关键词： Biopsychosocial screening   Children   Integrated care   Inflammatory bowel disease   Crohn's disease   Ulcerative colitis  

摘要： Objective: The adult INTERMED is used to determine case complexity and psychosocial needs. We developed and validated a pediatric version of the INTERMED for children and adolescents with inflammatory bowel disease (IBD) and assessed its utility in predicting healthcare utilization. Methods: We performed a cross-sectional study of children (aged 8-17 y) with IBD (n = 148) and their parents, seen in a hospital-based clinic. Subjects completed semi-structured interviews that were scored on the 34 pIBD-INTERMED items. To assess inter-rater reliability, 40 interviews were videotaped and scored by a second assessor. Convergent and predictive validity were assessed by examining the relation of the pIBD-INTERMED to standardized measures of psychological, social, and family functioning, disease activity, and healthcare utilization. Results: Correlational analyses supported the validity of all five pIBD-INTERMED domains with very good inter rater reliability (median r = 0.87) and internal consistency (a = 0.91) for the total complexity index. Ratings of 2-3 on the pIBD-INTERMED "mental health/cognitive threat" item were associated with greater odds of behavior and social problems (CBCL-Internalizing scale OR = 7.27, 95% CI 2.17-24.36);CBCL-Externalizing scale OR = 24.79, 95% CI 5.00-122.84), depression (Children's Depression Inventory OR = 8.52, 95% CI 1.70-43.02) and anxiety (Multidimensional Anxiety for Children OR = 11.57, 95% CI 3.00-45.37). The pIBD-INTERMED complexity index added significantly to the prediction of healthcare utilization, beyond the contribution of disease severity. Conclusions: The pIBD-INTERMED is a reliable and valid tool for identifying psychosocial risks and needs of children with IBD. It can be used to guide planning of individualized care and enhance interdisciplinary pediatric IBD care.

关键词： inflammatory bowel disease   red flag   spondyloarthritis  

摘要： Collaboration between gastroenterologists and rheumatologists is recommended for the correct management of patients with associated spondyloarthritis (SpA) and inflammatory bowel disease (IBD). We aimed to establish the appropriateness of several red flags for a prompt specialist referral. A systematic review of the literature was performed using the GRADE method to describe the prevalence of co-existing IBD-SpA and the diagnostic accuracy of red flags proposed by a steering committee. Then, a consensus among expert gastroenterologists and rheumatologists (10 in the steering committee and 13 in the expert panel) was obtained using the RAND method to confirm the appropriateness of each red flag as 'major' (one sufficient for patient referral) or 'minor' (at least three needed for patient referral) criteria for specialist referral. The review of the literature confirmed the high prevalence of co-existing IBD-SpA. Positive and negative predictive values of red flags were not calculated, given the lack of available data. A consensus among gastroenterology and rheumatology specialists was used to confirm the appropriateness of each red flag. Major criteria to refer patients with SpA to the gastroenterologist included: rectal bleeding, chronic abdominal pain, perianal fistula or abscess, chronic diarrhoea and nocturnal symptoms. Major criteria to refer patients with IBD to the rheumatologist included: chronic low back pain, dactylitis, enthesitis and pain/swelling of peripheral joints. Several major and minor red flags have been identified for the diagnosis of co-existing IBD-SpA. The use of red flags in routine clinical practice may avoid diagnostic delay and reduce clinic overload.

关键词： infliximab   mass spectrometry   therapeutic drug monitoring  

摘要： Aims Therapeutic drug monitoring (TDM) of infliximab (IFX) appears to be beneficial for patients with inflammatory bowel disease (IBD). However, the recommended target concentrations depend partly on the method used to quantify IFX. Since we recently developed a liquid chromatography-tandem mass spectrometry method to quantify IFX, we aimed to determine IFX trough concentrations (Cmin) associated with biological remission. Methods We retrospectively measured IFX Cmin in sera from 55 patients with IBD, on IFX maintenance therapy, and for whom demographic, biological and clinical data were collected from medical records. A threshold of IFX Cmin associated with biological remission (defined by C-reactive protein < 5 mg l(-1) and faecal calprotectin <150 mu g g(-1)) was determined using receiver operating characteristics analysis. Results IFX Cmin ranged from <1 mg l(-1) to 57.2 mg l(-1). IFX Cmin were higher (P = 0.038) in patients with biological remission and a cut-off of IFX Cmin set to 6.2 mg l(-1) was associated with biological remission (sensitivity = 0.75, 95% confidence interval 0.58-0.75;specificity = 0.61, 95% confidence interval 0.39-0.83). Conclusion Liquid chromatography-tandem mass spectrometry measurement of IFX Cmin and the determination of a new threshold of IFX Cmin associated with biological remission are new steps towards IFX treatment personalization in patients with IBD.

关键词： INFLAMMATORY bowel diseases   CROHN’S disease   ULCERATIVE colitis   TUMOR necrosis factor receptors   THERAPEUTICS  

摘要： Crohn's disease and ulcerative colitis are driven by both common and distinct underlying mechanisms of pathobiology. Both diseases, exhibit heterogeneity underscored by the variable clinical responses to therapeutic interventions. We aimed to identify disease-driving pathways and classify individuals into subpopulations that differ in their pathobiology and response to treatment. We applied hierarchical clustering of enrichment scores derived from gene set variation analysis of signatures representative of various immunological processes and activated cell types, to a colonic biopsy dataset that included healthy volunteers, Crohn's disease and ulcerative colitis patients. Patient stratification at baseline or after anti-TNF treatment in clinical responders and non-responders was queried. Signatures with significantly different enrichment scores were identified using a general linear model. Comparisons to healthy controls were made at baseline in all participants and then separately in responders and non-responders. Fifty-nine percent of the signatures were commonly enriched in both conditions at baseline, supporting the notion of a disease continuum within ulcerative colitis and Crohn's disease. Signatures included T cells, macrophages, neutrophil activation and poly:IC signatures, representing acute inflammation and a complex mix of potential disease-driving biology. Collectively, identification of significantly enriched signatures allowed establishment of an inflammatory bowel disease molecular activity score which uses biopsy transcriptomics as a surrogate marker to accurately track disease severity. This score separated diseased from healthy samples, enabled discrimination of clinical responders and non-responders at baseline with 100% specificity and 78.8% sensitivity, and was validated in an independent data set that showed comparable classification. Comparing responders and non-responders separately at baseline to controls, 43% and 70% of signatures were enri

关键词： Drug development   Irritable bowel syndrome  

摘要： A new drug restores a compromised intestinal barrier and ameliorates colitis in mice by modulating paracellular permeability through a newly discovered mechanism.

关键词： Complications   Neoplasm   Prevention   Noninvasive Test   Biomarker  

摘要： BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, are at increased risk for colorectal cancer (CRC). Analyses of DNA methylation patterns in stool samples have been reported to detect CRC in patients with IBD. We sought to validate these findings in larger cohorts and assess the accuracy of analysis of DNA methylation patterns in stool for detection of CRC and high-grade dysplasia (HGD) normalized to methylation level at ZDHHC1. METHODS: We obtained buffered, frozen stool samples from a US case-control study and from 2 European surveillance cohorts (referral or population based) of patients with chronic ulcerative colitis (n = 248), Crohn's disease (n = 82), indeterminate colitis (n = 2), or IBD with primary sclerosing cholangitis (n = 38). Stool samples were collected before bowel preparation for colonoscopy or at least 1 week after colonoscopy. Among the study samples, stools from individuals with IBD but without neoplasia were used as controls (n = 291). DNA was isolated from stool, exposed to bisulfite, and then assayed by multiplex quantitative allele-specific real-time target and signal amplification. We analyzed methylation levels of BMP3, NDRG4, VAV3, and SFMBT2 relative to the methylation level of ZDHHC1, and compared these between patients with CRC or HGD and controls. RESULTS: Levels of methylation at BMP3 and VAV3, relative to ZDHHC1 methylation, identified patients with CRC and HGD with an area under the curve value of 0.91 (95% CI, 0.77-1.00). Methylation levels at specific promotor regions of these genes identified 11 of the 12 patients with CRC and HGD, with 92% sensitivity (95% CI, 60%-100%) and 90% specificity (95% CI, 86%-93%). The proportion of false-positive results did not differ significantly among the case-control, referral cohort, and population cohort studies (P = .60) when the 90% specificity cut-off from the whole sample set was applied. CONCLUSIONS: In an analysis of st

关键词： Crohn disease   school attendance   ulcerative colitis  

摘要： Objectives: Inflammatory bowel diseases (IBDs) are chronic diseases which negatively affect the schooling of children. The aim is to analyze school absenteeism and its causes in children followed for IBD. Methods: A prospective multicenter study of IBD patients aged from 5 to 18 years old, from September 2016 to June 2017. Data on absenteeism and its causes were collected via a monthly questionnaire completed by patients or their family by mail. The results were compared with existing data supplied by the school authorities (497 students without IBD divided by class). Results: A total of 106 patients (62 boys), median age of 14 (5-18), were included. The global response rate was 83.1%. The patients with IBD were absent an average of 4.8% +/- 5.5% of school days during the school year, against 3.2% +/- 1.6% for non IBD group (P = 0.034). Digestive disorders accounted for 34% of the causes of absenteeism. Approximately 27% of the absences were due to scheduled events (hospitalizations, endoscopy, or consultations). By excluding the absences for scheduled care, the rate of school absenteeism of patients with IBD is significantly lower than that of non-IBD group. Conclusion: Children with IBD are more frequently absent from school than non-IBD group. The main cause of school absenteeism appears to be associated with the disease itself. The share of scheduled absenteeism is quite large. The organization and scheduling of the patients' care path must be a priority to maximally limit the negative impact of their disease on the patients' schooling.

关键词： Inflammatory bowel disease   Mucosal healing   Histological healing   Target to treat approach  

摘要： Management of inflammatory bowel diseases has witnessed paradigm shift from 5-aminosalicylic acid and glucocorticoids to various immunosuppressant and biological agents. Targets of therapy have also been changed drastically from symptomatic improvement to mucosal, histological healing, and recently transmural healing. Mucosal healing is associated with reduced need of steroid therapy, hospitalization, and surgery. However, whether mucosal healing alters the natural history of disease remains to be proven. Though assessment of mucosal healing is traditionally done by endoscopic examination, newer tests like fecal calprotectin, capsule endoscopy, and magnetic resonance enterography have also shown promising results. Various immunosuppressants and biologicals are the main therapy being used to achieve mucosal healing. This review focuses on the need for achieving mucosal healing, its long-term benefits, various methods and algorithm for diagnosis, and achievement of mucosal healing.