[Approach to refractory gastroesophageal reflux disease]. / Abordaje de la enfermedad por reflujo gastroesofágico refractaria.

An adequate approach to refractory gastroesophageal reflux disease (rGERD) is essential for achieving therapeutic success. From the precise definition of rGERD to the detailed characterization of its phenotypes, it will pave the way for the customization of optimal therapy for each patient. In this narrative literature review, the aim is to provide an updated synthesis of the utility of various diagnostic tools and explore the wide range of therapeutic options, both medical and invasive, available for this condition.

Laryngopharyngeal reflux disease: Updated examination of mechanisms, pathophysiology, treatment, and association with gastroesophageal reflux disease.

Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus. LPRD commonly presents with sym-ptoms such as hoarseness, cough, sore throat, a feeling of throat obstruction, excessive throat mucus. This complex condition is thought to involve both reflux and reflex mechanisms, but a clear understanding of its molecular mechanisms is still lacking. Currently, there is no standardized diagnosis or treatment protocol. Therapeutic strategies for LPRD mainly include lifestyle modifications, proton pump inhibitors and endoscopic surgery. This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms, patho-physiology and treatment of LPRD. We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.

Positive effect of deep diaphragmatic breathing training on gastroesophageal reflux-induced chronic cough: a clinical randomized controlled study.

BACKGROUND AND OBJECTIVE: To explore the efficacy of deep diaphragmatic breathing training (DEP) in patients with gastroesophageal reflux-induced chronic cough (GERC). METHODS: A randomized controlled study was conducted involving 60 GERC patients who were divided into the intervention group and the control group (each with 30 patients). Both groups received routine medication treatment for GERC, while the intervention group received DEP training additionally. Both groups were evaluated by cough symptom scores, Hull airway reflux questionnaire (HARQ), gastroesophageal reflux diagnostic questionnaire (GerdQ), generalized anxiety disorder scale-7 (GAD-7), patient health questionnaire-9 (PHQ-9), Pittsburgh sleep quality index (PSQI), the Leicester cough questionnaire (LCQ), as well as capsaicin cough sensitivity testing, B-ultrasound and surface electromyography (sEMG) of the diaphragmatic muscles before and after treatment. The cough resolution rate and changes of the above indictors was compared between the two groups after eight weeks of treatment. RESULTS: After eight weeks of treatment, cough symptoms improved in both groups, but the cough resolution rate in the intervention group of 94% was significantly higher than that in the control group of 77% (χ2 = 6.402, P = 0.041). The intervention group showed significant improvements to the control group in GerdQ (6.13(0.35) VS 6.57(0.77)), GAD-7 (0(0;1) VS 1(0;3)), PSQI (2(1;3) VS 4(3;6)), LCQ (17.19(1.56) VS 15.88(1.92)) and PHQ-9 (0(0;0) VS 0(0;3)) after treatment. Compared to control group, sEMG activity of the diaphragmatic muscle was significantly increased in the intervention group after treatment, measured during DEP (79.00(2.49) VS 74.65 (1.93)) and quiet breathing (72.73 (1.96) VS 67.15 (2.48)). CONCLUSION: DEP training can improve cough symptoms as an adjunctive treatment in GERC patients. TRIAL REGISTRATION: The protocol was registered in February 2, 2022 via the Chinese Clinical Trials Register ( http://www.chictr.org.cn/ ) [ChiCTR2200056246].

Relationship between endoscopic gastroesophageal valve grading and mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index in patients with gastroesophageal reflux disease.

This study aimed to investigate the relationship between endoscopic gastroesophageal valve grading and mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave index (PSPWI) in patients with gastroesophageal reflux disease (GERD). A total of 120 patients diagnosed with GERD disease were included in the study. According to the classification of endoscopic gastroesophageal valves, the patients were divided into 5 groups, group 1 as baseline group, and Group 2-4 as Hill grade I-IV. Basic information about the patients was collected, including age and gender. The mean nocturnal baseline impedance and creep wave index induced by swallowing after rumination were measured by high resolution creep measurement technique. Through statistical analysis, the relationship between valve classification and observation index was discussed. In terms of MNBI, impedance values gradually decreased with increasing valve classification. The average impedance of the Grade 1 group was 23.5 mm Hg/cm2, while the average impedance of the Grade 5 group was 15.2 mm Hg/cm2. This reduction showed a significant decreasing trend (P < .001). In addition, in terms of the peristaltic wave index caused by swallowing after regurgitation, the peristaltic wave index gradually increased with the increase of valve classification. The mean index in the Grade 1 group was 1.8 beats/min, while the mean index in the Grade 5 group was 3.6 beats/min. This increase showed a significant positive relationship (P < .001). Endoscopic gastroesophageal valve grading was significantly correlated with MNBI and PSPWI in patients with GERD. These observations can serve as useful tools for assessing the severity of GERD and monitoring disease progression.

Good clinical practice recommendations for the diagnosis and treatment of gastroesophageal reflux disease. An expert review from the Asociación Mexicana de Gastroenterología.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is very prevalent in the general population, with a broad spectrum of clinical manifestations, requiring accurate diagnosis and treatment. AIM: The aim of this expert review is to establish good clinical practice recommendations for the diagnosis and personalized treatment of GERD. METHODS: The good clinical practice recommendations were produced by a group of experts in GERD, members of the Asociación Mexicana de Gastroenterología (AMG), after carrying out an extensive review of the published literature and discussing each recommendation at a face-to-face meeting. This document does not aim to be a clinical practice guideline with the methodology such a document requires. RESULTS: Fifteen experts on GERD formulated 27 good clinical practice recommendations for recognizing the symptoms and complications of GERD, the rational use of diagnostic tests and medical treatment, the identification and management of refractory GERD, the overlap with functional disorders, endoscopic and surgical treatment, and GERD in the pregnant woman, older adult, and the obese patient. CONCLUSIONS: An accurate diagnosis of GERD is currently possible, enabling the prescription of a personalized treatment in patients with this condition. The goal of the good clinical practice recommendations by the group of experts from the AMG presented in this document is to aid both the general practitioner and specialist in the process of accurate diagnosis and treatment, in the patient with GERD.

Validity and reliability of the Persian version of the Gastroesophageal Reflux Disease Health-Related Quality of Life questionnaire.

OBJECTIVE: The Gastroesophageal Reflux Disease Health-Related Quality of Life (GERD-HRQL) is one of the most widely used questionnaires for assessing typical gastro-oesophageal reflux disease (GORD) symptoms. It is simple, concise, and treatment responsive, yet it has not been validated in the Persian language. This study aimed to translate the GERD-HRQL questionnaire into Persian and assess its validity and reliability. DESIGN: In this cross-sectional validation study, a team of gastroenterologists, general surgeons, and professional translators conducted the forward-backward translation. A gastroenterologist interviewed 10 patients with GORD to insure understandability of the questionnaire. Fifty-four patients with GORD and 60 patients with gastrointestinal complaints other than GORD were enrolled using convenience sampling method. To assess concurrent validity, patients with GORD completed the Persian GERD-HRQL and the WHO Quality of Life Brief Version (WHOQOL-BREF) questionnaires. To assess discriminant validity, GERD-HRQL scores were compared between GORD and non-GORD patients. After 2 weeks, the patients with GORD completed the GERD-HRQL questionnaire again to assess test-retest reliability. The internal consistency was measured using Cronbach's alpha. RESULTS: The mean age of the GORD participants was 36.90±10.44, and the majority were women (78%). All GERD-HRQL domains and total scores exhibited significant negative correlations with WHOQOL-BREF domains (ranging from -0.28 to -0.97). The GERD-HRQL scores were significantly different in GORD and non-GORD patients (p<0.001). Test and retest scores did not show any significant differences (p=0.49). Cronbach's alpha was 0.85. CONCLUSION: The Persian GERD-HRQL questionnaire is valid and reliable and can effectively assess the GORD symptoms in Persian-speaking individuals.

Enhanced Runge-Kutta-driven feature selection model for early detection of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) profoundly compromises the quality of life, with prolonged untreated cases posing a heightened risk of severe complications such as esophageal injury and esophageal carcinoma. The imperative for early diagnosis is paramount in averting progressive pathological developments. This study introduces a wrapper-based feature selection model based on the enhanced Runge Kutta algorithm (SCCRUN) and fuzzy k-nearest neighbors (FKNN) for GERD prediction, named bSCCRUN-FKNN-FS. Runge Kutta algorithm (RUN) is a metaheuristic algorithm designed based on the Runge-Kutta method. However, RUN's effectiveness in local search capabilities is insufficient, and it exhibits insufficient convergence accuracy. To enhance the convergence accuracy of RUN, spiraling communication and collaboration (SCC) is introduced. By facilitating information exchange among population individuals, SCC expands the solution search space, thereby improving convergence accuracy. The optimization capabilities of SCCRUN are experimentally validated through comparisons with classical and state-of-the-art algorithms on the IEEE CEC 2017 benchmark. Subsequently, based on SCCRUN, the bSCCRUN-FKNN-FS model is proposed. During the period from 2019 to 2023, a dataset comprising 179 cases of GERD, including 110 GERD patients and 69 healthy individuals, was collected from Zhejiang Provincial People's Hospital. This dataset was utilized to compare our proposed model against similar algorithms in order to evaluate its performance. Concurrently, it was determined that features such as the internal diameter of the esophageal hiatus during distention, esophagogastric junction diameter during distention, and external diameter of the esophageal hiatus during non-distention play crucial roles in influencing GERD prediction. Experimental findings demonstrate the outstanding performance of the proposed model, with a predictive accuracy reaching as high as 93.824 %. These results underscore the significant advantage of the proposed model in both identifying and predicting GERD patients.

Correlation of the Endoscopic Gastroesophageal Flap Valve with Pathologic Reflux.

BACKGROUND: The Hill classification characterizes the geometry of gastroesophageal junction and Hill grades (HGs) III and IV have a high association with pathologic reflux. This study aimed to understand the use of the Hill classification and correlate the prevalence of pathologic reflux across different HGs. STUDY DESIGN: A retrospective review of 477 patients who underwent upper endoscopy and BRAVO pH monitoring between August 2018 and October 2021 was performed. These charts were reviewed for endoscopic findings for hiatal hernia and association of HGs with pathologic reflux, defined as an abnormal esophageal acid exposure time (AET) of ≥4.9%. RESULTS: Of 477 patients, 252 (52.8%) had an HG documented on the endoscopy report. Of the 252 patients, 61 had HG I (24.2%), 100 had HG II (39.7%), 61 had HG III (24.2%), and 30 had HG IV (11.9%). The proportion of patients with abnormal AET increases with increasing HGs (p < 0.001) as follows: I (39.3%), II (52.5%), III (67.2%), and IV (79.3%). The mean overall AET is as follows: HG I (5.5 ± 6%), HG II (7.0 ± 5.9%), HG III (10.2 ± 10.3%), and HG IV (9.5 ± 5.5%). The proportion of patients with hiatal hernia was 18% for HG I, 28% for HG II, 39.3% for HG III, and 80% for HG IV. CONCLUSIONS: Use of the Hill classification in clinical practice is low. There is an association of increasing HGs with increasing proportion of patients with abnormal AET. There is a high proportion of patients within HGs I and II with documented pathologic reflux and the presence of a hiatal hernia as observed on endoscopic examination. Our study suggests that endoscopic grading of the gastroesophageal junction may not adequately differentiate between normal vs abnormal reflux status, particularly for HGs I and II.

A multidisciplinary approach to identifying and managing heterotopic gastric inlet patches.

INTRODUCTION: Gastric inlet patches are often incidental, but can also be a treatable cause of laryngo-esophageal symptoms. METHODS: We retrospectively reviewed all patients whose gastric inlet patches were diagnosed following assessment for laryngopharyngeal and swallowing symptoms. Improvement following Argon Plasma Coagulation (APC) was assessed using Minimum Clinically-Important Difference methodology combining voice, throat, and swallowing domains. Correlations between APC response and measures of reflux and mucosal barrier integrity, measured during 24-h pH-impedance manometry, were obtained. Proximal and Distal Mean Nocturnal Baseline Impedance (MNBI) values were separately calculated and the novel variable of Mucosal Impedance Gradient was derived as [((Distal MNBI-Proximal MNBI)/((Distal MNBI + Proximal MMBI)/2)) x 100]. KEY RESULTS: Inlet patches were detected in 57 of 651 patients who had Transnasal Panendoscopy (8.7 ± 2.2%). There were 34 males. Mean age was 58 years. Mean duration of symptoms was 2 years. The commonest symptoms were hoarseness (n = 33), throat symptoms (n = 24), and dysphagia (n = 21), respectively. APC was used to ablate patches in 34 patients. Treatment response was 71% at a mean followup of 5.5 months. MIG > - 25% predicted response to APC, with area under the receiver operating characteristic curve of 0.875 (Sensitivity = 81%; Specificity = 100%; p < 0.0001). CONCLUSIONS: Gastric inlet patches are common and under-recognized. They can cause protracted pharyngo-esophageal symptoms. Patch ablation is an effective treatment for carefully selected patients. Optimal patient selection requires multidisciplinary teamwork. Mucosal Impedance Gradient could further refine patient selection.

Obesity and Upper Gastrointestinal Diseases.

Obesity increases gastroesophageal reflux disease through several factors. As a result, Barrett's esophagus, esophageal adenocarcinoma, and gastroesophageal junctional gastric cancer are increasing. Existing studies usually defined obesity by body mass index and analyzed the correlation. Recently, more studies have shown that central obesity is a more important variable in upper gastrointestinal diseases related to gastroesophageal reflux. Studies have reported that weight loss is effective in reducing gastroesophageal reflux symptoms. Obesity also affects functional gastrointestinal diseases. A significant correlation was shown in upper abdominal pain, reflux, vomiting, and diarrhea rather than lower abdominal diseases.

Analyzing the correlation between gastroesophageal reflux disease and anxiety and depression based on ordered logistic regression.

Numerous studies have indicated a connection between psychiatric symptoms, specifically anxiety and depression, and gastroesophageal reflux. However, the precise nature of the link between the severity of gastroesophageal reflux disease and the severity of anxiety and depression remains uncertain. Here, we gathered 24-h pH monitoring data and baseline patient information from a cohort of 518 individuals. Additionally, we evaluated their psychological well-being using the Hospital Anxiety and Depression Scale. The relationship between baseline characteristics and varying degrees of anxiety, depression, and gastroesophageal reflux disease (GERD) was assessed using R software version 4.1.3 and logistic regression models. The findings indicate a statistically significant variation in anxiety levels based on gender, as well as a significant disparity in depression groups when considering age and literacy levels. Kruskal-Wallis test analysis revealed a significant positive correlation between the severity of anxiety and depression and the 24-h pH monitoring results in our patient cohort. As the anxiety and depression levels increased, the rank mean for each examination result also increased. Logistic regression modeling analysis showed that a higher anxiety level was associated with a higher level of GERD. In the presence of mild anxiety, there is a statistically significant association with a higher incidence of GERD with an odds ratio (OR) of 2.64 (95% CI 1.50, 4.64). Similarly, the moderately severe anxiety group also exhibits a causal relationship with an increased GERD incidence, with an OR of 6.84 (95% CI 3.92, 12.17). Additionally, moderate to severe depression is associated with a higher incidence of GERD, with an OR of 2.32 (95% CI 1.23, 4.37). The prevalence of GERD was greater among males compared to females (OR 2.29, 95% CI 1.51-3.49). Additionally, an elevated body mass index (BMI) demonstrated a positive correlation with the susceptibility to GERD (OR 1.07, 95% CI 1.01-1.14). Increasing age may promote the occurrence of GERD in patients. These findings may help to provide a better basis for psychological or pharmacological interventions for GERD patients with psychosomatic symptoms in the future, and provide a reference basis for clinical treatment of the disease.

A systematic review of Sandifer syndrome in children with severe gastroesophageal reflux.

PURPOSE: Sandifer syndrome (SS), which combines gastroesophageal reflux (GER) and a neurological or psychiatric disorder, is an uncommon condition that often takes a long time to diagnosis. We aimed to systematically review available papers regarding SS. METHODS: After presenting our two cases of SS, we systematically reviewed articles published in MEDILINE/PubMed, Cochrane Library, and Web of Science. RESULTS: The meta-analysis included 54 reported cases and 2 of our own cases. Our results showed that all cases achieved symptom improvement with appropriate treatment for GER. Notably, 19 of the 56 cases exhibited anatomical anomalies, such as hiatal hernia and malrotation. Significantly more patients with than without anatomical anomalies required surgery (p < 0.001). However, 23 of the 29 patients without anatomical anomalies (79%) achieved symptom improvement without surgery. Patients who did not undergo surgery had a median (interquartile range) duration to symptom resolution of 1 (1-1) month. CONCLUSION: The primary care providers should keep SS in the differential diagnosis of patients presenting with abnormal posturing and no apparent neuromuscular disorders. Fundoplication may be effective especially for patients with anatomical anomalies or those whose symptoms do not improve after more than 1 month with nonsurgical treatment.

Impact of Gender on Gastroesophageal Reflux Disease Complications: Analysis of 27 Million Hospitalizations.

BACKGROUND AND AIMS: Previous studies have reported gender differences in patients with gastroesophageal reflux disease (GERD). These studies have also reported differences based on gender in the rates of complications. In this study, we aim to identify gender disparities in the rates of GERD complications in the United States. METHODS: We queried the 2016-2020 National Inpatient Sample database to identify patients with GERD. Patients with eosinophilic esophagitis or missing demographics were excluded. We compared patient demographics, comorbidities and complications based on gender. Multivariate logistic regression analysis was used to identify the impact of gender on complications of GERD. RESULTS: 27.2 million patients were included in the analysis. Out of them, 58.4% of the hospitalized patients with GERD were female. Majority of the women were White (75%), aged>65 years (57.5%) and were in the Medicare group (64%). After adjusting for confounders, females were noted to have lower odds of esophagitis (aOR=0.85, 95%CI: 0.84-0.86, p<0.001), esophageal stricture (aOR=0.95, 95%CI: 0.93-0.97, p<0.001), Barrett's esophagus (aOR=0.58, 95%CI: 0.57-0.59, p<0.001) and esophageal cancer (aOR=0.22, 95%CI: 0.21-0.23, p<0.001). CONCLUSIONS: Our study confirms the findings of previous literature that females, despite comprising the majority of the study population, had a lower incidence of GERD related complications. Further studies identifying the underlying reason for these differences are required.

Proximal esophageal impedance baseline increases the yield of impedance-pH and is associated with response to PPIs in chronic cough patients.

BACKGROUND: Chronic cough significantly impairs the quality of life. Although various studies focused on MNBI as assessed in the distal esophagus, scarce data are available on the clinical value of proximal measurements. AIM: To investigate the role of proximal MNBI in the workup of patients with chronic cough and its ability to predict PPI response. METHODS: Demographic, clinical, endoscopy findings, impedance-pH and HRM tracings from consecutive cough patients were evaluated. MNBI was calculated at proximal and distal esophagus. RESULTS: One hundred and sixty four patients were included. In addition to traditional variables, when considering also the PSPW index or MNBI at 3 cm or 15 cm, the proportion of patients with pathological impedance-pH monitoring significantly increased. 70/164 patients were responders, while 94 (57.3%) were non-responder to double PPI dose (p < 0.05). Patients with pathologic MNBI at 3 cm and/or 15 cm as well as those with pathologic PSPW index were characterized by a significantly higher proportion of responders than that observed among patients with normal impedance-pH variables (p < 0.001). The proportion of responders with pathological MNBI at 15 cm was significantly higher than the proportion of responders with pathological MNBI at 3 cm (82.8% vs. 64.3%, p < 0.05). At multivariable model, pathological MNBI at both 3 cm and 15 cm as well as PSPW index were associated with PPI responsiveness. The strongest association with PPI response was observed for MNBI at 15 cm. CONCLUSIONS: The assessment of MNBI at proximal esophagus increases the diagnostic yield of impedance-pH monitoring and may represent a useful predictor of PPI responsiveness in the cumbersome clinical setting of suspected reflux-related cough.

[Reflux symptoms and upper abdominal pain: Reflux, Gastritis and whatever could be behind it]. / Sodbrennen und Oberbauchschmerzen: Reflux, Gastritis und was noch infrage kommt.

Reflux symptoms and upper abdominal pain are very common symptoms in general population. Both symptoms are visceral and thus cannot be linked to an organ or a disease. Diagnostic work-up revealed organic disease in up to 30%, when patients present with dyspeptic symptoms. Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) represent the most frequent and important disorders in western countries, when diagnostic work-up is done in patients with reflux symptoms and abdominal pain.

Applying Lyon consensus criteria in the work-up of patients with extra-oesophageal symptoms - A multicentre retrospective study.

BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) based on otolaryngologist's assessment of laryngoscopic findings remains contentious in terms of sensitivity and specificity. AIMS: To evaluate GERD prevalence, applying Lyon 2.0 Consensus criteria, in patients with extra-oesophageal symptoms undergoing laryngoscopic examination and impedance-pH monitoring. METHODS: In this retrospective assessment, we included 470 patients with extra-oesophageal symptoms, either isolated or combined with typical symptoms, who had been referred to six tertiary Italian Gastroenterology Units between January and December 2020. Of these, 274 underwent 24-h impedance-pH monitoring and laryngoscopy off PPI therapy. GERD diagnosis followed Lyon Consensus 2.0 criteria, incorporating mean nocturnal baseline impedance when pH-impedance monitoring was inconclusive. RESULTS: Laryngoscopic examination revealed pathological findings (predominantly posterior laryngitis) in 71.2% (195/274). GERD was diagnosed in 29.2% (80/274) via impedance-pH monitoring. The prevalence of GERD in patients with positive or negative laryngoscopy was similar (32.3% vs. 21.5%, p = 0.075). No significant difference in proximal reflux occurrences was noted between positive and negative laryngoscopy groups (33.3% vs. 24.1%, p = 0.133). Laryngoscopy demonstrated sensitivity and specificity of 78.8% and 32.0%, respectively, with a positive predictive value (PPV) of 32.3% and negative predictive value (NPV) of 28.4%. In contrast, a threshold of four concurrent laryngoscopic signs, identified in only eight patients, demonstrated a PPV of 93.8% and a NPV of 73.6% (sensitivity 25.4%, specificity 99.2%). CONCLUSION: This study underscores the limited diagnostic accuracy of laryngoscopy, emphasising the necessity of impedance-pH monitoring for confirming GERD diagnoses using Lyon 2.0 criteria in patients with suspected extra-oesophageal symptoms.