Impact of Back-to-Base Normothermic Machine Perfusion on Complications and Costs: A Multicenter, Real-World Risk-Matched Analysis.

OBJECTIVE: Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). BACKGROUND: End-ischemic NMP is often used to aid logistics, yet its impact on outcomes after LT remains unclear, as does its true impact on costs associated with transplantation. METHODS: Deceased donor liver recipients at 2 centers (January 1, 2019, to June 30, 2023) were included. Retransplants, splits, and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra) was implemented in October 2022 for extended-criteria donation after brain death (DBDs), all donations after circulatory deaths (DCDs), and logistics. NMP cases were matched 1:2 with static cold storage controls (SCS) using the Balance-of-Risk [donation after brain death (DBD)-grafts] and UK-DCD Score (DCD-grafts). RESULTS: Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day comprehensive complications index (27.6 vs 41.9, P =0.028). NMP also reduced the need for early relaparotomy and renal replacement therapy, with subsequently less frequent major complications (Clavien-Dindo ≥IVa). This effect was more pronounced in DCD transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pretransplant costs in the context of shorter waiting list times. Overall costs were comparable for both cohorts. CONCLUSIONS: This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD grafts, and overall complications and post-LT renal replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day health care costs-per-transplantation were comparable.

Combination of Euro-Collins and University of Wisconsin Solution: An Effective and Economic Substitute for Organ Procurement.

PURPOSE: Many types of preservation fluid were used in liver procurement. Undoubtedly, the gold standard is the University of Wisconsin (UW) solution. But the solution is expensive. The aim of this study was to evaluate the results of combined acetated Ringer solution, Euro-Collins solution, and UW solution. MATERIALS AND METHODS: All patients undergoing adult liver transplantation from cadaveric donor during January 2013 to December 2017 in King Chulalongkorn Memorial Hospital were included in this study. Donor and recipient characteristics, preservation fluid, operative data, and postoperative outcomes were recorded. RESULTS: A total of 102 patients receiving liver transplants were enrolled into the study. The mean age of donors was 34.2 years. The mean total ischemic time was 420.93 minutes. In recipients, posttransplantation complications were the following: (1) primary nonfunction in 1 patient (0.98%); (2) early allograft dysfunction in 23 patients (22.5%); (3) hepatic artery thrombosis in 3 patients (2.7%); (4) hepatic venous outflow obstruction in 2 patients (1.96%); (5) biliary leakage in 1 patient (0.98%); (6) biliary anastomosis stenosis in 4 patients (3.92%); and (7) biliary nonanastomosis stenosis in 1 patient (0.98%). No inhospital mortality was occurred. Overall mortality rate is 7.8% (8/102). One-, 3-, and 5-year survival were 95.9%, 91.5%, and 88.4%, respectively. CONCLUSIONS: The combination of acetated Ringer solution, Euro-Collins solution, and UW solution is effective and economic for liver preservation. Further study should be conducted.

A Cost-Effectiveness Analysis of Organ Preservation Methods for Deceased Donor Kidneys at High Risk for Delayed Graft Function in Brazil.

The clinical benefit of machine perfusion (MP) was recently assessed in a 1-year Brazilian multicenter prospective randomized trial, that showed that the use of MP was associated with a reduced incidence of delayed graft function (DGF) compared to static cold storage (SCS) in kidney transplant recipients (45% vs 61%). The objective of the present analysis is to consider the cost-effectiveness of MP relative to SCS based on clinical data from this Brazilian cohort. A decision tree model was constructed to simulate a population of 1000 kidney transplant recipients based on data derived from this Brazilian multicenter clinical trial. The model accounts for different health state utilities to estimate the cost-effectiveness of deceased donor kidney transplantation in Brazil comparing 2 kidney preservation methods: MP and SCS. The model accounts for 3 possible graft outcomes at 1 year post-transplantation: success (an immediate functioning kidney), failure (primary nonfunction requiring a return to dialysis), or DGF 1 year post-transplant. MP provided 612 total quality-adjusted life years (QALYs) (0.61 QALYs per patient) as compared to SCS (553 total QALYs, 0.55 QALYs per patient). MP was cost effective relative to SCS (US$22,117/QALY, R$70,606/QALY). The use of MP also resulted in more functioning grafts than SCS (821 vs 787), leading to a cost per functioning graft of US$38,033 (R$121,417). In conclusion, this analysis indicates that, despite the initial added cost associated with MP, the use of MP results in more functioning grafts (821 vs 787) and higher patient quality of life relative to SCS in Brazil.

Social, economic, and policy implications of organ preservation advances.

PURPOSE OF REVIEW: Despite over 60 years of progress in the field of since the first organ transplant, insufficient organ preservation capabilities still place profound constraints on transplantation. These constraints play multiple and compounding roles in the predominant limitations of the field: the severe shortages of transplant organs, short-term and long-term posttransplant outcomes and complications, the unmet global need for development of transplant infrastructures, and economic burdens that limit patient access to transplantation and contribute to increasing global healthcare costs. This review surveys ways that advancing preservation technologies can play a role in each of these areas, ultimately benefiting thousands if not millions of patients worldwide. RECENT FINDINGS: Preservation advances can create a wide range of benefits across many facets of organ transplantation, as well as related areas of transplant research. As these technologies mature, so will the policies around their use to maximize the benefits offered by organ preservation. SUMMARY: Organ preservation advances stand to increase local and global access to transplantation, improve transplant outcomes, and accelerate progress in related areas such as immune tolerance induction and xenotransplantation. This area holds the potential to save the healthcare system many billions of dollars and reduce costs across many aspects of transplantation. Novel preservation technologies, along with other technologies facilitated by preservation advances, could potentially save millions of lives in the coming years.

Explotación y bioética. Ética individual y regulación jurídica / Exploitation and bioethics. Individual ethics and legal regulation

En este artículo discuto los contratos o transacciones explotativas en bioética. El caso más problemático teóricamente parece ser el de lo que Allan Wertheimer llama explotación «mutuamente ventajosa»: el consentimiento de la parte débil (D) para realizar la transacción es un consentimiento efectivo y racional. Además, D no sufre un daño mediante la transacción, sino que, por el contrario, esta transacción lo beneficia en comparación con no realizar la transacción. Mi objetivo en este trabajo es, por un lado, presentar, desde el punto de vista de la ética individual, un modelo para pensar la naturaleza de la incorrección que podemos asignarle a la conducta de la parte fuerte al contratar con D en forma explotativa. En segundo lugar, ofrezco algunas razones por las cuales, en el plano de la ética jurídica, la prohibición jurídica de este tipo de conductas explotativas es problemática y sólo podría ser justificada en casos muy excepcionales

In this paper, I discuss exploitative transactions in bioethics. The most problematic case is what Allan Wertheimer calls «mutually advantageous» exploitation: the weak party’s (W’s) consent for the transaction is an effective and rational consent. Moreover, W does not suffer any harm by the transaction; on the contrary, the transaction benefits W. My aim in this paper is twofold. From the perspective of individual ethics, I offer a model to conceive the nature of the wrongfulness of strong party’s action. From the perspective of legal ethics, I suggest some reasons to believe that the prohibition of beneficial, exploitative, contracts is problematic and can only be justified in very exceptional cases

Survival extrapolation using the poly-Weibull model.

Recent studies of (cost-) effectiveness in cardiothoracic transplantation have required estimation of mean survival over the lifetime of the recipients. In order to calculate mean survival, the complete survivor curve is required but is often not fully observed, so that survival extrapolation is necessary. After transplantation, the hazard function is bathtub-shaped, reflecting latent competing risks which operate additively in overlapping time periods. The poly-Weibull distribution is a flexible parametric model that may be used to extrapolate survival and has a natural competing risks interpretation. In addition, treatment effects and subgroups can be modelled separately for each component of risk. We describe the model and develop inference procedures using freely available software. The methods are applied to two problems from cardiothoracic transplantation.

Economic impact of the introduction of machine perfusion preservation in a kidney transplantation program in the expanded donor era: cost-effectiveness assessment.

BACKGROUND: Kidney transplantations (KT) from expanded criteria donors (ECD) show a higher rate of delayed graft function (DGF) that increases postoperative costs because of the prolonged hospital stay as well as the needs for dialysis and additional diagnostic procedures. Hypothermic machine perfusion (MP) might be superior to cold storage (CS) to reduce the relative risks of DGF and primary nonfunction (PNF) as well as to increase 1-year graft survival. OBJECTIVE: The aim of the study was to determine the relative cost-effectiveness of two different storage methods: MP versus CS. METHODS: A probabilistic decision tree was developed to compare MP and CS as graft preservation methods. The structure of the model was populated by review of the literature and outcomes of KT from ECD in our center. The model estimated budget impact and incremental cost-effectiveness ratio in terms of DGF and PNF cases. The cost comparison of methods for KT preservation included: hospitalization and intermediate care unit stay; post-KT dialysis; graft removal; immunosuppressive regimen; treatment of acute rejection episodes; as well as costs of preservation solutions and pulsatile preservation device or storage containers. RESULTS: Resource consumption for CS stratified by graft function varied from $8,159 for immediate graft function (IGF) recipients to $10,865 for DGF recipients to $25,933 for PNF recipients. Meanwhile, resource consumption for MP varied from $9,522 for IGF to $12,228 for DGF to $27,297 for PNF recipients. The main components of resource consumption were hospitalization stay (41.5%-53.9%); graft explantation (20.2%), and the need for dialysis (16.0%). The budget impact per patient for the introduction of MP was $505. However, the incremental cost-effectiveness ratio was $3,369 for each DGF- or PNF- saved case. CONCLUSIONS: The introduction of the MP preservation technology in a KT program form ECD is cost-effective in terms of savings for DGF and PNF cases.

Cost-effectiveness of hypothermic machine preservation versus static cold storage in renal transplantation.

Static cold storage (CS) is the most widely used organ preservation method for deceased donor kidney grafts but there is increasing evidence that hypothermic machine perfusion (MP) may result in better outcome after transplantation. We performed an economic evaluation of MP versus CS alongside a multicenter RCT investigating short- and long-term cost-effectiveness. Three hundred thirty-six consecutive kidney pairs were included, one of which was assigned to MP and one to CS. The economic evaluation combined the short-term results based on the empirical data from the study with a Markov model with a 10-year time horizon. Direct medical costs of hospital stay, dialysis treatment, and complications were included. Data regarding long-term survival, quality of life, and long-term costs were derived from literature. The short-term evaluation showed that MP reduced the risk of delayed graft function and graft failure at lower costs than CS. The Markov model revealed cost savings of $86,750 per life-year gained in favor of MP. The corresponding incremental cost-utility ratio was minus $496,223 per quality-adjusted life-year (QALY) gained. We conclude that life-years and QALYs can be gained while reducing costs at the same time, when kidneys are preserved by MP instead of CS.

A newly developed container for safe, easy, and cost-effective overnight transportation of tissues and organs by electrically keeping tissue or organ temperature at 3 to 6°C.

BACKGROUND: As there is only one skin procurement organization in Japan the Japan Skin Bank Network (JSBN), all skin grafts procured in Japan are sent by a commercialized delivery system. Preliminarily, bottles containing saline were transported in a cardboard box using a so-called "cooled home delivery service" using a truck with a refrigerated cargo container. During transportation the temperature in the cardboard box increased to 18°C in summer and decreased to -5°C in winter. For these reasons, we investigated whether a newly developed container "Medi Cube" would be useful to transport skin grafts. OBJECTIVES: Four bottles with a capacity of 300 mL containing 150 mL of saline in a Medi Cube container were transported from Osaka to the JSBN in Tokyo between 4 PM and 10 AM using a commercialized cooled home delivery service. Two bottles were transported in a Medi Cube container without phase change materials (PCM) in winter and summer, respectively. Another two bottles were transported in the Medi Cube with PCMs in winter. The temperatures inside saline, inside a transportation container, and outside the container, and air temperature were monitored continuously with a recordable thermometer. RESULTS: The temperatures inside saline and inside a Medi Cube container were maintained between 3 and 6°C, even when the temperature outside the container increased during parking. The temperature inside a Medi Cube container without PCM decreased to -3°C when the inside of the cargo container was overcooled in winter. However, the temperatures inside saline and inside a Medi Cube container with PCM were between 3 and 6°C, even when the temperature outside the container decreased to below 0°C in winter. CONCLUSION: A Medi Cube container with PCM provided a safe, easy, and cost-effective method for overnight transportation of skin grafts.

Simple novel bone bank storage: the Singapore General Hospital experience.

INTRODUCTION: Since 1981, the Singapore General Hospital (SGH) bone bank has proven to be a safe, reliable, and economical source of bone allografts. Femoral heads are used exclusively and are procured from patients undergoing hip arthroplasty. Screening for HIV, hepatitis B, and hepatitis C is carried out prior to surgery. Patients with ongoing infection and past history of malignancy are excluded. The bone graft procured is washed and autoclaved to 134°C for 3 minutes. It is then stored in saline solution containing penicillin and streptomycin at -80°C. Based on our experience, such a system can be readily duplicated in developing nations with minimal cost and equipment. This article presents our experience in the procurement and storage of femoral head allografts with clinical results to support the safety profile. METHODS: Ten femoral heads were harvested from patients who underwent hip arthroplasty. The femoral heads were autoclaved and stored at -80°C in an antibiotic solution. Bone chips were sent for culture immediately after autoclaving and at 3 and 6 months. RESULTS: All specimens passed the initial sterility testing and remained sterile up to 6 months. A retrospective study of 9 patients who had 13 allografts implanted between 2008 and 2010 showed that none of the recipients acquired an infection or transmissible disease due to the allografts. CONCLUSION: This study showed that our protocol allows for procurement of femoral head allografts with minimal contamination and that they can maintain sterility for up to 6 months. This finding is further supported by our clinical results. Hence, this protocol will be useful for bone banks in developing nations where sterility conditions are suboptimal and cost is an issue.

The cost-effectiveness of organ preservation methods in renal transplantation: US projections based on the machine preservation trial.

INTRODUCTION: The European Machine Preservation Trial (MPT) found a significantly lower rate of delayed graft function and improved graft survival in machine-perfused kidneys compared to cold-stored kidneys in the first year following kidney transplantation. Little is known about the cost-effectiveness of various organ preservation methods. METHODS: Outcome data from the MPT have been used to conduct a comparative cost-effectiveness analysis based on preservation method for both standard criteria (SCD) and expanded criteria donor (ECD) kidney transplants in the United States. Using graft survival as the primary outcome measure, a cost-effectiveness model was developed using Medicare and private payer cost/payment data, as well as clinical transition probabilities based on the MPT and other studies. RESULTS: At 1-year posttransplant, machine perfusion is a more cost-effective option than cold storage for organ preservation in transplants involving either SCD ($92,561 vs $104,118) or ECD ($106,012 vs $114,530) kidneys. Moreover, the cost-effectiveness ratios for transplants involving machine-perfused ECD kidneys ($106,012) are similar to those for transplants using cold-stored SCD kidneys ($104,118). CONCLUSION: Machine perfusion is preferable to cold storage for organ preservation in both SCD and ECD donor kidney transplants. Not only is it more cost-effective, but from all relevant perspectives it adds substantial value.

Long term medical and economical benefit of machine perfusion (MP) kidney storage in comparison to cold storage (CS).

BACKGROUND: Despite documented positive effect of MachinePerfusion (MP) on long-term kidneys-graft function its wide use is restricted due to higher costs. The aim of this study was to analyze the difference in costs of kidney transplantation in patients who received organ stored in ColdStorage (CS) vs those who received kidneys stored with MP.
MATERIAL/METHODS: Analysis was done on kidney transplantations performed between 1994-1999 in 415 patients.. Kidneys were not randomized to MP or to CS: 188 kidneys were stored in CS, 227-in MP. Recipients didn't differ in regard to the age, sex, PRA, HLA mismatch, and immunosupression.The costs of organ procurement,transportation,surgical and anesthetic procedures, episodes of acute rejection were similar for both group of patients and were not included into the analysis. Costs of first month post-transplantation included: the cost of MP, post-transplantation hemodialysis, costs of hospitalization.Analysis of costs difference in between two groups of patients during follow-up included the costs of immunosupression and the monthly cost of dialysis. Statistical analysis was done using linear regression model.
RESULTS: Long graft survival was 68,2% in MP group vs.54,2% in CS group (p=0.02) Return to dialysis treatment was 20% in MP group vs.36% in CS group (p=0.01).Since 2 month post-transplant, mean cost of treatment for one patient was higher of 59,7 USD in CS group vs. MP group (p<0.001)in each month. Costs of investments on MP were equalized in 16 month post-transplantation.
CONCLUSIONS: Despite higher costs of MP use in the first month post transplantation, it is money-saving method of kidneys preservation and its cost of use, are equalized after 16 months post transplantation.

A modified CZ-1 preserving solution for organ transplantation: comparative study with UW preserving solution.

BACKGROUND: The University of Wisconsin colloid based preserving solution (UW solution) is the most efficient preserving solution for multiorgan transplantation. Unfortunately, unavailability of delayed organ preserving solutions hindered further progression of cardinal organ transplantation in China. In this study, we validated an organ preserving Changzheng Organ Preserving Solution (CZ-1 solution) and compared it with UW solution. METHODS: A series of studies were conducted on how and how long CZ-1 solution could preserve the kidneys, livers, hearts, lungs and pancreas of New Zealand rabbits and SD rats. Morphology of transplanted organs was studied by visible microscopy and electron microscopy; biochemical and physiological functions and the survival rate of the organs during prolonged cold storage were studied. RESULTS: There was no significant difference between CZ-1 and UW solutions in preserving the kidneys, livers, hearts or lungs of rabbits; kidneys, livers, intestinal mucosa or pancreases of SD rats or five deceased donors' testicles. In some aspects, such as preserving rabbits' hearts, rats' intestinal mucosa and pancreases, the effect of CZ-1 solution was superior to UW solution. CZ-1 could safely preserve kidneys for 72 hours, livers for 24 hours, hearts for 18 hours and lungs for 8 hours for SD rats. Twelve kidneys preserved in cold CZ-1 solution for 22 - 31 hours were transplanted successfully and the mean renal function recovery time was (3.83 +/- 1.68) days. CONCLUSIONS: CZ-1 solution is as effective as UW solution for organ preservation. The development of CZ-1 solution not only reduces costs and improves preservation of organs, but also promotes future development of organ transplantation in China.

PBS140: new competition in the organ preservation market?

PBS140 offers good cold preservation in renal transplantation and now, crucially, has been shown to promote immediate function following warm ischemia. For a new cold preservation solution to compete with UW solution, improved efficacy and lower price may not be enough. Reducing rates of delayed graft function in organs from non-heart-beating and marginal donors might be the key.