Extended Criteria Research Articles

Surgical techniques for cardiac procurement, preparation and perfusion using the Organ Care System

We provide an audio-visual step-by-step guide to the preparation of a donor heart for the application of normothermic, ex situ cardiac perfusion on the TransMedics Organ Care System using a heart donated after brain death. The use of the Organ Care System increases heart transplantation activity by enabling the utilization of hearts donated after circulatory death, the use of extended criteria grafts and the extension of out-of-body time, which can help overcome geographic or surgical barriers. Ex situ cardiac perfusion is a new technique and is therefore not yet routinely performed in many centres. However, it can be assumed that this technique will become more established and widespread in the future. Our video tutorial, which summarizes all important steps, can therefore be of benefit to surgical teams for planning, training or as a refresher.

P.191: The outcomes of the deceased donor kidney transplantation using extended criteria donor.

P.191: The outcomes of the deceased donor kidney transplantation using extended criteria donor.

Extended Criteria Donor Use in Lung Transplants From Donation After Controlled Circulatory Death

BackgroundMost institutions apply the criteria for controlled donation after cardiac death (cDCD) lung retrieval identical to the criteria for donation after brain death (DBD). The availability of extended criteria donor (ECD) in lung transplants from cDCD remains unclear. MethodsThe United Network for Organ Sharing (UNOS) database was queried for adult lung transplants from cDCD, from May 03, 2005, to March 15, 2022. ECDs were defined by one or more items at variance from standard criteria: age 55 years or more, PaO2:FiO2 300 or less, smoking 20 pack-years or more, diabetes, or purulent secretions upon bronchoscopy. Recipients were divided into the standard criteria donor (SCD) group and the ECD group, and assessed for short- and long-term survival and postoperative events. ResultsAmong 827 records, the SCD and ECD group showed no differences in 5-year (P = .56) survival. No significant differences were found in 30-day, 90-day, 1-year mortality and postoperative outcomes before discharge, whether in length of hospital stay, rate of ventilator support for >48 hours or reintubation, incidence of grade 3 PGD 72 hours posttransplant, acute rejection, or dialysis. None of the 5 donor factors used as criteria for lung retrieval was independently associated with cDCD recipient survival. ConclusionsUsing donor lungs that extend the DBD criteria may be a safe strategy in cDCD lung transplantation. However, the current criteria may not be a perfect fit for cDCD lung retrieval. The specific DCD criteria for standard lung retrieval need to be determined.

Are we on track to increase organ utilization? An analysis of machine perfusion preservation for liver transplantation in the United States.

Efforts to improve the quality of marginal grafts for transplantation are essential. Machine perfusion preservation appears as a promising solution. The United Network for Organ Sharing (UNOS) database was queried for deceased liver donor records between 2016 and 2022. The primary outcome of interest was the organ nonutilization rate. Long-term graft and patient survival among extended criteria donors (ECDs) were also analyzed. During the study period, out of 54 578 liver grafts recovered for transplant, 5085 (9.3%) were nonutilized. Multivariable analysis identified normothermic machine perfusion (NMP) preservation as the only predictor associated with a reduction in graft nonutilization (OR = 0.12; 95% CI = 0.06-0.023, p < 0.001). Further analysis of ECD grafts that were transplanted revealed comparable 1-,2- and 3-years graft survival (89%/88%/82% vs. 90%/85%/81%, p = 0.60), and patient survival (92%/91%/84% vs. 92%/88%/84%, p = 0.65) between grafts that underwent MP vs. those who did not, respectively. Liver nonutilization rates in the United States are at an all-time high. Available data, most likely including cases from clinical trials, showed that NMP reduced the odds of organ nonutilization by 12% among the entire deceased donor pool and by 16% among grafts from ECD. Collective efforts and further evidence reflecting day-to-day clinical practice are needed to fully reach the potential of MP for liver transplant.

Potential kidney donors among patients with out-of-hospital cardiac arrest and a termination of resuscitation rule

ImportanceUncontrolled donation after circulatory determination of death (uDCD) has been developed and can serve as a source of kidneys for transplantation, especially when considering patients that meet extended criteria donation (ECD). ObjectiveThis study assessed the theorical size and characteristics of the potential pool of kidney transplants from uDCD with standard criteria donation (SCD) and ECD among patients who meet Termination of Resuscitation (TOR) criteria following Out of Hospital Cardiac Arrest (OHCA). Methods and participantsThis study focused on adult patients experiencing unexpected OHCA, who were prospectively enrolled in the Parisian registry from May 16th, 2011, to December 31st, 2020. ResultsDuring the study period, EMS attempted resuscitation for 19,976 OHCA patients, of which 64.5% (12,890) had no return of spontaneous circulation. Among them, 47.4% (9,461) had TOR criteria, representing no chance of survival, and from them, 8.8% (1,764) met SCD criteria and could be potential organ donors and 33.6% (6,720) met ECD for kidney donors. The mean potential number per year of uDCD candidates with SCD and ECD remain stable respectively around 98 (±10.8) and 672 (±103.8) cases per year. Elderly patients (≥65 y.o.) represented 61.2% (n = 5,763/9,461) of patients who met TOR and 100% (5763/5763) of patients who could have matched both ECD criteria and TOR. Conclusion and relevanceImplementing uDCD program including SCD and ECD for kidney transplantation among OHCA cases quickly identified by the TOR, holds significant potential to substantially broaden the pool of organ donors. These programs could offer a viable solution to address the pressing burden of kidney shortage, particularly benefiting elderly recipients who may otherwise face prolonged waiting times and limited access to suitable organs.

Coronary Angiography During Ex-Situ Heart Perfusion in a Porcine Model.

Heart transplantation is the gold standard treatment for advanced heart failure. The procurement of extended criteria donors (ECD) increases due to the current organ shortage. Coronary angiography is recommended in ECD at risk for coronary artery disease but is not systematically performed. These hearts are, therefore, either declined for transplant or procured without screening for coronary artery disease. Coronary angiography during normothermic ex-situ heart perfusion (NESP) could be an interesting approach to enhance the rate of ECD procurement and to reduce the risk of primary graft failure in the absence of coronary angiography in ECD. The present protocol aims to provide material details along with optimal imaging views for coronary angiography during NESP. Reproducible angiographic views were observed, including one dedicated to the right coronary artery, two for the left anterior descending artery, two for the circumflex artery, and a spider view. Continuous lactate extraction was observed in all procedures with a final median concentration of 1.10 mmol/L (0.61-1.75 mmol/L) two hours after coronary angiography, consistent with myocardial viability. The median contrast agent volume used for ex-situ imaging of the isolated perfused heart was 48 mL (38-108 mL). This protocol was reproducible for coronary artery imaging and did not impair myocardial viability during NESP.

Routine end-ischemic hypothermic machine perfusion in liver transplantation from donors after brain death: results of two-year follow-up of a randomized controlled trial.

Data on routine hypothermic machine perfusion of livers procured from donors after brain death (DBD) are scarce, and the benefits of the method have only been demonstrated in extended criteria grafts. The aim of this study was to assess if end-ischemic dual hypothermic oxygenated machine perfusion (dHOPE) is superior to static cold storage (SCS) in preservation of livers procured from DBD donors with respect to long-term outcomes. Existing data on short-term outcomes favours dHOPE in patients receiving high-risk grafts. This prospective randomized controlled trial included 104 recipients of DBD livers randomly assigned to static cold storage arm (78 patients) and dHOPE arm (26 patients). Endpoints of interest were occurrence of biliary complications (biliary fistula, anastomotic, and nonanastomotic strictures) and overall patient (OS) and graft survival (GS) during two-year follow-up. A total of 36 patients developed biliary complications (at least one event) - 6 events in dHOPE arm and 30 in SCS arm. There was no significant difference in biliary complications between groups (23.7% vs. 43.4% [P=0.11]). No differences were found significant with respect to anastomotic (19.9% vs. 33.7% [P=0.20]) and non-anastomotic strictures (0% vs. 11.1% [P=0.10]) as well as biliary fistulas (11.7% vs. 12.2% [P=0.93]). Survival analysis did not show significantly different result in the study population - OS: 92.3% in dHOPE and 83.9% in SCS (P=0.35), and GS: 92.3% and 81.4% (P=0.23), respectively. However, significant difference in GS was noted in recipients of high-risk grafts - 100% in dHOPE and 73.1% in SCS, respectively (P=0.038). The long-term outcome data suggest that the routine use of dHOPE may be beneficial for recipients of high-risk grafts from DBD donors. The present study does not provide any evidence for benefits of dHOPE in low-risk grafts.

Medial incision approach in modified small double-opposing Z-plasty for Veau II cleft repair

An encouraging outcome was described for the use of modified Furlow small double-opposing Z-plasty (sDOZ) using the medial incision (MIsDOZ) approach in repair of Veau type I cleft palate. This retrospective study assessed early results of using extended indication criterion of MIsDOZ for the management of consecutive non-syndromic patients with Veau II cleft palate treated by a single surgeon. Bardach two-flap plus sDOZ (two-flap approach) or medial incision approach with a tension-driven stepwise application of lateral palatal incisions (soft palate only, von Langenbeck type, or two-flap type) were applied. Surgical (age, cleft width, operative time, hospital stay, and complication)- and auditory-perceptual assessment-related data were collected. Two-flap approach (n = 21) demonstrated a significantly (p < 0.001) increased operative time (132.8 ± 12.2 versus 114.8 ± 19.9 min, respectively) and higher use of lateral incisions (100% versus 44.4%) than medial incision approach (n = 27), with no significant (p > 0.05) difference for age at surgery (13.0 ± 6.1 versus 13.6 ± 5.8 months), cleft width (8.5 ± 4.1 versus 8.7 ± 3.8 mm), hospital stay (1.0 ± 0 versus 1.0 ± 0 day), and complication (0% versus 0%) and hypernasality (9.5% versus 7.4%) rates. In conclusion, the medial incision approach for Veau II cleft repair resulted in reduced need for lateral palatal incision with no increase of complication or hypernasality rates.

Liver Graft Machine Perfusion: From History Perspective to Modern Approaches in Transplant Surgery.

The shortage of donor organs remains an unresolved issue in livertransplantation worldwide. Consequently, strategies for expanding the donor pool are currently being developed. Donors meeting extended criteria undergo thorough evaluation, as livers obtained from marginal donors yield poorer outcomes in recipients, including exacerbated reperfusion injury, acute kidney injury, early graft dysfunction, and primary nonfunctioning graft. However, the implementation of machine perfusion has shown excellent potential in preserving donor livers and improving their characteristics to achieve better outcomes for recipients. In this review, we analyzed the global experience of using machine perfusion in livertransplantation through the history ofthe development ofthis method to the latest trends and possibilities for increasing the number of liver transplants.

A comprehensive, multifaceted strategy to increase pediatric donor heart utilization

BACKGROUNDMany hearts offered for pediatric heart transplantation (HT) are not placed. In 2016, we initiated a quality improvement endeavor to increase heart offer acceptance. This study assessed the effect of these interventions at our center. METHODSEvaluation of pre-/post-implementation cohorts (1/1/2008-12/31/2016 vs. 1/1/2017- 7/1/2023) comparing donor heart utilization. Six interventions were iterated over time to increase offer acceptance (“extended criteria”): ABO-incompatible transplant, ex vivo perfusion for distanced donors, 3-dimensional total cardiac volume (TCV) assessment, acceptance of Hepatitis-C or SARS-COV-2 infected donors, and institutional culture change favoring consideration of donors previously considered unacceptable (Public Health Service Risk, long CPR duration, etc.). Outcomes studied included annual HT volume, median waitlist duration, sequence number at acceptance, and post-transplant clinical outcomes. RESULTSFrom 1/2008–7/2023 annual transplant volume increased from 16/year to 25/year pre-/post-implementation. Three hundred-thirteen/389 (80%) listed patients were transplanted. Waitlist duration shortened post-implementation (P=0.01), as did the percentage of accepted heart offers utilizing at least one extended criterion (P<0.001). Institutional culture change and TCV assessment had the largest impact on donor heart utilization (P=0.04 &P<0.001). There was no difference in post-HT intubation or cardiovascular intensive care unit (CVICU) days (P= 0.05-0.9), though post-transplant hospitalization duration (P<0.001) increased. Post-transplant survival was unaffected by use of extended criteria hearts (P=0.3). CONCLUSIONSWe report increased donor heart offer acceptance resulting from a longitudinal, multi-faceted effort to increase organ offer utilization, with institutional culture change and TCV assessments having the greatest impact. Use of extended criteria hearts was not associated with inferior survival.

Advancements in Predictive Tools for Primary Graft Dysfunction in Liver Transplantation: A Comprehensive Review.

Orthotopic liver transplantation stands as the sole curative solution for end-stage liver disease. Nevertheless, the discrepancy between the demand and supply of grafts in transplant medicine greatly limits the success of this treatment. The increasing global shortage of organs necessitates the utilization of extended criteria donors (ECD) for liver transplantation, thereby increasing the risk of primary graft dysfunction (PGD). Primary graft dysfunction (PGD) encompasses early allograft dysfunction (EAD) and the more severe primary nonfunction (PNF), both of which stem from ischemia-reperfusion injury (IRI) and mitochondrial damage. Currently, the only effective treatment for PNF is secondary transplantation within the initial post-transplant week, and the occurrence of EAD suggests an elevated, albeit still uncertain, likelihood of retransplantation urgency. Nonetheless, the ongoing exploration of novel IRI mitigation strategies offers hope for future improvements in PGD outcomes. Establishing an intuitive and reliable tool to predict upcoming graft dysfunction is vital for early identification of high-risk patients and for making informed retransplantation decisions. Accurate diagnostics for PNF and EAD constitute essential initial steps in implementing future mitigation strategies. Recently, novel methods for PNF prediction have been developed, and several models for EAD assessments have been introduced. Here, we provide an overview of the currently scrutinized predictive tools for PNF and EAD evaluation strategies, accompanied by recommendations for future studies.

Effect of Donor Cigarette Smoking in Kidney Transplantation: Re-Evaluation of Long-Term Outcomes.

Cigarette smoking is a common risk factor associated with negative long-term outcomes in kidney transplant recipients. However, whether donor smoking decreases graft longevity or negatively impacts recipient survival after kidney transplantation remains unknown. Therefore, this study aims to investigate the long-term outcome in patients who received a kidney graft from a deceased smoking or non-smoking donor. A total of 580 patients were divided into two groups: patients who received a graft from a smoking donor (n = 276) and those who received a graft from a non-smoking donor (n = 304). Analysis of demographic factors showed that the non-smoking cohort was older, had more extended criteria donors and longer warm ischemia times. The primary composite endpoint of patient and graft survival was better in the smoking donor cohort when analyzed using Kaplan-Meier method but not when controlled for covariates in multivariate analyses. These findings do not support a previously reported negative impact of deceased donor smoking on kidney transplant recipients. Thus, the underlying results should not be interpreted in favor of a positive donor smoking history, but rather remind the transplant community that donor smoking should not be considered as a deciding factor in refusing an otherwise acceptable kidney graft.

Viability assessment and transplantation of extended criteria donor liver grafts using normothermic machine perfusion

BackgroundThe scarcity of available liver grafts necessitates the use of organs from extended criteria donors, a practice associated with an increased risk of graft failure. A notable percentage of deceased donor liver allografts are rejected due to subjective criteria. Normothermic machine perfusion holds promise for introducing objective parameters into this decision-making process. The aim of this study was to compare the outcomes of standard criteria and extended criteria donor allografts after liver transplantation, following viability assessment, using normothermic machine perfusion. MethodsLiver allografts preserved by normothermic machine perfusion before liver transplantation at the University Hospital of Münster were retrospectively analyzed. Organs were stratified according to the Eurotransplant Donor Risk Index. In total, 101 liver grafts were included in this study and divided into 2 groups: (1) standard criteria donors with a Donor Risk Index <1.8 (DRI-low) and (2) extended criteria donors with a Donor Risk Index ≥1.8 (DRI-high). ResultsAn increased risk profile of donor livers, as assessed by the Eurotransplant Donor Risk Index, did not correlate with patient or graft survival. High-risk liver grafts were effectively transplanted into recipients with different risk levels after viability assessment by normothermic machine perfusion. However, the recipients’ model for end-stage liver disease scores showed a significant association with both overall patient and graft survival. ConclusionThe use of normothermic machine perfusion for viability assessment allows safe transplantation of high-risk donor livers and effectively addresses the disparity between donor liver availability and transplantation demand.

The impact of normothermic machine perfusion and acuity circles on waitlist time, mortality, and cost in liver transplantation: A multicenter experience.

Ex situ normothermic machine perfusion (NMP) helps increase the use of extended criteria donor livers. However, the impact of an NMP program on waitlist times and mortality has not been evaluated. Adult patients listed for liver transplant (LT) at 2 academic centers from January 1, 2015, to September 1, 2023, were included (n=2773) to allow all patients ≥6 months follow-up from listing. Routine NMP was implemented on October 14, 2022. Waitlist outcomes were compared from pre-NMP pre-acuity circles (n=1460), pre-NMP with acuity circles (n=842), and with NMP (n=381). Median waitlist time was 79 days (IQR: 20-232d) at baseline, 49 days (7-182) with acuity circles, and 14 days (5-56) with NMP ( p <0.001). The rate of transplant-per-100-person-years improved from 61-per-100-person-years to 99-per-100-person-years with acuity circles and 194-per-100-person-years with NMP ( p <0.001). Crude mortality without transplant decreased from 18.3% (n=268/1460) to 13.3% (n=112/843), to 6.3% (n=24/381) ( p <0.001) with NMP. The incidence of mortality without LT was 15-per-100-person-years before acuity circles, 19-per-100 with acuity circles, and 9-per-100-person-years after NMP ( p <0.001). Median Model for End-Stage Liver Disease at LT was lowest with NMP, but Model for End-Stage Liver Disease at listing was highest in this era ( p <0.0001). The median donor risk index of transplanted livers at baseline was 1.54 (1.27-1.82), 1.66 (1.42-2.16) with acuity circles, and 2.06 (1.63-2.46) with NMP ( p <0.001). Six-month post-LT survival was not different between eras ( p =0.322). The total cost of health care while waitlisted was lowest in the NMP era ($53,683 vs. $32,687 vs. $23,688, p <0.001); cost-per-day did not differ between eras ( p =0.152). The implementation of a routine NMP program was associated with reduced waitlist time and mortality without compromising short-term survival after liver transplant despite increased use of riskier grafts. Routine NMP use enables better waitlist management with reduced health care costs.

A novel nomogram to predict the recurrence of hepatocellular carcinoma after liver transplantation using extended selection criteria

BackgroundLiver transplantations (LTs) with extended criteria have produced surgical results comparable to those obtained with traditional standards. However, it is not sufficient to predict hepatocellular carcinoma (HCC) recurrence after LT according to morphological criteria alone. The present study aimed to construct a nomogram for predicting HCC recurrence after LT using extended selection criteria. MethodsRetrospective data on patients with HCC, including pathology, serological markers and follow-up data, were collected from January 2015 to April 2020 at Huashan Hospital, Fudan University, Shanghai, China. Logistic least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analyses were performed to identify and construct the prognostic nomogram. Receiver operating characteristic (ROC) curves, Kaplan-Meier curves, decision curve analyses (DCAs), calibration diagrams, net reclassification indices (NRIs) and integrated discrimination improvement (IDI) values were used to assess the prognostic capacity of the nomogram. ResultsA total of 301 patients with HCC who underwent LT were enrolled in the study. The nomogram was constructed, and the ROC curve showed good performance in predicting survival in both the development set (2/3) and the validation set (1/3) (the area under the curve reached 0.748 and 0.716, respectively). According to the median value of the risk score, the patients were categorized into the high- and low-risk groups, which had significantly different recurrence-free survival (RFS) rates (P < 0.01). Compared with the Milan criteria and University of California San Francisco (UCSF) criteria, DCA revealed that the new nomogram model had the best net benefit in predicting 1-, 3- and 5-year RFS. The nomogram performed well for calibration, NRI and IDI improvement. ConclusionsThe nomogram, based on the Milan criteria and serological markers, showed good accuracy in predicting the recurrence of HCC after LT using extended selection criteria.

Introduction of ex vivo perfusion of extended-criteria donor hearts in a single center in Asia.

The shortage of organs for heart transplantation has created a need to explore the use of extended-criteria organs. We report the preliminary use of normothermic TransMedics Organ Care System-an ex vivo approach to preserve extended-criteria brain-dead donor hearts. This System maintains a normal temperature, provides continuous perfusion and oxygenation, reduces ischemic time, and enables additional viability assessment options. In a retrospective single-centre study conducted from April 2020 to March 2023, four extended criteria brain-dead donor hearts were perfused and monitored using the Organ Care System. Suitability for transplantation was assessed based on stable or decreasing lactate levels, along with appropriate perfusion parameters. The Organ Care for use of the Organ Care System were coronary artery disease, left ventricular hypertrophy, high-dose inotrope use in the donor, a downtime exceeding 20min, and a left ventricular ejection fraction of 40-50%. Three out of the four donor hearts were transplanted, while one was discarded due to rising lactate concentration. The three recipients had a higher surgical risk profile for heart transplant. All showed normal cardiac function and no primary graft dysfunction postoperatively. At 2-3years post-transplant, all recipients have a ventricular function of > 60%, with only one showing evidence of mild rejection. The Organ Care System enables the successful transplantation of marginal donor organs in high-risk recipients, showcasing the feasibility of recruiting donors with extended criteria. This technique is safe and promising, expanding the donor pool and addressing the organ shortage in heart transplantation in Hong Kong.

Graft repair during machine perfusion: a current overview of strategies.

With changing donor characteristics (advanced age, obesity), an increase in the use of extended criteria donor (ECD) livers in liver transplantation is seen. Machine perfusion allows graft viability assessment, but still many donor livers are considered nontransplantable. Besides being used as graft viability assessment tool, ex situ machine perfusion offers a platform for therapeutic strategies to ameliorate grafts prior to transplantation. This review describes the current landscape of graft repair during machine perfusion. Explored anti-inflammatory therapies, including inflammasome inhibitors, hemoabsorption, and cellular therapies mitigate the inflammatory response and improve hepatic function. Cholangiocyte organoids show promise in repairing the damaged biliary tree. Defatting during normothermic machine perfusion shows a reduction of steatosis and improved hepatobiliary function compared to nontreated livers. Uptake of RNA interference therapies during machine perfusion paves the way for an additional treatment modality. The possibility to repair injured donor livers during ex situ machine perfusion might increase the utilization of ECD-livers. Application of defatting agents is currently explored in clinical trials, whereas other therapeutics require further research or optimization before entering clinical research.

Steatotic Donor Transplant Livers: Preservation Strategies to Mitigate against Ischaemia-Reperfusion Injury.

Liver transplantation (LT) is the only definitive treatment for end-stage liver disease, yet the UK has seen a 400% increase in liver disease-related deaths since 1970, constrained further by a critical shortage of donor organs. This shortfall has necessitated the use of extended criteria donor organs, including those with evidence of steatosis. The impact of hepatic steatosis (HS) on graft viability remains a concern, particularly for donor livers with moderate to severe steatosis which are highly sensitive to the process of ischaemia-reperfusion injury (IRI) and static cold storage (SCS) leading to poor post-transplantation outcomes. This review explores the pathophysiological predisposition of steatotic livers to IRI, the limitations of SCS, and alternative preservation strategies, including novel organ preservation solutions (OPS) and normothermic machine perfusion (NMP), to mitigate IRI and improve outcomes for steatotic donor livers. By addressing these challenges, the liver transplant community can enhance the utilisation of steatotic donor livers which is crucial in the context of the global obesity crisis and the growing need to expand the donor pool.

Non-asymptotic model selection for models of network data with parameter vectors of increasing dimension

Model selection for network data is an open area of research. Using the β-model as a convenient starting point, we propose a simple and non-asymptotic approach to model selection of β-models with and without constraints. Simulations indicate that the proposed model selection approach selects the data-generating model with high probability, in contrast to classical and extended Bayesian Information Criteria. We conclude with an application to the Enron email network, which has 181,831 connections among 36,692 employees.

A novel modified Steen solution limits inflammatory processes during ex vivo lung perfusion and improves graft function post-transplantation

BackgroundEx vivo lung perfusion allows donor lung preservation, assessment and reconditioning prior to transplantation, but is associated with increased inflammatory injury over time. Addition of anti-oxidative and anti-inflammatory agents to perfusate formulations could limit iatrogenic injury during perfusion. The effectiveness of a modified Steen solution containing acetyl salicylic acid, retinoic acid and methylprednisolone, was examined using a porcine extended criteria donor ex vivo lung perfusion and transplantation model. MethodsPorcine donor lungs underwent 24 hours cold storage and were then randomised to 4 hours normothermic ex vivo lung perfusion with modified Steen or original Steen, followed by single lung transplantation into a recipient pig. RNA-sequencing was used to assess tissue inflammatory changes during perfusion. Organ function was examined during perfusion and following transplantation and compared between groups. ResultsLungs perfused with modified Steen showed reduced pulmonary vascular resistance (p=0.0391) and stable pulmonary artery pressure despite achieving higher flows (p=0.0001) compared to Steen. Lung tissue showed negative enrichment of the TNF-α signalling via NF-κB pathway (p=0.0040) in modified Steen compared to Steen. Recipients of lungs perfused with modified Steen also showed improved post-transplantation oxygenation (p=0.0462). ConclusionsThis study highlights the superiority of modified Steen compared with original Steen. The modifications to Steen solution appear to limit inflammatory injury via the NF-κB signalling pathway during perfusion, leading to improved post-transplant function. Modified Steen provides the potential to improve post-transplant outcomes following EVLP of extended criteria lungs and could also facilitate extended assessment and preservation, as well as administration of advanced therapies.