Prescriptions of anti-reflux drugs in neonatology and neonatal intensive care units: A large multicentre observational study (2014-2022).

AIMS: Gastro-oesophageal reflux is common in newborns, especially in premature infants. Treatment by medication is controversial as the drugs prescribed have not been consistently proven to be effective and are known to have adverse effects. This study sought to identify trends in the prescription of anti-reflux medication in a large group of French neonatal units. METHODS: Data on prescriptions of anti-reflux treatments-proton pump inhibitors (PPIs), antacids, histamine-2 receptor antagonists (H2RAs), and prokinetics-from 2014 to 2022 for infants with a corrected gestational age <45 weeks, were extracted from a prescription database (Logipren®) used by 63 French neonatal units, and then analysed. RESULTS: Of all infants recorded in the database during the study period (n = 152 743), 10.2% (n = 15 650) were prescribed anti-reflux medication (95% confidence interval [CI] 10.0-10.4%), mainly as monotherapy (77.5%). The rate was higher in the subgroup of preterm infants born before 28 weeks of gestation (n = 9493) (20.6%, 95% CI 19.8-21.4%; n = 1956). PPIs were the most commonly prescribed anti-reflux medications (6.9% of infants, 95% CI 6.8-7.0), followed by antacids (5.2%, 95% CI 5.1-5.3%), while H2RAs and prokinetics were rarely prescribed. Over the period, the prescription rate remained stable for PPIs, decreased for H2RAs (τ = -0.86, P = .02), and, among preterm infants born at gestational ages of 28-31 or 32-36 weeks, increased for antacids. CONCLUSIONS: Anti-reflux medications were frequently prescribed by neonatal units, especially for extremely premature infants. Most of these prescriptions were for PPIs and antacids.

The impact of gastroesophageal reflux disease and its treatment on interstitial lung disease outcomes.

BACKGROUND: To determine the relationship between gastroesophageal reflux disease (GORD) and its treatment and interstitial lung disease in patients with systemic sclerosis (SSc). METHODS: SSc patients from the Australian Scleroderma Cohort Study (ASCS) were included. GORD was defined as self-reported GORD symptoms, therapy with a proton pump inhibitor (PPI) or histamine 2 receptor antagonist (H2RA) and/or the presence of reflux oesophagitis diagnosed endoscopically. The impact of GORD and its treatment on ILD features (including severity and time to ILD development) and survival was evaluated. RESULTS: GORD was a common manifestation affecting 1539/1632 (94%) of SSc patients. GORD affected 450/469 (96%) of those with SSc-ILD cohort. In SSc-ILD, there was no relationship between the presence of GORD or its treatment and time to ILD development or ILD severity. However, GORD treatment was associated with improved survival in those with ILD (p = 0.002). Combination therapy with both a PPI and a H2RA was associated with a greater survival benefit than single agent therapy with PPI alone (HR 0.3 vs 0.5 p < 0.050 respectively). CONCLUSION: GORD is a common SSc disease manifestation. While the presence or treatment of GORD does not influence the development or severity of ILD, aggressive GORD treatment, in particular with a combination of PPI and H2RA, is associated with improved survival in those with SSc-ILD.

Wake up to gastro-oesophageal reflux disease: The interplay between arousal and night-time reflux.

This review examines the temporal association between nocturnal gastro-oesophageal reflux and sleep-arousal cycles. Most nocturnal gastro-oesophageal reflux events occur during the awake cycle, and arousals precede most nocturnal gastro-oesophageal reflux events, indicating that arousal from sleep predisposes to nocturnal gastro-oesophageal reflux. This sheds light on the complex relationship between nocturnal gastro-oesophageal reflux and sleep, and has implications for managing nocturnal gastro-oesophageal reflux symptoms. The appearance of symptoms and the pathophysiology of nocturnal gastro-oesophageal reflux are influenced by sleep hygiene, sleep disturbances and the misalignment of circadian rhythms. Nocturnal gastro-oesophageal reflux and its related sleep disorders are prevalent and negatively impact the quality of life. There is conflicting evidence on whether nocturnal gastro-oesophageal reflux and sleep disturbances are causally linked, and whether sleep disturbances drive nocturnal gastro-oesophageal reflux. Poor sleep quality increases oesophageal hypersensitivity and overall acid exposure. The nocturnal gastro-oesophageal reflux is linked to the more severe forms of gastro-oesophageal reflux disease, especially with atypical/extra-oesophageal manifestations and complications of mucosal damage such as oesophagitis and stricture, Barret's oesophagus, and oesophageal adenocarcinoma. This review highlights the role of sleep problems in presenting nocturnal gastro-oesophageal reflux, and the potential benefits of treating sleep disturbances in enhancing patient care and quality of life.

Eosinophilic oesophagitis in a Nigerian adolescent: a case report.

Eosinophilic oesophagitis (EoE) is a chronic immune and antigen-mediated disease characterized by symptoms related to oesophageal dysfunction, and histologically, is marked by eosinophilic infiltrate in the oesophageal mucosa. It is prevalent in developed countries and considered rare in developing countries. There is an interplay of allergic and genetic factors in the aetiology of EoE. This is a report of EoE in a 15-year-old female adolescent in Nigeria who presented to the University of Calabar Teaching Hospital with recurrent vomiting, abdominal pain, weight loss, and dysphagia. She had received treatment for Gastro-oesophageal disease three years earlier and was lost to follow-up. Weight on admission was 39 kg and height 170 cm with a BMI below the 3rd centile. Peripheral blood showed an eosinophil count of four percent. The abdominal computed tomography (CT) scan and upper gastrointestinal (GI) series were normal. Faecal antigen for H. pylori and ova for stool parasites were negative. Histologic findings of proximal and distal oesophageal mucosal biopsies showed greater than 20 eosinophils per high power field. The histology of the stomach and duodenum were normal. She was initially treated with a protein pump inhibitor, with no improvement. Swallowed fluticasone propionate and eliminating peanuts, wheat, egg, and milk from her diet were introduced. Symptoms improved with the patient no longer vomiting and had an increase in weight gain. She was discharged to follow up. This case shows that EoE occurs in developing countries, but diagnosis may be missed. There is a need for a high index of suspicion among gastroenterologists in patients with symptoms suggestive of GERD not responding to therapy.

Budget Impact of RefluxStop™ as a Treatment for Patients with Refractory Gastro-oesophageal Reflux Disease in the United Kingdom.

Background: Gastro-oesophageal reflux disease (GORD) is a common condition associated with heartburn and regurgitation. Standard of care for GORD patients in the UK involves initial treatment with proton pump inhibitors (PPIs) and laparoscopic antireflux surgery in patients unwilling to continue or intolerant of long-term PPI treatment. Recently, RefluxStop™, a novel, implantable medical device, has proven to be an efficacious and cost-effective treatment for patients with GORD. The current analysis aimed to describe the budget impact of introducing RefluxStop™ within National Health Service (NHS) England and Wales. Objectives: To estimate the more immediate, short-term clinical and economic effects of introducing RefluxStop™ as a therapeutic option for patients with GORD treated within NHS England and Wales. Methods: A model adherent to international best practice guidelines was developed to estimate the budget impact of introducing RefluxStop™ over a 5-year time horizon, from an NHS perspective. Two hypothetical scenarios were considered, one without RefluxStop™ (comprising PPI treatment, laparoscopic Nissen fundoplication, and magnetic sphincter augmentation using the LINX® system) and one with RefluxStop™ (adding RefluxStop™ to the aforementioned treatment options). Clinical benefits and costs associated with each intervention were included in the analysis. Results: Over 5 years, introducing RefluxStop™ allowed the avoidance of 347 surgical failures, 39 reoperations, and 239 endoscopic esophageal dilations. The financial impact of introducing RefluxStop™ was £3 029 702 in year 5, corresponding to a 1.68% increase in annual NHS spending on GORD treatment in England and Wales. Discussion: While the time horizon was too short to capture some of the adverse events of PPIs and complications of GORD, such as the development of Barrett's esophagus or esophageal cancer, the use of RefluxStop™ was associated with a substantial reduction in surgical complications, including surgical failures, reoperations, and endoscopic esophageal dilations. This favorable clinical profile resulted in cost offsets for the NHS and contributed to the marginal budget impact of RefluxStop™ estimated in the current analysis. Conclusions: Introducing RefluxStop™ as a treatment option for patients with GORD in England and Wales may be associated with clinical benefits at the expense of a marginal budget impact on the NHS.

Mucosal neuroimmune mechanisms in gastro-oesophageal reflux disease (GORD) pathogenesis.

Gastro-oesophageal reflux disease (GORD) is a chronic condition characterised by visceral pain in the distal oesophagus. The current first-line treatment for GORD is proton pump inhibitors (PPIs), however, PPIs are ineffective in a large cohort of patients and long-term use may have adverse effects. Emerging evidence suggests that nerve fibre number and location are likely to play interrelated roles in nociception in the oesophagus of GORD patients. Simultaneously, alterations in cells of the oesophageal mucosa, namely epithelial cells, mast cells, dendritic cells, and T lymphocytes, have been a focus of GORD research for several years. The oesophagus of GORD patients exhibits both macro- and micro-inflammation as a response to chronic acidic reflux at the epithelium. In other conditions of the GI tract, such as IBS and IBD, well-characterised bidirectional processes between immune cells and mucosal nerve fibres contribute to pathogenesis and symptom generation. Sensory alterations in these conditions such as nerve fibre outgrowth and hypersensitivity can be driven by inflammatory processes, which promote visceral pain signalling. This review will examine what is currently known of the molecular pathways linking inflammation and sensory perception leading to the development of GORD symptoms and explore potentially relevant mechanisms in other GI regions which may indicate new areas in GORD research.

Outcomes of Concurrent Hiatus Hernia Repair with Different Bariatric Surgery Procedures: a Systematic Review and Meta-analysis.

BACKGROUND: Hiatus hernia (HH) is prevalent among patients with obesity. Concurrent repair is often performed during metabolic and bariatric surgery (MBS), but a consensus on the safety and effectiveness of concurrent HH repair (HHR) and MBS remains unclear. We performed a systematic review of the safety and effectiveness of concurrent HHR and MBS through the measurement of multiple postoperative outcomes. METHOD: Seventeen studies relating to concurrent MBS and HHR were identified. MBS procedures included laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (LRYGB), and adjustable gastric banding (LAGB). Studies with pre- and postoperative measurements and outcomes were extracted. RESULTS: For LSG, 9 of 11 studies concluded concurrent procedures to be safe and effective with no increase in mortality. Reoperation and readmission rates however were increased with HHR, whilst GORD rates were seen to improve, therefore providing a solution to the predominant issue with LSG. For LRYGB, in all 5 studies, concurrent procedures were concluded to be safe and effective, with no increase in mortality, length of stay, readmission and reoperation rates. Higher complication rates were observed compared to LSG with HHR. Among LAGB studies, all 4 studies were concluded to be safe and effective with no adverse outcomes on mortality and length of stay. GORD rates were seen to decrease, and reoperation rates from pouch dilatation and gastric prolapse were observed to significantly decrease. CONCLUSION: Concurrent HHR with MBS appears to be safe and effective. Assessment of MBS warrants the consideration of concurrent HHR depending on specific patient case and the surgeon's preference.

Long-term efficacy of total versus posterior partial fundoplication in patients with gastro-oesophageal reflux disease: a systematic review and meta-analysis.

INTRODUCTION: Laparoscopic fundoplication remains the standard treatment for patients with severe gastro-oesophageal reflux disease (GORD). Multiple randomised controlled trials (RCTs) have compared the two most commonly performed surgical techniques, total and posterior partial fundoplication (Nissen [NF] and Toupet [TF]), in terms of symptom control and treatment failure in patients without subsequent dysmotility disorders. We aimed to conduct a systematic review and meta-analysis of these two techniques with regard to the long-term effect on reflux control and associated dysphagia. METHODS: The MEDLINE®, Embase®, PubMed® and Cochrane Library databases were searched, and all the relevant published RCTs were shortlisted according to the inclusion criteria. The summated outcomes of long-term results relating to the recurrence of GORD and dysphagia were evaluated in a meta-analysis using RevMan software. RESULTS: Eight studies (all RCTs) on 1,545 patients undergoing NF or TF were eligible for inclusion in this meta-analysis. There were 799 patients in the NF group and 746 in the TF group. In the random effects model analysis, the incidence of long-term recurrence of GORD was not statistically different between the NF and TF cohorts (odds ratio [OR]: 0.69, 95% confidence interval [CI]: 0.34-1.41, z=1.01, p=0.31). However, the incidence of long-term dysphagia was statistically lower in the TF group (OR: 2.92, 95% CI: 1.49-5.72, z=3.13, p=0.002) with low between-study heterogeneity (I2=0%). CONCLUSIONS: The findings of this systematic review and meta-analysis on symptomatic GORD appear to be in favour of partial posterior fundoplication (TF) as the optimal treatment. It provides equivalent outcomes in reflux symptom control with a lower risk of postoperative dysphagia compared with total fundoplication (NF).

Comparative preoperative sonological assessment of gastric contents in patients with chronic kidney disease versus those with normal renal function - A prospective observational study.

Background and Aims: Though the role of fasting preoperative gastric ultrasound has been validated in different patient populations, namely, obese, pregnant and diabetics, it has not been explored in patients with chronic kidney disease (CKD). This prospective, observational study compared the fasting sonological assessment of gastric contents in patients with CKD versus those with normal renal function scheduled for elective surgery. Methods: After ethical approval and trial registration were obtained, preoperative gastric ultrasound was done in 115 CKD patients and 115 with normal renal function. Qualitative and quantitative assessment of residual gastric volume was done. Also, the patients were administered the Porto Alegre Dyspeptic Symptoms Questionnaire (PADYQ) to evaluate gastroparesis objectively. The researcher was not blinded to the patient groups. Data analyses were done using the Statistical Package for Social Sciences (SPSS) for Windows software (version 22.0). Results: Gastric volumes exceeding 1.5 ml/kg or particulate or solid contents were found in 57 patients with CKD and 36 patients with normal renal function (P = 0.004). The PADYQ scores were 6.54 ± 8.49 for CKD and 2.15 ± 5.71 for normal renal function (P < 0.0001) groups. CKD patients had a higher age (P < 0.001), lower body mass index (P = 0.005) and higher incidence of diabetes mellitus (P < 0.001). There were no incidents of gastric aspiration. Conclusion: Renal dysfunction contributes to delayed gastric emptying. PADYQ can also help identify those at high risk of gastroparesis. Combining the questionnaire and preoperative gastric ultrasound must be considered in these patients to ensure optimum safety.

Outcomes of de-prescribing proton pump inhibitors during acute admissions in a general medical unit: a pilot study.

The study describes the feasibility and short-to-medium-term efficacy of an evidence-based proton pump inhibitor (PPI) de-prescribing initiative undertaken as part of routine clinical care during acute admissions in a general medical unit. Of the 44 (median (IQR) age 75.5 (13.75) years; females 25 (57%)) who participated in the study, de-prescription was maintained in 29 (66%) and 27 (61%) patients at 12 and 26 weeks respectively.

Impact of Ramadan Fasting on the Severity of Symptoms Among a Cohort of Patients With Gastroesophageal Reflux Disease (GERD).

INTRODUCTION:  Gastroesophageal reflux disease (GERD) is a condition caused by the reflux of stomach contents into the esophagus. Heartburn, chest discomfort, and regurgitation are the main symptoms. Medications, surgical procedures, and lifestyle modification are considered treatment options. Fasting is believed to be one of the lifestyle modifications that helps minimize GERD symptoms. Muslims abstain from eating, drinking, and smoking from dawn until dusk. The objectives of our study were to investigate the relationship between fasting and GERD symptoms and evaluate how fasting affects GERD symptoms in Saudi Arabia. METHODOLOGY: This was a longitudinal study that selected GERD patients for its consecutive sampling. The patients answered the questionnaires at two separate times: once during Ramadan and once after Ramadan. A validated gastroesophageal reflux disease health-related quality of life (GERD-HRQL) self-administered survey was used. RESULT: After Ramadan, heartburn symptoms significantly decreased, particularly when lying down. Overall, the 45-point heartburn score decreased from 17.9 during Ramadan to 14.3 thereafter. The regurgitation score decreased from 12.3 during Ramadan to 9.9 after fasting, with statistical significance (P = .049). Although satisfaction was much higher after Ramadan (17% vs. 15.1%), there was no statistical significance (P = .422), and 45.3% of the patients were satisfied with their health state during Ramadan compared to 34% after Ramadan. There was no relationship between the severity of GERD symptoms before or after fasting and the type of food, the timing of eating, or the amount of food consumed. CONCLUSION: The results suggested that Ramadan fasting may improve GERD symptoms. However, more studies are required to validate these results and comprehend the underlying mechanisms.

TRPV1 is a risk factor for sleep disturbance in patients with gastro-oesophageal reflux disease: a case control study.

BACKGROUND/AIMS: Gastro-oesophageal reflux disease (GORD) is a chronic high-morbidity disease with a bidirectional relationship with sleep disturbance (SD) that may occur via the transient receptor potential vanilloid type 1 receptor (TRPV1) in the oesophageal mucosa. Yet the related mechanism was still unclear, the aim of this study is to investigate whether TRPV1 is associated with the presence of SD in GORD patients. METHODS: A case-control study was performed. After the screening, A total of 88 subjects were assigned to GORD without sleep disturbance (GORD + NOSD, n = 28), GORD comorbid sleep disturbance (GORD + SD, n = 30) and matched healthy controls (n = 30). Mucosal tissue was obtained from the participants by digestive endoscopy, the levels of TRPV1 expressed in the oesophageal mucosa were detected via RT-qPCR and western blot in different groups, and the correlation between GORD and SD were also analysed. RESULTS: In this study, we found that the Gastroesophageal Reflux Disease Diagnostic Questionnaire (GerdQ) scores was positively correlated with Pittsburgh Sleep Quality Index (PSQI) scores but negatively correlated with total sleep time (TST). We also found that the level of TRPV1 expressed in the oesophageal mucosa of GORD + SD was significantly higher than GORD + NOSD patients, and they were all higher than healthy controls. CONCLUSION: The current study suggested a closer link exists between GORD and sleep disturbance, and TRPV1 in oesophageal mucosa may be a crucial factor affecting sleep in GORD patients.

Antireflux surgery versus medical management of gastro-oesophageal reflux after lung transplantation.

OBJECTIVES: Gastro-oesophageal reflux disease after lung transplantation may be associated with chronic lung allograft dysfunction. Aspiration may continue on medical management of reflux, but antireflux surgery potentially reduces all reflux. We compared outcomes between medical and surgical management of reflux in lung recipients. METHODS: Lung recipients with an elevated DeMeester score (≥14.72) on post-transplant reflux testing between 2015 and 2020 were included. Patients were divided into 2 groups: group A (underwent surgery) and group B (medically managed). Endpoints were pulmonary function, allograft dysfunction-free survival and overall survival. Further analysis included subgroups: A1 (early surgery, <6 months) and A2 (late surgery, >6 months), and B1 (DeMeester <29.9) and B2 (DeMeester ≥30). RESULTS: A total of 186 included subjects were divided into groups A [n = 46 (A1, n = 36; A2, n = 10)] and B [n = 140 (B1, n = 78; B2, n = 62)]. Compared to medically managed patients, patients who underwent surgery had a higher prevalence of hiatal hernia (P < 0.001) and a lower prevalence of oesophageal motility disorders (P = 0.036). Recipients who underwent surgery had superior pulmonary function at 5 years compared to group B (P < 0.05) and longer allograft dysfunction-free survival than subgroup B2 (P = 0.028). Furthermore, early surgery was associated with longer survival than late surgery (P = 0.021). CONCLUSIONS: Antireflux surgery in recipients with reflux improved long-term allograft function, and early surgery showed a survival benefit. Allograft dysfunction-free survival of lung recipients who underwent surgery was significantly better than that of medically managed patients with DeMeester ≥30. We present an algorithm for appropriate selection of candidates for antireflux surgery after lung transplantation.

'Critical circle of fundoplication' - A key concept towards creating identical, replicable and consistent fundoplication wraps.

Background: There is a significant learning curve associated with laparoscopic Nissen's fundoplication, during which, complications due to surgical errors are more likely to occur. Moreover, length of the wrap, its situation on the lower esophagus and the points of the fundus brought together to create the wrap are arbitrary and as per the surgeon's judgement and estimation. This leads to a lot of variation in the wraps created, not only from surgeon to surgeon, but also from case to case for each individual surgeon. We propose a new concept of 'Critical Circle of Fundoplication' and the new approach to construct the fundoplication based on this concept, by application of which, a mathematically precise fundoplication can be created which is consistent, accurate and optimum. Patients and Methods: A total of 132 patients were operated based on the concept of 'Critical Circle of Fundoplication' between 2015 and 2020, of which 116 patients completed one year of follow-up and are included in the paper. Results: The demographic characteristics, intraoperative findings and postoperative are described in detail. An additional average time of 10.5 minutes (range: 8-26 minutes) was required in the precise measurements and markings that were required by this approach. Conclusion: By application of the concept of 'Critical Circle of Fundoplication', precise, consistent and optimum wraps can be created. By eliminating the errors of structural construction and placement of the wrap, overall results can be improved.

Oropharyngeal dysphagia in head and neck cancer: how to reduce aspiration pneumonia.

OBJECTIVE: Oropharyngeal dysphagia is caused by difficulty in bolus preparation and transport from the mouth to the oesophagus; this may result in malnutrition and aspiration pneumonia. It has a high prevalence in head and neck cancer patients. The objective of this study is to reduce these complications using a new protocol of diagnosis and evaluation of oropharyngeal dysphagia. METHOD: This is a prospective study developed in a secondary hospital. All patients diagnosed with head and neck cancer in 2021 and 2022 are subjected to this protocol: an oropharyngeal dysphagia screening test, a swallowing-related quality of life questionnaire and a flexible endoscopic evaluation of swallow. RESULTS: A total of 72 evaluations are reported using this protocol, before and after cancer treatment, and only 1 presents with aspiration pneumonia. CONCLUSION: Using this protocol, the incidence of aspiration pneumonia can be reduced, and diet recommendations can be given earlier in order to maintain a patient's nutritional requirements.

Ex vivo evaluation of adhesive strength and barrier effect of a novel treatment for esophagitis.

AIM: To investigate the mucoadhesive strength and barrier effect of Esophacare® (Atika Pharma SL, Las Palmas de Gran Canaria) in an ex vivo model of gastro-oesophageal reflux. METHODS: An ex vivo evaluation through the Falling Liquide Film Technique with porcine esophagi was performed, compared to a positive control (Ziverel®; Norgine, Amsterdam), after different washing periods with saline, acidified saline (pH 1.2) and acidified saline with pepsin (2000U/mL). RESULTS: The adhesive mean strength on the oesophageal mucosa of Esophacare was 94.7 (6.0)%, compared to 27.6 (19.1)% of the positive control (p<0.05). These results were homogeneous across the different washes and throughout the tissue. The area covered by 1mL of Esophacare, and its respective persistence after washing was also assessed, yielding a mean global persistence of 74.29 (19.7)% vs. 18.9 (12.3)% for the control (p<0.05). In addition, after 30min exposure to acidified saline with pepsin, Esophacare shows a protective effect on the oesophageal mucosa, detectable histologically: preserved integrity and structure of the apical layers was observed, as well as reduced permeability to the washing solution. CONCLUSIONS: Esophacare shows an adhesive strength close to 100%, irrespective of the washing solution applied or the oesophageal region studied. Histologically, it reduces the abrasive effects of the acidic solution on the oesophageal epithelium, reducing permeability to the washing solution. The results in this ex vivo model of gastro-oesophageal reflux disease (GERD) support its therapeutic potential.

Laryngopharyngeal reflux induced sleep-related laryngospasm.

BACKGROUND: Sleep-related laryngospasm (SRL) has been defined as the sustained closure of the vocal cords during sleep. Studies have suggested that it is a rare manifestation of laryngopharyngeal reflux (LPR). Difficulties in diagnosing SRL and LPR have led to the condition being under-recognised in the clinical setting. AIMS: The aim of this study was to determine if LPR was the cause of the SRL symptoms seen in our patients. METHODS: A retrospective chart assessment of patients with SRL. Patients with risk factors for LPR were identified. These included smoking status, alcohol intake, a history of dyspepsia or history of gastroesophageal reflux disease, a history of late-night eating and a history of eating spicy or fatty foods before bed. A clinical diagnosis based on the history and response to management was made for the diagnosis of LPR. All were advised to refrain from late meals and those with signs of nasopharyngitis were commenced on proton pump inhibitor therapy. RESULTS: Nineteen patients (mean age ± SD: 57.21 ± 15.18) were included in the study. All had at least one risk factor for LPR. Ten (52.6%) had signs of nasopharyngitis on nasendoscopy. Following treatment, 17 (89.5%) reported no further SRL symptoms at 1-year follow-up. CONCLUSION: SRL is a largely unknown and under-diagnosed condition. We believe this study provides supportive evidence for the causal relationship between LPR and SRL.

Late age at first birth is a protective factor for oesophageal cancer and gastro-oesophageal reflux: the evidence from the genetic study.

Objective: The primary objective of this research endeavor was to examine the underlying genetic causality between the age at first birth (AFB) and four prevalent esophageal diseases, namely oesophageal obstruction (OO), oesophageal varices (OV), gastro-oesophageal reflux (GOR), and oesophageal cancer (OC). Methods: We conducted a two-sample Mendelian randomization (MR) analysis to examine the causal association between AFB and four prevalent esophageal disorders. We employed eight distinct MR analysis techniques to evaluate causal relationships, encompassing random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and fixed-effects IVW. The random-effects IVW method served as the primary approach for our analysis. Furthermore, we executed several sensitivity analyses to assess the robustness of the genetic causal inferences. Results: The random-effects IVW analysis revealed a significant negative genetic causal association between AFB and both GOR (P < 0.001, Odds Ratio [OR] 95% Confidence Interval [CI] = 0.882 [0.828-0.940]) and OC (P < 0.001, OR 95% CI = 0.998 [0.998-0.999]). Conversely, there was insufficient evidence support to substantiate a genetic causal link between AFB and OO (P = 0.399, OR 95% CI = 0.873 [0.637-1.197]) or OV (P = 0.881, OR 95% CI = 0.978 [0.727-1.314]). The results of sensitivity analyses underscore the robustness and reliability of our MR analysis. Conclusion: The findings of this investigation substantiate the notion that elevated AFB confers a protective effect against GOR and OC. In addition, no causative association was discerned between AFB and OO or OV at the genetic level.