Prolonged Cold Ischemia Time Research Articles

Impact of Cold Ischemia Time and Donor Age on Donation After Circulatory Death Kidney Transplant Outcomes: A UNOS Mate-Kidney Analysis.

The association between prolonged cold ischemia times (CIT), donor age, and outcomes in kidney transplant recipients (KTRs) from donors after circulatory death (DCD) remains uncertain. We aimed to compare allograft outcomes in DCD-donor KTRs according to CIT and age. UNOS database study (2010-2024) of DCD-donor KTRs on tacrolimus maintenance. We developed a mate-kidney analysis, comparing outcomes where one mate kidney had CIT >24 and the other ≤24h. We evaluated patient death, all-cause allograft failure, and death-censored graft failure (DCGF) using multivariable stratified Cox proportional hazards models. We compared outcomes across age groups (≥50 or <50 years) and 6-h-period CIT deltas between mate kidneys. We assessed delayed graft function (DGF) occurrence with multivariable conditional logistic regression. We included 4092 DCD-donor mate-kidney pairs. There were no differences between CIT >24 versus ≤24h in patient death (aHR 1.12, 95% CI 0.97-1.30), all-cause allograft failure (aHR 1.10, 95% CI 0.98-1.24), or DCGF (aHR 1.07, 95% CI 0.90-1.27). Similar results were observed when comparing outcomes by age group and 6-h-period CIT deltas between mate kidneys. Compared to shorter CITs, CITs >24h were associated with increased DGF likelihood (aOR 1.42, 95% CI 1.25-1.60), as were increasing CIT deltas. CITs >24h in DCD-donor KTRs were not associated with adverse allograft outcomes, irrespective of age group. However, prolonged CITs were associated with increased DGF likelihood. Increasing the acceptance of both mate kidney from DCD donors should be considered despite projected CITs >24h.

Impact of Warm Ischemia Time on HER2 Expression in Breast Cancer Surgical Specimens.

Tissue sample quality control has become increasingly crucial as these samples are integral to basic research and clinical practice, particularly in immunohistochemistry and gene panel testing. Standard PREanalytical Code (SPREC) was developed to standardize pre-analytical processes, including warm ischemia time (WIT), cold ischemia time (CIT), and fixation time (FT), which can influence the surgical specimen quality. This study investigated the impact of WIT, CIT, and FT on estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) expression in breast cancer (BC) surgical specimens. We enrolled 277 patients with first-time BC who underwent surgery at Kanagawa Cancer Center between May 2018 and April 2019. WIT, CIT, and FT were recorded using SPREC ver. 3.0, and their effects on ER, PgR, and HER2 expression were analyzed using immunohistochemistry. Surgical specimens were compared with preoperative needle biopsy samples from the same tumors to control for WIT, CIT, and FT variability. The median WIT, CIT, and FT were 23 min, 37 min, and 43 h, respectively. Compliance with the American Society of Clinical Oncology/College of American Pathologists guidelines was 91.7% for CIT and 94.9% for FT. ER and PgR expression in surgical specimens decreased with prolonged CIT and FT, but differences were non-significant. However, HER2 expression increased significantly when WIT exceeded 30 min. WIT could significantly influence HER2 expression in BC surgical specimens, highlighting the need for meticulous WIT control during BC surgery to ensure accurate HER2 assessment, which is critical for guiding therapeutic decisions.

Cold ischemia time alters cell-type specific senescence leading to loss of cellular integrity in mouse lungs

Purpose: Ischemia-reperfusion injury (IRI) is a major challenge in lung transplantation often causing graft dysfunction and chronic airway illnesses in recipients. To prevent potential transplant related complications, strict guidelines were put in place to choose viable donor lungs with minimal risk of IRI. These regulations deem most of the donor organs unfit for transplant which then are donated for research to understand the mechanisms of health and diseases in human. However, resected organs that are being transported undergo cold ischemia that can negatively affect the tissue architecture and other cellular functions under study. Thus, it is important to assess how cold ischemia time (CIT) affects the physiological mechanism. In this respect, we are interested in studying how CIT affects cellular senescence in normal aging and various pulmonary pathologies. We thus hypothesized that prolonged CIT exhibits cell-type specific changes in lung cellular senescence in mice. Methods: Lung lobes from C57BL/6J (n = 5–8) mice were harvested and stored in UW Belzer cold storage solution for 0, 4-, 9-, 12-, 24-, and 48-h CIT. Lung cellular senescence was determined using fluorescence (C12FdG) assay and co-immunolabelling was performed to identify changes in individual cell types. Results: We found a rapid decline in the overall lung cellular senescence after 4-h of CIT in our study. Co-immunolabelling revealed the endothelial cells to be most affected by cold ischemia, demonstrating significant decrease in the endothelial cell senescence immediately after harvest. Annexin V-PI staining further revealed a prominent increase in the number of necrotic cells at 4-h CIT, thus suggesting that most of the cells undergo cell death within a few hours of cold ischemic injury. Conclusions: We thus concluded that CIT significantly lowers the cellular senescence in lung tissues and must be considered as a confounding factor for mechanistic studies in the future.

Prolonged Cold Ischemia Time in Pancreas Transplantation Yields Similar Outcomes Compared with Standard of Care Outcomes: Single-Center Experience, a Call to Action to Decrease Nonuse Rates

Prolonged Cold Ischemia Time in Pancreas Transplantation Yields Similar Outcomes Compared with Standard of Care Outcomes: Single-Center Experience, a Call to Action to Decrease Nonuse Rates

Analyzing the Impact of CIT on the Largest Reported Cohort of Robotic Kidney Transplantation From the Deceased Donors.

Robotic-assisted kidney transplant (RAKT) has proven to be a successful approach for patients with morbid obesity and more centers are encouraged to apply robotic approach also for deceased donor kidney transplantation. Prolonged cold ischemia time (CIT) is accompanied by delayed graft function (DGF) and early graft loss after traditional open kidney transplant (OKT). This study examines the impact of CIT after robotic kidney transplantation on settings of deceased donation. We present a single-center retrospective analysis of 115 cases of RAKT and 128 cases of OKT from deceased donors performed from deceased donor from 2009 to July 2022. Cohort was divided in 3 groups based on CIT ("high" CIT > 15 h, n = 43; "medium" CIT 11-15 h, n = 38; "low" CIT< 11 h, n = 40). The subgroup analysis of DGF and CIT was performed. The median CIT in the cohort was 13.46 (7) h, and overall rate of DGF was 30.6%. The correlation between CIT and DGF was statistically significant (P = 0.008), and DGF negatively correlated with 1-y graft survival (P = 0.04). The rate of DGF was significantly different between the groups (P = 0.05). Results from our study demonstrate that the effect of CIT on DGF in settings of RAKT follows a similar pattern as in traditional OKT.

Risk factors and prognostic modeling in bridging extracorporeal membrane oxygenation patients before lung transplantation.

The increased use of preoperative extracorporeal membrane oxygenation (ECMO) as a life support system before lung transplantation demands a better understanding of the associated prognostic factors. This study aims to discern the critical factors influencing the survival outcomes of ECMO patients and design a prognostic model tailored to this patient group. We retrospectively gathered and analyzed baseline and clinical data of patients who underwent preoperative bridging ECMO before lung transplantation from the United Network for Organ Sharing (UNOS) database. Univariate and multivariate Cox regression analyses were conducted and a prognostic model was generated to identify the independent factors influencing survival outcomes in these patients. The predictive model was cross-validated using the k-fold method where k=5. Our study included 1,202 patients. Both single and multiple analyses showed that age over 51 years, high body mass index (BMI), a history of dialysis before transplantation, donor hypertension, prolonged cold ischemia time, and high serum total bilirubin are adverse prognostic factors for the survival of ECMO-bridged lung transplant patients. Using the multivariate analysis, we created a prognosis model and a nomogram to predict 1-year post-transplant survival, with a receiver operating characteristic (ROC) curve area of 0.760 in internal validation. The 1-year survival rate calibration curve supported the nomogram's accuracy. This study involved the development of a survival prognosis model for patients undergoing lung transplantation with preoperative ECMO bridging, which was validated through extensive data analysis. The prognosis model exhibited high accuracy and predictive capability, effectively predicting the survival outcomes of patients both pre- and post-surgery.

Efficacy and Safety of Perioperative Angiotensin II Versus Phenylephrine as a First-Line Continuous Infusion Vasopressor in Kidney Transplant Recipients.

Angiotensin II (ATII) maintains blood pressure via RAAS with a beneficial adverse effect profile versus catecholamines and phenylephrine. Head-to-head data comparing ATII to phenylephrine are lacking regarding renal allograft function, hemodynamic efficacy, and safety within the perioperative period of kidney transplantation. This single-center, retrospective study included adult kidney transplant recipients who received continuous infusions of ATII or phenylephrine within a 24-h perioperative period as a first-line vasopressor according to an institutional algorithm. The primary endpoint was allograft function. Secondary endpoints were hemodynamic efficacy and adverse effects. Among 105 patients, there was no significant difference in IGF (p = 0.545), SGF (p = 0.557), or DGF (p = 0.878) between patient cohorts. In the 34 patients with cold ischemia time (CIT) > 14-h, IGF was higher (p = 0.013) and DGF (p = 0.045) was lower in the ATII cohort versus phenylephrine. In all patients, ATII was associated with a decreased need for additional vasopressor agents (p < 0.001). Adverse effect profiles were similar between cohorts (p > 0.05). Among kidney transplant recipients, ATII may be a suitable first-line alternative compared with phenylephrine in the perioperative period for hypotension management with a reduced need for additional vasopressor support. Allograft benefits were observed in patients with prolonged CIT.

1087 Factors That Impact Cold Ischaemia Time for Deceased Donor Kidney Transplants: Results of a National Transplant Access to Theatre Audit (NTACT)

Abstract Aim Deceased donor kidney utilisation confronts challenges leading to prolonged cold ischemia time (CIT), affecting graft survival. Despite these challenges, an understanding of the obstacles remains unclear. This audit aims to identify the factors that prolong CIT. Method A multicentre, prospective audit of adult deceased donor kidney-only transplants spanned 14 UK transplant centres from February to September 2022. Data, encompassing time intervals between important checkpoints pre-transplantation and perceived reasons for delays, were collected through RedCap. Descriptive statistics was used for analysis. Results Data from 476 kidney-only transplants were gathered (29 excluded for incomplete/incorrect data). Of these, 230 were donations after brainstem death (DBD) organs, and 202 were donations after circulatory death (DCD) organs. Median CIT was 10:55 (IQR:08:11-15:13) for DBD organs and 11:19 (IQR:08:31-15:10) for DCD organs, with 42% of DCD and 15% of DBD organs surpassing national CIT recommendations. Median time from organ arrival to knife to skin was 04:02 (IQR:02:35-07:35). Full and virtual crossmatches constituted 35% and 65%, respectively, with 16% of results arriving after the organ arrives at centre. Anaesthetic time had a median duration of 00:55 (IQR:00:39-01:10) and Knife to skin to organ perfusion was 01:25 (01:10-01:51). Delays reported in 34% of transplant cases, most common causes were the availability of surgical and anaesthetic teams, porters, and the operating theatre. Conclusions This audit allowed us to uncover the factors that prolong CIT at each stage of the transplantation post-arrival. These findings will guide the establishment of realistic targets for optimizing processes in the future.

Impact of Prolonged Cold Ischemia Time on Long-Term Survival in Lung Transplant Recipients

Cold ischemia time (CIT) influences short- and long-term outcomes in lung transplant recipients. Most studies proved that prolonged CIT causes increased mortality. This study aimed to investigate the impact of prolonged CIT on patient survival time after lung transplantation (LTx). The retrospective study group consisted of 139 patients who underwent double LTx in a single center between January 2018 and August 2022. Prolonged ischemic time (PIT) was defined as total ischemic time >6 hours and divided into smaller time intervals according to increasing PIT (6-8, 8-10, 10-12, >12 hours). The assessed outcomes were 1- and 4-year survival. Among the study group, PIT was observed in 98% (n = 137), and its average value was 10.33 hours. The prolonged CIT of 6 to 8 hours occurred in 10% (n = 14), 8 to 10 hours in 34% (n = 47), 10 to 12 hours in 36% (n = 49), and >12 hours in 20% (n = 27). In a comparison of 1-year survival between the PIT 6- to 10-hour group and the >10-hour arm (88% vs 78%), the difference was not statistically significant (P > .05). PIT is a risk factor for reduced long-term survival in LTx recipients. Increasing PIT may be associated with higher mortality at 1 and 4 years. All efforts to reduce the duration of ischemic time can benefit patient survival after LTx.

Efficiency of machine perfusion in pediatric liver transplantation.

Liver transplantation is the only life-saving procedure for children with end-stage liver disease. The field is however heterogenic with various graft types, recipient age, weight, and underlying diseases. Despite recently improved overall outcomes and the expanded use of living donors, waiting list mortality remains unacceptable, particularly in small children and infants. Based on the known negative effects of elevated donor age, higher body mass index, and prolonged cold ischemia time, the number of available donors for pediatric recipients is limited. Machine perfusion has regained significant interest in the adult liver transplant population during the last decade. Ten randomized controlled trials are published with an overall advantage of machine perfusion techniques over cold storage regarding postoperative outcomes, including graft survival. The concept of hypothermic oxygenated perfusion (HOPE) was the first and only perfusion technique used for pediatric liver transplantation today. In 2018 the first pediatric candidate received a full-size graft donated after circulatory death with cold storage and HOPE, followed by a few split liver transplants after HOPE with an overall limited case number until today. One series of split procedures during HOPE was recently presented by colleagues from France with excellent results, reduced complications, and better graft survival. Such early experience paves the way for more systematic use of machine perfusion techniques for different graft types for pediatric recipients. Clinical reports of pediatric liver transplants with other perfusion techniques are awaited. Strong collaborative efforts are needed to explore the effect of perfusion techniques in this vulnerable population impacting not only the immediate posttransplant outcome but the development and success of an entire life.

(617) - Does Prolonged Cold Ischemia Time Associate with an Increased Risk of Airway Complications in Lung Transplantation

(617) - Does Prolonged Cold Ischemia Time Associate with an Increased Risk of Airway Complications in Lung Transplantation

Cold Ischemia Time and Delayed Graft Function in Kidney Transplantation: A Paired Kidney Analysis.

We aimed to understand the association between cold ischemia time (CIT) and delayed graft function (DGF) after kidney transplantation and the impact of organ pumping on that association. Retrospective cohort study using US registry data. We identified kidney pairs from the same donor where both kidneys were transplanted but had a CIT difference >0 and ≤20 h. We determined the frequency of concordant (both kidneys with/without DGF) or discordant (only 1 kidney DGF) DGF outcomes. Among discordant pairs, we computed unadjusted and adjusted relative risk of DGF associated with longer-CIT status, when then repeated this analysis restricted to pairs where only the longer-CIT kidney was pumped. Among 25 831 kidney pairs included, 71% had concordant DGF outcomes, 16% had only the longer-CIT kidney with DGF, and 13% had only the shorter-CIT kidney with DGF. Among discordant pairs, longer-CIT status was associated with a higher risk of DGF in unadjusted and adjusted models. Among pairs where only the longer-CIT kidney was pumped, longer-CIT kidneys that were pumped had a lower risk of DGF than their contralateral shorter-CIT kidneys that were not pumped regardless of the size of the CIT difference. Most kidney pairs have concordant DGF outcomes regardless of CIT difference, but even small increases in CIT raise the risk of DGF. Organ pumping may mitigate and even overcome the adverse consequences of prolonged CIT on the risk of DGF, but prospective studies are needed to better understand this relationship.

Long-term outcome of combined radiologic and surgical strategy for the management of biliary complications after pediatric liver transplantation

ObjectivesWe aimed to analyze the risk factors for management failure of BC after pediatric liver transplantation (pLT) by retrospectively analyzing primary pLT performed between 1997 and 2018 (n = 620 patients).ResultsIn all, 117/620 patients (19%) developed BC. The median (range) follow-up was 9 (1.4–21) years. Patient survival at 1, 5 and 10 years was 88.9%, 85.7%, 84.4% and liver graft survival was 82.4%, 77.4%, and 74.3% respectively. Graft not patient survival was impaired by BC (p = 0.01). Multivariate analysis identified the number of dilatation courses > 2 (p = 0.008), prolonged cold ischemia time (p = 0.004), anastomosed multiple biliary ducts (p = 0.019) and hepatic artery thrombosis (p = 0.01) as factors associated with impaired graft survival. The number of dilatation courses > 2 (p < 0.001) and intrahepatic vs anastomotic stricture (p = 0.014) were associated with management failure. Thus, repeated (> 2) radiologic dilatation courses are associated with impaired graft survival and management failure. Overall, graft but not patient survival was impaired by BC.

O197: Quality Assessment of Human Kidneys by Ex-vivo Normothermic Machine Perfusion prior to Transplantation

Abstract Introduction Ex-vivo normothermic machine perfusion (NMP) is a technique of preservation that can be used to assess the quality and suitability of a kidney for transplantation. This may prevent the unnecessary discard and increase the number of transplanted kidneys. Methods A total of 22 kidneys declined for transplant by all UK transplant centres, were assessed over a three-year period across three centres in the UK. Prior to NMP, most kidneys were declined due to poor quality cold flushing at retrieval. All kidneys were assessed during 1h of NMP. A quality assessment score (QAS) based on the appearance, blood flow and urine output was applied to each kidney. Scores ranged from 1 (best) to 5 (worst). Results Sixteen kidneys (72%) had a QAS of 1 to 3 and were transplanted into matched recipients. One patient died with a non-functioning kidney 12 days post-transplant due to a cardiac arrest. Six recipients (37.5%) had delayed graft function. The mean serum creatinine levels and estimated glomerular filtration rate at 3 months was 154±74µmol/L and 45±15mL/min/1.73m2, respectively. Graft and patient survival at 12 months were 94%. Of the 6 non-transplanted kidneys, 3 were deemed unsuitable after assessment during NMP, 1 was not transplanted due to logistical reasons and a prolonged cold ischaemic time, and the remaining 2 due to chronic degenerative changes assessed by histology scores. Conclusion This clinical research study demonstrated the ability to use NMP technology to successfully increase the number of transplants by assessing kidneys that would otherwise be discarded.

Comparison of different porcine models simulating myocardial cold ischemia of pediatric donor hearts.

Our team previously identified a stem cell-derived cardioprotective additive that can be added to standard cardioplegia to extend myocardial viability during prolonged myocardial cold ischemic time (CIT) in rodent models. The purpose of this study was to utilize a porcine model to compare in-vivo versus ex-vivo porcine simulation of CIT that accompanies cardiac transplantation in humans, in order to determine an optimal method for translation of our studies to larger animals. Eight 39-55kg Yorkshire X pigs were randomly assigned to either in-vivo or ex-vivo simulation. After administration of general anesthesia and endotracheal intubation, baseline measurement of left ventricular performance was obtained via transesophageal echocardiography (TEE). After midline sternotomy and heparin administration, the aorta was cross-clamped and twoliters of HTK-Custodiol were introduced via the aortic root. The in-vivo method utilized cold ischemic heart storage in the chest cavity while supporting the experimental animal with cardiopulmonary bypass (CPB). The ex-vivo method involved standard cardiac procurement, cold ischemic storage outside of the body, and subsequent cardiac reperfusion utilizing cardiac reanimation in a Langendorff heart perfusion mode. After CIT, measurements of post-ischemic left ventricular performance were obtained via echocardiography. Results are presented as: Mean ± Standard Deviation (Median, Minimum-Maximum). Weight (kilograms) was similar in the in-vivo group and the ex-vivo group: 44 ± 1.8 (44, 42-46) versus 44 ± 5.1 (43.5, 39-51), respectively. Cold ischemic time (minutes) was longer in the ex-vivo group: 360 ± 0 (360, 360-360) versus 141 ± 26.7 (149, 102-163). Temperature (degrees Celsius) was colder in the ex-vivo group: 8 ± 0 (8, 8-8) versus 16.5 ± 4.2 (16, 12-16).In the in-vivo group, baseline ejection fraction and ejection fraction after CIT were: 48.25% ± 14.95% (48.5%, 33%-63%) and 41.25% ± 22.32% (41.5%, 20%-62%), respectively. In the ex-vivo group, baseline ejection fraction and ejection fraction after CIT were: 56.4% ± 5.9% (57%, 50%-67%) and 60.4% ± 7.7% (61.5%, 51.9%-67%), respectively. The ex-vivo technique is suitable to evaluate cardioplegia additives that may substantially extend myocardial tolerance to cold ischemia.

The Advent of Semi-Elective Lung Transplantation-Prolonged Static Cold Storage at 10°C.

Since the early days of clinical lung transplantation the preservation of donor organs has become a fairly standardized procedure and most centers do follow similar processes. This includes the use of low-potassium high dextran flush solutions and static cold storage (SCS) in a cooler filled with ice. Depending on the length of SCS, organs usually arrive at the recipient hospital at a temperature of 0°C-4°C. The question of the optimal storage temperature for donor lung preservation has been revisited as data from large animal experiments demonstrated that organs stored at 10°C experience less mitochondrial damage. Thus, prolonged cold ischemic times can be better tolerated at 10°C-even in pre-damaged organs. The clinical applicability of these findings was demonstrated in an international multi-center observational study including three high-volume lung transplant centers. Total clinical preservation times of up to 24hrs have been successfully achieved in organs stored at 10°C without hampering primary organ function and short-term outcomes. Currently, a randomized-controlled trial (RCT) is recruiting patients with the aim to compare standard SCS on ice with prolonged SCS protocol at 10°C. If, as anticipated, this RCT confirms data from previous studies, lung transplantation could indeed become a semi-elective procedure.

Beyond graft function impairment after liver transplantation: the prolonged cold ischemia time impact on recurrence of hepatocellular carcinoma after liver transplantation-a single-center retrospective study.

Hepatocellular carcinoma (HCC) is one of the malignant tumors responsible for high mortality and recurrence rates. Although liver transplantation (LT) is an effective treatment option for HCC, ischemia-reperfusion injury (IRI) is a contributor to HCC recurrence after LT. Moreover, prolonged cold ischemia time (CIT) is a risk factor for IRI during LT, and there is insufficient clinical evidence regarding the impact of CIT on HCC recurrence after LT. This retrospective study analyzed 420 patients who underwent LT for HCC between February 2015 and November 2020 at The First Affiliated Hospital, Sun Yat-sen University. The duration of CIT was defined as the time from clamping of the donor aorta until portal reperfusion. A total of 133 patients (31.7%) experienced tumor recurrence after LT, and CIT > 568 min was the independent risk factor for HCC recurrence (OR, 2.406; 95% CI [1.371-4.220]; p = 0.002). Multivariate Cox's regression analysis revealed that the recipients' gender, exceeding Milan criteria, poor differentiation, and alpha-fetoprotein (AFP) ≥400 ng/ml in CIT > 568 min group were independent risk factors for disease-free survival. The peak 7-day postoperative alanine aminotransferase (ALT) level (p<0.001), the peak 7-day postoperative aspartate aminotransferase (AST) level (p<0.001), the peak 7-day postoperative peak total bilirubin (TBIL) level (p=0.012), and the incidence of early allograft dysfunction (EAD) (p=0.006) were significantly higher in the CIT > 568 min group compared to the CIT ≤ 568 min group. Moreover, the amount of fresh frozen plasma (FFP) infusion during the operation increased (p=0.02), and the time of mechanical ventilation postoperative was longer (p=0.045). An effective strategy to improve the prognosis is to reduce CIT; this strategy lowers the recurrence of HCC in patients undergoing LT, especially those within the Milan criteria.

Vascular Reconstruction of Multiple Renal Arteries-A Risk Factor for Transplant Renal Artery Stenosis: Insight From a Matched Case-Control Study.

Transplant Renal Artery Stenosis (TRAS) is the leading vascular complication following kidney transplantation (KT), causing premature allograft loss and increased post-KT mortality. While risk factors for TRAS, such as prolonged cold ischemia time and delayed graft function, are well-documented in deceased donor-KT, the risk factors remain less clearly defined in living donor-KT. This matched case-control study, conducted at a leading national transplant center predominantly performing living donor-KT, evaluated risk factors and long-term outcomes of clinical TRAS (cTRAS). cTRAS cases diagnosed from January 2009 to December 2022 were matched with four control kidney transplant recipients (KTRs) in a study powered to assess whether ex-vivo arterial vascular reconstruction of multiple renal arteries (VR-MRA) increases the risk of cTRAS. Among 2,454 KTs, 28 KTRs (1.14%) were diagnosed with cTRAS around 3.62 ± 1.04months post-KT, with renal allograft dysfunction (92.86%) as the most common presenting feature. Notably, 27 cTRAS cases were successfully treated with endovascular intervention, yielding favorable outcomes over a 6-180months follow-up period. The study identified ex-vivo VR-MRA as an independent risk factor for cTRAS (P < 0.001). cTRAS cases receiving timely treatment exhibited long-term outcomes in graft and patient survival similar to control KTRs. Early screening and timely intervention for cTRAS post-KT may improve graft and patient outcomes.

Re-assessing prolonged cold ischemia time in kidney transplantation through machine learning consensus clustering.

We aimed to cluster deceased donor kidney transplant recipients with prolonged cold ischemia time (CIT) using an unsupervised machine learning approach. We performed consensus cluster analysis on 11615 deceased donor kidney transplant patients with CIT exceeding 24h using OPTN/UNOS data from 2015 to 2019. Cluster characteristics of clinical significance were identified, and post-transplant outcomes were compared. Consensus cluster analysis identified two clinically distinct clusters. Cluster 1 was characterized by young, non-diabetic patients who received kidney transplants from young, non-hypertensive, non-ECD deceased donors with lower KDPI scores. In contrast, the patients in cluster 2 were older and more likely to have diabetes. Cluster 2 recipients were more likely to receive transplants from older donors with a higher KDPI. There was lower use of machine perfusion in Cluster 1 and incrementally longer CIT in Cluster 2. Cluster 2 had a higher incidence of delayed graft function (42%vs. 29%), and lower 1-year patient (95%vs. 98%) and death-censored (95%vs. 97%) graft survival compared to Cluster 1. Unsupervised machine learning characterized deceased donor kidney transplant recipients with prolonged CIT into two clusters with differing outcomes. Although Cluster 1 had more favorable recipient and donor characteristics and better survival, the outcomes observed in Cluster 2 were also satisfactory. Overall, both clusters demonstrated good survival suggesting opportunities for transplant centers to incrementally increase CIT.

Breaking distance barriers in liver transplantation: Risk factors and outcomes of long-distance liver grafts

BackgroundLong-distance-traveling liver grafts in liver transplantation present challenges due to prolonged cold ischemic time and increased risk of ischemia–reperfusion injury. We identified long-distance-traveling liver graft donor and recipient characteristics and risk factors associated with long-distance-traveling liver graft use. MethodsWe conducted a retrospective analysis of data from donor liver transplantation patients registered from 2014 to 2020 in the United Network for Organ Sharing registry database. Donor, recipient, and transplant factors of graft survival were compared between short-travel grafts and long-distance-traveling liver grafts (traveled >500 miles). ResultsDuring the study period, 28,265 patients received a donation after brainstem death liver transplantation and 3,250 a donation after circulatory death liver transplantation. The long-distance-traveling liver graft rate was 6.2% in donation after brainstem death liver transplantation and 7.1% in donation after circulatory death liver transplantation. The 90-day graft survival rates were significantly worse for long-distance-traveling liver grafts (donation after brainstem death: 95.7% vs 94.5%, donation after circulatory death: 94.5% vs 93.9%). The 3-year graft survival rates were similar for long-distance-traveling liver grafts (donation after brainstem death: 85.5% vs 85.1%, donation after circulatory death: 81.0% vs 80.4%). Cubic spline regression analyses revealed that travel distance did not linearly worsen the prognosis of 3-year graft survival. On the other hand, younger donor age, lower donor body mass index, and shorter cold ischemic time mitigated the negative impact of 90-day graft survival in long-distance-traveling liver grafts. ConclusionThe use of long-distance-traveling liver grafts negatively impacts 90-day graft survival but not 3-year graft survival. Moreover, long-distance-traveling liver grafts are more feasible with appropriate donor and recipient factors offsetting the extended cold ischemic time. Mechanical perfusion can improve long-distance-traveling liver graft use. Enhanced collaboration between organ procurement organizations and transplant centers and optimized transportation systems are essential for increasing long-distance-traveling liver graft use, ultimately expanding the donor pool.