A Multi-Center International Analysis of Lung Transplantation Outcomes in Patients With COVID-19.

INTRODUCTION: Lung transplantation has become increasingly utilized in patients with COVID-19. While several single-center and UNOS database studies have been published on lung transplants (LTs) for end-stage lung disease (ESLD) from Coronavirus disease 2019 (COVID-19), there is a lack of multi-center and international data. METHODS: This is a multicenter analysis from 11 high-volume lung transplant centers in the United States and Europe. Data were collected through the Multi-Institutional ECLS Registry and stratified by ESLD due to COVID-19 versus other etiologies. Demographics and clinical variables were compared using Chi-square test and Fisher's exact test. Survival was assessed by Kaplan-Meier curves and compared by log-rank test with propensity score matching. RESULTS: Of 1606 lung transplant recipients, 46 (2.9%) were transplanted for ESLD from COVID-19 compared to 1560 (97.1%) without a history of COVID-19. Among COVID-19 patients, 30 (65.2%) had COVID-19-associated ARDS and 16 (34.8%) had post-COVID-19 fibrosis. COVID-19 patients had higher lung allocation scores (78.0 vs. 44.4, p < 0.0001), had severely limited functional status (37.0% vs. 2.9%, p < 0.0001), had higher preoperative ECMO usage (65.2% vs. 5.4%, p < 0.0001), and spent less time on the waitlist (32 vs. 137 days, p < 0.0001). A 30-day survival was comparable between COVID-19 and non-COVID-19 patients before (100% vs. 98.7%, p = 0.39) and after propensity matching (p = 0.15). CONCLUSIONS: Patients who received LTs due to COVID-19 had short-term survival comparable to that of patients without COVID-19. Our findings support the idea that lung transplantation should be considered for select patients with ESLD due to COVID-19.

Textbook Outcomes in Solid Transplantation: A Systematic Review.

Background: The concept of TO is expanding across various surgical disciplines to establish a standardized, comprehensive quality benchmark. Traditional metrics such as 1-y patient and graft survival have been key for evaluating transplant program performance but are now deemed inadequate because of significant field advancements. This systematic review aims to provide a comprehensive understanding of the applicability and validity of textbook outcome (TO) in the setting of solid organ transplantation. Methods: A structured search, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, was conducted across PubMed, Embase, and Scopus databases on March 10, 2024. Results: Fourteen articles were identified for inclusion in this review. Of these, 2 studies addressed TO in heart transplantation, 3 in lung transplantation, 2 in kidney transplantation, and 7 in liver transplantation. A subgroup analysis was conducted to categorize the different definitions of TOs and identify the most common reasons for TO failure. Conclusions: Our systematic review highlights the ongoing efforts in the field of solid organ transplantation to define TO and emphasizes the importance of developing a universally recognized set of TO criteria for each type of transplant. TO provides a valuable framework for transplant centers to benchmark their performance against similar institutions on a risk-adjusted basis and to pinpoint specific areas for enhancing patient outcomes. Even the most successful programs may discover aspects within the composite outcome with scope for improvement.

Use of a novel donor lung scoring system as a tool for increasing lung recovery for transplantation.

BACKGROUND: There is a critical shortage of donor lungs for transplantation. We previously developed a parsimonious, highly discriminatory 9-variable Lung Donor (LUNDON) acceptability score. Here we assessed the utility of this score as a tool for improving lung recovery rates for transplantation. METHODS: We examined all brain-dead donors between 2014 and 2020 from 3 US organ procurement organizations and validated the score's predictive performance. We examined the trajectory of donors with low (<40) and high (>60) initial LUNDON scores, their corresponding lung recovery rates, factors contributing to score improvement using multivariable regression models, and 1-year post-transplant recipient survival. RESULTS: Overall lung recovery was 32.4% (1410 of 4351). Validation of the LUNDON score in our cohort revealed a C statistic of 0.904 and required intercept calibration. Low initial LUNDON donors that improved to a high final score had an increase in lung recovery rate from 29.3% (1100 of 3765) to 86.8% (441 of 508), associated with lower body mass index, management in a specialized donor care facility (SDCF), and more bronchoscopies. Donors with high initial and final LUNDON scores had a lung recovery rate of 85.2% (98 of 115), associated with shorter length of hospital stay. One-year survival was similar in recipients of low-to-high versus high-to-high LUNDON score donors (0.89 vs 0.84; P = .2). CONCLUSIONS: The LUNDON score performs well as a predictor of lung recovery in a contemporary cohort but may require organ procurement organization-specific calibration. SDCF care, increasing use of bronchoscopy, and decreasing the time from brain death to organ procurement may improve lung utilization. The LUNDON score can be used to guide donor management to expand the donor pool.

Implications of the Composite Allocation Score System for Lung Transplantation in the United States: Review of the New System.

Due to criticism regarding undue adherence to fixed geographic boundaries, the Lung Allocation Score system was recently replaced by the more holistic allocation via continuous distribution. This review highlights the historical evolution of US lung allocation paradigms, outlines rationale for continuous distribution under the Composite Allocation Score system and discusses expected implications of this new system.

Longitudinal Follow-up of Medicare Patients After Esophageal Cancer Resection in the STS Database.

BACKGROUND: Understanding characteristics associated with survival after esophagectomy for cancer is critical to preoperative risk stratification. This study sought to define predictors for long-term survival after esophagectomy for cancer in Medicare patients. METHODS: The Society of Thoracic Surgeons General Thoracic Surgery Database was queried for patients aged ≥65 years who underwent esophagectomy for cancer between 2012 and 2020 and linked to Centers for Medicare and Medicaid Services (CMS) data using a deterministic matching algorithm. Patient, hospital, and treatment variables were assessed using a multivariable Cox proportional hazards model to evaluate characteristics associated with long-term mortality and readmission. Kaplan-Meier and cumulative incidence curves were generated and differences evaluated using the log-rank test and Gray's test, respectively. RESULTS: After CMS linkage, 4798 patients were included. Thirty-day and 90-day mortality in the study group was 3.84% and 7.45%, respectively. In the multivariable model, American Society of Anesthesiologists score >3, body mass index >35, and diabetes were associated with increased mortality <90 days post-surgery, while pN/pT upstaging was associated with increased mortality >90 days post-surgery. Patients upstaged to pN(+) had a 147% increased mortality risk (adjusted hazard ratio [aHR], 2.47; 95% CI, 2.02-3.02) and those that remained pN(+) a 75% increased mortality risk (aHR, 1.75; 95% CI, 1.57-1.95) compared with downstaged patients. Patients who were pT upstaged had a 109% (aHR, 2.09; 95% CI, 1.73-2.53) increased mortality risk compared with pT downstaged patients. Risk for readmission was independent of procedure type or approach and was higher in c stage ≥2, American Society of Anesthesiologists score ≥4, and pN+. CONCLUSIONS: Medicare patients undergoing esophagectomy for cancer have identifiable patient-specific predictors for short-term mortality and tumor-specific predictors for long-term mortality and readmission. In the absence of pathologic T and N downstaging, risk for long-term mortality and readmission are increased.

Consensus Statement: Technical Standards for Thoracoabdominal Normothermic Regional Perfusion.

BACKGROUND: Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. METHODS: A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. RESULTS: The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. CONCLUSIONS: The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.

Optimizing DCD Liver Grafts With Prolonged Warm Ischemic Time Using Stabilized Plasmin in a Static Cold Storage Orthotopic Rat Liver Transplant Model.

Background: The clinical success of liver transplantation has led to increased demand, requiring further expansion of the donor pool. Therapeutic interventions to optimize organs from donation after circulatory death (DCD) have significant potential to mitigate the organ shortage. Dysfunction in DCD liver grafts is mediated by microvascular thrombosis during the warm ischemic period, and strategies that reduce this thrombotic burden may improve graft function. We hypothesized that the administration of the fibrinolytic enzyme plasmin to the donor organ during the cold storage period would reduce the thrombotic burden and improve DCD liver graft function. Methods: In 2 separate cohorts, 32 syngeneic orthotopic rat liver transplants were performed in Lewis rats. Livers were procured from donors with 45 min of warm ischemic injury. Liver grafts were flushed with histidine-tryptophan-ketoglutarate preservation solution mixed with either plasmin (experimental group) or albumin (control group). All investigators were blinded to treatment group. After preparing the liver for implant using a modified cuff technique, the liver was stored for 1 h by static cold storage at 4 °C. Immediately before implantation, the liver graft was flushed, and this effluent was analyzed for fibrin degradation products to determine graft clot burden. Twenty-four hours following transplantation, animals were euthanized, and samples were collected. Results: Recipient survival was significantly higher for DCD liver grafts treated with plasmin compared with control. Moreover, histology of liver graft tissue immediately before implant reflected significantly reduced congestion in plasmin-treated livers (score, mean ± SD: 0.73 ±â€…0.59 versus 1.12 ±â€…0.48; P = 0.0456). The concentration of fibrin degradation products in the final flush before implantation was significantly reduced in plasmin-treated livers (743 ±â€…136 versus 10 919 ±â€…4642 pg/mL; P = 0.0001), reflecting decreased clot burden in the graft. Conclusions: The present study demonstrates that plasmin improves survival and may reduce thrombotic burden in DCD liver grafts with prolonged warm ischemic injury, meriting further study.

Consensus Statement: Technical Standards for Thoracoabdominal Normothermic Regional Perfusion.

BACKGROUND: Thoracoabdominal normothermic regional perfusion (TA-NRP) has emerged as a powerful technique for optimizing organ procurement from donation after circulatory death donors. Despite its rapid adoption, standardized guidelines for TA-NRP implementation are lacking, prompting the need for consensus recommendations to ensure safe and effective utilization of this technique. METHODS: A working group composed of members from The American Society of Transplant Surgeons, The International Society of Heart and Lung Transplantation, The Society of Thoracic Surgeons, and The American Association for Thoracic Surgery was convened to develop technical guidelines for TA-NRP. The group systematically reviewed existing literature, consensus statements, and expert opinions to identify key areas requiring standardization, including predonation evaluation, intraoperative management, postdonation procedures, and future research directions. RESULTS: The working group formulated recommendations encompassing donor evaluation and selection criteria, premortem testing and therapeutic interventions, communication protocols, and procedural guidelines for TA-NRP implementation. These recommendations aim to facilitate coordination among transplant teams, minimize variability in practice, and promote transparency and accountability throughout the TA-NRP process. CONCLUSIONS: The consensus guidelines presented herein serve as a comprehensive framework for the successful and ethical implementation of TA-NRP programs in organ procurement from donation after circulatory death donors. By providing standardized recommendations and addressing areas of uncertainty, these guidelines aim to enhance the quality, safety, and efficiency of TA-NRP procedures, ultimately contributing to improved outcomes for transplant recipients.

The cost of lung transplantation in the United States: How high is too high?

Objectives: To identify patient and process factors that contribute to the high cost of lung transplantation (LTx) in the perioperative period, which may allow transplant centers to evaluate situations in which transplantation is most cost-effective to inform judicious resource allocation, avoid futile care, and reduce costs. Methods: The MarketScan Research databases were used to identify 582 privately insured patients undergoing single or bilateral LTx between 2013 and 2019. The patients were subdivided into groups by disease etiology using the United Network of Organ Sharing classification system. Multivariable generalized linear models using a gamma distribution with a log link were fit to examine the associations between the etiology of lung disease and costs during the index admission, 3 months before admission, and 3 months after discharge. Results: Our results indicate that the index admission contributed the most to the total transplantation costs compared to the 3 months before admission and after discharge. The regression-adjusted mean index hospitalization cost was 35% higher for patients with pulmonary vascular disease compared to those with obstructive lung disease ($527,156 vs $389,055). The use of extracorporeal membrane oxygenation, mechanical ventilation, and surgical complications in the post-transplantation period were associated with higher costs during the index admission. Surprisingly, age ≥55 was associated with lower costs during the index admission. Conclusions: This analysis identifies pivotal factors influencing the high cost of LTx, emphasizing the significant impact of the index admission, particularly for patients with pulmonary vascular disease. These insights offer transplant centers an opportunity to enhance cost-effectiveness through judicious resource allocation and service bundling, ultimately reducing overall transplantation costs.

Subnormothermic Oxygenated Machine Perfusion (24 h) in DCD Kidney Transplantation.

Background: Ex vivo kidney perfusion is an evolving platform that demonstrates promise in preserving and rehabilitating the kidney grafts. Despite this, there is little consensus on the optimal perfusion conditions. Hypothermic perfusion offers limited functional assessment, whereas normothermic perfusion requires a more complex mechanical system and perfusate. Subnormothermic machine perfusion (SNMP) has the potential to combine the advantages of both approaches but has undergone limited investigation. Therefore, the present study sought to determine the suitability of SNMP for extended kidney preservation. Methods: SNMP at 22-25 °C was performed on a portable device for 24 h with porcine kidneys. Graft assessment included measurement of mechanical parameters and biochemical analysis of the perfusate using point-of-care tests. To investigate the viability of kidneys preserved by SNMP, porcine kidney autotransplants were performed in a donation after circulatory death (DCD) model. SNMP was also compared with static cold storage (SCS). Finally, follow-up experiments were conducted in a subset of human kidneys to test the translational significance of findings in porcine kidneys. Results: In the perfusion-only cohort, porcine kidneys all displayed successful perfusion for 24 h by SNMP, evidenced by stable mechanical parameters and biological markers of graft function. Furthermore, in the transplant cohort, DCD grafts with 30 min of warm ischemic injury demonstrated superior posttransplant graft function when preserved by SNMP in comparison with SCS. Finally, human kidneys that underwent 24-h perfusion exhibited stable functional and biological parameters consistent with observations in porcine organs. Conclusions: These observations demonstrate the suitability and cross-species generalizability of subnormothermic machine perfusion to maintain stable kidney perfusion and provide foundational evidence for improved posttransplant graft function of DCD kidneys after SNMP compared with SCS.

Efforts to improve the billing accuracy of robotic-assisted thoracic surgery through education, updated procedure cards, and electronic medical record system changes.

Precise medical billing is essential for decreasing hospital liability, upholding environmental stewardship and ensuring fair costs for patients. We instituted a multifaceted approach to improve the billing accuracy of our robotic-assisted thoracic surgery programme by including an educational component, updating procedure cards and removing the auto-populating function of our electronic medical record. Overall, we saw significant improvements in both the number of inaccurate billing cases and, specifically, the number of cases that overcharged patients.

Ex vivo lung perfusion in donation after circulatory death: A post hoc analysis of the Normothermic Ex Vivo Lung Perfusion as an Assessment of Extended/Marginal Donors Lungs trial.

OBJECTIVE: Donation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multicenter setting. METHODS: This was an unplanned post hoc analysis of a multicenter, prospective, nonrandomized trial that took place during 2011 to 2017 with 3 years of follow-up. Patients were placed into 3 groups based off procurement strategy: brain-dead donor (control), brain-dead donor evaluated by EVLP, and DCD donors evaluated by EVLP. The primary outcomes were severe primary graft dysfunction at 72 hours and survival. Secondary outcomes included select perioperative outcomes, and 1-year and 3-years allograft function and quality of life measures. RESULTS: The DCD EVLP group had significantly higher incidence of severe primary graft dysfunction at 72 hours (P = .03), longer days on mechanical ventilation (P < .001) and in-hospital length of stay (P = .045). Survival at 3 years was 76.5% (95% CI, 69.2%-84.7%) for the control group, 68.3% (95% CI, 58.9%-79.1%) for the brain-dead donor group, and 60.7% (95% CI, 45.1%-81.8%) for the DCD group (P = .36). At 3-year follow-up, presence observed bronchiolitis obliterans syndrome or quality of life metrics did not differ among the groups. CONCLUSIONS: Although DCD EVLP allografts might not be appropriate to transplant in every candidate recipient, the expansion of their use might afford recipients stagnant on the waitlist a viable therapy.

Validation of a novel donor lung scoring system based on the updated lung Composite Allocation Score.

Lung transplantation (LTx) continues to have lower rates of long-term graft survival compared with other organs. Additionally, lung utilization rates from brain-dead donors remain substantially lower compared with other solid organs, despite a growing need for LTx and the significant risk of waitlist mortality. This study aims to examine the effects of using a combination of the recently described novel lung donor (LUNDON) acceptability score and the newly adopted recipient lung Composite Allocation Score (CAS) to guide transplantation. We performed a review of nearly 18 000 adult primary lung transplants from 2015-2022 across the US with retroactive calculations of the CAS value. The medium-CAS group (29.6-34.5) had superior 1-year posttransplant survival. Importantly, the combination of high-CAS (> 34.5) recipients with low LUNDON score (≤ 40) donors had the worst survival at 1 year compared with any other combination. Additionally, we constructed a model that predicts 1-year and 3-year survival using the LUNDON acceptability score and CAS values. These results suggest that caution should be exercised when using marginally acceptable donor lungs in high-priority recipients. The use of the LUNDON score with CAS value can potentially guide clinical decision-making for optimal donor-recipient matches for LTx.

The Society of Thoracic Surgeons Database Analysis: Comparing Sublobar Techniques in Stage IA Lung Cancer.

BACKGROUND: This study compares sublobar resections-wedge resection and segmentectomy-in clinical stage IA lung cancers. It tests the hypothesis that overall survival after wedge resection is similar to segmentectomy. METHODS: Adults undergoing wedge resection or segmentectomy for clinical stage IA lung cancer were identified from The Society of Thoracic Surgeons General Thoracic Surgery Database. Eligible patients were linked to the Centers for Medicare and Medicaid Services database using a matching algorithm. The primary outcome was long-term overall survival. Propensity scores overlap weighting (PSOW) adjustment of wedge resection using validated covariates was used for group difference mitigation. Kaplan-Meier and Cox regression models analyzed survival. All-cause first readmission, and morbidity and mortality were examined using PSOW regression models. RESULTS: Of 9756 patients, 6141 met inclusion criteria, comprising 2154 segmentectomies and 3987 wedge resections. PSOW reduced differences between the groups. Unadjusted perioperative mortality was comparable, but wedge resection showed lower major morbidity rates. Weighted regression analysis indicated reduced mortality and major morbidity risks in wedge resection. Kaplan-Meier analysis revealed no mortality difference between groups, which was confirmed by PSOW Cox regression models. The cumulative risk of readmission was also comparable for both groups, with Cox Fine-Gray models showing no difference in rehospitalization risks. CONCLUSIONS: In clinical stage IA lung cancer, relative to segmentectomy, wedge resection has comparable overall survival and lower perioperative morbidity, suggesting it is an equally effective option for the broader population of patients with clinical stage IA lung cancer, not only those at highest risk of complications.

Knowledge gaps in heart and lung donation after the circulatory determination of death: Report of a workshop of the National Heart, Lung, and Blood Institute.

In a workshop sponsored by the U.S. National Heart, Lung, and Blood Institute, experts identified current knowledge gaps and research opportunities in the scientific, conceptual, and ethical understanding of organ donation after the circulatory determination of death and its technologies. To minimize organ injury from warm ischemia and produce better recipient outcomes, innovative techniques to perfuse and oxygenate organs postmortem in situ, such as thoracoabdominal normothermic regional perfusion, are being implemented in several medical centers in the US and elsewhere. These technologies have improved organ outcomes but have raised ethical and legal questions. Re-establishing donor circulation postmortem can be viewed as invalidating the condition of permanent cessation of circulation on which the earlier death determination was made and clamping arch vessels to exclude brain circulation can be viewed as inducing brain death. Alternatively, TA-NRP can be viewed as localized in-situ organ perfusion, not whole-body resuscitation, that does not invalidate death determination. Further scientific, conceptual, and ethical studies, such as those identified in this workshop, can inform and help resolve controversies raised by this practice.

Development and validation of primary graft dysfunction predictive algorithm for lung transplant candidates.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Accurate prediction of PGD risk could inform donor approaches and perioperative care planning. We sought to develop a clinically useful, generalizable PGD prediction model to aid in transplant decision-making. METHODS: We derived a predictive model in a prospective cohort study of subjects from 2012 to 2018, followed by a single-center external validation. We used regularized (lasso) logistic regression to evaluate the predictive ability of clinically available PGD predictors and developed a user interface for clinical application. Using decision curve analysis, we quantified the net benefit of the model across a range of PGD risk thresholds and assessed model calibration and discrimination. RESULTS: The PGD predictive model included distance from donor hospital to recipient transplant center, recipient age, predicted total lung capacity, lung allocation score (LAS), body mass index, pulmonary artery mean pressure, sex, and indication for transplant; donor age, sex, mechanism of death, and donor smoking status; and interaction terms for LAS and donor distance. The interface allows for real-time assessment of PGD risk for any donor/recipient combination. The model offers decision-making net benefit in the PGD risk range of 10% to 75% in the derivation centers and 2% to 10% in the validation cohort, a range incorporating the incidence in that cohort. CONCLUSION: We developed a clinically useful PGD predictive algorithm across a range of PGD risk thresholds to support transplant decision-making, posttransplant care, and enrich samples for PGD treatment trials.