Prediction,prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy:An update

Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and regurgitation.The principal therapeutic approaches for achalasia encompass pneumatic dilatation(PD),Heller's myotomy,and the more recent per-oral endoscopic myotomy(POEM).POEM has been substantiated as a safe and efficacious modality for the management of achalasia.Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy,the incidence of gastroesophageal reflux disease(GERD)following POEM is notably higher than with the aforementioned techniques.While symptomatic reflux post-POEM is relatively infrequent,the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications.Contemporary advancements in the field have enhanced our comprehension of the risk factors,diagnostic methodologies,preventative strategies,and therapeutic management of GERD subsequent to POEM.This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux,potential modifications in the POEM technique to mitigate GERD risk,and the strategies for managing reflux following POEM.

Association between physical activity and risk of gastroesophageal reflux disease:A systematic review and meta-analysis

Background:Lifestyle plays an important role in preventing and managing gastroesophageal reflux disease(GERD).In response to the conflicting results in previous studies,we performed a systematic review and meta-analysis to investigate this association.Methods:Relevant studies published until January 2023 were retrieved from 6 databases,and the prevalence of symptomatic gastroesophageal reflux(GER)or GERD was determined from the original studies.A random effects model was employed to meta-analyze the association by computing the pooled relative risk(RR)with 95%confidence intervals(95%CIs).Furthermore,subgroup and dose-response analyses were performed to explore subgroup differences and the association between cumulative physical activity(PA)time and GERD.Results:This meta-analysis included 33 studies comprising 242,850 participants.A significant negative association was observed between PA and the prevalence of symptomatic GER(RR=0.74,95%CI:0.66-0.83;p<0.01)or GERD(RR=0.80,95%CI:0.76-0.84;p<0.01),suggesting that engaging in PA might confer a protective benefit against GERD.Subgroup analyses consistently indicated the presence of this association across nearly all subgroups,particularly among the older individuals(RR_(<40 years):RR_(≥40 years)=0.85:0.69,p<0.01)and smokers(RR_(smoker):RR_(non-smoker)=0.67:0.82,p=0.03).Furthermore,a dose-response analysis revealed that individuals who engaged in 150 min of PA per week had a 72.09%lower risk of developing GERD.Conclusion:Maintaining high levels of PA decreased the risk of GERD,particularly among older adults and smokers.Meeting the recommended PA level of 150 min per week may significantly decrease the prevalence of GERD.

Causal associations between gastroesophageal reflux disease and essential hypertension: A bidirectional Mendelian randomization study

BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential hypertension.METHODS Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and hypertension.The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs.The MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental variable.RESULTS IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD patients.And the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD patients.Moreover,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension patients.CONCLUSION We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.

Diagnostic value associated with the combination of saliva pepsin and microorganisms in functional heartburn and gastroesophageal reflux disease

Heartburn is a common symptom shared by both gastroesophageal reflux disease(GERD)and functional heartburn(FHB),which can make it challenging to differentiate between the two conditions.However,examining oral manifestations of GERD can be a cost-effective and readily available method to aid in this differentiation process.It may serve as a valuable tool in distinguishing GERD from FHB.

Clinical features of gastroesophageal reflux disease and erosive esophagitis:Insights from patients undergoing esophagogastroduodenoscopy in resource-limited Ethiopia

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

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.

Therapeutic effect of Wendan Decoction combined with mosapride on gastroesophageal reflux disease after esophageal cancer surgery

BACKGROUND Gastroesophageal reflux disease(GERD)is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal stricture and anastomotic leakage.Wendan Decoction(WDD)is a traditional Chinese herbal formula used to treat various gastrointestinal disorders,such as gastritis,functional dyspepsia,and irritable bowel syndrome.Mosapride,a prokinetic agent,functions as a selective 5-hydroxytryptamine 4 agonist,enhancing gastrointestinal motility.AIM To evaluate the therapeutic effects of WDD combined with mosapride on GERD after esophageal cancer surgery.METHODS Eighty patients with GERD were randomly divided into treatment(receiving WDD combined with mosapride)and control(receiving mosapride alone)groups.The treatment was conducted from January 2021 to January 2023.The primary outcome was improved GERD symptoms as measured using the reflux disease questionnaire(RDQ).The secondary outcomes were improved esophageal motility(measured using esophageal manometry),gastric emptying(measured using gastric scintigraphy),and quality of life[measured via the Short Form-36(SF-36)Health Survey].RESULTS The treatment group showed a notably reduced RDQ score and improved esophageal motility parameters,such as lower esophageal sphincter pressure,peristaltic amplitude,and peristaltic velocity compared to the control group.The treatment group showed significantly higher gastric emptying rates and SF-36 scores(in both physical and mental domains)compared to the control group.No serious adverse effects were observed in either group.CONCLUSION WDD combined with mosapride is an effective and safe therapy for GERD after esophageal cancer surgery.It can improve GERD symptoms,esophageal motility,gastric emptying,and the quality of life of patients.Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.

Socioeconomic traits and the risk of Barrett’s esophagus and gastroesophageal reflux disease: A Mendelian randomization study

BACKGROUND Previous observational studies have shown that the prevalence of gastroesophageal reflux disease(GERD)and Barrett’s esophagus(BE)is associated with socioeconomic status.However,due to the methodological limitations of traditional observational studies,it is challenging to definitively establish causality.AIM To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization(MR).METHODS We initially screened single nucleotide polymorphisms(SNPs)to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis.The inverse variance weighted(IVW)method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE.We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR(MVMR)analyses based on the IVW MVMR model.Furthermore,a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index,major depressive disorder(MDD),smoking,alcohol consumption,and sleep duration.RESULTS The study identified three socioeconomic statuses that had a significant impact on GERD.These included household income[odds ratio(OR):0.46;95% confidence interval(95%CI):0.31-0.70],education attainment(OR:0.23;95%CI:0.18-0.29),and the Townsend Deprivation Index at recruitment(OR:1.57;95%CI:1.04-2.37).These factors were found to independently and predominantly influence the genetic causal effect of GERD.Furthermore,the mediating effect of educational attainment on GERD was found to be mediated by MDD(proportion mediated:10.83%).Similarly,the effect of educational attainment on BE was mediated by MDD(proportion mediated:10.58%)and the number of cigarettes smoked per day(proportion mediated:3.50%).Additionally,the mediating effect of household income on GERD was observed to be mediated by sleep duration(proportion mediated:9.75%)CONCLUSION This MR study shed light on the link between socioeconomic status and GERD or BE,providing insights for the prevention of esophageal cancer and precancerous lesions.

Investigating causal links between gastroesophageal reflux disease and essential hypertension

Gastroesophageal reflux disease(GERD)is a prevalent global health concern with a rising incidence.Various risk factors,including obesity,hiatal hernia,and smo-king,contribute to its development.Recent research suggests associations bet-ween GERD and metabolic syndrome,cardiac diseases,and hypertension(HTN).Mechanisms linking GERD to HTN involve autonomic dysfunction,inflammatory states,and endothelial dysfunction.Furthermore,GERD medications such as pro-ton-pump inhibitors may impact blood pressure regulation.Conversely,antihy-pertensive medications like beta-blockers and calcium channel blockers can exacerbate GERD symptoms.While bidirectional causality exists between GERD and HTN,longitudinal studies are warranted to elucidate the precise relationship.Treatment of GERD,including anti-reflux surgery,may positively influence HTN control.However,the interplay of lifestyle factors,comorbidities,and medications necessitates further investigation to comprehensively understand this relation-ship.In this editorial,we comment on the article published by Wei et al in the recent issue of the World Journal of Clinical Cases.We evaluate their claims on the causal association between GERD and HTN.

Different effects of 24 dietary intakes on gastroesophageal reflux disease: A mendelian randomization

BACKGROUND In observational studies,dietary intakes are associated with gastroesophageal re-flux disease(GERD).AIM To conduct a two-sample mendelian randomization(MR)analysis to determine whether those associations are causal.METHODS To explore the relationship between dietary intake and the risk of GERD,we extracted appropriate single nucleotide polymorphisms from genome-wide asso-ciation study data on 24 dietary intakes.Three methods were adopted for data analysis:Inverse variance weighting,weighted median methods,and MR-Egger's method.The odds ratio(OR)and 95%confidence interval(CI)were used to eva-luate the causal association between dietary intake and GERD.RESULTS Our univariate Mendelian randomization(UVMR)results showed significant evidence that pork intake(OR,2.83;95%CI:1.76-4.55;P=1.84×10–5),beer intake(OR,2.70,95%CI:2.00-3.64;P=6.54×10–11),non-oily fish intake(OR,2.41;95%CI:1.49-3.91;P=3.59×10–4)have a protective effect on GERD.In addition,dried fruit intake(OR,0.37;95%CI:0.27-0.50;6.27×10–11),red wine intake(OR,0.34;95%CI:0.25-0.47;P=1.90×10-11),cheese intake(OR,0.46;95%CI:0.39-0.55;P=3.73×10-19),bread intake(OR,0.72;95%CI:0.56-0.92;P=0.0009)and cereal intake(OR,0.45;95%CI:0.36-0.57;P=2.07×10-11)were negatively associated with the risk of GERD.There was a suggestive asso-ciation for genetically predicted coffee intake(OR per one SD increase,1.22,95%CI:1.03-1.44;P=0.019).Multi-variate Mendelian randomization further confirmed that dried fruit intake,red wine intake,cheese intake,and cereal intake directly affected GERD.In contrast,the impact of pork intake,beer intake,non-oily fish intake,and bread intake on GERD was partly driven by the common risk factors for GERD.However,after adjusting for all four elements,there was no longer a suggestive association between coffee intake and GERD.CONCLUSION This study provides MR evidence to support the causal relationship between a broad range of dietary intake and GERD,providing new insights for the treatment and prevention of GERD.

Endoscopic full-thickness plication along with argon plasma coagulation for treatment of proton pump inhibitor dependent gastroesophageal reflux disease

BACKGROUND Most endoscopic anti-reflux interventions for gastroesophageal reflux disease(GERD)management are technically challenging to practice with inadequate data to support it utility.Therefore,this study was carried to evaluate the effectiveness and safety newer endoscopic full-thickness fundoplication(EFTP)device along with Argon Plasma Coagulation to treat individuals with GERD.AIM To evaluate the effectiveness and safety newer EFTP device along with Argon Plasma Coagulation to treat individuals with GERD.METHODS This study was a single-center comparative analysis conducted on patients treated at a Noble Institute of Gastroenterology,Ahmedabad,hospital between 2020 and 2022.The research aimed to retrospectively analyze patient data on GERD symptoms and proton pump inhibitor(PPI)dependence who underwent EFTP using the GERD-X system along with argon plasma coagulation(APC).The primary endpoint was the mean change in the total gastroesophageal reflux disease health-related quality of life(GERD-HRQL)score compared to the baseline measurement at the 3-month follow-up.Secondary endpoints encompassed enhancements in the overall GERD-HRQL score,improvements in GERD symptom scores at the 3 and changes in PPI usage at the 3 and 12-month time points.RESULTS In this study,patients most were in Hill Class II,and over half had ineffective esophageal motility.Following the EFTP procedure,there were significant improvements in heartburn and regurgitation scores,as well as GERDHRQL scores(P<0.001).PPI use significantly decreased,with 82.6%not needing PPIs or prokinetics at end of 1 year.No significant adverse events related to the procedures were observed in either group.CONCLUSION The EFTP along with APC procedure shows promise in addressing GERD symptoms and improving patients'quality of life,particularly for suitable candidates.Moreover,the application of a lone clip with APC yielded superior outcomes and exhibited greater cost-effectiveness.

Epidemiological, Clinical Aspects and Factors Associated with Typical Gastroesophageal Reflux Disease in the General Population of Parakou, Republic of Benin

Introduction: Gastroesophageal reflux disease (GERD) is a benign and chronic disease that can impair the quality of life. Objective: To study the epidemiological, clinical aspects and factors associated with typical GERD in the general population of Parakou in the Republic of Benin. Methods: This was a descriptive and analytical cross-sectional study with prospective data collection which took place from May 1, 2019 to June 30, 2019. The study population consisted of any subject aged at least 15 years and living in Parakou. Subjects aged at least 15 years, present on the day of the survey and having given their free and informed verbal consent were included. The Short form of QRS®(Reflux-Qual Short form) questionnaire and the “Hospital Anxiety and Depression” score were used to assess the quality of life and anxiety/depression, respectively. The sampling was probabilistic through a 2-stage cluster sampling. The variable of interest was the presence of GERD. Results: Out of 390 subjects surveyed, 28 had symptoms of typical GERD, representing a prevalence of 7.18%. The average age of these subjects was 27.11 ± 7.88 years. Fifteen subjects (53.57%) were male, giving a sex ratio of 1.15. Fourteen (50%) had a secondary level of education, 12 (42.86%) were pupils/students, 18 (64.29%) were single. The monthly income of 22 subjects (78.57%) was lower than the guaranteed interprofessional minimum wage (40,000 FCFA). The average duration of progression of symptoms was 15.89 ± 4.97 months. Symptoms occurred less than twice a week in 22 subjects (78.57%). The clinical manifestations were both diurnal and nocturnal in 12 subjects (42.86%). None of the 28 subjects with GERD had clinical warning signs. Asthma, diabetes, consumption of high fat or spice foods, carbonated drinks, non-steroidal anti-inflammatory drugs, alcoholic beverages and tobacco were statistically associated with the occurrence of GERD. Each of the 28 subjects had at least one associated factor. A significant impair in quality of life was observed in 27 patients (96.43%). Conclusion: Typical GERD is relatively common in the general population of Parakou in the Republic of Benin. It often affects young males. Among the risk factors identified, the most common are carbonated drinks, spicy meals and diabetes. GERD significantly impairs quality of life. Raising awareness about the disease and its associated factors is necessary among the general population.

Multicenter Clinical Randomized Controlled Trial and Network Pharmacology Analysis of Zhenzhu Qingyuan Granules for the Treatment of Gastroesophageal Reflux Disease

Objective To evaluate the clinical efficacy and safety of Zhenzhu Qingyuan Granules through a clinical randomized controlled trial and to analyze the potential action targets and pathways of this formula using network pharmacology.Methods Patients with gastroesophageal reflux disease(GERD)of liver–stomach stagnant heat pattern who met the inclusion and exclusion criteria were randomly divided into the control group and the observation group.The control group received oral rabeprazole,whereas the observation group were given Zhenzhu Qingyuan Granules in addition to the rabeprazole.The treatment duration was 8 weeks.Clinical efficacy was observed in both groups after 8 weeks.Network pharmacology was used to analyze the action targets of ZhenzhuQingyuanGranules and the genes related to GERD,and core targets were inferred.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to explore the potential mechanisms of this formula.Results The clinical research results showed that the total effective rate in the treatment group was 92.68%,compared with 70.00%in the control group,with a statistically significant difference(p<0.05).After treatment,both Chinese medicine syndrome score and endoscopic score improved in both groups compared with before treatment(p<0.05),and the treatment group showed greater improvement than the control group(p<0.05).Network pharmacology identified effective components of Zhenzhu Qingyuan Granules for treating GERD,including quercetin,luteolin,andβ-sitosterol,with potential action targets such as tumor protein 53(TP53),protein kinase B(AKT1),and tumor necrosis factor.Conclusion Zhenzhu Qingyuan Granules can significantly improve clinical symptoms in patients with GERD of liver–stomach stagnated heat pattern,enhance clinical efficacy,and have high safety.This formula may exert therapeutic effects through multiple targets and pathways.

Gastric fundoplication with endoscopic technique:A novel approach for gastroesophageal reflux disease treatment

BACKGROUND Gastric fundoplication with endoscopic technique(GFET)is an innovative approach to managing gastroesophageal reflux disease(GERD).This minimally invasive procedure utilizes the GEN-2 Apollo endosuture device and Olympus H2T180 gastroscope to perform partial fundoplication by strategically placing Prolene 2-0 sutures at the 11,7,5,1,and 3 o’clock positions around the gastroesophageal junction.AIM To evaluate whether GFET enhances the lower esophageal sphincter function by creating comprehensive plication to improve the barrier against reflux.METHODS This single-center prospective study included patients undergoing GFET.Before beginning GFET,pH metrics and subsequent manometric measurements were obtained.An analysis of variance was performed to determine statistically significant differences between quality of life(QOL)and DeMeester scores at the time of the procedure and 6 and 12 months postoperatively.Pearson’sχ2 test was performed to identify statistically significant differences between categorical variables at the time of the procedure and 6 and 12 months postoperatively.RESULTS Eighteen participants were enrolled(11 males and 7 females;mean age,35 years).More than 70%had an initial Hill grade of IIb.One adverse event was recorded after the procedure.One patient underwent valve reinforcement at 12 months.The mean QOL score was markedly higher at the time of the procedure(39.9±4.0)compared to those at 6 and 12 months postoperatively(P<0.001).Scores at 12 months were slightly higher than those at 6 months.The highest mean QOL score was observed at the time of the procedure,followed by those at 6 and 12 months postoperatively(P<0.001).A similar trend was noted for the mean DeMeester scores(P<0.001).CONCLUSION GFET is a minimally invasive alternative to traditional surgical interventions and endoscopic techniques for managing GERD.Further research is warranted to validate its long-term efficacy and effectiveness over existing treatments.

Research on the Progress of Treating Gastroesophageal Reflux Disease with Modified Classic Traditional Chinese Medicine Prescription

Gastroesophageal reflux disease (GERD) is a high-incidence digestive system disease. Western medicine mainly uses drugs such as proton pump inhibitors to inhibit gastric acid secretion, but some patients are accompanied by symptoms such as non-acid reflux and gas reflux, which cannot effectively treat the disease. It is necessary to actively explore other treatment schemes. Traditional Chinese medicine (TCM) has a long history of research on gastroesophageal reflux disease, which emphasizes the treatment based on syndrome differentiation as a whole. Through the treatment of various and multi-component TCM prescriptions, the patient’s body condition can be adjusted, and the treatment effect on gastroesophageal reflux disease is reliable, which has obvious therapeutic advantages. To further clarify the treatment of gastroesophageal reflux disease, this study reviewed and analyzed the research progress of the treatment of liver disease with modified prescriptions, and the report is as follows.

Dental evaluation is helpful in the differentiation of functional heartburn and gastroesophageal reflux disease

BACKGROUND Heartburn is identically the key symptom of both,gastroesophageal reflux disease(GERD)and functional heartburn(FHB),making the differential diagnosis resource-intensive.Oral manifestations of GERD can be easily examined;therefore,their exploration might be a cheap,widely available,and useful tool in the differentiation of GERD and FHB.AIM To evaluate the prevalence of dental erosions(DE)and periodontal diseases(PD)in patients with heartburn and their association with GERD and FHB.METHODS A total of 116[M/F:51/65,mean age:54(17-80)years]consecutive patients with heartburn were enrolled for detailed esophageal function and orodental examinations.RESULTS Dental disorders were detected in 89%(103/116).Patients with PD+DE had significantly more often pathologic reflux(90.0%vs 27.8%;P<0.05),higher esophagitis scores(1.8 vs 0.9;P<0.05),and a significantly different mean impedance curve(P=0.04)than those without any dental diseases.The opposite approach established that patients with GERD had significantly higher prevalence of DE and PD,especially if both were present(28.9%vs 2.0%;P<0.01),more severe PD(1.5 vs 1.0;P<0.01),and longer history of heartburn(15 years vs 9 years;P<0.01)than those with FHB.CONCLUSION The dental evaluation of patients with heartburn seems to be useful in the differential diagnosis of GERD and FHB.Among the studied parameters,the co-appearance of DE and PD seems to be the best predictor of GERD,whereas the absence of dental disorders was mostly observed in FHB.

Evaluating the causal relationship between human blood metabolites and gastroesophageal reflux disease

BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes.As a powerful statistical tool,Mendelian randomization(MR)is widely used to explore the causal relationship between exposure and outcome.AIM To analyze of the relationship between 486 blood metabolites and GERD.METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD.A genome-wide association study(GWAS)of 486 metabolites was the exposure,and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis.Bonferroni correction is used to determine causal correlation features(P<1.03×10^(-4)).The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy.Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD.In addition,metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.RESULTS In MR analysis,four blood metabolites are negatively correlated with GERD:Levulinate(4-oxovalerate),stearate(18:0),adrenate(22:4n6)and p-acetamidophenylglucuronide.However,we also found a positive correlation between four blood metabolites and GERD:Kynurenine,1-linoleoylglycerophosphoethanolamine,butyrylcarnitine and guanosine.And bonferroni correction showed that butyrylcarnitine(odd ratio 1.10,95% confidence interval:1.05-1.16,P=7.71×10^(-5))was the most reliable causal metabolite.In addition,one significant pathways,the"glycerophospholipid metabolism"pathway,can be involved in the pathogenesis of GERD.CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD,which will help further elucidate the pathogenesis of GERD and better guide its treatment.At the same time,this also contributes to early screening and prevention of GERD.However,the results of this study require further confirmation from both basic and clinical real-world studies.

Gastroesophageal reflux disease in children: What’s new right now?

Gastroesophageal reflux(GER)in children is very common and refers to the involuntary passage of gastric contents into the esophagus.This is often physiological and managed conservatively.In contrast,GER disease(GERD)is a less common pathologic process causing troublesome symptoms,which may need medical management.Apart from abnormal transient relaxations of the lower esophageal sphincter,other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense,impaired esophageal and gastric motility and clearance,as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia.The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation.Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD.The following review focuses on up-to-date information regarding of the pathogenesis,diagnostic evaluation and management of GERD in children.

Ineffective esophageal motility is associated with acute rejection after lung transplantation independent of gastroesophageal reflux

BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.

Left lateral decubitus sleeping position is associated with improved gastroesophageal reflux disease symptoms: A systematic review and meta-analysis

BACKGROUND A limited number of studies have demonstrated that sleeping in the left lateral decubitus(LLD)decreases nocturnal reflux in patients with gastroesophageal reflux disease(GERD)compared to right lateral decubitus(RLD)and supine.AIM This systematic review summarizes the association between sleeping in the LLD position and nocturnal reflux in patients with GERD.METHODS Studies published up to July 17,2023,in MEDLINE,EMBASE,and CENTRAL were searched.Eligible studies were randomized and nonrandomized studies assessing the effect of sleeping in LLD compared to RLD and supine in reducing nocturnal reflux in GERD patients.Outcomes include the acid exposure time(AET)(%time in pH<4),acid clearance time(ACT)(in sec/episode),number of reflux episodes,and improvement in N-GSSIQ scores.RESULTS Two nonrandomized studies showed decreased AET and ACT in LLD sleep position in comparison to RLD(mean difference[MD]-2.03[95%CI:-3.62 to-0.45];-81.84[95%CI:-127.48 to-36.20],respectively)and supine position(MD-2.71[95%CI:-4.34 to-1.09];-74.47[95%CI:-116.26 to-32.69],respectively).There was no difference in AET and ACT between RLD sleep position and supine.Furthermore,one randomized controlled trial investigating the use of electronic sleep positional therapy,which increased the duration of LLD sleep and decreased the duration of RLD sleep compared to sham,showed nocturnal symptoms improvement(improved N-GSSIQ score,increased reflux-free nights,and resolution of nocturnal reflux symptoms).CONCLUSION Current evidence suggests that sleeping on the left side could reduce nocturnal reflux and improve GERD-related quality of life,therefore warranting interventions that promote LLD sleep position.