Impact of Dual Thoracic Recovery from Circulatory Death Donors on Heart and Lung Transplant Outcomes.

OBJECTIVES: Concomitant heart and lung recovery can result in increased operative complexity, ischemic time, and competition for resources and anatomic territory. Dual thoracic recovery from circulatory death donors (DCD) may have additional risks that are not fully understood. We investigated the effects of dual heart and lung recovery from DCD donors on thoracic transplant outcomes. METHODS: Using the United Network for Organ Sharing database, we categorized all adult thoracic DCD transplants 2019-2023 by whether the donor heart, lung, or both (dual donors) were recovered. Heart and lung transplant outcomes were compared between dual recovery donors and heart-only or lung-only donors, respectively, using multivariable analyses. RESULTS: Of the 2,513 donors included, 42.9% were heart-only,45.0% were lung-only, and 12.0% were dual donors. Recipients of dual versus heart-only donors had similar likelihood of post-transplant dialysis (18.9% vs. 18.3%, p=0.84), likelihood of stroke (2.9% vs. 4.7%, p=0.34), and 2-year risk of mortality (aHR 1.15 [95% CI: 0.90-1.47], p=0.26), but lower likelihood of acute rejection (10.2% vs. 16.1%, p=0.04). Recipients of dual and lung-only donors had similar likelihood of pre-discharge acute rejection (7.6% vs. 8.5%, p=0.70), intubation at 72 hours (38.9% vs. 45.1%, p=0.13), and ECMO at 72 hours (13.1% vs. 18.1%, p=0.11), as well as 2-year risk of mortality (aHR 1.16 [95% CI: 0.74-1.82], p=0.52). CONCLUSIONS: Recovering both the heart and lungs from a DCD donor does not negatively impact transplant outcomes. Outcomes in this population should continue to be investigated as more data and longer-term follow up become available.

Incidence and Risk Factors for Stroke After Combined Heart-Kidney and Heart-Liver Transplantation.

OBJECTIVE: While stroke is a well-recognized complication of isolated heart transplantation, stroke in patients undergoing simultaneous heart-liver (HLT) and heart-kidney transplantation (HKT) has not been explored. This study assessed postoperative stroke incidence, risk factors, and outcomes in HLT and HKT compared with isolated heart transplant. METHODS: The United Network for Organ Sharing database was queried for adult patients undergoing HLT, HKT, and isolated heart transplants between 1994 and 2022. Patients were stratified by presence of in-hospital stroke after transplant. Post-transplant survival at 1-year was assessed using Kaplan-Meier analysis and log-rank tests. Separate multivariable logistic regression models were constructed to identify risk factors for stroke after HKT and HLT. RESULTS: Of 2326 HKT recipients, 85 experienced stroke, and of 442 HLT recipients, 19 experienced stroke. Stroke was more common after HKT and HLT than after an isolated heart transplant (3.7% vs. 4.3% vs. 2.9%, p = 0.01). One-year post-transplant survival was lower in those with stroke among both HKT recipients (64.5% vs. 88.7%, p(log-rank) < 0.001) and HLT recipients (43.8% vs. 87.4%, p(log-rank) < 0.001. Pre-transplant pVAD, prior stroke, postoperative dialysis, diabetes, prior cardiac surgery, and heart cold ischemic time were independent risk factors for stroke after HKT, after adjusting for age, sex, and need for blood transfusion on the waitlist. For HLT, postoperative dialysis was a significant risk factor. CONCLUSIONS: Stroke is more common after HKT and HLT than after isolated heart transplant, and results in poor survival. Independent risk factors for stroke include pre-transplant percutaneous VAD (HKT) and postoperative dialysis (HKT and HLT).

Reoperative approach after extra-anatomic ascending-to-descending aortic bypass graft.

BACKGROUND: Extra-anatomic ascending-to-descending aortic bypass grafts have historically been utilized as a safe and effective solution for repairs of complex coarctation of the aorta. However, reports on reoperation in these patients remain rare. We present a case of an aortic valve replacement and coronary artery bypass grafting in a patient with an extra-anatomic ascending-to-descending aortic bypass graft. CASE PRESENTATION: The patient is a 59-year-old male with a complex aortic history, including repair of aortic coarctation with an ascending-to-descending aortic bypass graft 13 years prior, was admitted to the hospital for shortness of breath and chest pain that had developed over the past year. On further workup, he was found to have severe bileaflet aortic valve stenosis, non-ST elevation myocardial infarction, and moderate coronary artery disease. He underwent surgical aortic valve replacement and coronary artery bypass grafting. Given his unique anatomy, cardiopulmonary bypass approach involved separate cannulation of the right axillary and left common femoral arteries with cross-clamp of both the aorta and the extra-anatomic graft. Using this approach, the redo operation was successfully performed. CONCLUSIONS: Reports on reoperation after ascending-to-descending aortic bypass grafting are rare. We describe our approach to cardiopulmonary bypass and reoperation in a patient with an extra-anatomic ascending-to-descending aortic bypass graft.

Cytokines drive the formation of memory-like NK cell subsets via epigenetic rewiring and transcriptional regulation.

Activation of natural killer (NK) cells with the cytokines interleukin-12 (IL-12), IL-15, and IL-18 induces their differentiation into memory-like (ML) NK cells; however, the underlying epigenetic and transcriptional mechanisms are unclear. By combining ATAC-seq, CITE-seq, and functional analyses, we discovered that IL-12/15/18 activation results in two main human NK fates: reprogramming into enriched memory-like (eML) NK cells or priming into effector conventional NK (effcNK) cells. eML NK cells had distinct transcriptional and epigenetic profiles and enhanced function, whereas effcNK cells resembled cytokine-primed cNK cells. Two transcriptionally discrete subsets of eML NK cells were also identified, eML-1 and eML-2, primarily arising from CD56bright or CD56dim mature NK cell subsets, respectively. Furthermore, these eML subsets were evident weeks after transfer of IL-12/15/18-activated NK cells into patients with cancer. Our findings demonstrate that NK cell activation with IL-12/15/18 results in previously unappreciated diverse cellular fates and identifies new strategies to enhance NK therapies.

Outcomes of Heart Transplant Using High Donor Sequence Number Offers.

INTRODUCTION: Higher donor sequence numbers (DSNs) might spark provider concern about poor donor quality. We evaluated characteristics of high-DSN offers used for transplant and compared outcomes of high- and low-DSN transplants. MATERIALS AND METHODS: Adult isolated heart transplants between January 1, 2015, and December 31, 2022, were identified from the organ procurement and transplantation network database and stratified into high (≥42) and low (<42) DSN. Postoperative outcomes, including predischarge complications, hospital length of stay, and survival at 1 and 3 y, were evaluated using multivariable regressions. RESULTS: A total of 21,217 recipients met the inclusion criteria, with 2131 (10.0%) classified as high-DSN. Donor factors associated with greater odds of high-DSN at acceptance included older age, higher creatinine, diabetes, hypertension, and lower left ventricular ejection fraction. Recipients accepting high-DSN offers were older and more likely to be female, of blood type O, and have lower status at transplant. High- and low-DSN transplants had similar likelihood of stroke (3.2% versus 3.5%; P = 0.97), dialysis (12.3% versus 13.5%; P = 0.12), pacemaker implant (2.3% versus 2.1%; P = 0.64), had similar lengths of stay (16 [12-24] versus 16 [12-25] days, P = 0.38), and survival at 1 (91.6% versus 91.6%; aHR 0.85 [0.72-1.02], P = 0.08) and 3 y (84.2% versus 85.1%; aHR 0.91 [0.79-1.05], P = 0.21) post-transplant. CONCLUSIONS: High-DSN (≥42) was not an independent risk factor for post-transplant mortality and should not be the sole deterrent to acceptance. Accepting high-DSN organs may increase access to transplantation for lower-status candidates.

Utilization and outcomes of expanded criteria donors in adults with congenital heart disease.

BACKGROUND: Use of donation after circulatory death (DCD) and hepatitis C virus (HCV) positive donors in heart transplantation have increased the donor pool. Given poor waitlist outcomes in the adult congenital heart disease (ACHD) population, we investigated waitlist outcomes associated with willingness to consider DCD and HCV+ offers and post-transplant outcomes following HCV+ and DCD transplantation for these candidates. METHODS: Using the United Network for Organ Sharing database, we identified adult ACHD candidates and recipients listed or transplanted, respectively, between 01/01/2016 and 09/30/2023 for the HCV analysis and between 12/01/2019 and 09/30/2023 for the DCD analysis. Among candidates, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider HCV+ and DCD offers. Among recipients of HCV+ (vs HCV-) and DCD (vs brain death [DBD]) transplants, we compared perioperative outcomes and post-transplant survival. RESULTS: Of 1,436 ACHD candidates from 01/01/2016 to 09/30/2023, 37.0% were willing to consider HCV+ heart offers. Of 886 ACHD candidates from 12/01/2019 to 09/30/2023, 15.5% were willing to consider DCD offers. On adjusted analysis, willingness to consider HCV+ offers was associated with 84% increased likelihood of transplant, and willingness to consider DCD offers was associated with 56% increased likelihood of transplant. Of 904 transplants between 01/01/2016 and 09/30/2023, 6.4% utilized HCV+ donors, and of 540 transplants between 12/01/2019 and 09/30/2023, 6.9% utilized DCD donors. Recipients of HCV+ (vs HCV-) and DCD (vs DBD) heart transplants had similar likelihood of perioperative outcomes and 1-year survival. CONCLUSIONS: ACHD candidates who were willing to consider HCV+ and DCD offers were more likely to be transplanted and had similar post-transplant outcomes compared to recipients of HCV- and DBD organs.

For Your Consideration: Benefits of Listing as Willing to Consider Heart Offers from Donors with Hepatitis C.

OBJECTIVE: Despite excellent outcomes of heart transplants from donors with hepatitis C (HCV D+), many candidates are not listed to even consider HCV D+ offers. METHODS: Using the Scientific Registry of Transplant Recipients, we identified adult (≥18y) heart transplant candidates prevalent on the waitlist 2018-03/2023. We compared likelihood of waitlist mortality or heart transplant by candidate willingness to consider HCV D+ offers using competing risk regression. RESULTS: We identified 19,415 heart transplant candidates, 68.9% of whom were willing to consider HCV D+ offers. Heart candidates willing to consider HCV D+ offers had 37% lower risk of waitlist mortality (SHR 0.63, 95%CI 0.56-0.70, p<0.001) than candidates not willing to consider HCV D+ offers, after adjustment for covariates and center-level clustering. Over the same period, heart transplant candidates willing to consider HCV D+ offers had 21% higher likelihood of receiving a transplant (SHR 1.21, 95%CI 1.7-1.26, p<0.001). As a result, among candidates willing to consider HCV D+ offers, 74.9% received a transplant and 6.1% died/deteriorated after three years, versus 68.3% and 9.1% of candidates not willing to consider HCV D+ offers. Lower waitlist mortality was also observed on subgroup analyses of candidates on temporary and durable mechanical circulatory support. CONCLUSION: Willingness to consider HCV D+ heart offers was associated with a 37% lower risk of waitlist mortality and a 21% higher likelihood of receiving a transplant. We urge providers encourage candidates to list as willing to consider offers from donors with hepatitis C to optimize their waitlist outcomes and access to transplant.

Impact of Extracorporeal Membrane Oxygenation Bridging Duration on Lung Transplant Outcomes.

BACKGROUND: We sought to characterize the association between venovenous extracorporeal membrane oxygenation (VV-ECMO) bridging duration and outcomes in patients listed for lung transplantation. METHODS: A retrospective observational study was conducted using the Organ Procurement and Transplantation Network (OPTN) database to identify adults (aged ≥18 years) who were listed for lung transplantation between 2016 and 2020 and were bridged with VV-ECMO. Patients were then stratified into groups, determined by risk inflection points, depending on the amount of time spent on pretransplant ECMO: group 1 (≤5 days), group 2 (6-10 days), group 3 (11-20 days), and group 4 (>20 days). Waiting list survival between groups was analyzed using Fine-Gray competing risk models. Posttransplant survival was compared using Cox regression. RESULTS: Of 566 eligible VV-ECMO bridge-to-lung-transplant patients (median age, 54 years, 49% men), 174 (31%), 124 (22%), 130 (23%), and 138 (24%) were categorized as groups 1, 2, 3, and 4, respectively. Overall, median duration of VV-ECMO was 10 days (interquartile range, 1-211 days), and 178 patients (31%) died on the waiting list. In the Fine-Gray model, compared with group 1, patients bridged with longer ECMO durations in group 2 (subdistribution hazard ratio [SHR], 2.95; 95% CI, 1.63-5.35), group 3 (SHR, 3.96; 95% CI, 2.36-6.63), and group 4 (SHR, 4.33; 95% CI, 2.59-7.22, all P < .001) were more likely to die on the waiting list. Of 388 patients receiving a transplant, pretransplant ECMO duration was not associated with 1-year survival in Cox regression. CONCLUSIONS: Prolonged duration of ECMO bridging was associated with worse waiting list mortality but did not impact survival after lung transplant. Prioritization of very early transplantation may improve waiting list outcomes in this population.

Memory-like differentiation enhances NK cell responses against colorectal cancer.

Metastatic (m) colorectal cancer (CRC) is an incurable disease with a poor prognosis and thus remains an unmet clinical need. Immune checkpoint blockade (ICB)-based immunotherapy is effective for mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRC patients, but it does not benefit the majority of mCRC patients. NK cells are innate lymphoid cells with potent effector responses against a variety of tumor cells but are frequently dysfunctional in cancer patients. Memory-like (ML) NK cells differentiated after IL-12/IL-15/IL-18 activation overcome many challenges to effective NK cell anti-tumor responses, exhibiting enhanced recognition, function, and in vivo persistence. We hypothesized that ML differentiation enhances the NK cell responses to CRC. Compared to conventional (c) NK cells, ML NK cells displayed increased IFN-γ production against both CRC cell lines and primary patient-derived CRC spheroids. ML NK cells also exhibited improved killing of CRC target cells in vitro in short-term and sustained cytotoxicity assays, as well as in vivo in NSG mice. Mechanistically, enhanced ML NK cell responses were dependent on the activating receptor NKG2D as its blockade significantly decreased ML NK cell functions. Compared to cNK cells, ML NK cells exhibited greater antibody-dependent cytotoxicity when targeted against CRC by cetuximab. ML NK cells from healthy donors and mCRC patients exhibited increased anti-CRC responses. Collectively, our findings demonstrate that ML NK cells exhibit enhanced responses against CRC targets, warranting further investigation in clinical trials for mCRC patients, including those who have failed ICB.

Changes in Donor Utilization and Outcomes for Patients Bridged With Durable Left Ventricular Assist Device.

We studied the impact of the 2018 heart allocation policy change on donor characteristics and posttransplant outcomes of left ventricular assist device (LVAD)-bridged heart transplant (HT) recipients. Left ventricular assist device-bridged adult HT recipients from October 2014 to October 2022 in the United Network for Organ Sharing database were categorized into old allocation policy (OAP) and new allocation policy (NAP) cohorts. Baseline characteristics, posttransplant outcomes, and subgroup analyses of unstable and stable LVAD-bridged recipients were assessed. The study included 7,384 HT recipients; 4,345 (58.8%) were transplanted in the OAP era and 3,039 (41.2%) in the NAP era. Old allocation policy recipients were most frequently status 1A at transplantation (71.1%), whereas NAP recipients were most frequently status 3 (40.0%), and status 4 (31.9%). Median donor sequence number (DSN) was higher in the NAP versus OAP era (9 vs. 3, p < 0.001). On multivariable analysis, NAP recipients had 20% higher 1 year mortality compared to OAP (adjusted hazard ratio [aHR] = 1.20 [95% confidence interval {CI}: 1.04-1.40], p = 0.01). Status 1 or 2 recipients had 28% higher 1 year mortality compared to status 1A (aHR = 1.28 [95% CI: 1.01-1.63], p = 0.04). Status 1 and 2 LVAD-supported recipients had higher mortality following the 2018 allocation change, indicating the need for closer surveillance of LVAD-bridged patients who may decompensate on the waitlist.

Case report: Increased efficacy of cetuximab after pembrolizumab failure in cutaneous squamous cell carcinoma.

Immunotherapy is the first-line option for treating advanced cutaneous squamous cell carcinoma (cSCC). However, up to half of patients experience no benefit and treatment resistance, warranting newer therapeutic approaches. Combinatory approaches, including cetuximab, may help overcome immunotherapy resistance and improve response rates in advanced cSCC. We report three cases of metastatic cSCC that achieved significant clinical responses after cetuximab therapy following initial progression on pembrolizumab. We have retrospectively reviewed these cases at a single academic center between 2018 and 2023. All patients initially progressed on pembrolizumab, after which cetuximab (mono- or combination therapy) was added with two complete responses and one partial response. Initial responses were noted within 2 to 7 months of starting cetuximab. While the benefit of cetuximab and immunotherapy in head-and-neck squamous cell carcinoma has growing evidence, information regarding cSCC remains limited. This study adds three cases to the underreported literature on treating advanced cSCC with cetuximab after initially failing immunotherapy.

Debunking the July Effect in lung transplantation recipients.

Objective: The "July Effect" is a theory that the influx of trainees from July to September negatively impacts patient outcomes. We aimed to study this theoretical phenomenon in lung transplant recipients given the highly technical nature of thoracic procedures. Methods: Adult lung transplant hospitalizations were identified within the National Inpatient Sample (2005-2020). Recipients were categorized as academic Q1 (July to September) or Q2-Q4 (October to June). In-hospital mortality, operator-driven complications (pneumothorax, dehiscence including wound dehiscence, bronchial anastomosis, and others, and vocal cord/diaphragm paralysis, all 3 treated as a composite outcome), length of stay, and inflation-adjusted hospitalization charges were compared between both groups. Multivariable logistic regression was performed to assess the association between academic quarter and in-hospital mortality and operator-driven complications. The models were adjusted for recipient demographics and transplant characteristics. Subgroup analysis was performed between academic and nonacademic hospitals. Results: Of 30,788 lung transplants, 7838 occurred in Q1 and 22,950 occurred in Q2-Q4. Recipient demographic and clinical characteristics were similar between groups. Dehiscence (n = 922, 4% vs n = 236, 3%), post-transplant cardiac arrest (n = 532, 2% vs n = 113, 1%), and pulmonary embolism (n = 712, 3% vs n = 164, 2%) were more common in Q2-Q4 versus Q1 recipients (all P < .05). Other operator-driven complications, in-hospital mortality, and resource use were similar between groups (P > .05). These inferences remained unchanged in adjusted analyses and on subgroup analyses of academic versus nonacademic hospitals. Conclusions: The "July Effect" is not evident in US lung transplantation recipient outcomes during the transplant hospitalization. This suggests that current institutional monitoring systems for trainees across multiple specialties, including surgery, anesthesia, critical care, nursing, and others, are robust.

National Incidence, Outcomes, and Management Strategies for Pre- and Post-Transplant Atrial Fibrillation in Heart Transplant Recipients.

Background: Among heart transplant candidates, atrial fibrillation (AF) is a common comorbidity; however, little is known about the impact of pre-transplant AF on incidence of post-transplant AF or other transplant outcomes. Methods: Adult heart transplant recipients transplanted from 07/01/2012 to 07/01/2021 with data available in both the Scientific Registry of Transplant Recipients and Symphony Health pharmacy databases were included. Recipients were categorized by presence of pre-transplant AF using prescription fill data. Perioperative outcomes and survival out to 5 years post-transplant were compared between those with and without pre-transplant AF. Results: Of the 11,789 heart transplant recipients, 2,477 (21.0%) had pre-transplant AF. Pre-transplant AF was associated with an increased likelihood of pre-discharge stroke (aOR 2.13 [95%CI: 1.07-4.26], p=0.03) and dialysis (aOR 1.45 [1.05-2.00], p=0.02), as well as of post-transplant AF at 6 months (aOR 2.42 [1.44-1.48], p=0.001) and 1 year (aOR 2.81 [1.72-4.56], p<0.001). Pre-transplant AF was associated with increased post-transplant mortality at 30 days (aHR 2.39 [1.29-4.44], p=0.006) and 1 year (aHR 1.46 [95% CI: 1.01-2.13], p=0.04), but similar mortality at 5 years (aHR 1.23 [0.96-1.58], p=0.11). Conclusion: Heart transplant recipients with pre-transplant AF had worse short-term outcomes and increased risk of developing post-transplant AF but comparable survival at 5 years post-transplant. Our findings emphasize the importance of increased monitoring for perioperative complications and highlight the long-term safety of heart transplantation in this population. What Is New?: Patients with atrial fibrillation who undergo heart transplantation have worse short term survival (30-days and 1-year) but similar long term survival (5-years) compared to recipients without pre-transplant atrial fibrillation.Pre-transplant atrial fibrillation increases the risk of clinically significant post-transplant atrial fibrillation and peri-operative stroke.Rate vs rhythm control pharmacotherapy for atrial fibrillation is not associated with differences in survival in heart transplant recipients with pre-transplant atrial fibrillation. What are the Clinical Implications?: Atrial fibrillation should not deter heart transplantation in appropriate candidates, though cardiovascular and stroke risk adjustment may be warranted.Use of amiodarone at doses ≤ 200 mg/day is not associated with reduced survival in heart transplant recipients with pre-transplant atrial fibrillation.

Induced CD8α identifies human NK cells with enhanced proliferative fitness and modulates NK cell activation.

The surface receptor CD8α is present on 20-80% of human (but not mouse) NK cells, yet its function on NK cells remains poorly understood. CD8α expression on donor NK cells was associated with a lack of therapeutic responses for leukemia patients in prior studies, thus we hypothesized that CD8α may impact critical NK cell functions. Here, we discovered that CD8α- NK cells had improved control of leukemia in xenograft models, compared to CD8α+ NK cells, likely due to an enhanced capacity for proliferation. Unexpectedly, CD8α expression was induced on approximately 30% of previously CD8α- NK cells following IL-15 stimulation. These 'induced' CD8α+ ('iCD8α+') NK cells had the greatest proliferation, responses to IL-15 signaling, and metabolic activity, compared to those that sustained existing CD8α expression ('sustained CD8α+) or those that remained CD8α- ('persistent CD8α-'). These iCD8α+ cells originated from an IL-15Rß high NK cell population, with CD8α expression dependent on the transcription factor RUNX3. Moreover, CD8A CRISPR/Cas9 deletion resulted in enhanced responses through the activating receptor NKp30, possibly by modulating KIR inhibitory function. Thus, CD8α status identifies human NK cell capacity for IL-15-induced proliferation and metabolism in a time-dependent fashion and exhibits a suppressive effect on NK cell activating receptors.

Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs.

Xenotransplantation represents a possible solution to the organ shortage crisis and is an imminent clinical reality with long-term xenograft survival in pig-to-nonhuman primate (NHP) heart and kidney large animal models, and short-term success in recent human decedent and clinical studies. However, concerns remain about safe clinical translation of these results, given the inconsistency in published survival as well as key differences between preclinical procurement and immunosuppression and clinical standards-of-care. Notably, no studies of solid organ pig-to-NHP transplantation have achieved xenograft survival longer than one month without CD40/CD154 costimulatory blockade, which is not currently an FDA-approved immunosuppression strategy. We now present consistent survival in consecutive cases of pig-to-NHP kidney xenotransplantation, including long-term survival after >3 hours of xenograft cold preservation time as well as long-term survival using FDA-approved immunosuppression. These data provide critical supporting evidence for the safety and feasibility of clinical kidney xenotransplantation. Moreover, long-term survival without CD40/CD154 costimulatory blockade may provide important insights for immunosuppression regimens to be considered for first-in-human clinical trials.

Special Considerations for Advanced Heart Failure Surgeries: Durable Left Ventricular Devices and Heart Transplantation.

Heart transplantation and durable left ventricular assist devices (LVADs) represent two definitive therapies for end-stage heart failure in the modern era. Despite technological advances, both treatment modalities continue to experience unique risks that impact surgical and perioperative decision-making. Here, we review special populations and factors that impact risk in LVAD and heart transplant surgery and examine critical decisions in the management of these patients. As both heart transplantation and the use of durable LVADs as destination therapy continue to increase, these considerations will be of increasing relevance in managing advanced heart failure and improving outcomes.

Bigger pies, bigger slices: Increased hospitalization costs for lung transplantation recipients in the non-donation service area allocation era.

OBJECTIVE: On November 24, 2017, lung transplant allocation switched from donation service area to a 250-nautical mile radius policy to improve equity in access to lung transplantation. Given the growing consideration of healthcare costs, we evaluated changes in hospitalization costs after this policy change. METHODS: Lung transplant hospitalizations were identified within the National Inpatient Sample from 2005 to 2020. Recipients were categorized as donation service area era (August 2015 to October 2017) or non-donation service area era (December 2017 to February 2020). Median total hospitalization costs (inflation adjusted) were compared by era nationally and regionally. Multivariable generalized linear regression was performed to determine if the removal of the donation service area was associated with total hospitalization costs. The model was adjusted for recipient demographics, Charlson Comorbidity Index, hospitalization region, transplant type (single, double), and use of extracorporeal membrane oxygenation, ex vivo lung perfusion, and mechanical ventilation. RESULTS: We analyzed 12,985 lung transplant recipients (median age of 61 years, 66% were male): 7070 in the donation service area era and 5915 in the non-donation service area era. Demographics were not different between recipients in both eras. Non-donation service area era recipients had greater extracorporeal membrane oxygenation use, mechanical ventilation (<24 hours), and longer length of stay than donation service area era recipients. Median total hospitalization costs for non-donation service area versus donation service area era recipients increased by $24,198 ($157,964 vs $182,162, percentage change = 15.32%, P < .001). Median costs increased in East North Central ($42,281) and Mountain ($35,521) regions (both P < .01). After adjustment, median costs for non-donation service area versus donation service area era recipients still increased ($19,168, 95% CI, 145-38,191, P = .048). CONCLUSIONS: Hospitalization costs for lung transplant hospitalizations have increased from 2015 to 2020. The transition from donation service area-based allocation to the non-donation service area system may have contributed to this increase after 2017 by increasing access to transplant for sicker recipients.