First clinical-grade porcine kidney xenotransplant using a human decedent model.

A radical solution is needed for the organ supply crisis, and the domestic pig is a promising organ source. In preparation for a clinical trial of xenotransplantation, we developed an in vivo pre-clinical human model to test safety and feasibility tenets established in animal models. After performance of a novel, prospective compatible crossmatch, we performed bilateral native nephrectomies in a human brain-dead decedent and subsequently transplanted two kidneys from a pig genetically engineered for human xenotransplantation. The decedent was hemodynamically stable through reperfusion, and vascular integrity was maintained despite the exposure of the xenografts to human blood pressure. No hyperacute rejection was observed, and the kidneys remained viable until termination 74 h later. No chimerism or transmission of porcine retroviruses was detected. Longitudinal biopsies revealed thrombotic microangiopathy that did not progress in severity, without evidence of cellular rejection or deposition of antibody or complement proteins. Although the xenografts produced variable amounts of urine, creatinine clearance did not recover. Whether renal recovery was impacted by the milieu of brain death and/or microvascular injury remains unknown. In summary, our study suggests that major barriers to human xenotransplantation have been surmounted and identifies where new knowledge is needed to optimize xenotransplantation outcomes in humans.

Time series analysis of variables associated with daily mean emergency department length of stay.

STUDY OBJECTIVE: We measure the effect of various input, throughput, and output factors on daily emergency department (ED) mean length of stay per patient (daily mean length of stay). METHODS: The study was a retrospective review of 93,274 ED visits between April 15, 2002, and December 31, 2003. The association between the daily mean length of stay and the independent variables was assessed with autoregressive moving average time series analysis (ARIMA). The following independent variables were measured per 24-hour period: number of elective surgical admissions, ED volume, number of ED admissions, number of ED ICU admissions, number of ED clinical attending hours, hospital medical-surgical occupancy (hospital occupancy), and day of the week. RESULTS: Three factors were independently associated with daily mean length of stay in time series analysis: number of elective surgical admissions, number of ED admissions, and hospital occupancy. The daily mean length of stay increased by 0.21 minutes for every additional elective surgical admission, 2.2 minutes for every additional admission, and 4.1 minutes for every 5% increase in hospital occupancy. Elective surgical admissions were associated with a maximum of 35 hours of additional ED dwell time. The model accounted for 31.5% of the variability in daily mean length of stay. The final model parameters for the ARIMA analysis were autoregressive term (1) moving average (1). CONCLUSION: Hospital occupancy and the number of ED admissions are associated with daily mean length of stay. Every additional elective surgical admission prolonged the daily mean length of stay by 0.21 minutes per ED patient. Autocorrelation exists between the daily mean length of stay of the current day and the previous day.