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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 [ABSTRACT FROM AUTHOR]

Background/Aims It has been suggested that STW5 (Iberogast) reduces heartburn symptoms in patients with functional dyspepsia, but underlying mechanisms of action are unclear. The aim of this study is to investigate whether STW5 affects esophageal sensitivity or esophageal motility, thereby reducing occurrence and perception of reflux events. Methods We performed a double-blind, randomized, placebo-controlled, crossover trial in patients with functional dyspepsia (Rome IV) and reflux symptoms. After 4 weeks of treatment with either placebo or STW5, patients were studied with an esophageal acid perfusion test and ambulatory 24-hour pH-impedance monitoring. Results A total of 18 patients (7 men, median age 54, range [19-76]), were included in the study. Although we found no statistical difference in our primary outcome the total Reflux Disease Questionnaire score 2.33 (0.25-4.33) vs 2.67 (1.17-4.00), P = 0.347, "gastroesophageal reflux disease" and "regurgitation" subscale scores were lower after STW5 treatment compared to placebo (P = 0.049 and P = 0.007). There was no statistical difference in number of reflux events, acid exposure time and acid sensitivity scores between STW5 and placebo. In a subgroup analysis of patients with pH-metry confirmed gastroesophageal reflux disease, treatment with STW5 significantly reduced the total number of acidic reflux events (P = 0.028). Moreover, in patients with reflux esophagitis, the median lag time to acid perception increased after STW5 treatment (P = 0.042). Conclusions We found some indications pointing towards a beneficial effect of STW5 on reflux symptoms in dyspeptic patients, with reduction of esophageal hypersensitivity as a potential underlying mechanism. Our findings will have to be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Introduction: Although inability to belch has previously been linked to dysfunction of the upper esophageal sphincter (UES), its underlying pathogenesis remains unclear. Our aim was to study mechanisms underlying inability to belch and the effect of UES botulinum toxin (botox) injections in these patients. Methods: We prospectively enrolled consecutive patients with symptoms of inability to belch. Patients underwent stationary high‐resolution impedance manometry (HRIM) with belch provocation and ambulatory 24‐h pH‐impedance monitoring before and 3 months after UES botox injection. Results: Eight patients (four males, age 18–37 years) were included. Complete and normal UES relaxation occurred in response to deglutition in all patients. A median number of 33(15–64) gastroesophageal gas reflux episodes were observed. Despite the subsequent increase in esophageal pressure (from −4.0 [−7.7–4.2] to 8 [3.3–16.1] mmHg; p < 0.012), none of the gastroesophageal gas reflux events resulted in UES relaxation. Periods of continuous high impedance levels, indicating air entrapment (median air presence time 10.5% [0–43]), were observed during 24‐h impedance monitoring. UES botox reduced UES basal pressure (from 95.7[41.2–154.0] to 29.2 [16.7–45.6] mmHg; p < 0.02) and restored belching capacity in all patients. As a result, esophageal air presence time decreased from 10.5% (0–43.4) to 0.7% (0.1–18.6; p < 0.02) and esophageal symptoms improved in all patients (VAS 6.0 [1.0–7.9] to 1.0 [0.0–2.5]; p < 0.012). Conclusion: The results of this study underpin the existence of a syndrome characterized by an inability to belch and support the hypothesis that ineffective UES relaxation, with subsequent esophageal air entrapment, may lead to esophageal symptoms. [ABSTRACT FROM AUTHOR]

Background During the natural course of eosinophilic esophagitis (EoE), the risk for esophageal stricture formation increases. It remains unknown whether motility abnormalities in EoE also develop over time. We aimed to determine the relationship between disease duration, clinical characteristics, and manometric pattern of EoE patients. Methods We compared esophageal high-resolution manometry ( HRM) measurements of 31 adult EoE patients with HRM data from 31 GERD controls and 31 healthy controls. Subsequently, we assessed differences in disease duration and clinical characteristics between EoE patients with normal and those with abnormal esophageal motility. Key Results In EoE patients, peristaltic integrity was more frequently failed (12 vs 6%) or weak (27 vs 15%; p < 0.001) compared with healthy controls; however, this pattern was also seen in GERD controls (failed 14%, weak 27%). We found no differences regarding symptoms and signs of EoE between EoE patients with normal (42%) and abnormal motility (58%). However, disease duration was longer in EoE patients with abnormal motility than in those with normal motility (13 (6-18) years vs 4 (1-11) years; p < 0.05). In EoE, but not GERD, disease duration was identified as a risk factor for abnormal motility ( OR for each year 1.142; 95% CI 1.004-1.299), and with longer disease duration, the prevalence of abnormal motility increased from 36% (duration 0-5 years) to 83% (duration ≥16 years; p < 0.05). Conclusions & Inferences Weak and failed peristaltic integrity are more often present in adult EoE patients than in healthy controls. The prevalence of manometric abnormalities in EoE patients increases with longer disease duration. [ABSTRACT FROM AUTHOR]

Background/aims: It has been suggested that STW5 (Iberogast) reduces heartburn symptoms in patients with functional dyspepsia, but underlying mechanisms of action are unclear. The aim of this study is to investigate whether STW5 affects esophageal sensitivity or esophageal motility, thereby reducing occurrence and perception of reflux events., Methods: We performed a double-blind, randomized, placebo-controlled, crossover trial in patients with functional dyspepsia (Rome IV) and reflux symptoms. After 4 weeks of treatment with either placebo or STW5, patients were studied with an esophageal acid perfusion test and ambulatory 24-hour pH-impedance monitoring., Results: A total of 18 patients (7 men, median age 54, range [19-76]), were included in the study. Although we found no statistical difference in our primary outcome the total Reflux Disease Questionnaire score 2.33 (0.25-4.33) vs 2.67 (1.17-4.00), P = 0.347, "gastroesophageal reflux disease" and "regurgitation" subscale scores were lower after STW5 treatment compared to placebo ( P = 0.049 and P = 0.007). There was no statistical difference in number of reflux events, acid exposure time and acid sensitivity scores between STW5 and placebo. In a subgroup analysis of patients with pH-metry confirmed gastroesophageal reflux disease, treatment with STW5 significantly reduced the total number of acidic reflux events ( P = 0.028). Moreover, in patients with reflux esophagitis, the median lag time to acid perception increased after STW5 treatment ( P = 0.042)., Conclusions: We found some indications pointing towards a beneficial effect of STW5 on reflux symptoms in dyspeptic patients, with reduction of esophageal hypersensitivity as a potential underlying mechanism. Our findings will have to be confirmed in larger studies.