关键词： Association (Psychology)   Pregnancy   parenthood   Pathway   Inflammatory Bowel Diseases   Intestinal Diseases   American  

关键词： TLR   Chlorine   CTLA4 gene   NOD2 gene   Inflammatory Bowel Diseases   UNIVERSITY OF CALIFORNIA   Patients  

摘要： Background Anti-tumor necrosis factor-alpha (TNF-alpha) is used for the treatment of severe cases of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. We have previously investigated whether single nucleotide polymorphisms (SNPs) in genes involved in inflammation were associated with response to anti-TNF therapy among patients with CD or UC. Aim A new cohort of patients was established for replication of the previous findings and to identify new SNPs associated with anti-TNF response. Methods Fifty-three SNPs assessed previously in cohort 1 (482 CD and 256 UC patients) were genotyped in cohort 2 (587 CD and 458 UC patients). The results were analysed using logistic regression (adjusted for age and gender). Results Ten SNPs were associated with anti-TNF response either among patients with CD (TNFRSF1A(rs4149570) (OR: 1.92, 95% CI: 1.02-3.60, P = 0.04), IL18(rs187238) (OR: 1.35, 95% CI: 1.00-1.82, P = 0.05), and JAK2(rs12343867) (OR: 1.35, 95% CI: 1.02-1.78, P = 0.03)), UC (TLR2(rs11938228) (OR: 0.55, 95% CI: 0.33-0.92, P = 0.02), TLR4(rs5030728) (OR: 2.23, 95% CI: 1.24-4.01, P = 0.01) and (rs1554973) (OR: 0.49, 95% CI: 0.27-0.90, P = 0.02), NFKBIA(rs696) (OR: 1.45, 95% CI: 1.06-2.00, P = 0.02), and NLRP3(rs4612666) (OR: 0.63, 95% CI: 0.44-0.91, P = 0.01)) or in the combined cohort of patient with CD and UC (IBD) (TLR4(rs5030728) (OR: 1.46, 95% CI: 1.01-2.11, P = 0.04) and (rs1554973)(OR: 0.80, 95% CI: 0.65-0.98, P = 0.03), NFKBIA(rs696) (OR: 1.25, 95% CI: 1.01-1.54, P = 0.04), NLRP3(rs4612666) (OR: 0.73, 95% CI: 0.57-0.95, P = 0.02), IL1RN(rs4251961) (OR: 0.81, 95% CI: 0.66-1.00, P = 0.05), IL18(rs1946518) (OR: 1.24, 95% CI: 1.01-1.53, P = 0.04), and JAK2(rs12343867) (OR: 1.24, 95% CI: 1.01-1.53, P = 0.04)). Conclusions The results support that polymorphisms in genes involved in the regulation of the NF kappa B pathway (TLR2, TLR4, and NFKBIA), the TNF-alpha signalling pathway (TNFRSF1

关键词： colorectal neoplasms   endoscopy   inflammatory bowel diseases   meta-analysis  

摘要： Objective To compare chromoendoscopy (CE) and white light endoscopy (WLE) for dysplasia surveillance in patients with inflammatory bowel disease (IBD). Methods We conducted a meta-analysis of 6 randomized controlled trials (RCTs) and 5 prospective studies and compared the CE and WLE groups. A fixed-effect model was used unless the heterogeneity was high. Results CE detected more patients with dysplasia (relative risk [RR] 2.05, 95% confidence interval [CI]: 1.62-2.61) and more dysplastic lesions (RR 2.04, 95% CI: 1.40-2.98) than WLE. When magnification was added to CE, the detection rate of patients with dysplasia and dysplastic lesions improved. CE also detected more patients with dysplasia than high-definition WLE (RR 1.60, 95% CI: 1.11-2.29). Compared with WLE, the incremental yield of CE for detecting patients with dysplasia was 9%. CE was superior to WLE in detecting non-polypoid dysplastic lesions (RR 1.38, 95% CI:1.02-1.88). CE had no advantage for detecting polypoid dysplastic lesions compared with WLE. Conclusions CE is superior to WLE in the surveillance of dysplasia in IBD patients. It is thus necessary to use CE in the surveillance of dysplasia in patients with IBD in clinical practice. Adding magnification improves the detection rate.

关键词： IQR   Cmin   monotherapy   Azathioprine   Infliximab   Inflammatory Bowel Diseases   Combined Modality Therapy   Crohn Disease   Consumer Behavior  

摘要： Background Combination treatment with azathioprine for 6-12 months is the preferred strategy for starting infliximab due to improved pharmacokinetics. However, optimised infliximab monotherapy with proactive dose escalations in case of low trough levels is a safer but under-studied alternative. Aim To compare the clinical success and infliximab consumption of combination vs optimised monotherapy strategies. Methods We studied the clinical success and infliximab consumption of both strategies in 149 patients (94 Crohn's disease;55 ulcerative colitis) starting infliximab and undergoing intensive drug monitoring assisted treatment optimisation. Results The drug retention rates were similar for optimised monotherapy and combination treatment after induction (96% vs 97%, P = 0.73), after the first year (90% vs 83%, P = 0.23) and at the end of follow-up (74% vs 75%, P = 0.968). Similarly, no differences were observed for steroid use at year 1 (5% vs 14%, P = 0.08) or mucosal healing at the end of follow-up (64% vs 67%, P = 0.8). Higher infliximab consumption (7.6 mg/kg q8 weeks [interquartile range (IQR): 5.9-10.3] vs 6.4 mg/kg q8 weeks [IQR: 5.2-8.0], P = 0.019) combined with lower trough levels (1.7 mu g/mL [IQR: 0.3-6.6] vs 5.0 mu g/mL [2.5-8.7], P = 0.012) resulted in almost 3-fold higher drug-to-trough ratio (3.9 vs 1.5) in monotherapy compared to combination strategy at year 1. At the end of follow-up, when azathioprine had been discontinued for a median of 14 [IQR: 3-33] months, these differences disappeared. Conclusions In this study, optimised infliximab monotherapy was as clinically effective as combination therapy but was associated with significantly higher infliximab consumption. The infliximab-sparing effect disappeared after azathioprine withdrawal.

关键词： apoptosis   autophagy   inflammatory bowel disease   inflammation   microRNA  

摘要： Inflammatory bowel disease (IBD), as a chronic and recurrent inflammatory disorder, is caused by a dysregulated and aberrant immune response to exposed environmental factors in genetically susceptible individuals. Despite huge efforts in determining the molecular pathogenesis of IBD, an increasing worldwide incidence of IBD has been reported. MicroRNAs (miRNAs) are a set of noncoding RNA molecules that are about 22 nucleotides long, and these molecules are involved in the regulation of the gene expression. By clarifying the important role of miRNAs in a number of diseases, their role was also considered in IBD;numerous studies have been performed on this topic. In this review, we attempt to summarize a number of studies and discuss some of the recent developments in the roles of miRNAs in the pathophysiology, diagnosis, and treatment of IBD.

关键词： Preventive Medicine   Inflammatory Bowel Diseases   Intestinal Diseases  

关键词： Pathophysiology   Intestinal Diseases   Health Care   Inflammatory Bowel Diseases   Western Europe  

摘要： Linked Content This article is linked to Shah et al paper. To view this article, visit https://***/10.1111/apt.15178. [ABSTRACT FROM AUTHOR]

关键词： Intestinal Diseases   Biosimilar Pharmaceuticals   Inflammatory Bowel Diseases   Biologic Products   switching  

关键词： Chromoendoscopy   Dysplasia   Endoscopic mucosal resection   Inflammatory bowel disease   Ulcerative colitis  

摘要： Background: Patients with ulcerative colitis and Crohn's colitis have an increased risk of developing dysplasia and colorectal cancer as compared to the general population;surveillance colonoscopy is recommended in this patient population. Methods: This review of the published literature aimed to assess the published evidence. Results: Detection of dysplasia requires examination of mucosa with targeted biopsies of the visible lesions as well as random biopsies to detect invisible lesions. Newer endoscopic techniques, in particular chromoendoscopy, increase the yield of identifying dysplastic lesions. The surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients International Consensus (SCENIC) guidelines recommends that colonoscopy using chromoendoscopy is the optimal endoscopic surveillance strategy to detect dysplasia. Once dysplastic lesions are discovered on surveillance endoscopic examination, careful and meticulous descriptions of lesions is mandatory to aid in further decision making. Management of dysplastic lesions in inflammatory bowel disease patients depends on endoscopic (morphological) and histologic findings and patient characteristics such as age, general condition of the patient, and patient preferences. Endoscopic mucosal resection, endoscopic submucosal dissection, and surgery are different therapeutic options for colonic dysplastic lesions detected in the setting of inflammatory bowel disease. Conclusions: In this review, we discuss the various techniques for endoscopic resection of dysplasia in patients with inflammatory bowel disease. Further research is required to determine the optimal approach to diagnosis and management of dysplasia in patients with inflammatory bowel disease.