关键词： Crohn's Disease   Biologics   Pharmacokinetics   Serum Drug Level  

摘要： BACKGROUND & AIMS: It is not clear whether combination therapy with immunomodulators affects the immunogenicity of tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel disease. We performed a meta-analysis to quantify the effects of combined immunomodulator therapy on the presence of antibodies against TNF antagonists (antidrug antibodies [ADAs]) and trough levels of anti-TNF agents. METHODS: We systematically searched publication databases for studies that reported prevalence of ADAs in patients who received anti-TNF agents. Raw data from studies that met the inclusion criteria were pooled to determine effect estimates. We performed subgroup and metaregression analyses to determine the level of heterogeneity among study outcomes. RESULTS: We analyzed findings from 35 studies that met inclusion criteria (results reported from 6790 patients with inflammatory bowel disease). The pooled risk ratio for formation of ADAs in patients receiving combined therapy with immunomodulators, versus that of patients receiving anti-TNF monotherapy, was 0.49 (95% confidence interval, 0.41-0.59;P < .001). However, the pooled analysis did not demonstrate a significant difference in trough levels of anti-TNF agents between patients with versus without concurrent use of immunomodulators (standardized mean difference, 0.11;95% confidence interval, 0.19-0.41;P = .47). Subgroup analyses of patients treated with different TNF antagonists revealed no difference in the formation of ADAs (P = .50 for interaction);the protective effect of immunomodulators did not differ with type of drug patients were given (methotrexate vs thiopurines), or assay for ADA. We observed heterogeneity only among studies of patients with ulcerative colitis (I-2 = 76%). Funnel plot and Egger test analyses indicated publication bias in the studies (P = .001). CONCLUSIONS: In a meta-analysis of published studies, we associated combined treatment with immunomodulators with reduced risk of formation

关键词： Proteomics   Inflammatory bowel disease   Biomarkers   Animal models of colitis, inflammation  

摘要： Recently, proteomics studies have provided important information on the role of proteins in health and disease. In the domain of inflammatory bowel disease, proteomics has shed important light on the pathogenesis and pathophysiology of inflammation and has contributed to the discovery of some putative clinical biomarkers of disease activity. By being able to obtain a large number of specimens from multiple sites and control for confounding environmental, genetic, and metabolic factors, proteomics studies using animal models of colitis offered an alternative approach to human studies. Our aim is to review the information and lessons acquired so far from the use of proteomics in animal models of colitis. These studies helped understand the importance of different proteins at different stages of the disease and unraveled the different pathways that are activated or inhibited during the inflammatory process. Expressed proteins related to inflammation, cellular structure, endoplasmic reticulum stress, and energy depletion advanced the knowledge about the reaction of intestinal cells to inflammation and repair. The role of mesenteric lymphocytes, exosomes, and the intestinal mucosal barrier was emphasized in the inflammatory process. In addition, studies in animal models revealed mechanisms of the beneficial effects of some therapeutic interventions and foods or food components on intestinal inflammation by monitoring changes in protein expression and paved the way for some new possible inflammatory pathways to target in the future. Advances in proteomics technology will further clarify the interaction between intestinal microbiota and IBD pathogenesis and investigate the gene-environmental axis of IBD etiology.

关键词： IBD   Crohn's disease   Ulcerative colitis   NLRP3 inflammasome   ATG16L1  

摘要： NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1 beta to IL-1 beta. To investigate NLRP3 inflammasome activation in inflammatory bowel disease. Peripheral blood mononuclear cells from Crohn's disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU. After incubation, concentrations of IL-1 beta, IL-6, and TNF alpha were measured in cell supernatants and concentration of pro-IL-1 beta was measured in cell lysates. NLRP3 activation was defined as more than 30% increase in IL-1 beta production after MSU addition. In separate experiments, PBMCs were lysed for RNA isolation transcripts of IL-1 beta, TNF alpha, NLRP3, and CASP1 were measured by RT-PCR. DNA was isolated from CD patients for ATG16L1 gene genotyping. NLRP3 inflammasome was activated in 60% of CD patients compared to 28.6% of controls (p = 0.042);no significant difference was detected between UC and controls. Among UC patients, NLRP3 activation was associated (p = 0.008) with long-standing disease (> 1.5 years). IL-1 beta levels were significantly higher in CD patents in comparison with controls (p = 0.032). No difference was detected in the levels of IL-6, TNF alpha, pro-IL-1 beta and in the numbers IL-1 beta, TNF alpha, NLRP3, and CASP1 transcripts among groups. IL-1 beta production was similar between carriers of wild-type and of SNP alleles of the rs2241880. NLRP3 inflammasome is activated in CD patients and in UC patients with long-standing disease.

关键词： Incisional hernia   Mesh repair   Hernia recurrence   Crohn's disease   Ulcerative colitis   Enterocutaneous fistula  

摘要： Background: Incisional Hernia (IH) repair in patients with Inflammatory Bowel Disease (IBD) has not been well studied. Methods: Outcomes of 170 patients with IBD who underwent IH repair were included in the study. Results: The incidence of recurrence after IH repair in IBD is 27%. Patients with Crohn's disease (CD) had larger defects at the time of repair, higher proportion of bowel resection and a longer postoperative stay when compared to Ulcerative colitis (UC). The only significant predictor of recurrence after IH repair was the number of previous bowel resections prior to hernia repair (HR 1.59, p < 0.01). Three cases (10%) of late onset enterocutaneous fistulas were identified in patients who underwent IH repair with synthetic mesh inlay. Conclusion: Surgical repair results in a recurrence of IH in 27% of patients with IBD. The number of previous bowel resections is the only factor that correlates with development of recurrent IH in IBD. Published by Elsevier Inc.

关键词： neutrophils   immunomodulation   inflammatory bowel diseases   CD177  

摘要： Inflammatory bowel diseases (IBD), comprising of ulcerative colitis and Crohn's disease, are inflammatory disorders of the gastrointestinal tract characterized by chronically relapsing mucosal inflammation. Neutrophils, as the effector cells of acute inflammation, have long been reported to play a role in the maintenance of intestinal homeostasis and pathogenesis of IBD. At the early stage of mucosal inflammation in patients with IBD, neutrophils flood into intestinal mucosa, phagocytose pathogenic microbes, and promote mucosal healing and resolution of inflammation. However, large numbers of neutrophils infiltrating in the inflamed mucosa and accumulating in the epithelia cause damage of mucosal architecture, compromised epithelial barrier and production of inflammatory mediators. In this review we discuss the critical roles of neutrophils in modulating innate and adaptive immune responses in intestinal mucosa, and, importantly, clarify the potential roles of neutrophils related to their production of inflammatory mediators, transenthothelial and transepithelial migration into intestinal mucosa, and the underlying mechanisms in regulating mucosal inflammation of IBD. Moreover, we also describe a new subset of neutrophils (i.e., CD177(+) neutrophils) and illustrate its protective role in modulating intestinal mucosal immune responses in IBD.

关键词： Inflammatory bowel disease   Dysplasia   Endoscopic resection  

摘要： Long-standing intestinal inflammation in patients with inflammatory bowel disease (IBD) induces dysplastic change in the intestinal mucosa and increases the risk of subsequent colorectal cancer. The evolving endoscopic techniques and technologies, including dye spraying methods and high-definition images, have been replacing random biopsies and have been revealed as more practical and efficient for detection of dysplasia in IBD patients. In addition, they have potential usefulness in detailed characterization of lesions and in the assessment of endoscopic resectability. Most dysplastic lesions without an unclear margin, definite ulceration, non-lifting sign, and high index of malignant change with suspicion for lymph node or distant metastases can be removed endoscopically. However, endoscopic resection of dysplasia in chronic IBD patients is usually difficult because it is often complicated by submucosal fibrosis. In patients with dysplasias that demonstrate submucosa fibrosis or a large size (>= 20 mm), endoscopic submucosal dissection (ESD) or ESD with snaring (simplified or hybrid ESD) is an alternative option and may avoid a colectomy. However, a standardized endoscopic therapeutic approach for dysplasia in IBD has not been established yet, and dedicated specialized endoscopists with interest in IBD are needed to fully investigate recent emerging techniques and technologies.

关键词： hypercoagulability   inflammatory bowel disease   low-molecular-weight heparins   thrombophilia   thrombosis   thrombosis prophylaxis  

摘要： The close relationship between inflammation and thrombosis affects the progression and severity of inflammatory bowel disease (IBD). The prevalence of venous thromboembolism (VTE) varies between 1% and 7% among patients with IBD. The VTE risk in patients with IBD is at least 3 times higher than that in the normal general population. The absolute risk is very high during hospitalization, active disease, and surgery. The IBD-related VTE occurs at younger ages and recurs more frequently. The development of thrombosis in IBD is due to the interaction of many hereditary and acquired risk factors. Each patient diagnosed with IBD should be evaluated for a personal and family history of thrombosis and for prothrombotic drug use. Although procoagulant factors are increased during the natural course of inflammation, natural anticoagulants and fibrinolytic activity are decreased. Although IBD is accepted as a prothrombotic condition, there is no treatment that can remove this risk from daily practice. Patient training is required to control important factors, such as long-term immobilization and smoking. Oral contraceptives and hormone replacement therapy should be avoided. Inducing permanent disease remission must be the key approach for the prevention of thrombosis. Low-molecular-weight heparin (LMWH) is the basis of prophylactic treatment, which reduces the thrombosis risk by 50%. Prophylaxis with LMWH should be administered to all patients with IBD hospitalized due to disease attack or surgery. Long-term or even life-long anticoagulation therapy should be planned if there is insufficient disease control, recurrent VTE attacks, positive thrombophilia tests, or thrombosis in vital veins.

关键词： Cost of illness   Gastroenterology   Inflammatory bowel disease   Pharmacoeconomics  

摘要： Frequent relapses sometimes necessitating hospitalization and the absence of pharmacological cure contribute to substantial healthcare costs in inflammatory bowel diseases (IBDs). The costs of health care in Indian patients with IBD are unknown. To evaluate the annual costs for treating Crohn's disease and ulcerative colitis. A prevalence-based, micro-costing method was used to assess the components of annual costs in a prospective, observational study conducted in a tertiary healthcare center enrolled over a 24-month period beginning of July 2014. At enrollment, 43/59 (72.88%) patients with UC and 18/25 (72%) with CD were in remission. The annual median (IQR) cost per UC and CD patient in remission was INR 43,140 (34,357-51,031) [USD $707 (563-836)] and INR 43,763.5 (32,202-57,372) [USD $717 (527-940)], respectively, and in active disease was INR 52,436.5 (49,229-67,567.75) [$859 (807-1107)] and INR 72,145 (49,447-92,212) [USD $1182 (811-1512)], respectively. Compared with remission, active disease had a 1.4-fold higher cost for CD as compared to UC. In both groups, the greatest component of direct costs was drugs. Thirteen (22%) and 7 (28%) patients with UC and CD needed hospitalization accounting for 23.1 and 20.4% of the total costs, respectively. At one year, direct costs surmounted indirect costs in UC and CD (p < 0.001). Productivity losses contributed to 18.5 and 16% of the overall costs for UC and CD, respectively. This first, panoptic, health economic study for IBD from India shows that the costs are driven by medication, productivity losses, and not merely hospitalization alone.

关键词： Hypoxia   Inflammation   Metabolite   Microbiota   Nucleotide  

摘要： The intestinal mucosa provides a selective barrier between the anaerobic lumen and a highly metabolic lamina propria. A number of recent studies indicate that acute inflammation of the mucosa can result in tissue hypoxia and associated shifts in tissue metabolism. The activation of hypoxiainducible factor (HIF) under these conditions has been demonstrated to function as an endogenous molecular cue to promote resolution of inflammation, particularly through the orchestration of barrier repair toward homeostasis. Given the central role of oxygen in tissue metabolism, ongoing studies have defined metabolic endpoints of HIF stabilization as important biomarkers of disease activity. Such findings make HIF and HIF-associated metabolic pathways particularly attractive therapeutic targets in inflammatory bowel disease (IBD). Here, we review the recent literature related to tissue metabolism in IBD.

关键词： Children   diet   fruit   inflammatory bowel disease   Saudi Arabia  

摘要： Background/Aim: Inflammatory bowel disease (IBD) is increasing in Saudi Arabia but there's little knowledge about its risk factors. Our aim is to investigate the dietary risk factors of this disease in Saudi children. Patients and Methods: The children investigated for IBD were prospectively enrolled. Those with confirmed IBD were designated cases and the others were controls. The average food frequency intake at least 3 months before onset of illness was obtained by direct interview and recorded on a modified food frequency questionnaire. Fast food, sweet gaseous soft drinks, fruits, and vegetables were selected. Statistical analysis included descriptive statistics, multivariate logistic regression was used, and the odds ratio was calculated to report the statistical significance of the results. Results: A total of 91 children, 52 IBD (38 CD, 14 UC) and 39 controls were enrolled. Consumption of fast food and sweet gaseous drinks was more frequent in children with IBD than controls, whereas consumption of fruits and vegetables was less frequent in children with IBD. Only less fruits consumption was significantly associated with IBD as the odds of children getting IBD was 2.89 (1.06, 7.87). Conclusions: We report statistically significant positive association between less fruits consumption and IBD. Awaiting the results of larger sample size and more quantitative studies, the benefits of frequent fruit consumptions should be part of public health education.