Quantification of Mucosal Activity from Colonoscopy Reports via the Simplified Endoscopic Mucosal Assessment for Crohn’s Disease

Background Endoscopic mucosal healing is the gold standard for evaluating Crohn’s disease (CD) treatment efficacy. Standard endoscopic indices are not routinely used in clinical practice, limiting the quality of retrospective research. A method for retrospectively quantifying mucosal activity from documentation is needed. We evaluated the simplified endoscopic mucosal assessment for CD (SEMA-CD) to determine if it can accurately quantify mucosal severity recorded in colonoscopy reports. Methods Pediatric patients with CD underwent colonoscopy that was video recorded and evaluated via Simple Endoscopic Score for CD (SES-CD) and SEMA-CD by central readers. Corresponding colonoscopy reports were de-identified. Central readers blinded to clinical history and video scoring were randomly assigned colonoscopy reports with and without images. The SEMA-CD was scored for each report. Correlation with video SES-CD and SEMA-CD were assessed with Spearman rho, inter-rater, and intrarater reliability with kappa statistics. Results Fifty-seven colonoscopy reports were read a total of 347 times. The simplified endoscopic mucosal assessment for CD without images correlated with both SES-CD and SEMA-CD from videos (rho = 0.82, P < .0001 for each). The addition of images provided similar correlation. Inter-rater and intrarater reliability were 0.93 and 0.92, respectively. Conclusions The SEMA-CD applied to retrospective evaluation of colonoscopy reports accurately and reproducibly correlates with SES-CD and SEMA-CD of colonoscopy videos. The SEMA-CD for evaluating colonoscopy reports will enable quantifying mucosal healing in retrospective research. Having objective outcome data will enable higher-quality research to be conducted across multicenter collaboratives and in clinical registries. External validation is needed.

Treatment of Inflammatory Bowel Disease: A Comprehensive Review

Inflammatory bowel disease (IBD), as a global disease, has attracted much research interest. Constant research has led to a better understanding of the disease condition and further promoted its management. We here reviewed the conventional and the novel drugs and therapies, as well as the potential ones, which have shown promise in preclinical studies and are likely to be effective future therapies. The conventional treatments aim at controlling symptoms through pharmacotherapy, including aminosalicylates, corticosteroids, immunomodulators, and biologics, with other general measures and/or surgical resection if necessary. However, a considerable fraction of patients do not respond to available treatments or lose response, which calls for new therapeutic strategies. Diverse therapeutic options are emerging, involving small molecules, apheresis therapy, improved intestinal microecology, cell therapy, and exosome therapy. In addition, patient education partly upgrades the efficacy of IBD treatment. Recent advances in the management of IBD have led to a paradigm shift in the treatment goals, from targeting symptom-free daily life to shooting for mucosal healing. In this review, the latest progress in IBD treatment is summarized to understand the advantages, pitfalls, and research prospects of different drugs and therapies and to provide a basis for the clinical decision and further research of IBD.

The Association Between Genetic Variants, Pharmacokinetics, and Infliximab Efficacy in Pediatric Patients With Crohn's Disease in China

Background: Infliximab is an effective therapy for Crohn's disease (CD). Early non-invasive predictors of disease remission allow for modification of treatments. The aim of this study was to investigate the associations between genetic variants, pharmacokinetics, and infliximab efficacy in pediatric patients with CD.Methods: This retrospective observational study included CD patients under infliximab therapy between August 2015 and December 2020. Information on demographics, laboratory tests, medication data, and disease activity index was collected. The trough levels of infliximab (TLI) and antibodies to infliximab (ATI) were measured at week 14, and reactive drug monitoring was performed during follow-up. Ten single-nucleotide polymorphisms involved in the NF-κB-mediated inflammatory response, pharmacokinetics, and therapeutic response to infliximab were genotyped.Results: A total of 62 pediatric CD patients were enrolled. The clinical remission (CR) rate was 69.4 and 63.2% at week 14 and week 30, respectively. TLI at week 14 was significantly independently associated with CR at week 14 and mucosal healing (MH) at week 30 (p = 0.007 and p = 0.025, respectively). The optimal TLI threshold level capable of distinguishing between the CR and non-CR groups was 2.62 μg/ml (p < 0.001, area under the curve = 0.79, sensitivity = 69.2%, specificity = 78.9%), while that capable of distinguishing between the MH and non-MH groups was 3.34 μg/ml (p < 0.001, area under the curve = 0.85, sensitivity = 78.6%, specificity = 79.4%). Rs3397 in TNFRSF1B was associated with time to ATI production in CD patients (p < 0.001).Conclusions: Higher TLI contributed to achieving MH. Genotyping rs3397 in TNFRSF1B may identify patients who are prone to generating immunogenicity to drugs.

Current Use of EEN in Pre-Operative Optimisation in Crohn’s Disease

Despite the increasing array of medications available for the treatment of Crohn’s disease and a focus on mucosal healing, approximately 35% of patients with Crohn’s disease undergo bowel surgery at some stage. The importance of nutritional optimisation before Crohn’s surgery is well-highlighted by surgical, nutritional, and gastroenterological societies with the aim of reducing complications and enhancing recovery. Surgical procedures are frequently undertaken when other treatment options have been unsuccessful, and, thus, patients may have lost weight and/or required steroids, and are therefore at higher risk of post-operative complications. EEN is used extensively in the paediatric population to induce remission, but is not routinely used in the induction of remission of adult Crohn’s disease or in pre-operative optimisation. Large prospective studies regarding the role of pre-operative EEN are lacking. In this review, we evaluate the current literature on the use of EEN in pre-operative settings and its impact on patient outcomes.

Cells and Mediators of Inflammation as Effectors of Epithelial Repair in the Inflamed Intestine

Mucosal and histological healing have become the gold standards for assessing the efficacy of therapy in patients living with inflammatory bowel diseases (IBD). Despite these being the accepted goals in therapy, the mechanisms that underlie the healing of the mucosa after an inflammatory insult are not well understood, and many patients fail to meet this therapeutic endpoint. Here we review the emerging evidence that mediators (e.g. prostaglandins, cytokines, proteases, reactive oxygen and nitrogen species) and innate immune cells (e.g. neutrophils and monocytes/macrophages), that are involved in the initiation of the inflammatory response, are also key players in the mechanisms underlying mucosal healing to resolve chronic inflammation in the colon. The dual function mediators comprise an inflammation/repair program that returns damaged tissue to homeostasis. Understanding details of the dual mechanisms of these mediators and cells may provide the basis for the development of drugs that can help to stimulate epithelial repair in patients affected by IBD.

Induction of Remission in Pediatric Crohn’s Disease Patients Assessed by the Mucosal Inflammation Noninvasive Index

Mucosal healing (MH) is the main therapeutic goal of Crohn’s disease (CD). The Mucosal Inflammation Noninvasive Index (MINI) appears to be a promising tool for distinguishing MH from its inflammation. This study aims to evaluate MINI in monitoring remissions induced by exclusive enteral nutrition (EEN) in pediatric CD patients. Out of 55 newly diagnosed CD children, 31 who completed 6–8 weeks of EEN were analyzed. Clinical and biochemical data, activity of CD assessed with the Pediatric Crohn’s Disease Activity Index (PCDAI) and MINI were compared within seven days pre- and post-EEN. Response to induction therapy was defined as a decrease of PCDAI by >12.5 points. The follow-up was performed up to 12 months after EEN termination. Out of 31 children who completed 6–8 weeks of EEN, eight required corticosteroids in addition to EEN. Twenty-four patients (77%) responded to induction therapy. In responders, MINI decreased from 19 (Q1:17; Q3:22) to 12 (Q1:6; Q3:14), p < 0.001. The diagnostic accuracy of post-EEN MINI and post-EEN fecal calprotectin (FC) for treatment failure were AUC: 0.899 (95%CI: 0.737–1.000) and 0.762 (95%CI: 0.570–0.954), respectively. In the follow-up of 25 patients (80.6%), the post-EEN MINI of ≥13 points predicted CD relapse (87.5% sensitivity; 64.7% specificity), while FC had no prognostic value. MINI allows for monitoring of EEN and is superior in predicting disease relapse to FC.