Reliability and Initial Validation of the Ulcerative Colitis Endoscopic Index of Severity

Background & AimsWe studied the reliability of the previously described Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and validated it with an independent cohort of investigators.MethodsWe created a new library of 57 videos of flexible sigmoidoscopy and stratified them based on disease severity. Twenty-five investigators were each randomly assigned to assess 28 videos (which included 4 duplicates to assess intraobserver reliability). Investigators were blinded to clinical details except for 2 of 4 duplicated videos (to assess the impact of knowledge of symptoms on assessment). Three descriptors (“vascular pattern”, “bleeding”, and “erosions and ulcers”) comprising the UCEIS were scored with a visual analogue scale (VAS) to assess overall severity. Intrainvestigator and interinvestigator agreement was characterized by κ statistical analysis; reliability ratios were used to compare VAS and UCEIS scores.ResultsThere was a high level of correlation between UCEIS scores and overall assessment of severity (correlation coefficient, 0.93). Internal consistency (Cronbach α analysis) was 0.86. Intrainvestigator and interinvestigator reliability ratios for UCEIS scores were 0.96 and 0.88, respectively. Intrainvestigator agreement in determination of the UCEIS score was good (κ = 0.72), with individual descriptors ranging from a κ of 0.47 (for bleeding) to 0.87 (for vascular pattern). Interinvestigator agreement in determination of UCEIS scores was moderate (κ = 0.50), with descriptors ranging from a κ of 0.48 (for bleeding) to 0.54 (for vascular pattern). Intrainvestigator variability in determining UCEIS scores did not change appreciably when a video was presented with clinical details.ConclusionsThe UCEIS and its components show satisfactory intrainvestigator and interinvestigator reliability. Among investigators, the UCEIS accounted for a median of 86% of the variability in evaluation of overall severity on the VAS when assessing the endoscopic severity of UC and was unaffected by knowledge of clinical details

IL-23–responsive innate lymphoid cells are increased in inflammatory bowel disease

Increased numbers of innate lymphoid cells in patients with inflammatory bowel disease

Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor–neutralizing therapy in patients with inflammatory bowel disease

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex chronic inflammatory conditions of the gastrointestinal tract that are driven by perturbed cytokine pathways. Anti-tumor necrosis factor-α (TNF) antibodies are mainstay therapies for IBD. However, up to 40% of patients are nonresponsive to anti-TNF agents, which makes the identification of alternative therapeutic targets a priority. Here we show that, relative to healthy controls, inflamed intestinal tissues from patients with IBD express high amounts of the cytokine oncostatin M (OSM) and its receptor (OSMR), which correlate closely with histopathological disease severity. The OSMR is expressed in nonhematopoietic, nonepithelial intestinal stromal cells, which respond to OSM by producing various proinflammatory molecules, including interleukin (IL)-6, the leukocyte adhesion factor ICAM1, and chemokines that attract neutrophils, monocytes, and T cells. In an animal model of anti-TNF-resistant intestinal inflammation, genetic deletion or pharmacological blockade of OSM significantly attenuates colitis. Furthermore, according to an analysis of more than 200 patients with IBD, including two cohorts from phase 3 clinical trials of infliximab and golimumab, high pretreatment expression of OSM is strongly associated with failure of anti-TNF therapy. OSM is thus a potential biomarker and therapeutic target for IBD, and has particular relevance for anti-TNF-resistant patients

Chromoendoscopy versus autofluorescence imaging for neoplasia detection in patients with longstanding ulcerative colitis (FIND-UC): an international, multicentre, randomised controlled trial

Background: Patients with longstanding ulcerative colitis (UC) undergo regular dysplasia surveillance because of increased colorectal cancer risk. Previous studies demonstrated that autofluorescence imaging (AFI) and chromoendoscopy (CE) increased dysplasia detection. The aim of this study was to determine whether AFI should be further studied as an alternative method for dysplasia surveillance in patients with longstanding UC. Methods: In this prospective international, randomised trial, 210 patients undergoing colonoscopy surveillance for longstanding UC were randomised between 1 August 2013 and 10 March 2017 for inspection with either AFI or CE (105:105). Randomisation was minimised for a previous history of dysplasia and a previous history of primary sclerosing cholangitis. The main outcome was the relative dysplasia detection rate calculated by the ratio of AFI versus CE. This relative dysplasia detection rate was determined for the proportion of UC patients in which at least one dysplastic lesion was detected and for the mean number of dysplastic lesions per patient. The relative dysplasia detection rate needed to be above 0·67 for both outcomes to support performing a subsequent large non-inferiority trial, using an 80% confidence interval. Analysis was performed per protocol. The trial is registered at Netherlands Trial Register (NTR4062). Findings: AFI detected dysplasia in 13 (12·4%) patients, compared to 20 patients (19·1%) with CE. The relative dysplasia detection rate of CE versus AFI for the proportion of UC patients with at least one dysplastic lesion was 0·65 (80% CI; 0·43-0·99). The mean number of detected dysplastic lesions per patient was 0·13 for AFI compared to 0·37 for CE (relative dysplasia detection rate 0·36, 80% CI; 0·21-0·61). Two patients experienced an adverse event (intraprocedural mild bleeding = 1, abdominal pain = 1) in the AFI-arm and three patients (intraprocedural mild bleeding = 2, perforation = 1) in the CE-arm. Interpretation: In this randomised study comparing AFI with CE for dysplasia surveillance in patients with longstanding UC, AFI did not meet criteria for proceeding to a large non-inferiority trial. Therefore, current AFI technology should not be further investigated as an alternative dysplasia surveillance method. Funding: Olympus Europe and Olympus Keymed, Oxford and Nottingham NIHR biomedical research centres

Developing an instrument to assess the endoscopic severity of ulcerative colitis : The Ulcerative Colitis Endoscopic Index of Severity (UCEIS)

Full list of Investigators is given at the end of the article.Background: Variability in endoscopic assessment necessitates rigorous investigation of descriptors for scoring severity of ulcerative colitis (UC). Objective: To evaluate variation in the overall endoscopic assessment of severity, the intra- and interindividual variation of descriptive terms and to create an Ulcerative Colitis Endoscopic Index of Severity which could be validated. Design: A two-phase study used a library of 670 video sigmoidoscopies from patients with Mayo Clinic scores 0-11, supplemented by 10 videos from five people without UC and five hospitalised patients with acute severe UC. In phase 1, each of 10 investigators viewed 16/24 videos to assess agreement on the Baron score with a central reader and agreed definitions of 10 endoscopic descriptors. In phase 2, each of 30 different investigators rated 25/60 different videos for the descriptors and assessed overall severity on a 0-100 visual analogue scale. κ Statistics tested inter- and intraobserver variability for each descriptor. A general linear mixed regression model based on logit link and β distribution of variance was used to predict overall endoscopic severity from descriptors. Results: There was 76% agreement for 'severe', but 27% agreement for 'normal' appearances between phase I investigators and the central reader. In phase 2, weighted κ values ranged from 0.34 to 0.65 and 0.30 to 0.45 within and between observers for the 10 descriptors. The final model incorporated vascular pattern, (normal/patchy/ complete obliteration) bleeding (none/mucosal/luminal mild/luminal moderate or severe), erosions and ulcers (none/erosions/superficial/deep), each with precise definitions, which explained 90% of the variance (pR2, Akaike Information Criterion) in the overall assessment of endoscopic severity, predictions varying from 4 to 93 on a 100-point scale (from normal to worst endoscopic severity). Conclusion: The Ulcerative Colitis Endoscopic Index of Severity accurately predicts overall assessment of endoscopic severity of UC. Validity and responsiveness need further testing before it can be applied as an outcome measure in clinical trials or clinical practice.publishersversionPeer reviewe

Clinical Genomics for the Diagnosis of Monogenic Forms of Inflammatory Bowel Disease: A Position Paper From the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition

BACKGROUND: It is important to identify patients with monogenic IBD as management may differ from classical IBD. In this position statement we formulate recommendations for the use of genomics in evaluating potential monogenic causes of IBD across age groups. METHODS: The consensus included paediatric IBD specialists from the Paediatric IBD Porto group of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and specialists from several monogenic IBD research consortia. We defined key topics and performed a systematic literature review to cover indications, technologies (targeted panel, exome and genome sequencing), gene panel setup, cost-effectiveness of genetic screening, and requirements for the clinical care setting. We developed recommendations that were voted upon by all authors and Porto group members (32 voting specialists). RESULTS: We recommend next-generation DNA-sequencing technologies to diagnose monogenic causes of IBD in routine clinical practice embedded in a setting of multidisciplinary patient care. Routine genetic screening is not recommended for all IBD patients. Genetic testing should be considered depending on age of IBD-onset (infantile IBD, very early-onset IBD, paediatric or young adult IBD), and further criteria, such as family history, relevant comorbidities, and extraintestinal manifestations. Genetic testing is also recommended in advance of hematopoietic stem cell transplantation. We developed a diagnostic algorithm that includes a gene panel of 75 monogenic IBD genes. Considerations are provided also for low resource countries. CONCLUSIONS: Genomic technologies should be considered an integral part of patient care to investigate patients at risk for monogenic forms of IBD