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This study aimed to define the pharmacokinetics (PKs) of oral mannitol used as an osmotic laxative for bowel preparation for colonoscopy. The PKs of oral mannitol was evaluated in a substudy as part of a phase II dose-finding, international, multicenter, randomized, parallel-group, endoscopist-blinded study. Patients were randomly assigned to take 50, 100, or 150 g mannitol. Venous blood samples were drawn at baseline (T 0 ), 1 h (T 1 ), 2 h (T 2 ), 4 h (T 4 ), and 8 h (T 8 ) after completion of mannitol self-administration. The mean mannitol plasma concentrations (mg/ml) were dose-dependent with a consistent difference among doses. The mean maximum concentration (C max ) ± SD was 0.63 ± 0.15, 1.02 ± 0.28, and 1.36 ± 0.39 mg/ml, in the three dosage groups, respectively. The mean area under the curve from zero to infinity (AUC 0-∞ ) was 2.667 ± 0.668, 4.992 ± 1.706, and 7.403 ± 3.472 mg/ml*h in the 50, 100, and 150 g mannitol dose groups, respectively. Bioavailability was similar in the three dose groups and was just over 20% (0.243 ± 0.073, 0.209 ± 0.081, and 0.228 ± 0.093 in the 50, 100, and 150 g mannitol dose groups, respectively). The present study showed that the bioavailability of oral mannitol is just over 20% and is similar for the three tested doses (50, 100, and 150 g). The linear increase in C max , AUC 0-t8 , and AUC 0-∞ must be considered when choosing the oral mannitol dose for bowel preparation to avoid its systemic osmotic effects., (© 2022 NTC SRL and The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background : Gastrointestinal stromal tumors (GISTs) are most frequently located in the stomach. In the setting of a multidisciplinary approach, surgery represents the best therapeutic option, consisting mainly in a wedge gastric resection. (1) Materials and methods: Between January 2010 to September 2020, 105 patients with a primary gastrointestinal stromal tumor (GISTs) located in the stomach, underwent surgery at three surgical units. (2) Results: A multi-institutional analysis of minimally invasive series including 81 cases (36 laparoscopic and 45 robotic) from 3 referral centers was performed. Males were 35 (43.2%), the average age was 66.64 years old. ASA score ≥3 was 6 (13.3%) in the RS and 4 (11.1%) in the LS and the average tumor size was 4.4 cm. Most of the procedures were wedge resections ( N = 76; 93.8%) and the main operative time was 151 min in the RS and 97 min in the LS. Conversion was necessary in five cases (6.2%). (3) Conclusions: Minimal invasive approaches for gastric GISTs performed in selected patients and experienced centers are safe. A robotic approach represents a useful option, especially for GISTs that are more than 5 cm, even located in unfavorable places.

Background/aims: Symptom reflux association analysis is especially helpful for evaluation and management of proton pump inhibitor (PPI) re-fractory patients. An accurate calculation requires manual editing of 24-hour multichannel intraluminal impedance-pH (MII-pH) tracings after automatic analysis. Intra- and inter-observer agreement as well as reliability of rapid editing confined to the time around symptomatic episodes are unknown. Aim of this study was to explore these topics in a prospective multicenter study., Methods: Forty consecutive patients who were off PPI therapy underwent MII-pH recordings. After automatic analysis, their tracings were anonymized and randomized. Three experienced observers, each one trained in a different European center, independently per-formed manual editing of 24-hour tracings on 2 separate occasions. Values of symptom index and symptom association proba-bility for acid and non acid reflux were transformed into binary response (i.e., positive or negative)., Results: Intra-observer agreement on symptom reflux association was 92.5% to 100.0% for acid and 85.0% to 97.5% for non-acid reflux. Inter-observer agreement was 100.0% for acid and 82.5% to 95.0% for non-acid reflux. Values for symptom index and symptom association probability were similar. Concordance between 24-hour and rapid (2 minutes-window before each symp-tomatic episode) editings for symptom reflux association occured in 39 to 40 patients (acid) and in 37 to 40 (non-acid), de-pending on the observer., Conclusions: Intra- and inter-observer agreement in classifying patients with or without symptom reflux association at manual editing of 24-hour tracings was high, especially for acid reflux. Classifying patients according to a rapid editing showed excellent con-cordance with the 24-hour one and can be adopted in clinical practice.

Background/aims: Swallowing of cold liquids decreases amplitude and velocity of peristalsis in healthy subjects, using standard manometry. Patients with achalasia and non obstructive dysphagia may have degeneration of sensory neural pathways, affecting motor response to cooling. To elucidate this point, we used high-resolution manometry., Methods: Fifteen healthy subjects, 15 non-obstructive dysphagia and 15 achalasia patients, after pneumatic dilation, were studied. The 3 groups underwent eight 5 mL single swallows, two 20 mL multiple rapid swallows and 50 mL intraesophageal water infusion (1 mL/sec), using both water at room temperature and cold water, in a randomized order., Results: In healthy subjects, cold water reduced distal contractile integral in comparison with water at room temperature during single swallows, multiple rapid swallows and intraesophageal infusion (ratio cold/room temperature being 0.67 [95% CI, 0.48-0.85], 0.56 [95% CI, 0.19-0.92] and 0.24 [95% CI, 0.12-0.37], respectively). A similar effect was seen in non-obstructive dysphagia patients (0.68 [95% CI, 0.51-0.84], 0.69 [95% CI, 0.40-0.97] and 0.48 [95% CI, 0.20-0.76], respectively), whereas no changes occurred in achalasia patients (1.06 [95% CI, 0.83-1.29], 1.05 [95% CI, 0.77-1.33] and 1.41 [95% CI, 0.84-2.00], respectively)., Conclusions: Our data suggest impairment of esophageal reflexes induced by cold water in patients with achalasia, but not in those with non obstructive dysphagia.

Background & Aims: Many patients with gastroesophageal reflux disease (GERD) have persistent reflux despite treatment with proton pump inhibitors (PPIs). Mixed gas-liquid reflux events are more likely to be perceived as symptomatic. We used esophageal impedance monitoring to investigate whether esophageal gas is processed differently among patients with GERD who do and do not respond to PPI therapy., Methods: We performed a prospective study of 44 patients with typical reflux symptoms with high levels of esophageal acid exposure during a 24-hour period; 18 patients were fully responsive, and 26 did not respond to PPI therapy. Twenty-four-hour pH impedance recordings were analyzed for fasting and prandial air swallows and reflux characteristics, including the presence of gas in the refluxate., Results: PPI-refractory patients had a higher number (83.1 ± 12.7 vs 47.8 ± 7.3, P < .05) and rate (10.5 ± 1.4 vs 5.9 ± 0.8/10 minutes, P < .05) of prandial air swallows than patients who responded to PPI therapy; they also had a higher number (25.5 ± 4.0 vs 16.8 ± 3.3, P < .05) and proportion (70% ± 0.03% vs 54% ± 0.06%, P < .05) of postprandial, mixed gas-liquid reflux. Symptoms of PPI-refractory patients were more often preceded by mixed gas-liquid reflux events than those of PPI responders. Fasting air swallowing and other reflux characteristics did not differ between patients who did and did not respond to PPIs., Conclusions: Some patients with GERD who do not respond to PPI therapy swallow more air at mealtime than those who respond to PPIs and also have more reflux episodes that contain gas. These factors, combined with mucosal sensitization by previous exposure to acid, could affect perception of symptoms. These patients, who can be identified on standard 24-hour pH impedance monitoring, might be given behavioral therapy to reduce mealtime air swallowing., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The diffuse variant of supravalvular aortic stenosis (SVAS) is one of the most rare congenital vascular pathological conditions of adulthood. Due to its rarity, surgical treatment of this clinical entity is still a matter of debate because of the variable degree of aortic narrowing, presence of multilevel obstruction, and age at presentation, all factors that strongly influence the disease prognosis. We report a case of an adult patient with an extremely calcified diffuse SVAS who underwent successful replacement of the ascending aorta through the interposition of a tubular prosthesis. Six months' follow-up showed complete relief of the aortic gradient and an improvement in clinical performance.

The authors present a case of heterotopic central nervous system tissue observed in an 81-year-old male in the form of an ethmoidal polyp. A review of the literature indicates that this is a rare condition characterised by a connective tissue lesion with astrocytic and oligodendrocytic glial cells, which may be located outside the nasal pyramid in some cases and inside the nasal cavity in others. The most important diagnostic aspect involves differentiating these from meningoencephalocele, which maintains an anatomical connection with central nervous system tissue. Contrast-enhanced imaging is essential for diagnosis, as in cases of heterotopic central nervous system tissue, it will demonstrate that there are no connections with intra-cranial tissue. Endoscopic excision is the treatment of choice.