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Endoscopic and deep remission at 1 year prevents disease progression in early Crohn's disease : long-term data from CALM

SummaryBackground Increased knowledge of pathways involved in the pathogenesis of IBD has led to the development of new treatment options for Crohn's disease (CD) and ulcerative colitis (UC). Two new biological agents have been recently approved for IBD: vedolizumab and ustekinumab. They have different therapeutic targets (α4β7 integrin for vedolizumab and interleukin-12/23 pathways for ustekinumab) than the primary biological class, anti-tumour necrosis factor alpha (anti-TNF) agents. As the armamentarium for IBD increases in coming years, it will become important to understand factors associated with response in order to best position and personalise therapy. Aim To summarise the current data on predictors of response to vedolizumab and ustekinumab in IBD patients. Methods We conducted a comprehensive literature review. A PubMed search was performed using pre-defined key words and terms to identify relevant studies on predictors of response. Results Patients with severe disease (by clinical activity and inflammatory biomarkers), or prior anti-TNF exposure are less likely to respond to vedolizumab. Ileocolonic disease, no prior surgery and uncomplicated phenotype were associated with better responses to ustekinumab in CD. Initial response seems to predict a better long-term maintenance in both therapies (P < 0.001). Contrary to anti-TNF therapies, immunogenicity appears to play less of a role in response. Conclusion As the number of new biological therapies increase in IBD, identifying patients who are most likely to benefit from specific agents is of paramount importance to help best position IBD therapies.

GOALS To investigate the effect of implementing full-spectrum endoscopy (Fuse) on adenoma detection rate (ADR) at an ambulatory surgical center (ASC). BACKGROUND Traditional forward viewing (TFV) endoscopes have 1 camera and provide an angle of view of 140 to 170 degrees, whereas Fuse provides a 330 degrees view through the addition of 2 side cameras. Although randomized studies have shown that Fuse decreases adenoma miss rates, its impact on ADR in a screening population is currently unknown. STUDY We conducted a retrospective analysis of data from average risk screening colonoscopies at a 5-room ASC. This ASC transitioned from TFV to Fuse in April 2014. The primary outcome was ADR defined as the percentage of patients who underwent screening colonoscopy and were found to have at least 1 adenomatous polyp. RESULTS A total of 1696 screening colonoscopies were performed with TFV and 2302 with Fuse. Overall ADR was 23.7% with TFV and 29.0% with Fuse (P

Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome.To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis.We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis.A total of 12 RCTs were included in the meta-analysis (CD - 2 induction, 4 maintenance; UC - 8 induction, 5 maintenance). Duration of follow-up was 6-12 weeks for induction and 32-54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51-110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25-0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12-0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC.Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD.

SummaryBackground Disease extent in ulcerative colitis is one of the major factors determining prognosis over the long-term. Disease extent is dynamic and a proportion of patients presenting with limited disease progress to more extensive forms of disease over time. Aim To perform a systematic review and meta-analysis of epidemiological studies reporting on extension of ulcerative colitis to determine frequency of disease extension in patients with limited ulcerative colitis at diagnosis. Methods We performed a systematic literature search to identify studies on disease extension of ulcerative colitis (UC) and predictors of disease progression. Results Overall, 41 studies were eligible for systematic review but only 30 for meta-analysis. The overall pooled frequency of UC extension was 22.8% with colonic extension being 17.8% at 5 years and 31% at 10 years. Extension was 17.8% (95% CI 11.2-27.3) from E1 to E3, 27.5% (95% CI 7.6-45.6) from E2 to E3 and 20.8% (95% CI 11.4-26.8) from E1 to E2. Rate of extension was significantly higher in patients younger than 18 years (29.2% (CI 6.4-71.3) compared to older patients (20.2% (CI 13.0-30.1) (P

Summary Clinical benefits of cytokine blockade in ileal Crohn’s disease (iCD) are limited to a subset of patients. Here, we applied single-cell technologies to iCD lesions to address whether cellular heterogeneity contributes to treatment resistance. We found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which we named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. Strikingly, the GIMATS module was also present in a subset of patients in four independent iCD cohorts (n = 441), and its presence at diagnosis correlated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy. These results emphasize the limitations of current diagnostic assays and the potential for single-cell mapping tools to identify novel biomarkers of treatment response and tailored therapeutic opportunities.

Background & aimsPatients with Crohn's disease (CD), but not ulcerative colitis (UC), of shorter duration have higher rates of response to tumor necrosis factor (TNF) antagonists than patients with longer disease duration. Little is known about the association between disease duration and response to other biologic agents. We aimed to evaluate response of patients with CD or UC to vedolizumab, stratified by disease duration.MethodsWe analyzed data from a retrospective, multicenter, consortium of patients with CD (n = 650) or UC (n = 437) treated with vedolizumab from May 2014 through December 2016. Using time to event analyses, we compared rates of clinical remission, corticosteroid-free remission (CSFR), and endoscopic remission between patients with early-stage (≤2 years duration) and later-stage (>2 years) CD or UC. We used Cox proportional hazards models to identify factors associated with outcomes.ResultsWithin 6 months initiation of treatment with vedolizumab, significantly higher proportions of patients with early-stage CD, vs later-stage CD, achieved clinical remission (38% vs 23%), CSFR (43% vs 14%), and endoscopic remission (29% vs 13%) (P < .05 for all comparisons). After adjusting for disease-related factors including previous exposure to TNF antagonists, patients with early-stage CD were significantly more likely than patients with later-stage CD to achieve clinical remission (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.02-2.49), CSFR (aHR, 3.39; 95% CI, 1.66-6.92), and endoscopic remission (aHR, 1.90; 95% CI, 1.06-3.39). In contrast, disease duration was not a significant predictor of response among patients with UC.ConclusionsPatients with CD for 2 years or less are significantly more likely to achieve a complete response, CSFR, or endoscopic response to vedolizumab than patients with longer disease duration. Disease duration does not associate with response vedolizumab in patients with UC.

Over the years, the use of ultrasound has moved solely from the domain of the radiologist to that of the intensivist and emergentologist for use in acute care settings. By virtue of its ease of use and rapid learning curve to proficiency, we are now seeing an increased desire by internists to learn the modality and apply it at the patient's bedside. The rapid response system represents a rational starting point for the introduction of point-of-care ultrasound to the inpatient ward setting.

Statins are among the most widely prescribed medications in the world. In addition to lowering cholesterol, statins have been shown to have immunomodulatory effects in multiple studies. For example, statins modulate the interaction between T cells and antigen-presenting cells, resulting in decreased T-cell activation and reduced levels of inflammatory cytokines. Statins have also been demonstrated to inhibit the migration of leukocytes across vascular endothelium into tissues. Although most research on the immune effects of statins has been conducted in the context of cardiovascular, rheumatological, or metabolic disease, various studies have shown that statins may have a significant impact on intestinal immunity and mucosal inflammation. Clinical research has suggested that statins may have benefit in inflammatory bowel disease. In this article, we review the effect of statins on the immune system and gastrointestinal tract, highlighting the potential for novel therapeutic applications in inflammatory bowel disease.

To assess the prevalence of headache in clinic and support group patients with celiac disease and inflammatory bowel disease (IBD) compared with a sample of healthy controls.European studies have demonstrated increased prevalence of headache of patients with celiac disease compared with controls.Subjects took a self-administered survey containing clinical, demographic, and dietary data, as well as questions about headache type and frequency. The ID-Migraine screening tool and the Headache Impact Test (HIT-6) were also used.Five hundred and two subjects who met exclusion criteria were analyzed - 188 with celiac disease, 111 with IBD, 25 with gluten sensitivity (GS), and 178 controls (C). Chronic headaches were reported by 30% of celiac disease, 56% of GS, 23% of IBD, and 14% of control subjects (P.0001). On multivariate logistic regression, celiac disease (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.78-8.10), GS (OR 9.53, 95%CI 3.24-28.09), and IBD (OR 2.66, 95%CI 1.08-6.54) subjects all had significantly higher prevalence of migraine headaches compared with controls. Female sex (P=.01), depression, and anxiety (P=.0059) were independent predictors of migraine headaches, whereas age65 was protective (P=.0345). Seventy-two percent of celiac disease subjects graded their migraine as severe in impact, compared with 30% of IBD, 60% of GS, and 50% of C subjects (P=.0919). There was no correlation between years on gluten-free diet and migraine severity.Migraine was more prevalent in celiac disease and IBD subjects than in controls. Future studies should include screening migraine patients for celiac disease and assessing the effects of gluten-free diet on migraines in celiac disease.

Protein-losing enteropathy (PLE) is a debilitating potential complication of ulcerative colitis (UC). We report a case of PLE in a 26-year-old male patient with UC. The patient lost 50 pounds in the setting of a UC flare and was found to have an albumin level of 1.2 g/dl. Although the patient’s UC was clinically controlled with steroids, the weight loss and hypoalbuminemia persisted with the patient’s course complicated by development of deep vein thrombosis and pulmonary embolism. The diagnosis of PLE was confirmed with measurement of stool alpha-1-antitrypsin clearance. The patient’s condition significantly improved following procto-colectomy.