Donation After Cardiac Death Research Articles

Rupture of the Ascending Aorta in a Donor Heart during Ex-Vivo Transport: A Case Report

<h3>Purpose</h3> Problems encountered during transport of an ex-vivo donor heart perfusion device can have drastic consequences on graft function. We describe a case of aortic rupture occurring during ex-vivo transport for donation after cardiac death (DCD) heart transplantation. <h3>Methods</h3> Cardiac procurement in a DCD donor was performed in the standard fashion. Upon connection to the Transmedics Organ Care System, bleeding was noted to be originating from the posterior aortic wall, likely secondary to injury caused by the cardioplegia needle, inserted into the flaccid aorta of relatively small diameter. The site was successfully repaired and transport begun. The aorta was noted to be fragile during repair. Organ function parameters remained in the acceptable ranges throughout the transfer. <h3>Results</h3> As the transport vehicle approached the recipient center, an abrupt movement of the vehicle over a speed hump was followed by sudden drop in the perfusion pressure of the donor heart. Catastrophic bleeding was noted from a defect in the ascending aorta. Bleeding was controlled with digital pressure resulting in return of satisfactory perfusion pressures. The donor heart had minimal perfusion pressure for a total of five minutes. The donor heart was transported on the OCS emergently to the operating room where cardioplegia was delivered and the organ topically cooled. A defect adjacent to the original repair site was noted (image). As this was 2cm above the sinotubular junction, this area was trimmed and the heart was implanted in the standard fashion. Subsequent graft function was good, and the recipient was separated from cardiopulmonary bypass with routine levels of support. The recipient made an uneventful post-operative recovery. <h3>Conclusion</h3> This case illustrates an injury to the posterior wall of the aorta with subsequent major bleeding occurring during ex-vivo transport. Procurement teams should be familiar with the process of emergent conversion to conventional cold static preservation during organ transport.

Effects of SP600125 and hypothermic machine perfusion on livers donated after cardiac death in a pig allograft transplantation model

BackgroundHypothermic machine perfusion (HMP) improves the quality of donor livers for transplantation, both in animal models and in clinical practice. Treatment with SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), can suppress the JNK signaling pathway to alleviate donor liver ischemia–reperfusion injury (IRI). We performed the present study with the objective of exploring the protective effects exerted by a combination of HMP and SP600125 on liver xenograft viability for donation after cardiac death (DCD) in a porcine model.Methods54 adult BAMA mini-pigs were randomly assigned to 5 groups, including sham, cold storage for 4 h (CS 4 h), CS 4 h + SP600125, CS 2 h + HMP 2 h, and CS 2 h + HMP 2 h + SP600125 groups. Donor livers in the CS 4 h and CS 4 h + SP600125 groups were conventionally cold preserved for 4 h, whereas donor livers in the CS 2 h + HMP 2 h and CS 2 h + HMP 2 h + SP600125 groups were cold preserved for 2 h and then treated with HMP for 2 h. The preservation and perfusion solutions contained SP600125 (20 µM). Follow-up was conducted for 5 days after liver transplantation to compare the surgical outcomes by means of serological examination, pathological results, and survival rate.ResultsThe most satisfactory outcome after liver transplantation was observed in the CS 2 h + HMP 2 h + SP600125 group, which presented with minimal damage of donor livers during 5 days’ follow-up. Additionally, serological examination, pathological results, and survival rate concurred in showing better results in the CS 2 h + HMP 2 h ± SP600125 group than in the CS 4 h ± SP600125 group.ConclusionHMP in combination with SP600125 has hepatoprotective properties and improves the quality and viability of porcine livers collected after DCD, thus improving prognosis after liver transplantation.

Robotic hepaticojejunostomy for biliary stricture after liver transplantation: technical description and case series

Presenter: Jason Hawksworth MD | MedStar Georgetown University Hospital Background: Biliary strictures after liver transplantation are common and when refractive to endoscopic and percutaneous intervention require surgical biliary revision. Traditional open biliary revision may result in substantial wound morbidity and prolonged hospitalization in this high-risk population. Robotic technology facilitates minimally invasive biliary reconstruction and has not previously been described following liver transplantation. Methods: A brief description of the robotic approach is as follows: Peritoneal access is obtained at the umbilicus and a 12mm assist port is placed. Robotic ports are placed across the mid abdomen parallel to the umbilical port including 3x 8mm ports and 1x 12mm port. Lysis of adhesions is performed until the liver hilum is isolated. The bile duct is encircled and the stricture resected until healthy appearing donor bile duct is visualized. The hilar inflow structures are carefully preserved during this dissection. The inframesocolic compartment is exposed and the first jejunal loop divided with the robotic stapler. The roux limb is routed retrocolic and an isoperistaltic end-to-side jejunojejunostomy created with the robotic stapler. The common enterotomy is closed with running suture. Attention is returned to the liver hilum where an end-to-side hepaticojejunostomy is created with interrupted monofilament suture. Ultrasound is used during the case to aid in identification of the hilar structures and at the end of the case to confirm patency of the hepatic artery. The robotic cases were retrospectively compared to historical open cases over a time period from May 2013 to October 2020, including demographics, perioperative complications and outcomes. All patients had at least 3 months follow up. Results: During the study period there were 3 robotic and 4 open surgical biliary revisions. All cases were hepaticojejunostomies for choledochocholedochostomy related anastomotic strictures. In one robotic case involving a donation after cardiac death (DCD) graft, the bile duct was also noted to be sclerotic up to the liver hilum and the anastomosis was fashioned to the right and left hepatic ducts. In all cases the biliary strictures presented >90 days after transplant and were refractive to multiple endoscopic and percutaneous interventions. Median (range) case time was longer the in the robotic (373 minutes (286-373)) compared to open (280 minutes (163-321)) group. Blood loss was minimal ( < 50mL) in all robotic and open cases. The median length of stay was lower in the robotic (4 days (1-4)) compared to open (7 days (4-10)) group. Morbidity included 2 wound infections in the open group (grade 2), 1 gastrointestinal bleed requiring a blood transfusion in the robotic group (grade II), 1 infected hematoma in the robotic group (grade IIIa) and 1 bile leak on the open group (grade IIIa). Nadir bilirubin was similar between the robotic (0.2 (0.2-0.3)) and the open (0.3 (0.2-0.4)) group. Nadir alkaline phosphatase was also similar between the robotic (154 (92-245)) and the open (132 (72-166)) groups. There was no mortality in either group. Conclusion: Robotic biliary revision is a safe alternative to traditional open surgery for refractive biliary strictures after liver transplantation.

Fast Vascular Reconstruction With Magnetic Devices in Liver Transplant: A Novel Surgical Technique.

Minimizing the anhepatic period is critical to reduce allograft dysfunction, intestinal bacterial translocation, and acute liver failure among liver transplant (LT) recipients. The current study introduced a new surgical technique for fast major vascular reconstruction by utilization of magnetic devices in recipients. A prospective study was conducted among patients who underwent orthotopic LT using Donation after Cardiac Death (DCD) between November 2018 and December 2019. The procedures of magnetic-assisted LT was clinically performed and introduced. In brief, three pairs of C-shaped magnetic rings and matched base members were placed and fixed in the stump of supra- and infra-hepatic inferior vena cava, as well as portal vein of the donors and recipients. The donor liver was implanted, and the magnet rings at the donor and recipient vessels attached immediately for a rapid reconstruction. Final continuous suture of the vessels was then performed under restoration of the blood flow. A total of six patients were finally enrolled in magnetic-assisted LT. The median age of the recipients was 40.0 (IQR 37.0-49.3) years, and all were male patients as well. The median anhepatic time of patients undergoing magnetic-assisted LT was 10.3 min (IQR 9.5-13.2 min). With a median follow-up of 10.5 (range 7.2-19.8) months, all patients recovered well with normal liver function. Two patients had experienced partial portal vein thrombosis or acute rejection, respectively, which were unrelated to the surgical techniques, and treated successfully. The magnetic-assisted vascular anastomosis shortened the anhepatic phase to only about 10 min during LT. Fast revascularization of the donor liver by using the novel magnetic technique is safe and feasible in LT.

Update on liver transplantation-newer aspects

Liver transplantation (LT) remains the only therapeutic option offering gold standard treatment for end-stage liver disease (ESLD) and acute liver failure (ALF), as well as for certain early-stage liver tumors. Currently, the greatest challenge facing LT is the simple fact that there are not enough adequate livers for all the potential patients that could benefit from LT. Despite efforts to expand the donor pool to include living and deceased donors, organ shortage is still a major problem in many countries. To solve this problem, the use of marginal liver grafts has become an inevitable choice. Although the definition of marginal grafts or criteria for expanded donor selection has not been clarified yet, they are usually defined as grafts that may potentially cause primary nonfunction, impaired function, or late loss of function. These include steatotic livers, older donors, donors with positive viral serology, split livers, and donation after cardiac death (DCD). Therefore, to get the best outcome from these liver grafts, donor-recipient selection should be vigilant. Alcohol-related liver disease (ALD) is one of the most common indications for LT in Europe and North America. Traditionally, LT for alcoholic liver disease was kept limited for patients who have achieved 6 months of abstinence, in part due to social and ethical concerns regarding the use of a limited resource. However, the majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. Besides, the initial results of early liver transplantation (ELT) without waiting for 6 months of abstinence period are satisfactory in severe alcoholic hepatitis (SAH). It will be important to take care of these patients from a newer perspective.

Assessing the Outcome of Adult Kidney Transplantation from a Deceased Expanded Criteria Donor: A Descriptive Study.

BackgroundEnd-stage renal disease (ESRD) creates a great burden on the quality of life. Patients after kidney transplantation have been reported to have a greater quality of life and better outcomes health outcomes. Therefore, it is important to optimize the best method of following well-constructed criteria such as the expanded criteria donor (ECD) to reduce the chances of rejection rate and deaths post-transplantation particularly in elderly patients in conjunction with the kidney profile donor index (KDPI).MethodsThis is a retrospective descriptive study of all patients who received kidney transplantation from a deceased donor from the ECD as well as ECD with donation after cardiac death (DCD) at St. Joseph Health Care Hospital over a 24 month time period from January 2017 to January 2019. All adult recipients from standard criteria donor (SCD) and living donors were excluded from the study.ResultsThe study included 60 patients with 36 (60%) from the ECD and 24 (40%) were from the ECD/DCD group. The most common cause of ESRD among recipients was diabetes mellitus (DM) involving 23 (38.3%) of the patients. The creatinine outcome was the highest in the ECD/DCD group at one month (211 ± 71) and the lowest creatinine recorded was also in the ECD/DCD at 12 months (160 ± 78). Lastly, only four patients died in 12 months and only six recipients reported graft loss over 12 months.ConclusionDescriptive data of the included ECD/DCD showed increase trend in survivability of the recipients when used among the elderly, giving us more insight on the benefits of ECD/DCD transplantation.

Nonanastomotic Biliary Strictures After Liver Transplantation.

Biliary strictures constitute a major source of morbidity and mortality following liver transplantation (LT). However, studies on the impact of nonanastomotic biliary strictures (NABS) on grafts after LT are limited. 649 patients who underwent LT between January 2013 and June 2017 at our center were retrospectively analyzed and 2.6% (n = 17) of the recipients developed NABS following LT. There were no differences between recipients with and without NABS in indication of LT, graft ischemia time, and type of biliary anastomosis. The incidence of post-LT hepatic artery thrombosis (HAT) (odds ratio [OR]: 15.75, P < .001) and the use of livers from donation after cardiac death (DCD) donors (OR: 8.292, P = .004) were identified as independent significant predictors of NABS by multivariate analysis. Graft survival in those with NABS was significantly worse than in patients without NABS (1-, 3-, and 5-years survival: 64.7%, 57.5%, 0%, vs. 89.8%, 84.0%, 76.4%, P < .001). In conclusion, while the incidence of NABS in our study was relatively low compared to previous reports, NABS was still found to be associated with poor graft survival. Special attention should be paid to NABS occurrence in grafts that develop HAT as well as those from DCD donors.

Simultaneous liver-kidney transplantation from donation after cardiac death donors: an updated perspective.

Outcomes of both donation after cardiac death (DCD) liver and kidney transplants are improving. Experience in simultaneous liver-kidney transplant (SLK) using DCD donors, however, remains limited. In an updated cohort (2010-2018), outcomes of 30 DCD SLK and 131 donation after brain death (DBD) SLK from Mayo Clinic Arizona and Mayo Clinic Minnesota were reviewed. The Model for End-Stage Liver Disease score was lower in the DCD SLK group (23 vs 29, P=.01). Kidney delayed graft function (DGF) rates were similar between the 2 groups (P=.11), although the duration of DGF was longer for DCD SLK recipients (20 vs 4days, P=.01). Liver allograft (93.3% vs 93.1%, P=.29), kidney allograft (93.3% vs 93.1%, P=.91), and patient (96.7% vs 95.4%, P=.70) 1-year survival rates were similar. At 1 year, there were no differences in the estimated glomerular filtration rate (57.7±18.2 vs 56.3±17.7, P=.75) or progression of fibrosis (ci) on protocol kidney biopsy (P=.67). A higher incidence of biliary complications was observed in the DCD SLK group, with ischemic cholangiopathy being the most common (10.0% vs 0.0%, P=.03). The majority of biliary complications resolved with endoscopic management. With appropriate selection, DCD SLK recipients can have results equivalent to those of DBD SLK recipients.

Liver transplantation using grafts from donors after circulatory death - the first Czech Republic experience.

Liver transplantation is established as alifesaving procedure for patients with acute and chronic liver failure, as well as certain selected malignancies. Due to acontinuing organ shortage and ever-growing patient waiting lists, donation after cardiac death (DCD) is becoming more frequently utilized in order to close the gap between &#8220;supply and demand&#8221;. Aretrospective analysis of DCD and subsequent liver transplantations was performed. From May 2016 to September 2019, atotal of 9 DCD liver transplantations were performed in our institution. All cases except one were primary liver transplantations. The recipients comprised 5 (56%) males and 4 (44%) females. The mean DCD donor age was 41±12 (22-57) years, with ventilation duration of 7±1 days and warm ischemia time 19±3 minutes. The average recipient age was 51±22 (4-73) years, with an average cold ischemia 3h:59m±27m and manipulation time of 23±5 minutes. Periprocedural mortality was 1 (11%). Hepatitis C recurrence was documented in 1 (11%) patient. The mean follow-up time was 19±13 (7-37) months. Until now, we have not observed any signs of ischemic cholangiopathy. DCD liver transplantation allows us to enlarge the pool of potential liver grafts, thus decreasing the time spent on the liver recipient waiting list. This paper documents the first series of DCD liver transplantations in the Czech Republic.

Liver Transplantation in a Patient With Acute-on-Chronic Liver Failure Due to Traditional Chinese Medicine Intoxication Using Donation After Circulatory Death From a Renal Transplant Recipient: A Case Report

Acute-on-chronic liver failure (ACLF) is a clinical manifestation of acute liver failure and decompensation on the basis of chronic liver disease. To date, hepatitis B virus–related ACLF is still the main cause of liver failure in China. Liver transplantation is currently the most likely treatment option to cure ACLF, but the shortage of donor livers is a barrier to its widespread use. The shortage of organs has led to increased use of expanded-criteria donors (ECDs), that is, donation after cardiac death (DCD) and its variant donation after brain and cardiac death (DBCD-China, DCBD-Switzerland). Here we report a case of liver transplantation, whose recipient was diagnosed with ACLF as a result of use of traditional Chinese medicine while the donor liver was retrieved from a renal transplant patient 4 years after transplantation. This transplant was carried out in accordance with the Helsinki Congress and the Declaration of Istanbul.

Outcomes of liver transplantation using moderately steatotic liver from donation after cardiac death (DCD).

BackgroundLiver grafts from donation after cardiac death (DCD) with moderate steatosis (MS) are generally considered unsui for liver transplantation (LT) because DCD and MS are independent risk factors of poor prognosis of LT. Many centers have begun to accept this type of liver graft. However, the clinical outcomes are indeed controversial. This study aimed to examine the outcomes after LT of using such liver grafts.MethodsThis study retrospectively reviewed our experiences in 80 allografts from May 2015 to September 2019. A total of 16 allografts using MS liver grafts from DCD (MS-DCD group) were compared with a matched control group of 64 allografts using a nonsteatotic liver graft (NS group) (1:4 ratio). Postoperative outcomes, including primary nonfunction (PNF), initial poor function (IPF), postoperative complications, and graft/patient survival rates, were extracted for pooled analysis.ResultsRecipient and surgical characteristics of patients and clinical data of donors between MS-DCD group and NS group were balanced. No significant differences were observed in hepatitis B virus (HBV) infection, model for end-stage liver disease (MELD) score, cold ischemia time (CIT), donor risk index, warm ischemia time (WIT). A significant difference was detected in the incidence of initial poor function (IPF) (11/16 vs. 26/64; P=0.02), and the average peak value of aspartate transaminase (AST) (3,469 vs. 1,295; P<0.01) was significantly higher in the steatosis group. Meanwhile, alanine transaminase (ALT) was only higher on day 1, and international normalized ratio (INR) level was only higher on days 1 and 3 and disappeared on day 7. The serum total bilirubin (TB) was the same between the two groups. Postoperative complications were similar between the two groups. The 90-day, 1-year, and 3-year survival rates in patients and grafts between the two groups were similar (patient survival(MS-DCD group vs. NS group): 75% vs. 85.9%, 75% vs. 78.1%, 68.8% vs. 71.9%, log-rank test, P=0.77; graft survival(MS-DCD group vs. NS group): 75% vs. 84.4%, 75% vs. 75%, 68.8% vs. 68.8%, log-rank test, P=0.79).ConclusionsAfter rigorous evaluation, it was found that moderately steatotic liver from DCD is an effective means to expand the source of liver supply.

EFFICACY AND SAFETY OF ISLET TRANSPLANTATION IN PATIENTS WITH TYPE 1 DIABETES: A JAPANESE SINGLE-CENTER EXPERIENCE

Background: Pancreatic islet transplantation (ITx) provides a treatment option for patients with type 1 diabetes (T1D); the clinical results have improved with the introduction of improved immunosuppressive therapies. In Japan, the number of ITxs is small because of donor shortage, and ITx has been performed using the pancreas provided by “marginal” donors, such as donors after cardiac death (DCD) and elderly donors. We report the efficacy and safety of ITx at a single-center in Japan. Methods: Five C-peptide negative T1D patients with severe hypoglycemic events (SHE) received 2–3 intraportal allogeneic ITxs and received immunosuppressive agents, including antithymocyte globulin, tacrolimus, and mycophenolate mofetil from 2012 to 2019. We assessed sustained islet graft function duration, glycemic control, SHE, and post-transplant complications. Results: Thirteen islet isolations were performed from two DCD and 11 who were donors after brain death, and 12 preparations met the transplant criteria. The mean age of the donors was 45.5 years, and the cold ischemia time was 387 ± 89 min. Patients received a mean total number of islet equivalent (IEQ)/body weight(kg) of 19,406 IEQ/kg in 2 (n = 3) or 3 (n = 2) ITxs. The portal vein pressure after transplantation was 10.8 ± 4.4 mmHg (change in portal vein pressure was + 2.6 ± 1.7 mmHg). No complications associated with intraportal transplantation, such as liver dysfunction, intraperitoneal hemorrhage, or portal vein embolism was observed. One patient experienced graft rejection at 26 months after the transplantation, with islet graft survival being observed in the other 4 patients (follow-up: 16–54 months). It is noteworthy that these patients had almost normal glycosylated hemoglobin and creatinine levels. Moreover, 2 patients (40%) in the recent ITx group achieved insulin independence, and SHE was resolved in all recent ITx group recipients. As an adverse event, severe leukopenia was temporarily observed in one patient. No infectious complications occurred in any patient. Conclusion: ITx is considered a highly safe treatment with good clinical results, even in Japan, where there are few donors, and donor conditions are marginal. The future goal is to achieve a higher insulin independent rate and evaluate the long-term outcomes.

MITOCHONDRIAL METABOLISM IS PRESERVED FOLLOWING NORMOTHERMIC EX-VIVO KIDNEY PERFUSION OF GRAFTS PROCURED FOLLOWING CARDIAC DEATH

Background: Normothermic ex-vivo kidney perfusion (NEVKP) preservation has demonstrated superior graft outcomes for kidneys procured following donation-after-cardiac death (DCD) over static cold storage (SCS). To determine the mechanisms for this advantage, we compared the transcriptome from both groups through an unbiased genome-wide microarray analysis. Methods: Kidneys from 30kg Yorkshire pigs were subjected to 30min of warm ischemia and then 8hrs of pressure-controlled NEVKP or SCS prior to heterotopic autotransplantation. Renal biopsies were collected on POD3 and RNA transcript expression was determined utilizing the Affymetrix GeneChip® Porcine Gene 1.0 ST Array platform examining over 23,000 transcripts. Gene set enrichment analysis (GSEA) was completed using the Hallmark gene sets and Gene Ontology (GO) pathways. Results: NEVKP-stored grafts demonstrated parameters associated with improved post-transplant graft function including lactate clearance (0hr:10.29+/-0.48mmol/L vs 8hr:1.67+/-0.67mmol/L,n=5,p<0.01), decreasing intra-renal resistance (0hr:1.63+/-0.20mmHg/mL/min vs 8hr:0.41+/-0.13 mmHg/mL/min,n=5,p<0.01), and continuous urine production. Graft function was significantly improved with NEVKP compared to SCS following transplantation with lower peak serum creatinine (POD1:4.0+/-1.15mg/dL vs POD3:12.0+/-0.78mg/dL,n=5,p<0.01) and higher creatinine clearance on POD3 (39.6+/-11.8mL/min vs 2.6+/-0.9ml/min,n=5,p<0.01). GSEA demonstrated 11 Hallmark Gene Sets enriched in NEVKP compared to SCS including sets associated with fatty-acid metabolism and oxidative phosphorylation, while 7 Gene Sets were enriched in SCS compared to NEVKP (FDR-value<0.25,p<0.05). GO analysis demonstrated pathways associated with lipid oxidation/metabolism, the Krebs cycle, and pyruvate metabolism enriched in NEVKP vs SCS (FDR-value<0.05) Conclusions: NEVKP maintained or enriched transcripts of key mitochondrial metabolic pathways compared to SCS in grafts procured following DCD, likely accounting for the improved post-transplant graft function.

PULSATILE PERFUSION IN PEDIATRIC KIDNEY TRANSPLANTATION

Introduction: Pulsatile perfusion of deceased donor kidneys is commonly practiced in adult kidney transplantation. We examined the practice of pulsatile perfusion in pediatric patients undergoing kidney transplantation and compared outcomes from preservation using pulsatile perfusion (PUMP) and static cold storage (COLD) in pediatric recipients. Methods: The UNOS database was used to determine outcomes in all pediatric kidney recipients (<18 years) who were transplanted between 1994—2018. Living donor and multi-organ transplant recipients were excluded. Patients were divided according to preservation method into PUMP or COLD groups. Donor and recipient demographic data were examined, as were survival and outcomes. A p-value of <0.05 was considered to be significant. Results: There were 10,045 pediatric kidney transplants performed during the study period, of which 1,619 were PUMP (16.1%) and 8,426 were COLD (83.9%). PUMP donors were significantly younger (22.7 vs. 23.8 years), had a higher KDPI (22.4% vs. 19.7%), longer cold storage time (18.8 vs. 14.1 hours), more frequent donation after cardiac death (DCD) donor status (12.9% vs. 1.3%), and more likely to be an increased risk of disease (IRD) transmission donor (9.1% vs. 4.8%). PUMP kidneys were also more likely to have been biopsied (18.1% vs. 3.3%). There were no differences in donor creatinine (0.99 vs. 0.96 mg/dL). Recipients of PUMP kidneys were significantly older (12.0 vs. 11.6 years), had a shorter wait time (287.7 vs. 320.2 days), and greater HLA mismatch (4.5 vs. 4.3). There were no differences in BMI, initial or final cPRA, length of stay, or serum creatinine at the time of discharge (1.42 vs. 1.42 mg/dL). No differences in allograft survival at 10 years were noted between PUMP and COLD groups (Figure 1). Additionally, delayed graft function (DGF) occurrence (8.5% vs. 12.5%, p<0.05) and rejection rate in the initial 12 months post transplant (11.5% vs. 13.8%) were significantly lower in the PUMP group compared with the COLD group.Conclusions: Despite multiple unfavorable characteristics noted in PUMP donors, recipients of these kidneys have no difference in allograft survival and have a lower DGF rate. These data support the utilization of pulsatile perfusion during the evaluation of higher risk pediatric kidney donors and a possible role in improving outcomes for pediatric kidney transplantation.

OLDER LIVERS SHOULD NOT BE UTILIZED IN PEDIATRIC LIVER TRANSPLANTATION

Introduction: Organ scarcity in liver transplantation has required expansion of the acceptable criteria used for donor selection. The utilization of older donors (>60 years) has become common practice in adult liver transplantation. We examined outcomes in pediatric liver transplantation where recipients received a liver from a donor >60 years in age. Methods: The UNOS database was used to identify all pediatric liver transplant recipients (<18 years) transplanted between 1987—2018. Only recipients of solitary, deceased donor organs were included. Pediatric recipients were grouped according to donor age; <60 years (YOUNG) and >60 years (OLD). Donor and recipient demographic data were examined, as were survival and outcomes. A p-value of <0.05 was considered to be significant. Results: Of 15,448 pediatric transplants, 71 received an OLD liver while 15,377 received a YOUNG liver. Donors were significantly older in the OLD group (67.3 vs. 11.7 years), with higher BMI (24.1 vs. 19.5 kg/m2), more frequently Caucasian (85.9% vs. 62.6%) and female (62.0% vs. 41.2%) compared with YOUNG donors. Cause of death was frequently a cerebrovascular accident (85.9% vs. 12.5%) in OLD donors. There were no differences in cold ischemia time, biopsy fat content, or transaminases. OLD donors were not donation after cardiac death (DCD) donors. Recipients of OLD livers were significantly older (11.3 vs. 5.1 years), had a shorter wait time (23.5 vs. 148.5 days), increased BMI (21.1 vs. 18.3 kg/m2), and higher initial and final PELD/MELD scores (34 vs. 12 initial; 31 vs. 14 final). OLD donors were more likely to have used in treatment of fulminant hepatic failure (FHF, 74.7% vs. 35.1%). In addition, recipients of older livers were more likely to be on life support (62.0% vs. 16.6%) or the ventilator (57.8% vs. 13.8%), have had dialysis in the week prior to transplant (9.9% vs. 5.0%) and to have had a previous liver transplant (23.4% vs. 13.8%). Importantly, allograft survival in recipients of OLD livers were found to be significantly diminished when compared to YOUNG livers (Figure 1).Conclusions: Pediatric recipients of older liver allografts are significantly sicker than those who receive younger allografts. Allograft survival, however, was greatly reduced when compared to younger allografts. Use of older liver donors should be avoided, especially in younger or fulminant recipients.

Cell-free DNA in human ex vivo lung perfusate as a potential biomarker to predict the risk of primary graft dysfunction in lung transplantation

BackgroundCell-free DNA (cfDNA), such as mitochondrial DNA (mtDNA) and nuclear DNA (nuDNA), are known to be released from injured cells and as such have been explored as biomarkers for tissue injury in different clinical settings. Ex vivo lung perfusion (EVLP) has been developed as an effective technique for marginal donor lung functional assessment. We hypothesized that the level of cfDNA in EVLP perfusate may reflect tissue injury and thus can be developed as a biomarker to quantify the degree of donor lung injury or predict the development of primary graft dysfunction (PGD) after lung transplantation (LTx). MethodsThe perfusate from 62 donor lungs transplanted at our institution between May 2010 and December 2015 was sampled for cfDNA at 1 and 4 hours of perfusion. Sequences of genes encoding nicotinamide adenine dinucleotide dehydrogenase 1 (NADH-1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were used to represent mtDNA and nuDNA, respectively. Levels were quantified by real-time polymerase chain reaction and correlated with clinical outcome after LTx. ResultsIn our entire cohort, 14 patients developed PGD grade 3 (PGD3) within 72 hours after LTx. The non-PGD group included 48 patients (PGD0-1). Concentrations of mtDNA in the perfusate of the PGD3 group were significantly higher than those in non-PGD group at 1 hour of EVLP (1874 ± 844 vs 1259 ± 885 copies/μL; P = .011). The perfusate of the PGD3 group had significantly higher levels of nuDNA compared with the non-PGD group at both 1 hour (1498 ± 1895 vs 675 ± 391 copies/μL; P = .008) and 4 hours (4521 ± 5810 vs 1764 ± 1494 copies/μL; P = .001). In donation after cardiac death (DCD) cases, mtDNA levels were significantly higher in the PGD3 group compared with the non-PGD group at 1 hour of EVLP (2060 ± 997 vs 1184 ± 782 copies/μL; P = .040), and the levels of nuDNA were significantly higher in the PGD3 group compared with the non-PGD group at both 1 hour (1021 ± 495 vs 606 ± 305 copies/μL; P = .041) and 4 hours (2358 ± 1028 vs 1185 ± 967 copies/μL; P = .006). In donation after brain death (DBD) cases, cfDNA scores did not show a significant difference. ConclusionsWe found that the amount of cfDNA, especially nuDNA, in EVLP perfusate was higher in the severe PGD group (PGD3) compared with the non-PGD group. This proof-of-concept study supports the concept that the analysis of cfDNA levels in EVLP perfusate can help estimate the damage to donor lungs before implantation. Larger studies are needed to validate this concept.

Novel oxygenation technique for hypothermic machine perfusion of liver grafts: Validation in porcine Donation after Cardiac Death (DCD) liver model

BackgroundHypothermic oxygenated machine perfusion improves outcomes in Liver Transplantation, but application is limited as O2 is supplied by a stationary circuit. A novel technique of O2 “pre-charge” in a portable pump would broaden use and further mitigate ischemia damage from organ transport. MethodsPorcine DCD livers were randomized to static cold storage (SCS, n = 8) or hypothermic machine perfusion (HMP). HMP was stratified into HMP-O2 (n = 5), non-O2 open to air HMP-RA (n = 5), and non-O2 with sealed lids or no air HMP-NA (n = 5). HMP-O2 was “pre-charged” using 100% O2 delivered at 10 L/min over 15 min. Perfusate and tissue O2 tension (pO2), liver biopsies, and fluid chemistries were analyzed. Results“Pre-charge” achieves sustained tissue and perfusate pO2 vs others. HMP-O2 results in decreased markers of hepatocyte injury: ALT (p < 0.05) and LDH (p < 0.05), lower expression of CRP and higher expression of SOD1 vs SCS. This suggests decreased inflammation and improved ROS scavenging. Conclusions“Pre-charge” is an effective technique, which allows portability and transport without an O2 source and improves graft parameters.

Making Every Liver Count: Increased Transplant Yield of Donor Livers Through Normothermic Machine Perfusion.

Normothermic machine perfusion (NMP) enables optimized ex-vivo preservation of a donor liver in a normal physiologic state. The impact of this emerging technology on donor liver utilization has yet to be assessed. NMP of the donor liver and ex-vivo enhancement of its function has been envisioned for decades, however only with recent technological advances have devices been suitable for transition to clinical practice. The present study examines the effect NMP on liver utilization in the United States. The United Network for Organ Sharing database was queried to identify deceased donor livers procured from 2016 to 2019 (n = 30596). Donor livers were divided by preservation method: standard cold-static preservation (COLD, n = 30,368) versus NMP (n = 228). Donor and recipient risk factors, liver disposition, and discard reasons were analyzed. The primary outcome was liver discard rate between 2 groups. A total of 4037 livers were discarded. The NMP group had a 3.5% discard rate versus 13.3% in the COLD group (P < 0.001), and this was despite NMP donors being older (47.7 vs 39.5 years, P < 0.0001), more frequently donation after cardiac death (DCD) (18% vs 7%, P < 0.001), and having a greater donor risk index (1.6 vs 1.5, P < 0.05). The most common reasons for liver discard in the COLD group were biopsy findings (38%), DCD warm ischemic time (11%), and prolonged preservation time (10%). Survival analysis, following propensity score matching, found no significant difference in 1-year overall survival between recipients of NMP versus COLD livers. NMP reduces the discard rate of procured livers despite its use in donors traditionally considered of more marginal quality. NMP maintains excellent graft and patient survival. Broader application of NMP technology holds the potential to generate a significant number of additional liver grafts for transplantation every year, thus greatly reducing the nationwide disparity between supply and demand.

Pancreas preservation: clinical practice and future developments.

To summarize recently published studies of preservation strategies including machine perfusion in pancreas transplantation. The shortage of conventional donors is leading units to use extended criteria donors (ECDs) and donors after cardiac death (DCD). Static cold storage (SCS) is still the standard method of preservation for pancreases and University of Wisconsin remains the gold standard preservation solution. In experimental studies, oxygen delivered during preservation reduced tissue injury and improved islet cell yield and function. Hypothermic machine perfusion of discarded human pancreases has been shown to improve adenosine triphosphate levels without adversely effect histology and oedema compared with SCS. Normothermic machine perfusion of discarded human organs has so far been challenging and led to increasing injury, rather than preservation. There are currently no clinical studies in pancreas transplant with the exception of a small number of pancreases being transplanted following normothermic regional perfusion. The storm of new organ preservation methods is now being more widely studied in the pancreas, with some promising results. These new strategies have the potential to allow expansion of the donor pool and greater utilization of ECD and DCD organs.

4139 Risk Aversion in Lung Transplantation: Organ Procurement Organizations Differ in Willingness to Pursue Non-ideal Donor Organs

OBJECTIVES/GOALS: Lung transplant (LTx) candidates benefit from use of non-ideal donor organs. Each organ procurement organization (OPO) defines “acceptable” donor organs introducing unmeasured variation in donor pursuit. We characterized non-ideal donor pursuit among OPOs to identify drivers of risk aversion in LTx. METHODS/STUDY POPULATION: We queried the UNOS registry for adult donors who donated ≥1 organ for transplantation from 12/2007-12/2018. Non-ideal donors were those with any of age&gt;50, smoking history ≥20 pack-years, PaO2/FiO2 (P/F) ratio&lt;350, donation after cardiac death (DCD) status, or CDC increased risk (IRD) status. Non-ideal donor pursuit rate was defined as the proportion of non-ideal donors at each OPO from whom consent for lung donation was requested with lower numbers indicating increased risk aversion. We estimated the correlation between non-ideal and overall donor pursuit using a Spearman correlation coefficient. Adjusted non-ideal donor pursuit rates were estimated using multivariable logistic regression. RESULTS/ANTICIPATED RESULTS: Overall, 18,333 deceased donors were included and classified as ideal or non-ideal. Among 58 OPOs, rates of non-ideal donor pursuit ranged from 0.24-1.00 Figure). Of 5 non-ideal characteristics, DCD and IRD status were associated with the most and least risk aversion, respectively. Non-ideal donor pursuit was strongly correlated with overall donor pursuit (r = 0.99). On adjusted analysis, older age (OR 0.15, 95% CI 0.13-0.16), smoking history (OR 0.38, 95% CI 0.34-0.44), low P/F ratio (OR 0.12, 95% CI 0.11-0.14), and DCD status (OR 0.04, 95% CI 0.03-0.04) were all independently associated with significant risk aversion, corresponding to decreased rates of donor pursuit. DISCUSSION/SIGNIFICANCE OF IMPACT: OPOs differ in their levels of risk aversion in LTx and risk aversion is not uniform across selected categories of non-ideal lung donor. Consideration of new OPO performance metrics that encourage the pursuit of non-ideal lung donors is warranted.