关键词： Complications   Neoplasm   Prevention   Noninvasive Test   Biomarker  

摘要： BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are at increased risk for colorectal cancer (CRC). Analyses of DNA methylation patterns in stool samples have been reported to detect CRC in patients with IBD. We sought to validate these findings in larger cohorts and assess the accuracy of analysis of DNA methylation patterns in stool for detection of CRC and high-grade dysplasia (HGD) normalized to methylation level at ZDHHC1. METHODS: We obtained buffered, frozen stool samples from a US case-control study and from 2 European surveillance cohorts (referral or population based) of patients with chronic ulcerative colitis (n = 248), Crohn's disease (n = 82), indeterminate colitis (n = 2), or IBD with primary sclerosing cholangitis (n = 38). Stool samples were collected before bowel preparation for colonoscopy or at least 1 week after colonoscopy. Among the study samples, stools from individuals with IBD but without neoplasia were used as controls (n = 291). DNA was isolated from stool, exposed to bisulfite, and then assayed by multiplex quantitative allele-specific real-time target and signal amplification. We analyzed methylation levels of BMP3, NDRG4, VAV3, and SFMBT2 relative to the methylation level of ZDHHC1, and compared these between patients with CRC or HGD and controls. RESULTS: Levels of methylation at BMP3 and VAV3, relative to ZDHHC1 methylation, identified patients with CRC and HGD with an area under the curve value of 0.91 (95% CI, 0.77-1.00). Methylation levels at specific promotor regions of these genes identified 11 of the 12 patients with CRC and HGD, with 92% sensitivity (95% CI, 60%-100%) and 90% specificity (95% CI, 86%-93%). The proportion of false-positive results did not differ significantly among the case-control, referral cohort, and population cohort studies (P = .60) when the 90% specificity cut-off from the whole sample set was applied. CONCLUSIONS: In an analysis of st

关键词： Crohn disease   school attendance   ulcerative colitis  

摘要： Objectives: Inflammatory bowel diseases (IBDs) are chronic diseases which negatively affect the schooling of children. The aim is to analyze school absenteeism and its causes in children followed for IBD. Methods: A prospective multicenter study of IBD patients aged from 5 to 18 years old, from September 2016 to June 2017. Data on absenteeism and its causes were collected via a monthly questionnaire completed by patients or their family by mail. The results were compared with existing data supplied by the school authorities (497 students without IBD divided by class). Results: A total of 106 patients (62 boys), median age of 14 (5-18), were included. The global response rate was 83.1%. The patients with IBD were absent an average of 4.8% +/- 5.5% of school days during the school year, against 3.2% +/- 1.6% for non IBD group (P = 0.034). Digestive disorders accounted for 34% of the causes of absenteeism. Approximately 27% of the absences were due to scheduled events (hospitalizations, endoscopy, or consultations). By excluding the absences for scheduled care, the rate of school absenteeism of patients with IBD is significantly lower than that of non-IBD group. Conclusion: Children with IBD are more frequently absent from school than non-IBD group. The main cause of school absenteeism appears to be associated with the disease itself. The share of scheduled absenteeism is quite large. The organization and scheduling of the patients' care path must be a priority to maximally limit the negative impact of their disease on the patients' schooling.

关键词： Inflammatory bowel disease   Mucosal healing   Histological healing   Target to treat approach  

摘要： Management of inflammatory bowel diseases has witnessed paradigm shift from 5-aminosalicylic acid and glucocorticoids to various immunosuppressant and biological agents. Targets of therapy have also been changed drastically from symptomatic improvement to mucosal, histological healing, and recently transmural healing. Mucosal healing is associated with reduced need of steroid therapy, hospitalization, and surgery. However, whether mucosal healing alters the natural history of disease remains to be proven. Though assessment of mucosal healing is traditionally done by endoscopic examination, newer tests like fecal calprotectin, capsule endoscopy, and magnetic resonance enterography have also shown promising results. Various immunosuppressants and biologicals are the main therapy being used to achieve mucosal healing. This review focuses on the need for achieving mucosal healing, its long-term benefits, various methods and algorithm for diagnosis, and achievement of mucosal healing.

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： 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： 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： 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