Scarcity Of Organs Research Articles

Utilization of deceased donors during a pandemic: argument against using SARS-CoV-2-positive donors.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has rapidly become an unprecedented pandemic that has impacted society, disrupted hospital functions, strained health care resources, and impacted the lives of transplant professionals. Despite this, organ failure and the need for transplant continues throughout the United States. Considering the perpetual scarcity of deceased donor organs, Kates et al present a viewpoint that advocates for the utilization of coronavirus disease 2019 (COVID‐19)–positive donors in selected cases. We present a review of the current literature that details the potential negative consequences of COVID‐19–positive donors. The factors we consider include (1) the risk of blood transmission of SARS‐CoV‐2, (2) involvement of donor organs, (3) lack of effective therapies, (4) exposure of health care and recovery teams, (5) disease transmission and propagation, and (6) hospital resource utilization. While we acknowledge that transplant fulfills the mission of saving lives, it is imperative to consider the consequences not only to our recipients but also to the community and to health care workers, particularly in the absence of effective preventative or curative therapies. For these reasons, we believe the evidence and risks show that COVID‐19 infection should continue to remain a contraindication for donation, as has been the initial response of donation and transplant societies.

New updates in the world of hepatitis C virus infected organ transplantation.

With the advent of direct acting antiviral (DAA) therapy, the use of organs from hepatitis C virus infected (HCV+) donors is gaining more traction. In this review, we aim to: provide an overview of recent literature that supports the use of HCV+ organs, outline ongoing challenges to the use of these organs, and highlight the areas within this field where active investigation is ongoing. The present review describes clinical outcomes related to the transplantation of both HCV+ nonviremic and viremic organs and the distinction between hepatic and nonhepatic transplants. It also discusses the current debate pertaining to the ideal treatment strategy for donor-derived HCV infection, that is pre-emptive therapy versus prophylaxis therapy. Data suggest that the use of HCV+ organs is an effective and relatively well tolerated strategy to combat the organ scarcity. However, clinicians must be vigilant to a signal of increased inflammation as HCV+ organ transplantation becomes more universal. Recent studies suggest that shorter courses of DAA may sufficiently treat donor-derived HCV infection, however the best treatment approach to minimize risk, cost, and toxicity is still under investigation.

Case report: Liver Transplantation in a highly dependent Down Syndrome patient

Despite the malformations commonly associated with Down Syndrome, the average life expectancy of individuals nowadays may reach 60-70 years of age. With these increased survival rates, the spectrum of diseases reported in these patients has been growing, particularly autoimmune diseases. This report describes a 44-year-old patient with Down Syndrome with a high degree of family dependence and end-stage liver disease (MELD-Na 38) caused by overlapping Primary Sclerosing Cholangitis and Autoimmune Hepatitis, who needed Liver Transplantation. Here, we point out two relevant aspects: the overlap of rare autoimmune diseases in patients with Trisomy 21 and the performance of Liver Transplantation in these patients. We then highlight the ethical dilemma between organ scarcity and the use of the graft in patients with neurocognitive disorders.

Pediatric lung transplantation: Results of volume reduction in smaller children.

Pediatric LTX is challenged by the scarcity of suitable donor organs. To alleviate the problem of size matching, volume reduction of the donor is a possible option. Previous reports address mostly older teenagers, and data about younger patients are lacking. The purpose of this study was to investigate whether trimming had influence on the morbidity and mortality in slightly younger recipients, operated in a single center. Between 2015 and 2018, 20 patients were transplanted at the GOSH London. The mean age was 11.5 (±4.6)years. Nine patients underwent volume reduction prior to transplantation (T group). The other patients received classical bilateral LTX (NT group). Ischemia times were longer in the T group, but this difference was not statistically significant. We observed no 30-day mortality. Hospital survival in the T group was 78% vs 90% in the NT group. After almost 3years, mortality in the T group was 22% vs 28% in the NT group. None of these differences was statistically significant. The mean duration of MV, intensive care stay, and hospital stay were 11.5, 19.9, and 44.8days, respectively. Results were equal in terms of morbidity, defined as respiratory and neurological complications or the need for ECMO. Results show that volume reduction prior to LTX is a feasible option, even in smaller children. While awaiting long-term results, accepting larger donor organs could be a strategy to further reduce waiting list time and subsequently lower the mortality on the waiting list.

Hepatic Progenitor Specification from Pluripotent Stem Cells using a Defined Differentiation System.

Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to shortages in donor organ availability. Organ scarcity also affects the routine supply of human hepatocytes for basic research and the clinic. Therefore, the development of renewable sources of human liver progenitor cells is desirable and is the goal of this study. To be able to effectively generate and deploy human liver progenitors on a large scale, a reproducible hepatic progenitor differentiation system was developed. This protocol aids experimental reproducibility between users in a range of cell cultureware formats and permits differentiations using both, human embryonic and induced pluripotent stem cell lines. These are important advantages over current differentiation systems that will enhance the basic research and may pave the way towards clinical product development.

Donor-Transmitted Melanoma: Is It Still Bothering Us?

Global organ scarcity remains a severe obstacle because of the rapid growth in the number of patients on the transplant waiting list. Transplant centres strive to raise the number of donors by proposing more mild criteria for donor selection, among them donors with a history of malignancy and older age. Recipients are at hazard of acquiring tumour that existed in the donor at the time of transplantation with the most common cancers been renal cell carcinoma (57%), melanoma (10%), and choriocarcinoma (9%). Tumour origin can be established by PCR-based DNA analysis for microsatellite markers, HLA typing, immunohistochemistry, or fluorescent in situ hybridisation. The general recommendation for treatment of donor-related melanoma is a cessation of immunosuppression therapy to allow rejection of the allograft and its immediate removal. In non-renal transplant patients with life-sustaining organs or if allograft removal is denied, reduction of immunosuppression, chemoradiation therapy, and urgent retransplantation are the only potential strategies. Checkpoint inhibitors were reported to be effective in several cases of donor-transmitted melanoma and now emerge as an innovative option to standard chemotherapy and the potential for cure.

Children With Intellectual and Developmental Disabilities as Organ Transplantation Recipients.

The demand for transplantable solid organs far exceeds the supply of deceased donor organs. Patient selection criteria are determined by individual transplant programs; given the scarcity of solid organs for transplant, allocation to those most likely to benefit takes into consideration both medical and psychosocial factors. Children with intellectual and developmental disabilities have historically been excluded as potential recipients of organ transplants. When a transplant is likely to provide significant health benefits, denying a transplant to otherwise eligible children with disabilities may constitute illegal and unjustified discrimination. Children with intellectual and developmental disabilities should not be excluded from the potential pool of recipients and should be referred for evaluation as recipients of solid organ transplants.

The impact of donor urine chemical toxicology analysis on outcomes of kidney transplantation.

Acceptance of organs from acute chemical intoxicated donors remains controversial and outcomes are insufficiently explored. This is a single-center retrospective cohort analysis of 484 patients undergoing deceased donor kidney transplantation (DDKT). We assessed the association of positive urine drug screen before transplantation with cohort statistics, delayed graft function (DGF), and graft outcomes at 2 years. Multiple logistical regression (MLR) analysis was used to assess the odds ratio for DGF. Of 484 random DDKTs performed at our institution between January 2010 and October 2015, 280 deceased kidney donors were current drug users. Mean age was 35.4 (15) years, 39% male, 61% were African Americans, and 38.2% had more than one test positive. The main chemical toxins detectable in donor urine were alcohol, heroin, opioid/methadone, cocaine, marijuana, benzodiazepines, methamphetamine, ecstasy, and LSD. Single and multiple urine chemical toxicology of kidney donors did not have a significant effect on KT outcomes of DGF and graft failure during a median follow-up (P for odds ratios > 0.05). The use of deceased donor kidney grafts from donors with positive urine chemical toxicology may be a worthwhile method of increasing the availability of scarce donor kidney organs as such exposure to illicit drug(s) is not associated with major adverse transplant outcomes.

Liver Transplantation for Cholangiocarcinoma: Insights into the Prognosis and the Evolving Indications.

Cholangiocarcinoma (CCA) is a rare malignancy of the biliary ducts that can be classified as intrahepatic, perihilar, or distal based on anatomic location. Although surgical resection can be curative, complete excision with negative margins is often difficult to achieve. In patients with unresectable disease, long-term survival is rarely seen with medical therapy alone. A multimodal treatment approach, including liver transplantation (LT) for select patients with unresectable CCA, should be considered. While currently only an approved indication for early, liver-limited, perihilar cholangiocarcinoma, promising results have been achieved for LT in localized intrahepatic disease. The absolute indication for transplant for intrahepatic tumors is currently the subject of multiple investigations. Continued advances in neoadjuvant/adjuvant therapy and better understanding of tumor biology may further augment the number of candidates for surgical therapies, with liver transplant acting as a promising tool to improve patient outcomes. Thorough consideration for any expansion in the indication for liver transplant in malignancy is necessary in order to balance patient outcomes with utilization of the scarce donor organ resources.

Age change in healthcare settings: a reply to Lippert-Rasmussen and Petersen

Lippert-Rasmussen and Petersen discuss my ‘Moral case for legal age change’ in their article ‘Age change, official age and fairness in health’. They argue that in important healthcare settings (such...

Pediatric Kidney Transplantation in Perú: A Single-Center Initial Experience

BackgroundPediatric kidney transplantation (PKTx) is the preferred therapy for children with end-stage renal disease (ESRD) worldwide. Regrettably, in Perú, access to PKTx is extremely difficult due to recipient/donor socio-economic status, health care structure and especially, scarcity of organs. Our center (the only pediatric institute in the country) has recently started a PKTx program with good midterm results. The aim of this study was to present our outcomes. MethodsRetrospective analysis of prospectively collected data between December 2017 and August 2019. Fourteen PKTx (< 18 years old) were achieved. As per our protocol: pre-implantation/protocol biopsies, antibody assessment (T/B cell flow cytometric plus HLA testing applying polymerase chain reaction–based technology), triple immunosuppression (tacrolimus, mycophenolate mofetil, steroids) and induction therapy was performed in every case. ResultsThe recipient’s mean age at the time of PKTx was 14.14 ± 2.62, 8/14 (57.14%) were male, 50% developed ESRD due to undetermined etiology, 11/14 (78.57%) received a deceased donor allograft, and 9/14 (64.28%) required induction with thymoglobulin. Postoperative complications included: delayed graft function (1/14, 7.14%), 1 (7.14%) developed gross hematuria associated with allograft disfunction post-protocol allograft biopsy that was managed conservatively and 1 recipient (7.14%) developed grade II oligoastrocytoma, at 10 months post PKTx. ConclusionsPKTx is the best therapeutic option for children with ESRD. Our group demonstrated that even in countries with limited resources like Perú, good midterm results can be achieved. Emphasis should be given to improve access to transplantation especially in the setting of pediatric recipients.

Generation of human endothelium in pig embryos deficient in ETV2.

The scarcity of donor organs may be addressed in the future by using pigs to grow humanized organs with lower potential for immunological rejection after transplantation in humans. Previous studies have demonstrated that interspecies complementation of rodent blastocysts lacking a developmental regulatory gene can generate xenogeneic pancreas and kidney1,2. However, such organs contain host endothelium, a source of immune rejection. We used gene editing and somatic cell nuclear transfer to engineer porcine embryos deficient in ETV2, a master regulator of hematoendothelial lineages3-7. ETV2-null pig embryos lacked hematoendothelial lineages and were embryonic lethal. Blastocyst complementation with wild-type porcine blastomeres generated viable chimeric embryos whose hematoendothelial cells were entirely donor-derived. ETV2-null blastocysts were injected with human induced pluripotent stem cells (hiPSCs) or hiPSCs overexpressing the antiapoptotic factor BCL2, transferred to synchronized gilts and analyzed between embryonic day 17 and embryonic day 18. In these embryos, all endothelial cells were of human origin.

Pharmacological stimulation of Wnt/beta-catenin signaling pathway attenuates the course of thioacetamide-induced acute liver failure.

Acute liver failure (ALF) is known for extremely high mortality rate, the result of widespread damage of hepatocytes. Orthotopic liver transplantation is the only effective therapy but its application is limited by the scarcity of donor organs. Given the importance in the liver biology of Wnt/beta-catenin signaling pathway, we hypothesized that its stimulation could enhance hepatocyte regeneration and attenuate the course of thioacetamide (TAA)-induced ALF in Lewis rats. Chronic treatment with Wnt agonist was started either immediately after hepatotoxic insult ("early treatment") or when signs of ALF had developed ("late treatment"). Only 23 % of untreated Lewis rats survived till the end of experiment. They showed marked increases in plasma alanine aminotransferase (ALT) activity and bilirubin and ammonia (NH3) levels; plasma albumin decreased significantly. "Early" and "late" Wnt agonist treatment raised the final survival rate to 69 % and 63 %, respectively, and normalized ALT, NH3, bilirubin and albumin levels. In conclusion, the results show that treatment with Wnt agonist attenuates the course of TAA-induced ALF in Lewis rats, both with treatment initiated immediately after hepatotoxic insult and in the phase when ALF has already developed. Thus, the pharmacological stimulation of Wnt/beta-catenin signaling pathway can present a new approach to ALF treatment.

Evolving Cell-Based and Cell-Free Clinical Strategies for Treating Severe Human Liver Diseases.

Liver diseases represent a major global health issue, and currently, liver transplantation is the only viable alternative to reduce mortality rates in patients with end-stage liver diseases. However, scarcity of donor organs and risk of recidivism requiring a re-transplantation remain major obstacles. Hence, much hope has turned towards cell-based therapy. Hepatocyte-like cells obtained from embryonic stem cells or adult stem cells bearing multipotent or pluripotent characteristics, as well as cell-based systems, such as organoids, bio-artificial liver devices, bioscaffolds and organ printing are indeed promising. New approaches based on extracellular vesicles are also being investigated as cell substitutes. Extracellular vesicles, through the transfer of bioactive molecules, can modulate liver regeneration and restore hepatic function. This review provides an update on the current state-of-art cell-based and cell-free strategies as alternatives to liver transplantation for patients with end-stage liver diseases.

Defining a Willingness-to-transplant Threshold in an Era of Organ Scarcity: Simultaneous Liver-kidney Transplant as a Case Example.

Organ scarcity continues in solid organ transplantation, such that the availability of organs limits the number of people able to benefit from transplantation. Medical advancements in managing end-stage organ disease have led to an increasing demand for multiorgan transplant, wherein a patient with multiorgan disease receives >1 organ from the same donor. Current allocation schemes give priority to multiorgan recipients compared with single-organ transplant recipients, which raise ethical questions regarding equity and utility. We use simultaneous liver and kidney (SLK) transplant, a type of multiorgan transplant, as a case study to examine the tension between equity and utility in multiorgan allocation. We adapt the health economics willingness-to-pay threshold to a solid organ transplant setting by coining a new metric: the willingness-to-transplant (WTT) threshold. We demonstrate how the WTT threshold can be used to evaluate different SLK allocation strategies by synthesizing utility and equity perspectives. We submit that this new framework enables us to distill the question of SLK allocation down to: what is the minimum amount of benefit we require from a deceased donor kidney to allocate it for a particular indication? Addressing the above question will prove helpful to devising a rational system of SLK allocation and is applicable to other transplant settings.

Should living donor liver transplant selection be subject to the same restrictions as deceased donor transplant?

In the United States, most of the liver allografts come from deceased donors, and our current liver recipient selection process is heavily centered on the ethical principle of utility to maximize the net benefit to the liver recipient community as a group rather than individuals due to the organ scarcity. Although living donor liver transplantation contributes less than 5% of total liver transplant in the United States, these living donor recipients are being subjected to the same selection process designed to benefit the group as a whole rather than the individuals. We would like to examine if these recipients who have living donors should be subjected to the same selection process. There are several disease processes where liver transplantation is the only curative option, and recent studies have shown clear survival benefits with liver transplantation. For those who have living donors, different selection criteria based on their specific disease, not based on the principle of utilization should be used to evaluate their candidacy.

Solid organ donation after death in the United States: Data-driven messaging to encourage potential donors.

US deceased donor solid organ transplantation (dd-SOT) depends upon an individual's/family's altruistic willingness to donate organs after death; however, there is a shortage of deceased organ donors in the United States. Informing individuals of their own lifetime risk of needing dd-SOT could reframe the decision-making around organ donation after death. Using United Network for Organ Sharing (UNOS) data (2007-2016), this cross-sectional study identified (1) deceased organ donors, (2) individuals waitlisted for dd-SOT (liver, kidney, pancreas, heart, lung, intestine), and (3) dd-SOT recipients. Using US population projections, life tables, and mortality estimates, we quantified probabilities (Pr) of (1) becoming deceased organ donors, (2) needing dd-SOT, and (3) receiving dd-SOT. Lifetime Pr (per 100000 US population) for males and females of becoming deceased organ donors were 212 and 146, respectively, and of needing dd-SOT were 1323 and 803, respectively. Lifetime Pr of receiving dd-SOT was 50% for males, 48% for females. Over a lifetime, males were 6.2 and females 5.5 times more likely to need dd-SOT than to become deceased organ donors. Organ donation is traditionally contextualized in terms of charity toward others. Our analyses yield a new tool, in the form of quantifying an individual's own likelihood of needing dd-SOT, which may assist with reframing motivations toward deceased donor organ donation.

Machine perfusion in abdominal organ transplantation: Current use in the Netherlands.

Scarcity of donor organs and the increment in patients awaiting a transplant increased the use of organs from expanded criteria donors or donation after circulatory death. Due to the suboptimal outcomes of these donor organs, there is an increased interest in better preservation methods, such as ex vivo machine perfusion or abdominal regional perfusion to improve outcomes. This state-of-the-art review aims to discuss the available types of perfusion techniques, its potential benefits and the available evidence in kidney, liver and pancreas transplantation. Additionally, translational steps from animal models towards clinical studies will be described, as well as its application to clinical practice, with the focus on the Netherlands. Despite the lack of evidence from randomized controlled trials, currently available data suggest especially beneficial effects of normothermic regional perfusion on biliary complications and ischemic cholangiopathy after liver transplantation. For ex vivo machine perfusion in kidney transplantation, hypothermic machine perfusion has proven to be beneficial over static cold storage in a randomized controlled trial, while normothermic machine perfusion is currently under investigation. For ex vivo machine perfusion in liver transplantation, normothermic machine perfusion has proven to reduce discard rates and early allograft dysfunction. In response to clinical studies, hypothermic machine perfusion for deceased donor kidneys has already been implemented as standard of care in the Netherlands.

Survey of Patient's Experience of Altruistic Nondirected Kidney Donation.

The scarcity of organs for donation is an ongoing issue. Change in legislative framework allows for altruistic donations in the UK, but, whereas the number of donations from deceased donors has increased, there has been a slow decline in altruistic living donors. The aim of this study was to review perspectives of altruistic nondirected kidney donors (ANDKD) at our center and outcome of all enquiries to inform service improvement and increase the numbers of donors. All enquiries by potential ANDKD at our center from September 2005 to September 2017 were analyzed. Donor assessment was performed as per the UK Guidelines, prior to obtaining Human Tissue Authority approval. The outcome of donation and results of questionnaires sent to 50 ANDKD were analyzed. During the period, 51 of the 180 enquiries (28.3%) resulted in kidney donation. Questionnaire responses were: 66% donors were retired; most heard about altruistic donation through media (60%); 72% thought psychological or psychiatric assessment was necessary; 95% found the information provided prior to donation adequate; 82% rated their overall experience as good/excellent; and 90% would recommend kidney donation to others. Thirteen of 50 donated kidneys were fed into the kidney exchange program. The mean ± standard error of the mean of the duration from human tissue authority approval to donation were 60.4 ± 5.4 and 131.2 ± 11.2 days, respectively (P = 0.00001). A significant proportion of enquiries for altruistic donation would result in donation but the assessment process needs to be quicker. ANDKD is useful way of priming the National Living Donor Kidney Sharing Scheme.

Survival Benefit of Heart Transplant Varies by Center

The allocation of donor hearts has long been controversial because of organ scarcity and the vulnerability of the U.S. allocation system to gaming, due