BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given offlabel. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n ¼ 59) or placebo (n ¼ 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity 2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label Gastroenterology 2019;157:74-86 CLINICAL AT treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.
α-Synuclein inclusions have been identified in the brain and some parts of the enteric nervous system in Parkinson's disease cases. We aimed to assess these inclusions in gastric mucosa samples from patients with symptomatic Parkinson's disease. Random biopsies were performed by gastroscopy in 28 patients with Parkinson's disease and in 29 age- and sex-matched controls. Gastroscopy was performed to start enteral levodopa (L-dopa) therapy in cases and for diagnostic purposes in controls (gastroesophageal reflux, anemia, and abdominal pain were the main indications). The clinical definition of cases and controls was made a priori. Six controls had data suggestive of "mild presymptomatic parkinsonism". Biopsy specimens were immunostained for α-synuclein. The neuropathological diagnosis was established post hoc. No differences were found in the baseline characteristics of the groups. Positive fibers for the α-synuclein protein were observed in 17 of 28 (60.7%) Parkinson's disease patients, 1 of 23 controls (4.3%), and 1 of 6 (16.7%) cases of incident "mild presymptomatic parkinsonism." Neuropathological diagnosis based on α-synuclein immunostaining showed a sensitivity of 85% (95% confidence interval [CI] 62.1-96.8), specificity of 95% (95% CI 76.2-99.9) and area under the receiver operating characteristics curve (AUC) of 0.90 (95% CI 0.80-1.00). No adverse events occurred. Detection of α-synuclein inclusions in the gastric mucosa is a useful and safe tool providing in vivo evidence of the underlying neurodegenerative peripheral involvement linked to Parkinson's disease. Further studies are warranted to determine its pathophysiological implications.
Background/AimsThe body position can influence esophageal motility data obtained with high-resolution manometry (HRM). To examine whether the body position influences HRM diagnoses in patients with esophageal dysphagia and gastroesophageal reflux disease (GERD).Methods HRM (Manoscan) was performed in 99 patients in the sitting and supine positions; 49 had dysphagia and 50 had GERD assessed by 24-hour pH monitoring. HRM plots were analyzed according to the Chicago classification. ResultsHRM results varied in the final diagnoses of the esophageal body (EB) in patients with dysphagia (P = 0.024), the result being more distal spasm and weak peristalsis while sitting. In patients with GERD, the HRM diagnoses of the lower esophageal sphincter (LES), the esophagogastric junction (EGJ) morphology, and EB varied depending on the position; (P = 0.063, P = 0.017, P = 0.041 respectively). Hypotensive LES, EGJ type III (hiatal hernia), and weak peristalsis were more frequently identified in the sitting position. The reliability (kappa) of the position influencing HRM diagnoses was similar in dysphagia and GERD ("LES diagnosis": dysphagia 0.32 [0.14-0
Increased age, overweight and central obesity pose a higher risk of GEJ type III (hiatal hernia). The greater disruption of the GEJ is associated with lower resting pressure, esophageal shortening, and higher acid exposure in the pH-monitoring.
Introduction: There exits a great variability in the manometric findings between patients with anal incontinence (AI) and healthy subjects. The correlation between the pressures of the anal canal and the AI is not exact by the wide rank of normal values.Objectives: Prospective study to evaluate differences in the pressures of the anal canal and in rectal sensitivity in patients with AI, chronic constipation (CC) and healthy subjects.Material and methods: Ninety four patients with AI, 36 patients with CC and 15 healthy subjects were included. The following data were obtained: age, sex, resting pressure, anal canal length (ACL), squeeze maximum pressure (SMP), squeeze pressure duration (SPD), first sensation, urge and maximum tolerated volume (MTV). Statistical study: test of Kruskal-Wallis, test of Mann-Whitney, and multinomial logistic regression test.Results: There were significant differences in the resting pressure (p < 0.001), the ACL (p < 0.001) and the SMP (p < 0.01) in the group of AI with respect to the other two groups. The volume for the first sensation was significantly lower in the healthy subjects than that in the other two groups (p < 0.05). The urge volume and the MVT were smaller in the group with AI with respect to the other groups (p < 0.001). In multivariate analysis the age, the resting pressure and the volume for the first sensation and urge increase the relative risk for AI.Conclusions: The greater age, the decrease in anal canal resting pressure and the alteration of rectal sensation increase the risk for AI.Key words: Incontinencia fecal. Manometría ano-rectal. Presiones del canal anal. Sensibilidad rectal. RESUMENIntroducción: Existe gran variabilidad en los hallazgos manométricos entre pacientes con incontinencia anal (IA) y sujetos sanos. La correlación entre las presiones del canal anal y la IA no es exacta por el amplio rango de valores normales.Objetivos: Estudio prospectivo para evaluar diferencias en las presiones del canal anal y en la sensibilidad rectal en pacientes con IA, estreñimiento crónico (EC) y sujetos sanos.Material y métodos: Noventa y cuatro pacientes con IA, 36 pacientes con EC y 15 sujetos sanos. Se obtuvieron: edad, sexo, presión de reposo, longitud del canal anal (LCA), presión de máxi-ma contracción voluntaria (PMCV), duración de la contracción voluntaria, primera sensación, sensación de urgencia y máximo volumen tolerado (MVT). Estudio estadístico: test de Kruskal-Wallis, test de Mann-Whitney, regresión logística multinomial.Resultados: Se encontraron diferencias significativas en la edad (p < 0,001), la presión de reposo (p < 0,001), la LCA (p < 0,001) y la PMCV (p < 0,01) en el grupo de IA con respecto a los otros dos grupos. El volumen para la primera sensación fue significativamente más bajo en los sujetos sanos que en los otros dos grupos (p < 0,05). El volumen de urgencia y el MVT fueron menores en el grupo con IA con respecto a los otros dos grupos (p < 0,001). En el análisis multivariante la edad, la presión de reposo y el volumen de la primera sensació...
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