Variation across operating sites in urinary and sexual outcomes after radical prostatectomy in localized and locally advanced prostate cancer.

PURPOSE: The extent of variation in urinary and sexual functional outcomes after radical prostatectomy (RPE) between prostate cancer (PC) operating sites remains unknown. Therefore, this analysis aims to compare casemix-adjusted functional outcomes (EPIC-26 scores incontinence, irritative/obstructive function and sexual function) between operating sites 12 months after RPE. MATERIALS AND METHODS: Analysis of a cohort of 7065 men treated with RPE at 88 operating sites (prostate cancer centers, "PCCs") between 2016 and 2019. Patients completed EPIC-26 and sociodemographic information surveys at baseline and 12 months after RPE. Survey data were linked to clinical data. EPIC-26 domain scores at 12 months after RPE were adjusted for relevant confounders (including baseline domain score, clinical and sociodemographic information) using regression analysis. Differences between sites were described using minimal important differences (MIDs) and interquartile ranges (IQR). The effects of casemix adjustment on the score results were described using Cohen's d and MIDs. RESULTS: Adjusted domain scores at 12 months varied between sites, with IQRs of 66-78 (incontinence), 89-92 (irritative/obstructive function), and 20-29 (sexual function). Changes in domain scores after casemix adjustment for sites ≥ 1 MID were noted for the incontinence domain (six sites). Cohen's d ranged between - 0.07 (incontinence) and - 0.2 (sexual function), indicating a small to medium effect of casemix adjustment. CONCLUSIONS: Variation between sites was greatest in the incontinence and sexual function domains for RPE patients. Future research will need to identify the factors contributing to this variation. TRIAL REGISTRY: The study is registered at the German Clinical Trial Registry ( https://www.drks.de/drks_web/ ) with the following ID: DRKS00010774.

Relationship between pharmacokinetics and pharmacodynamics of calcineurin inhibitors in renal transplant patients.

The calcineurin inhibitors (CNIs) cyclosporine A (CsA) and tacrolimus (Tac) are immunosuppressive drugs, which are typically employed in the field of organ transplantation. Both drugs have narrow therapeutic indices, highly variable pharmacokinetics, and are associated with severe adverse effects. In current clinical routine, the dose finding of CNIs is based on the measurement of their blood concentrations. However, this method is limited in its ability to determine the biological impact of the drug. Alternative monitoring strategies, focusing on the pharmacodynamics of CNIs, could help to personalize drug dosing and optimize the treatment with CNIs. Therefore, we analyzed the relationship between pharmacokinetic and pharmacodynamic of the CNIs CsA (n = 9) and Tac (n = 8) in stable renal transplant patients during a 12-h dosing period. We observed a significant decrease in the drug-blood concentration during the course of the day and in parallel a significant recovery of T cell function. In addition, our data document that analysis of intracellular interleukin (IL)-2 production and determination of the IL-2 release are accurate parameters for monitoring the pharmacodynamics of CNIs.

Short-term treatment with the calcineurin inhibitor cyclosporine A decreases HPA axis activity and plasma noradrenaline levels in healthy male volunteers.

Treatment with the selective calcineurin inhibitor and immunosuppressive drug cyclosporine A (CsA) is associated with neurotoxicity and neurocognitive impairments. Whether and to what extent CsA is inducing alterations of the neuroendocrine status is unknown so far. Therefore, the present study investigated the effect of short-term CsA treatment on hypothalamus-pituitary-adrenal (HPA) axis activity and catecholamine release as well as state anxiety in healthy male subjects. Treatment with CsA significantly reduced plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, and noradrenaline whereas adrenaline levels and state anxiety remained unaffected. Future studies should analyze the mechanisms of CsA-induced effects on neuroendocrine variables, neurocognitive functions and mood.