The Revised Reflux Symptom Index (R-RSI): Development, Internal and External Validation Study.

INTRODUCTION: This study proposes a revised version of the Reflux Symptom Index (R-RSI), a seventeen-item questionnaire that was revised to increase the suspicion of laryngopharyngeal reflux disease (LPRD). METHODS: Internal validation involved 213 participants, comprising 160 subjects without a previous LPRD diagnosis and 53 subjects with a self-reported previous diagnosis of LPRD with or without gastroesophageal reflux disease (GERD). Test-retest reliability and internal consistency were calculated. For the external validation, 56 patients (independent from the previous cohort) were enrolled to explore the R-RSI screening properties and determine a cutoff using 24-h MII-pH as the gold standard. RESULTS: R-RSI test-retest reliability was high, both for the total score (ICC: 0.970) and for each item (ranging from 0.876 to 0.980). Cronbach's alpha was 0.910, indicating excellent internal consistency of the questionnaire. Participants with a previous self-reported diagnosis scored significantly higher (mean 24.94 ± 7.4; median 26, IQR 20-29) than those without a previous diagnosis (mean 4.66 ± 5.3; median 4, IQR 1-6) (p value <0.0001). Participants with both previous LPRD and GERD diagnoses had higher scores (27.20 ± 7.8) compared to those with only LPRD (21.77 ± 5.5) (p value = 0.003). Using 24-h MII-pH diagnosis as a gold standard, the optimal R-RSI cutoff point was determined to be 18, with a sensitivity of 84.5% and a specificity of 81.8%, positive predictive value of 95%, and negative predictive value of 60%. CONCLUSIONS: Our results suggest that the R-RSI may be useful to suspect LPRD, with or without GERD. The R-RSI is a self-administered patient-reported outcome questionnaire that demonstrates excellent reliability and high screening properties. Employing a cutoff of ≥18 in the R-RSI can assist in diagnosing and monitoring LPRD.

Study on Nocturnal Infant Crying Evaluation (NICE) and Reflux Disease (RED).

BACKGROUND: Nocturnal infant crying is often empirically treated with acid suppressants. The aim of this study was to evaluate the prevalence and characteristics of gastroesophageal reflux (GER) in infants with unexplained persistent crying. METHODS: We enrolled all infants (0-12 months) referred for suspected GER disease who underwent esophageal impedance-pH monitoring (MII-pH) for unexplained persistent crying not improved by parental reassurance, dietary modification or alginate. Gastrointestinal malformation/surgery, neurological impairment and infections were exclusion criteria. Demographic and anthropometric parameters, GER symptoms and questionnaires (I-GERQ-R) and MII-pH data were recorded and analyzed. Normal MII-pH was defined when acid exposure was <3%, symptom index was <50% and symptom association probability was <95%. Acid exposure >5% and >10% was also considered. Statistical analysis was performed using Chi-Square and univariate and multivariable regression analysis. RESULTS: We included 50 infants (median age 3.5 months) who fulfilled the study criteria: 30 (60%) had normal MII-pH. I-GERQ-R score was abnormal in 33 (66%) infants, and 21/33 (64%) had normal MII-pH (p = 0.47). In the 26 (52%) infants with nocturnal crying, MII-pH was normal in 16 (54%) (p = 0.82). Associated regurgitation (>3 or >10 episodes/die) did not predict abnormal MII-pH (p = 0.74, p = 0.82, respectively). Univariate and multivariable regression analysis did not identify any clinical variable significantly associated with abnormal MII-pH. CONCLUSIONS: Infants with persistent unexplained and nocturnal crying should not be empirically treated with acid inhibitors.

Effect of Laryngopharyngeal Reflux and Potassium-Competitive Acid Blocker (P-CAB) on the Microbiological Comprise of the Laryngopharynx.

OBJECTIVE: To probe the microbiota composition progressing from healthy individuals to those with laryngopharyngeal reflux disease (LPRD) and subsequently undergoing potassium-competitive acid inhibitor (P-CAB) therapy. STUDY DESIGN: Prospective case-control study. SETTING: Academic Medical Center. METHODS: Forty patients with LPRD and 51 patients without LPRD were recruited. An 8-week P-CAB therapy was initiated (post-T-LPRD), and 39 had return visits. In total, 130 laryngopharyngeal saliva samples were collected and sequenced by targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene using an Illumina MiSeq. Amplicon sequence variants (ASVs) and clinical indices were analyzed. RESULTS: Alpha and beta diversities were compared among the non-LPRD, LPRD, and post-T-LPRD groups, and the Observed_ASVs were not significantly different. At the same time, the Shannon and Simpson indices, unweighted Unifrac, weighted Unifrac, and binary Jaccard distance were significantly different between non-LPRD and LPRD groups. In addition, significant differences were found in the abundance of Streptococcus, Prevotella, and Prevotellaceae in the LPRD versus non-LPRD groups, and Neisseria, Leptotrichia, and Allprevotella in the LPRD versus post-T-LPRD groups. The genera model was used to distinguish patients with LPRD from those without, and a better receiver operating characteristic curve was formed after combining the clinical indices of reflux symptom index, reflux finding score, and pepsin, with an area under the curve of 0.960. CONCLUSION: Laryngopharyngeal microbial communities changed after laryngopharyngeal reflux and were modified further after P-CAB treatment, which provides a potential diagnostic value for LPRD, especially when combined with clinical indices.

A comparison between a gastroesophageal reflux disease questionnaire-based algorithm and multichannel intraluminal impedance-pH monitoring for the treatment of gastroesophageal reflux-induced chronic cough.

BACKGROUND: Empiric therapy with multichannel intraluminal impedance-pH monitoring (MII-pH) has been used for the initial treatment of gastroesophageal reflux-induced chronic cough (GERC). However, an algorithm based on the gastroesophageal reflux disease questionnaire (GerdQ) has the potential to achieve a simple, structured, and effective treatment approach for patients with GERC. OBJECTIVES: This study compared the efficacy of anti-reflux therapy based on GerdQ (new structured pathway, NSP) with medical treatment after MII-pH examination (ordinary clinical pathway, OCP) in the management of GERC. DESIGN: For the NSP, we adapted the GerdQ score to establish the basis for a treatment algorithm. For the OCP, treatment was determined using the MII-pH examination results. METHODS: The non-inferiority (NI) hypothesis was used to evaluate NSP versus OCP. RESULTS: Overall, the NSP and OCP-based therapeutic algorithms have similar efficacy for GERC [NI analysis: 95% confidence interval (CI), -4.97 to 17.73, p = 0.009; superiority analysis: p = 0.420]. Moreover, the cough symptom scores and cough threshold improved faster in the NSP group than in the OCP group at week 8 (p < 0.05). In the subgroup analyses using the GerdQ and GerdQ impact scale (GIS) scores, patients with low-likelihood GERC (GerdQ < 8) were more likely to benefit from OCP (NI analysis: 95% CI, -19.73 to 18.02, p = 0.213). On the other hand, in patients with high-likelihood and low-reflux impact GERC patients (GerdQ > 8 and GIS < 4), the NSP arm was not inferior to the standard treatment of OCP (NI analysis: 95% CI, -8.85 to 28.21%, p = 0.04; superiority analysis: p = 0.339), indicating that GerdQ- and GIS-guided diagnosis and management of patients with GERC could be an alternative to MII-pH management, especially in settings with reduced medical resources. CONCLUSIONS: The use of the GerdQ algorithm should be considered when handling patients with GERC in the primary care setting. TRIAL REGISTRATION: This research was registered in the Chinese Clinical Trials Registry (ChiCTR-ODT-12001899).

The clinical application value of salivary pepsin in the diagnosis of gastroesophageal reflux diseases.

BACKGROUND: Peptest is a noninvasive and convenient diagnostic kit for gastroesophageal reflux disease (GERD). We aimed to explore the application value of Peptest in the diagnosis of GERD. METHODS: Patients suspected of GERD all completed 24 h pH-impedance monitoring (24 h MII-pH) and then took proton pump inhibitor (PPI) 2 weeks. The postprandial, post-symptom and random salivary samples were taken. Receiver operating characteristic analysis was used to identify the best cutoff value of Peptest, to differentiate GERD patients from non-GERD patients and the optimal sampling time of Peptest was analyzed. Reflux characteristics and esophageal motility between Peptest (+) group and Peptest (-) group were compared in negative 24 h MII-pH patients. Peptest concentration were compared among non-reflux, distal reflux, and proximal reflux groups according to 24 h MII-pH curve. RESULTS: The area under the curve of post-symptom Peptest was highest in three time points and the diagnostic specificity was 81.0% and sensitivity was 53.3% with the diagnostic value of 86 ng/mL. Compared with negative Peptest group, distal mean nocturnal baseline impedance was significantly lower, gastroesophageal junction contractile integral was substantially lower in positive Peptest group in negative 24 h MII-pH patients. The concentration of post-symptom and postprandial Peptest increased gradually in the non-reflux, distal reflux, and proximal reflux groups. CONCLUSIONS & INFERENCES: Peptest has a relatively low diagnostic value for GERD. Post-symptom Peptset is the best sampling time with the optimal value of 86 ng/mL and may have auxiliary diagnostic value for negative 24 h MII-pH patients. Peptest may assist 24 h MII-pH in monitoring proximal reflux.

Non-acid reflux and esophageal dysmotility is associated with early esophageal squamous cell carcinoma.

BACKGROUND: Studies have demonstrated that non-acid reflux (NAR) is associated with esophageal squamous cell carcinoma (ESCC). Esophageal dysmotility is associated with NAR but few studies have focused on the esophageal motility of ESCC patients. We explored the relationship between ESCC, NAR and esophageal dysmotility with the aid of multichannel intraluminal impedance and pH (MII-pH) and high-resolution manometry (HRM). METHODS: From Jan 2021 to Oct 2022, 20 patients with superficial ESCC were enrolled as the ESCC group, while 20 age and gender matched individuals without gastroesophageal reflux disease (GERD) symptoms and 20 age and gender matched patients with GERD symptoms were recruited as the control groups. Patients received 24 h MII-pH and HRM procedure before endoscopic submucosal dissection (ESD), and the data were then collected to identify the type of reflux and esophageal dysmotility. RESULTS: Prevalence of esophageal dysmotility was significantly different among the three groups, 75.0% in the ESCC group, 35.0% in the non-GERD group and 70.0% in the GERD group (P = 0.029). NAR episodes at 15 cm above the lower esophageal sphincter (LES) in the ESCC group were significantly higher than that in the non-GERD group (6.5 (3.5-9.3) vs 1.0 (0.8-4.0), P = 0.001) and were similar with that in the GERD group (6.5 (3.5-9.3) vs 5.5 (3.0-10.5), P > 0.05). NAR episodes at 5 cm above LES was significantly higher in the ESCC group than that in the non-GERD group (38.0 (27.0-60.0) vs 18.0 (11.8-25.8), P = 0.001) and was significantly higher than that in the GERD group (38.0 (27.0-60.0) vs 20.0 (9.8-30.5)), P = 0.010). Prevalence of pathologic non-acid reflux was significantly different among the three groups, 30.0% in the ESCC group, 0.0% in the non-GERD group and 10.0% in the GERD group (P < 0.001). CONCLUSION: Our study found NAR and esophageal dysfunction frequently occur in ESCC patients. NAR and esophageal dysmotility may be associated with ESCC. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2200061456.

Laryngopharyngeal Reflux Disease and Gastroesophageal Reflux Disease Can Mutually Influence.

OBJECTIVE: To investigate the mutually relationship between gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux disease (LPRD). METHODS: All included patients completed simultaneous 24-hour hypopharyngeal intraluminal multichannel impedance pH monitoring (24h-MII-pH), Reflux Symptom Index (RSI), and Reflux Finding Score (RFS). The LPRD diagnosis was based on the occurrence of ≥1 acid or non-acid hypopharyngeal proximal reflux episode(HRE), GERD was defined as a length of time >4.0% of the 24-hour recording spent below pH 4.0 or a DeMeester score >14.72. Patients with both positive LPRD and GERD were classified as LPRD & GERD group, patients with positive LPRD and negative GERD were classified as ILPRD group, patients with negative LPRD and positive GERD were classified as IGERD group, and patients with both negative LPRD and GERD were classified as N group. The differences in clinical characteristics of reflux between the groups were statistically analyzed. RESULTS: A total of 437 patients were included, including 248 (56.75%) in the ILPRD group, 98 (22.43%) in the LPRD & GERD group, 23 (5.26%) in the IGERD group, and 68 (15.56%) in the N group. There was no significant difference between the types of gastroesophageal reflux in patients with GERD. The number of weak acid/acid/gas/liquid HREs was significantly more in LPRD & GERD patients than in ILPRD patients (P < 0.01), and the number of distal acid reflux events and Longest distal acid clearance time were significantly higher in LPRD & GERD patients than in IGERD patients (P > 0.01). CONCLUSION: GERD and LPRD are not the same disease but can mutually influence. Combined GERD increased all types of laryngopharyngeal reflux events in patients with LPRD, whereas combined LPRD only increased acidic distal reflux events and acid clearance time in patients with GERD.

The effects of assisted autogenic drainage, combined or not with bouncing on gastroesophageal reflux in infants.

AIM: This study aimed to determine the effect of assisted autogenic drainage (AAD) with or without bouncing (BAAD) on both acid and non-acid gastroesophageal reflux (GER) in infants <1 year. METHODS: During a 24-h multichannel intraluminal impedance-pH monitoring (MII-pH), infants were treated with a 20-min intervention of AAD (in supine position) or BAAD (in upright position), 2 h postprandial. In this controlled trial with intra-subject design, the number of reflux episodes (REs) was the primary outcome measure. The results during AAD and BAAD were compared to a baseline period before intervention and 20 min after intervention. RESULTS: Overall, 50 infants were included in both groups. During AAD a significant decrease of RE's was found compared to baseline (p = 0.001). No significant differences were found in the BAAD group compared to baseline (p = 0.125). CONCLUSION: AAD and BAAD do not cause or increase GER in infants under the age of 1 year.

24-Hour Multichannel Intraluminal Impedance-pH in Proton Pump Inhibitor Nonresponders vs Responders in Patients With Laryngopharyngeal Reflux.

OBJECTIVE: This study aimed to evaluate the characteristics of reflux in proton pump inhibitor (PPI) nonresponders vs responders in patients with laryngopharyngeal reflux (LPR) by using 24-hour multichannel intraluminal impedance-pH (MII-pH) monitoring. STUDY DESIGN: Prospective cohort study. SETTING: A tertiary care otolaryngology clinic. METHODS: Patients with typical LPR symptoms showing >1 proximal reflux episode were considered to have LPR and investigated prospectively. Patients were prescribed high-dose PPI twice daily and followed up for at least 2 months. Patients with LPR showing a ≥50% decrease in the follow-up reflux symptom index score during treatment periods as compared with pretreatment were defined as responders; others were defined as nonresponders. Various parameters in 24-hour MII-pH monitoring between nonresponders and responders with LPR were compared with Student's t test and receiver operating characteristic curve. RESULTS: Eighty patients were diagnosed with LPR and categorized as nonresponders (n = 19) and responders (n = 61). Proximal all reflux time and proximal longest reflux time in various MII parameters were higher in responders than in nonresponders (P = .0040 and .0216, respectively). Proximal all reflux time >0.000517% was a better cutoff value to predict responders with LPR as compared with the proximal longest reflux time >0.61 minutes (sensitivity + specificity: 1.317 vs 1.291). CONCLUSION: Proximal all reflux time in various 24-hour MII-pH monitoring parameters can be helpful to predict the response to PPI therapy in patients with LPR. These findings will help establish a personalized therapeutic scheme for patients with LPR.

Refractory Gastroesophageal Reflux Disease: A Management Update.

Gastroesophageal reflux disease (GERD) is one of the most frequent gastrointestinal disorders. Proton pump inhibitors (PPIs) are effective in healing lesions and improving symptoms in most cases, although up to 40% of GERD patients do not respond adequately to PPI therapy. Refractory GERD (rGERD) is one of the most challenging problems, given its impact on the quality of life and consumption of health care resources. The definition of rGERD is a controversial topic as it has not been unequivocally established. Indeed, some patients unresponsive to PPIs who experience symptoms potentially related to GERD may not have GERD; in this case the definition could be replaced with "reflux-like PPI-refractory symptoms." Patients with persistent reflux-like symptoms should undergo a diagnostic workup aimed at finding objective evidence of GERD through endoscopic and pH-impedance investigations. The management strategies regarding rGERD, apart from a careful check of patient's compliance with PPIs, a possible change in the timing of their administration and the choice of a PPI with a different metabolic pathway, include other pharmacologic treatments. These include histamine-2 receptor antagonists (H2RAs), alginates, antacids and mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists and metabotropic glutamate receptor-5 (mGluR5) antagonists, and pain modulators. If there is no benefit from medical therapy, but there is objective evidence of GERD, invasive antireflux options should be evaluated after having carefully explained the risks and benefits to the patient. The most widely performed invasive antireflux option remains laparoscopic antireflux surgery (LARS), even if other, less invasive, interventions have been suggested in the last few decades, including endoscopic transoral incisionless fundoplication (TIF), magnetic sphincter augmentation (LINX) or radiofrequency therapy (Stretta). Due to the different mechanisms underlying rGERD, the most effective strategy can vary, and it should be tailored to each patient. The aim of this paper is to review the different management options available to successfully deal with rGERD.

Pharyngeal reflux episodes in patients with suspected laryngopharyngeal reflux versus healthy subjects: a prospective cohort study.

PURPOSE: This study aimed to analyze pharyngeal reflux episodes in patients with suspected LPR versus healthy subjects using 24-h MII-pH monitoring. METHODS: One hundred twenty-one patients who visited our clinic with a chief complaint of LPR-related symptoms and underwent 24-h MII-pH monitoring were enrolled prospectively. Also, 27 healthy subjects were enrolled and underwent 24-h MII-pH monitoring during the same period. We analyzed sensitivity, specificity, and accuracy comprehensively to determine appropriate cut-off values of pharyngeal reflux episodes in 24-h MII-pH monitoring to diagnose patients with LPR. RESULTS: Twenty-nine of 121 patients with suspected LPR showed no pharyngeal reflux episodes, while 92 showed more than one pharyngeal reflux event. In contrast, the 22 healthy subjects showed no pharyngeal reflux episodes, three showed one reflux event, and two showed two reflux events. A cut-off value of ≥ 1 showed best accuracy reflected by combined sensitivity and specificity values, while ≥ 2 demonstrated better specificity with slight loss of sensitivity and slightly lower overall accuracy, suggesting cut-off value of ≥ 1 pharyngeal reflux episodes is a good clinical indicator. CONCLUSION: A cut-off value of ≥ 1 in pharyngeal reflux episodes on 24-h MII-pH monitoring in patients with suspected LPR might be an acceptable diagnostic tool for LPR.

Response to therapy among neonates with gastro-esophageal reflux is associated with esophageal clearance.

BACKGROUND: Few studies evaluated the efficacy of pharmacological therapy for gastro-esophageal reflux disease (GERD) in newborns, whose safety has been questioned. Esophageal basal impedance (BI) is a marker of mucosal integrity, and treatment with proton pump inhibitors significantly increases BI in infants; however, no correlation with clinical improvement was reported. AIMS: To evaluate the relationship between BI and other esophageal pH-impedance parameters and clinical response to therapy in newborns with GERD. STUDY DESIGN: Multicenter retrospective study. SUBJECTS: Infants who received omeprazole or ranitidine for GERD. OUTCOME MEASURES: Complete response to therapy was defined as symptom decrease by ≥50% compared to baseline, partial response as symptom decrease <50%, no response as no symptom decrease based on chart analysis. Response to therapy was assessed 2 and 4 weeks after the onset of therapy. Univariate and multivariate statistics were performed to assess associations between response to therapy and clinical/pH-impedance parameters. RESULTS: We studied 60 infants (51 born preterm): 47 received omeprazole, 13 ranitidine. Response to therapy was associated with decreasing esophageal clearance time: odds ratio 0.308, 95%CI 0.126-0.753, p = 0.010 at 2 weeks, odds ratio 0.461, 95%CI 0.223-0.955, p = 0.037 at 4 weeks. CONCLUSIONS: Clinical response to therapy among infants with GERD was associated with esophageal clearance but not with esophageal BI level.

High-resolution impedance manometry and 24-hour multichannel intraluminal impedance with pH testing before and after sleeve gastrectomy: de novo reflux in a prospective series.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is increasingly popular but concern regarding its effect on gastroesophageal reflux disease remain. The current literature is conflicting, and there have been little objective data. OBJECTIVES: To objectively and more accurately assess the impact of SG on esophago-gastric physiology. SETTING: Centre of Excellence in Metabolic and Bariatric Surgery, Private Hospital, Australia. METHODS: Prospective cohort study of 31 patients undergoing SG with high-resolution impedance manometry (HRM), 24-hour multichannel intraluminal impedance combined with pH testing (MII-pH), and Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) questionnaire 1 month before and 6 months after SG. RESULTS: There were 31 patients that underwent SG, 20 with synchronous hiatal repair and fixation, and 6 that were excluded. HRM demonstrated significantly increased intragastric pressures (15.5-29.6 mm Hg) and failed swallows (3.1-7.5%) but no other change in esophageal motility. MII-pH did not demonstrate significant changes in acid exposure time (8.5%-7.5%) or number of reflux episodes, although the numbers of long reflux episodes (2.3-4.7) and weak acid reflux episodes were significantly increased (15.4-55.2). DeMeester and GSAS scores were not significantly changed. There was no significant difference in patients with preexisting reflux. However, for patients without preexisting reflux, acid exposure time increased significantly (1.3%-6.7%), as did DeMeester scores (5.8-24.5) and the numbers of long reflux episodes (.1-4.4) and weakly acidic episodes (22.1-89.2). CONCLUSION: SG was associated with increased intragastric pressures, without changes in esophageal motility or acid exposure. For patients without preexisting reflux, there were increases in acid exposure time, long reflux episodes, weakly acidic reflux episodes, and DeMeester score.

Effects on Gastroesophageal Reflux of Donkey Milk-Derived Human Milk Fortifier Versus Standard Fortifier in Preterm Newborns: Additional Data from the FortiLat Study.

BACKGROUND: Feeding intolerance is a frequent diagnosis in very preterm infants. As seen in the FortiLat trial, human milk fortification with the new donkey milk-derived human milk fortifier (DF) seems to improve feeding tolerance in these infants. The aim of this study was to evaluate the effects of using the DF compared with bovine milk-derived fortifier (BF) on gastroesophageal reflux (GER) in very low birth weight (VLBW) infants. METHODS: Over a total of 156 preterm infants were enrolled into the FortiLat trial (GA <32 weeks and birth weight <1500 g) and randomized into the BF arm or DF arm, and we selected all infants with clinical signs of GER and cardiorespiratory (CR) symptoms. All the infants underwent CR and multichannel intraluminal impedance and pH (MII/pH) monitoring associated with gastric ultrasound to evaluate GER and gastric emptying time. RESULTS: 10 infants were enrolled, and 5 were in the DF arm. At MII/pH, infants enrolled into the DF arm showed a lower GER frequency than BF arm infants (p = 0.036). Half gastric emptying time was similar in DF and BF arm infants (p = 0.744). CONCLUSION: The use of donkey-derived human milk fortifier reduced the GER frequency and consequently should be recommended in infants with feeding intolerance.

Study on laryngopharyngeal and esophageal reflux characteristics using 24-h multichannel intraluminal impedance-pH monitoring in healthy volunteers.

OBJECTIVE: We aimed to analyze the results of 24-h multichannel intraluminal impedance and pH-monitoring (MII-pH) of the laryngopharynx and esophagus in asymptomatic volunteers. Moreover, we also aimed to gain insight into and establish a baseline for laryngopharyngeal reflux in the healthy population by quantitatively and qualitatively comparing the reflux and pH distribution in both the laryngopharynx and the esophagus. METHODS: Healthy volunteers were recruited and observed; they underwent 24-h ambulatory combined MII-pH monitoring. The proximal sensor (pH1) was positioned approximately 1 cm above the upper esophageal sphincter with the aid of a solid-state high-resolution esophageal manometer. Laryngopharyngeal reflux events were detected and characterized by the incidence and property of reflux both in the laryngopharynx and the esophagus. RESULTS: Thirty-eight asymptomatic volunteers who completed all the examinations were included in this study. The median pH detected by the proximal sensor was 6.6 (6.2, 7.0), with an average of 6.58 ± 0.74. A total of 814 laryngopharyngeal reflux events were detected, including 722 (89%) in the upright position and 92 (11%) in the supine position with incidence (0%) in the liquid state, 44 (5%) in the mixture, and 769 (95%) in the gaseous state. Furthermore, 5 incidences (1%) of acid reflux and 809 incidences of non-acid reflux (99%) were noted. A total of 5779 esophageal reflux events were detected, including 5020 (87%) in the upright position, 759 (13%) in the supine position, with 2051 (36%) in the liquid state, 2050 (35%) in the mixed condition, and 1678 (29%) in the gaseous state; adding up to 805 incidences (14%) of acid reflux and 4974 incidences (86%) of non-acid reflux. CONCLUSION: Non-acid reflux in the upright position is characteristic of laryngopharyngeal reflux. Acid reflux is almost undetectable in healthy subjects. Hence, the diagnostic indicators of gastroesophageal reflux disease are not suitable for laryngopharyngeal reflux disease.

Sleeve Gastrectomy and Anterior Fundoplication (D-SLEEVE) Prevents Gastroesophageal Reflux in Symptomatic GERD.

BACKGROUND: A worrying increase of gastroesophageal reflux disease (GERD) and Barrett esophagus has been reported after sleeve gastrectomy (SG). Recent reports on combined fundoplication and SG seem to accomplish initial favorable results. However, no study included manometry or pH monitoring to evaluate the impact of fundoplication in SG on esophageal physiology. METHOD: In this study, 32 consecutive bariatric patients with GERD and/or esophagitis had high-resolution impedance manometry (HRiM) and combined 24-h pH and multichannel intraluminal impedance (MII-pH) before and after laparoscopic sleeve gastrectomy associated to anterior fundoplication (D-SLEEVE). The following parameters were calculated at HRiM: lower esophageal sphincter pressure and relaxation, peristalsis, and mean total bolus transit time. The acid and non-acid GER episodes were assessed by MII-pH, symptom index association (SI), and symptom-association probability (SAP) were also analyzed. RESULTS: At a median follow-up of 14 months, HRiM showed an increased LES function, and MII-pH showed an excellent control of both acid exposure of the esophagus and number of reflux events. Bariatric outcomes (BMI and EWL%) were also comparable to regular SG (p = NS). CONCLUSION: D-SLEEVE is an effective restrictive procedure, which recreates a functional LES pressure able to control and/or prevent mild GERD at 1-year follow-up.

The evaluation of recumbent reflux by multichannel intraluminal impedance pH testing for patients with gastroesophageal reflux disease and sleep disturbance.

BACKGROUND AND AIM: The relationship between gastroesophageal reflux disease (GERD) and sleep disturbance has recently been pointed out and is garnering substantial attention. Although there are reports that point out the effectiveness of medical treatment for sleep disturbance associated with GERD, examinations of the pathological condition, including reflux during sleep, are inadequate. In the present study, we evaluated the recumbent reflux in patients with GERD and sleep disturbance using multichannel intraluminal impedance pH (MII-pH), and attempted to suppress recumbent reflux by surgical treatment to examine the pathophysiology of patients with GERD and sleep disturbance. MATERIALS AND METHODS: Of the 47 patients with GERD-related diseases in whom laparoscopic fundoplication was performed at The Jikei University Hospital from January 2016 to June 2017, 31 patients (average age: 55.9 ± 13.8 years, male in 25), excluding 9 with surgical indications only for esophageal hiatal hernia and 7 without postoperative evaluation, were the subjects of this study. All surgical procedures were performed by the Toupet method. We used the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep disturbance, setting 5.5 as the cut-off value, based on the report by Doi et al., with any conditions beyond this value deemed sleep disturbance. The evaluation of gastroesophageal reflux was carried based on the MII-pH using the Sleuth, manufactured by Sandhill Corporation, with an automatic analysis carried out by computer. Furthermore, recumbent abnormal reflux was defined as recumbent all reflux (times) > 7. All evaluations were performed preoperatively and at 3 months after the operation. The data were expressed in medians and interquartile ranges, with p < 0.05 defined as statistically significant by the Mann-Whitney, Wilcoxon, or Chi-squared test. RESULTS: Although sleep disturbance was found in 19 cases (61%), 8 (42%) of which were actually confirmed as nighttime abnormal reflux, of whom 5 cases (63%) showed significant improvement in their sleep disturbance following the operation, with a PSQI score of lower than 5.5. Among these 5 cases, postoperative recumbent abnormal reflux was also significantly reduced as compared with the preoperative condition (17 vs. 2 times/day, p = 0.042). Furthermore, sleep disturbance improved and recumbent abnormal reflux also decreased in two cases, with sleep disturbance improved by controlling the nighttime reflux via surgery in a total of 7 cases (87.5%). Although the PSQI score was as high as 14 points before and after the operation in one case, the rate of recumbent abnormal reflux was remarkably reduced, with sleep disturbance and recumbent reflux considered irrelevant. Furthermore, regarding the frequency of recumbent acid/non-acid reflux, while non-acid reflux was significantly more frequent in the patients with recumbent reflux complications (9 vs. 1 time/day, p < 0.001), there was no marked difference in the frequency of acid reflux. CONCLUSIONS: Among cases with GERD and sleep disturbance, approximately one-third of them showed findings suggestive of the involvement of recumbent reflux in sleep disturbance, with reflux characterized by non-acid reflux.

Reflux characteristics in patients with gastroesophageal reflux-related chronic cough complicated by laryngopharyngeal reflux.

BACKGROUND: This study aimed to investigate the reflux characteristics in patients with gastroesophageal reflux-related chronic cough (GERC) complicated by laryngopharyngeal reflux (LPR). METHODS: Patients with chronic cough were recruited. Reflux symptom index (RSI) scoring, cough symptom scoring, assessment of capsaicin cough sensitivity, and multichannel intraluminal impedance and pH monitoring (MII-pH) were performed. RESULTS: RSI score in GERC patients was significantly higher than that in patients with atopic cough (AC), cough variant asthma, eosinophilic bronchitis (EB), and upper airway cough syndrome (UACS) (P<0.05). The RSI score in non-acid GERC patients was significantly higher than that in acid GERC patients (P=0.003). The cut-off value of the RSI score was defined as 19 during diagnosis of non-acid GERC. In the RSI ≥19 group, there was more proximal reflux and more significant gas and non-acid reflux, and the efficacy of a combined use of baclofen or gabapentin was better than that of the RSI <19 group (P<0.05). The efficacy of proton pump inhibitor (PPI) at a routine dosage together with prokinetic agents in the RSI <19 group was better than that in the RSI ≥19 group (P=0.009). CONCLUSIONS: LPR overlaps with GERC in part. GERC patients with higher RSI scores may present more proximal reflux, non-acid reflux, and gas reflux, and get better efficacy with neuromodulators (gabapentin or baclofen) used as an add-on therapy.

Esophagogastric junction function and gastric pressure profile after minigastric bypass compared with Billroth II.

BACKGROUND: Minigastric bypass (MGB) is being performed widely with effective weight loss and improvement in co-morbidities. Because of similarity to Billroth II (BII), there are concerns about bile reflux. OBJECTIVES: To assess the esophagogastric junction (EGJ) function, esophageal peristalsis, and reflux exposure after MGB and BII. SETTING: University Hospital, Italy; Public Hospital, Italy. METHODS: Obese patients underwent symptom questioning, endoscopy, high-resolution impedance manometry, and impedance-pH monitoring, before and 1 year after MGB. Esophageal motor function, EGJ, EGJ-contractile integral, intragastric pressure (IGP), and gastroesophageal pressure gradient were determined. Acid exposure time, number of refluxes, and symptom-association probability were assessed. A group of patients who underwent BII were studied with the same protocol and served as controls. RESULTS: Twenty-two MGB and 20 BII patients were studied. After surgery, none of the patients reported de novo heartburn or regurgitation. At endoscopic follow-up, esophagitis and bile findings were absent in all. High-resolution impedance manometry features did not vary significantly after MGB, whereas IGP and gastroesophageal pressure gradient statistically diminished (P < .01). BII patients had significantly lower values in IGP, sphincter pressure, and EGJ-contractile integral. In MGB patients, a marked decrease in number of refluxes (from median 41 to 7, P < .01) was observed, whereas BII patients had statistically significant higher acid exposure and number of refluxes (57, P < .001). CONCLUSIONS: In contrast to BII, MGB does not increase any kind of reflux. Also, the differences in IGP and gastroesophageal pressure gradient suggest that bile reflux occurs more readily after BII than after MGB, and that these 2 operations share more differences than similarities.

Characteristics of gastroesophageal reflux in pediatric patients with neurological impairment.

PURPOSE: To clarify the characteristics of gastroesophageal reflux (GER) in pediatric patients with neurological impairment (NI). METHODS: Twenty-six patients with NI, 1-17-year-old, fed via a nasogastric tube were categorized based on the absence (group I) or presence (group II) of abnormal GER, defined with multichannel intraluminal impedance-pH monitoring as %time with an esophageal pH <4.0 being ≥5.0% or number of liquid/mixed bolus reflux events(RE) >70 in 24 h. RESULTS: %Time and number of distal and proximal bolus REs were not significantly different between acid and nonacid REs. %Time of acid bolus RE and that of acid and total number of distal and proximal bolus REs were significantly higher in group II than in group I. Mean acid clearance time was significantly longer in group II. Median bolus clearance time was similar between the groups. No bolus RE parameters were significantly different between acid and nonacid REs in group I. Acid bolus RE was significantly higher than nonacid RE in terms of %time and number of proximal bolus RE in group II. CONCLUSION: Acid REs significantly increased in pediatric patients with NI with abnormal GER. The number of acid and nonacid REs was comparable in patients without abnormal GER.