Endoscopic findings and outcomes of gastric mucosal changes relating to potassium-competitive acid blocker and proton pump inhibitor therapy.

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.

Endoscopic Management Options for Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a prevalent condition that affects a significant portion of the Western population. Despite its benign pathophysiology, it has the potential to cause serious complications over time, ranging from conditions that are benign, premalignant, and/or malignant. Traditional treatment options include lifestyle measures, anti-secretory medications (e.g., proton pump inhibitor (PPI)), and surgical options (e.g., Nissen and Toupet fundoplication). However, recent studies have revealed long-term side effects of anti-secretory medications. Moreover, surgical options, though effective, are considered invasive and associated with potential complications. In the current age of ongoing research in minimally invasive options, endoscopic treatment of GERD has become popular. As a result, procedures such as radiofrequency treatment and transoral incisionless fundoplication (TIF) have gained FDA approval and are currently being covered by most insurance. In this review article, we will discuss pre-procedural workup, appropriate patient selection, advantages, disadvantages, procedure techniques, and follow-up of patients who undergo various endoscopic treatments for GERD. In addition, we will review the short and long-term success of these techniques in improving quality of life, use of PPI, and improvement in symptoms considering published data in high-quality peer-reviewed journals.

Value of endoscopic grading of gastroesophageal flap valve in gastroesophageal reflux disease.

OBJECTIVE: To investigate the significance of endoscopic grading (Hill's classification) of gastroesophageal flap valve (GEFV) in the examination of patients with gastroesophageal reflux disease (GERD). METHODS: One hundred and sixty-two patients undergoing gastroscopy in the Department of Gastroenterology, Xingyi People's Hospital between Apr. 2022 and Sept. 2022 were selected by convenient sampling, and data such as GEFV grade, and findings of esophageal high-resolution manometry (HRM) and esophageal 24-h pH/impedance reflux monitoring, and Los Angeles (LA) classification of reflux esophagitis (RE) were collected and compared. RESULTS: Statistically significant differences in age (F = 9.711, P < 0.001) and hiatal hernia (χ = 35.729, P < 0.001) were observed in patients with different GEFV grades. The resting LES pressures were 12.12 ± 2.79, 10.73 ± 2.68, 9.70 ± 2.29, and 8.20 ± 2.77 mmHg (F = 4.571, P < 0.001) and LES lengths were 3.30 ± 0.70, 3.16 ± 0.68, 2.35 ± 0.83, and 2.45 ± 0.62 (F = 3.789, P = 0.011), respectively, in patients with GEFV grades I-IV. DeMeester score (Z = 5.452, P < 0.001), AET4 (Z = 5.614, P < 0.001), acid reflux score (upright) (Z = 7.452, P < 0.001), weak acid reflux score (upright) (Z = 3.121, P = 0.038), liquid reflux score (upright) (Z = 3.321, P = 0.031), acid reflux score (supine) (Z = 6.462, P < 0.001), mixed reflux score (supine) (Z = 3.324, P = 0.031), gas reflux score (supine) (Z = 3.521, P = 0.024) were different in patients with different GEFV grades, with statistically significant differences. Pearson correlation analysis revealed a positive correlation between RE grade and LA classification of GERD (r = 0.662, P < 0.001), and the severity of RE increased gradually with the increase of the Hill grades of GEFV. CONCLUSION: The Hill grade of GEFV is related to age, hiatal hernia, LES pressure, and the consequent development and severity of acid reflux and RE. Evaluation of esophageal motility and reflux based on the Hill grade of GEFV is of significance for the diagnosis and treatment of GERD.

The real occurrence of gastroesophageal reflux disease after sleeve gastrectomy - a prospective pH-monitoring study.

Introduction: Sleeve gastrectomy (SG) is currently the most frequently performed bariatric procedure in the world. However, the occurrence of gastroesophageal reflux disease (GERD) after SG remains controversial and questionable. Aim: To determine the occurrence of GERD after SG using a pH-monitoring study. Material and methods: This is a prospective study involving patients undergoing SG in one surgical centre. Inclusion criteria were eligibility for bariatric surgery, no symptoms of GERD, normal gastroscopy, and pH-monitoring before the surgery. Postoperative examinations were performed 6 months after surgery. Results: A total of 38 patients were analysed in the study. The mean age was 44.9 years, and the mean preoperative BMI was 42.6 kg/m2. Before surgery, all patients had normal pH values. After surgery, mean acid exposure time (AET), number of refluxes, and DeMeester score increased statistically significantly (p < 0.001). 27 (71.1%) patients each had AET > 6%, but only 9 (23.7%) reported GERD symptoms and the need for PPIs. The correlation between AET and %TWL was moderate positive, and the correlation between DeMeester score and %TWL was low positive (p = 0.011, p = 0.014, respectively). Conclusions: GERD after SG seems to be a significant problem. More than two-thirds of patients had de novo GERD after SG in pH-monitoring, but only one-quarter of them required PPIs.

Gastroesophageal reflux after per-oral endoscopic myotomy: Management literature.

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.

Symptom profiles compatible with disorders of gut-brain interaction (DGBI) in organic gastrointestinal diseases: A global population-based study.

BACKGROUND: Patients with organic gastrointestinal (GI) diseases and diabetes mellitus (DM) can have concomitant disorders of gut-brain interaction (DGBI). OBJECTIVE: This study aimed to compare the global prevalence of DGBI-compatible symptom profiles in adults with and without self-reported organic GI diseases or DM. METHODS: Data were collected in a population-based internet survey in 26 countries, the Rome Foundation Global Epidemiology Study (n = 54,127). Individuals were asked if they had been diagnosed by a doctor with gastroesophageal reflux disease, peptic ulcer, coeliac disease, inflammatory bowel disease (IBD), diverticulitis, GI cancer or DM. Individuals not reporting the organic diagnosis of interest were included in the reference group. DGBI-compatible symptom profiles were based on Rome IV diagnostic questions. Odds ratios (ORs [95% confidence interval]) were calculated using mixed logistic regression models. RESULTS: Having one of the investigated organic GI diseases was linked to having any DGBI-compatible symptom profile ranging from OR 1.64 [1.33, 2.02] in GI cancer to OR 3.22 [2.80, 3.69] in IBD. Those associations were stronger than for DM, OR 1.26 [1.18, 1.35]. Strong links between organic GI diseases and DGBI-compatible symptom profiles were seen for corresponding (e.g., IBD and bowel DGBI) and non-corresponding (e.g., IBD and esophageal DGBI) anatomical regions. The strongest link was seen between fecal incontinence and coeliac disease, OR 6.94 [4.95, 9.73]. After adjusting for confounding factors, associations diminished, but persisted. CONCLUSION: DGBI-compatible symptom profiles are more common in individuals with self-reported organic GI diseases and DM compared to the general population. The presence of these concomitant DGBIs should be considered in the management of organic (GI) diseases.

Conversion of Sleeve Gastrectomy to Roux-en-Y Gastric Bypass: Is Intrathoracic Migration of the Sleeve of High Incidence?

BACKGROUND: Conversion of SG to Roux-en-Y gastric bypass (RYGB) is increasing. Intrathoracic migration of the sleeve (ITM) often seems associated and is increasingly reported. MATERIAL AND METHODS: Patients who underwent a conversion of SG to RYGB from August 2013 to December 2022 were included. Two groups were compared: patients operated on for weight loss failure (WLF gp) and those operated on for gastroesophageal reflux disease (GERD gp). Demographic data, the incidence of ITM, weight loss outcomes, resolution of symptoms, and morbidity were analyzed. RESULTS: Fifty-nine patients were included with an average follow-up of 32 months: 46 patients in the GERD gp (78%) were compared to 13 patients (22%) in the WLF gp. Groups were comparable regarding age and gender, but BMI and commodities were significantly higher in the WLF gp. In the GERD gp, on preoperative gastroscopy, 30% had a esophagitis, 48% had an ITM which required a posterior crural closure versus no esophagitis (p=0.02) and 23% of ITM in the WLF gp (p=0.11). Conversion led to 93% of GERD symptom improvement. In the WLF gp, mean TWL% was 15.3%, significantly greater than in the GERD gp (TWL% = 4.6%, p = 0.01). The complication rate was 10% at 30 days and 3.4% after 30 days, not significantly different between groups. CONCLUSION: The main indication of conversion of SG to RYGB was because of GERD: in these indications, the incidence of ITM was high requiring a surgical treatment with a very good efficacy on symptoms. Weight loss results were disappointing.

Symptoms of gastroesophageal reflux disease predicts low voltage zones in the posteroinferior left atrium in patients with persistent atrial fibrillation.

Background: The presence of low voltage zones (LVZs) in the left atrium (LA) is associated with the recurrence of atrial fibrillation (AF) after pulmonary vein isolation. Numerous studies have posited a link between gastroesophageal reflux disease (GERD) and AF, attributing this relationship to the anatomical proximity of the esophagus to the posteroinferior wall of the LA. Objective: The objective of this study was to investigate whether GERD can predict the presence of LVZs in the posteroinferior wall of the LA. Methods: Five hundred fifty-one patients with persistent AF, scheduled for their first AF ablation procedure, were prospectively enrolled. Voltage maps were collected using a multipolar catheter, and LVZs were defined as areas measuring ≥3 cm2 with a peak-to-peak bipolar voltage of <0.5 mV. Information on GERD symptoms was collected from the participants through a self-administered questionnaire. Results: Long-standing persistent AF was present in 22.3% of the total cohort. GERD was present in 29% of patients and LVZs in the posteroinferior wall in 12.7%. In the multivariable analysis, patients with GERD were found to have more than twice the odds (odds ratio 2.26; 95% confidence interval 1.24-4.13; P = .008) of exhibiting LVZs in the posteroinferior wall of the LA than patients without GERD. GERD was not associated with LVZs in any other region of the LA. Conclusion: GERD was found to be independently associated with LVZs in the posteroinferior LA. This association may be attributable to inflammation and may partly explain the link between GERD and AF.

Genetic correlation between smoking behavior and gastroesophageal reflux disease: insights from integrative multi-omics data.

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. CONCLUSION: 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.

Gastroesophageal reflux disease in chronic obstructive pulmonary disease.

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.

Results of sleeve gastrectomy conversion to Roux-en-Y gastric bypass on gastroesophageal reflux disease symptoms and proton pump inhibitors use evolution over time.

BACKGROUND: Although sleeve gastrectomy (SG) is associated with excellent results in the short term, it has been shown that it is plagued by weight regain and new onset or worsening of gastroesophageal reflux disease (GERD). These 2 clinical conditions are currently the 2 most frequent indications for revisional surgery. To date, only a few studies have focused exclusively on GERD. In a selected series of patients complaining of GERD symptoms after SG as a main complaint, we analyzed the efficacy of conversion to Roux-en-Y gastric bypass (RYGB), with a standardized surgical technique. METHODS: This is a retrospective study including all consecutive cases of SG to RYGB conversion for GERD not controlled by medical treatment. We excluded all patients undergoing conversion for weight regain without GERD. Quality of life and GERD symptoms were evaluated at outpatient's clinic visits before and after surgery with 2 standardized questionnaires (Gastroesophageal Reflux Disease Questionnaire and Simplified Form 6). RESULTS: This study showed that 70% of patients had complete resolution of GERD symptoms and 60% had completely discontinued proton pump inhibitors (PPIs). The conversion to RYGB resulted in a significant decrease in the rate of patients presenting daily symptoms of GERD and use of PPIs (10% and 16.6%, respectively; P < .019) and a dramatic increase in those without symptoms and no need for PPIs (70% and 60%, respectively; P < .001). CONCLUSION: Conversion to RYGB is a good option for GERD complications after SG providing a high rate of symptom remission and PPI discontinuation. Conversion to RYGB in the setting of GERD complications after SG improves postoperative outcomes decreasing GERD symptoms and improving quality of life.

Characterizing Biomarkers of Continuous Peristalsis and Bolus Transit during Oral Feeding in Infants at pH-Impedance Evaluation: Clinical and Research Implications.

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. STUDY DESIGN: 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.

Clinicopathologic Characterization of Sarcina ventriculi in the Upper Gastrointestinal Tract.

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.

Significant and Distinct Impacts of Sleeve Gastrectomy and Roux-en-Y Gastric Bypass on Esophageal Acid Exposure, Esophageal Motility and Endoscopic Findings: A Systematic Review and Meta-analysis.

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.

Relationship between proton pump inhibitor prescription and asthma exacerbation among adult patients: a self-controlled case series study.

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.

Gastroesophageal reflux disease may causally associate with the increased atrial fibrillation risk: evidence from two-sample Mendelian randomization analyses.

Background: The risk of atrial fibrillation (AF) is increased in individuals with gastroesophageal reflux disease (GERD), according to observational research. The causal significance of this association is still unclear. This study sought to assess GERD's role as a potential contributing factor in AF. Methods: With the use of a two-sample Mendelian randomization (MR) technique, we assessed the causal relationship between GERD and AF. The association of genetic variants with GERD was examined using data from a recent genome-wide association study (GWAS) that included 602,604 people. Data on the association between genetic variations and AF was obtained from a second GWAS with 1,030,836 participants. The effect sizes were examined based on the inverse-variance weighted method. Additional statistical techniques, including MR-Egger, simple mode, weighted mode, MR Pleiotropy Residual Sum, outlier, and weighted median were used in the sensitivity analysis. Results: MR analyses in inverse-variance weighted models, using 76 single nucleotide polymorphisms (SNPs) as markers, revealed a relationship between genetically predicted GERD and a greater AF incidence [odds ratio (OR): 1.165, 95% CI 1.102-1.231; P = 7.637 × 10-8]. According to MR-Egger, there was no evidence of gene pleiotropy that could be found (intercept = 0.003, P = 0.581). The findings of the sensitivity study, which used several MR methods, were found to be reliable. Conclusion: The MR analysis revealed a correlation between GERD and increased AF incidence, supporting the idea that treating patients with GERD as early as possible might reduce their chance of developing AF.

Prevalence of functional esophageal disorders and associated clinical characteristics in patients with proton-pump-inhibitor-unresponsive reflux symptoms.

BACKGROUND AND AIM: Patients with proton-pump-inhibitor (PPI)-unresponsive reflux symptoms, often caused by functional esophageal disorders (FED), are frequently encountered in clinical practice. We aimed to investigate the prevalence of FED and its associated clinical characteristics in patients with PPI-unresponsive reflux symptoms. METHODS: We retrospectively identified patients who were evaluated for persistent typical reflux symptoms, despite ≥8 weeks of PPI treatment, at the National Taiwan University Hospital from 2014 to 2023. All patients underwent a comprehensive evaluation comprising validated gastroesophageal reflux disease (GERD) symptom questionnaires, 5-item Brief Symptom Rating Scale (BSRS-5), Pittsburgh Sleep Quality Index (PSQI), esophagogastroduodenoscopy, high-resolution impedance manometry, and 24-h impedance-pH monitoring off PPI therapy. Diagnosis of FED and non-erosive reflux disease (NERD) was based on the Rome IV criteria. RESULTS: We analyzed 190 patients [46.8% male, median age 52 (interquartile range, 42-61) years], of whom 32 (16.8%) had NERD and 158 (83.2%) had FED (57.9% with functional heartburn and 25.3% with reflux hypersensitivity). Patients with FED had a lower body mass index than those with NERD and a higher prevalence of psychological comorbidities and poor sleep quality than healthy volunteers. The severity of reflux symptoms among FED patients was significantly associated with the severity of psychological comorbidities and sleep quality. CONCLUSIONS: A notably high prevalence (83.2%) of FED was observed among patients experiencing PPI-unresponsive reflux symptoms. Patients with FED had a higher level of psychological distress and diminished sleep quality, both of which were associated with reflux symptom severity.

Association between gut microbiota and common overlapping gastrointestinal disorders: a bidirectional two-sample Mendelian randomization study.

Background: The main functional gastrointestinal disorders (FGIDs) include functional dyspepsia (FD) and irritable bowel syndrome (IBS), which often present overlapping symptoms with gastroesophageal reflux disease (GERD), posing a challenge for clinical diagnosis and treatment. The gut microbiota is closely associated with FGIDs and GERD, although the causal relationship has not been fully elucidated. Therefore, we aimed to investigate the potential causal relationship using bidirectional two-sample Mendelian randomization (MR) analysis. Materials and methods: The genetic data of the 211 gut microbiota were obtained from the MiBioGen consortium (N = 14,306, from phylum to genus level) and species level of gut microbiota were acquired from the Dutch Microbiome Project (N = 7,738). For FD and IBS, we utilized the FinnGen consortium, whereas, for GERD data analysis, we obtained the IEU OpenGWAS project. The inverse-variance weighted (IVW) method was used as the primary method to calculate causal effect values. Sensitivity analyses were also performed to confirm the robustness of the primary findings of the MR analyses. Moreover, a reverse MR analysis was conducted to assess the likelihood of reverse causality. Results: Combining the results of the preliminary and sensitivity analyses, we identified that 8 gut microbial taxa were associated with FD. Genus Lachnospiraceae NK4A136 group (p = 3.63 × 10-3) and genus Terrisporobacter (p = 1.13 × 10-3) were strongly associated with FD. At the same time, we found that 8 gut microbial taxa were associated with IBS. Family Prevotellaceae (p = 2.44 × 10-3) and species Clostridium leptum (p = 7.68 × 10-3) display a robust correlation with IBS. In addition, 5 gut microbial taxa were associated with GERD using the IVW approach. In the reverse MR analysis, 2 gut microbial taxa were found to be associated with FD, 5 gut microbial taxa were found to be associated with IBS, and 21 gut microbial taxa were found to be associated with GERD. Conclusion: The study reveals the potential causal effects of specific microbial taxa on FD, IBS, and GERD and may offer novel insights into the diagnosis and treatment of these conditions.

The Impact of Gastroesophageal Disease on Clostridium difficile Infection Hospitalization: A Nationwide Analysis From the United States.

Background Enterocolitis due to Clostridium difficile infection (CDI) is one of the most common infectious causes of healthcare-associated diarrhea and a significant cause of morbidity and mortality among hospitalized patients. Gastroesophageal reflux disease (GERD) is notable for its high prevalence, variety of clinical presentations, and underrecognized morbidity. It is widely treated with acid suppression, both with over-the-counter and prescription medications. There are no studies evaluating the impact of GERD on CDI hospitalization. In this study, we aimed to analyze the influence of concomitant GERD on patients hospitalized for CDI enterocolitis. Methodology This was a retrospective, observational study where we extracted data from 2016 to 2020 from the National Inpatient Sample database. We included all patients hospitalized with a primary discharge diagnosis of CDI with or without a secondary diagnosis of GERD. We compared the demographics, comorbidities, and in-hospital outcomes between these two groups. Results This study identified 239,603 hospitalizations with a discharge diagnosis of CDI. Of these, 67,000 (28%) had a concurrent diagnosis of GERD. Patients with GERD had a higher prevalence of hypertension (41% vs. 35.5%, p < 0.01), hyperlipidemia (50% vs. 36.5%, p < 0.01), obesity (13.7% vs. 10.5%, p < 0.01), coronary artery disease (24.4% vs. 19.6%, p < 0.01), and chronic kidney disease (20.7% vs. 19.2%, p < 0.01). Notably, inpatient mortality was lower in CDI hospitalizations with GERD (0.66% vs. 1.46%, p < 0.01). The total hospital charge was reduced in the CDI with GERD group in comparison to the CDI without GERD group (39,599 vs. 43,589, p < 0.01). The length of hospital stay was similar between the two groups (5.3 vs. 5.4 days, p = 0.07). Regarding complications, CDI hospitalizations with GERD demonstrated lower rates of hypovolemic shock (0.5% vs. 0.73%, p = 0.06), septic shock (0.6% vs. 1.05%, p < 0.01), acute kidney injury (1.48% vs. 2.04%, p < 0.01), intestinal perforation (0.008% vs. 0.16%, p = 0.03), and lactic acidosis (0.008% vs. 0.16%, p = 0.03). Conversely, CDI patients with GERD had a higher rate of ileus (2.66% vs. 2.16%, p < 0.01). Conclusions Patients with CDI and concurrent GERD exhibited favorable in-hospital outcomes in terms of complication rates, mortality, and total hospital charges. Further research is required to comprehensively explore and validate these findings.

A practical approach to ineffective esophageal motility.

BACKGROUND AND PURPOSE: Ineffective esophageal motility (IEM) is the most frequently diagnosed esophageal motility abnormality and characterized by diminished esophageal peristaltic vigor and frequent weak, absent, and/or fragmented peristalsis on high-resolution esophageal manometry. Despite its commonplace occurrence, this condition can often provoke uncertainty for both patients and clinicians. Although the diagnostic criteria used to define this condition has generally become more stringent over time, it is unclear whether the updated criteria result in a more precise clinical diagnosis. While IEM is often implicated with symptoms of dysphagia and gastroesophageal reflux disease, the strength of these associations remains unclear. In this review, we share a practical approach to IEM highlighting its definition and evolution over time, commonly associated clinical symptoms, and important management and treatment considerations. We also share the significance of this condition in patients undergoing evaluation for anti-reflux surgery and consideration for lung transplantation.