In this editorial, we respond to a review article by Nabi et al, in which the authors discussed gastroesophageal reflux (GER) following peroral endoscopic myotomy (POEM). POEM is presently the primary therapeutic option for achalasia, which is both safe and effective. A few adverse effects were documented after POEM, including GER. The diagnostic criteria were not clear enough because approximately 60% of patients have a long acid exposure time, while only 10% experience reflux symptoms. Multiple predictors of high disease incidence have been identified, including old age, female sex, obesity, and a baseline lower esophageal sphincter pressure of less than 45 mmHg. Some technical steps during the procedure, such as a lengthy or full-thickness myotomy, may further enhance the risk. Proton pump inhibitors are currently the first line of treatment. Emerging voices are increasingly advocating for the routine combining of POEM with an endoscopic fundoplication method, such as peroral endoscopic fundoplication or transoral incisionless fundoplication. However, more research is necessary to determine the safety and effectiveness of these procedures in the long term for patients who have undergone them.

Gastroesophageal reflux disease (GERD) is one of the most common comorbidities of chronic obstructive pulmonary disease (COPD). Decreased lower and upper esophageal sphincter pressures, esophageal dysmotility, high transdiaphragmatic pressure, and decreased saliva secretion have been implicated as mechanisms leading to the development of GERD in COPD. Clinically, comorbid GERD in COPD is reportedly associated with worse symptoms, quality of life, and lung function, as well as a high risk of exacerbations. Aspiration of regurgitation and the cholinergic-mediated esophagobronchial reflex play a significant role in the pathophysiology. Abnormal swallowing reflexes and discoordination of swallowing can worsen aspiration. The diagnosis of GERD is not based on a single criterion; however, various approaches, including questionnaires and endoscopic evaluations, can be widely applied in clinical settings. Due to the increased risk of esophageal and gastric cancers in patients with COPD, the threshold for endoscopic examination should be low. Acid inhibitory agents, such as proton pump inhibitors and histamine H2 receptor antagonists, and prokinetic agents, including mosapride and itopride, are clinically used to treat GERD. Endoscopic fundoplication can be performed in patients with GERD refractory to medical treatment. There is still insufficient evidence, but an increasing number of studies have suggested the clinical efficacy of treatment in patients with COPD and GERD. As GERD is an evaluative and treatable common disease, and access to evaluation and treatment is relatively easy, clinicians should provide adequate care for GERD in the management of COPD.

OBJECTIVE: This study aimed to explore the potential causal relationship between dietary habits and Gastroesophageal Reflux Disease (GERD).
METHODS: Using the inverse-variance weighted method, a two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship between 22 dietary habits and GERD. The stability and reliability of the results were assessed using leave-one-out analysis, heterogeneity tests, and tests for horizontal pleiotropy based on the effect measure odds ratio (OR) and 95% confidence interval (CI).
RESULTS: The results of the MR analysis indicated a positive association between alcohol drinking (OR=1.472; 95% CI, 1.331 to 1.629; p<1.0×10-3) and salt added to food (OR=1.270; 95% CI, 1.117 to 1.443; p<1.0×10-3) with the risk of GERD. Conversely, bread intake (OR=0.613; 95% CI, 0.477 to 0.790; p<1.0×10-3), cereal intake (OR=0.613; 95% CI, 0.391 to 0.677; p<1.0×10-3), cheese intake (OR=0.709; 95% CI, 0.593 to 0.846; p<1.0×10-3), dried fruit intake (OR=0.535; 95% CI, 0.404 to 0.709; p<1.0×10-3), fresh fruit intake (OR=0.415; 95% CI, 0.278 to 0.619; p<1.0×10-3), and oily fish intake (OR=0.746; 95% CI, 0.633 to 0.879; p<1.0×10-3) were negatively associated with the risk of GERD. Sensitivity analysis showed no evidence of reverse causation, pleiotropy, or heterogeneity.
CONCLUSIONS: Alcohol and salt added to food raised GERD risk, while bread intake, cereal intake, cheese intake, intake of certain dried fruits and certain fresh fruits, and oily fish lowered it. Our study affirms the potential causal link between these diets and GERD, offering insights into targeted prevention strategies.

BACKGROUND: Observational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal relationship and shared genetic architecture between the two. This study aims to explore their common genetic correlations by leveraging genome-wide association studies (GWAS) of smoking behavior-specifically, smoking initiation (SI), never smoking (NS), ever smoking (ES), cigarettes smoked per day (CPD), age of smoking initiation(ASI) and GERD.
METHODS: Firstly, we conducted global cross-trait genetic correlation analysis and heritability estimation from summary statistics (HESS) to explore the genetic correlation between smoking behavior and GERD. Then, a joint cross-trait meta-analysis was performed to identify shared \"pleiotropic SNPs\" between smoking behavior and GERD, followed by co-localization analysis. Additionally, multi-marker analyses using annotation (MAGMA) were employed to explore the degree of enrichment of single nucleotide polymorphism (SNP) heritability in specific tissues, and summary data-based Mendelian randomization (SMR) was further utilized to investigate potential functional genes. Finally, Mendelian randomization (MR) analysis was conducted to explore the causal relationship between the smoking behavior and GERD.
RESULTS: Consistent genetic correlations were observed through global and local genetic correlation analyses, wherein SI, ES, and CPD showed significantly positive genetic correlations with GERD, while NS and ASI showed significantly negative correlations. HESS analysis also identified multiple significantly associated loci between them. Furthermore, three novel \"pleiotropic SNPs\" (rs4382592, rs200968, rs1510719) were identified through cross-trait meta-analysis and co-localization analysis to exist between SI, NS, ES, ASI, and GERD, mapping the genes MED27, HIST1H2BO, MAML3 as new pleiotropic genes between SI, NS, ES, ASI, and GERD. Moreover, both smoking behavior and GERD were found to be co-enriched in multiple brain tissues, with GMPPB, RNF123, and RBM6 identified as potential functional genes co-enriched in Cerebellar Hemisphere, Cerebellum, Cortex/Nucleus accumbens in SI and GERD, and SUOX identified in Caudate nucleus, Cerebellum, Cortex in NS and GERD. Lastly, consistent causal relationships were found through MR analysis, indicating that SI, ES, and CPD increase the risk of GERD, while NS and higher ASI decrease the risk.
CONCLUSIONS: We identified genetic loci associated with smoking behavior and GERD, as well as brain tissue sites of shared enrichment, prioritizing three new pleiotropic genes and four new functional genes. Finally, the causal relationship between smoking behavior and GERD was demonstrated, providing insights for early prevention strategies for GERD.

Background Gastroesophageal reflux disease (GERD) is a global gastrointestinal disorder, and obesity is a particular risk factor. Symptoms of GERD, such as heartburn and acid reflux, are caused by abnormal relaxation in the lower esophagus, causing gastric acid reflux. Persistent symptoms can affect the patient\'s quality of life (QOL) and can cause complications, such as esophageal adenocarcinoma. Management of GERD includes lifestyle changes, antacids, and anti-reflux surgery. Even though GERD is a common disease, few research has been carried out on it in Saudi Arabia. Aim This study aimed to estimate the prevalence of GERD and its associated risk factors among obese individuals in the Al-Baha region population and the effect of GERD on their QOL. Methods A cross-sectional study included 314 obese participants from the Al-Baha region. A questionnaire was filled out to measure the prevalence of GERD, risk factors, and effects on the QOL of the participants. Data were analyzed by the IBM SPSS Statistics for Windows, version 26.0 (released 2019, IBM Corp., Armonk, NY). Descriptive statistics and the chi-squared test were applied. Logistic regression analysis was used to determine the factors associated with the incidence of GERD. A p-value of <0.05 was considered statistically significant. Results A total of 314 patients who met our inclusion criteria completed the survey; 42% of them were women, the mean age of all patients was 35.3 ± 12.9 years, and 38.2% of the patients were diagnosed with GERD. Epigastric pain and burning sensation were the most common symptoms (44.9%). Five out of six domains in the QOL questionnaire showed more effects among GERD participants than non-GERD participants, and the results were statistically significant (p = 0.001). Logistic regression analysis showed that men are 1.8 times more likely than women to be diagnosed with GERD, and smokers have 2.6 times the risk of being diagnosed with GERD than non-smokers. Conclusion The present study showed a high prevalence of GERD among obese patients in the Al-Baha region, negatively affecting their QOL. Major risk factors included gender, smoking, dyslipidemia, and hypertension. Public health programs to raise awareness of these risk factors and lifestyle habits are necessary to improve QOL and prevent complications.

Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, Helicobacter pylori infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to H. pylori infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.

Proton-pump inhibitors (PPI) are empirically used to treat asthma symptoms such as cough; however, the effectiveness of PPI on asthma exacerbation has not been well studied. We aimed to evaluate the relationship between PPI use and asthma exacerbation using a large administrative claims database in Japan. We conducted a self-controlled case series using the JMDC Claims Database (JMDC, Inc., Tokyo, Japan). The cases included adult patients with asthma who were prescribed PPI and experienced at least one outcome event between January 2015 and December 2019. The primary outcome was the composite outcome of hospital admissions and unscheduled outpatient clinic visits due to asthma exacerbation. We also conducted stratified analyses based on PPI generation, the presence of gastroesophageal reflux disease (GERD), asthma severity, and the number of allergic comorbidities. A total of 7379 eligible patients were included in the study. PPI prescription was associated with a decrease in the composite outcomes (incidence rate ratio, 0.90; 95% confidence interval, 0.87-0.93). However, PPI prescriptions did not affect the outcomes of hospital admissions (incidence rate ratio, 1.34; 95% confidence interval, 0.86-2.10). Stratified analyses based on PPI generation, the presence of GERD, asthma severity (except for severe asthma), and the number of allergic comorbidities yielded consistent results. PPI use was associated with a moderate decrease in asthma exacerbation, regardless of the patient profile. However, this effect was not as strong as the prevention of hospital admissions, and outcome events were not prevented in patients with severe asthma.

OBJECTIVE: To study esophageal acid exposure, esophageal motility, and endoscopic findings before and after Sleeve Gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB BACKGROUND: The lack of standardized objective assessment of esophageal physiology and anatomy contributes to the controversies regarding the impact of SG and RYGB on gastroesophageal reflux disease.
METHODS: We conducted a systematic review and meta-analysis of studies reporting at least one objective measure of esophageal physiology and/or EGD, at baseline and after SG or RYGB. The changes in pH-test, manometry, and EGD parameters were summarized.
RESULTS: Acid exposure time (AET) and DeMeester Score (DMS) significantly increased after SG: Mean Difference (MD) 2.1 (95%CI 0.3 to 3.9) and 8.6 (95%CI 2 to 15.2), respectively. After RYGB, both AET and DMS significantly decreased: MD -4.2 (95%CI -6.1 to -2.3) and - 16.6 (95%CI -25.4 to -7.8). Lower esophageal sphincter resting pressure and length significantly decreased following SG: MD - 2.8 (95%CI - 4.6 to - 1.1) and - 0.1 (95%CI - 0.2 to - 0.02), respectively. There were no significant changes in esophageal manometry after RYGB. The Relative Risk of erosive esophagitis after SG was 2.3 (95%CI 1.5 to 3.5), while after RYGB it was 0.4 (95%CI 0.2 - 0.8). The prevalence of Barrett\'s Esophagus changed from 0% to 3.6% after SG, and from 2.7% to 1.4% after RYGB.
CONCLUSIONS: SG resulted in worsening of all objective parameters, while RYGB showed improvement in AET, DMS, and EGD findings. Determining the risk factors associated with those outcomes could aid in surgical choice.

The bacterium Sarcina ventriculi (SV) is rarely identified in the upper gastrointestinal (GI) tract and has been associated with diverse clinical presentations. We aimed to characterize the clinicopathologic features of SV in the GI tract. Seventeen specimens (3 gastrectomy and 14 biopsy specimens) with histologic diagnosis of SV were identified and analyzed. The patients (9 female, 8 male) had a median age of 65 (range 32-86) years. Five (30%) patients presented acutely with GI bleeding or altered mental status. Other relevant symptoms included abdominal pain (n = 6, 35%), diarrhea (n = 4, 24%), dysphagia/dyspepsia (n = 3, 18%), and nausea/vomiting (n = 3, 18%). SV organisms were mainly identified in the stomach (n = 14, 82%), rarely at the gastroesophageal junction (n = 2, 12%), esophagus (n = 2, 12%), or duodenum (n = 1, 6%). Endoscopically, retained food debris was found in 5 of 13 (38%) examined patients. Histologically, the majority of specimens (12 out of 17, 71%) showed mild alterations including reactive gastropathy, inactive gastritis, or reflux (Grade 1). The other 5 specimens (29%) demonstrated erosion, ulcer, necrosis, or perforation (Grade 2). The most commonly associated comorbidities were diabetes mellitus (n = 10, 59%), gastroparesis/outlet obstruction (n = 10, 59%), and gastroesophageal reflux disease (n = 6, 35%). Upon follow-up, 3 (18%) patients with acute phlegmonous gastritis died shortly after gastrectomy. Our case series, the largest reported so far, describes a spectrum of histologic severity associated with SV infection. Diabetes and gastroparesis/outlet obstruction manifested as retained food debris endoscopically are common findings with SV, and may provide a growth medium for this organism and provoke pathogenicity contributing to fatality in acute conditions.

OBJECTIVE: To examine the biomarkers of pharyngoesophageal swallowing during oral feeding sessions in infants undergoing pH-impedance testing and determine if swallow frequencies are distinct between oral- and partially oral-fed infants.
METHODS: One oral feeding session was performed in 40 infants during pH-impedance studies and measurements included swallowing frequency, multiple swallow rate, air and liquid swallow rates, esophageal swallow clearance time (ESCT), and gastroesophageal reflux (GER) characteristics. Linear and mixed statistical models were applied to examine the swallowing markers and outcomes.
RESULTS: Infants (30.2 ± 4.4 weeks birth gestation) were evaluated at 41.2 ± 0.4 weeks postmenstrual age (PMA). Overall, 10,675 swallows were analyzed during the oral feeding sessions (19.3 ± 5.4 min per infant) and GER events were noted (2.5 ± 0.3 per study). Twenty-four-hour acid reflux index (ARI) was 9.5 ± 2.0%. Differences were noted in oral- and partially oral-fed infants for: volume consumption (p<0.01), consumption rate (p<0.01), and length of hospital stay in days (p<0.01). Infants with ARI >7% had greater frequency of swallows (p=0.01). The oral-fed group had greater ARI (12.7 ± 3.3%, p=0.05).
CONCLUSIONS: Oropharyngeal swallowing regulatory characteristics decrease over the feeding duration and were different between ARI >7% vs ≤7%. Although GER is less in infants who are partially oral-fed, the neonates with increased acid exposure achieved greater oral intakes and shorter hospitalizations, despite the presence of comorbidities. Pharyngoesophageal stimulation as during consistent feeding or GER events can activate peristaltic responses and rhythms, which may be contributory to the findings.