Artificial Intelligence for Real-Time Prediction of the Histology of Colorectal Polyps by General Endoscopists.

BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.

Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis.

BACKGROUND: The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE). OBJECTIVE: We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both. METHODS: We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed. RESULTS: In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P < .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P < .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r = -0.352, P < .001) and both inflammatory and fibrostenotic features scores (r = -0.665, P < .001; r = -0.446, P < .001, respectively), but not with symptoms and complications scores (r = 0.047, P = .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity. CONCLUSIONS: I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation.

Long-term Durability Between Parent and Child Patient Reported Outcomes in Eosinophilic Esophagitis.

BACKGROUND: Because young children cannot self-report symptoms, there is a need for parent surrogate reports. While early work suggested parent child alignment for eosinophil esophagitis (EoE) patient reported outcomes (PROs), the longitudinal alignment is unclear. OBJECTIVE: To assess the agreement and longitudinal stability of PROs between children with EoE and their parents. METHODS: 292 parent-child respondents completed 723 completed questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models. RESULTS: The cohort had a median disease duration equalling 3.7 years and was predominantly male (73.6%) and white (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent report (PEESSv2.0 0.83, PedsQL-EoE 0.74) with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (p ≥ 0.32), whereas child-reported PedsQL-EoE scores improved (p = 0.026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (p < 0.001) and differences were driven by psychosocial PRO domains. CONCLUSION: There is strong longitudinal alignment between child and parent report using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children.

Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell-Fibroblast Crosstalk.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences. METHODS: Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers sites (n = 311) and 2 independent replication cohorts (n = 83). Inclusion criteria for fibrostenotic EoE were endoscopic rings, stricture, and/or a history of dilation. Endoscopic, histologic, and molecular features were assessed by the EoE Endoscopic Reference Score, EoE Histology Scoring System, EoE Diagnostic Panel, and RNA sequencing. Esophageal endothelial TSPAN12 expression and functional effects on barrier integrity and gene expression were analyzed in vitro. RESULTS: TSPAN12 was the gene most correlated with fibrostenosis (r = -0.40, P < .001). TSPAN12 was lower in fibrostenotic EoE and correlated with EoE Endoscopic Reference Score, EoE Diagnostic Panel, and EoE Histology Scoring System (r = 0.34-0.47, P < .001). Lower TSPAN12 associated with smaller esophageal diameter (r = 0.44, P = .03), increased lamina propria fibrosis (r = -0.41, P < .001), and genes enriched in cell cycle-related pathways. Interleukin (IL)-13 reduced TSPAN12 expression in endothelial cells. Conversely, anti-IL-13 therapy increased TSPAN12 expression. TSPAN12 gene silencing increased endothelial cell permeability and dysregulated genes associated with extracellular matrix pathways. Endothelial cell-fibroblast crosstalk induced extracellular matrix changes relevant to esophageal remodeling. CONCLUSIONS: Patients with fibrostenotic EoE express decreased levels of endothelial TSPAN12. We propose that IL-13 decreases TSPAN12, likely contributing to the chronicity of EoE by promoting tissue remodeling through fibroblast-endothelial cell crosstalk.

Mucosal Microbiota Associated With Eosinophilic Esophagitis and Eosinophilic Gastritis.

OBJECTIVE: The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) in a geographically diverse cohort of patients compared to controls. METHODS: We conducted a prospective study of individuals with eosinophilic gastrointestinal disease (EGID) in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies, and stool collected. Total bacterial load was determined from mucosal biopsy samples by quantitative polymerase chain reaction (PCR). Community composition was determined by small subunit rRNA gene amplicons. RESULTS: One hundred thirty-nine mucosal biopsies were evaluated corresponding to 93 EoE, 17 EoG, and 29 control specimens (18 esophageal) from 10 sites across the United States. Dominant community members across disease activity differed significantly. When comparing EoE and EoG with controls, the dominant taxa in individuals with EGIDs was increased ( Streptococcus in esophagus; Prevotella in stomach). Specific taxa were associated with active disease for both EoE ( Streptococcus , Gemella ) and EoG ( Leptotrichia ), although highly individualized communities likely impacted statistical testing. Alpha diversity metrics were similar across groups, but with high variability among individuals. Stool analyses did not correlate with bacterial communities found in mucosal biopsy samples and was similar in patients and controls. CONCLUSIONS: Dominant community members ( Streptococcus for EoE, Prevotella for EoG) were different in the mucosal biopsies but not stool of individuals with EGIDs compared to controls; taxa associated with EGIDs were highly variable across individuals. Further study is needed to determine if therapeutic interventions contribute to the observed community differences.

Comparison of Zenker's per-oral endoscopic myotomy (Z-POEM) with standard flexible endoscopic septotomy for Zenker's diverticulum: a prospective study with 2-year follow-up.

BACKGROUND: Flexible endoscopic therapy of Zenker's diverticulum using submucosal tunneling (Z-POEM) similar to esophageal Per-Oral Endoscopic Myotomy (POEM) is becoming increasingly common. However, data comparing Z-POEM with traditional flexible endoscopic septotomy (FES) are sparse. The aim of this study was to compare outcomes of Z-POEM with traditional FES over a medium-term follow-up period. METHODS: This was a prospective study of patients who underwent Z-POEM for treatment of Zenker's diverticulum between 2018 and 2020 at a tertiary academic medical center compared to prior patients who had FES (between 2015 and 2018). Procedural characteristics and clinical outcomes (technical and clinical success, and adverse events) were compared between patients who underwent each treatment. RESULTS: A total of 28 patients underwent ZD therapy during the study period. 13 patients (mean age 70 years; 77% male) underwent Z-POEM and 15 patients (mean age 72 years; 73% male) underwent traditional FES. The mean Zenker's diverticulum size was 2.4 ± 0.6 cm in the ZPOEM group vs 2.5 ± 0.8 cm in the FES group. The mean procedure time was similar between groups: 43.9 min (range 26-66) in the Z-POEM group and 60.2 min (range 25-92) in the traditional FES group (t = 1.74 p = 0.19). Overall technical success was seen in 100% of patients. There was one adverse event in the FES group (dehydration resulting in near-syncope) (1/28, 3.6%). Overall clinical success was seen in 92.8% (26/28) of patients and was not significantly different between groups (Z-POEM; 13/13, 100% vs FES; 13/15, 86.7%, t = - 1.36 p = 0.18). CONCLUSION: This prospective study suggests that ZPOEM is an effective technique for the treatment of Zenker's diverticulum with no significant differences in clinical outcomes or adverse event rates when compared to traditional FES.

Role of short interval FLIP panometry in predicting long-term outcomes after per-oral endoscopic myotomy.

BACKGROUND: The Eckardt score (ES) is used to assess symptom response to Per-Oral Endoscopic Myotomy (POEM), but reliable methods to assess physiologic success are needed. Functional lumen imaging probe (FLIP) panometry has a potential role in post-POEM follow-up to predict long-term outcomes. The aim of this study was to assess the correlation between clinical success and FLIP parameters following POEM to determine if short interval FLIP could predict long-term outcomes. METHODS: This was a prospective study of adult patients who underwent POEM with short interval follow-up FLIP between 11/2017 and 3/2020. Clinical success was defined as post-procedure ES ≤ 3. Physiologic success was based on an esophago-gastric junction distensibility index (EGJ-DI) > 2.8 mm2/mmHg on FLIP. RESULTS: 47 patients (55% female, mean age 55 years) were included in the study. Clinical success after POEM was seen in 45 (96%) patients (mean ES 6.5 ± 2.2 pre and 0.83 ± 1.0 post-POEM, p < 0.001). Physiologic success was noted in 43 (91.5%) patients (mean EGJ-DI 6.1 mm2/mmHg ± 2.5). Among 4 patients not meeting criteria for physiologic success, EGJ-DI was 2.5-2.6. There was no correlation between post-POEM EGJ-DI and ES in the short term or long term. Significant reflux esophagitis was seen in 6 (12.8%) patients with no difference in mean EGJ-DI with vs without esophagitis (5.9 vs 6.1, p = 0.44). CONCLUSION: Post-POEM endoscopy with FLIP is useful to both assess EGJ physiology and to examine for reflux esophagitis. Short interval FLIP has limited utility to predict long-term patient outcomes or risk of acid reflux.

Gastroesophageal Balloon Tamponade Simulation Training with 3D Printed Model Improves Knowledge, Skill, and Confidence.

BACKGROUND: Gastroesophageal balloon tamponade (BT) tube placement is a life-saving procedure for refractory bleeding from gastroesophageal varices performed by gastroenterologists, intensivists, internists, and emergency medicine physicians. Despite a recognized need for procedural training, no standard curriculum or assessment tools exist. Given the infrequent performance of this procedure, the development of a representative and accessible simulation model would permit hands-on training to practice and maintain proficiency with BT tube placement. AIMS: To assess BT tube placement performance before and after a novel simulation-based learning module in gastroenterology fellows and faculty. METHODS: A 16-item knowledge questionnaire and 22-item procedural skill checklist utilizing a novel 3D printed esophagus model were developed to assess participant knowledge, procedural skills, and confidence prior to our simulation-based intervention and again 8-12 weeks after. Performance metrics were compared pre- and post-intervention within groups and between participant groups. RESULTS: Fifteen gastroenterology fellows (of 15 eligible; 100%) and 14 gastroenterology faculty (of 29 eligible; 48%) completed training. Fellows demonstrated improvement in knowledge (55% to 79%, p < 0.001) and procedural skill (35% to 57%, p < 0.001) following training. Baseline faculty performance did not differ from fellows' performance and post-intervention showed similar improvement in knowledge (61% to 77%, p = 0.001) and procedural skill (40% to 49%, p = 0.147). Overall satisfaction with training was high in both groups post-intervention and faculty felt more confident teaching fellows. CONCLUSION: The presented learning module offers a unique, low stakes opportunity for learners to improve skills, gain knowledge, and build confidence in placing BT tubes using a realistic simulation model.

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.

Distinct Clinical Physiologic Phenotypes of Patients With Laryngeal Symptoms Referred for Reflux Evaluation.

BACKGROUND & AIMS: Heterogeneous presentations and disease mechanisms among patients with laryngeal symptoms account for misdiagnosis of laryngopharyngeal reflux (LPR), variations in testing, and suboptimal outcomes. We aimed to derive phenotypes of patients with laryngeal symptoms based on clinical and physiologic data and to compare characteristics across phenotypes. METHODS: A total of 302 adult patients with chronic laryngeal symptoms were prospectively enrolled at 3 centers between January 2018 to October 2020 (age 57.2 ± 15.2 years; 30% male; body mass index 27.2 ± 6.0 kg/m2). Discriminant analysis of principal components (DAPC) was applied to 12 clinical and 11 physiologic variables collected in stable condition to derive phenotypic groups. RESULTS: DAPC identified 5 groups, with significant differences across symptoms, hiatal hernia size, and number of reflux events (P < .01). Group A had the greatest hiatal hernia size (3.1 ± 1.0 cm; P < .001) and reflux events (37.5 ± 51; P < .001), with frequent cough, laryngeal symptoms, heartburn, and regurgitation. Group B had the highest body mass index (28.2 ± 4.6 kg/m2; P < .001) and salivary pepsin (150 ± 157 ng/mL; P = .03), with frequent cough, laryngeal symptoms, globus, heartburn, and regurgitation. Group C frequently reported laryngeal symptoms (93%; P < .001), and had fewest esophageal symptoms (9.6%; P < .001) and reflux events (10.7 ± 11.0; P < .001). Group D commonly reported cough (88%; P < .001) and heartburn. Group E (18%) was oldest (62.9 ± 14.3 years; P < .001) and distinguished by highest integrated relaxation pressure. CONCLUSIONS: DAPC identified distinct clinicophysiologic phenotypes of patients with laryngeal symptoms referred for reflux evaluation: group A, LPR and gastroesophageal reflux disease (GERD) with hiatal hernia; group B, mild LPR/GERD; group C, no LPR/No GERD; group D, reflex cough; and group E, mixed/possible obstructive esophagogastric junction. Phenotypic differences may inform targeted clinical trials design and improve outcomes.

Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms After Dilation in Adults With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Esophageal dilation improves dysphagia but not inflammation in eosinophilic esophagitis (EoE) patients. We investigated if dilation modifies the association between symptoms and peak esophageal eosinophils per high-power field (eos/hpf). METHODS: Adults enrolled in a multisite prospective Consortium of Gastrointestinal Eosinophilic Disease Researchers Outcome Measures for Eosinophilic Gastrointestinal Diseases Across Ages observational study (NCT02523118) completed the symptom-based EoE activity index (EEsAI) patient-reported outcome instrument and underwent endoscopy with biopsy specimens. Patients were stratified based on dilation status as absent, performed 1 year or less before endoscopy, and performed more than 1 year before endoscopy. Assessments included Spearman correlations of the relationship between symptoms and eos/hpf and linear regression with EEsAI as the outcome, eos/hpf as predictor, and interaction for dilation and eos/hpf. RESULTS: Among 100 patients (n = 61 males; median age, 37 y), 15 and 40 patients underwent dilation 1 year or less and more than 1 year before index endoscopy, respectively. In nondilated patients, the association between eos/hpf and symptoms was moderate (ρ = 0.49; P < .001); for a 10-eos/hpf increase, the predicted EEsAI increased by 2.69 (P = .002). In patients dilated 1 or less and more than 1 year before index endoscopy, this association was abolished (ρ = -0.38; P = .157 for ≤1 y and ρ = 0.02; P = .883 >1 y); for a 10-eos/hpf increase, the predicted EEsAI changed by -1.64 (P = .183) and 0.78 (P = .494), respectively. Dilation modified the association between symptoms and eos/hpf (P = .005 and P = .187 for interaction terms of eos/hpf and dilation 1 or less years before and more than 1 year before index endoscopy, respectively). CONCLUSIONS: In nondilated EoE adults, eos/hpf correlate modestly with symptoms; this correlation was no longer appreciated in dilated patients, and the dilation effects lasted longer than 1 year. Dilation status should be considered in studies evaluating EoE treatment and for clinical follow-up evaluation.

Prospective Endoscopic Activity Assessment for Eosinophilic Gastritis in a Multisite Cohort.

INTRODUCTION: Eosinophilic gastritis (EG) is a chronic inflammatory disease of the stomach characterized by eosinophil-predominant gastric mucosal inflammation and gastrointestinal symptoms. The aim of this study was to prospectively evaluate endoscopic features in a large series of children and adults with EG to better understand the endoscopic manifestations and develop a standardized instrument for investigations. METHODS: Data were prospectively collected as part of the Consortium for Eosinophilic Gastrointestinal Disease Researchers, a national collaborative network. Endoscopic features were prospectively recorded using a system specifically developed for EG, the EG Endoscopic Reference System (EG-REFS). Correlations were made between EG-REFS and clinical and histologic features. RESULTS: Of 98 patients with EG, 65 underwent assessments using EG-REFS. The most common findings were erythema (72%), raised lesions (49%), erosions (46%), and granularity (35%); only 8% of patients with active histology (≥30 eosinophils/high-power field) exhibited no endoscopic findings. A strong correlation between EG-REFS scores and physician global assessment of endoscopy severity was demonstrated (Spearman r = 0.84, P < 0.0001). The overall score and specific components of EG-REFS were more common in the antrum than in the fundus or body. EG-REFS severity was significantly correlated with active histology, defined by a threshold of ≥30 eosinophils/high-power field (P = 0.0002). DISCUSSION: Prospective application of EG-REFS identified gastric features with a strong correlation with physician global assessment of endoscopic activity in EG. Endoscopic features demonstrated greater severity in patients with active histology and a predilection for the gastric antrum. Further development of EG-REFS should improve its utility in clinical studies.

Virtual Gastroenterology Fellowship Recruitment During COVID-19 and Its Implications for the Future.

BACKGROUND AND AIMS: Amid the COVID-19 pandemic, medical education organizations endorsed a virtual recruitment format, representing a stark change from traditional in-person interviews. We aimed to identify the attitudes and perceptions of Gastroenterology Fellowship Program Directors (PDs) and applicants regarding the virtual interview experience and the role of virtual interviews (VI) in the future. METHODS: We designed separate surveys targeting PDs and applicants using the Qualtrics software. At the end of the interview season, we e-mailed both survey links to all PDs and requested that they forward the applicant survey to their interviewed candidates. Surveys were voluntary and anonymous. Descriptive statistics were used to analyze the data with results presented as percentages. RESULTS: A total of 29.7% of PDs completed the survey. Compared to traditional interviews, VI were viewed by 46.5% of PDs to be very suboptimal or suboptimal. Yet, 69.1% envisioned a role for VI in the future. A total of 14.2% of applicants completed the survey. Compared to traditional interviews, VI were viewed by 42.3% of applicants to be very suboptimal or suboptimal. However, 61.8% saw a future role for VI. While both applicants and PDs reported that establishing an interpersonal connection was a disadvantage with VI, applicants placed more emphasis on this need for connection (p = 0.001). CONCLUSION: Overall, PDs and applicants report mixed views with regard to VI but anticipate that it may continue to have a future role. VI may augment future recruitment cycles with care taken to not disadvantage applicants, who rely heavily on the interview process to create personal connections with programs.

Upper Esophageal Sphincter Compression Device as an Adjunct to Proton Pump Inhibition for Laryngopharyngeal Reflux.

BACKGROUND: The Reflux Band, an external upper esophageal sphincter (UES) compression device, reduces esophago-pharyngeal reflux events. This study aimed to assess device efficacy as an adjunct to proton pump inhibitor (PPI) therapy in patients with laryngopharyngeal reflux (LPR). METHODS: This two-phase prospective clinical trial enrolled adults with at least 8 weeks of laryngeal symptoms (sore throat, throat clearing, dysphonia) not using PPI therapy at two tertiary care centers over 26 months. Participants used double dose PPI for 4 weeks in Phase 1 and the external UES compression device nightly along with PPI for 4 weeks in Phase 2. Questionnaire scores and salivary pepsin concentration were measured throughout the study. The primary endpoint of symptom response was defined as reflux symptom index (RSI) score ≤ 13 and/or > 50% reduction in RSI. RESULTS: Thirty-one participants completed the study: 52% male, mean age 47.9 years (SD 14.0), and mean body mass index (BMI) 26.2 kg/m2 (5.1). Primary endpoint was met in 11 (35%) participants after Phase 1 (PPI alone) and 17 (55%) after Phase 2 (Device + PPI). Compared to baseline, mean RSI score (24.1 (10.9)) decreased at end of Phase 1 (PPI alone) (21.9 (9.7); p = 0.06) and significantly decreased at end of Phase 2 (Device + PPI) (15.5 (10.3); p < 0.01). Compared to non-responders, responders to Device + PPI had a significantly lower BMI (p = 0.02) and higher salivary pepsin concentration (p = 0.01). CONCLUSION: This clinical trial highlights the potential efficacy of the external UES compression device (Reflux Band) as an adjunct to PPI for patients with LPR (ClinicalTrials.Gov NCT03619811).

Esophageal type 2 cytokine expression heterogeneity in eosinophilic esophagitis in a multisite cohort.

BACKGROUND: There is strong evidence for a role of type 2 cytokines in the pathogenesis of eosinophilic esophagitis (EoE); however, heterogeneity in type 2 gene expression has not been examined. OBJECTIVE: We examined type 2 immunity-associated gene expression in esophageal biopsy specimens, aiming to determine the degree of cytokine heterogeneity and its potential clinical significance. METHODS: Patients (n = 312) were recruited from 10 sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. In addition to histologic and endoscopic assessment, esophageal biopsy specimens were examined for expression of 96 genes within the EoE diagnostic panel. RESULTS: Five subgroups of patients with active EoE were identified by unsupervised clustering based on expression of IL4, IL5, IL13, C-C motif chemokine ligand 26 (CCL26), thymic stromal lymphopoietin (TSLP), Charcot-Leyden crystal (CLC), C-C motif chemokine receptor 3 (CCR3), and CPA3. These groups differed in age (P < .02) and EoE diagnostic panel score (P < 1.08E-30) but not in eosinophil levels. The group V patients had the highest expression of IL5, TSLP, and CCL26 and genes associated with tissue remodeling, such as COL8A1, actin γ-2 (ACTG2), and tetraspanin 12 (TSPAN12). IL5 and IL13 were highly expressed in group IV; however, groups IV and V differed in age (34 vs 14 years [P < .05]). Groups II and III, which exhibited intermediate expression of IL5 and CPA3, were differentiated by high TSLP and IL13 in group III. CONCLUSION: We observed heterogeneous type 2 gene expression among patients with active EoE. Type 2 gene overexpression was not directly proportional to disease features; this was especially true for tissue remodeling events. These findings highlight a clinical opportunity for leveraging molecular endotypes to implement personalized medicine in EoE.

Esophageal Manometry Competency Program Improves Gastroenterology Fellow Performance in Motility Interpretation.

INTRODUCTION: Competency-based medical education (CBME) for interpretation of esophageal manometry is lacking; therefore, motility experts and instructional designers developed the esophageal manometry competency (EMC) program: a personalized, adaptive learning program for interpretation of esophageal manometry. The aim of this study was to implement EMC among Gastroenterology (GI) trainees and assess the impact of EMC on competency in manometry interpretation. METHODS: GI fellows across 14 fellowship programs were invited to complete EMC from February 2018 to October 2018. EMC includes an introductory video, baseline assessment of manometry interpretation, individualized learning pathways, and final assessment of manometry interpretation. The primary outcome was competency for interpretation in 7 individual skill sets. RESULTS: Forty-four GI trainees completed EMC. Participants completed 30 cases, each including 7 skill sets. At baseline, 4 (9%) participants achieved competency for all 7 skills compared with 24 (55%) at final assessment (P < 0.001). Competency in individual skills increased from a median of 4 skills at baseline to 7 at final assessment (P < 0.001). The greatest increase in skill competency was for diagnosis (Baseline: 11% vs Final: 68%; P < 0.001). Accuracy improved for distinguishing between 5 diagnostic groups and was highest for the Outflow obstructive motility disorder (Baseline: 49% vs Final: 76%; P < 0.001) and Normal motor function (50% vs 80%; P < 0.001). DISCUSSION: This prospective multicenter implementation study highlights that an adaptive web-based training platform is an effective tool to promote CBME. EMC completion was associated with significant improvement in identifying clinically relevant diagnoses, providing a model for integrating CBME into subspecialized areas of training.

Effect of individualized feedback on learning curves in EGD and colonoscopy: a cluster randomized controlled trial.

BACKGROUND AND AIMS: Gastroenterology fellowships need to ensure that trainees achieve competence in upper endoscopy (EGD) and colonoscopy. Because the impact of structured feedback remains unknown in endoscopy training, this study compared the effect of structured feedback with standard feedback on trainee learning curves for EGD and colonoscopy. METHODS: In this multicenter, cluster, randomized controlled trial, trainees received either individualized quarterly learning curves or feedback standard to their fellowship. Assessment was performed in all trainees using the Assessment of Competency in Endoscopy tool on 5 consecutive procedures after every 25 EGDs and colonoscopies. Individual learning curves were created using cumulative sum (CUSUM) analysis. The primary outcome was the mean CUSUM score in overall technical and overall cognitive skills. RESULTS: In all, 13 programs including 132 trainees participated. The intervention arm (6 programs, 51 trainees) contributed 558 EGD and 600 colonoscopy assessments. The control arm (7 programs, 81 trainees) provided 305 EGD and 468 colonoscopy assessments. For EGD, the intervention arm (-.7 [standard deviation {SD}, 1.3]) had a superior mean CUSUM score in overall cognitive skills compared with the control arm (1.6 [SD, .8], P = .03) but not in overall technical skills (intervention, -.26 [SD, 1.4]; control, 1.76 [SD, .7]; P = .06). For colonoscopy, no differences were found between the 2 arms in overall cognitive skills (intervention, -.7 [SD, 1.3]; control, .7 [SD, 1.3]; P = .95) or overall technical skills (intervention, .1 [SD, 1.5]; control, -.1 [SD, 1.5]; P = .77). CONCLUSIONS: Quarterly feedback in the form of individualized learning curves did not affect learning curves for EGD and colonoscopy in a clinically meaningful manner. (Clinical trial registration number: NCT02891304.).

Reduced Esophageal Contractility Is Associated with Dysplasia Progression in Barrett's Esophagus: A Multicenter Cohort Study.

BACKGROUND: The incidence of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) continues to rise, and risk stratification of patients with BE is needed. Impaired esophageal motility is associated with gastroesophageal reflux disease; however, whether esophageal dysmotility is a risk factor for dysplasia progression in BE is incompletely understood. This study aimed to characterize esophageal motility patterns in patients with BE and identify physiologic factors associated with dysplasia progression in BE. METHODS: This multicenter retrospective study assessed data from adult patients with histologically confirmed BE who underwent high-resolution esophageal manometry from 1/2014 to 1/2018 at four tertiary care centers. Longitudinal data were collected when available among patients with non-dysplastic BE (NDBE) and separated as: no dysplastic progression or positive dysplastic progression. Multivariable logistic regression assessed for independent predictors of dysplasia progression. RESULTS: Among 193 patients, histology at index endoscopy identified 152 (79%) NDBE, 23 (12%) low-grade dysplasia, 14 (7%) high-grade dysplasia, and 4 (2%) EAC. Ninety-eight (51%) had abnormal esophageal motor function on manometry. Longitudinal data were available for 84 of 152 patients with initial NDBE. Twelve (14%) exhibited dysplastic progression to low-grade (6) or high-grade (6) dysplasia. Mean esophageal distal contractile integral was lower for patients that progressed [455 mmHg s cm (SD 515)] compared with patients who did not progress [987 mmHg s cm (SD 953); aOR 1.21 (95% CI 1.01, 1.44)]. CONCLUSION: In this retrospective study of 193 BE patients, the majority exhibited abnormal esophageal motor function. Reduced esophageal contractility was independently associated with dysplastic progression in BE. Characterizing esophageal physiology in BE may help to risk stratify patients.

Alignment of parent- and child-reported outcomes and histology in eosinophilic esophagitis across multiple CEGIR sites.

BACKGROUND: Patient-reported outcome metrics for eosinophilic esophagitis (EoE) have been developed and validated but not used in a multicenter pediatric population or systematically aligned with histology. OBJECTIVE: We sought to understand (1) the potential of caregiver report to predict patient self-reported symptoms and (2) the correlation of patient-reported outcome domains with histology. METHODS: Patients with EoE (n = 310) and their parents participating in the Consortium of Gastrointestinal Eosinophilic Disease Researchers (CEGIR) observational clinical trial were queried for baseline patient symptoms and quality of life (QOL) by using the Pediatric Eosinophilic Esophagitis Symptom Score, version 2 (PEESSv2.0), and the Pediatric QOL EoE module (PedsQL-EoE), and biopsy specimens were analyzed by using the EoE Histology Scoring System. RESULTS: PEESSv2.0 parental and child reports aligned across all domains (r = 0.68-0.73, P < .001). PedsQL-EoE reports correlated between parents and children across ages and multiple domains (r = 0.48-0.79, P < .001). There was a tight correlation between symptoms on PEESSv2.0 and their effects on QOL both on self-report and parental report (P < .001). Self-reported symptoms on PEESSv2.0 (positively) and PedsQL-EoE (inversely) showed a weak correlation with proximal, but not distal, peak eosinophil counts and features and architectural tissue changes on the EoE Histology Scoring System (P < .05). CONCLUSIONS: Parents of children with EoE aged 3 to 18 years accurately reflected their children's disease symptoms and QOL. Self- and parent-reported symptoms correlate with proximal esophageal histology. Our data suggest that parental report in young children can function as an adequate marker for self-reported symptoms and that self-reported symptoms can reflect changes in tissue histology in the proximal esophagus. These findings should be considered during clinical trials for drug development.

Lack of Knowledge and Low Readiness for Health Care Transition in Eosinophilic Esophagitis and Eosinophilic Gastroenteritis.

OBJECTIVES: A growing population of adolescents/young adults with eosinophilic esophagitis (EoE) and eosinophilic gastroenteritis (EGE) will need to transition from pediatric to adult health providers. Measuring health care transition (HCT) readiness is critical, but no studies have evaluated this process in EoE/EGE. We determined the scope and predictors of HCT knowledge in patients and parents with EoE/EGE and measured HCT readiness in adolescents/young adults. METHODS: We conducted an online survey of patients 13 years or older and parents of patients with EoE/EGE who were diagnosed when 25 years or younger. Parents answered questions regarding their children and their own knowledge of HCT. HCT readiness was assessed in adolescents/young adults aged 13 to 25 years with the Self-Management and Transition to Adulthood with Rx Questionnaire (a 6-domain self-report tool) with a score range of 0 to 90. RESULTS: Four hundred fifty participants completed the survey: 205 patients and 245 parents. Included in the analysis (those diagnosed with EoE/EGE at age 25 years or younger) were 75 of 205 patients and children of 245 parent respondents. Overall, 78% (n = 52) of the patients and 76% (n = 187) of parents had no HCT knowledge. Mean HCT readiness score in adolescents/young adults (n = 50) was 30.4 ±â€Š11.3 with higher scores in domains of provider communication and engagement during appointments. Mean parent-reported (n = 123) score was 35.6 ±â€Š9.7 with higher scores in medication management and disease knowledge. CONCLUSIONS: There was a significant deficit in HCT knowledge, and HCT readiness scores were lower than other chronic health conditions. HCT preparation and readiness assessments should become a priority for adolescents/young adults with EoE/EGE and their parents.