GOALS: To assess the predictive value of baseline peripheral absolute eosinophil counts (AECs) for proton pump inhibitor (PPI) response in eosinophilic esophagitis (EoE).

BACKGROUND: PPI leads to histologic remission in  50% of EoE patients, although there are few distinguishing clinical features between PPI-responsive (PPI-r-EoE) and nonresponsive (PPI-nr-EoE) diseases. Peripheral eosinophilia is present in  50% of EoE cases and is associated with eosinophil density on esophageal biopsy and worse clinical outcomes. The association between peripheral eosinophilia and PPI-responsiveness in EoE remains unclear.

STUDY: This is a retrospective cohort study of adult EoE patients at a tertiary center between 2012 and 2016. All patients underwent twice daily PPI trials for ≥8 weeks followed by repeat esophageal biopsies and were classified as PPI-r-EoE or PPI-nr-EoE based on histologic response (<15 eosinophils/high power field). Baseline peripheral AEC was obtained within 1 month before index endoscopy. Analyses were performed using Fisher exact/Student t test (univariate) and logistic regression (multivariable).

RESULTS: One hundred eighty-three patients (91 PPI-nr-EoE and 92 PPI-r-EoE) were included. Mean peripheral AEC was higher among PPI-nr-EoE patients (0.41 vs 0.24 K/µL, P = 0.013). Baseline peripheral eosinophilia (>0.5 K/µL) was more prevalent among patients with PPI-nr-EoE (70.4% vs 45.5%, P = 0.023) and a history of food impaction (51.9% vs 23.7%, P = 0.0082). On multivariable analyses, peripheral eosinophilia remained an independent predictor for PPI response (adjacent odds ratio = 2.86, CI: 1.07-7.62, P = 0.036) and food impaction (adjacent odds ratio = 2.80, CI: 1.07-7.35, P = 0.037).

CONCLUSIONS: Baseline peripheral eosinophilia independently predicts PPI nonresponse and food impaction in EoE patients. Peripheral AEC may help therapy selection in EoE and prevent delays in achieving histologic remission.

BACKGROUND: The optimal proton pump inhibitor (PPI) regimen for eosinophilic esophagitis (EoE) is unclear. We compared histologic response rates of different dosing combinations.

METHODS: 305 newly-diagnosed EoE patients received standard (omeprazole 20mg daily), once-daily moderate (40mg daily), twice-daily moderate (20mg twice daily), or high (40mg twice daily) dose PPI for ≥8 weeks.

RESULTS: 42.3% achieved histologic response to PPI, with higher rates for twice-daily (moderate:52.8%/high:54.3%) than once-daily (standard:11.8%/moderate:10%) dosing (p<0.0001). On multivariable analysis, twice-daily moderate (aOR:6.75, CI:2.53-18.0,p=0.0008) and high (aOR:12.8, CI:4.69-34.8,p<0.0001) doses independently predicted histologic response.

CONCLUSION: Twice-daily PPI is associated with higher EoE histologic response rates than once-daily regimen.

INTRODUCTION: Anorectal function testing is traditionally relegated to subspecialty centers. Yet, it is an office-based procedure that appears capable of triaging care for the many patients with Rome IV functional constipation that fail empiric over-the-counter therapy in general gastroenterology, as an alternative to empirical prescription drugs. We aimed to evaluate cost-effectiveness of routine anorectal function testing in this specific population.

METHODS: We performed a cost-effectiveness analysis from the patient perspective and a cost-minimization analysis from the insurer perspective to compare 3 strategies: (i) empiric prescription drugs followed by pelvic floor physical therapy (PFPT) for drug failure, (ii) empiric PFPT followed by prescription drugs for PFPT failure, or (iii) care directed by up-front anorectal function testing. Model inputs were derived from systematic reviews of prospective clinical trials, national cost data sets, and observational cohort studies of the impact of chronic constipation on health outcomes, healthcare costs, and work productivity.

RESULTS: The most cost-effective strategy was upfront anorectal function testing to triage patients to appropriate therapy, in which the subset of patients without anal hypocontractility on anorectal manometry and with a balloon expulsion time of at least 6.5 seconds would be referred to PFPT. In sensitivity analysis, empiric PFPT was more cost effective than empiric prescription drugs except for situations in which the primary goal of treatment was to increase bowel movement frequency. If adopted, gastroenterologists would refer ∼17 patients per year to PFPT, supporting feasibility.

DISCUSSION: Anorectal function testing seems to be an emergent technology to optimize cost-effective outcomes, overcoming testing costs by phenotyping care.

BACKGROUND & AIMS: Discerning whether laryngeal symptoms result from gastroesophageal reflux is clinically challenging and a reliable tool to stratify patients is needed. We aimed to develop and validate a model to predict likelihood of gastroesophageal reflux disease (GERD) among patients with chronic laryngeal symptoms.

METHODS: This multicenter international study collected data from adults with chronic laryngeal symptoms that underwent objective testing (upper GI endoscopy and/or ambulatory reflux monitoring) between 3/2018-5/2023. The training phase identified a model with optimal receiver operating characteristic curves, and beta coefficients informed a weighted model. The validation phase assessed performance characteristics of the weighted model.

RESULTS: 856 adults, 304 in training cohort and 552 in the validation cohort, were included. In the training phase the optimal predictive model [AUC 0.68 (95% CI 0.62, 0.74)] - the COuGH RefluX score - consisted of Cough, Overweight/obesity, Globus, Hiatal Hernia, Regurgitation, and male seX with a lower threshold of 2.5 and upper threshold of 5.0 to predict proven GERD. In the validation phase, the COuGH RefluX score had an AUC of 0.67 (0.62, 0.71) with 79% sensitivity and 81% specificity for proven GERD.

CONCLUSIONS: The externally validated COuGH RefluX score is a clinically practical model to predict likelihood of proven GERD. The score classifies most patients with chronic laryngeal symptoms as low/high likelihood of proven GERD, with only 38% remaining as indeterminate. Thus, the COuGH RefluX score can guide diagnostic strategies and reduce inappropriate proton pump inhibitor use or testing for patients referred for evaluation of chronic laryngeal symptoms.

INTRODUCTION: Adenoma per colonoscopy (APC) has recently been proposed as a quality measure for colonoscopy. We evaluated the impact of a novel AI system, compared to standard HD colonoscopy, for APC measurement.

METHODS: This was a U.S. based, multi-center, prospective randomized trial examining a novel AI detection system (EW10-EC02) that enables a real-time colorectal polyp detection enabled with the colonoscope (CAD-EYE™). Eligible average risk subjects (≥45 years) undergoing screening or surveillance colonoscopy were randomized to undergo either CAD-EYE-assisted colonoscopy (CAC) or conventional colonoscopy (CC). Modified Intention-to-treat (mITT) analysis was performed for all patients that completed colonoscopy with primary outcome of APC. Secondary outcomes included positive predictive value (PPV, total number of adenomas divided by total polyps removed) and adenoma detection rate (ADR).

RESULTS: In mITT analysis, of 1031 subjects (age: 59.1+/-9.8; 49.9% male), 510 underwent CAC vs. 523 underwent CC with no significant differences in age, gender, ethnicity, or colonoscopy indication between the 2 groups. CAC led to a significantly higher APC compared to CC: 0.99± 1.6 vs. 0.85±1.5, p=0.02, Incidence Rate Ratio 1.17 (1.03-1.33, p=0.02) with no significant difference in the withdrawal time: 11.28±4.59 min vs. 10.8±4.81 min; p=0.11 between the 2 groups. Difference in PPV of a polyp being an adenoma among CAC and CC was less than 10% threshold established: 48.6% vs 54%, 95% CI -9.56%, -1.48%. There were no significant differences in ADR (46.9% vs. 42.8%), advanced adenoma (6.5% vs. 6.3%), sessile serrated lesion detection rate (12.9% vs. 10.1%) and polyp detection rate (63.9% vs 59.3%) between the 2 groups. There was a higher polyp per colonoscopy with CAC compared to CC: 1.68 ± 2.1 vs. 1.33 ± 1.8 (incidence rate ratio 1.27; 1.15-1.4; p<0.01).

CONCLUSION: Use of a novel AI detection system showed to a significantly higher number of adenomas per colonoscopy compared to conventional HD colonoscopy without any increase in colonoscopy withdrawal time, thus supporting use of AI-assisted colonoscopy to improve colonoscopy quality. (Clinicaltrials.gov NCT04979962).

BACKGROUND AND AIM: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE.

METHODS: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE).

RESULTS: Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI-nr-EoE.

CONCLUSION: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE.

INTRODUCTION: Guidelines advise esophageal motility testing for dysphagia when structural disorders are ruled out, but cost concerns impede adoption. We evaluated cost-effective positioning of esophageal motility testing in the algorithm to evaluate esophageal dysphagia.

METHODS: We developed a decision analytic model comparing 3 strategies: (i) esophageal manometry, (ii) screening impedance planimetry followed by esophageal manometry if needed, or (iii) nonalgorithmic usual care. Diagnostic test accuracy was adapted to expected rates of esophageal motility disorders in general gastroenterology populations. We modeled routine testing for all patients with nonstructural/mechanical dysphagia compared with selective testing with strong suspicion for achalasia. Cost outcomes were defined on national commercial and Medicare datasets stratified on age and sex. Health outcomes were modeled on populations with achalasia. The time horizon was 1 year.

RESULTS: Motility testing was preferred over nonalgorithmic usual care due to cost savings rather than health gains. To commercial insurers, routine esophageal manometry for nonstructural/mechanical dysphagia would be cost-saving below a reimbursed cost of $2,415. Screening impedance planimetry would be cost saving below a reimbursed cost of $1,130. The limit for reimbursed costs would be lower for patients older than 65 years to achieve cost savings mainly due to insurance. Sex did not significantly influence cost-effectiveness. Patients and insurers preferred routine screening impedance planimetry before manometry when the index of suspicion for achalasia was below 6%.

DISCUSSION: Aligning with practice guidelines, routine esophageal motility testing seems cost saving to patients and insurers compared with nonalgorithmic usual care to evaluate nonstructural/mechanical dysphagia. Choice of testing should be guided by index of suspicion.

BACKGROUND: Patients with obesity often report esophageal symptoms, with abnormal reflux and esophageal motility suggested as potential mechanisms. However, prior studies showed varying results, often limited by study design/size and esophageal function/symptom measures utilized. We aimed to examine the relationship between obesity and objective esophageal function testing and patient-reported outcomes, utilizing prospective symptom, manometric and reflux monitoring data with impedance.

METHODS: Adults referred for high-resolution impedance-manometry (HRiM) and multichannel intraluminal impedance-pH monitoring (MII-pH) to evaluate esophageal symptoms were enrolled. Validated symptom and health-related quality of life (HR-QOL) instruments were prospectively collected: GERDQ, reflux symptoms index (RSI), dominant symptom intensity (DSI, multiplied 5-point Likert scales for symptom frequency/severity), global symptom severity (GSS, 100-point visual analog scale), and Short Form-12 (SF-12) for HR-QOL. Esophageal function testing measures were compared across body mass index (BMI) categories and correlated with patient-reported outcomes.

KEY RESULTS: Seven hundred and fifty four patients were included (Normal:281/Overweight:253/Class I obesity:137/Class II/III obesity:83). Reflux burden measures on MII-pH (acid exposure time, total reflux episodes, bolus exposure time), conclusive pathologic reflux (Lyon), and hiatal hernia were increased in higher obesity classes compared to normal BMI. Class II/III obesity was associated with more normal/hypercontractile swallows, less ineffective swallows, and better bolus transit on HRiM. BMI correlated positively with GERDQ/RSI/DSI/GSS, and negatively with physical component score (SF-12). Esophageal symptom severity and HR-QOL correlated strongly with MII-pH findings, but not HRiM measures.

CONCLUSIONS/INFERENCES: Obesity is associated with increased esophageal symptom burden and worse physical HR-QOL, which correlate with higher acid/bolus reflux burden but not altered esophageal motility/transit/contractile reserve.