Outcomes of Donation After Circulatory Death (DCD) and Ex-Vivo Lung Perfusion (EVLP) Lung Transplantation.

BACKGROUND: Donation after circulatory death (DCD) and ex-vivo lung perfusion (EVLP) have been adopted to expand the donor pool in lung transplantation, but outcomes data have been conflicting. This study explores mid-term outcomes of DCD lung transplantation in the modern era, with a focus on EVLP and risk factors for graft failure. METHODS: The United Network for Organ Sharing (UNOS) database was queried for adult lung transplants from 1/1/2015 to 3/1/2023. Loss to follow-up, multiorgan and prior lung transplants were excluded. DCD vs DBD (donation after brain death) lung transplants were compared, with subgroup analysis +/- EVLP. Outcomes were survival and postoperative complications. Overall survival was analyzed separately for an early era (2015-2018) and modern era (2019-2023). RESULTS: The study included 1103 DCD (221 with EVLP, and 882 without) and 17973 donation after brain death (DBD) lung transplants (524 with EVLP, and 17449 without). Median follow-up was 3 years. DCD donors were less likely to be CDC high risk (19.3% vs 24.1%, p<0.001), have purulence on bronchoscopy (13.3% vs 18.3%, p<0.001) or infiltrates on chest x-ray (66.7% vs 67.8%, p=0.013). EVLP was more likely to be used for DCD transplants (20.0% vs 2.9%, p<0.001). After transplant, DCD recipients were more likely to be reintubated (24.3% vs 18.5%, p<0.001) and require ECMO within 72 hours (14.9% vs 7.8%, p<0.001), and DCD donation was an independent risk factor for these complications on multivariable logistic regression. Overall survival did not differ significantly between DCD and DBD transplants on adjusted survival analysis in the early or modern era (p=0.774 and p=0.468 respectively). On multivariable Cox regression, DCD and EVLP were not independent risk factors for mortality. On subgroup analysis, the DCD+EVLP cohort had significantly worse survival in the modern era, which remained significant after adjusting for donor and recipient factors (p=0.005). EVLP was an independent risk factor for graft failure in the DCD cohort (HR 1.33, 95% CI 1.00-1.77, p=0.047), but did not significantly affect DBD graft survival (p=0.870). Risk factors for graft failure and mortality in the DCD+EVLP cohort included pulmonary hypertension (HR 77.5, 95% CI 6.15-979, p<0.001), transfusion prior to transplant (HR 2.60, 95% CI 1.07-6.31, p=0.035), elevated creatinine (HR 2.82, 95% CI 1.34-5.90, p=0.006), and higher allocation score (HR 1.02, 95% CI 1.00-1.04, p=0.017) CONCLUSION: Study findings suggest increased risks of mortality and perioperative complications following transplantation with DCD lungs that have undergone EVLP. DCD lung transplantation without EVLP confers equivalent survival but with some increase in perioperative complications. Further investigation and careful recipient selection is warranted to optimize the use of these extended criteria donors in the modern era.

Cardiac Loading using Passive Left Atrial Pressurization and Passive Afterload for Graft Assessment.

Ex vivo machine perfusion or normothermic machine perfusion is a preservation method that has gained great importance in the transplantation field. Despite the immense opportunity for assessment due to the beating state of the heart, current clinical practice depends on limited metabolic trends for graft evaluation. Hemodynamic measurements obtained from left ventricular loading have garnered significant attention within the field due to their potential as objective assessment parameters. In effect, this protocol provides an easy and effective manner of incorporating loading capabilities to established Langendorff perfusion systems through the simple addition of an extra reservoir. Furthermore, it demonstrates the feasibility of employing passive left atrial pressurization for loading, an approach that, to our knowledge, has not been previously demonstrated. This approach is complemented by a passive Windkessel base afterload, which acts as a compliance chamber to maximize myocardial perfusion during diastole. Lastly, it highlights the capability of capturing functional metrics during cardiac loading, including left ventricular pulse pressure, contractility, and relaxation, to uncover deficiencies in cardiac graft function after extended periods of preservation times (˃6 h).

Acute rejection in donation after circulatory death (DCD) heart transplants.

BACKGROUND: Donation after circulatory death (DCD) heart transplantation has promising early survival, but the effects on rejection remain unclear. METHODS: The United Network for Organ Sharing database was queried for adult heart transplants from December 1, 2019, to December 31, 2021. Multiorgan transplants and loss to follow-up were excluded. The primary outcome was acute rejection, comparing DCD and donation after brain death (DBD) transplants. RESULTS: A total of 292 DCD and 5,582 DBD transplants met study criteria. Most DCD transplants were transplanted at status 3-4 (61.0%) compared to 58.6% of DBD recipients at status 1-2. DCD recipients were less likely to be hospitalized at transplant (26.7% vs 58.3%, p < 0.001) and to require intra-aortic balloon pumping (IABP; 9.6% vs 28.9%, p < 0.001), extracorporeal membrane oxygenation (ECMO; 0.3% vs 5.9%, p < 0.001) or temporary left ventricular assist device (LVAD; 1.0% vs 2.7%, p < 0.001). DCD recipients were more likely to have acute rejection prior to discharge (23.3% vs 18.4%, p = 0.044) and to be hospitalized for rejection (23.4% vs 11.4%, p = 0.003) at a median follow-up of 15 months; the latter remained significant after propensity matching. On multivariable logistic regression, DCD donation was an independent predictor of acute rejection (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.00-2.15, p = 0.048) and hospitalization for rejection (OR 2.03, 95% CI 1.06-3.70, p = 0.026). On center-specific subgroup analysis, DCD recipients continued to have higher rates of hospitalization for rejection (23.4% vs 13.8%, p = 0.043). CONCLUSIONS: DCD recipients are more likely to experience acute rejection. Early survival is similar between DCD and DBD recipients, but long-term implications of increased early rejection in DCD recipients require further investigation.

Preemptive antiviral therapy in lung transplantation from hepatitis C donors results in a rapid and sustained virologic response.

Objective: The study objective was to assess the safety and efficacy of a preemptive direct-acting antiviral therapy in lung transplants from hepatitis C virus donors to uninfected recipients. Methods: This study is a prospective, open-label, nonrandomized, pilot trial. Recipients of hepatitis C virus nucleic acid test positive donor lungs underwent preemptive direct-acting antiviral therapy with glecaprevir 300 mg/pibrentasvir 120 mg for 8 weeks from January 1, 2019, to December 31, 2020. Recipients of nucleic acid test positive lungs were compared with recipients of lungs from nucleic acid test negative donors. Primary end points were Kaplan-Meier survival and sustained virologic response. Secondary outcomes included primary graft dysfunction, rejection, and infection. Results: Fifty-nine lung transplantations were included: 16 nucleic acid test positive and 43 nucleic acid test negative. Twelve nucleic acid test positive recipients (75%) developed hepatitis C virus viremia. Median time to clearance was 7 days. All nucleic acid test positive patients had undetectable hepatitis C virus RNA by week 3, and all alive patients (n = 15) remained negative during follow-up with 100% sustained virologic response at 12 months. One nucleic acid test positive patient died of primary graft dysfunction and multiorgan failure. Three of 43 nucleic acid test negative patients (7%) had hepatitis C virus antibody positive donors. None of them developed hepatitis C virus viremia. One-year survival was 94% for nucleic acid test positive recipients and 91% for nucleic acid test negative recipients. There was no difference in primary graft dysfunction, rejection, or infection. One-year survival for nucleic acid test positive recipients was similar to a historical cohort of the Scientific Registry of Transplant Recipients (89%). Conclusions: Recipients of hepatitis C virus nucleic acid test positive lungs have similar survival as recipients of nucleic acid test negative lungs. Preemptive direct-acting antiviral therapy results in rapid viral clearance and sustained virologic response at 12 months. Preemptive direct-acting antiviral may partially prevent hepatitis C virus transmission.

Outcomes of Lung Transplantation From Hepatitis C Viremic Donors.

BACKGROUND: Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) has encouraged lung transplantation with HCV positive donors. Early trials have been promising; however, nationwide data have not been previously examined. METHODS: The United Network for Organ Sharing registry was queried for adult patients receiving lung transplants from 2016 to 2019. We excluded multiorgan transplants, incomplete data, and loss to follow-up. Nucleic acid testing (NAT) determined HCV status. Propensity matching was performed for comparison of outcomes. RESULTS: Hepatitis C virus NAT-positive lungs were transplanted in 189 patients, compared with 9511 recipients of NAT-negative lungs. The HCV NAT-positive donors were younger (mean 33 vs 35 years, P = .017) with higher rates of Pao2/Fio2 greater than 300 (83.6% vs 76.5%, P = .029). Recipients of NAT-positive lungs had lower lung allocation scores (mean 39.3 vs 42.4, P = .009). Distance traveled was significantly further for HCV viremic donor lungs (mean 416 vs 206 miles, P < .001). Kaplan-Meier survival analysis demonstrated no difference in survival (P = .56). There were no differences in airway dehiscence (P = .629), acute rejection (P > .999), or reintubation (P = .304). At mean follow-up of 395 days, 63 recipients of NAT-positive lungs (40%) seroconverted, 14 with viremia. One-year mortality rates among seroconverted patients was 6% and did not differ significantly from 14% in nonseroconverted patients or 13.2% in recipients of HCV-negative lungs. CONCLUSIONS: Short-term outcomes of lung transplantation from HCV viremic donors are promising, with no difference in early complications or survival. The effects of seroconversion and long-term outcomes including chronic rejection and infection need to be further explored.

Rationale and Design of the Randomized Controlled Trial of New Oral Anticoagulants Versus Warfarin for Post Cardiac Surgery Atrial Fibrillation: The NEW-AF Trial.

OBJECTIVE: This manuscript describes the rationale and design of a randomized, controlled trial comparing outcomes with Warfarin vs Novel Oral Anticoagulant (NOAC) therapy in patients with new onset atrial fibrillation after cardiac surgery. BACKGROUND: New onset atrial fibrillation commonly occurs after cardiac surgery and is associated with increased rates of stroke and mortality. in nonsurgical patients with atrial fibrillation, NOACs have been shown to confer equivalent benefits for stroke prevention with less bleeding risk and less tedious monitoring requirements compared with Warfarin. However, NOAC use has yet to be adopted widely in cardiac surgery patients. METHODS: The NEW-AF study has been designed as a pragmatic, prospective, randomized controlled trial that will compare financial, convenience and safety outcomes for patients with new onset atrial fibrillation after cardiac surgery that are treated with NOACs versus Warfarin. RESULTS: Study results may contribute to optimizing the options for stroke prophylaxis in cardiac surgery patients and catalyze more widespread application of NOAC therapy in this patient population. CONCLUSIONS: The study is ongoing and actively enrolling at the time of the publication. The trial is registered with clinicaltrials.gov under registration number NCT03702582.

Trends in the use of hepatitis C viremic donor hearts.

OBJECTIVE: To examine trends in utilization of hearts from hepatitis C virus (HCV) viremic donors for transplantation, a strategy to expand organ availability. METHODS: The United Network for Organ Sharing (UNOS) registry was queried for adult patients undergoing heart transplantation between 2015 and 2019. We excluded multiorgan transplants, incomplete data, and loss to follow-up. Nucleic acid testing (NAT) defined HCV status. RESULTS: Between 2015 and 2019, a total of 11,393 adults underwent heart transplantation: 326 from HCV NAT+ donors and 11,067 from NAT- donors. The use of NAT+ hearts increased from 1 in 2015 to 137 in 2018 against a static number of NAT- organs. The use of NAT+ hearts varied significantly across regions and individual centers. More than 75% of NAT+ hearts were transplanted in the Northeast region, leading to further travel (mean, 299 miles vs 173 miles for NAT- transplantations; P < .001), with longer ischemic times (mean: 3.52 hours vs 3.10 hours; P < .001). More than one-half of NAT+ transplantations were performed by 5 individual centers, and a single institution accounted for >20% of all transplantations from viremic donors. Survival in the 2 groups did not differ by Kaplan-Meier analysis (P = .240), and multivariable regression showed no differences in acute rejection (P = .455) or 30-day mortality (P = .490). Of the 326 recipients of NAT+ hearts, 38 seroconverted and 14 became viremic within 1 year. Survival was 100% in the viremic patients and 97.4% in seroconverted patients at 1 year. CONCLUSIONS: Heart transplantation from HCV viremic donors continues to increase but varies significantly across UNOS regions and individual centers. Short-term outcomes are comparable, but effects of seroconversion and long-term outcomes remain unclear.

How to Turn It Down: The Evidence and Opinions Behind Adult Venoarterial Extracorporeal Membrane Oxygenation Weaning.

Adequate and durable recovery in patients supported with venoarterial (VA) extracorporeal membrane oxygenation (ECMO) can be challenging to predict. Extracorporeal membrane oxygenation weaning is the process by which the ECMO flows are decreased to assess if a patient is ready for decannulation. The optimal strategies for deciding who to wean and how to wean VA ECMO remain undefined. A retrospective literature review was performed to understand the evidence supporting current practices in ECMO weaning and in particular patient selection and methods. Most published work and expert opinions agree that once the underlying process has resolved, the minimum required physiologic parameters for weaning from ECMO include: hemodynamic stability and cardiac pulsatility, adequate lung function to support oxygenation and ventilation, and evidence of recovered end organ function. Echocardiography is universally used to assess cardiac function during the weaning process. Currently, there is no consensus regarding who is eligible to wean or how to wean ECMO in adults. We have reviewed the literature to summarize the evidence and expert opinions behind VA ECMO weaning, and give an example of the protocol used at our center. We believe this protocol optimizes patient selection for weaning and helps to predict successful decannulation.

Factors Related to Survival in Low-Glomerular Filtration Rate Cohorts Undergoing Lung Transplant.

BACKGROUND: Historically, a glomerular filtration rate (GFR) of less than 50 mL/min per 1.73 m2 has been considered a contraindication to lung transplantation. Combined or sequential lung-kidney transplantation is an option for those with a GFR less than 30 mL/min per 1.73 m2. Patients with a GFR of 30 to 50 mL/min per 1.73 m2 are provided with no options for transplantation. This study explores factors associated with improved survival in patients who undergo isolated lung transplantation with a GFR of 30 to 50 mL/min per 1.73 m2. METHODS: The United Network for Organ Sharing database was queried for adult patients undergoing primary isolated lung transplantation between January 2007 and March 2018. Regression models were used to identify factors associated with improved survival in lung recipients with a preoperative GFR of 30 to 50 mL/min per 1.73 m2. The propensity score method was used to match highly performing patients (outpatient recipients aged less than 60 years) with a GFR of 30 to 50 mL/min per 1.73 m2 with patients who had a GFR greater than 50 mL/min per 1.73 m2. Kaplan-Meier, Cox, and logistic regression analyses compared outcomes in matched populations. RESULTS: A total of 21,282 lung transplantations were performed during the study period. Compared with patients with a GFR greater than 50 mL/min per 1.73 m2, survival was significantly worse for patients with a GFR of 30 to 50 mL/min per 1.73 m2. Multivariate analysis of patients with a GFR of 30 to 50 mL/min per 1.73 m2 demonstrated outpatient status and age less than 60 years to be predictive of superior survival. After propensity matching, survival of this highly performing subset with a GFR of 30 to 50 mL/min per 1.73 m2 was no different from that of patients with a normal GFR. CONCLUSIONS: Outpatient recipients aged less than 60 years represent an optimal subset of patients with a GFR of 30 to 50 mL/min per 1.73 m2. Lung transplant listing should not be declined based only on a GFR less than 50 mL/min per 1.73 m2.

Impact of Treatment Sequencing on Survival for Patients with Locally Advanced Gastric Cancer.

BACKGROUND: Data are limited concerning the survival outcomes of locally advanced gastric cancer patients according to the multimodality therapy (MMT) administered. METHODS: Single institution, retrospective analysis of 235 patients with locally advanced gastric cancer from 2001 to 2015. All patients met criteria for curative-intent surgery and chemotherapy ± radiation therapy. Treatment regimens were: (1) surgery first with adjuvant chemoradiation therapy (S + Adj); (2) perioperative chemotherapy + surgery (Periop); and (3) total neoadjuvant therapy followed by surgery (TNT + S). RESULTS: One hundred twenty-eight (60.0%) patients received S + Adj, 69 (26.8%) Periop, and 38 (13.2%) TNT + S. Of the 235 patients, 222 (94.5%) received surgery. All intended therapy was received by 81.6% of TNT + S, 44.5% of S + Adj, and 42.0% of Periop patients. MMT was significantly more likely to be completed by TNT + S patients (HR 6.67, p < 0.001). At a median follow-up of 37 months, survival rates on an intention-to-treat basis with TNT + S, Periop, and S + Adj were 52.6%, 59.4%, and 45.3%, respectively. Regimen and completion of MMT significantly affected overall mortality risk. Compared with Periop, TNT + S had similar mortality risk (hazard ratio [HR] 1.28, p = 0.421), whereas S + Adj had increased mortality risk (HR 1.64, p = 0.027). CONCLUSIONS: The choice of treatment sequencing has a major impact on completion rates of multimodal therapy in patients with locally advanced gastric cancer. Less than 50% of patients treated with upfront surgery or perioperative chemotherapy receive all intended therapies. TNT has higher intended therapy completion rates and comparable survival compared with perioperative therapy in our data. Further prospective investigations of TNT are warranted.

Impact of Postoperative Complication and Completion of Multimodality Therapy on Survival in Patients Undergoing Gastrectomy for Advanced Gastric Cancer.

BACKGROUND: Postoperative complication (POC) adversely impacts long-term survival in patients with gastric cancer, perhaps due in part to lower rates for receipt of multimodality therapy (MMT). We sought to determine the impact of POC on MMT completion rates and overall survival (OS) in patients with locally advanced gastric cancer. STUDY DESIGN: We analyzed 206 patients with locally advanced gastric cancer undergoing curative-intent resection from 2001 to 2015. POCs were graded using Clavien-Dindo classification and survival outcomes were compared between groups. RESULTS: One hundred and twenty patients underwent operation followed by chemoradiation therapy, 58 received perioperative chemotherapy, and 28 received total neoadjuvant therapy (TNT). Minor (Clavien-Dindo grade I to II) and major (Clavien-Dindo grade III to IV) POC occurred in 72 (35.0%) and 39 (18.9%) patients, respectively. At median follow-up of 37 months, the 3-year OS of patients experiencing a major, minor, or no POC were 33.3%, 56.9%, and 62.1% (p = 0.023), respectively. In contrast, there was no difference in 3-year OS rates in patients experiencing POC if they completed all intended MMT. Non-TNT patients who experienced a major POC were less likely to complete MMT (hazard ratio 0.36, p = 0.017), and a major POC in these patients had a significant impact on OS (hazard ratio 2.76, p = 0.011), and it did not in patients who completed MMT (hazard ratio 1.58, p = 0.336). CONCLUSIONS: Major POC adversely affects long-term survival after gastrectomy for gastric cancer, at least in part via lower completion rates of MMT. Treatment strategy designed to ensure the completion of MMT, such as TNT, might be preferable, particularly for patients at high risk for POCs.

Morbidity and Mortality of Total Gastrectomy: a Comprehensive Analysis of 90-Day Outcomes.

BACKGROUND: Total gastrectomy (TG) is a complex procedure that carries a high risk of morbidity and mortality and in which patients may experience post-operative sequelae well past the standard 30-day follow-up period. Large studies from high-volume centers with detailed 90-day follow-up data are needed to provide benchmarks for high-quality care for this complex procedure. METHODS: Single-institution, retrospective review of a comprehensive gastric cancer database of 148 patients undergoing curative intent TG from 2000 to 2017. Clinicopathologic and treatment factors were analyzed for their impact on 90-day outcomes. RESULTS: The median age of the cohort was 66 years, and 61% were male. Neoadjuvant chemotherapy and radiation therapy were delivered to 32% and 11% of patients, respectively. Open and laparoscopic TG were performed in 93% (n = 137) and 7% (n = 11) of patients, respectively. Extended lymphadenectomy, pancreatectomy, and splenectomy were performed in 37%, 4.7%, and 19% of patients, respectively. The 30- and 90-day mortality rates were 2.0% and 3.4%, respectively. At least one 90-day complication was experienced by 43.9% (n = 65) of patients, and 14% (n = 21) experienced a Clavien-Dindo grade 3 or 4 complication. Anastomotic leak occurred in 5.4% (n = 8) of patients, half of which required an invasive intervention. Median length of stay was 8 days. The readmission rate was 22%, and most readmissions were due to dehydration and/or nutritional compromise. CONCLUSIONS: This study defines 30- and 90-day post-operative outcomes after total gastrectomy in a high-volume center. These outcomes data are critical to the improvement of the informed consent process and as benchmarks for future quality improvement initiatives.

Outcomes of Extended Lymphadenectomy for Gastroesophageal Carcinoma: A Large Western Series.

BACKGROUND: The extent of lymph node dissection for patients with gastroesophageal carcinoma remains controversial. We sought to examine the perioperative risk and survival outcomes in a large Western series of patients undergoing limited (D0/D1) vs extended (D1+/D2) lymphadenectomy (LAD) for gastroesophageal carcinoma. STUDY DESIGN: Clinicopathologic and treatment factors for 520 patients with gastroesophageal carcinoma undergoing potentially curative resection at a single institution from 1995 to 2017 were analyzed for their impact on perioperative morbidity and mortality, lymph node yield, and overall survival. RESULTS: A total of 362 (70%) patients underwent D0/D1 LAD and 158 (30%) underwent D1+/D2 LAD. Median follow-up was 3.1 years. Patients undergoing D1+/D2 LAD were more likely to have distal tumors, to undergo distal/subtotal/total gastrectomy, and to undergo operation at a more contemporary time than patients undergoing D0/D1 LAD. The median number of lymph nodes examined and the percentage of patients with 16 or more lymph nodes examined was 16 and 53%, respectively, in the D0/D1 group vs 27 and 89%, respectively, in the D1+/D2 group. There were no differences in the rates of major complications (16.6% vs 14.6%) or operative mortality (2.8% vs 0.6%) between the D0/D1 and D1+/D2 groups, respectively. Patients undergoing D1+/D2 LAD had significantly improved overall survival (hazard ratio 0.74; p = 0.035) compared with those undergoing D0/D1 LAD on univariate analysis, but this survival benefit disappeared when controlling for the time period of operation. CONCLUSIONS: Gastrectomy with extended (D1+/D2) LAD can be performed safely at a high-volume Western center, and it improves nodal yield significantly and ensures accurate pathologic staging.