Association of cardiac preservation solution with short-term outcomes after heart transplantation.

AIMS: There is wide variability in the practice of cardiac preservation for heart transplantation. Prior reports suggest that the type of solution may be linked with a reduced incidence of posttransplantation complications. METHODS: Adult (≥18 years old) heart recipients who underwent transplantation between 2015 and 2021 in the United States were examined. Recipients were stratified by solution utilized for their grafts at the time of recovery: University of Wisconsin, histidine-tryptophan-ketoglutarate (HTK), or Celsior solution. The primary endpoint was a composite of 30-day mortality, primary graft dysfunction, or re-transplantation. Risk adjustment was performed for the recipient, donor, and procedural characteristics using regression modeling. RESULTS: Among 16 884 recipients, the group distribution was University of Wisconsin solution 53%, HTK 22%, Celsior solution 15%, and other 10%. The observed incidence of the composite endpoint (University of Wisconsin solution = 3.6%, HTK = 4.0%, Celsior solution = 3.7%, P = 0.301) and 1-year survival (University of Wisconsin solution = 91.7%, HTK = 91.3%, Celsior solution = 91.7%, log-rank P = 0.777) were similar between groups. After adjustment, HTK was associated with a higher risk of the composite endpoint [odds ratio (OR) 1.249, 95% confidence interval (CI) 1.019-1.525, P = 0.030] in reference to University of Wisconsin solution. This association was substantially increased among recipients with ischemic periods of greater than 4 h (OR 1.817, 95% CI 1.188-2.730, P = 0.005). The risks were similar between University of Wisconsin solution and Celsior solution (P = 0.454). CONCLUSION: The use of the histidine-tryptophan-ketoglutarate solution during cold static storage for cardiac preservation is associated with increased rates of early mortality or primary graft dysfunction. Clinician discretion should guide its use, especially when prolonged ischemic times (>4 h) are anticipated.

Impact of statin treatment and exposure on the risk of chronic allograft dysfunction in Chinese lung transplant recipients.

PURPOSE: Chronic lung allograft dysfunction (CLAD) was a common complication following lung transplantation that contributed to long-term morbidity and mortality. Statin therapy had been suggested to attenuate recipient inflammation and immune response, potentially reducing the risk and severity of CLAD. This study aimed to evaluate the impact of statin use and in vivo exposure on the incidence of CLAD in lung transplant recipients (LTRs), as well as their effects on immune cells and inflammatory factors. METHODS: A retrospective cohort study was conducted on patients who underwent lung transplantation between January 2017 and December 2020. The incidence of CLAD, as per the 2019 ISHLT criteria, was assessed as the clinical outcome. The plasma concentrations of statin were measured using a validated UPLC-MS/MS method, while inflammation marker levels were determined using ELISA kits. RESULTS: The statin group exhibited a significantly lower rate of CLAD (P = 0.002). Patients receiving statin therapy showed lower CD4+ T-cell counts, total T-lymphocyte counts, and IL-6 levels (P = 0.017, P = 0.048, and P = 0.038, respectively). Among the CLAD groups, the atorvastatin level (2.51 ± 1.31 ng/ml) was significantly lower than that in the non-CLAD group (OR = 1.438, 95%CI (1.007-2.053), P = 0.046). CONCLUSION: Statin therapy significantly reduced the incidence of CLAD, as well as immune cell counts and inflammatory cytokine levels in LTRs. Although the statin exposure was significantly lower in CLAD patients, it was not associated with the incidence of CLAD.

The Glasgow Experience of Extended Myocardial Protection: A Novel Method of Implantation to Reduce Primary Graft Dysfunction After Heart Transplant.

OBJECTIVES: Around 2000 heart transplants are performed in Europe annually. The rates of primary graft dysfunction in Europe are among the highest in the world. With increasing demand for organs and the limited supply of donors, novel techniques such as ex vivo normothermic perfusion have garnered incre-asing interest. We present a series of patients who underwent heart transplant at our unit in which we used a novel implantation technique to reduce primary graft dysfunction. MATERIALS AND METHODS: We compared our experience with the novel method detailed in our article (Glasgow experience group) with a contemporary UK cohort (2015-2016) of patients (control group). We performed multivariable logistic regression to compare the Glasgow experience with the control group with primary graft dysfunction as the outcome measure. We adjusted for donor age, recipient diabetes mellitus, urgent listing status, bypass time, and total ischemic time. RESULTS: Among 194 patients in both cohorts, 140 patients (72.1%) were men and 36 (18.6%) had ischemic cardiomyopathy. The odds ratio of primary graft dysfunction in the control group was 2.99 (95% CI, 1.02- 8.75) compared with the Glasgow experience group. CONCLUSIONS: Our novel approach was associated with significant reductions in primary graft dysfunction, with a trend toward improved 1-year survival. Larger studies are needed to show differences after further adjustment for known confounders of primary graft dysfunction. We believe this novel technique is safe, cost-effective, and reproducible.

Impact of pre-lung transplant statin use on the development of primary graft dysfunction.

BACKGROUND: Primary graft dysfunction (PGD) is a common occurrence following lung transplantation and contributes to short- and long-term morbidity and mortality. Current management strategies are limited, and robust data to support their use is lacking. Preventative strategies attenuating the recipient's inflammatory state suggest statin therapy may decrease the incidence and severity of PGD. This study aims to evaluate the impact of pre-transplant statin use on the incidence and severity of PGD following lung transplantation. METHODS: A retrospective cohort study was performed evaluating all patients undergoing bilateral lung transplantation from September 2012 to December 2019. The primary outcome was the incidence of PGD by grade, defined as the highest grade of PGD experienced in the first 72 h. Secondary outcomes included length of intensive care unit and hospital stays and mortality. RESULTS: Of the 357 patients included in the study, 107 received statin therapy prior to transplant (statin group) and 250 did not (no statin group). PGD occurred in 257 (72%) patients; in the entire cohort, 99 (28%) patients experienced PGD grade 1, 59 (17%) grade 2, and 99 (28%) grade 3. A significantly lower incidence of PGD was observed in the statin group (64.5% vs 75.2%, p = 0.039); however, the association did not remain significant on multinominal analysis for an overall incidence of any PGD (p = 0.275) or incidence of severe PGD (p = 0.240). Statin intensity was not associated with the development of PGD. CONCLUSIONS: Pre-transplant statin therapy did not appear to impact the development of PGD following lung transplantation. Future prospective studies should further evaluate the impact of statin intensity and duration on the incidence and severity of PGD.

CD11b suppresses TLR activation of nonclassical monocytes to reduce primary graft dysfunction after lung transplantation.

Primary graft dysfunction (PGD) is the leading cause of postoperative mortality in lung transplant recipients and the most important risk factor for development of chronic lung allograft dysfunction. The mechanistic basis for the variability in the incidence and severity of PGD between lung transplant recipients is not known. Using a murine orthotopic vascularized lung transplant model, we found that redundant activation of Toll-like receptors 2 and 4 (TLR2 and -4) on nonclassical monocytes activates MyD88, inducing the release of the neutrophil attractant chemokine CXCL2. Deletion of Itgam (encodes CD11b) in nonclassical monocytes enhanced their production of CXCL2 and worsened PGD, while a CD11b agonist, leukadherin-1, administered only to the donor lung prior to lung transplantation, abrogated CXCL2 production and PGD. The damage-associated molecular pattern molecule HMGB1 was increased in peripheral blood samples from patients undergoing lung transplantation after reperfusion and induced CXCL2 production in nonclassical monocytes via TLR4/MyD88. An inhibitor of HMGB1 administered to the donor and recipient prior to lung transplantation attenuated PGD. Our findings suggest that CD11b acts as a molecular brake to prevent neutrophil recruitment by nonclassical monocytes following lung transplantation, revealing an attractive therapeutic target in the donor lung to prevent PGD in lung transplant recipients.

Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation.

Despite improvements, lung transplantation remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine adsorption as a means of treating ARDS donor lungs. We induced mild to moderate ARDS using lipopolysaccharide in 16 donor pigs. Lungs were then treated with or without cytokine adsorption during ex vivo lung perfusion (EVLP) and/or post-transplantation using extracorporeal hemoperfusion. The treatment significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. Overall, cytokine adsorption was able to restore lung function and reduce PGD in lung transplantation. We suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient.

Controlled temperatures in cold preservation provides safe heart transplantation results.

BACKGROUND: We aimed to investigate the short-term outcomes of heart transplant patients who underwent SherpaPak™ donor organ preservation. METHOD: We prospectively collected the data of patients who underwent heart transplantation using SherpaPak™ system for donor organ transportation from February 2020 to March 2021. Donor and recipient demographic data, preoperative and postoperative echocardiographic and hemodynamic parameters, total ischemic time and SherpaPak temperatures, vasoactive inotropic scores (VIS), primary graft dysfunction (PGD) status, intensive care unit stay, complications, and mortality during follow-up were assessed. RESULTS: A total of 39 consecutive heart transplant patients with SherpaPak system were included in the study. The mean donor age was 32.2 ± 6.7 (range: 16-46). The mean recipient age was 57.5 ± 12 (range: 19-73). The mean preoperative ejection fraction (EF) was 23.7 ± 15.4 (range: 5-75). All recipients underwent a standard bicaval technique for orthotopic heart implantation. The mean total ischemic time was 230.1 ± 41 (range: 149-342) min. The mean Sherpa temperature was 5.6 ± 0.8°C (range: 3.7-7.5). The mean VIS was 10.2 ± 6.5 (range: 2-32). The number of mild PGD was 5 (14.7%), and moderate PGD was 4 (11.8%). There was no severe PGD. The postoperative EF was 64.3 ± 5.5 (range: 50-78). Mean intubation time was 47.4 ± 64 (range: 8-312, median: 22) h. The mean time of intensive care unit stay was 6.3 ± 5 (range: 2-31, median: 5) days. Two patients required chest revision (5.8%), two patients had lung infection (5.8%). Two patients had a stroke (5.8%). There was no mortality. CONCLUSION: Using the SherpaPak system during heart transplantation is safe and not associated with significant recipient morbidity. None of the recipients experienced significant PGD and mortality.

Indications and outcome after lung transplantation in children under 12 years of age: A 16-year single center experience.

OBJECTIVE: Paediatric lung transplantation poses unique management challenges. Experience regarding indications and outcome is scarce, especially in younger children. The primary aim of this study was to investigate outcome after first lung transplantation in children <12 years of age in comparison to adolescents (12-17 years old). METHODS: Records of patients <18 years who underwent first lung transplantation between 01/2005 and 01/2021 were retrospectively reviewed, and compared between children <12 years old and adolescents. Median (IQR) follow-up was 51 (23-91) months. RESULTS: Of the 117 patients underwent first lung transplantation at our institution, of whom 42 (35.8%) patients were <12 years and 75 (64.2%) ≥12 years old. Compared to adolescents, children were more often transplanted for interstitial lung disease (33.3% vs 12%, p = 0.005) and precapillary pulmonary hypertension (28.6% vs 12%, p = 0.025), and required more often intraoperative cardiopulmonary bypass (31% vs 14.7%, p = 0.036) and postoperative ECMO support (47.6% vs 13.3%, p < 0.001). Postoperatively, children required longer ventilation times (78 vs 18 hours, p = 0.009) and longer ICU stay (9.5 vs 3 days, p < 0.001) compared to their older counterparts. Primary graft dysfunction grade 3 at 72 hours (9.5% vs 9.3%, p = 0.999), in-hospital mortality (2.4% vs 6.7%, p = 0.418), graft survival (80% vs 62%, p = 0.479) and freedom from chronic lung allograft dysfunction (76% vs 59%, p = 0.41) at 8-year follow-up did not differ between groups. CONCLUSIONS: Lung transplantation in children under 12 years is challenging due to underlying medical conditions and operative complexity. Nevertheless, outcomes are comparable to those in older children.

The potential of ex vivo lung perfusion on improving organ quality and ameliorating ischemia reperfusion injury.

Allogeneic lung transplantation (LuTx) is considered the treatment of choice for a broad range of advanced, progressive lung diseases resistant to conventional treatment regimens. Ischemia reperfusion injury (IRI) occurring upon reperfusion of the explanted, ischemic lung during implantation remains a crucial mediator of primary graft dysfunction (PGD) and early allo-immune responses. Ex vivo lung perfusion (EVLP) displays an advanced technique aiming at improving lung procurement and preservation. Indeed, previous clinical trials have demonstrated a reduced incidence of PGD following LuTx utilizing EVLP, while long-term outcomes are yet to be evaluated. Mechanistically, EVLP may alleviate donor lung inflammation through reconditioning the injured lung and diminishing IRI through storing the explanted lung in a non-ischemic, perfused, and ventilated status. In this work, we review potential mechanisms of EVLP that may attenuate IRI and improve organ quality. Moreover, we dissect experimental treatment approaches during EVLP that may further attenuate inflammatory events deriving from tissue ischemia, shear forces or allograft rejection associated with LuTx.

Methods of Attenuating Ischemia-Reperfusion Injury in Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent indications for liver transplantation. However, the transplantation is ultimately associated with the occurrence of ischemia-reperfusion injury (IRI). It affects not only the function of the graft but also significantly worsens the oncological results. Various methods have been used so far to manage IRI. These include the non-invasive approach (pharmacotherapy) and more advanced options encompassing various types of liver conditioning and machine perfusion. Strategies aimed at shortening ischemic times and better organ allocation pathways are still under development as well. This article presents the mechanisms responsible for IRI, its impact on treatment outcomes, and strategies to mitigate it. An extensive review of the relevant literature using MEDLINE (PubMed) and Scopus databases until September 2020 was conducted. Only full-text articles written in English were included. The following search terms were used: "ischemia reperfusion injury", "liver transplantation", "hepatocellular carcinoma", "preconditioning", "machine perfusion".

Lung transplantation using allografts with more than 8 hours of ischemic time: A single-institution experience.

BACKGROUND: Six hours was historically regarded as the limit of acceptable ischemic time for lung allografts. However, broader sharing of donor lungs often necessitates use of allografts with ischemic time >6 hours. We characterized the association between ischemic time ≥8 hours and outcomes after lung transplantation using a contemporary cohort from a high-volume institution. METHODS: Patients who underwent primary isolated bilateral lung transplantation between 1/2016 and 5/2020 were included. Patients bridged to transplant with extracorporeal membrane oxygenation or mechanical ventilation, and ex-vivo perfusion cases were excluded. Recipients were stratified by total allograft ischemic time <8 hours (standard) vs ≥8 hours (long). Perioperative outcomes and post-transplant survival were compared between groups. RESULTS: Of 358 patients, 95 (26.5%) received long ischemic time (≥8 hours) lungs. Long ischemic time recipients were more likely to be male and have donation after circulatory death donors than standard ischemic time recipients. On unadjusted analysis, long and standard ischemic time recipients had similar survival, and similar rates of grade 3 primary graft dysfunction at 72 hours, extracorporeal membrane oxygenation post-transplant, acute rejection within 30 days, reintubation, and post-transplant length of stay. After adjustment, long and standard ischemic time recipients had comparable risks of mortality or graft failure. CONCLUSIONS: In a modern cohort, use of lung allografts with "long" ischemic time ≥8 hours were associated with acceptable perioperative outcomes and post-transplant survival. Further investigation is required to better understand how broader use impacts post-lung transplant outcomes and the implications for smarter sharing under an evolving national allocation policy.

Lung Transplantation, Pulmonary Endothelial Inflammation, and Ex-Situ Lung Perfusion: A Review.

Lung transplantation (LTx) is the gold standard treatment for end-stage lung disease; however, waitlist mortality remains high due to a shortage of suitable donor lungs. Organ quality can be compromised by lung ischemic reperfusion injury (LIRI). LIRI causes pulmonary endothelial inflammation and may lead to primary graft dysfunction (PGD). PGD is a significant cause of morbidity and mortality post-LTx. Research into preservation strategies that decrease the risk of LIRI and PGD is needed, and ex-situ lung perfusion (ESLP) is the foremost technological advancement in this field. This review addresses three major topics in the field of LTx: first, we review the clinical manifestation of LIRI post-LTx; second, we discuss the pathophysiology of LIRI that leads to pulmonary endothelial inflammation and PGD; and third, we present the role of ESLP as a therapeutic vehicle to mitigate this physiologic insult, increase the rates of donor organ utilization, and improve patient outcomes.

Donor Hepatic Occult Collagen Deposition Predisposes to Peritransplant Stress and Impacts Human Liver Transplantation.

BACKGROUND AND AIMS: Environmentally triggered chronic liver inflammation can cause collagen deposits, whereas early stages of fibrosis without any specific symptoms could hardly be detectable. We hypothesized that some of the human donor grafts in clinical liver transplantation (LT) might possess unrecognizable fibrosis, affecting their susceptibility to LT-induced stress and hepatocellular damage. This retrospective study aimed to assess the impact of occult hepatic fibrosis on clinical LT outcomes. APPROACH AND RESULTS: Human (194) donor liver biopsies were stained for collagen with Sirius red, and positive areas (Sirius red-positive area; SRA) were measured. The body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score was calculated using 962 cases of the donor data at the procurement. LT outcomes, including ischemia-reperfusion injury (IRI), early allograft dysfunction (EAD), and survival rates, were analyzed according to SRA and BARD scores. With the median SRA in 194 grafts of 9.4%, grafts were classified into low-SRA (<15%; n = 140) and high-SRA (≥15%; n = 54) groups. Grafts with high SRA suffered from higher rates of IRI and EAD (P < 0.05) as compared to those with low SRA. Interestingly, high SRA was identified as an independent risk factor for EAD and positively correlated with the donor BARD score. When comparing low-BARD (n = 692) with high-BARD (n = 270) grafts in the same period, those with high BARD showed significantly higher post-LT transaminase levels and higher rates of IRI and EAD. CONCLUSIONS: These findings from the largest clinical study cohort to date document the essential role of occult collagen deposition in donor livers on LT outcomes. High-SRA and donor BARD scores correlated with an increased incidence of hepatic IRI and EAD in LT recipients. This study provides the rationale for in-depth and prospective assessment of occult fibrosis for refined personalized LT management.

Primary graft dysfunction.

PURPOSE OF REVIEW: Primary graft dysfunction (PGD) is a devastating complication in the acute postoperative lung transplant period, associated with high short-term mortality and chronic rejection. We review its definition, pathophysiology, risk factors, prevention, treatment strategies, and future research directions. RECENT FINDINGS: New analyses suggest donation after circulatory death and donation after brain death donors have similar PGD rates, whereas donors >55 years are not associated with increased PGD risk. Recipient pretransplant diastolic dysfunction and overweight or obese recipients with predominant abdominal subcutaneous adipose tissue have increased PGD risk. Newly identified recipient biomarkers and donor and recipient genes increase PGD risk, but their clinical utility remains unclear. Mixed data still exists regarding cold ischemic time and PGD risk, and increased PGD risk with cardiopulmonary bypass remains confounded by transfusions. Portable ex vivo lung perfusion (EVLP) may prevent PGD, but its use is limited to a handful of centers. Although updates to current PGD treatment are lacking, future therapies are promising with targeted therapy and the use of EVLP to pharmacologically recondition donor lungs. SUMMARY: There is significant progress in defining PGD and identifying its several risk factors, but effective prevention and treatment strategies are needed.

Effects of GLP-1 receptor agonists and SGLT-2 inhibitors in heart transplant patients with type 2 diabetes: Initial report from a cardiometabolic center of excellence.

Type 2 diabetes mellitus (T2D) is a common comorbidity among patients who have undergone heart transplantation. Recently two classes of glucose-lowering medications (sodium-glucose cotransporter type-2 inhibitors [SGLT-2Is] and glucagon-like-peptide-1 receptor agonists [GLP-1RAs]), have been shown to significantly improve cardiovascular outcomes. There is a paucity of data regarding their use in immunosuppressed patients, with many studies specifically excluding this population. We retrospectively evaluated the safety and efficacy of GLP-1RAs and SGLT-2Is in patients who had undergone orthotopic heart transplant at a high-volume center. Among 21 patients, we found significant weight loss, reductions in insulin use, hemoglobin A1c, and low-density lipoprotein-cholesterol. Moreover, both SGLT-2Is and GLP-1RAs were well tolerated with no adverse events leading to discontinuation of either therapy. While larger studies of patients after solid organ transplant are needed, this small hypothesis-generating study demonstrates that SGLT-2Is and GLP-1RAs appear safe and effective therapies among patients with T2D after heart transplant.

Procedural mechanical support for lung transplantation.

PURPOSE OF REVIEW: The use of procedural mechanical support during lung transplantation (LTx) varies between centers and the optimal support strategy is still controversially discussed. The two main questions are if cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) should be preferred and whether mechanical support should be reserved for specific patient groups or a routine use can be recommended. RECENT FINDINGS: Recent cohort studies have consistently shown that LTx on CPB leads to inferior outcomes when compared to venoarterial (va)-ECMO. Thus, ECMO should be preferred in lung transplantation except for special indications. Despite its higher invasiveness, ECMO offers some pivotal advantages over off-pump lung transplantation. It has been shown to remarkably reduce rates of primary graft dysfunction, supporting the concept of a routine intraoperative ECMO use in LTx. SUMMARY: Although randomized-controlled trials addressing this question are still lacking, current evidence appears to favor the routine use of ECMO support during lung transplantation.

Prediction of donor related lung injury in clinical lung transplantation using a validated ex vivo lung perfusion inflammation score.

BACKGROUND: Ex vivo lung perfusion (EVLP) is an isolated organ assessment technique that has revolutionized the field of lung transplantation and enabled a safe increase in the number of organs transplanted. The objective of this study was to develop a protein-based assay that would provide a precision medicine approach to lung injury assessment during EVLP. METHODS: Perfusate samples collected from clinical EVLP cases performed from 2009 to 2019 were separated into development (n = 281) and validation (n = 57) sets to derive and validate an inflammation score based on IL-6 and IL-8 protein levels in perfusate. The ability of an inflammation score to predict lungs suitable for transplantation and likely to produce excellent recipient outcomes (time on ventilator ≤ 3 days) was assessed. Inflammation scores were compared to conventional clinical EVLP assessment parameters and associated with outcomes, including primary graft dysfunction and patient care in the ICU. RESULTS: An inflammation score accurately predicted the decision to transplant (AUROC 68% [95% CI 62-74]) at the end of EVLP and those transplants associated with short ventilator times (AUROC 73% [95% CI 66-80]). The score identified lungs more likely to develop primary graft dysfunction at 72-hours post-transplant (OR 4.0, p = 0.03). A model comprised of the inflammation score and ∆PO2 was able to determine EVLP transplants that were likely to have excellent recipient outcomes, with an accuracy of 87% [95% CI 83-92]. CONCLUSIONS: The adoption of an inflammation score will improve accuracy of EVLP decision-making and increase confidence of surgical teams to determine lungs that are suitable for transplantation, thereby improving organ utilization rates and patient outcomes.

Common Criteria for Ex Vivo Lung Perfusion Have No Significant Impact on Posttransplant Outcomes.

BACKGROUND: Although it is intense in health care resources, by facilitating assessment and reconditioning, ex vivo lung perfusion (EVLP) has the potential to expand the donor pool and improve lung transplant outcomes. However, inclusion criteria used in EVLP trials have not been validated. METHODS: This retrospective study from 2014 to 2018 reviewed our local state-based donation organization donor records as well as subsequent recipient outcomes to explore the relation between EVLP indications used in clinical trials and recipient outcomes. The primary outcome was primary graft dysfunction grade 3 at 24 hours, with 30-day mortality and posttransplant survival time as secondary outcomes, compared with univariate and multivariate analysis. RESULTS: From 705 lung donor referrals, 304 lung transplantations were performed (use rate of 42%); 212 of recipients (70%) met at least 1 of the commonly cited EVLP initiation criteria. There was no significant difference in primary graft dysfunction grade 3 or 30-day mortality between recipients with or without an EVLP indication (10.2% versus 7.8%, P = .51; and 2.4% versus 0%, P = .14, respectively). Multivariate analyses showed no significant relationship between commonly cited EVLP criteria and primary graft dysfunction grade 3 or survival time. Recipient outcomes were significantly associated with recipient diagnosis. CONCLUSIONS: At least 1 commonly cited criterion for EVLP initiation was present in 70% of the transplanted donors, and yet it did not predict clinical results; acceptable outcomes were seen in both subgroups. To discover the true utility of EVLP beyond good clinical management and focus EVLP on otherwise unacceptable lungs, a reconsideration of EVLP inclusion criteria is required.

The Potential Role of Efficacy and Safety Evaluation of N-Acetylcysteine Administration During Liver Procurement. The NAC-400 Single Center Randomized Controlled Trial.

BACKGROUND: N-acetylcysteine infusions have been widely used to reduce ischemia/reperfusion damage to the liver; however, convincing evidence of their benefits is lacking. OBJECTIVE: To perform the largest randomized controlled trial to compare the impact of N-acetylcysteine infusion during liver procurement on liver transplant outcomes. METHODS: Single center, randomized trial with patients recruited from La Fe University Hospital, Spain, from February 2012 to January 2016. A total of 214 grafts were transplanted and randomized to the N-acetylcysteine group (n = 113) or to the standard protocol without N-acetylcysteine (n = 101). The primary endpoint was allograft dysfunction (Olthoff criteria). Secondary outcomes included metabolomic biomarkers of oxidative stress levels, interactions between cold ischemia time and alanine aminotransferase level and graft and patient survival (ID no. NCT01866644). RESULTS: The incidence of primary dysfunction was 34% (31% in the N-acetylcysteine group and 37.4% in the control group [P = 0.38]). N-acetylcysteine administration reduced the alanine aminotransferase level when cold ischemia time was longer than 6 h (P = 0.0125). Oxidative metabolites (glutathione/oxidized glutathione and ophthalmic acid) were similar in both groups (P > 0.05). Graft and patient survival rates at 12 mo and 3 y were similar between groups (P = 0.54 and P = 0.69, respectively). CONCLUSIONS: N-acetylcysteine administration during liver procurement does not improve early allograft dysfunction according to the Olthoff classification. However, when cold ischemia time is longer than 6 h, N-acetylcysteine improves postoperative ALT levels.