Inferior Outcomes on the Waiting List in Low-Volume Pediatric Heart Transplant Centers.

Low case volume has been associated with poor outcomes in a wide spectrum of procedures. Our objective was to study the association of low case volume and worse outcomes in pediatric heart transplant centers, taking the novel approach of including waitlist outcomes in the analysis. We studied a cohort of 6482 candidates listed in the Organ Procurement and Transplantation Network for pediatric heart transplantation between 2002 and 2014; 4665 (72%) of the candidates underwent transplantation. Candidates were divided into groups according to the average annual transplantation volume of the listing center during the study period: more than 10, six to 10, three to five, or fewer than three transplantations. We used multivariate Cox regression analysis to identify independent risk factors for waitlist and posttransplantation mortality. Of the 6482 candidates, 24% were listed in low-volume centers (fewer than three annual transplantations). Of these listed candidates in low-volume centers, only 36% received a transplant versus 89% in high-volume centers (more than 10 annual transplantations) (p < 0.001). Listing at a low-volume center was the most significant risk factor for waitlist death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 3.5-5.7 in multivariate Cox regression and HR 5.6, CI 4.4-7.3 in multivariate competing risk regression) and was significant for posttransplantation death (HR 1.27, 95% CI 1.0-1.6 in multivariate Cox regression). During the study period, one-fourth of pediatric transplant candidates were listed in low-volume transplant centers. These children had a limited transplantation rate and a much greater risk of dying while on the waitlist.

Intra-operative kinetics of anti-HLA antibody in simultaneous liver-kidney transplantation.

During simultaneous liver-kidney transplantation (SLK) in highly sensitized patients, donor specific anti-human leukocyte antigen antibodies (DSA, HLA) can be present prior to transplant leading to positive crossmatch, yet these recipients have relatively low incidences of acute rejection. The mechanisms and timing underlying immunologic changes that occur intra-operatively remain largely unknown. Therefore, we measured the intra- and peri-operative kinetics of anti-HLA antibodies in highly sensitized SLK recipients. In this study, pre- and post-operative blood samples were obtained from sensitized SLK candidates with documented DSA. Intra-operative samples were obtained from a sub-group of SLK recipients. Pretransplant anti-HLA antibody profiles were created and flow cytometry and anti-human globulin complement-dependent cytotoxic crossmatches were performed. Significant reductions in anti-HLA class I and II DSA were seen intra-operatively shortly after reperfusion of the liver allograft. This effect was most pronounced for anti-HLA class I DSA (mean change, -85%, p < 0.05); changes to anti-HLA class II DSA were less robust (mean change, -47%, p = 0.15). Importantly, non-DSA anti-HLA antibodies remained unchanged throughout the perioperative period, suggesting the mechanism(s) by which the liver lowers DSA levels are specific to the DSA. These data demonstrate the immunologic benefit of performing SLK is lasting and occurs very shortly after liver reperfusion.

Time-of-day-dependent dietary fat consumption influences multiple cardiometabolic syndrome parameters in mice.

BACKGROUND: Excess caloric intake is strongly associated with the development of increased adiposity, glucose intolerance, insulin resistance, dyslipidemia, and hyperleptinemia (that is the cardiometabolic syndrome). Research efforts have focused attention primarily on the quality (that is nutritional content) and/or quantity of ingested calories as potential causes for diet-induced pathology. Despite growing acceptance that biological rhythms profoundly influence energy homeostasis, little is known regarding how the timing of nutrient ingestion influences development of common metabolic diseases. OBJECTIVE: To test the hypothesis that the time of day at which dietary fat is consumed significantly influences multiple cardiometabolic syndrome parameters. RESULTS: We report that mice fed either low- or high-fat diets in a contiguous manner during the 12 h awake/active period adjust both food intake and energy expenditure appropriately, such that metabolic parameters are maintained within a normal physiologic range. In contrast, fluctuation in dietary composition during the active period (as occurs in human beings) markedly influences whole body metabolic homeostasis. Mice fed a high-fat meal at the beginning of the active period retain metabolic flexibility in response to dietary challenges later in the active period (as revealed by indirect calorimetry). Conversely, consumption of high-fat meal at the end of the active phase leads to increased weight gain, adiposity, glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hyperleptinemia (that is cardiometabolic syndrome) in mice. The latter perturbations in energy/metabolic homeostasis are independent of daily total or fat-derived calories. CONCLUSIONS: The time of day at which carbohydrate versus fat is consumed markedly influences multiple cardiometabolic syndrome parameters.