Elevated serum sodium in recipients of liver transplantation has a substantial impact on outcomes.

Dysnatremias are a rare but significant event in liver transplantation. While recipient pre-transplant hypernatremia has been demonstrated to increase post-transplant mortality, the degree of hypernatremia and the impact of its resolution have been less well characterized. Here, we used multivariate Cox regression with a comprehensive list of donor and recipient factors in order to conduct a robust multivariate retrospective database study of 54,311 United Network for Organ Sharing (UNOS) liver transplant patients to analyze the effect of pre-transplant serum sodium on post-transplant mortality, post-transplant length of hospitalization, and post-transplant graft survival. Mortality and graft failure increased in a stepwise fashion with increasing pre-transplant hypernatremia: 145 -150 mEq/L (HR = 1.118 and HR = 1.113), 150-155 mEq/L (HR = 1.324 and HR = 1.306), and > 155 mEq/L (HR = 1.623 and HR = 1.661). Pre-transplant hypo- and hypernatremia also increased length of post-transplant hospitalization: < 125 mEq/L (HR = 1.098), 125-130 mEq/L (HR = 1.060), 145 -150 mEq/L (HR = 1.140), and 150-155 mEq/L (HR = 1.358). Resolution of hypernatremia showed no significant difference in mortality compared with normonatremia, while unresolved hypernatremia significantly increased mortality (HR = 1.254), including a durable long-term increased mortality risk for patients with creatinine < 2 mg/dL and MELD < 25. Pre-transplant hypernatremia serves as a morbid prognostic indicator for post-transplant morbidity and mortality.

Pediatric discard risk index for predicting pediatric liver allograft discard.

BACKGROUND: Of the 600 pediatric candidates added to the liver waiting list annually, 100 will remain waiting while over 100 liver allografts are discarded, often for subjective reasons. METHODS: We created a risk index to predict discard to better optimize donor supply. We used the UNOS database to retrospectively analyze 17 367 deceased donors (≤18 years old) through univariate and multivariate logistic regression models. Deceased donor clinical characteristics and laboratory values were independent variables with discard being the dependent variable in the analysis. Significant univariate factors (P-value < .05) comprised the multivariate analysis. Significant variables from the multivariate analysis were incorporated into the pDSRI, producing a risk score for discard. RESULTS: From 17 potential factors, 11 were identified as significant predictors (P < .05) of pediatric liver allograft discard. The most significant risk factors were as follows: DCD; total bilirubin >10 mg/dL, and alanine transaminase (ALT) ≥500 IU/L. The pDSRI has a C-statistic of 0.846 for the training set and 0.840 for the validation set. CONCLUSION: The pDSRI uses 11 significant risk factors, including elevated liver function tests, donor demographics, and donor risk/type to accurately predict risk of pediatric liver allograft discard and serve as a tool that may maximize donor yield.

A Surgical Collaborative to Empower Medical Student Research.

Mini abstracts: Faculty at the Baylor College of Medicine have developed a flexible research collaborative through which students gain research skills and individualized mentorship. This division has produced 86 trainee first author publications, 64 manuscripts by 34 different medical students with an average Scimago Journal Rank of 1.293 (range: 1.035-1.551) since 2015.

A humanized mouse model for adeno-associated viral gene therapy.

Clinical translation of AAV-mediated gene therapy requires preclinical development across different experimental models, often confounded by variable transduction efficiency. Here, we describe a human liver chimeric transgene-free Il2rg-/-/Rag2-/-/Fah-/-/Aavr-/- (TIRFA) mouse model overcoming this translational roadblock, by combining liver humanization with AAV receptor (AAVR) ablation, rendering murine cells impermissive to AAV transduction. Using human liver chimeric TIRFA mice, we demonstrate increased transduction of clinically used AAV serotypes in primary human hepatocytes compared to humanized mice with wild-type AAVR. Further, we demonstrate AAV transduction in human teratoma-derived primary cells and liver cancer tissue, displaying the versatility of the humanized TIRFA mouse. From a mechanistic perspective, our results support the notion that AAVR functions as both an entry receptor and an intracellular receptor essential for transduction. The TIRFA mouse should allow prediction of AAV gene transfer efficiency and the study of AAV vector biology in a preclinical human setting.

Prediction of Kidney Allograft Discard Before Procurement: The Kidney Discard Risk Index.

OBJECTIVES: There is an 18.9% discard rate among kidney allografts. Here, we aimed to determine predictors of kidney discard and construct an index to identify high-probability discard kidney allografts prior to procurement. MATERIALS AND METHODS: A total of 102 246 potential kidney allograft donors from the Organ Procurement and Transplantation Network database were used in this analysis. The cohort was randomized into 2 groups. The training set included 67% of the cohort and was used to derive a predictive index for discard that comprised 21 factors identified by univariate and multivariate logistic regression analysis. The validation set included 33% and was used to internally validate the kidney discard risk index. RESULTS: In 77.3% of donors, at least 1 kidney was used for transplant, whereas in 22.7% of donors, both kidneys were discarded. The kidney discard risk index was highly predictive of discard with a C statistic of 0.89 (0.88-0.89). The bottom 10th percentile had a discard rate of 0.73%, whereas the top 10th percentile had a discard rate of 83.65%. The 3 most predictive factors for discard were age, creatinine level, and hepatitis C antibody status. CONCLUSIONS: We identified 21 factors predictive of discard prior to donor procurement and used these to develop a kidney discard risk index with a C statistic of 0.89.

Most pediatric transplant centers are low volume, adult-focused, and in proximity to higher volume pediatric centers.

BACKGROUND: Independent studies provide evidence that low volume pediatric solid organ transplant centers have inferior outcomes compared to high volume pediatric centers. The study assessed whether patients treated at low volume pediatric centers have access to higher volume pediatric centers, which offer potentially better outcomes. METHODS: We analyzed center specific data on 467 pediatric solid organ transplant centers in the U.S using the Organ Procurement and Transplantation Network database from 2002 to 2014. The proximities of low volume pediatric centers to high volume pediatric centers were determined using Maptive, a tool based on Google Maps. RESULTS: Most low volume pediatric transplant centers focused on transplantation of adults (84% heart, 83% liver, and 93% kidney programs). A majority of low volume pediatric centers (77% for heart, 53% for lung, 68% for liver and 90% for kidney) were within 150 miles of high volume centers. Among all children listed for transplantation, 30.7% were listed in low volume pediatric centers. Most low volume pediatric centers are adult focused and near high volume pediatric centers. CONCLUSION: We need greater scrutiny of outcomes, particularly waitlist outcomes, of low volume pediatric solid organ transplant centers located close to high volume pediatric solid organ transplant centers. TYPE OF STUDY AND LEVEL OF EVIDENCE: Retrospective Comparative Study, Level III.

Combined Lung-Liver and Delayed Kidney Transplantation for Cystic Fibrosis Clinical Approach and Outcome: A Case Report.

Reports on the long-term outcomes and immunosuppressive regimens of multiorgan transplant patients are limited. Here, we describe a patient with cystic fibrosis complicated by multiorgan failure who was successfully treated with combined liver lung transplant and delayed kidney transplant, resulting in excellent outcomes. Delayed kidney transplant was done to reduce the operative stress of a single procedure, giving time for adequate resuscitation and weaning from vasopressors. Our patient's postoperative course was complicated by post-transplant lymphoproliferative disease, which was successfully treated with rituximab and reduced dosages of immunosuppression.