Preservation methods for kidney and liver

With the successful testing of the immunosuppressive effects of cyclosporine in transplant patients in 1978, the field of organ transplants began an exponential growth. With that, the field of organ preservation became increasingly important as the need to increase preservation time and improve graft function became paramount. However, for every patient that receives a transplanted organ, there are four more on the waiting list. In addition, a patient dies from the lack of a transplant almost every 1½ hour. To alleviate this donor crisis, there is a need to expand the donor pool to marginal donor organs. The main reason these organs are underutilized is because the current method of static preservation, simple cold storage, is ineffective. This article will provide a general review of the methods of preservation including simple cold storage, hypothermic machine perfusion, normothermic machine perfusion, and oxygen persufflation. In addition, the article will provide a review of how these dynamic preservation methods have improved the recovery and preservation of marginal donor organs including Donation after Cardiac Death and Fatty livers.     

INDUCTIVE RISK AND JUSTICE IN KIDNEY ALLOCATION

How should UNOS deal with the presence of scientific controversies on the risk factors for organ rejection when designing its allocation policies? The answer I defend in this paper is that the more undesirable the consequences of making a mistake in accepting a scientific hypothesis, the higher the degree of confirmation required for its acceptance. I argue that the application of this principle should lead to the rejection of the hypothesis that ‘less than perfect’ Human Leucocyte Antigen (HLA) matches are an important determinant of kidney graft survival. The scientific community has been divided all along on the significance of partial antigen matches. Yet reliance on partial matches has emerged as one of the primary factors leading blacks to spend a much longer time than whites on the waiting list for kidneys, thereby potentially impacting the justice of the kidney allocation policy. My case study illustrates one of the legitimate roles non‐epistemic values can play in science and calls into question the ideal of a value‐free science.     

Preservation methods for kidney and liver

With the successful testing of the immunosuppressive effects of cyclosporine in transplant patients in 1978, the field of organ transplants began an exponential growth. With that, the field of organ preservation became increasingly important as the need to increase preservation time and improve graft function became paramount. However, for every patient that receives a transplanted organ, there are 4 more on the waiting list. In addition, a patient dies from the lack of a transplant almost every 1½ hour. To alleviate this donor crisis, there is a need to expand the donor pool to marginal donor organs. The main reason these organs are underutilized is because the current method of static preservation, simple cold storage, is ineffective. This article will provide a general review of the methods of preservation including simple cold storage, hypothermic machine perfusion, normothermic machine perfusion, and oxygen persufflation. In addition, the article will provide a review of how these dynamic preservation methods have improved the recovery and preservation of marginal donor organs including donation after cardiac death and fatty livers.     

Access to adult liver transplantation in Canada: a survey and ethical analysis.

OBJECTIVES: To describe the substantive and procedural criteria used for placing patients on the waiting list for liver transplantation and for allocating available livers to patients on the waiting list; to identify principal decision-makers and the main factors limiting liver transplantation in Canada; and to examine how closely cadaveric liver allocation resembles theoretic models of source allocation. DESIGN: Mailed survey. PARTICIPANTS: Medical directors of all seven Canadian adult liver transplantation centres, or their designates. Six of the questionnaires were completed. OUTCOME MEASURES: Relative importance of substantive and procedural criteria used to place patients in the waiting list for liver transplantation and to allocate available livers. Identification of principal decision-makers and main limiting factors to adult liver transplantation. RESULTS: Alcoholism, drug addiction, HIV positivity, primary liver cancer, noncompliance and hepatitis B were the most important criteria that had a negative influence on decisions to place patients on the waiting list for liver transplantation. Severity of disease and urgency were the most important criteria used for selecting patients on the waiting list for transplantation. Criteria that were inconsistent across the centres included social support (for deciding who is placed on the waiting list) and length of time on the waiting list (for deciding who is selected from the list). Although a variety of people were reported as being involved in these decisions, virtually all were reported to be health to be health care professionals. Thirty-seven patients died while waiting for liver transplantation in 1991; the scarcity of cadaveric livers was the main limiting factor. CONCLUSIONS: Criteria for resource allocation decisions regarding liver transplantation are generally consistent among the centres across Canada, although some important inconsistencies remain. Because patients die while on the waiting list and because the primary limiting factor is organ supply, increased organ acquisition efforts are needed.     

THE DEAD DONOR RULE,VOLUNTARY ACTIVE EUTHANASIA,AND CAPITAL PUNISHMENT

We argue that the dead donor rule, which states that multiple vital organs should only be taken from dead patients, is justified neither in principle nor in practice. We use a thought experiment and a guiding assumption in the literature about the justification of moral principles to undermine the theoretical justification for the rule. We then offer two real world analogues to this thought experiment, voluntary active euthanasia and capital punishment, and argue that the moral permissibility of terminating any patient through the removal of vital organs cannot turn on whether or not the practice violates the dead donor rule. Next, we consider practical justifications for the dead donor rule. Specifically, we consider whether there are compelling reasons to promulgate the rule even though its corresponding moral principle is not theoretically justified. We argue that there are no such reasons. In fact, we argue that promulgating the rule may actually decrease public trust in organ procurement procedures and medical institutions generally – even in states that do not permit capital punishment or voluntary active euthanasia. Finally, we examine our case against the dead donor rule in the light of common arguments for it. We find that these arguments are often misplaced – they do not support the dead donor rule. Instead, they support the quite different rule that patients should not be killed for their vital organs.     

Optimal Decisions for Organ Exchanges in a Kidney Paired Donation Program

The traditional concept of barter exchange in economics has been extended in the modern era to the area of living-donor kidney transplantation, where one incompatible donor-candidate pair is matched to another pair with a complementary incompatibility, such that the donor from one pair gives an organ to a compatible candidate in the other pair and vice versa. Kidney paired donation (KPD) programs provide a unique and important platform for living incompatible donor-candidate pairs to exchange organs in order to achieve mutual benefit. In this paper, we propose novel organ allocation strategies to arrange kidney exchanges under uncertainties with advantages, including (i) allowance for a general utility-based evaluation of potential kidney transplants and an explicit consideration of stochastic features inherent in a KPD program; and (ii) exploitation of possible alternative exchanges when the originally planned allocation cannot be fully executed. This allocation strategy is implemented using an integer programming (IP) formulation, and its implication is assessed via a data-based simulation system by tracking an evolving KPD program over a series of match runs. Extensive simulation studies are provided to illustrate our proposed approach.     

多功能植物区系名录管理系统

本文探讨了计算机技术在植物区系名录管理中的应用,分析该系统的创建与编程原理。植物区系名录管理系统（ＦｌｏｒａＬｉｓｔＭａｎａｇｅｍｅｎｔＳｙｓｔｅｍ）以下简称ＦＬＭＳ。ＦＬＭＳ在ＩＢＭ及其兼容系列机上通过,它能提供植物区系名录的查询、统计、补充、修改、打印、数据通讯等服务     

Computational Eurotransplant kidney allocation simulations demonstrate the feasibility and benefit of T-cell epitope matching

The EuroTransplant Kidney Allocation System (ETKAS) aims at allocating organs to patients on the waiting list fairly whilst optimizing HLA match grades. ETKAS currently considers the number of HLA-A, -B, -DR mismatches. Evidently, epitope matching is biologically and clinically more relevant. We here executed ETKAS-based computer simulations to evaluate the impact of epitope matching on allocation and compared the strategies. A virtual population of 400,000 individuals was generated using the National Marrow Donor Program (NMDP) haplotype frequency dataset of 2011. Using this population, a waiting list of 10,400 patients was constructed and maintained during simulation, matching the 2015 Eurotransplant Annual Report characteristics. Unacceptable antigens were assigned randomly relative to their frequency using HLAMatchmaker. Over 22,600 kidneys were allocated in 10 years in triplicate using Markov Chain Monte Carlo simulations on 32-CPU-core cloud-computing instances. T-cell epitopes were calculated using the www.pirche.com portal. Waiting list effects were evaluated against ETKAS for five epitope matching scenarios. Baseline simulations of ETKAS slightly overestimated reported average HLA match grades. The best balanced scenario maintained prioritisation of HLA A-B-DR fully matched donors while replacing the HLA match grade by PIRCHE-II score and exchanging the HLA mismatch probability (MMP) by epitope MMP. This setup showed no considerable impact on kidney exchange rates and waiting time. PIRCHE-II scores improved, whereas the average HLA match grade diminishes slightly, yet leading to an improved estimated graft survival. We conclude that epitope-based matching in deceased donor kidney allocation is feasible while maintaining equal balances on the waiting list.     

THE ONGOING CHARITY OF ORGAN DONATION. CONTEMPORARY ENGLISH SUNNI FATWAS ON ORGAN DONATION AND BLOOD TRANSFUSION

Background: Empirical studies in Muslim communities on organ donation and blood transfusion show that Muslim counsellors play an important role in the decision process. Despite the emerging importance of online English Sunni fatwas, these fatwas on organ donation and blood transfusion have hardly been studied, thus creating a gap in our knowledge of contemporary Islamic views on the subject. Method: We analysed 70 English Sunni e‐fatwas and subjected them to an in‐depth text analysis in order to reveal the key concepts in the Islamic ethical framework regarding organ donation and blood transfusion. Results: All 70 fatwas allow for organ donation and blood transfusion. Autotransplantation is no problem at all if done for medical reasons. Allotransplantation, both from a living and a dead donor, appears to be possible though only in quite restricted ways. Xenotransplantation is less often mentioned but can be allowed in case of necessity. Transplantation in general is seen as an ongoing form of charity. Nearly half of the fatwas allowing blood transfusion do so without mentioning any restriction or problem whatsoever. The other half of the fatwas on transfusion contain the same conditional approval as found in the arguments pro organ transplantation. Conclusion: Our findings are very much in line with the international literature on the subject. We found two new elements: debates on the definition of the moment of death are hardly mentioned in the English Sunni fatwas and organ donation and blood transfusion are presented as an ongoing form of charity.     

Justice for children: the child as organ donor

I argue that parents ought to be allowed to authorize their child's participation as an organ donor for another family member. I introduce a model of decisionmaking for children in intimate families which I call Constrained Parental Autonomy. This model permits wide parental discretion which is constrained absolutely by a broadly defined principle of respect for persons. In general, parental authorization alone is sufficient but I argue that the respect for persons constraint prevents certain donations and requires the child's assent for other donations. I also consider two controversial implications of the application of this model: the objection that the model does not respect the child's right to bodily integrity, and the objection that the model does not and is unable to address intrafamilial disgreement.     

Opt‐in or opt‐out to increase organ donation in South Africa? Appraising proposed strategies using an empirical ethics analysis

Utilising empirical ethics analysis, we evaluate the merits of systems proposed to increase deceased organ donation in South Africa (SA). We conclude that SA should maintain its soft opt‐in policy, and enhance it with ‘required transplant referral’ in order to maximise donor numbers within an ethically and legally acceptable framework. In SA, as is the case worldwide, the demand for donor organs far exceeds the supply thereof. Currently utilising a soft opt‐in system, SA faces the challenge of how to increase donor numbers in a context which is imbued with inequalities in access to healthcare, multiplicitous personal beliefs and practices, distrust of organ transplant and varying levels of education and health literacy. We argue that a hard opt‐in, opt‐out or mandated consent system would be problematic, and we present empirical data from Gauteng Province illustrating barriers to ethically sound practice in soft consent systems. Ultimately, we argue that in spite of some limitations, a soft opt‐in system is most realistic for SA because its implementation does not require extensive public education campaigns at national level, and it does not threaten to further erode trust at a clinical level. However, to circumvent some of the clinical‐level barriers identified in our empirical study, we propose a contextually sensitive option for “enabling” soft opt‐in through “required transplant referral”. We argue that this system is legally defensible, enhances ethical practice and could also increase donor numbers as it has in many other countries.     

Organ Donation: Who Should Decide?—A Canadian Perspective

This paper examines an under-explored issue in organ donation: whose decision making authority should be privileged posthumously in the context of known, explicit consent for donation? Current practices in Canada support the family as the ultimate decision maker, despite the existence of legislative support in many Canadian provinces for the potential donor as legitimate decision maker. Arguments for and against privileging the family and the potential donor are identified. Informing the question of “who should decide” are considerations of individual and relational autonomy, distributive and social justice, personhood, and arguments “from distress”. Tensions and competing obligations emerge from an exploration of these considerations that call for further, inclusive dialogue and deliberation on this important organ donation issue.     

Waiting list for kidney transplant. Some patients wait too long.

The selection of a kidney graft recipient should be made not only taking into account biological and clinical parameters, for assuring the maximum possible clinical success; the ethical objective to allow every patient equal opportunity of receiving a transplant should also be pursued. In every waiting list of transplant candidates a proportion of patients remains in the list for a particularly long time. The present analysis aimed to find out the factors associated with a prolonged waiting time, in order to allow the implementation of patient selection criteria able to balance unfavourable factors. The analysis of the waiting list of our kidney transplant centre allowed to observe that blood group 0, anti-HLA immunisation, presence of rare HLA antigens and, at a lesser extent, HLA homozygosity are associated with a longer waiting time for a kidney transplant.     

Technique of Subnormothermic Ex Vivo Liver Perfusion for the Storage,Assessment, and Repair of Marginal Liver Grafts

The success of liver transplantation has resulted in a dramatic organ shortage. In most transplant regions 20-30% of patients on the waiting list for liver transplantation die without receiving an organ transplant or are delisted for disease progression. One strategy to increase the donor pool is the utilization of marginal grafts, such as fatty livers, grafts from older donors, or donation after cardiac death (DCD). The current preservation technique of cold static storage is only poorly tolerated by marginal livers resulting in significant organ damage. In addition, cold static organ storage does not allow graft assessment or repair prior to transplantation.These shortcomings of cold static preservation have triggered an interest in warm perfused organ preservation to reduce cold ischemic injury, assess liver grafts during preservation, and explore the opportunity to repair marginal livers prior to transplantation. The optimal pressure and flow conditions, perfusion temperature, composition of the perfusion solution and the need for an oxygen carrier has been controversial in the past.In spite of promising results in several animal studies, the complexity and the costs have prevented a broader clinical application so far. Recently, with enhanced technology and a better understanding of liver physiology during ex vivo perfusion the outcome of warm liver perfusion has improved and consistently good results can be achieved.This paper will provide information about liver retrieval, storage techniques, and isolated liver perfusion in pigs. We will illustrate a) the requirements to ensure sufficient oxygen supply to the organ, b) technical considerations about the perfusion machine and the perfusion solution, and c) biochemical aspects of isolated organs.     

Organ transplantation in Bulgaria

The transplantation program in Bulgaria started in 1968 with renal transplantations to a child and adult woman. In 1986 the first heart transplantation was performed. To date a total of 10 heart transplants have been performed, including one combined heart/lung. A liver transplantation program was launched in 2005 with a total number of 16 transplantations—7 from living donors and 9 from deceased donors. The highest transplantation activity is registered in the field of renal transplantation. During the period 1980–2006, 462 Bulgarian recipients of kidney were transplanted in Bulgaria. The ratio between transplantations from deceased and living related donors is approximately 1:0.9. Annual transplantation activity varies among the years from 1 to 12 renal transplantations p.m.p./per year. The 1- (80.7% vs. 63.1%), 5- (57.86% vs. 39.0%) and 10-year (42.65% vs. 23.62%) graft survival rates are higher for recipients of living donor kidneys compared to those of deceased donor. In 1983 a National kidney waiting list was established. Currently the number of the registered patients eligible for renal transplantation is 885. The proportion of sensitized patients in the waiting list is 20.45% and 4.34% of them are hyperimmunized. Recently HLAMatchmaker program has been implemented not only for sensitized patients but also for those with rare alleles and haplotypes. Post-transplant immunological monitoring showed a strong association between alloantibody presence and delayed graft function (Chi-square = 10.73, P < 0.001), acute rejection (Chi-square = 14.504, P < 0.001), chronic rejection (Chi-square = 12.84, P < 0.001) and graft loss (Chi-square = 20.283, P < 0.001). Based on the experience in our transplant center a strategy for improvement of long-term renal graft survival was developed and implemented.     

Heart transplantation in the Netherlands: quo vadis?

Heart transplantation is limited by the lack of donor organs. Twenty years after the start of the Dutch transplant programmes in Rotterdam and Utrecht the situation has even worsened, despite efforts to increase the donor pool. The Dutch situation seems to be worse than in other surrounding countries, and several factors that may influence donor organ availability and organ utilisation are discussed. The indications and contraindications for heart transplantation are presented, which are rather restrictive in order to select optimal recipients for the scarce donor hearts. Detailed data on donor hearts, rejected for transplantation, are shown to give some insight into the difficult process of dealing with marginal donor organs. It is concluded that with the current low numbers of acceptable quality donor hearts, there is no lack of capacity in the two transplanting centres nor is the waiting list limiting the number of transplants. The influence of our current legal system on organ donation, which requires (prior) permission from donor and relatives, is probably limited. The most important determinants of donor organ availability are: 1. The potential donor pool, consisting of brain dead victims of (traffic) accidents and CVAs and 2. Lack of consent to a request for donation. The potential donor pool is remarkably small in the Netherlands, due to relatively low numbers of (traffic) accidents, with an almost equal number of CVA-related brain dead patients compared with neighbouring countries. Lack of consent can only be pushed back by improved public awareness of the importance of donation and improved skills of professionals in asking permission in case there is no previous consent.     

Influencing relatives to respect donor autonomy: Should we nudge families to consent to organ donation?

Refusing consent to organ donation remains unacceptably high, and improving consent rates from family or next‐of‐kin is an important step to procuring more organs for solid organ transplantation in countries where this approval is sought. We have thus far failed to translate fully our limited understanding of why families refuse permission into successful strategies targeting consent in the setting of deceased organ donation, primarily because our interventions fail to target underlying cognitive obstacles. Novel interventions to overcome these hurdles, incorporating an understanding of cognitive psychology and behavioral change therapy, may be beneficial. One potential intervention is to use the concept of nudge theory, where decision‐making is influenced by encouraging positive reinforcement and indirect suggestion. Purposefully nudging families to given consent for organ donation by understanding, and then overcoming, their inherent cognitive biases is novel but also controversial. This article explores the roles of relatives in decisions about organ donation, how nudge theory translates to organ donation and discusses the arguments for and against its application.     

Permanence can be Defended

In donation after the circulatory‐respiratory determination of death (DCDD), the dead donor rule requires that the donor be dead before organ procurement can proceed. Under the relevant limb of the Uniform Determination of Death Act 1981 (USA), a person is dead when the cessation of circulatory‐respiratory function is ‘irreversible’. Critics of current practice in DCDD have argued that the donor is not dead at the time organs are procured, and so the procurement of organs from these donors violates the dead donor rule. We offer a new argument here in defence of current DCDD practice, and, in particular, of the interpretation of the requirement of ‘irreversibility’ as permanence.     

How effective are cognitive behavior therapies for major depression and anxiety disorders? A meta‐analytic update of the evidence

We report the current best estimate of the effects of cognitive behavior therapy (CBT) in the treatment of major depression (MDD), generalized anxiety disorder (GAD), panic disorder (PAD) and social anxiety disorder (SAD), taking into account publication bias, the quality of trials, and the influence of waiting list control groups on the outcomes. In our meta‐analyses, we included randomized trials comparing CBT with a control condition (waiting list, care‐as‐usual or pill placebo) in the acute treatment of MDD, GAD, PAD or SAD, diagnosed on the basis of a structured interview. We found that the overall effects in the 144 included trials (184 comparisons) for all four disorders were large, ranging from g=0.75 for MDD to g=0.80 for GAD, g=0.81 for PAD, and g=0.88 for SAD. Publication bias mostly affected the outcomes of CBT in GAD (adjusted g=0.59) and MDD (adjusted g=0.65), but not those in PAD and SAD. Only 17.4% of the included trials were considered to be high‐quality, and this mostly affected the outcomes for PAD (g=0.61) and SAD (g=0.76). More than 80% of trials in anxiety disorders used waiting list control groups, and the few studies using other control groups pointed at much smaller effect sizes for CBT. We conclude that CBT is probably effective in the treatment of MDD, GAD, PAD and SAD; that the effects are large when the control condition is waiting list, but small to moderate when it is care‐as‐usual or pill placebo; and that, because of the small number of high‐quality trials, these effects are still uncertain and should be considered with caution.     

Self‐ownership,relational dignity,and organ sales

Material property has traditionally been conceived of as separable from its owner and thus alienable in an exchange. So it seems that you could sell your watch or even your kidney because it can be removed from your wrist or abdomen and transferred to another. However, if we are each identical to a living human animal, self‐ownership is impossible for self‐separation is impossible. We thus cannot sell our parts if we don't own the whole that they compose. It would be incoherent to own all of your body's parts but not the whole body; and it would be arbitrary to own some but not all of your removable parts. These metaphysical obstacles to organ sales do not apply to the selling of the organs of the deceased. The human being goes out of existence at death and is not identical to the body's remains. Any objections to selling the organs of the deceased must instead be due to dignity rather than metaphysical or conceptual considerations. But the remains lack the intrinsic dignity of the human being, instead possessing, at best, relational dignity. Relational dignity would not provide sufficient reason to prohibit life‐saving sales.