Bismuth-based quadruple therapy following H. Pylori eradication failures: A multicenter study in clinical practice

Background & Aims: Helicobacter pylori (H. pylori) eradication in patients who failed one or more therapeutic attempts remains challenging. This study aimed to assess the efficacy of three-in-one capsules bismuth-based quadruple therapy (Pylera®) in these patients managed in clinical practice. Methods: This was a prospective, open-label, multicenter study enrolling consecutive, adult patients with persistent H. pylori infection following at least one standard therapy. All patients received a rescue quadruple therapy with Pylera (3 capsules four times daily) and esomeprazole 20 mg (1 tablet twice daily) for 10 days. H. pylori eradication was assessed by using Urea Breath Test 4-6 weeks following therapy ending. H. pylori eradication rates, compliance, and side-effects were calculated. Results: A total of 208 patients in the 9 participating centres were enrolled. Overall, 180 patients were successfully cured from the infection, accounting for 86.5% (95% CI 81.9-91.2) and 92.3% (95% CI 88.6-96.1) eradication rates at intention-to-treat analysis and at per protocol analysis, respectively. Cure rates were similar across patients who failed one to three previous therapy attempts, but the success rate fell to 67% after 4 or more therapy failures. Compliance to therapy was good in 198 (95.2%) patients, whilst in 7 (5.3%) cases the therapy was interrupted within 5 days due to side effects. A total of 97 (46.6%) patients complained of at least one side effect; nausea, diarrhea and vomiting were the most frequently reported. Conclusions: Our study found that this bismuth-based quadruple therapy is highly effective as second-line and rescue therapy for H. pylori eradication in clinical practic

Bismuth-based quadruple therapy following H. Pylori eradication failures: A multicenter study in clinical practice

Background & Aims: Helicobacter pylori (H. pylori) eradication in patients who failed one or more therapeutic attempts remains challenging. This study aimed to assess the efficacy of three-in-one capsules bismuth-based quadruple therapy (Pylera®) in these patients managed in clinical practice. Methods: This was a prospective, open-label, multicenter study enrolling consecutive, adult patients with persistent H. pylori infection following at least one standard therapy. All patients received a rescue quadruple therapy with Pylera (3 capsules four times daily) and esomeprazole 20 mg (1 tablet twice daily) for 10 days. H. pylori eradication was assessed by using Urea Breath Test 4-6 weeks following therapy ending. H. pylori eradication rates, compliance, and side-effects were calculated. Results: A total of 208 patients in the 9 participating centres were enrolled. Overall, 180 patients were successfully cured from the infection, accounting for 86.5% (95% CI 81.9-91.2) and 92.3% (95% CI 88.6-96.1) eradication rates at intention-to-treat analysis and at per protocol analysis, respectively. Cure rates were similar across patients who failed one to three previous therapy attempts, but the success rate fell to 67% after 4 or more therapy failures. Compliance to therapy was good in 198 (95.2%) patients, whilst in 7 (5.3%) cases the therapy was interrupted within 5 days due to side effects. A total of 97 (46.6%) patients complained of at least one side effect; nausea, diarrhea and vomiting were the most frequently reported. Conclusions: Our study found that this bismuth-based quadruple therapy is highly effective as second-line and rescue therapy for H. pylori eradication in clinical practic

The Effects of Antipsychotics on the Synaptic Plasticity Gene Homer1a Depend on a Combination of Their Receptor Profile, Dose, Duration of Treatment, and Brain Regions Targeted

Antipsychotic agents modulate key molecules of the postsynaptic density (PSD), including the Homer1a gene, implicated in dendritic spine architecture. How the antipsychotic receptor profile, dose, and duration of administration may influence synaptic plasticity and the Homer1a pattern of expression is yet to be determined

A Postsynaptic Density Immediate Early Gene-Based Connectome Analysis of Acute NMDAR Blockade and Reversal Effect of Antipsychotic Administration

: Although antipsychotics' mechanisms of action have been thoroughly investigated, they have not been fully elucidated at the network level. We tested the hypothesis that acute pre-treatment with ketamine (KET) and administration of asenapine (ASE) would modulate the functional connectivity of brain areas relevant to the pathophysiology of schizophrenia, based on transcript levels of Homer1a, an immediate early gene encoding a key molecule of the dendritic spine. Sprague-Dawley rats (n = 20) were assigned to KET (30 mg/kg) or vehicle (VEH). Each pre-treatment group (n = 10) was randomly split into two arms, receiving ASE (0.3 mg/kg), or VEH. Homer1a mRNA levels were evaluated by in situ hybridization in 33 regions of interest (ROIs). We computed all possible pairwise Pearson correlations and generated a network for each treatment group. Acute KET challenge was associated with negative correlations between the medial portion of cingulate cortex/indusium griseum and other ROIs, not detectable in other treatment groups. KET/ASE group showed significantly higher inter-correlations between medial cingulate cortex/indusium griseum and lateral putamen, the upper lip of the primary somatosensory cortex, septal area nuclei, and claustrum, in comparison to the KET/VEH network. ASE exposure was associated with changes in subcortical-cortical connectivity and an increase in centrality measures of the cingulate cortex and lateral septal nuclei. In conclusion, ASE was found to finely regulate brain connectivity by modelling the synaptic architecture and restoring a functional pattern of interregional co-activation

Plasma lipoproteins affect rate of cholesterol absorbed from bile by gallbladder: preliminary data

Abstract: Background. The excessive accumulation of cholesterol absorbed from bile by the gallbladder impairs its contractility and favours gallstone formation. The fetal low plasma and high density lipoprotein cholesterol concentrations are associated with gallstone disease. Aims, To investigate the effect of plasma lipoproteins on gallbladder cholesterol and phosphatidylcholine absorption from bile and to establish whether cholesterol absorption is Brefeldin A-sensitive Methods. Gallbladder mucosa lipid absorption rates were measured using: 1) in vitro isolated intra-arterially perfused pig gallbladder model with and without plasma lipoproteins perfusing the vascular tree; 2) human gallbladder fragments mounted in Ussing chambers with plasma lipoproteins at different concentrations in the serosal side; 3) pig gallbladder fragments mounted in Ussing chambers in the presence and absence of Brefeldin A. Results. Total lipoproteins and high density lipoprotein significantly increased the release of biliary cholesterol and phosphatidylcholine in plasma and significantly decreased the tissue accumulation of cholesterol absorbed from bile. The scavenger effect of plasma lipoproteins on cholesterol absorbed from bile was concentration dependent Brefeldin A did not influence gallbladder absorption of biliary cholesterol. Conclusions, Biliary cholesterol is absorbed by gallbladder mucosa via a Brefeldin-insensitive pathway and is removed by plasma lipoproteins

Comparison of changes in lipid profile after bilio-intestinal bypass and gastric banding in patients with morbid obesity

Background: The presence of hypercholesterolemia is currently not considered a selection criteria for performing gastric restrictive or diversionary bariatric surgery. Methods: We prospectively investigated the effects of the billo-intestinal bypass (BI-bypass) with a wide cholecysto-jejunal anastomosis and of adjustable gastric banding (AGB) on blood lipid concentrations in obese patients. To clarify the mechanism of the hypocholesterolemic effect of the Bl-bypass, daily fecal sterol excretion was measured by gas-liquid chromatography (GLC). Results: At 1 year after Bl-bypass compared to baseline, the hypercholesterolemic (n=18) and the normocholesterolemic (n=19) patients significantly reduced total (-38% and -27%, respectively), LDL (47% and -24%, respectively) and HDL (-11% and -13%, respectively) cholesterol and total /HDL cholesterol ratio (-25% and -13%, respectively). At 1 year after AGB, the total / HDL cholesterol ratio was significantly decreased (-11%) compared to baseline in hypercholesterolemic (n=12) but not in normocholesterolemic (n=6) patients, while total and LDL cholesterol were not affected in both groups. At 3 years after Bl-bypass compared to baseline, the hypercholesterolemic (n=9) and the normocholesterolemic (n=11) patients significantly reduced total (-43% and -28%, respectively) and LDL (-53% and -29%, respectively) cholesterol and total / HDL cholesterol ratio (-38% and -21%, respectively). The BI-bypass induced a significant (P<0.005; n=7) 6-fold increase in mean fecal cholesterol output. Conclusions: The Bl-bypass but not the AGB leads to a persistent and marked beneficial effect on blood LDL cholesterol associated with an increased cholesterol fecal output. Bl-bypass but not AGB is indicated in morbidly obese patients with hypercholesterolemia

Preharvest donor hyperoxia predicts good early graft function and longer graft survival after liver transplantation

Abstract A total of 44 donor/recipient perioperative and intraoperative variables were prospectively analyzed in 89 deceased-donor liver transplantations classified as initial good graft function (IGGF) or initial poor graft function (IPGF) according to a scoring system based on values obtained during the 1st 72 postoperative hours from the serum alanine aminotransferase (ALT) concentration, bile output, and prothrombin activity. The IGGF compared with the IPGF group showed: 1) longer graft (P = .002) and patient (P = .0004) survival; 2) at univariate analysis, a higher (mean [95% confidence interval]) preharvest donor arterial partial pressure of oxygen (PaO(2)) (152 [136-168] and 104 [91-118] mmHg, respectively; P = .0008) and arterial hemoglobin oxygen saturation (97.9 [97.2-98.7] and 96.7 [95.4-98.0]%, respectively; P = .0096), a lower percentage of donors older than 65 years (13 and 33%, respectively; P = .024), a lower percentage of donors treated with noradrenaline (16 and 41%, respectively; P = .012). At multivariate analysis, IGGF was associated positively with donor PaO(2) and negatively with donor age greater than 65 years and with donor treatment with noradrenaline. Independently from the grouping according to initial graft function, graft survival was longer when donor PaO(2) was >150 mmHg than when donor PaO(2) was < or =150 mmHg (P = .045). In conclusion, preharvest donor hyperoxia predicts IGGF and longer graft survival