Ravi, Karthik

SummaryBackgroundDietary therapy successfully treats eosinophilic oesophagitis (EoE), but limited data exist on predictors of patient response.AimsTo determine response rates and to identify predictors of histologic response to elimination diets in adults with EoEMethodsThis was a retrospective, single‐centre study of adults with PPI‐refractory EoE undergoing dietary therapy with six food elimination diet (SFED) or extended six food elimination diet (ExSFED) in an outpatient setting from January 2012 to January 2019. Patient demographics, radiologic and endoscopic findings, endoscopic reference (EREF) scores, histology and symptoms were evaluated before and after food elimination. Histologic response was assessed via tissue obtained from endoscopically‐guided biopsy or Cytosponge. Dietary therapy adherence was assessed via structured phone interview. Multivariable logistic regression analysis was performed to identify predictors of dietary response.ResultsWe included 68 patients, of whom 62% had a histologic response to dietary therapy (81% to SFED, 19% to ExSFED). Median duration of follow‐up was 45 months (IQR, 34–53 months). On multivariable analysis, higher pre‐SFED EREF score was the only variable associated with dietary non‐response (OR 0.07, 95% CI 0.49, 0.98; p = 0.04).ConclusionsIn adults with EoE, histologic dietary non‐response to SFED was associated with a higher pre‐SFED EREF score, suggesting that fixed structural disease may predict dietary non‐response. Our additional observations of poor correlation between symptomatic and histologic flares, and identification of ExSFED responders, suggest that histologic confirmation should be sought before committing patients to lifelong dietary changes. We also recommend the consideration of restricting legumes and corn in SFED non‐responders as ExSFED detected additional dietary responders.

Summary Topical steroids are commonly used in treatment of eosinophilic esophagitis (EoE), but currently there is lack of data to clarify most effective regimen. We aimed to study the achievement of histologic remission using the same dose of budesonide in two different delivery formulations. Patients with established EoE treated with pharmacy compounded budesonide capsule or budesonide Rincinol gel (both 3 mg twice daily) were studied retrospectively. Those with pre-treatment and post-treatment histologic assessment were included with main endpoint being histologic remission. 103 patients (62 gel, 41 capsule) were included, with higher rate of histologic remission with gel (84 vs. 59%, P=0.004). A subset of patients in both groups had lack of steroid response (<50% drop in eosinophils) (15% for gel, 32% for capsule). Formulation/delivery vehicle of steroid treatments to esophageal mucosa in EoE appears important for treatment efficacy, with budesonide gel having higher likelihood of histologic remission compared to budesonide capsules in our population. A truly steroid refractory group appears likely in our population. Larger, prospective studies may help clarify best regimen of topical steroids in EoE and may work to identify patients likely to benefit from alternative therapies.

Abstract Background Diffuse Midline Glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis. Methods We conducted a multi-site Phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma (NCT03416530). Patients enrolled on Arm D of the trial (n = 24) underwent serial lumbar puncture for cell-free tumor DNA (cf-tDNA) analysis and patients on all arms at the University of Michigan underwent serial plasma collection. We performed digital droplet polymerase chain reaction (ddPCR) analysis of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal 2D tumor area on MRI). Results Change in H3.3K27M VAF over time (“VAF delta”) correlated with prolonged PFS in both CSF and plasma samples. Nonrecurrent patients that had a decrease in CSF VAF displayed a longer progression free survival (P = .0042). Decrease in plasma VAF displayed a similar trend (P = .085). VAF “spikes” (increase of at least 25%) preceded tumor progression in 8/16 cases (50%) in plasma and 5/11 cases (45.4%) in CSF. In individual cases, early reduction in H3K27M VAF predicted long-term clinical response (>1 year) to ONC201, and did not increase in cases of later-defined pseudo-progression. Conclusion Our work demonstrates the feasibility and potential utility of serial cf-tDNA in both plasma and CSF of DMG patients to supplement radiographic monitoring. Patterns of change in H3K27M VAF over time demonstrate clinical utility in terms of predicting progression and sustained response and possible differentiation of pseudo-progression and pseudo-response.

Summary Background Upper endoscopy (EGD) is frequently performed in patients with esophageal complaints following anti-reflux surgery such as fundoplication. Endoscopic evaluation of fundoplication wrap integrity can be challenging. Our primary aim in this pilot study was to evaluate the accuracy and confidence of assessing Nissen fundoplication integrity and hiatus herniation among gastroenterology (GI) fellows, subspecialists, and foregut surgeons. Methods Five variations of post-Nissen fundoplication anatomy were included in a survey of 20 sets of EGD images that was completed by GI fellows, general GI attendings, esophagologists, and foregut surgeons. Accuracy, diagnostic confidence, and inter-rater agreement across providers were evaluated. Results There were 31 respondents in the final cohort. Confidence in pre-survey diagnostics significantly differed by provider type (mean confidence out of 5 was 1.8 for GI fellows, 2.7 for general GI attendings, 3.6 for esophagologists, and 3.6 for foregut surgeons, P = 0.01). The mean overall accuracy was 45.9%, which significantly differed by provider type with the lowest rate among GI fellows (37%) and highest among esophagologists (53%; P = 0.01). The accuracy was highest among esophagologists across all wrap integrity variations. Inter-rater agreement was low across wrap integrity variations (Krippendorf’s alpha <0.30), indicating low to no agreement between providers. Conclusion In this multi-center survey study, GI fellows had the lowest accuracy and confidence in assessing EGD images after Nissen fundoplication, whereas esophagologists had the highest. Diagnostic confidence varied considerably and inter-rater agreement was poor. These findings suggest experience may improve confidence, but highlight the need to improve the evaluation of fundoplication wraps.

The purpose of this review is to highlight the impact of common medications on esophageal motility. Esophageal motility is mediated through a complex network of neural innervation. Opioids lead to excitatory esophageal motor abnormalities termed opioid-induced esophageal dysfunction or OIED. Prokinetics have mixed effects on esophageal motility. Nitrates and calcium channel blockers relax esophageal smooth muscle, but they are limited clinically due to side effects. Sildenafil also relaxes smooth muscle, but it is costly. Peppermint oil may reduce distal esophageal spasm. Anticholinergics, selective serotonin reuptake inhibitors, estrogen, and cannabis need further study to evaluate their effects on esophageal motility.

Goals: The aim was to quantify proton pump inhibitor (PPI) practice habits among gastroenterology (GI) practitioners. Background: Reports of side effects have prompted patients and practitioners alike to discontinue PPI use. Emerging evidence-based literature on PPI risks and safety seek to guide practitioners, but the impact of this literature on PPI prescribing patterns has not been evaluated. Study: We performed an anonymous online survey of US GI practitioners across 6 academic and community affiliated medical centers. Demographic data including practice type and number of weekly gastroesophageal reflux disease patients seen were obtained. Survey questions evaluated practitioners’ monitoring for PPI side effects, dose adjustments, and sources of information about PPI risks. Results: The survey response rate was 60% (256/429). The majority of respondents were male (169, 66%) attending physicians (178, 70%) practicing general GI (63, 25%). There were 92 (36%) respondents who reported testing for PPI side effects at least once a year. Most respondents (143, 56%) reported discontinuing PPIs at least 50% of the time because of patients’ concerns about PPI side effects. The majority of respondents reported getting their information regarding PPI safety from published journals (239, 98%) as well as colleagues (222, 91%). Conclusions: Despite best available evidence suggesting safety of long-term PPI use without routine monitoring, stopping PPIs and monitoring for potential side effects occurs frequently, even within a cohort of mostly academic GI practitioners. Alternative strategies are needed to improve adherence to best practices, especially since gastroenterologists often serve as PPI experts.