关键词： Crohn's disease   Inflammatory bowel diseases   Long-term outcomes   Treat-to-target   Ulcerative colitis  

摘要： Inflammatory bowel diseases, including Crohn disease (CD)and ulcerative colitis (UC), are chronic, progressive, immune-mediated inflammatory diseases of the gastrointestinal tract. Early therapy using a treat-to-target (T2T)approach, which implies identification of a pre-defined target, followed by optimization of therapy and regular monitoring until the goal is achieved is critical in preventing adverse long-term outcomes. In this review, the authors discuss the T2T guidance developed by the Selecting Therapeutic Targets in Inflammatory Bowel Disease committee, new evidence published on the role of various targets in CD and UC, as well as the real-world applicability of T2T.” © 2019 Elsevier Inc.

关键词： Burden   Crohn's disease   Professional life   Ulcerative colitis  

摘要： Background: Inflammatory bowel diseases (IBD) affect working-age patients. Data was lacking concerning the impact on working life. Aims: The French IBD patient association conducted a nationwide survey to assess the burden of IBD at work. Methods: An online survey was performed in 2016, targeting IBD patients working or having worked previously. The results were compared to those observed in the general population. Results: Data from 1410 IBD patients were analyzed (62% Crohn's disease, 35% ulcerative colitis). Four-fifth of respondents were actively employed. Half of them stated that working with IBD was a problem. Compared to the general population, IBD employees had higher rates of permanent contracts, public employment but also of part-time contracts, and highly graduated patients were less likely to reach high qualified jobs. Among the disabling symptoms at work, fatigue was the most frequent (41%) followed by diarrhea (25%) and fecal incontinence (18%). Despite these difficulties, 76% were satisfied with their job. Most patients shared their IBD diagnosis with their colleagues, but 25% of them regretted it. Conclusion: IBD has a strong negative impact on working life. While work satisfaction remains high, IBD affects career plans, highlighting the need for supporting measures to improve patients' work experience. (C) 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

关键词： Crohn's disease   inflammatory bowel disease   ulcerative colitis   vedolizumab  

摘要： Background Cohort studies have described the short-term effectiveness and safety of vedolizumab in treating patients with Crohn's disease (CD) and ulcerative colitis (UC), but data beyond 1 year are lacking. Aim To assess the effectiveness and safety of vedolizumab after 162 weeks in patients with UC and CD. Methods Between June and December 2014, 294 patients including 173 patients with CD and 121 with UC were treated with vedolizumab induction therapy. Among them, 149 continued to be treated with vedolizumab beyond week 54 (78 patients with CD and 71 with UC). Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid-free clinical remission at week 162, computed for the whole population included at week 0. Results Steroid-free clinical remission rates at week 162 were 19.9% and 36.1% in patients with CD and UC respectively. Vedolizumab dose optimisation to 300 mg every 4 weeks instead of 300 mg every 8 weeks was at investigator's discretion and occurred in 58.7% and 52.1% of patients with CD and UC respectively. The 1-, 2- and 3-year persistence rates of vedolizumab were 48.5%, 31.4% and 26.3% respectively, in patients with CD and 61.0%, 49.9% and 42.9% respectively, in patients with UC. No new safety signal was identified. Conclusion Vedolizumab is able to maintain steroid-free clinical remission in patients with UC and CD up to week 162. Loss of response resulting in discontinuation of vedolizumab occurred in 10% of patients per year.

关键词： miR-125a   Inflammatory bowel disease   CD4(+) T cells   Ets-1   Th1   Th17  

摘要： MicroRNA (miR)-125a is highly expressed in T cells and regulates the functions of Treg through the IL-6-STAT3 signaling pathway. However, the role of miR-125a in regulating immune responses in intestinal mucosa of patients with inflammatory bowel diseases (IBD) is still not understood. Here we showed that miR-125a expression was decreased in PBMC and inflamed intestinal mucosa from IBD patients compared with that in healthy controls. Transduction with LV-miR-125a into IBD CD4(+) T cells could significantly inhibit proinflammatory cytokine production, including IFN-gamma, TNF-alpha and IL-17A. RNA-seq analysis of miR-125a(-/-) CD4(+) T cells revealed enhanced genes (e.g., Stat1, Stat3, ROR gamma t, Irf4, Klf13) in T cell activation and effector pathways, while ETS-1 as its functional target promoted IBD CD4(+) T cell differentiation into Th1 cells. Consistently, miR-125a(-/-) mice developed more severe colitis induced by TNBS compared with WT mice. Thus, our data suggest that miR-125a protects intestinal mucosa from inflammatory injury and that ETS-1 as its target participates in the pathogenesis of IBD.

关键词： Bifidobacterium infantis   Inflammatory bowel disease   Programmed cell death ligand 1   T-Lymphocytes, regulatory  

摘要： Background/Aims: The current study aims to investigate the protective effects of Bifidobacterium infantis on the abnormal immune response to inflammatory bowel disease (IBD) in dextran sodium sulfate (DSS)-induced colitis. Methods: Eight-week-old BALB/c mice were separated into five groups at random (control, DSS, DSS+ B9 [B. infantis 1x10(9) CFU], DSS+ B8 [B. infantis 1x10(8) CFU], and DSS+ B7 [B. infantis 1x10(7) CFU]). Colitis was induced by 5% DSS ad libitum for 7 days, at which time we assessed weight, the disease activity index (DAI) score, and the histological damage score. The nuclear transcription factor Foxp3 (a marker of Treg cells), cytokines interleukin-10 (IL-10) and transforming growth factor beta 1 (TGF-beta 1), and related proteins (programmed cell death ligand 1 [PD-L1] and programmed cell death 1 [PD-1]) were detected by an immunohistochemical method and Western blot. Results: B. infantis increased weight, decreased DAI scores and histological damage scores, increased the protein expression of Foxp3 (p< 0.05) and cytokines IL-10 and TGF-beta 1 in mouse colon tissue (p< 0.05), and increased the expression of PD-L1 in the treatment groups relative to that in the DSS group (p< 0.05). The effect of B. infantis on Foxp3 and PD-L1 was dose dependent in the treatment groups (p< 0.05). PD-L1 was positively correlated with Foxp3, IL-10, and TGF-beta 1. Conclusions: In a mouse model of IBD, B. infantis can alleviate intestinal epithelial injury and maintain intestinal immune tolerance and thus may have potential therapeutic value for the treatment of immune damage in IBD.

关键词： Inflammatory bowel disease   2018   Update  

摘要： The global incidence and prevalence of inflammatory bowel disease (IBD) has increased over the last 2-4 decades, likely because of the adoption of a more "western" lifestyle as well as improved detection and awareness, and Taiwan is no exception. To characterize the increasing burden of IBD, we conducted a comprehensive review of IBD in the existing literature. The following parameters were reviewed: background knowledge and current standard care for IBD, including natural history, epidemiology, pathogenesis, diagnosis, monitoring, and treatment. In addition, new imaging modalities and treatment options such as combined positron emission tomography and magnetic resonance enterography, new biologic agents, small-molecule therapy, biosimilar therapeutics, mesenchymal stem cell transplantation, and fecal microbiota transplantation, all of which have been introduced for IBD management, were reviewed. We also used the hospital-based as well as population-based Taiwan National Health Insurance Research Database to assess Taiwan-specific trends for comparison with global trends. Copyright (C) 2018, Formosan Medical Association. Published by Elsevier Taiwan LLC.

关键词： Inflammatory bowel disease   Crohn's disease   Ulcerative colitis   Pathogenesis   Risk factors   Genetics   Environment  

摘要： Crohn's disease and ulcerative colitis constitute two major subgroups of inflammatory bowel diseases (IBD), a group of complex polygenic diseases characterized by chronic and progressive inflammation in the gastrointestinal tract. In recent years, methodological advances in genetic analysis have greatly expanded our understanding of the genetic background of IBD. So far, more than 240 genetic risk loci have been identified for IBD. However, these risk alleles explain less than 30% of the susceptibility to disease development, suggesting that environmental factors contribute considerably. The increasing occurrence of IBD in Eastern countries following their westernization', as well as the increased risk of disease among those who migrate to high-incidence regions, also suggest that the environment is key in the pathogenesis of IBD. In this review, we summarize the current evidence on the role of genetic and environmental factors in the susceptibility to, and disease course of, IBD, and we suggest how these findings might be applied to clinical practice.

关键词： inflammatory bowel disease   monitoring   ultrasound  

摘要： Objective: The aim of the study was to identify the most significant ultrasound (US) parameters that predict inflammatory activity and develop a simple US activity score. Methods: Patients were identified through retrospective evaluation of an established database of children with inflammatory bowel disease (IBD). Patients with endoscopy and US within 60 days were included (N = 75). US parameters evaluated included: bowel wall thickness (BWT), mesenteric inflammatory fat, lymphadenopathy, and hyperemia. The weighted kappa statistic was calculated to assess agreement between sonographic and endoscopically identified disease location. Using a proportional odds model and ordinal logistic regression, statistically significant (P < 0.05) parameters were used to generate a score. Variables were weighted to classify individuals into severity classes. Receiver operating characteristic curves were plotted to demonstrate the score's discriminative and predictive capacity. Results: There was substantial agreement between US and endoscopy for all disease locations (weighted kappa = 0.85) and substantial agreement for ileocolonic disease (weighted kappa = 0.96). Two sonographic parameters were identified as contributing significantly to disease activity: BWT and mesenteric inflammatory fat (P < 0.05). A predictive score was developed incorporating BWT, hyperemia and inflammatory fat, and receiver operating characteristic curve curves demonstrated good predictive capacity to distinguish between the absence of disease (normal) and active disease with an area under the curve of 82.1%. Conclusions: The most important sonographic parameters for predicting disease activity were BWT and mesenteric inflammatory fat. When combined with hyperemia into a simple score, there was accurate detection of inflammatory activity in children with inflammatory bowel disease. This score may facilitate noninvasive, bedside detection of inflammation, and standardize the use of US in children.

关键词： bedside   biomarkers   endoscopy   point-of-care   smartphones  

摘要： Objectives: Owing to the invasiveness of endoscopy, the use of biomarkers, especially faecal calprotectin (FC), has become standard for remission assessment. This study aimed to compare the accuracy for detection of endoscopic activity using recently developed FC home test using smartphone application (FC-IBDoc) against standard enzyme-linked immunosorbent assay (ELISA). Methods: In all, 102 consecutive observations (89 participants) were included in prospective observational study. FC-IBDoc was performed parallelly with FC-ELISA in paediatric patients with inflammatory bowel disease indicated for endoscopy. Both tests were performed by trained staff. Mucosal healing was defined using Simple Endoscopic Score for Crohn disease (CD) <= 2 in patients with CD (n = 44), ulcerative colitis (UC) Endoscopic Index of Severity <= 4 in patients with UC (n = 27) and Rutgeerts score i0 and i1 without colon involvement in patients with CD after ileocaecal resection (n = 19). Results: Out of 102 endoscopic findings 23 were assessed as mucosal healing. We found an association of the mucosal healing scores of the entire group both with FC-ELISA (P = 0.002) and FC-IBDoc (P = 0.001). The area under the receiver operating characteristic curve for FC-ELISA was 0.883 (95% confidence interval 0.807-0.960), with optimal cut-off at 136.5 mu g/g. The area under the receiver operating characteristic curve for FC-IBDoc was 0.792 (95% confidence interval 0.688-0.895) with optimal cut-off at 48 mu g/g. The FC-ELISA was more accurate than FC-IBDoc when tested by a Delong test (P = 0.023). Conclusions: Standard FC-ELISA for FC evaluation is more reliable predictor of mucosal healing than the FC-IBDoc in paediatric patients with inflammatory bowel disease. The cut-off values for both tests were incongruous.