关键词： INFLAMMATORY bowel diseases   CHILDREN   ADULTS   CROHN'S disease   ULCERATIVE colitis   BIOLOGICAL response modifiers   QUANTITATIVE research   SENSITIVITY analysis  

摘要： Background Cohort studies comparing the characteristics of childhood-onset and adulthood-onset inflammatory bowel disease (IBD) in the biologics era are scarce. Aim To compare disease characteristics, the use of immunomodulators and biologic agents and the need for surgery between childhood- and adulthood-onset IBD. Methods Inflammatory bowel disease patients from the ENEIDA registry diagnosed between 2007 and 2017 were included. The childhood-onset cohort comprised patients diagnosed at <= 16 years of age and the adulthood-onset cohort those diagnosed at >16 years. The cumulative incidences of immunosuppressive therapy, biologic therapy and surgery were estimated using Kaplan-Meier curves, compared by the log-rank test. Cox regression analysis was performed to identify potential predictive factors of treatment with immunosuppressants, biologic agents or surgery. Results The adulthood-onset cohort comprised 21 200 patients out of 20 354 (96%) and the childhood-onset cohort 846 (4%). Median follow-up was 54 months in the childhood-onset cohort and 38 months in the adulthood-onset cohort (P < 0.01). Proportions of Crohn's disease, ileocolonic involvement and inflammatory behaviour at diagnosis were higher in the childhood-onset cohort. In the multivariate analysis, after adjusting for sex, type of IBD, extraintestinal manifestations, family history and smoking habit, childhood-onset IBD was associated with higher risk of immunomodulator use (hazard ratio [HR] = 1.2, 95% confidence interval [95% CI] = 1.1-1.2) and higher probability of receiving biologic treatment (HR = 1.2, 95% CI = 1.1-1.3). However, childhood-onset IBD was not associated with higher risk of surgery (HR = 0.9, 95% CI = 0.8-1.2). Conclusions Childhood-onset IBD has differential characteristics and higher risk of treatment with immunomodulators and biologic agents, compared with adulthood-onset IBD. Nevertheless, paediatric IBD is not associated with higher risk of surgery.

关键词： 1,25(OH)(2)D-3   Colitis   IBD   Macrophage   miR-125b  

摘要： Macrophages are highly plastic cells. Depending on stimulation, macrophages rapidly polarize to functionally distinct phenotypes that are involved in the pathogenesis of inflammatory bowel disease (IBD). 1,25-Dihydroxyvitamin D (1,25(OH)(2)D-3) has immunomodulatory activity, and 1,25(OH)(2)D-3 deficiency is correlated with autoimmune diseases, especially IBD. This study aimed to explore whether 1,25(OH)(2)D-3 modulates macrophage polarization in inflammation. Peripheral blood mononuclear cells and colitis mice were treated with 1,25(OH)(2)D-3. Macrophages were transfected with siRNA-vitamin D receptor (VDR) or miR-125b mimic or inhibitor, and 1,25(OH)(2)D-3-pretreated colitis mice were injected with a miR-125b agomir. The distribution of macrophage subsets and macrophage subtype characteristics was analyzed. As expected, 1,25(OH)(2)D-3 transformed lipopolysaccharide-induced M1 macrophages to the M2 subset, downregulated tumor necrosis factor-alpha and interleukin (IL)-6 expression and interferon regulatory factor 5 (IRF5) phosphorylation, and upregulated IL-10, arginase-1, VDR, and IRF4 expression. SiRNA-VDR and miR-125b mimic significantly impaired 1,25(OH)(2)D-3 activity. In colitis mice, 1,25(OH)(2)D-3 pretreatment ameliorated disease activity, converted M1 macrophages to the M2 subtype, suppressed IRF5 phosphorylation, and increased IRF4 expression in lamina propria mono-nuclear cells (LPMC). miR-125b agomir injections reversed 1,25(OH)(2)D-3 action. Collectively, the results demonstrate that 1,25(OH)(2)D-3 downregulates miR-125b expression and promotes M1 macrophage polarization to the M2 subtype. 1,25(OH)(2)D-3 pretreatment ameliorated colitis by restoring the LPMC macrophage subtype balance.

关键词： VEO-IBD   Primary immunodeficiencies   Inflammation   Monogenic  

摘要： The epidemiology of inflammatory bowel disease has changed over the past 4 decades. The incidence is rising dramatically and the age of onset has become younger. This changing landscape of inflammatory bowel disease reflects the new recognition that the youngest children with inflammatory bowel disease are enriched in cases with underlying primary immunodeficiency and monogenic causes. The management of these cases can be quite different, with specific genetic etiologies supporting unique interventions and some requiring hematopoietic cell transplantation for effective treatment.

关键词： Fungi   Candida   IBD  

摘要： Background and aimsThere are no previous reports describing the fecal fungal microbiome of a Japanese population using advanced molecular techniques. In this study, we performed a molecular analysis on the fungal microbial community of a healthy Japanese population and patients with inflammatory bowel diseases (IBDs).Patients and methodsFecal samples were obtained from 18 patients with inactive ulcerative colitis (UC, n=18), Crohn's disease (CD, n=20) and healthy volunteers (n=20). Bacterial and fungal microbiome was analyzed by sequencing of 16S rRNA and the internal transcribed spacer (ITS) region, ***16S rRNA sequencing of the bacterial microbiome revealed that the -diversity indicated by the Chao-1 and Shannon indices was significantly lower in CD patients compared to healthy controls and/or UC patients. Principal coordinate (PCo) analysis of the bacterial community revealed significant structural differences in microbiome among healthy controls, UC and CD patients (PERMANOVA P=0.0001). ITS sequencing of the fungal microbiome indicated no significant differences in -diversity between healthy controls and IBD patients. However, the overall structure of the fungal microbial community of CD patients was significantly different from those of healthy controls and UC patients (PERMANOVA=0.03). At the genus level, the genus Saccharomyces was dominant and this was followed by the genus Sarocladium in healthy controls. The abundance of the genus Candida was significantly higher in CD patients than healthy controls and/or UC *** fecal fungal microbiome of a Japanese population differed considerably from that of a Western population. We identified fungal dysbiosis in Japanese patients with IBD.

关键词： Risk-Benefit Analysis   Crohn's Disease   Ulcerative Colitis   Emotional Bias  

摘要： Inflammatory bowel diseases (IBD) and their treatments, particularly immunosuppressive drugs, increase risk of infections and cancers. However, by promoting mucosal healing, these agents should reduce risks of infections related to intestinal lesions, malnutrition, intravenous devices, and IBD surgeries and reduce risk of cancers associated with chronic mucosal inflammation-although there are few data to support this concept. Corticosteroids increase the risk of vascular thromboembolic events, yet other immunosuppressive drugs that induce deep remission from IBD could decrease the incidence of cardiovascular events attributable to systemic inflammation and IBD-related hospitalizations and/or surgeries. The nature and magnitude of the risks of infections and cancers vary with immunosuppressive drug class and patient sex and age. For example, thiopurines increase risk of viral infections that might be fatal in young patients, whereas tumor necrosis factor antagonists increase risk of bacterial and intracellular infections that can be fatal in patients of any age, but particularly in older patients. The ability of drugs to prevent IBD-associated colorectal cancer varies with IBD location and duration. Models to assess the benefit: risk ratio of long-term use of immunosuppressive drugs for patients with IBD should be adapted based on patients' age, sex, and IBD phenotype, to properly guide patient management. The decision-making process should begin with a clear explanation of treatment risks and then integrate the patient's emotional perception of risks.

关键词： inflammatory bowel disease   inflammatory markers   sleep disturbance   symptom severity and children  

摘要： Supplemental Digital Content is available in the text

关键词： IBD   Colon cancer   Cytokines   IL-23   Immune response  

摘要： Studies in recent years have identified a pivotal role of the cytokine IL-23 in the pathogenesis of inflammatory bowel diseases (IBD: Crohn's disease, ulcerative colitis) and colitis-associated colon cancer. Genetic studies revealed that subgroups of IBD patients have single nucleotide polymorphisms in the IL-23R gene suggesting that IL-23R signaling affects disease susceptibility. Furthermore, increased production of IL-23 by macrophages, dendritic cells or granulocytes has been observed in various mouse models of colitis, colitis-associated cancer and IBD patients. Moreover, in several murine models of colitis, suppression of IL-12/IL-23 p40, IL-23 p19 or IL-23R function led to marked suppression of gut inflammation. This finding was associated with reduced activation of IL-23 target cells such as T helper 17 cells, innate lymphoid cells type 3, granulocytes and natural killer cells as well as with impaired production of proinflammatory cytokines. Based on these findings, targeting of IL-23 emerges as important concept for suppression of gut inflammation and inflammation-associated cancer growth. Consistently, neutralizing antibodies against IL-12/IL-23 p40 and IL-23 p19 have been successfully used in clinical trials for therapy of Crohn's disease and pilot studies in ulcerative colitis are ongoing. These findings underline the crucial regulatory role of IL-23 in chronic intestinal inflammation and colitis-associated cancer and indicate that therapeutic strategies aiming at IL-23 blockade may be of key relevance for future therapy of IBD patients.

关键词： HBI   SCCAI   alpha 4 Integrin   Response to Therapy  

摘要： BACKGROUND & AIMS: Little is known about the efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab for patients with Crohn's disease (CD) or ulcerative colitis (UC). We analyzed the outcomes of patients receiving vedolizumab along with calcineurin inhibitors. METHODS: We collected data on patients with CD (n = 9) or UC (n = 11) who began treatment with vedolizumab from May 20, 2014, through March 30, 2015, and received calcineurin inhibitors (tacrolimus or cyclosporin) during the first 12 months of vedolizumab therapy. Clinical activity scores and inflammatory markers were measured at baseline and at weeks 14, 30, and 52 of vedolizumab treatment. Clinical remission was defined as a Harvey-Bradshaw index score <= 4 or short clinical colitis activity index score <= 2;steroid-free clinical remission was defined as clinical remission without corticosteroids. RESULTS: By week 14 of treatment, 44% of the patients with CD and 55% of the patients with UC achieved steroid-free clinical remission;after 52 weeks of treatment, 33% of the patients with CD and 45% of the patients with UC were in steroid-free clinical remission. Seven patients received salvage therapy with a calcineurin inhibitor after primary nonresponse to vedolizumab-1 of the 2 patients with UC and 2 of 5 patients with CD stopped taking the calcineurin inhibitors and achieved steroid-free remission at week 52. In total, 16 patients (59%) received 52 weeks of treatment with vedolizumab. Three serious adverse events were associated with calcineurin inhibitors. CONCLUSIONS: Combination therapy of vedolizumab with either cyclosporin or tacrolimus is effective and safe at inducing and maintaining clinical remission in patients with CD and UC with up to 52 weeks of follow-up evaluation. Larger studies of the ability of calcineurin inhibitors to induce remission in patients on vedolizumab are warranted.