Purpose Inhaled pulmonary vasodilators (iPVD) are commonly used in lung transplant recipients to mitigate the risk of primary graft dysfunction (PGD). While inhaled nitric oxide (iNO) is the gold standard for iPVD therapy, inhaled epoprostenol (Veletri®) has been introduced as a cost-conscious iNO-alternative without high-grade evidence. Thus, we conducted a clinical trial to primarily determine if inhaled epoprostenol is equivalent to iNO in the ability to modify grade 3 PGD after orthotopic lung transplantation. Methods Our group has enrolled 200 lung transplant recipients in a triple-blinded (clinician, patient, statistician) randomized controlled trial conducted between June 2017-October 2020 (NCT03081052). Participants were first grouped into strata according to key clinical, prognostic features (Fig.1). Within each stratum, patients were assigned to receive either iNO or inhaled epoprostenol via 1:1 randomization. For our primary outcome analysis, to assess equivalency between the two treatment groups, we will calculate absolute and relative risk estimates and corresponding confidence intervals (CI). If the CI do not contain the margin of difference (15%), then we will conclude there is sufficient evidence that the risk of the primary outcome in each treatment group is similar. For each secondary outcome, we will construct univariable effect estimates and corresponding CI, which will allow for assessment of difference between treatment groups. In the case that patients have switched to the other treatment arm, we will perform the intent-to-treat (ITT) analysis without reclassifying treatment assignment. To verify ITT results, we will perform a per-protocol analysis. Endpoints Primary. PGD-3 as defined by ISHLT 2016 criteria and an adjudicated PGD score at 72-hours after surgery. Secondary. Duration of postoperative mechanical ventilation, iPVD duration and cost, ICU and hospital lengths-of-stay, postoperative acute kidney Injury, and early postoperative mortality (in-hospital, 30-days, 90-days).

Purpose Perioperative acute kidney injury (AKI) is associated with worsened outcomes after bilateral orthotopic lung transplantation (BOLT). While elective veno-arterial (VA ECMO) strategies are increasingly common, the incidence of perioperative AKI in the context of various surgical strategies is unclear. In this retrospective observational study of BOLT patients, we propose that AKI rates differ between elective VA ECMO and off-pump (OP) strategies. Methods Adult patients undergoing BOLT from 1/1/17 to 9/6/2020 were included. As of Feb 2020, all BOLTs were performed on elective VA ECMO. Patients requiring preoperative or urgent conversion to ECMO, cardiopulmonary bypass, concomitant cardiac surgery, re-transplantation, severe pulmonary hypertension (mean PA pressures >40 mmHg), or missing creatinine (Cr) data were excluded. Patients were stratified into OP and VA ECMO cohorts. VA ECMO patients were matched 1:1 to OP patients based on transplant indication, baseline Cr and transfusion requirements. The primary outcome compared was AKI rates (KDIGO criteria). Secondary outcomes included the ratio of maximum postoperative Cr to baseline, and peak Cr. Results 383 BOLT patients were identified. 188 met inclusion criteria, while 19 were missing creatinine data. Of those, 134 patients were available prior to Feb 2020 and 35 between Feb-Sep 2020. We identified 33 matched pairs for comparison. Minimal differences in donor, recipient, and procedural characteristics were seen between matched, paired groups. AKI was more common in the OP compared to the VA ECMO group (27/33 vs. 17/33, p=0.009). Both the ratio of peak relative to baseline Cr (1.6 vs 1.3 g/DL; p=0.022) and peak Cr (1.3 vs 1.0 g/dL; p=0.012) were higher in the OP compared to the VA-ECMO group (Table). Conclusion In this retrospective study using matched pairs of BOLT patients, we observed a lower incidence of AKI associated with elective intraoperative VA-ECMO when compared to an off-pump strategy.

BACKGROUND:Sensitized candidates with unacceptable antigens are a group that demands special attention in organ transplantation. Calculated panel reactive antigen (cPRA) is not used to modify allocation priorities in lung transplantation. The impact of cPRA on waiting list time and mortality is unknown. METHODS:We performed a retrospective review of candidates for lung transplantation listed from May 2005 to 2018. Data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing STAR (Standard Analysis and Research) dataset was paired with additional unacceptable human leukocyte antigen (UA-HLA) data, which were used to calculate the listing cPRA. Candidates were stratified based on the lack of UA-HLAs or cPRA level for candidates with unacceptable antigens reported. Unadjusted competing risks and adjusted subdistribution hazard models were fit. RESULTS:A total of 29,085 candidates met inclusion criteria for analysis. Of these, 23,562 (81%) with no UA-HLAs, 3472 (11.9%) with a cPRA less than 50, and 2051 with a cPRA greater than or equal to 50 (7.1%). On adjusted analysis, a cPRA greater than or equal to 50 was independently associated with increased waitlist mortality at 1 year (hazard ratio, 1.71; 95% confidence interval, 1.55-1.88; P < .001) and decreased rate of transplantation (71.9% vs 69.5% vs 44.4%; P < .001). Furthermore, patients with a cPRA greater than or equal to 50 had a longer waitlist time compared with a cPRA less than 50 and no UA-HLA candidates (mean 293.69 days vs 162.38 days and 143.26 days, respectively; P < .001). However, once transplanted, posttransplant survival among the cohorts was similar. CONCLUSIONS:Further evaluation of organ allocation with consideration of a candidate's cPRA may be warranted in order to optimize equity in access to transplants.

While we previously described a consistent reduction of median RBC units transfused post-protocol over 12 months, this protocol did not result in a consistently reduced severe PGD rate. Over 12 months, we observed a trend in reduced PGD rates after implementing our transfusion protocol. Teams should consider goal-directed transfusion protocols for LT.

Predictors of transfusion free LT surgery include older males undergoing a single, off-pump LT procedure, with lower LAS scores and higher starting hemoglobin. This may guide decision making in exploring candidacy for transfusion-free LT or blood refusal patients in the era of ECMO.

Purpose Heart transplantation is limited by the supply of donor organs. Previous studies have associated donor/recipient gender mismatch with decreased post-transplant survival and increased rates of primary graft dysfunction. We evaluate whether this risk can be mitigated. Methods We performed a retrospective analysis of the OPTN/UNOS registry encompassing years 1987 to 2018 for all male adult recipients (>18 years) who underwent isolated heart transplantation with grafts from female donors. Comparison was made to transplants from male donors. Recipients were primarily stratified into two groups, those with BMI less than or greater than donor BMI. Patients were stratified by BSA on secondary analysis. Kaplan-Meier analysis was used to estimate survival post-transplant. Cox Proportional Hazards modeling was performed to identify independent predictors of survival. Results A total of 8,232 candidates met inclusion criteria. Male recipients receiving hearts from higher BMI female donors were more likely to be in the ICU pre-transplant (39.5% vs 36.6%, p = 0.001), on IV inotropes at listing (35.7% vs 33.0%, p = 0.013), and were less likely to have a history of diabetes (21.4% vs 23.9%, p = 0.012). On Kaplan-Meier analysis, recipients transplanted with hearts from higher BMI female donors had improved overall survival. When stratified by BSA (Figure 1), male recipients transplanted with hearts from higher BSA female donors had similar post-transplant survival as male recipients who received hearts from male donors. On Cox Proportional Hazards analysis, increased donor BMI/BSA relative to recipient BMI/BSA remained an independent predictor of improved survival (p < 0.05). Conclusion Prior studies have associated transplanting hearts from female donors into male recipients with decreased post-transplant survival. In this study we have demonstrated that this may be mitigated by matching grafts from female donors to male recipients with lower BMI and especially BSA.

Purpose It has been suggested that the length of time between donor brain death and cross clamp impacts post-transplant graft function and recipient survival in lung transplantation. Methods The 2007-2018 United Network for Organ Sharing (UNOS) Registry was queried for all adult recipients undergoing isolated lung transplantation (single or bilateral) for the first time. Donation after circulatory death (DCD) donors or those with an unknown time from brain death until cross clamp were excluded. Recipients were stratified by those who received an allograft from donors with times from brain death until cross clamp less than (SHORT) or greater than (LONG) the median. The primary outcome of interest was post-transplant survival, which was evaluated with Kaplan-Meier and Cox Proportional Hazards analyses. Results 15,914 lung transplant recipients met inclusion criteria. Median time from donor brain death until cross clamp was 36 hours (IQR 17). Recipients of SHORT donors were more likely treated with IV antibiotics pre-transplant (12.3% vs 10.6%, p = 0.001) and spent a longer time on the waiting list (median 64 vs 58 days, p = 0.016). Both cohorts had similar lung allocation scores (median 40.8 vs 41.0, p = 0.292). Overall survival between the two cohorts was equivalent on Kaplan-Meier analysis (Figure 1, log-rank p = 0.776). On evaluation of other thresholds, time from donor brain death until cross clamp greater than the 75th percentile or less than the 25th percentile similarly did not impact recipient survival. After adjustment for donor and recipient characteristics, graft ischemic time, and year of transplant on Cox Proportional Hazards assessment, donor time from brain death until cross clamp was not associated with decreased survival (AHR 1.00, p = 0.981). Conclusion Time from donor brain death until cross clamp is not associated with decreased post-transplant survival. Therefore, lung allografts from donors with a prolonged length of time from brain death until explant should not be viewed less favorably.

Purpose Transfusion during lung transplantation (LT) is associated with worsened outcomes. When recipients require anticoagulation at listing, they are at increased risk of bleeding during LT if the drug effects are not rapidly reversed. Four-factor prothrombin complex concentrate (4-F PCC) is recently available for rapid warfarin reversal. Here we describe clinical outcomes in waitlisted recipients who were anticoagulated on warfarin and reversed with 4-F PCC at the time of LT. Methods The electronic medical records of all adult LT patients between 2/2014-8/2018 were queried. 4-F PCC became available in 2014, and routinely used for warfarin reversal in 2017. When indicated, patients were anticoagulated with warfarin at listing. During LT, 4-F PCC was administered immediately upon arrival to the OR and prior to incision, per recommended dose. We report 72-hour transfusion requirements, as well as short and long-term clinical outcomes. Results 451 LT patients’ records were queried; of those, 4 patients received full dose 4-F PCC for warfarin reversal, for off pump LT. We describe clinical characteristics of the recipient, the surgery, relevant medications administered, and outcomes in Table 1. 72-hr transfusion requirements ranged from 0 to 2 RBCs, with cryoprecipitate and platelets ranging from 0 to 2 U. FFP use varied tremendously because 1 patient required plasmapheresis perioperatively. Patient 2 had a deep vein thrombosis after 30 days during the index hospitalization. All patients were discharged home and have survived to date. Conclusion When warfarin is utilized as a therapeutic anticoagulation strategy at listing for lung transplant, 4F-PCC safely and effectively reverses its effects. Transfusion during lung transplantation (LT) is associated with worsened outcomes. When recipients require anticoagulation at listing, they are at increased risk of bleeding during LT if the drug effects are not rapidly reversed. Four-factor prothrombin complex concentrate (4-F PCC) is recently available for rapid warfarin reversal. Here we describe clinical outcomes in waitlisted recipients who were anticoagulated on warfarin and reversed with 4-F PCC at the time of LT. The electronic medical records of all adult LT patients between 2/2014-8/2018 were queried. 4-F PCC became available in 2014, and routinely used for warfarin reversal in 2017. When indicated, patients were anticoagulated with warfarin at listing. During LT, 4-F PCC was administered immediately upon arrival to the OR and prior to incision, per recommended dose. We report 72-hour transfusion requirements, as well as short and long-term clinical outcomes. 451 LT patients’ records were queried; of those, 4 patients received full dose 4-F PCC for warfarin reversal, for off pump LT. We describe clinical characteristics of the recipient, the surgery, relevant medications administered, and outcomes in Table 1. 72-hr transfusion requirements ranged from 0 to 2 RBCs, with cryoprecipitate and platelets ranging from 0 to 2 U. FFP use varied tremendously because 1 patient required plasmapheresis perioperatively. Patient 2 had a deep vein thrombosis after 30 days during the index hospitalization. All patients were discharged home and have survived to date. When warfarin is utilized as a therapeutic anticoagulation strategy at listing for lung transplant, 4F-PCC safely and effectively reverses its effects.

Posterior reversible encephalopathy syndrome (PRES) is a rare neurologic complication following lung transplantation. PRES requires the avoidance of certain immunosuppressant therapies, potentially increasing risk of poor long-term clinical outcomes. Few studies have characterized demographic or perioperative risk factors for PRES or its impact on clinical outcomes. We propose that the characteristics of lung transplant patients who developed PRES were different than those who did not develop PRES.

Donors with characteristics that may increase the likelihood of disease transmission with transplantation are noted as increased risk via Public Health Service (PHS) criteria. This distinction makes no reference to organ quality. The implications of the refusal increased risk donors (IRD) is not established in lung transplantation.

BACKGROUND: Blood type O lung allografts may be allocated to blood type identical (type O) or compatible (non-O) candidates. We tested the hypothesis that the current organ allocation schema in the United States-based on the Lung Allocation Score-prejudices against the allocation of allografts to type O candidates, given that the pool of potential donors is smaller. METHODS: We performed a retrospective cohort review of the Organ Procurement and Transplantation Network/United Network of Organ Sharing registry from May 2005 to March 2017 for adult candidates on the waiting list for first-time isolated lung transplantation. Demographic data were compiled and described, and 1:1 nearest-neighbor propensity score matching was used to adjust for age and Lung Allocation Score at listing. RESULTS: A total of 26,396 candidates met inclusion criteria: 14,329 type non-O and candidates and 12,068 type O candidates. After matching, 11,951 candidates were included in each group. Of these, 77.0% of type non-O underwent lung transplantation vs 73.1% type O (p < 0.001). At 1 year, the waiting list mortality was higher for type O candidates (12.5%) than for non-O candidates (10.1%, p < 0.001). Of those undergoing transplantation, 5-year survival rates were similar. CONCLUSIONS: Type O candidates experience lower rates of transplantation and higher rates of waiting list mortality compared with matched type non-O candidates. Further evaluation of regional sharing of allografts to increase transplantation rates for type O candidates may be warranted to optimize equity in access to transplants. (C) 2018 International Society for Heart and Lung Transplantation. All rights reserved.

Ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique developed to evaluate candidate donor lungs in a normothermic and metabolically active state. Donor leukocytes are linked to the development of transplant related ischemia reperfusion injury, primary graft dysfunction, and acute rejection. Pharmacologic strategies to enhance donor leukocyte depletion during EVLP have not yet been described. Plerixafor (Mozobil) is a clinically available CXCR4 receptor antagonist, which disrupts the interaction between CXCR4 and SDF-1α and facilitates mobilization of hematopoietic stem cells into peripheral circulation. Thus, we tested the hypothesis that Plerixafor improves donor leukocyte depletion during ex vivo lung perfusion.