Patients with typical reflux symptoms and normal acid exposure time (AET) are classified as either reflux hypersensitivity (RH) or functional heartburn (FH), some of whom respond to proton pump inhibitors (PPIs). We determined if esophageal psychophysiological parameters predict PPI response in symptomatic RH and FH patients.

We prospectively recruited adults with heartburn diagnosed with RH or FH on 24-h impedance-pH monitoring off PPI. Mucosal integrity was evaluated using mean nocturnal baseline impedance (MNBI). Symptom response required ≥50 % reduction in global symptom severity. Infusion of hydrochloric acid (0.1 N) into the mid-esophagus evaluated acid sensitivity, using time to initial typical symptom perception (lag time) and intensity rating. Factors influencing PPI response were identified using logistic regression.

Of 102 study participants (age 21-64 years, 69.6 % women, 54 RH, 48 FH), 37.3 % demonstrated PPI response (RH: 44.4 %, FH: 29.2 %, p = NS). On multivariable logistic regression, lower MNBI correlated with PPI response in both RH and FH, shorter lag time also correlated in RH. The optimal MNBI threshold for predicting PPI response was 2500 ohms.

Lower MNBI indicating mucosal acid damage, and esophageal acid sensitivity prompting early symptom reporting are physiomarkers of PPIs response in RH and FH patients.

Intestinal barrier function lies at a critical interface of a range of peripheral and central processes that influence disorders of gut-brain interactions (DGBI). Although rigorously tested, the role of barrier dysfunction in driving clinical phenotype of DGBI remains to be fully elucidated. In vitro, in vivo, and ex vivo strategies can test various aspects of the broader permeability and barrier mechanisms in the gut. Luminal mediators of host, bacterial, and dietary origin can influence the barrier function and a disrupted barrier can also influence the luminal milieu. Critical to our understanding is how barrier dysfunction is influenced by stress and other comorbidities that associate with DGBI and the crosstalk between barrier and neural, hormonal, and immune responses. Additionally, the microbiome's significant role in the communication between the brain and gut has led to the integrative model of a microbiome gut-brain axis with reciprocal interactions between brain networks and networks composed of multiple cells in the gut, including immune cells, enterochromaffin cells, gut microbiota and the derived luminal mediators. This review highlights the techniques for assessment of barrier function, appraises evidence for barrier dysfunction in DGBI including mechanistic studies in humans, as well as provides an overview of therapeutic strategies that can be used to directly or indirectly restore barrier function in DGBI patients.

Among the various factors implicated in the pathogenesis of gastroesophageal reflux disease (GERD), visceral hypersensitivity and mucosal resistance have been recently re-evaluated in relation to the increasing phenomenon of proton pump inhibitor failure, particularly in patients with nonerosive reflux disease (NERD). Intensive research has allowed us to understand that noxious substances contained in the refluxate are able to interact with esophageal epithelium and to induce the elicitation of symptoms. The frequent evidence of microscopic esophagitis able to increase the permeability of the mucosa, the proximity of sensory afferent nerve fibers to the esophageal lumen favoring the higher sensitivity to noxious substances and the possible activation of inflammatory pathways interacting with sensory nerve endings are pathophysiological alterations confirming that mucosal resistance is impaired in GERD patients. Accordingly, the reinforcement of protective mechanisms of esophageal mucosa by topical therapies has become a novel treatment target. Alginate, the combination of hyaluronic acid+chondroitin sulphate and Poliprotect have been shown to adhere to esophageal mucosa and to have good protective properties. Several placebo-controlled clinical trials have shown that these compounds, given alone or as add-on therapy for short periods, enable to relieve symptoms and to improve the quality of life in NERD patients. Further studies are needed to confirm the above results and to find new mucosal protectants in order to improve the management of NERD patients.

The results of empirical trials with proton pump inhibitors (PPIs) for management of gastro-oesophageal reflux-induced chronic cough (GERC) have resulted in considerable controversy, and the mechanism of PPI refractoriness remains unclear. Our study aims to identify the predictors of PPI refractoriness of GERC in a retrospective clinical study.

In total, 128 GERC patients were enrolled between March 2018 and October 2022. Regression analysis was utilised to create a model for predicting PPI-refractory of GERC using retrospective analysis of the general data and MII-pH indicators.

The post-reflux swallow induced peristaltic wave index (PSPWI) was lower in the PPI-refractory group than the PPI-responsive group (33.89±7.38 versus 39.45±9.47, respectively, p<0.001), as were the mean nocturnal baseline impedance (MNBI) and proximal MNBI (2092.11 (IQR: 652.23)] versus 2426.52 (IQR: 917.39) Ω, respectively, p=0.012; 1599.50 (IQR: 1206.63) versus 2274.50 (IQR: 1775.29) Ω, respectively, p=0.001). Multivariate logistic regression analysis identified the PSPWI (odds ratio 0.919, p=0.001) as an independent predictor of PPI-refractory GERC.

The diagnostic value of both proximal MNBI ≤39.90% and MNBI ≤2233.58 Ω had moderate sensitivity (71.67%) and specificity (75.00%) to identify PPI-refractory GERC.

Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases in the western world. Proton pump inhibitors (PPIs) are the cornerstone of GERD management however a subset of patients seeks for (natural) alternative therapies. Benesco™ is an over-the-counter supplement, of which the active ingredient is quercetin and has a presumed positive effect on esophageal barrier function. The aim of this study was therefore to evaluate the effect of benesco™ on esophageal sensitivity, mucosal barrier function, and reflux symptoms.

Patients with GERD were evaluated using acid perfusion tests, an upper endoscopy with electrical tissue impedance spectroscopy, and esophageal biopsies.

8 patients (3 men, median age 45 (34-64)) were included. The perfusion sensitivity score (PSS) did not change significantly after treatment with benesco™ (90.5 (21.4-129.7) to 62.5 (16.4-96.9) p = 0.123). Esophageal sensitivity based on the maximum reported VAS score during the esophageal acid perfusion test did not change significantly after treatment with benesco™ (7.4 (5.3-9.8) to 7.7 (5.3-8.7) p = 0.482). Furthermore, no effects were seen on measures of mucosal barrier function such as extracellular in vivo impedance (ETIS) (6807 (5153-8883) Ω·m vs 6702 (5106-7847) Ω·m, p = 0.575), in vitro transepithelial electrical resistance (TEER) (183 (153-204) Ω.cm2 vs 201 (128-250) Ω.cm2, p = 1.000), or fluorescein flux (896 (73-1922) nmol/cm2/h vs 811 (187-2693) nmol/cm2/h, p = 0.237).

We did not observe an improvement of acid perception, mucosal barrier function, or reflux symptoms by benesco™ in this study.

Dutch Trial Register number: NL9324.

Novel impedance pH monitoring parameters, such as mean nocturnal baseline impedance and post-reflux swallow induced peristaltic wave index, may be better markers for assessing chronic cough related to oesophageal hypersensitivity https://bit.ly/41woxTD.

Decrease of esophageal mean nocturnal baseline impedance reflects loss of mucosal integrity. It can predict response to anti-reflux therapy. Mean nocturnal baseline impedance after transoral incisionless fundoplication for gastroesophageal reflux disease has never been assessed. The aim of the study is to investigate mean nocturnal baseline impedance and conventional pathophysiological parameters following transoral incisionless fundoplication.

Patients prospectively treated by transoral incisionless fundoplication in a single center were retrospectively reviewed regarding 1- and 2-year 24-hour pH-metry and multichannel intraluminal impedance with calculation of mean nocturnal baseline impedance, gastroesophageal reflux disease-health related quality of life and reflux symptom index scores.

Thirty-eight and 17/38 patients with 1- and 2-year 24-hour pH-multichannel intraluminal impedance assessment and mean nocturnal baseline impedance's calculation after transoral incisionless fundoplication, respectively, were identified. Mean nocturnal baseline impedance significantly increased up to 2-year follow-up (P = 0.033), along with significant decrease in % of acid exposure time (P = 0.003), gastroesophageal reflux disease-health related quality of life score (P < 0.001), and reflux symptom index (P = 0.008), compared with baseline. The longest orthostatic reflux decreased too, approaching statistical significance (P = 0.054). These significant changes occurred in patients experiencing ≥ 50% reduction of symptom questionnaires' scores ("responders"). Conversely, mean nocturnal baseline impedance worsened and no significant changes of 24-hour pH-multichannel intraluminal impedance metrics were observed in "non-responder" patients (symptom questionnaires' scores decrease < 50%).ConclusionIn patients who responded a significant improvement of mean nocturnal baseline impedance and % acid exposure time was observed up to 2-year follow-up, suggesting that transoral incisionless fundoplication achieves an effective esophageal mucosa healing besides symptom improvement.

To evaluate the efficacy of distal esophageal mean nocturnal baseline impedance (MNBI), a general marker of esophageal mucosal barrier integrity, in predicting laryngopharyngeal reflux (LPR) and symptomatic response to acid reflux therapy.

This retrospective study analyzed 173 patients who presented with symptoms of laryngopharyngeal reflux and underwent 24-h multichannel intraluminal impedance-pH (MII-pH) testing. Mean nocturnal baseline impedance values were calculated and assessed for their association and ability to predict LPR symptoms, MII-pH results, treatment response, and other markers of LPR.

Notably, 153 of the 173 patients were tested off acid suppression medication and included in statistical analysis. Based on the MII-pH probe data, 108 (71%) patients had LPR, 8 (5%) had gastroesophageal reflux disease (GERD), and 37 (24%) were without pathologic reflux. Distal esophageal MNBI of LPR patients was significantly lower in LPR patients than patients with negative studies (1332 ± 94.8 vs. 2158 ± 173.5, p = 0.001). Among 118 patients who trialed antireflux therapy, a distal esophageal MNBI cutoff value of <1580 Ω was an independent predictor of treatment response (OR = 4.148 [1.877-9.189]). This value better predicted improvement with antireflux therapy for LPR than other objective MII-pH probe data, which were not independent predictors of treatment response.

Distal esophageal MNBI values may have value in the diagnosis of LPR and potentially predict medication responsiveness in LPR patients.

3 Laryngoscope, 134:4071-4077, 2024.

Mucosal impedance is a marker of esophageal mucosal integrity and a novel technique for assessing esophageal function and pathology. This article highlights its development and clinical application for gastroesophageal reflux disease (GERD), Barrett's esophagus, and eosinophilic esophagitis. A narrative review of key publications describing the development and use of mucosal impedance in clinical practice was conducted. A low mean nocturnal baseline impedance (MNBI) has been shown to be an independent predictor of response to anti-reflux therapy. MNBI predicts medication-responsive heartburn better than distal esophageal acid exposure time. Patients with equivocal evidence of GERD using conventional methods, with a low MNBI, had an improvement in symptoms following the initiation of PPI therapy compared to those with a normal MNBI. A similar trend was seen in a post fundoplication cohort. Strong clinical utility for the use of mucosal impedance in assessing eosinophilic esophagitis has been repeatedly demonstrated; however, there is minimal direction for application in Barrett's esophagus. The authors conclude that mucosal impedance has potential clinical utility for the assessment and diagnosis of GERD, particularly when conventional investigations have yielded equivocal results.

This study aims to enhance the effectiveness of high resolution manometry (HRM) and pH-impedance monitoring metrics in distinguishing between gastro-esophageal reflux disease (GERD) and non-GERD. A retrospective propensity score matching (PSM) study was conducted on 643 patients with GERD symptoms. PSM matched 134 GERD patients with 134 non-GERD controls. Body mass index (BMI), intra-esophageal pressure (IEP) and intra-gastric pressure (IGP) were significantly higher in the GERD group compared to the non-GERD group. BMI was correlated with IEP and IGP positively. IGP was positively correlated with esophagogastric (EGJ) pressure (EGJ-P) in participants with EGJ type 1 and 2, but not in participants with EGJ type 3. BMI was correlated with distal MNBI negatively. Logistic regression showed BMI as an independent risk factor for GERD. Receiver operating characteristic curve (ROC) and decision curve analysis (DCA) showed that BMI adjusted EGJ contractile integral (EGJ-CI) and BMI adjusted MNBI were superior to the corresponding original ones in predicting GERD susceptibility. According to the findings, BMI and IGP are the main factors contributing to the development of GERD. BMI affects IEP through the adaptive response of EGJ-P to IGP. Incorporating BMI into the calculations of EGJ-CI and MNBI can improve their ability in predicting GERD susceptibility.

Gastroesophageal reflux disease (GERD) remains a significant global health concern, with increasing prevalence and a substantial impact on quality of life. This narrative review explores recent advances in our understanding of GERD pathophysiology, diagnosis, and management. The complex interplay of factors contributing to GERD, including lower esophageal sphincter dysfunction, transient sphincter relaxations, and esophageal motility disorders, is discussed. Emerging diagnostic techniques, such as high-resolution manometry and impedance-pH monitoring, have enhanced our ability to accurately identify and characterize GERD. The review highlights the evolving landscape of GERD treatment, from conventional approaches like lifestyle modifications and proton pump inhibitors to novel strategies including potassium-competitive acid blockers, endoscopic therapies, and minimally invasive surgical techniques. The potential role of the microbiome in GERD pathogenesis and as a therapeutic target is examined. The concept of personalized medicine in GERD management is explored, considering genetic factors, biomarkers, and individual patient profiles. Complications of GERD, including erosive esophagitis, Barrett's esophagus, and esophageal adenocarcinoma, are reviewed, emphasizing the importance of early detection and appropriate management. The economic burden and impact on the quality of due to GERD are also addressed. This comprehensive review underscores the multifaceted nature of GERD and the need for a personalized, multidisciplinary approach to its management. It highlights ongoing research efforts and emerging therapies that promise to improve outcomes for GERD patients, while also identifying areas requiring further investigation to optimize diagnosis and treatment strategies.

Diagnosing gastroesophageal reflux disease (GERD) is sometimes challenging because the performance of available tests is not entirely satisfactory. This study aims to directly measure the esophageal mucosal impedance during upper gastrointestinal endoscopy for the diagnosis of GERD.

Sixty participants with typical symptoms of GERD underwent high-resolution esophageal manometry, 24-hour multichannel intraluminal impedance-pH monitoring, upper gastrointestinal endoscopy, and mucosal impedance measurement. Mucosal impedance measurement was performed at 2, 5, 10, and 18 cm above the esophagogastric junction during gastrointestinal endoscopy using a specific catheter developed based on devices described in the literature over the last decade. The patients were divided into groups A (acid exposure time < 4%) and B (acid exposure time ≥ 4%).

The mucosal impedance was significantly lower in group B at 2 cm (2264.4 Ω ± 1099.0 vs 4575.0 Ω ± 1407.6 [group A]) and 5 cm above the esophagogastric junction (4221.2 Ω ± 2623.7 vs 5888.2 Ω ± 2529.4 [group A]). There was no significant difference in the mucosal impedance between the 2 groups at 10 cm and 18 cm above the esophagogastric junction. Mucosal impedance value at 2 cm > 2970 Ω resulted in a sensitivity of 96.4% and a specificity of 87.5% to exclude GERD.

Direct measurement of mucosal impedance during endoscopy is a simple and promising method for diagnosing GERD. Individuals with an abnormal acid exposure time have lower mucosal impedance measurements than those with a normal acid exposure time.

The gut barrier is a sophisticated and dynamic system that forms the frontline defense between the external environment and the body's internal milieu and includes various structural and functional components engaged not only in digestion and nutrient absorption but also in immune regulation and overall health maintenance.

When one or more components of the intestinal barrier lose their structure and escape their function, this may result in a leaky gut. Mounting evidence emphasizes the crucial role of the gut microbiome in preserving the integrity of the gut barrier and provides insights into the pathophysiological implications of conditions related to leaky gut in humans. Assessment of intestinal permeability has evolved from invasive techniques to noninvasive biomarkers, but challenges remain in achieving consensus about the best testing methods and their accuracy. Research on the modulation of gut permeability is just starting, and although no medical guidelines for the treatment of leaky gut syndrome are available, several treatment strategies are under investigation with promising results.

This review discusses the composition of the intestinal barrier, the pathophysiology of the leaky gut and its implications on human health, the measurement of intestinal permeability, and the therapeutic strategies to restore gut barrier integrity.

Clinical practice guidelines drive clinical practice and clinicians rely to them when trying to answer their most common questions. One of the most important position papers in the field of gastro-esophageal reflux disease (GERD) is the one produced by the Lyon Consensus. Recently an updated second version has been released. Mean nocturnal baseline impedance (MNBI) was proposed by the first Consensus to act as supportive evidence for GERD diagnosis. Originally a cut-off of 2292 Ohms was proposed, a value revised in the second edition. The updated Consensus recommended that an MNBI < 1500 Ohms strongly suggests GERD while a value > 2500 Ohms can be used to refute GERD. The proposed cut-offs move in the correct direction by diminishing the original cut-off, nevertheless they arise from a study of normal subjects where cut-offs were provided by measuring the mean value ± 2SD and not in symptomatic patients. However, data exist that even symptomatic patients with inconclusive disease or reflux hypersensitivity (RH) show lower MNBI values in comparison to normal subjects or patients with functional heartburn (FH). Moreover, according to the data, MNBI, even among symptomatic patients, is affected by age and body mass index. Also, various studies have proposed different cut-offs by using receiver operating characteristic curve analysis even lower than the one proposed. Finally, no information is given for patients submitted to on-proton pump inhibitors pH-impedance studies even if new and extremely important data now exist. Therefore, even if MNBI is an extremely important tool when trying to approach patients with reflux symptoms and could distinguish conclusive GERD from RH or FH, its values should be interpreted with caution.

Post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI) are novel parameters reflect esophageal clearance capacity and mucosal integrity. They hold potential in aiding the recognition of gastroesophageal reflux-induced chronic cough (GERC). Our study aims to investigate their diagnostic value in GERC.

This study included patients suspected GERC. General information and relevant laboratory examinations were collected, and final diagnosis were determined following guidelines for chronic cough. The parameters of multichannel intraluminal impedance-pH monitoring (MII-pH) in patients were analyzed and compared to explore their diagnostic value in GERC.

A total of 186 patients were enrolled in this study. The diagnostic value of PSPWI for GERC was significant, with the area under the working curve (AUC) of 0.757 and a cutoff value of 39.4%, which was not statistically different from that of acid exposure time (AET) (p > 0.05). The combined diagnostic value of AET > 4.4% and PSPWI < 39.4% was superior to using AET > 4.4% alone (p < 0.05). Additionally, MNBI and distal MNBI also contributed to the diagnosis of GERC, with AUC values of 0.639 and 0.624, respectively. AET > 4.4% or PSPWI < 39.4% is associated with a 44% reduction in missed diagnoses of non-acid GERC compared to AET > 6.0% or symptom association probability (SAP) ≥ 95%, and may be more favorable for identifying GERC.

The diagnostic value of PSPWI for GERC is comparable to that of AET. Combining PSPWI < 39.4% or AET > 4.4% can improve the diagnostic efficiency by reducing the risk of missed diagnoses in cases where non-acid reflux is predominant. Distal MNBI and MNBI can serve as secondary reference indices in the diagnosis of GERC.

Chronic cough significantly impairs the quality of life. Although various studies focused on MNBI as assessed in the distal esophagus, scarce data are available on the clinical value of proximal measurements.

To investigate the role of proximal MNBI in the workup of patients with chronic cough and its ability to predict PPI response.

Demographic, clinical, endoscopy findings, impedance-pH and HRM tracings from consecutive cough patients were evaluated. MNBI was calculated at proximal and distal esophagus.

One hundred and sixty four patients were included. In addition to traditional variables, when considering also the PSPW index or MNBI at 3 cm or 15 cm, the proportion of patients with pathological impedance-pH monitoring significantly increased. 70/164 patients were responders, while 94 (57.3%) were non-responder to double PPI dose (p < 0.05). Patients with pathologic MNBI at 3 cm and/or 15 cm as well as those with pathologic PSPW index were characterized by a significantly higher proportion of responders than that observed among patients with normal impedance-pH variables (p < 0.001). The proportion of responders with pathological MNBI at 15 cm was significantly higher than the proportion of responders with pathological MNBI at 3 cm (82.8% vs. 64.3%, p < 0.05). At multivariable model, pathological MNBI at both 3 cm and 15 cm as well as PSPW index were associated with PPI responsiveness. The strongest association with PPI response was observed for MNBI at 15 cm.

The assessment of MNBI at proximal esophagus increases the diagnostic yield of impedance-pH monitoring and may represent a useful predictor of PPI responsiveness in the cumbersome clinical setting of suspected reflux-related cough.

It is thought that esophageal hypersensitivity in combination with an impaired mucosal barrier function contributes to PPI-resistant reflux symptoms. Ziverel, a bioadhesive agent that coats the esophageal wall, was shown to have a positive effect on reflux symptoms. However, the mechanisms of action are unclear. We aimed to assess the effect of Ziverel on esophageal sensitivity to acid and mucosal barrier function.

We performed a double-blind randomized placebo-controlled crossover trial in PPI-refractory patients with reflux symptoms. Patients were assigned (1:1) to 14 days of Ziverel followed by 14 days of placebo or opposite treatment order. The effect was evaluated using acid perfusion tests, an upper endoscopy with electrical tissue impedance spectroscopy (ETIS) and esophageal biopsies. The primary outcome was the esophageal sensitivity based on perfusion sensitivity score. Secondary outcomes included mucosal barrier function and reflux symptoms and correlations between the different outcomes.

Perfusion sensitivity score was not significantly different during treatment with Ziverel (106 (73-115)) and placebo (102 (67-110)) (p = 0.508) along with total RDQ score (2.6 (1.9-3.3) vs 2.8 (1.6-3.5) p = 0.456). ETIS showed comparable values during treatment with Ziverel (13514 (8846-19734)Ω·m) and placebo (13217 (9127-24942)Ω·m (p = 0.650)). Comparing Ziverel and placebo no difference was seen in transepithelial electrical resistance (TEER) 203 (163-267) Ω.cm2 vs 205 (176-240) Ω.cm2 (p = 0.445) and fluorescein flux 775 (17-6964) nmol/cm2/h vs 187 (4-12209) nmol/cm2/h (p = 0.638).

Ziverel did not show a benefit on acid sensitivity, reflux symptoms or esophageal mucosal integrity compared to placebo in PPI-refractory patients with reflux symptoms.Trial registration: Netherlands Trial Register number: NL7670.

Diagnosing gastroesophageal reflux disease (GERD) can be challenging given varying symptom presentations, and complex multifactorial pathophysiology. The gold standard for GERD diagnosis is esophageal acid exposure time (AET) measured by pH-metry. A variety of additional diagnostic tools are available. The goal of this consensus was to assess the individual merits of GERD diagnostic tools based on current evidence, and provide consensus recommendations following discussion and voting by experts.

This consensus was developed by 15 experts from nine countries, based on a systematic search of the literature, using GRADE (grading of recommendations, assessment, development and evaluation) methodology to assess the quality and strength of the evidence, and provide recommendations regarding the diagnostic utility of different GERD diagnosis tools, using AET as the reference standard.

A proton pump inhibitor (PPI) trial is appropriate for patients with heartburn and no alarm symptoms, but nor for patients with regurgitation, chest pain, or extraesophageal presentations. Severe erosive esophagitis and abnormal reflux monitoring off PPI are clearly indicative of GERD. Esophagram, esophageal biopsies, laryngoscopy, and pharyngeal pH monitoring are not recommended to diagnose GERD. Patients with PPI-refractory symptoms and normal endoscopy require reflux monitoring by pH or pH-impedance to confirm or exclude GERD, and identify treatment failure mechanisms. GERD confounders need to be considered in some patients, pH-impedance can identify supragrastric belching, impedance-manometry can diagnose rumination.

Erosive esophagitis on endoscopy and abnormal pH or pH-impedance monitoring are the most appropriate methods to establish a diagnosis of GERD. Other tools may add useful complementary information.

Supragastric belching (SGB) and aerophagia are behavioral disorders characterized by air induced esophageal distension. SGB is known to be associated with Gastro Esophageal Reflux Disease (GERD). Low Mean Nocturnal Baseline Impedance (MNBI) values support GERD diagnosis. We aimed to assess if chronic esophageal distension by air affects the esophageal mucosa integrity by assessing changes in MNBI.

In a single-center database study, we searched retrospectively for patients with a diagnosis of pathological SGB (n = 146) or aerophagia (n = 34) based on impedance-pH reflux monitoring. During the examined period, patients with a conclusive negative diagnosis of SGB and no evidence of aerophagia were used as a control cohort (n = 191). MNBI at 3, 5, and 17 cm over Lower Esophageal Sphincter (LES) was evaluated. GERD was diagnosed if acid exposure time (AET) >6%. All impedance studies of included patients were prospectively reevaluated.

GERD was diagnosed in 31.7% patients with SGB, a rate not different in comparison to patients without SGB (30.8%, p = 0.906). MNBI at 3 and 5 cm above the LES was significantly decreased among patients with SGB. SGB was not correlated with MNBI at 3 cm over the LES, (p: 0.086 OR: 1.000 95% CI: 0.999-1.001) when using multivariate analysis. Moreover no difference was spotted as far as MNBI at 3, 5, and 17 cm over the LES is concerned among patients with or without aerophagia.

Even if patients with SGB do show lower MNBI values, esophageal distention due to excessive air movement does not directly lead to impairment of esophageal mucosa integrity.

Gastroesophageal reflux disease (GERD) is common, with increasing worldwide disease prevalence and high economic burden. A significant number of patients will remain symptomatic following an empiric proton pump inhibitor (PPI) trial. Persistent symptoms despite PPI therapy are often mislabeled as refractory GERD. For patients with no prior GERD evidence (unproven GERD), testing is performed off antisecretory therapy to identify objective evidence of pathologic reflux using criteria outlined by the Lyon consensus. In proven GERD, differentiation between refractory symptoms (persisting symptoms despite optimized antisecretory therapy) and refractory GERD (abnormal reflux metrics on ambulatory pH impedance monitoring and/or persistent erosive esophagitis on endoscopy while on optimized PPI therapy) can direct subsequent management. While refractory symptoms may arise from esophageal hypersensitivity or functional heartburn, proven refractory GERD requires personalization of the management approach, tapping from an array of non-pharmacologic, pharmacologic, endoscopic, and surgical interventions. Proper diagnosis and management of refractory GERD is critical to mitigate undesirable long-term complications such as strictures, Barrett's esophagus, and esophageal adenocarcinoma. This review outlines the diagnostic workup of patients presenting with refractory GERD symptoms, describes the distinction between unproven and proven GERD, and provides a comprehensive review of the current treatment strategies available for the management of refractory GERD.

The Lyon consensus classifies the evidence of gastroesophageal reflux (GERD) based on endoscopic features and results of pH/impedance monitoring (pH-MII) including the post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI). The Wingate consensus established criteria to reduce inter-reviewer variability when assessing reflux episodes and PSPWI by impedance. This study aims to assess the influence of the Wingate criteria on the different pH-MII parameters obtained by automated analysis.

Thirty consecutive pH-MII off PPI were reviewed according to Wingate criteria. Number of impedance episodes and PSPWI were compared before and after censoring from automatic analysis. Reflux categorization according to Lyon consensus between censored and uncensored data was compared. Pearson correlations between impedance parameters and censored episodes were calculated.

Censoring the tracings significantly reduced the number of reflux episodes (66 [42-90.25] vs. 44.5 [21.5-61.5], p = 0.0105). Reasons for censoring were as follows: 1/ anterograde episode: 9.5 [6-13], 2/ impedance drop <50%: 1 [0-3], 3/ duration <4 s: 1 [0-2], 4/ <2 distal channels: 2.5 [1-4], and 5/ artifacts: 2 [1-5]. Censored episodes were in majority non-acid (16.5 [13-26.5] vs. 2 [0-4], p < 0.00001). Censoring altered the categorization of impedance episodes (<40 episodes, 6 vs. 13 for resp. uncensored vs. censored tracings, 40-80 episodes: 13 vs. 13, and >80 episodes: 11 vs. 4, p = 0.0264), but not the symptom index, the symptom association probability, or the categorization according to the Lyon consensus. Nevertheless, individual tracings were affected. The percentage of censored episodes was inversely correlated with the number of acidic impedance episodes (r = -0.62, p = 0.0002).

Manual interpretation of impedance tracings based on the Wingate consensus reduces the number of impedance episodes, impacting on reflux categorization. Acidic reflux episodes are less likely to be censored, harboring a potential at improving automatic pH-MII analysis.

Reflux hypersensitivity (RH) is one of the phenotypes of gastroesophageal reflux disease. The latest Rome IV defines RH as a condition with typical reflux symptoms and positive reflux-symptom association despite normal acid exposure. Subsequently, the Lyon consensus proposed detailed cutoff values for the criteria on the basis of experts' consensus. Rome IV brought a clear-cut perspective into the pathophysiology of gastroesophageal reflux disease and the importance of esophageal hypersensitivity. This perspective can be supported by the fact that other functional gastrointestinal disorders such as irritable bowel syndrome and functional dyspepsia often overlap with RH. Although several possible pathophysiological mechanisms of esophageal hypersensitivity have been identified, there is still unmet medical needs in terms of treatment for this condition. This review summarizes the current knowledge regarding RH.

Gastroesophageal reflux disease (GERD) is one of the most prevalent gastrointestinal diseases in the western world. Lifestyle modifications and proton pump inhibitors (PPIs) form the basis of the management of GERD. A subset of patients seeks for (natural) alternative therapies besides PPIs. benesco™ is an over-the-counter nutrition based on quercetin which has a presumed positive effect on esophageal barrier function. Therefore we aim to assess the effect of benesco™ on reflux symptoms.

We performed a double-blind randomized placebo-controlled trial in participants with reflux symptoms. Participants were assigned randomly (1:1) to receive 6 weeks of benesco™ (three times daily one lozenge containing 200 mg of quercetin) or placebo. The primary outcome was treatment success (≥50% reduction in Reflux Disease Questionnaire Score). Secondary outcomes included GERD-related quality of life, reflux-free days and nights, and participant-reported treatment success.

One hundred participants were randomized. Treatment success was seen in 18 (39%) of 46 participants in the intervention group versus 21 (47%) of 45 in the placebo group (p = 0.468). In the intervention group 10 (1-21) reflux-free days were reported compared to 10 (2-25) in the placebo group (p = 0.673). In addition, 38 (34-41) versus 39 (35-42) reflux-free nights were reported (p = 0.409).

In our trial benesco™ showed no significant benefit over placebo at group level.

Low mean nocturnal baseline impedance (MNBI) values support gastroesophageal reflux disease (GERD) diagnosis. Recent data denote that age and obesity may affect MNBI. We aimed to evaluate diagnostic MNBI cutoffs as also the effect of aging and body mass index (BMI) on MNBI.

In total 311 patients (M/F: 139/172, mean age: 47 ± 13) referred for typical GERD symptoms that have undertaken both high-resolution manometry (HRM) and pH-Impedance studies off PPI were evaluated. MNBI at 3, 5, and 17 cm over lower esophageal sphincter (LES) were evaluated. GERD was diagnosed if acid exposure time (AET) >6%.

Mean BMI was 26.6 ± 5.9 kg/cm2 . GERD was diagnosed in 39.2% and 13.5% had inconclusive GERD. MNBI was correlated to patients' age, BMI, AET, and the length of LES-CD separation and at 3 cm also to the total number of reflux and LES hypotension. In the multivariate analysis MNBI at 3 and 5 cm was independently correlated only to age, BMI, and AET. Patients with definite GERD showed lower MNBI at 3 cm compared with inconclusive GERD though both showed lower values when compared with GERD absence. At 3 cm MNBI ability for diagnosing GERD was good (0.815, p < 0.001 95% CI: 0.766-0.863) with an optimal cutoff point of 1281 Ohm.

According to our study findings age and BMI affect independently lower esophageal MNBI values in patients evaluated for GERD. MNBI significantly aids toward GERD diagnosis though in a real-life setting MNBI values much lower than the one previously proposed should be used.

The incidence of obesity in the population is gradually increasing. Obesity can cause a variety of complications in the digestive system such as gastroesophageal reflux disease, and impacts the integrity of the esophageal mucosal barrier and esophageal motility. However, not many studies have focused on the effect of varying degrees of obesity on the esophagus. A total of 611 participants were included in this study. We divided them into three groups according to their body mass index (BMI): the normal weight group, the overweight group, and the obesity group. We performed a retrospective comparison between groups based on indicators from high resolution esophageal manometry (HREM) and 24-hour pH impedance monitoring, and did a correlation analysis on multiple indicators such as esophageal mucosal barrier, esophageal motility, and acid reflux. The mean nocturnal baseline impedance (MNBI) in the overweight and obesity groups was lower than that in the normal group. The MNBI of the subjects in Z5-Z6 channels in the overweight group was significantly lower than that in the normal group. With respect to Z3-Z6 channels, MNBI values in the obesity group were significantly lower than those in the normal group. 'The acid exposure time (AET), the DeMeester scores (DMS) and 24-hour total reflux episodes was significantly higher in the obesity group than those in the normal and overweight groups. The upper esophageal sphincter (UES) residual pressure, and intrabolus pressure (IBP) in the overweight and obesity groups were significantly higher than those in the normal group. In addition, lower esophageal sphincter (LES) resting pressure, and esophagogastric junction contractile integral (EGJ-CI) in the obesity group were significantly higher than those in the normal group. We found that increase in body weight affected the integrity of esophageal mucosa, and different degrees of increase associated with different degrees and different aspects of changes in esophageal motility.

Gastroesophageal reflux disease (GERD) has the highest prevalence among diseases of the digestive system and is characterized by a significant decrease in patients' quality of life, comparable to arterial hypertension and coronary heart disease. One in every ten cases of reflux esophagitis leads to the formation of Barrett's esophagus, which is associated with a high risk of esophagus adenocarcinoma. The key factors determining the progression of the disease are the frequency and duration of the reflux of the stomach's contents. As a result, refluxate, which includes hydrochloric acid, pepsin, and, in the case of concomitant duodeno-gastric reflux, bile acids and lysolecithin, is thrown into the overlying sections of the digestive tract. At the same time, in addition to aggression factors, it is necessary to take into account the state of resistance in the esophageal mucosa to the effects of aggressive refluxate molecules. This review was prepared using systematized data on the protective properties of the esophageal mucosa and modern methods to assess the mucosal barrier in reflux esophagitis. Lesions of the epithelial barrier structure in the esophagus are recognized as the main pathogenetic factor in the development of reflux esophagitis and are a potentially significant therapeutic target in the treatment of GERD and Barrett's esophagus. This article presents the characteristics of the esophageal mucosal barrier and the protective mechanisms of the esophagus's mucous membrane in conditions of gastroesophageal reflux. Diagnostic approaches for assessing the course of reflux esophagitis are described for both histological criteria and the possibility of a comprehensive assessment of the state of mucins, tight-junction proteins, and the proliferative activity of the mucosa, including under the conditions of ongoing therapy.

Impairment of esophageal mucosal integrity as assessed by low mean nocturnal baseline impedance (MNBI) measured in the distal esophagus increases the diagnostic yield of impedance-pH in patients with inconclusive GERD diagnosis as defined by Lyon criteria.

To assess the diagnostic yield of MNBI measurement in the proximal esophagus, and its relationship with PPI response.

Expert review of off-therapy impedance-pH tracings from consecutive patients with heartburn, 80 responders and 80 non-responders to label-dose PPI. Data were compared to those from 36 healthy controls using ROC analysis. Multivariate analysis was performed to measure the strength of association of MNBI with PPI response.

A threshold value of 2665 Ω was defined for proximal MNBI by ROC analysis, affording 91.7% sensitivity and 86.5% specificity. Proximal and distal MNBI were significantly lower in non-responder cases as compared to responders. Adding proximal MNBI positivity to pathologic (>6%) acid exposure time (AET) and positive symptom-reflux association, the proportion of patients with abnormal impedance-pH findings increased from 74/160 (46%) to 106/160 (66.3%) (p = 0.0016). Among the 12 patients with pathologic proximal MNBI as the only positive impedance-pH finding, 9 cases (75%) were PPI responders. According to multivariate analysis, AET and pathological distal and proximal MNBI were significantly associated with PPI response, the strongest association observed for proximal MNBI.

Impedance baseline assessment in the proximal esophagus may increase the diagnostic yield of impedance-pH monitoring. Heartburn response to PPI is directly related to ultrastructural mucosal damage in the distal and in the proximal esophagus as well.

Inflammatory bowel diseases (IBD) represent a global phenomenon, with a continuously rising prevalence. The strategies concerning IBD management are progressing from clinical monitorization to a targeted approach, and current therapies strive to reduce microscopic mucosal inflammation and stimulate repair of the epithelial barrier function. Intestinal permeability has recently been receiving increased attention, as evidence suggests that it could be related to disease activity in IBD. However, most investigations do not successfully provide adequate information regarding the morphological integrity of the intestinal barrier. In this review, we discuss the advantages of confocal laser endomicroscopy (CLE), which allows in vivo visualization of histological abnormalities and targeted optical biopsies in the setting of IBD. Additionally, CLE has been used to assess vascular permeability and epithelial barrier function that could correlate with prolonged clinical remission, increased resection-free survival, and lower hospitalization rates. Moreover, the dynamic evaluation of the functional characteristics of the intestinal barrier presents an advantage over the endoscopic examination as it has the potential to select patients at risk of relapses. Along with mucosal healing, histological or transmural remission, the recovery of the intestinal barrier function emerges as a possible target that could be included in the future therapeutic strategies for IBD.

Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near future.

Gastroesophageal reflux disease (GORD) affects up to 20% of Western populations, yet sensory mechanisms underlying heartburn pathogenesis remain incompletely understood. While central mechanisms of heartburn perception have been established in earlier studies, recent studies have highlighted an important role of neurochemical, inflammatory, and cellular changes occurring in the oesophageal mucosa itself. The localization and neurochemical characterisation of sensory afferent nerve endings differ among GORD phenotypes, and could explain symptom heterogeneity among patients who are exposed to similar levels of reflux. Acid-induced stimulation of nociceptors on pain-sensing nerve endings can regulate afferent signal transmission. This review considers the role of peripheral mechanisms of sensitization in the amplification of oesophageal sensitivity in patients with GORD.

The clinical management of nonacid gastroesophageal reflux-induced chronic cough (GERC) is challenging, and patient response to standard antireflux therapy (omeprazole 20 mg twice daily plus mosapride 10 mg thrice daily) is suboptimal. This study aimed to identify predictors of standard antireflux therapy efficacy and provide evidence for standardized management algorithms of nonacid GERC.

A total of 115 nonacid GERC patients who underwent multichannel intraluminal impedance-pH monitoring (MII-pH) were enrolled between March 2017 and March 2021. Retrospective analysis of general information and MII-pH indications were used to establish a regression analysis model for multiple factors affecting standard antireflux therapy efficacy.

90 patients met the inclusion criteria, and the overall response rate to standard antireflux therapy was 55.5% (50/90). The mean nocturnal baseline impedance (MNBI) (1817.75 ± 259.26 vs. 2369.93 ± 326.35, P = 0.030) and proximal MNBI (1833.39 ± 92.16 vs. 2742.57 ± 204.64, P ≤ 0.001) of responders were lower than those of nonresponders. Weakly acid reflux (56.00 (31.70, 86.00) vs. 14.00 (14.00, 44.20), P = 0.022), nonacid reflux (61.35 (15.90.86.50) vs. 21.60 (0.00, 52.50), P = 0.008), and proximal extent (19.00 (5.04, 24.00) vs. 5.50 (2.56, 11.13), P = 0.011) were markedly higher in responders than nonresponders. Proximal MNBI (OR = 0.997, P = 0.042, and optimal cutoff = 2140 Ω) and weakly acid reflux (OR = 1.051, P = 0.029, and optimal cutoff = 45) were independent predictors of standard antireflux therapy efficacy. The combination predictive value did not show better results than either individual predictor.

Proximal MNBI < 2140 Ω may be used to screen patients with nonacid GERC suitable for standard antireflux therapy and in standardized management algorithms for nonacid GERC. In the absence of MNBI, weakly acid reflux > 45 can be used as an auxiliary indicator.

Impedance-pH monitoring allows evaluation of esophageal chemical clearance, a response to reflux elicited by the esophago-salivary reflex, by means of the post-reflux swallow-induced peristaltic wave (PSPW) index; mucosal integrity can be evaluated by means of mean nocturnal baseline impedance (MNBI) and is regarded as a GERD marker. Currently, the relationship between PSPW index and MNBI has not yet been fully investigated and represents the aim of the present study.

Impedance-pH tracings from consecutive patients were reviewed. ROC analysis and multivariate regression models were generated to evaluate the association between acid exposure time (AET), total refluxes (TRs), PSPW index, and MNBI. Patients were classified by means of AET thresholds and symptom-reflux association indexes into conclusive and inconclusive GERD, reflux hypersensitivity (RH), and functional heartburn (FH). Pathologic MNBI <2292 Ω was defined according to published outcome studies.

Two hundred and thirty patients constituted the study cohort. Overall, a significant direct correlation was observed between PSPW index and MNBI (0.759, p < 0.001). At ROC analysis, a PSPW index cut-off value of 53% was the best discriminator between normal from pathologic MNBI values (sensitivity 88%, specificity 86.4%). Considering AET cut-off of 4% or 6%, a sensitivity of 80.7% and 46% and a specificity of 62.5% and 93.2% were found, respectively. According to multivariate analysis, AET >4% and PSPW index value <53% or <61% were significantly associated with pathologic MNBI values.

Esophageal chemical clearance is a major defense mechanism against reflux and its impairment represents a major determinant of reflux-associated mucosal damage.

At present, there are few studies related to mean nocturnal baseline impedance (MNBI), esophageal dynamic reflux monitoring, high-resolution esophageal manometry (HRM) parameter indexes, and its diagnostic value in gastroesophageal reflux disease (GERD).

To analyze the factors influencing MNBI and examine the diagnostic value of MNBI in GERD.

A retrospective analysis on 434 patients with typical reflux symptoms who underwent gastroscopy, 24-hour multichannel intraluminal impedance and pH monitoring (MII/pH) and HRM. They were divided into the conclusive evidence group (103 cases), borderline evidence group (229 cases), and exclusion evidence group (102 cases) according to the level of diagnostic evidence of GERD based on the Lyon Consensus. We analyzed the differences in MNBI, esophagitis grade, MII/pH and HRM index among the groups; the correlation between MNBI and the above indexes and its influence on MNBI; and to evaluate the diagnostic value of MNBI in GERD.

There were significant differences in MNBI, Acid Exposure Time (AET) 4%, DeMeester score, and total reflux episodes among the three groups (P< 0.001). EGJ contractile integral (EGJ-CI) of the conclusive evidence group and the borderline evidence group was significantly lower than that in the exclusion evidence group (P< 0.001). MNBI was significantly and negatively correlated with age, BMI, AET 4%, DeMeester score, total reflux episodes, EGJ classification, esophageal motility abnormalities, and esophagitis grade (all P< 0.05), and significantly and positively correlated with EGJ-CI (P< 0.001). Age, BMI, AET 4%, EGJ classification, EGJ-CI, and esophagitis grade had significant effects on MNBI (P< 0.05); MNBI was used to diagnose GERD with a diagnostic cutoff of 2061 Ω, and AUC was 0.792 (sensitivity 74.9%, specificity 67.4%); MNBI was used to diagnose exclusion evidence group with a diagnostic cutoff of 2432 Ω, AUC was 0.774 (sensitivity 67.6%, specificity 72%).

AET, EGJ-CI, and esophagitis grade are the most important influence factors of MNBI. MNBI has good diagnostic value in identifying conclusive GERD.

Eosinophilic esophagitis (EoE) is the second most common cause of chronic esophageal inflammation after GERD, with increasing incidence and prevalence across all age groups. Since current diagnosis and follow up of EoE require endoscopy with biopsies, there is an increased interest in non or less invasive tests for its diagnosis and follow up. Baseline mucosal impedance measurement allows evaluation of mucosal barrier properties and is widely accepted as an adjunct method in GERD diagnosis. As EoE is associated with increased mucosal permeability, the use of baseline impedance to evaluate mucosal integrity has been investigated in several studies. It was found that baseline mucosal impedance, measured either during 24 h reflux monitoring or during endoscopy, was significantly lower in all parts of the esophagus in EoE patients. Impedance measurement correlated with eosinophil counts on biopsies, offering a tool to monitor treatment response. Additionally, baseline impedance patterns differed between those responding to proton pump inhibitor (PPI) treatment and those resistant to PPI, potentially allowing to tailor future treatment to the individual patient. In summary, baseline impedance measurement offers a potential tool for diagnosis and follow up in EoE. Its exact place in EoE treatment is yet to be determined and requires further future studies.

Obesity is a risk factor for gastroesophageal reflux disease. Studies addressing the brain-esophagus axis in obese are lacking. In obese with and without heartburn, we assessed: (i) the brain responses to esophageal acid perfusion during functional brain imaging; (ii) esophageal impedance baseline before and after acid perfusion; and (iii) abdominal fat distribution. In this exploratory study, 26 obese underwent functional magnetic resonance imaging (fMRI) of the brain combined with esophageal acid perfusion. Esophageal impedance baseline was determined before and after fMRI, followed by tomographic quantification of the abdominal fat. Among 26 obese (54% men, 39.7 years old, 33.5 kg/m2), there were 17 with heartburn and 9 without heartburn. Before fMRI, the esophageal impedance baseline was lower in obese with heartburn than without heartburn (median 1187 vs. 1890 Ω; P = 0.025). After acid perfusion, impedance baseline decreased in obese with heartburn (from 1187 to 899 Ω; P = 0.011) and was lower in this group than in obese without heartburn (899 vs. 1614 Ω; P = 0.001). fMRI task-residual analysis showed that obese with heartburn presented higher functional connectivity in several brain regions than obese without heartburn. Abdominal fat area did not differ between obese with and without heartburn either for total (72.8 ± 4.4% vs. 70.3 ± 6.0%; P = 0.280), subcutaneous (42.2 ± 9.0% vs. 37.4 ± 9.0%; P = 0.226), or visceral (30.6 ± 7.9% vs. 33.0 ± 7.8%; P = 0.484). In subjects with obesity, the brain-esophagus axis is disrupted centrally with higher functional brain connectivity and peripherally with decreased esophageal mucosa integrity in the presence of heartburn.

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).

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.

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 &lt; 0.001).

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.

Gastroesophageal reflux disease (GERD), a disorder resulting from the retrograde flow of gastric contents into the esophagus, affects an estimated 10-30% of the Western population, which is characterized by multifactorial pathogenesis. Over the past few decades, there have been many aspects of uncertainty regarding GERD leading to an ongoing interest in the field as reflected by a large number of publications, whose heterogeneity and variable quality may present a challenge for researchers to measure their scientific impact, identify scientific collaborations, and to grasp actively researched themes in the GERD field. Accordingly, we aim to evaluate the knowledge structure, evolution of research themes, and emerging topics of GERD research between 2012 and 2022 with the help of bibliometric approaches.

The literature focusing on GERD from 2012 to 2022 was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection. The overall publication performance, the most prolific countries or regions, authors, journals and resources-, knowledge- and intellectual-networking, as well as the co-citation analysis of references and keywords, were analyzed through Microsoft Office Excel 2019, CiteSpace, and VOSviewer.

A total of 8,964 publications were included in the study. The USA published the most articles (3,204, 35.74%). Mayo Clin ranked first in the number of articles published (201, 2.24%). EDOARDO SAVARINO was the most productive author (86, 0.96%). The most productive journal in this field was SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES (304, 3.39%). AMERICAN JOURNAL OF GASTROENTEROLOGY had the most co-citations (4,953, 3.30%). Keywords with the ongoing strong citation bursts were transoral incision less fundoplication, eosinophilic esophagitis, baseline impedance, and functional heartburn.

For the first time, we obtained deep insights into GERD research through bibliometric analysis. Findings in this study will be helpful for scholars seeking to understand essential information in this field and identify research frontiers.

Gastroesophageal reflux disease (GERD) is still a challenging and difficult to treat condition in children. Although acid suppression represents the mainstay of treatment in adolescents, it is not devoid of adverse events, especially in the long-term.

In this investigation we explored a new therapeutic avenue in GERD, that is esophageal mucosal protection.

To this end, we performed an investigator-initiated, retrospective study to evaluate the efficacy and safety of a short-term treatment with Esoxx™ medical device in 25 adolescents with GERD-related symptoms. This mucoadhesive formulation contains two natural mucopolysaccharides (sodium hyaluronate and chondroitin sulphate) and adheres to the esophageal mucosa, exerting a protective effect against refluxed gastric contents and allowing mucosal healing.

Heartburn, epigastric burning and post-prandial regurgitation were scored with a pain VAS scale and re-evaluated after 3-week treatment with Esoxx (one stick post-prandially, three times daily).

All patients completed the treatment without adverse effects and with good tolerability and compliance. All the three major symptoms significantly (p<0.001) improved after treatment. No patient required additional investigation (i.e. upper Gastrointestinal endoscopy) or medication (i.e. antisecretory drugs).

The results of this pilot study suggest that esophageal mucosal protection is a promising therapeutic avenue for GERD also in children. Provided, these data be confirmed by a large, randomized clinical trial, this medical device can enter our therapeutic armamentarium against this challenging disease.

Gastroesophageal reflux disease (GERD) is a common disease with increasing prevalence worldwide. However, the diagnosis of GERD is challenging because there are no definite gold standard criteria. Recently, a novel impedance parameter, namely mean nocturnal baseline impedance (MNBI), has been proposed, which reflects the burden of longitudinal reflux and the integrity of esophageal mucosa. MNBI has shown an immense promise for increasing the diagnostic rate of multichannel intraluminal impedance-pH (MII-pH) monitoring and predicting the response to proton pump inhibitor (PPI) or anti-reflux intervention in patients with reflux symptoms. The present paper reviews the association between baseline impedance and esophageal mucosal integrity, the acquisition of MNBI in 24-h MII-pH monitoring, the clinical utilization of MNBI in improving the diagnosis rate of GERD in patients with typical reflux symptoms, predicting the response to PPI or anti-reflux treatment in these patients, the utilization of MNBI in diagnosing patients with atypical symptoms or extra-esophageal symptoms, and the correlation between reflux burden and MNBI. MNBI should be routinely assessed using MII-pH monitoring.

An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ.

Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised.

Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO).

This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.

Intestinal epithelium functions as a tissue barrier to prevent interaction between the internal compartment and the external milieu. Intestinal barrier function also determines epithelial polarity for the absorption of nutrients and the secretion of waste products. These vital functions require strong integrity of tight junction proteins. In fact, intestinal tight junctions that seal the paracellular space can restrict mucosal-to-serosal transport of hostile luminal contents. Tight junctions can form both an absolute barrier and a paracellular ion channel. Although defective tight junctions potentially lead to compromised intestinal barrier and the development and progression of gastrointestinal (GI) diseases, no FDA-approved therapies that recover the epithelial tight junction barrier are currently available in clinical practice. Here, we discuss the impacts and regulatory mechanisms of tight junction disruption in the gut and related diseases. We also provide an overview of potential therapeutic targets to restore the epithelial tight junction barrier in the GI tract.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder that requires repeat endoscopic evaluation(s) to assess response to treatment. This results in high health care costs and a procedural burden in affected children. Noninvasive alternate modalities to reassess disease activity have not been established. Low baseline impedance measured by multichannel pH impedance (pH-MII) is seen in adults with EoE, in keeping with poor mucosal integrity. We aimed to investigate the relationship between esophageal eosinophilia (or severity of eosinophilic infiltration) and baseline impedance in children with EoE.

We retrospectively identified 15 children diagnosed with EoE at our institution who had undergone pH-MII within 30 days of 3-level esophageal biopsy. This group were not concurrently prescribed proton pump inhibitors and had negligible reflux parameters on pH-MII. Average impedance baseline was calculated upper, mid, and lower esophageal segments via baseline impedance automated analysis (RIAA) and mean nocturnal baseline impedance (MNBI) methods. Eosinophil count data for upper, mid, and lower esophageal segments in the EoE group was collated.

A significantly lower baseline impedance was seen across the esophageal length in children with EoE, compared with 30 controls who had no differences in age or reflux burden on nonparametric testing. A relationship between baseline impedance and eosinophil number at corresponding esophageal segments was not established.

Baseline impedance may be an important, less invasive adjunct in clinical practice to monitor treatment response in children with EoE. Larger prospective cohort studies should delineate optimally predictive baseline impedance thresholds for active and inactive disease.