| 1. |
- Gustavsson, Anders, et al.
(författare)
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Clinical trial : colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
- 2010
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 32:8, s. 984-989
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Tidskriftsartikel (refereegranskat)abstract
- Background The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.
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| 2. |
- Sjöberg, Mats, et al.
(författare)
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Infliximab as rescue therapy in hospitalised patients with steroid-refractory acute ulcerative colitis: a long-term follow-up of 211 Swedish patients
- 2013
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 38:4, s. 377-387
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRescue therapy with infliximab (IFX) has been proven effective in a steroid-refractory attack of ulcerative colitis (UC). The long-term efficacy is not well described. less thanbrgreater than less thanbrgreater thanAimTo present a retrospective study of IFX as rescue therapy in UC. Primary end points were colectomy-free survival at 3 and 12months. less thanbrgreater than less thanbrgreater thanMethodsIn this multicentre study, 211 adult patients hospitalised between 1999 and 2010 received IFX 5mg/kg as rescue therapy due to a steroid-refractory, moderate-to-severe attack of UC. Exclusion criteria were duration of current flare for andgt;12weeks, corticosteroid treatment for andgt;8weeks before hospitalisation, previous IFX therapy or Crohns disease. less thanbrgreater than less thanbrgreater thanResultsProbability of colectomy-free survival at 3months was 0.71 (95% CI, 0.64-0.77), at 12months 0.64 (95% CI, 0.57-0.70), at 3years 0.59 (95% CI, 0.52-0.66) and at 5years 0.53 (95% CI, 0.44-0.61). Steroid-free, clinical remission was achieved in 105/211 (50%) and 112/209 (54%) patients at 3 and 12months respectively. Of 75 colectomies during the first year, 48 (64%) were carried out during the first 14days, 13 (17%) on days 15-90 and 14 (19%) between 3 and 12months. There were three (1.4%) deaths during the first 3months. less thanbrgreater than less thanbrgreater thanConclusionsInfliximab is an effective rescue treatment, both short- and long-term, in a steroid-refractory attack of UC. Most IFX failures underwent surgery during the first 14days, which calls for studies on how to optimise induction treatment with IFX. Serious complications, including mortality, were rare.
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| 3. |
- Sjöberg, Mats, 1965-, et al.
(författare)
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Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis : a retrospective observational study
- 2012
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Ingår i: Inflammatory Bowel Diseases. - : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 18:2, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Willing, Ben P., et al.
(författare)
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A Pyrosequencing Study in Twins Shows That Gastrointestinal Microbial Profiles Vary With Inflammatory Bowel Disease Phenotypes
- 2010
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 139:6, s. 1844-U105
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: The composition of the gastrointestinal microbiota is thought to have an important role in the etiology of inflammatory bowel diseases (IBDs) such as Crohn's disease (CD) and ulcerative colitis (UC). Interindividual variation and an inability to detect less abundant bacteria have made it difficult to correlate specific bacteria with disease. METHODS: We used 454 pyrotag sequencing to determine the compositions of microbial communities in feces samples collected from a cohort of 40 twin pairs who were concordant or discordant for CD or UC, and in mucosal samples from a subset of the cohort. The cohort primarily comprised patients who were in remission, but also some with active disease. RESULTS: The profiles of the microbial community differed with disease phenotypes; relative amounts of bacterial populations correlated with IBD phenotypes. The microbial compositions of individuals with CD differed from those of healthy individuals, but were similar between healthy individuals and individuals with UC. Profiles from individuals with CD that predominantly involved the ileum differed from those with CD that predominantly involved the colon; several bacterial populations increased or decreased with disease type. Changes specific to patients with ileal CD included the disappearance of core bacteria, such as Faecalibacterium and Roseburia, and increased amounts of Enterobacteriaceae and Ruminococcus gnavus. CONCLUSIONS: Bacterial populations differ in abundance among individuals with different phenotypes of CD. Specific species of bacteria are associated with ileal CD; further studies should investigate their role in pathogenesis.
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| 5. |
- Hjortswang, Henrik, et al.
(författare)
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Health-related quality of life is impaired in active collagenous colitis
- 2011
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Ingår i: Digestive and Liver Disease. - : Elsevier BV. - 1590-8658 .- 1878-3562. ; 43:2, s. 102-109
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The characteristic clinical symptoms of collagenous colitis are non-bloody diarrhoea, urgency and abdominal pain. Treatment is aimed at reducing the symptom burden and the disease impact on patients' health-related quality of life. The objective of this study was to analyse health-related quality of life in patients with collagenous colitis. Methods: In a cross-sectional, postal HRQL survey, 116 patients with collagenous colitis at four Swedish hospitals completed four health-related quality of life questionnaires, two disease-specific (Inflammatory Bowel Disease Questionnaire and Rating Form of IBD Patient Concerns), and two generic (Short Form 36, SF-36, and Psychological General Well-Being, PGWB), and a one-week symptom diary. Demographic and disease-related data were collected. Results for the collagenous colitis population were compared with a background population controlled for age and gender (n = 8931). Results: Compared with a Swedish background population, patients with collagenous colitis scored significantly worse in all Short Form 36 dimensions (p < 0.01), except physical function. Patients with active disease scored worse health-related quality of life than patients in remission. Co-existing disease had an impact on health-related quality of life measured with the generic measures. Lower education level and shorter disease duration were associated with decreased well-being. Conclusion: Health-related quality of life was impaired in patients with collagenous colitis compared with a background population. Disease activity is the most important factor associated with impairment of health-related quality of life. Patients in remission have a health-related quality of life similar to a background population. (C) 2010 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.
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| 6. |
- Momozawa, Yukihide, et al.
(författare)
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Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease
- 2011
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 43:1, s. 43-47
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ∼20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease.
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| 7. |
- Soderman, Jan, et al.
(författare)
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Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease
- 2013
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 19:30, s. 4935-4943
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To investigate a possible genetic influence of claudin (CLDN) 1, CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS: Allelic association between genetic regions of CLDN1, CLDN2 or CLDN4 and patients with inflammatory bowel disease, Crohn's disease (CD) or ulcerative colitis were investigated using both a case-control study approach (one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls) and a family-based study (463 non-Swedish European inflammatory bowel disease-families). A nonsynonymous coding single nucleotide polymorphism in MORC4, located on the same linkage block as CLDN2, was investigated for association, as were two novel CLDN2 single nucleotide polymorphism markers, identified by resequencing.RESULTS: A single nucleotide polymorphism marker (rs12014762) located in the genetic region of CLDN2 was significantly associated to CD (case-control allelic OR = 1.98, 95% CI: 1.17-3.35, P = 0.007). MORC4 was present on the same linkage block as this CD marker. Using the case-control approach, a significant association (case control allelic OR = 1.61, 95% CI: 1.08-2.41, P = 0.018) was found between CD and a nonsynonymous coding single nucleotide polymorphism (rs6622126) in MORC4. The association between the CLDN2 marker and CD was not replicated in the family-based study. Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION: These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.
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| 8. |
- Zhulina, Yaroslava, 1973-, et al.
(författare)
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Subclinical Inflammation with Increased Neutrophil Activity in Healthy Twin Siblings Reflect Environmental Influence in the Pathogenesis of Inflammatory Bowel Disease
- 2013
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Ingår i: Inflammatory Bowel Diseases. - Philadelphia, USA : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 19:8, s. 1725-1731
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Stenberg, Reidun, 1954-, et al.
(författare)
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Increased prevalence of antibodies against dietary proteins in children and young adults with cerebral palsy
- 2013
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Lippincott, Williams and Wilkins. - 0277-2116 .- 1536-4801. ; 56:2, s. 233-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Undernourishment is common in children with cerebral palsy (CP), but the reasons are unknown. We previously reported elevated levels of immunoglobulin (Ig) A and IgG antibodies against gliadin (AGA) and tissue transglutaminase (tTG) in 99 children and young adults with CP without characteristic findings of gluten enteropathy in small bowel biopsies. Our aim was to perform a case-control study of IgG antibodies against other dietary antigens, AGA, anti-tTG, and IgE antibodies against wheat and gluten.METHODS: Sera from 99 cases with CP and 99 healthy, age- and sex-matched controls were analysed with fluorescence enzyme-linked immunosorbent assay for detection of IgG antibodies against β-lactoglobulin, casein, egg white, IgG- and IgA-AGA, IgA-anti-tTG, and IgE antibodies against gluten and wheat.RESULTS: Compared with controls, the odds ratio in cases with CP for having elevated levels of IgG antibodies against β-lactoglobulin was 17.0 (95% confidence interval [CI] 2.3-128), against casein 11.0 (95% CI 2.6-46.8), and against egg white 7.0 (95% CI 1.6-30.8). The IgE responses for wheat/gluten were generally low. The tetraplegic and dyskinetic CP subtypes had significantly higher frequencies of elevated levels for all of the tested antibodies except IgG against egg white, and IgA-anti-tTG. A significantly lower weight was seen in cases with CP with positive versus negative serology.CONCLUSIONS: Elevated levels of IgG against dietary antigens were more frequent in the CP group compared with controls, and particularly in the tetraplegic and dyskinetic CP subtypes with the most severe neurologic handicap and undernourishment. Hypothetically, malnourishment may cause increased intestinal permeability and thus immunization against dietary antigens.
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| 10. |
- Vigren, Lina, et al.
(författare)
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Celiac disease and other autoimmune diseases in patients with collagenous colitis
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 48:8, s. 944-950
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims. Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Methods. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. Results. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjogren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Conclusion. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.
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