Donor Pool Research Articles

211.2: Kidney transplantation from small paediatric donors is a feasible option to expand donor pool; report of two cases from the United Arab Emirates.

211.2: Kidney transplantation from small paediatric donors is a feasible option to expand donor pool; report of two cases from the United Arab Emirates.

P2.1: Increasing the kidney donor pool by moving from an agonal time to a modified functional warm ischemic time (fWIT) in New South Wales (NSW) - Australia.

P2.1: Increasing the kidney donor pool by moving from an agonal time to a modified functional warm ischemic time (fWIT) in New South Wales (NSW) - Australia.

Influence of Donor Type—Donation After Brain Death Versus Donation After Circulatory Death—on Lung Transplant Outcomes

We sought to analyze the influence of lung donor type (brain death [BD] vs controlled donation after cardiac death [DCD]) on lung graft viability and to compare short-term outcomes of lung transplantation using grafts from BD and DCD donors. This was a retrospective study of the lung donor population and lung transplants performed at our Institution between January 2020 and December 2022. Demographic characteristics of the donors and donation type (BD vs DCD) were assessed. Lung graft viability rate and post-transplant outcomes were analyzed and compared between donor types. There were 203 donors; among them, 149 (73%) were viable. There were 176 BD donors (87%) and 27 DCD donors (13%), with viability rates of 75% and 59%, respectively, performing 81 single (40%) and 122 double-lung transplants (60%). Recipient PaO2/fraction of inspired oxygen and primary graft dysfunction at 24 and 72 hours did not differ between donor types. Thirty-day mortality did not differ between recipients from BD donors and recipients from DCD donors: n=28 (21%) vs n=3 (18%), respectively (P=.81). Donation after cardiac death donors is a safe source to increase the donor pool for lung transplantation, allowing similar short-term outcomes as lung transplants from BD donors regarding graft function and early survival.

The clinical practice and consideration for donor liver expansion

Liver transplantation is the most effective method to address end-stage liver disease. However, there is a huge imbalance between organ supply and demand in China. Recently,effective expansion of the donor liver has become a hot research direction in academia. Authors' group comprehensively integrates domestic and foreign evidence-based medical evidence, the latest academic outcomes and clinical experience. Based on the innovative viewshed of crossfusion between biomedical engineering and medicine, author group systematically elaborate in the main strategies for expanding the liver donor pool, including the multichannel expansion of marginal donor liver,multidimensional innovation of technologies in transplant surgery and diversified exploration of alternative resources of organs. The author group aims to promote the construction of a large cohort,the integration of big data,and the output of high quality research,achieving innovative theory and clinical translation in organ transplantation,thus promoting the higher quality development of liver transplantation in China.

Advancing Understandings of Blood Donation Motivation and Behavior

In this review, we provide critical analysis of social science research into blood donation motivation and behavior. We first share an understanding of the existing literature and recommendations for future research collectively developed by members of the Working Group on Blood Donors and the Supply: Diversifying while Maintaining the Donor Pool, Donor Selection, and Optimizing Blood Availability and Safety, as part of the National Heart, Lung, and Blood Institute's 2022 State of the Science in Transfusion Medicine symposium. Then, rather than aim for a comprehensive treatment, we review 4 newer manuscripts that exemplify aspects of the group's recommendations and report results from countries where the blood supply is based on voluntary, nonremunerated donations. From the substantial existing literature, we selected: (1) a study that employed motivational interviewing techniques, thematic analysis, and surveys to link donation motivations and barriers reported by diverse young donors in the United States to actual donation behavior over a year of subsequent eligibility; (2) a survey regarding donation motivations and barriers and monetary amounts associated with willingness to participate in whole blood, plasma, or platelet collection; (3) a survey-based assessment of various emotional states reported by donors at 2 time points during donation and the relationship between emotional experience and subsequent vasovagal reactions; and (4) an interpretive discourse analysis of blood collection agency messaging to donors and the public in the beginning of the COVID-19 pandemic. We close by noting several challenges posed by the structure of the United States blood system and the current funding environment to conducting rigorous research and translating findings into practice.

Non-inferior outcomes in lower urgency patients transplanted with extended criteria donor hearts

Recent work has suggested that outcomes among heart transplant patients listed at the lower-urgency (United Network for Organ Sharing Status 4 or 6) status may not be significantly impacted by donor comorbidities. The purpose of this study was to investigate outcomes of extended criteria donors (ECD) in lower vs. higher urgency patients undergoing heart transplantation. The United Network for Organ Sharing (UNOS) database was queried for all adult patients undergoing heart transplantation from 10/18/2018 through 12/31/2021. Patients were stratified by degree of urgency (higher urgency: UNOS 1 or 2 vs. lower urgency: UNOS 4 or 6) and receipt of ECD hearts, as defined by donor hearts failing to meet established acceptable use criteria. Outcomes were compared using propensity score matched cohorts. Among 9,160 patients included, 2,320 (25.4%) were low urgency. ECD hearts were used in 35.5% of HU patients and 39.2% of LU patients. While ECD hearts had an impact on survival among high-urgency patients (p<0.01), there was no difference in 1- and 2-year survival (p>0.05) found among low urgency patients receiving ECD vs. standard hearts. Neither ECDs nor individual ECD criteria were independently associated with mortality in low urgency patients (p>0.05). Post-transplant outcomes among low urgency patients are not adversely affected by receipt of ECD vs. standard hearts. Expanding the available donor pool by optimizing use of ECDs in this population may increase transplant frequency, decrease waitlist morbidity, and improve postoperative outcomes for the transplant community at large.

Computed tomography–based machine learning for donor lung screening before transplantation

Assessment and selection of donor lungs remain largely subjective and experience based. Criteria to accept or decline lungs are poorly standardized and are not compliant with the current donor pool. Using ex vivo computed tomography (CT) images, we investigated the use of a CT-based machine learning algorithm for screening donor lungs before transplantation. Clinical measures and ex situ CT scans were collected from 100 cases as part of a prospective clinical trial. Following procurement, donor lungs were inflated, placed on ice according to routine clinical practice, and imaged using a clinical CT scanner before transplantation while stored in the icebox. We trained and tested a supervised machine learning method called dictionary learning, which uses CT scans and learns specific image patterns and features pertaining to each class for a classification task. The results were evaluated with donor and recipient clinical measures. Of the 100 lung pairs donated, 70 were considered acceptable for transplantation (based on standard clinical assessment) before CT screening and were consequently implanted. The remaining 30 pairs were screened but not transplanted. Our machine learning algorithm was able to detect pulmonary abnormalities on the CT scans. Among the patients who received donor lungs, our algorithm identified recipients who had extended stays in the intensive care unit and were at 19 times higher risk of developing chronic lung allograft dysfunction within 2years posttransplant. We have created a strategy to ex vivo screen donor lungs using a CT-based machine learning algorithm. As the use of suboptimal donor lungs rises, it is important to have in place objective techniques that will assist physicians in accurately screening donor lungs to identify recipients most at risk of posttransplant complications.

Breaking Barriers and Bridging Gaps: Advancing Diversity, Equity, and Inclusion in Kidney Transplant Care for Black and Hispanic Patients in the United States.

Kidney transplantation offers better mortality and quality of life outcomes to patients with end-stage renal failure compared to dialysis. Specifically, living donor kidney transplantation is the best treatment for end-stage renal disease, since it offers the greatest survival benefit compared to deceased donor kidney transplant or dialysis. However, not all patients from all racial/ethnic backgrounds enjoy these benefits. While black and Hispanic patients bear the predominant disease burden within the United States, they represent less than half of all kidney transplants in the country. Other factors such as cultural barriers that proliferate myths about transplant, financial costs that impede altruistic donation, and even biological predispositions create a complex maze and can also perpetuate care inaccessibility. Therefore, blanket efforts to increase the overall donation pool may not extend access to vulnerable populations, who may require more targeted attention and interventions. This review uses US kidney transplantation data to substantiate accessibility differences amongst racial minorities as well as provides examples of successful institutional and national systemic level changes that have improved transplantation outcomes for all.

Mechanisms and aetiology-dependent treatment of acute liver failure.

This review compiles the mechanisms of acute liver failure (ALF) as well as the current and potential therapeutic approaches, including aetiology-specific treatment, and the issues encountered with such approaches. On a cellular level, ALF is characterized by massive hepatocyte death due to different types of cellular demise. Compensatory hyperplasia and functional recovery are possible when the regenerative capacity is sufficient to sustain hepatic function. ALF has a high mortality of about 30% and can lead to death in a very short time despite maximum therapeutic intervention. Besides aetiology-specific therapy and intensive care, the therapeutic option of emergency liver transplantation has significantly improved the prognosis of patients with ALF. However, due to limiting factors such as organ shortage, many patients die on the waiting list. In addition to graft assessment, machine perfusion may have the potential to recondition marginal organs and thus expand the organ donor pool.

Complications in Post-Liver Transplant Patients.

Liver transplantation (LT) is the treatment of choice for liver failure and selected cases of malignancies. Transplantation activity has increased over the years, and indications for LT have been widened, leading to organ shortage. To face this condition, a high selection of recipients with prioritizing systems and an enlargement of the donor pool were necessary. Several authors published their case series reporting the results obtained with the use of marginal donors, which seem to have progressively improved over the years. The introduction of in situ and ex situ machine perfusion, although still strongly debated, and better knowledge and treatment of the complications may have a role in achieving better results. With longer survival rates, a significant number of patients will suffer from long-term complications. An extensive review of the literature concerning short- and long-term outcomes is reported trying to highlight the most recent findings. The heterogeneity of the behaviors within the different centers is evident, leading to a difficult comparison of the results and making explicit the need to obtain more consent from experts.

Composition of ex vivo perfusion solutions and kinetics define differential cytokine/chemokine secretion in a porcine cardiac arrest model of lung preservation.

Ex vivo lung perfusion (EVLP) uses continuous normothermic perfusion to reduce ischemic damage and to improve post-transplant outcomes, specifically for marginal donor lungs after the donation after circulatory death. Despite major efforts, the optimal perfusion protocol and the composition of the perfusate in clinical lung transplantation have not been identified. Our study aims to compare the concentration levels of cytokine/chemokine in different perfusion solutions during EVLP, after 1 and 9 h of cold static preservation (CSP) in a porcine cardiac arrest model, and to correlate inflammatory parameters to oxygenation capacities. Following cardiac arrest, the lungs were harvested and were categorized into two groups: immediate (I-EVLP) and delayed EVLP (D-EVLP), after 1 and 9 h of CSP, respectively. The D-EVLP lungs were perfused with either Steen or modified Custodiol-N solution containing only dextran (CD) or dextran and albumin (CDA). The cytokine/chemokine levels were analyzed at baseline (0 h) and after 1 and 4 h of EVLP using Luminex-based multiplex assays. Within 4 h of EVLP, the concentration levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-1α, and IL-1β increased significantly (P < 0.05) in all experimental groups. The CD solution contained lower concentration levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-2, IL-12, IL-10, IL-4, IL-1RA, and IL-18 (P < 0.05) compared with those of the Steen solution. The concentration levels of all experimental groups have correlated negatively with the oxygenation capacity values (P < 0.05). Protein concentration levels did not reach statistical significance for I-EVLP vs. D-EVLP and CD vs. CDA solutions. In a porcine cardiac arrest model, a longer period of CSP prior to EVLP did not result in an enhanced protein secretion into perfusates. The CD solution reduced the cytokine/chemokine secretion most probably by iron chelators and/or by the protecting effects of dextran. Supplementing with albumin did not further reduce the cytokine/chemokine secretion into perfusates. These findings may help in optimizing the preservation procedure of the lungs, thereby increasing the donor pool of organs.

Intermittent Ex Vivo Lung Perfusion in a Porcine Model for Prolonged Lung Preservation.

Ex vivo lung perfusion expands the lung transplant donor pool and extends preservation time beyond cold static preservation. We hypothesized that repeated regular ex vivo lung perfusion would better maintain lung grafts. Ten pig lungs were randomized into 2 groups. The control underwent 16 h of cold ischemic time and 2 h of cellular ex vivo lung perfusion. The intermittent ex vivo lung perfusion group underwent cold ischemic time for 4 h, ex vivo lung perfusion (first) for 2 h, cold ischemic time for 10 h, and 2 h of ex vivo lung perfusion (second). Lungs were assessed, and transplant suitability was determined after 2 h of ex vivo lung perfusion. The second ex vivo lung perfusion was significantly associated with better oxygenation, limited extravascular water, higher adenosine triphosphate, reduced intraalveolar edema, and well-preserved mitochondria compared with the control, despite proinflammatory cytokine elevation. No significant difference was observed in the first and second perfusion regarding oxygenation and adenosine triphosphate, whereas the second was associated with lower dynamic compliance and higher extravascular lung water than the first. Transplant suitability was 100% for the first and 60% for the second ex vivo lung perfusion, and 0% for the control. The second ex vivo lung perfusion had a slight deterioration in graft function compared to the first. Intermittent ex vivo lung perfusion created a better condition for lung grafts than cold static preservation, despite cytokine elevation. These results suggested that intermittent ex vivo lung perfusion may help prolong lung preservation.

Transplant Candidate Outcomes After Declining a DCD Liver in the United States.

In the context of the organ shortage, donation after circulatory death (DCD) provides an opportunity to expand the donor pool. Although deceased-donor liver transplantation from DCD donors has expanded, DCD livers continue to be discarded at elevated rates; the use of DCD livers from older donors, or donors with comorbidities, is controversial. Using US registry data from 2009 to 2020, we identified 1564 candidates on whose behalf a DCD liver offer was accepted ("acceptors") and 16 981 candidates on whose behalf the same DCD offers were declined ("decliners"). We characterized outcomes of decliners using a competing risk framework and estimated the survival benefit (adjusted hazard ratio [95% confidence interval]) of accepting DCD livers using Cox regression. Within 10 y of DCD offer decline, 50.9% of candidates died or were removed from the waitlist before transplantation with any type of allograft. DCD acceptors had lower mortality compared with decliners at 10 y postoffer (35.4% versus 48.9%, P < 0.001). After adjustment for candidate covariates, DCD offer acceptance was associated with a 46% reduction in mortality (0.54 [0.49-0.61]). Acceptors of older (age ≥50), obese (body mass index ≥30), hypertensive, nonlocal, diabetic, and increased risk DCD livers had 44% (0.56 [0.42-0.73]), 40% (0.60 [0.49-0.74]), 48% (0.52 [0.41-0.66]), 46% (0.54 [0.45-0.65]), 32% (0.68 [0.43-1.05]), and 45% (0.55 [0.42-0.72]) lower mortality risk compared with DCD decliners, respectively. DCD offer acceptance is associated with considerable long-term survival benefits for liver transplant candidates, even with older DCD donors or donors with comorbidities. Increased recovery and utilization of DCD livers should be encouraged.

Aging exacerbates murine lung ischemia-reperfusion injury by excessive inflammation and impaired tissue repair response

Donor shortage is a major problem in lung transplantation (LTx), and the use of lungs from elderly donors is one of the possible solutions in a rapidly aging population. However, the utilization of organs from donors aged >65 years has remained infrequent and may be related to a poor outcome. To investigate the molecular events in grafts from elderly donors early after LTx, the left lungs of young and old mice were subjected to 1 hour of ischemia and subsequent reperfusion. The left lungs were collected at 1 hour, 1 day, and 3 days after reperfusion and subjected to wet-to-dry weight ratio measurement, histological analysis, and molecular biological analysis, including RNA sequencing. The lungs in old mice exhibited more severe and prolonged pulmonary edema than those in young mice after ischemia reperfusion, which was accompanied by upregulation of the genes associated with inflammation and impaired expression of cell cycle-related genes. Apoptotic cells increased and proliferating type 2 alveolar epithelial cells decreased in the lungs of old mice compared with young mice. These factors could become conceptual targets for developing interventions to ameliorate lung ischemia-reperfusion injury after LTx from elderly donors, which may serve to expand the old donor pool.

Epidemiology and Long-Term Outcomes in Thoracic Transplantation.

Over the past five decades, outcomes for lung transplantation have significantly improved in the early post-operative period, such that lung transplant is now the gold standard treatment for end-stage respiratory disease. The major limitation that impacts lung transplant survival rates is the development of chronic lung allograft dysfunction (CLAD). CLAD affects around 50% of lung transplant recipients within five years of transplantation. We must also consider other factors impacting the survival rate such as the surgical technique (single versus double lung transplant), along with donor and recipient characteristics. The future is promising, with more research looking into ex vivo lung perfusion (EVLP) and bioengineered lungs, with the hope of increasing the donor pool and decreasing the risk of graft rejection.

Renal allograft procurement from living unrelated donors in Iran: What falls under the eclipse.

Renal transplantation is the treatment of choice for end stage kidney disease. However, despite all the efforts to expand the donor pool, the shortage of donors is increasing and as a consequence, there has been a significant increase in the number of patients on transplant waiting lists globally. Societies worldwide have employed different methods to address this, each with specific ethical concerns surrounding them. Over three decades ago, a governmentally regulated program of kidney transplantation from living unrelated donors was introduced in Iran and since practiced which has been the subject of hot debate in the literature. Nevertheless, despite all these extensive discussions and publications, several key aspects of the program have still not been properly elucidated and addressed. In this article, the author aims to illuminate some dark corners related to this issue that have largely escaped the notice of ethicists.

Bone marrow transplant: A two-decade single centre hematology experience

BackgroundBone Marrow Transplant (BMT) is a curative form of therapy for many hematological disorders in both the adult and pediatric patients. The availability of BMT in the AFMS at AHRR for the last 02 decades has been a game changer for the patients. MethodsWe reviewed our BMT data since the inception of the program till Feb 2023. ResultsOver 700 patients with more than 23 different types of hematological disorders have undergone this procedure 58%% patients underwent an Autologous BMT and 42% an allogenic BMT. Autologous BMT for Multiple Myeloma and Allogenic BMT for Aplastic Anemia and Acute Leukemias have been the most common indications. 73% patients were adults, and 27% patients were of the pediatric age group. The male: female ratio was 2:1. The spectrum of allogenic Hematopoietic Stem Cell Transplant (HSCT) has expanded from Matched Sibling Donor (MSD) transplants to Matched Unrelated Donor (MUD) Transplants and Haploidentical Donor Transplants. 93% of our Allogenic BMT patients underwent a MSD BMT, 1% MUD BMT and 06% Haploidentical BMT. Today no patient with a malignant hematological disorder requiring a BMT is denied the procedure due to the lack of an HLA donor due to the availability of haploidentical BMT. ConclusionThe evolution of a BMT program has a long learning curve and the expanded pool of eligible donors has led to a situation of “transplant for all”. Haploidentical HSCT for nonmalignant hematological disorders is an unmet need. CART cell therapy and Cellular therapies need to be prioritized for future inclusion.

Exotic success following disturbance explained by weak native resilience and ruderal exotic bias

Abstract Disturbance is a primary driver of exotic plant invasions, but why disturbance commonly favours exotics over natives is unresolved. To address this question, we conducted the first biogeographic study of disturbance across multiple plant species. We experimentally disturbed grasslands and added seeds of 34 plant species to plots in their native range and in two introduced ranges that differed in invasibility (susceptibility to invasion) to evaluate recruitment while examining potential influences of resource availability, native community recovery from disturbance (resilience) and life‐history traits in local species pools. Species pools in the native (donor) range were more strongly skewed towards ruderal taxa than species pools in the introduced ranges. This bias in the donor pool was exacerbated by introduction filters that further selected for ruderal traits, strongly skewing exotic species pools in the introduced ranges towards ruderals. Sown species, which reflected these trait patterns, benefited from disturbance universally, but their disturbance response was 10‐fold greater in the more invasible introduced range. This result was not explained by nutrient availability, which responded similar to disturbance across ranges. Nor was it driven by background propagule pressure, which was minimal. Rather, the exaggerated disturbance effect in the more invasible introduced range appeared to be driven by weak recovery of the native plant community that allowed ruderal‐biased exotics to proliferate. Overall, disturbance appeared to favoured exotics because they were much more likely than natives to be ruderal. However, this trait bias only corresponded with an invader advantage in the more invasible range where weak community resilience was linked to slow‐growing, stress‐tolerant natives that failed to rapidly recover space and resources. In contrast, in the less invasible introduced range, highly competitive native perennials quickly filled the disturbance gap, demonstrating high community resilience that appeared to limit invader recruitment. Synthesis: Biogeographic influences on local species pools can facilitate invader success following disturbance, but final invasion outcomes are conditioned by native community resilience.

Increased-risk versus standard-risk donation in lung transplantation: A United Network of Organ Sharing analysis

ObjectivesDonors with characteristics that increase risk of hepatitis B virus, hepatitis C virus, and HIV transmission are deemed increased-risk donors (IRDs) per Public Health Service guidelines. Compared with organs from standard-risk donors (SRDs), IRD organs are more frequently declined. We sought to investigate the outcomes of IRD lung transplant recipients following the 2013 guideline change. MethodsWe retrospectively identified lung transplant recipients using the United Network of Organ Sharing registry (February 2014 to March 2020). Patients were divided into 2 cohorts, based on Centers for Disease Control and Prevention risk status of the donor: SRD or IRD. Demographics and clinical parameters were compared across groups. Survival was compared using Kaplan–Meier curves and log-rank tests. Cox proportional hazard model was performed to identify variables associated with survival outcome. ResultsWe identified 13,205 lung transplant recipients, 9963 who received allografts from SRDs and 3242 who received allografts from IRDs. In both groups, most donors were White, male, and <30 years old. IRDs demonstrated greater rates of heavy alcohol, cigarette, and cocaine use. SRDs had greater rates of cancer, hypertension, previous myocardial infarction, and diabetes. Survival analysis demonstrated no significant difference in 90-day, 1-year, 3-year, or 5-year survival outcome between SRD and IRD recipients (P = .34, P = .67, P = .40, P = .52, respectively). Cox regression demonstrated that double-lung transplants were associated with 13% decreased mortality risk compared with single-lung (P = .0009). ConclusionsIRD and SRD recipients demonstrated equivalent survival outcomes. Our study suggests that IRDs offer a safe approach to expand the donor pool and increase availability of lungs for transplantation.

Abstract 16 Insights into Highly Engraftable Hematopoietic Cells from 27-Year Cryopreserved Umbilical Cord Blood

Abstract Introduction Cord blood banking has consistently outpaced the utilization of cord blood units (CBUs). Thus, the average duration of cryopreservation among banked CBUs will likely continue to increase. It remains unclear how long cryopreserved CBUs remain functional, and it is critical to determine whether duration of cryopreservation should be used as an exclusionary criterion during selection for clinical use or if alternative post-thaw metrics can identify potent cryopreserved CBUs regardless of age. Objectives Our goal was to determine whether long-term (27-year) cryopreserved CBUs retain viable and functional hematopoietic stem (HSCs) and progenitor cells (HPCs). We further sought to leverage differences in HSC/HPC function (measured by in vivo engraftment) to demonstrate the utility of using omics approaches to identify candidate genes for use as molecular potency markers. Methods We performed comprehensive ex vivo, in vivo, and molecular analyses on the numbers, viability, and function of three 27-year cryopreserved CBUs using 3-year cryopreserved and fresh CBUs for comparison. Assays included viability staining, immunophenotyping by flow cytometry, primary and secondary colony forming unit (CFU) assays, ex vivo expansion of immunophenotypic HSCs/HPCs/CFUs, limiting dilution transplantations into immune-deficient mice, secondary transplantations, and RNA-sequencing of sorted HSCs and multipotent progenitor cells. Results Compared to fresh and recently cryopreserved CBU controls, long-term cryopreserved CBUs yield statistically similar numbers of viable immunophenotypic HSCs, multipotent HPCs, and committed myeloid and lymphoid HPCs. They retain highly functional cells, demonstrating similar primary and secondary CFU numbers and expansion capacity compared to controls, as well as robust engraftment, SCID repopulating cell frequency, and secondary engraftment capacity in mouse models of transplantation. Transcriptomic modelling revealed 18 genes, including MALT1 and MAP2K1, and several gene programs, including lineage determination programs and oxidative stress responses, that are strongly enriched in high engrafting HSCs/HPCs. Discussion CBUs cryopreserved for up to 27 years retain highly functional HSCs/HPCs. Thus, duration of cryopreservation alone is not an ideal exclusionary criteria for selection of CBUs. Preserving older CBUs may help to maintain a large and diverse pool of donors for clinical selection. Further, transcriptomics can identify candidate genes associated with engraftment for elucidation of possible CBU potency markers regardless of the duration of cryopreservation.