Lacroix Gibbs (salaryhoe71)
What is known and objective Nephrotoxicity is a frequently occurring side effect of cisplatin, which may be reduced by applying ample hydration. The aim of this study was to determine whether there is a difference in decline in renal function due to cisplatin between a short hydration (SH) and long hydration scheme (LH). Methods A retrospective, observational, cohort study was conducted in two hospitals. Patients in one hospital received an SH scheme (SH group), whereas patients in the other hospital received an LH scheme (LH group). Other aspects of treatment and hydration were comparable between both patient groups. Consecutive patients (≥18 years) treated for non-small-cell lung cancer with cisplatin-pemetrexed with ≥1 cisplatin dose were included. Patients were excluded when serum creatinine at baseline was less then 40 μmol/L. Primary outcome was the difference in estimated glomerular filtration rate (eGFR) between baseline and after the last cisplatin cycle for the SH and LH patients, regardless of theematurely due to nephrotoxicity. Therefore, a short hydration scheme provides adequate and safe hydration, with a lower risk of nephrotoxic side effects and therefore better outcomes for patients and a reduction of healthcare costs.Telomerase reverse transcriptase (TERT) promoter mutations are frequently found in tumors or urine from patients with urothelial carcinoma (UC). TERT promoter mutations are also detected in urine from patients with no evidence of cancer but are associated with subsequent UC development. Mutations in the TERT promoter are thought to be present in nonmalignant urothelium (NMU) during early stages of tumor formation prior to pathological change, but this has not been proven directly. In this proof-of-concept study, we investigated the clinical utility of TERT promoter mutation analysis in NMU of patients with non-muscle-invasive bladder cancer (NMIBC). This single-institute study included 53 primary tumors and 428 systematic bladder biopsy specimens from 54 patients with NMIBC. All patients underwent systematic random biopsy and transurethral resection of the bladder tumor. Genomic DNA was analyzed for TERT C228T and C250T mutations using droplet digital PCR (ddPCR). The association between TERT promoter mutation of NMU and bladder recurrence was examined by the Kaplan-Meier method and Cox proportional hazards model. Of the 54 patients, 16 (29.6%) had a TERT C228T mutation and three (5.6%) had a TERT C250T mutation in NMU. Of 428 biopsy specimens, the TERT C228T mutation was detected in 9% (31/364) of normal urothelium, 27% (4/15) of urothelial dysplasia (UD), 50% (9/18) of UD suspicious for carcinoma in situ (CIS), and 58% (18/31) of CIS. During follow-up (median 3.7 years), 22 (40.7%) patients experienced bladder recurrence and five (9.3%) experienced disease progression. Cox proportional hazard analysis showed that TERT C228T mutation in NMU was significantly associated with bladder recurrence after adjustment for cofounding factors (P = 0.0128). Thus, TERT C228T mutation was detected in NMU, which was a reliable independent prognostic factor of bladder tumor recurrence.Background Although humans are exposed to mixtures of endocrine disruptor chemicals, few studies have examined their toxicity on male reproduction. We previously found that fetal exposure to a mixture of the phytoestrogen genistein (GEN) and the plasticizer di(2-ethylhexyl) phthalate (DEHP) altered gene expression in adult rat testes. Objectives Our goal was to investigate the effects of fetal exposure to GEN-DEHP mixtures at two doses relevant to humans on testicular function and transcriptome in neonatal and adult rats. Materials and methods Pregnant SD rats were gavaged with vehicle, GEN or DEHP, alone or mixed at 0.1 and 10 mg/kg/day, from gestation day 14 to birth. Fertility, steroid levels, and testis morphology were examined in neonatal and adult rats. Testicular transcriptomes were examined by gene array and functional p