The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: a 4-week, open-label trial.

BACKGROUND: Acute administration of the oral 5-HT1A receptor agonist buspirone, which is commonly used as an anxiolytic drug, may improve compromised lower esophageal sphincter function. In an open-label trial we assessed the effects of buspirone on esophageal motor function and symptoms in patients with esophageal involvement associated with systemic sclerosis (SSc). METHODS: Thirty consecutive patients with SSc and symptomatic esophageal involvement, despite treatment with proton pump inhibitors, underwent high resolution manometry and chest computed tomography for assessment of motor function and esophageal dilatation, respectively. Regurgitation, heartburn, dysphagia, and chest pain severity was subjectively scored by visual analog scales. Manometric parameters (primary endpoint) and symptom severity (secondary endpoint) were re-examined after 4-week daily administration of 20 mg buspirone. Other medications remained unchanged. RESULTS: Eight patients did not complete the trial because of buspirone-associated dizziness (n = 2), or nausea (n = 2), or reluctancy to undergo final manometry. In the remaining 22 patients lower esophageal sphincter (LES) resting pressure increased from 7.7 ± 3.9 to 12.2 ± 4.6 mmHg (p = 0.00002) after buspirone administration; other manometric parameters did not change. Statistical analysis revealed negative correlation between individual increases in resting LES pressure and supra-aortic esophageal diameter (r = -0.589, p = 0.017), suggesting a more beneficial effect in patients with less severely affected esophageal function. Heartburn and regurgitation scores decreased at 4 weeks compared to baseline (p = 0.001, and p = 0.022, respectively). CONCLUSION: Our findings warrant more conclusive evaluation with a double-blind controlled study; however, buspirone could potentially be given under observation for objective improvement in all patients with SSc who report reflux symptoms despite undergoing standard treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02363478 Registered: 21-02-2014.

Beneficial effect of the 5-HT1A receptor agonist buspirone on esophageal dysfunction associated with systemic sclerosis: A pilot study.

BACKGROUND: Esophageal involvement in systemic sclerosis (SSc) carries significant morbidity and is empirically managed with domperidone, albeit with questionable efficacy. The oral 5-HT1A receptor agonist buspirone may enhance esophageal peristalsis and lower esophageal sphincter (LES) function in healthy volunteers. AIM: We aimed to test the hypothesis that buspirone may exert a beneficial acute effect on esophageal motor dysfunction in symptomatic patients with SSc. METHODS: Twenty consecutive patients with SSc reporting esophageal symptoms underwent high-resolution manometry before and 30 minutes after administration of buspirone (10 mg). Ten other patients received domperidone (10 mg) and served as control group. Changes in LES resting and residual pressure, amplitude, duration, and velocity of distal esophageal body contractions were examined. RESULTS: Esophageal hypomotility and hypotensive LES was found in 63% and 67% of patients, respectively. Demographic and clinical characteristics, including baseline manometric parameters, were comparable between groups. Resting pressure of LES increased after buspirone from 9.42 ± 2.6 to 11.53 ± 3.4 mmHg (p = 0.0002 by paired t-test), but not after domperidone; a trend for increase of amplitude of contractions was also observed after buspirone (p = 0.09). Comparison of the individual changes revealed that buspirone was superior to domperidone in enhancing LES pressure ( + 2.11 ± 2.0 versus -0.45 ± 2.3 mmHg, p = 0.006). No significant effects of either drug were noted on other examined parameters of esophageal function. CONCLUSION: The beneficial acute effect of buspirone on impaired LES function associated with SSc suggests a role of 5-HT1A receptor-mediated interactions in these patients. Prospective studies to examine whether buspirone is of long-term therapeutic value for SSc-associated esophageal disease are warranted.

The impact of newer nucleos(t)ide analogues on patients with hepatitis B decompensated cirrhosis.

BACKGROUND/AIM: Patients with HBV-related decompensated cirrhosis (HBV-DeCi) should be treated with potent nucleos(t)ide analogues (NA)[entecavir (ETV) or tenofovir (TDF)]. The aim was the evaluation of safety and efficacy in terms of changes in liver disease course in HBV-DeCi patients treated with ETV or TDF. METHODS: In 52 HBV-DeCi patients clinical and laboratory data, including glomerular filtration rates (GFR), were recorded. The changes in MELD (DMELD) and Child-Pugh (DCTP) scores between baseline and after 6 months of treatment were evaluated. The independent factors associated with survival were evaluated. RESULTS: 31 patients under TDF and 21 under ETV were evaluated. During a median follow-up of 22.5 months (range: 6-68), there were no differences between the two groups in GFR and serum phosphate levels. At the end of follow up, in the TDF group, 2 patients died and 3 received liver transplantations (LT), while in the ETV group, 1 patient died and 3 received LT. In multivariable Cox regression analysis, DMELD was independently associated with the outcome in the total cohort (HR: 1.78, 95%C.I.:1.12-2.79, P=0.013) as well as in the subgroup of naïve (n=37) patients (HR: 1.8, 95%C.I.:1.19-4.5, P=0.03). Finally, in the non-hepatocellular carcinoma patients, the DCTP score was independently associated with the outcome in the total cohort (HR: 2.64, 95%C.I.: 1.21-7.29, P=0.015). CONCLUSIONS: TDF and ETV appear to have similar renal safety profile in HBV-DeCi patients. DMELD score in the total cohort and DCTP score in non-HCC patients were independently associated with the outcome; these findings need confirmation in larger studies.

Effects of moxonidine on sympathetic nervous system activity: An update on metabolism, cardio, and other target-organ protection.

Moxonidine is the newest, second-generation, centrally acting antihypertensive agent. It has selective agonist activity at imidazoline I1 receptors and less adverse effects than the other centrally acting drugs. This fact authorizes the frequent use of moxonidine in clinical practice, as monotherapy or in combination with other antihypertensive agents. Also, moxonidine has beneficial effects in obese and metabolic syndrome and in target-organs, such as heart and kidneys.

Clinical characteristics in patients with non-cardiac chest pain could favor gastroesophageal reflux disease diagnosis.

BACKGROUND: In patients with non-cardiac chest pain (NCCP), gastroesophageal reflux disease (GERD) is thought to be the commonest cause. Ambulatory pH monitoring and/or endoscopy are usually performed in order to confirm GERD diagnosis. At present, clinical diagnosis of reflux in patients with NCCP is uncertain.The aim of the study was to determine clinical characteristics that could identify GERD in patients with NCCP. METHODS: A total of 52 (age 52.8±1.8 yrs, 29 women) patients with NCCP underwent combined impedance-pH monitoring and gastroscopy. GERD diagnosis was based on the presence of esophagitis and/or a positive impedance-pH study (symptom index >50% and/or esophageal acid exposure time >4.0%). Patients were then divided into 2 groups: GERD- and non-GERD-related NCCP. Demographic and clinical parameters were compared between these two groups. RESULTS: GERD-related NCCP was found in 30 (58%) patients. Demographic characteristics were similar in both groups. Chest pain showed no difference in severity, radiation, relation to exercise and relation to sleep between the two groups. In the GERD-related NCCP group, chest pain was more prevalent during the postprandial period (P<0.05) and was relieved by spontaneous use of antireflux drugs (P<0.05). The presence of typical reflux symptoms favored a GERD diagnosis (P<0.05). CONCLUSIONS: A proportion of patients with NCCP showed clinical characteristics suggesting a GERD diagnosis. Typical reflux symptoms, postprandial chest pain and use of anti-reflux drugs for pain relief were the best predictors for GERD-related NCCP.