关键词： Functional material   Drug delivery   Hydrogen sulfide   Anti-Inflammatory mediator   Inflammatory bowel disease  

摘要： Inflammatory bowel disease (IBD) is an intestinal inflammatory disorder. Exogenous hydrogen sulfide (H2S) donors such as diallyl trisulfide (DATS) have been used as anti-inflammatory mediators. However, an ideal method of administering DATS has yet to be established owing to its poor water solubility. Herein, a self-spray coating system that is derived from a DATS-loaded capsule with foaming capability (CAP-w-FC) is proposed for treating colitis. Following the rectal administration of CAP-w-FC into rats bearing colitis and its subsequent dissolution in the intestinal fluid, a spray coating system is self-assembled in situ. This system greatly promotes the dissolution of the poorly water-soluble DATS by producing nano-scaled micellar particles that are sprayed onto the large luminal surface of the colorectal tract. Following the internalization of the micellar particles by colon epithelial cells, their loaded DATS reacts with intracellular glutathione to yield H2S. This exogenous H2S then diffuses through plasma membranes to carry out its biological functions, including suppressing the overproduction of pro-inflammatory cytokines, inhibiting the adhesion of macrophages on the vascular endothelium, and repairing colonic inflamed tissues. Analytical results demonstrate that this self-spray coating system may be used as a unique drug delivery technique for covering the large colorectal surface to treat IBD. (C) 2018 Elsevier Ltd. All rights reserved.

摘要： The emergence of biologic therapies is arguably the greatest therapeutic advance in the care of inflammatory bowel disease (IBD) to date, allowing directed treatments targeted at highly specific molecules shown to play critical roles in disease pathogenesis, with advantages in potency and selectivity. Furthermore, a large number of new biologic and small-molecule therapies in IBD targeting a variety of pathways are at various stages of development that should soon lead to a dramatic expansion in our therapeutic armamentarium. Additionally, since the initial introduction of biologics, there have been substantial advances in our understanding as to how biologics work, the practical realities of their administration, and how to enhance their efficacy and safety in the clinical setting. In this review, we will summarize the current state of the art for biological therapies in IBD, both in terms of agents available and their optimal use, as well as preview future advances in biologics and highly targeted small molecules in the IBD field.

关键词： PURINES   INFLAMMATORY bowel diseases   AZATHIOPRINE   LYMPHOPROLIFERATIVE disorders   LYMPHOMAS  

摘要： Linked Content This article is linked to de Francisco et al papers. To view these articles visit https://***/10.1111/apt.14933 and https://***/10.1111/apt.14502.

关键词： Anti-TNF therapy   Crohn's disease   Ulcerative colitis   Antibodies to adalimumab   Therapeutic drug monitoring  

摘要： BackgroundA treat-to-target therapeutic approach is emerging as the new standard of care for treating inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC).AimsWe aimed to investigate the association of serum adalimumab concentrations during maintenance therapy with biochemical, endoscopic, and histologic remission in *** retrospective multicenter study included consecutive IBD patients on adalimumab maintenance therapy who had a C-reactive protein (CRP) within 1week and/or endoscopic evaluation within 12weeks of therapeutic drug monitoring between July 2013 and December 2016. Biochemical remission was defined as a normal CRP (5mg/L). Endoscopic remission was defined as the absence of any ulceration/erosion or a Rutgeerts score ofi1 for patients with an ileocolonic resection for CD and a Mayo endoscopic score of1 for UC. Histologic remission was defined as the absence of any sign of active inflammation. Adalimumab concentrations were measured using the homogeneous mobility shift ***-one CRP levels and 72 colonoscopies from 98 IBD patients [CD: n=72 (73%)] were evaluated. Based on receiver operating characteristic analyses, we identified an adalimumab concentration threshold of 11.8, 12, and 12.2g/mL in CD and 10.5, 16.2, and 16.2g/mL in UC to stratify patients with or without biochemical, endoscopic, or histologic remission, respectively. Adalimumab concentrations12g/mL (OR 8;95% CI 2-31.9;p=0.003) and12.2g/mL (OR 9.6;95% CI 1.7-56.1;p=0.012) were independently associated with endoscopic and histologic remission in CD, *** study demonstrates that higher maintenance adalimumab concentrations are associated with objective therapeutic outcomes in IBD.

关键词： inflammatory bowel disease   bacterial translocation   microbiome  

摘要： Background: Using culture-based methods, bacterial translocation from the gut to draining mesenteric lymph nodes is seen in 5% of normal controls and up to 33% of patients with inflammatory bowel diseases (IBD). Many bacteria cannot be cultured, so these methods are unable to capture the full spectrum of bacteria present. Aims: To detect viable bacteria in lymph nodes of patients with IBD and non-IBD controls using bacterial RNA as a surrogate for viability and to compare them with the same patient's gut microbiome. Methods: Bacterial RNA was extracted from lymph nodes and mucosa of 20 patients who had undergone intestinal resection (10 IBD, 10 non-IBD). A previous study had detected bacterial DNA in these patients' lymph nodes;16S rRNA gene highthroughput sequencing was performed. Results: Bacterial RNA was detected in the lymph nodes of five patients with IBD and three controls (volvulus, diverticulitis and bowel obstruction). Lymph nodes had higher alpha (within sample) diversity compared to mucosal samples (Shannon diversity index 2.41 vs 1.81, one-way ANOVA P = 0.035). Beta diversity (inter-sample variation: lymph node vs intestine) was similar within individuals and did not differ between groups. Common gene polymorphisms linked with IBD (NOD2, ATG16L1, IRGM and IL23R) were not associated with bacterial translocation. Conclusions: Metabolically active bacteria mirroring the individual's gut microbiome were commonly found in the lymph nodes of patients with IBD undergoing resection. An increase in lymph node alpha diversity is likely due to the larger drainage area. The presence of viable bacteria in non-IBD controls is also not unexpected given the underlying pathology in these patients.

关键词： Cytomegalovirus   Inflammatory bowel disease   Meta-analysis  

摘要： AimsMany studies have suggested Cytomegalovirus infection might be implicated in steroid-refractory inflammatory bowel disease (IBD), in which situation management is extremely difficult. CMV infection being a potential cause of IBD have drawn great attention of clinicians, with insufficient evidence to reach *** conduct this meta-analysis to explore the association of CMV infection and steroid-refractory IBD by collecting relevant articles. Literature collections were conducted by searching PubMed, EMBASE, and the cochrane library databases. Pooled risk ratios (RR) with corresponding 95% confidence intervals (CIs) were calculated to estimate the strength of the link between CMV infection and steroid resistance in IBD using Stata *** eligible studies with a total of 1119 patients conducted in eight countries were included. The steroid resistance rate in the CMV (+) groups was 62.8%, while that in the CMV (-) groups was 29.2%. The pooled RR of steroid resistance rate in CMV (+) groups compared to CMV (-) groups was 2.343 (95% CI 1.715-3.202, P=0.0000). Due to marginal heterogeneity across studies (I-2=77.6%), the random effects model was used. Subgroup analysis based on geographic differences did not alter the overall positive association between CMV infection and steroid resistance in IBD. There is no significant publication bias observed based on the funnel plot and Begg's *** meta-analysis disclosed 2.34 fold increased risk of progressing into steroid-refractory IBD in CMV (+) group compared with the CMV (-) group, indicating that CMV infection might be a plausible cause of steroid-refractory IBD.

关键词： Inflammatory bowel disease   regulatory T cells   IL-10   IL-23  

摘要： Background: IL-10 is an anti-inflammatory cytokine required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type 1 regulatory T (T(R)1) cells but is also produced by CD25(+) regulatory T (Treg) cells. Objective: We aimed to identify and characterize human intestinal T(R)1 cells and to investigate whether they are a relevant cellular source of IL-10 in patients with inflammatory bowel diseases (IBDs). Methods: CD4(+) T cells isolated from the intestinal lamina propria of human subjects and mice were analyzed for phenotype, cytokine production, and suppressive capacities. Intracellular IL-10 expression by CD4(+) T-cell subsets in the inflamed guts of patients with IBD (Crohn disease or ulcerative colitis) was compared with that in cells from noninflamed control subjects. Finally, the effects of proinflammatory cytokines on T-cell IL-10 expression were analyzed, and IL-1 beta and IL-23 responsiveness was assessed. Results: Intestinal T(R)1 cells could be identified by coexpression of CCR5 and programmed cell death protein 1 (PD-1) in human subjects and mice. CCR5(+) PD-1(+) T(R)1 cells expressed IFN-gamma and efficiently suppressed T-cell proliferation and transfer colitis. Intestinal IFN-gamma(+) T(R)1 cells, but not IL-7 receptor-positive T-H cells or CD25(+) Treg cells, showed lower IL-10 expression in patients with IBDs. T(R)1 cells were responsive to IL-23, and IFN-gamma(+) T(R)1 cells downregulated IL-10 with IL-1 beta and IL-23. Conversely, CD25(+) Treg cells expressed higher levels of IL-1 receptor but showed stable IL-10 expression. Conclusions: We provide the first ex vivo characterization of human intestinal T(R)1 cells. Selective downregulation of IL-10 by IFN-gamma(+) T(R)1 cells in response to proinflammatory cytokines is likely to drive excessive intestinal inflammation in patients with IBDs.

关键词： Inflammatory bowel disease   Crohn disease   Ulcerative colitis   Kidney disease   Renal biopsy   Glomerulonephritis   Tubulointerstitial nephritis   Aminosalicylates  

摘要： Renal and urinary involvement has been reported to occur in 4% to 23% of patients with inflammatory bowel disease (IBD). Parenchymal renal disease is rare and most commonly affects glomerular and tubulointerstitial compartments. The most common findings on renal biopsy of patients with IBD are IgA nephropathy and tubulointerstitial nephritis. Overall morbidity of IBD-related renal manifestations is significant, and there is often only a short window of injury reversibility. This, along with subtle clinical presentation, requires a high index of suspicion and routine monitoring of renal function. There are no established guidelines for the optimal screening and monitoring of renal function in patients with IBD.

关键词： Biologic agents   inflammatory bowel disease   internet   patient education   website  

摘要： Background/Aims: Many patients currently seek the Internet for health-related information without discerning the quality or bias of the evidence presented. Biologic agents have become the mainstay of therapy in inflammatory bowel disease (IBD), and it is important that patients have access to high-quality information when exploring the various available agents to make informed decisions about their therapy. The primary aim of this study was to evaluate the quality of patient-searched Internet websites that describe the biologic agents used as treatment options for IBD. The secondary aim was to compare the quality of patient-searched with physician-recommended websites and to evaluate any differences. Materials and Methods: The DISCERN model was used to evaluate the quality of the information content of a total of 110 websites of all the biologic agents used in the treatment of IBD from July to September 2017. The first 10 "Google search" hits meeting the inclusion criteria for each agent were included. There were four additional physician-recommended websites that were evaluated for the purpose of the secondary aim of this study. Results: The mean DISCERN score among all websites combined was 3.21 out of a 5-point scale. The highest scoring website was "*** " at 4.13 whereas the lowest scoring website was "https:// *** " at 1.97 for Entyvio. There was no significant difference between patient-searched and physician-recommended websites, with a mean total score of 3.21 versus 3.63, respectively (P value of 0.158). Conclusions: The combined quality of Internet web-based resources used for each drug was fairly consistent in scoring (intermediate to slightly above average). There was no significant advantage in the overall combined scores of the pooled physician-recommended websites when compared with the patient-searched websites.