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The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to summarize the available evidence and offer expert Best Practice Advice on the integration of potassium-competitive acid blockers (P-CABs) in the clinical management of foregut disorders, specifically including gastroesophageal reflux disease, Helicobacter pylori infection, and peptic ulcer disease. This expert review was commissioned and approved by the AGA Institute Governing Board and CPU Committee to provide timely guidance on a topic of high clinical importance to the AGA membership. This CPU expert review underwent internal peer review by the CPU Committee and external peer review through the standard procedures of Gastroenterology. These Best Practice Advice statements were developed based on review of the published literature and expert consensus opinion. Because formal systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements Based on nonclinical factors (including cost, greater obstacles to obtaining medication, and fewer long-term safety data), clinicians should generally not use P-CABs as initial therapy for acid-related conditions in which clinical superiority has not been shown. Based on current costs in the United States, even modest clinical superiority of P-CABs over double-dose proton pump inhibitors (PPIs) may not make P-CABs cost-effective as first-line therapy. Clinicians should generally not use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. Although there is currently insufficient evidence for clinicians to use P-CABs as first-line on-demand therapy for patients with heartburn symptoms who have previously responded to antisecretory therapy, their rapid onset of acid inhibition raises the possibility of their utility in this population. Clinicians should generally not use P-CABs as first-line therapy in patients with milder erosive esophagitis (EE) (Los Angeles classification of erosive esophagitis grade A/B EE). Clinicians may use P-CABs in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs. Clinicians may use P-CABs as a therapeutic option for the healing and maintenance of healing in patients with more severe EE (Los Angeles classification of erosive esophagitis grade C/D EE). However, given the markedly higher costs of the P-CAB presently available in the United States and the lack of randomized comparisons with double-dose PPIs, it is not clear that the benefits in endoscopic outcomes over standard-dose PPIs justify the routine use of P-CABs as first-line therapy. Clinicians should use P-CABs in place of PPIs in eradication regimens for most patients with H pylori infection. Clinicians should generally not use P-CABs as first-line therapy in the treatment or prophylaxis of peptic ulcer disease. Although there is currently insufficient evidence for clinicians to use P-CABs as first-line therapy in patients with bleeding gastroduodenal ulcers and high-risk stigmata, their rapid and potent acid inhibition raises the possibility of their utility in this population. [ABSTRACT FROM AUTHOR]

Background: The diverse clinical characteristics of erosive esophagitis (EE) and symptom perception in patients with gastroesophageal reflux disease (GERD) remain a major challenge in understanding their underlying pathogenesis. This study aimed to investigate the association between the levels of IL-8, TNF-α, and IL-17 in serum and the presence of erosive esophagitis and symptoms related to GERD. Method: We enrolled 65 subjects presenting with GERD symptoms. Based on the findings of upper endoscopy, the subjects were categorized into two groups: (1) erosive esophagitis (EE LA grades B-D) and (2) non-erosive esophagitis (normal-EE LA grade A). Symptom perception was assessed via GERD questionnaire (GERD-Q) and the frequency scale for the symptoms of GERD (FSSG). The enzyme-linked immunosorbent assay (ELISA) method was used to analyze serum levels of IL-8, TNF-α, and IL-17. Analysis of cytokine levels between different symptoms severity was performed using the Kruskal-Wallis H test. Results: Median serum IL-8 levels were significantly higher in the erosive esophagitis group compared to those with non-erosive esophagitis (20.2 (IQR 16.9–32.2) vs. 17.7 (IQR 15.2–19.6), p < 0.05). The study found a significant association between IL-8 levels and the presence of globus symptoms (median IL8 level 46.961 (38.622–92.644) in subjects with globus vs. 18.06 (16.68–20.49) in those without globus; p < 0.05). Similarly, TNF-α levels were associated with the frequency of regurgitation symptoms (H index = 10.748; dr = 3; p < 0.05). We observed a significant correlation between IL-17 levels and the frequency of heartburn and early satiety symptoms. Conclusions: IL-8 may play a role in the development of mucosal erosion in GERD. IL-8, TNF- α, and IL-17 might be involved in the development of globus symptoms, the frequency of regurgitation, and the frequency of heartburn and early satiety, respectively. The diverse symptom phenotypes observed in patients with GERD symptoms may be mediated by distinct profiles of proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Tao He,1,2,&ast; Xiao-Yu Sun,1,2,&ast; Meng-Han Tong,1,2 Ming-Jie Zhang,1,2 Zhi-Jun Duan1,2 1Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Dalian Central Laboratory of Integrative Neuro-Gastrointestinal Dynamics and Metabolism Related Diseases Prevention and Treatment, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Jun Duan, Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian, 161000, People’s Republic of China, Tel +86 83635963, Email cathydoctor@sina.comBackground and Aim: Obesity is association with elevated risks of erosive esophagitis (EE), and metabolic abnormalities play crucial roles in its development. The aim of the study was to assess the association between metabolic obesity phenotypes and the risk of EE.Methods: This retrospective study enrolled 11,599 subjects who had undergone upper gastrointestinal endoscopy at the First Affiliated Hospital of Dalian Medical University from January 1, 2008, to December 31, 2023. The enrolled individuals were grouped into four cohorts based on their metabolic health and obesity profiles, namely, metabolically healthy non-obesity (MHNO; n=2134, 18.4%), metabolically healthy obesity (MHO; n=1736, 15.0%), metabolically unhealthy non-obesity (MUNO; n=4290, 37.0%), and metabolically unhealthy obesity (MUO; n=3439, 29.6%). The relationships of the different phenotypes of metabolic obesity with the risks of developing EE in the different sexes and age groups were investigated by multivariate logistic regression analysis.Results: The MUNO, MHO, and MUO cohorts exhibited elevated risks of developing EE than the MHNO cohort. The confounding factors were adjusted for, and the findings revealed that the MUO cohort exhibited the greatest risk of EE, with odds ratios (ORs) of 5.473 (95% CI: 4.181– 7.165) and 7.566 (95% CI: 5.718– 10.010) for males and females, respectively. The frequency of occurrence of EE increased following an increase in proportion of metabolic risk factors. Subgroup analyses showed that the individuals under and over 60 years of age in the MHO, MUNO, and MUO cohorts exhibited elevated risks of developing EE. Further analysis suggested that obesity has a stronger influence on the risks of developing EE compared to metabolic disorders.Conclusion: Metabolic disorders and obesity are both related with an elevated risk of EE, in which obesity has a potentially stronger influence. Clinical interventions should target both obesity and metabolic disorders to reduce EE risk. Keywords: metabolic obesity phenotype, erosive esophagitis, metabolic disorders

Background: Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE. Objectives: This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose. Design: A systematic review and network meta-analysis. Data sources and methods: Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted. Results: In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline. Conclusion: This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients. Trial registration: The study protocol was registered with INPLASY (registration number INPLASY2023120053). Plain language summary: A review and network meta-analysis of different medications for treating erosive esophagitis: potassium-competitive acid blockers and proton-pump inhibitors Why was the study done? Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are commonly used to treat Erosive esophagitis (EE) due to their good safety and tolerance. This study aimed to compare the effectiveness of P-CABs and PPIs in healing EE patients. We wanted to determine the best treatment choice in terms of the duration of treatment (4 or 8 weeks) and the dosage (standard or double-dose). What did the researchers do? The researchers searched relevant databases for randomized controlled trials that studied the use of PPIs and P-CABs in treating EE up until May 31, 2023. They included studies that evaluated the healing effects of standard or double-dose PPIs or P-CABs over a period of 4 or 8 weeks. A network meta-analysis was performed to compare the effectiveness of these treatments. They also conducted sensitivity analysis and subgroup analysis to examine the effects on patients with different levels of EE. What did the researchers find? The results showed that the healing rate after 4 weeks of treatment was significantly lower than the healing rate after 8 weeks for most treatments. Additionally, the higher healing rate observed with double-dose treatment compared to standard-dose treatment was not seen in the initial treatment of most drugs. In the main analysis, which included studies with patients both with and without severe EE at the beginning, Keverprazan 20mg qd was ranked as the most effective treatment with a healing rate of 84.7, followed by Ilaprazole 10mg qd with a healing rate of 82.0 at 8 weeks. The results were robust in sensitivity analysis. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, especially for patients with severe EE. What do the findings mean? Treating EE patients for 8 weeks was more effective than treating them for 4 weeks. Keverprazan (20mg once a day) with the 8-week treatment is the optimal method. [ABSTRACT FROM AUTHOR]

Background and Aim: We aimed to compare the risk of erosive esophagitis (EE) among individuals with different phenotypes based on metabolic health status and obesity and investigate the role of changes in metabolic health in EE risk. Methods: A cohort of 258 892 asymptomatic adults without EE at baseline who underwent ollow‐up esophagogastroduodenoscopy (EGD) were categorized into the following four groups according to metabolic health and obesity status: (i) metabolically healthy (MH) non‐obese; (ii) metabolically unhealthy (MU) non‐obese; (iii) MH obese; and (iv) MU obese. EE was defined as the presence of grade A or higher mucosal breaks on EGD. Results: During a median follow‐up of 4.5 years, the incidence rates of EE were 0.6/103 person‐years (PY), 1.7/103 PY, 1.7/103 PY, and 3.1/103 PY in the MH non‐obese, MU non‐obese, MH obese, and MU obese groups, respectively. The multivariable‐adjusted hazard ratio (HR) (95% confidence intervals [CI]) for developing EE comparing the MH obese, MU non‐obese, and MU obese groups with the MH non‐obese group were 1.49 (1.29–1.71), 1.56 (1.25–1.94), and 2.18 (1.90–2.49), respectively. The multivariable‐adjusted HR (95% CI) comparing the progression of MH to MU, regression of MU to MH, and persistent MU with the persistent MH group were 1.39 (1.10–1.76), 1.39 (1.09–1.77), and 1.86 (1.56–2.21), respectively. The increased risk of EE among the persistent MU group was consistently observed in individuals without obesity or abdominal obesity. Conclusion: Metabolic unhealthiness and obesity were independent risk factors for the development of EE, suggesting that maintaining both normal weight and metabolic health may help reduce the risk of EE. [ABSTRACT FROM AUTHOR]

Background and Aim: Healing rates of severe erosive esophagitis (EE; Los Angeles [LA] Grade C/D) in patients treated with a proton pump inhibitor (PPI) is suboptimal (~60–70%). Vonoprazan, a potassium‐competitive acid blocker, is suggested to have better healing rates in patients with severe EE. This meta‐analysis compares the efficacy and safety of vonoprazan 20 mg versus lansoprazole 30 mg daily in healing EE, specifically in those with LA Grade C/D. Methods: We searched MEDLINE, Embase, and CENTRAL on May 24, 2023. Studies that randomized EE patients to vonoprazan 20 mg daily or lansoprazole 30 mg daily and compared healing rates were included. The risk of bias was assessed using Cochrane's Risk of Bias 2 tool. The fixed‐effect model was used to obtain the pooled efficacy and safety outcomes. Subgroup analysis was done to compare healing rates in mild (LA Grade A/B) versus severe EE and based on study location. Results: Four randomized controlled trials (RCTs) with low risks of bias comprising 2208 participants were included. Vonoprazan 20 mg was superior to lansoprazole 30 mg daily in healing severe EE at all weeks (Week 2 RR 1.294 [95% CI 1.169–1.433], Week 4 1.160 [1.059–1.270], and Week 8 1.175 [95% CI 1.107–1.247]), but was similar for mild EE at all weeks (P‐interaction < 0.01). Vonoprazan 20 mg was more efficacious than lansoprazole 30 mg at Week 8 in Western versus Asian studies (P‐interaction < 0.01). Any, serious, and drug‐related treatment‐emergent adverse events were comparable between groups. Conclusion: Vonoprazan 20 mg is superior to lansoprazole 30 mg for healing severe EE but not mild EE. Vonoprazan 20 mg daily has a similar safety profile to lansoprazole 30 mg daily. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10 months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver-operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time

INTRODUCTION: Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive acid blockers (P-CAB) are promising alternatives to proton pump inhibitors (PPI). We aimed to compare the efficacy and safety of P-CAB and PPI in healing grade C/D esophagitis to aid clinical decision-making. METHODS: A systematic literature search was performed using PubMed,MEDLINE, and Cochrane Central Register of Controlled Trials. Randomized controlled trials were eligible for inclusion if efficacy of P-CAB and PPI in healing grade C/D esophagitis was reported. Pooled risk ratios and risk difference with 95% credible intervals were used to summarize estimated effect of each comparison. The benefit of treatments was ranked using the surface under the cumulative probability ranking score. RESULTS: Of 5,876 articles identified in the database, 24 studies were eligible. Studies included incorporated 3 P-CAB (vonoprazan, tegoprazan, and keverprazan) and 6 PPI (lansoprazole, esomeprazole, omeprazole, rabeprazole extended-release (ER), pantoprazole, and dexlansoprazole). Based on the failure to achieve mucosal healing, 20 mg of vonoprazan q.d. ranked the first among PPI in initial and maintained healing of grade C/D esophagitis (surface under the cumulative probability ranking score 5 0.89 and 0.87, respectively). Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI. For those who attempted lower maintenance treatment dose, 10 mg of vonoprazan q.d. was a reasonable choice, considering its moderate efficacy and safety. DISCUSSION: Vonoprazan has considerable efficacy in initial and maintained healing of grade C/D esophagitis compared with PPI, with moderate short-term and long-term safety. [ABSTRACT FROM AUTHOR]

Background: Prior studies have demonstrated that obesity may be associated with the development of gastroesophageal reflux disease (GERD) and GERD‐related complications. However, such association has never been assessed in a global‐wide real‐world patient population. Methods: The TriNetX electronic health records network, which involves 92 healthcare organizations in 12 countries, was utilized for this multicenter global health research network study. The cohort with obesity comprised adult patients with body mass index (BMI) of more than 30 kg/m2. We performed 1:1 propensity score matching to decrease confounders effects. The prevalence of GERD and GERD‐related complications including erosive esophagitis, Barrett's esophagus (BE), BE with dysplasia, and esophageal adenocarcinoma were assessed. Results: A total of 2,356,548 patients were included in the obesity and non‐obesity groups after propensity score matching. In the group with obesity, patients had a significantly higher prevalence of GERD (30% vs. 24%, OR 1.35, 95% CI 1.34–1.36) compared to the group without obesity. Further analysis showed a higher prevalence of GERD‐related complications in the group with obesity with statistical significance: Erosive esophagitis (OR 1.07, 95% CI 1.05–1.08), Barrett's esophagus (1.08, 1.05–1.10), BE with dysplasia (1.11, 1.04–1.18), esophageal cancer (1.32, 1.15–1.51). Conclusion: Globally, obesity was associated with a higher prevalence of GERD and GERD‐related complications. [ABSTRACT FROM AUTHOR]

Introduction: Proton pump inhibitor (PPI) is the mainstay therapy for the maintenance of healed erosive esophagitis (EE). It is unknown whether potassium‐competitive acid blockers (PCABs) are more efficacious and safer than PPIs. Methods: Only randomized controlled trials (RCTs) comparing PCABs to PPIs in the maintenance of healing rates of endoscopically proven healed EE and indexed in MEDLINE, EMBASE, and CENTRAL until 3 February 2024, were included. A fixed‐effects model meta‐analysis was performed to pool primary efficacy outcome (maintenance of healing rates at week 24) and safety data (any treatment‐emergent adverse event or TEAE). The risk of bias was assessed using Cochrane's Risk of Bias 2 (RoB2) tool. Results: Four RCTs with a total of 2554 patients were eligible for inclusion. All trials were of low risk of bias. Compared to lansoprazole 15 mg, the maintenance rates of healed EE at week 24 were significantly higher with vonoprazan 10 mg (RR 1.13; 95% CI 1.07–1.19) and vonoprazan 20 mg (RR 1.15; 95% CI 1.10–1.21). Likewise, compared to lansoprazole 15 mg, any TEAEs were significantly greater with vonoprazan 20 mg (RR 1.10; 95% CI 1.01–1.20) but not vonoprazan 10 mg. Conclusion: Vonoprazan 10 and 20 mg were superior to lansoprazole 15 mg in the maintenance of the healing of EE. Any TEAEs were greater with vonoprazan 20 mg. [ABSTRACT FROM AUTHOR]

Introduction: Erosive esophagitis (EE) is a severe form of gastroesophageal reflux disease commonly treated with proton pump inhibitors (PPIs). The aim of this retrospective, observational cohort study was to describe the characteristics and healthcare burden of patients with EE. Methods: We identified adults in the USA with an EE diagnosis between January 1, 2016 and February 28, 2019 in a linked dataset containing electronic health records (EHR) from the Veradigm Network EHR and claims data from Komodo Health. Patients were required to have 1 year of baseline data and 3 years of follow-up data. Patients were stratified by the number of PPI lines of therapy (LOT) during the 4-year study period. We descriptively captured patient characteristics and treatment patterns, along with all-cause and EE-related healthcare utilization and costs. Results: Among the 158,347 qualifying adults with EE, 71,958 (45.4%) had 1 PPI LOT, 14,985 (9.5%) had 2 LOTs, 15,129 (9.6%) had 3+ LOTs, and 56,275 (35.5%) did not fill a PPI prescription. Omeprazole and pantoprazole comprised more than 70% of any LOT, with patients commonly switching between the two. Mean (standard deviation) annualized all-cause and EE-related healthcare costs in the follow-up period were $16,853 ($70,507) and $523 ($3659), respectively. Both all-cause and EE-related healthcare costs increased with LOTs. Conclusions: Patients with EE are commonly treated with prescription PPIs; however, 19.0% of patients cycled through multiple PPIs. Higher PPI use was associated with a higher comorbidity burden and higher healthcare costs compared to 0 PPI use. [ABSTRACT FROM AUTHOR]

Abstract Introduction Proton pump inhibitor (PPI) is the mainstay therapy for the maintenance of healed erosive esophagitis (EE). It is unknown whether potassium‐competitive acid blockers (PCABs) are more efficacious and safer than PPIs. Methods Only randomized controlled trials (RCTs) comparing PCABs to PPIs in the maintenance of healing rates of endoscopically proven healed EE and indexed in MEDLINE, EMBASE, and CENTRAL until 3 February 2024, were included. A fixed‐effects model meta‐analysis was performed to pool primary efficacy outcome (maintenance of healing rates at week 24) and safety data (any treatment‐emergent adverse event or TEAE). The risk of bias was assessed using Cochrane's Risk of Bias 2 (RoB2) tool. Results Four RCTs with a total of 2554 patients were eligible for inclusion. All trials were of low risk of bias. Compared to lansoprazole 15 mg, the maintenance rates of healed EE at week 24 were significantly higher with vonoprazan 10 mg (RR 1.13; 95% CI 1.07–1.19) and vonoprazan 20 mg (RR 1.15; 95% CI 1.10–1.21). Likewise, compared to lansoprazole 15 mg, any TEAEs were significantly greater with vonoprazan 20 mg (RR 1.10; 95% CI 1.01–1.20) but not vonoprazan 10 mg. Conclusion Vonoprazan 10 and 20 mg were superior to lansoprazole 15 mg in the maintenance of the healing of EE. Any TEAEs were greater with vonoprazan 20 mg.

Background: Dyspepsia exhibits a diverse range of underlying causes, with functional dyspepsia (FD) surpassing organic etiologies in prevalence. However, there exists a noticeable absence of prior research delineating the etiological spectrum of dyspepsia among the tribal regions of Himachal Pradesh (HP). The present study was carried out to determine the etiological profile of dyspepsia within this specific population. Materials and Methods: Conducted as a cross‑sectional observational study centered around an endoscopy health camp, this investigation took place at the community health center in Kaza – a pivotal administrative hub in the remote Spiti Valley of the Lahaul and Spiti tribal district in HP. The study encompassed consecutive patients above 18 years of age presenting with gastrointestinal complaints. Those predominantly reporting dyspepsia were selected and subsequently underwent thorough endoscopic examination. Data analysis incorporated factors such as age, gender, history of smoking, alcohol consumption, nonsteroidal anti‑inflammatory drug usage, and endoscopic findings. Results: Encompassing a total of 187 patients with an average age of 48.5 ± 13.4, the study found that endoscopy yielded normal results in 59.9% of cases (categorized as FD), whereas 40.1% displayed abnormal findings (categorized as organic dyspepsia). Among the latter, the most prevalent organic lesions were peptic ulcer disease (PUD) (62.7%) and erosive esophagitis (22.7%). Furthermore, gastric malignancy was detected in 4% of the cases. Conclusion: The primary organic causes of dyspepsia within the tribal areas of HP appear to be dominated by PUDs, closely followed by erosive esophagitis. Gastric malignancy, although less frequent, was identified in approximately 4% of the dyspeptic cases studied. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal reflux disease (GERD) has three classical phenotypes, namely erosive esophagitis (EE), nonerosive reflux disease, and Barrett's esophagus. Patients with GERD are managed with lifestyle changes, dietary interventions, and proton-pump inhibitors (PPI). Aim: To determine the patterns of PPI use in patients with documented EE. Methods: This prospective study recruited all patients with symptoms of GERD (heartburn and/or regurgitation with or without chest pain) and documented significant reflux esophagitis (Los Angeles grading LA-B or beyond on endoscopy). Lifestyle and dietary changes were initiated and all patients were prescribed twice daily PPI for 8 weeks. PPI was tapered as the requirement beyond 8 weeks. Follow-up was done at weeks 8, 12, and 24. The outcomes analysed included number of patients where complete PPI withdrawal was possible at week 24 and determinants of continued PPI use at 24 weeks of therapy. Statistical analysis was performed using Chi-square test, Mann–Whitney U-test, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. P < 0.05 was considered statistically significant. Results: The study cohort included 53 patients-42 with reflux esophagitis LA-B and 11 with reflux esophagitis LA-C (median age 46 years [22–77 years]; 28 [52.3%] males). There was significant difference in consumption pattern of PPI between week 12 and 24 (P = 0.008). At week 12, 15.1% were off PPI and 67% required intermittent dosing. At week 24, 45.3% of cases were off PPI therapy and 43.4% required intermittent dosing. Only 11.3% patients continued drug use at once a day dosing. Lower body mass index (BMI) (P 0.01) and age (P 0.01) were linked with complete PPI withdrawal at week 24. Conclusion: The present study highlights that PPI withdrawal is possible in 15.1% and 45.3% cases with EE after week 12 and week 24 of therapy, respectively. Lower BMI and age are likely to be associated with PPI withdrawal at week 24. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are a mainstay treatment for acid peptic disorders such as gastroesophageal reflux disease (GERD). Although PPIs are considered first-line medications for acid suppression, they have notable limitations such as requiring acid-mediated activation, short half-life and duration of action, and metabolic variability. Fexuprazan is a newly developed potassium-competitive acid blocker (P-CAB), which inhibits acid generation and secretion in a competitive and reversible manner. Fexuprazan, like other P-CABs, has significantly different pharmacodynamic and pharmacokinetic properties than PPIs with potential advantages including rapid, robust, and durable acid suppression, lack of CYP2C19 metabolism, independence from food intake, and no requirement for activation into an active form. Completed clinical trials of fexuprazan have demonstrated comparable efficacy to PPIs for the healing of erosive esophagitis and relief of GERD-related esophageal symptoms without concerning safety signals. Ongoing clinical trials are evaluating fexuprazan for the prevention of NSAID-induced peptic ulcer disease, non-erosive GERD, and acute and chronic gastritis, as well as healing efficacy and maintenance of erosive esophagitis (EE). Fexuprazan is approved in South Korea for the treatment of EE and at the time of this writing is being considered for regulatory approval in several other countries. In this article, we summarize and discuss the pharmacology, efficacy, and safety of fexuprazan. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic sleeve gastrectomy (LSG) has become the preferred bariatric procedure in many countries. However, new onset erosive esophagitis (EE) is a major shortcoming. Current recommendation is esophago-gastro-duodenoscopy (EGD) should be performed routinely at 1 year and subsequently every 2–3 years to enable the early detection of Barrett's or esophageal adenocarcinoma. This would put significant strains on resources and costs of bariatric program. Our study assesses the association between and diagnostic value of salivary pepsin concentration and endoscopically proven EE in post-LSG patients as a surrogate for EGD. Methods: Twenty patients on routine post-LSG endoscopy between June and September 2022 were recruited for this correlational pilot study. Under supervision, fasting and post-prandial saliva sample was collected and analyzed by Peptest lateral flow device. EGD examinations were performed, and patients completed a validated 25-item QoLRAD questionnaire. Results: We found a significant correlation between positive endoscopy findings of EE and salivary pepsin concentrations. The normal group had a lower mean fasting pepsin level (13.13 ng/mL ± 18.97) versus the EE-group (90.55 ng/mL ± 81.28, p = 0.009) and lower mean post-prandial pepsin level (30.50 ng/mL ± 57.72) versus the EE-group (135.09 ng/mL ± 130.17, p = 0.02). The predictive probabilities from the binary regression of fasting and post-prandial pepsin concentrations yield AUC of 0.955 ± 0.044 (95% CI 0.868 to 1.000, p < 0.001). Conclusion: Our study distinctively identified salivary pepsin to have excellent sensitivity and negative predictive value in EE, potentially useful to preclude the need for post-LSG EGD in asymptomatic patients with low salivary pepsin. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of obesity is increasing in developed societies, and surgical treatment is one treatment option. The most common surgical treatment for obesity is laparoscopic sleeve gastrectomy (LSG). Gastroesophageal reflux disease (GERD) is a complication of both obesity and the surgical treatment of obesity. Materials and methods: In this study, the PubMed database was searched using the keywords "GERD" and "bariatric surgery", and 987 papers published between 1 July 2017 and 30 June 2022 were retrieved. Results: Nine papers met the inclusion criteria and were included in the meta-analysis. The articles were analyzed for the de novo occurrence of GERD after the treatment of its symptoms, the occurrence of erosive esophagitis, and Barrett's esophagus. In addition, interesting conclusions are presented from the papers that did not meet the inclusion criteria but shed light on the pathophysiology of GERD in obese patients undergoing LSG. Conclusion: In conclusion, the authors draw attention to the need for endoscopic surveillance in patients undergoing LSG, even in the absence of clinical signs of GERD. [ABSTRACT FROM AUTHOR]

Background and Aim: Achalasia often presents with chronic food stasis and fermentation in the esophageal lumen, which may lead to alterations of the esophageal microbiome, with associated mucosal inflammation and dysplastic changes. The study aims to evaluate the characteristics of the esophageal microbiome in achalasia and changes of the esophageal microbiome before and after peroral endoscopic myotomy (POEM). Methods: This is a prospective case–control study. This study enrolled patients with achalasia and asymptomatic subjects as control group. Endoscopic brushing for esophageal microbiome collection was performed in all subjects, with additional follow‐up endoscopy and brushing 3 months after POEM in achalasia patients. The composition of the esophageal microbiome was determined and compared between (1) achalasia patients and asymptomatic controls and (2) achalasia patients before and after POEM. Results: Thirty‐one achalasia patients (mean age 53.5 ± 16.2 years; male 45.2%) and 15 controls were analyzed. We observed a distinct esophageal microbial community structure in achalasia patients, with increased Firmicutes and decreased Proteobacteria when compared with the control group at the phylum level. The discriminating enriched genera in achalasia patients were Lactobacillus, followed by Megasphaera and Bacteroides, and the amount of Lactobacillus was associated with the severity of achalasia. Twenty patients were re‐examined after POEM, and a high prevalence of erosive esophagitis (55%) was noted, alongside an increase in genus Neisseria and decrease in Lactobacillus and Bacteroides. Conclusions: The altered esophageal microenvironment in achalasia leads to dysbiosis with a high abundance of genus Lactobacillus. Increased Neisseria and decreased Lactobacillus were observed after POEM. The long‐term effect of microbial changes warrants further study. [ABSTRACT FROM AUTHOR]

Background: Proton-pump inhibitors (PPIs) are the mainstay of treatment in erosive esophagitis (EE). An alternative to PPIs in EE is Vonoprazan, a potassium competitive acid blocker. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing vonoprazan to lansoprazole. Methods: Multiple databases searched through November 2022. Meta-analysis was performed to assess endoscopic healing at two, four and eight weeks, including for patients with severe EE (Los Angeles C/D). Serious adverse events (SAE) leading to drug discontinuation were assessed. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Results: Four RCTs with 2208 patients were included in the final analysis. Vonoprazan 20 mg once-daily was compared to lansoprazole 30 mg once-daily dosing. Among all patients, at two and eight weeks post-treatment, vonoprazan resulted in significantly higher rates of endoscopic healing as compared to lansoprazole, risk ratios (RR) 1.1, p<0.001 and RR 1.04, p=0.03. The same effect was not observed at four weeks, RR 1.03 (CI 0.99–1.06, I2=0%) following therapy. Among patients with severe EE, vonoprazan resulted in higher rates of endoscopic healing at two weeks, RR 1.3 (1.2–1.4, I2=47%), p=<0.001, at four weeks, RR 1.2 (1.1–1.3, I2=36%), p=<0.001 and at eight weeks post-treatment, RR 1.1 (CI 1.03–1.3, I2=79%), p=0.009. We found no significant difference in the overall pooled rate of SAE and pooled rate of adverse events leading to drug discontinuation. Finally, the overall certainty of evidence for our main summary estimates was rated as high (grade A). Conclusion: Based on limited number of published non-inferiority RCTs, our analysis demonstrates that among patients with EE, vonoprazan 20 mg once-daily dosing achieves comparable and in those with severe EE, higher endoscopic healing rates as compared to lansoprazole 30 mg once-daily dosing. Both drugs have a comparable safety profile. [ABSTRACT FROM AUTHOR]

Background: Dyspepsia exhibits a diverse range of underlying causes, with functional dyspepsia (FD) surpassing organic etiologies in prevalence. However, there exists a noticeable absence of prior research delineating the etiological spectrum of dyspepsia among the tribal regions of Himachal Pradesh (HP). The present study was carried out to determine the etiological profile of dyspepsia within this specific population. Materials and Methods: Conducted as a cross-sectional observational study centered around an endoscopy health camp, this investigation took place at the community health center in Kaza – a pivotal administrative hub in the remote Spiti Valley of the Lahaul and Spiti tribal district in HP. The study encompassed consecutive patients above 18 years of age presenting with gastrointestinal complaints. Those predominantly reporting dyspepsia were selected and subsequently underwent thorough endoscopic examination. Data analysis incorporated factors such as age, gender, history of smoking, alcohol consumption, nonsteroidal anti-inflammatory drug usage, and endoscopic findings. Results: Encompassing a total of 187 patients with an average age of 48.5 ± 13.4, the study found that endoscopy yielded normal results in 59.9% of cases (categorized as FD), whereas 40.1% displayed abnormal findings (categorized as organic dyspepsia). Among the latter, the most prevalent organic lesions were peptic ulcer disease (PUD) (62.7%) and erosive esophagitis (22.7%). Furthermore, gastric malignancy was detected in 4% of the cases. Conclusion: The primary organic causes of dyspepsia within the tribal areas of HP appear to be dominated by PUDs, closely followed by erosive esophagitis. Gastric malignancy, although less frequent, was identified in approximately 4% of the dyspeptic cases studied.

Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10 months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver–operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time < 4% no GERD) and 50% with elevated acid exposure (GERD). Mean pepsin concentrations were significantly lower in the AM (22.6 ± 25.2 ng/mL) compared to post-prandial (44.5 ± 36.7 ng/mL) and PM (55.4 ± 47.0 ng/mL). Agreement between pepsin concentrations across 3 days was substantial for AM samples (kappa 0.61), with lower agreement for post-prandial and PM samples. A single AM pepsin concentration of 25 ng/mL was 67% accurate for GERD with 56% sensitivity and 78% specificity. This validation study highlights fair accuracy and performance characteristics of a single fasting AM salivary pepsin concentration for the diagnosis of GERD. [ABSTRACT FROM AUTHOR]

Aim: 20 mg of vonoprazan (VPZ20) is recommended in most countries to treat erosive esophagitis (EE). Whether other doses of vonoprazan, such as 5 mg (VPZ5), 10 mg (VPZ10), 20 mg (VPZ20), and 40 mg (VPZ40) are more effective is unknown. Materials & methods: Three databases were electronically searched to identify studies published before November 2021. Network meta-analysis was performed using STATA 14.0. Results: VPZ20 and VPZ40 were comparable to PPI, VPZ5 and VPZ10 in 4- and 8-week healing rates, and this was also detected in patients with refractory EE. All regimens resulted in similar treatment-emergent adverse events (TEAEs). However, VPZ40 ranked first for healing rate and TEAEs; however, VPZ20 ranked worst for TEAEs. Conclusion: Different doses of VPZ are comparable in efficacy and safety, but VPZ40 may be best in both effectiveness and safety.

Purpose: Weight reduction decreases gastroesophageal reflux disease (GERD), but laparoscopic sleeve gastrectomy (LSG) that damages the structure of the stomach may worsen GERD. We aimed to elucidate the factors associated with increased severity of erosive esophagitis (EE) at 1 year after LSG. Materials and Methods: Data on patients who underwent LSG between February 2007 and March 2016 were reviewed. Endoscopic findings and anthropometric data before and after surgery were recorded. The severity of EE was assessed according to the Los Angeles classification; severe EE was defined as grade C or D esophagitis. Results: Totally, 316 patients were enrolled. Before LSG, 96 patients (30.4%) had grade A or B EE. One year after LSG, 215 patients (68%) had EE, including 136 (43%) with grade A, 62 (19.6%) with grade B, and 17 (5.4%) with grade C or D EE. One-hundred and twenty-seven of 220 patients (57.7%) without EE before LSG developed de novo EE following LSG. The incidence of severe EE after LSG in patients without pre-operative EE, grade A EE, or grade B EE at baseline was 3.2%, 6.8%, and 50%, respectively. Independent factors for an increased severity of EE after LSG were male gender (OR = 2.55, 95% CI = 1.52–4.28) and post-operative hiatal hernia (OR = 3.17, 95% CI = 1.66–6.06). Conclusion: The prevalence and severity of EE increased after LSG. Male gender and post-operative hiatal hernia are independent factors for an increased severity of EE after LSG. The incidence of severe EE after LSG is low for patients without pre-operative EE or grade A EE at baseline. [ABSTRACT FROM AUTHOR]

Potassium-competitive acid blockers (P-CABs) such as vonoprazan represent a novel class of acid suppressants that show tremendous promise to enhance care of acid peptic disorders. P-CAB characteristics distinct from those of proton pump inhibitors--such as acid stability with dosing independent of food consumption, rapid onset of action, less variability with CYP2C19 polymorphisms, and extended half-lives--may add value in clinical practice. With recently reported data beyond Asian populations and expanding regulatory approval of P-CABs, clinicians should be aware of these medications and their potential roles in the management of acid peptic disorders. This article provides an up-to-date summary of the evidence around P-CABs for the treatment of gastroesophageal reflux disease (especially erosive esophagitis healing and maintenance), eosinophilic esophagitis, Helicobacter pylori infection, and peptic ulcer healing and secondary prophylaxis. [ABSTRACT FROM AUTHOR]

Esophageal strictures are a leading cause of dysphagia, but data regarding the epidemiology of esophageal strictures are limited. This study aimed to investigate the prevalence, health care utilization, and financial burden of esophageal strictures in the United States. We performed a retrospective cohort study using 2 large national insurance claims databases (MarketScan and Medicare). Using International Classification of Diseases-9 and -10 diagnostic codes, annual prevalence was calculated for both cohorts overall, and stratified by age and sex strata. Most common diagnostic and procedural codes associated with esophageal strictures were extracted and analyzed to estimate health care utilization. Direct annual medical costs of esophageal strictures were calculated. The annual prevalence of esophageal strictures in MarketScan in 2021 was 203.14 cases/100,000 people, whereas the annual prevalence in Medicare cohort in 2017 was 1123.47 cases/100,000. Although rates were relatively stable over time, esophageal stricture prevalence increased with advancing age. No prevalence differences were noticed between males and females. Gastroesophageal reflux disease/erosive esophagitis was the top diagnostic code associated with esophageal strictures, although an increase in the proportion of eosinophilic esophagitis codes was noted over time. Esophageal dilation codes were present in ∼50% of stricture cases. The total health care costs associated with esophageal strictures were estimated at $1.39 billion in 2017. Esophageal strictures are common, affecting between 1/100 and 1/1000 patients in the United States, with the highest rates seen in patients aged 75 years and older. Accordingly, strictures have a significant financial burden on the health care system, with costs greater than $1 billion annually. [ABSTRACT FROM AUTHOR]

The influence of changes in alcohol consumption on erosive esophagitis (EE) development in both sexes is unclear. This observational study investigated sex differences in the influence of alcohol consumption on EE development, and included 2582 patients without EE at baseline from 13,448 patients who underwent >2 health check-ups over >1 year. The rates of non-drinkers who started drinking, and drinkers who abstained from drinking, who increased, and who decreased their weekly alcohol consumption were 7.2%, 9.7%, 14.7%, and 24.1% and 7.3%, 17.8%, 12.8%, and 39.0% in men and women, respectively. In the final cohort, 211/1405 (15.0%) men and 79/1177 (6.7%) women newly developed EE. The odds ratio (OR) for drinking in EE development was 1.252 (95% confidence interval (CI), 0.907–1.726) among men and 1.078 (95% CI, 0.666–1.747) among women. Among men aged <50 years, the OR for drinking ≥70 g/week in EE development was 2.825 (95% CI, 1.427–5.592), whereas among women, the OR for drinking ≥140 g/week in EE development was 3.248 (95% CI, 1.646–6.410). Among participants aged <50 years, the OR for daily drinking in EE development was 2.692 (95% CI, 1.298–5.586) among men and 4.030 (95% CI, 1.404–11.57) among women. The influence of alcohol consumption on EE development differed between the sexes. We recommend no alcohol consumption for individuals aged <50 years to avoid EE development. Daily drinkers should be assessed for EE development. [ABSTRACT FROM AUTHOR]

Erosive esophagitis (EE) occurs when refluxate from the stomach causes T-lymphocyte infiltration of the esophageal mucosa, resulting in mucosal breaks. Currently, therapy with proton-pump inhibitors (PPIs) is the standard treatment for EE in the United States, but few comprehensive reviews exist on the efficacy of PPIs in US populations. Here, we present the most contemporary, thorough analysis of PPI efficacy rates, and identify and characterize patient subgroups at risk for poor healing outcomes. We searched the literature to identify studies reporting rates of endoscopic healing and maintained healing of EE with PPI therapies in the US and found a paucity of recent evidence and real-world evidence. Twenty-two studies from 2009 and earlier were included in the final dataset. Rates of EE healing with PPIs were highest after 8 weeks of treatment, with over 80% of patients in most treatment arms demonstrating endoscopic healing, compared to lower efficacy (<80%) at 4 weeks. Rates of maintained healing with PPIs at 6 and 12 months were mostly lower than 80%, although the data were limited. Symptomatic patients and those with severe EE were less likely to achieve healing. Obese patients experienced similar healing rates as non-obese patients. [ABSTRACT FROM AUTHOR]

Acid suppression is the primary therapy for erosive esophagitis (EE). Although proton pump inhibitors (PPIs) are considered as the first-line medication for EE, 10–20% of patients with Los Angeles C and D grade EE do not gain complete mucosal healing and symptom control despite 8-week double-dose PPI treatment. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB), which blocks the H+, K+-adenosine triphosphatase enzymes in a K+-competitive and reversible manner. Vonoprazan exhibits different pharmacological and pharmacokinetic profiles from conventional PPIs, and has a rapid, potent and sustained acid inhibitory effect. In this review, we summarized and discussed current evidence regarding the role of vonoprazan in terms of mucosal healing, maintaining remission and symptom relief for the management of EE, including the initial and maintenance treatment of EE, as well as for PPI-resistant EE patients. Safety concerns and cost-effectiveness analysis of vonoprazan were also mentioned in the article. As a potent and well-tolerated acid blocker, vonoprazan has the potential to become a novel option for the management of EE. [ABSTRACT FROM AUTHOR]

Background A new classification criterion for diagnosing ineffective esophageal motility (IEM) was proposed at the 2018 Stanford symposium, but limited data exists about the utility of this criterion. Methods We conducted a cross-sectional study among 3826 patients treated at the Institute of Gastroenterology and Hepatology, Hanoi, Vietnam, between March 2018 and May 2020. Patients were classified as having normal motility, mild IEM, severe IEM, or absent contractility based on the Chicago classification version 3.0 and the new IEM criterion (severe IEM was defined as having >70% ineffective swallows). We examined the association between these 4 motility subgroups and the presence of erosive esophagitis and Barrett's esophagus, using multivariate logistic regression analysis. Results The mean age of the study sample was 44.7 years and 66.3% were women. The prevalence of symptoms, hiatal hernia, and Helicobacter pylori-positive patients was similar in the 4 study groups. The 4-second integrated relaxation pressures and lower esophageal sphincter resting pressures were lower in patients with severe IEM and absent contractility. Severe IEM and absent contractility, but not mild IEM, were significantly associated with Los Angeles (LA) grade B-D esophagitis (relative risk ratio [RRR] for severe IEM 1.81, 95% confidence interval [CI] 1.17-2.80; and RRR for absent contractility 2.37, 95%CI 1.12-5.04). None of the hypomotility subgroups were associated with LA grade A esophagitis and Barrett's esophagus. Conclusions Patients with severe IEM have a high prevalence of severe erosive esophagitis. These findings suggest the need for a more meaningful classification criterion for IEM. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate gene expression profiles, identify potential hub genes, and predict drugs for patients with erosive esophagitis (EE). Despite its clinical significance, molecular-level exploration of this condition has been limited., Patients and Methods: RNA sequencing was performed on clinical biopsy samples from eight EE patients and eight healthy controls. Integrated bioinformatic tools were then utilized to analyze the data, including functional enrichment analysis, protein-protein interaction network analysis, weighted gene co-expression network analysis, immune infiltration analysis, and identification of small-molecule compounds. Additionally, the expressions of the identified hub genes were assessed in clinical samples., Results: A total of 2801 genes with differential expression were identified, including four potential hub genes: SOX9, SPP1, TIMP1, and TLR4. Moreover, the overexpression of these hub genes was verified in clinical samples. Analysis of Immune infiltration indicated an imbalance in the distribution of immune cell types in patients with EE. Correlation analysis between immune cells and hub genes unveiled noteworthy relationships. Specifically, SOX9 exhibited a negative correlation with CD8 T cells but a positive correlation with resting memory CD4 T cells. SPP1 displayed a positive correlation with naïve B cells, while TIMP1 exhibited a negative correlation with resting dendritic cells. Furthermore, the study identified ten small-molecule drugs with potential therapeutic effects for EE, including loreclezole and mercaptopurine., Conclusion: This study provides valuable insights into the molecular understanding of EE, offering new perspectives on disease mechanisms. The findings may inspire further research leading to the development of novel treatment strategies for EE., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Zhao et al.)

Introduction: Proton pump inhibitor (PPI) has revolutionized the treatment of erosive esophagitis (EE) in the past few decades. However, roughly 30-40% of the patients, especially those with severe EE (Los Angeles Grade C/D), remain poorly responsive to this medication. Novel drugs have been formulated and/or repurposed to address this problem., Areas Covered: This review highlights novel drugs that have been investigated for use in EE, such as mucosal protectants, prokinetics, transient lower esophageal sphincter relaxation (TLESR) reducers, novel PPIs, and the new potassium-competitive acid blocker (PCAB). Studies have demonstrated that PCAB has promising results (efficacy and safety) compared to PPI for the healing of EE, especially in severe diseases., Expert Opinion: PCAB has gained interest in recent years, with pharmacokinetics and pharmacodynamics properties surpassing PPI. Although recent data on PCABs, which comprised mainly of Vonoprazan, have shown promising results, more randomized controlled trials for other PCAB drugs are needed to elucidate and confirm the superiority of this drug class to PPI, the current first-line treatment of EE.

Background: Gastroesophageal reflux disease (GERD) is a common disease worldwide with varying clinical presentations and risk factors. Prevalence data for Africa is lacking, but an increasing trend is expected due to demographic and epidemiological transitions. Although endoscopic studies for general gastrointestinal disorders have shown some patients with erosive esophagitis (EE), no studies in Ethiopia have investigated the clinical characteristics, risk factors, and severity of GERD using esophagogastroduodenoscopy (EGD)., Aim: To assess the clinical features of GERD in Ethiopian patients who underwent EGD and determine the severity and risk factors of EE., Methods: We conducted a multicenter, retrospective cross-sectional study of 221 patients diagnosed with GERD and endoscopic findings of EE at Trauma Associated Severe Hemorrhage and Amniotic Membrane Stem Cell between January 2019 and August 2022. Data were collected from electronic medical records and phone call interviews. We used descriptive statistics and binary logistic regression analysis with SPSS version 26 to identify the association between variables with a statistical significance set at P value < 0.05., Results: The mean ± SD age of the patients was 44.8 (± 15.9) years, with a male-to-female ratio of 1.6:1. The most commonly reported symptom was epigastric pain (80.5%), followed by heartburn (43%). Los Angeles (LA)-A EE was diagnosed in 71.1% of patients, followed by LA-B (14.9%), LA-C (7.7%), and LA-D (5.9%). Multivariate analysis showed that age 50 or above, presence of bleeding, and endoscopic findings of duodenitis/duodenopathy were significantly associated with severe EE ( P < 0.05). Stricture and Barrett's esophagus were observed in 4.5% and 1.36% of patients with EE, respectively., Conclusion: Most of the patients had milder EE with fewer complications. However, severe EE was more prevalent in older patients and those with duodenitis/duodenopathy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Gastroesophageal reflux disease (GERD) is a chronic illness characterized by complications arising from the reflux of stomach contents, which significantly lower the quality of life, increase morbidity, and increase medical expenses associated with treating the condition. The main goal of treatment in GERD is symptomatic relief, relapse prevention, and healing of erosive esophagitis. The treatment mainly involves lifestyle changes to control acid production and proton pump inhibitors (PPIs) as the first line of treatment. Endoscopic interventions or anti-reflux surgery may be beneficial in relieving symptoms in people whose symptoms are triggered by reflux. In this review, we discuss the pathophysiology and newer diagnostic and treatment modalities including available surgical management options to manage refractory GERD., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ganesh Shashi et al.)

Although several studies have shown that each of the metabolic syndrome (MetS) components can be a risk factor for erosive esophagitis (EE), the association between MetS and EE is still a challenging subject, as studies about this association have shown inconsistent results. Therefore, this study was conducted to evaluate the association between MetS and EE. In this study, we followed the MOOSE protocol and the PRISMA guidelines for reporting the results. Web of Science (ISI), Cochrane Library (Cochrane Database of Systematic Reviews - CDSR), EMBASE, Scopus, Science Direct, PubMed/Medline, EBSCO, CINAHL, and Google Scholar search engine were searched for articles published until January 2021. Heterogeneity between studies was estimated by I2 index and Q test. All analyses were performed using Comprehensive Meta-Analysis Software. Finally, 12 studies entered the meta-analysis process after qualitative assessment. MetS was significantly associated with increased risk of EE (OR=1.488 [95 % CI: 1.352-1.638], P

Background: Gastroesophageal reflux disease (GERD) has been associated with psychiatric and neurocognitive disorders. Those with autism spectrum disorder (ASD) are prone to gastrointestinal (GI) diseases, but most research has been done on children. Our aim was to determine the relationship between GERD and autism in adults and assess GERD‐related complications in those with autism. Methods: A national cohort of adults aged 18 and above with GERD with and without ASD were compared to those without GERD. Complications of GERD that were studied included Barrett's esophagus, erosive esophagitis, esophageal stricture, ulcer, and malignancy. Conditions associated with GERD were evaluated including chronic cough, wheezing, sore throat, non‐cardiac chest pain, and hoarseness. GERD treatment that was evaluated included proton pump inhibitors (PPIs), H2 receptor antagonists (H2RA), and anti‐reflux surgery. Key Results: There was an increased risk of GERD in subjects with ASD (p = 0.0001). Erosive esophagitis and esophageal ulcer were more likely to occur in those with GERD and ASD (p = 0.0001). Those with ASD were at higher risk of suffering from wheezing following a diagnosis of GERD compared to those without ASD (p = 0.0001). Those with GERD and ASD were more likely to be treated with an H2RA both as monotherapy and in combination with PPI versus those without ASD (p = 0.0001 and p = 0.0037, respectively). Conclusions and Inferences: Adult patients with ASD are more likely to have GERD as well as complications including erosive esophagitis and esophageal ulcer. Treatment of patients with GERD and ASD is not consistent and may suggest health care disparities. [ABSTRACT FROM AUTHOR]

Context: Previous cross-sectional studies show diabetes and higher levels of plasma hemoglobin A1c (HbA1c) are associated with a higher prevalence of gastrointestinal (GI) complications. However, whether the glycemic status is associated with incident acid-related upper GI disorders remains unclear. Objective: We aimed to determine the effect of hyperglycemia per se, in terms of HbA1c, on the incidence of acid-related disorders. Methods: We analyzed consecutive subjects who had undergone repeated upper endoscopies as part of the health examinations at the National Taiwan University Hospital from 2005 to 2011. Acid-related endoscopic abnormalities were defined as erosive esophagitis (EE), Barrett's esophagus (BE), and peptic ulcer disease (PUD), which included gastric ulcers (GUs) and duodenal ulcers (DUs). All subjects were categorized by 3 tertiles of HbA1c levels. We analyzed the occurrence of respective acid-related disorders during the follow-up period. Results: A total of 11 391 participants (mean HbA1c level 5.6 ± 0.7%) were enrolled in this longitudinal study. During the 38 426.3 person-years of follow-up (mean duration 3.37 ± 1.59 years), the incidence of EE, BE, GU, DU, PUD, and any acid-related disorders were 22.1%, 0.5%, 4.5%, 8.6%, 12.3%, and 30.3%, respectively. The higher HbA1c level was associated with higher risk of disease incidents, except BE, during the follow-up (all log-rank P < .001). In the Cox regression analyses with confounding factors fully adjusted, the hazard ratios for EE, GU, DU, PUD, and acid-related disorders were 1.174, 1.339, 1.24, 1.24, and 1.186, respectively, for the third tertile of HbA1c (all P < .05). Conclusion: Higher HbA1c level was associated with a higher risk of acid-related upper GI endoscopic abnormalities. Efforts toward better glycemic control may help to prevent the development of late GI complications. [ABSTRACT FROM AUTHOR]

ABSTRACT BACKGROUND: The intestinal microbiota influences the appropriate function of the gastrointestinal tract. Intestinal dysbiosis may be associated with a higher risk of esophageal lesions, mainly due to changes in gastroesophageal motility patterns, elevation of intra-abdominal pressure, and increased frequency of transient relaxation of the lower esophageal sphincter. OBJECTIVE: The aim of this study was to evaluate the intestinal microbiota in individuals with erosive esophagitis and in healthy individuals using metagenomics. METHODS: A total of 22 fecal samples from adults aged between 18 and 60 years were included. Eleven individuals had esophagitis (eight men and three women) and 11 were healthy controls (10 men and one woman). The individuals were instructed to collect and store fecal material into a tube containing guanidine solution. The DNA of the microbiota was extracted from each fecal samples and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion Torrent PGM platform and the data were analyzed using the QIIME™ software version 1.8. Statistical analyses were performed using the Mann-Whitney non-parametric test and the ANOSIM non-parametric method based on distance matrix. RESULTS: The alpha-diversity and beta-diversity indices were similar between the two groups, without statistically significant differences. There was no statistically significant difference in the phylum level. However, a statistically significant difference was observed in the abundance of the family Clostridiaceae (0.3% vs 2.0%, P=0.032) and in the genus Faecaliumbacterium (10.5% vs 4.5%, P=0.045) between healthy controls and esophagitis patients. CONCLUSION: The findings suggest that reduced abundance of the genus Faecaliumbacterium and greater abundance of the family Clostridiaceae may be risk factors for the development of erosive esophagitis. Intervention in the composition of the intestinal microbiota should be considered as an adjunct to current therapeutic strategies for this clinical condition.

Masahiro Sogabe,1,2 Toshiya Okahisa,1,2 Takeshi Kurihara,2 Miwako Kagawa,2 Kaizo Kagemoto,1 Yoshifumi Kida,1 Tetsu Tomonari,1 Tatsuya Taniguchi,1 Koichi Okamoto,1 Hiroshi Miyamoto,1 Yasushi Sato,1 Masahiko Nakasono,3 Tetsuji Takayama1 1Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan; 2Department of Internal Medicine, Shikoku Central Hospital of the Mutual Aid Association of Public School Teachers, Shikokuchuo, Japan; 3Department of Internal Medicine, Tsurugi Municipal Handa Hospital, Tsurugi, JapanCorrespondence: Masahiro SogabeDepartment of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-Cho, Tokushima City, Tokushima, 770-8503, JapanTel +81-88-633-7124Fax +81-88-633-9235Email sogabe.masahiro@tokushima-u.ac.jpBackground: Erosive esophagitis (EE) is strongly associated with metabolic syndrome (MS), but is not always recognized in individuals with MS and the prevalence of EE in individuals with non-MS is not low.Aim: To examine the differences in clinical factors associated with EE at various stages of MS, as well as the differences in metabolites between subjects with MS, with and without EE.Methods: A total of 7,097 persons who underwent health checkups including esophagogastroduodenoscopy were analyzed. We examined the differences in clinical factors for EE among subjects with non-MS, pre-MS, and MS and compared metabolites between 34 subjects with MS, with and without EE.Results: EE prevalence was significantly higher in the MS and pre-MS groups than in the non-MS group (p < 0.001). EE severity was higher in the MS group than in the pre-MS and non-MS groups (p < 0.001). In the non-MS group, there were significant differences between subjects with and without EE with respect to Helicobacter pylori (H. pylori) and smoking. In the pre-MS and MS groups, there were significant differences in H. pylori, hiatal hernia, and drinking in those with and without EE. The levels of glutamine, hypoxanthine, and lactic acid metabolites were significantly different between subjects with MS, with and without EE (all p < 0.05).Conclusion: Although H. pylori and lifestyle factors such as smoking and drinking are important for EE, differences in these factors should be considered at various stages of MS. Additionally, several metabolites may be involved in the development of EE in MS.Keywords: metabolic syndrome, erosive esophagitis, metabolite analysis

Aim: This article aimed to evaluate nitric oxide (NO) and nitric oxide synthase (iNOS) markers in patients with erosive esophagitis (EE) and those with non-erosive reflux disease (NERD) and compare them with the control group. Background: Gastro-esophageal reflux disease (GERD) is one of the most common disturbances of the upper digestive tract. Inducible nitric oxide synthase (iNOS) is expressed in esophageal adenocarcinoma. NO, the product of this enzyme, has been implicated in the pathogenesis of this condition. Nevertheless, the data on whether iNOS and NO are expressed in the early stages of GERD is conflicting. Methods: In this study, tissue samples were obtained from fifty-four patients (27 with erosive esophagitis and 27 with non-erosive reflux disease) and 27 controls. Tissue concentrations of nitrite, nitrate, and iNOS were measured using Enzyme-Linked Immunesorbent Assay (ELISA). The Bradford method was used to determine the protein concentration of samples. The results were analyzed by SPSS software (version 22.0). In multiple comparisons, the Tukey test was performed, and p < 0.05 was considered as the level of significance. Results Tissue amounts of iNOS were significantly higher (p= 0.001) in EE patients compared with the control group. There was a significant difference (p= 0.01) in this factor between EE patients and patients with NERD. Moreover, tissue levels of nitrite and nitrate were significantly higher (p = 0.001) in patient groups compared with the control group. Conclusion: It was observed that NO and iNOS protein were increased in human esophagitis tissue. The results indicated that nitric oxide and iNOS levels are useful and effective markers in the pathogenesis of GERD. While the results are not certain, it is thought that a link exists between the expressions of iNOS and disease progression. [ABSTRACT FROM AUTHOR]

Background & Aims: Sleeve gastrectomy (SG) is one of the most commonly performed bariatric procedures worldwide. Gastroesophageal reflux disease (GERD) is a major concern in patients undergoing SG and is a risk factor for Barrett's esophagus (BE). We conducted a systematic review and meta-analysis to assess the incidence of and analyze predictive factors for post-SG BE., Methods: A comprehensive literature search was conducted in April 2024, for studies reporting on incidence of BE, erosive esophagitis (EE), and hiatal hernia (HH) post-SG. Primary outcomes were post-SG pooled rates of de novo BE, EE, GERD symptoms, proton pump inhibitor use, and HH. Meta-regression analysis was performed to assess if patient and post-SG factors influenced the rates of post-SG BE., Results: Nineteen studies with 2046 patients (79% females) were included. Mean age was 42.2 years (standard deviation, 11.1) and follow-up ranged from 2 to 11.4 years. The pooled rate of de novo BE post-SG was 5.6% (confidence interval, 3.5-8.8). Significantly higher pooled rates of EE (risk ratio [RR], 3.37], HH (RR, 2.09), GER/GERD symptoms (RR, 3.32), and proton pump inhibitor use (RR, 3.65) were found among patients post-SG. GER/GERD symptoms post-SG positively influenced the pooled BE rates, whereas age, sex, body mass index, post-SG EE, and HH did not., Conclusions: Our analysis shows that SG results in a significantly increased risk of de novo BE and higher rates of EE, proton pump inhibitor use, and HH. Our findings suggest that clinicians should routinely screen patients with SG for BE and future surveillance intervals should be followed as per societal guidelines., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Study Objectives: The relationship between obstructive sleep apnea (OSA) and gastroesophageal reflux disease (GERD) is complex. We aimed to determine the association of self-reported and objective sleep parameters with diverse manifestations of the GERD spectrum., Methods: We prospectively recruited 561 individuals who underwent an electrocardiogram-based cardiopulmonary coupling for OSA screening during a health check-up. All participants received the Reflux Disease Questionnaire and an upper endoscopy to determine the presence of troublesome reflux symptoms and erosive esophagitis (EE). Sleep quality was evaluated by the Pittsburgh Sleep Quality Index and sleep dysfunction was defined as a Pittsburgh Sleep Quality Index score > 5. OSA was defined as a cardiopulmonary coupling-derived apnea-hypopnea index exceeding 15 events/h. Comparisons were made between participants on the GERD spectrum with respect to their various self-reported and objective sleep parameters., Results: Among the 277 patients with GERD (49.4%), 198 (35.3%) had EE. Patients with GERD had higher PSQI scores (6.99 ± 3.97 vs 6.07 ± 3.73, P = .005) and a higher prevalence of sleep dysfunction (60.6% vs 49.6%, P = .009). Patients with EE had a higher prevalence of OSA (42.9% vs 33.9%, P = .034). Along the GERD spectrum, symptomatic patients with EE had the highest PSQI scores and prevalence of sleep dysfunction (70.7%), while asymptomatic patients with EE had the highest prevalence of OSA (44%)., Conclusions: Our findings indicate a high prevalence of sleep dysfunction among individuals with GERD. Furthermore, patients on the GERD spectrum are prone to experiencing a range of self-reported and objective sleep disturbances., Citation: Hu K-Y, Tseng P-H, Hsu W-C, et al. Association of self-reported and objective sleep disturbance with the spectrum of gastroesophageal reflux disease. J Clin Sleep Med . 2024;20(6):911-920., (© 2024 American Academy of Sleep Medicine.)

Purpose of review: Endoscopic intervention is one of the therapeutic modalities that are currently available for GERD. Endoscopic treatment for GERD has been recently positioned as an alternative for chronic medical therapy or anti-reflux surgery. Patients who are candidates for these procedures include those with typical symptoms of GERD, low-grade erosive esophagitis (Los Angeles A and B), abnormal esophageal acid exposure if normal endoscopy, small hiatal hernia (< 3 cm), and partial or complete response to PPI treatment. This review will highlight the present and emerging data available about current and new endoscopic therapeutic modalities for GERD. Recent findings: Presently, there are three endoscopic techniques that are approved for GERD, including the Stretta procedure, transoral incisionless fundoplication (TIF), and Medigus ultrasonic surgical endostapler (MUSE). Overall, all endoscopic techniques for GERD have reported excellent control of GERD-related symptoms, improvement of health-related quality of life, durability, and safety. However, the quality of evidence to support these claims varies greatly from one procedure to the other. Furthermore, there is an important discrepancy between improvement of subjective clinical parameters versus objective clinical parameters. There is a growing interest in positioning the endoscopic techniques in patient's post-bariatric surgery, after peroral endoscopic myotomy (POEM), and in those who also require hiatal hernia repair. There are several new endoscopic interventions for GERD that are currently under investigation. Summary: Endoscopic techniques are currently part of our therapeutic armamentarium for GERD. Criticism about their limited effect on objective clinical endpoints has tempered the enthusiasm of patients and physicians alike about their therapeutic value. However, endoscopic therapy for GERD is here to stay as more patients are looking for alternatives to medical and surgical therapy. [ABSTRACT FROM AUTHOR]

The influence of changes in alcohol consumption on erosive esophagitis (EE) development in both sexes is unclear. This observational study investigated sex differences in the influence of alcohol consumption on EE development, and included 2582 patients without EE at baseline from 13,448 patients who underwent >2 health check-ups over >1 year. The rates of non-drinkers who started drinking, and drinkers who abstained from drinking, who increased, and who decreased their weekly alcohol consumption were 7.2%, 9.7%, 14.7%, and 24.1% and 7.3%, 17.8%, 12.8%, and 39.0% in men and women, respectively. In the final cohort, 211/1405 (15.0%) men and 79/1177 (6.7%) women newly developed EE. The odds ratio (OR) for drinking in EE development was 1.252 (95% confidence interval (CI), 0.907–1.726) among men and 1.078 (95% CI, 0.666–1.747) among women. Among men aged

Aim. To study the prevalence of gastroesophageal reflux disease (GERD) and erosive-ulcerative lesions of the gastroduodenal zone and their association among various age groups of Siberian schoolchildren.Material and methods. In order to identify gastrointestinal complaints, a cross-sectional survey of schoolchildren at the age of 7–17 years in the settlements of the Republic of Tyva, Evenkia and Buryatia was conducted. In total, 1535 schoolchildren were examined (7–11 years old — 855 and 12–17 years old — 680 people) in Tyva, 790 (7–11 years old — 333 and 12–17 years old — 457 people) in Buryatia and 1369 (7–11 years old — 633 and 12–17 years old — 736 people) in Evenkia. GERD diagnosis in schoolchildren was based on the presence of heartburn complaints following the worldwide consensus on the GERD definition among the pediatric population. An esophagogastroduodenoscopy (283 children in Tyva, 110 in Buryatia and 205 in Evenkia) was performed by random selection in the age groups of schoolchildren with gastrointestinal complaints in each region.Results. The GERD prevalence among schoolchildren in Siberia was 6.4 %. At the same time, the clinical signs of GERD were mainly noted in schoolchildren of the older age group: at the age of 12–17 years old in 9.4 % of cases, at the age of 7–11 years old in 3.2 % (p = 0.01) of cases. The indicators in the Republic of Tyva were 9.5 %, which is higher than those for schoolchildren in Buryatia (4.1 %; p = 0.01) and Evenkia (4.2 %; p = 0.01). The disease was represented mainly by a non-erosive form. In younger schoolchildren, the non-erosive form of GERD is diagnosed much less frequently and only in Tyva (14.0 %). Erosive esophagitis was diagnosed in 4 cases (0.7 %), 3 of which were in older schoolchildren in Tyva. Erosive-ulcerative diseases of the stomach and duodenum were recorded, to a greater extent, in older children, and largely in Tyva. A more frequent combination of GERD and erosive-ulcerative lesions of the gastroduodenal zone was noted in Tyva, particularly in the older age group.Conclusion. In Siberian schoolchildren, an association of erosive and ulcerative lesions of the mucosa of the gastroduodenal zone with GERD was established, the severity of which has age-related features and is closely related to the region of residence.