Objective. Despite widespread use of colchicine, the evidence basis for oral colchicine therapy and dosing in acute gout remains limited. The aim of this trial was to compare low-dose colchicine (abbreviated at 1 hour) and high-dose colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens producing comparable maximum plasma concentrations in healthy volunteers.Methods. This multicenter, randomized, doubleblind, placebo-controlled, parallel-group study compared self-administered low-dose colchicine (1.8 mg total over 1 hour) and high-dose colchicine (4.8 mg total over 6 hours) with placebo. The primary end point was >50% pain reduction at 24 hours without rescue medication.Results. There were 184 patients in the intent-totreat analysis. Responders included 28 of 74 patients (37.8%) in the low-dose group, 17 of 52 patients (32.7%) in the high-dose group, and 9 of 58 patients (15.5%) in the placebo group (P ‫؍‬ 0.005 and P ‫؍‬ 0.034, respectively, versus placebo). Rescue medication was taken within the first 24 hours by 23 patients (31.1%) in the low-dose group (P ‫؍‬ 0.027 versus placebo), 18 patients (34.6%) in the high-dose group (P ‫؍‬ 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low-dose group had an adverse event (AE) profile similar to that of the placebo group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7-3.2). High-dose colchicine was associated with significantly more diarrhea, vomiting, and other AEs compared with low-dose colchicine or placebo. With high-dose colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9-56.9]), 10 (19.2%) had severe diarrhea, and 9 (17.3%) had vomiting. With low-dose colchicine, 23.0% of the patients had diarrhea (OR 1.9 [95% CI 0.8-4.8]), none had severe diarrhea, and none had vomiting.Conclusion. Low-dose colchicine yielded both maximum plasma concentration and early gout flare efficacy comparable with that of high-dose colchicine, ClinicalTrials.gov identifier: NCT00506883.

No abstract

Gemcitabine plus cisplatin is an active regimen for the treatment of urothelial cancer.

The survival with DOX and VNB is not superior to DOX alone in MBC.

Insulin-like growth factors (IGFs) are essential for local skeletal muscle growth and organismal physiology, but these actions are entwined with glucose homeostasis through convergence with insulin signaling. The objective of this work was to determine whether the effects of IGF-I on growth and metabolism could be separated. We generated muscle-specific IGF-I-deficient (MID) mice that afford inducible deletion of Igf1 at any age. After Igf1 deletion at birth or in young adult mice, evaluations of muscle physiology and glucose homeostasis were performed up to 16 wk of age. MID mice generated at birth had lower muscle and circulating IGF-I, decreased muscle and body mass, and impaired muscle force production. Eight-wk-old male MID had heightened insulin levels with trends of elevated fasting glucose. This phenotype progressed to impaired glucose handling and increased fat deposition without significant muscle mass loss at 16 wk of age. The same phenotype emerged in 16-wk-old MID mice induced at 12 wk of age, compounded with heightened muscle fatigability and exercise intolerance. We assert that muscle IGF-I independently modulates anabolism and metabolism in an age-dependent manner, thus positioning muscle IGF-I maintenance to be critical for both muscle growth and metabolic homeostasis.-Vassilakos, G., Lei, H., Yang, Y., Puglise, J., Matheny, M., Durzynska, J., Ozery, M., Bennett, K., Spradlin, R., Bonanno, H., Park, S., Ahima, R. S., Barton, E. R. Deletion of muscle Igf-I transiently impairs growth and progressively disrupts glucose homeostasis in male mice.

No abstract

The recommended dose of BAY 12-9566 for further studies is 800 mg b.i.d. as this dose provides maximal plasma levels that can be achieved with a convenient dosing schedule for a chronically administered oral agent.

In the era of personalized medicine, the introduction of translational studies in clinical trials has substantially increased their costs, but provides the possibility of improving the productivity of trials with a better selection of recruited patients. With the overall goal of creating a roadmap to improve translational design for future gynecological cancer trials and of defining translational goals, a main discussion was held during a brainstorming day of the Gynecologic Cancer InterGroup (GCIG) Translational Research Committee and overall conclusions are here reported. A particular emphasis was dedicated to the new frontier of the immunoprofiling of gynecological cancers. The discussion pointed out that to maximize patients’ benefit, translational studies should be integral to clinical trial design with standardization and optimization of procedures including a harmonization program of Standard Operating Procedures. Pathology-reviewed sample collection should be mandatory and ensured by dedicated funding. Biomarker validation and development should be made public and transparent to ensure rapid progresses with positive outcomes for patients. Guidelines/templates for patients’ informed consent are needed. Importantly for the public, recognized goals are to increase the involvement of advocates and to improve the reporting of translational data in a forum accessible to patients.