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

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

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

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

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

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

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

Acid reflux has been associated with allograft injury and rejection in lung transplant patients; however, the pathogenic role of non-acid reflux remains debated. We aimed to evaluate the impact of concurrent abnormal non-acid reflux with acid reflux on chronic rejection in lung transplant patients with acid reflux. This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined impedance-pH study off acid suppression. Only subjects with acid exposure >4% were included. Non-acid reflux (pH > 4) episodes >27 was considered abnormal per prior normative studies. Chronic rejection was defined as chronic lung allograft dysfunction (CLAD) per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods, with censoring at death, anti-reflux surgery, or last follow-up. In total, 68 subjects (28 abnormal/40 normal non-acid reflux) met inclusion criteria for the study. Baseline demographic/clinical characteristics were similar between groups. Among this cohort of patients with increased acid exposure, subjects with concurrent abnormal non-acid reflux had significantly higher risk of CLAD than those without on Kaplan-Meier analysis (log-ranked P = 0.0269). On Cox multivariable regression analysis controlling for body mass index, age at transplantation, and proton pump inhibitor use, concurrent abnormal non-acid reflux remained independently predictive of increased CLAD risk (hazard ratio 2.31, confidence interval: 1.03-5.19, P = 0.04). Presence of concurrent abnormal non-acid reflux in lung transplant subjects with increased acid exposure is associated with additional risk of chronic rejection. Non-acid reflux may also contribute to pathogenicity in lung allograft injury/rejection, supporting a potential role for impedance-based testing in this population.

Gastroesophageal Reflux Disease (GERD) is a prevalent condition in Brazil, affecting 12% to 20% of the urban population, with significant implications for patient quality of life and potential for complications.

This paper focuses on the recent update of the Brazilian guidelines for GERD, a necessary revision due to advancements in knowledge and practice since the last publication over a decade ago. The update pays particular attention to the role and safety of proton pump inhibitors (PPIs), acknowledging the growing concerns about their long-term use, adverse events, and overprescription.

The methodology of the guideline update involved an extensive literature review in multiple languages (English, French, Italian, Spanish, and Portuguese), drawing from major databases such as Medline, Embase, and SciELO-Lilacs.

This comprehensive approach resulted in a carefully curated selection of studies, systematic reviews, and meta-analyses, specifically focusing on PPIs and other therapeutic strategies for GERD. The updated guidelines are presented in a user-friendly question-and-answer format, adhering to the PICO system (Population, Intervention, Comparison, Outcomes) for clarity and ease of interpretation. The recommendations are supported by robust scientific evidence and expert opinions, enhancing their practical applicability in clinical settings. To ensure the reliability and clarity of the recommendations, the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation) was employed. This system categorizes the strength of recommendations as strong, weak, or conditional and classifies evidence quality as high, moderate, low, or very low. These classifications provide insight into the confidence level of each recommendation and the likelihood of future research impacting these guidelines.

The primary aim of these updated guidelines is to offer practical, evidence-based advice for the management of GERD in Brazil, ensuring that healthcare professionals are equipped with the latest knowledge and tools to deliver optimal patient care.

•Gastrointestinal specialists rely heavily on guidelines to manage digestive pathologies effectively. The Brazilian clinical guideline for therapeutic management of gastroesophageal reflux disease (GERD) is an invaluable tool for these specialists.

•It critically analyzes practical aspects of therapy through 12 questions covering a wide range of topics, from behavioral measures to surgical and endoscopic indications.

•The recommendations in this guideline are justified using the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation), and experienced experts provide comments and suggestions at the end of each question.

This study aimed to determine the effect of assisted autogenic drainage (AAD) with or without bouncing (BAAD) on both acid and non-acid gastroesophageal reflux (GER) in infants <1 year.

During a 24-h multichannel intraluminal impedance-pH monitoring (MII-pH), infants were treated with a 20-min intervention of AAD (in supine position) or BAAD (in upright position), 2 h postprandial. In this controlled trial with intra-subject design, the number of reflux episodes (REs) was the primary outcome measure. The results during AAD and BAAD were compared to a baseline period before intervention and 20 min after intervention.

Overall, 50 infants were included in both groups. During AAD a significant decrease of RE's was found compared to baseline (p = 0.001). No significant differences were found in the BAAD group compared to baseline (p = 0.125).

AAD and BAAD do not cause or increase GER in infants under the age of 1 year.

Measures of mood and effective coping strategies have notable correlations with quality of life and treatment responses. There is evidence that patients with previously diagnosed anxiety disorders have less improvement in patient-reported outcome measures (PROMs) after laparoscopic anti-reflux surgery (LARS) and that objective pathology does not correlate well with symptom severity. We were interested in investigating whether anxiety and hypervigilance, as measured preoperatively with the esophageal hypervigilance anxiety scale (EHAS), is associated with the improvement in GERD-specific PROMs and EHAS scores 6 months after LARS.

We performed a retrospective cohort study of 102 adult patients (31% men, average age 64) who underwent LARS. In the preoperative evaluation, baseline gastroesophageal reflux disease-health-related quality of life (GERD-HRQL), laryngopharyngeal reflux symptom index (LPR-RSI) and EHAS scores were collected in addition to the standard reflux workup, including endoscopy, manometry, barium swallow, and pH study. For all three surveys, a higher score represents worse symptom severity. At 6 months postoperatively, 70 patients completed repeat GERD-HRQL, LPR-RSI, and EHAS surveys. We then analyzed for surgical and patient-related factors associated with improvement in the 6-month postoperative GERD-HRQL and LPR-RSI scores.

There was a statistically significant decrease in the GERD-HRQL (25 vs. 2, p < 0.001), LPR-RSI (17 vs. 3, p < 0.001) and EHAS (34 vs. 15, p < 0.001) 6 months after LARS. On multivariable linear regression, a higher baseline EHAS score was independently associated with a greater improvement in GERD-HRQL (β 0.35, p < 0.001) and LPR-RSI (β 0.19, p = 0.03) 6-months after LARS. Additionally, the degree of improvement in EHAS, GERD-HRQL, and LPR-RSI was not influenced by the type of LARS performed or by the severity of disease.

These findings are consistent with literature suggesting that measures of psychoemotional health correlate better with symptom intensity than objective pathology. We found that patients with a higher EHAS score have greater symptom severity and lower quality of life at baseline. Novel findings to this study are that patients with a higher preoperative EHAS, a measure of psychoemotional health, actually benefitted more from surgery and not less, which has been the traditional view in the literature. Future studies are warranted to establish directionality and explore the role of preoperative cognitive behavioral therapy with LARS for patients with significant symptoms of hypervigilance and anxiety.

Magnetic sphincter augmentation (MSA) is a modern surgical anti-reflux technique with proven efficacy and low postoperative morbidity in patients with acidic reflux. The aim of this retrospective review study was to evaluate the symptomatic outcome of MSA in patients with weakly acidic reflux.

From a prospectively collected clinical database, comprising all 327 patients that underwent MSA at our institution, a total of 67 patients with preoperative weakly acidic reflux measured in the 24-h impedance-pH-metry were identified. Postoperative gastrointestinal symptoms, proton pump inhibitor intake (PPI), GERD Health-Related Quality-of-Life (GERD-HRQL), alimentary satisfaction (AS), and patients' overall satisfaction were evaluated within highly standardized follow-up appointments. Furthermore, outcome of these patients was compared to the postoperative outcome of a comparable group of patients with a preoperative acidic reflux.

At a median follow-up of 24 months, none of the patients with weakly acidic reflux presented with persistent dysphagia, or underwent endoscopic dilatation or reoperation. The postoperative GERD-HRQL score was significantly reduced (2 vs. 20; p = 0.001) and the median AS was 9/10. Preoperative daily heartburn, regurgitations, and respiratory complaints were improved in 95%, 95%, and 96% of patients, respectively. A total of 10% of the patients continued to use PPIs postoperatively. No significant difference was observed in terms of postoperative outcome or quality of life when comparing weakly acidic reflux patients with those diagnosed with preoperative acidic reflux.

Magnetic sphincter augmentation significantly improves GERD-related symptoms and quality of life in patients with weakly acidic reflux with very low postoperative morbidity.

This narrative review focuses on the presentation, contributing factors, diagnosis, and treatment of non-acid reflux. We also propose algorithms for diagnosis and treatment.

There is a paucity of recent data regarding non-acid reflux. The recent Porto and Lyon consensus statements do not fully address non-acid reflux or give guidance on classification. However, recent developments in the lung transplantation field, as well as older data in the general population, argue for the importance of non-acid reflux. Extrapolating from the Porto and Lyon consensus, we generally classify pathologic non-acid reflux as impedance events > 80, acid exposure time < 4%, and positive symptom correlation on a standard 24-h pH/impedance test. Other groups not meeting this criteria also deserve consideration depending on the clinical situation. Potential treatments include lifestyle modification, increased acid suppression, alginates, treatment of esophageal hypersensitivity, baclofen, buspirone, prokinetics, and anti-reflux surgery in highly selected individuals. More research is needed to clarify appropriate classification, with subsequent focus on targeted treatments.

Microscopic esophagitis (ME) is common in patients with non-erosive reflux disease (NERD), and dilation of intercellular spaces (DIS) has been regarded as the potential main mechanism of symptom generation. We aimed to compare these histological abnormalities in healthy volunteers (HVs) and patients with erosive esophagitis (EE), NERD, and functional heartburn (FH).

Consecutive patients with heartburn prospectively underwent upper endoscopy and impedance-pH off-therapy. Twenty EE patients and fifty-seven endoscopy-negative patients (NERD), subclassified as 22 with pH-POS (positive for abnormal acid exposure), 20 with hypersensitive esophagus (HE; normal acid/symptom association probability [SAP]+ or symptom index [SI]+), and 15 with FH (normal acid/SAP-/SI-/ proton pump inhibitor [PPI] test-), were enrolled. Twenty HVs were also included. In each patient/control, multiple specimens (n = 5) were taken from the distal esophagus and histological alterations were evaluated. ME was diagnosed when the global histological score was >0.35.

The prevalence of ME was higher (p < 0.0001) in EE (95 %), pH-POS (77 %), and HE (65 %) NERD patients than in FH patients (13 %) and HVs (15 %). Also, basal cell hyperplasia (p < 0.0023), DIS (p < 0.0001), and papillae elongation (p < 0.0002) showed similar rates of prevalence in the above populations (p < 0.0001). ME, including each histological lesion, had similar low frequencies in FH and HVs (p = 0.9990). Considering the histological abnormalities together, they permitted us to clearly differentiate EE and NERD from FH and HVs (p < 0.0001 and p < 0.0001, respectively).

The lack of ME in the esophageal distal biopsies of FH patients indicates a limited role of these histological abnormalities in symptom generation in them. ME can be considered as an accurate and reliable diagnostic marker for distinguishing FH patients from GERD patients and has the potential to be used to guide the correct therapy.

Proton pump inhibitors (PPIs) are the gold standard treatment for gastroesophageal reflux disease. In clinical practice, failure of PPIs occurs frequently, and may affect up to 30% of patients in a typical gastroenterology practice. Multichannel impedance monitoring combined with pH monitoring helps to detect nonacid reflux, and if symptoms correlate with these nonacid reflux episodes, nonacid reflux disease can be diagnosed. In contrast to PPIs, reflux inhibitors target transient lower esophageal sphincter relaxations, which are involved in the pathophysiology of reflux disease and may be the appropriate future treatment for nonacid reflux disease. The present article discusses the current understanding of nonacid reflux disease, its diagnosis and treatment.

Gastro-esophageal reflux is considered a major culprit in the pathogenesis of Barrett's esophagus (BE). Still, there is controversy on the role of weakly acidic and weakly alkaline reflux in BE. To compare characteristics of reflux episodes patients with BE, erosive esophagitis (EE), and healthy volunteers (HV).

One hundred consecutive patients with BE (75 short-segment BE, 25 long-segment BE), 50 with EE and 48 HV underwent multichannel intraluminal impedance-pH off-therapy. We quantified esophageal acid exposure, characteristics, and proximal extension of reflux episodes.

Total and acid reflux episodes gradually increased from HV [28 (17.5-43) and 18 (8-31)] to EE [73.5 (54-96) and 52 (39-68)], short-segment BE (SSBE) [83 (73.2-131) and 65 (43.3-95)] and long-segment BE (LSBE) [105 (102-187) and 77 (75-107)]. Weakly acidic reflux episodes were significantly higher (P < 0.05) in LSBE [36 (27.5-50.5)] and SSBE [34 (18.5-41)] compared to EE [21.5 (15-37)] and HV [19 (14-25)]. No differences in terms of proportion of acid, weakly acidic and weakly alkaline reflux were found [HV (49%-49%-2%) vs EE (68%-32%-1%) vs SSBE (65%-34%-1%) vs LSBE (69%-30%-1%); P = ns]. In LSBE, a higher percentage of reflux episodes (P < 0.05) reached the proximal esophagus (59%) compared with SSBE (43%).

 Barrett esophagus patients have more severe reflux as shown by the number of acid and weakly acidic reflux episodes, re-reflux episodes and proximal migration. Given that PPI change only the pH of the refluxate, the role of weakly acidic reflux in Barrett's patients on acid suppressive therapy warrants further investigation.

Up to a third of patients undergoing coronary angiography for angina-like chest pain are found to have normal coronary arteries and a substantial proportion of these individuals continue to consult and even attend emergency departments. Initially, these patients are usually seen by cardiologists but with accumulating evidence that the pain might have a gastrointestinal origin, it may be more appropriate for them to be cared for by the gastroenterologist once a cardiological cause has been excluded. This review covers the assessment and management of this challenging condition, which includes a combination of education, reassurance, and pharmacotherapy. For the more refractory cases, behavioral treatments, such as cognitive behavioral therapy or hypnotherapy, may have to be considered.