关键词： Neuroscience   Stem cells  

摘要： Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a disease associated with dysbiosis, resulting in compromised intestinal epithelial barrier and chronic mucosal inflammation. Patients with IBD present with increased incidence of psychiatric disorders and cognitive impairment. Hippocampus is a brain region where adult neurogenesis occurs with functional implications in mood control and cognition. Using a well-established model of experimental colitis based on the administration of dextran sodium sulfate (DSS) in the drinking water, we sought to characterize the short and long-term effects of colitis on neurogenesis and glia responses in the hippocampus. We show that acute DSS colitis enhanced neurogenesis but with deficits in cell cycle kinetics of proliferating progenitors in the hippocampus. Chronic DSS colitis was characterized by normal levels of neurogenesis but with deficits in the migration and integration of newborn neurons in the functional circuitry of the DG. Notably, we found that acute DSS colitis-induced enhanced infiltration of the hippocampus with macrophages and inflammatory myeloid cells from the periphery, along with elevated frequencies of inflammatory M1-like microglia and increased release of pro-inflammatory cytokines. In contrast, increased percentages of tissue-repairing M2-like microglia, along with elevated levels of the anti-inflammatory cytokine, IL-10 were observed in the hippocampus during chronic DSS colitis. These findings uncover key effects of acute and chronic experimental colitis on adult hippocampal neurogenesis and innate immune cell responses, highlighting the potential mechanisms underlying cognitive and mood dysfunction in patients with IBD.

关键词： adipokines   visceral obesity   mesenteric fat   inflammatory bowel disease   microbiome  

摘要： Inflammatory bowel diseases (IBDs), chronic inflammatory disorders affecting the gastrointestinal tract, include Crohn's disease and ulcerative colitis. There are increasing clinical and experimental data showing that obesity, especially visceral adiposity, plays a substantial role in the pathogenesis of IBD. Obesity seems to be an important risk factor also for IBD disease severity and clinical outcomes. Visceral adipose tissue is an active multifunctional metabolic organ involved in lipid storage and immunological and endocrine activity. Bowel inflammation penetrates the surrounding adipose tissue along the mesentery. Mesenteric fat serves as a barrier to inflammation and controls immune responses to the translocation of gut bacteria. At the same time, mesenteric adipose tissue may be the principal source of cytokines and adipokines responsible for inflammatory processes associated with IBD. This review is particularly focusing on the potential role of adipokines in IBD pathogenesis and their possible use as promising therapeutic targets.

关键词： adolescents and young adults   inflammatory bowel disease   transition  

摘要： Objectives: Adolescents and young adults (AYAs) are at risk for disease exacerbations and increased health care utilization around the time of transition to adult care. Our aim was to identify risk factors predictive of a suboptimal transition for AYA with inflammatory bowel disease. Materials and Methods: We performed a retrospective chart review of patients with pediatric inflammatory bowel disease transferred to adult care from our institution in 2016 and 2017, recording demographic, psychosocial, and disease-specific data. Post-transfer data were obtained via the health care information exchange from the adult provider within our electronic medical record. We defined suboptimal transition as either a return to pediatric care or requiring care escalation within 1 year of transfer. Results: Out of 104 subjects 37 (36%) were found to have had a suboptimal transition. Our models suggest that a suboptimal transition is associated with several risk factors including any mental health diagnosis (odds ratio [OR] = 4.15;95% confidence interval [95% CI]: 1.18-14.59), history of medication nonadherence (OR = 5.15 [95% CI: 1.52-17.42]), public insurance (OR = 6.60 [95% CI: 1.25-34.96]), higher Physician Global Assessment score at time of transition (OR = 6.64 [95% CI: 1.60-27.58], and short Pediatric Crohn Disease Activity Index scores (OR = 1.17 [95% CI: 1.03-1.33]). Higher hemoglobin levels at transition were protective (OR = 0.69 [95% CI: 0.48-0.98]). Age at time of transition, disease duration, and medication type at transition were not found to be associated with transition outcomes. Conclusion: AYA with public insurance, a mental health history, medication nonadherence, and evidence of active disease may be at greater risk for suboptimal and poor health outcomes at transition.

关键词： Biomarker   Prognostic Factor   Outcome   Efficacy  

摘要： BACKGROUND & AIMS: A substantial proportion patients with inflammatory bowel disease (IBD) have a primary nonresponse to infliximab;markers are needed to identify patients most likely to respond to treatment. We investigated whether production of tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMCs) can be used as a marker to predict response. METHODS: Weperformed a prospective study of 41 adults with IBD (mean age, 38 years;21male;21 with Crohn's disease and 20 with ulcerative colitis) not treated with a biologic agent within the past 6 months;patients were given their first infusion of infliximab at a hospital or clinic in Berlin, Germany. We collected data on clinical scores, levels of C-reactive protein, and ultrasound results (Limberg scores) atbaseline (before thefirst infusion) andafter6weeks(3rd infliximab infusion). PMBCswereobtained from patients at baseline and 10 healthy individuals (controls) and incubated with lipopolysaccharide. Wemeasured production of cytokines (TNF, interleukin 1 [IL1], IL6, IL8, IL10, IL12p70, and IL22) by ELISA and performed cytometric bead array and flow cytometry analyses. The primary endpoint was clinical response (decrease in Harvey Bradshaw Index scores of 2 ormore or decrease in partial Mayo scores of 3 ormore at week 6) in patients with PBMCs that produced highvs lowlevels of TNF. RESULTS: Responders had a shorter median disease duration (P = .018) and higher median Limberg score (P = .021), than nonresponders. Baseline PBMCs from responders produced significantly more TNF (P = .049) and IL6 (P = .028) than from nonresponders;a level of 500 pg/ml TNF identified responders with 82% sensitivity and 78% specificity. In patients with Crohn's disease, this cutoff value (500 pg/ml TNF) identified responders with 100% sensitivity and 82% specificity;TNF levels above this level were independently associated with response to infliximab in multivariate analysis (odds ratio, 16.2;95% CI, 1.8-148.7;P = .014). The p

关键词： Surgery   Right colectomy   Enhanced recovery programme   Postoperative outcome   Inflammatory bowel disease  

摘要： Purpose Enhanced recovery programmes (ERPs) after surgery reduce postoperative complications and hospital stay. Patients with inflammatory bowel disease (IBD) often present risk factors for postoperative complications. This accounts for reluctance to include them in ERPs. We compared outcome after right colectomy with an ERP in IBD and non-IBD patients. Methods In our GRACE colorectal surgery database comprising 508 patients, we analysed patients scheduled for right colectomy (n = 160). Adherence to the protocol, postoperative complications and length of hospital stay of IBD patients (n = 45) were compared with those of non-IBD patients (n = 115). Data (mean +/- SD, median [IQR], count (%)) were compared by Student's t, Mann-Whitney U and chi-square tests when appropriate;p < 0.05 taken as statistically significant. Results IBD patients were significantly younger (38.9 +/- 13.8 vs. 58.9 +/- 18.5 years, p < 0.001) and had lower BMI (23.0 +/- 5.0 vs. 25.1 +/- 5.0 kg m(-2), p < 0.01). Adherence to ERP was similar in the two groups. Resumption of eating on the day of the operation was less well tolerated (73.3% vs. 85.2%, p < 0.05) and postoperative pain (p < 0.001) was greater in IBD patients. The incidence of postoperative complications (13.3% vs. 17.3%) and the length of hospital stay (3 [3-4.5] vs. 3 [2-5] days) were comparable in IBD and non-IBD patients, respectively. Conclusion The management of IBD patients in an ERP is not only feasible but also indicated. These patients benefit as much from ERP as non-IBD patients.

关键词： Crohn's disease   Ulcerative colitis   Treat-to-target   Monitoring   Biomarkers  

摘要： With the advent of biologic and small molecule therapies, there has been a substantial change in the treatment of inflammatory bowel disease. These advances have had a great impact in preventing disease progression, intestinal damage and, therefore, have contributed to a better quality of life. Discordance between symptom control and mucosal healing has been demonstrated. This has led to the search for new disease control targets. The treat to target strategy, based on expert recommendations and now a randomized controlled trial, has determined that clinical and endoscopic remission should be the goal of therapy. Biomarkers (fecal calprotectin) can be a surrogate target. Although histological healing has shown benefits, there is inadequate evidence and inadequate therapy for that to be a fixed goal at this time. This review will focus on therapeutic goals, according to the evidence currently available, and evaluate strategies to achieve them. (C) 2020 Elsevier Espana, S.L.U. All rights reserved.

关键词： Endoscopic resection   Non-polypoid dysplasia   Inflammatory bowel disease   Meta-analysis  

摘要： Background This systematic review and meta-analysis aims to evaluate efficacy and safety of endoscopic treatment for the non-polypoid dysplasia in patients with long-standing IBD. Methods Medline, Embase, Cochrane, and *** registry were comprehensively searched. Pooled estimates of curative, R0, en-bloc resection rates, CRC, metachronous dysplasia, and local recurrence rates were calculated. Subgroup analysis according to areas, lesion size, endoscopic resection techniques, and grades of dysplasia were conducted. Data synthesis was completed in R using the package "meta". Results Of the 973 studies initially identified, 7 met the inclusion/exclusion criteria. These were all single-arm cohorts and included a total of 202 patients with IBD and non-polypoid dysplasia. The combined R0 and en-bloc resection rate were 0.70 (95% CI 0.55-0.81) and 0.86 (95% CI 0.65-0.95), respectively, with a recurrence rate of 0.08 (95% CI 0.05-0.13). CRC and metachronous dysplasia incidences were pooled as 32.53 (95% CI 12.21-86.67) and 90.24 (95% CI 44.91-181.33) per 1000 patient years. Conclusions Non-polypoid dysplasia associated with IBD can be resected endoscopically, especially by ESD. However, these patients have higher CRC and metachronous dysplasia incidence rates than patients with polypoid dysplasia, indicating a closer endoscopic surveillance.

摘要： Comparison data regarding anti–tumor necrosis factor drug concentrations in inflammatory bowel disease (IBD) between the enzyme-linked immunosorbent assay (ELISA) and the homogenous mobility shift assay (HMSA) are scarce.1–3 As decisions in clinical practice depend on the thresholds that define a therapeutic drug concentration, it is important to determine if this varies based on the type of assay used for therapeutic drug monitoring.4 We recently showed a discrepancy between a commercially available ELISA and the HMSA for both infliximab and adalimumab concentrations in patients with IBD.5 Based on the results of the study, Prometheus Laboratories (San Diego, CA) initiated a comprehensive review of their HMSA assays and found that there was an upward drift for both infliximab (from December 2017 to May 2019) and adalimumab (from August 2017 to May 2019), including when our study was performed. Prometheus Laboratories corrected the errant values and reported the revised drug concentrations to physicians (Supplementary Methods). We aimed to compare the corrected infliximab and adalimumab concentrations with the original ELISA values.