Crossing national borders for transplantation: A focused evaluation of deceased donor lung exports from the United States.

Organ transplantation is a life-saving treatment for end-stage organ failure patients, but the United States (US) faces a shortage of available organs. US policies incentivize identifying recipients for all recovered organs. Technological advancements have extended donor organ viability, creating new opportunities for long-distance transport and international sharing. We aimed to assess organ exports from deceased US donors to candidates abroad, a component of allocation policy allowed without suitable domestic candidates. Based on the national Scientific Registry of Transplant Recipients data from January 2014 to September 2023, 388 342 organs were recovered for transplantation, with 511 (0.13%) exported. Most exported organs were lungs (80%). Exported lung donors were older (41 vs 34 years, P < .001), more likely hepatitis C positive (22% vs 4%, P < .001), and more likely donors after circulatory death (20% vs 7%, P < .001). Lungs that were eventually exported were offered to more US potential transplant recipients (median = 65) than those kept in the US (median = 21 and 41 for lungs recovered by nonexporting and exporting organ procurement organizations, respectively; P < .001). Our study highlights the necessity for further research and clear policy initiatives to balance the benefits of cross-border sharing while considering potential opportunities for more aggressive organ allocation within the US.

Diaphragmatic palsy following lung transplantation.

Diaphragmatic palsy after lung transplantation has been reported infrequently. Given the role of the diaphragm in respiration, the palsy may play a significant role in the post-surgical recovery as well as morbidity and mortality. This review summarises the current literature to better understand diaphragmatic palsy in the post lung-transplant setting among adults. A thorough literature search was conducted through multiple databases and 91 publications were identified that fit the research question. The review aimed to report the burden of this problem, explore different modalities of diagnosis reported, the effect of various clinical factors and treatment modalities, as well as their effects on outcomes. Additionally, it aimed to highlight the variability, limitations of reported data, and the absence of a standardised approach. This review emphasises the crucial need for more dedicated research to better address this clinical challenge.

Real-time lung weight measurement during clinical ex vivo lung perfusion.

BACKGROUND: Real-time lung weight (LW) measurement is a simple and noninvasive technique for detecting extravascular lung water during ex vivo lung perfusion (EVLP). We investigated the feasibility of real-time LW measurement in clinical EVLP as a predictor of transplant suitability and post-transplant outcomes. METHODS: In our clinical acellular EVLP protocol, real-time LW was measured in 117 EVLP cases from June 2019 to June 2022. The estimated LW gain at each time point was calculated using a scale placed under the organ chamber. The lungs were classified into 4 categories based on LW adjusted for height and compared between suitable and unsuitable cases. The relationship between estimated LW gain and primary graft dysfunction was also investigated. RESULTS: The estimated LW gain during the EVLP significantly correlated with the LW gain (post-EVLP LW and pre-EVLP LW) measured on the back table (R2 = 0.61, p < 0.01). In the adjusted LW categories 2 to 4, the estimated LW gain at 0-1 hour after EVLP was significantly higher in unsuitable cases than in suitable cases. The area under the curve for the estimated LW gain was ≥0.80. Primary graft dysfunction grades 0 to 1 had a significantly lower estimated LW gain at 60 minutes than grades 2 to 3 (-43 vs 1 g, p < 0.01). CONCLUSIONS: Real-time lung measurements can predict transplant suitability and post-transplant outcomes by the early detection of extravascular lung water during the initial 1 hour of EVLP.

Intermittent Ex Vivo Lung Perfusion in a Porcine Model for Prolonged Lung Preservation.

BACKGROUND: Ex vivo lung perfusion expands the lung transplant donor pool and extends preservation time beyond cold static preservation. We hypothesized that repeated regular ex vivo lung perfusion would better maintain lung grafts. METHODS: Ten pig lungs were randomized into 2 groups. The control underwent 16 h of cold ischemic time and 2 h of cellular ex vivo lung perfusion. The intermittent ex vivo lung perfusion group underwent cold ischemic time for 4 h, ex vivo lung perfusion (first) for 2 h, cold ischemic time for 10 h, and 2 h of ex vivo lung perfusion (second). Lungs were assessed, and transplant suitability was determined after 2 h of ex vivo lung perfusion. RESULTS: The second ex vivo lung perfusion was significantly associated with better oxygenation, limited extravascular water, higher adenosine triphosphate, reduced intraalveolar edema, and well-preserved mitochondria compared with the control, despite proinflammatory cytokine elevation. No significant difference was observed in the first and second perfusion regarding oxygenation and adenosine triphosphate, whereas the second was associated with lower dynamic compliance and higher extravascular lung water than the first. Transplant suitability was 100% for the first and 60% for the second ex vivo lung perfusion, and 0% for the control. CONCLUSIONS: The second ex vivo lung perfusion had a slight deterioration in graft function compared to the first. Intermittent ex vivo lung perfusion created a better condition for lung grafts than cold static preservation, despite cytokine elevation. These results suggested that intermittent ex vivo lung perfusion may help prolong lung preservation.

Retransplantation for COVID-19-related lung graft failure: A case report of successful outcome in a critically ill lung transplant recipient.

End-stage lung disease from nonrecovered COVID-19 acute respiratory distress syndrome has become an increasingly frequent indication for lung transplant. Although reports of lung transplant recipients (LTRs) with COVID-19 suggest an increased risk for hospitalization, respiratory failure, and death, little is known about retransplant for COVID-19-related lung graft failure. In this manuscript, we present a 49-year-old man who received bilateral lung retransplantation for COVID-19-related lung graft failure, 7½ years after his initial transplant for idiopathic pulmonary fibrosis. Our case suggests that retransplantation may be a viable option for critically ill LTRs with COVID-19-related graft failure, even in the presence of other organ dysfunction, provided that they are in good condition and have an immunologically favorable donor.

Increasing surgeon experience and cumulative institutional experience drive decreasing hospital mortality after reoperative cardiac surgery.

OBJECTIVE: The study objective was to identify the effects of surgeon experience and age, in the context of cumulative institutional experience, on risk-adjusted hospital mortality after cardiac reoperations. METHODS: From 1951 to 2020, 36 surgeons performed 160,338 cardiac operations, including 32,871 reoperations. Hospital death was modeled using a novel tree-bagged, generalized varying-coefficient method with 6 variables reflecting cumulative surgeon and institutional experience up to each cardiac operation: (1) number of total and (2) reoperative cardiac operations performed by a surgeon, (3) cumulative institutional number of total and (4) reoperative cardiac operations, (5) year of surgery, and (6) surgeon age at each operation. These were adjusted for 46 patient characteristics and surgical components. RESULTS: There were 1470 hospital deaths after cardiac reoperations (4.5%). At the institutional level, hospital death decreased exponentially and became less variable, leveling at 1.2% after approximately 14,000 cardiac reoperations. For all surgeons as a group, hospital death decreased rapidly over the first 750 reoperations and then gradually decreased with increasing experience to less than 1% after approximately 4000 reoperations. Surgeon age up to 75 years was associated with ever-decreasing hospital death. CONCLUSIONS: Surgeon age and experience have been implicated in adverse surgical outcomes, particularly after complex cardiac operations, with young surgeons being novices and older surgeons having declining ability. However, at Cleveland Clinic, outcomes of cardiac reoperations improved with increasing primary surgeon experience, without any suggestion to mid-70s of an age cutoff. Patients were protected by the cumulative background of institutional experience that created a culture of safety and teamwork that mitigated adverse events after cardiac surgery.

Left ventricular assist device mode: Co-pulse left ventricular unloading in a working mode of ex vivo heart perfusion.

BACKGROUND: For normothermic ex vivo heart perfusion (EVHP), a resting mode and working mode have been proposed. We newly developed a left ventricular assist device (LVAD) mode that supports heart contraction by co-pulse synchronized LVAD. METHODS: Following resting mode during time 0 to 1 hour, pig hearts (n = 18) were perfused in either resting, working, or LVAD mode during time 1 to 5 hour, and then myocardial function was evaluated in working mode at 6 hour. The preservation ratio was defined as the myocardial mechanical function at 330 minute divided by the function at 75 minute. In LVAD mode, LVAD unloaded the pressure and the volume in the left ventricle in the systolic phase. RESULTS: The LVAD group was significantly associated with higher preservation ratios in cardiac output (resting, 33 ± 3; working, 35 ± 5; LVAD, 76% ± 5%; p < 0.001), stroke work, dP/dt maximum, and dP/dt minimum compared with the other groups. Glucose consumption was significantly reduced in the resting group. The LVAD group was significantly associated with higher myocardial oxygen consumption (resting, 2.2 ± 0.3; working; 4.6 ± 0.5; LVAD, 6.1 ± 0.5 mL O2/min/100 g, p < 0.001) and higher adenosine triphosphate (ATP) levels (resting, 1.1 ± 0.1; working, 0.7 ± 0.1; LVAD, 1.6 ± 0.2 µmol/g, p = 0.001) compared with the others. CONCLUSION: These data suggest that myocardial mechanical function was better preserved in LVAD mode than in resting and working modes. Although our data suggested similar glycolysis activity in the LVAD and working groups, the higher final ATP in the LVAD group might be explained by reduced external work in LVAD.

Effect of donor smoking and substance use on post-lung transplant outcomes.

OBJECTIVE: The study objective was to determine effects of donor smoking and substance use on primary graft dysfunction, allograft function, and survival after lung transplant. METHODS: From January 2007 to February 2020, 1366 lung transplants from 1291 donors were performed in 1352 recipients at Cleveland Clinic. Donor smoking and substance use history were extracted from the Uniform Donor Risk Assessment Interview and medical records. End points were post-transplant primary graft dysfunction, longitudinal forced expiratory volume in 1 second (% of predicted), and survival. RESULTS: Among lung transplant recipients, 670 (49%) received an organ from a donor smoker, 163 (25%) received an organ from a donor with a 20 pack-year or more history (median pack-years 8), and 702 received an organ from a donor with substance use (51%). There was no association of donor smoking, pack-years, or substance use with primary graft dysfunction (P > .2). Post-transplant forced expiratory volume in 1 second was 74% at 1 year in donor nonsmoker recipients and 70% in donor smoker recipients (P = .0002), confined to double-lung transplant, where forced expiratory volume in 1 second was 77% in donor nonsmoker recipients and 73% in donor smoker recipients. Donor substance use was not associated with allograft function. Donor smoking was associated with 54% non-risk-adjusted 5-year survival versus 59% (P = .09) and greater pack-years with slightly worse risk-adjusted long-term survival (P = .01). Donor substance use was not associated with any outcome (P ≥ 8). CONCLUSIONS: Among well-selected organs, lungs from smokers were associated with non-clinically important worse allograft outcomes without an inflection point for donor smoking pack-years. Substance use was not associated with worse allograft function. Given the paucity of organs, donor smoking or substance use alone should not preclude assessment for lung donation or transplant.

Real-time Lung Weight Measurement During Cellular Ex Vivo Lung Perfusion: An Early Predictor of Transplant Suitability.

BACKGROUND: Increased extravascular lung water during ex vivo lung perfusion (EVLP) is associated with ischemia reperfusion injury and poor pulmonary function. A non-invasive technique for evaluating extravascular lung water during EVLP is desired to assess the transplant suitability of lungs. We investigated real-time lung weight measurements as a reliable method for assessing pulmonary functions in cellular EVLP using a porcine lung model. METHODS: Fifteen pigs were randomly divided into 3 groups: control (no warm ischemia) or donation after circulatory death groups with 60 or 90 min of warm ischemia (n = 5, each). Real-time lung weight gain was measured by load cells positioned at the bottom of the organ chamber. RESULTS: Real-time lung weight gain at 2 h was significantly correlated with lung weight gain as measured on a back table ( R = 0.979, P < 0.01). Lung weight gain in non-suitable cases (n = 6) was significantly higher than in suitable cases (n = 9) at 40 min (51.6 ± 46.0 versus -8.8 ± 25.7 g; P < 0.01, cutoff = +12 g, area under the curve = 0.907). Lung weight gain at 40 min was significantly correlated with PaO 2 /FiO 2 , peak inspiratory pressure, shunt ratio, wet/dry ratio, and transplant suitability at 2 h ( P < 0.05, each). In non-suitable cases, lung weight gain at 66% and 100% of cardiac output was significantly higher than at 33% ( P < 0.05). CONCLUSIONS: Real-time lung weight measurement could potentially be an early predictor of pulmonary function in cellular EVLP.

Prone ex vivo lung perfusion protects human lungs from reperfusion injury.

BACKGROUND: We previously reported beneficial effects of prone positioning during ex vivo lung perfusion (EVLP) using porcine lungs. In this study, we sought to determine if prone positioning during EVLP was beneficial in human donor lungs rejected for clinical use. METHODS: Human double lung blocs were randomized to prone EVLP (n = 5) or supine EVLP (n = 5). Following 16 h of cold storage at 4°C and 2 h of cellular EVLP in either the prone or supine position. Lung function, compliance, and weight were evaluated and transplant suitability determined after 2 h of EVLP. RESULTS: Human lungs treated with prone EVLP had significantly higher partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio [348 (291-402) vs. 199 (191-257) mm Hg, p = 0.022] and significantly lower lung weight [926(864-1078) vs. 1277(1029-1483) g, p = 0.037] after EVLP. 3/5 cases in the prone group were judged suitable for transplant after EVLP, while 0/5 cases in the supine group were suitable. When function of upper vs. lower lobes was evaluated, prone EVLP lungs showed similar P/F ratios and inflammatory cytokine levels in lower vs. upper lobes. In contrast, supine EVLP lungs showed significantly lower P/F ratios [68(59-150) vs. 467(407-515) mm Hg, p = 0.012] and higher tissue tumor necrosis factor alpha levels [100.5 (46.9-108.3) vs. 39.9 (17.0-61.0) ng/ml, p = 0.036] in lower vs. upper lobes. CONCLUSIONS: Prone lung positioning during EVLP may optimize the outcome of EVLP in human donor lungs, possibly by improving lower lobe function.

Clinical significance of donor lung weight at procurement and during ex vivo lung perfusion.

BACKGROUND: Elevated donor lung weight may adversely affect donor lung transplant suitability and post-transplant outcomes. The objective of this study is to investigate the impact of lung weight after procurement and ex vivo lung perfusion (EVLP) on transplant suitability, post-transplant graft dysfunction, and clinical outcomes and define the donor lung weight range most relevant to clinical outcomes. METHODS: From February 2016 to August 2020, 365 human lung donors to a single transplant center were retrospectively reviewed. 239 were transplanted without EVLP, 74 treated with EVLP (50 went on to transplant), and 52 declined for transplant without EVLP consideration. Donor lung weights were measured immediately after procurement and, when performed, after EVLP. Lung weights were adjusted by donor height and divided into 4 quartiles. RESULTS: Donor lungs in the highest weight quartile at donor hospital had a significantly lower transplant suitability rate after EVLP, higher rates of primary graft dysfunction grade 3 at 72 hours, and longer intensive care unit/hospital stay. For lungs treated with lung perfusion, the highest lung weight quartile at the end of lung perfusion was associated with a significantly lower transplant suitability rate, higher incidence of primary graft dysfunction grade 3 at 72 hours, and longer intensive care unit/hospital stay, compared to the other categories. CONCLUSIONS: Donor lung weight stratified by quartile categories can assist decision-making regarding need for EVLP at the donor hospital as well as during EVLP evaluation. Caution should be used when considering donor lungs in the highest weight quartile for transplantation.

Lung thermography during the initial reperfusion period to assess pulmonary function in cellular ex vivo lung perfusion.

BACKGROUND: Thermography is a noninvasive technology to detect low temperatures in poorly circulated areas. In ex vivo lung perfusion (EVLP), lungs are rewarmed to body temperature during the initial 1 h. Currently, the effect of graft thermal changes during the rewarming phase on pulmonary function is unknown. In this study, we evaluated the correlation of lung surface temperature with physiological parameters, wet/dry ratio, and transplant suitability in Lund-type EVLP. METHODS: Fifteen pigs were divided into three groups: control group (no warm ischemia) or donation after circulatory death groups with 60 or 90 min of warm ischemia (n = 5, each). Thermal images of the lower lobes were continuously collected from the bottom of an organ chamber using infrared thermography throughout EVLP. RESULTS: At 8 min, lung surface temperatures of nonsuitable cases were significantly lower than in suitable cases (25.1 ± 0.6 vs. 27.8 ± 1.2°C, p < 0.001), while there was no difference in lung surface temperatures between the two groups at 0-4 min and 12-120 min. There was a significant negative correlation between lung surface temperatures at 8 min and wet/dry ratio at 2 h in the lower lobes (R = -0.769, p < 0.001, cutoff = 26°C, area under the curve = 1.0). A lung surface temperature of <26°C was significantly correlated with poor pulmonary function and transplant nonsuitability. CONCLUSION: A lung surface temperature of ≥26°C at 8 min is a good early predictor of transplant suitability in cellular EVLP and might be applicable in clinical EVLP.

Optical oxygen saturation imaging in cellular ex vivo lung perfusion to assess lobular pulmonary function.

Ex vivo lung perfusion (EVLP) is an emerging tool to evaluate marginal lungs in lung transplantation. However, there is no objective metric to monitor lobular regional oxygenation during EVLP. In this study, we developed oxygen saturation (SaO2) imaging to quantitatively assess the regional gas exchange potential of the lower lobes. Ten porcine lungs were randomly divided into control and donation after circulatory death (DCD) groups (n = 5, each). Lungs were perfused in cellular EVLP for 2 h, and multispectral images were continuously collected from the dorsal sides of the lower lobes. We examined whether lower lobe SaO2 correlated with PaO2/FiO2 (P/F) ratios in lower pulmonary veins (PV). The wet/dry ratio in lower lobes was measured and Monte Carlo simulations were performed to investigate the method's feasibility. There was a significant correlation between lower lobe SaO2 and the P/F ratio in lower PV (r = 0.855, P < 0.001). The DCD group was associated with lower SaO2 and higher wet/dry ratio than the control group (P < 0.001). The error of estimated SaO2 was limited according to Monte Carlo simulations. The developed technology provides a noninvasive and regional evaluative tool of quantitative lobular function in EVLP.

Right Internal Thoracic Artery Patency Is Affected More by Target Choice Than Conduit Configuration.

BACKGROUND: Although coronary artery bypass grafting using bilateral internal thoracic arteries (ITA) maximizes long-term survival, knowledge of the effect of different right ITA (RITA) inflow configurations on graft patency is limited. We have compared RITA occlusion among these configurations and identified its risk factors while adjusting for outflow coronary target location. METHODS: From January 1972 to January 2016, of 7092 patients undergoing bilateral ITA grafting at a single center, 1331 received one ITA to the left anterior descending coronary artery and had one or more evaluable postoperative coronary angiograms: 835 (63%) in situ, 496 free RITA grafts (311 [63%] originating from aorta; 98 [20%] left ITA [LITA], 76 [15%] saphenous vein graft, 11 [2%] radial graft). RITA occlusion reported on 1983 angiograms performed a median of 5.8 years later was estimated using nonlinear mixed-effects longitudinal modeling. RESULTS: RITA patency was 90% at 1 year, 87% at 5 years, and 86% at 10 and 15 years. At 15 years, in situ RITA patency was 91% and free RITA patency from aorta was 91%, LITA 89%, and saphenous vein graft 77%. After adjusting for coronary target location and degree of stenosis, occlusion was similar in free RITAs from aorta (P = .15), LITA (P = .4), saphenous vein grafts (P = .13), and in situ RITAs. However, RITAs grafted to the left anterior descending coronary artery had fewer occlusions (P < .001), with patency similar to LITAs. CONCLUSIONS: Among patients with bilateral ITA grafting requiring interval coronary angiography, long-term RITA patency was high and independent of its inflow configuration. Therefore, priority should be a RITA configuration optimizing its reach to important coronary targets, including the left anterior descending coronary artery.

Trends, risk factors, and outcomes of post-operative stroke after heart transplantation: an analysis of the UNOS database.

BACKGROUND: Post-operative stroke increases morbidity and mortality after cardiac surgery. Data on characteristics and outcomes of stroke after heart transplantation (HTx) are limited. METHODS AND RESULTS: We conducted a retrospective analysis of the United Network for Organ Sharing (UNOS) database from 2009 to 2020 to identify adults who developed stroke after orthotropic HTx. Heart transplant recipients were divided according to the presence or absence of post-operative stroke. The primary endpoint was all-cause mortality. A total of 25 015 HT recipients were analysed, including 719 (2.9%) patients who suffered a post-operative stroke. The stroke rates increased from 2.1% in 2009 to 3.7% in 2019, and the risk of stroke was higher after the implantation of the new allocation system [odds ratio 1.29, 95% confidence intervals (CI) 1.06-1.56, P = 0.01]. HTx recipients with post-operative stroke were older (P = 0.008), with higher rates of prior cerebrovascular accident (CVA) (P = 0.004), prior cardiac surgery (P < 0.001), longer waitlist time (P = 0.04), higher rates of extracorporeal membrane oxygenation (ECMO) support (P < 0.001), left ventricular assist devices (LVADs) (P < 0.001), mechanical ventilation (P = 0.003), and longer ischaemic time (P < 0.001). After multivariable adjustment for recipient and donor characteristics, age, prior cardiac surgery, CVA, support with LVAD, ECMO, ischaemic time, and mechanical ventilation at the time of HTx were independent predictors of post-operative stroke. Stroke was associated with increased risk of 30 day and all-cause mortality (hazard ratio 1.49, 95% CI 1.12-1.99, P = 0.007). CONCLUSIONS: Post-operative stroke after HTx is infrequent but associated with higher mortality. Redo sternotomy, LVAD, and ECMO support at HTx are among the risk factors identified.

Evolution of Recipient Characteristics Over 3 Decades and Impact on Survival After Lung Transplantation.

BACKGROUND: Lung transplantation (LTx) is a definitive treatment for end-stage lung disease. Herein, we reviewed our center experience over 3 decades to examine the evolution of recipient characteristics and contemporary predictors of survival for LTx. METHODS: We retrospectively reviewed the data of LTx procedures performed at our institution from January 1990 to January 2019 (n = 1819). The cohort is divided into 3 eras; I: 1990-1998 (n = 152), II: 1999-2008 (n = 521), and III: 2009-2018 (n = 1146). Univariate and multivariate analyses of survival in era III were performed. RESULTS: Pulmonary fibrosis has become the leading indication for LTx (13% in era I, 57% in era III). Median recipient age increased (era I: 46 y-era III: 61 y) as well as intraoperative mechanical circulatory support (era I: 0%-era III: 6%). Higher lung allocation score was associated with primary graft dysfunction (P < 0.0001), postoperative extracorporeal mechanical support (P < 0.0001), and in-hospital mortality (P = 0.002). In era III, hypoalbuminemia, thrombocytopenia, and high primary graft dysfunction grade were multivariate predictors of early mortality. The 5-y survival in eras II (55%) and III (55%) were superior to era I (40%, P < 0.001). Risk factors for late mortality in era III included recipient age, chronic allograft dysfunction, renal dysfunction, high model for end-stage liver disease score, and single LTx. CONCLUSIONS: In this longitudinal single-center study, recipient characteristics have evolved to include sicker patients with greater complexity of procedures and risk for postoperative complications but without significant impact on hospital mortality or long-term survival. With advancing surgical techniques and perioperative management, there is room for further progress in the field.