BACKGROUND AND AIMS: The pattern of inflammation in eosinophilic esophagitis (EoE) is patchy, necessitating multiple biopsies to optimize diagnostic yield. Current consensus-based guidelines recommend 6 total biopsies at two sites: distal and either middle or proximal esophagus, although based on limited data. We aimed to determine whether this biopsy protocol sufficiently captures EoE diagnoses by evaluating the distribution of eosinophilia in a large EoE cohort.

METHODS: This was a retrospective study of consecutive, newly-diagnosed EoE patients with ≥2 esophageal segments biopsied. Demographics, clinical characteristics/history, endoscopic findings, and histologic results were manually reviewed. Distribution (proximal, middle, and/or distal) of eosinophilia (>15 eosinophils/hpf) was assessed. Predictors for non-distal disease (<15 eosinophils/hpf on distal biopsies) were evaluated using multivariable logistic regression.

RESULTS: 511 newly-diagnosed EoE patients with ≥2 segments biopsied were included. All patients had distal esophageal biopsy. Overall, 286 (56.0%) had ≥1 site with <15 eosinophils/hpf, including 51 (10%) non-distal disease. Among patients with three segments biopsied (n=60), 19 (31.7%) had eosinophilia at only one site, including 6 (10%) isolated mid esophageal disease and no isolated proximal eosinophilia. Discordant mid and proximal biopsy results were found in 18 (30%) patients, with 17/18 (94.4%) mid esophageal eosinophilia. On multivariable analysis, increasing age (OR:1.02, CI:1.002-1.04, p=0.03) and male gender (OR:1.89, CI:1.002-3.55, p=0.049) independently predict non-distal disease.

CONCLUSIONS: Isolated segmental eosinophilia is common in EoE, including up to 10% non-distal disease. Discordant mid and proximal biopsy findings are prevalent, with no isolated proximal eosinophilia. Standard protocol should include routine biopsies of both distal and middle esophagus to maximize diagnostic yield.

BACKGROUND: Chronic constipation, diarrhea, and fecal incontinence (FI) are prevalent with significant impact on quality of life and healthcare utilization. Thyroid dysfunction was recognized as a potential contributor to bowel disturbances in selected populations, but the strength/consistency of this association remain unclear.

AIMS: To investigate the relationship between thyroid function and bowel health measures (constipation, diarrhea, and FI) in a nationally representative sample of the U.S.

METHODS: We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) in 2005-2008. Adults aged ≥ 20 with TSH, free T4 (fT4), and bowel health data were included. Multivariable logistic regression models were constructed to examine associations between thyroid function and bowel health measures, adjusting for potential confounders.

RESULTS: Among 6,552 participants, 93.6%, 4.3%, 1.7%, and 0.4% had TSH levels of 0.24-5.4, 5.4-10, < 0.24, and ≥ 10 mIU/L, respectively. There were no significant differences in prevalence of thyroid dysfunction between individuals with constipation or diarrhea and those without. In fully adjusted models, TSH was not a significant predictor of constipation, diarrhea, or FI, but higher fT4 was protective against constipation as a continuous variable (OR 0.47, CI: 0.26-0.85, p = 0.014)). Neither hypothyroid nor hyperthyroid status significantly correlated with constipation or diarrhea, although hyperthyroidism was associated with FI (OR 3.58, CI:1.51-8.49, p = 0.005).

CONCLUSION: While bowel disturbances were common in this nationally representative sample, the yield of thyroid function testing was low. Overt hypo- and hyperthyroidism were not significantly associated with constipation or diarrhea. Clinical utility of routine thyroid testing for bowel symptoms may be low in patients without systemic manifestations of severe thyroid disease.

BACKGROUND: Hindgut symptoms are poorly understood complications of obesity. The impact of obesity on fecal incontinence (FI) and anorectal physiology remains unclear, with inconsistent results in prior studies. We aimed to evaluate the relationship between obesity and FI, and the physiological changes in anorectal function.

METHODS: This was a retrospective cohort study of consecutive adults who underwent high-resolution anorectal manometry (HRAM) at a tertiary center for anorectal symptoms. Demographics, clinical history, surgical/obstetric history, medications and HRAM findings were reviewed. Patients were classified as non-obese (BMI <25 kg/m2), overweight (BMI 25-29.9 kg/m2), class I obesity (30-34.9 kg/m2), and class II+III obesity (>35 kg/m2). Fisher-exact/student t-test for univariate analyses and logistic/general linear regression for multivariable analyses were performed.

RESULTS: 552 adults were included. Mean BMI was higher among patients with FI (27.5 vs 25.9 kg/m2, p=0.013). Compared to non-obese group, FI was more prevalent in class II+III obesity (31.7% vs 13.2%, p=0.0024), but not class I obesity or overweight groups. On multivariable analysis controlling for potential confounders, class II+III obesity (adjusted OR 2.89, CI:1.28-6.50, p=0.02) remained an independent risk factor for FI. Among patients with FI, both BMI (β-coefficient 1.09, p=0.016) and class II+III obesity (β-coefficient 18.9, p=0.027) independently predicted increased first rectal sensation volume on HRAM on multivariable regression.

CONCLUSIONS: Classes II+III obesity was an independent risk factor for FI. Among patients with FI, increasing BMI and class II+III obesity were associated with altered rectal sensitivity. Anorectal function testing should be considered to help guide management of FI among patients with obesity.

INTRODUCTION: The management strategies for eosinophilic esophagitis include proton pump inhibitors (PPIs), swallowed topical corticosteroids (tCSs), elimination diets, and the biologic agent dupilumab, although there remains little guidance on the selection of initial treatment. We performed cost-effectiveness analyses to compare these approaches of first-line therapy.

METHODS: A Markov model was constructed from a payer perspective to evaluate the cost-effectiveness of first-line therapies for eosinophilic esophagitis, including PPI, tCS, and 6-food elimination diet (SFED), with crossover in treatments for primary and secondary nonresponse. The primary outcome was incremental cost-effectiveness ratio at 2 and 5-year time horizons. Secondary analyses included modeling from a societal perspective that also accounted for patient-specific costs, as well as a separate simplified model comparing dupilumab with tCS and PPI.

RESULTS: In the base-case scenario (5-year time horizon), the average costs were SFED: $15,296.81, PPI: $16,153.77, and tCS: $20,975.33 as initial therapy, with SFED being the dominant strategy (more effective/less costly), while PPI offered the lowest cost on a 2-year time horizon. From a societal perspective, PPI was the dominant initial strategy on both 2 and 5-year time horizons. Among pharmacologic therapies, PPI was the most cost-effective first-line option. Dupilumab was not cost-effective relative to tCS, unless the quarterly cost is reduced from $7,311 to $2,038.50 per price threshold analysis under permissive modeling conditions.

DISCUSSION: SFED was the most effective/least costly first-line therapy from the payer perspective while PPI was more cost-effective from the societal perspective. PPI is also the most cost-effective pharmacologic strategy. Dupilumab requires substantial cost reductions to be considered cost-effective first-line pharmacotherapy.

Gastroesophageal reflux disease occurs when the barrier at the esophagogastric junction is weakened, allowing for transient relaxations of the lower esophageal sphincter or disruption of the esophagogastric junction. This leads to the refluxate traveling up the esophagus, and potentially into the pharynx, where it can be aspirated into the airway. The refluxate can cause a range of symptoms, including sore throat, coughing, wheezing, and shortness of breath, which may occur with or without visible airway inflammation. Both experimental and clinical studies have shown that aspirated refluxate can directly damage the airway lining and trigger immune responses that contribute to airway injury and inflammation. While traditional diagnostic tests for gastroesophageal reflux disease can identify abnormal reflux patterns, there is a need for more specific methods to predict airway inflammation or therapeutic outcomes related to reflux aspiration.

BACKGROUND: The impact of pelvic bone structure on fecal incontinence (FI) is unclear. We assessed the association between weight-adjusted pelvic area and FI.

METHODS: This was a population-based analysis of the National Health and Nutrition Examination Survey in 2005-2006. Participants who completed the bowel health survey and dual-energy x-ray absorptiometry (DXA) were included.

RESULTS: On multivariable analysis of 2,772 participants, the lowest pelvic area quartile predicted increased FI compared to the third (OR:2.05, CI:1.18-3.56, p=0.014) and fourth (OR:1.94, CI:1.02-3.70, p=0.045) quartiles. Sex-stratified analyses found similar association among female patients only.

CONCLUSION: Small pelvic area on DXA is a potential risk factor for FI.

INTRODUCTION: We explored if a score derived from parameters from esophageal testing could increase confidence in diagnosing conclusive gastroesophageal reflux disease and in predicting outcome.

METHODS: A prediction score was developed using metrics based on Lyon Consensus 2.0 thresholds extracted from endoscopy and pH-impedance monitoring. The Lyon score was the sum of weighted scores derived from a logistic regression model. The outcome was response to antireflux therapy, defined as 50% reduction in global symptoms on validated questionnaires. An existing database of endoscopy-negative patients with typical reflux symptoms undergoing esophageal testing from 2 centers (Europe and the United States) constituted the developmental cohort, while 2 separate cohorts (Europe and Asia) served as validation cohorts. Receiver operating characteristics analysis determined performance of the Lyon score in predicting treatment response.

RESULTS: In 281 developmental cohort patients (median age 53 years, 57.7% female), the Lyon score demonstrated an area under the curve (AUC) of 0.819 in predicting 50% symptom improvement ( P < 0.001) on receiver operating characteristics, with an optimal threshold of 6.25 (sensitivity 81.2%, specificity 73.4%). Of the individual components, only acid exposure time (AUC 0.799, P < 0.001), mean nocturnal baseline impedance (AUC 0.785, P < 0.001), and reflux episodes (AUC 0.764, P < 0.001) approached the Lyon score performance. The Lyon score segregated treatment response in both the European (AUC 0.908, P < 0.001) and Asian validation cohorts (AUC 0.637, P < 0.001) and outperformed the DeMeester score in sensitivity for predicting outcome in the developmental and Asian validation cohorts.

DISCUSSION: The novel Lyon score segregates reflux phenotypes and identifies likelihood of symptom response from antireflux therapy.