Budesonide Foam Has a Favorable Safety Profile for Inducing Remission in Mild-to-Moderate Ulcerative Proctitis or Proctosigmoiditis.

BackgroundBudesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis.AimThe aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam.MethodsData from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam.ResultsA similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0%, respectively). Adverse events occurred in 41.4 and 36.3% of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic-pituitary-adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration.ConclusionsThis integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis

Tegaserod Treatment for Dysmotility-Like Functional Dyspepsia: Results of Two Randomized, Controlled Trials

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74639/1/j.1572-0241.2008.01953.x.pd

Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study

Objective: To compare the predictive accuracy and clinical utility of five risk scoring systems in the assessment of patients with upper gastrointestinal bleeding. Design: International multicentre prospective study. Setting: Six large hospitals in Europe, North America, Asia, and Oceania. Participants: 3012 consecutive patients presenting over 12 months with upper gastrointestinal bleeding. Main outcome measures: Comparison of pre-endoscopy scores (admission Rockall, AIMS65, and Glasgow Blatchford) and post-endoscopy scores (full Rockall and PNED) for their ability to predict predefined clinical endpoints: a composite endpoint (transfusion, endoscopic treatment, interventional radiology, surgery, or 30 day mortality), endoscopic treatment, 30 day mortality, rebleeding, and length of hospital stay. Optimum score thresholds to identify low risk and high risk patients were determined. Results: The Glasgow Blatchford score was best (area under the receiver operating characteristic curve (AUROC) 0.86) at predicting intervention or death compared with the full Rockall score (0.70), PNED score (0.69), admission Rockall score (0.66, and AIMS65 score (0.68) (all P<0.001). A Glasgow Blatchford score of ≤1 was the optimum threshold to predict survival without intervention (sensitivity 98.6%, specificity 34.6%). The Glasgow Blatchford score was better at predicting endoscopic treatment (AUROC 0.75) than the AIMS65 (0.62) and admission Rockall scores (0.61) (both P<0.001). A Glasgow Blatchford score of ≥7 was the optimum threshold to predict endoscopic treatment (sensitivity 80%, specificity 57%). The PNED (AUROC 0.77) and AIMS65 scores (0.77) were best at predicting mortality, with both superior to admission Rockall score (0.72) and Glasgow Blatchford score (0.64; P<0.001). Score thresholds of ≥4 for PNED, ≥2 for AIMS65, ≥4 for admission Rockall, and ≥5 for full Rockall were optimal at predicting death, with sensitivities of 65.8-78.6% and specificities of 65.0-65.3%. No score was helpful at predicting rebleeding or length of stay. Conclusions: The Glasgow Blatchford score has high accuracy at predicting need for hospital based intervention or death. Scores of ≤1 appear the optimum threshold for directing patients to outpatient management. AUROCs of scores for the other endpoints are less than 0.80, therefore their clinical utility for these outcomes seems to be limited. Trial registration: Current Controlled Trials ISRCTN16235737

Demonstration of Metabolic and Cellular Effects of Portal Vein Ligation Using Multi-Modal PET/MRI Measurements in Healthy Rat Liver.

OBJECTIVES: In the early recognition of portal vein ligation (PVL) induced tumor progression, positron emission tomography and magnetic resonance imaging (PET/MRI) could improve diagnostic accuracy of conventionally used methods. It is unknown how PVL affects metabolic patterns of tumor free hepatic tissues. The aim of this preliminary study is to evaluate the effect of PVL on glucose metabolism, using PET/MRI imaging in healthy rat liver. MATERIALS AND METHODS: Male Wistar rats (n = 30) underwent PVL. 2-deoxy-2-(18F)fluoro-D-glucose (FDG) PET/MRI imaging (nanoScan PET/MRI) and morphological/histological examination were performed before (Day 0) and 1, 2, 3, and 7 days after PVL. Dynamic PET data were collected and the standardized uptake values (SUV) for ligated and non-ligated liver lobes were calculated in relation to cardiac left ventricle (SUVVOI/SUVCLV) and mean liver SUV (SUVVOI/SUVLiver). RESULTS: PVL induced atrophy of ligated lobes, while non-ligated liver tissue showed compensatory hypertrophy. Dynamic PET scan revealed altered FDG kinetics in both ligated and non-ligated liver lobes. SUVVOI/SUVCLV significantly increased in both groups of lobes, with a maximal value at the 2nd postoperative day and returned near to the baseline 7 days after the ligation. After PVL, ligated liver lobes showed significantly higher tracer uptake compared to the non-ligated lobes (significantly higher SUVVOI/SUVLiver values were observed at postoperative day 1, 2 and 3). The homogenous tracer biodistribution observed before PVL reappeared by 7th postoperative day. CONCLUSION: The observed alterations in FDG uptake dynamics should be taken into account during the assessment of PET data until the PVL induced atrophic and regenerative processes are completed

Percutaneous thoracic endovascular aortic repair is not contraindicated in obese patients

ObjectiveThere are limited data describing the preclose technique with the Perclose ProGlide device (Abbott Vascular, Redwood City, Calif) in percutaneous thoracic endovascular aortic repair (P-TEVAR), particularly in obese patients, in whom use of this technique is thought to be relatively contraindicated. The purpose of this analysis was to describe our experience with P-TEVAR and to compare outcomes in patients with or without obesity.MethodsAll TEVAR procedures at a single institution from 2005 to 2011 were reviewed, and P-TEVAR patients were stratified by body mass index (obesity ≥ 30 kg/m2). Preoperative computed tomography scans were analyzed for access vessel depth, calcification, and morphology. Technical success was defined as the ability to achieve hemostasis and to maintain limb perfusion without the need for common femoral artery exposure or obligate surgical repair of the vessel within a 30-day postoperative period. Generalized estimating equations and stepwise logistic regression were used to develop prediction models of preclose failure.ResultsThe review identified 536 patients, in whom 355 (66%) P-TEVAR procedures were completed (366 arteries; n = 40 [11%] bilateral). Compared with nonobese patients (n = 264), obese patients (n = 91) were typically younger (59 ± 16 years vs 66 ± 16 years; P = .0004) and more likely to have renal insufficiency (28% vs 17%; P = .05) or diabetes mellitus (19% vs 9%; P = .02). The number of Perclose deployments was similar between groups (P = NS). Mean sheath size (25.4F vs 25.0F; P = .04), access vessel inner diameters (8.5 ± 1.9 mm vs 7.9 ± 2.0 mm; P = .02), and vessel depth (50 ± 20 mm vs 30 ± 13 mm; P < .0001) were greater in obese patients. Adjunctive iliac stents were used in 7% of cases (10 [11%] in obese patients vs 16 [6%] in nonobese patients; P = .2). Overall technical success was 92% (92% for nonobese patients vs 93% for obese patients; P = .7). Three patients required subsequent operations for access complications, two obese patients (2%) and one nonobese patient (0.4%) (P = .3). Independent predictors of failure were adjunctive iliac stent (odds ratio [OR], 9.5; 95% confidence interval [CI], 3.3-27.8; P < .0001), more than two Perclose devices (OR, 7.0; 95% CI, 2.3-21; P = .0005), and smaller access vessel diameter to sheath size ratio (OR multiplies by 1.1 for each .01 decrease in ratio; 95% CI, 1.02-1.2; P = .007) (area under the receiver operating characteristic curve = .75).ConclusionsObesity is not a contraindication to P-TEVAR. P-TEVAR can be performed safely, despite the need for larger diameter sheaths. However, patients predicted to need adjunctive stenting or possessing smaller access vessel diameter to sheath size ratios are at highest risk of preclose failure with the Perclose ProGlide device, and selective use of this technique is recommended