Effects of metformin and statins on outcomes in men with castration-resistant metastatic prostate cancer: Secondary analysis of COU-AA-301 and COU-AA-302

Abiraterone acetate; Metastatic castration-resistant prostate cancer; MetforminAcetato de abiraterona; Cáncer de próstata metastásico resistente a la castración; MetforminaAcetat d'abiraterona; Càncer de pròstata resistent a la castració metastàtic; MetforminaBackground The associations of metformin and statins with overall survival (OS) and prostate specific antigen response rate (PSA-RR) in trials in metastatic castration-resistant prostate cancer remain unclear. Objective To determine whether metformin or statins ± abiraterone acetate plus prednisone/prednisolone (AAP) influence OS and PSA-RR. Design, setting and participant COU-AA-301 and COU-AA-302 patients were stratified by metformin and statin use. Cox proportional hazards models were used to estimate hazards ratio (HR) stratified by concomitant medications, and a random effects model was used to pool HR. We compared PSA-RR using Chi χ2 test. Results In COU-AA-301-AAP, metformin was associated with improved PSA-RR (41.1% versus 28.6%) but not prolonged OS. In COU-AA-301-placebo-P, there was no association between metformin and prolonged OS or PSA-RR. In COU-AA-302-AAP, metformin was associated with prolonged OS (adjHR 0.69, 95% CI 0.48–0.98) and improved PSA-RR (72.7% versus 60.0%). In COU-AA-302-P, metformin was associated with prolonged OS (adjHR 0.66, 95% CI 0.47–0.93). In pooled analysis, OS was prolonged among those treated with metformin (pooled HR 0.77, 95% CI 0.62–0.95).In COU-AA-301-AAP, statins were associated with an improved OS (adjHR 0.76, 95% CI 0.62–0.93), while there was no difference in COU-AA-301-P. There was no association with statins and OS in either COU-AA-302 groups. When pooling HR, OS was prolonged among those treated with statins (pooled HR 0.78, 95% CI 0.68–0.88). Conclusion Within the limitations of post-hoc sub-analyses, metformin and statins are associated with a prolonged OS and increased PSA-RR, particularly in combination with AAP

Luminosity Functions of Spitzer Identified Protostars in Nine Nearby Molecular Clouds

We identify protostars in Spitzer surveys of nine star-forming molecular clouds within 1 kpc: Serpens, Perseus, Ophiuchus, Chamaeleon, Lupus, Taurus, Orion, Cep OB3, and Mon R2, which combined host over 700 protostar candidates. Our diverse cloud sample allows us to compare protostar luminosity functions in these varied environments. We combine photometry from 2MASS J, H, and Ks bands and Spitzer IRAC and MIPS 24 micron bands to create 1 - 24 micron spectral energy distributions (SEDs). Using protostars from the c2d survey with well-determined bolometric luminosities (Lbol), we derive a relationship between Lbol, L_MIR (integrated from 1 - 24 microns), and SED slope. Estimations of Lbol for protostar candidates are combined to create luminosity functions for each cloud. Contamination due to edge-on disks, reddened Class II sources, and galaxies is estimated and removed from the luminosity functions. We find that luminosity functions for high mass star forming clouds peak near 1 Lsun and show a tail extending toward luminosities above 100 Lsun. The luminosity functions of the low mass star forming clouds do not exhibit a common peak, however the combined luminosity function of these regions peaks below 1 Lsun. Finally, we examine the luminosity functions as a function of the local surface density of YSOs. In the Orion molecular cloud, we find a significant difference between the luminosity functions of protostars in regions of high and low stellar density, the former of which is biased toward more luminous sources. This may be the result of primordial mass segregation, although this interpretation is not unique. We compare our luminosity functions to those predicted by models and find that our observed luminosity functions are best matched by models which invoke competitive accretion, although we do not find strong agreement of the high mass star forming clouds with any of the models.Comment: 76 pages, 18 figures, 7 tables. Accepted for publication in the Astronomical Journa

Effects of fecal microbiome transfer in adolescents with obesity: the gut bugs randomized controlled trial

Peer reviewe

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD