Normothermic machine perfusion (NMP) offers a unique opportunity to objectively assess donor organ quality. This study describes the evaluation of inulin clearance as a potential marker for the ex vivo function of porcine kidneys during NMP. The function assessment was performed in both kidneys from slaughterhouse pigs (n = 20) and kidneys from pigs in a laboratory setting (n = 28). The kidneys were exposed to different warm ischemia times (WIT). After a period of static cold storage, the kidneys underwent a 4-hour NMP with autologous whole blood. Inulin clearance, hemodynamic parameters, and urine output were measured. Based on the inulin excretion behavior laboratory pig kidneys were assigned to three classes (functional, limited functional, and nonfunctional), slaughterhouse pig kidneys to two classes (limited functional and nonfunctional), respectively. Contrary to the marginal kidneys of the slaughterhouse pigs, the functional variation of kidneys of the laboratory pigs was associated with the WIT. A correlation between functional kidneys and a WIT less than 25 min was shown. Because none of the slaughterhouse pig kidneys could be assigned to the functional class, only the laboratory pig kidneys were used for examinations with functional markers. Renal blood flow and urine output during NMP correlated significantly (p < 0.01) with ex vivo kidney function. This study demonstrated that inulin is a marker of high quality for the evaluation of suggested kidney function after NMP with whole blood. Furthermore, surrogate markers measured during NMP can be used to describe and predict the physiologic behavior of kidneys before transplantation.
Facing organ shortages, increasing wait times and considerable mortality on dialysis, we question the current policy of HU allocation and propose more restrictive criteria with regard to individuals with vascular complications or repeated retransplantations in order to support patients on the non-HU waiting list with a much better long-term prognosis.
For decades, mono androgen deprivation therapy (ADT) has been the gold standard for metastatic hormone-sensitive prostate cancer (mHSPC) treatment. Several studies have been published within the last seven years demonstrating a significant survival advantage by combination treatment with standard ADT plus docetaxel or androgen receptor-axis-targeted therapy (ARAT) compared to ADT monotherapy. As a result, overall survival can be prolonged by at least 18 months. Recently published congress data of the PEACE-1 study suggests that in the future, triple therapy might be the new gold standard. In addition to this study, which has shown that triple treatment with standard ADT plus docetaxel plus abiraterone is superior to standard ADT plus docetaxel, several other phase III triple therapy studies are currently ongoing. The different modes of action that are investigated reach from AR-targeting over mitotic inhibition and immunotherapy to PARP and AKT inhibition. In this review we will explore if triple therapy has the potential to be the new standard for mHSPC treatment in the near future.
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