Behavioral Therapy for Functional Heartburn: Recommendation Statements.

BACKGROUND & AIMS: Brain-gut behavior therapies (BGBT) are increasingly recognized as effective therapeutic interventions for functional heartburn. However, recommendations regarding candidacy for treatment, initial treatment selection, and navigating treatment non-response have not been established for functional heartburn specifically. The aim of this study was to establish expert-based recommendations for behavioral treatment in patients with functional heartburn. METHODS: The validated RAND/University of California, Los Angeles Appropriateness Method was applied to develop recommendations. A 15-member panel composed of 10 gastrointestinal psychologists and 5 esophageal specialists ranked the appropriateness of a series of statements on a 9-point interval scale over 2 ranking periods. Statements were within the following domains: pre-therapy evaluation, candidacy criteria for BGBT, selection of initial BGBT, role of additional therapy for initial non-response to BGBT, and role of pharmacologic neuromodulation. The primary outcome was appropriateness of each intervention based on the recommendation statements. RESULTS: Recommendations for psychosocial assessment (eg, hypervigilance, symptom-specific anxiety, health-related quality of life), candidacy criteria (eg, motivated for BGBT, acknowledges the role of stress in symptoms), and treatment were established. Gut-directed hypnotherapy or cognitive behavioral therapy were considered appropriate BGBT for functional heartburn. Neuromodulation and/or additional BGBT were considered appropriate in the context of non-response. CONCLUSIONS: Gut-directed hypnotherapy and/or cognitive behavioral therapy are recommended as appropriate behavioral interventions for heartburn symptoms, depending on clinical indication, specific gut-brain targets, and preferred treatment modality (pharmacologic vs non-pharmacologic). Pre-therapy evaluation of psychosocial processes and candidacy for BGBT are important to determine eligibility for referral to psychogastroenterology services.

Psychological Processes, Not Physiological Parameters, Are Most Important Contributors to Symptom Severity in Patients With Refractory Heartburn/Regurgitation Symptoms.

BACKGROUND & AIMS: Physiological and psychological factors have been found to influence esophageal symptom reporting. We aimed to evaluate which of these factors are associated with 3 reflux symptom severity outcomes (ie, Total Reflux, Heartburn, and Sleep Disturbance) through a traditional statistical and a complementary machine-learning approach. METHODS: Consecutive adult patients with refractory heartburn/regurgitation symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing past and current gastrointestinal and psychological health. In the traditional statistical approach, hierarchical general linear models assessed relationships of psychological and physiological variables (eg, total number of reflux episodes) with reflux severity scores. Mediation analyses further assessed pathways between relevant variables. In the machine-learning approach, all psychological and physiological variables were entered into 11 different models and cross-validated model performance was compared among the different models to select the best model. RESULTS: Three hundred ninety-three participants (mean [SD] age, 48.5 [14.1] years; 60% were female) were included. General psychological functioning emerged as an important variable in the traditional statistical approach, as it was significantly associated with all 3 outcomes and mediated the relationship between childhood trauma and both Total Reflux and Heartburn Severity. In the machine-learning analyses, general psychological variables (eg, depressive symptoms) were most important for Total Reflux and Sleep Disturbance outcomes, and symptom-specific variables, like visceral anxiety, were more influential for Heartburn Severity. Physiological variables were not significant contributors to reflux symptom severity outcomes in our sample across reflux classifications and statistical methodology. CONCLUSIONS: Psychological processes, both general and symptom-specific, should be considered as another important factor within the multifactorial processes that impact reflux symptom severity reporting across the reflux spectrum.

Vonoprazan is Efficacious for Treatment of Heartburn in Non-erosive Reflux Disease: A Randomized Trial.

BACKGROUND & AIMS: Potassium-competitive acid blockers have documented efficacy for erosive esophagitis. We performed a randomized trial in United States subjects diagnosed with non-erosive reflux disease of vonoprazan vs placebo for 4 weeks, followed by a 20-week active-treatment extension. METHODS: Adult subjects with heartburn ≥4 days/week during screening without erosive esophagitis on endoscopy were randomized to placebo, vonoprazan 10 mg, or vonoprazan 20 mg. After 4 weeks, subjects on placebo were re-randomized to vonoprazan 10 mg or 20 mg, and those already on vonoprazan continued at the same dose for 20 weeks. Electronic diaries were completed twice daily. The primary endpoint was percentage of days without daytime or nighttime heartburn (24-hour heartburn-free days). RESULTS: Among 772 randomized subjects, the percentage of 24-hour heartburn-free days was 27.7% for placebo vs 44.8% for vonoprazan 10 mg (least squares mean difference, 17.1%; P < .0001) and 44.4% for vonoprazan 20 mg (least squares mean difference, 16.7%; P < .0001). Differences in percentage of subjects with a 24-hour heartburn-free day for vonoprazan 10 mg vs placebo and vonoprazan 20 mg vs placebo were 8.3% and 11.6% on day 1 and 18.1% and 23.2% on day 2. The mean/median percentages of 24-hour heartburn-free days over the extension period were similar across the 4 study arms: 61%-63%/76%-79%. CONCLUSIONS: Vonoprazan reduced heartburn symptoms in subjects diagnosed with non-erosive reflux disease, with the benefit appearing to begin as early as the first day of therapy. Treatment effect persisted after the initial 4-week placebo-controlled period throughout the 20-week extension period. The 2 vonoprazan doses (10 mg and 20 mg) were similar in efficacy. (ClinicalTrials.gov: NCT05195528).

A new grading assessment of eosinophilic esophagitis using red dichromatic imaging: a pilot study.

BACKGROUND AND AIMS: The endoscopic reference score using white-light imaging (WLI) is utilized for objectively evaluating the severity of findings in patients with eosinophilic esophagitis. A novel image-enhanced endoscopy technique, red dichromatic imaging (RDI), can visualize deeper vessels in the GI tract, which may assess edema more precisely than WLI. METHODS: A total of 21 consecutive patients with eosinophilic esophagitis were prospectively evaluated. Patients were categorized according to 3 grades based on the visibility of vessels with RDI. Clinical features, such as peak eosinophil counts and presence of symptoms, were reviewed. RESULTS: There were 10 patients with RDI Grade 0/1 and 11 patients with RDI Grade 2. Peak eosinophil counts and the prevalence of heartburn were significantly higher in patients with RDI Grade 2 than in patients with RDI Grade 0/1. CONCLUSIONS: The severity of eosinophilic infiltration could be predicted more precisely using RDI than by evaluations with WLI.

Reflux Symptoms Increase Following Sleeve Gastrectomy Despite Triage of Symptomatic Patients to Roux-en-Y Gastric Bypass.

BACKGROUND AND AIMS: Bariatric surgical options in obese patients include sleeve gastrectomy (SG) and roux-en-Y gastric bypass (RYGB), which may not be equivalent in risk of postoperative reflux symptoms. We evaluated risk and predictive factors for postbariatric surgery reflux symptoms. METHODS: Patients with obesity evaluated for bariatric surgery over a 15-month period were prospectively followed with validated symptom questionnaires (GERDQ, dominant symptom index: product of symptom frequency and intensity from 5-point Likert scores) administered before and after SG and RYGB. Esophageal testing included high-resolution manometry in all patients, and ambulatory reflux monitoring off therapy in those with abnormal GERDQ or prior reflux history. Univariate comparisons and multivariable analysis were performed to determine if preoperative factors predicted postoperative reflux symptoms. RESULTS: Sixty-four patients (median age 49.0 years, 84% female, median BMI 46.5 kg/m 2 ) fulfilled inclusion criteria and underwent follow-up assessment 4.4 years after bariatric surgery. Baseline GERDQ and dominant symptom index for heartburn were significantly higher in RYGB patients ( P ≤0.04). Despite this, median GERDQ increased by 2 (0.0 to 4.8) following SG and decreased by 0.5 (-1.0 to 5.0) following RYGB ( P =0.02). GERDQ became abnormal in 43.8% after SG and 18.8% after RYGB ( P =0.058); abnormal GERDQ improved in 12.5% and 37.5%, respectively ( P =0.041). In a model that included age, gender, BMI, acid exposure time, and type of surgery, multivariable analysis identified SG as an independent predictor of postoperative heartburn (odds ratio 16.61, P =0.024). CONCLUSIONS: Despite preferential RYGB when preoperative GERD was identified, SG independently predicted worsening heartburn symptoms after bariatric surgery.

Prevalence and risk factors of gastro-oesophageal reflux symptoms among adolescents, the HUNT study.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is recognized by symptoms of heartburn and acid regurgitation. These gastro-oesophageal reflux symptoms (GORS) are common in adults, but data from adolescents are sparse. This study aimed to assess the prevalence and risk factors of GORS among adolescents in a large and unselected population. METHODS: This study was based on the Trøndelag Health Study (HUNT), a longitudinal series of population-based health surveys conducted in Nord-Trøndelag County, Norway. This study included data from Young-HUNT4 performed in 2017-2019, where all inhabitants aged 13-19 years were invited and 8066 (76.0%) participated. The presence of GORS (any or frequent) during the past 12 months and tobacco smoking status were reported through self-administrated questionnaires, whereas body mass index (BMI) was objectively measured. RESULTS: Among 7620 participating adolescents reporting on the presence of GORS, the prevalence of any GORS and frequent GORS was 33.2% (95% confidence interval [CI] 32.2 - 34.3%) and 3.6% (95% CI 3.2 - 4.0%), respectively. The risk of frequent GORS was lower among boys compared to girls (OR 0.61; 95% CI 0.46 - 0.79), higher in current smokers compared to never smokers (OR 1.80; 95% CI 1.10 - 2.93) and higher among obese compared to underweight/normal weight adolescents (OR 2.50; 95% CI 1.70 - 3.66). CONCLUSION: A considerable proportion of adolescents had GORS in this population-based study, particularly girls, tobacco smokers, and individuals with obesity, but frequent GORS was relatively uncommon. Measures to avoid tobacco smoking and obesity in adolescents may prevent GORS.

Patient-reported symptoms and burden of eosinophilic esophagitis: evidence from real-world clinical practice.

BACKGROUND: Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus. This real-world study used patient and physician surveys to describe the clinical characteristics and disease burden of eosinophilic esophagitis-overall and in a subgroup of patients with dysphagia despite treatment. METHODS: Data analyzed in this study were collected in 2020 from US and EU patients with eosinophilic esophagitis. Eligible patients were aged ≥ 12 years with a diagnosis of eosinophilic esophagitis, had an esophageal count of ≥ 15 eosinophils/high-power field at diagnosis, and were currently prescribed treatment for eosinophilic esophagitis. RESULTS: Overall, 1001 patients were included, of whom 356 (36%) had dysphagia despite treatment. Demographics and clinical characteristics were similar in both populations. The severity of eosinophilic esophagitis was mild in more patients overall (69%) versus those with dysphagia despite treatment (48%). Patient disease history was similar in both populations, with some exceptions: common patient-reported symptoms were dysphagia (70% and 86%) and heartburn/acid reflux (55% and 49%), and common physician-reported symptoms were dysphagia (75% and 91%) and food impaction (46% and 52%). Treatment history was similar in both populations; overall, the most common treatments were proton pump inhibitors (83%) and topical corticosteroids (51%). Patients reported slightly more days with symptoms, higher impacts on activities of daily living, and slightly higher anxiety or depression in the dysphagia-despite-treatment population versus the overall population. CONCLUSIONS: Eosinophilic esophagitis presents severe symptoms and comorbidities that substantially impact patients' well-being and quality of life. Greater awareness of and novel treatments for eosinophilic esophagitis are needed.

Differences Between Patients with Heartburn Refractory to Vonoprazan and Those Refractory to Proton Pump Inhibitors.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, demonstrates more potent acid inhibition than proton pump inhibitors (PPIs). This study aimed to evaluate the effect of vonoprazan in patients with unproven gastroesophageal reflux disease (GERD) by comparing patients with vonoprazan-refractory heartburn with those with PPI-refractory heartburn. METHODS: This study included 104 consecutive patients with vonoprazan- or PPI-refractory heartburn (52 patients each), no erosive esophagitis on endoscopy and who underwent combined multichannel intraluminal impedance-pH (MII-pH) testing with vonoprazan/PPI discontinuation. Patients' backgrounds, symptom scores from four questionnaires, MII-pH results and high-resolution manometry results were compared between the two groups. RESULTS: The vonoprazan group demonstrated significantly higher GERD symptoms and scores of abdominal pain and diarrhea on the Gastrointestinal Symptom Rating Scale questionnaire. MII-pH results revealed that the vonoprazan group demonstrated 40.4%, 17.3%, and 42.3% and the PPIs group exhibited 26.9%, 17.3%, and 55.8% of abnormal acid reflux [true non-erosive reflux disease (NERD)], reflux hypersensitivity and functional heartburn, respectively. The vonoprazan group demonstrated higher true NERD rates but with no significant difference (p = 0.307). Among the vonoprazan group, eight patients with true NERD underwent another MII-pH test on vonoprazan, and all cases demonstrated normal acid exposure times (0.0% [0.0-0.3]). CONCLUSION: Patients with unproven GERD with vonoprazan-refractory heartburn demonstrated more symptoms, including not only GERD symptoms but also functional dyspepsia and irritable bowel syndrome symptoms, than those with PPI-refractory heartburn.

Risk factors associated with functional esophageal disorders (FED) versus gastroesophageal reflux disease (GERD).

INTRODUCTION: Despite the high prevalence of typical symptoms of gastroesophageal reflux disease (GERD), approximately 30% of patients have functional esophageal disorders (FED) on ambulatory reflux monitoring, which may include reflux hypersensitivity (RH; defined as physiologic acid exposure but temporally correlated symptoms of reflux), or functional heartburn (FH; defined as physiologic acid exposure and negative symptom correlation). There are limited epidemiological data characterizing these conditions. We investigated demographic and socioeconomic factors as well as medical comorbidities which may predispose to FED versus pathologic GERD. METHODS: Adult patients with reflux symptoms for at least 3 months were studied with 24-h pH-impedance testing from 11/2019 to 3/2021. Participants were categorized into pathologic GERD, FH, or RH using pH-impedance data and reported symptom correlation. Demographic data, including age, gender, race/ethnicity, zip code, insurance status, and medical comorbidity data were retrospectively retrieved from the electronic medical record on all participants. RESULTS: 229 patients were included. Non-Hispanic Asian ethnicity (OR 5.65; p = 0.01), underweight BMI (OR 7.33; p = 0.06), chronic pain (OR 2.33; p < 0.01), insomnia (OR 2.83; p = 0.06), and allergic rhinitis (OR 3.90; p < 0.01) were associated with a greater risk for FED. Overweight BMI (OR 0.48; p = 0.03) and alcohol use (OR 0.57; p = 0.06) were associated with a decreased risk for FED. DISCUSSION: This is the first report of a greater risk of FED in patients with underweight BMI, insomnia, chronic pain, allergic rhinitis, or of Asian or Hispanic ethnicities. The weak associations between female gender and anxiety are corroborated in other studies. Our findings enable clinicians to better screen patients with reflux for this disorder.

Diffuse Gastrointestinal Motor Compromise in Patients with Scleroderma: Utility of Minimally Invasive Techniques.

BACKGROUND: Scleroderma is a systemic inflammatory disorder that can compromise the gastrointestinal tract in up to 90% of patients. AIM: The purpose of this work is to characterize esophageal, gastric, and intestinal compromise in patients with scleroderma by means of minimally invasive methods and its association with symptoms and severity of their rheumatological condition. METHODS: Patients with systemic sclerosis were recruited according to the criteria of the American College of Rheumatology. The study of digestive involvement was carried out on four consecutive days: esophageal manometry was performed on the first day, intestinal manometry on the second day, surface electrogastrography on the third, and hydrogen breath test on the fourth. The Mann-Whitney test was used for quantitative variables and the chi-squared test for categorical variables (p < 0.05). RESULTS: A total of 30 patients were included, with an average age of 52.7 years and 93% women. Average disease evolution duration was 6.5 years, 70% with limited variety. Rodnan averaged 12 points, being higher in the diffuse variety. The main symptom was heartburn, followed by abdominal distension, with no differences between subtypes except for diffuse nausea; 80% had intestinal manometric compromise, 76% esophageal manometric compromise, and 30% electrogastrographic compromise. Bacterial overgrowth was evidenced in two-thirds (66%) of the patients, and 23% of the patients had simultaneous esophageal, gastric, and intestinal involvement, which correlated with greater skin involvement but not with gastrointestinal symptoms. CONCLUSIONS: Gastrointestinal involvement in patients with scleroderma is frequent and is observed regardless of the symptoms and clinical characteristics of the latter, except for skin involvement.

Long-term outcomes of laparoscopic Heller's myotomy with angle of His accentuation in patients of achalasia cardia.

BACKGROUND: Laparoscopic Heller's myotomy (LHM) is an established treatment for achalasia cardia. Anti-reflux procedures (ARP) are recommended with LHM to reduce the post-operative reflux though the optimal anti-reflux procedure is still debatable. This study reports on the long-term outcomes of LHM with Angle-of-His accentuation (AOH) in patients of achalasia cardia. METHODS: One hundred thirty-six patients of achalasia cardia undergoing LHM with AOH between January 2010 to October 2021 with a minimum follow-up of one year were evaluated for symptomatic outcomes using Eckardt score (ES), DeMeester heartburn (DMH) score and achalasia disease specific quality of life (A-DsQoL) questionnaire. Upper gastrointestinal endoscopy, high resolution manometry (HRM) and timed barium esophagogram (TBE) were performed when feasible and rates of esophagitis and improvement in HRM and TBE parameters evaluated. Time dependent rates of success were calculated with respect to improvement in ES and dysphagia-, regurgitation- and heartburn-free survival using Kaplan-Meier analysis. RESULTS: At a median follow-up of 65.5 months, the overall success (ES ≤ 3) was 94.1%. There was statistically significant improvement in ES, heartburn score and A-DsQoL score (p < 0.00001, p = 0.002 and p < 0.00001). Significant heartburn (score ≥ 2) was seen in 12.5% subjects with 9.5% patients reporting frequent PPI use (> 3 days per week). LA-B and above esophagitis was seen in 12.7%. HRM and TBE parameters also showed a significant improvement as compared to pre-operative values (IRP: p < 0.0001, column height: p < 0.0001, column width: p = 0.0002). Kaplan-Meier analysis showed dysphagia, regurgitation, and heartburn free survival of 75%, 96.2% and 72.3% respectively at 10 years. CONCLUSIONS: LHM with AOH gives a lasting relief of symptoms in patients of achalasia cardia with heartburn rates similar to that reported in studies using Dor's or Toupet's fundoplication with LHM. Hence, LHM with AOH may be a preferred choice in patients of achalasia cardia given the simplicity of the procedure.

Clinical value of random esophageal biopsies in patients with dysphagia and normal endoscopy who are treated with a proton pump inhibitor.

Rome IV recommended esophageal biopsies in patients with dysphagia and normal endoscopy to exclude mucosal disease. Thus far, studies evaluating the utility of this recommendation remain scarce. The aims of this study were to determine the value of random esophageal biopsies in heartburn patients with dysphagia and normal endoscopy and compare the yield of random esophageal biopsies between younger versus older patients. Data were collected from consecutive patients presenting with dysphagia, 18 years and older, who were on proton pump inhibitors and had normal upper endoscopy. Biopsy results of patients with and without heartburn were recorded. Logistic regression analysis was used to compare normal versus abnormal biopsy results in younger and older patients accounting for confounding variables. The number of abnormal biopsies was significantly higher than normal biopsies (68% and 32%, respectively, P = 0.0001). Among abnormal biopsy results, microscopic gastroesophageal reflux disease was significantly more common than all other findings (39%, P = 0.0495). There was no significant difference in biopsy results in patients with and without heartburn as well as younger versus older patients (P = 0.3384, P = 0.1010, and P = 0.8468, respectively). Our study demonstrated that most patients with dysphagia and normal upper endoscopy who are on proton pump inhibitor have some type of histologic mucosal abnormality, which can direct future management. Among abnormal biopsies, microscopic reflux was by far the most common finding in patients with or without a history of heartburn. While this supports the management strategy proposed by Rome IV, age did not drive esophageal biopsy results.

The Effect of Dexlansoprazole on Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor-PPI) in resolving heartburn, reflux, and other symptoms and complications resulting from gastroesophageal reflux disease (GERD). The study followed PRISMA 2020 and was registered in PROSPERO (CRD42020206513). The search strategy used MeSH and free terms appropriately adapted for each database. Only randomized clinical trials (RCTs) were included. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the certainty of evidence was rated using GRADE. Ten RCTs were included. Dexlansoprazole outperformed the placebo and other PPIs in the resolution of heartburn and reflux symptoms in patients with GERD, with benefits during and after treatment, especially in those with moderate and severe symptoms. The meta-analyses indicated that dexlansoprazole at doses of 30 and 60 mg had more 24 h heartburn-free days and nights compared to the placebo medications; no difference was reported between dexlansoprazole at doses of 30 and 60 mg in heartburn-free nights. A low bias risk and a moderate certainty of evidence were observed. This review confirms the therapeutic effect of dexlansoprazole (placebo-controlled) and its improvements in GERD symptoms compared to another PPI. However, the interpretation of the results should be carried out cautiously due to the small number of included studies and other reported limitations.

Managing heartburn and reflux in primary care.

ABSTRACT: This article describes an algorithmic approach to caring for patients presenting with heartburn and reflux, including empiric treatment with acid-suppression therapy and a data-driven approach to diagnostic testing. This article also reviews the efficacy and safety profile of the widely available and commonly used proton pump inhibitors. Refining our approach to diagnostic testing can reduce time to diagnosis, better control patients' symptoms, and limit complications of longstanding disease.

Psychological symptoms do not discriminate between reflux phenotypes along the organic-functional refractory GERD spectrum.

OBJECTIVE: Historically, psychological processes are associated with disorders at the functional end of the gastro-oesophageal reflux disease (GERD) spectrum. However, recent research suggests that psychological symptoms are relevant across the entire GERD spectrum. We aim to investigate whether psychological symptoms are associated with reflux phenotype (True GERD, Borderline GERD, reflux hypersensitivity, functional heartburn) along the GERD spectrum in a cohort of refractory reflux patients. DESIGN: Consecutive adult patients with refractory reflux symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing demographic, clinical and psychological information. Bayesian one-way analysis of variance assessed whether psychological variables differed across reflux phenotypes. Next, we applied multinomial and ordinal logistic regressions with clinical, demographic and psychological variables set as independent variables and reflux phenotype as the outcome variable. The complementary machine-learning approach entered all demographic, clinical and psychological variables into models, with reflux phenotype set nominally and ordinally. Cross-validated model performance was used to select the best model. RESULTS: 393 participants (mean (SD) age=48.5 (14.1); 60% female) were included. The Bayesian analyses found no difference in psychological variables across reflux phenotypes. Similarly, age, gender and proton pump inhibitor use were the only significant variables in the multinomial logistic regression and body mass index was significant in both regressions. Machine-learning analyses revealed poorly performing models with high misclassification rates (67-68%) in both models. CONCLUSION: Psychological symptoms do not differ between nor predict reflux phenotype membership in refractory reflux patients. Findings suggest that psychological symptoms are relevant across the spectrum of GERD, rather than specific to functional oesophageal disorders.

Sex and smoking differences in the association between gastroesophageal reflux and risk of esophageal squamous cell carcinoma in a high-incidence area: Golestan Cohort Study.

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.

Relationships among intragastric meal distribution during gastric emptying scintigraphy, water consumption during water load satiety testing, and symptoms of gastroparesis.

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD0)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD0 and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis underwent GES to obtain gastric retention and IMD0, WLST, and filled out patient assessment of upper GI symptoms. A total of 234 patients with symptoms of gastroparesis were assessed (86 patients with diabetes, 130 idiopathic, 18 postfundoplication) and 175 (75%) delayed gastric emptying. Low IMD0 <0.568 suggesting initial rapid transit to the distal stomach was present in 8% and correlated with lower gastric retention, less heartburn, and lower volumes consumed during WLST. Low WLST volume (<238 mL) was present in 20% and associated with increased severity of early satiety, postprandial fullness, loss of appetite, and nausea. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. Thus, IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.NEW & NOTEWORTHY IMD0 and WLST were assessed for their clinical utility in assessing patients with symptoms of gastroparesis. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.

Higher Body Mass Index Is Associated With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis.

BACKGROUND & AIMS: Understanding which eosinophilic esophagitis (EoE) patients will respond to treatment with topical corticosteroids (tCS) remains challenging, and it is unknown whether obesity impacts treatment response. This study aimed to determine whether treatment outcomes to tCS in EoE patients vary by body mass index (BMI). METHODS: This retrospective cohort study of the University of North Carolina EoE Clinicopathologic database assessed subjects age 14 years or older with a new diagnosis of EoE. Their BMI was calculated and histologic, symptom, and endoscopic responses were recorded after tCS treatment. The treatment response of obese (BMI, ≥30 kg/m2) and nonobese EoE status was compared using bivariate and multivariate analyses. RESULTS: We identified 296 EoE patients treated with tCS. Baseline characteristics were similar, although obese EoE patients had more heartburn and hiatal hernias. Histologic response was higher for those who were nonobese compared with obese at fewer than 15 (61% vs 47%; P = .049) and 6 or fewer (54% vs 38%; P = .02) eosinophils per high-power field, respectively. In addition, nonobese patients had significantly greater endoscopic and symptomatic responses. On multivariate analysis, increasing BMI was associated independently with decreased histologic response after accounting for age, heartburn, dilation, and hiatal hernia whether BMI was assessed as a continuous variable (adjusted odds ratio [aOR], 0.93; 95% CI, 0.89-0.98), as nonobese vs obese (aOR, 0.38; 95% CI, 0.21-0.68), or in 4 categories (overweight vs normal [aOR, 0.46; 95% CI, 0.26-0.84] or obese vs normal [aOR, 0.26; 95% CI, 0.13-0.51]). CONCLUSIONS: As BMI increases in EoE patients, the odds of histologic, symptomatic, and endoscopic responses to tCS decreases, with obese patients having an approximately 40% decrease in odds of response.

Poliprotect vs Omeprazole in the Relief of Heartburn, Epigastric Pain, and Burning in Patients Without Erosive Esophagitis and Gastroduodenal Lesions: A Randomized, Controlled Trial.

INTRODUCTION: In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure. METHODS: In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed. RESULTS: A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm. DISCUSSION: Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).

Upregulation of acid sensing ion channels is associated with esophageal hypersensitivity in GERD.

Proton pump inhibitors (PPIs) are the mainstay of therapy for gastroesophageal reflux disease (GERD) but up to 60% of patients have inadequate response to therapy. Acid sensing ion channels (ASICs) play important roles in nociception. This study aimed to investigate whether the increased expression of ASICs results in neuronal hyperexcitability in GERD. Esophageal biopsies were taken from GERD patients and healthy subjects to compare expression of ASIC1 and 3. Next, gene and protein expression of ASIC1 and 3 from esophageal mucosa and dorsal root ganglia (DRG) neurons were measured by qPCR, Western-blot and immunofluorescence in rodent models of reflux esophagitis (RE), non-erosive reflux disease (NERD), and sham operated groups. Excitability of DRG neurons in the GERD and sham groups were also tested by whole-cell patch-clamp recordings. We demonstrated that ASIC1 and 3 expression were significantly increased in patients with RE compared with healthy controls. This correlated positively with symptom severity of heartburn and regurgitation (p < .001). Next, ASIC1 and 3 gene and protein expression in rodent models of RE and NERD were similarly increased in esophageal mucosa as well as T3-T5 DRG neurons compared with sham operation. DRG neurons from RE animals showed hyperexcitability compared with sham group. However, intrathecal injection of ASIC specific inhibitors, PcTx1 and APTEx-2, as well as silencing ASIC1 and 3 genes with specific siRNAs prevented visceral hypersensitivity. Overall, upregulation of ASIC1 and 3 may lead to visceral hypersensitivity in RE and NERD and may be a potential therapeutic target for PPI non-responsive patients.