Cerebrovascular events in inflammatory bowel disease patients treated with anti-tumour necrosis factor alpha agents.

Background And Aims: Cerebrovascular accidents [CVA] have rarely been reported in inflammatory bowel disease [IBD] patients treated with anti-tumour necrosis alpha [anti-TNF alpha] agents. Our aim here was to describe the clinical course of CVA in these patients.

Methods: This was a European Crohn's and Colitis Organisation [ECCO] retrospective observational study, performed as part of the CONFER [COllaborative Network For Exceptionally Rare case reports] project.

Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial.

Background & Aims: The phytochemical compound curcumin was reported to be effective in maintaining remission in patients with ulcerative colitis (UC). We investigated curcumin's efficacy in inducing remission in patients with active mild-to-moderate UC.

Methods: We performed a multicenter randomized, placebo-controlled, double-blind study of 50 mesalamine-treated patients with active mild-to-moderate UC (defined by the Simple Clinical Colitis Activity Index [SCCAI]) who did not respond to an additional 2 weeks of the maximum dose of mesalamine oral and topical therapy.

Significance of low level infliximab in the absence of anti-infliximab antibodies.

Aim: To evaluate the prevalence of double negative (DN) sera and the mechanisms responsible for DN status.

Methods: Sera of inflammatory bowel disease patients treated with infliximab (IFX) were tested for drug/antibodies to infliximab (ATI) trough levels and the proportion of DN results was compared between a commercially available double antigen ELISA (with labeled IFX as the detection antibody) and an anti-lambda ELISA (with anti-human lambda chain detection antibody). Repeat testing with lower than customary serum dilution (1:10) was performed.

Inflammatory bowel disease: an emergent disease among Ethiopian Jews migrating to Israel.

Background: The development and characteristics of inflammatory bowel disease (IBD) in Ethiopian Jewish immigrants to Israel were investigated.

Methods: A case-control study was conducted in 7 tertiary care hospitals in Israel. Patients of Ethiopian origin with IBD >6 months were included.

Therapeutic drug monitoring in inflammatory bowel disease.

Tumor necrosis factor (TNF)-α inhibitors and thiopurines are among the most important classes of medications utilized in the clinical management of Crohn's disease and ulcerative colitis. A significant proportion of patients loses response to these agents or develops adverse effects during the course of the treatment. Monitoring of drug levels and anti-drug antibodies (for TNF-α inhibitors) and metabolite levels (for thiopurines) can provide valuable insight into the possible etiology of unfavorable outcomes and allow for an appropriate management strategy for these patients.

Magnetic resonance enterography in pregnant women with Crohn's disease: case series and literature review.

Background: Evaluation of pregnant women with known or suspected Crohn's disease (CD) remains a challenge. Magnetic Resonance Enterography (MRE) is a promising diagnostic tool in these patients; however, the clinical data on MRE utilization in pregnancy is scarce. The aim of the study was to describe the experience with MRE in pregnant CD patients in a tertiary referral center.

Partners of patients with inflammatory bowel disease: how important is their support?

Background: Chronic inflammatory bowel disease (IBD) causes significant distress for patients and their families. Data assessing the need of these patients for support and sharing with their partners are scarce. The aim of this study was to assess patients' views regarding sharing of information with their partners.

Adalimumab monotherapy versus combination therapy with immunomodulators in patients with Crohn's disease: a systematic review and meta-analysis.

Background And Aims: Combination therapy with infliximab and azathioprine has been shown to be superior to either treatment alone in Crohn's disease (CD). However, the benefit of combining adalimumab with an immunomodulator remains controversial. The aim of this study was to compare the efficacy of adalimumab monotherapy with combination therapy for induction and maintenance of response and remission in CD using a meta-analysis of the current literature.

Levels of drug and antidrug antibodies are associated with outcome of interventions after loss of response to infliximab or adalimumab.

Background & Aims: There is controversy about whether levels of anti-tumor necrosis factor (TNF) and antidrug antibodies (ADAs) are accurate determinants of loss of response to therapy. We analyzed the association between trough levels of anti-TNF agents or ADAs and outcomes of interventions for patients with loss of response to infliximab or adalimumab.

Methods: We performed a retrospective study of pediatric and adult patients with inflammatory bowel disease and suspected loss of response to anti-TNF agents treated at medical centers throughout Israel from October 2009 through February 2013.

Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn's disease.

Background: Adalimumab is an effective treatment for Crohn's disease (CD). Anti-adalimumab antibodies (AAA) and low trough serum drug concentrations have been implicated as pre-disposing factors for treatment failure.

Aims: To assess adalimumab and AAA serum levels, and to examine their association and discriminatory ability with clinical response and serum C-reactive protein (CRP).

Loss of response to anti-tumor necrosis factors: what is the next step?

The management of patients with inflammatory bowel disease (IBD) presenting with loss of response (LOR) to anti-tumor necrosis factor (TNF) biologics is an increasingly encountered challenge for clinicians caring for these patients. Clinical decisions are complicated by the lack of consistent terminology and diagnostic criteria to define LOR, the myriad of causes that may give rise to symptoms mimicking LOR, and the multiplicity of possible medical interventions. Choosing the best next step is dependent first on accurate identification of the etiology of symptoms and specifically on ascertaining that IBD activity is responsible for the flares.

Determination of risk for sterile preparations.

A quick and reliable system is described to quantify risk assessment for compounded sterile pharmaceuticals, which are "compounded in anticipation" for hospitals and clinics, having shelf lives assessed on documented literature and other criteria. These shelf lives are well in excess of the recommendations of the United States Pharmacopeia without placing patients at risk due to inadequate safety, quality, or efficacy.

Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed.

Background & Aims: There is an increasing need for new treatments for patients with Crohn's disease (CD) in whom previous therapy with tumor necrosis factor (TNF) antagonists has failed. We performed a placebo-controlled, phase 3, double-blind trial to evaluate the efficacy and safety of vedolizumab, an antibody against the integrin α4β7, as induction therapy.

Methods: Patients with moderately to severely active CD (CD activity index [CDAI] score, 220-400 points) were assigned randomly to groups given vedolizumab (300 mg) or placebo intravenously at weeks 0, 2, and 6.

Reprogrammed and transmissible intestinal microbiota confer diminished susceptibility to induced colitis in TMF-/- mice.

Tata Element Modulatory Factor (TMF/ARA160) is a multifunctional Golgi-associated protein, which accumulates in colonic enterocytes and goblet cells. Mice lacking TMF/ARA160 (TMF(-/-)) produce thick and uniform colonic mucus that resists adherent bacterial colonization and diminishes susceptibility of these mice to induced acute colitis, through a mechanism that is not fully understood. Here, we show that mucus secretion by goblet cells is altered in the colon of TMF(-/-) mice, resulting in the formation of a highly oligomerized colonic gel-forming mucin, MUC2.

Antiviral therapy in cytomegalovirus-positive ulcerative colitis: a systematic review and meta-analysis.

Aim: To evaluate the impact of antiviral treatment on cytomegalovirus (CMV)-positive ulcerative colitis patients.

Methods: We performed a systematic review and meta-analysis (MA) of comparative cohort and case-control studies published between January 1966 and March 2013. Studies focusing on colectomy series and studies including only less than 3 patients in the treated or non-treated arm were excluded.

Expression of IL-2, IL-17 and TNF-alpha in patients with Crohn's disease treated with anti-TNF antibodies.

Background: The T cell cytokine IL-17 and the Th-17 pathway appear to have a role in the pathogenesis of inflammatory bowel diseases. IL-2 is a potent stimulator of lymphocyte proliferation and IL2/IL21 receptor polymorphisms have recently been associated with susceptibility to IBD.

Aims: To evaluate the expression of IL-17, IL-2 and TNFα in Crohn's disease (CD) patients with and without anti-TNFs.

Tailoring anti-TNF therapy in IBD: drug levels and disease activity.

The treatment of IBD with anti-TNF agents has substantially evolved since their first introduction more than a decade ago. The robust efficacy witnessed in many patients has raised new questions pertaining to the observation of subgroups of patients who fail to respond or who lose response to these otherwise very effective drugs. Conversely, the exorbitant cost of biologic agents coupled with their efficacy in inducing lasting remission has introduced new concepts addressing the possibility of therapy cessation in some patients after deep remission has been achieved.

Dose optimization is effective in ulcerative colitis patients losing response to infliximab: a collaborative multicentre retrospective study.

Background: Subjects maintained on infliximab scheduled therapy for inflammatory bowel disease may require dose optimization due to secondary loss of response. There are limited data on infliximab dose optimization for ulcerative colitis.

Aims: To investigate dose optimization in ulcerative colitis patients with secondary loss of response.

Celiac disease resolution after allogeneic bone marrow transplantation is associated with absence of gliadin-specific memory response by donor-derived intestinal T-cells.

Purpose: To elucidate the relative role of the immune system and intestinal epithelium in the ethiopatogenesis of Celiac disease (CD).

Methods: A patient with childhood CD who underwent allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia was followed for 5 years after resumption of gluten containing diet. Immunological memory to gliadin epitopes was assessed in the index patient and in 5 newly diagnosed CD patients by standard serology testing and by CFSE-based proliferation assays of peripheral blood CD4+ cells and of intestinal LPL towards gliadin-TTG antigens.

The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab.

Objective: To characterise the temporal evolution of antibodies to infliximab (ATI).

Design: Prospective observational study of infliximab-treated patients with inflammatory bowel disease between 2009 and 2012.

Interventions: Trough levels of infliximab and ATI were measured before each infusion by anti-λ ELISA.

Severe and morbid obesity in Crohn's disease patients: prevalence and disease associations.

Background: Crohn's disease (CD) is frequently associated with weight loss and malnutrition. However, as the prevalence of obesity increases worldwide, it may become a clinical problem even in CD.

Aim: To assess the prevalence of severe/morbid obesity in CD patients and to compare their disease characteristics to nonobese CD patients.

Optimizing anti-TNF treatments in inflammatory bowel disease.

Background: Failure of anti-TNF treatment in inflammatory bowel disease (IBD) patients can take on several forms, each posing distinct etio-pathogenic considerations and management dilemmas.

Aim: The aim of this study is to review the mechanisms responsible for the various forms of anti-TNF failures in IBD and to elucidate strategies for optimizing clinical efficacy.

Results: Primary failures of anti-TNF induction therapy occur in up to 40% of patients in clinical trials and in 10-20% in clinical series.

The impact of pseudomembrane formation on the outcome of Clostridium difficile-associated disease.

Purpose: Although pseudomembranes are the hallmark manifestation of Clostridium difficile-associated diarrhea (CDAD), there are scant data specifically addressing their impact on the clinical outcome. We investigated whether the formation of pseudomembranes predicts a worse CDAD outcome.

Methods: CDAD patients hospitalized during 2010 underwent sigmoidoscopy and were followed prospectively.