Crowell, Michael D.

Abstract Topic Benign Disease: Eosinophilic Esophagitis Background Active inflammation in eosinophilic esophagitis (EoE) disrupts the mucosal barrier, leading to dilated intercellular spaces and decreased transepithelial electrical resistance. Mucosal impedance (MI) has been used to assess mucosal integrity in EoE. We evaluated whether baseline MI measured by high-resolution impedance manometry (HRIM) distinguishes active and inactive EoE. Methods We retrospectively reviewed data from patients with EoE who underwent endoscopic esophageal biopsies within three months of HRIM from 2018-2026 at our tertiary referral center and had no treatment changes between studies. We excluded patients with a history of foregut surgery, erosive esophagitis, or Barrett’s esophagus. Demographics, endoscopy and pathology results were collected by chart review. Active EoE was histologically defined as ≥15 eosinophils per high-power field. Esophageal baseline MI was measured in the 30-second landmark period for the whole esophagus (from 2 cm above LES to 2 cm below UES), distal esophagus (from 2–7 cm above LES), and mid/proximal esophagus (from 10 cm above LES to 2 cm below UES). Mann–Whitney U or T tests were used for comparisons . Optimal MI thresholds were identified by Youden index with 10,000 bootstrap validations, and interrater reliability was assessed using two-way mixed effects intraclass correlation coefficients. Results Seventy-three patients were included: 37 (51%) female, median age 52 years, median BMI 27.2 kg/m2. Fifty-seven patients (78%) had atopic history, including seasonal allergies (38, 52%), asthma (31, 42%), eczema (21, 29%), and food allergies (19, 26%). Thirty-nine patients (53%) were receiving proton pump inhibitors, 25 (34%) were not on EoE therapy, 5 (6.8%) were on swallowed topical steroids, 3 (4.1%) were on dupilumab, and 1 (1.4%) was on an elimination diet. Esophageal strictures were present in 23 patients (32%), and 45 (62%) had active EoE. Baseline MI measurement showed high interrater reliability (n=50, 2 raters; intraclass correlation coefficient 0.937–0.963, p<0.001). Basal mean and minimal impedance were significantly lower in active EoE across all segments, greatest in the distal esophagus (all p<0.05; Figure 1). ROC analysis showed high discrimination of distal mean MI, with a cutoff ≤1.91 kΩ (AUC=0.837, sensitivity 67.9%, specificity 86.7%, Youden 0.545; Figure 2). Conclusion Baseline mucosal impedance during HRIM distinguishes active from inactive EoE, with strongest discrimination in the distal esophagus, supporting MI as a potential, minimally-invasive physiologic marker of mucosal inflammation and disease activity. Clinically, MI may serve as an adjunct tool in dysphagia evaluation, prompting EoE-directed biopsy when abnormal, aiding management in biopsy–symptom discordance, and potentially supporting disease monitoring in selected patients. Larger prospective studies are warranted.

Abstract Topic Benign Disease: Gastro-Esophageal Reflux and Hiatal Hernia Background Ambulatory reflux monitoring (wireless pH or catheter-based pH-impedance) performed off acid suppression is the gold standard for diagnosing gastroesophageal reflux disease (GERD). Barium esophagram (BE), commonly used to evaluate esophageal symptoms, routinely assesses reflux, yet its diagnostic accuracy relative to ambulatory monitoring remains unclear. Existing studies are limited, relied on outdated reflux criteria, and demonstrated poor concordance with BE-based GERD diagnoses. We aimed to determine whether BE reliably identifies GERD compared with ambulatory reflux monitoring interpreted using updated Lyon 2.0 consensus criteria. Methods Retrospective analysis of adult patients that underwent BE and ambulatory reflux monitoring (wireless pH or pH-impedance) off PPI within an 8-month interval. Patients with a history of fundoplication were excluded. Esophagram was performed with standard technique and reported by radiology, considered positive for GERD if there was reflux above the thoracic inlet with or without provocative maneuvers. Reflux monitoring studies were considered positive or negative for GERD based on Lyon consensus 2.0 recommendations. Inter-rater reliability, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and received operating characteristic (ROC) curve analysis were calculated for esophagram, with reflux monitoring diagnosis as the gold standard. Results 64 patients were included, 31 % male, mean age = 60 years, mean Body Mass Index = 26. GERD was diagnosed by esophagram in 20 patients (31%), and by reflux monitoring in 19 (30%). Compared to reflux monitoring, BE had sensitivity: 47%, specificity: 76%, PPV: 45%, NPV: 77%, and area under the ROC curve: 0.61 (Figure 1). Inter-rater reliability between BE and ambulatory reflux monitoring was poor (Cohen's Kappa = 0.226). Conclusion There was poor concordance between BE and ambulatory reflux monitoring for diagnosing GERD. BE overall had suboptimal diagnostic performance, with low sensitivity, and moderate specificity. Furthermore, the area under the ROC curve indicates limited ability to distinguish correctly between patients with and without GERD. These findings indicate that barium esophagram should not be relied upon as a diagnostic tool for GERD.

Abstract Topic Benign Disease: Gastro-Esophageal Reflux and Hiatal Hernia Background Ambulatory reflux monitoring off acid suppression is the gold standard for diagnosing gastroesophageal reflux disease (GERD). Barium esophagram (BE) routinely evaluates reflux, but its diagnostic accuracy remains uncertain. We assessed whether BE reliably identifies GERD compared with ambulatory reflux monitoring interpreted using updated Lyon 2.0 consensus criteria. Methods Retrospective analysis of adult patients that underwent BE and ambulatory reflux monitoring (wireless pH or pH-impedance) off PPI within an 8-month interval. Patients with a history of fundoplication were excluded. Esophagram was performed with standard technique and reported by radiology, considered positive for GERD if there was reflux above the thoracic inlet with or without provocative maneuvers. Reflux monitoring studies were considered positive or negative for GERD based on Lyon consensus 2.0 recommendations. Inter-rater reliability, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and received operating characteristic (ROC) curve analysis were calculated for esophagram, with reflux monitoring diagnosis as the gold standard. Results 64 patients were included, 31 % male, mean age = 60 years, mean Body Mass Index = 26. GERD was diagnosed by esophagram in 20 patients (31%), and by reflux monitoring in 19 (30%). Compared to reflux monitoring, BE had sensitivity: 47%, specificity: 76%, PPV: 45%, NPV: 77%, and area under the ROC curve: 0.61 (Figure 1). Inter-rater reliability between BE and ambulatory reflux monitoring was poor (Cohen's Kappa = 0.226). Conclusion There was poor concordance between BE and ambulatory reflux monitoring for diagnosing GERD. BE overall had suboptimal diagnostic performance, with low sensitivity, and moderate specificity. Furthermore, the area under the ROC curve indicates limited ability to distinguish correctly between patients with and without GERD. These findings indicate that barium esophagram should not be relied upon as a diagnostic tool for GERD.

ABSTRACT Background Eosinophilic esophagitis is associated with epithelial barrier dysfunction. Epidemiologic studies suggest environmental factors promote disease pathogenesis. The common household detergent sodium dodecyl sulfate (SDS) induces epithelial barrier dysfunction and eosinophilic inflammation in mice. We hypothesized that acute SDS exposure would compromise the esophageal mucosal barrier in humans. Methods Healthy adults brushed with 2 g of an SDS‐containing toothpaste. Esophageal impedance was measured continuously pre‐/post‐toothbrushing to assess the effect of toothpaste on epithelial barrier function. SDS was measured in saliva using a methylene blue anionic substances assay. Participants completed 1‐h esophageal string tests (ESTs) pre‐/post‐toothbrushing and protein isolates from EST eluates from the proximal and distal esophagus were analyzed by tandem mass tag mass spectrometry. Results Ten of twelve subjects completed the clinical study. SDS in the initial expectorate measured immediately after toothbrushing varied markedly (median: 321.40 μg/mL; range: 169.90–1243.00 μg/mL) and was detectable in saliva in 80% of subjects (median: 9.55 μg/mL; range: 0–123.40 μg/mL) at 60 min post toothbrushing. Esophageal mucosal impedance decreased within 30 min of toothbrushing ( p < 0.01). Toothbrushing increased salivary viscosity and proteins associated with mucosal defense in EST eluates. The tight junction pathway was downregulated while the salivary secretion and complement and coagulation cascades pathways were upregulated in the proximal esophagus. Conclusion In healthy individuals, SDS remained detectable in saliva for a prolonged period after toothbrushing at concentrations previously shown to disrupt esophageal epithelial barrier function in vitro. Toothbrushing with an SDS‐containing toothpaste was associated with reduced esophageal mucosal impedance, altered salivary properties, and activated mucosal immune responses.

Background and Objective: Weight loss and small intestinal bacterial overgrowth (SIBO) are common in Parkinson’s disease (PD). We aimed to study the relationship between weight loss and SIBO in PD. Methods: This was a cross-sectional study with a prospective, interventional component. Consecutive patients seen in the PD clinic who agreed to participate underwent extensive history, movement exam, SIBO breath testing and answered questionnaires. A subset of those in the weight loss group were treated with rifaximin for 14 days and returned 3 months later for an assessment of their weight, GI symptoms, quality of life and SIBO status. All analyses were adjusted for age and disease duration. Results: Fifty-one patients participated in the study; 37 without weight loss and 14 with weight loss. Total energy intake including the distribution of macronutrient intake was similar between groups while physical activity was less in those with weight loss. PD severity scores did not differ between groups; however, PD-specific quality of life scores were significantly worse for the summary index and the subscales of emotional well-being, social support and communication. The prevalence of constipation, dyspepsia and abdominal pain/discomfort was higher in those with weight loss. The prevalence of SIBO was 14% in the weight loss group and was not different between groups. Eight PD patients with weight loss were treated with rifaximin; no significant change in GI symptoms, quality of life or weight was seen 3 months later. Conclusion: Although a number of differences were identified in quality of life and gastrointestinal symptoms between groups with and without weight loss, SIBO was not associated with weight loss in patients with PD. Given the exploratory nature and small number of patients with weight loss, however, further study is suggested.

Abstract Introduction Ineffective esophageal motility (IEM) is a common finding on high resolution esophageal manometry (HRM) and is often of unclear clinical significance as its impact on dysphagia and bolus transit is variable. Multiple rapid swallow (MRS) testing is a provocative maneuver performed during HRM that assesses peristaltic reserve, documented by the presence of contractile augmentation (defined by contractile vigor after MRS greater than that seen with single swallows). Lack of augmentation after MRS is associated with dysphagia after anti-reflux surgery. To date, no studies have evaluated the impact of peristaltic reserve on dysphagia and bolus transit in IEM patients. Methods Retrospective review of 159 patients with Chicago classification 4.0 IEM. 52 patients were excluded due to prior esophageal surgery, technically inadequate MRS, or concomitant esophagogastric junction outflow obstruction. Demographics and brief esophageal dysphagia questionnaire (BEDQ) results were obtained from a prospectively maintained database. MRS and bolus transit data were analyzed using a commercially available software. Impedance analysis documented complete versus incomplete bolus transit. Augmentation was defined as the ratio of post-MRS DCI to mean single swallow DCI &gt; 1. Fisher's exact test for continuous data and linear model ANOVA were used to assess for statistical significance. Results 107 IEM patients were included, 46 of them had loss of peristaltic reserve (no augmentation on MRS). Compared to IEM patients with augmentation, those without augmentation had more severe dysphagia documented by higher mean BEDQ score (6.8 versus 4.8, p= 0.045), and increased rates of impaired bolus transit (73% versus 55%, p-= 0.013). Discussion IEM patients without augmentation on MRS have more severe dysphagia and more frequent incomplete bolus clearance. These findings support adding MRS response to the diagnosis of IEM or using it to describe a subset of patients with more severe disease.

AbstractBackgroundAbdominal bloating and distension are prevalent gastrointestinal symptoms. Our aim was to design and validate a questionnaire to reliably measure the multiple symptom components of bloating and distension in the outpatient setting.MethodsA 45‐item questionnaire was developed after an extensive literature review. Face and content validity were established through expert review and a focus group. Validation was achieved by administering an identical questionnaire 1 week apart. Data were assessed using standard methods.Key resultsForty one patients returned both questionnaires (85% women; mean age = 44 years). Respondents reported a variety of diagnoses, including irritable bowel syndrome (63%), gastroesophageal reflux disease (54%), functional dyspepsia (27%), small intestinal bacterial overgrowth (22%), and gastroparesis (17%). Test‐retest reliability revealed excellent agreement (k ≥ 0.81) and substantial agreement (0.61 ≤ k < 0.81) for 29% and 43% of categorical questions, respectively. Alternate‐parallel form reliability was supported by association between responses for questions that evaluated missing school/work and questions that evaluated symptom impact on daily activities (p < 0.05). Patients who missed school/work due to bloating symptoms were more likely to report a severe impact on their ability to enjoy life (p < 0.05) and their overall well‐being (p < 0.01). Contingency analyses revealed an association between overall 7‐day symptom severity and impact on daily activities (p < 0.001), enjoying life (p < 0.001), and overall well‐being (p < 0.001).Conclusions and InferencesThis novel questionnaire demonstrated good validity and reliability in patients with symptoms of bloating and distension. The questionnaire was easy to use and score, making it a potentially useful tool for both research studies and clinical purposes.

Abstract: Disorders of gastric motor and sensory function affect 10%-20% of the world’s population and adversely impact nutrition, quality of life, work productivity, and health care costs. Classifying these disorders can be challenging given the heterogeneity of symptom presentation, the presence of symptoms unexplained by endoscopic, radiographic and/or laboratory evaluation, and overlap with other luminal gastrointestinal disorders. Accurately diagnosing these highly prevalent disorders relies upon an understanding of epidemiology and risk factors, the ability to take a careful clinical history focused on symptoms, and the presence of predisposing medical, surgical, and psychological conditions. A variety of diagnostic studies are now available to assess gastric motor function and identify maladaptive relaxation, accommodation, and abnormal sensation. FDA-approved treatment options are limited and thus many patients undergo a series of empirical treatment trials that target individual symptoms, often without much benefit. This article provides updated recommendations for identifying and classifying the most common gastric motor and sensory disorders using currently accepted diagnostic tests, and provides a brief supplemental overview on treatment options. “Things sweet to taste prove in digestion sour.” –Shakespeare, Richard II , 1595.