关键词： circulating biomarker   inflammatory bowel disease   microRNA classifier   microRNA-146b-5p  

摘要： Background Owing to the importance of early treatment, simple and reliable methods for monitoring inflammatory bowel disease (IBD) are needed. Aims To determine whether circulating microRNAs are reliable biomarkers for IBD monitoring. Methods Serum levels of 17 candidate microRNAs were measured by quantitative real-time polymerase chain reaction in a discovery cohort (n = 120). Differentially expressed serum microRNAs were further investigated in an independent training cohort (n = 341). Correlations between relative microRNA levels and disease activity were evaluated. A disease control group was included to investigate the specificity of microRNA. Logistical regression was used to construct a microRNA classifier to identify endoscopic activity. Its predictive value was explored in the validation cohort (n = 66) using the area under the receiver operating characteristic curve (AUC). Results Serum microRNA146b-5p (miR-146b-5p) expression was 2.87- and 2.72-fold higher in patients with Crohn's disease and ulcerative colitis, respectively, than in healthy controls. Serum miR-146b-5p was significantly correlated with disease activity and was more specific than C-reactive protein (CRP). A classifier was built for Crohn's disease, ie P [Endoscopically active] = 11+e2.937-0.737(miR-146b-5p)-0.008PLT, with a greater AUC of 0.869 [0.764-0.940] than that for CRP (0.680 [0.554-0.790]) (P = 0.0043). Conclusions MiR-146b-5p may better reflect mucosal inflammation in IBD than CRP. The Crohn's disease classifier developed in this study may be valuable for identifying endoscopic activity in patients with Crohn's disease.

关键词： Ulcerative colitis   Crohn's Disease   Ileal pouch-anal anastomosis   Dysplasia   Rectal cancer   Intestinal lymphoma   Squamous cell cancer   Anal cancer   Small bowel cancer   Mucosectomy  

摘要： Patients with inflammatory bowel disease who undergo ileal pouch-anal anastomosis are at finite risk of developing neoplasia of various parts of the pouch. In this review article, we will describe different forms of pelvic pouch-related cancers, with a focus on diagnosis and management of small bowel adenocarcinomas of the pouch body, rectal neoplasia of the rectal cuff and anal transition zone, small intestinal lymphoma of the pouch, and anal dysplasia and squamous cell cancer of the anal canal. (C) 2019 Elsevier Inc. All rights reserved.

关键词： Ustekinumab   Vedolizumab   Biologics   Colorectal surgery   Outcomes   Morbidity   Mortality   Comparison  

摘要： Aim The association between preoperative use of monoclonal antibodies in inflammatory bowel disease (IBD) patients and postoperative complications is controversial, especially for the latest approved biologics, ustekinumab and vedolizumab, where data is limited. We hypothesized that ustekinumab-treated patients would have a similar overall postoperative complication rate as vedolizumab-treated patients. The aim of this study was to compare postoperative complications in patients receiving preoperative ustekinumab vs. vedolizumab. Methods We queried our IRB-approved prospective database to identify Crohn's patients who underwent colorectal surgery and pretreatment with ustekinumab or vedolizumab within 12 weeks of surgery. Ustekinumab-treated patients were matched to vedolizumab-treated patients based on sex, age +/- 5 years, date of operation +/- 3 years, and type of surgery. Paired univariate analysis and conditional logistic regression of the matched pairs were performed. Our primary outcome was the short-term postoperative complication rate. Secondary outcomes included infectious complications, readmission, reoperation, and length of stay. Results A total of 103 patients with Crohn's disease (CD) met the inclusion criteria (mean age 38.7 +/- 13.4years;male 51.2%). Overall, 30 patients received preoperative ustekinumab and 73 vedolizumab. In the univariate analysis, vedolizumab-treated patients had a higher postoperative complication rate (p = 0.009) and ileus rate (p = 0.015). After matching, 26 matched pairs were compared and logistic regression models demonstrated no significant difference in the primary outcome. Conclusions For our limited experience, the choice of preoperative biologic treatment between ustekinumab and vedolizumab should not be influenced by fear of surgical complications.

关键词： confocal laser scanning microscopy   ARCHITECTURE   Building construction   NOD2 gene   Mucous Membrane   Sequence-based Analysis   Inflammatory Bowel Diseases   Interobserver Variation   Intestinal Diseases   Healthy Volunteers   UNIVERSITY OF CALIFORNIA   CTLA4 gene   Crohn Disease  

摘要： Background and Aims: Confocal laser endomicroscopy (CLE) might discriminate mucosal lesions between Crohn's disease (CD) and ulcerative colitis (UC). However, the analysis of CLE images requires timeconsuming methods, a long training time, and potential impediments, such as significant interobserver variability. Therefore, we developed a computer-based method to analyze mucosal architecture from CLE images and discriminate between healthy subjects and patients with inflammatory bowel disease (IBD) as well as between UC and CD patients. Methods: We retrospectively screened patients who had undergone CLE either for an evaluation of IBD in remission or for colorectal cancer screening (control subjects) between 2009 and 2016. We assessed 14 morphologic and functional parameters in each CLE recording from 23 CD patients, 27 UC patients, and 9 control patients. Next, we constructed 2 scores, 1 for the IBD diagnosis and 1 for the differential diagnosis between UC and CD. Results: In IBD patients, the mean intercrypt distance, wall thickness, and fluorescein leakage through the colonic mucosa were significantly increased compared with control patients by 155%, 188%, and 297%, respectively (P<.05). In UC patients, the same parameters were significantly increased by 109%, 117%, and 174%, respectively (P <.05), compared with CD patients. IBD diagnosis had 100% (95% CI, 93%;100%) sensitivity and 100% (95% CI, 66%;100%) specificity. IBD differential diagnosis provided discrimination of UC from CD patients with 92% (95% CI, 75%;99%) sensitivity and 91% (95% CI, 72%;99%) specificity. Conclusions: Confirming these results using prospective validation cohorts can substantiate that computer-based analysis of CLE images may provide new biomarkers for the diagnosis and characterization of IBD.

关键词： Crohn's disease   inflammation   neuro-immune interactions   ulcerative colitis  

摘要： Background Mast cells (MCs) and vasoactive intestinal polypeptide (VIP) have been proposed as regulators of the intestinal barrier and inflammation. Our aim was to map the distribution in inflammatory bowel disease (IBD) and murine colitis. Methods MCs, VIP, and VIP-receptors (VPACs) were quantified by immunofluorescence and enzyme-immunoassay (EIA) in ileal tissues (villus epithelium (VE) and adjacent VE, ie, VE next to the follicle-associated epithelium, (FAE)) from Crohn's disease (CD;n = 16) and non-IBD patients, and in colonic specimens of ulcerative colitis (UC;n = 12) and healthy controls (HCs). In addition, VIP levels were measured in plasma from HCs, non-IBD, and IBD in remission (CD n = 30;UC n = 30). Colon, ileum, and plasma from mice with dextran sulfate sodium (DSS)-induced colitis and control mice were analyzed likewise. Key Results FAE-adjacent VE in ileum of CD possessed more MCs (P < 0.05) and MCs expressing VPAC1 (P < 0.05), but not VPAC2, compared to controls. Both adjacent and regular VE of CD had more MCs co-localizing/in close proximity to VIP (P < 0.05). In UC colon, more MCs (P < 0.0005), MCs close to VIP (P < 0.0005), and MCs expressing VPAC1 (P < 0.05) were found compared to controls. VIP levels were elevated in plasma from CD and UC compared to controls (P < 0.0005). Colon of DSS mice showed more MCs and MCs close to VIP (P < 0.05) compared to control mice. In vitro experiments revealed MCs expressing VPACs and internalized VIP after 120 minutes of VIP-stimulation. Conclusions and Inferences Communication between MCs and VIP is upregulated during IBD and mice colitis. In CD patients, the epithelium next to FAE seems to be more involved than the surrounding VE, suggesting increased MC-VIP-interactions in this intestinal region.

关键词： Children   Crohn's disease   Erythropoiesis   Inflammation   Ulcerative colitis  

摘要： Background: There is no single reliable marker of iron homeostasis in inflammatory bowel disease. Aims: To determine diagnostic usefulness of soluble transferrin receptor and soluble transferrin receptor/log ferritin index in iron deficiency anemia in children with inflammatory bowel disease. Methods: We assessed soluble transferrin receptor in serum and calculated soluble transferrin receptor/log ferritin index in 75 children with inflammatory bowel disease. Diagnostic ability to identify iron deficiency anemia was examined by receiver operating characteristic analysis. Results: Study group comprised 27 cases of iron deficiency anemia, 6 anemia of chronic disease with iron deficiency, 5 anemia of chronic disease. Soluble transferrin receptor was significantly increased in children with iron deficiency anemia (median: 1.63 mu g/ml) compared to non-anemic children (median: 1.02 mu g/ml). Soluble transferrin receptor/log ferritin index was significantly higher in iron deficiency anemia (median: 1.76) than in anemia of chronic disease (median: 0.55), anemia of chronic disease with iron deficiency (median: 0.68) or patients without anemia (median: 0.72). Soluble transferrin receptor and its index were not correlated with disease activity or inflammatory markers. Diagnostic power for soluble transferrin receptor/log ferritin index (0.864) was superior to soluble transferrin receptor (0.768) in iron deficiency anemia recognition. Conclusion: Soluble transferrin receptor/log ferritin index has better diagnostic utility than soluble transferrin receptor for iron deficiency anemia detection in pediatric inflammatory bowel disease. (C) 2018 The Authors. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： Microbial genetics   Medical risk factors   Genetics of disease   Gut bacteria   Bacterial genetics   Microbiome   Inflammatory bowel disease   Bacterial pathogens  

摘要： Several bacteria in the gut microbiota have been shown to be associated with inflammatory bowel disease (IBD), and dozens of IBD genetic variants have been identified in genome-wide association studies. However, the role of the microbiota in the etiology of IBD in terms of host genetic susceptibility remains unclear. Here, we studied the association between four major genetic variants associated with an increased risk of IBD and bacterial taxa in up to 633 IBD cases. We performed systematic screening for associations, identifying and replicating associations between NOD2 variants and two taxa: the Roseburia genus and the Faecalibacterium prausnitzii species. By exploring the overall association patterns between genes and bacteria, we found that IBD risk alleles were significantly enriched for associations concordant with bacteria-IBD associations. To understand the significance of this pattern in terms of the study design and known effects from the literature, we used counterfactual principles to assess the fitness of a few parsimonious gene-bacteria-IBD causal models. Our analyses showed evidence that the disease risk of these genetic variants were likely to be partially mediated by the microbiome. We confirmed these results in extensive simulation studies and sensitivity analyses using the association between NOD2 and F. prausnitzii as a case study. Author summary In this study, we used observational data to explore associations between host genetics and the commensal microbiome in inflammatory bowel disease cases. Our analysis identified four associations involving two genes and four bacterial taxa and replicated two of these associations in independent cohorts. Then, we developed a counterfactual framework to assess the fitness of a few parsimonious gene-bacteria-IBD causal models. These analyses confirmed the robustness of the identified associations and highlighted microbiota mediation as a potential mechanism underlying the association between IBD and those g

关键词： Inflammatory bowel disease   Psychological Stress   Acceptance and Commitment Therapy   Hair Cortisol Concentration  

摘要： BACKGROUND & AIMS: Patients with Crohn's disease or ulcerative colitis have relatively high levels of stress and psychological dysfunction. Acceptance and commitment therapy (ACT) is a psychological intervention that comprises acceptance and mindfulness procedures, along with commitment and behavior change strategies, to increase psychological flexibility and reduce stress. We performed a randomized controlled trial to investigate the effect of ACT on stress in patients with inflammatory bowel diseases (IBD). METHODS: A total of 122 patients with quiescent or stable, mildly active IBD were randomly assigned to an 8-week ACT program or treatment as usual (control group). Clinical, demographic, disease activity, and psychological data and blood and feces were collected at baseline and at 8 weeks and 3 months after the intervention (week 20). Scalp hair was collected at baseline and week 20 for measurement of steroid concentrations. The primary endpoint was change in stress symptoms, assessed with the Depression Anxiety Stress Scale. Secondary endpoints included changes in perceived stress, anxiety, depression, quality-of-life domains, disease activity, and cortisol concentration in hair. RESULTS: Overall, 79 participants were included in the complete case intention-to-treat analysis. There were 39% and 45% reductions in stress in the treatment group from baseline to 8 and 20 weeks, respectively, compared with 8% and 11% in the control group (group x time interaction, P = .001). ACT was associated with reduced perceived stress (P = .036) and depression (P = .010), but not anxiety (P = .388), compared with control individuals. In the intention-to-treat analysis, changes in all 4 quality-of-life domains over time were similar in the ACT and control groups. In the per-protocol analysis, the overall well-being quality-of-life domain improved in the ACT group compared with the control group (P = .009). Subjective and objective disease activity measurements were similar betw

关键词： INFLAMMATORY bowel diseases   PYROPHOSPHATES   COLON cancer  

关键词： breastfeeding   breast milk   human milk   celiac disease   inflammatory bowel disease   Crohn disease   ulcerative colitis   systematic review  

摘要： Background: During the Pregnancy and Birth to 24 Months Project, the USDA and US Department of Health and Human Services initiated an evidence review on diet and health in these populations. Objective: The aim of these systematic reviews was to examine the relationships of never versus ever feeding human milk, shorter versus longer durations of any and exclusive human milk feeding, and feeding a lower versus a higher intensity of human milk to mixed-fed infants with diagnosed celiac disease and inflammatory bowel disease (IBD). Methods: The Nutrition Evidence Systematic Review team (formerly called the Nutrition Evidence Library) conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January, 1980 to March, 2016, dual-screened the results using predetermined criteria, extracted data from and assessed risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. Results: We included 9 celiac disease and 17 IBD articles. Limited case-control evidence suggests never versus ever being fed human milk is associated with higher risk of celiac disease, but concerns about reverse causality precluded a conclusion about the relationship of shorter versus longer durations of any human milk feeding with celiac disease. Evidence examining never versus ever feeding human milk and IBD was inconclusive, and limited, but consistent, case-control evidence suggests that, among infants fed human milk, shorter versus longer durations of any human milk feeding are associated with higher risk of IBD. For both outcomes, evidence examining the duration of exclusive human milk feeding was scant and no articles examined the intensity of human milk fed to mixed-fed infants. Conclusion: Limited case-control evidence suggests that feeding humanmilk for short durations or not at all associates with higher risk of diagnosed IBD and celiac dis