Extended Criteria Donors Research Articles

Indocyanine Green Angiography for Quality Assessment of Renal Graft Before Transplantation: A Pilot Study

Criteria for donation have been expanded to meet the great demand for organ transplant, resulting in different tools and classifications to help physicians to better assess the quality of the transplanted kidney. In this study, we evaluated the use of indocyanine green angiography as an additional tool to evaluate the renal microcirculation and the quality of the potential kidney graft. All kidneys from extended criteria donors or donors after cardiac death available for transplant underwent indocyanine green angiog-raphy before implantation and after reconditioning, when hypothermic perfusion was required. We performed fluorescent angiography with a 10-mm-view laparoscope connected to a high-definition camera system while a solution of indocyanine green and Celsior was injected into the renal artery. We compared fluorescence intensities with postoperative graft function and then analyzed increases in fluorescence intensity before and after hypothermic machine perfusion treatment. In transplanted kidneys preserved in traditional cold storage, we found a statistically significant difference in fluorescence intensity values between groups with early graft function and delayed graft function. Fluorescence intensity increased significantly in all perfused kidneys after hypothermic machine perfusion treatment, indicating that intensity was directly proportional to improved renal microcirculation. Among 21 kidneys retrieved for transplant that adhered to the inclusion criteria, 11 were examined histopathologically, with a Karpinski score ranging from 2 to 7. The kidney that scored 7 was immediately discarded. Five underwent hypothermic pulsatile perfusion since they came from donors after cardiac death. Fluorescence intensity increased significantly in all perfused kidneys (4/5 were closest to doubling). Histopathological evaluations and Karpinski scores of the grafts indicated that all 5 were considered suitable for transplant. Indocyanine green angiography can be used in the future as an additional useful tool to help physicians to assess graft quality before implantation.

Experimental and Clinical Aspects of Sevoflurane Preconditioning and Postconditioning to Alleviate Hepatic Ischemia-Reperfusion Injury: A Scoping Review.

Ischemia-reperfusion injury (IRI) is an inflammatory process inherent in organ transplantation procedures. It is associated with tissue damage and, depending on its intensity, can impact early graft function. In liver transplantation (LT), strategies to alleviate IRI are essential in order to increase the use of extended criteria donor (ECD) grafts, which are more susceptible to IRI, as well as to improve postoperative graft and patient outcomes. Sevoflurane, a commonly used volatile anesthetic, has been shown to reduce IRI. This scoping review aims to give a comprehensive overview of the existing experimental and clinical data regarding the potential benefits of sevoflurane for hepatic IRI (HIRI) and to identify any gaps in knowledge to guide further research. We searched Medline and Embase for relevant articles. A total of 380 articles were identified, 45 of which were included in this review. In most experimental studies, the use of sevoflurane was associated with a significant decrease in biomarkers of acute liver damage and oxidative stress. Administration of sevoflurane before hepatic ischemia (preconditioning) or after reperfusion (postconditioning) appears to be protective. However, in the clinical setting, results are conflicting. While some studies showed a reduction of postoperative markers of liver injury, the benefit of sevoflurane on clinical outcomes and graft survival remains unclear. Further prospective clinical trials remain necessary to assess the clinical relevance of the use of sevoflurane as a protective factor against HIRI.

Extended criteria donor organ use for heart-lung transplantation in the modern era

BackgroundDemand for donor hearts and lungs exceeds their supply. Extended Criteria Donor (ECD) organs are used to help meet this demand, but their impact on heart-lung transplantation outcomes is poorly characterized. Methods and results: The United Network for Organ Sharing was queried for data on adult heart-lung transplantation recipients (n = 447) from 2005‒2021. Recipients were stratified based on whether they received ECD hearts and/or lungs. Morbidity was analyzed using Kruskal-Wallis, chi-square, and Fisher's exact tests. Mortality was analyzed using Kaplan-Meier estimation, log-rank tests and Cox regression. Sixty-five (14.5%) patients received two ECD organs, 134 (30.0%) received only an ECD lung, and 65 (14.5%) only an ECD heart. Recipients of two ECD organs were older, more likely to have diabetes, and more likely transplanted from 2015‒2021 (p < 0.05). Groups did not differ by pre-transplant diagnosis, intensive care unit disposition, life support use, or hemodynamics. Group five-year survival rates ranged from 54.5% to 63.2% (p = 0.428). Groups did not differ by 30-day mortality, strokes, graft rejection, or hospital length of stay. Conclusions: Using ECD hearts and/or lungs for heart-lung transplantation is not associated with increased mortality and is a safe strategy for increasing donor organ supply in this complex patient population.

Pre-Implantation Kidney Biopsies in Extended Criteria Donors: From On Call to Expert Pathologist, from Conventional Microscope to Digital Pathology

The number of patients awaiting a kidney transplant is constantly rising but lack of organs leads kidneys from extended criteria donors (ECD) to be used to increase the donor pool. Pre-transplant biopsies are routinely evaluated through the Karpinski-Remuzzi score but consensus on its correlation with graft survival is controversial. This study aims to test a new diagnostic model relying on digital pathology to evaluate pre-transplant biopsies and to correlate it with graft outcomes. Pre-transplant biopsies from 78 ECD utilized as single kidney transplantation were scanned, converted to whole-slide images (WSIs), and reassessed by two expert nephropathologists using the Remuzzi-Karpinski score. The correlation between graft survival at 36 months median follow-up and parameters assigned by either WSI or glass slide score (GSL) by on-call pathologists was evaluated, as well as the agreement between the GSL and the WSIs score. No relation was found between the GSL assessed by on-call pathologists and graft survival (&lt;i&gt;P&lt;/i&gt; &amp;#61; 0.413). Conversely, the WSI score assigned by the two nephropathologists strongly correlated with graft loss probability, as confirmed by the ROC curves analysis (DeLong test &lt;i&gt;P&lt;/i&gt; &amp;#61; 0.046). Digital pathology allows to share expertise in the transplant urgent setting, ensuring higher accuracy and favoring standardization of the process. Its employment may significantly increase the predictive capability of the pre-transplant biopsy evaluation for ECD, improving the quality of allocation and patient safety.

The perioperative period of liver transplantation from unconventional extended criteria donors: data from two high-volume centres

BackgroundAs literature largely focuses on long-term outcomes, this study aimed at elucidating the perioperative outcomes of liver transplant patients receiving a graft from two groups of unconventional expanded criteria donors: brain dead aged > 80 years and cardiac dead.MethodsData of 247 cirrhotic patients transplanted at two high volume liver transplant centers were analysed. Confounders were balanced using a stabilized inverse probability therapy weighting and a propensity score for each patient on the original population was generated. The score was created using a multivariate logistic regression model considering a Comprehensive Complication Index ≥ 42 (no versus yes) as the dependent variable and 11 possible clinically relevant confounders as covariate.ResultsForty-four patients received the graft from a cardiac-dead donor and 203 from a brain-dead donor aged > 80 years. Intraoperatively, cardiac-dead donors liver transplant cases required more fresh frozen plasma units (P < 0.0001) with similar reduced need of fibrinogen to old brain-dead donors cases. The incidence of reperfusion syndrome was similar (P = 0.80). In the Intensive Care Unit, both the groups presented a comparable low need for blood transfusions, renal replacement therapy and inotropes. Cardiac-dead donors liver transplantations required more time to tracheal extubation (P < 0.0001) and scored higher Comprehensive Complication Index (P < 0.0001) however the incidence of a severe complication status (Comprehensive Complication Index ≥ 42) was similar (P = 0.52). ICU stay (P = 0.97), total hospital stay (P = 0.57), in hospital (P = 1.00) and 6 months (P = 1.00) death were similar.ConclusionSelected octogenarian and cardiac-dead donors can be used safely for liver transplantation.

State-of-the-Art and Future Directions in Organ Regeneration with Mesenchymal Stem Cells and Derived Products during Dynamic Liver Preservation.

Transplantation is currently the treatment of choice for end-stage liver diseases but is burdened by the shortage of donor organs. Livers from so-called extended-criteria donors represent a valid option to overcome organ shortage, but they are at risk for severe post-operative complications, especially when preserved with conventional static cold storage. Machine perfusion technology reduces ischemia-reperfusion injury and allows viability assessment of these organs, limiting their discard rate and improving short- and long-term outcomes after transplantation. Moreover, by keeping the graft metabolically active, the normothermic preservation technique guarantees a unique platform to administer regenerative therapies ex vivo. With their anti-inflammatory and immunomodulatory properties, mesenchymal stem cells are among the most promising sources of therapies for acute and chronic liver failure, but their routine clinical application is limited by several biosafety concerns. It is emerging that dynamic preservation and stem cell therapy may supplement each other if combined, as machine perfusion can be used to deliver stem cells to highly injured grafts, avoiding potential systemic side effects. The aim of this narrative review is to provide a comprehensive overview on liver preservation techniques and mesenchymal stem cell-based therapies, focusing on their application in liver graft reconditioning.

The current and future role of artificial intelligence in optimizing donor organ utilization and recipient outcomes in heart transplantation

Heart failure (HF) is a leading cause of morbidity and mortality in the United States. While medical management and mechanical circulatory support have undergone significant advancement in recent years, orthotopic heart transplantation (OHT) remains the most definitive therapy for refractory HF. OHT has seen steady improvement in patient survival and quality of life (QoL) since its inception, with one-year mortality now under 8%. However, a significant number of HF patients are unable to receive OHT due to scarcity of donor hearts. The United Network for Organ Sharing has recently revised its organ allocation criteria in an effort to provide more equitable access to OHT. Despite these changes, there are many potential donor hearts that are inevitably rejected. Arbitrary regulations from the centers for Medicare and Medicaid services and fear of repercussions if one-year mortality falls below established values has led to a current state of excessive risk aversion for which organs are accepted for OHT. Furthermore, non-standardized utilization of extended criteria donors and donation after circulatory death, exacerbate the organ shortage. Data-driven systems can improve donor-recipient matching, better predict patient QoL post-OHT, and decrease needless organ waste through more uniform application of acceptance criteria. Thus, we propose a data-driven future for OHT and a move to patient-centric and holistic transplantation care processes.

Expanding Criteria in Controlled Cardiac Death Donors: Now With 70-Year-Old Donors

Outcomes of kidney transplant (KT) after controlled cardiac death with older donors are under review. We aimed to analyze early and midterm clinical outcomes using older (≥70 years) controlled cardiac death donors (cDCD). Retrospective observational single-center study including all KTs from donors ≥70 years from cDCD and donors after brain death (DBD) performed from January 2017 to January 2022. We performed a comparative study between the 2 groups (cDCD and DBD). An analysis of clinical characteristics, early clinical outcomes, and patient and graft survival rates was made. We included 25 cDCD KTs and 63 DBD KTs ≥70 years. The median follow-up was 18.7 months. Recipients from cDCD were more comorbid. Donors from DBD showed higher hypertension and stroke rate. The KTs from older cDCD showed similar delayed graft function rate (cDCD: 34.6% vs DBD extended criteria donor: 35.3%, P=.59) and primary nonfunction (cDCD 16% vs DBD 17.4%, P=.85) compared with older DBD. Medium (3 years) graft death-censored survival was satisfying (cDCD 73% vs DBD 72%) despite a relevant early graft failure rate in both groups (cDCD 16% vs DBD 23%, P=.26). No differences were observed in patient survival at year 1 (cDCD 94% vs DBD 93%, P=.62). In our series, the outcomes with older cDCD are similar compared with older DBD. Although older donors showed an increase of early graft failure, these kidneys allowed us to maximize the opportunities for candidates that otherwise should remain on dialysis.

Liver Resuscitation With Hypothermic Oxygenated Perfusion After Donation in Asystolic Type Iii With Regional Perfusion in Normothermia: A Case Report About First Experience in Spain

Extended criteria donor livers are increasingly being accepted for transplant in an attempt to bridge the gap between the number of patients on the waiting list and the number of available donor livers. Our objective was to describe our first case of hepatic resuscitation by means of an ex situ perfusion machine in hypothermia with oxygen insufflation of a liver graft extracted from a donor in type 3 asystole after regional perfusion in normothermia. A 53-year-old woman with disabling polycystic liver disease was included on the liver transplant waiting list. Donation was offered in type 3 asystole with regional perfusion in normothermia. Given that it was an elderly donor with a low-weight graft, hepatic resuscitation was decided by means of an ex situ perfusion machine in hypothermia with oxygen insufflation. After performing the bench work, the injector is selectively cannulated via the portal to connect it to the hypothermic perfusion machine. The average temperature of the perfusate (3 L modified Belzer) was 10°C for 120 minutes at 250 mL/min. The implant was completed without the need for transfusion of blood products, postreperfusion Sd, or vasoactive support. Peak of GOT/GPT was 803/276 at 24 hours posttransplant.

The altruistic elderly, a valuable but unrecognised kidney donor group. A case report of an 85-year-old unspecified kidney donor

BackgroundKidney transplantation is the definitive treatment for end stage renal disease (ESRD), offering improved quality of life and survival benefit over remaining on dialysis. There is, however, a prevailing significant mismatch between patients awaiting transplantation and available donor kidneys. Over time, initial stringent donor criteria have broadened and organs from extended criteria donors (ECDs) and older donors are now being accepted for transplantation. The spectrum of living donors has also undergone a change from close family members to an increasingly non-related, non-directed altruistic donors, newly classified as ‘unspecified’ donors. Unspecified elderly donors could be a potential untapped resource to expanding the kidney donor pool globally.Case PresentationWe present a case of an 85 year and 8 months old individual, who donated to an unrelated non-directed matched recipient in the national deceased donor transplant waiting list with excellent donor and recipient outcomes at 7 years.ConclusionTo our knowledge she is one of the oldest reported unspecified living kidney donors in the world to date. This case illustrates that elderly donors in good health can come forward to donate, knowing that it is safe and valuable. Once the immediate perioperative challenges after kidney donation are managed, elderly donors rarely encounter long term sequelae. We therefore report this case to increase awareness and refocus attention of transplant teams on elderly donors as a potential untapped group to help address the organ shortage problem in renal transplantation.

The Role of IGL-2 Preservation Solution on Rat Livers during SCS and HOPE.

The scarcity of livers for transplantation is rising, and new strategies to extend the donor pool are being explored. One solution is to use marginal grafts from extended criteria donors, presenting, for example, liver steatosis. As current preservation solutions (UW, HTK, and IGL-1) were mainly designed for static cold storage (SCS) only, IGL-2, a modified version of IGL-1, was developed to be suitable for SCS and dynamic preservation, such as hypothermic oxygenated perfusion (HOPE). In this study, we investigated the combined effect of IGL-2, SCS, and HOPE and compared it to the most used preservation solution (UW and Belzer MPS). Four experimental groups with six rats each were designed using Zucker rats. All groups underwent 24 h of SCS (in IGL-2 or UW) + 2 h of normothermic machine perfusion (NMP) at 37 °C to mimic transplantation. HOPE (IGL-2 or Belzer MPS) was performed before NMP on half of the rats. The IGL-2 group demonstrated lower transaminases and a significantly low level of glycocalyx proteins, CASP3, and HMGB1 in the perfusates. These data suggest the protective role of IGL-2 for fatty livers in preserving the endothelial glycocalyx, apoptosis, and inflammation.

Normothermic Ex Vivo Perfusion with Hemofiltration Maintains Heart Performance after Prolonged Cold Ischemia Time

Introduction: A potential solution to increase hearts available for transplantation is to use extended criteria donor hearts that are deemed unacceptable at initial evaluation. This study uses normothermic ex vivo heart perfusion (NEVHP) to resuscitate, recover, and assess performance of hearts after prolonged cold ischemia time. METHODS: Piglet (6 to 10 kg) hearts were procured after delivering antegrade cardioplegia. Catheters were placed in the left ventricle (functional assessment), aorta (inflow), and pulmonary artery (outflow) to support NEVHP, followed by either initiation of NEVHP (“direct group,” n = 5) or cold static storage in CoStorSol solution at 5°C for 12 hours (“12-hour group,” n = 5) or 24 hours (“24-hour group,” n = 5). All hearts were recovered and supported using NEVHP with in-parallel hemofiltration. Coronary perfusion was maintained at 1 mL/min/g. One-way ANOVA was used for statistical analysis. RESULTS: All hearts were resuscitated to normal sinus rhythm and were viable at 8 hours NEVHP. There were no significant differences between the direct, 12-hour, and 24-hour groups in hemodynamic or metabolic performance at the end of NEVHP. Mean heart rate was 95 ± 4, 90 ± 2, and 101 ± 3 beats per minute (p = 0.08); left ventricle pressure was 45 ± 4.7, 51 ± 5.0, and 56.0 ± 3.0 mmHg (p = 0.24); coronary resistance was 0.77 ± 0.29, 0.76 ± 0.18, and 0.48 ± 0.13 mmHg/mL/min (p = 0.08); lactate was 2.6 ± 0.3, 2.84 ± 0.3, and 3.5 ± 0.2 mmol/L (p = 0.10); and oxygen consumption was 0.015 ± 0.001, 0.021 ± 0.004, and 0.015 ± 0.004 mL/min/g (p = 0.24) for the direct, 12-hour, and 24-hour groups, respectively. Conclusion: Use of extended criteria donor hearts would increase organs available for transplantation. NEVHP with hemofiltration offers a solution to successfully recover and assess these hearts while maintaining organ performance.

The Enhanced Recovery after Surgery (ERAS) Pathway Is a Safe Journey for Kidney Transplant Recipients during the "Extended Criteria Donor" Era.

Enhanced recovery after surgery (ERAS) protocols are still underused in kidney transplantation (KT) due to recipients’ “frailty” and risk of postoperative complications. We aimed to evaluate the feasibility and safety of ERAS in KT during the “extended-criteria donor” era, and to identify the predictive factors of prolonged hospitalization. In 2010–2019, all patients receiving KT were included in ERAS program targeting a discharge home within 5 days of surgery. Recipient, transplant, and outcomes data were analyzed. Of 454 KT [male: 280, 63.9%; age: 57 (19–77) years], 212 (46.7%) recipients were discharged within the ERAS target (≤5 days), while 242 (53.3%) were discharged later. Patients within the ERAS target (≤5 days) had comparable recipient and transplant characteristics to those with longer hospital stays, and they had similar post-operative complications, readmission rates, and 5 year graft/patient survival. In the multivariate analysis, DGF (HR: 2.16, 95% CI: 1.08–4.34, p < 0.030) and in-hospital dialysis (HR: 3.68, 95% CI: 1.73–7.85, p < 0.001) were the only predictive factors for late discharge. The ERAS approach is feasible and safe in all KT candidates, and its failure is primarily related to the postoperative graft function, rather than the recipient’s clinical status. ERAS pathways, integrated with strict collaboration with local nephrologists, allow early discharge after KT, with clinical benefits.

Viability Criteria during Liver Ex-Situ Normothermic and Hypothermic Perfusion.

With the increased use of extended-criteria donors, machine perfusion became a beneficial alternative to cold storage in preservation strategy for donor livers with the intent to expand donor pool. Both normothermic and hypothermic approach achieved good results in terms of mid- and long-term outcome in liver transplantation. Many markers and molecules have been proposed for the assessment of liver, but no definitive criteria for graft viability have been validated in large clinical trials and key parameters during perfusion still require optimization.In this review, we address the current literature of viability criteria during normothermic and hypothermic machine perfusion and discuss about future steps and evolution of these technologies.

PERFUSION PROGRAMMES START-UP AND VIABILITY ASSESSMENT: A PRACTICAL GUIDE TO EX-SITU NORMOTHERMIC MACHINE PERFUSION IN LIVER TRANSPLANTATION

Machine perfusion of the liver has been an increasingly adopted approach to overcome the shortcomings of static cold storage, that are most prominent in extended criteria donors. Normothermic machine perfusion (NMP) safety and efficacy were demonstrated in several prospective trials and multiple cohort series. The real-world benefits of this approach are liver functional assessment and extended preservation times. In this review, we aim to provide information regarding the practical aspects of starting an NMP programme and pragmatic guidance towards assessing liver viability for teams new to this field. There are two key areas of focus in assessing liver viability, examining both the hepatocyte and cholangiocyte compartments. Analysis of these areas can predict risk of primary non-function and non-anastomotic biliary strictures, respectively. There is a learning curve in adopting and gaining confidence with the NMP technology. Viability assessment allows transplantation of more marginal livers, but a cautious approach is advised for new centres entering the field.

Hypothermic oxygenated perfusion in extended criteria donor liver transplantation—A randomized clinical trial

Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p=.007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p=.05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival oneyear after LT (p=.03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at sixmonths, in particular cardio-vascular adverse events (p=.04 and p=.03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.

MACHINE PERFUSION IN ITALY. THE EVOLUTION OF THE CLINICAL PRACTICE

The use of extended criteria donors (ECD) became widespread due to the shortage of organs available for transplantation. The use of ex-situ machine perfusion (MP) after organ retrieval is strongly recommended in this field, to improve clinical outcomes following transplantation. Adopting MP strategies requires huge financial resources that can only be optimized if MP is introduced more widely, with evidence of significant benefits. Objective. 1) to evaluate the evolution of MP use in Italy over the time and its potential impact on the organ pool available for transplantation; 2) to measure the quality of the MP program. Methods. The “Methods of organ perfusion in transplantation” was adopted in 2017, including recommendations for implementing a national program; a database was set up to collect the data of ex-situ perfused organs, procured from DCD or DBD donors. Results. The ex-situ MP program started slowly in Italy, but it developed over time thanks to the good results obtained. Most Italian transplant centers currently participate in the program, and most perfused organs (60-95%, depending on the type of organ) undergo transplantation, increasing the use of organs that would otherwise have been discarded. Conclusions. The Italian experience shows the effectiveness of using MP for organ preservation and the potential positive effect of this activity on the health care system. National data recording needs to be better structured to reinforce this evidence so that the competent authority can support transplant centers in obtaining funds or reimbursements from health care institutions.

SOULMATE: the Swedish study of liver transplantation for isolated colorectal cancer liver metastases not suitable for operation or ablation, compared to best established treatment—a randomized controlled multicenter trial

BackgroundAround one fourth of patients with colorectal cancer present themselves with distant metastases at the time of diagnosis, and one additional one fifth of the patients will develop distant metastases during the disease, most commonly in the liver.Surgical treatment such as liver resection or ablation, often combined with chemotherapy and targeted therapy, is the only treatment option with curative potential, but only about 20% of the patients with liver metastases are candidates for surgical intervention. Standard treatment for unresectable patients is palliative oncological therapy; however, less than 10% of these patients will achieve a 5-year survival.Non-randomized studies indicate that liver transplantation could be an option for selected patients with colorectal liver metastases (CRLM), which are not suitable for operation or ablation due to surgical technical reasons such as massive tumor burden and small future liver remnant, or oncological reasons, for example, early relapse after liver surgery. Since there is a shortage of donated liver grafts, it is important to select the patient group that benefit most from the treatment. Although some studies present positive results from liver transplantation of CRLM, the results must be validated in a randomized controlled trial before this new indication for liver transplantation can be introduced as a clinical routine.MethodsThe SOULMATE study is a randomized study evaluating if liver transplantation with liver grafts, primarily from extended criteria donors, increases overall survival in patients with CRLM, not suitable for resection or ablation, in comparison with best established treatment.Patients will be randomized to liver transplantation (LT)+ best established treatment (BET) or to best established treatment only.In the SOULMATE trial, we will evaluate the use of livers from extended criteria donors to decrease the risk of prolonging waiting time for patients on the waiting list for LT.DiscussionThe SOULMATE study has the possibility to confirm the positive results of previous studies in a randomized setting. The use of extended criteria donors will make the results transferable globally, as most countries are struggling with organ shortage.Trial registrationClinical Trial number: NCT04161092 registered 13 November 2019.

Trends in Outcomes of Heart Transplants Using Extended Criteria Donors: A United Network for Organ Sharing Database Analysis

BackgroundAlthough the use of extended criteria donors (ECDs) is traditionally avoided because of poorer outcomes, management of heart transplant (HTx) recipients has evolved over the past decades. We sought to examine the temporal trends in outcomes of ECDs in HTx. MethodsWe queried the United Network for Organ Sharing database for adult HTx recipients who fit the EXPAND Trial criteria for ECDs: ischemic time ≥ 4 hours, ejection fraction < 50%, age > 55 years, and history of coronary artery disease. Transplant years were stratified into the following 4 periods: (1) 2000 to 2004, (2) 2005 to 2009, (3) 2010 to 2014, and (4) 2014 to 2018. The 2-sample t test, Kaplan-Meier survival analysis, log-rank test, analysis of variance, multivariable Cox proportional hazards, and multinomial logistic regression were used to compare data between periods. ResultsThrough periods 1 to 4, 39,028 patients were stratified as follows: 9217 (2942 ECDs, 31.9%), 9224 (2730 ECDs, 29.6%), 10,309 (2762 ECDs, 26.8%), and 10,278 (2190 ECDs, 21.3%). Transplants using ECDs in periods 1 and 2 had increased 1-year mortality compared with periods 3 and 4 (16.9% and 15.6% vs 11.9% and 10.9% respectively, P < .001). Later periods also demonstrated improved Karnofsky scores (P < .001). ConclusionsAlthough use of ECDs decreased across the periods, we noted significant improvement in 1-year survival rates and postoperative functional status.

Ex Vivo Liver Machine Perfusion: Comprehensive Review of Common Animal Models.

The most common preservation technique for liver grafts is static cold storage. Due to the organ shortage for liver transplantation (LT), extended criteria donor (ECD) allografts are increasingly used-despite the higher risk of inferior outcome after transplantation. Ex vivo liver machine perfusion (MP) has been developed to improve the outcome of transplantation, especially with ECD grafts, and is currently under evaluation in clinical trials. We performed a literature search on PubMed and ISI Web of Science to assemble an overview of rodent and porcine animal models of ex vivo liver MP for transplantation, which is essential for the present and future development of clinical liver MP. Hypothermic, subnormothermic, and normothermic MP systems have been successfully used for rat and pig LT. In comparison with hypothermic systems, normothermic perfusion often incorporates a dialysis unit. Moreover, it enables metabolic assessment of liver grafts. Allografts experiencing warm ischemic time have a superior survival rate after MP compared with cold storage alone, irrespective of the temperature used for perfusion. Furthermore, ex vivo MP improves the outcome of regular and ECD liver grafts in animal models. Small and large animal models of ex vivo liver MP are available to foster the further development of this new technology. Impact Statement Ex vivo machine perfusion is an important part of current research in the field of liver transplantation. While evidence for improve storage is constantly rising, the development of future applications such as quality assessment and therapeutic interventions necessitates robust animal models. This review is intended to provide an overview of this technology in common large and small animal models and to give an outlook on future applications. Moreover, we describe developmental steps that can be followed by others, and which can help to decrease the number of animals used for experiments based on the replace, reduce, refine concept.