摘要： Background Hepatosplenic T-cell lymphoma (HSTCL) is a rare, poorly treatable malignancy associated with therapy for IBD. Current knowledge of HSTCL risk in IBD comes from an era of step-up therapy, before earlier use of biologics or combination therapy was advocated to achieve deep mucosal healing. HSTCL risk among newer biologic classes has also not been evaluated. Aims To systematically characterise the association of HSTCL with biologic therapy for IBD. Methods We conducted a literature search and query of the Food and Drug Administration Adverse Event Reporting System to summarise HSTCL cases among IBD patients with prior biologic exposure. Demographics and immunosuppression exposure were extracted. Patients were stratified by current regimen (combination therapy, biologic monotherapy or no biologic), and biologic class (anti-TNF, anti-integrin, anti-interleukin 12/23). Results Sixty-two cases of HSTCL were identified from 2486 abstracts and 181 FDA Adverse Events Reporting System reports. The median age of affected patients was 28 years (range 12-81), and 83.6% were male, 84.7% had Crohn's disease. Five of 62 patients had no reported azathioprine/mercaptopurine exposure. Three patients within the cohort developed HSTCL after exposure to natalizumab, vedolizumab or ustekinumab;all three also had anti-TNF and azathioprine/mercaptopurine exposure. Forty-three of 49 (87.8%) patients with known outcomes died with a median survival of 5 months. Conclusions Consistent with existing data, almost all identified HSTCL cases among IBD patients on biologic therapy had azathioprine/mercaptopurine exposure, and all cases on patients exposed to biologics had anti-TNF exposure. These data suggest initiating a patient-centred discussion before starting anti-TNF therapy or other biologics.

摘要： OBJECTIVES: Infliximab (IFX) or adalimumab (ADA) use in patients with inflammatory bowel disease (IBD) leads to increased risk of tuberculosis (TB). This meta-analysis evaluated the factors which determine this risk, with special focus on local TB incidence. METHODS: All studies until January 31, 2019, which reported the development of TB in patients with IBD on IFX/ADA, were included after searching PubMed and Embase. Data regarding disease type, number of patients on IFX/ADA, number of patients who developed TB, mean age at IFX/ADA initiation, median duration of development of TB, and latent TB (LTB) were extracted. The details on local TB incidence were obtained from the World Health Organization database, and the studies were stratified into low (<10/100,000), intermediate (10-40/100,000), and high TB burden countries (>40/100,000). Random effect meta-analysis was performed to calculate the overall pooled prevalence and prevalence based on local TB burden. RESULTS: Of 130,114 patients (128 studies), 373 developed TB (pooled prevalence: 0.08% [95% confidence interval {CI}: 0.05%-0.10%]). The risk increased with increasing TB burden, pooled prevalence being 0.02% (95% CI: 0.02%-0.03%), 0.21% (95% CI: -0.02% to 0.43%), and 1.59% (95% CI: 1.19%-2.00%) for low, intermediate, and high TB burden countries, respectively. Seventy-three percent of patients who developed TB had no evidence of LTB on screening, the proportion being independent of TB burden. There was no effect of disease or treatment type, study type, gender, age at IFX/ADA initiation, and follow-up duration on TB prevalence. DISCUSSION: TB risk in patients with IBD on IFX/ADA depends on the local TB burden and is independent of disease/treatment type.

关键词： Crohn's disease   Quality of life   Ulcerative colitis  

摘要： Inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis, is an immune-mediated, chronic relapsing disorder characterised by severe gastrointestinal symptoms that dramatically impair patients' quality of life, affecting psychological, physical, sexual, and social functions. As a consequence, patients suffering from this condition may perceive social stigmatisation, which is the identification of negative attributes that distinguish a person as different and worthy of separation from the group. Stigmatisation has been widely studied in different chronic conditions, especially in mental illnesses and HIV-infected patients. There is a growing interest also for patients with inflammatory bowel disease, in which the possibility of disease flare and surgery-related issues seem to be the most important factors determining stigmatisation. Conversely, resilience represents the quality that allows one to adopt a positive attitude and good adjustments despite adverse life events. Likewise, resilience has been studied in different populations, age groups, and chronic conditions, especially mental illnesses and cancer, but little is known about this issue in patients with inflammatory bowel disease, even if this could be an interesting area of research. Resilience can be strengthened through dedicated interventions that could potentially improve the ability to cope with the disease. In this paper, we focus on the current knowledge of stigmatisation and resilience in patients with inflammatory bowel disease.

关键词： Pouchitis   Fecal microbiota transplantation   Probiotics   Prebiotics   Synbiotics   Diet   Live biotherapeutic products   Dysbiosis   Microbiota  

摘要： Inflammatory bowel diseases (IBD), including Crohn's disease, ulcerative colitis, and pouchitis, are chronic, relapsing intestinal inflammatory disorders mediated by dysregulated immune responses to resident microbiota. Current standard therapies that block immune activation with oral immunosuppressives or biologic agents are generally effective, but each therapy induces a sustained remission in only a minority of patients. Furthermore, these approaches can have severe adverse events. Recent compelling evidence of a role of unbalanced microbiota (dysbiosis) driving immune dysfunction and inflammation in IBD supports the therapeutic rationale for manipulating the dysbiotic microbiota. Traditional approaches using currently available antibiotics, probiotics, prebiotics, and synbiotics have not produced optimal results, but promising outcomes with fecal microbiota transplant provide a proof of principle for targeting the resident microbiota. Rationally designed oral biotherapeutic products (LBPs) composed of mixtures of protective commensal bacterial strains demonstrate impressive preclinical results. Resident microbial-based and microbial-targeted therapies are currently being studied with increasing intensity for IBD primary therapy with favorable early results. This review presents current evidence and therapeutic mechanisms of microbiota modulation, emphasizing clinical studies, and outlines prospects for future IBD treatment using new approaches, such as LBPs, bacteriophages, bacterial function-editing substrates, and engineered bacteria. We believe that the optimal clinical use of microbial manipulation may be as adjuvants to immunosuppressive for accelerated and improved induction of deep remission and as potential safer solo approaches to sustained remission using personalized regimens based on an individual patient's microbial profile.

关键词： Crohn's disease   Ulcerative colitis   Bariatric surgery   Inflammatory bowel disease  

摘要： Background The rate of obesity is rapidly increasing in patients with inflammatory bowel disease (IBD), but whether bariatric surgery in patients with IBD is safe and effective is not well understood. Methods A retrospective review of patients with IBD undergoing bariatric surgery across a multi-state health system was performed. Thirty-day postoperative outcomes, weight loss, and long-term complications were recorded. Results Thirty-one patients (81% female) with IBD and a mean preoperative body mass index (BMI) of 42.4 kg/m(2) underwent 32 bariatric operations (n = 14 Roux-en-Y gastric bypass, n = 14 sleeve gastrectomy, n = 4 gastric band). Short-term infectious complications included superficial surgical site infection (n = 2), infected intra-abdominal hematoma (n = 1), and a hepatic abscess (n = 1). Percent excess weight loss was 57.2% (n = 25) at 6 months, 62.9% (n = 22) at 12 months, and 57.4% (n = 11) at 24 months. No IBD flares requiring surgery were observed at a median follow-up of 2.7 years (interquartile range, 0.8-4.2 years). Conclusion In carefully selected patients with IBD, bariatric surgery appears safe with respect to short-term infectious complications and results in sustained weight loss until at least 2 years postoperatively.

关键词： inflammatory bowel disease therapies   methotrexate treatment   targeted delivery systems   yeast glucan particles  

摘要： Therapy of inflammatory bowel disease (IBD) has been a difficult task in the medical field. There is a great clinical need for more effective treatments for IBD. Herein, a targeted oral delivery system of yeast glucan particles (YGPs) carrying a clinically used anti-inflammatory drug methotrexate (MTX) to the inflamed sites in IBD mice for therapy is reported. In the findings, MTX is effectively loaded into YGPs through re-precipitation followed by gelation reaction of alginate to obtain the composite YGPs/MTX, which are internalized into RAW264.7 macrophage cells through dectin-1 and CR3 receptors. Furthermore, YGPs/MTX can suppress the proliferation of macrophage cells efficiently, leading to down-regulation of pro-inflammatory cytokines induced by lipopolysaccharides. Additionally, YGPs accumulate in the inflammation site of colitis mice, enabling YGPs/MTX to target the inflammatory site, significantly improve the efficacy of MTX, and reduce the cytotoxicity of MTX. Therefore, the YGPs-based drug delivery system provides a new strategy for MTX application in the clinical treatment of IBD.

关键词： comorbidity   DSS   gut-brain-axis   N-palmitoylethanolamine-oxazoline  

摘要： Inflammatory bowel disease (IBD) is a chronic disorder characterized by inflammation of the gastrointestinal (GI) tract, and it is associated with different neurological disorders. Recent evidence has demonstrated that the gut-brain-axis has a central function in the perpetuation of IBS, and for this reason, it can be considered a possible therapeutic target. N-Palmitoylethanolamine-oxazoline (PEA-OXA) possesses anti-inflammatory and potent neuroprotective effects. Although recent studies have explained the neuroprotective properties of PEA-OXA, nothing is known about its effects on the gut-brain axis during colitis. The aim of this study is to explore the mechanism and the effect of PEA-OXA on the gut-brain axis in rats subjected to experimental colitis induced by intracolonic administration of dextran sulfate sodium (DSS). Daily oral administration of PEA-OXA (10 mg/kg daily o.s.) was able to decrease the body weight loss, macroscopic damage, colon length, histological alteration, and inflammation after DSS induction. Additionally, PEA-OXA administration enhanced neurotrophic growth factor release and decreased the astroglial and microglial activation induced by DSS. Moreover, PEA-OXA restored intestinal permeability and tight junctions (TJs) as well as reduced apoptosis in the colon and brain. In our work, we demonstrated, for the first time, the action of PEA-OXA on the gut-brain axis in a model of DSS-induced colitis and its implication on the "secondary" effects associated with colonic disturbance.

关键词： CD   UC   Microbiome   Comparison  

摘要： BACKGROUND & AIMS: Altering the intestinal microbiota has been proposed as a treatment for inflammatory bowel diseases (IBDs), but there are no established associations between specific microbes and IBD. We performed a systematic review to identify frequent associations. METHODS: We searched the MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases, through April 2, 2018 for studies that compared intestinal microbiota (from fecal or colonic or ileal tissue samples) among patients (adult or pediatric) with IBD vs healthy individuals (controls). The primary outcome was difference in specific taxa in fecal or intestinal tissue samples from patients with IBD vs controls. We used the Newcastle-Ottawa scale to assess the quality of studies included in the review. RESULTS: We identified 2631 citations;48 studies from 45 articles were included in the analysis. Most studies evaluated adults with Crohn's disease or ulcerative colitis. All 3 studies of Christensenellaceae and Coriobacteriaceae and 6 of 11 studies of Faecalibacterium prausnitzii reported a decreased amount of those organisms compared with controls, whereas 2 studies each of Actinomyces, Veillonella, and Escherichia coli revealed an increased amount in patients with Crohn's disease. For patients with ulcerative colitis, Eubacterium rectale and Akkermansia were decreased in all 3 studies, whereas E coli was increased in 4 of 9 studies. The microbiota diversity was either decreased or not different in patients with IBD vs controls. Fewer than 50% of the studies stated comparable sexes and ages of cases and controls. CONCLUSIONS: In a systematic review, we found evidence for differences in abundances of some bacteria in patients with IBD vs controls, but we cannot make conclusions due to inconsistent results and methods among studies. Further large-scale studies, with better methods of assessing microbe populations, are needed.