Computer-Aided Imaging Analysis of Probe-Based Confocal Laser Endomicroscopy With Molecular Labeling and Gene Expression Identifies Markers of Response to Biological Therapy in IBD Patients: The Endo-Omics Study

Abstract Background We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response. Methods Twenty-nine patients (15 with Crohn’s disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4β7 therapy. Biopsies were taken for fluorescein isothiocyanate–labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort. Results In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn’s disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7). Conclusions Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF–responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders

Salerno's model of DNA reanalysed: could solitons have biological significance?

We investigate the sequence-dependent behaviour of localised excitations in a toy, nonlinear model of DNA base-pair opening originally proposed by Salerno. Specifically we ask whether ``breather'' solitons could play a role in the facilitated location of promoters by RNA polymerase. In an effective potential formalism, we find excellent correlation between potential minima and {\em Escherichia coli} promoter recognition sites in the T7 bacteriophage genome. Evidence for a similar relationship between phage promoters and downstream coding regions is found and alternative reasons for links between AT richness and transcriptionally-significant sites are discussed. Consideration of the soliton energy of translocation provides a novel dynamical picture of sliding: steep potential gradients correspond to deterministic motion, while ``flat'' regions, corresponding to homogeneous AT or GC content, are governed by random, thermal motion. Finally we demonstrate an interesting equivalence between planar, breather solitons and the helical motion of a sliding protein ``particle'' about a bent DNA axis.Comment: Latex file 20 pages, 5 figures. Manuscript of paper to appear in J. Biol. Phys., accepted 02/09/0

Impact of COVID-19 outbreak on clinical practice and training of young gastroenterologists: A European survey

Background: SARS-CoV-2 disease (COVID-19) is a major challenge for the healthcare system and physicians, imposing changes in daily clinical activity. Aims: we aimed to describe what European trainees and young gastroenterologists know about COVID-19 and identify training gaps to implement educational programs. Methods: A prospective web-based electronic survey was developed and distributed via e-mail to all members of the Italian Young Gastroenterologist and Endoscopist Association and to European representatives. Results: One hundred and ninety-seven subjects participated in the survey, of whom 14 (7.1%) were excluded. The majority were gastroenterologists in training (123, 67.7%) working in institutions with COVID-19 inpatients (159, 86.9%), aged 6430 years (113, 61.8%). The activity of Gastroenterology Units was restricted to emergency visits and endoscopy, with reductions of activities of up to 90%. 84.5% of participants felt that the COVID-19 outbreak impacted on their training, due to unavailability of mentors (52.6%) and interruption of trainee's involvement (66.4%). Most participants referred absence of training on the use of personal protective equipment, oxygen ventilation systems and COVID-19 therapies. Conclusion: COVID-19 outbreak significantly impacted on gastroenterologists\u2019 clinical activity. The resources currently deployed are inadequate, and therefore educational interventions to address this gap are warranted in the next future

A Virtual Chromoendoscopy Artificial Intelligence system to detect endoscopic and histologic activity/remission and predict clinical outcomes in Ulcerative Colitis

Background and study aims Endoscopic and histologic remission (ER, HR) are therapeutic targets in ulcerative colitis (UC) and virtual chromoendoscopy (VCE) improves the endoscopic assessment and the prediction of histology. However, interobserver variability is a limitation for widespread standardised endoscopic assessment using all scoring systems. We aimed to develop an artificial intelligence tool to distinguish ER/activity, and predict histology and risk of flare from white-light-endoscopy (WLE) and VCE videos. Patients and methods 1090 endoscopic videos (638287 frames), from 283 patients, were used to develop a convolutional neural network (CNN). UC endoscopic activity was graded by experts with Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and PICaSSO. The CNN was trained to distinguish ER/activity on endoscopy videos, and retrained to predict HR/activity, defined according to multiple indices, and predict outcome; CNN and humans agreement was measured. Results The AI system detected ER (UCEIS ≤1) in WLE videos with 72% sensitivity (Se), 87% specificity (Sp), and area under the ROC curve (AUROC) of 0.85; For detection of ER in VCE videos (PICaSSO ≤3) Se was 79%, Sp 95%, and the AUROC 0.94. Prediction of HR was similar between WLE and VCE videos (accuracies ranging 80%-85%). The model’s stratification of risk of flare was similar to that of physician-assessed endoscopy scores. Conclusions Our system accurately distinguished ER/activity and predicted HR and clinical outcomes from colonoscopy videos. This is the first computer model developed to detect inflammation/healing using VCE through the PICaSSO score and the first computer tool providing endoscopic, histologic, and clinical assessmen

Supplementary Material for: Beyond Irritable Bowel Syndrome: The Efficacy of the Low Fodmap Diet for Improving Symptoms in Inflammatory Bowel Diseases and Celiac Disease

<b><i>Background and Aim:</i></b> To evaluate the usefulness of a low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) diet on patients with irritable bowel syndrome (IBS), non-active inflammatory bowel diseases (IBD), and celiac disease (CD) on a gluten-free diet (GFD). <b><i>Methods:</i></b> Dietetic interventional prospective study. IBS, IBD, and CD subjects were evaluated to check if they fulfilled the Rome III criteria. Each subject was educated to follow a low FODMAP diet after being evaluated by filling out questionnaires that assessed the quality of life (QoL) and symptoms experienced (IBS-SSS and SF-36), and was reevaluated after 1 and 3 months. <b><i>Results:</i></b> One hundred twenty-seven subjects were enrolled: 56 with IBS, 30 with IBD, and 41 with CD. IBS-SSS showed that abdominal symptoms improved after 1 and 3 months of diet in all subjects, with significant difference among the 3 groups at T0 (average scores IBS: 293 ± 137, IBD: 206 ± 86, CD: 222 ± 65, <i>p</i> < 0.001), but no difference at T3 (IBS: 88 ± 54, IBD: 73 ± 45, CD: 77 ± 49, <i>p</i> = ns). By analyzing the SF-36 questionnaire, we did not observe any difference between the 3 groups, in terms of response to diet (<i>p</i> = ns), we observed a clinical improvement from T0 to T3 for most of the questionnaire’s domains. <b><i>Conclusions:</i></b> A low FODMAP diet could be a valid option to counter ­abdominal symptoms in patients with IBS, non-active IBD, or CD on a GFD, and thus, improve their QoL and social ­relations