关键词： Inflammatory bowel disease   Mucosal immunology  

摘要： Inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis are characterized by uncontrolled activation of intestinal immune cells in a genetically susceptible host. Due to the progressive and destructive nature of the inflammatory process in IBD, complications such as fibrosis, stenosis or cancer are frequently observed, which highlights the need for effective anti-inflammatory therapy. Studies have identified altered trafficking of immune cells and pathogenic immune cell circuits as crucial drivers of mucosal inflammation and tissue destruction in IBD. A defective gut barrier and microbial dysbiosis induce such accumulation and local activation of immune cells, which results in a pro-inflammatory cytokine loop that overrides anti-inflammatory signals and causes chronic intestinal inflammation. This Review discusses pathogenic cytokine responses of immune cells as well as immune cell trafficking as a rational basis for new translational therapies in IBD.

关键词： Arthritis, Juvenile   Metabolic Diseases   Inflammatory Bowel Diseases   Meta-Analysis   Review, Systematic   Motor Activity   Child   Nylons  

摘要： BACKGROUND: Physical activity (PA) is essential for children throughout their growth and maturation. It improves physiological and psychological health and limits the risk of developing metabolic disorders. However, some chronic physiological and metabolic diseases may lead to decreased PA. The diversity of outcomes in the literature offers no consensus for physical activity and sedentary levels in children with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD). METHODS: A literature review and a meta-analysis were carried out with original studies from a Medline database search. Only high-quality studies (STROBE checklist) written in English comparing PA level or sedentary behavior (SB) between children with the disorders and their healthy peers were considered. The aim was to examine PA and SB in children with JIA or IBD compared to their healthy peers. RESULTS: The literature review and meta-analysis identified decreased PA and increased time spent in SB in these populations, which may exacerbate both their lower physical fitness and the symptoms of their health disorders. CONCLUSION: Results nevertheless show discrepancies due to the different materials and methods used and the variables measured. Further studies are needed to establish a gold standard method for assessing PA level in these populations.

摘要： Prior to the biologic era, the medical management of patients with inflammatory bowel disease (IBD) was dominated by the use of aminosalicylates, corticosteroids, and immunosuppressants. In the past two decades, the advent of biologic agents that target specific components of the immune response has greatly improved the care of patients with Crohn's disease and ulcerative colitis (UC). However, not all patients respond or maintain response to biologic therapy and some patients develop adverse events that necessitate treatment discontinuation. Furthermore, sensitization with formation of anti-drug antibodies is an inherent limitation to administration of monoclonal antibodies. This circumstance has generated renewed interest in the development of novel oral small-molecule drugs (SMDs) that are effective and well tolerated. Several classes of SMDs are currently progressing through the pipeline and offer the promise of oral delivery and high potency. In this review, we summarize different mechanisms of oral drug delivery to the gastrointestinal tract, highlight key findings from phase II and III randomized trials of novel oral SMDs, and discuss how oral SMDs are likely to be integrated into future IBD treatment paradigms. The most advanced development programs currently involve evaluation of compounds blocking Janus kinase (JAK) receptors or modulating sphingosine-1-phosphate (S1P) receptors. Tofacitinib, an oral JAK inhibitor, was recently approved for the treatment of moderate-to-severe UC. Several more selective JAK-1 inhibitors, including filgotinib and upadacitinib, have also shown positive results in phase II studies and are currently enrolling in phase III development programs. Similarly, ozanimod, an S1P1 and S1P5 receptor agonist, has shown early favorable results and is enrolling in phase III trials. As these and other novel oral SMDs come to market, several questions will need to be answered. The cost effectiveness, comparative treatment efficacy, predictors

关键词： Genetic defect   IL-10   Interleukin-10 receptor   Inflammatory bowel disease   Immunodeficiency   Children  

摘要： Defects in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) are closely related to very early onset (infantile) inflammatory bowel disease (VEO-IBD). In the present study, we report a novel homozygous null mutation within interleukin-10 receptor B (IL10RB) gene in a child presenting with severe VEO-IBD. In accordance with previous reports, our patient manifested with chronic diarrhea, failure to thrive, intermittent fever and multiple anal ulcers associated with Candidiasis. Homozygous null mutation within IL10RB gene (c.92C > T, p.S31P) affecting the extracellular domain of protein was discovered in this patient. In conclusion, the diagnosis of IL-10R gene mutations should always be considered as a possible cause of refractory diarrhea and failure to thrive. Mutation analysis could help detect the genetic defects associated with these clinical manifestations and to determine the most appropriate treatment option for patients affected by this disease.

关键词： inflammatory bowel disease   intravenous administration   mesenchymal stromal cells   therapy   trials  

摘要： Inflammatory bowel disease (IBD), namely, Crohn's disease and ulcerative colitis, remains a grievous and recalcitrant problem incurring significant human and health care costs, even in consideration of the growing incidence. Initial goals of care aimed to achieve the induction and maintenance of clinical remission. The advent of novel treat-to-target approaches using patient stratification, early introduction of immunosuppressants and rapid escalation to biologics or early use of combination therapy has refocused the goals of care toward the achievement of mucosal healing. This is in an attempt to preserve intestinal function, decrease hospitalization and surgery rates and improve the quality of life of affected patients. Cellular therapeutics for the treatment of IBD offers an unprecedented opportunity to change the current paradigm from single-targeted to systems-targeted therapy, trying to dampen the whole inflammatory cascade instead of a only molecule. Therefore, as we move forward, the importance of designing informative and possibly adaptive trial designs, standardizing methodologies, harmonizing goals of therapy and evaluating methods cannot be underemphasized. In this article, we review the current literature on the application of mesenchymal stromal cells for the treatment of IBD in an effort to establish a consensus on designing efficient and consistent clinical trials for the intravenous use of this cellular therapy in IBD.

摘要： Background In rheumatoid arthritis and psoriasis female sex has been shown to be associated with discontinuation of anti-tumour necrosis factor-alpha (TNF-alpha) therapy. Aim To retrospectively assess the association between sex and TNF-alpha drug persistence in patients with inflammatory bowel disease (IBD). Methods All IBD patients on anti-TNF-alpha therapy with a minimum follow-up of 12 months in a single tertiary centre were identified. Patient and treatment characteristics and reasons for anti-TNF-alpha discontinuation were recorded. Overall and cause-specific drug persistence was analysed with Kaplan-Meier followed by Cox proportional hazards regression models. Results We included 529 patients (49.9% male) with 631 treatment episodes (2280 anti-TNF-alpha treatment years) and 289 discontinuations of therapy. Female sex (adjusted hazard ratio [aHR] 1.42, 95% confidence interval [CI] 1.16-1.74), greater age at start of therapy per decade (aHR 1.15, 95% CI 1.04-1.27] and dose escalation (aHR 3.74, 95% CI 2.78-5.02) were associated with TNF-alpha inhibitor discontinuation. Total cohort cause-specific analysis identified female sex to be associated with side effects (aHR 4.05, 95% CI 2.36-6.98) but not to other discontinuation reasons. Adalimumab (aHR 1.70, 95% CI 1.11-2.60) and golimumab (aHR 4.97, 95% CI 2.30-10.74) use and dose-escalation (aHR 7.71, 95% CI 5.28-11.26) were associated with secondary loss of response. Conclusion Drug persistence of anti-TNF-alpha therapy is lower in females as compared to males, mainly because of higher rates of side effects in females. Understanding the sex specific differences in effectiveness and safety of anti-TNF-alpha compounds can aid physicians in clinical decision-making.

关键词： Crohn's disease   Ulcerative colitis   Vedolizumab   Remission   Safety  

摘要： Background: Italian data currently available in managing ulcerative colitis (UC) and Crohn's disease (CD) patients with vedolizumab (VDZ) are coming just from secondary and tertiary centers. The present study aimed to assess the real-life efficacy and safety of VDZ to achieve remission in inflammatory bowel diseases (IBD) outpatients in primary gastroenterology centers. Methods: Clinical activity was scored according to the Mayo score in UC and to the Harvey-Bradshaw Index (HBI) in CD. The primary endpoints were the achievement of clinical remission and safety. Secondary endpoints were clinical response to treatment, achievement of mucosal healing (MH), and steroid discontinuation. Results: One hundred and thirty-six pts. were enrolled (91 UC and 45 CD pts). During an 18-month median follow-up, clinical remission was present in 63 (46.3%) pts.: in particular, it occurred in 48 (52.7%) patients in UC group and in 15 (33.3%) patients in CD group (p = 0.003). more in UC group. Fecal calprotectin >= 400 mu g/g and presence of comorbidities were factors significantly related to the failure of remission in UC and CD, respectively. Ten (7.3%) cases of adverse events were recorded (2 required suspension of treatment). Clinical response was present in 105 (72.2%) pts.: 71 (78.0%) in UC and 34 (75.5%) in CD group. MH occurred in 47 (62.7%) UC and in 9 (50.0%) CD patients. Steroids discontinuation occurred in 92 (67.6%) pts.;61 (67.0%) UC and 31 (68.9%) CD pts. Conclusion: VDZ is effective and safe in IBD outpatients, especially in UC patients.

关键词： Inflammatory bowel disease   Risk factors  

摘要： Cytomegalovirus promotes mucosal injury in patients with inflammatory bowel disease, historically affecting 10-25% of ulcerative colitis patients with refractory disease. Viral reactivation is likely related to long-term corticosteroid therapy, which is no longer central to maintenance of patients with inflammatory bowel disease. We hypothesize that viral detection rates have decreased in the modern era, reflecting widespread use of immunomodulatory agents to control inflammation. We performed this study to evaluate the relationships between medical regimens and cytomegalovirus detection rates among patients with inflammatory bowel disease. We searched our database for all patients with established inflammatory bowel disease and severe flares diagnosed from 2002 to 2017. Patients maintained with corticosteroid therapy were considered to be corticosteroid-dependent and those treated with other agents were classified as corticosteroid-independent, provided they had not received corticosteroids within 6 months of colonoscopy. Biopsy samples were reviewed for viral inclusions and subjected to cytomegalovirus immunohistochemistry, and rates of viral detection were compared between groups. There were 135 corticosteroid-dependent patients;most had ulcerative colitis flares occurring during the 2002-2009 period. Patients with ulcerative colitis and Crohn disease were equally represented in the corticosteroid-independent group (n = 133) and most were evaluated for disease flares during the 2010-2017 interval. Cytomegalovirus was detected in 13 (8%) cases;9 (69%) were diagnosed from 2002 to 2009 and all were obtained from corticosteroid-dependent patients (p = < 0.001). We conclude that rates of cytomegalovirus-related enterocolitis are declining among inflammatory bowel disease patients, reflecting a shift away from corticosteroid-based maintenance therapy in favor of more effective agents that do not promote viral reactivation.

摘要： BackgroundUp to December 2018, eight cases of new-onset inflammatory bowel disease (IBD) were reported in the literature in patients being treated with secukinumab, an interleukin-17A antagonist prescribed for dermatologic or rheumatologic indications. The duration of secukinumab treatment ranged from a single administration to 12 months of *** aim of our investigation was to estimate the cumulative incidence of new-onset IBD in patients treated with secukinumab for either dermatologic or rheumatologic *** carried out a survey among the dermatology and rheumatology centres in the Sicilian region (Italy) in order to identify the number of patients treated with secukinumab in the previous 24 months (November 2016-November 2018), and to understand how many of these patients eventually developed IBD after the start of secukinumab ***, four cases of IBD during secukinumab treatment were identified, with higher variability in time to onset compared with what has been previously reported, i.e. from 1 month to 5 years of secukinumab exposure. Overall, 434 patients were treated with secukinumab in Sicily between November 2016 and November 2018, and approximately 1% of these patients developed new-onset *** clinical examination of patients with respect to possible susceptibility to IBD prior to secukinumab therapy is advised.