Outcomes of Combined Heart and Kidney Transplantation Under the New Heart Allocation Policy: A United Organ Network for Organ Sharing Database Analysis.

BACKGROUND: The impact of the new heart allocation policy, which prioritizes acutely ill patients on temporary mechanical circulatory support and provides broader sharing of donor organs, on patient and graft survival in combined heart and kidney transplantation (HKT) is unknown. METHODS: In the United Network for Organ Sharing data, patients were divided in groups before and after the policy change (OLD, January 1, 2015 to October 17, 2018, N=533; and NEW, October 18, 2018 to December 31, 2020, N=370). Propensity score matching was performed utilizing recipient characteristics (283 pairs). The median follow-up was 1099 days. RESULTS: The annual volume of HKT increased approximately 2-fold during this period (N=117 in 2015 and N=237 in 2020), predominantly among patients not on hemodialysis at time of transplantation. Ischemic times for heart (OLD, 2.94 versus NEW, 3.37 hours; P<0.001) and kidney grafts (14.1 versus 16.0 hours; P<0.001) were longer under the new policy, as was the travel distance (47 versus 183 miles; P<0.001). In the matched cohort, 1-year overall survival (OLD, 91.1% versus NEW, 84.8%; P<0.001), and freedom from heart and kidney graft failure rate were worse under the new policy. Patients not on hemodialysis at time of HKT demonstrated worse survival and a higher risk of kidney graft failure under the new policy compared with the old policy. In multivariate Cox proportional-hazards analysis, the new policy was associated with an increased risk of mortality (hazard ratio, 1.81; P=0.007), and graft failure among HKT recipients (heart, hazard ratio, 1.81; P=0.007; and kidney, hazard ratio, 1.83; P=0.002). CONCLUSIONS: The new heart allocation policy was associated with worse overall survival and decreased freedom from heart and kidney graft failure in HKT recipients.

The effect of mifepristone (RU 486) on plasma cortisol in Alzheimer's disease.

The glucocorticoid receptor (GR) antagonist mifepristone (RU-486) has been reported to increase early morning plasma ACTH/cortisol in diverse non-demented populations. This pilot study examined the cortisol response to RU 486 in patients with Alzheimer's disease (AD), a condition associated with abnormalities in various aspects of the hypothalamic-pituitary-adrenal (HPA) axis. Nine AD subjects were randomized in a placebo-controlled parallel study: 4 in the placebo group and 5 in the RU 486 group. Subjects received oral doses of RU 486 (200 mg) or placebo daily for 6-weeks. Morning plasma cortisol was determined at baseline, at 12 h following the first study drug dose, and weekly thereafter. RU 486 resulted in a significant increase in cortisol levels [F(1,6)=65.32; P<0.001]. The magnitude of this increase grew over the course of the study [F(1,6)=63.17; P<0.001], was not related to cortisol suppression after dexamethasone and appeared greater than that reported in the literature in younger populations in response to the same drug regimen. However, further studies with age-matched controls should be done to determine possible AD related changes in this response.