska Univ Hospital, Div Gastroenterol, Dept Med, Gothenburg, Sweden.
    Larsson, Lasse
    Sahlgrenska Univ Hospital, Div Gastroenterol, Dept Med, Gothenburg, Sweden.
    Vigren, Lira
    MAS Univ Hosp, Dept Med, Div Gastroenterol, Malmo, Sweden.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    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 greater than= 3 stools/day or a mean of greater than= 1 watery stool/day had a significantly impaired HRQOL compared to those with less than3 stools/day and less than 1 watery stool/day. Conclusions: We propose that clinical remission in collagenous colitis is defined as a mean of less than3 stools/day and a mean of less than 1 watery stool per clay and disease activity to be a daily mean of greater than= 3 stools or a mean of greater than= 1 watery stool.

  • 10.
    Lewis, Kimberley
    et al.
    University of Calgary.
    Lutgendorff, Femke
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Phan, Van
    University of Calgary.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Sherman, Philip M.
    University of Toronto.
    McKay, Derek M.
    University of Calgary.
    Enhanced Translocation of Bacteria Across Metabolically Stressed Epithelia is Reduced by Butyrate2010In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 16, no 7, p. 1138-1148Article in journal (Refereed)
    Abstract [en]

    Background: The gut microflora in some patients with Crohns disease can be reduced in numbers of butyrate-producing bacteria and this could result in metabolic stress in the colonocytes. Thus, we hypothesized that the short-chain fatty acid, butyrate, is important in the maintenance and regulation of the barrier function of the colonic epithelium. Methods: Confluent monolayers of the human colon-derived T84 or HT-29 epithelial cell lines were exposed to dinitrophenol (DNP (0.1 mM), uncouples oxidative phosphorylation) + Escherichia coil (strain HB101, 10(6) cfu) +/- butyrate (3-50 mM). Transepithelial resistance (TER), and bacterial internalization and translocation were assessed over a 24-hour period. Epithelial ultrastructure was assessed by transmission electron microscopy. Results: Epithelia under metabolic stress display decreased TER and increased numbers of pseudopodia that is consistent with increased internalization and translocation of the E. coli. Butyrate (but not acetate) significantly reduced the bacterial translocation across DNP-treated epithelia but did not ameliorate the drop in TER in the DNP+E. coli exposed monolayers. Inhibition of bacterial transcytosis across metabolically stressed epithelia was associated with reduced I-kappa B phosphorylation and hence NF-kappa B activation. Conclusions: Reduced butyrate-producing bacteria could result in increased epithelial permeability particularly in the context of concomitant exposure to another stimulus that reduces mitochondria function. We speculate that prebiotics, the substrate for butyrate synthesis, is a valuable prophylaxis in the regulation of epithelial permeability and could be of benefit in preventing relapses in IBD.

  • 11.
    Mesterton, Johan
    et al.
    i3 Innovus, Stockholm, Sweden.
    Jonsson, Linus
    i3 Innovus, Stockholm, Sweden.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Befrits, Ragnar
    Karolinska Univ Hosp, Div Gastroenterol, Stockholm, Sweden.
    Friis-Liby, Ingalill
    Sahlgrens Univ Hosp, Div Gastroenterol Hepatol, Gothenburg, Sweden.
    Lindgren, Stefan
    Univ Hosp MAS, Dept Clin Sci, Div Gastroenterol Hepatol, S-20502 Malmo, Sweden.
    Resource Use and Societal Costs for Crohns Disease in Sweden2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 12, p. 1882-1890Article in journal (Refereed)
    Abstract [en]

    Background: The usual onset of Crohns disease (CD) is between 15 and 30 years of age, thus affecting people during their most economically productive period in life. Methods: This study intended to estimate societal costs and health-related quality of life (HRQoL) in Swedish patients in different stages of CD. Cross-sectional data on disease activity (measured with the Harvey-Bradshaw Index [HBI]), direct medical resource use, work productivity, and HRQoL (assessed using the 15D instrument) were collected for 420 patients by questionnaires to patients, to the treating physician, and from medical records. Based on HBI, current treatment, and response to treatment, patients were classified into the following disease states: Remission, Response, Active, Refractory, and Surgery. Results: The average 4-week cost per patient in 2007 was estimated at (sic)721 (USD 988), of which 64% was due to lost productivity. The total 4-week cost of care was (sic)255 (USD 349) in Remission, (sic)831 (USD 1138) in Response, (sic)891 (USD 1220) in Active, (sic)1360 (USD 1864) in Refractory, and (sic)16984 (USD 23269) in Surgery. HBI was the most important predictor of costs of care-a 1-point increase in HBI increased total costs by 25% (P less than 0.001). HRQoL differed between the disease states: 0.92 in Remission, 0.90 in Response, 0.82 in Active, 0.81 in Refractory, and 0.77 in Surgery. Conclusions: Patients in remission have the lowest costs and the highest HRQoL. Patients responding to treatment have lower costs of care than patients with high disease activity who are not treated or do not respond to treatment:. Thus, total costs of care might be reduced by efficient treatment.

  • 12.
    Nordenvall, Caroline
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Olen, Ola
    Karolinska Inst, Sweden; Sachs Childrens Hosp, Sweden.
    Nilsson, Per Johan
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Ekbom, Anders
    Karolinska Inst, Sweden.
    Bottai, Matteo
    Karolinska Inst, Sweden.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Bergquist, Annika
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Restorative Surgery in Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis Following a Colectomy2018In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, no 3, p. 624-632Article in journal (Refereed)
    Abstract [en]

    Background: Studies on surgical procedures in patients with concomitant primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) have mainly been restricted to single centers. The aim was to compare surgical treatment of UC with or without PSC in a nationwide study. Methods: A cohort study including all patients diagnosed with UC between 1987 and 2014 in Sweden was undertaken. The impact of PSC on the risk of colectomy, the chance of restorative surgery, and risk of failure (presence of a stoma) following restorative surgery were estimated. Survival analyses were performed using the Kaplan-Meier method and multivariable Cox regression models. Results: Of 49 882 UC patients, 2079 had a PSC diagnosis at the end of follow-up. The risk of colectomy was unaffected by PSC diagnosis, whereas the chance of restorative surgery was elevated in PSC-UC patients (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.02-1.44). Ileorectal anastomosis (IRA) was performed in 63% of the PSC-UC patients and 43% of the non-PSC-UC-patients, and the corresponding numbers for ileal pouch anal anastomosis (IPAA) were 35% and 53%. There was no significantly increased risk of failure following restorative surgery in PSC patients (HR, 1.44; 95% CI, 0.93-2.22). In PSC-UC patients, the cumulative failure rates following an IRA at 3 and 5 years were 15% and 18%, and following an IPAA they were 11% and 18%, respectively. Conclusions: Presence of PSC is not associated with the risk of colectomy, whereas the chance of restorative surgery in PSC-UC patients is higher than in UC alone.

  • 13.
    Schoultz, Ida
    et al.
    University of Calgary.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    McKay, Derek M
    University of Calgary.
    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. 2008-2018Article, 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.

  • 14.
    Sjöberg, Mats
    et al.
    Skaraborgs hospital, Lidköping.
    Walch, Andrea
    Medical University of Vienna.
    Meshkat, Mina
    Medical University of Vienna.
    Gustavsson, Anders
    Örebro University Hospital.
    Järnerot, Gunnar
    Örebro University Hospital.
    Vogelsang, Harald
    Medical University of Vienna.
    Hertervig, Erik
    Skåne University Hospital, Lund University.
    Novacek, Gottfried
    Medical University of Vienna.
    Friis-Liby, Ingalill
    Sahlgrenska University Hospital, Gothenburg.
    Blomquist, Lars
    Karolinska University Hospital, Solna.
    Angelberger, Sieglinde
    Medical University of Vienna.
    Karlen, Per
    Södersjukhuset, Stockholm.
    Grännö, Christer
    Ryhov Hospital, Jönköping.
    Vilien, Mogens
    Hilleroed Hospital, Denmark.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Verbaan, Hans
    Skåne University Hospital, Malmö.
    Hellström, Per M
    Karolinska University Hospital, Solna.
    Dejaco, Clemens
    Medical University of Vienna.
    Magnuson, Anders
    Örebro University Hospital.
    Halfvarson, Jonas
    Örebro University Hospital.
    Reinisch, Walter
    Medical University of Vienna.
    Tysk, Curt
    Örebro University Hospital.
    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. less thanbrgreater than less thanbrgreater thanMethods: 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. less thanbrgreater than less thanbrgreater thanResults: 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. less thanbrgreater than less thanbrgreater thanConclusions: 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.

  • 15.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Grännö, Christer
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Järnerot, Gunnar
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ockander, Leif
    Division of Gastroenterology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
    Tysk, Curt
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden, Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Blomberg, Björn
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Short health scale: A valid, reliable, and responsive instrument for subjective health assessment in Crohn's disease2008In: 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 (rS = 0.74-0.83). Reliability was confirmed with strong test-retest correlations (rS = 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. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

  • 16.
    Stjernman, Henrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Tysk, Curt
    Orebro Univ Hosp, Dept Med, Div Gastroenterol, Orebro, Sweden.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Factors Predicting the Outcome of Disease Activity Assessment in Crohns 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 Crohns 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 greater than 150, 72% of the total score were derived froth 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.

  • 17.
    Theibaut, R
    et al.
    AP HP, INSERM.
    Douchin, V
    AP HP, INSERM.
    Jung, C
    AP HP, INSERM.
    Merlin, F
    AP HP, INSERM.
    Colombel, J F
    Hop Calmette.
    Lemann, M
    Hop St Louis.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tysk, C
    Orebro University Hospital.
    OMorain, C
    Trinity College Dublin.
    Gassull, M
    Hospital Badalona Germans Trias and Pujol.
    Finkel, Y
    Karolinska Institute.
    Zouali, H
    Fdn Jean Dausset.
    Pascoe, L
    Fdn Jean Dausset.
    Hugot, J P
    AP HP, INSERM.
    Letter: 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 (Other academic)
    Abstract [en]

    n/a

  • 18.
    Zhou, Yin
    et al.
    Sichuan University, Peoples R China.
    Li, Yibo
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Chen, Keling
    Sichuan University, Peoples R China.
    Lyv, Zhaoying
    Sichuan University, Peoples R China.
    Huang, Dongmei
    Sichuan University, Peoples R China.
    Liu, Bin
    Sichuan University, Peoples R China.
    Xu, Zhicheng
    Sichuan University, Peoples R China.
    Xiang, Bo
    Sichuan University, Peoples R China.
    Jin, Shuguang
    Sichuan University, Peoples R China.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Li, Yuan
    Sichuan University, Peoples R China.
    Inflammation and Apoptosis: Dual Mediator Role for Toll-like Receptor 4 in the Development of Necrotizing Enterocolitis2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 1, p. 44-56Article in journal (Refereed)
    Abstract [en]

    Background: Necrotizing enterocolitis (NEC) is the leading cause of neonatal gastrointestinal mortality; effective interventions are lacking with limited understanding of the pathogenesis of NEC. The importance of Toll-like receptor 4 (TLR4) signaling in NEC is well documented; however, the potential mechanisms that regulate enterocyte inflammation and apoptosis remain unclear. The aim of this study was to characterize the role of TLR4-mediated inflammation and apoptosis in the development of NEC and to determine the major apoptotic pathways and regulators in the process. Methods: TLR4-deficient C57BL/10ScNJ mice and lentivirus-mediated stable TLR4-silent cell line (IEC-6) were used. NEC was induced by formula gavage, cold, hypoxia, combined with lipopolysaccharide in vivo or lipopolysaccharide stimulation in vitro. Enterocyte apoptosis was evaluated by TUNEL or Annexin analysis. The expression of TLR4, caspase3, caspase8, caspase9, Bip, Bax, Bcl-2, and RIP was detected by Western blot and immunofluorescence. Inflammatory factors such as tumor necrosis factor-a and interleukin-2 were examined by Luminex. Results: Defect of TLR4 led to suppressed enterocytes apoptosis both in vitro and in vivo; the expression of caspase3, caspase8, Bip, and Bax was decreased; and caspase9 and Bcl-2 were increased. NEC severity was attenuated in TLR4-deficient mice compared with wild-type counterparts, and enterocytes apoptosis was correlated with NEC severity. RIP and cytokine level of tumor necrosis factor-a and interleukin-2 were also decreased. Conclusions: TLR4-induced inflammation and apoptosis play a critical role in the pathogenesis of NEC. TLR4 inhibition, combined with extrinsic (caspase8) and/or endoplasmic reticulum stress (Bip) apoptosis signaling blockade could serve as a potential effective treating strategy for NEC.

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