No abstract

Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplant (KT) with short-term outcomes similar to those obtained from donation after brain death (DBD) donors. However, heterogeneous results in the long term have been reported. We compared 10-year outcomes between 237 KT recipients from uDCD donors maintained by normothermic extracorporeal membrane oxygenation (nECMO) and 237 patients undergoing KT from standard criteria DBD donors during the same period at our institution. We further analyzed risk factors for death-censored graft survival in the uDCD group. Delayed graft function (DGF) was more common in the uDCD group (73.4% vs 46.4%; P < .01), although glomerular filtration rates at the end of follow-up were similar in the 2 groups. uDCD and DBD groups had similar rates for 10-year death-censored graft (82.1% vs 80.4%; P = .623) and recipient survival (86.2% vs 87.6%; P = .454). Donor age >50 years was associated with graft loss in the uDCD group (hazard ratio: 1.91; P = .058), whereas the occurrence of DGF showed no significant effect. uDCD KT under nECMO support resulted in similar graft function and long-term outcomes compared with KT from standard criteria DBD donors. Increased donor age could negatively affect graft survival after uDCD donation.

No abstract

Purpose: Bladder cancer is a clinical and social problem due to its high incidence and recurrence rates. It frequently appears in elderly patients showing other medical comorbidities that hamper the use of standard chemotherapy. We evaluated the activity of CDK4/6 inhibitor as a new therapy for patients unfit for cisplatin (CDDP).Experimental Design: Bladder cancer cell lines were tested for in vitro sensitivity to CDK4/6 inhibition. A novel metastatic bladder cancer mouse model was developed and used to test its in vivo activity.Results: Cell lines tested were sensitive to CDK4/6 inhibition, independent on RB1 gene status. Transcriptome analyses and knockdown experiments revealed a major role for FOXM1 in this response. CDK4/6 inhibition resulted in reduced FOXM1 phosphorylation in vitro and in vivo and showed synergy with CDDP, allowing a significant tumor regression. FOXM1 exerted important oncogenic roles in bladder cancer.Conclusions: CDK4/6 inhibitors, alone or in combination, are a novel therapeutic strategy for patients with advanced bladder cancer previously classified as unfit for current treatment options. , and PIE 15/00076 and CB/16/00228 (to J.M. Paramio); FEDER cofounded MINECO ISCIII grant PI15/00993 (to M. Santos); FEDER cofounded MINECO grants SAF2013-49147-P and SAF2016-80874-P and Ramon y Cajal contract RYC-2011-09242 (to S. Ruiz); and a grant from Asociaci on Española contra el C ancer Rubio et al.