Donation After Circulatory Death Research Articles

Ex Vivo Lung Perfusion in Donation after Cardiac and Brain Death Donation.

Allografts from donation after circulatory death (DCD) or brain death donors may be evaluated by ex vivo lung perfusion (EVLP) to assess quality for transplantation. We sought to determine the association of donor type with transplantation outcomes at a national level. The United Network for Organ Sharing database was queried for lung transplant recipients, which were stratified into: DCD EVLP, brain death EVLP, standard DCD and standard brain death, followed by an unadjusted analysis. 1:1 propensity matching based on donor and recipient characteristics was used to compare DCD v DCD EVLP, brain death v brain death EVLP and brain death v DCD EVLP. The cohorts were assessed with comparative statistics. Finally, static and portable EVLP were compared to determine independent association with increased mortality. The unadjusted DCD EVLP group had significantly higher incidence of post-operative morbidity and mortality. 3-year survival was significantly lower in the DCD EVLP group, 65.3% (p=0.026). Following matching, the EVLP groups had significantly higher morbidity, and in-hospital mortality (DCD EVLP v brain death), but mid-term survival was no longer significantly different. However, the DCD EVLP group had about ∼6% lower survival than the DCD group (p=0.05) and about ∼7% lower survival than the brain death group (p=0.12). Within the EVLP groups, static and portable EVLP were not independently associated with increased mortality. Expansion of DCD EVLP allografts increases organ access, though providers should be aware of potential increases in complications and mortality as compared to DCD alone.

Utilization rates and heart transplantation outcomes of donation after circulatory death donors with prior cardiopulmonary resuscitation.

Heart donation after circulatory death (DCD) involves mandatory exposure to warm ischemic injury (WII) due to donor cardiac arrest resulting from withdrawal of life-support (WLS). However, potential DCD donors may also experience a cardiac arrest and undergo cardiopulmonary resuscitation (CPR) and associated WII before WLS. We sought to investigate the effect of previous donor-CPR in DCD heart-transplantation (HT). Between January-2020 and April-2023, we identified 11,415 adult HTs in UNOS of whom 9456 met study criteria and had information on donor-CPR. Follow-up was available till April-2024. Study cohort was divided into four groups based on DCD vs. donation after brain death (DBD) status and donor-CPR i.e., DCD/CPR+ (n = 387), DCD/noCPR (n = 305), DBD/CPR+ (n = 5158) and DBD/noCPR (n = 3606); and compared for HT characteristics and outcomes. With DBD/noCPR HTs as reference cohort, there were no significant differences in mortality in other HT cohorts (DCD/CPR+, DCD/noCPR and DBD/CPR+) upto 1-year of follow up using Kaplan-Meier analysis; and both unadjusted and adjusted Cox hazards-ratio models. Results were similar in propensity-matched cohorts. Duration of donor-CPR (≤20 min vs >20 min) did not influence HT survival; and rates of in-hospital secondary outcomes were similar. The utilization rates of both adult DCD/CPR+ (3.39 % to 9.71 %) and DCD/noCPR donors (4.41 % to 10.34 %) increased significantly (p < 0.01) during study period. The utilization rates of both DCD/CPR+ and DCD/noCPR donors have increased at an equal pace. A significant proportion of DCD HTs were from donors with prior CPR, but this was not associated with worse short-term survival.

Donor Time to Death and Kidney Transplant Outcomes in the Setting of a 3-Hour Minimum Wait Policy.

Lengthening waiting lists for organ transplant mandates the development of strategies to expand the deceased donor pool. Due to concerns regarding organ viability, most organ donation organizations internationally wait no longer than 1 to 2 hours for potential donation after circulatory death (DCD), possibly underutilizing an important organ source; UK policy mandates a minimum 3-hour wait time. To assess whether time to death (TTD) from withdrawal of life-sustaining treatment (WLST) is associated with kidney transplant outcomes. This population-based cohort study used data from the prospectively maintained UK Transplant Registry from all 23 UK kidney transplant centers from January 1, 2013, to December 31, 2021; follow-up was until the date of data extraction (October 2023). Participants comprised 7183 adult recipients of DCD kidney-alone transplants. Duration of TTD, defined as time from WLST to donor mechanical asystole. Primary outcome was 12-month estimated glomerular filtration rate (eGFR; for the main eGFR model, variables with significant right skew [histogram visual assessment] were analyzed on the log2 scale), with secondary outcomes of delayed graft function and graft survival (censored at death or 5 years). This study included 7183 kidney transplant recipients (median age, 56 years [IQR, 47-64 years]; 4666 men [65.0%]). Median donor age was 55 years (IQR, 44-63 years). Median TTD was 15 minutes (range, 0-407 minutes), with 885 kidneys transplanted from donors with TTD over 1 hour and 303 kidneys transplanted from donors with TTD over 2 hours. Donor TTD was not associated with recipient 12-month eGFR on adjusted linear regression (change per doubling of TTD, -0.25; 95% CI, -0.68 to 0.19; P = .27), nor with delayed graft function (adjusted odds ratio, 1.01; 95% CI, 0.97-1.06; P = .65) or graft survival (adjusted hazard ratio, 1.00; 95% CI, 0.95-1.07; P = .92). These findings were confirmed with restricted cubic spline models (assessing nonlinear associations) and tests of interaction (including normothermic regional perfusion). In contrast, donor asystolic time, cold ischemic time, and reperfusion time were independently associated with outcomes. Compared with a theoretical 1-hour maximum wait time, the UK policy (minimum 3-hour wait time) has been associated with 885 extra DCD transplants compared with 6298 transplants (14.1% increase). In this cohort study of DCD kidney recipients, donor TTD was not associated with posttransplant outcomes, in contrast to subsequent ischemic times. Altering international transplant practice to mandate minimum 3-hour donor wait times could substantially increase numbers of kidney transplants performed without prejudicing outcomes.

Abstract 4147630: Towards transplantation of hearts from donation after circulatory death - stem cell derived therapy for ameliorating donor organ damage

The use of heart transplantation (HTx), a key life-saving therapy for end-stage heart failure, is limited by the shortage of acceptable donor hearts. Although donation after circulatory death (DCD) offers a potentially promising resource for clinical transplantation, its adoption for HTx is concerned by warm ischemic damage during the death process. Mesenchymal stem cell (MSC)-derived paracrine action has been proved to mediate cardioprotection. Based on our previous study showing that MSC conditioned media (MSC CM) and MSC-exosomes (MSC Exo) confer improved donor heart preservation during cold ischemic storage, we aimed to test the effect of MSC CM and MSC Exo on ex vivo recovery of ischemia-damaged myocardium and on promoting the implanted DCD heart function using an in vivo murine heterotopic heart transplantation model. Methods: Donor hearts from adult male C57BL/6 mice with 0, 30’ or 50’ in vivo warm ischemia (WI) were divided into (n=5-7/group): 1) no WI; 2) 30’-WI; 3) 50’-WI; 4) no WI+4h cold storage at 0-4°C (no WI+CS); 5) 30’-WI+CS; 6) 50’-WI+CS; 7) 50’-WI+CS+vehicle; 8) 50’-WI+CS+MSC CM; and 9) 50’-WI+CS+MSC Exo. The CM and Exo were obtained from cultivation of human bone marrow-MSCs in serum-free media for 72h and was added into preservation solution. Donor hearts were implanted into C57BL/6 male recipients using cervical heterotopic heart transplantation. At 24h post-surgery, left ventricular (LV) function was detected in transplanted hearts. Abdominal artery pressure was measured in recipients to validate technical reproducibility of the HTx model. Mitochondrial structure was detected by electron microscopy on the fixed human LV (hDCD&amp;hDBD). Results: WI significantly impaired LV function in transplanted DCD hearts vs. no-WI (Fig. A, B). Intriguingly, markedly improved graft function was observed in MSC CM- or Exo-treated DCD hearts vs. vehicle (Fig. C). Short and disrupted cristae in mitochondria were noticed in hDCD vs. hDBD (Fig. D). Conclusions: Our results represent the initial evidence that MSC secretome (CM&amp;Exo) mediates ex vivo cardiac repair in DCD hearts and validate an approach on MSC derived therapy to rescue marginal DCD donor hearts and improve post-transplant graft function.

Imaging of Ischemic Cholangiopathy Following Donation after Circulatory Death Liver Transplant.

Ischemic cholangiopathy (IC) is the leading cause of inferior long-term outcomes following donation after circulatory death (DCD) liver transplant. Biliary strictures related to IC are nonanastomotic strictures (NASs) by definition and involve the donor hepatic ducts proximal to the anastomosis, compared with postsurgical anastomotic strictures that form due to fibrotic healing. IC-related NASs can be microangiopathic with patent hepatic artery or macroangiopathic with occluded or stenotic hepatic artery. Recently, IC with NASs have been described to have four distinct patterns at imaging: diffuse necrosis, multifocal progressive, confluence dominant, and minor form, which correlate clinically with graft prognosis. Severe IC can lead to ductal wall breakdown with subsequent bile leaks that can cause significant patient morbidity, with imaging playing a vital role in diagnosis and guiding intervention. IC also predisposes the transplanted liver to biliary stasis and subsequent formation of stones, casts, and sludge. Some cases of posttransplant biliary stricturing are not IC but are a sequela of reflux cholangitis seen with choledochojejunal anastomosis. Other biliary findings in the posttransplant liver can be explained by sphincter of Oddi dysfunction that results from denervation. The authors describe and comprehensively categorize the various IC types and their imaging patterns at MRI and MR cholangiopancreatography, review the prognostic significance of these imaging patterns, and discuss imaging features of additional biliary complications associated with IC after DCD liver transplant. ©RSNA, 2024 Supplemental material is available for this article.

Perfusate Biomarkers of DCD Cardiac Graft Quality Identified With Proteomics: Studies in an Isolated Rat Heart Model.

Heart transplantation with donation after circulatory death (DCD) enhances cardiac graft availability, but exposes hearts to potentially damaging conditions, such as warm ischemia. Normothermic machine perfusion (NMP), used for graft transportation, allows biomarker determination in perfusate. Using our isolated, rat heart model of DCD, we evaluated potent. Isolated, perfused adult male Wistar rat hearts (n = 5/group) underwent different warm ischemic durations to simulate DCD, followed by reperfusion to simulate NMP. Perfusate samples were collected after 10 min reperfusion, and proteins were analyzed using mass spectrometry. Cardiac recovery was evaluated after 60 min reperfusion. The relationship between perfusate proteins and cardiac recovery was investigated. Cardiac recovery decreased with increasing ischemic duration. Principal component analysis of perfusate proteins demonstrated segregation by ischemic group. Several proteins demonstrated an On-Off pattern, and correlated with key outcome measurements. Other proteins were released by all hearts and were confirmed as predictors of cardiac recovery, for example, heat shock protein 70 and valosin-containing protein (area under the curve [AUC] = 0.962-0.968, respectively; P < 0.05 for all). Additionally, proteins such as glycogen phosphorylase, muscle associated (AUC = 0.9632; P < 0.05) showed potential as novel biomarkers for evaluating cardiac graft quality, unlike lactate release after 10 min of reperfusion (AUC = 0.60). Multiple perfusate proteins, such as heat shock protein 70, valosin-containing protein, or glycogen phosphorylase, muscle associated, released during early reperfusion are promising as biomarkers for assessing graft quality during NMP. Perfusate proteins, as biomarkers, offer the possibility of both rapid immune detection and out-of-hospital implementation, and may provide valuable information about graft quality, especially when profiled with serial sampling during NMP.

A Global Experience of Donation after Circulatory Death for Pediatric Lung Transplantation.

Donation after circulatory death (DCD) lung transplantation has increased, but there is limited data in children. We sought to characterize the international experience of pediatric DCD lung transplant (LT) in comparison to donation after brain death (DBD) to address extreme donor organ shortages in children needing LT. Using the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry, 1453 children (<18yo) LT recipients from January 2004 to June 2018 were identified: 34 (3%) were DCD and 1419 (97%) were DBD recipients. Post-transplant outcomes were compared between groups. Propensity score method was used to derive matched cohorts and were compared between groups. DCD and DBD recipients were of similar age, with cystic fibrosis being the most frequent indication for LT in both groups (64.5% vs. 57.5%, respectively). Kaplan-Meier analysis demonstrated similar survival between DCD and DBD cohorts, whereas propensity score-matched recipients also identified similar post-transplant survival in both groups (P=0.098). Secondary analysis found that DCD LT recipients had a longer post-transplant length of hospital stay (unmatched cohorts: 36.5d vs. 20d, p=0.022; matched cohort: 26d vs. 19d, p=0.016), and shorter time to acute cellular rejection (ACR) (unmatched cohorts: 248d vs. 560d, p=0.039; matched cohorts: 248d vs. 1650d,p=0.059). Due to DCD being a key contributor to the increasing number of lung transplants being performed worldwide, the results of this analysis support this organ donation approach in children requiring LT, which would increase access to donor organs. The identification of a potential shorter time to ACR needs further exploration as more DCD pediatric LTs are performed.

Outcomes of Multiorgan Heart Transplant Between Donation After Circulatory Death and Brain Death.

There is insufficient data on the outcomes of donation after circulatory death (DCD) multiorgan transplant that includes heart. The primary objective of this study is to compare the overall survival outcomes of DCD and donation after brain death (DBD) multiorgan transplants. We identified all heart transplant patients from 2019 to June of 2023 using the United Network for Organ Sharing (UNOS) Database who also received an additional organ (kidney, liver, and lungs). A total of 1,844 DBD and 91 DCD multiorgan transplants occurred within the study period, the majority being combined heart-kidney transplantation. More patients were listed at a higher status in the DBD group (p < 0.05) and were in the intensive care unit (ICU) before transplant (p < 0.05). Despite the higher ischemia time in the DCD group (p < 0.05), the overall unmatched survival did not differ between the two groups (p < 0.05). Within the heart-kidney transplants, the overall survival between DBD and DCD heart-kidney transplants did not differ in either unmatched or matched groups (unmatched p = 0.5, matched p = 0.5). In conclusion, the data on the outcomes of DCD multiorgan transplants are limited. Still, our analysis of the currently available data suggests that the overall survival is comparable in the DCD multiorgan transplants.

Early Renal Outcomes Following Heart Transplantation Using Organs Procured After Circulatory Death.

Transplantation using hearts obtained through donation after circulatory death (DCD) is increasing, but data on recipient renal outcomes are limited. Patients at a single institution who underwent heart transplantation using organs procured through DCD or donation after brain death (DBD) from April 2016 to August 2022 were included in this retrospective cohort study. Hemodynamic measures were collected via right heart catheterization performed 1 week after transplantation. Posttransplantation renal outcomes included estimated glomerular filtration rate at 1 week, 4 weeks, and 16 weeks, and the incidence of acute kidney injury (AKI) and renal replacement therapy within 1 week. The analysis included 225 patients (55 recipients of DCD). Baseline characteristics were comparable between recipients of DCD and DBD. Renal outcomes within 1 week posttransplantation in recipients of DCD were similar to recipients of DBD, including percent change in estimated glomerular filtration rate (-37.9% [-58.6 to -6.2] versus -31.9% [-52.4 to -9.9]; P=0.91), incidence of AKI (47.3% versus 46.5%; P>0.99) and incidence of renal replacement therapy (3.6% versus 4.7%; P>0.99). Recipients of DCD with AKI within 1 week ("early AKI") did not recover to baseline estimated glomerular filtration rate (75.8 [60.2-91.3] mL/min per 1.73 m2) by week 16 (59.3 [46.9-73.6] mL/min per 1.73 m2; P=0.002), whereas recipients without early AKI exhibited comparable estimated glomerular filtration rate to baseline by week 4 (84.5 [70.8-98.5] mL/min per 1.73 m2; P=0.084). Similar trends were observed in recipients of DBD. Recipients of DCD demonstrated similar renal outcomes compared with recipients of DBD, supporting the ongoing use of DCD transplantation. Early AKI was associated with persistent renal dysfunction for recipients of both DCD and DBD.

Cost-effectiveness of Dual Hypothermic Oxygenated Machine Perfusion Versus Static Cold Storage in DCD Liver Transplantation.

Ex situ machine perfusion of the donor liver, such as dual hypothermic oxygenated machine perfusion (DHOPE), is increasingly used in liver transplantation. Although DHOPE reduces ischemia/reperfusion-related complications after liver transplantation, data on cost-effectiveness are lacking. Our objective was to evaluate the cost-effectiveness of DHOPE in donation after circulatory death (DCD) liver transplantation. We performed an economic evaluation of DHOPE versus static cold storage (SCS) based on a multicenter randomized controlled trial in DCD liver transplantation (DHOPE-DCD trial; ClinicalTrials.gov number, NCT02584283). All patients enrolled in the 3 participating centers in the Netherlands were included. Costs related to the transplant procedure, hospital stay, readmissions, and outpatients treatments up to 1 y posttransplant were calculated. The cost for machine perfusion was calculated using 3 scenarios: (1) costs for machine perfusion, (2) machine perfusion costs plus costs for personnel, and (3) scenario 2 plus depreciation expenses for a dedicated organ perfusion room. Of 119 patients, 60 received a liver after DHOPE and 59 received a liver after SCS alone. The mean total cost per patient up to 1 y posttransplant was €126 221 for the SCS group and €110 794 for the DHOPE group. The most significant reduction occurred in intensive care costs (28.4%), followed by nonsurgical interventions (24.3%). In cost scenario 1, DHOPE was cost-effective after 1 procedure. In scenarios 2 and 3, cost-effectiveness was achieved after 25 and 30 procedures per year, respectively. Compared with conventional SCS, machine perfusion using DHOPE is cost-effective in DCD liver transplantation, reducing the total medical costs up to 1 y posttransplant.

Outcomes of donation after circulatory death (DCD) and ex-vivo lung perfusion (EVLP) lung transplantation

BackgroundDonation after circulatory death (DCD) and ex-vivo lung perfusion (EVLP) have been adopted to expand the donor pool in lung transplantation, but outcomes data have been conflicting. This study explores mid-term outcomes of DCD lung transplantation in the modern era, with a focus on EVLP and risk factors for graft failure. MethodsThe United Network for Organ Sharing (UNOS) database was queried for adult lung transplants from 1/1/2015 to 3/1/2023. Loss to follow-up, multiorgan and prior lung transplants were excluded. DCD vs DBD (donation after brain death) lung transplants were compared, with subgroup analysis +/- EVLP. Outcomes were survival and postoperative complications. Overall survival was analyzed separately for an early era (2015-2018) and modern era (2019-2023). ResultsThe study included 1103 DCD (221 with EVLP, and 882 without) and 17973 donation after brain death (DBD) lung transplants (524 with EVLP, and 17449 without). Median follow-up was 3 years. DCD donors were less likely to be CDC high risk (19.3% vs 24.1%, p<0.001), have purulence on bronchoscopy (13.3% vs 18.3%, p<0.001) or infiltrates on chest x-ray (66.7% vs 67.8%, p=0.013). EVLP was more likely to be used for DCD transplants (20.0% vs 2.9%, p<0.001).After transplant, DCD recipients were more likely to be reintubated (24.3% vs 18.5%, p<0.001) and require ECMO within 72 hours (14.9% vs 7.8%, p<0.001), and DCD donation was an independent risk factor for these complications on multivariable logistic regression. Overall survival did not differ significantly between DCD and DBD transplants on adjusted survival analysis in the early or modern era (p=0.774 and p=0.468 respectively). On multivariable Cox regression, DCD and EVLP were not independent risk factors for mortality.On subgroup analysis, the DCD+EVLP cohort had significantly worse survival in the modern era, which remained significant after adjusting for donor and recipient factors (p=0.005). EVLP was an independent risk factor for graft failure in the DCD cohort (HR 1.33, 95% CI 1.00-1.77, p=0.047), but did not significantly affect DBD graft survival (p=0.870). Risk factors for graft failure and mortality in the DCD+EVLP cohort included pulmonary hypertension (HR 77.5, 95% CI 6.15-979, p<0.001), transfusion prior to transplant (HR 2.60, 95% CI 1.07-6.31, p=0.035), elevated creatinine (HR 2.82, 95% CI 1.34-5.90, p=0.006), and higher allocation score (HR 1.02, 95% CI 1.00-1.04, p=0.017) ConclusionStudy findings suggest increased risks of mortality and perioperative complications following transplantation with DCD lungs that have undergone EVLP. DCD lung transplantation without EVLP confers equivalent survival but with some increase in perioperative complications. Further investigation and careful recipient selection is warranted to optimize the use of these extended criteria donors in the modern era.

Inflammatory Gene Expression in Livers Undergoing Ex Situ Normothermic Perfusion Is Attenuated by Leukocyte Removal From the Perfusate.

Ex situ normothermic perfusion (ESNP) is a method to evaluate and potentially recondition organs before transplantation. However, increased expression of inflammatory molecules, including by tissue-resident immune cells, may occur during the perfusion process, potentially negating the beneficial effects of perfusion. We used RNA sequencing to assess gene expression in 31 livers undergoing ESNP, including 23 donated after circulatory death (DCD) and 8 donated after brain death. In 7 DCD livers, a leucocyte filter was added to the circuit during perfusion. Biopsies were available for transcriptomic assessment in all cases at the start of perfusion and at varying time points postperfusion. During ESNP in DCD livers, we observed an increase in proinflammatory, profibrinolytic, and prorepair pathway genes. SERPINE1, encoding plasminogen activator inhibitor-1, was among the genes most significantly upregulated during perfusion in DCD livers, potentially promoting fibrin clot persistence in vasculature. We also found increased expression of monocyte and neutrophil recruiting chemokine and proinflammatory cytokine transcripts during ESNP, but several prorepair molecules, including thymic stromal lymphopoietin, were also upregulated. In both DCD and donation after brain death livers, interferon-gamma response genes were enriched, whereas oxidative phosphorylation genes decreased in organs with high perfusate alanine transaminase, a biomarker associated with adverse clinical outcomes. The inclusion of a leukocyte filter in the perfusion circuit mitigated the induction of inflammation/immune pathway genes during perfusion and was associated with enrichment in oxidative phosphorylation genes. Leukocyte removal during ESNP abrogates transcriptional changes that are associated with unfavorable clinical outcomes, potentially benefiting human livers undergoing ESNP.

The Year in Cardiothoracic Transplant Anesthesia: Selected Highlights From 2022 Part II: Cardiac Transplantation

These highlights focus on the research that has been published in the year 2022 and is divided into preoperative, intraoperative, and postoperative sections. The preoperative section includes research pertaining to the assessment and optimization of candidates for HTX, donor optimization and the use of extended donors, organ protection systems, and donation after circulatory death (DCD) allografts, recipient factors including cannabis use, sex, race, and comorbidities such as obesity, diabetes mellitus, and peripartum cardiomyopathy, the effects of the 2018 heart allocation policy change on waitlist and postoperative mortality, updates on HTX in patients with Covid-19, in pediatric patients, and those who require a bridge to transplant. The intraoperative section includes the use of a multidisciplinary team, a proposed transfusion algorithm, bench surgery on the allograft, and size matching. The postoperative section focuses on the research pertaining to the development and management of tricuspid regurgitation, echocardiography, arrhythmia management, and finally xenotransplantation.

Expression of c-jun/c-fos mRNA Indicates Persistent Myocardial Stretch During Asphyxia-Induced Cardiac Arrest.

Right ventricular dysfunction is a key clinical issue for the viability of donation-after-circulatory-death (DCD) heart transplantation. DCD hearts with volume overload have the potential to exhibit aggravated right ventricular dysfunction following heart transplantation. The c-jun/c-fos mRNAs are genes that immediately respond to myocardial cell stretch. We assessed myocardial cell stretch during asphyxia-induced cardiac arrest by measuring c-jun/c-fos mRNA expression levels. The trachea was dissected and ligated to initiate asphyxiation in anesthetized Wistar rats under paralyzed ventilation. The hearts were harvested at 4 time points: 0, 15, 30, and 45 minutes after the termination of ventilation. Free walls of the right and left ventricles and the interventricular septum were sectioned. Total RNA was extracted from these tissues, and cDNA was synthesized using reverse transcription. The c-jun/c-fos mRNA expression levels were quantified using the droplet digital polymerase chain reaction method. In the left ventricle, c-jun/c-fos expression levels rapidly increased at 15 minutes, but the expression levels returned to the baseline level at 30 minutes after tracheal ligation. In contrast, in the right ventricle, c-jun/c-fos expression levels gradually increased and peaked 30 minutes after tracheal ligation. Myocardial cell stretching in the right ventricle is prolonged after asphyxia-induced cardiac arrest compared to that in the left ventricle, which may lead to right ventricular dysfunction after DCD heart transplantation.

A novel cytoprotective organ perfusion platform for reconstructing homeostasis of DCD liver while alleviating IRI injury

AbstractPump is a vital component for expelling the perfusate in small animal isolated organ normothermic machine perfusion (NMP) systems whose flexible structure and rhythmic contraction play a crucial role in maintaining perfusion system homeostasis. However, the continuous extrusion forming with the rigid stationary shaft of the peristaltic pumps can damage cells, leading to metabolic disorders and eventual dysfunction of transplanted organs. Here, we developed a novel biomimetic blood‐gas system (BBGs) for preventing cell damage. This system mimics the cardiac cycle and features an adjustable inspiratory‐to‐expiratory (IE) ratio to mitigate acidosis caused by continuous oxygen inhalation. In our study, adipose stem cells (ADSCs) were cultured within the circulatory system for 10 min, 2, and 4 h. Compared to the peristaltic pump, the BBGs significantly reduced cell apoptosis and morphological injury while enhancing cell proliferation and adhesion. Additionally, when the supernatant from ADSCs was introduced to LPS‐induced macrophages for 24 h, the BBGs group demonstrated a more pronounced anti‐inflammatory effect, characterized by reduced M1 macrophage expression. Besides, with isolated rat livers from donation after circulatory death (DCD) perfusion with ADSCs for 6 h by the BBGs, we detected fewer apoptotic cells and a reduced inflammatory response, evidenced by down‐regulated TNF‐α expression. The development of BBGs demonstrates the feasibility of recreating physiological liquid–gas circulation in vitro, offering an alternative platform for isolated organ perfusion, especially for applications involving cell therapy.

Pushing the Survival Bar Higher: Two Decades of Innovation in Lung Transplantation.

Survival after lung transplantation has significantly improved during the last two decades. The refinement of the already existing extracorporeal life support (ECLS) systems, such as extracorporeal membrane oxygenation (ECMO), and the introduction of new techniques for donor lung optimization, such as ex vivo lung perfusion (EVLP), have allowed the extension of transplant indication to patients with end-stage lung failure after acute respiratory distress syndrome (ARDS) and the expansion of the donor organ pool, due to the better evaluation and optimization of extended-criteria donor (ECD) lungs and of donors after circulatory death (DCD). The close monitoring of anti-HLA donor-specific antibodies (DSAs) has allowed the early recognition of pulmonary antibody-mediated rejection (AMR), which requires a completely different treatment and has a worse prognosis than acute cellular rejection (ACR). As such, the standardization of patient selection and post-transplant management has significantly contributed to this positive trend, especially at high-volume centers. This review focuses on lung transplantation after ARDS, on the role of EVLP in lung donor expansion, on ECMO as a principal cardiopulmonary support system in lung transplantation, and on the diagnosis and therapy of pulmonary AMR.

The Association Between the Origin of the Donation After Circulatory Death Liver Recovery Team and Graft Survival: A National Study

Background. Transplant centers have traditionally relied upon procurement teams from their own programs (transplant program procurement team [TPT]) to recover donation after circulatory death (DCD) livers and rarely use surgical procurement teams not affiliated with the recipient center (nontransplant program procurement team [NTPT]). However, in the era of wider geographic organ sharing, greater reliance on NTPTs is often necessary. Methods. We used national data to study the association between the origin of the donor procurement team (NTPT versus TPT) and the risk of DCD liver allograft failure. Results. Five hundred NTPT and 2257 TPT DCD transplants were identified: 1-y graft survival was 88.9 and 88.6%, respectively (P = 0.962). In a multivariable model, the origin of the procurement team was not associated with graft failure NTPT versus TPT (hazard ratio, 0.92; 95% confidence interval, 0.71-1.22; P = 0.57) but rather with known risks for DCD graft loss including donor age, degree of recipient illness, cold ischemic time, and retransplantation. The overall incidence of retransplantation and ischemic cholangiopathy as an indication for retransplantation were similar between NTPT and TPT. Conclusions. This data suggests that transplant centers may be able to safely use DCD livers recovered by local surgical teams.

Innovations in Liver Preservation Techniques for Transplants from Donors after Circulatory Death: A Special Focus on Transplant Oncology.

Liver transplantation is the preferred treatment for end-stage liver disease. Emerging evidence suggests a potential role for liver transplantation in treating liver tumors such as colorectal liver metastases and cholangiocarcinoma. However, due to a limited donor pool, the use of marginal grafts from donation after circulatory death (DCD) donors is increasing to meet demand. Machine perfusion is crucial in this context for improving graft acceptance rates and reducing ischemia-reperfusion injury. Few studies have evaluated the role of machine perfusion in the context of transplant oncology. Perfusion machines can be utilized in situ (normothermic regional perfusion-NRP) or ex situ (hypothermic and normothermic machine perfusion), either in combination or as a complement to conventional in situ cold flush and static cold storage. The objective of this analysis is to provide an up-to-date overview of perfusion machines and their function in donation after circulatory death with particular attention to their current and likely potential effects on transplant oncology. A literature review comparing standard cold storage to machine perfusion methods showed that, so far, there is no evidence that these devices can reduce the tumor recurrence rate. However, some evidence suggests that these innovative perfusion techniques can improve graft function, reduce ischemia-reperfusion injury, and, based on this mechanism, may lead to future improvements in cancer recurrence.

Advancements in Donation after Circulatory Death Heart Procurement and Preservation: A Comprehensive Review of Recent Innovations.

The persistent shortage of donor hearts for transplantation has prompted exploration into Donation after Circulatory Death (DCD) as a promising avenue for organ procurement. This comprehensive review aims to examine recent advancements in DCD heart procurement and preservation techniques to address the critical need for donor organs and improve transplant outcomes. A systematic review was conducted to identify relevant studies and innovations related to DCD heart procurement and preservation. Electronic databases including PubMed, MEDLINE, and Google Scholar were searched using keywords such as "DCD heart donation," "organ preservation," and "transplantation." Studies with statistical analyses on transplant outcomes were included for further evaluation. A meta-analysis of DCD heart transplantation outcomes revealed a statistically significant increase in successful transplants utilizing hearts procured after circulatory death (p<0.05). Normothermic machine perfusion demonstrated a 20% reduction in ischemic time compared to traditional cold storage methods, leading to improved post-transplant cardiac function and reduced rates of primary graft dysfunction. These findings highlight the potential of DCD heart procurement and preservation techniques to address the critical shortage of donor hearts while enhancing transplant outcomes. Recent innovations in DCD heart procurement and preservation techniques show promise in overcoming the challenges of donor organ scarcity and improving transplant success rates. Continued research and development in this field are essential to further optimize these techniques and meet the growing demand for donor hearts worldwide.

The differential impact of early graft dysfunction in kidney donation after brain death and after circulatory death: Insights from the Dutch National Transplant Registry

Kidneys donated after circulatory death (DCD) perform similarly to kidneys donated after brain death (DBD). However, the respective incidences of delayed graft function (DGF) differ. This questions the donor type-specific impact of early graft function on long-term outcomes. Using competing risk and Cox-regression analysis, we compared death-censored graft loss between types of early graft function: DGF (temporary dialysis dependency started within 7 days after transplantation), slow graft function (3-day plasma creatinine decline less than 10% per day), and immediate graft function. In 1061 DBD and 1605 DCD graft recipients (January 2014 until January 2023), graft survival was similar. DGF was associated with death-censored graft loss in DBD and DCD (adjusted hazard ratios: DGF in DBD: 1.79 [1.04-2.91], P = .027, DGF in DCD: 1.84 [1.18-2.87], P = .008; Reference: no DGF). Slow graft function was associated with death-censored graft loss in DBD, but not significantly in DCD (adjusted hazard ratios DBD: 2.82 (1.34-5.93), P = .007, and DCD: 1.54 (0.72-3.35), P = .262; Reference: immediate graft function). Early graft dysfunction has a differential impact on graft outcome in DBD and DCD. The differences between DBD and DCD should be accounted for in research and the clinic.