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.

Risk factors for proton pump inhibitor refractoriness in Chinese patients with non-erosive reflux disease

AIM:To analyze risk factors for refractoriness to proton pump inhibitors(PPIs) in patients with non-erosive reflux disease(NERD).METHODS:A total of 256 NERD patients treated with the PPI esomeprazole were enrolled.They were classified into symptom-free and residual symptoms groups according to Quality of Life in Reflux and Dyspepsia(QolRad) scale.All subjects completed questionnaires on psychological status(self-rating anxiety scale;selfrating depression scale) and quality of life scale(Short Form 36).Multivariate analysis was used to determine the predictive factors for PPI responses.RESULTS:According to QolRad,97 patients were confirmed to have residual reflux symptoms,and the remaining 159 patients were considered symptom free.There were no significant differences between the two groups in lifestyle factors(smoking and alcohol consumption),age,Helicobacter pylori infection,and hiatal hernia.There were significant differences between the two groups in relation to sex,psychological distress including anxiety and depression,body mass index(BMI),and irritable bowel syndrome(IBS)(P < 0.05).Logistic regression analysis found that BMI < 23,comorbid IBS,anxiety,and depression were major risk factors for PPI resistance.Symptomatic patients had a lower quality of life compared with symptom-free patients.CONCLUSION:Some NERD patients are refractory to PPIs and have lower quality of life.Residual symptoms are associated with psychological distress,intestinal disorders,and low BMI.

Non-erosive and uncomplicated erosive reflux diseases:Difference in physiopathological and symptom pattern

AIM:To investigate differences in the physiopathological findings(manometry and pH monitoring) and symptoms between cases of non-erosive reflux disease(NERD) and erosive reflux disease(ERD) found positive at 24 h pH monitoring. METHODS:For a total of 670 patients who underwent 24 h pH monitoring,esophageal manometry and upper endoscopy were retrospectively evaluated,assessing the reflux symptoms,manometric characteristics of the lower esophageal sphincter(LES) and esophageal body and the presence or absence of esophagitis and hiatal hernia. Typical and atypical symptoms were also evaluated. For inclusion in the study,patients had to have NERD or ERD and be found positive on pH monitoring(NERD+) . Patients with Gastroesophageal reflux disease(GERD) complicated by stenosis,ulcers or Barrett's esophagus were ruled out. RESULTS:214 patients were involved in the study,i.e. 107 cases of NERD+ and 107 of ERD. There were no significant gender-or age-related differences between the two groups. The ERD group had more cases of hiatal hernia(P = 0.02) and more acid reflux,both in terms of number of reflux episodes(P = 0.01) and as a percentage of the total time with a pH < 4(P = 0.00) ,when upright(P = 0.007) and supine(P = 0.00) . The NERD+ cases had more reflux episodes while upright(P = 0.02) and the ERD cases while supine(P = 0.01) . The LES pressure was higher in cases of NERD+(P = 0.03) while the amplitude and duration of their esophageal peristaltic waves tended to be better than in the ERD group(P >0.05) . The NERD+ patients presented more often with atypical symptoms(P = 0.01) . CONCLUSION:The NERD+ patients' fewer reflux episodes and the fact that they occurred mainly while in the upright position(unlike the cases of ERD) may be two factors that do not favor the onset of esophagitis. The frequently atypical symptoms seen in patients with NERD+ need to be accurately evaluated for therapeutic purposes because patients with GERD and atypical symptoms generally respond only partially to medical and surgical treatments.

Fiber-enriched diet helps to control symptoms and improves esophageal motility in patients with non-erosive gastroesophageal reflux disease

AIM To investigate the effect of dietary fiber on symptoms and esophageal function testing parameters in nonerosive gastroesophageal reflux disease(GERD)(NERD) patients.METHODS Thirty-six NERD patients with low(< 20 g/d) dietary fiber intake were enrolled in the study. They were examined with the use of symptom questionnaire(GERD-Q), highresolution esophageal manometry, 24-h esophageal p Himpedance examinations, and food frequency questionnaire before and after 10 d of usual diet supplemented by psyllium 5.0 g TID. Complete data of 30 patients were available to the final analysis. The obtained results were analyzed with the use of non-parametric statistics(Wilcoxon matched pairs test). RESULTS The number of patients experiencing heartburn was less(93.3% at baseline vs 40% at the end of the study, P < 0.001) and the GERD-Q score decreased(mean ± SD: 10.9 ± 1.7 vs 6.0 ± 2.3, P < 0.001) after the treatment period. Minimal resting lower esophageal sphincter(LES) pressure increased from 5.41 ± 10.1 to 11.3 ± 9.4 mm Hg(P = 0.023), but no change in residual LES pressure and mean resting pressure was found. Total number of gastroesophageal refluxes(GER) decreased from 67.9 ± 17.7 to 42.4 ± 13.5(P < 0.001) predominantly by acid and weak acid types of GERs. No significant change in mean esophageal p H and % of time p H < 4 was registered. Maximal reflux time decreased from 10.6 ± 12.0 min to 5.3 ± 3.7 min(P < 0.05). CONCLUSION Fiber-enriched diet led to a significant increase of minimal lower esophageal sphincter resting pressure, a decrease of number of gastroesophageal refluxes, and a decrease of heartburn frequency per week in NERD.

Irsogladine maleate and rabeprazole in non-erosive reflux disease: A double-blind, placebo-controlled study

AIM:To evaluate the efficacy of adding irsogladine maleate(IM) to proton-pump inhibitor(PPI) therapy in non-erosive reflux disease(NERD) treatment.METHODS:One hundred patients with NERD were recruited and randomized to receive rabeprazole plus IM(group I) or rabeprazole plus placebo(group P).The efficacy of the treatment was assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease(FSSG) and the short form(SF)-36 quality of life questionnaires after four weeks of treatment.We also assessed whether patients with NERD with minimal changes(grade M) had different responses to the therapies compared with patients who did not have minimal changes(grade N).RESULTS:Group I and group P showed significant improvements in their FSSG scores after the treatment(from 17.9 ± 7.9 to 9.0 ± 7.6, and from 17.7 ± 7.3 to 11.2 ± 7.9, respectively, P = 0.0001), but there was no statistically significant difference between the FSSG scores in group I and those in group P.Subgroup analysis showed that significant improvements in the FSSG scores occurred in the patients in group I who had NERD grade N(modified Los Angeles classification)(7.8 ± 7.4 vs 12.5 ± 9.8, P = 0.041).The SF-36 scores for patients with NERD grade N who had received IM and rabeprazole were significantly improved in relation to their vitality and mental health scores.CONCLUSION:The addition of IM to rabeprazole significantly improves gastroesophageal reflux diseasesymptoms and the quality of the lives of patients with NERD grade N.

Proton pump inhibitor for non-erosive reflux disease:A meta-analysis

AIM:To evaluate the efficacy,safety and influential factors of proton pump inhibitor(PPI)treatment for non-erosive reflux disease(NERD).METHODS:PubMed,MEDLINE,EMBASE and the Cochrane Library were searched up to April 2013 to identify eligible randomized controlled trials(RCTs)that probed into the efficacy,safety and influential factors of PPI treatment for NERD.The rates of symptomatic relief and adverse events were measured as the outcomes.After RCT selection,assessment and data collection,the pooled RRs and 95%CI were calculated.This meta-analysis was performed using the Stata 12.0 software(Stata Corporation,College Station,Texas,United States).The level of evidence was estimated by the Grading of Recommendations Assessment,Development and Evaluation system.RESULTS:Seventeen RCTs including 6072 patients met the inclusion criteria.The results of the metaanalysis showed that PPI treatment was significantly superior to H2receptor antagonists(H2RA)treatment(RR=1.629,95%CI:1.422-1.867,P=0.000)and placebo(RR=1.903,95%CI:1.573-2.302,P=0.000)for the symptomatic relief of NERD.However,there were no obvious differences between PPI and H2RA(RR=0.928,95%CI:0.776-1.110,P=0.414)or PPI and the placebo(RR=1.000,95%CI:0.896-1.116,P=0.997)regarding the rate of adverse events.The overall rate of symptomatic relief of PPI against NERD was 51.4%(95%CI:0.433-0.595,P=0.000),and relief was influenced by hiatal hernia(P=0.030).The adverse rate of PPI against NERD was 21.0%(95%CI:0.152-0.208,P=0.000),and was affected by hiatal hernia(P=0.081)and drinking(P=0.053).CONCLUSION:PPI overmatched H2RA on symptomatic relief rate but not on adverse rate for NERD.Its relief rate and adverse rate were influenced by hiatal hernia and drinking.

Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients

AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease(NERD) patients.METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance- p H on rabeprazole. The symptom index(SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter.RESULTS: In 14(40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes(46.7%) than in distal ones(5.7%)(P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(38.5%) and distal ones(20.5%)(NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent(31.0%) than in distal reflux ones(3.3%)(P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(29.4%) and distal ones(14.3%)(NS).CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.

Cell proliferation of esophageal squamous epithelium in erosive and non-erosive reflux disease

AIM： To elucidate cell proliferation in erosive reflux disease （ERD） and non-erosive reflux disease （NERD）, we evaluated markers in squamous epithelial cells.METHODS： Thirty-four consecutive patients with gas- troesophageal-reflux-disease-related symptoms （21 NERD and 13 ERD） were evaluated for the enrolment into the study. All patients underwent 24-h pH moni- toring, standard endoscopy, and biopsy for histological evaluation. The expression of cyclins D and A was eval- uated by real-time reverse transcription polymerase chain reaction （RT-PCR） from isolated epithelial cells. In all samples, analysis of the isolated cell population revealed the presence of epithelial cells only.RESULTS： Real-time RT-PCR showed that, in patientswith ERD, the relative expression of cyclin D1 mRNA in esophageal epithelium was strongly decreased in comparison with NERD patients. The mean value of relative expression of cyclin D1 mRNA in NERD patients was 3.44 ± 1.9, whereas in ERD patients, it was 1.32 ± 0.87 （P = 0.011）. Real-time RT-PCR showed that, in patients with ERD, relative expression of cyclin A mRNA in esophageal epithelium was decreased in comparison with that in NERD patients （2.31 ± 2.87 vs 0.66 ± 1.11）. The mean bromodeoxyuridine labeling index in the NERD patients was 5.42% ± 1.68%, whereas in ERD patients, it was 4.3% ± 1.59%.

Autofluorescence imaging endoscopy can distinguish non-erosive reflux disease from functional heartburn: A pilot study

AIM: To investigate whether autofluorescence imaging (AFI) endoscopy can distinguish non-erosive reflux disease (NERD) from functional heartburn (FH).METHODS: In this prospective observational trial, 127 patients presenting with typical reflux symptoms for &#x0003e; 6 mo were screened. All the participants underwent endoscopy, during which white light imaging (WLI) was followed by AFI. Finally 84 patients with normal esophageal appearance on WLI were enrolled. It was defined as being suggestive of NERD if one or more longitudinal purple lines longer than one centimeter were visualized in the distal part of the esophagus during AFI endoscopy. Ambulatory 24-h multichannel intraluminal impedance and pH monitoring was also performed. After standard proton-pump inhibitor (PPI) tests, subjects were divided into an NERD group and an FH group and the diagnostic performance of AFI endoscopy to differentiate NERD from FH was evaluated.RESULTS: Of 84 endoscopy-negative patients, 36 (42.9%) had a normal pH/impedance test. Of these, 26 patients with favorable responses to PPI tests were classified as having NERD. Finally 10 patients were diagnosed with FH and the others with NERD. Altogether, 68 (81.0%) of the 84 patients were positive on AFI endoscopy. In the NERD group, there were 67 (90.5%) patients with abnormal esophageal findings on AFI endoscopy while only 1 (10%) patient was positive on AFI endoscopy in the FH group. The sensitivity and specificity of AFI in differentiating NERD from FH were 90.5% (95%CI: 81.5%-96.1%) and 90.0% (95%CI: 55.5%-99.7%), respectively. Meanwhile, the accuracy, positive predictive value and negative predictive value of AFI in differentiating between NERD and FH were 90.5% (95%CI: 84.2%-96.8%), 98.5% (95%CI: 92.1%-99.9%) and 56.3% (95%CI: 30.0%-80.2%), respectively.CONCLUSION: Autofluorescence imaging may serve as a complementary method in evaluating patients with NERD and FH.

Mechanism of Wumei Pill in the Treatment of Non-Erosive reflux disease from the Perspective of Network Pharmacology and Molecular docking

Objective:Based on network pharmacology and molecular docking to explore the mechanism of Wumei Pill in the treatment of non-erosive reflux disease(NERD).Method:We collected the active ingredients and targets of Wumei Pill by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and collected NERD related targets through Genecards,PharmGKB,Drugbank,DisGeNET,OMIM,CTD and TTD databases.Intersection targets of Wumei Pill targets and NERD related targets were the potential targets of Wumei Pill in the treatment of NERD.We imported the intersection targets into the STRING database to obtain the PPI network,and obtained the hub targets.The network diagram of"Drugs-Potential active ingredients-Potential targets"was constructed by Cytoscape 3.7.2 software.We used R software to perform Gene Ontology function enrichment analysis(GO)and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis(KEGG)on hub targets,and then performed molecular docking verification.Results:There were 129 active ingredients and 213 drug targets of Wumei Pill of which 114 were the intersection targets.1587 GO enrichment items were identified(P<0.05),including 1,491 biological processes,11 cell components,and 85 molecular functions.143 KEGG pathways(P<0.05),mainly related to Kaposi sarcoma-associated herpesvirus infection,IL-17 signaling pathway,the TNF signaling pathway,MAPK signaling pathway.Results of molecular docking showed that the potential active ingredients in Wumei Pill had relatively stable binding activity to the key targets.Conclusion:Wumei pill for the treatment of non-erosive reflux disease are main active ingredients quercetin,kaempferol,beta sitosterol,Isocorypalmine,Stigmasterol,rutaecarpine,etc,the main targets is JUN,TP53,AKT1,may inhibit excessive inflammation,antioxidant therapy effect into full play.This provided a certain theoretical basis for clinical application.

Therapeutic Advantages of Traditional Chinese Medicine in Non-erosive Reflux Disease

The incidence of gastroesophageal reflux disease(GERD) is increasing year by year. Non-erosive reflux disease(NERD) is not only the most common subtype of GERD, but also has the highest proportion of refractory GERD. The pathogenesis may be closely related to mixed reflux, non-acid reflux, esophageal hypersensitivity, psychology and so forth. On the one hand, the treatment with acid suppression drugs alone has a high recurrence rate, and the maintenance treatment continues to be controversial. On the other hand, the comprehensive treatment with the traditional Chinese medicine(TCM), which is based on a number of hybrid mechanisms, is more prominent in individualization with more advantages in long-term efficacy and improvement of quality of life for the patient. The authors conduct a comprehensive analysis on characteristics of NERD and advantages of TCM in treatment, in order to provide more ideas for clinical treatment.

Changes in the esophageal mucosa of patients with non erosive reflux disease:How far have we gone?

The normal esophageal mucosa creates a protective epithelial barrier that constrains the acidic reflux in the esophageal lumen. Microscopic findings and functional studies indicate that this barrier might be impaired in patients with non erosive reflux disease(NERD) but not in patients with functional heartburn(FH). Whereas endoscopy and pH monitoring are the most important diagnostic tools in the diagnosis of NERD, recent studies suggest that esophageal biopsies might have a complementary role. Particularly in the differential diagnosis between NERD and FH, the application of histological severity scores showed very promising results. Further evaluation of the scores could lead to routine application of histology in specific NERD populations.

Alginate controls heartburn in patients with erosive and nonerosive reflux disease

AIM:To evaluate the effect of a novel alginate-based compound,Faringel,in modifying reflux characteristics and controlling symptoms.METHODS:In this prospective,open-label study,40 patients reporting heartburn and regurgitation with proven reflux disease(i.e.,positive impedance-pH test/evidence of erosive esophagitis at upper endoscopy) underwent 2 h impedance-pH testing after eating a refluxogenic meal.They were studied for 1 h under basal conditions and 1 h after taking 10 mL Faringel.In both sessions,measurements were obtained in right lateral and supine decubitus positions.Patients also completed a validated questionnaire consisting of a 2-item 5-point(0-4) Likert scale and a 10-cm visual analogue scale(VAS) in order to evaluate the efficacy of Faringel in symptom relief.Tolerability of the treatment was assessed using a 6-point Likert scale ranging from very good(1) to very poor(6).RESULTS:Faringel decreased significantly(P < 0.001),in both the right lateral and supine decubitus positions,esophageal acid exposure time [median 10(25th75th percentil 6-16) vs 5.8(4-10) and 16(11-19) vs 7.5(5-11),respectively] and acid refluxes [5(3-8) vs 1(1-1) and 6(4-8) vs 2(1-2),respectively],but increased significantly(P < 0.01) the number of nonacid reflux events compared with baseline [2(1-3)vs 3(2-5) and 3(2-4) vs 6(3-8),respectively].Percentage of proximal migration decreased in both decubitus positions(60% vs 32% and 64% vs 35%,respectively;P < 0.001).Faringel was significantly effective in controlling heartburn,based on both the Likert scale [3.1(range 1-4) vs 0.9(0-2);P < 0.001] and VAS score [7.1(3-9.8) vs 2(0.1-4.8);P < 0.001],but it had less success against regurgitation,based on both the Likert scale [2.6(1-4) vs 2.2(1-4);P = not significant(NS)] and VAS score [5.6(2-9.6) vs 3.9(1-8.8);P = NS].Overall,the tolerability of Faringel was very good 5(2-6),with only two patients reporting modest adverse events(i.e.,nausea and bloating).CONCLUSION:Our findings demonstrate that Faringel is well-tolerated and effective in reducing heartburn by modifying esophageal acid exposure time,number of acid refluxes and their proximal migration.

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.

Heartburn and regurgitation have different impacts on life quality of patients with gastroesophageal reflux disease

AIM: To investigate the impact of heartburn and regurgitation on the quality of life among patients with gastroesophageal reflux disease (GERD).

Treatment of uncomplicated reflux disease

Uncomplicated reflux disease comprises the non-erosive reflux disease (NERD) and erosive reflux disease (ERD).The objectives of treatment are the adequate control of symptoms with restoration of quality of life, healing of lesions and prevention of relapse. Treatment of NERD consists in the administration of proton pump inhibitors (PPI) for 2-4 wk, although patients with NERD show an overall poorer response to PPI treatment than patients with ERD owing to the fact that patients with NERD do not form a pathophysiologically homogenous group. For long-term management on-demand treatment with a PPI is probably the best option. In patients with ERD, therapy with a standard dose PPI for 4-8 wk is always recommended.Long-term treatment of ERD is applied either intermittently or as continuous maintenance treatment with an attempt to reduce the daily dosage of the PPI (step-down principle).In selected patients requiring long-term PPI treatment,antireflux surgery is an alternative option. In patients with troublesome reflux symptoms and without alarming features empirical PPI therapy is another option for initial management. Therapy should be withdrawn after initial success. In the case of relapse, the long-term care depends on a careful risk assessment and the response to PPI therapy.

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.

Maintenance for healed erosive esophagitis:PhaseⅢcomparison of vonoprazan with lansoprazole

AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg(n = 201), vonoprazan 10 mg(n = 202), or vonoprazan 20 mg(n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events(AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen Ⅰ/Ⅱ levels, and gastric mucosa histopathology results.RESULTS Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg(P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg(5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan(P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.CONCLUSION Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.

Efficacy and safety of Amla(Phyllanthus emblica L.) in non-erosive reflux disease:a double-blind,randomized,placebo-controlled clinical trial

Background： Gastroesophageal reflux disease （GERD） is one of the most common gastrointestinal com- plaints. GERD, caused by the reflux of stomach contents into the esophagus, leads to troublesome symptoms such as heartburn and regurgitation. It is classified into two types： erosive esophagitis, characterized by visible esophageal mucosa erosion in endoscopy, and non-erosive reflux disease （NERD）. GERD is a chronic and recurrent disease that impairs the quality of life and imposes socioeco- nomic and therapeutic burdens to both patients and society. Objective： Due to the failure of the conventional treatments for GERD and to the traditional use of Amla （Phyllanthus emblica L.）, in addition to beneficial effects shown in recent studies, we evaluated the safety and efficacy of Amla tablet for improvement of symptoms of patients with NERD. Design, setting, participants and interventions： We designed a double-arm, randomized, double-blind, placebo-controlled clinical trial. Sixty-eight patients who had classic symptoms of GERD （heartburn, regurgitation and epigastralgia） for at least three months before the start of the trial were randomized in two parallel groups. Patients in the Amla group received two 500 mg Amla tablets twice a day, after meals, for 4 weeks. In the control group, patients received placebo tablets similar to the Amla prescription. Main outcome measures： The patients were visited at baseline, and at the end of the 2nd and 4th weeks of intervention; their symptoms were measured on a frequency and severity scale for the symptoms of NERD, according to the quality of life in reflux-associated disease questionnaire. Results： Frequencies of heartburn and regurgitation in both groups of the study were significantly reduced after intervention （P 〈 0.001）. Repeated measures logistic regression analysis showed that, in the Amla group, there was a more significant reduction in regurgitation frequency, heartburn frequency, regurgita- tion severity and heartburn severity during the study period, compared with the placebo group （P 〈 0.001 ）. Conclusion： This randomized double-blind, placebo-controlled clinical trial demonstrated that Amla could reduce frequencies of heartburn and regurgitation and improve heartburn and regurgitation severity in patients with NERD.

Association between body mass index and erosive esophagitis:A meta-analysis

AIM:To conduct a meta-analysis to estimate the determinants of the association between erosive esophagitis (EE)and body mass index(BMI). METHODS:We identified the studies using PubMed. Studies were selected for analysis based on certain inclusion and exclusion criteria.Data were extracted from each study on the basis of predefined items.Metaanalyses were performed to verify the risk factors,such as obesity and gender. RESULTS:Twenty-one studies were included in this systematic review.These studies demonstrated an association between increasing BMI and the presence of EE[95%confidence interval(CI):1.35-1.88,overweight,odds ratio(OR)=1.60,P value homogeneity =0.003,95%CI:1.65-2.55,obese,OR=2.05,P< 0.01].The heterogeneity disappeared by stratifying for gender.No publication bias was observed in this metaanalysis by the Egger method. CONCLUSION:This analysis demonstrates a positive association between BMI and the presence of EE,especially in males.The risk seems to progressively increase with increasing weight.