Erratum: Chondroitin Sulfate and Hyaluronic Acid Perfusion for Interstitial Cystitis/Bladder Pain Syndrome: A Systematic Review and Meta-Analysis

Paper link corrected: https://bonoi.org/index.php/si/article/view/636 It has been brought to authors attention that there is a missing part in “Materials and Methods” of the Systematic Review article by Xiao et al., entitled “Chondroitin Sulfate and Hyaluronic Acid Perfusion for Interstitial Cystitis/Bladder Pain Syndrome: A Systematic Review and Meta-Analysis” in the Volume 39, No. 4 of Science Insights (pp.363-373). The missing part of the “Materials and Methods” is as below: Population: Patients with IC/BPS.Intervention: All patients underwent intravesical HA and/or CS treatment regimen.Comparison: Improvement in symptoms pre-treatment and post-treatment or other treatment regimen.Outcome: The primary outcome was the change in visual analogue scale (VAS) for pain symptom from baseline to the follow-up period; secondary outcomes were the changes in total scores of the O’Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI), storage symptoms including frequency and urgency, and bladder capacity.

Reflux symptoms and oesophageal acidification in treated achalasia patients are often not reflux related

ObjectiveAfter treatment, achalasia patients often develop reflux symptoms. Aim of this case–control study was to investigate mechanisms underlying reflux symptoms in treated achalasia patients by analysing oesophageal function, acidification patterns and symptom perception.DesignForty treated achalasia patients (mean age 52.9 years; 27 (68%) men) were included, 20 patients with reflux symptoms (RS+; Gastro-Oesophageal Reflux Disease Questionnaire (GORDQ) ≥8) and 20 without reflux symptoms (RS−: GORDQ <8). Patients underwent measurements of oesophagogastric junction distensibility, high-resolution manometry, timed barium oesophagogram, 24 hours pH-impedance monitoring off acid-suppression and oesophageal perception for acid perfusion and distension. Presence of oesophagitis was assessed endoscopically.ResultsTotal acid exposure time during 24 hours pH-impedance was not significantly different between patients with (RS+) and without (RS−) reflux symptoms. In RS+ patients, acid fermentation was higher than in RS− patients (RS+: mean 6.6% (95% CI 2.96% to 10.2%) vs RS−: 1.8% (95% CI −0.45% to 4.1%, p=0.03) as well as acid reflux with delayed clearance (RS+: 6% (95% CI 0.94% to 11%) vs RS−: 3.4% (95% CI −0.34% to 7.18%), p=0.051). Reflux symptoms were not related to acid in both groups, reflected by a low Symptom Index. RS+ patients were highly hypersensitive to acid, with a much shorter time to heartburn perception (RS+: 4 (2–6) vs RS−:30 (14-30) min, p<0.001) and a much higher symptom intensity (RS+: 7 (4.8–9) vs RS−: 0.5 (0–4.5) Visual Analogue Scale, p<0.001) during acid perfusion. They also had a lower threshold for mechanical stimulation.ConclusionReflux symptoms in treated achalasia are rarely caused by gastro-oesophageal reflux and most instances of oesophageal acidification are not reflux related. Instead, achalasia patients with post-treatment reflux symptoms demonstrate oesophageal hypersensitivity to chemical and mechanical stimuli, which may determine symptom generation.

Destruction of the Dorsal Motor Nucleus of the Vagus Aggravates Inflammation and Injury from Acid-Induced Acute Esophagitis in a Rat Model

Background/Aims. The aim of this study is to examine the protective effect of the cholinergic anti-inflammatory pathway (CAP) in experimental esophagitis in rats. Methods. A total of 40 male Sprague-Dawley (SD) rats were randomly divided into five groups as follows: control group, sham + saline group, sham + acid group, operation + saline group, and operation + acid group. Two weeks after the dorsal motor nucleus of the vagus (DMV) destruction, hydrochloric acid with pepsin was perfused into the lower part of the esophagus for 90 min. The rats were sacrificed 60 min after perfusion. The esophagus was prepared for hematoxylin and eosin (HE) staining, and the degree of inflammation and NF-κB activation in the esophagus was measured. Inflammatory cytokines (TNF-α, IL-6, IL-1β, and PGE2) in the esophagus were measured by ELISA. The brain was removed and processed for c-fos immunohistochemistry staining. The c-fos-positive neurons were counted and analyzed. Results. The TNF-α, IL-1β, IL-6, and PGE2 concentrations in the esophageal tissue increased after acid perfusion. The microscopic esophagitis scores and the activation of NF-κB p65 in the esophagus were significantly higher in the operation + acid group than in the operation + saline group. c-fos-positive neurons significantly increased in rats receiving acid perfusion in the amygdala (AM), the paraventricular nucleus of the hypothalamus (PVN), the parabrachial nucleus (PBN), the nucleus of the solitary tract (NTS)/DMV, the nucleus ambiguous (NA), the reticular nucleus of the medulla (RNM), and the area postrema (AP). After DMV destruction, c-fos expression was reduced in the AM, PVN, PBN, NTS/DMV, NA, RNM, and AP, especially in the AM, PVN, NTS/DMV, RNM, and AP. Conclusions. The DMV is an important nucleus of the CAP. The DMV lesion can aggravate esophageal inflammation and injury from acid-induced acute esophagitis in a rat model. The CAP has a protective effect on the acute esophagitis rat model and could be a new therapy for reflux esophagitis (RE).

Mucosal integrity and sensitivity to acid in the proximal esophagus in patients with gastroesophageal reflux disease

Acid reflux episodes that extend to the proximal esophagus are more likely to be perceived. This suggests that the proximal esophagus is more sensitive to acid than the distal esophagus, which could be caused by impaired mucosal integrity in the proximal esophagus. Our aim was to explore sensitivity to acid and mucosal integrity in different segments of the esophagus. We used a prospective observational study, including 12 patients with gastroesophageal reflux disease (GERD). After stopping acid secretion-inhibiting medication, two procedures were performed: an acid perfusion test and an upper endoscopy with electrical tissue impedance spectroscopy and esophageal biopsies. Proximal and distal sensitivity to acid and tissue impedance were measured in vivo, and mucosal permeability and epithelial intercellular spaces at different esophageal levels were measured in vitro. Mean lag time to heartburn perception was much shorter after proximal acid perfusion (0.8 min) than after distal acid perfusion (3.9 min) ( P = 0.02). Median in vivo tissue impedance was significantly lower in the distal esophagus (4,563 Ω·m) compared with the proximal esophagus (8,170 Ω·m) ( P = 0.002). Transepithelial permeability, as measured by the median fluorescein flux was significantly higher in the distal (2,051 nmol·cm−2·h−1) than in the proximal segment (368 nmol·cm−2·h−1) ( P = 0.033). Intercellular space ratio and maximum heartburn intensity were not significantly different between the proximal and distal esophagus. In GERD patients off acid secretion-inhibiting medication, acid exposure in the proximal segment of the esophagus provokes symptoms earlier than acid exposure in the distal esophagus, whereas mucosal integrity is impaired more in the distal esophagus. These findings indicate that the enhanced sensitivity to proximal reflux episodes is not explained by increased mucosal permeability.

Effects of acid on vagal nociceptive afferent subtypes in guinea pig esophagus

Acid reflux-induced heartburn and noncardiac chest pain are processed peripherally by sensory nerve endings in the wall of the esophagus, but the underlying mechanism is still unclear. This study aims to determine the effects of acid on esophageal vagal nociceptive afferent subtypes. Extracellular single-unit recordings were performed in guinea pig vagal nodose or jugular C fiber neurons by using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. We recorded action potentials (AP) of esophageal nodose or jugular C fibers evoked by acid perfusion and compared esophageal distension-evoked AP before and after acid perfusion. Acid perfusion for 30 min (pH range 7.4 to 5.8) did not evoke AP in nodose C fibers but significantly decreased their responses to esophageal distension, which could be recovered after washing out acid for 90 min. In jugular C fibers, acid perfusion not only evoked AP but also inhibited their responses to esophageal distension, which were not recovered after washing out acid for 120 min. Lower concentration of capsaicin perfusion mimicked acid-induced effects in nodose and jugular C fibers. Pretreatment with TRPV1 antagonist AMG9810, but not acid-sensing ion channel (ASIC) inhibitor amiloride, significantly inhibited acid-induced effects in nodose and jugular C fiber. These results demonstrate that esophageal vagal nociceptive afferent nerve subtypes display distinctive responses to acid. Acid activates jugular, but not nodose, C fibers and inhibits both of their responses to esophageal distension. These effects are mediated mainly through TRPV1. This inhibitory effect is a novel finding and may contribute to esophageal sensory/motor dysfunction in acid reflux diseases.