Thoracic Organ Donors Research Articles

Patient management for thoracic organ donor candidates: the lung transplantation team's view.

Despite the increasing demand for lung transplants, donor lungs remain in short supply. Although organ donations have been steadily increasing in Korea, with the utilization rate for donor lungs increasing to 40% in recent years, many potential donor organs remain unused. To match the increasing number of patients on the lung transplant waitlist, it is essential to increase the donor procurement rate through optimal management. Improvements in donor lung management programs can lead to expansion of the donor pool and optimal posttransplant outcomes. This review focuses on basic protocols for the optimal management of donor lungs and summarizes coronavirus disease 2019-related considerations for donor lung evaluation.

Abstract 18901: Critical Role of Endothelial Injury in the Initiation of Aortic Dissection

Introduction: Endothelium forms a protective barrier and maintains vascular hemostasis. However, the role of endothelial injury in aortic aneurysms and dissections (AAD) remains poorly understood. Receptor-interacting protein kinase 3 (RIP3)-mediated necroptosis and gasdermin D (GSDMD)-mediated pyroptosis trigger necrotic cell death. We hypothesize endothelial cell (EC) death induced by necroptosis and pyroptosis contributes to AAD formation. Methods: Endothelial integrity and gene expression were examined in ascending aortic tissues from ascending thoracic aortic aneurysm (ATAA) patients (n=9) and organ donor controls (n=8) by single-cell transcriptome analysis. Effects of EC death on AAD formation were determined in EC-specific Rip3 knockout (EC-Rip3 -/- , n=26), EC-specific Gsdmd knockout (EC-Gsdmd -/- , n=21), and necroptosis/pyroptosis inhibitor necrosulfonamide (NSA) treated mice (n=15) in sporadic AAD models induced by angiotensin II (Ang II) infusion. Evans blue staining and nanoparticle-mediated contrast-enhanced CT (n-CECT) detected endothelial hyperpermeability Results: Single-cell transcriptome and immunostaining analyses revealed significant upregulation of pro-death genes (e.g., RIP3 and GSDMD), but downregulation of cell junction genes (e.g., TJP1 and GJA1) in ECs of ATAA patients compared with controls. In the mouse AAD model, endothelial injury and hyperpermeability were detected 2-5 days after Ang II infusion and were associated with intramural nanoparticle accumulation, elastic fiber fragmentation, and macrophage infiltration. Importantly, EC-Rip3 -/- mice and EC-Gsdmd -/- mice showed preserved EC barrier function, reduced nanoparticle accumulation and elastic fiber fragmentation, and reduced AAD incidence (including aneurysm, dissection, and rupture) compared to their littermate controls (EC-Rip3 -/- mice: 52% vs 23.1%, P=0.033; EC-Gsdmd -/- mice: 52.6% vs 14.3%, P=0.01). Blocking necroptosis/pyroptosis by NSA treatment reduced the incidence (65% vs 27%; P=0.04) and severity of AAD. Conclusions: Endothelial injury and subsequent barrier dysfunction and infiltration are key features of AAD formation. Prevention of EC necrotic cell death can be a potential AAD therapeutic target.

Direct Procurement of Thoracic Organs Along with Abdominal Normothermic Regional Perfusion in Donation After Circulatory Death

<h3>Purpose</h3> Direct procurement of thoracic organs as compared to using abdominal normothermic regional perfusion (aNRP) is the preferred method for thoracic organ procurement in donors after circulatory death (DCD). The use of aNRP improves outcomes from liver transplantation. We have developed a technique for thoracic organ isolation during aNRP that allows successful co-procurement of thoracic and abdominal organs. <h3>Methods</h3> In order to achieve successful thoracic isolation both the brain perfusion and volume loss must be prevented. After certification of circulatory death and a standoff period the thoraco-abdominal incision is performed. Blood is collected from the donor right atrium or a side-arm of the aNRP circuit to prime the organ care system (OCS) before isolation of vascular structures in a systematic way. 1. The left pleura is opened, and the lung retracted to allow identification and clamping of the descending thoracic aorta above the diaphragm. 2. The ascending aorta is clamped, and the aortic arch vented cranial to the clamp. Abdominal NRP can then commence. 3. The inferior vena-cava is clamped within the pericardium. 4. The superior vena-cava and azygos vein are tied off. 5. The heart is vented on the left and right side before induction of cardioplegia. The diagram illustrates complete vascular isolation of the thoracic cavity enabling explantation of the heart and lung after delivery of selective antegrade pneumoplegia while abdominal organs continue to be perfused for 2-hours before the start of abdominal procurement. <h3>Results</h3> Between 2019-21 we successfully performed seven such procurements. Three heart and lungs, three lungs and one heart procurement alone. All organs were successfully implanted with successful immediate outcome in all thoracic and abdominal recipients. <h3>Conclusion</h3> Direct procurement of thoracic organs is a feasible option during aNRP. This will potentially expand the thoracic organ donor pool and improve outcome of liver transplantation.

Economic evaluation of the specialized donor care facility for thoracic organ donor management.

BackgroundOver the last decade two alternative models of donor care have emerged in the United States: the conventional model, whereby donors are managed at the hospital where brain death occurs, and the specialized donor care facility (SDCF), in which brain dead donors are transferred to a SDCF for medical optimization and organ procurement. Despite increasing use of the SDCF model, its cost-effectiveness in comparison to the conventional model remains unknown.MethodsWe performed an economic evaluation of the SDCF and conventional model of donor care from the perspective of U.S. transplant centers over a 2-year study period. In this analysis, we utilized nationwide data from the Scientific Registry of Transplant Recipients and controlled for donor characteristics and patterns of organ sharing across the nation’s organ procurement organizations (OPOs). Subgroup analysis was performed to determine the impact of the SDCF model on thoracic organ transplants.ResultsA total of 38,944 organ transplants were performed in the U.S. during the study period from 13,539 donors with an observed total organ cost of $1.36 billion. If every OPO assumed the cost and effectiveness of the SDCF model, a predicted 39,155 organ transplants (+211) would have been performed with a predicted total organ cost of $1.26 billion (−$100 million). Subgroup analysis of thoracic organs revealed that the SDCF model would lead to a predicted 156 additional transplants with a cost saving of $24.6 million.ConclusionsThe U.S. SDCF model may be a less costly and more effective means of multi-organ donor management, particularly for thoracic organ donors, compared to the conventional hospital-based model.

Use of Organs from Hepatitis C Viremic Donors: Addressing the Needs of a Changing Waitlist and the Effect of a Public Health Crisis

The combination of broad screening initiatives and development of effective antiviral therapies have led to a revolution in the treatment of hepatitis C virus and has reduced the proportion of patients with the virus who develop a need for liver transplantation in favor of other etiologies, such as alcohol-related liver disease and non-alcoholic steatohepatitis. However, the opioid epidemic and rise in injection drug use in the United States has simultaneously led to otherwise healthy hepatitis C viremic patients dying of overdoses. The sum total of all of these factors has large implications for the transplant community and those patients on the wait list for multiple different organs: lower numbers of people on transplant wait list have active HCV, while HCV is becoming more common in potential liver, kidney and thoracic organ donors. We will review the history of solid organ transplant from donors with hepatitis C as well as to describe the current understanding of the potential use of these grafts in light of the shifting demographics on the waiting list and potential donor population.

Donor and Recipient Racial Mismatch Impacts Thoracic Organ Transplant Survival

Purpose The purpose of this study is to look at impact of race on thoracic organ recipient (TOR) survival with respect to the donor, recipient, and donor/ recipient matching. Methods The United Network for Organ Sharing (UNOS) database was retrospectively reviewed from 1/2000-3/2018 for donor hearts or lungs. After exclusions for multiorgan transplant and age (donor Results Donor age ranged from 15-77 y (mean 33.2y, median 31y). 66% were male, and 4% were diabetic. The mean donor ejection fraction (EF) was 60% (median 60%) and ischemic time ranged from 0.04-15 hours (h) for both heart and lungs (mean 4.00h, median 3.72h). There were 9914 (17%) AA, 9081 (15%) H, and 40003 (68%) W thoracic organ donors. Adjusted 30-day and 1 year survival of TORs was 96.2% and 87.7% from AA donors, 96.2% and 87.6% from H donors, and 96.5% and 89% from W donors. This equates to a 13% reduction in 1-year survival among AA and H donors when compared to W donors (both OR=0.87; p 0.068). AA exhibited lower long-term survival when compared to W (HR=1.12; p Conclusion While there is evidence of racial disparity in survival outcomes after thoracic organ transplant matched race donor/ recipient may improve thoracic transplant survival.

Hepatitis and Thoracic Transplantation - No More Virus Non-Grata

Purpose There remains an urgent need to expand the donor pool for thoracic organ transplant recipients. Utilizing donors who are actively viremic with hepatitis C (HCV) is rapidly becoming standard practice, although no consensus exists regarding when to treat post-transplant, with which drug, and for how long. Cost remains an issue with direct acting antivirals (DAA). Hepatitis B (HBV) viremic donors are predicted to become more common. We designed and implemented a protocol to utilize HCV and HBV NAT+ donors. Methods We designed an open-label, ongoing safety and efficacy protocol to allow all transplant programs at our center, adult and pediatric, to enroll patients for whom there is an emergent need to expand the donor pool. Patients are consented and stratified into 2 groups: those who received NAT+ donors vs NAT- donor comparators. Patients are followed for a minimum of 12m post-transplant, with hepatitis viral loads measured at d5, 10 and 21 (and at clinical discretion thereafter). The primary end points are 3, 12month graft and patient survival. Secondary end points include viral cure rates, therapy associated adverse events, attributable hepatitis mortality, functional status, rejection rates and time to transplantation. HCV therapy of choice is started after discharge, or if needed urgently, begun inpatient and paid for by the hospital. HBV therapy is initiated at the time of transplantation. The protocol is monitored by a Data Safety Monitoring Board. Results 11 pts have enrolled to date and progressed to NAT+ transplant, including 8 adult heart transplants, 1 bilateral lung, 1 heart-lung and 1 lung-liver transplant. All have received HCV-viremic donors, within 1 month of consent. Median age is 56yrs (range 25-72). 3 recipients were HCV-viremic pre-transplant, 8 were HCV-naive. All 8 D+/R- pts became infected with HCV, 7 were actively viremic by day 5, one became viremic at d21. 9/9 patients are alive at 3months, with HCV therapy having been initiated in 6, and SVR12 achieved in 5 to date. So far we report 100% grafts survival, and no adverse events attributable to hepatitis. 1 patient required HCV therapy initiation in the hospital. Conclusion We present real world experience about the implementation of a protocol allowing HCV and HBV NAT+ donors to be used for thoracic and multivisceral transplants. Using a multidisciplinary approach, our protocol offers a means to expand the thoracic organ donor pool safely.

Does the OPTN cPRA Calculator Accurately Predict HLA Antigen Frequencies in Pediatric Donors?

The calculated panel reactive antibody (cPRA) is an estimate of the likelihood of receiving an HLA-incompatible organ based on an historical sample of solid organ donors of all ages, but has not been validated specifically for pediatric donors. We hypothesized that differences in the ethnic makeup of pediatric and infant vs. adult thoracic organ donors would correspond to differences in HLA antigen frequencies not accurately predicted by the current cPRA calculator. All US thoracic donors for the calendar years 2012-2013 were analyzed for the frequencies of A/B/C and DQ antigen frequencies in pediatric (< 18 years) and infant (< 1year) donors as compared to the overall donor pool and to that predicted by the cPRA calculator. A comparison of the ethnic frequencies for each donor group was also conducted. 10,290 thoracic donors were analyzed, including 1119 < 18 years old and 386 < 1 year old. Caucasians made up 73% of the total cohort, 66% of the pediatric cohort, but only 53% of the infant cohort. (P=0.001) African-Americans and Latinos represented larger percentages of the pediatric and infant donor pools when compared to the total donor pool (p=0.001). Although the cPRA calculator accurately predicted the actual antigen frequency in the total cohort within 4 percentage points, it inaccurately predicted the antigen frequency by as much as 9% for 7/70 (10%) and 9/70 (13%) antigens in the pediatric and infant cohorts, respectively (P = 0.02 and 0.05). Differences were most common for antigens commonly found in African-Americans and Latinos (e.g. A36, B53). The national cPRA calculator underestimates the frequency of certain HLA antigens in the pediatric and infant donor pools and may inaccurately estimate the likelihood of receiving an HLA-incompatible organ in these populations. Differences in antigen frequency are likely the result of minority overrepresentation in the pediatric and infant donor pools.

(739) - Process Improvement in Thoracic Organ Donor Retrieval: Implementation of a Donor Assessment Checklist

(739) - Process Improvement in Thoracic Organ Donor Retrieval: Implementation of a Donor Assessment Checklist

The 40 Donors Per Million Population Plan: An Action Plan for Improvement of Organ Donation and Transplantation in Spain

Introduction Spain has been showing the highest rate of deceased donor organ recovery in the world for a whole country, namely, 33–35 donors per million population (pmp) during the last years. This activity is attributed to the so-called Spanish Model of organ donation, an integrated approach to improve organ donation since the start of the Organización Nacional de Trasplantes (ONT) in 1989. However, in 2007 there were 7/17 regions with >40 donors pmp and a marked regional variability. Thus, ONT has set a large-scale, comprehensive strategy to achieve a substantial improvement in donation and transplantation in Spain in the coming years: The 40 Donors pmp Plan. Purpose and Scope The overall objective is to increase the average rate of deceased donors to 40 pmp between 2008 and 2010. The areas of improvement, specific objectives, and actions have come from deep reflection on the data and the material generated from multidisciplinary discussions and open consultation with the donation and transplantation community. Key Areas Selected for Action Detection and management of brain-dead donors, with 4 specific subareas: access to intensive care units, new forms of hospital management, foreigners and ethnic minorities, and evaluation/maintenance of thoracic organ donors. Expanded criteria donors, with 3 subareas: aging, donors with positive tests to certain viral serologies, and donors with rare diseases. Special surgical techniques. Donation after cardiac death.

Modulación hormonal del donante de órganos. Utilidad de los esteroides

Recently, the work group made up of the National Transplant Organization (Organización Nacional de Trasplantes, ONT), Spanish Society of Intensive, Critical Medicine and Coronary Units (Sociedad Española de Medicina Intensiva, Crítica y de Unidades Coronarias, SEMICYUC) and other Scientific Societies have recommended using 15 mg/kg of methyl prednisolone during the management of lung donors after brain death. This recommendation is based on descriptive and retrospective studies. However, the review of different experimental and clinical studies also suggests a potential benefit of using steroids in either thoracic or abdominal organ donors during management strategies. In brain death management, early steroid administration may decrease cytokine production and also may prevent alterations induced by proinflammatoy mediators, stabilize cell membranes, reduce expression of cell surface adhesion molecules and avoid lipid peroxidation after the ischemic period. This could be beneficial in increasing number and quality of organs harvested and in decreasing rejection episodes after transplant. It would be very recommendable to carry out prospective and comparative studies to demonstrate these potential utilities. Meanwhile and knowing the deleterious effects of inflammatory activity arising during and after brain death, we recommend using 15 mg/kg of methyl prednisolone in the organ donor management, as soon as possible. The potential benefit of its immunomodulation effects, its low cost and the absence of major side effects can justify this recommendation.

Intrathoracic organ transplantation

Thoracic organ transplantation is the therapeutic option of choice for patients suffering from end-stage cardiac and pulmonary disease. Over the past few decades, there have been numerous advances made in methods of organ preservation and postoperative management. This has substantially improved the outcome of heart and lung transplantation. Progress in the fields of immunosuppression, combined with a better understanding of rejection, has also contributed to the success of intrathoracic organ transplantation. However, there are important obstacles that limit the utility of heart and lung transplantation. There are concerns about a shortage of suitable donor organs. Organ preservation techniques allow for only relatively short ischaemic times to be tolerated. Complications related to graft rejection and infection remain important barriers to long-term survival. The thoracic organ donor requires careful attention to optimally evaluate and, if necessary, resuscitate transplantable organs; this involves detailed assessment before organ procurement. Of vital importance is the careful selection and evaluation of patients who would benefit most from transplantation, particularly in view of the limited availability of organs. If patients are deemed suitable, emphasis is placed on their management to optimize their condition before transplantation. There have also been changes in surgical practice, such an increase in the number of bilateral lung transplants and a concomitant decrease in heart–lung transplantation. This contribution summarizes the basic principles of heart and lung transplantation, particularly those related to patient selection, surgical techniques and postoperative management.

Thoracic organ donor characteristics associated with successful lung procurement.

A shortage of suitable donors is the major impediment to clinical lung transplantation. The rate of lung recovery from potential donors is lower than that for other organs. The purpose of this study was to evaluate what factors could be modified to improve the rate of cadaver lung recovery. We performed a retrospective review of records from all thoracic organ donors procured by the California Transplant Donor Network between 1 January 1995 and 31 May 1997 (251 donors) to determine which donor management factors were associated with an increased likelihood of successful lung procurement. There were 88 lung donors (L) and 163 donors from which hearts but no lungs were procured (H). Longer time to donor network referral was associated with a reduced chance for successful lung procurement. Donor age, cause of death, and time of admission were not important factors. Most donors in this study had an acceptable A-a gradient at admission to the hospital but lung function deteriorated in group H. Corticosteroid usage and initially clear breath sounds were independent predictors of successful procurement by multivariate analysis. Early contact with the donor referral network, and corticosteroids may help to improve the lung procurement rate from potential donors.

Successful transplantation of marginally acceptable thoracic organs.

This study evaluates the efficacy of personally inspecting marginal thoracic organ donors to expand the donor pool. The present donor criteria for heart and lung transplantation are very strict and result in exclusion of many potential thoracic organ donors. Due to a limited donor pool, 20-30% of patients die waiting for transplantation. The authors have performed a prospective study of personally inspecting marginal donor organs that previously would have been rejected by standard donor criteria. Fourteen marginal hearts and eleven marginal lungs were inspected. All 14 marginal hearts and 10 of the marginal lungs were transplanted. All cardiac transplant patients did well. The mean ejection fraction of the donor hearts preoperatively was 39 +/- 11% (range 15-50%). Postoperatively, the ejection fraction of the donor hearts improved significantly to 55 +/- 3% (p < 0.002). Nine of the ten lung transplant patients did well and were operative survivors. Our donor pool expanded by 36% over the study period. The present donor criteria for heart and lung transplantation are too strict. Personal inspection of marginal thoracic donor organs will help to maximize donor utilization.

Double-lung transplantation for cystic fibrosis

One hundred twenty cystic fibrosis patients were accepted for transplantation. Twenty-five patients underwent double-lung transplantation. Twenty-five patients died awaiting transplantation (20.6%). There were 13 female and 12 male patients. Their mean age was 28 years (range, 7 to 34 years), and mean percentage ideal body weight was 76% (range, 58.5% to 91.9%). Most patients were hypoxic and hypercarbic. Two patients underwent tracheal anastomosis, 15 had en bloc bronchial anastomoses, and 8 had sequential single-lung transplants. Operative mortality was 16%; all deaths were related to bleeding from extensive adhesions. Actuarial survival at 1 year was 64%. Rejection and infection were frequent during the first month and decreased thereafter. Airway complications occurred in 5 patients but were amenable to laser therapy and stenting. We conclude that double-lung transplantation is an acceptable modality for the treatment of cystic fibrosis patients with end-stage lung disease. It may be a better alternative to heart-lung transplantation considering the paucity of thoracic organ donors.