Small bowel MR enterography: problem solving in Crohn’s disease

Magnetic resonance enterography (MRE) is fast becoming the first-line radiological investigation to evaluate the small bowel in patients with Crohn’s disease. It can demonstrate both mural and extramural complications. The lack of ionizing radiation, together with high-contrast resolution, multiplanar capability and cine-imaging make it an attractive imaging modality in such patients who need prolonged follow-up. A key question in the management of such patients is the assessment of disease activity. Clinical indices, endoscopic and histological findings have traditionally been used as surrogate markers but all have limitations. MRE can help address this question. The purpose of this pictorial review is to (1) detail the MRE protocol used at our institution; (2) describe the rationale for the MR sequences used and their limitations; (3) compare MRE with other small bowel imaging techniques; (4) discuss how MRE can help distinguish between inflammatory, stricturing and penetrating disease, and thus facilitate management of this difficult condition

Adapting agricultural water use to climate change in a post-Soviet context: challenges and opportunities in southeast Kazakhstan

The convergence of climate change and post-Soviet socio-economic and institutional transformations has been underexplored so far, as have the consequences of such convergence on crop agriculture in Central Asia. This paper provides a place-based analysis of constraints and opportunities for adaptation to climate change, with a specific focus on water use, in two districts in southeast Kazakhstan. Data were collected by 2 multi-stakeholder participatory workshops, 21 semi-structured in-depth interviews, and secondary statistical data. The present-day agricultural system is characterised by enduring Soviet-era management structures, but without state inputs that previously sustained agricultural productivity. Low margins of profitability on many privatised farms mean that attempts to implement integrated water management have produced water users associations unable to maintain and upgrade a deteriorating irrigation infrastructure. Although actors engage in tactical adaptation measures, necessary structural adaptation of the irrigation system remains difficult without significant public or private investments. Market-based water management models have been translated ambiguously to this region, which fails to encourage efficient water use and hinders adaptation to water stress. In addition, a mutual interdependence of informal networks and formal institutions characterises both state governance and everyday life in Kazakhstan. Such interdependence simultaneously facilitates operational and tactical adaptation, but hinders structural adaptation, as informal networks exist as a parallel system that achieves substantive outcomes while perpetuating the inertia and incapacity of the state bureaucracy. This article has relevance for critical understanding of integrated water management in practice and adaptation to climate change in post-Soviet institutional settings more broadly

The London position statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: safety.

This paper in the series from the World Congress of Gastroenterology addresses the safety and immunogenicity of biological therapy. The safety profile in randomized controlled studies of all biological agents in Crohn's disease (CD) and ulcerative colitis has been generally favorable, but a small percentage of patients experience severe side effects on biological therapy, including pneumonia, tuberculosis, lymphoma, demyelination, drug-induced lupus, or hepatotoxicity. Although there is unequivocal evidence of an increased risk of serious infection among patients with rheumatoid arthritis treated with anti-tumor necrosis factor therapy, the evidence is less clear in CD. The risk of infection may be increased by combination therapy with steroids and/or immunomodulators. There is a specific risk of the rare γ δ hepatosplenic lymphoma that appears to have a predeliction for young males on combination therapy. The α4 integrin antagonist natalizumab also carries a specific risk of progressive multifocal leucoencephalopathy and reactivation of JC virus infection. The immunogenicity of biological therapy is complex: all agents are potentially immunogenic and this can be reduced by combination with immunomodulators. This may enhance both therapeutic efficacy and the risk of infection or malignancy, so the balance of risk and benefit must be judged for individual patients

The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis

Background & Aims Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations. Methods We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.8 g/day. Endoscopic images were reviewed by a single expert central reader. The primary outcome was clinical remission (UCDAI, stool frequency and bleeding scores of 0, and no fecal urgency) at week 6. Results The primary outcome was achieved by 30.0% of patients treated with mesalamine and 20.6% of those given placebo, a difference of 9.4% (95% confidence interval [CI], −0.7% to 19.4%; P = .069). Significant differences in results from secondary analyses indicated the efficacy of mesalamine. Thirty-one percent of participants, all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator, were considered ineligible by the central reader. After exclusion of these patients, the remission rates were 29.0% and 13.8% in the mesalamine and placebo groups, respectively (difference of 15%; 95% CI, 3.5%–26.0%; P = .011). Conclusions Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC, based on an intent-to-treat analysis, the totality of the data supports a benefit of treatment. Central review of endoscopic images is critical to the conduct of induction studies in UC; ClinicalTrials.gov Number, NCT01059344

The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis

Background and Aims Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations. Methods We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.8 g/day. Endoscopic images were reviewed by a single expert central reader. The primary outcome was clinical remission (UCDAI, stool frequency and bleeding scores of 0, and no fecal urgency) at week 6. Results The primary outcome was achieved by 30.0% of patients treated with mesalamine and 20.6% of those given placebo, a difference of 9.4% (95% confidence interval [CI], −0.7% to 19.4%; P = .069). Significant differences in results from secondary analyses indicated the efficacy of mesalamine. Thirty-one percent of participants, all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator, were considered ineligible by the central reader. After exclusion of these patients, the remission rates were 29.0% and 13.8% in the mesalamine and placebo groups, respectively (difference of 15%; 95% CI, 3.5%–26.0%; P = .011). Conclusions Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC, based on an intent-to-treat analysis, the totality of the data supports a benefit of treatment. Central review of endoscopic images is critical to the conduct of induction studies in UC; ClinicalTrials.gov Number, NCT01059344