3D bioprinting in microgravity: An end to organ donor shortages?

Countless lives have been saved with the advent of modern organ transplantation. However, the current shortage of compatible organ donors is limiting the life-saving potential of transplantation. According to the United Network for Organ Sharing, approximately 20 patients die each day in the United States while waiting for a transplant [1]. The discrepancy between supply and demand of organ donors is accentuated by a fundamental ethical dilemma associated with deceased organ donation: one person must die so that another may live [2]. The current viewpoint considers the viability of 3D bioprinting in microgravity as a solution to organ donor shortages. Current alternatives to deceased organ donation, including xenotransplantation and other state-of-the-art bioprinting techniques, are reviewed and compared to bioprinting in microgravity. The limitations of bioprinting within Earth’s gravitational field are also discussed, revealing the need for further research.

Race/Ethnicity Is Not Independently Associated with Risk of Adverse Waitlist Removal among Patients with HCC Exception Points

(1) Background: Since 2015, exception points have been awarded to appropriate candidates after six months of waitlist time to allow more equitable access to liver transplants regardless of hepatocellular carcinoma status. However, it remains unknown whether racial disparities in outcomes among waitlisted patients remain after the introduction of a 6-month waiting period for exception points. (2) Methods: Using the United Network for Organ Sharing database, we identified 2311 patients diagnosed with hepatocellular carcinoma listed for liver transplant who received exception points from 2015 to 2019. The outcome of interest was waitlist survival defined as the composite outcome of death or removal for clinical deterioration. Competing risk analysis was used to identify factors associated with death or removal for clinical deterioration. The final model adjusted for age, sex, race/ethnicity, blood type, diabetes, obesity, laboratory MELD score, tumor size, AFP, locoregional therapies, UNOS region, and college education. (3) Results: No difference was found in the risk of adverse waitlist removal among ethnic/racial groups.

Transjugular Intrahepatic Portosystemic Shunt and Locoregional Therapies in Patients Undergoing Orthotopic Liver Transplantation: A Protocol for a Retrospective, Linked United Network for Organ Sharing Cohort

ABSTRACTIntroductionOrthotopic Liver Transplantation (OLT) is the potential curative treatment option for patients with end-stage liver disease (ESLD) or hepatocellular carcinoma (HCC) within organ procurement and transplantation network (OPTN) criteria. However, these groups of patients may require bridging interventions, including Transjugular Intrahepatic Portosystemic Shunt (TIPS) or Locoregional Therapies (LRTs), given the nationwide organ shortage and increasing waitlist time. The perioperative and long-term post-OLT survival and clinical outcomes require further investigation to evaluate the clinical utility and therapeutic advantages of these bridging interventions, if any. We propose a large retrospective database analysis that will evaluate both perioperative and long-term effects of these OLT-related interventions.Methods and analysisThree datasets from the United Network for Organ Sharing (UNOS) database will be included and linked to estimate the causal effect of 1) Transjugular Intrahepatic Portosystemic Shunts and 2) Locoregional therapies in patients undergoing OLT, the latter among patients with HCC. Only therapy naïve adult patients, without multivisceral transplants, and without living donor transplants will be included. The primary outcome will be overall survival. Secondary outcomes will include perioperative clinical outcomes, post-operative survival, and postoperative clinical outcomes. The inverse probability of treatment weighted models with Cox regression will be utilized to analyze survival outcomes, logistic regression for categorical outcomes, and ordinary least squares regression for continuous outcomes. A sensitivity analysis will be conducted to assess the appropriateness of a complete-case analysis for the primary outcome and ensure the robustness of the findings.Ethics and DisseminationThis study protocol was reviewed by the Emory University School of Medicine Institutional Review Board (IRB), and ethical approval was waived due to the retrospective analysis of the originally anonymized database. The results will be disseminated in peer-reviewed journals and presented at relevant conferences. It was not appropriate or possible to involve patients or the public in the design, or conduct, or reporting, or dissemination plans of our research.STRENGTHS AND LIMITATIONS OF THIS STUDYStrengthsThe proposed study:Will be the first study evaluating the causal effect of TIPS in OLT candidates and of locoregional therapies in OLT candidates with HCCWill be the first study to link UNOS datasets to investigate the estimands, thereby providing insight into the clinical impact of TIPS and LRTs at various stages in the clinical pathway.LimitationsThe proposed study:Will be a retrospective study and thus subject to poor or inadequate reporting in the registry, though propensity score matching will be doneMay be subject to unmeasured confounding and sensitive to model misspecificationMay lack the necessary sample size and subsequently be underpowered to estimate the target estimands

Intoxicated Donors and Heart Transplant Outcomes: Long-Term Safety

Background: The opioid crisis has led to an increase in available donor hearts, although questions remain about the long-term outcomes associated with the use of these organs. Prior studies have relied on historical information without examining the toxicology results at the time of organ offer. The objectives of this study were to examine the long-term survival of heart transplants in the recent era, stratified by results of toxicological testing at the time of organ offer as well as comparing the toxicology at the time of donation with variables based on reported history. Methods: The United Network for Organ Sharing database was requested as well as the donor toxicology field. Between 2007 and 2017, 23 748 adult heart transplants were performed. United Network for Organ Sharing historical variables formed a United Network for Organ Sharing Toxicology Score and the measured toxicology results formed a Measured Toxicology Score. Survival was examined by the United Network for Organ Sharing Toxicology Score and Measured Toxicology Score, as well as Cox proportional hazards models incorporating a variety of risk factors. Results: The number and percent of donors with drug use has significantly increased over the study period ( P <0.0001). Cox proportional hazards modeling of survival including toxicological and historical data did not demonstrate differences in post-transplant mortality. Combinations of drugs identified by toxicology were not associated with differences in survival. Lower donor age and ischemic time were significantly positively associated with survival ( P <0.0001). Conclusions: Among donors accepted for transplantation, neither history nor toxicological evidence of drug use was associated with significant differences in survival. Increasing use of such donors may help alleviate the chronic donor shortage.

Ethics of split liver transplantation: should a large liver always be split if medically safe?

Split liver transplantation (SLT) provides an opportunity to divide a donor liver, offering transplants to two small patients (one or both could be a child) rather than keeping it whole and providing a transplant to a single larger adult patient. In this article, we attempt to address the following question that is identified by the Organ Procurement and Transplant Network and United Network for Organ Sharing: ‘Should a large liver always be split if medically safe?’ This article aims to defend an answer—‘not always’—and clarify under what circumstances SLT is ethically desirable. Our answer will show why a more dynamic approach is needed to the ethics of SLT. First, we discuss a case that does not need a dynamic approach. Then, we explain what is meant by a dynamic approach and why it is needed.

An Adapted Process and Organ Procurement Perspective on Heart Retransplantation for a Healthy Heart’s Third Life

As organ procurement organizations nationwide see an increased opportunity to retransplant already transplanted hearts, we would like to share the overview and process of our 2 successful cases. Heart retransplantation increased our cardiac placement rates by 2.64% and 2% in 2015 and 2019, respectively. Spread across a nation that sees over 3500 heart placements annually, a 2% increase would be substantial. Since 2009, our cases stand as the only documented heart retransplantations in the United States. However, United Network for Organ Sharing data shows that potential exists. From a facilitation perspective, we have developed a protocol to ease the matching process. From a surgical perspective, these cases had no complications and saved 2 lives, with each heart now beating in a third person. We hope that by sharing our process and success, we can familiarize fellow organ procurement organizations and transplant communities with this viable opportunity.

Exception Status Listing in the New Adult Heart Allocation System: A New Solution to an Old Problem?

Background: One of the goals of the revised 6-tiered US adult heart allocation policy was to improve risk stratification of patients to lower exception status utilization for transplant listing. We sought to define the characteristics and outcomes of waitlisted patients using exception status and to examine region- and center-level differences in utilization of exception status in the new heart allocation system. Methods: This retrospective cohort analysis of the United Network for Organ Sharing database included adult waitlisted patients for heart transplant between October 18, 2018, and June 30, 2020, in the United States, stratified by use of exception status versus standard criteria. Results: Out of 6351 patients, 1907 (30.0%) were waitlisted under exception status. Patients using exception status were more likely to have a nonischemic cause of heart failure, blood type O, United Network for Organ Sharing status 2 at listing and were less likely to have a durable left ventricular assist device at listing. Exception status utilization varied significantly between and within United Network for Organ Sharing regions. Listing by exception criteria was associated with a significantly higher incidence of heart transplantation compared with listing by standard criteria (hazard ratio, 1.25 [1.15–1.38], P <0.001), without increased risk of death or delisting for worsening clinical status (hazard ratio, 0.83 [0.65–1.05], P =0.12) after multivariable adjustment. Conclusions: The status tiers of the new heart allocation system may not fully capture medical urgency and complexity of waitlisted patients as assessed by transplant physicians and review committees and may limit the ability to develop a heart allocation score.