Extended Criteria Donors Research Articles

Use of Extended Criteria Donor Hearts in Simultaneous Heart-Kidney Transplantation

PurposeInsufficiency of donor organ supply has led to the utilization of extended criteria donor (ECD) hearts. Several groups have demonstrated that careful use of ECD hearts has acceptable outcomes in select patients. However, the use of ECD hearts has yet to be studied in patients undergoing simultaneous heart-kidney transplantation (SKHT). This study evaluates the outcomes of patients receiving standard criteria donor (SCD) vs. ECD hearts in the setting of SHKT.MethodsRetrospective review of the Organ Procurement and Transplantation Network database was performed for adults undergoing SHKT since 1/1/2010. Patients were stratified by receipt of an ECD heart. SCD hearts were defined by the 2020 International Society for Heart and Lung Transplantation Consensus Statement on Donor Heart and Lung Procurement. ECD hearts were defined as those that failed to meet any of these criteria. The primary outcome was patient survival. Secondary outcomes included several post-operative complications.ResultsOverall 1,389 SHKTs were performed during the study period, of which 345 (24.8%) utilized ECD hearts. Recipients of ECD hearts were more likely to have a higher body mass index (25.6 vs. 29.5, p<0.001) and were more likely to have diabetes (39.5% vs. 48.5%, p=0.005). Postoperatively, the SCD and ECD cohorts experienced similar rates of pacemaker implantation (2.1% vs. 0.9%, p=0.16), hemodialysis (29.9% vs. 32.2%, p=0.42), and stroke (3.3% vs. 3.5%, p=0.86). However, the ECD cohort experienced greater incidence of cardiac graft failure due to primary nonfunction (0.7% vs. 2.9%). ECD patients experienced decreased survival at 30 days (96.6% vs. 91.2%, p=0.001) and at 5 years (80.2% vs. 72.5%, p=0.002) as shown in Figure 1.ConclusionUse of ECD hearts in the setting of SHKT is associated with increased mortality. Careful consideration should be given before accepting an ECD heart for SHKT given the increased consequences of recipient death on responsible organ allocation in dual organ transplantation. Insufficiency of donor organ supply has led to the utilization of extended criteria donor (ECD) hearts. Several groups have demonstrated that careful use of ECD hearts has acceptable outcomes in select patients. However, the use of ECD hearts has yet to be studied in patients undergoing simultaneous heart-kidney transplantation (SKHT). This study evaluates the outcomes of patients receiving standard criteria donor (SCD) vs. ECD hearts in the setting of SHKT. Retrospective review of the Organ Procurement and Transplantation Network database was performed for adults undergoing SHKT since 1/1/2010. Patients were stratified by receipt of an ECD heart. SCD hearts were defined by the 2020 International Society for Heart and Lung Transplantation Consensus Statement on Donor Heart and Lung Procurement. ECD hearts were defined as those that failed to meet any of these criteria. The primary outcome was patient survival. Secondary outcomes included several post-operative complications. Overall 1,389 SHKTs were performed during the study period, of which 345 (24.8%) utilized ECD hearts. Recipients of ECD hearts were more likely to have a higher body mass index (25.6 vs. 29.5, p<0.001) and were more likely to have diabetes (39.5% vs. 48.5%, p=0.005). Postoperatively, the SCD and ECD cohorts experienced similar rates of pacemaker implantation (2.1% vs. 0.9%, p=0.16), hemodialysis (29.9% vs. 32.2%, p=0.42), and stroke (3.3% vs. 3.5%, p=0.86). However, the ECD cohort experienced greater incidence of cardiac graft failure due to primary nonfunction (0.7% vs. 2.9%). ECD patients experienced decreased survival at 30 days (96.6% vs. 91.2%, p=0.001) and at 5 years (80.2% vs. 72.5%, p=0.002) as shown in Figure 1. Use of ECD hearts in the setting of SHKT is associated with increased mortality. Careful consideration should be given before accepting an ECD heart for SHKT given the increased consequences of recipient death on responsible organ allocation in dual organ transplantation.

Trends in Outcomes of Extended Criteria Donors for Heart Transplants

<h3>Purpose</h3> Recent studies have explored use of extended criteria donors (ECD) as a means of expanding the donor pool for heart transplantation. Here we examine the temporal trends in outcomes of ECDs in heart transplantation. <h3>Methods</h3> We performed a retrospective analysis on adult heart transplants using the UNOS Database from 2000 to 2019. EXPAND Trial criteria for ECD was used; ischemic time > 4 hours, ejection fraction < 50%, age > 55 years, history of coronary artery disease. Transplants were divided into 4 groups by transplant year; 2000-2004, 2005 - 2009, 2010 - 2014, and 2014 - 2019. Where appropriate two-sample t-test, Kaplan Meier survival analysis, log-rank test, and analysis of variance, multivariable Cox proportional hazards analysis, and Pearson's Correlation Coefficient were used to compare data between different Periods. <h3>Results</h3> 42,642 patients were included in our study. ECD utilization declined over the periods analyzed (31.9% to 29.6% to 26.8% to 23.9%). Transplants utilizing ECDs in Periods 1 and 2 had worse outcomes compared to Periods 3 and 4 (Figure 1). Pearson's Coefficient Correlation test demonstrated a significant trend of 7% decrease in mortality risk for ECDs with each year after 2000. Cox proportional hazards analysis demonstrated transplant year to be in an independent predictor of mortality (HR 0.97, P < 0.001). We saw improved Karnofsky score with later time periods (Figure 2). <h3>Conclusion</h3> There was an improvement in 1-year survival rate and postoperative function status for transplants utilizing ECDs. Additional research is needed to further improve outcomes as use of warm-perfusion devices may lead to significant increases in the donor pool.

A Closer Look at Risk Factors Associated with Airway Complications in Lung Transplantation

Purpose Airway complications can cause significant morbidity in lung transplantation; prevalence varies between 8-20%. In 2018, the ISHLT created a new grading system for airway complications. This study's aim was to grade airway complications using the new system and identify associated risk factors including the use of ex-vivo lung perfusion (EVLP). Methods This was a retrospective, single-center study of 188 lung transplants done between Feb 2016 and Mar 2020. Clinically significant airway ischemia (CSAI) was defined as ischemia severity equal to or worse than grade B2, > 50% stenosis, or dehiscence. EVLP was performed using the Organ Care System (OCS) Lung, in the setting of extended criteria donors (ECD) which included any combination of the following: age >55 yrs, > 6-hr ischemia, death from circulatory arrest, >20 pack-yr smoke history, or PF ratio Results 188 recipients or 339 lung allografts were transplanted within the study period. The average age was 52.4 years; 58% were male. Out of 339 lung allografts, 116 (34%) met criteria for CSAI. 15.3% of allografts were preserved using EVLP and of these, 88.5% were ECD. Recipients with diabetes mellitus were more likely to have CSAI than those without (OR 2.46, p value = 0.04). CSAI was associated with several factors in the unadjusted analysis including EVLP (OR 1.65, 95% CI 0.90-3.01), continuous running suture technique versus interrupted suture technique (OR 1.84, 95% CI 1.05-3.33), right versus left allograft (OR 1.41, 95% CI 0.90-2.21), right versus left side of first anastomosis (OR 0.71, 95% CI 0.45-1.11) and extracorporeal life support (ECLS) versus off-pump (OR 1.77, 95% CI 0.93-3.41). In particular, 23 of the 52 (44%) of the lung allografts performed with EVLP had CSAI compared to 93 of the 287 (32%) allografts procured traditionally. CSAI was significantly associated with EVLP (OR 1.98, 95% CI 1.05-3.76) and continuous running suture technique (OR 2.00, 95% CI 1.05-3.94) after adjusting for recipient, donor and intraoperative factors. Conclusion A high burden of CSAI was detected in our study. Analysis suggests that ECD lungs preserved with EVLP may be at higher risk of CSAI than donor lungs preserved on ice, but use of interrupted suture technique and avoidance of ECLS may reduce this risk.

Warm Ischemic Time in Orthotopic Heart Transplantation: Is Faster Really Better?

<h3>Purpose</h3> As donor criteria expand to meet increasing demand for transplantable hearts, increased focus has fallen on mitigating risk associated with extended criteria donors. It has been postulated that warm ischemic time may be as significant a factor as total ischemic time, and reduction is associated with better outcomes. This study investigates the impact of warm ischemic time on post-operative events and survival in orthotopic heart transplantation patients at a high-volume center. <h3>Methods</h3> From 2015 to 2020, patients who underwent heart transplantation were identified at a single institution in a prospectively maintained database with long-term clinical outcomes. After excluding heart-lung transplants and those with missing warm ischemic time, 388 patients were identified. Patients were classified in to three groups: < 45 minutes warm ischemic time (106), 45 ≥ warm ischemic time < 60 minutes (170), and ≥ 60 minutes warm ischemic time (112). Demographics and outcomes were analyzed by warm ischemic time group. A subgroup analysis of patients with over 4 hours total ischemic time was analyzed according to warm ischemic times. <h3>Results</h3> Between warm ischemic time groups, there were significant differences in recipient sex, age, and body mass index (BMI), all p < 0.05 (Table 1). Post-operative device requirements were similar between all groups, p > 0.05, as was 30-day freedom from PGD, 80.2% (85) vs 82.9% (141) vs 76.8% (86), 30-day survival, 98.1% (104) vs 98.2% (167) vs 97.3% (109), and one-year survival, 92.5% (98) vs 93.5% (159) vs 91.1% (102) (all p > 0.05). Warm ischemic time was not a predictor of one-year mortality, odds ratio (OR) 0.99 (95% CI, 0.97-1.02). In subgroup analysis with over 4 hours of total ischemic time, warm ischemic time was not a predictor of PGD, OR 0.94 (95% CI, 0.82-1.07), or one-year survival, OR 0.94 (95% CI, 0.82-1.07). <h3>Conclusion</h3> Although increased warm ischemic time did not predict increased adverse post-operative outcomes, continued emphasis on reducing total ischemic time is paramount.

Use of Ex Vivo Lung Perfusion for Lung Transplantation: Midterm Results

Purpose Ex vivo lung perfusion (EVLP) offers a unique potential in evaluation, optimization and transplantation of lungs that would otherwise potentially be rejected. Between 2016 and 2020 208 lung transplants (LuTx) were performed and 22 donor lungs were evaluated by EVLP of which 16 were transplanted. Aim of the study was to compare mid-term results in LuTx recipients with or without the use of EVLP. Methods In a retrospective single-center analysis data from a prospectively collected database were analysed. The EVLP group (n=16) consisted of donor lungs classified as marginal and were evaluated by EVLP and afterwards transplanted. The non EVLP group (n=16) consisted of conventional LuTx recipients matched for age and pulmonary disease. Both groups were compared for the endpoints survival, primary graft dysfunction, rejection episodes and chronic allograft dysfunction. Results Recipient age was 55 ± 6 years in EVLP group and 57 ± 5 years non EVLP group (n.s.). Female gender was present in 36% EVLP patients and 50% non EVLP (n.s.). The rate PGD grade 1 at 72 h post-LTx was 14% in both groups (each2/16). In non EVLP group 1recipient was PGD 2 (7%). PGD3 was present only in the EVLP group 14% (2/16) vs. 0% in control. At last visit, post-LuTx, forced expiratory volume in 1 s (FEV1%) as percentage of predicted best was similar in the EVLP and non-EVLP group (77% vs. 78%). Chronic lung allograft dysfunction was diagnosed in one non EVLP patient and one EVLP patient during follow up post-LuTx. In the EVLP group 2 patients had rejection episodes subjected to treatment and 6 patients in the non EVLP group (n.s.). Survival at 1 year was 81% for the EVLP group and 94% in non EVLP group (n.s.). Conclusion Recipients transplanted with extended criteria donor lungs, thoroughly evaluated by EVLP show similar mid term outcomes as conventionally transplanted lungs from standard donors. EVLP shall increase the number of acceptable donor lungs. Future clinical trials will bring further evidence; clear guidelines regarding application of machine perfusion have to be developed.

Geographic Distribution in Use of Extended Criteria Donors

<h3>Purpose</h3> Recent research has explored extended criteria donors (ECDs) as a means of increasing the donor pool in heart transplantation. Here we explored the current geographic distribution of ECD utilization use with the goal of identifying areas which may most benefit from such warm perfusion devices. <h3>Methods</h3> We performed a retrospective analysis on adult heart transplants using the UNOS Database from 2000 to 2019. EXPAND Trial definition of ECD was used; ischemic time > 4 hours, ejection fraction < 50%, age > 55 years, history of coronary artery disease. Geographic data and 2019 population estimates from the US Census Bureau were used. <h3>Results</h3> Of the 42,642 transplants included in our analysis, 11,750 (27.6%) utilized ECDs. Region utilization of ECDs ranged from 18.4% to 46.5% of transplants (Table 1). Sub-analysis of ECD criteria revealed ischemic time > 4 hours to be the biggest contributing factor (ranging from 14.3 to 43.2% of all transplants), with reduced ejection fraction being second (2.8% to 9.5%), followed last by older donors > 55 years of age (0.9% to 4.1%) and donor with coronary artery disease (1.4% to 3.4%). Region 6 had the highest utilization rate at 46.5%, this was primarily driven by number of transplants with ischemic time > 4 hours. Region 6 encompasses the largest total area (1.08 million square miles), and smallest population density (15.6 people/square mile). Region 8 had the lowest marginal donor utilization rate at 18.4%. Even regions with high utilization of low EF, older donors, and donors with CAD (i.e. Region 1 and 2) were able to maintain an average utilization rate of ECDs by maintaining short ischemic times. <h3>Conclusion</h3> There exists large discrepancies in utilization of ECDs across the different UNOS regions. This is primarily driven by longer ischemic times - which we believe is influenced by large geographic area and low population densities in some Regions. Warm perfusion devices which may extend the viable warm ischemic time of donor hearts may be particularly useful in these regions.

Impact of Donor Quality on Recipient Outcomes in Lung Transplantation: 10-year Single-Center Experience Using the Eurotransplant Lung Donor Score

Purpose Although use of extended-criteria donor organs (ECD) has increased in lung transplantation, their impact on outcomes remains unclear. The Eurotransplant (ET) lung donor score (ELDS) was designed to classify lung donor quality, taking into account donor history, tobacco exposure, age, arterial blood gases, chest x-ray and bronchoscopic findings. This retrospective single-center study evaluates the impact of ECD on graft function and survival. Methods Records of lung allograft recipients transplanted at our institution between 01/2010 and 10/2020 were reviewed. Individual ELDS were calculated from the corresponding ET donor reports. Outcomes were compared between recipients of ideal donors (ELDS 6, Group 1), of intermediate-risk donors (ELDS 7-8, Group 2), and of extended-criteria donors (ELDS 9-15, Group 3). Median (IQR) follow-up was 46 (20-77) months. Results In total, 238/1,283 (19%) patients received Group 1 donor organs, 651 (51%) patients Group 2 donor organs, and 394 (30%) patients Group 3 donor organs. Group 2 and 3 recipients were older than group 1 recipients (median age, 52 and 54 vs. 43 years, p Conclusion ECD lungs constituted one third of our donor pool. Their use did not negatively impact the recipient survival, but CLAD-free survival was worse in ECD recipients.

Ex-Vivo Pharmacological Defatting of the Liver: A Review.

The ongoing organ shortage has forced transplant teams to develop alternate sources of liver grafts. In this setting, ex-situ machine perfusion has rapidly developed as a promising tool to assess viability and improve the function of organs from extended criteria donors, including fatty liver grafts. In particular, normothermic machine perfusion represents a powerful tool to test a liver in full 37 °C metabolism and add pharmacological corrections whenever needed. In this context, many pharmacological agents and therapeutics have been tested to induce liver defatting on normothermic machine perfusion with promising results even on human organs. This systematic review makes a comprehensive synthesis on existing pharmacological therapies for liver defatting, with special focus on normothermic liver machine perfusion as an experimental ex-vivo translational model.

Advances in Kidney Preservation Techniques and Their Application in Clinical Practice.

The use of cold preservation solutions to rapidly flush and cool the kidney followed by static cold storage in ice has been the standard kidney preservation technique for the last 50 y. Nonetheless, changing donor demographics that include organs from extended criteria donors and donation after circulatory death donors have led to the adoption of more diverse techniques of preservation. Comparison of hypothermic machine perfusion and static cold storage techniques for deceased donor kidneys has long been debated and is still contested by some. The recent modification of hypothermic machine perfusion techniques with the addition of oxygen or perfusion at subnormothermic or near-normothermic temperatures are promising strategies that are emerging in clinical practice. In addition, the use of normothermic regional perfusion to resuscitate abdominal organs of donation after circulatory death donors in situ before cold flushing is also increasingly being utilized. This review provides a synopsis of the different types of preservation techniques including their mechanistic effects and the outcome of their application in clinical practice for different types of donor kidney.

Protective Effects of Bone Marrow Mesenchymal Stem Cells (BMMSCS) Combined with Normothermic Machine Perfusion on Liver Grafts Donated After Circulatory Death via Reducing the Ferroptosis of Hepatocytes.

BackgroundTo improve the quality of liver grafts from extended-criteria donors donated after circulatory death (DCD), this study explored whether bone marrow mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP) have protective effects on DCD donor livers and the effects of ferroptosis in this procedure.Material/MethodsTwenty-four male rat DCD donor livers were randomly and averagely divided into normal, static cold storage (SCS), NMP, and NMP combined with BMMSCs groups. Liver function, bile secretion, and pathological features of DCD donor livers were detected to evaluate the protective effects of NMP and BMMSCs on DCD donor livers. Hydrogen peroxide was used to induce an oxidative stress model of hepatocyte IAR-20 cells to evaluate the protective effects of BMMSCs in vitro.ResultsLivers treated with NMP combined with BMMSCs showed better liver function, relieved histopathological damage, reduced oxidative stress injury and ferroptosis, and the mechanism of reduction was associated with downregulation of intracellular reactive oxygen species (ROS) and free Fe2+ levels. BMMSCs showed significant protective effects on the ultrastructure of DCD donor livers and ROS-induced injury to IAR-20 cells under electron microscopy. BMMSCs also significantly improved the expression level of microtubule-associated protein 1 light chain 3 (LC3)-II in both DCD donor livers and ROS-induced injured IAR-20 cells, including upregulating the expression of ferritin.ConclusionsBMMSCs combined with NMP could reduce the level of ROS and free Fe2+ in oxidative stress damaged rat DCD donor livers, potentially reduce the ferroptosis in hepatocytes, and repair both morphology and function of DCD donor livers.

Post-transplant outcomes of standard and extended criteria donation after circulatory death donor lungs categorized by donation after brain death lung criteria.

Most transplant centres use donation after brain death (DBD) criteria to assess the quality of controlled donation after circulatory death (cDCD) lungs. However, research on the relationship between DBD extended criteria and cDCD lung transplantation outcomes is limited. We investigated the outcomes of using DBD extended criteria donor organs in cDCD lung transplantation, compared to the standard criteria cDCD lung transplantation. A retrospective chart review of consecutive cDCD lung referrals to Hospital Universitario Puerta de Hierro-Majadahonda from June 2013 to December 2019 was undertaken. Donors were divided into standard and extended criteria groups. Early outcomes after lung transplant were compared between these groups using the Kaplan-Meier method and log-rank test. Thirty out of 91 cDCD donor lung offers were accepted for transplantation, of which 11 were from standard criteria donors and 19 were extended criteria donors. The baseline characteristics of the 2 recipient groups were similar. There were no differences in the rates of grade 3 primary graft dysfunction at 72 h after lung transplantation (21% vs 18%), duration of mechanical ventilation (48 h vs 36 h), total intensive care unit stay (10 days vs 7 days) and 1-year survival (89% vs 90%). Carefully selecting cDCD lungs from outside the standard acceptability criteria may expand the existing donor pool with no detrimental effects on lung transplantation outcomes.

Mesenchymal stromal cell treatment of donor kidneys during ex vivo normothermic machine perfusion: A porcine renal autotransplantation study.

Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior to transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti-inflammatory effects in ischemia-reperfusion injury. The aims of this study were to evaluate the safety and feasibility of MSC treatment of kidneys during NMP using a porcine autotransplantation model, and examine potential MSC treatment-associated kidney improvements up to 14days posttransplant. After 75min of kidney warm ischemia, four experimental groups of n=7 underwent 14h of oxygenated hypothermic machine perfusion. In three groups this was followed by 240min of NMP with infusion of vehicle, 10million porcine, or 10million human adipose-derived MSCs. All kidneys were autotransplanted after contralateral nephrectomy. MSC treatment did not affect perfusion hemodynamics during NMP or cause adverse effects at reperfusion, with 100% animal survival. MSCs did not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase-associated lipocalin concentrations or kidney damage assessed by histology during the 14days, and MSCs retention was demonstrated in renal cortex. Infusing MSCs during ex vivo NMP of porcine kidneys was safe and feasible. Within the short posttransplant follow-up period, no beneficial effects of ex vivo MSC therapy could be demonstrated.

Evaluation of Patients on the Deceased Kidney Waiting List of Bursa Uludağ University Medical Faculty according to Gender, Age, Blood Type and Renal Replacement Therapies

In Turkey, there is 22953 end-stage kidney disease patient in national deceased kidney waiting list (1). According to the 2019 Registry Report of the Turkish Society of Nephrology, the number of patients receiving hemodialysis (HD) and peritoneal dialysis (PD) treatment is 64633 (2). However, patients registered on the national kidney waiting list consist of preemptive, PD, and HD patients. Due to the increase in the average life expectancy of the elderly population in our country, chronic kidney disease and comorbid diseases are increasing day by day.&#x0D; In this study, the patients’ characteristics on the deceased kidney waiting list from our kidney transplant center were evaluated retrospectively. Our center's patient data were obtained from Transplantation Dialysis Monitoring System records. Turkey’s general patient data were obtained from the Turkish Statistical Institute and the 2019 Registry Report of the Turkish Society of Nephrology. In our center, the number of patients on the deceased donor kidney waiting list was 420 (HD: 301, PD: 24, preemptive 95). The number of female patients was 162 (38.6%), and the number of male patients was 258 (61.4%). The age distribution of the patients 0-9: 1.1%, 10-19: 3%, 20-29: 4.4%, 30-39: 11.6%, 40-49: 20%, 50-59: 24.4%, 60-69: 26.8%, 70-79: 7.8% and 80-89: 0.2%. The blood group distribution of patients was consistent with Turkey's general data. [0 Rh (+): 26.7%, 0 Rh (-): 3.1%, A Rh (+) 43.3%, A Rh (-) 5.7%, B Rh (+) 11%, B Rh (-) 1.7%, AB Rh (+) 8.1% and AB Rh (-) 0.5%]. The number of male patients was higher than female patients in other age groups except the 40-49 and 80-89 age range (Figure 1). Our patients' distribution by gender and kidney replacement therapies was in line with the 2019 Registry Report of the Turkish Society of Nephrology. An increase in comorbid diseases and kidney failure in advanced age also increases health expenditures. The Republic of Turkey Ministry of Health aims to increase the awareness of kidney disease and the rate of early diagnosis with the "Turkey Kidney Diseases Prevention and Control Program" (3). In our center, the highest number of patients on the deceased kidney waiting list was observed in the age range of 60-69, 50-59, and 40-49, respectively. Physical quality of life worsens as the dialysis period prolongs and the patient ages. Therefore, elderly HD patients need more social and mental support (4). The donor's age is 60 years and above is one of the extended donor criteria (EDC). Using kidneys with advanced age and EDC criteria in candidates of similar age may increase patient and graft survival and physical quality of life. For this reason, policies should be developed to ensure the transplantation of EDC grafts to patients who will benefit most.

A marginal liver graft with hyperbilirubinemia transplanted successfully by ischemia-free liver transplantation

The shortage of transplant organs remains a serious issue worldwide, and using liver grafts from extended criteria donors could expand the donor pool. Extended criteria donor liver allografts have a high chance of complications such as primary nonfunction, early allograft dysfunction, and ischemic-type biliary lesions. How to employ these extended criteria donors safely and effectively warrants further investigation. Herein, we report the successful use of a marginal donor liver with hyperbilirubinemia to save the life of an acute-on-chronic liver failure recipient using a new surgical technique: ischemia-free liver transplantation (IFLT). The graft was retrieved for transplantation due to the following reasons: (I) the recipient was in a life-threatening situation and no living donor donation candidate was available; (II) the graft was considered transplantable except for cholestasis; and (III) IFLT could reduce ischemia/reperfusion injury (IRI), resuscitate the allograft ex situ, and maintain organ viability before transplantation. The graft was transplanted successfully using the IFLT procedure. Although anatomic biliary stricture occurred after surgery, no IRI-related complications were found during the follow-up. The use of liver grafts from extended criteria donors is safe and effective under IFLT. Additional IFLT clinical studies need to be performed, particularly concerning donor management, graft selection, and ex situ resuscitation.

Coronary angiography utilization in the evaluation of a potential heart donor by age: a narrative review.

Heart transplant is the gold standard treatment for patients with heart failure. The limitation to providing heart transplantation to patients suffering from end stage heart disease is the stable organ supply within the United States despite increasing demand. Transplant centers across the United States have begun to expand traditional cardiac donor selection metrics previously utilized. As a result, the use of extended criteria donors, such as older donors, those with longer ischemic times, and donors considered high risk has increased. Current guidelines suggest that coronary angiography be performed when evaluating a donor above the age of 45. Angiographic guidelines for evaluation of the donor heart are based specifically on age, with little evidence based guidance surrounding the use of angiography in a younger donor with comorbidities or increased risk behavior which may lead to premature coronary artery disease. Recently, we have seen an increase in younger heart donors, many of whom have succumbed due to drug overdose with ensuing high risk behaviors. Given the increased risk nature of these donors, consideration of performing coronary angiography is determined by clinical “gestalt” of the transplant center evaluating the heart for use, which may lead to underutilization of donor organs without evidence to support the practice. Here, we review the guidelines, literature, and controversy surrounding the use of coronary angiography in evaluating donor hearts for transplantation.

Considering extended right lobe grafts as major extended donor criteria in liver transplantation is justified.

The outcomes of split-liver transplantation are controversial. This study compared outcomes and morbidity after extended right lobe liver transplantation (ERLT) and whole liver transplantation (WLT) in adults. MEDLINE and Web of Science databases were searched systematically and unrestrictedly for studies on ERLT and its impact on graft and patient survival, and postoperative complications. Graft loss and patient mortality odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Vascular and biliary complications, primary nonfunction, 3-month, 1-, and 3-year graft and patient survival, and retransplantation after ERLT and WLT were analyzed. The literature search yielded 10594 articles. After exclusion, 22 studies (n=75799 adult transplant patients) were included in the analysis. ERLT was associated with lower 3-month (OR=1.43, 95% CI=1.09-1.89, P=0.01), 1-year (OR=1.46, 95% CI=1.08-1.97, P=0.01), and 3-year (OR=1.37, 95% CI=1.01-1.84, P=0.04) graft survival. WL grafts were less associated with retransplantation (OR=0.57; 95% CI=0.41-0.80; P<0.01), vascular complications (OR=0.53, 95% CI=0.38-0.74, P<0.01) and biliary complications (OR=0.67; 95% CI=0.47-0.95; P=0.03). Considering ERLT as major Extended Donor Criteria is justified because ERL grafts are associated with vasculobiliary complications and the need for retransplantation, and have a negative influence on graft survival.

Tryptophan Metabolism via Kynurenine Pathway: Role in Solid Organ Transplantation.

Solid organ transplantation is a gold standard treatment for patients suffering from an end-stage organ disease. Patient and graft survival have vastly improved during the last couple of decades; however, the field of transplantation still encounters several unique challenges, such as a shortage of transplantable organs and increasing pool of extended criteria donor (ECD) organs, which are extremely prone to ischemia-reperfusion injury (IRI), risk of graft rejection and challenges in immune regulation. Moreover, accurate and specific biomarkers, which can timely predict allograft dysfunction and/or rejection, are lacking. The essential amino acid tryptophan and, especially, its metabolites via the kynurenine pathway has been widely studied as a contributor and a therapeutic target in various diseases, such as neuropsychiatric, autoimmune disorders, allergies, infections and malignancies. The tryptophan-kynurenine pathway has also gained interest in solid organ transplantation and a variety of experimental studies investigating its role both in IRI and immune regulation after allograft implantation was first published. In this review, the current evidence regarding the role of tryptophan and its metabolites in solid organ transplantation is presented, giving insights into molecular mechanisms and into therapeutic and diagnostic/prognostic possibilities.

Heart Retransplantation From an Hepatitis B Core Antibody (Anti-HBcore)–Positive Donor: A Case Report

Heart transplantation is performed in patients with end-stage heart failure. The number of suitable donors for patients on the urgent heart transplantation waiting list is still low, and effort has been made to increase the number of suitable donors, including extended-criteria donors. We present a case report of heart retransplantation because of graft failure from an hepatitis B core antibody (anti-HBcore–positive, HBcAb [+]) and HBs antigen–negative (HBsAg [-]) donor to a seronegative recipient. We show that the procedure, with the use of antiviral prophylaxis, is a safe option for the recipient. Based on anatomopathologic and histopathologic examination of the explanted graft, we also suggest that acute cellular rejection in the transplanted heart may exist despite negative findings in right-sided endomyocardial biopsy.

Assessing Kidney Graft Viability and Its Cells Metabolism during Machine Perfusion.

Kidney transplantation is the golden treatment for end-stage renal disease. Static cold storage is currently considered the standard method of preservation, but dynamic techniques, such as machine perfusion (MP), have been shown to improve graft function, especially in kidneys donated by extended criteria donors and donation after circulatory death. With poor organ quality being a major reason for kidneys not being transplanted, an accurate, objective and reliable quality assessment during preservation could add value and support to clinicians’ decisions. MPs are emerging technologies with the potential to assess kidney graft viability and quality, both in the hypothermic and normothermic scenarios. The aim of this review is to summarize current tools for graft viability assessment using MP prior to implantation in relation to the ischemic damage.

Urological Complications in Kidney Transplant Recipients: Analysis of the Risk Factors and Impact on Transplant Outcomes in the Era of “Extended Criteria Donors”

Urological complications (UC) following kidney transplantation (KT) are associated with increased morbidity. The aim of this study is to evaluate the risk factors for UC in the era of “extended criteria donors” (ECD) and their impact on patient and graft survivals. A retrospective monocentric study of all patients undergoing KT from 2010 to 2019 with a follow-up ≥30 days was performed. Out of 459 patients (males: 296 (64.5%); age: 57 (19–77) years) enrolled, 228 (49.7%) received ECD organs, moreover, 166 (67.2%) grafts had a cold ischemia time ≥10 h. UCs were reported in 32 (7%) patients. In 21 (65.6%) cases UC occurred within 3 months post-KT and 24 (5.2%) were associated with early urinary tract infection (UTI). The overall 5 year patient and graft survival rates were 96.5% and 90.6%, respectively. UC decreased graft survival (UC-group: 75.0% vs. noUC-group: 91.8%, p &lt; 0.001), especially if associated with early UTI (UC-group: 71.4% vs. noUC-group: 77.8%, p &lt; 0.001). At multivariate analysis, early UTI after KT (OR: 9.975, 95%-IC: 2.934–33.909, p &lt; 0.001) and delayed graft function (DGF) (OR: 3.844, 95%-IC: 1.328–11.131, p: 0.013) were significant risk factors for UC, while ECD graft did not increase the risk of post-transplant UC. ECD grafts are not associated with UC. DGF and early UTI post-KT increase the risks of UC and reduce graft survival in the long-term. Therefore, aggressive management of early post-transplant UTI and strategies to reduce DGF incidence, such as machine preservation, are essential to prevent UC after KT.