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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. [ABSTRACT FROM AUTHOR]

Aim. To determine the phenotypic variants of patients with symptoms of gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), hypersensitive esophagus (HSE), functional heartburn (FH) using 24-hour pH-impedance testing and high-resolution esophageal manometry (HSEM). Materials and methods. Fifty-five treatment-native symptomatic patients with newly diagnosed GERD and 48 control group subjects (CG) were examined. The mean age of the subjects was 45.0 years (95% confidence interval [CI] 41.0–48.9). Patients were grouped based on typical symptoms (heartburn, belching, regurgitation, odynophagy, dysphagia), medical history, endoscopy results, and 24-hour pH-impedance testing. Patients with typical symptoms of GERD and Grade B, C, D erosive esophagitis (EE) according to the Los Angeles Classification (LA) based on endoscopy were excluded from the further study. All patients without changes in the esophageal mucosa on endoscopy or with LA grade A EE (presumably NERD) underwent 24-hour pH-impedance testing and HSEM without proton pump inhibitors. Acid exposure, acid reflux count, symptom association with reflux (with symptom index and symptom association with reflux), mean nocturnal impedance, and post-reflux swallow-induced peristaltic wave index were assessed. The structure (presence or absence of a hiatal hernia) and function (presence or absence of the lower esophageal sphincter hypotonia) of the esophagogastric junction, as well as the motor function of the thoracic esophagus, were assessed using HSEM. The results of the HSEM were interpreted according to the Chicago Classification, 3rd edition (2015). Results. The number of acid refluxes in patients with NERD was 71.0 (95% CI 58.4–83.7), in subjects with HSE – 38.5 (95% CI 28.3–49.0), with FH – 13.0 (95% CI 6.5–18.2), in CG – 16.5 (95% CI 9.0–21.0). The average nocturnal basal impedance was 1300 ohms (95% CI 1000–1986) in patients with NERD, 1725 ohms (95% CI 1338–2261) in patients with HSE, 2760 ohms (95% CI 2453–3499) in FH, 2515 ohms (95% CI 2283–2700) in CG. The index of post-reflux swallow-induced peristaltic wave in patients with NERD was 61% (95% CI 57–71), with HSE – 85% (95% CI 82–88), with FH – 71% (95% CI 64–78), in CG – 66% (95% CI 63–69). Hiatal hernia and/or hypotonia of the LES were more common in patients with NERD (23%) than in CG (13.3%). Ineffective motility was detected in 34% of patients with NERD, in 23% of subject with FH and in 66.7% of patients with HSE. Conclusion. The results support the hypothesis that patients with GERD symptoms represent a heterogeneous population. 24-hour pH-impedance testing and HSEM helps to differentiate endoscopically negative patients with GERD symptoms and patients with Grade A EE by LA to NERD, HSE and FH.

Purpose of Review: In this manuscript, we aim to review the proposed mechanisms of the pathophysiology of functional heartburn (FH) and functional chest pain (FCP) as well as highlight the different neuromodulatory therapies available to providers and the evidence for each of them. Recent Findings: Understanding the basis for the symptoms that patients are presenting with is essential when evaluating patients with possible esophageal motility disorders or gastroesophageal reflux disease. Objective testing to understand these conditions is a key component to that understanding. Patients undergoing evaluation for heartburn or chest pain, following cardiac evaluation, often require a combination of endoscopy, esophageal manometry, and pH testing. Treatment for FH or FCP often involves some combination of neuromodulatory pharmacologic or behavioral therapies based on their understood pathophysiology. Summary: When a diagnosis of functional heartburn or functional chest pain is reached, it is important for the managing provider to understand the available therapeutic options. Often, treatment requires management with neuromodulation. [ABSTRACT FROM AUTHOR]

Background Purpose GI‐specific psychological factors are important contributors to patients' symptom experience and quality of life across all disorders of gut‐brain interaction (DGBI). Clinicians' ability to recognize the role of these psychological factors is essential for formulating a biopsychosocial case conceptualization and informing treatment decisions.This article will familiarize gastroenterology providers with conceptualizing the role of GI‐specific psychological factors in DGBI and provides stepwise, practical guidance for how to assess these during clinical encounters in a time‐efficient manner. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10 months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver-operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time

Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders in the world. Two parameters, mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPW), have been recently proposed to help differentiate GERD phenotypes. Our study aimed to assess whether there is any correlation between the two parameters, while also taking a look at their ability to distinguish between GERD phenotypes. We recruited 81 patients who were divided into 4 groups based on their GERD phenotype: erosive reflux disease (ERD), non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Both MNBI (AUROC 0.855) and PSPW (AUROC 0.835) had very good performances in separating ERD patients from non-ERD patients. PSPW (AUROC 0.784) was superior to MNBI (AUROC 0.703) in distinguishing NERD patients from patients with RH or FH. The PSPW index (AUROC 0.762) was more effective than MNBI (AUROC 0.668) in separating RH from FH. We found that PSPW and MNBI have a strong statistical correlation (Pearson correlation coefficient, r = 0.722, p < 0.001). Furthermore, PSPW predicted pathological MNBI (<2292 Ω) with good performance (AUROC 0.807). MNBI and PSPW are useful in distinguishing GERD phenotypes, with a strong correlation between the two parameters. [ABSTRACT FROM AUTHOR]

Background: Reflux hypersensitivity (RH) is characterized by normal esophageal exposure to acid and positive correlation of symptoms to reflux episodes. Positivity of Symptomatic Index (SI) and/or Symptom Association Probability (SAP) is used diagnostically, though experts support that concordance of both is needed. We evaluated differences among patients with RH and concordance of SI/SAP or not. Methods: Patients with typical reflux symptoms without previous GERD diagnosis, submitted simultaneously to Ph‐Impedance off PPI and high resolution manometry were included. Self‐response to PPI was evaluated. Patients showing SI and/or SAP positivity were considered having RH and further classified to definite RH if both SI/SAP were positive or indefinite if only one positive. Key Results: Totally 2659 patients (M/F: 35.6%/64.7%, mean age: 45 ± 14) were included. Final diagnosis was; FH: 21.8%, RH: 29.3% (definite: 14.3%/indefinite: 15%), GERD: 36% and inconclusive GERD: 12.9%. Patients with definite RH showed increased total reflux time, total number of reflux episodes and length of hiatus hernia, and also numerically but not statistically significant increased rates of PPI responsiveness versus indefinite RH and decreased mean nocturnal baseline impedance. Moreover, they showed significantly increased rate of PPI response versus patients with functional heartburn (FH). Conclusion & Inferences: Some PPI responsiveness is frequent among patients with RH as also with FH, and cannot discriminate those entities clinically when diagnosing RH using SI and/or SAP positive criterion. Patients with RH and SI/SAP concordance differ from patients without. Implementation of a strict RH definition (both SI and SAP positive) can better distinguish RH from FH and should be used in the future. [ABSTRACT FROM AUTHOR]

Physiological and psychological factors have been found to influence esophageal symptom reporting. We aimed to evaluate which of these factors are associated with 3 reflux symptom severity outcomes (ie, Total Reflux, Heartburn, and Sleep Disturbance) through a traditional statistical and a complementary machine-learning approach. Consecutive adult patients with refractory heartburn/regurgitation symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing past and current gastrointestinal and psychological health. In the traditional statistical approach, hierarchical general linear models assessed relationships of psychological and physiological variables (eg, total number of reflux episodes) with reflux severity scores. Mediation analyses further assessed pathways between relevant variables. In the machine-learning approach, all psychological and physiological variables were entered into 11 different models and cross-validated model performance was compared among the different models to select the best model. Three hundred ninety-three participants (mean [SD] age, 48.5 [14.1] years; 60% were female) were included. General psychological functioning emerged as an important variable in the traditional statistical approach, as it was significantly associated with all 3 outcomes and mediated the relationship between childhood trauma and both Total Reflux and Heartburn Severity. In the machine-learning analyses, general psychological variables (eg, depressive symptoms) were most important for Total Reflux and Sleep Disturbance outcomes, and symptom-specific variables, like visceral anxiety, were more influential for Heartburn Severity. Physiological variables were not significant contributors to reflux symptom severity outcomes in our sample across reflux classifications and statistical methodology. Psychological processes, both general and symptom-specific, should be considered as another important factor within the multifactorial processes that impact reflux symptom severity reporting across the reflux spectrum. This study found that psychological symptoms are significantly and independently associated with symptom severity reporting in a sample of patients with refractory heartburn/regurgitation symptoms. Meanwhile, physiological reflux variables showed no association. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIMS: Proton pump inhibitor (PPI) therapy fails to provide adequate symptom control in up to 50% of patients with gastroesophageal reflux symptoms. Although a proportion do not require ongoing PPI therapy, a diagnostic approach to identify candidates appropriate for PPI cessation is not available. This study aimed to examine the clinical utility of prolonged wireless reflux monitoring to predict the ability to discontinue PPIs. METHODS: This double-blinded clinical trial performed over 3 years at 2 centers enrolled adults with troublesome esophageal symptoms of heartburn, regurgitation, and/or chest pain and inadequate PPI response. Participants underwent prolonged wireless reflux monitoring (off PPIs for ≥7 days) and a 3-week PPI cessation intervention. Primary outcome was tolerance of PPI cessation (discontinued or resumed PPIs). Symptom burden was quantified using the Reflux Symptom Questionnaire electronic Diary (RESQ-eD). RESULTS: Of 128 enrolled, 100 participants met inclusion criteria (mean age, 48.6 years; 41 men). Thirty-four participants (34%) discontinued PPIs. The strongest predictor of PPI discontinuation was number of days with acid exposure time (AET) > 4.0% (odds ratio, 1.82; P < .001). Participants with 0 days of AET > 4.0% had a 10 times increased odds of discontinuing PPI than participants with 4 days of AET > 4.0%. Reduction in symptom burden was greater among the discontinued versus resumed PPI group (RESQ-eD, -43.7% vs -5.3%; P = .04). CONCLUSIONS: Among patients with typical reflux symptoms, inadequate PPI response, and absence of severe esophagitis, acid exposure on reflux monitoring predicted the ability to discontinue PPIs without symptom escalation. Upfront reflux monitoring off acid suppression can limit unnecessary PPI use and guide personalized management. (ClinicalTrials.gov, Number: NCT03202537).

Ambulatory esophageal pH monitoring is a diagnostic tool in patients with heartburn and regurgitation. The aim of this study is to evaluate 96-hour esophageal pH monitoring in patients with gastroesophageal reflux disease (GERD), at baseline and under diet that impedes GER. We hypothesized that diet would potentially reduce pathologic acid exposure time (AET). Retrospective series of 88 patients with GERD undergoing wireless 96-hour pH monitoring. Two-day (48 hours) tandem periods, one on liberal, followed by another on restricted diet assessed esophageal AET. Primary end point was >30% reduction in AET while on anti-GER diet. Of the 88 patients, 16 were excluded because of probe migration. Endoscopy and biopsies assessed erosive esophagitis (EE) and Barrett's esophagus (BE), or normal esophagus. Abnormal AET (% pH < 4.0 ≥ 6) further defined nonerosive reflux disease (NERD), whereas normal AET (% pH < 4.0 < 6) with normal endoscopy defined patients as functional heartburn (FH). There were 6 patients with EE (n  = 5) and BE (n  = 1), 23 with NERD and 43 with FH. Anti-GER diet led to >30% reduction in AET in EE and NERD patients, but not in those with FH. Most patients (n  = 43/72; 60%) had FH and could have avoided acid suppression. Furthermore, (14/23; 61%) of patients with NERD completely normalized AET with diet, potentially negating acid suppression. Ninety-six-hour esophageal pH distinguishes GERD patients from those with FH. Fifty percent of EE/BE patients and 61% of those with NERD completely normalize AET with diet. If pathologic AET occurs despite diet, acid suppression is indicated. [ABSTRACT FROM AUTHOR]

Background and study aims: The feasibility and barriars of escitalopram use in patients with functional gastrointestinal disorders (FGIDs) are still debated. We aimed to evaluate the feasibility, safety and efficacy and barriars of escitalopram use in managing FGIDs in the Saudi population. Patients and Methods: We included 51 patients who received escitalopram for irritable bowel syndrome (n = 26), functional heartburn (n = 10), globus sensation (n = 10) or combined disorders (n = 5). We used an irritable bowel syndromeseverity scoring system IBS-SSS), GerdQ questionnaire and Glasgow Edinburg Throat Scale (GETS) to assess disease severity change before and after treatment. Results: The median age was 33 years (25th-75th percentiles: 29-47), and 26 (50.98%) were males. Forty-one patients experienced side effects (80.39%), but most side effects were mild. The most common side effects were drowsiness/fatigue/dizziness (54.9%), xerostomia (23.53%), nausea/vomiting (21.57%) and weight gain (17.65%). IBS-SSS was 375 (255-430) and 90 (58-205) before and after treatment, respectively (p < 0.001). GerdQ score was 12 (10-13) before treatment and 7 (6-10) after treatment (p = 0.001). GETS score before treatment was 32.5 (21-46) and after treatment became 22 (13-31) (p = 0.002). Thirty-five patients refused to take the medications, and seven patients discontinued the medication. Possible causes of the poor compliance were fear of the medications and not being convinced of taking psychiatric medications for functional disorders (n = 15). Conclusion: Escitalopram could be a safe and effective treatment for functional gastrointestinal disorders. Targeting and managing factors leading to poor compliance could further improve the treatment outcome. [ABSTRACT FROM AUTHOR]

Patients with gastroesophageal reflux disease (GERD) present with heterogeneous symptoms, response to treatment, and physiologic profiles, requiring distinct and personalized management. This article provides a stepwise framework to phenotype GERD beginning with (1) characterization of symptom profile and response to acid suppression; (2) endoscopic evaluation of mucosal and anatomic integrity; (3) ambulatory reflux monitoring to characterize reflux burden and sensitivity; and (4) esophageal physiologic testing to assess gastroesophageal reflux mechanism and effectors of reflux clearance, and evaluate for alternate causes.

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. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10 months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver–operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time < 4% no GERD) and 50% with elevated acid exposure (GERD). Mean pepsin concentrations were significantly lower in the AM (22.6 ± 25.2 ng/mL) compared to post-prandial (44.5 ± 36.7 ng/mL) and PM (55.4 ± 47.0 ng/mL). Agreement between pepsin concentrations across 3 days was substantial for AM samples (kappa 0.61), with lower agreement for post-prandial and PM samples. A single AM pepsin concentration of 25 ng/mL was 67% accurate for GERD with 56% sensitivity and 78% specificity. This validation study highlights fair accuracy and performance characteristics of a single fasting AM salivary pepsin concentration for the diagnosis of GERD. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders in the world. Two parameters, mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPW), have been recently proposed to help differentiate GERD phenotypes. Our study aimed to assess whether there is any correlation between the two parameters, while also taking a look at their ability to distinguish between GERD phenotypes. We recruited 81 patients who were divided into 4 groups based on their GERD phenotype: erosive reflux disease (ERD), non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Both MNBI (AUROC 0.855) and PSPW (AUROC 0.835) had very good performances in separating ERD patients from non-ERD patients. PSPW (AUROC 0.784) was superior to MNBI (AUROC 0.703) in distinguishing NERD patients from patients with RH or FH. The PSPW index (AUROC 0.762) was more effective than MNBI (AUROC 0.668) in separating RH from FH. We found that PSPW and MNBI have a strong statistical correlation (Pearson correlation coefficient, r = 0.722, p < 0.001). Furthermore, PSPW predicted pathological MNBI (

The literature review focuses on the current understanding of visceral hypersensitivity mechanisms in the esophagus. Mechanisms of peripheral and central sensitization and their relation to heartburn symptoms are covered in detail. Diagnostic criteria and algorithms for non-erosive reflux disease, functional heartburn, and esophagus hypersensitivity based on pH-impedance testing and high-resolution esophageal manometry data are presented.

Background and study aims: The feasibility and barriars of escitalopram use in patients with functional gastrointestinal disorders (FGIDs) are still debated. We aimed to evaluate the feasibility, safety and efficacy and barriars of escitalopram use in managing FGIDs in the Saudi population.Patients and Methods: We included 51 patients who received escitalopram for irritable bowel syndrome (n = 26), functional heartburn (n = 10), globus sensation (n = 10) or combined disorders (n = 5). We used an irritable bowel syndrome-severity scoring system IBS-SSS), GerdQ questionnaire and Glasgow Edinburg Throat Scale (GETS) to assess disease severity change before and after treatment.Results: The median age was 33 years (25th- 75th percentiles: 29–47), and 26 (50.98%) were males. Forty-one patients experienced side effects (80.39%), but most side effects were mild. The most common side effects were drowsiness/fatigue/dizziness (54.9%), xerostomia (23.53%), nausea/vomiting (21.57%) and weight gain (17.65%). IBS-SSS was 375 (255–430) and 90 (58–205) before and after treatment, respectively (p < 0.001). GerdQ score was 12 (10–13) before treatment and 7 (6–10) after treatment (p = 0.001). GETS score before treatment was 32.5 (21–46) and after treatment became 22 (13–31) (p = 0.002). Thirty-five patients refused to take the medications, and seven patients discontinued the medication. Possible causes of the poor compliance were fear of the medications and not being convinced of taking psychiatric medications for functional disorders (n = 15).Conclusion: Escitalopram could be a safe and effective treatment for functional gastrointestinal disorders. Targeting and managing factors leading to poor compliance could further improve the treatment outcome.

Gastroesophageal reflux disease (GERD) is one of the most common causes of health care seeking at the primary care level in many countries. At an epidemiological level, GERD has been shown to be associated with a number of risk factors: obesity, tobacco smoking, alcohol abuse, certain patterns of eating behaviour, and the use of several medications. GERD is now regarded as a heterogeneous disease and includes different phenotypes (erosive reflux disease, non-erosive reflux disease, hypersensitive oesophagus, functional heartburn), the proper diagnosis of which improves the effectiveness of therapy in patients with heartburn symptoms. Daily impedance–pH monitoring is known to be an integral part of the diagnostic algorithm for GERD and is a functional diagnostic method to record all types of refluxes entering the oesophagus regardless of pH, to assess their association with symptoms, and to determine whether patients with heartburn symptoms belong to a particular phenotype. Esophageal manometry plays a key role in the evaluation of patients with heartburn symptoms, as it helps to rule out other conditions that may mimic GERD: achalasia cardia and scleroderma esophagus. This technique is used to assess thoracic esophageal motility and sphincter function and in the assessment of patients prior to antireflux surgery or in the refractory course of GERD. The article describes in detail GERD risk factors (triggers of heartburn), as well as diagnostic aspects, taking into account a differentiated approach to patients with heartburn based on daily impedance–pH monitoring data in accordance with the current guidelines and recommendations.

Digestive diseases are closely associated with mood disorders such as anxiety and depression, studies have shown that symptoms of mood disorders in most patients with digestive tract diseases often cannot be recognized by doctors by gastroenterologists, and 40–90% of patients with psychological problems do not receive proper medical services and treatment. Functional gastro-intestinal disorders (FSID) have a significant impact on daily activities and quality of life, and cause great economic hardship due to direct medical costs and loss of productivity. FGID are psychosomatic diseases that are divided into esophageal, gastroduodenal, intestinal, functional abdominal pain syndrome, biliary and anorectal disorders. The article provides various pathophysiological mechanisms for the development of psychosomatic FGID. The article also presents several typical clinical cases of FGID. The principles of treating these disorders with an emphasis on psychotropic therapy are described.

Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder posing diagnostic and therapeutic challenges. Diagnosis should be objectively defined with endoscopy and pH testing, while novel metrics may augment diagnosis for inconclusive GERD cases, including the postreflux swallow-induced peristaltic wave index and esophageal mucosal impedance. Conditions that overlap with or mimic GERD should be considered such as achalasia, rumination, and eosinophilic esophagitis. Genetic testing for proton pump inhibitor metabolism is an option for precision therapy in complex persistent GERD. Proton pump inhibitor refractory GERD may require medical, surgical, or endoscopic therapies. The presence of GERD should be objectively evaluated in achalasia patients treated with peroral endoscopic myotomy, and further studies are needed to determine timing of this evaluation. Patients with scleroderma are at a high risk for GERD owing to abnormal esophageal motility and should be managed with aggressive medical therapy and lifestyle changes given the high prevalence of esophagitis and Barrett’s esophagus in this population. Further studies are needed to understand the complex mechanisms of GERD in idiopathic pulmonary fibrosis and lung transplantation.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder. High-resolution esophageal manometry (HREM) and 24-h pH study help to properly evaluate GERD patients. The aim of the present study was to classify patients with refractory GERD symptoms into various groups based on endoscopic and physiological testing. The present study is a retrospective analysis of patients referred for HREM and 24-h pH recording between 2019 and 2021. We included all adult patients (age > 18 years) who were referred for evaluation of refractory GERD symptoms. Upper gastrointestinal endoscopy findings, HREM, and 24-h pH findings were noted. Patients were divided into erosive reflux disease (ERD), non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH) based on test results. Demographic details and HREM parameters were compared in the four groups. Statistics used are one-way analysis of variance (ANOVA) and Chi-squared tests. A p-value of <0.05 was considered statistically significant. A total of 144 patients were included—NERD (56, 38.9%), ERD (42, 29.2%), RH (28, 19.5%), and FH (18, 12.5%). Age (p 0.74), and sex distribution (p 0.47), and symptom profile (p 0.12) were similar. The presence of type 2/3 esophagogastric junction (EGJ) morphology was commoner in ERD and NERD (p <0.001). Moreover, the esophagogastric junction contractile integral (EGJ-CI) and basal inspiratory pressures were significantly lower in these two groups (p<0.05). EGJ-CI was low in 32 cases of ERD (76.2%), 41 cases with NERD (73.2%), 7 cases with RH (25%), and 3 cases with FH (16.7%), respectively (p-value < 0.00001). FH and RH account for 32% of cases with refractory GERD symptoms. Impaired EGJ function was more common in ERD and NERD patients compared to FH and RH patients. [ABSTRACT FROM AUTHOR]

Background: This review addresses the intricate spectrum of gastroesophageal reflux disease (GERD), a condition affecting 10-30% of the Western population. GERD is characterized by the backflow of gastric contents into the esophagus, causing typical and atypical symptoms. Its pathophysiology involves various factors such as hiatal hernia, esophageal motor disorders, and dietary triggers. The review explores the complexities of GERD spectrum, including nonerosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH)., Summary: The diagnostic process for GERD, based on the Lyon Consensus 2.0 criteria, encompasses clinical evaluation, endoscopy, and functional tests, including pH-impedance and wireless-pH monitoring. NERD, a significant subset of GERD, is defined by reflux symptoms and abnormal reflux burden without mucosal damage. RH, classified under functional esophageal disorders by Rome IV criteria, presents with typical esophageal symptoms associated with reflux but lacks of structural, inflammatory, or motor causes. FH is identified by heartburn with normal endoscopy, reflux testing, and esophageal manometry results. The management of RH and FH, focusing on reducing esophageal hypersensitivity, varies from standard GERD treatments., Key Messages: The review emphasizes the necessity of personalized treatment strategies due to the complexity and overlap of GERD subtypes. It highlights the importance of a multidisciplinary approach, involving gastroenterologists, psychologists, and other specialists, to improve patient outcomes and quality of life. The article underscores that understanding the distinctions and overlaps among NERD, RH, and FH is crucial for effective management, and the need for innovative approaches in diagnosis and treatment to address the unique challenges of each subtype., Competing Interests: E.M., A.P., F.C., M.R., A.M., and V.S. declared no conflict of interest. E.V.S. has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr. Falk, E.G. Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, J.B. Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Takeda, and Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, and Zeta Farmaceutici., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Aim: To determine the phenotypic variants of patients with symptoms of gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), hypersensitive esophagus (HSE), functional heartburn (FH) using 24-hour pH-impedance testing and high-resolution esophageal manometry (HSEM)., Materials and Methods: Fifty-five treatment-native symptomatic patients with newly diagnosed GERD and 48 control group subjects (CG) were examined. The mean age of the subjects was 45.0 years (95% confidence interval [CI] 41.0-48.9). Patients were grouped based on typical symptoms (heartburn, belching, regurgitation, odynophagy, dysphagia), medical history, endoscopy results, and 24-hour pH-impedance testing. Patients with typical symptoms of GERD and Grade B, C, D erosive esophagitis (EE) according to the Los Angeles Classification (LA) based on endoscopy were excluded from the further study. All patients without changes in the esophageal mucosa on endoscopy or with LA grade A EE (presumably NERD) underwent 24-hour pH-impedance testing and HSEM without proton pump inhibitors. Acid exposure, acid reflux count, symptom association with reflux (with symptom index and symptom association with reflux), mean nocturnal impedance, and post-reflux swallow-induced peristaltic wave index were assessed. The structure (presence or absence of a hiatal hernia) and function (presence or absence of the lower esophageal sphincter hypotonia) of the esophagogastric junction, as well as the motor function of the thoracic esophagus, were assessed using HSEM. The results of the HSEM were interpreted according to the Chicago Classification, 3rd edition (2015)., Results: The number of acid refluxes in patients with NERD was 71.0 (95% CI 58.4-83.7), in subjects with HSE - 38.5 (95% CI 28.3-49.0), with FH - 13.0 (95% CI 6.5-18.2), in CG - 16.5 (95% CI 9.0-21.0). The average nocturnal basal impedance was 1300 ohms (95% CI 1000-1986) in patients with NERD, 1725 ohms (95% CI 1338-2261) in patients with HSE, 2760 ohms (95% CI 2453-3499) in FH, 2515 ohms (95% CI 2283-2700) in CG. The index of post-reflux swallow-induced peristaltic wave in patients with NERD was 61% (95% CI 57-71), with HSE - 85% (95% CI 82-88), with FH - 71% (95% CI 64-78), in CG - 66% (95% CI 63-69). Hiatal hernia and/or hypotonia of the LES were more common in patients with NERD (23%) than in CG (13.3%). Ineffective motility was detected in 34% of patients with NERD, in 23% of subject with FH and in 66.7% of patients with HSE., Conclusion: The results support the hypothesis that patients with GERD symptoms represent a heterogeneous population. 24-hour pH-impedance testing and HSEM helps to differentiate endoscopically negative patients with GERD symptoms and patients with Grade A EE by LA to NERD, HSE and FH.

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（P<0. 05）. The number of acid reflux，the upright acid exposure time（AET）， the supine position AET，the total AET，and the DeMeester score were higher in NERD than in RH and FH（P<0. 05）. The non-acid reflux， distal MNBI and PSPW indexes were lower in NERD than in RH and FH（P<0. 05）. The distal MNBI and PSPW indexes were lower in RH than in FH（P<0. 05）. However， there was no significant difference in proximal MNBI among the three groups（P>0. 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. [ABSTRACT FROM AUTHOR]

One of the main symptoms of gastroesophageal reflux disease is heartburn, for the relief of which proton pump inhibitors are traditionally prescribed. However, there are frequent cases of heartburn, refractory to antisecretory therapy, when there is no complete relief of the symptom or only a partial clinical effect. The reason for an unsatisfactory response may be the functional genesis of heartburn. The purpose of the presented clinical observation is to demonstrate the heterogeneity of patients with heartburn, the role of functional research methods in the differential diagnosis of various conditions that accompany this symptom. A 42-year-old patient was admitted for an additional clinical examination with complaints of heartburn refractory to antisecretory therapy, which included high-resolution esophageal manometry, 24-hours pH-impedance. The manometric assessment of the structure and function of the lower esophageal sphincter, as well as the contractility of the thoracic esophagus, revealed no violations. The data of 24-hours pH-impedance demonstrated the absence of pathological reflux and the association of active symptoms with refluxes, which determined the functional nature of heartburn and explained the ineffectiveness of treatment with proton pump inhibitors. Heartburn can be functional in nature and significantly reduce the quality of life of patients. Functional heartburn requires different management tactics from gastroesophageal reflux disease, which is based on an adequate differential diagnosis, including functional research methods such as high-resolution esophageal manometry and 24-hours pH-impedance measurement, which allow to exclude other conditions accompanied by similar symptoms.

Background: Recently, Lyon consensus and ROME IV were published as there was a need to create a more objective evaluation for gastroesophageal reflux disease (GERD) in order to better predict treatment outcomes. However, with classical pH-impedance measures, some patients would still have diagnostic uncertainty, and new metrics, such as mean nocturnal basal impedance (MNBI), have emerged to corroborate with GERD diagnosis. The aim of the present study was to describe the prevalence of GERD, functional heartburn (FH), reflux hypersensitivity (RH), and undetermined diagnosis using current consensuses and to evaluate if MNBI could be considered a supportive measure for the diagnosis of GERD. Methods: Patients who underwent pH-multichannel intraluminal impedance (MII-pH) for suspected GERD between 2013 and 2018 were included. Subjects with previous diagnosis of GERD (e.g., esophagitis grade C or D according to Los Angeles classification, Barrett's esophagus, or peptic stricture), atypical symptoms, major esophageal motor disorder, eosinophilic esophagitis, or under proton pump inhibitor were excluded from the analysis. Results: We included 75 patients. The prevalence of GERD, FH, RH and undetermined diagnosis was 44%, 14.7%, 12%, and 29.3%, respectively. MNBI was lower in patients with GERD (GERD: 1,307.5 ± 817.9 Ω vs. FH: 3,039.6 ± 1,040.8 Ω, RH: 2,617.1 ± 1,342.2 Ω, undetermined: 2,351.9 ± 1,018.2, p < 0.001), although it was similar between patients with FH and RH (p = 0.44) or between undetermined diagnosis and FH/RH (p = 0.15). More patients with a GERD diagnosis had a MNBI under 2,292 Ω (GERD: 93.9% vs. non-GERD: 31.7%, p < 0.001). Conclusion: In our study, using MII-pH criteria, less than half of the patients had a GERD diagnosis. MNBI showed additional value as another metric for the diagnosis of GERD. [ABSTRACT FROM AUTHOR]

Background: Although rikkunshito was reported to be effective for treatment-resistant nonerosive gastroesophageal reflux disease (NERD), it is unclear which Rome IV subgroups of NERD patients benefit from rikkunshito. This study investigated the efficacy of rikkunshito in patients with functional heartburn. Methods: Ten patients with functional heartburn who experienced symptoms of dyspepsia were enrolled and received rikkunshito for 8 weeks. The Frequency Scale for Symptoms of GERD (FSSG), the Japanese translation of the Quality of Life in Reflux and Dyspepsia (QOLRAD-J) questionnaire, and the Hospital Anxiety and Depression Scale (HADS) before, and 4 and 8 weeks after, administration were evaluated. Overall treatment efficacy (OTE) was evaluated at 8 weeks after administration. Results: One patient voluntarily withdrew from treatment at 4 weeks. Total FSSG score was significantly (P = 0.039) lower 8 weeks after treatment or at discontinuation (13.2 ± 8.0) than before treatment (18.3 ± 10.7). Although QOLRAD-J score was higher 8 weeks after treatment or at discontinuation than before treatment, the difference was not significant different. HADS score was not significantly lower 8 weeks after treatment or at discontinuation, as compared with before treatment. However, total FSSG and HADS anxiety scores were positively correlated (correlation coefficient: 0.684, P = 0.027). Conclusions: The findings from this first study of the efficacy of rikkunshito for functional heartburn suggest that it might be effective in such patients. [ABSTRACT FROM AUTHOR]

Abstract Background Functional dyspepsia (FD), belching disorders (BD) and functional heartburn (FH) are the three most common upper functional gastrointestinal disorders (FGID) in IBS patients. FD is known to exert deleterious effects on health-related quality of life (HRQoL) and the psychological status of IBS patients; however, the impact of overlapping BD and FH on anxiety, depression and HRQoL of IBS patients remains unknown. This cross-sectional study was conducted to investigate the impact of overlapping FD, BD and FH on anxiety, depression and HRQoL in patients with IBS. Methods This study enrolled 319 consecutive outpatients with IBS from 2 tertiary hospitals in Beijing and Shijiazhuang of China. IBS, FD, BD and FH were diagnosed using the Rome III Criteria. Hospital Anxiety and Depression Scale and a 36-item Short-Form Health Survey (SF-36) were used to assess the psychological distress and HRQoL of patients respectively. Results Among the 319 patients with IBS, the IBS subtypes were diarrhoea (67%), constipation (16%), unsubtyped (12%) and mixed (5%). These IBS patients were further classified into IBS + FD, IBS + BD/FH (BD and/or FH), IBS + FD + BD/FH, or IBS only according to the patients’ overlapping upper GI symptoms. IBS+FD patients reported higher levels of anxiety than IBS+BD/FH and elevated depression scores than IBS only patients (P

Objectives: Esophagogastric junction contractile integral (EGJ‐CI) is a novel indicator to evaluate quantitatively the esophagogastric junction (EGJ) barrier function. We aimed to assess the role of EGJ‐CI in patients with refractory gastroesophageal reflux disease (GERD) symptoms and the correlation between EGJ‐CI and impedance‐pH monitoring characteristics. Methods: In total 82 patients with proton pump inhibitors (PPIs)‐refractory gastroesophageal reflux symptoms (heartburn or regurgitation) were enrolled. These patients were further divided into two groups based on their EGJ‐CI value (39 mmHg·cm). The mean nocturnal baseline impedance (MNBI) was measured to explore its association with EGJ‐CI. Results: The median EGJ‐CI in patients with PPI‐refractory symptoms was 30.8 mmHg·cm. EGJ‐CI was inversely correlated with acid exposure time and reflux episodes; while it was positively correlated with MNBI, distal contractile integral, lower esophageal sphincter basal pressure and integrated relaxation pressure. Patients were further divided into the high (n = 27) and low (n = 55) EGJ‐CI groups using a cut‐off value of 39.0 mmHg·cm. Patients with a low EGJ‐CI had a lower MNBI level than those with a high EGJ‐CI (2703 Ω vs 3545 Ω, P = 0.034). Conclusions: In patients with PPIs‐refractory symptoms, EGJ‐CI is associated with acid exposure and conventional high‐resolution manometry parameters. EGJ‐CI may play an important role in the diagnosis and treatment of patients with refractory GERD. [ABSTRACT FROM AUTHOR]

Background: When esophageal acid exposure time (AET) is physiologic, ROME IV stratifies functional esophageal disorders into functional heartburn (FH, with negative reflux‐symptom association) and reflux hypersensitivity (RH, with positive reflux‐symptom association), and hypothesizes that FH/RH could overlap with proven gastroesophageal reflux disease (GERD). We compared conventional FH/RH diagnosed off antisecretory therapy with overlap FH/RH coexisting with proven GERD. Methods: Adult patients with heartburn underwent pH‐impedance testing on therapy (proven GERD) and off therapy (unproven GERD) and completed validated questionnaires defining symptoms (Reflux Diagnostic Questionnaire, RDQ), affective state (Hospital Anxiety and Depression Scale, HADS; Visceral Sensitivity Index, VSI), and functional diagnoses (irritable bowel syndrome, IBS; functional dyspepsia, FD on ROME diagnostic questionnaire). AET (pathologic: >6%, physiologic <4%) and mean nocturnal baseline impedance (MNBI) were calculated. Clinical, psychological, and functional profiles were compared between FH and RH and to a comparison cohort of non‐erosive reflux disease (NERD, AET > 6%). Key Results: Study patients included 19 with RH (10 with overlap RH), 60 with FH (31 with overlap FH), and 26 patients with NERD. Clinical, psychological, and functional profiles of conventional FH/RH were similar to overlap FH/RH. Compared with NERD, combined FH and RH cohorts had higher anxiety scores, and lower proportions with IBS. Compared with FH with low MNBI, FH defined using both normal AET and normal MNBI had higher depression scores (p = 0.008), and trended toward higher anxiety scores (p = 0.059). Conclusions and Inferences: Conventional and overlap FH and RH have similar clinical, psychological and functional profiles, thereby proving ROME IV hypotheses. [ABSTRACT FROM AUTHOR]

Refractory gastroesophageal reflux disease is defined as heartburn that persists after 8 weeks of optimal proton pump inhibitors treatment. Two of its main causes are functional heartburn and reflux hypersensitivity defined in accordance to Rome IV's criteria, which are typical reflux signs and normal endoscopy (including biopsies), pH-impedance monitoring tests and high-resolution esophageal manometry. Functional heartburn has negative association indexes on the pH-impedance monitoring tests while reflux hypersensitivity has positive association indexes and both these pathologies represent more than 90% of all patients with heartburn that fail to a double dose proton pump inhibitors regime. They are more prevalent in middle aged women with other functional gastrointestinal disorders and they are associated to psychological comorbidities. Their treatment is based on neuromodulators such as tricyclic anti-depressants and selective serotonin reuptake inhibitors (SSRI). Surgical interventions may play a role in the treatment of reflux hypersensitivity but not in the case of functional heartburn. [ABSTRACT FROM AUTHOR]

Purpose of review: To use recent insights on the causes and treatment of PPI-refractory heartburn to formulate an effective approach to patient management. Recent findings: PPI-refractory heartburn results from 5 major potential mechanisms: (1) PPIs have not normalized esophageal acid exposure; (2) PPIs have normalized esophageal acid exposure, but there is reflux hypersensitivity in which persistent "physiologic" reflux events evoke heartburn; (3) the sensation of heartburn is caused by an esophageal disorder other than GERD (e.g., eosinophilic esophagitis, achalasia); (4) the sensation of heartburn is caused by an extra-esophageal disorder (e.g., heart disease, pancreaticobiliary disease); or (5) heartburn is functional. A systematic work-up that includes careful medical history, endoscopy with esophageal biopsy, esophageal manometry, and esophageal impedance-pH monitoring can distinguish among these mechanisms. Summary: A systematic work-up will reveal that GERD is not the cause of PPI-refractory heartburn in the large majority of cases. In the minority of patients for whom the work-up establishes that PPI-refractory heartburn is reflux-related, however, antireflux surgery is superior to medical therapy. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) is a common disorder, and empirical proton pump inhibitor (PPI) treatment is often the first step of management; however, up to 40% of patients remain symptomatic despite PPI treatment. Refractory reflux refers to continued symptoms despite an adequate trial of PPI, and management remains challenging. The differential diagnosis is important; other oesophageal (e.g. eosinophilic oesophagitis) and gastroduodenal disorders (e.g. functional dyspepsia) should be ruled out, as this changes management. A combination of clinical assessment, endoscopic evaluation and in selected cases oesophageal function testing can help characterize patients with refractory reflux symptoms into oesophageal phenotypes so appropriate therapy can be more optimally targeted. Medical options then may include adding a H2 receptor antagonist, alginates, baclofen or antidepressant therapy, and there is emerging evidence for bile acid sequestrants and diaphragmatic breathing. The demonstration of a temporal association of symptoms with reflux events on pH‐impedance testing (reflux hypersensitivity) serves to focus the management on modulating oesophageal perception and reducing the reflux burden, or identifies those with no obvious pathophysiologic abnormalities (functional heartburn). Anti‐reflux surgery based on randomized controlled trial evidence has a role in reflux hypersensitivity or continued pathological acid reflux despite PPI in carefully considered, fully worked up cases that have failed medical therapy; approximately two of three cases will respond but there is a small risk of complications. In patients with persistent volume reflux despite medical therapy, given the lack of alternatives, anti‐reflux surgery is a consideration. Promising newer approaches include endoscopic techniques. This review aims to summarize current diagnostic approaches and critically evaluates the evidence for the efficacy of available treatments. [ABSTRACT FROM AUTHOR]

The most recent iteration of the classifications for functional esophageal disorders, Rome IV, proposed relevant modifications of the previous definitions for Rome III. They specifically considered increased esophageal acid exposure as the marker of gastroesophageal reflux disease (GERD), including the remaining part of non-erosive reflux disease patients with normal acid in the group with functional alterations, considering both reflux hypersensitivity and functional heartburn. However, recent pathophysiological and therapeutic data suggest the need for a return to including reflux hypersensitivity in the GERD spectrum. Indeed, physiologic alterations in esophageal mucosal integrity and chemical clearance, the presence of microscopic esophagitis, and strict symptom-reflux association support the concept that reflux hypersensitivity pertains to GERD. Surgical anti-reflux therapy has resulted in positive outcomes, even in the long term, in patients with reflux hypersensitivity and not in those with functional heartburn. Moreover, clinical trials using neuromodulators have been scarce and provided conflicting results. As a result, the real progress of the Rome IV classifications is in dispute. This article aims to summarize the most recent knowledge of non-erosive reflux disease and reflux hypersensitivity to discuss the utility of Rome IV criteria in the identification and management of functional esophageal disorders. [ABSTRACT FROM AUTHOR]

The following factors of gastroesophageal reflux disease (GERD) pathogenesis are addressed in the abstract: activation of nociceptors, hyperexpression of pro-inflammatory cytokines and increase of functional activity of immune competent cells. The current classification of GERD is given which is based on identification of 4 phenotypes of the disease according to diagnostic criteria and prognosis of treatment effectiveness. Importance of pH-impedance monitoring in GERD diagnostics is demonstrated based on its primary significance for identification of reflux nature and determination of relationship between GERD symptoms and reflux. The diagnostics criteria of functional heartburn and hypersensitive oesophagus according to Rome IV criteria (2016) are presented. The data of the private investigation are demonstrated according to which irritated oesophagus was observed in 26.2% of healthy persons and in 24.2% of GERD patients with endoscopic or pH-metric symptoms of the disease. Implication of oesophagus clearance disorder in GERD pathogenesis has been pointed out. An overview of the current literature data about effectiveness of surgical treatment in patients with different GERD phenotypes and also assessment of clinical effectiveness of long-term treatment with PPI are given. Advantages of anti-secretory drug of the last generation rabeprazole in different patient groups and possibilities of its use in all GERD phenotypes have been discussed.

Background: Functional dyspepsia (FD), belching disorders (BD) and functional heartburn (FH) are the three most common upper functional gastrointestinal disorders (FGID) in IBS patients. FD is known to exert deleterious effects on health-related quality of life (HRQoL) and the psychological status of IBS patients; however, the impact of overlapping BD and FH on anxiety, depression and HRQoL of IBS patients remains unknown. This cross-sectional study was conducted to investigate the impact of overlapping FD, BD and FH on anxiety, depression and HRQoL in patients with IBS.Methods: This study enrolled 319 consecutive outpatients with IBS from 2 tertiary hospitals in Beijing and Shijiazhuang of China. IBS, FD, BD and FH were diagnosed using the Rome III Criteria. Hospital Anxiety and Depression Scale and a 36-item Short-Form Health Survey (SF-36) were used to assess the psychological distress and HRQoL of patients respectively.Results: Among the 319 patients with IBS, the IBS subtypes were diarrhoea (67%), constipation (16%), unsubtyped (12%) and mixed (5%). These IBS patients were further classified into IBS + FD, IBS + BD/FH (BD and/or FH), IBS + FD + BD/FH, or IBS only according to the patients' overlapping upper GI symptoms. IBS+FD patients reported higher levels of anxiety than IBS+BD/FH and elevated depression scores than IBS only patients (P< 0.05). The latter observation remained consistent after confounder-adjustment. The IBS + FD and IBS + FD + BD/FH groups exhibited statistically significant impairment in most of SF-36 scales, while the IBS + BD/FH group only showed lower HRQoL results in general health, when compared to the IBS only group. Multiple linear regression analysis demonstrated IBS + FD + BD/FH was linked to worse mental, physical and global HRQoL. Furthermore, IBS + FD was a strong predictor of poorer physical and global HRQoL compared to IBS only.Conclusions: Among the diarrhoea-prevalent IBS patients, those with concomitant FD experienced more psychological distress and demonstrated poorer physical HRQoL. Overlapping FD + BD/FH is a significant predictor of worse mental and physical HRQoL for IBS patients. The impact of concomitant BD and FH on the psychological status and HRQoL of IBS patients was limited. These findings implied that the overlapping upper FGIDs in IBS might be treated distinctively when developing comprehensive management strategies for IBS treatment. [ABSTRACT FROM AUTHOR]

A diagnosis of functional heartburn should be considered when retrosternal burning pain or discomfort persists despite maximal (double-dose) proton pump inhibitor (PPI) therapy taken appropriately before meals during a 3-month period. A diagnosis of functional heartburn requires upper endoscopy with esophageal biopsies to rule out anatomic and mucosal abnormalities, esophageal high-resolution manometry to rule out major motor disorders, and pH monitoring off PPI therapy (or pH-impedance monitoring on therapy in patients with proven gastroesophageal reflux disease [GERD]), to document physiologic levels of esophageal acid exposure in the distal esophagus with absence of reflux–symptom association (ie, negative symptom index and symptom association probability). Overlap of functional heartburn with proven GERD is diagnosed according to Rome IV criteria when heartburn persists despite maximal PPI therapy in patients with history of proven GERD (ie, positive pH study, erosive esophagitis, Barrett's esophagus, or esophageal ulcer), and pH impedance testing on PPI therapy demonstrates physiologic acid exposure without reflux–symptom association (ie, negative symptom index and symptom association probability). PPIs have no therapeutic value in functional heartburn, the exception being proven GERD that overlaps with functional heartburn. Neuromodulators, including tricyclic antidepressants, selective serotonin reuptake inhibitors, tegaserod, and histamine-2 receptor antagonists have benefit as either primary therapy in functional heartburn or as add-on therapy in functional heartburn that overlaps with proven GERD. Based on available evidence, acupuncture and hypnotherapy may have benefit as monotherapy in functional heartburn, or as adjunctive therapy combined with other therapeutic modalities. Based on available evidence, anti-reflux surgery and endoscopic GERD treatment modalities have no therapeutic benefit in functional heartburn and should not be recommended. [ABSTRACT FROM AUTHOR]

The focus on a symptom-based definition for gastroesophageal reflux disease (GERD) in adults and children has contributed to widespread use of acid suppression medications in patients with so-called typical reflux symptoms to treat the possibility of acid-mediated disease. Diagnostic testing with upper endoscopy, esophageal biopsies, ambulatory reflux monitoring, and/or esophageal manometry is often pursued when patients do not respond optimally to these medications. By using information from this diagnostic testing, GERD has shifted from a single diagnosis to a phenotypic spectrum, and each phenotype has unique pathophysiologic mechanisms driving symptom perception. Understanding these mechanisms is important to tailor individualized treatment plans and guide therapeutic interventions. The aim of this article is to discuss the different reflux phenotypes, the utility of esophageal reflux testing, the mechanisms underlying symptoms, and the management strategies for each phenotype. [ABSTRACT FROM AUTHOR]

ᅟRefractory GERD is very common, and while many different underlying mechanisms have been identified, the main focus has remained on residual reflux (acidic or non-acidic). Recently, Rome IV introduced two new concepts with important impact on patients with refractory GERD. They include the introduction of the reflux hypersensitivity group and the proposal that GERD can overlap with a functional esophageal disorder. Recent studies have demonstrated that the latter affects approximately three quarters of the GERD patients who failed PPI once daily. [ABSTRACT FROM AUTHOR]

Background: Combined 24-h intraesophageal pH-multichannel intraluminal impedance (24MII-pH) used for assessing gastroesophageal reflux disease by measuring baseline impedance (BI) requires a 24-h measuring period. In the present study, we developed a quick method of measuring BI and evaluated its usefulness in classifying patients with proton pump inhibitor (PPI)-refractory non-erosive reflux diseases (NERD) as having functional heartburn (FH) or endoscopic-negative reflux disease (ENRD). Methods: Ninety-one NERD patients without esophageal motility disorder underwent 24MII-pH monitoring while on a PPI. The measurements of the mean nocturnal BI (MNBI) and short MNBI were assessed at 3 times (at about 1: 00, 2: 00, and 3: 00 am) for 10 min and 30 s respectively. The measurement of the simple mean BI (MBI) was performed once 30 s at about 11: 00 am. Results: Ninety-one patients were divided into 2 groups: 59 with ENRD and 32 with FH. The cutoff, specificity, and sensitivity for distinguishing patients with FH were as follows: MNBI, 2,874.1 Ω, 72%, and 72%; short MNBI, 2,857.6 Ω, 74%, and 84%; and simple MBI, 2,874.1 Ω, 86%, and 78% respectively. Conclusion: Measuring the simple MBI is a quick method and is useful for distinguishing patients with FH from those in a cohort with PPI-refractory NERD. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlation between reflux disease and abnormal esophageal motility in patients with gastroesophageal reflux disease (GERD). Methods: Participants (patients with GERD and controls) who underwent 24‐h impedance‐pH monitoring (MII‐pH monitoring) and high‐resolution manometry between January 2012 and February 2017 were retrospectively studied. The patients were divided into two groups (acid reflux and nonacid reflux) based on their MII‐pH monitoring data. Reflux episodes, endoscopic findings, and esophageal dynamic parameters were assessed and compared. Results: A total of 142 patients were included (acid reflux [n = 58], nonacid reflux [n = 60], control group [n = 24]). There were more patients with esophagitis and more severe esophageal mucosal injury in the acid reflux group than in the nonacid reflux group. The acid reflux group had reduced lower esophageal sphincter (LES) basal pressure, shorter LES length, lower esophageal pressure and distal contractile integral index than the nonacid reflux group. Patients in the acid reflux group had more large breaks and a higher incidence of type II and III esophagogastric junction morphology than those in the nonacid reflux group. Acid exposure time, the incidence of long‐term acid reflux, recumbent acid reflux, and the incidence of acid and nonacid reflux had a significant negative correlation with esophageal body motility or LES function. Conclusion: This study suggests that an increase in esophageal acid exposure is correlated with an increase in esophageal dysmotility in patients with GERD. [ABSTRACT FROM AUTHOR]