Trends in pediatric donor heart discard rates and the potential use of unallocated hearts for allogeneic valve transplantation.

Objectives: Allogeneic valve transplantation is an emerging therapy that delivers a living valve from a donor heart. We reviewed the national discard rate of pediatric and young adult (aged 25 years or younger) donor grafts to estimate the number of hearts potentially available to source valve allotransplantation. Methods: We queried the United Network for Organ Sharing database to identify pediatric and young adult heart donors from 1987 to 2022. Donor heart discard was defined as nontransplantation of the allograft. Results: Of 72,460 pediatric/young adult heart donations, 41,065 (56.7%) were transplanted and 31,395 (43.3%) were unutilized. The average annual number of discarded hearts in era 1 (1987-2000), era 2 (2000-2010), and era 3 (2010-2022) was 791 (42.8%), 1035 (46.3%), and 843 (41.2%), respectively. From 2017 to 2021, the average annual number of discards by age was: 39 (31.8%) neonates/infants, 78 (38.0%) toddlers, 41 (49.4%) young children, 240 (38.0%) adolescents, and 498 (40.1%) young adults. High-volume procurement regions had the greatest proportion of nonutilization, with the national average discard rate ranging from 39% to 49%. The most frequently documented reasons for nonallocation were distribution to the heart valve industry (26.5%), presumably due to suboptimal graft function, poor organ function (22.7%), and logistical challenges (10.8%). Conclusions: With ∼900 pediatric/young adult donor hearts discarded annually, unutilized grafts represent a potential source of valves for allogeneic valve transplant to supplement current conduit and valve replacement surgery. The limited availability of neonatal and infant hearts may limit this technique in the youngest patients, for whom cryopreserved homografts or xenografts will likely remain the primary valve substitute.

Ex-vivo lung perfusion therapies: do they add value to organ donation?

PURPOSE OF REVIEW: Significant limitations in organ availability and postoperative graft dysfunction plague lung transplantation and there is continual need for innovation. Ex-vivo lung perfusion (EVLP) has emerged over the last decade as an alternative and/or complementary allograft storage and assessment tool, however logistical hurdles have limited its widespread dissemination. As such, the overall current and potential value of EVLP on modern-day lung transplantation should be considered as innovation moves forward. RECENT FINDINGS: Since inception, EVLP has made important safety strides in conclusively showing noninferiority to cold storage in several trials. Recent advances have highlighted potential mechanisms by which EVLP in its current form may reduce the pathogenic origins of primary graft dysfunction. Exciting work on organ reconditioning with EVLP via reduction in intermediaries of acute inflammation and oxidative stress have been performed in animal models. In addition, cross-circulation during EVLP has emerged as a method to achieve more prolonged ex situ storage. The impending translation of these to clinical use will markedly improve the overall value of EVLP. SUMMARY: This review will highlight the current status of EVLP as it pertains to overall value in lung transplantation, focusing on historical and recent preclinical work and how innovation therein will improve lung transplantation as a field.

HCV-Positive Allograft Use in Heart Transplantation Is Associated With Increased Access to Overdose Donors and Reduced Waitlist Mortality Without Compromising Outcomes.

BACKGROUND: Because of ongoing shortages of donors for heart transplantation, the use of donor candidates whose availabilities are the result of drug overdoses (ODs) has become increasingly prevalent, even though these donors carry a high preponderance of the now curable hepatitis C virus (HCV). This study investigated temporal trends and regional variabilities in HVC-positive (HCV+) allograft use in heart transplantation and assessed the relationship between the use of HCV+ graft donors and the use of OD donors as well as assessing waitlist and post-transplant outcomes. METHODS AND RESULTS: A retrospective review of the United Network for Organ Sharing database assessed adults listed for heart transplantation. Patients were stratified both temporally into pre-HCV and HCV eras related to HCV+ graft use trends and regionally by degree of HCV+ allograft use. Regions of high HCV+ donor use were associated with an increase in OD donor access by 7.8% across eras compared to 0.4% in low HCV+ donor-use regions. One-year waitlist mortality decreased from 4.7% to 2.5% across eras in high HCV+ donor-use regions (P= 0.001) and remained roughly the same as before in low HCV+ donor-use regions (3.0% vs 2.4%; P= 0.244.). Post-transplant survival at 1 year remained similar across eras. CONCLUSIONS: HCV+ donor allograft use can help to optimize donor use, decreasing waitlist mortality without compromising early survival. Ongoing assessment is essential to ensure long-term safety and efficacy of using HCV+ donors.

Loss of renal olfactory receptor 1393 leads to improved glucose homeostasis in a type 1 diabetic mouse model.

Renal olfactory receptor 1393 (Olfr1393) is an understudied sensory receptor that contributes to glucose handling in the proximal tubule. Our previous studies have indicated that this receptor may serve as a regulator of the sodium glucose co-transporters (SGLTs) and contributes to the development of glucose intolerance and hyperfiltration in the setting of diet-induced obesity. We hypothesized that Olfr1393 may have a similar function in Type 1 Diabetes. Using Olfr1393 wildtype (WT) and knockout (KO) mice along with streptozotocin (STZ) to induce pancreatic ß-cell depletion, we tracked the development and progression of diabetes over 12 weeks. Here we report that diabetic male Olfr1393 KO mice have a significant improvement in hyperglycemia and glucose tolerance, despite remaining susceptible to STZ. We also confirm that Olfr1393 localizes to the renal proximal tubule, and have uncovered additional expression within the glomerulus. Collectively, these data indicate that loss of renal Olfr1393 affords protection from STZ-induced type 1 diabetes and may be a general regulator of glucose handling in both health and disease.

Superoxide Dismutase-Loaded Nanoparticles Attenuate Myocardial Ischemia-Reperfusion Injury and Protect Against Chronic Adverse Ventricular Remodeling.

Early revascularization is critical to reduce morbidity after myocardial infarction, although reperfusion incites additional oxidative injury. Superoxide dismutase (SOD) is an antioxidant that scavenges reactive oxygen species (ROS) but has low endogenous expression and rapid myocardial washout when administered exogenously. This study utilizes a novel nanoparticle carrier to improve exogeneous SOD retention while preserving enzyme function. Its role is assessed in preserving cardiac function after myocardial ischemia-reperfusion (I/R) injury. Here, nanoparticle-encapsulated SOD (NP-SOD) exhibits similar enzyme activity as free SOD, measured by ferricytochrome-c assay. In an in vitro I/R model, free and NP-SOD reduce active ROS, preserve mitochondrial integrity and improve cell viability compared to controls. In a rat in vivo I/R injury model, NP-encapsulation of fluorescent-tagged SOD improves intramyocardial retention after direct injection. Intramyocardial NP-SOD administration in vivo improves left ventricular contractility at 3-hours post-reperfusion by echocardiography and 4-weeks by echocardiography and invasive pressure-volume catheter analysis. These findings suggest that NP-SOD mitigates ROS damage in cardiac I/R injury in vitro and maximizes retention in vivo. NP-SOD further attenuates acute injury and protects against myocyte loss and chronic adverse ventricular remodeling, demonstrating potential for translating NP-SOD as a therapy to mitigate myocardial I/R injury.