Genetic variants of Wnt transcription factor TCF-4 (TCF7L2) putative promoter region are associated with small intestinal Crohn's disease.

Reduced expression of Paneth cell antimicrobial alpha-defensins, human defensin (HD)-5 and -6, characterizes Crohn's disease (CD) of the ileum. TCF-4 (also named TCF7L2), a Wnt signalling pathway transcription factor, orchestrates Paneth cell differentiation, directly regulates the expression of HD-5 and -6, and was previously associated with the decrease of these antimicrobial peptides in a subset of ileal CD. To investigate a potential genetic association of TCF-4 with ileal CD, we sequenced 2.

Adalimumab for the treatment of fistulas in patients with Crohn's disease.

Objective: To evaluate the efficacy of adalimumab in the healing of draining fistulas in patients with active Crohn's disease (CD).

Design: A phase III, multicentre, randomised, double-blind, placebo controlled study with an open-label extension was conducted in 92 sites.

Patients: A subgroup of adults with moderate to severely active CD (CD activity index 220-450) for >or=4 months who had draining fistulas at baseline.

Increasing incidence of Clostridium difficile-associated diarrhea in inflammatory bowel disease.

Introduction And Aim: Over the last decade a rise in Clostridium difficile-associated diarrhea (CDAD) has been observed. A higher incidence of CDAD has also been suggested in patients with inflammatory bowel disease (IBD), and may be a challenging factor in the differential diagnosis of flares. It is unclear if the increase is caused by the enhanced use of immunosuppressive therapy in IBD.

Confirmation of multiple Crohn's disease susceptibility loci in a large Dutch-Belgian cohort.

Objectives: Inflammatory bowel diseases (IBD)-Crohn's disease (CD) and ulcerative colitis (UC)-are chronic gastrointestinal inflammatory disorders with a complex genetic background. A genome-wide association scan by the Wellcome Trust Case Control Consortium (WTCCC) recently identified several novel susceptibility loci.

Methods: We performed a large replication study in 2,731 Dutch and Belgian IBD patients (1,656 CD and 1,075 UC) and 1,086 controls.

Development of a screening method to determine the pattern of fermentation metabolites in faecal samples using on-line purge-and-trap gas chromatographic-mass spectrometric analysis.

An on-line screening method to analyse volatile organic compounds (VOCs) in faecal samples was developed. VOCs were isolated from a standard solution or faecal samples using a purge-and-trap system and identified and quantified by GC-MS. The experimental conditions were optimised and the performance of the system was evaluated.

Corticosteroids but not infliximab increase short-term postoperative infectious complications in patients with ulcerative colitis.

Background: Recent reports suggest that the preoperative use of infliximab (IFX) increases postoperative infectious complications in patients with ulcerative colitis (UC). Therefore, we determined the impact of IFX on postoperative infectious complications.

Methods: A consecutive group of 141 UC patients (41% female, median age 39.

Extracorporeal photopheresis for the treatment of refractory Crohn's disease: results of an open-label pilot study.

Background: Extracorporeal photopheresis (ECP) is effective in immune-mediated disorders. A prospective, uncontrolled pilot study was conducted to evaluate the safety and efficacy of ECP in patients with active Crohn's disease (CD) who were refractory to or intolerant of immunosuppressants and/or anti-TNF therapies.

Methods: Patients with moderate-to-severely active CD (Crohn's Disease Activity Index [CDAI] 220-450 points) underwent 12 weeks of ECP treatment (Weeks 1-4: twice weekly, every week; Weeks 5-12: twice weekly, every other week).

Common variants in the NLRP3 region contribute to Crohn's disease susceptibility.

We used a candidate gene approach to identify a set of SNPs, located in a predicted regulatory region on chromosome 1q44 downstream of NLRP3 (previously known as CIAS1 and NALP3) that are associated with Crohn's disease. The associations were consistently replicated in four sample sets from individuals of European descent. In the combined analysis of all samples (710 father-mother-child trios, 239 cases and 107 controls), these SNPs were strongly associated with risk of Crohn's disease (P(combined) = 3.

Polymorphisms in innate immunity genes predispose to bacteremia and death in the medical intensive care unit.

Objective: Critically ill patients are at risk of sepsis, organ failure, and death. Studying the impact of genetic determinants may improve our understanding of the pathophysiology and allow identification of patients who would benefit from specific treatments. Our aim was to study the influence of single nucleotide polymorphisms in selected genes involved in innate immunity on the development of bacteremia or risk of death in patients admitted to a medical intensive care unit.

Oral budesonide for maintenance of remission of Crohn's disease: a pooled safety analysis.

Background: Budesonide exhibits similar efficacy to systemic glucocorticosteroids (GCSs) in Crohn's disease (CD), but with fewer adverse events (AEs). Aim To evaluate budesonide's safety profile in CD patients, in particular, incidences of clinically important AEs known to be associated with systemic GCSs.

Methods: Five 1-year, double-blind, placebo-controlled trials evaluating budesonide for mild-to-moderate CD were pooled for analysis.

Optimizing treatment of inflammatory bowel diseases with biologic agents.

Despite more than a decade of clinical experience in the treatment of inflammatory bowel disease with biologic agents, particularly anti-tumor necrosis factor (TNF) antibodies, optimal treatment strategies are still debated. Secondary loss of response due to immuno-genicity is intrinsic to the use of therapeutic antibodies and has important implications. With the chimeric anti-TNF antibody, infliximab, scheduled maintenance therapy minimizes the risk of loss of response, and there is no clear evidence that concomitant immunosuppressives have added value in this setting.

Cystic fibrosis transmembrane conductance regulator gene polymorphisms in patients with primary sclerosing cholangitis.

Background/aims: Primary sclerosing cholangitis (PSC) is a progressive cholestatic disease commonly associated with inflammatory bowel disease (IBD) and characterized by fibrosing inflammatory destruction of bile ducts. The histological features in the liver of PSC patients are similar to those observed in cystic fibrosis (CF). Our aim was to study whether variants in the CFTR gene are associated with the occurrence and/or evolution of PSC.

Dose-response effect of arabinoxylooligosaccharides on gastrointestinal motility and on colonic bacterial metabolism in healthy volunteers.

Objective: Arabinoxylooligosaccharides (AXOS) are non-digestible in the upper gastrointestinal tract and have been shown to exert prebiotic effects in animals. The aim of this study was to characterize the influence of AXOS with an average degree of polymerization of 15 and an average degree of arabinose substitution of 0.26 (AXOS-15-0.

Pouchitis, similar to active ulcerative colitis, is associated with impaired butyrate oxidation by intestinal mucosa.

Background: Healthy colonic mucosa uses butyrate as the major energy source. In ulcerative colitis (UC) butyrate oxidation has been shown to be disturbed, but it remains unclear whether this is a primary defect. The aim of this study was to measure mucosal butyrate oxidation in UC (involved and noninvolved colon) and in pouchitis and to study the relationship with endoscopic as well as histological disease activity.

Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM study.

Background & Aims: We determined the effects of adalimumab maintenance treatment on the risks of hospitalization and surgery in Crohn's disease (CD).

Methods: A total of 778 patients with CD were randomized to placebo, adalimumab 40 mg every other week or adalimumab 40 mg weekly, all after an 80-mg/40-mg adalimumab induction regimen. All-cause and CD-related hospitalizations and major CD-related surgeries were compared between the placebo and adalimumab groups (every other week, weekly, and both combined) using Kaplan-Meier analysis and Cox proportional hazard models.

Infliximab for pediatric Crohn's disease.

The natural history of Crohn's disease (CD) is characterized by recurrent flares combined with periods of inactive disease. The goal of therapy should be to induce and maintain clinical remission, to strive for endoscopic healing of the intestinal mucosa and to improve the quality of life. The nineties have been characterized by the introduction of biological therapies designed to block or neutralize pro-inflammatory cytokines which play a role in the pathogenesis of the disease.

Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility.

Inflammatory bowel disease (IBD) typically manifests as either ulcerative colitis (UC) or Crohn's disease (CD). Systematic identification of susceptibility genes for IBD has thus far focused mainly on CD, and little is known about the genetic architecture of UC. Here we report a genome-wide association study with 440,794 SNPs genotyped in 1,167 individuals with UC and 777 healthy controls.

Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study.

Background And Aims: This study evaluates the long-term safety of infliximab in patients with inflammatory bowel disease (IBD) treated with the drug over a 14-year period.

Methods: The medical records of 734 patients with IBD treated with infliximab and 666 control patients not treated with infliximab were reviewed for adverse events. The time of onset and outcome, severity and concomitant medication were recorded.

Long-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort.

Background And Aims: This observational study assessed the long-term clinical benefit of infliximab (IFX) in 614 consecutive patients with Crohn's disease (CD) from a single centre during a median follow-up of 55 months (interquartile range (IQR) 27-83).

Methods: The primary analysis looked at the proportion of patients with initial response to IFX who had sustained clinical benefit at the end of follow-up. The long-term effects of IFX on the course of CD as reflected by the rate of surgery and hospitalisations and need for corticosteroids were also analysed.