摘要： Paediatric inflammatory bowel disease (PIBD), comprising Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease unclassified (IBDU) is a complex and multifactorial condition with increasing incidence. An accurate diagnosis of PIBD is necessary for a prompt and effective treatment. This study utilises machine learning (ML) to classify disease using endoscopic and histological data for 287 children diagnosed with PIBD. Data were used to develop, train, test and validate a ML model to classify disease subtype. Unsupervised models revealed overlap of CD/UC with broad clustering but no clear subtype delineation, whereas hierarchical clustering identified four novel subgroups characterised by differing colonic involvement. Three supervised ML models were developed utilising endoscopic data only, histological only and combined endoscopic/histological data yielding classification accuracy of 71.0%, 76.9% and 82.7% respectively. The optimal combined model was tested on a statistically independent cohort of 48 PIBD patients from the same clinic, accurately classifying 83.3% of patients. This study employs mathematical modelling of endoscopic and histological data to aid diagnostic accuracy. While unsupervised modelling categorises patients into four subgroups, supervised approaches confirm the need of both endoscopic and histological evidence for an accurate diagnosis. Overall, this paper provides a blueprint for ML use with clinical data.

关键词： Inflammatory bowel disease   Tight junctions   Single nucleotide polymorphism   Genetic predisposition   Gene expression  

摘要： Background: Inflammatory bowel disease (IBD) is associated with increased intestinal permeability, which involves paracellular passage regulated through tight junctions (TJ). The aim of the study was to investigate single nucleotide polymorphisms (SNP) located in genes encoding interacting TJ proteins and corresponding expressions, in relation to IBD. Methods: Allelic associations between TJ-related genes (F11R, MAGI1, MAGI2, MAGI3, PARD3, PTEN, and TJP1) and IBD, Crohn's disease (CD), or ulcerative colitis (UC) were investigated. PTPN22 was included since it's located in the same genetic region as MAGI3. Gene expression levels were investigated in relation to genotype, inflammatory status, phenotype, and medical treatment. Results: The two strongest allelic associations were observed between IBD and SNPs in MAGI2 (rs6962966) and MAGI3 (rs1343126). Another MAGI3 SNP marker (rs6689879) contributed to increased ileal MAGI3 expression level in non-IBD controls. Furthermore, association between inflammation and decreased expression levels of MAGI3, PTEN, and TJP1 in colonic IBD as well as UC mucosa, and between inflammation and increased expression of PTPN22 in colonic IBD mucosa, was observed. Conclusions: Our findings lend support to a genetic basis for modulation of intestinal epithelial barrier in IBD, and we have identified MAGI3 as a new candidate gene for IBD.

关键词： 肛肠疾病术后   并发症   中医外治法   综述  

摘要： 对近年来中医外治法治疗肛肠疾病术后主要并发症(切口疼痛、出血、水肿、感染、尿潴留)进行综述,中西医结合临床治疗肛肠疾病术后较常用的外治法有熏洗坐浴法和栓剂、药膏外用、针灸疗法等。

关键词： Atrial fibrillation   CHA(2)DS(2)-VASc score   Cohort   Ischemic bowel disease  

摘要： Purpose: This study aimed to evaluate the predictive role of CHA(2)DS(2)-VASc score specifically for the development of ischemic bowel disease (IBD) among atrial fibrillation (AF) patients. Methods: Using a nationwide dataset, an AF cohort was established. The study participants were followed up from the index date until they withdrew from the health insurance system, the occurrence of IBD or until the end of 2011. The hazard ratios (HRs) and 95% confidence intervals (CIs) were examined by Cox models to present the subsequent risk of IBD among AF patients by CHA(2)DS(2)-VASc score. The area under the receiver operating characteristic (ROC) curve was used to assess the predictive power of CHA(2)DS(2)-VASc score for IBD development among AF patients. Results: The cumulative incidence of IBD was higher for AF patients with a CHA(2)DS(2)-VASc score >= 2 than those with a CHA(2)DS(2)-VASc score < 2 by 2.30% (p < 0.001) at the end of follow-up. After adjustment for hyperlipidemia, chronic obstructive pulmonary disease, and chronic kidney disease, the AF patients with a CHA(2)DS(2)-VASc score >= 2 had a 3.35 times higher risk for IBD development compared to those with a CHA(2)DS(2)-VASc score < 2 [ adjusted HR (aHR) - 3.35, 95% CI - 2.71-4.13]. Among AF patients, the C-statistic of the CHA(2)DS(2)-VASc score as a predictor of IBD was 0.56 (95% CI = 0.55-0.57). Conclusions: In conclusion, the study is the first to investigate the predictive role of CHA(2)DS(2)-VASc score specifically for IBD development among AF patients. However, the predictive power was relatively low;further studies are necessary to confirm our findings. (C) 2017 Elsevier B.V. All rights reserved.

关键词： Postoperative ileus   Colorectal surgery   Inflammatory bowel diseases   Colorectal cancer   Enhanced recovery after surgery  

摘要： Background: Postoperative ileus is a common problem after colorectal surgery. The aim of the study was to investigate the incidence and risk factors for prolonged postoperative ileus (POI) after colectomy for inflammatory bowel diseases (IBDs). Methods: Consecutive patients who underwent colorectal resection for IBD versus colorectal cancer (CRC) patients under enhanced recovery after surgery protocol were retrospectively analyzed. Primary assessment end point is the incidence of prolonged POI (>4 days);secondary end points were GI-2 recovery (time to first toleration of solid food and first bowel movement), nasogastric tube reinsertion, and postoperative length of stay. Risk factors for prolonged POI in IBD patients were assessed by multiple logistic regression analysis with P score matching. Results: The incidence of prolonged POI was higher in IBD versus CRC group (28.8% versus 14.8%, P < 0.001). Patients with IBD had a longer time to GI-2 recovery (4.8 +/- 2.1 versus 3.7 +/- 1.4 d, P < 0.001), postoperative length of stay (10.7 +/- 6.2 versus 7.9 +/- 5.3 d, P < 0.001), higher incidence of nasogastric tube reinsertion (9.8% versus 4.0%, P = 0.02). After propensity-score matching analysis, the differences were still significant. Preoperative steroid use >20 mg/d (odds ratio, [ OR] = 2.19, P = 0.048), hypoalbuminemia (<35 g/L;OR 2.72, P = 0.03), systemic inflammatory response syndrome status (OR 4.91, P = 0.03), and postoperative intraabdominal sepsis (OR 9.31, P = 0.001) were independent risk factors for prolonged POI in IBD patients. Conclusions: In the setting of enhanced recovery after surgery, colectomy for IBD is associated with delayed gastrointestinal function recovery and higher incidence of prolonged POI compared to CRC patients. Normalizing preoperative albumin level, weaning off steroids, reducing preoperative systemic inflammatory response syndrome, and early management of postoperative intraabdominal sepsis may reduce POI in IBD population. (C) 2017 E

关键词： Biomarkers   Complications of IBD   Serologic testing   Prognosis   Mucosal disease activity  

摘要： Background: Cathelicidin (LL-37) is an antimicrobial peptide known to be associated with various autoimmune diseases. We attempt to determine if cathelicidin can accurately reflect IBD disease activity. We hypothesize that serum cathelicidin correlates with mucosal disease activity, stricture, and clinical prognosis of IBD patients. Methods: Serum samples were collected from two separate cohorts of patients at the University of California, Los Angeles. Cohort 1 consisted of 50 control, 23 UC, and 28 CD patients. Cohort 2 consisted of 20 control, 57 UC, and 67 CD patients. LL-37 levels were determined by ELISA. Data from both cohorts were combined for calculation of accuracies in indicating mucosal disease activity, relative risks of stricture, and odds ratios of predicting disease development. Results: Serum cathelicidin levels were inversely correlated with Partial Mayo Scores of UC patients and Harvey-Bradshaw Indices of CD patients. Among IBD patients with moderate or severe initial disease activity, the patients with high initial LL-37 levels had significantly better recovery than the patients with low initial LL-37 levels after 618 months, suggesting that high LL-37 levels correlate with good prognosis. Co-evaluation of LL-37 and CRP levels was more accurate than CRP alone or LL-37 alone in the correlation with Mayo Endoscopic Score of UC patients. Low LL-37 levels indicated a significantly elevated risk of intestinal stricture in CD patients. Conclusion: Co-evaluation of LL-37 and CRP can indicate mucosal disease activity in UC patients. LL-37 can predict future clinical activity in IBD patients and indicate risk of intestinal stricture in CD patients.

关键词： apoptosis   cell biology   human genetics   inflammatory bowel disease (IBD)   mitochondria   ANKZF1   infantile-onset inflammatory bowel disease   mitochondrial stress   whole-exome sequencing  

摘要： Infantile-onset inflammatory bowel disease (IO IBD) is an invalidating illness with an onset before 2 years of age and has a complex pathophysiology in which genetic factors are important. Homozygosity mapping and whole-exome sequencing in an IO IBD patient and subsequent sequencing of the candidate gene in 12 additional IO IBD patients revealed two patients with two mutated ankyrin repeat and zinc-finger domain-containing 1 (ANKZF1) alleles (homozygous ANKZF1 R585Q mutation and compound heterozygous ANKZF1 E152K and V32_Q87del mutations, respectively) and two patients with one mutated ANKZF1 allele. Although the function of ANKZF1 in mammals had not been previously evaluated, we show that ANKZF1 has an indispensable role in the mitochondrial response to cellular stress. ANKZF1 is located diffusely in the cytoplasm and translocates to the mitochondria upon cellular stress. ANKZF1 depletion reduces mitochondrial integrity and mitochondrial respiration under conditions of cellular stress. The ANKZF1 mutations identified in IO IBD patients with two mutated ANKZF1 alleles result in dysfunctional ANKZF1, as shown by an increased level of apoptosis in patients' lymphocytes, a decrease in mitochondrial respiration in patient fibroblasts with a homozygous ANKZF1 R585Q mutation, and an inability of ANKZF1 R585Q and E152K to rescue the phenotype of yeast deficient in Vms1, the yeast homologue of ANKZF1. These data indicate that loss-of-function mutations in ANKZF1 result in deregulation of mitochondrial integrity, and this may play a pathogenic role in the development of IO IBD.

关键词： Inflammatory Bowel Diseases   Intestinal Diseases   Acrylates   bioluminescence resonance energy transfer  

摘要： Pharmacological inhibition of NLRP3 inflammasome activation may offer a new option in the treatment of inflammatory bowel disease. In this work, we report the design, synthesis, and biological screening of a series of acrylate derivatives as NLRP3 inhibitors. The in vitro determination of reactivity, cytotoxicity, NLRP3 ATPase inhibition, and antipyroptotic properties allowed the selection of 11 (INF39), a nontoxic, irreversible NLRP3 inhibitor able to decrease interleukin-1 beta release from macrophages. Bioluminescence resonance energy transfer experiments proved that this compound was able to directly interfere with NLRP3 activation in cells. In vivo studies confirmed the ability of the selected lead to alleviate the effects of colitis induced by 2,4-dinitrobenzenesulfonic acid in rats after oral administration.

关键词： Microbiome   vedolizumab   treatment response   roseburia   butyrate   remission  

摘要： The gut microbiome plays a central role in inflammatory bowel diseases (IBDs) pathogenesis and propagation. To determine whether the gut microbiome may predict responses to IBD therapy, we conducted a prospective study with Crohn's disease (CD) or ulcerative colitis (UC) patients initiating anti-integrin therapy (vedolizumab). Disease activity and stool metagenomes at baseline, and weeks 14, 30, and 54 after therapy initiation were assessed. Community a-diversity was significantly higher, and Roseburia inulinivorans and a Burkholderiales species were more abundant at baseline among CD patients achieving week 14 remission. Several significant associations were identified with microbial function;13 pathways including branched chain amino acid synthesis were significantly enriched in baseline samples from CD patients achieving remission. A neural network algorithm, vedoNet, incorporating microbiome and clinical data, provided highest classifying power for clinical remission. We hypothesize that the trajectory of early microbiome changes may be a marker of response to IBD treatment.

关键词： Crohn's disease   Ulcerative colitis   Hepatitis B vaccine   Meta-analysis  

摘要： Introduction: The response rate to hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD) is low and varies markedly. We performed a systematic review and meta-analysis to determine the response rate to HBV vaccination and identified the factors predictive of an immune response. Methods: We searched PubMed, Cochrane Library, and Embase databases, and reviewed the titles and abstracts of studies on the efficacy of HBV vaccination in IBD patients performed through July 2016. Anti-HBs levels > 10 IU/L was considered to be an effective immune response. The primary outcome measure was the response rate to HBV vaccination after series completion, and the secondary outcome was identification of factors at baseline predictive of an immune response. Results: Thirteen studies including 1688 patients were eligible for inclusion. Based on a random-effects model, the pooled rate of a response to HBV vaccination among patients with IBD was 61% (95% confidence interval [CI]: 53-69). Young age (mean difference [MD]: -5.7;95% CI: -8.46, -2.95) and vaccination during disease remission (relative risk [RR]: 1.62;95% CI: 1.15-2.29) were associated with a positive response to HBV vaccination. In addition, no immunosuppressive therapy was predictive of an immune response compared to immunomodulatory (RR: 1.33;95% CI: 1.08-1.63) or anti-tumor necrosis factor-alpha, (anti-TNF-alpha) (RR: 1.57;95% CI: 1.19-2.08) therapy. Conclusions: Based on this meta-analysis, only three of five IBD patients will show a serological response to HBV vaccination. Vaccination should be performed at the time of IBD diagnosis, during disease remission, or before starting immunosuppressive therapy. (C) 2017 Elsevier Ltd. All rights reserved.