Prevalence of functional esophageal disorders and associated clinical characteristics in patients with proton-pump-inhibitor-unresponsive reflux symptoms.

BACKGROUND AND AIM: Patients with proton-pump-inhibitor (PPI)-unresponsive reflux symptoms, often caused by functional esophageal disorders (FED), are frequently encountered in clinical practice. We aimed to investigate the prevalence of FED and its associated clinical characteristics in patients with PPI-unresponsive reflux symptoms. METHODS: We retrospectively identified patients who were evaluated for persistent typical reflux symptoms, despite ≥8 weeks of PPI treatment, at the National Taiwan University Hospital from 2014 to 2023. All patients underwent a comprehensive evaluation comprising validated gastroesophageal reflux disease (GERD) symptom questionnaires, 5-item Brief Symptom Rating Scale (BSRS-5), Pittsburgh Sleep Quality Index (PSQI), esophagogastroduodenoscopy, high-resolution impedance manometry, and 24-h impedance-pH monitoring off PPI therapy. Diagnosis of FED and non-erosive reflux disease (NERD) was based on the Rome IV criteria. RESULTS: We analyzed 190 patients [46.8% male, median age 52 (interquartile range, 42-61) years], of whom 32 (16.8%) had NERD and 158 (83.2%) had FED (57.9% with functional heartburn and 25.3% with reflux hypersensitivity). Patients with FED had a lower body mass index than those with NERD and a higher prevalence of psychological comorbidities and poor sleep quality than healthy volunteers. The severity of reflux symptoms among FED patients was significantly associated with the severity of psychological comorbidities and sleep quality. CONCLUSIONS: A notably high prevalence (83.2%) of FED was observed among patients experiencing PPI-unresponsive reflux symptoms. Patients with FED had a higher level of psychological distress and diminished sleep quality, both of which were associated with reflux symptom severity.

Systematic Review on Herbal Preparations for Controlling Visceral Hypersensitivity in Functional Gastrointestinal Disorders.

BACKGROUND: Visceral hypersensitivity (VH) is an overreaction of the gastrointestinal (GI) tract to various stimuli and is characterized by hyperalgesia and/or allodynia. VH contributes to the etiology of many GI dysfunctions, particularly irritable bowel syndrome (IBS). Although the exact mechanisms underlying VH are yet to be found, inflammation and oxidative stress, psychosocial factors, and sensorimotor alterations may play significant roles in it. OBJECTIVE: In this review, we provide an overview of VH and its pathophysiological function in GI disorders. Adverse effects of synthetic drugs may make herbal agents a good candidate for pain management. Therefore, in this review, we will discuss the efficacy of herbal agents in the management of VH with a focus on their anti-inflammatory and antioxidant potentials. METHODS: Data were extracted from clinical and animal studies published in English between 2004 and June, 2020, which were collected from PubMed, Google Scholar, Scopus, and Cochrane Library. RESULTS: Overall, Radix, Melissia, Glycyrrhizae, Mentha, and Liquorice were the most efficient herbals for VH management in IBS and dyspepsia, predominantly through modulation of the mRNA expression of transient receptor potential vanilloid type-1 (TRPV1) and suppression of 5- hydroxytryptamine 3 (5-HT3) or the serotonin receptors. CONCLUSION: Considering the positive effects of herbal formulations in VH management, further research on novel herbal and/or herbal/chemical preparations is warranted.

Among females older than 50 years, saliva secretion is significantly lower in non-erosive reflux disease patients than in healthy controls.

BACKGROUND: Saliva secretion is significantly lower in patients with non-erosive reflux disease (NERD) than in healthy controls (HC). A previous study on HC showed that saliva secretion was lower in females than in males. Saliva secretion may be lower in female patients with NERD than in male patients. Therefore, the present study investigated sex differences in saliva secretion in patients with NERD. METHODS: Subjects older than 50 years were included in the present study and consisted of 20 male patients with NERD, 19 male HC, 25 female patients with NERD, and 23 female HC. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured. RESULTS: In males, no significant differences were observed in the amount of stimulated saliva secretion or salivary pH between NERD patients and HC. However, the acid-buffering capacity (NERD: 6.1 [5.9-6.5], HC: 6.4 [6.2-6.6]) was significantly lower in NERD patients than in HC. In females, the amount of stimulated saliva secretion (NERD: 2.6 [2.0-4.1], HC: 5.8 [3.7-7.5]), salivary pH (NERD: 7.0 [6.8-7.2], HC: 7.2 [7.0-7.2]), and the acid-buffering capacity (NERD: 5.8 [5.4-6.2], HC: 6.2 [6.0-6.5]) were significantly lower in NERD patients than in HC. CONCLUSION: Among females older than 50 years, saliva secretion was significantly lower in NERD patients than in HC. This reduction in saliva secretion may contribute to the pathophysiology of NERD in females.

Differences in Dietary and Lifestyle Triggers between Non-Erosive Reflux Disease and Reflux Esophagitis-A Multicenter Cross-Sectional Survey in China.

The occurrence of gastroesophageal reflux disease (GERD) and symptom onset are closely associated with diet. We aimed to compare the dietary and lifestyle triggers between non-erosive reflux disease (NERD) and reflux esophagitis (RE) in Chinese patients and to provide evidence for development of practical dietary modifications for GERD. A multicenter cross-sectional survey was conducted. A total of 396 GERD patients with typical gastroesophageal reflux symptoms who received upper endoscopy in the previous month were enrolled, including 203 cases of NERD patients and 193 cases of RE patients. All participants completed questionnaires including demographic data, reflux symptoms, previous management, dietary and lifestyle habits, triggers of reflux symptoms, psychological status, and quality of life. There were no significant differences in GERD symptom scores between NERD and RE. RE patients had a higher male proportion and smoking/drinking and overeating rates than NERD patients. In the NERD group, more patients reported that fruits, dairy products, yogurt, bean products, cold food, and carbonated beverages sometimes and often induced reflux symptoms and had more triggers compared to RE patients. The number of triggers was positively correlated to GERD symptom score and GERD-HRQL score in both NERD and RE patients. However, 74.0% of GERD patients still often consumed the triggering foods, even those foods that sometimes and often induced their reflux symptoms, which might be related to the reflux relapse after PPI withdrawal considering NERD and RE patients had similar GERD symptom severity. There were some differences in terms of dietary habits, dietary and lifestyle triggers, and related quality of life between NERD and RE, and these results may provide evidence of different approaches toward the dietary modification of NERD and RE patients.

Significantly Lower Saliva Secretion in Females With Gastroesophageal Reflux Disease and Healthy Subjects Than in Males.

OBJECTIVE: Saliva secretion in healthy subjects is lower in females than in males. The present study investigated sex differences in saliva secretion in patients with gastroesophageal reflux disease (GERD) and healthy controls. METHODS: This case-control study included 39 (male/female: 16/23) with non-erosive reflux disease (NERD), 49 (25/24) patients with mild reflux esophagitis, 45 (23/22) with severe reflux esophagitis (A1), and 46 (24/22) healthy controls. Saliva secretion was examined as follows: before endoscopy, patients chewed sugar-free gum for three minutes, and the amount and pH of saliva before and after acid loading as an index of acid-buffering capacity were evaluated. The relationships between saliva secretion and body mass index, height, and weight were also examined. RESULTS: The amount of saliva secreted was significantly lower in females than in males in all four groups (NERD, mild reflux esophagitis, severe reflux esophagitis, and healthy controls). Salivary pH and acid-buffering capacity were similar in all groups. The amount of saliva secreted positively correlated with height and body weight, albeit more strongly with height. CONCLUSION: A sex difference in saliva secretion exists in GERD patients, similar to healthy controls. Saliva secretion was significantly lower in female GERD patients than in male GERD patients.

Prevalence of Non-erosive Esophageal Phenotypes in Children: A European Multicenter Study.

Background/Aims: Since available data on pediatric non-erosive esophageal phenotypes (NEEPs) are scant, we investigated their prevalence and the phenotype-dependent treatment response in these children. Methods: Over a 5-year period, children with negative upper endoscopy, who underwent esophageal pH-impedance (off-therapy) for persisting symptoms not responsive to proton pump inhibitor (PPI)-treatment, were recruited. Based on the results of acid reflux index (RI) and symptom association probability (SAP), patients were categorized into: (1) abnormal RI (non-erosive reflux disease [NERD]), (2) normal RI and abnormal SAP (reflux hypersensitivity [RH]), (3) normal RI and normal SAP (functional heartburn [FH]), and (4) normal RI and not-reliable SAP (normal-RI-not otherwise-specified [normal-RI-NOS]). For each subgroup, treatment response was evaluated. Results: Out of 2333 children who underwent esophageal pH-impedance, 68 cases, including 18 NERD, 14 RH, 26 FH, and 10 normal-RI-NOS were identified as fulfilling the inclusion criteria and were analyzed. Considering symptoms before endoscopy, chest pain was more reported in NERD than in other cases (6/18 vs 5/50, P = 0.031). At long-term follow-up of 23 patients (8 NERD, 8 FH, 2 RH, and 5 normal-RI-NOS): 17 were on PPIs and 2 combined alginate, 1 (FH) was on benzodiazepine + anticholinergic, 1 (normal-RI-NOS) on citalopram, and 3 had no therapy. A complete symptom-resolution was observed in 5/8 NERD, in 2/8 FH, and in 2/5 normal-RI-NOS. Conclusions: FH may be the most common pediatric NEEP. At long-term follow-up, there was a trend toward a more frequent complete symptom resolution with PPI-therapy in NERD patients while other groups did not benefit from extended acid-suppressive-treatment.

Differences in salivary secretion and epidermal growth factor concentrations in mild reflux esophagitis and non-erosive reflux disease.

BACKGROUND: Sex differences in salivary secretion have been reported among healthy subjects. In the present study, salivary secretion and salivary epidermal growth factor (EGF) concentrations were investigated in mild reflux esophagitis patients, non-erosive reflux disease (NERD) patients, and healthy controls by matching the sex ratio. METHODS: Thirty-three (male:female = 11:22) patients with NERD, 33 (11:22) with mild reflux esophagitis, and 33 (11:22) healthy controls were recruited for this case-control study. Salivary secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount of saliva secretion, salivary pH, and salivary pH after acid loading as an index of the acid-buffering capacity were measured. Salivary EGF concentrations were measured by ELISA. RESULTS: No significant differences were observed in the amount of saliva secretion, salivary pH, or the acid-buffering capacity between the mild reflux esophagitis and NERD groups. However, the amount of saliva secretion and the acid-buffering capacity in the mild reflux esophagitis group and the amount of saliva secretion, salivary pH, and the acid-buffering capacity in the NERD group were significantly lower than those in the healthy control group. No significant differences were noted in salivary EGF concentrations between the mild reflux esophagitis and NERD groups. CONCLUSION: After matching the sex ratio, the saliva secretion was significantly lower in patients with mild reflux esophagitis and NERD than in healthy controls. However, no significant differences were observed in the amount of saliva secretion or salivary EGF concentrations between both groups.

Dynorphin participates in interaction between depression and non-erosive reflux disease.

BACKGROUND: To explore the relationships between anxiety/depression and NERD, we focused on dynorphin (Dyn), an important member of visceral hypersensitivity, and its related pathways. METHODS: Pearson's correlation analysis on patients with NERD and in vivo experiment on NERD rat model. Part 1: Pearson's correlation analysis among serum levels of Dyn, clinical symptoms and HADS scores of NERD patients were carried on. Part 2: Wistar rats were randomly divided into 2 groups: control group and model group. The data of pH value, immobility time, serum Dyn concentration, NMDAR1 and SP expression were, respectively, derived from automatic pH recorder, tail suspension test, enzyme-linked immunosorbent assay, immunohistochemistry and immunofluorescence. RESULTS: Part 1: Pearson's correlation analysis showed that there was a linear correlation between Clinical Symptom (CS) score and HADS score (HAD-A, HAD-D), and the correlation coefficients were 0.385 and 0.273 respectively; the correlation coefficient between lg (Dyn) and lg (CS score) was r = 0.441, P = 0.002; the correlation coefficient between lg(Dyn) and lg (HAD-D score) was r = 0.447, P = 0.002. Part 2: The pH value of the lower esophagus in the model group was lower than that in the control group (P < 0.01). The tail suspension immobility time of model group was significantly longer than that of control group (P < 0.01). The serum Dyn concentration and the expression level of NMDAR1 in spinal cord and SP in lower esophageal mucosa of model group were significantly higher than those of control group (P < 0.05). CONCLUSION: Increased serum dynorphin level may be a sign of correlation between depression and NERD.

Characteristics of reflux and manifestation under probe-based confocal laser endoscopy in patients with endoscopic negative heartburn / 中华消化内镜杂志

Objective:To study reflux characteristics of patients with endoscopic negative heartburn and their manifestation under probe-based confocal laser endoscopy (pCLE) based on the Rome Ⅳ standard.Methods:Thirty-six endoscopic negative outpatients with typical heartburn at the Department of Gastroenterology of the Second Affiliated Hospital of Baotou Medical College from September 2020 to March 2021 were included, and underwent 24-hour multichannel intraluminal impedance-pH monitor and pCLE. According to Rome Ⅳ diagnostic process, patients were divided into non-erosive reflux disease (NERD) group ( n=16), reflux hypersensitivity (RH) group ( n=8) and functional heartburn (FH) group ( n=12). The Gerd-Q scale score, 24-hour pH monitoring results and microstructure changes under pCLE were compared among the three groups. Results:There was no significant difference in the total score, positive symptom score, negative symptom score or positive influence score of Gerd-Q scale among the three groups ( P>0.05). DeMeester score [28.45 (20.08, 34.53)] and acid reflux times (24.88±9.05) in the NERD group were significantly higher than those in the RH group [7.30 (3.90, 11.38), P<0.001; 13.63±5.76, P=0.003] and FH group [6.90 (4.80, 9.73), P<0.001; 7.42±8.32, P<0.001]. But there was no significant difference between the RH group and the FH group ( P>0.05). The diameter of intra-papillary capillary loop (IPCL) (18.68±2.12 μm) and dilation of intercellular space (3.95±0.97 μm) in the NERD group were significantly higher than those in the RH group (13.91±1.99 μm, P<0.001; 2.97±0.55 μm, P=0.006) and FH group (13.83±2.00 μm, P<0.001; 2.31±0.54 μm, P<0.001), but there was no significant difference between the RH group and the FH group ( P>0.05). The number of IPCL in the NERD group, RH group and FH group were 2.0 (1.00, 2.75), 2.0 (1.00, 2.75) and 1.5 (1.00, 2.00), respectively with no significant difference ( P=0.697). Conclusion:Gerd-Q scale is not suitable for differential diagnosis of patients with endoscopic negative heartburn. Compared with functional esophageal diseases (RH and FH), acid reflux and mucosal microstructure changes are of more important pathogenic significance in NERD.

Advanced Endoscopy for Benign Esophageal Disease: A Review Focused on Non-Erosive Reflux Disease and Eosinophilic Esophagitis.

Advanced endoscopy (AVE) techniques include image-enhanced endoscopy methods, such as narrow-band imaging (NBI), and types of microscopic endoscopy, such as endocytoscopy. In the esophagus, AVE first showed diagnostic utility in the diagnosis of superficial esophageal cancer and was then applied to inflammatory disease. This review focuses on non-erosive reflux disease (NERD) and eosinophilic esophagitis (EoE), which sometimes show no abnormal findings on standard white light endoscopy alone. Studies have demonstrated that advanced endoscopy, including NBI magnification endoscopy and endocytoscopy, improved the diagnostic performance of white-light endoscopy alone for NERD and EoE. In this review, we explain why advanced endoscopy is needed for the diagnosis of these esophageal inflammatory diseases, summarize the study results, and discuss future perspectives.

Extrahepatic Manifestations in Alcoholic Liver Disease.

Though liver is the most commonly affected organ in patients with chronic and excessive intake of alcohol, no organ is immune to toxic effects of alcohol and patients with alcohol-related liver disease (ALD) can suffer from a wide list of extrahepatic manifestations involving gastrointestinal tract, central and peripheral nervous systems, cardio vascular system, musculo-skeletal system, disruption of nutritional status, endocrinological abnormalities, hematological abnormalities and immune dysfunction. These extrahepatic organ involvements are usually overlooked by hepatologists and physicians who are mostly focused on managing life threatening complications of ALD. As a result, there is delayed diagnosis, delay in the initiation of appropriate treatment and late referral to other specialists. Some of these manifestations are of utmost clinical importance (e.g. delirium tremans and Wernicke's encephalopathy) because an early diagnosis and treatment can lead to full recovery while delayed or no treatment can result in death. On the other hand, several extrahepatic manifestations are of prognostic significance (such as alcoholic cardiomyopathy and malignancies) in which there is an increased risk of morbidity and mortality. Hence, a clear understanding and awareness of the extrahepatic manifestations of ALD is quintessential for proper management of these patients.

A Study on the Correlation Between Endoscopic Findings and Symptoms of Gastroesophageal Reflux Disease (GERD).

Background Gastroesophageal reflux disease is a common disorder affecting a large section of the community. In addition, the numerous complications of chronic gastroesophageal reflux disease (GERD) necessitate adequate diagnosis and treatment of this common entity. Thus, to analyze the spectrum of GERD on the basis of symptoms and endoscopic findings along with the contributory effects of various risk factors including obesity, this specific study has been carried out. Study design A descriptive type of observational study was conducted on the patients visiting the outpatient department (OPD) at Acharya Vinoba Bhave Rural Hospital (AVBRH), affiliated with Datta Meghe Institute of Medical Sciences (DMIMS), Wardha, Maharashtra. The clinical symptoms, suspected risk factors, and endoscopic findings of the patients were studied, assessed, and correlated. Methods and material Patients, more than 18 years of age complaining of a minimum of two typical symptoms of GERD for at least one month, were included in the study. Demographic data, clinical symptomatology, and personal history of the patients were noted. All the patients were subjected to esophagogastroduodenoscopy, and findings were recorded. Correlation and analysis were done on clinical and endoscopic findings. Statistical analysis This descriptive study has been conducted after the approval of the Ethics Committee Department of Medical Education, Jawaharlal Nehru Medical College, Deemed University, Sawangi (DMIMS(DU)/IEC/Sept-2019/8403). The outcomes were recorded and analyzed at the end of the study using a Microsoft Excel Spreadsheet (version 16.40, Microsoft Corporation, Redmond, Washington, USA). Results and conclusion A total of 100 patients were included in the study. A number of male patients (58%) were more than that of female patients. Most of the patients were in the age group of 30-60 years (70%). The most common symptoms were epigastric pain (78%), regurgitation (71%), and heartburn (63%). Forty-five percent of the patients had erosive lesions suggestive of reflux esophagitis on endoscopic evaluation.

Nitric oxide and inducible nitric oxide synthase levels in EE and NERD patients.

Aim: This article aimed to evaluate nitric oxide (NO) and nitric oxide synthase (iNOS) markers in patients with erosive esophagitis (EE) and those with non-erosive reflux disease (NERD) and compare them with the control group. Background: Gastro-esophageal reflux disease (GERD) is one of the most common disturbances of the upper digestive tract. Inducible nitric oxide synthase (iNOS) is expressed in esophageal adenocarcinoma. NO, the product of this enzyme, has been implicated in the pathogenesis of this condition. Nevertheless, the data on whether iNOS and NO are expressed in the early stages of GERD is conflicting. Methods: In this study, tissue samples were obtained from fifty-four patients (27 with erosive esophagitis and 27 with non-erosive reflux disease) and 27 controls. Tissue concentrations of nitrite, nitrate, and iNOS were measured using Enzyme-Linked Immune-sorbent Assay (ELISA). The Bradford method was used to determine the protein concentration of samples. The results were analyzed by SPSS software (version 22.0). In multiple comparisons, the Tukey test was performed, and p < 0.05 was considered as the level of significance. Results: Tissue amounts of iNOS were significantly higher (p= 0.001) in EE patients compared with the control group. There was a significant difference (p= 0.01) in this factor between EE patients and patients with NERD. Moreover, tissue levels of nitrite and nitrate were significantly higher (p = 0.001) in patient groups compared with the control group. Conclusion: It was observed that NO and iNOS protein were increased in human esophagitis tissue. The results indicated that nitric oxide and iNOS levels are useful and effective markers in the pathogenesis of GERD. While the results are not certain, it is thought that a link exists between the expressions of iNOS and disease progression.

Effect of hiatus hernia on reflux patterns and mucosal integrity in patients with non-erosive reflux disease.

BACKGROUND: Hiatus hernia (HH) contributes to development of gastroesophageal reflux disease, Barrett's esophagus and esophageal adenocarcinoma. This study was aimed to investigate the influence of HH on reflux patterns and distal esophageal mucosal integrity in non-erosive reflux disease (NERD). METHODS: We retrospectively analyzed PPI-refractory NERD patients referred to three tertiary referral centers who underwent high-resolution manometry and off-PPI 24-h impedance-pH monitoring (with or without bile spectrophotometry). Patients with HH ≥2 cm (HH group, n = 42) or no HH (non-HH group, n = 40) with similar esophageal acid exposure time (AET 6%-12%) were included. KEY RESULTS: Age, gender, BMI, esophageal motility, AET, and esophageal clearance were similar between the two groups. The HH group had higher numbers of total reflux episodes (p = 0.015) with similar proportion of acid/non-acid reflux compared with the non-HH group. Mean nocturnal baseline impedance (MNBI) in the distal esophagus was significantly lower in the HH group than the non-HH group at both 5 cm (p = 0.002) and 3 cm (p = 0.015) above the lower esophageal sphincter. Multivariable regression analysis showed that HH, less non-acid reflux and lower post-reflux swallow-induced peristaltic wave index (PSPWI) were independently associated with lower MNBI. Among 31 patients tested with bile spectrophotometry, the HH group had significantly longer bile exposure time than the non-HH group (p = 0.011), and bile reflux inversely and significantly correlated with MNBI (rho = -0.75, p < 0.001). CONCLUSIONS AND INFERENCES: Hiatus hernia, less non-acid reflux and lower PSPWI were associated with lower MNBI. HH impairs distal esophageal mucosal integrity, the mechanism of which we speculate to be through excessive bile reflux.

Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021.

In Japan, with the increasing prevalence of gastroesophageal reflux disease (GERD) and growing public interest, the Japanese Society of Gastroenterology issued Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009 and a revised 2nd edition in 2015. A number of studies on GERD were subsequently conducted in Japan and abroad, and vonoprazan, a potassium-competitive acid blocker (P-CAB), became available for the first time in Japan in February 2015. The revised 3rd edition (Japanese edition), which incorporates new findings and information, was published in April 2021. These guidelines are summarized herein, particularly sections related to the treatment of GERD. The important clinical issues addressed in the present revision are (i) the introduction of treatment algorithms that classify GERD into reflux esophagitis and non-erosive reflux disease, (ii) the clarification of treatment algorithms based on to the severity of reflux esophagitis, and (iii) the positioning of vonoprazan in the treatment for GERD. The present guidelines propose vonoprazan as the initial/maintenance treatment for severe reflux esophagitis. They also recommend vonoprazan or PPI as an initial treatment for mild reflux esophagitis and recommended PPI and proposed vonoprazan as maintenance treatment. These updated guidelines offer the best clinical strategies for GERD patients in Japan and hope that they will be of global use for the diagnosis and treatment for GERD.

Determinants of reflux perception in patients with non-erosive reflux disease who have reflux-related symptoms on potassium-competitive acid blocker therapy.

BACKGROUND: This study investigated potential determinants of reflux perception in patients with non-erosive reflux disease (NERD) who had reflux-related symptoms on potassium-competitive acid blocker (P-CAB) therapy. METHODS: This study included 23 patients with reflux-related symptoms despite P-CAB therapy. Esophageal impedance-pH monitoring was performed on P-CAB and the following potential determinants of reflux perception were investigated: reflux nadir pH value; change in pH (baseline-nadir); bolus clearance time; reflux extent; proportions of acid, weakly acidic, and weakly alkaline reflux episodes; and proportions of liquid and mixed reflux episodes. RESULTS: Overall, ≥ 90% of all and symptomatic reflux episodes were weakly acidic reflux and 63% of symptomatic reflux episodes were reflux episodes with pH ≥ 5. There were no significant differences regarding potential determinants between symptomatic and asymptomatic reflux episodes. However, the proportion of symptomatic reflux episodes was significantly greater with pH < 5 (13.8%) than with pH ≥ 5 (9.5%) (P = 0.0431). In reflux episodes with pH < 5, the proportion of symptomatic reflux episodes was significantly greater in proximal sites (20.6%) than in distal sites (10.6%) (P = 0.0178). Conversely, in reflux episodes with pH ≥ 5, there was no significant difference regarding reflux perception according to reflux extent (proximal: 9.6% vs. distal: 9.0%, P = 0.9337). CONCLUSIONS: In patients with P-CAB-resistant NERD, reflux symptoms were mainly caused by reflux episodes with pH ≥ 5 on P-CAB therapy. The proportions of symptomatic reflux episodes among reflux sites differed according to reflux pH value; thus, the mechanisms of reflux perception may differ according to reflux pH value.

Correlation of Anxiety and Depression to the Development of Gastroesophageal Disease in the Younger Population.

Gastroesophageal reflux disease (GERD) is a condition characterized by the reflux of stomach contents into the esophagus, which leads to heartburn and regurgitation. GERD has been categorized its types according to severity. The categories that have been discussed in this study are reflux esophagitis (RE), non-erosive reflux disease (NERD), and Barrett's esophagus. Our study compared various studies and showed that the subjects with GERD had a high level of anxiety and depression. Gastroesophageal reflux disease has a significant negative impact on the quality of life (QoL) by perturbing daily activities. The majority of GERD patients use antacid drugs to control their acid symptoms. However, these symptoms are sometimes difficult to control, even with the most potent proton-pump inhibitors (PPIs), and these patients tend to have a lower response rate. According to the clinical data, Anxiety and Depression are linked to the development of GERD. A major focus of this study is to explore psychological influences such as anxiety and depression and how they relate to GERD. This study also reviews the effect of these conditions on the younger population. It is concluded that the quality of life (QoL) of subjects with GERD is reduced by depression and anxiety.

Comparison of esophageal motility and reflux characteristics of patients with endoscopic-negative heartburn based on the Lyon Consensus / 西安交通大学学报(医学版)

【Objective】 To explore the characteristics of esophageal motility and reflux of endoscopic-negative heartburn patients based on the Lyon Consensus Diagnostic Criteria and discuss the differential diagnosis value of the mean nocturnal baseline impedance （MNBI） and the postreflux swallow-induced peristaltic wave （PSPW） index for reflux hypersensitivity （RH） and functional heartburn （FH） patients. 【Methods】 We enrolled 132 patients with heartburn as the main symptom who visited the Gastroenterology Department of our hospital from January 2017 to June 2021， including 24 in the non-erosive reflux disease （NERD） group， 24 in the RH group， and 84 in the FH group. All the patients completed gastroscopy， esophageal high-resolution manometry and 24h-pH impedance monitoring. We analyzed and compared the related indexes of esophageal motility and reflux. The receiver operating characteristic （ROC） curve was used to analyze the esophageal proximal MNBI， distal MNBI， and PSPW indexes for the differential diagnosis of RH and FH. 【Results】 The lower esophageal sphincter （LES） average resting pressure， LES residual pressure and intact relaxation pressure （IRP） in NERD were lower than those in RH and FH （P0.05）. When the proximal MNBI， distal MNBI， and PSPW indexes were used alone respectively to diagnose RH， the area under the ROC curve was 0.480， 0.810， 0.682， respectively， with the sensitivities being 87.5%， 100% and 91.7%， and the specificities being 26.2%， 66.7% and 51.2%， respectively. 【Conclusion】 NERD patients have obvious abnormal esophageal dynamics， mainly manifested as LES relaxation， which further aggravates the pathological acid reflux， while patients with RH and FH are mainly exposed to physiological acid or non-acid reflux. In patients with endoscopic negative heartburn， distal MNBI value can improve the clinical diagnosis rate of RH and help distinguish RH from FH.

Gene expression profiling of inflammatory cytokines in esophageal biopsies of different phenotypes of gastroesophageal reflux disease: a cross-sectional study.

BACKGROUND: The clinical endoscopic phenotypes of gastroesophageal reflux disease (GERD) are classified as Barrett's esophagus (BE), erosive esophagitis (EE) and non-erosive gastroesophageal reflux disease (NERD). NERD is subclassified as abnormal acid exposure (AAE) and normal acid exposure (NAE) based on pH monitoring study results. The aim of this study was to characterize genes involved in the pathophysiology and immune response of GERD. METHODS: This is an observational and cross-sectional study. All patients with BE, EE, AAE, and NAE and a control group were subjected to superior endoscopy (with biopsies of esophageal mucosa). Relative mRNA quantification of cytokine and target genes was conducted by quantitative Polymerase Chain Reaction (RT-qPCR). Changes in the expression of genes associated with inflammation were assessed for each disease phenotype. Statistical analysis of differential gene expression was performed using the Mann-Whitney U non-parametric test. A p value < 0.05 was considered significant. RESULTS: A total of 82 patients were included and were divided into the following groups: Group BE, 16 (19.51%); Group EE, 23 (28.04%); Group AAE, 13 (15.86%); NAE 13 (15.86%); and Control Group, 17 (20.73%). Compared with the control group, patients with BE exhibited increased IL-8 expression (p < 0.05) and increased levels of IL-10, MMP-3, and MMP-9. Patients with EE exhibited increased levels of IL-1B, IL-6 and IL-10 (p < 0.05), and patients with AAE exhibited increased expression of IL-1B, IL-6, IFN-γ and TNF-α (p < 0.05). AAE exhibited increased IL-1B and TNF-α expression compared with NAE (p < 0.05). CONCLUSION: This study demonstrates the differential expression of mediators of inflammation in the esophageal mucosa of patients with different GERD endoscopic phenotypes. IL-1B and TNF-α could be useful to differentially diagnose AAE and NAE in the non-erosive phenotype using endoscopic biopsies.

Saliva secretion is reduced in proton pump inhibitor-responsive non-erosive reflux disease patients.

BACKGROUND: There is no consensus on the relationship between saliva secretion and non-erosive reflux disease (NERD). In this study, saliva secretion and salivary epidermal growth factor (EGF) in patients with NERD were examined. METHODS: Thirty-one PPI-responsive NERD patients and 31 control subjects were recruited for this case-control study. Saliva secretion testing was performed. Saliva secretion was assessed as follows: each patient chewed sugar-free gum for 3 min prior to endoscopy, and the amount and pH of saliva before and after acid loading as an index of the acid-buffering capacity were measured. The salivary EGF concentration was assessed by ELISA. RESULTS: The amount of saliva secreted was significantly lower in the NERD group than in the control group, with medians (25th-75th percentile) of 4.0 mL/3 min (2.0-6.0) and 6.0 (3.9-8.0), respectively (p = 0.0131). Salivary pH was significantly lower in the NERD group (7.0 [6.8-7.2]) than in the control group (7.2 [7.0-7.3], p = 0.0100). Salivary pH after acid loading was significantly lower in the NERD group (5.8 [5.4-6.2]) than in the control group (6.3 [6.1-6.5], p = 0.0002). The difference in pH of stimulated saliva after acid loading (1.2 [0.9-1.5], p = 0.0021) was significantly higher in the NERD group than in the control group (0.8 [0.7-1.1]). The salivary EGF concentration was significantly higher in the NERD group (2513.0 pg/mL [1497.5-5005.0] than in the PPI-responsive group (1641.0 [1139.8-2092.0], p = 0.0032). CONCLUSION: Stimulated saliva secretion was reduced in PPI-responsive NERD patients.