Extracorporeal photopheresis (ECP) in the treatment of chronic lung allograft dysfunction (CLAD): a prospective, multicentre, open-label, randomised controlled trial studying the addition of ECP to standard care in the treatment of bilateral lung transplant patients with CLAD (E-CLAD UK).

BACKGROUND: Long-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to the lung allograft. This damage, which can develop via multiple immune pathways, is captured under the umbrella term chronic lung allograft dysfunction (CLAD). Despite the availability of powerful immunosuppressive drugs, there are presently no treatments proven to reverse or reliably halt the loss of lung function caused by CLAD. The aim of the E-CLAD UK trial is to determine whether the addition of immunomodulatory therapy, in the form of extracorporeal photopheresis (ECP), to standard care is more efficacious at stabilising lung function in CLAD compared with standard care alone. METHODS AND ANALYSIS: E-CLAD UK is a Phase II clinical trial of an investigational medicinal product (Methoxsalen) delivered to a buffy coat prepared via an enclosed ECP circuit. Target recruitment is 90 bilateral lung transplant patients identified as having CLAD and being treated at one of the five UK adult lung transplant centres. Participants will be randomised 1:1 to intervention plus standard of care, or standard of care alone. Intervention will comprise nine ECP cycles spread over 20 weeks, each course involving two treatments of ECP on consecutive days. All participants will be followed up for a period of 24 weeks.The primary outcome is lung function stabilisation derived from change in forced expiratory volume in one second and forced vital capacity at 12 and 24 weeks compared with baseline at study entry. Other parameters include change in exercise capacity, health-related quality of life and safety. A mechanistic study will seek to identify molecular or cellular markers linked to treatment response and qualitative interviews will explore patient experiences of CLAD and the ECP treatment.A patient and public advisory group is integral to the trial from design to implementation, developing material to support the consent process and interview materials. ETHICS AND DISSEMINATION: The East Midlands-Derby Research Ethics Committee has provided ethical approval (REC 22/EM/0218). Dissemination will be via publications, patient-friendly summaries and presentation at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT number 2022-002659-20; ISRCTN 10615985.

Early experience of a new national lung allocation scheme in the UK based on clinical urgency.

INTRODUCTION: A new UK Lung Allocation Scheme (UKLAS) was introduced in 2017, replacing the previous geographic allocation system. Patients are prioritised according to predefined clinical criteria into a three-tier system: the super-urgent lung allocation scheme (SULAS), the urgent lung allocation scheme (ULAS) and the non-urgent lung allocation scheme (NULAS). This study assessed the early impact of this scheme on waiting-list and post-transplant outcomes. METHODS: A cohort study of adult lung transplant registrations between March 2015 and November 2016 (era-1) and between May 2017 and January 2019 (era-2). Outcomes from registration were compared between eras and stratified by urgency tier and diagnostic group. RESULTS: During era-1, 461 patients were registered. In era-2, 471 patients were registered (19 (4.0%) SULAS, 82 (17.4%) ULAS and 370 (78.6%) NULAS). SULAS patients were younger (median age 35 vs 50 and 55 for urgent and non-urgent, respectively, p=0.0015) and predominantly suffered from cystic fibrosis (53%) or pulmonary fibrosis (37%). Between eras 1 and 2, the odds of transplantation within 6 months of registration were increased (OR=1.41, 95% CI 1.07 to 1.85, p=0.0142) despite only a 5% increase in transplant activity. Median time-to-transplantation during era-1 was 427 days compared with waiting times in era-2 of 8 days for SULAS, 15 days for ULAS and 585 days for NULAS patients. Waiting-list mortality (15% era-1 vs 13% era-2; p=0.5441) and post-transplant survival at 1 year (81.3% era-1 vs 83.3% era-2; p=0.6065) were similar between eras. CONCLUSION: The UKLAS scheme prioritises the critically ill and improves transplantation odds. The true impact on waiting-list mortality and post-transplant survival requires further follow-up.

Variable Sequestration of Antifungals in an Extracorporeal Membrane Oxygenation Circuit.

Fungal infections are common and frequently associated with clinical failure in patients receiving extracorporeal membrane oxygenation (ECMO). Antifungal drugs have physicochemical characteristics associated with a higher likelihood of sequestration onto ECMO circuitry potentially leading to a subtherapeutic drug concentration. The percentage of sequestration of the antifungal drugs-caspofungin, posaconazole, and voriconazole-was determined using an ex vivo ECMO model. The circuits were primed with whole human blood, sodium chloride 0.9%, and human albumin solution. Serial 2 ml samples were taken at baseline, 0.5, 1, 2, 6, 12, and 24 hours after drug addition, paired with non-ECMO controls stored in a water bath at 37°C. Mean loss from the blood-primed ECMO circuits and controls at 24 hours relative to baseline were 80% and 61% for caspofungin ( p = ns), 64% and 11% for posaconazole ( p < 0.005), and 27% and 19% for voriconazole ( p < 0.05). Calculated AUC 0-24 showed a 44% for caspofungin ( p = ns), 30.6% posaconazole ( p < 0.005), and 9% loss for voriconazole ( p = 0.003) compared with the controls, suggesting therapeutic concentrations of these antifungal agents cannot be guaranteed with standard dosing in patients on ECMO. Posaconazole exhibited the greatest loss to the ECMO circuit correlating with both high lipophilicity and protein binding of the drug.

The role of extracorporeal life support in the management with severe idiopathic pulmonary artery hypertension undergoing lung transplantation: are those patients referred too late?

BACKGROUND: Idiopathic pulmonary artery hypertension (iPAH) is a relatively minor indication for lung transplantation (LTx) with comparatively poorer outcomes. Extracorporeal life support (ECLS) in various forms is increasingly being used in the management of this entity. However, the data and experience with this therapy remains limited. We evaluated the role of ECLS in the management of severe iPAH patients as a bridge to LTx as well as post LTx support. METHODS: A retrospective analysis of iPAH patients that received LTx between January 2007 and May 2014 was performed. Early- and mid-term outcomes were analyzed for this patient cohort. Also, early and mid-term outcomes after LTx were compared to the control group of patients with other diagnoses using unadjusted analysis and 1:3 propensity score matching. RESULTS: Of 321 LTx performed during the study period in our centre 15 patients had iPAH as a cause of end-stage lung disease. Four iPAH (27%) patients were bridged to LTx utilizing ECLS in the form of veno-arterial ECMO and extra-corporeal CO2 removal device, whereas 9 patients (60%) required ECLS support for primary graft dysfunction (PGD) after surgery. Patients with iPAH required more frequently on-pump LTx, both pre and post LTx ECLS, and had significantly lower pO2/FiO2 ratio at 24, 48 and 72 hours after LTx. Also iPAH patients had significantly longer ICU and hospital stay. Whereas the incidence of postoperative bronchiolitis obliterans syndrome (BOS) and rejection was comparable to the control group, overall cumulative survival with up to 6 years follow-up was significantly poorer in the iPAH group. After propensity score matching, the results in terms of postoperative outcomes remained as in the unadjusted analysis. CONCLUSIONS: ECLS is an essential tool in the armamentarium of any lung transplant program treating iPAH with a potential of bridge patients to transplantation and to overcome graft dysfunction after LTx. Despite utilization of ECLS in the management of iPAH, the outcomes in terms of primary graft failure and survival remain poor compared to patients with other diagnoses.

Patient outcomes from time of listing for lung transplantation in the UK: are there disease-specific differences?

BACKGROUND: The demand for lung transplantation vastly exceeds the availability of donor organs. This translates into long waiting times and high waiting list mortality. We set out to examine factors influencing patient outcomes from the time of listing for lung transplantation in the UK, examining for differences by patient characteristics, lung disease category and transplant centre. METHODS: Data were obtained from the UK Transplant Registry held by NHS Blood and Transplant for adult lung-only registrations between 1January 2004 and 31 March 2014. Pretransplant and post-transplant outcomes were evaluated against lung disease category, blood group and height. RESULTS: Of the 2213 patient registrations, COPD comprised 28.4%, pulmonary fibrosis (PF) 26.2%, cystic fibrosis (CF) 25.4% and other lung pathologies 20.1%. The chance of transplantation after listing differed by the combined effect of disease category and centre (p<0.001). At 3 years postregistration, 78% of patients with COPD were transplanted followed by 61% of patients with CF, 59% of other lung pathology patients and 48% of patients with PF, who also had the highest waiting list mortality (37%). The chance of transplantation also differed by height with taller patients having a greater chance of transplant (HR: 1.03, 95% CI: 1.02 to 1.04, p<0.001). Patients with blood group O had the highest waiting mortality at 3 years postregistration compared with all other blood groups (27% vs 20%, p<0.001). CONCLUSIONS: The way donor lungs were allocated in the UK resulted in discrepancies between the risk profile and probability of lung transplantation. A new donor lung allocation scheme was introduced in 2017 to try to address these shortcomings.

Delayed Chest Closure With Skin Approximation After Lung Transplant in Oversized Graft.

Closure of the chest after lung transplant in cases of oversized grafts is often difficult. Lung volume reduction and delayed closure of the chest with Bogota bag are the only options available in such situations. Here, we propose to keep the sternum and intercostal spaces open and approximate skin over it. Once lung function improves and reperfusion-related edema recovers, the chest can be closed.

Influence of history of cannabis smoking in selected donors on the outcomes of lung transplantation.

OBJECTIVES: Cannabis is the most commonly abused illicit drug and the smokers are at the risk of lung infections, bullous emphysema and lung cancer. However, no evidence about the outcomes of lung transplantation (LTx) utilizing the lungs from such donors is available in the literature. METHODS: We retrospectively analysed lung 'organ offers' and LTx at our centre between January 2007 and November 2013. The outcomes of LTx utilizing lungs from donors with a history of cannabis smoking were compared with the outcomes of those with no such history using unadjusted model as well as propensity score matching. RESULTS: A total of 302 LTxs were performed during this period and were grouped depending on the history of cannabis smoking in donors-'cannabis' (n = 19) and control group (n = 283). All the donors in 'cannabis' group were tobacco smokers compared with 43% in the control group. Preoperative characteristics in recipients in both groups were comparable. Intraoperative and post-LTx variables including 1- and 3-year survivals were comparable in both groups. CONCLUSIONS: The history of donor cannabis smoking does not appear to affect early and mid-term outcomes after LTx and potentially improve the donor pool. As it does not seem to negatively affect the outcomes after LTx, it should not be per se considered a contraindication for lung donation.

Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death.

RATIONALE: Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis. OBJECTIVES: To characterize the outcome of human macrophage infection with Aspergillus fumigatus and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants. METHODS: We defined the outcome of human macrophage infection with A. fumigatus, as well as the impact of calcineurin inhibitors, through a combination of single-cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies. MEASUREMENTS AND MAIN RESULTS: Macrophage phagocytosis of A. fumigatus enabled control of 90% of fungal germination. However, fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell-cell transfer of A. fumigatus between macrophages, which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein envelope. Its relevance to the control of fungal germination was also shown by direct visualization in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506 (tacrolimus) reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and also resulted in hyphal escape. CONCLUSIONS: These observations identify programmed, necrosis-dependent lateral transfer of A. fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host.

Challenging immunosuppression treatment in lung transplant recipients with kidney failure.

Kidney failure after lung transplantation is a risk factor for chronic kidney disease. Calcineurin inhibitors are immunosuppressants which play a major role in terms of postoperative kidney failure after lung transplantation. We report our preliminary experience with the anti-interleukin-2 monoclonal antibody Basiliximab utilized as a "calcineurin inhibitor-free window" in the setting of early postoperative kidney failure after lung transplantation. Between 2012 and 2015 nine lung transplant patients who developed kidney failure for more than 14 days were included. Basiliximab was administrated in three doses (Day 0, 4, and 20) whilst Tacrolimus was discontinued or reduced to maintain a serum level between 2 and 4 ng/mL. Baseline glomerular filtration rate pre transplant was normal for all patients. Seven patients completely recovered from kidney failure (67%, mean eGFR pre and post Basiliximab: 42.3 mL/min/1.73 m(2) and 69 mL/min/1.73 m(2)) and were switched back on Tacrolimus. Only one of these patients still needs ongoing renal replacement therapy. Two patients showed no recovery from kidney failure and did not survive. Basiliximab might be a safe and feasible therapeutical option in patients which are affected by calcineurin inhibitor-related kidney failure in the early post lung transplant period. Further studies are necessary to confirm our preliminary results.

Effect of donor cardiac arrest and arrest duration on outcomes of lung transplantation.

BACKGROUND: Limited data are available about lung transplantation (LTx) from donors suffering cardiac arrest (CA) prior to actual donation. METHODS: A retrospective analysis of LTx performed between January 2007 and September 2012 was done with the focus on CA in donors. The recipients were grouped depending on the history of donor CA and CA duration (downtime) as: No cardiac arrest ("NoCA"), CA downtime less than 20 min ("CA < 20"), and CA downtime equal to or more than 20 min ("CA > 20"). Early and mid-term outcomes after LTx were compared among the three groups. RESULTS: A total of 237 LTx were performed during the study period. One hundred eighty-eight patients received organs from "NoCA" donors, 25 from "CA < 20" donors, and 24 patients from "CA > 20" donors. There was a trend toward better overall cumulative survival in both CA groups (log rank p = 0.076) whereas the survival in the "CA > 20" group was significantly better than in the "NoCA" group in the subgroup analysis (log rank p = 0.045). Freedom from bronchiolitis obliterans syndrome (BOS) also increased with increase in CA duration, although it did not reach statistical significance. CONCLUSIONS: Transplantation of lungs from donors with a history of CA is safe and feasible. Longer duration of cardiac arrest may improve the outcomes after the LTx in terms of survival and freedom from BOS.

Outcomes of minimally invasive lung transplantation in a single centre: the routine approach for the future or do we still need clamshell incision?

OBJECTIVES: Minimally invasive lung transplantation (MILT) via bilateral anterior thoracotomies has emerged as a novel surgical strategy with potential patient benefits when compared with transverse thoracosternotomy (clamshell incision, CS). The aim of this study is to compare MILT with CS by focusing on operative characteristics, postoperative organ function and support and mid-term clinical outcomes at Harefield Hospital. METHODS: It was a retrospective observational study evaluating all bilateral sequential lung transplants between April 2010 and November 2013. RESULTS: CS was performed in 124 patients and MILT in 70 patients. Skin-to-skin surgical time was less in the MILT group [285 (265, 339) min] compared with CS [380 (306, 565) min] and MILT-cardiopulmonary bypass [426 (360, 478) min]. Ischaemic time was significantly longer (502 ± 116 vs 395 ± 145 min) in the MILT group compared with CS (P < 0.01). Early postoperative physiological variables were similar between groups. Patients in the MILT group required less blood [2 (0, 4) vs 3 (1, 5) units, P = 0.16] and platelet transfusion [0 (0, 1) vs 1 (0, 2) units, P < 0.01]. The median duration of mechanical ventilation was shorter (26 vs 44 h, P < 0.01) and intensive therapy unit stay was 2 days shorter (5 vs 7) in the MILT group. While overall survival was similar, fraction of expired volume in 1 s (FEV1) and forced vital capacity (FVC) were consistently higher in the MILT group compared with CS during mid-term follow-up after transplantation. Specifically, FEV1 and FVC were, respectively, 86 ± 21 and 88 ± 18% predicted in the MILT group compared with 74 ± 21 and 74 ± 19% predicted in the CS group (P < 0.01) at the 6-month follow-up. CONCLUSIONS: MILT was successfully introduced at our centre as a novel operative strategy. Despite longer ischaemic times and a more complex operation and management, MILT appears to offer early postoperative and mid-term clinical benefits compared with our traditional approach of clamshell operations. These observations warrant larger definite studies to further evaluate the impact of MILT on physiological, clinical and patient-reported outcomes.

Extended Recipient Criteria in Lung Transplantation: Impact of Pleural Abnormalities on Primary Graft Dysfunction.

BACKGROUND: Because of improved surgical expertise and intraoperative management, pleural disease (PD+) represents a relatively minor contraindication to lung transplantation (LTx). The presence of pleural abnormalities from previous procedures or pleural involvement from fungal or bacterial disease is not considered a limiting factor for LTx. However there are no studies available to assess the impact of pleural diseases on short- and midterm outcomes after LTx. METHODS: We retrospectively reviewed 163 consecutive patients who underwent LTx between 2010 and 2013. Patients were divided according to the presence of pleural abnormalities before the operation (PD+ versus PD-). The primary end point of the study was primary graft dysfunction (PGD; grade 3) and overall survival. To avoid possible selection bias and to heck the robustness of the results, a propensity score-matching analysis (1:3) was performed. RESULTS: A total of 26 patients (16%) had pleural abnormalities before transplantation. Intra- and postoperative variables were comparable. PD+ was associated with a significantly higher incidence of PGD at 0 and 48 hours postoperatively (p = 0.037 and p = 0.032, respectively). Moreover, PD+ was associated with significantly worse survival at 3 months (p = 0.021). Although there was a trend toward worse early overall survival in the Kaplan-Meier estimate (Breslow p = 0.050), midterm survival was comparable (log-rank p = 0.240). CONCLUSIONS: LTx in patients with preoperative pleural abnormalities is feasible. Identifying higher-risk recipients with pleural abnormalities might have important clinical relevance because of a higher incidence of PGD and worse early survival, even though midterm survival is comparable.

Mechanical ventilation after lung transplantation.

INTRODUCTION: To explore the hypothesis that early ventilation strategies influence clinical outcomes in lung transplantation, we have examined our routine ventilation practices in terms of tidal volumes (Vt) and inflation pressures. METHODS: A total of 124 bilateral lung transplants between 2010 and 2013 were retrospectively assigned to low (<6 mL/kg), medium (6-8 mL/kg), and high (>8 mL/kg) Vt groups based on ventilation characteristics during the first 6 hours after surgery. Those same 124 patients were also stratified to low-pressure (<25 cm H2O) and high-pressure (≥25 cm H2O) groups. RESULTS: Eighty percent of patients were ventilated using pressure control mode. Low, medium, and high Vt were applied to 10%, 43%, and 47% of patients, respectively. After correcting for patients requiring extracorporeal support, there was no difference in short-term to midterm outcomes among the different Vt groups. Low inflation pressures were applied to 61% of patients, who had a shorter length of intensive care unit stay (5 vs 12 days; P = .012), higher forced expiratory volume in 1 second at 3 months (77.8% vs 60.3%; P < .001), and increased 6-month survival rate (95% vs 77%; P = .008). CONCLUSION: Low Vt ventilation has not been fully adopted in our practice. Ventilation with higher inflation pressures, but not Vt, was significantly associated with poorer outcomes after lung transplantation.

GORD symptoms in lung transplantation: how efficient is the reflux symptom index questionnaire compared to the esophageal impedance test?

OBJECTIVE: As Gastroesophageal reflux disease (GORD) affects long-term survival in lung transplant recipients, the aim of this observational prospective study was to analyze the efficacy of The Reflux Symptom Index Questionnaire (RSI) compared to the esophageal impedance test. METHODS: Both esophageal impedance studies and RSI questionnaire were routinely performed in all patients who had completed rehabilitation following lung transplantation from June 2013 till March 2014. RSI generates a score of between zero and forty-five, taking into account any symptoms within four wk of the questionnaire. Our analysis considered RSI score cut-offs of 10 and 13 indicating significance of reflux. RESULTS: Out of 84 patients, 50 (59.5%) had evidence of GORD detected by impedance studies, whereas only 33 (39.2%) and 22 (26.2%) had RSI >10 and 13, respectively. An elevated RSI was not found to be associated with positive impedance studies using a score of either 10 or 13 (p = 0.127 and p = 0.142, respectively); 32.1% (n = 27) and 40.5% (n = 34) were found to have negative RSI and positive impedance test using 10 or 13 as cut-off, respectively. CONCLUSION: RSI Score is an unreliable predictor of GORD among lung transplant recipients. The authors therefore recommend the routine use of impedance testing in post-transplant patients.

The role of cardiopulmonary bypass in lung transplantation.

BACKGROUND: The risk-benefit for utilizing cardio-pulmonary bypass (CPB) in lung transplantation (LTx) remains debatable. This study compares outcomes after LTx utilizing different CPB strategies - elective CPB vs. off-pump vs. off-pump with unplanned conversion to CPB. METHODS: A total of 302 LTx performed over seven yr were divided into three groups: "off-pump" group (n = 86), "elective on-pump" group (n = 162), and "conversion" group (n = 54). The preoperative donor and recipient demographics and baseline characteristics and the postoperative outcomes were analyzed; 1:1 propensity score matching was used to identify patients operated upon using elective CPB who had risk profiles similar to those operated upon off-pump (propensity-matching 1) as well as those emergently converted from off-pump to CPB (propensity-matching 2). RESULTS: Preoperative group demographic characteristics were comparable; however, the "off-pump" patient group was significantly older. The "conversion" group had a significantly greater number of patients with primary pulmonary hypertension, pulmonary fibrosis, preoperative mechanical ventilation, and preoperative extracorporeal life support (ECLS). Postoperatively, patients from the "conversion" group had significantly poorer PaO2 /FiO2 ratios upon arrival in intensive care unit (ICU) and at 24, 48, and 72 h postoperatively, and they required more prolonged ventilation, longer ICU admission, and they experienced an increased need for ECLS than the other groups. Overall, cumulative survival at one, two, and three yr was significantly worse in patients from the "conversion" group compared to the "off-pump" and "elective on-pump" groups - 61.9% vs. 94.4% vs. 86.9%, 54.4% vs. 90.6% vs. 79.5% and 39.8% vs. 78.1% vs. 74.3%, respectively (p < 0.001). The "off-pump" group had significantly better PaO2 /FiO2 ratios, and a significantly shorter duration of ventilation, ICU stay, and hospital length of stay when compared to the propensity-matched "elective on-pump" group. There were no statistically significant differences in postoperative outcomes and overall survival between the "converted" group and the propensity-matched "elective on-pump" group. CONCLUSIONS: Despite segregation of unplanned CPB conversion cases from elective on-pump cases, patients with comparable preoperative demographic/risk profiles demonstrated better early postoperative outcomes and, possibly, an improved early survival with an off-pump strategy. A considerable proportion of high-risk patients require intraoperative conversion from off-pump to CPB, and this seems associated with suboptimal outcomes; however, there is no significant benefit to employing an elective on-pump strategy over emergent conversion in the high-risk group.

Extracorporeal Life Support in "Awake" Patients as a Bridge to Lung Transplant.

BACKGROUND: Traditionally, patients on extracorporeal membrane oxygenation (ECMO) are sedated and mechanically ventilated, which increases risk of complications related to immobility and mechanical ventilation. The purpose of this study was to assess the feasibility and highlight the benefits of a bridge to lung transplant (LTx) using "awake ECMO" support. METHODS: The peripheral venovenous or venoarterial ECMO was implanted at a bedside. A retrospective study of patients undergoing LTx between January 2007 and March 2013 was performed. Outcomes in patients supported on ECMO as a bridge to LTx and kept "awake" (Group 1) were compared with the rest of the LTx patients (Group 2). RESULTS: In this period, 249 LTx were performed and in them 7 patients were bridged to LTx using "awake ECMO" strategy. Two patients were awake at ECMO implantation and throughout the therapy, and two patients were on ventilator support at the time of ECMO implantation who were extubated later and maintained awake until LTx. The remaining three patients were awake for some time during the ECMO. There was no statistically significant difference in most donor characteristics and recipient baseline characteristics as well as post-LTx parameters between the two groups. One-year survival estimate was not different between the groups: Group 1, 85.7% vs. Group 2, 86.3% (log rank p = 0.99). CONCLUSION: In end-stage lung disease, the ECMO can be commenced in "awake" patients and patients can be awakened on ECMO. The "awake ECMO" strategy may avoid complications related to mechanical ventilation, sedation, and immobilization and provide comparable outcomes in the high-risk LTx patients.