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.

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.
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.
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.
The non-inferiority (NI) hypothesis was used to evaluate NSP versus OCP.
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.
The use of the GerdQ algorithm should be considered when handling patients with GERC in the primary care setting.
This research was registered in the Chinese Clinical Trials Registry (ChiCTR-ODT-12001899).

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).
CONCLUSIONS: Our study found NAR and esophageal dysfunction frequently occur in ESCC patients. NAR and esophageal dysmotility may be associated with ESCC.
BACKGROUND: ChiCTR2200061456.

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.
To evaluate the relationship between BI and other esophageal pH-impedance parameters and clinical response to therapy in newborns with GERD.
Multicenter retrospective study.
Infants who received omeprazole or ranitidine for GERD.
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.
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.
Clinical response to therapy among infants with GERD was associated with esophageal clearance but not with esophageal BI level.

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.
OBJECTIVE: To objectively and more accurately assess the impact of SG on esophago-gastric physiology.
METHODS: 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).
CONCLUSIONS: 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.

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.
METHODS: 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).
CONCLUSIONS: 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.

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.
OBJECTIVE: To assess the esophagogastric junction (EGJ) function, esophageal peristalsis, and reflux exposure after MGB and BII.
METHODS: 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.

BACKGROUND: At present, no objective data are available on the effect of omega-loop gastric bypass (OGB) on gastroesophageal junction and reflux.
OBJECTIVE: To evaluate the possible effects of OGB on esophageal motor function and a possible increase in gastroesophageal reflux.
METHODS: University Hospital, Italy; Public Hospital, Italy.
METHODS: Patients underwent clinical assessment for reflux symptoms, and endoscopy plus high-resolution impedance manometry (HRiM) and 24-hour pH-impedance monitoring (MII-pH) before and 1 year after OGB. A group of obese patients who underwent sleeve gastrectomy (SG) were included as the control population.
RESULTS: Fifteen OGB patients were included in the study. After surgery, none of the patients reported de novo heartburn or regurgitation. At endoscopic follow-up 1 year after surgery, esophagitis was absent in all patients and no biliary gastritis or presence of bile was recorded. Manometric features and patterns did not vary significantly after surgery, whereas intragastric pressures (IGP) and gastroesophageal pressure gradient (GEPG) statistically diminished (from a median of 15 to 9.5, P<.01, and from 10.3 to 6.4, P<.01, respectively) after OGB. In contrast, SG induced a significant elevation in both parameters (from a median of 14.8 to 18.8, P<.01, and from 10.1 to 13.1, P<.01, respectively). A dramatic decrease in the number of reflux events (from a median of 41 to 7; P<.01) was observed after OGB, whereas in patients who underwent SG a significant increase in esophageal acid exposure and number of reflux episodes (from a median of 33 to 53; P<.01) was noted.
CONCLUSIONS: In contrast to SG, OGB did not compromise the gastroesophageal junction function and did not increase gastroesophageal reflux, which was explained by the lack of increased IGP and in GEPG as assessed by HRiM.

OBJECTIVE: Mucosal integrity can be assessed in patients with gastroesophageal reflux disease (GERD) by measuring intraluminal baseline impedance (BI). However, it is not clear whether BI is abnormal in patients with functional heartburn (FH), or can be used to distinguish them from patients with GERD. We compared differences in BI between patients with FH vs GERD.
METHODS: We performed a prospective study of 52 patients (16 men; mean age, 55 y; range, 23-78 y) seen at a tertiary university hospital from February 2009 through December 2012. Thirty-five patients had GERD (19 had nonerosive reflux disease [NERD], 16 had erosive reflux disease [ERD]) and 17 had FH. All patients discontinued proton pump inhibitor therapy and then underwent esophagogastroduodenoscopy and multichannel intraluminal impedance and pH monitoring. BI was assessed at 3, 5, 7, 9, 15, and 17 cm proximal to the lower esophageal sphincter in recumbent patients. Biopsy specimens were taken from 3 cm above the gastroesophageal junction; histology analysis was performed to identify and semiquantitatively score (scale, 0-3) dilated intercellular spaces.
RESULTS: Baseline impedance in the distal esophagus was significantly lower in patients with NERD or erosive reflux disease (ERD) than FH (P = .0006). At a cut-off value of less than 2100 Ω, BI measurements identified patients with GERD with 78% sensitivity and 71% specificity, with positive and negative predictive values of 75%. Also in the proximal esophagus, reduced levels of BI levels were found only in patients with ERD. There were negative correlations between level of BI and acid exposure time (r = -0.45; P = .0008), number of acidic reflux episodes (r = -0.45; P = .001), and proximal extent (r = -0.40; P = .004). Biopsy specimens from patients with NERD or ERD had significant increases in dilation of intercellular spaces, compared with those from patients with FH; there was an inverse association between dilated intercellular spaces and BI in the distal esophagus (r = -0.28; P = .06).
CONCLUSIONS: Measurement of BI in the lower esophagus can differentiate patients with ERD or NERD from patients with FH (78% sensitivity and 71% specificity), and therefore should be considered as a diagnostic tool for patients with proton pump inhibitor-refractory reflux. Low levels of BI are associated with increased exposure to acid and dilation of intercellular spaces, indicating that BI is a marker of mucosal integrity.

Until now, it is uncertain if the so-called pH-only reflux episodes that consist of a pH drop without evidence of retrograde bolus movement in multichannel intraluminal impedance (MII) represent reflux episodes or artifacts. Hiatal hernia (HH) may allow reflux of small volumes to occur that can be detected by pH-metry but not by MII. The aim was to search for a mechanism that can explain pH-only reflux, 20 patients (12 females and 8 males, median age 52 years, interquartile range [IQR]: 40.5-60.75 years) were investigated with MII-pH off PPI. Impedance and pH-metry data were analyzed separately. The differences in detection rate of acid reflux between pH-metry and MII were correlated with the presence of HH. In an in vitro experiment, MII-pH probes were flushed with citric acid in plastic tubes of different size with capillary diameter and diameters of 2.5 mm and 4.5 mm, while recording pH values and impedance. HH was present in six patients and absent in 14 patients. In patients with HH in comparison with patients with absent HH, the difference of acid reflux detection between pH-metry and MII is significantly higher (70%, IQR: 15-88% and 3.6%, IQR: 0-31%, respectively). In vitro all simulated reflux lead to a fall in pH whereas a corresponding decrease in impedance was only recognizable in the 4.5-mm plastic tubes. Acid reflux episodes in patients with HH are more frequently detected by pH-metry than by MII. Small volume reflux that does not lead to a decrease in impedance is the likely explanation for this phenomenon.