关键词： herpes zoster virus   varicella zoster virus   inflammatory bowel disease   immunosuppressed   vaccination  

摘要： BackgroundImmunosuppressed inflammatory bowel disease (IBD) patients have an increased risk of herpes zoster virus (HZV) infection. The existing live-attenuated HZV vaccine is contraindicated in some of these patients and can only be used with caution in others. AimsTo describe characteristics of IBD patients suffering HZV to enable implementation of risk mitigation strategies for those at highest risk. MethodsGastroenterologists completed a proforma for IBD patients who experienced HZV infection: IBD phenotype, details of HZV infection, immunosuppression and any change to treatment upon diagnosis of HZV. ResultsA total of 30 cases was identified: Crohn disease (CD) (n=25) and ulcerative colitis (n=5). In total, 80% (20/25) of the CD patients had penetrating, stricturing or perianal disease. Time from commencement of immunosuppression to HZV infection was highly variable (range: 3months to over 10years). A total of 90% (27/30) of patients was on at least one immunosuppressive therapy;of those, one-third was on monotherapy (9/27) and two-thirds (18/27) on dual therapy. A total of 89% (24/27) of immunosupressed patients was on a thiopurine (monotherapy;6/27) or in combination (18/27). Complications of HZV occurred in 27% (8/30) of patients. ConclusionOur series is consistent with existing epidemiological analysis that identified more severe IBD and the use of multiple immunosuppressive therapies as risk factors for HZV. If the promise of an investigational subunit HZV vaccine is realised in immunocompromised patients, better protection may be possible in the future. Thiopurine medications were the most commonly used immunosuppressant in this series. Age and duration of immunosuppressive therapy do not appear to predict HZV infection.

关键词： biologics   corticosteroids   immunomodulators   pediatrics   vaccination  

摘要： Objectives: Patients with inflammatory bowel disease (IBD) often receive immunosuppressive therapy, which may make them vulnerable to infections such as hepatitis B. We hypothesized that hepatitis B virus titers are low in the vaccinated pediatric population with IBD. The aims of our study were to identify the incidence of lower titers of hepatitis B surface antibody (HBsAb) and determine which patient factors may be associated with lower HBsAb titers. Methods: Patients with diagnosis of IBD, ages 5 to 18 years, were prospectively enrolled. Patients were confirmed to have had a full series of hepatitis B vaccination. Quantitative serum HBsAb titers were measured and logistic regression analysis with independent variables of age, sex, race, disease phenotype, surgery, medications and a dependent variable of adequate HBsAb titers (> 10 mIU/mL) was performed. Results: Of the 116 patients enrolled, 57 were boys and 59 were girls. 75 patients had a diagnosis of Crohn disease;32 had a diagnosis of ulcerative colitis;and 9 patients had been diagnosed as having indeterminate colitis. At the time of the study, 15 patients were taking corticosteroid, 66 on an immunomodulator, and 53 on a biologic. Sixty percent of patients in the 5- to 10-year age group had protective titers versus 22% to 27% in the older groups, P = 0.04. Only 28% of the 116 patients had HBsAb titers of > 10m IU/mL. Twenty percent of the patients taking corticosteroids, 27% taking immunomodulators, and 24% taking biologics were found to be seroimmune. Conclusions: Nearly two-thirds of pediatric patients with IBD have low titers against hepatitis B virus. Titers were highest in the younger patients. No patient-specific variable, such as the use of immunosuppressants, appeared to influence these low titers.

关键词： Pharmaceutical Preparations   Intestinal Diseases   Enough   Inflammatory Bowel Diseases  

关键词： Drug   Optimization of Treatment   IBD   Patient Management  

摘要： BACKGROUND & AIMS: We investigated whether serum trough levels of vedolizumab, a humanized monoclonal antibody against integrin alpha 4 beta 7, during the induction phase of treatment can determine whether patients will need additional doses (optimization of therapy) within the first 6 months. METHODS: We conducted an observational study of 47 consecutive patients with Crohn's disease (CD;n = 31) or ulcerative colitis (UC;n = 16) who had not responded to 2 previous treatment regimens with antagonists of tumor necrosis factor and were starting therapy with vedolizumab at 2 hospitals in France, from June 2014 through April 2016. All patients were given a 300-mg infusion of vedolizumab at the start of the study, Week 2, Week 6, and then every 8 weeks;patients were also given corticosteroids during the first 4-6 weeks. Patients not in remission at Week 6 were given additional doses of vedolizumab at Week 10 and then every 4 weeks (extended therapy or optimization). Remission at Week 6 of treatment was defined as CD activity score below 150 points for patients with CD and a partial Mayo Clinic score of <3 points, without concomitant corticosteroids, for patients with UC. Blood samples were collected each week and serum levels of vedolizumab and antibodies against vedolizumab were measured using an enzyme-linked immunosorbent assay. Median trough levels of vedolizumab and interquartile ranges were compared using the nonparametric Mann-Whitney test. The primary objective was to determine whether trough levels of vedolizumab measured during the first 6 weeks of induction therapy associated with the need for extended treatment within the first 6 months. RESULTS: Based on response to therapy at Week 6, extended treatment was required for 30 of the 47 patients (23 patients with CD and 7 patients with UC). At Week 2, trough levels of vedolizumab for patients selected for extended treatment were 23.0 mu g/mL (interquartile range, 14.0-37.0 mg/mu L), compared with 42.5 mu g/mL in

关键词： Inflammatory bowel disease   Bacterial biofilm   Mechanism   Current and future therapeutics  

摘要： Inflammatory bowel disease (IBD) symbolizes a group of intestinal disorders in which prolonged inflammation occur in the digestive tract (esophagus, large intestine, small intestine mouth, stomach). Both genetic and environmental factors (infections, stress, diet) are involved in the development of IBD. As we know that bacteria are found in the intestinal mucosa of human and clinical observations revealed bacterial biofilms associated with patients of IBD. Various factors and microbes are found to play an essential role in biofilm formation and mucosal colonization during IBD. Biofilm formation in the digestive tract is dependent on an extracellular matrix synthesized by the bacteria and it has an adverse effect on the immune response of the host. There is no satisfactory and safe treatment option for IBD. Therefore, the current research aims to disrupt biofilm in IBD and concentrates predominantly on improving the drug. Here, we review the literature on bacterial biofilm and IBD to gather new knowledge on the current understanding of biofilm formation in IBD, host immune deregulation and dysbiosis in IBD, molecular mechanism, bacteria involved in biofilm formation, current and future regimen. It is urgently required to plan new ways to control and eradicate bacteria in biofilms that will open up novel diagnostic and therapeutic avenues for IBD. This article includes the mechanism of signaling molecules with respect to the biofilm-related genes as well as the diagnostic methods and new technologies involved in the treatment of IBD. (C) 2017 Elsevier Ltd. All rights reserved.

关键词： Crohn's disease   Inflammatory bowel disease   Infliximab   Therapeutic drug monitoring   Ulcerative colitis  

摘要： Aim: This study examined the impact of therapeutic drug monitoring (TDM) on clinical decision-making for children receiving infliximab for inflammatory bowel disease (IBD). Methods: The medical records of children with IBD who had infliximab trough levels (ITLs) measured between January 2013 and December 2015 at two Canadian tertiary-care centres were examined. The indications for TDM, clinical and laboratory disease activity indices and TDM-driven treatment changes to infliximab therapy were documented. Results: We included 107 consecutive serum measurements of ITLs in 73 children (40 boys), with a median age of 16.1years, including 52 with Crohn's disease. TDM was performed due to concerns about clinical disease activity in 24/107 (22.4%) measurements and 83 (77.6%) were ordered as routine tests. Of these, 38 (35.5%) ITLs were suboptimal (<3.5 mu g/mL) and 36 (34.0%) resulted in more frequent doses of infliximab, with subsequent improvements in disease biomarkers. Interval changes were implemented as a result of 34 (32.0%) ITLs, with shorter intervals in 19 (17.0%) cases, and seven (6.5%) ITLs resulted in adding or increasing doses of immunomodulators. In addition, four children were switched to adalimumab. Conclusion: Therapeutic drug monitoring was helpful in guiding the decision-making process for children with IBD on infliximab.

关键词： VIP-SSM   inflammatory bowel disease   ulcerative colitis   sterically stabilized micelles  

摘要： Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine, with increasing incidence worldwide. At present, the management of IBD is an unmet medical need due to the ineffectiveness of currently available drugs in treating all patients, and there is strong demand for novel therapeutics. In this regard, vasoactive intestinal peptide, a potent anti-inflammatory endogenous hormone, has shown promise in managing multiple immune disorders in animal models. However, when administered in the free form, VIP undergoes rapid degradation in vivo, and with continuous infusion, it causes severe dose limiting side effects. To overcome these barriers, we have developed a superior mode to deliver VIP in its native form, using sterically stabilized micelles (VIP-SSM). Our previous studies demonstrated that, VIP, when administered in SSM, prevented joint damage and inflammation in a mouse model of rheumatoid arthritis at a significantly lower dose than the free peptide, completely abrogating the serious side effect of hypotension associated with VIP. In the current study, we demonstrate the therapeutic benefit of VIP-SSM over free peptide in reversing severe colitis associated with IBD. First, we conducted preliminary studies with dextran sulfate sodium (DSS) induced colitis in mice, to determine the effectiveness of VIP administered on alternate days in reducing disease severity. Thereafter, a single intra peritoneal injection of VIP-SSM or the free peptide was used to determine its therapeutic effect on the reversal of colitis and associated diarrhea. The results demonstrated that when administered on alternate days, both VIP-SSM and VIP were capable of alleviating DSS colitis in mice. However, when administered as a single dose, in a therapeutic setting, VIP-SSM showed superior benefits compared to the free peptide in ameliorating colitis phenotype. Namely, the loss of solid fecal pellets and increased fluid accumulation in colon resulting from DSS insult w

关键词： Biomarker   Telemedicine   Point-of-care test   Monitoring IBD Activity  

摘要： BACKGROUND & AIMS: An increasing number of physicians use repeated measurements of stool calprotectin to monitor intestinal inflammation in patients with inflammatory bowel diseases (IBDs). A lateral flow-based rapid test allows patients to measure their own stool calprotectin values at home. The test comes with a software application (IBDoc;Buhlmann Laboratories AG, Schonenbuch, Switzerland) that turns a smartphone camera into a results reader. We compared results from this method with those from the hospital-based reader (Quantum Blue;Buhlmann Laboratories AG) and enzyme-linked immunosorbent assay (ELISA) analysis. METHODS: In a single-center comparison study, we asked 101 participants (10 years of age or older) in the Netherlands to perform the IBDoc measurement on stool samples collected at home, from June 2015 to October 2016. Participants then sent the residual extraction fluid and a fresh specimen from the same bowel movement to our pediatric and adult IBD center at the University Medical Center Groningen, where the level of calprotectin was measured by the Quantum Blue reader and ELISA analysis, respectively. The primary outcome was the agreement of results between IBDoc and the Quantum Blue and ELISA analyses, determined by Bland-Altman plot analysis. RESULTS: We received 152 IBDoc results, 138 samples of residual extraction fluid for Quantum Blue analysis, and 170 fresh stool samples for ELISA analysis. Spearman's rank correlation coefficient was 0.94 for results obtained by IBDoc vs Quantum Blue and 0.85 for results obtained by IBDoc vs ELISA. At the low range of calprotectin level (<500 mu g/g), 91% of IBDoc-Quantum Blue results were within the predefined limits of agreement (>= 100 mu g/g), and 71% of IBDoc-ELISA results were in agreement. At the high range of calprotectin level (>= 500 mu g/g), 81% of IBDoc-Quantum Blue results were within the predefined limits of agreement (+/- 200 mu g/g) and 64% of IBDoc-ELISA results were in agreement. CONCLUSIONS:

关键词： Inflammatory bowel disease   Vaccination   Immunization   Immunogenicity   Safety   Children  

摘要： The incidence of pediatric inflammatory bowel disease (IBD) is rising, as is the use of immunomodulatory and biological drugs. IBD patients are vulnerable to infections owing to disease-related immunological alterations and drug-induced systemic immunosuppression. Although many infections are vaccine preventable, vaccination coverage in IBD patients is insufficient. Current guidelines recommend that children with IBD follow the same routine immunization schedule as healthy children, avoiding live vaccines during immunosuppressive therapy. Immunization status should be checked at diagnosis, and patients should be immunized with the vaccines they need. Some studies have demonstrated a suboptimal immune response to vaccinations in IBD patients, but responsible mechanisms are poorly understood. In this manuscript, we provide a broad review of available data about vaccine coverage rates, immunogenicity and safety of both killed and live attenuated vaccinations in the pediatric IBD population;furthermore, we provide comprehensive information regarding current guidelines for immunization of children with IBD and their household contacts. A comprehensive search of published literature using the PubMed (http://***/pubmed/) database was carried out to identify all articles published in English from 1998 to March 2017, using the following key terms: "inflammatory bowel disease", "vaccination", "immunization", "immunogenicity", "safety" and "children". (C) 2017 Elsevier Ltd. All rights reserved.