关键词： Immunological disorders   Immunotherapy  

摘要： A synthetic yeast-based therapeutic that secretes an ATP-degrading enzyme in response to pro-inflammatory extracellular ATP in the gut reduces intestinal inflammation, fibrosis and dysbiosis in mouse models of colitis and enteritis. Inflammatory bowel disease (IBD) is a complex chronic inflammatory disorder of the gastrointestinal tract. Extracellular adenosine triphosphate (eATP) produced by the commensal microbiota and host cells activates purinergic signaling, promoting intestinal inflammation and pathology. Based on the role of eATP in intestinal inflammation, we developed yeast-based engineered probiotics that express a human P2Y2 purinergic receptor with up to a 1,000-fold increase in eATP sensitivity. We linked the activation of this engineered P2Y2 receptor to the secretion of the ATP-degrading enzyme apyrase, thus creating engineered yeast probiotics capable of sensing a pro-inflammatory molecule and generating a proportional self-regulated response aimed at its neutralization. These self-tunable yeast probiotics suppressed intestinal inflammation in mouse models of IBD, reducing intestinal fibrosis and dysbiosis with an efficacy similar to or higher than that of standard-of-care therapies usually associated with notable adverse events. By combining directed evolution and synthetic gene circuits, we developed a unique self-modulatory platform for the treatment of IBD and potentially other inflammation-driven pathologies.

摘要： Background Inflammatory bowel disease (IBD) can be exacerbated by stress and depression. Type D personality, characterised by high negative affectivity and social inhibition, represents a vulnerability towards stressors and is associated with adverse outcomes in coronary heart disease. Aims To assess the prevalence of Type D personality in IBD patients and investigate potential associations with disease course. Methods We tested for associations between Type D (Type D Scale-14), depressive symptoms (Hospital Anxiety and Depression Scale's depression subscore >= 11) and recurrent IBD amongst Swiss IBD cohort patients. We built regression models for cross-sectional and Cox proportional hazards models for time-to-event analyses. IBD disease course was assessed by the future occurrence of active disease (Crohn's Disease Activity Index >= 150/Modified Truelove & Witts activity index >= 10) and several IBD-relevant endpoints. Results Amongst 2275 patients (1005 ulcerative colitis, 1270 Crohn's disease), 672 (29.5%) had Type D. Type D was a significant risk factor for future active disease (adjusted hazard ratio, aHR: 1.60, corrected P value, q = 0.007) and predicted the future presence of depressive symptoms (aHR: 3.30, P < 0.001). The combination of Type D and depressive symptoms further increased the risk for active disease (aHR: 3.98, q < 0.001). However, Type D associated depressive symptoms seemed to be the main contributor to this effect as Type D's predictive power decreased considerably in models corrected for depressive symptoms (aHR: 1.32, CI: 0.97-1.79, q = 0.292). Conclusions Type D personality's prevalence amongst IBD patients was comparable with its prevalence in the general population. Type D was strongly associated with depressive symptoms and showed modest independent associations with IBD prognosis.

关键词： Inflammatory bowel disease   Crohn's disease   Ulcerative colitis   Innate immunity   Adaptive immunity   Toll-like receptors   SARS-CoV-2   COVID-19  

摘要： To date, the latest research results suggest that the novel severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) can enter host cells directly via the gastrointestinal tract by binding to the enterocyte-expressed ACE2 receptor, or indirectly as a result of infection of type II alveolar epithelial cells. At the same time, entry of SARS-CoV-2 through the gastrointestinal tract initiates the activation of innate and adaptive immune responses, the formation of an excessive inflammatory reaction and critical increase in the expression of proinflammatory cytokines, which, subsequently, can presumably increase inflammation and induce intestinal damage in patients suffering from inflammatory bowel disease (IBD). The aims of the present review were to reveal and analyze possible molecular pathways and consequences of the induction of an innate and adaptive immune response during infection with SARS-CoV-2 in patients with IBD. A thorough literature search was carried out by using the keywords: IBD, SARS-CoV-2, COVID-19. Based on the screening, a number of intracellular and extracellular pathways were considered and discussed, which can impact the immune response during SARS-CoV-2 infection in IBD patients. Additionally, the possible consequences of the infection for such patients were estimated. We further hypothesize that any virus, including the new SARS-CoV-2, infecting intestinal tissues and/or entering the host's body through receptors located on intestinal enterocytes may be a trigger for the onset of IBD in individuals with a genetic predisposition and/or the risk of developing IBD associated with other factors.

摘要： Several gastrointestinal symptoms and chronic inflammatory bowel diseases (IBDs) have been reported after therapy with IL-17 inhibitors. To date, however, no study has shown a clear association between these drugs and IBD onset. We searched on Vigibase, the worldwide pharmacovigilance database, to investigate reporting prevalence, characteristics, and prognosis of all gastroenterological adverse events in patients treated with IL-17 inhibitors. In total, 1,129 gastrointestinal Individual Case Safety Reports (ICSRs) were identified, including 850 IBD (42.5% Crohn's disease, 31.9% ulcerative colitis, and 25.6% undifferentiated IBD) and 279 colitis (mainly undifferentiated colitis (79.2%), and microscopic colitis (10.4%)). ICSRs were associated with secukinumab (SEC, 83.6%) or ixekizumab (IXE, 16.3%), whereas only one colitis occurred with brodalumab (0.1%). Most IBD and colitis cases were detected within 6 months from therapy start in both the SEC (68.8% and 73.5%) and IXE groups (100% and 66.7%). Patients' outcomes were reported in 428 ICSRs (37.9%). Complete or ongoing recovery from symptoms was detected in about two-thirds of patients experiencing IBD (59.5%) or colitis (64.2%), whereas in the other cases, there was no recovery (33.9% and 29.5%) or there were sequelae (5.4% and 4.2%). Fatal events occurred in four patients (1.2%) in the IBD group (3 after SEC and on1e with IXE) and two SEC-treated subjects in the colitis group (2.1%). Treatment with IL-17 inhibitors is associated with a relevant number of exacerbations and new onset of IBD and colitis. Careful evaluation of gastrointestinal symptoms and the monitoring of intestinal inflammatory biomarkers should be recommended before prescribing these drugs.

摘要： This article is linked to Jordi et al papers. To view these articles, visit https://***/10.1111/apt.16365 and https://***/10.1111/apt.16398

关键词： Stroke   TIA   Inflammatory bowel disease   Crohn's disease   Ulcerative colitis  

摘要： Background: As a chronic systemic inflammation may be associated with an increased risk of vascular events, the aim of the present study was to assess the incidence of stroke and transient ischemic attack (TIA) in patients with inflammatory bowel disease over a period of 15 years. Methods: This cohort study included patients for whom the initial diagnosis of an inflammatory bowel disease (IBD) (Crohn's disease: CD and ulcerative colitis: UC) was documented anonymously between 2000 and 2015 in 1,262 general practices in Germany. IBD patients were matched to patients without IBD using propensity scores based on age, sex, physician, co-diagnoses and co-therapies. Cox regression models were used to study the incidence of stroke and TIA as a function of CD and UC. Results: Each of the matched groups included 11,947 participants. In the IBD group, 43.5% had CD and 56.5% UC respectively. Higher incidences of both stroke and TIA were detected for IBD (stroke: 279.0 versus 222.6 cases per 100,000 patient years, HR 1.30, p=0.011;TIA: 203.1 versus 141.1 cases per 100,000 patient years, HR 1.42, p=0.006). Stroke and TIA incidences (cases per 100,000 patient years) were higher than in controls (stroke: 314.7 versus 204.5, HR: 1.50, p=0.013;TIA: 183.8 versus 95.3, HR: 1.93, p=0.004) in CD patients only. No relevant differences in incidences were found for patients with UC. Conclusion: While CD turned out to be a relevant precondition for stroke or TIA, this was not the case for UC.

关键词： biologics   biosimilar pharmaceuticals   combination therapy   immunomodulator   inflammatory bowel diseases  

摘要： Objective To compare the efficacy and safety of a combination therapy of biologics and immunosuppressants with biological monotherapy in inflammatory bowel disease (IBD) in a systematic review and meta-analysis. Methods Eligible randomized controlled trials (RCTs) on the comparison of the efficacy and safety of biologics and immunomodulators with biological monotherapy were identified from the EMBASE, PubMed and the Cochrane Library databases published up to 1 May 2020. Raw data were extracted, pooled relative risk (RR) and 95% confidence interval (CI) was calculated, the fixed-effect and inverse variance models were used. Funnel plots were performed to analyze publication bias. Results Twelve RCTs were eligible for analysis. Overall, there was statistically a benefit for combination treatment over biologic monotherapy (IFX/ADA) in inducing clinical remission and preventing relapse in patients with IBD (RR 0.89, 95% CI 0.80-0.98). Moreover, the combination therapy was superior to biological monotherapy for active CD (RR 0.83, 95% CI 0.73-0.94). Also, there were significant benefits for combination therapy in the subgroup treated with infliximab (IFX) (RR 0.83, 95% CI 0.70-0.97). Conclusions Combination therapy has slight benefits in inducing clinical remission in active CD compared with biological monotherapy. Patients with IBD who receive therapy with IFX and immunomodulator also have a mild advantage in comparison with those treated with IFX monotherapy.

关键词： inflammatory bowel disease   telehealth   COVID-19   outpatient clinic  

摘要： Background Advances in inflammatory bowel disease (IBD) monitoring, greater number of available treatments and a shift towards tight disease control, IBD care has become more dynamic with regular follow ups. Aims We assessed the impacts of the COVID-19 pandemic on outpatient IBD patient care at a tertiary centre in Melbourne. More specifically, we assessed patient satisfaction with a telehealth model of care, failure to attend rates at IBD clinics and work absenteeism prior to and during the pandemic. Methods We conducted a retrospective, qualitative analysis to assess our aims through an online survey. We invited patients who attended an IBD outpatient clinic from April to June 2020 to participate. This study was conducted at a single, tertiary referral hospital in Melbourne. The key data points that we analysed were patient satisfaction with a telehealth model of care and the effect of telehealth clinics on work absenteeism. Results One hundred and nineteen (88.1%) patients were 'satisfied' or 'very satisfied' with the care received in the telehealth clinic. Eighty-four (60.4%) patients reported needing to take time off work to attend a face-to-face appointment, compared to 29 (20.9%) patients who needed to take time off work to attend telehealth appointments (P < 0.001). Clinic non-attendance rates were similar prior to and during the pandemic with rates of 11.4% and 10.4% respectively (P = 0.840). Conclusions Patients report high levels of satisfaction with a telehealth model of care during the COVID-19 pandemic, with clinic attendance rates not being affected. Telehealth appointments significantly reduced work absenteeism when compared to traditional face-to-face clinics.