Although proton-pump inhibitors (PPIs) have long been the mainstay of therapy for endoscopy-negative reflux disease (ENRD), their therapeutic limitations have become apparent.

This study aimed to evaluate the efficacy and safety of potassium-competitive acid blockers (PCABs) compared to PPIs/placebos in treating ENRD.

Only randomized controlled trials (RCTs) comparing PCABs with PPIs/placebos in ENRD and indexed in MEDLINE, EMBASE, and CENTRAL until May 20, 2024, were included. A random-effects model meta-analysis was performed to pool the primary efficacy outcomes (heartburn resolution and mean heartburn severity at week four) and safety data (any treatment-emergent adverse event or TEAE). The risk of bias was assessed using the Cochrane's Risk of Bias 2 (RoB2) tool.

Four RCTs comparing PCABs and placebos with a total of 2387 participants, were included. All the trials had a low risk of bias. Compared with placebos, PCABs significantly increased the likelihood of heartburn resolution (risk ratio[RR]:1.43;95 %CI:1.22-1.68). The severity of heartburn was significantly reduced by PCABs (standardized mean difference[SMD]:0.19;95 %CI:0.35 to -0.02). TEAEs were comparable between the PCABs and placebos (odds ratio[OR]:1.06;95 %CI:0.82-1.37).

PCABs are non-inferior to placebos in enhancing heartburn resolution and reducing heartburn severity in patients with ENRD, and their safety profile is comparable to that of placebos.

Gastroesophageal reflux disease (GERD) is a very common condition characterized by chronic symptoms, such as heartburn or epigastric and/or substernal pain, that are frequently associated with mucosal damage resulting from abnormal reflux of gastric contents into the esophagus (Fass et al. in Nat Rev Dis Primers 7:55, 2021; Richter and Rubenstein in Gastroenterology 154:267-276, 2018). However, this damage can manifest in patients who do not exhibit typical GERD symptoms. Asymptomatic erosive esophagitis (AEE) is a condition in which there is esophageal mucosal injury typical for GERD, such as erosions, ulcerations, and/or Barrett's esophagus, visible in upper endoscopy, without concurrent symptoms attributable to GERD. AEE has been challenging to study, and it is not yet clear what causes this condition. As a result, there are no definitive guidelines on how to manage it. AEE also has the potential to be very impactful on public health, as those who are affected may go years without a diagnosis, putting them at risk for a variety of complications, including strictures and even cancer. Further careful study is necessary in order to more effectively address this condition. Here, we provide a comprehensive review of the scientific literature regarding AEE, examining its prevalence, clinical characteristics, potential causes and contributing factors, as well as identifying avenues for better characterization and management of this patient population.

Zastaprazan is a potent potassium-competitive acid blocker developed to treat gastroesophageal reflux disease. The aim of this study was to evaluate the efficacy and safety of zastaprazan compared with esomeprazole in patient with erosive esophagitis (EE).

A phase III, multicenter, randomized, double-blind, noninferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary end point was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary end points included the healing rate at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were also assessed.

In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) ( P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than the esomeprazole group (95.14% [137/144] vs 87.68% [121/138]; P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments, and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the 2 groups ( P = 0.047), but both decreased after treatment.

An 8-week therapy of zastaprazan 20 mg is noninferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

According to Rome IV, reflux hypersensitivity (RH) represents a novel form of functional esophageal disorder. This study was designed to compare the clinical features of three types of endoscopic-negative heartburn: RH, nonerosive reflux disease (NERD), and functional heartburn (FH).

Patients with heartburn in a medical center from 01/01/2017 to 10/31/2021 were included. This article presented a blinded retrospective analysis of 24 h MII-pH and HRM tracings from patients with NERD, RH, and FH to compare their clinical characteristics.

A total of 118 patients were included in the study. There were no significant differences in age, sex, BMI, smoking status, or drinking history among RH, NERD and FH. Functional dyspepsia (FD) symptoms were more prone to exist in FH than in NERD (P < 0.05), whereas hiatal hernia was more prevalent in NERD and RH than in FH (P < 0.05). The incidence of anxiety and depression gradually increased in the NERD, RH, and FH groups (P >  0.05). The distal MNBI and PSPW index of the NERD and RH groups were lower than those of the FH group (P < 0.05). The distal MNBI showed good diagnostic potential.

Clear pathological alterations, which are distinct from those of other FGIDs, are observable in RH. It might be inappropriate to categorize RHs within FGIDs.

Non-erosive reflux disease (NERD), the most frequent phenotype of gastroesophageal reflux disease, presents without visible esophageal mucosal damage but significantly impacts patients' quality of life. Current treatments like proton pump inhibitors show limited efficacy for many NERD patients, necessitating alternative approaches. Jianpi Qinghua (JQ) granules, a traditional Chinese medicine, have shown promise in treating NERD by targeting symptoms of spleen deficiency and damp-heat syndrome.

This study aims to evaluate the efficacy and safety of JQ granules in treating patients with NERD characterized by spleen deficiency and damp-heat syndrome.

A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted with a total of 78 NERD patients randomly assigned to receive either JQ granules or placebo for 4 weeks, followed by a 4-week follow-up period.

Seventy-eight NERD patients with spleen deficiency and damp-heat syndrome were recruited and randomly assigned to receive either JQ granules (n = 39) or placebo (n = 39). The trial included a 1-week lead-in, followed by a 4-week double-blind treatment, and a 4-week follow-up. Primary endpoints were the improvement rates of reflux and heartburn symptoms and VAS score changes. Secondary endpoints included atypical symptom scores, total TCM syndrome scores, GERD Health-Related Quality-of-Life (HRQL), and self-rated depression and anxiety scales. Safety assessments involved routine blood, urine, and liver and kidney function tests.

After 4 weeks, the improvement rate for reflux or heartburn symptoms was 79.49% in the JQ group vs. 58.97% in the placebo group (P < 0.05). VAS scores showed significant reductions in both groups but without notable inter-group differences. Total TCM syndrome scores significantly decreased in both groups, with the JQ group showing greater improvement trends. The JQ group had higher rates of effective TCM syndrome improvement and better GERD-HRQL scores. Both groups saw significant reductions in self-rated depression and anxiety scores, with trends favoring JQ granules. Safety assessments were comparable between groups.

JQ granules significantly outperform placebo in treating NERD symptoms and display long-term effectiveness. They effectively address spleen deficiency and damp-heat syndrome, improving patients' social functioning, and have a favorable safety profile.

https://clinicaltrials.gov/study/NCT04324138?term=NCT04324138&rank=1, identifier: NCT04324138.

Proton-pump-inhibitors (PPIs) are overprescribed, posing challenges to patients and healthcare systems. In Portugal, the public National Health Service (NHS) provides universal coverage and reimburses medication regardless of prescription origin, i.e., public or private. This study aimed to compare PPIs outpatient prescription patterns and costs among older adults in the private and public sectors.

A nationwide retrospective ecological study was conducted on PPIs prescribed for older adults in Portugal from 2020-2022. Data on defined daily doses (DDDs) and prices were obtained from a national public database by healthcare sector, sex, and age group (65-74, ≥ 75 years). The market share of DDD per 1000 older adults per day and the mean price per DDD (€/DDD) for all PPIs substances were compared between the public and private sectors.

PPIs-DDDs accounted for 5.3% of all outpatient DDDs prescribed in the private sector and 5.9% in the public sector. The private sector prescribed PPIs at a 20% higher price (0.126 €/DDD) than the public (0.106 €/DDD), with greater differences among the most expensive substances (rabeprazole, lansoprazole and esomeprazole). Omeprazole (cheapest) was mostly prescribed in the public sector. In the private sector, a similar pattern was observed among those aged ≥ 75 years, whereas esomeprazole was most prescribed for those aged 65-74 years.

Given the widespread prescription of PPIs and the associated cost, it is crucial to reinforce incentives to promote rational PPIs prescription and encourage deprescription when necessary, in both sectors. Since the NHS also reimburses medications prescribed in private units, implementing monitoring measures and financial incentives to promote responsible prescribing in this sector should also be considered.

Growing studies have indicated an association between dietary factors and gastroesophageal reflux disease (GERD). However, whether these associations refer to a causal relationship and the potential mechanism by which dietary factors affect GERD is still unclear.

A two-step mendelian randomization analysis was performed to obtain causal estimates of dietary factors, blood lipids on GERD. Independent genetic variants associated with 13 kinds of dietary factors and 5 kinds of blood lipids at the genome-wide significance level were selected as instrumental variables. The summary statistics for GERD were obtained from European Bioinformatics Institute, including 129,080 cases and 473,524 controls. Inverse variance weighted was utilized as the main statistical method. MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis were performed to evaluate possible heterogeneity and pleiotropy. And the potential reverse causality was assessed using Steiger filtering.

The results of the inverse variance weighted method indicated that genetically predicted total pork intake (OR = 2.60, 95% CI: 1.21-5.58, p = 0.0143), total bread intake (OR = 0.68, 95% CI: 0.46-0.99, p = 0.0497), total cereal intake (OR = 0.42, 95% CI: 0.31-0.56, p = 2.98E-06), and total cheese intake (OR = 0.41, 95% CI: 0.27-0.61, p = 1.06E-05) were associated with the risk of GERD. Multivariable Mendelian randomization analysis also revealed a negative association between total cereal intake, total cheese intake and the risk of GERD, but the effect of total pork intake and total bread intake on GERD disappeared after adjustment of smoking, alcohol consumption, use of calcium channel blockers, BMI, physical activity levels, and biological sex (age adjusted). Furthermore, the concentration of low-density lipoprotein cholesterol (LDL-C) is negatively correlated with total cheese intake, which mediates the impact of total cheese intake on GERD. The proportion mediated by LDL-C is 2.27% (95%CI: 1.57%, 4.09%).

This study provides evidence that an increase in total cereal intake and total cheese intake will decrease the risk of GERD. Additionally, LDL-C mediates the causal effect of total cheese intake on GERD. These results provide new insights into the role of dietary factors and blood lipids in GERD, which is beneficial for disease prevention.

Non-erosive reflux disease (NERD) is the most prevalent gastroesophageal reflux disease. Currently, proton pump inhibitors are the most commonly used treatment for NERD. Recently, the demand for herbal medicines with relatively few side effects is increasing and trials confirming the effectiveness and safety of herbal medicines for the treatment of NERD have been conducted. This study aimed to investigate the effectiveness and safety of herbal medicine in the treatment of NERD through published randomized-controlled trials.

Ten electronic databases were searched from inception until May 2023. Disease, intervention-related terms, and publication type keywords were combined as search terms. Studies designed as randomized controlled trials, including participants diagnosed with NERD with any type of herbal medicine as a treatment intervention were included. Data extraction and analysis were conducted by 2 independent reviewers. The total clinical efficacy rate was assessed as a primary outcome, while the secondary outcomes were recurrence rate, reflux diagnostic questionnaire score, short-form 36 health survey score, and serum motilin level. The risk of bias in each study and quality of evidence were assessed.

Thirty-four randomized controlled trials involving 3759 patients were analyzed. Herbal medicine was significantly more effective in improving total clinical efficacy, recurrence rate, reflux diagnostic questionnaire score, some domains of short-form 36 health survey, and serum motilin levels in patients with NERD than conventional medical therapy. No severe intervention-related adverse effects were observed. Regarding the quality of evidence, most outcomes were revealed to have moderate to low levels of evidence.

This systematic review and meta-analysis suggests that herbal medicine can be an effective and safe therapy for NERD; however, there are several limitations regarding the methodological quality of the included studies. Further research with high methodological quality is necessary to improve the quality of evidence.

The measurement of esophageal acid exposure time (AET) using combined multichannel intraluminal impedance-pH (MII-pH) tests is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, this catheter-based 24-h test can cause considerable patient discomfort. Our aim is to identify factors affecting AET and to develop a scoring model for predicting AET abnormalities before conducting the MII-pH test.

Of the 366 patients who underwent MII-pH test at two facilities in Japan and Vietnam, 255 patients who also had esophagogastroduodenoscopy and high-resolution manometry were included in this study. Logistic regression analysis was conducted using risk factors for AET > 6% identified from a derivation cohort (n = 109). A scoring system predicting AET > 6% was then constructed and externally validated with a separate cohort (n = 146).

Three variables were derived from the prediction model: male gender, Hill grades III-IV, and weak mean distal contractile integrals. Based on these scores, patients were classified into low (0 point), intermediate (1-3 points), and high (4 points) risk groups. The probabilities of having an AET > 6% were 6%, 34%, and 100% for these groups, respectively. A score of < 1 excluded patients with abnormal AET, with a negative predictive value of 93.8% in the derivation cohort and 80.0% in the validation cohort.

We derived and externally validated a prediction model for abnormal AET. This system could assist in guiding the appropriate treatment strategies for GERD.

Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes.

Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated.

In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs.

Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

This meta-analysis evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) compared to proton pump inhibitors (PPIs) in treating gastroesophageal reflux disease (GERD). A comprehensive literature search was conducted across multiple databases, and 11 randomized controlled trials comparing PCABs with PPIs were included. The primary outcome was the healing of erosive esophagitis (EE), with secondary outcomes, including relief of heartburn symptoms and adverse events. The analysis included 11 studies and a pooled sample of 4,108 GERD patients. Results showed that PCABs were significantly more effective in healing EE compared to PPIs (OR: 1.67, 95% CI: 1.24-2.24, p<0.01). PCABs also demonstrated a higher rate of complete resolution of heartburn symptoms, although this difference did not reach statistical significance (OR: 1.43, 95% CI: 0.98-2.09, p=0.06). In terms of safety, there was no significant difference in adverse events between PCABs and PPIs (OR: 0.91, 95% CI: 0.79-1.04, p=0.18), including serious adverse events. The superior efficacy of PCABs can be attributed to their unique pharmacological properties, which allow for more rapid and potent acid suppression compared to PPIs. However, the long-term safety profile of PCABs, particularly newer agents, requires further investigation. The study was limited by the predominance of vonoprazan among the PCABs studied and the focus on patients with EE rather than non-erosive reflux disease. In conclusion, this meta-analysis suggests that PCABs are more effective than PPIs in treating GERD, particularly in healing EE, while maintaining a comparable safety profile. Future research should focus on evaluating a wider range of PCABs, assessing their efficacy in non-erosive reflux disease, and investigating their long-term safety in GERD management.

Objective We assessed the factors associated with overlap between functional dyspepsia (FD) and nonerosive reflux disease (NERD) in endoscopy-based Helicobacter pylori-uninfected Japanese health checkup participants. Methods We utilized baseline data from 3,085 individuals who underwent upper endoscopy for health screening in a prospective, multicenter cohort study. The participants were asked to complete a questionnaire detailing their upper abdominal symptoms and lifestyle. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) score. FD, postprandial distress syndrome (PDS), and epigastric pain syndrome (EPS) were defined according to the Rome III criteria. NERD was defined as heartburn or regurgitation ≥1 day/week without erosive esophagitis. Results Of the 3,085 participants, 73 (2.4%), 97 (3.1%), and 84 (2.7%) had FD alone, NERD alone, and FD-NERD overlap, respectively. Factors associated with FD-NERD-overlap participants compared with participants with neither FD nor NERD were women [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.24-3.52], body mass index (BMI) <18.5 (OR: 2.87, 95% CI: 1.56-5.07), alcohol consumption ≥20 g/day (OR: 1.85, 95% CI: 1.06-3.15), and a high STAI score (OR: 2.53, 95% CI: 1.62-4.00). Increasing age (OR: 1.06, 95% CI: 1.01-1.11) and EPS symptoms [pure EPS (OR: 3.67, 95% CI: 1.65-8.51) and PDS-EPS overlap (OR: 11.6, 95% CI: 4.09-37.2)] were associated with FD-NERD overlap vs. FD alone. Women (OR: 3.17, 95% CI: 1.47-7.04), BMI <18.5 (OR: 3.03, 95% CI: 1.04-9.90), and acid reflux symptoms ≥2 days a week (OR: 3.57, 95% CI: 1.83-7.14) were associated with FD-NERD overlap vs. NERD alone. Conclusion Understanding the clinical features of overlap between FD and NERD will lead to better management.

Saliva secretion is significantly lower in patients with non-erosive reflux disease (NERD) than in healthy controls (HC). A previous study on HC showed that saliva secretion was lower in females than in males. Saliva secretion may be lower in female patients with NERD than in male patients. Therefore, the present study investigated sex differences in saliva secretion in patients with NERD.

Subjects older than 50 years were included in the present study and consisted of 20 male patients with NERD, 19 male HC, 25 female patients with NERD, and 23 female HC. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured.

In males, no significant differences were observed in the amount of stimulated saliva secretion or salivary pH between NERD patients and HC. However, the acid-buffering capacity (NERD: 6.1 [5.9-6.5], HC: 6.4 [6.2-6.6]) was significantly lower in NERD patients than in HC. In females, the amount of stimulated saliva secretion (NERD: 2.6 [2.0-4.1], HC: 5.8 [3.7-7.5]), salivary pH (NERD: 7.0 [6.8-7.2], HC: 7.2 [7.0-7.2]), and the acid-buffering capacity (NERD: 5.8 [5.4-6.2], HC: 6.2 [6.0-6.5]) were significantly lower in NERD patients than in HC.

Among females older than 50 years, saliva secretion was significantly lower in NERD patients than in HC. This reduction in saliva secretion may contribute to the pathophysiology of NERD in females.

Gastroesophageal reflux disease (GERD) is the most common diagnosis seen in outpatient gastroenterology clinics. The diagnosis is made by a variable combination of symptoms, response to acid suppressive therapy, endoscopic evaluation, and pH testing. In this review, we evaluate how to utilize various reflux testing in clinical practice based on current evidence.

Ambulatory reflux monitoring is a recognized diagnostic tool for clinical decision making in patients with/without established GERD, persistent reflux symptoms, and lack of response to proton pump inhibitor (PPI) therapy. Standard evaluation approaches include 24-hour pH or impedance monitoring via transnasal catheter, prolonged (48 to 96 hour) wireless pH monitoring, and the recently developed mucosal integrity testing. Testing using one of these methods allows for measurement of acid exposure, frequency of reflux, and to phenotype patients to personalize treatment recommendations.

The primary goal of future studies should be to simplify ambulatory reflux monitoring, reduce diagnostic latency, improve patient tolerance, and to obtain clinical outcomes-based studies. The current paradigm of reflux testing is vastly complex with multiple modalities and shifting cutoffs of pH abnormality that lead to high economic burden on the society.

Non-erosive reflux disease (NERD) accounts for over half of all gastroesophageal reflux cases and is characterized by reflux symptoms with pathologic acid exposure on pH monitoring but no evidence of erosions on upper endoscopy. Ambulatory pH monitoring is limited by availability and patient tolerance. The utility of performing esophageal mucosal biopsies in diagnosing NERD is unclear. We conducted a systematic review and meta-analysis to determine the sensitivity of esophageal mucosal biopsies in diagnosing NERD.

Data were obtained from Embase and Ovid MEDLINE from inception to April 2021. Studies were included if esophageal mucosal biopsies were taken and analyzed using conventional histopathologic analysis in symptomatic NERD patients. Relevant data was including histologic abnormalities and location of the biopsy. Sensitivity and specificity were calculated against healthy controls or those with functional heartburn.

The search yielded 2871 studies, of which 10 studies met our inclusion criteria and contained raw data. Histological abnormalities included histologic sum scores, papillary elongation, basal cell hyperplasia, and dilated intraepithelial spaces. When assessing for the presence of any abnormality, biopsies taken <3 cm from the lower esophageal sphincter (LES) had a pooled sensitivity of 0.71 (95% CI 0.64-0.77) and specificity of 0.64 (95% 0.54-0.73); however, analysis of individual histologic features such as the presence of eosinophils improved the sensitivity.

Although esophageal mucosal biopsies had poor sensitivity at diagnosing NERD, biopsies taken within 3 cm of the LES had higher sensitivity when pathologists reported upon eosinophils and dilated intraepithelial spaces.

Vonoprazan results in more potent acid suppression for gastroesophageal reflux disease (GERD) than proton pump inhibitors. It has only been approved for treating erosive esophagitis in China, but 30-40% of GERD patients cannot achieve the goal of treatment with vonoprazan 20 mg daily. This study aims to investigate whether vonoprazan could relieve the symptoms of Chinese patients with non-erosive reflux disease (NERD) and whether increased dosage or different times of dosing could increase the response rate of GERD.

This study is a pragmatic, open-label, crossover-cluster, randomized controlled trial with patient preference arms. Two thousand eight hundred eighty patients with GERD from 48 hospitals in China will be enrolled. These hospitals will be divided into a compulsory randomization cluster (24 hospitals) and a patient preference cluster (24 hospitals). Patients in the compulsory randomization cluster will be randomized to three regimens according to the crossover-cluster randomization. Patients in the patient preference cluster may choose to receive any regimen if they have a preference; otherwise, patients will be randomly assigned. The three treatment regimens will last 4 weeks, including (1) vonoprazan 20 mg p.o. after breakfast, (2) vonoprazan 20 mg p.o. after dinner, and (3) vonoprazan 20 mg p.o. after breakfast and after dinner. Patients will attend a baseline visit, a 4-week e-diary, a fourth-week visit, and a sixth-month visit online. The primary outcome is the symptom relief rate of all patients after 4-week therapy. Secondary outcomes include the healing rate of EE patients, the severity of symptoms, compliance with the therapy at the fourth-week follow-up visit, recurrent symptoms, and the frequency of self-conscious doctor visits at the sixth-month follow-up visit.

This trial will explore the effectiveness of different regimens of vonoprazan that will be implemented with GERD patients in China. The randomization with patient preferences considered and the crossover-cluster component may improve the robustness and extrapolation of study conclusions.

https://www.chictr.org.cn ChiCTR2300069857. Registered on 28 March 2023.

February 18, 2023, Version 2.

While proton pump inhibitor (PPI) therapy has proven to be effective in managing gastroesophageal reflux disease (GERD), a notable portion of patients who experience GERD symptoms may not respond to this treatment. Research suggests that roughly 30% of individuals with a presumed GERD diagnosis may continue to experience symptoms, whether partially or completely, even when receiving PPI therapy. The aim of this study was to assess the treatment of gastrointestinal diseases with a novel potassium-competitive acid blocker (P-CAB), vonoprazan, in terms of its effectiveness and safety in the Pakistani population.

This prospective, multicenter, observational study was conducted in Pakistan. This study included 1,642 patients from January 2023 to August 2023, aged 18 years, with gastrointestinal disorders. All demographic data, medical history, GERD severity assessment questionnaire (GerdQ), and laboratory parameters, including stool assessment for Helicobacter pylori (H. pylori), were observed. Patients were orally treated with vonoprazan at doses of 10 mg or 20 mg, once or twice daily. Statistical analysis was done by one-way ANOVA.

Out of 1,642 patients, 840 (51.2%) were males and 802 (48.8%) were females, with a mean age of 39.81±14.61 years. The mean GerdQ score at baseline was 20.37±15.87, 7.24±8.15 at the second week of treatment, and 3.70±6.31 at the fourth week of treatment (p<0.001). 90.74% of patients achieved H. pylori eradication. Most patients were acid regurgitation and heartburn-free for >70% of days. Most of the patients, 1,283 (78.13%), exhibited good treatment compliance. Mild adverse events were reported in 37 (2.3%) patients.

The use of vonoprazan significantly reduced the likelihood of GERD by improving symptoms and was also highly effective in the elimination of H. pylori infections. Vonoprazan was generally well tolerated.

Our comprehensive systematic review aimed to examine gastroesophageal reflux disease (GERD), a disorder that occurs when stomach contents flow back into the esophagus. It may manifest as either non-erosive reflux disease or erosive esophagitis. The activity depicts the assessment and medical management of GERD and emphasizes the interprofessional team's involvement to enhance care for people with this ailment. Data sources were PubMed/Medline and Embase. Our review investigated English-language articles (from 2014 to 2023) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Overall, there were seven articles. Surveys and analyses of national databases were the most widely used methods (n=7). The search identified 3,730 studies, and seven were eligible for inclusion in the analysis. Further understanding of GERD and treatment protocols may help improve evaluation and management in the future. Millions of individuals worldwide suffer from GERD, a common clinical condition. Patients can be identified by symptoms that are both common and uncommon. For many GERD patients, acid suppression treatment reduces symptoms and avoids clinical complications. Our capacity to recognize and treat disease consequences has improved with the advancement of diagnostic and treatment methods. Here, we go into the etiology and consequences of GERD and offer details on the treatment strategy for this prevalent illness.

Efficacy of proton pump inhibitors is limited in patients with nonerosive reflux disease (NERD). The aim of this study was to comparatively evaluate the efficacy and safety of esomeprazole with sodium bicarbonate and esomeprazole alone.

This was a multicenter, randomized, double-blind, active-controlled, noninferiority comparative study. A total of 379 patients with NERD were randomly allocated to receive either EsoduoⓇ (esomeprazole 20 mg with sodium bicarbonate 800 mg) or NexiumⓇ (esomeprazole 20 mg) once daily for 4 weeks from January 2019 to December 2019. The patients had a history of heartburn for at least 2 days in the week before randomization as well as in the last 3 months and no esophageal mucosal breaks on endoscopy. The primary endpoint was a complete cure of heartburn at week 4. The secondary and exploratory endpoints as well as the safety profiles were compared in the groups at weeks 2 and 4.

A total of 355 patients completed the study (180 in the EsoduoⓇ group and 175 in the NexiumⓇ group). The proportions of patients without heartburn in the entire 4th week of treatment were not different between the two groups (33.33% in the EsoduoⓇ group and 35% in the NexiumⓇ group, p=0.737). There were no significant differences in most of the secondary and exploratory endpoints as well as the safety profiles.

EsoduoⓇ is as effective and safe as NexiumⓇ for managing typical symptoms in patients with NERD (ClinicalTrial.gov identifier: NCT03928470).

Fexuprazan, a novel potassium-competitive acid blocker, reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells. Fexuprazan's suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner.

To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis (EE).

Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate of EE at week 4, symptom response, and quality of life assessment. Safety profiles and serum gastrin levels were compared between the groups.

Of the 263 randomized, 218 completed the study per protocol (fexuprazan 40 mg, n = 107; esomeprazole 40 mg, n = 111). Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8 [99.1% (106/107) vs 99.1% (110/111)]. There were no between-group differences in the EE healing rate at week 4 [90.3% (93/103) vs 88.5% (92/104)], symptom responses, and quality of life assessments. Additionally, serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups.

Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8. We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.

We previously reported that swallowing in the bridge position (bridge swallowing) increased distal esophageal contractions and lower esophageal sphincter pressure against gravity. Moreover, bridge swallowing had the potential to strengthen esophageal peristalsis. In this study, we sought to evaluate whether the bridge swallowing exercise could improve gastroesophageal reflux disease (GERD) symptoms and gastroscopy findings.

Seventeen subjects with scores of 8 points or higher on the Frequency Scale for Symptoms of GERD (FSSG) questionnaire participated in the study. The exercise of dry swallowing in the bridge posture lasted 4 weeks and was performed ten times per day. FSSG scores were compared before and after exercise. Three of the 17 participants underwent upper gastrointestinal endoscopy. The modified Los Angeles classification of reflux esophagitis was used for objective assessment before and after exercise.

No participants dropped out of this study. FSSG scores improved significantly after exercise (from median [range] 16 [13-21] points before exercise to 5 [4-10] points after exercise, P <0.001). Upper gastrointestinal endoscopy showed improvement in the modified Los Angeles classification grade in one participant.

The bridge swallowing exercise significantly improves FSSG scores. This exercise can be performed easily and safely without adverse events. Further multicenter prospective studies are needed to validate that the bridge swallowing exercise is effective in improving GERD.

We examined the accuracy of narrow-band imaging (NBI) findings in nonerosive reflux disease (NERD) patients compared with control subjects and the impact of proton pump inhibitor (PPI) therapy on these mucosal changes in a multicenter, double-blind, randomized controlled trial.

NERD patients (typical symptoms using a validated GERD questionnaire, absence of erosive esophagitis, and abnormal 48-hour pH study) and control subjects underwent high-definition white-light endoscopy followed by NBI and biopsy sampling of the distal esophagus. Then, NERD patients were randomized to esomeprazole 40 mg/day or placebo for 8 weeks, followed by repeat endoscopy. The presence of distal esophageal mucosal changes on NBI were recorded at baseline and after treatment: intrapapillary capillary loops (IPCLs; number, dilation, and tortuosity), microerosions, increased vascularity, columnar islands, and ridge/villous pattern (RVP) above the squamocolumnar junction.

Of 122 screened, 21 NERD and 21 control subjects were identified (mean age, 49.5 ± 14.6 years; 62% men; and 85% white). The combination of IPCL tortuosity, RVP, and microerosions (62% vs 19%, P < .05) had a high specificity (86%) and moderate sensitivity (60%) for NERD with an area under the curve of .74. In 10 NERD patients treated with PPIs, resolution of microerosions was most significant (P = .047) compared with placebo (n = 11). RVP resolved in all NERD patients after therapy (P = .02) and correlated with acid exposure time (P = .004). Papillary length (P = .02) and basal cell thickness (P = .02) significantly correlated with a combination of IPCL tortuosity, RVP, and microerosions.

In this randomized controlled trial, RVP on NBI demonstrated a high specificity, correlated with acid exposure time, and improved with PPI therapy, suggesting that it could be used as a surrogate marker for diagnosis of NERD. (Clinical trial registration number: NCT02081404.).

Direct comparison studies about the incidence of esophago-gastric complications between radiofrequency (RF) and cryoballoon (CB) catheter ablation (CA) for atrial fibrillation (AF) have been scarce. We sought to elucidate the relationship between the pulmonary vein isolation (PVI) modalities and esophago-gastric complications.

The study population consisted of 254 patients who underwent CA for AF from November 2017 to October 2018. Finally, 160 patients were enrolled and divided into the RF and CB groups. Esophageal ulcers, gastric hypomotility, and exfoliative esophagitis detected by esophago-gastro-duodenoscopy were defined as esophago-gastric complications in this study.

The median age was 68 years old, with 34% being females. Esophago-gastric complications were observed in 42.5% of patients who underwent CA. According to the detailed esophago-gastric complications, the RF group had a higher prevalence of esophageal ulcers than the CB group (19% vs. 0%, p <0.0001). There was no significant difference between the two groups regarding gastric hypomotility and exfoliative esophagitis (18% vs. 28%; p = 0.15, 16% vs. 21%; p = 0.42, respectively).

Asymptomatic esophago-gastric complications were common in catheter ablation for atrial fibrillation. The incidence of esophageal ulcers was higher in the radiofrequency group than cryoballoon group, whereas the other esophago-gastric complications did not significantly differ. This article is protected by copyright. All rights reserved.

In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD.

Esophageal motility disorders (EMDs) contribute to the pathophysiology of gastroesophageal reflux disease. However, the causes of EMDs and their impact on gastroesophageal reflux disease-associated symptoms remain unknown. This study aims to elucidate clinical features associated with various types of EMDs in patients with heartburn symptoms.

Of the 511 patients who underwent high-resolution manometry, 394 who were evaluated for heartburn symptoms were examined. Patients subjected to high-resolution manometry were classified into 4 groups: outflow obstruction group, hypermotility group, hypomotility group, and normal motility group. Symptoms were evaluated using 3 questionnaires. Patient characteristics and symptoms for each EMD type were compared with those of the normal motility group.

Of the 394 patients, 193 (48.9%) were diagnosed with EMDs, including 71 with outflow obstruction, 15 with hypermotility, and 107 with hypomotility. The mean dysphagia score was significantly higher in each of the 3 EMD groups compared with those with normal motility. The mean acid reflux and dyspepsia scores were significantly lower in the outflow obstruction group (P < 0.05). The mean body mass index and median Brinkman index were significantly higher in the hypermotility group (P = 0.001 and P = 0.018, respectively), whereas the mean diarrhea and constipation scores were significantly lower in the hypomotility group (P < 0.05).

The results of our study indicate that different EMDs have distinct characteristics. Cigarette smoking and high body mass index were associated with esophageal hypermotility. Assessment of the dysphagia symptom scores may help identify patients with EMDs.

Conflicting results exist on the association between Helicobacter pylori infection and gastro-oesophageal reflux (GOR), and its complications, such as erosive oesophagitis (EO) and Barrett's oesophagus (BO).

To explore the association of H. pylori infection with GOR symptoms and their complications METHODS: We searched Embase, PubMed, Web of Science and Scopus databases through December 2020 for relevant articles. Regarding the association between H. pylori and GOR symptoms (heartburn, regurgitation or reflux), we included observational studies comparing the prevalence of GOR symptoms between H. pylori-positive and -negative individuals. Concerning the association between H. pylori and complications of GOR, we included studies comparing the prevalence of EO or BO between H. pylori-positive and -negative individuals.

In total, 36 papers were eligible. Based on seven cross-sectional surveys, H. pylori infection was associated with a lower odds of GOR symptoms (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.61-0.90). However, in four case-control studies, H. pylori infection was not associated with odds of GOR symptoms (OR 1.10, 95% CI 0.85-0.1.43). In 26 cross-sectional studies in patients with GOR symptoms, the OR for EO was 0.70 (95% CI 0.58-0.84) in H. pylori-positive vs -negative cases. Based on nine cross-sectional studies in subjects with GOR complications, no significant association was found between H. pylori infection and either endoscopically-diagnosed (OR 1.84, 95% CI 0.67-5.02) or histologically confirmed (OR 0.85, 95% CI 0.60-1.20) BO.

Helicobacter pylori infection appears to be associated with a decreased odds of GOR symptoms and EO. In contrast, H. pylori infection did not seem to affect the odds of BO in patients with GER complications.

Tegoprazan is a novel, fast- and long-acting potassium-competitive acid blocker that suppresses gastric acid secretion, which could benefit patients with non-erosive reflux disease (NERD), a type of gastroesophageal reflux disease.

To evaluate the efficacy and safety profiles of tegoprazan compared with those of a placebo in Korean patients with NERD.

In this phase 3, double-blind, placebo-controlled, multicentre study, 324 Korean patients with NERD were randomised into three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and placebo. These drugs were provided once daily for 4 weeks. The primary endpoint was the proportion of patients with complete resolution of major symptoms (both heartburn and regurgitation) for the last 7 days of the 4-week treatment period. Other outcomes related to efficacy, safety and tolerability were also evaluated.

Among all, 42.5% (45/106), 48.5% (48/99) and 24.2% (24/99) of patients showed complete resolution of major symptoms at week 4 after receiving tegoprazan 50 mg, tegoprazan 100 mg, and placebo, respectively. Both doses of tegoprazan showed superior efficacy than the placebo (P = 0.0058 and P = 0.0004, respectively). The complete resolution rates of heartburn and proportions of heartburn-free days (as other efficacy outcomes) were significantly higher in both tegoprazan groups than in the placebo group (P < 0.05 for all). No significant difference in the incidence of treatment-emergent adverse events were noted.

Tegoprazan 50 and 100 mg showed superior therapeutic efficacy compared with the placebo, as well as a favourable safety profile in patients with NERD. Registration number: ClinicalTrials.gov identifier NCT02556021.

Gastro-oesophageal reflux disease (GERD) is a common disorder in adults and children. The global prevalence of GERD is high and increasing. Non-erosive reflux disease is the most common phenotype of GERD. Heartburn and regurgitation are considered classic symptoms but GERD may present with various atypical and extra-oesophageal manifestations. The pathophysiology of GERD is multifactorial and different mechanisms may result in GERD symptoms, including gastric composition and motility, anti-reflux barrier, refluxate characteristics, clearance mechanisms, mucosal integrity and symptom perception. In clinical practice, the diagnosis of GERD is commonly established on the basis of response to anti-reflux treatment; however, a more accurate diagnosis requires testing that includes upper gastrointestinal tract endoscopy and reflux monitoring. New techniques and new reflux testing parameters help to better phenotype the condition. In children, the diagnosis of GERD is primarily based on history and physical examination and treatment vary with age. Treatment in adults includes a combination of lifestyle modifications with pharmacological, endoscopic or surgical intervention. In refractory GERD, optimization of proton-pump inhibitor treatment should be attempted before a series of diagnostic tests to assess the patient's phenotype.

Heartburn is a common symptom in clinical practice, but as many as 70% of patients have normal findings from upper endoscopy. Most of these patients have nonerosive reflux disease (NERD) or functional esophageal disorders. NERD is the most common phenotype of gastroesophageal reflux disease, and functional heartburn is the most common cause for refractory heartburn. In patients with NERD, symptoms arise from gastroesophageal reflux and esophageal hypersensitivity, whereas in patients with functional heartburn, symptoms result from esophageal hypersensitivity. A diagnosis of NERD requires endoscopy and reflux testing, whereas a diagnosis of functional heartburn also requires esophageal manometry. NERD is treated most commonly with medical, endoscopic, and surgical antireflux approaches, whereas functional heartburn as well as NERD can be treated with neuromodulators, psychological intervention, and complementary medicine options.

Conflicting evidence exists regarding the effect of NSAIDs on the risk of Barrett's esophagus. The purpose of this study is to systematically assess this effect through a meta-analysis.

Accordingly, clinical studies on NSAID use and Barrett's esophagus risk were searched on PubMed, Embase, and the Cochrane Library. Following this, meta-analyses were conducted using the RevMan 5.3 software. The pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were used as the effect size.

Seven eligible studies (one cohort study and six case-control studies) were included for the present meta-analysis by adopting a fixed-effect model, which demonstrated that NSAIDs could reduce Barrett's esophagus risk (OR: 0.84, 95%CI:0.75-0.94, P＜0.05). Moreover, subgroup analyses done according to sex showed that NSAIDs could reduce Barrett's esophagus risk in females (OR 0.85; 95% CI 0.73-0.99; P = 0.04), without heterogeneity between studies (P = 1.00 and I² = 0%). However, this relationship was not evident in males (OR 0.85; 95% CI 0.68-1.07; P = 0.16).

Overall, this meta-analysis provided high quality evidence that use of NSAIDs is associated with a reduced risk of Barrett's esophagus. However, the presence of a sex-dependent difference remains to be clarified.

Gastroesophageal reflux disease (GERD) is a widely studied and highly prevalent condition. However, few are reported about the exact efficacy and safety of fundoplication (FPT) compared to oral intake proton-pump inhibitors (PPI). This systematic review and meta-analysis of randomized clinical trials (RCT) aims to compare PPI and FPT in relation to the efficacy, as well as the adverse events associated with these therapies. Search carried out in June 2020 was conducted on Medline, Cochrane, EMBASE and LILACS. Selection was restricted to RCT comparing PPI and FPT (open or laparoscopic) in GERD patients. Certainty of evidence and risk of bias were assessed with GRADE Pro and with Review Manager Version 5.4 bias assessment tool. Ten RCT were included. Meta-analysis showed that heartburn (RD =  - 0.19; 95% CI =  - 0.29, - 0.09) was less frequently reported by patients that underwent FPT. Furthermore, patients undergoing surgery had greater pressure on the lower esophageal sphincter than those who used PPI (MD = 7.81; 95% CI 4.79, 10.83). Finally, FPT did not increase significantly the risk for adverse events such as postoperative dysphagia and impaired belching. FPT is a more effective therapy than PPI treatment for GERD, without significantly increasing the risk for adverse events. However, before indicating a possible surgical approach, it is extremely important to correctly assess and select the patients who would benefit from FPT to ensure better results.

Objective: To assess the correlation between the incidence of non-erosive reflux disease (NERD) and psychological factors, especially somatoform disorders. To investigate the characteristics of gut microbiome in NERD patients. Methods: We enrolled 24 NERD patients and 24 healthy controls. All patients were evaluated via GerdQ, SOMS-7, SAS, HAMA, and HAMD. Fecal samples were collected and 16S rRNA sequencing was performed to evaluate the gut microbiome composition. Results: The main symptoms of the NERD patients were regurgitation (87.5%), belching (66.7%), pharyngeal discomfort (50%), and heartburn (37.5%). The average score of GerdQ was 13.42 ± 3.41. In 15 patients (62.5%), the total score of the last two items was <3 points, while the average score of 24 patients was 3.63 ± 2.32. NERD patients with somatoform disorders accounted for 50%. There were 17 patients without anxiety, 6 patients with mild anxiety (25%), 1 patient with moderate anxiety (4.2%), and no patient with severe anxiety. There were 22 patients (91.7%) without depression, 2 patients (8.3%) with mild depression, and no patient with moderate or severe depression. The alpha diversity of NERD group was higher than HC, which showed significant difference (P < 0.05). The beta-diversity was significantly different between HC and NERD patients (P = 0.026), male and female patients (P = 0.009). The beta-diversity was also significantly different between male and female patients (P = 0.009). There were several bacteria with significant differences between HC and NERD group, and NERD patients with or without somatoform disorders, such as Firmicutes, TM7 were enriched in the NERD group compared with the healthy control group, while Bacteroidetes were enriched in the healthy controls. Conclusions: NERD symptoms overlap with somatoform disorders. NERD symptoms have an impact on the daily life quality of patients. Some of them are accompanied by anxiety and depression of different degrees, and the two are significantly correlated. The diversity of gut microbiome in patients with NERD is significantly higher than healthy controls, which has its characteristics. The predominant bacteria in gut microbiome of patients with NERD are similar to the healthy population, with Firmicutes and Bacteroidetes as the main ones. The composition of gut microbiome in NERD patients with or without somatoform disorder is significantly different, which may be related to the interaction of microbiome-brain-gut axis.