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Item Donor Simvastatin Treatment Is Safe and Might Improve Outcomes After Liver Transplantation: A Randomized Clinical Trial(Wolters Kluwer, 2022) Pagano, Duilio; Bosch, Jaime; Tuzzolino, Fabio; Oliva, Elisabetta; Ekser, Burcin; Zito, Giovanni; Cintorino, Davide; di Francesco, Fabrizio; Petri, Sergio Li; Ricotta, Calogero; Bonsignore, Pasquale; Calamia, Sergio; Magro, Bianca; Trifirò, Gianluca; Alduino, Rossella; Barbara, Marco; Conaldi, Pier Giulio; Gallo, Alessia; Venuti, Francesca; Luca, Angelo; Gruttadauria, Salvatore; Surgery, School of MedicineBackground: The current curative approaches for ischemia/reperfusion injury on liver transplantation are still under debate for their safety and efficacy in patients with end-stage liver disease. We present the SIMVA statin donor treatment before Liver Transplants study. Methods: SIMVA statin donor treatment before Liver Transplants is a monocentric, double-blind, randomized, prospective trial aiming to compare the safety and efficacy of preoperative brain-dead donors' treatment with the intragastric administration of 80 mg of simvastatin on liver transplant recipient outcomes in a real-life setting. Primary aim was incidence of patient and graft survival at 90 and 180 d posttransplant; secondary end-points were severe complications. Results: The trial enrolled 58 adult patients (18-65 y old). The minimum follow-up was 6 mo. No patient or graft was lost at 90 or 180 d in the experimental group (n = 28), whereas patient/graft survival were 93.1% ( P = 0.016) and 89.66% ( P = 0.080) at 90 d and 86.21% ( P = 0.041) and 86.2% ( P = 0.041) at 180 d in the control group (n = 29). The percentage of patients with severe complications (Clavien-Dindo ≥IIIb) was higher in the control group, 55.2% versus 25.0% in the experimental group ( P = 0.0307). The only significant difference in liver tests was a significantly higher gamma-glutamyl transferase and alkaline phosphatase at 15 d ( P = 0.017), ( P = 0.015) in the simvastatin group. Conclusions: Donor simvastatin treatment is safe, and may significantly improve early graft and patient survival after liver transplantation, although further research is mandatory.Item Donor Utilization in the Recent Era: Effect of Sex, Drugs, and Increased Risk(American Heart Association, 2022) Baran, David A.; Long, Ashleigh; Lansinger, Justin; Copeland, Jack G.; Copeland, Hannah; Surgery, School of MedicineBackground: Heart transplantation volumes have increased in recent years, yet less than a third of donors are typically accepted for transplantation. Whether donor sex, donor drug use, or perception of increased risk affects utilization for transplantation is unclear. Methods: The United Network for Organ Sharing database was queried for donors from January 1, 2007, to December 31, 2017. Donor toxicology was collected when available. Multivariate analysis was conducted to examine correlations with donor utilization. Results: Between January 1, 2007, and December 31, 2017, there were 87 816 heart donors aged ≥15 years. The mean age was 42.7±15.8 years, and 24 831 donors (28.3%) were utilized for heart transplantation. Subsequent analyses focused on donors between 15 and 39 years old. The strongest associations with donor acceptance were for male donor sex, blood type, hepatitis C antibody, donor age, left ventricular hypertrophy, and history of donor drug use. After removing hepatitis C, Public Health Service Increased Risk was identified as a strong negative predictor. Most positive drug toxicology results were associated with donor nonuse except for donors between 15 and 19 years of age. Exceptions included alcohol, marijuana, and cocaine. Opiates were associated with less utilization at all donor ages. The Public Health Service Increased Risk status was associated with significantly less utilization in all age groups except 15- to 19-year-old donors. Conclusions: While male donors were preferentially utilized, donors with drug use or those deemed Public Health Service Increased Risk were significantly less utilized for heart transplantation. Further consideration of such donors would be appropriate particularly as the demand for transplantation continues to increase.Item Impact of Variant Donor Hepatic Arterial Anatomy on Clinical Graft Outcomes in Liver Transplantation(Wiley, 2018-10) Schroering, Joel R.; Kubal, Chandrashekhar A.; Fridell, Jonathan A.; Hathaway, Taylor J.; Robinson, Ross C.; Mangus, Richard S.; Surgery, School of MedicineStandard hepatic arterial anatomy is composed of the common hepatic artery proceeding from the celiac trunk and giving rise to the gastroduodenal artery (GDA) and proper hepatic arteries. Reconstruction of the hepatic arterial supply during liver transplantation, often complex in nature, can be required in cases of accessory or replaced vessels. A recent review summarized the hepatic arterial anatomy reported in over 19,000 cases from 20 individual studies. (1) It has been suggested that the presence of nonstandard donor arterial anatomy may be related to an increased incidence of hepatic artery thrombosis (HAT).(2) Although the overall incidence of HAT is low, it can have devastating effects, including the need for retransplantation, long-term biliary complications, and increased patient mortality. This article describes the arterial anatomy in a large number of liver transplants, with routine anastomosis of a very short hepatic artery and routine reconstruction of the accessory right hepatic artery to the GDA. Study outcomes include incidence of HAT within 30 days of transplant, early graft loss up to 1 year after transplant, and 10-year graft survival.Item Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes(Wolters Kluwer, 2021) Mansour, Sherry G.; Liu, Caroline; Jia, Yaqi; Reese, Peter P.; Hall, Isaac E.; El-Achkar, Tarek M.; LaFavers, Kaice A.; Obeid, Wassim; Rosenberg, Avi Z.; Daneshpajouhnejad, Parnaz; Doshi, Mona D.; Akalin, Enver; Bromberg, Jonathan S.; Harhay, Meera N.; Mohan, Sumit; Muthukumar, Thangamani; Schröppel, Bernd; Singh, Pooja; El-Khoury, Joe M.; Weng, Francis L.; Thiessen-Philbrook, Heather R.; Parikh, Chirag R.; Medicine, School of MedicineBackground: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes. Methods: Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages. Results: Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted β coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF. Conclusions: UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.