Ravi, Karthik

Abstract Background The clinical characteristics and treatment outcomes in patients with eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) have not been extensively investigated. Methods We determined treatment outcomes and frequencies of disease-related complications in patients with EoE and IBD. Results Among 69 patients who met inclusion criteria, 39 (56.5%) had a diagnosis of Crohn disease. Clinical and histologic response rates to proton pump inhibitors and topical steroids were 25.9% and 24.4%, respectively. Conclusions Lower than expected clinical and histologic response rates for EoE suggest the combination of EoE and IBD is a medically refractory phenotype with more difficult to treat EoE.

AbstractBackgroundOpioid‐induced esophageal dysfunction (OIED) is a recognized complication of chronic opioid use. However, the impact of acute opioid administration on esophageal motility remains unclear.MethodsOpioid naïve patients with high‐resolution manometry (HRM) <480 min following esophagogastroduodenoscopy (EGD) (opioid‐HRM) and a control group with HRM <36 h prior to EGD between January 1, 2016, and November 10, 2018, from a single institution were identified. EGDs were performed exclusively with versed and fentanyl.Key ResultsOne hundred and seventy‐four patients were identified, with 83 (47.7%) opioid‐HRM and 91 (52.3%) controls. Mean time from EGD to HRM was 229 (78–435) min. Baseline clinical features and HRM indications were similar between opioid‐HRM and controls. Chicago classification v3.0 defined HRM findings were similar between groups. Major motility disorders as defined by the Chicago classification v3.0 occurred at a similar frequency among opioid‐HRM and controls (27.7% vs. 36.3%, p = 0.23). Mean distal contractile integrity (DCI) was higher in opioid‐HRM (1939.3 ± 1318.9 vs. 1792.2 ± 2062.3 mmHg∙cm∙s, p = 0.043), but maximum DCI, distal latency, and integrated relaxation pressure did not differ between groups. Subgroup analysis assessing time and dose dependency did not identify differences in individual manometric parameters and Chicago classification v3.0 diagnosis between patients with HRM <240 min after EGD, >240 min after EGD, ≥125 mcg of IV fentanyl, <125 mcg IV fentanyl and controls.Conclusions and InferencesSame‐day acute opioid administration did not affect HRM findings in opioid naïve patients. Studies assessing the pathophysiology of and duration‐dependent relationship with opioids in OIED are needed.

Abstract Purpose: Pediatric high-grade glioma (pHGG) diagnosis portends poor prognosis and therapeutic monitoring remains difficult. Tumors release cell-free tumor DNA (cf-tDNA) into cerebrospinal fluid (CSF), allowing for potential detection of tumor-associated mutations by CSF sampling. We hypothesized that direct, electronic analysis of cf-tDNA with a handheld platform (Oxford Nanopore MinION) could quantify patient-specific CSF cf-tDNA variant allele fraction (VAF) with improved speed and limit of detection compared with established methods. Experimental Design: We performed ultra-short fragment (100–200 bp) PCR amplification of cf-tDNA for clinically actionable alterations in CSF and tumor samples from patients with pHGG (n = 12) alongside nontumor CSF (n = 6). PCR products underwent rapid amplicon-based sequencing by Oxford Nanopore Technology (Nanopore) with quantification of VAF. Additional comparison to next-generation sequencing (NGS) and droplet digital PCR (ddPCR) was performed. Results: Nanopore demonstrated 85% sensitivity and 100% specificity in CSF samples (n = 127 replicates) with 0.1 femtomole DNA limit of detection and 12-hour results, all of which compared favorably with NGS. Multiplexed analysis provided concurrent analysis of H3.3A (H3F3A) and H3C2 (HIST1H3B) mutations in a nonbiopsied patient and results were confirmed by ddPCR. Serial CSF cf-tDNA sequencing by Nanopore demonstrated correlation of radiological response on a clinical trial, with one patient showing dramatic multi-gene molecular response that predicted long-term clinical response. Conclusions: Nanopore sequencing of ultra-short pHGG CSF cf-tDNA fragments is feasible, efficient, and sensitive with low-input samples thus overcoming many of the barriers restricting wider use of CSF cf-tDNA diagnosis and monitoring in this patient population.

INTRODUCTION: Uncontrolled results suggest that diaphragmatic breathing (DB) is effective in gastroesophageal reflux disease (GERD) but the mechanism of action and rigor of proof is lacking. This study aimed to determine the effects of DB on reflux, lower esophageal sphincter (LES), and gastric pressures in patients with upright GERD and controls. METHODS: Adult patients with pH proven upright GERD were studied. During a high-resolution impedance manometry, study patients received a standardized pH neutral refluxogenic meal followed by LES challenge maneuvers (Valsalva and abdominal hollowing) while randomized to DB or sham. After that, patients underwent 48 hours of pH-impedance monitoring, with 50% randomization to postprandial DB during the second day. RESULTS: On examining 23 patients and 10 controls, postprandial gastric pressure was found to be significantly higher in patients compared with that in controls (12 vs 7 mm Hg, P = 0.018). Valsalva maneuver produced reflux in 65.2% of patients compared with 44.4% of controls ( P = 0.035). LES increased during the inspiratory portion of DB (42.2 vs 23.1 mm Hg, P < 0.001) in patients and healthy persons. Postprandial DB reduced the number of postprandial reflux events in patients (0.36 vs 2.60, P < 0.001) and healthy subjects (0.00 vs 1.75, P < 0.001) compared with observation. During 48-hour ambulatory study, DB reduced the reflux episodes on day 2 compared with observation on day 1 in both the patient and control groups ( P = 0.049). In patients, comparing DB with sham, total acid exposure on day 2 was not different (10.2 ± 7.9 vs 9.4 ± 6.2, P = 0.804). In patients randomized to DB, esophageal acid exposure in a 2-hour window after the standardized meal on day 1 vs day 2 reduced from 11.8% ±6.4 to 5.2% ± 5.1, P = 0.015. DISCUSSION: In patients with upright GERD, DB reduces the number of postprandial reflux events pressure by increasing the difference between LES and gastric pressure. These data further encourage studying DB as therapy for GERD.

INTRODUCTION: To assess the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on acid reflux and esophageal motor function and to evaluate the observation of esophageal adenocarcinoma (EAC) after bariatric surgery. METHODS: We searched 5 databases for adults who underwent SG or RYGB and had esophageal pH test and/or esophageal manometry before and after surgery. A separate systemic search of observational studies and a retrospective review at 3 institutions of adults who developed EAC after these surgeries were conducted. Outcomes were changes in manometric and pH parameters and EAC cases after SG and RYGB. RESULTS: A total of 27 nonrandomized studies (SG: 612 patients; RYGB: 470 patients) were included. After SG, lower esophageal sphincter pressure and esophageal body amplitude were decreased and the risk of ineffective esophageal motility was increased. Total and recumbent acid exposure times were increased. After RYGB, an increased risk of ineffective esophageal motility was observed. Total, upright, and recumbent acid exposure times were decreased. The total reflux episodes remained unchanged but with increased nonacid reflux and decreased acid reflux events. Including our largest series, 31 EAC cases have been reported to date after SG and RYGB. DISCUSSION: This systematic review demonstrates increased acid reflux after SG and decreased acid reflux after RYGB. An observed increased nonacid reflux after RYGB might contribute to failure of gastroesophageal reflux disease improvement. This refluxate might be noxious to the esophagus, warranting further studies. RYGB might not entirely preserve esophageal function as previously believed.

LINKED CONTENTThis article is linked to Moosavi et al and Liwinski and Shcramm papers. To view these articles, visit https://doi.org/10.1111/apt.15758 and https://doi.org/10.1111/apt.15831.

INTRODUCTION: Esophageal dysmotility including features of achalasia may develop because of bariatric surgery. However, the prevalence of these complications is unknown. We sought to define the prevalence of dysphagia and major esophageal motility disorders including achalasia after bariatric surgery through a large retrospective database review. METHODS: Patients with a history of laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass who underwent a diagnostic high-resolution impedance manometry (HRIM) either before or after bariatric surgery across 3 large tertiary referral sites from June 2012 through February 2019 were identified from a procedural database. HRIM studies were interpreted per the Chicago classification v3.0 by a blinded investigator (K.R.). Demographic/clinical features were collected. In addition, patients who underwent bariatric surgery from January 2014 to April 2015 were contacted and administered a validated symptom assessment survey to gauge the overall prevalence of dysphagia in a postbariatric population. RESULTS: A total of 137 patients were identified, including 97 who underwent HRIM after bariatric surgery (laparoscopic sleeve gastrectomy [n = 39, 40.1%]; Roux-en-Y gastric bypass [n = 58, 59.8%]) at a median of 5.84 years (interquartile range 2.1–12.5) postoperatively and 40 preoperative bariatric surgery candidates with medically complicated obesity. A manometric pattern consistent with achalasia was identified in 7 (7.2%) postsurgical patients compared with none in the preoperative group ( P = 0.08). We further identified a separate achalasia-like pattern defined by aperistalsis and increased intragastric pressure (postobesity surgery esophageal dysfunction [POSED]) in 5 (5.2%) postsurgical patients vs none found preoperatively ( P = 0.14). Achalasia or POSED was associated with postbariatric surgery (12.4% vs 0%, P = 0.02). Increasing time since surgery was independently associated with the development of achalasia (median 12.5 vs 5.8 years, P = 0.02), POSED (median 15.0 vs 5.8 years, P = 0.02) and major motility disorders (6.6 vs 4.9 years, P = 0.01). Furthermore, among 271 postbariatric surgery patients contacted for symptom assessment via survey, the prevalence of dysphagia was 13.7% at a mean 3.9 years after surgery. DISCUSSION: Postoperative dysphagia is a common long-term complication of bariatric surgery. This is potentially the consequence of a time-dependent association with the development of postoperative esophageal dysmotility, particularly achalasia and POSED. Consequently, esophageal dysmotility may be an important under-recognized complication of bariatric surgery.

OBJECTIVES: Symptoms are inconsistently associated with esophageal motor findings on high-resolution manometry (HRM). We aimed to evaluate predictors of dysphagia severity, including esophageal hypervigilance and visceral anxiety, among patients evaluated with HRM. METHODS: Adult patients undergoing HRM at 4 academic medical centers (United States and France) were prospectively evaluated. HRM was completed and analyzed per the Chicago Classification v3.0. Validated symptom scores, including the Brief Esophageal Dysphagia Questionnaire and Esophageal Hypervigilance and Anxiety Scale, were completed at the time of HRM. RESULTS: Two hundred thirty-six patients, aged 18–85 (mean 53) years, 65% female, were included. Approximately 59 (25%) patients had a major motor disorder on HRM: 19 achalasia, 24 esophagogastric junction outflow obstruction, 12 absent contractility, and 4 jackhammer. Approximately 177 (75%) patients did not have a major motor disorder: 71 ineffective esophageal motility and 106 normal motility. Having a major motor disorder was a significant predictor of dysphagia severity (R 2 adj = 0.049, P < 0.001), but the Esophageal Hypervigilance and Anxiety Scale score carried a predictive relationship of Brief Esophageal Dysphagia Questionnaire that was 2-fold higher than having a major motor disorder: R 2 adj = 0.118 ( P < 0.001). This finding remained when evaluated by the major motor disorder group. HRM metrics were nonsignificant. DISCUSSION: In a prospective, international multicenter study, we found that esophageal hypervigilance and visceral anxiety were the strongest predictors of dysphagia severity among patients evaluated with HRM. Thus, an assessment of esophageal hypervigilance and visceral anxiety is important to incorporate when evaluating symptom severity in clinical practice and research studies.

INTRODUCTION: Learning styles among gastroenterology providers have not been reported and may have implications in improving continuing medical education (CME). This study aims to 1) evaluate learning styles among gastroenterology providers participating in a board review course, 2) assess self-reported burnout, and 3) determine if demographic information, practice style, or burnout was associated with specific learning styles. METHODS: Participants at the 2018 Mayo GI and Hepatology Board Review Course had the opportunity to participate in an anonymous, survey-based study evaluating learning styles and burnout. Demographic and practice information, reason for participating in the course, questions regarding burnout and callousness, and the Kolb Learning Style Inventory (KLSI) (v3.1, Korn Ferry Hay Group, Boston, MA) were collected. Associations between demographic data, burnout, and learning styles were assessed using Fisher’s exact test. RESULTS: A total of 71 of 230 participants elected to participate and 47 completed the KLSI. Median age range was 41-50 years, 31 (43.7%) were female, and 60 (84.5%) had MD or DO degree. All regions of the United States were represented and 4 participants were from outside of the US. Reasons for participation included new certification (12.7%), recertification (45.1%), not passing prior board certification (4.2%), and general knowledge (38%). Burnout was noted by 27 (38%), callousness by 19 (26.8%), and both by 9 (12.7%). Kolb learning styles were diverging in 27.7%, assimilating in 31.9%, converging in 27.7%, and accommodating in 12.8%. There were no associations with demographics, practice type or reason for taking the course with specific learning styles; however, more frequent markers of burnout were associated with the accommodating learning style (50% burnout only, 33% callous only, and 16.7% reporting both; P = .03). CONCLUSION: All learning styles are represented at the studied board review course and are dispersed throughout ages, sex, geography, and practice style. This highlights the importance of a transition from lecture-based CME to more varied education modalities. Indices of self-reported burnout are seen frequently in this cohort, and seem to have increased association with the accommodating learning style. Future study with more participants is needed to further understand learning styles and burnout in gastroenterology providers, with the aim of improving CME.