关键词： endoplasmic reticulum stress   unfolded protein response   oxidative stress   antioxidant mechanisms   misfolded protein   inflammatory bowel disease  

摘要： The endoplasmic reticulum (ER) is a complex protein folding and trafficking organelle. Alteration and discrepancy in the endoplasmic reticulum environment can affect the protein folding process and hence, can result in the production of misfolded proteins. The accumulation of misfolded proteins causes cellular damage and elicits endoplasmic reticulum stress. Under such stress conditions, cells exhibit reduced functional synthesis, and will undergo apoptosis if the stress is prolonged. To resolve the ER stress, cells trigger an intrinsic mechanism called an unfolded protein response (UPR). UPR is an adaptive signaling process that triggers multiple pathways through the endoplasmic reticulum transmembrane transducers, to reduce and remove misfolded proteins and improve the protein folding mechanism, in order to improve and maintain endoplasmic reticulum homeostasis. An increasing number of studies support the view that oxidative stress has a strong connection with ER stress. During the protein folding process, reactive oxygen species are produced as by-products, leading to impaired reduction-oxidation (redox) balance conferring oxidative stress. As the protein folding process is dependent on redox homeostasis, the oxidative stress can disrupt the protein folding mechanism and enhance the production of misfolded proteins, causing further ER stress. It is proposed that endoplasmic reticulum stress and oxidative stress together play significant roles in the pathophysiology of bowel diseases.

摘要： Introduction Inflammatory bowel diseases (IBDs) have high social impact. Aetiology is still unknown, however multifactorial genesis is surely implicated. We tried to correlate IBDs and psychological distress through evaluated psychometrical instruments and subsequently to relate subjective influences with gastroenteric clinical manifestation, defining new critical elements on which IBD are based. Methods In our study, we included 57 participants, selected according to their diagnosis, between those attending our gastrointestinal ambulatory: 26 had Chron's disease, while 31 had ulcerative colitis. 78 people without gastroenteric or psychiatric disorder were also included in the study as control group. Psychometric questionnaires were administered to evaluate anxiety and depressive symptoms, quality of live, self-efficacy and resilience (Fig. 1). Results Levels of anxiety and depression were higher in patients with IBDs than in the control group. STAI-Y highlighted higher state anxiety and trait anxiety levels in first group. HADS showed higher scores in ill patients, as well as CD-RISC showed a more impaired resilience. EQ-VAS, PGWBI and GSE revealed significant differences in health status, psychological wellness and self-efficacy between the two groups. Conclusions IBDs seem related to psychological diseases. Affected patients have higher anxiety and depression levels than general population as well as lower self-efficacy and resilience. Those elements being strictly linked to physical discomfort contributes to develop a loop in which patients get caught. Creating a model of integrated cooperation between gastroenterologist and psychiatrist during treatment of patients with IBDs seems fundamental to grant at once all the professional figures each patient needs for better care. Disclosure of interest The authors have not supplied their declaration of competing interest.

关键词： INFLAMMATORY bowel diseases   SPIROMETRY  

摘要： The flaw lies in the methods used to derive reference equations, which involve arbitrary and circular criteria for exclusion of some members of the population, use potentially nonrepresentative reference populations, and include predictive variables that are really risk factors for disease or for adverse outcomes of disease. [...]235 reports were analyzed for end-of-test criteria, with 50.6% (119/235) complying to criteria, while 22.6% (78/345) of the reports were tested for more than 3 times, among which...

关键词： Crohn's disease   inflammatory bowel disease   pregnancy   ulcerative colitis   venous thromboembolism  

摘要： Background The incidence of inflammatory bowel disease (IBD) increases, and thus is more common, in pregnant women. IBD is a risk factor for venous thromboembolism (VTE) but it is not clear whether IBD predisposes women to an excess risk of VTE during pregnancy and the postpartum period. Methods This was a nationwide population-based cohort study of all deliveries during 1980-2013 in Denmark, using data from two nationwide health registries: the Danish National Patient Registry and the Medical Birth Registry. We computed incidence rates (IRs) per 1000 person-years, and crude and adjusted relative risks (RRs) with 95% confidence intervals (CIs) for VTE during pregnancy and the first 12 postpartum weeks in women with and without IBD. Results We included 1 046 754 women with 1 978 701 deliveries. We identified 3465 VTE events during pregnancy and 1302 VTE events postpartum. The IR for VTE during pregnancy was 4.20 (95% CI, 2.83-5.58) in IBD patients and 2.41 (95% CI, 2.33-2.50) in women without IBD, corresponding to an RR of 1.72 (95% CI, 1.22-2.43). Adjustment for maternal age and smoking (pregnancies during 1991-2013) yielded an adjusted RR of 1.67 (95% CI, 1.15-2.41). IBD flare was associated with an RR of 2.64 (95% CI, 1.69-4.14) for VTE during pregnancy. The IR for postpartum VTE was 7.03 (95% CI, 3.87-10.20) among IBD patients and 2.88 (95% CI, 2.72-3.04) in women without IBD, corresponding to an adjusted RR of 2.10 (95% CI, 1.33-3.30). Conclusions IBD is a risk factor for VTE during pregnancy and postpartum.

关键词： inflammatory bowel disease   mortality   outcome   standardized mortality ratios  

摘要： Background and Aim: Limited data are available regarding mortality from inflammatory bowel disease in non-Caucasian populations. Herein, we evaluated overall and cause-specific mortality in a hospital-based cohort of Korean inflammatory bowel disease patients. Methods: We determined mortality in 2414 Crohn's disease patients and 2798 ulcerative colitis patients diagnosed between 1977 and 2013. Standardized mortality ratios were calculated in several demographic and phenotypic subgroups. Results: During the mean 9-year follow up, 114 patients died: 35 with Crohn's disease and 79 with ulcerative colitis. The overall standardized mortality ratios were 1.40 (95% confidence interval: 0.97-1.94) in Crohn's disease and 0.73 (0.58-0.91) in ulcerative colitis. In Crohn's disease, female sex, age <30years at diagnosis, disease duration >10years, ileocolonic disease at diagnosis, perianal fistula, intestinal resection, and ever-use of corticosteroids were associated with higher mortality. In ulcerative colitis, male sex, age >= 30years at diagnosis, disease duration <= 5years, proctitis at diagnosis, and no history of colectomy were associated with lower mortality, while primary sclerosing cholangitis was associated with higher mortality. In both Crohn's disease and ulcerative colitis, high mortality rates due to nonmalignant gastrointestinal causes (standardized mortality ratios: 4.59 and 2.32, respectively) and gastrointestinal malignancies (standardized mortality ratios: 16.59 and 3.45, respectively) were observed. Cardiovascular mortality was lower in ulcerative colitis (standardized mortality ratio: 0.47). Conclusions: The overall mortality tended to be higher in Crohn's disease patients than in the general population;it was slightly lower in ulcerative colitis patients than in the general population.

关键词： adalimumab   5-aminosalicylic acid   Crohn   pharmacy benefit management   thiopurine   ulcerative colitis  

摘要： Objectives: The aim of the study was to use pharmacy benefit management (PBM) prescription claims data to assess refill adherence in pediatric inflammatory bowel disease (IBD) and correlate adherence with clinical outcomes in pediatric IBD. Methods: We identified 362 pediatric patients with IBD seen at Washington University from 9/1/2012 to 8/31/2013 and matched them within Express Scripts' member eligibility files for clients allowing use of prescription drug data for research purposes. Maintenance IBD medication possession ratios (MPR) were determined through PBM prescription claims data and chart review. Demographic and prospectively captured physician global assessments (PGA) were retrospectively extracted from the medical record. MPR was analyzed as continuous data and also dichotomized as greater or less than 80%. Results: Among our 362 patients, we matched 228 (63%) within Express Scripts' eligibility data files. Of those, 78 patients were continuously eligible for benefits and had at least one outpatient prescription IBD medication prescribed. Their mean MPR was 0.63 +/- 0.31 (standard deviation) and 40% had an MPR 80%. Patients in clinical remission had a higher mean MPR than those with an active PGA (0.72 +/- 0.28 vs 0.51 +/- 0.32, P=0.002) and patients whose MPR were >= 80% were more likely to have a PGA of remission than those with whose MPR were <80% (84% vs 43%, P = <0.001). Conclusions: We found a significant association between refill adherence and clinical remission. Nonadherence was common and was more common in adolescents. Use of PBM databases to identify and intervene on patients with poor adherence may improve outcomes in pediatric IBD.

关键词： metagenomics   microbiome   pediatric gastroenterology   inflammatory bowel diseases   fecal microbiota transplantation  

摘要： Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn's disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U-test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii, were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option.

关键词： INFLAMMATORY bowel diseases   INTESTINAL diseases   BIOLOGICAL response modifiers   IMMUNOLOGICAL adjuvants   TUMOR necrosis factor  

摘要： Linked Content This article is linked to Vegh et al and Conway et al papers. To view these articles visit https://***/10.1111/apt.13987 and https://***/10.1111/apt.13940. [ABSTRACT FROM AUTHOR]

关键词： INFLAMMATORY bowel diseases   GASTROENTERITIS   HEALTH of immigrants   IMMIGRANTS   DANES   HEALTH   ENVIRONMENTAL aspects   DENMARK  

摘要： Background The incidence of inflammatory bowel disease (IBD) is record high in the Faroe Islands, and many Faroese emigrate to Denmark, where the IBD incidence is considerably lower. Aim To study the IBD incidence in first-, second- and third-generation immigrants from the Faroe Islands to Denmark to assess the extent to which the immigrants adopt the lower IBD incidence of their new home country. Methods Data on Faroese-born Danish residents and their children were retrieved from the Danish Central Population Register for 1980-2014. Incident IBD cases were identified from the Danish National Patient Register. Standardised Incidence Ratios (SIRs) were used to compare the IBD risk in immigrants with that of Danes. 95% confidence intervals (CI) were calculated using the square-root transform. Results First-generation Faroese immigrants had a higher IBD incidence than Danes, SIR 1.25 (95% CI, 0.97-1.59) for men and 1.28 (95% CI, 1.05-1.53) for women. This excess risk derived from ulcerative colitis (UC), SIR 1.44 (95% CI, 1.10-1.87) for men and 1.36 (95% CI, 1.09-1.68) for women. No excess risk was found for Crohn's disease (CD). The UC risk was nearly doubled during the immigrants' first 10years in Denmark;SIR 2.13 (95% CI, 1.52-2.92) for men and 1.63 (95% CI, 1.19-2.18) for women. Conclusions Although some impact of genetic dilution cannot be excluded, our findings indicate importance of gene-environment interplay in UC, as the excess UC risk in Faroese immigrants to Denmark disappeared over time and over one generation in men and over two generations in women.