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Restoration of lymphatic drainage across the bronchial anastomosis after lung transplantation requires several weeks. As donor antigen and antigen presenting cell trafficking via lymphatics into graft-draining lymph nodes is an important component of the alloresponse, alternative pathways must exist that account for rapid rejection after pulmonary transplantation. Here, we describe a novel allorecognition pathway mediated through donor extracellular vesicle (EV) trafficking to mediastinal lymph nodes via the pleural space. Pleural fluid collected early after lung transplantation in rats and humans contains donor-specific EVs. In a fully MHC mismatched rat model of lung transplantation, we demonstrate EVs carrying donor antigen preferentially accumulate in mediastinal lymph nodes and colocalize with MHC II expressing cells within 4 h of engraftment. Injection of allogeneic EVs into pleural space of syngeneic lung transplant recipients confirmed their selective trafficking to mediastinal lymph nodes and resulted in activation of T cells in mediastinal, but not peripheral lymph nodes. Thus, we have uncovered an alternative pathway of donor antigen trafficking where pulmonary EVs released into the pleural space traffic to locoregional lymph nodes via pleural lymphatics. This pathway obviates the need for restoration of lymphatics across the bronchial anastomosis for trafficking of donor antigen to draining lymph nodes.

AIM OF THE STUDY Extracorporeal membrane oxygenation (ECMO) is considered a life-saving treatment option for patients in cardiogenic shock or cardiac arrest undergoing cardiopulmonary resuscitation (CPR) due to acute pulmonary embolism (PE). We sought to analyze use and outcome of ECMO with or without adjunctive treatment strategies in patients with acute PE. METHODS We retrospectively analyzed data on patient characteristics, treatments, and in-hospital outcomes for all PE patients (ICD-code I26) undergoing ECMO in Germany between 2005 and 2018. RESULTS At total of 1,172,354 patients were hospitalized with PE; of those, 2,197 (0.2%) were treated with ECMO support. Cardiac arrest requiring cardiopulmonary resuscitation was present in 77,196 (6.5%) patients. While more than one fourth of those patients were treated with systemic thrombolysis alone (n = 20,839 patients; 27.0%), a minority of patients received thrombolysis and VA-ECMO (n = 165; 0.2%), embolectomy and VA-ECMO (n = 385; 0.5%) or VA-ECMOalone (n = 588; 0.8%). A multivariable logistic regression analysis indicated the lowest risk for in-hospital death in patients who received embolectomy in combination with VA-ECMO (OR, 0.50 [95% CI, 0.41-0.61], p

Cerebral malperfusion and carotid artery dissection in patients with acute type A aortic dissections (TAAD) carry high morbidity and mortality. There are limited data on outcomes of concomitant carotid artery replacement with total arch replacement in the setting of TAAD.All patients with acute TAAD who underwent a total arch replacement between 2007 and 2018 were included. Data were retrospectively collected from a prospectively maintained database. Baselines variables were compared, and Kaplan-Meier estimates were used for long-term survival. Cox multivariable regression analysis was used to identify predictors of mortality.A total of 161 patients underwent total arch replacement for acute TAAD. Of these, 111 underwent conventional total arch reconstruction, and 50 had a concomitant carotid artery replacement. Baseline characteristics were similar between both cohorts apart from the carotid replacement cohort having a higher rate of preoperative cerebral malperfusion (48% vs 10.81%, P.01) and preoperative stroke (28% vs 11.71%, P = .02). There was no difference in (operative) 30-day mortality between the carotid replacement and conventional total arch replacement groups (22% vs 18.9%, P = .81), 1-year mortality (28% vs 27.9%, P = .99), or 5-year mortality (32% vs 29.7%, P = .917). Postoperative stroke was 0% vs 4.5% (P = .301) for the carotid vs conventional total arch replacement cohort.Concomitant carotid artery replacement is a feasible and safe technique to address perioperative cerebral malperfusion, carotid dissection, and neurologic dysfunction associated with carotid artery dissection, with no difference in long-term survival or postoperative stroke when compared with conventional total arch replacement.

There is a known association between need for transfusion and short-term outcomes in patients undergoing cardiac surgery. However long-term data are lacking in the contemporary literature.All patients who underwent open cardiac surgery from 2010 to 2018 were included, except those undergoing transplant, with a ventricular-assist device, and requiring circulatory arrest. Primary outcome included short- and long-term mortality. Secondary outcomes included postoperative complications and hospital readmissions.The total patient population included 14,281 patients with a median follow-up of 4.03 years (range, 2.25-6.1). Outcomes were stratified into patients with (n = 6239) or without (n = 8042) packed red blood cell (PRBC) use. Patients with PRBC transfusions had significantly (P.001) worse postoperative outcomes compared with those without PRBC use, including higher operative mortality (6.89% vs 0.98%), return to the operating room (17.8% vs 1.61%), pneumonia (7.84% vs 0.98%), stroke (3.22% vs 1.51%), sepsis (2.66% vs 0.20%), renal failure (8.42% vs 1.12%), and dialysis (5.74% vs 0.42%). On multivariate analysis PRBC transfusion was an independent predictor of mortality (hazard ratio [[HR], 2.39; 95% confidence interval [CI], 2.08-2.64; P.001) and hospital readmission (HR, 1.15; 95% CI, 1.09-1.21; P.001). Total units of PRBCs were directly associated with mortality (HR, 1.09; 95% CI, 1.08-1.09; P.001) and hospital readmissions (HR, 1.02; 95% CI, 1.01-1.03; P.005).Patients with perioperative PRBC transfusions have increased operative and long-term mortality and hospital readmissions. Total units of PRBCs transfused were directly associated with mortality and readmissions.

Objective There is a critical need for development of biomarkers to noninvasively monitor for lung transplant rejection. We investigated the potential of circulating donor lung-specific exosome profiles for time sensitive diagnosis of acute rejection in a rat orthotopic lung transplant model. Methods Left lungs from Wistar transgenic rats expressing human CD63-GFP, an exosome marker, were transplanted into fully MHC-mismatched Lewis recipients or syngeneic controls. Recipient blood was collected between 4 hours and 10 days after transplantation and plasma was processed for exosome isolation by size exclusion column chromatography and ultracentrifugation. Circulating donor exosomes were profiled using anti-human CD63 antibody quantum dot on the nanoparticle detector, and via GFP trigger on the nanoparticle flow cytometer (FACS). Results In syngeneic controls, steady state levels of circulating donor exosomes were detected at all post-transplant time points. Allogeneic grafts lost perfusion by day 8, consistent with acute rejection. Levels of circulating donor exosomes peaked on day 1, decreased significantly by day 2, and then reached baseline levels by day 3. Notably, decrease in peripheral donor exosome levels occurred before grafts had histological evidence of acute rejection. Conclusions Circulating donor lung-specific exosome profiles enable an early detection of acute rejection before histologic manifestation of injury to the pulmonary allograft. As acute rejection episodes are a major risk factor for the development of chronic lung allograft dysfunction, this biomarker may provide a novel noninvasive diagnostic platform that can translate into earlier therapeutic intervention for lung transplant patients.

Objective Hybrid arch procedures (arch vessel debranching with thoracic endovascular aneurysm repair [TEVAR] coverage of arch pathology) have been presented as an alternative to total arch replacement (TAR). But multicenter-based analyses of these two procedures are needed to benchmark the field and establish areas of improvement. Methods The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database from July 2014 to December 2015 was queried for elective TAR and hybrid arch procedures. Demographics and operative characteristics were compared and stepwise variable selection was used to create a risk-set used for adjustment of all multivariable models. Results A total of 1,011 patients met inclusion criteria, 884 underwent TAR, and 127 had hybrid arch procedures. TAR patients were younger (mean age: 62.7 ± 13.3 vs. 66.7 ± 11.9 years; p = 0.001) and had less peripheral vascular disease (34.0 vs. 49.6%; p Conclusion TAR remains the gold standard for elective aortic arch pathologies. Despite risk adjustment, hybrid arch procedures were associated with increased risk of mortality and stroke, advocating for careful adoption of these strategies.

The aim of the current study was to assess the impact of hospital readmissions within 30-days of discharge, on long-term postoperative outcomes. All patients who underwent cardiac surgery from 2011 - 2018 were included. Patients who had transcatheter procedures, VAD, and transplant were excluded. Inverse probability of treatment weighting (IPTW) propensity scoring was used for population risk adjustment. Multivariable analysis was performed to identify association with long-term mortality and readmission. The total risk adjusted (propensity scoring with IPTW) patient population consisted of 14,538 patients divided into those who were not readmitted in 30-days (nonreadmitted) (n = 12,627) and patients who were readmitted within 30-days (30-day readmitted) (n = 1911). Following IPTW, all baseline characteristics and postoperative complications were equivalent between cohorts (SMD0.10). Patients who required intraoperative [OR 1.178 (1.05, 1.32); P = 0.006] and postoperative [1.32 (1.18, 1.48); P0.001] blood transfusions were at greater risk for 30-day readmission. Median follow-up period was 4.19 years (2.45 - 6.10). The 30-day readmission cohort had a significantly higher mortality risk during early (6 months) follow-up [HR 2.49 (2.01-3.10); P0.001] and late (60 months) follow-up [HR 1.30 (1.16-1.47); P0.001]. After risk adjustment, the 30-day readmission cohort was significantly associated with increased mortality over the study follow-up period [HR 1.62 (1.48, 1.78); P0.001]. 30-day readmissions were an independent predictor of subsequent long-term hospital readmission [HR 1.61 (1.50, 1.73); P0.001]. Patients who require 30-day readmissions following cardiac surgery are at increased risk of long-term mortality and repeat readmissions. Early postoperative hospital readmission may be a marker for worse long-term outcomes in cardiac surgery.

Reoperative coronary artery bypass grafting (CABG) surgery has an established increased operative risk with worse perioperative morbidity and mortality. However, contemporary propensity-matched outcomes are limited in the existing literature.All patients who underwent CABG from 2011 to 2017 at the University of Pittsburgh Medical Center in Pittsburgh, Pennsylvania were included. Propensity matching yielded risk-adjusted patient populations. Cox regression analysis was performed to identify independent predictors of 30-day, 1-year, and 5-year mortality and readmission.The total population consisted of 7615 patients who underwent CABG; 7265 of these patients had first-time CABG, and 350 patients had reoperative CABG. After propensity score matching, blood product transfusion (45.5% vs 56.4%; P = .002) and delayed sternal closure (0.2% vs 2.5%; P.001) remained significantly higher for reoperative CABG. There was no difference in 30-day (5.3% vs 7.5%; P = .19) or 1-year (12.1% vs 14.8%; P = .23) mortality for first-time vs reoperative CABG. Five-year mortality was significantly higher for the reoperative cohort (28.5% vs 38.3%; P = .03). There was no difference in 30-day, 1-year, or 5-year hospital readmissions. On Cox multivariable regression analysis, reoperative CABG was not a predictor of mortality or readmission at 30 days, 1 year, or 5 years.After propensity score matching, there was no difference in postoperative mortality or readmission for reoperative CABG up to 1-year. This trend continued for 5-year readmissions; however, 5-year mortality was higher for the reoperative cohort. Risk adjustment did not identify reoperative CABG as a risk factor for long-term mortality.

BACKGROUND The wide availability of transcatheter aortic valve replacement (TAVR) and broadening of its indications to most patients with aortic stenosis may increase its utilization in the urgent setting. However, a comparison of long-term outcomes of patients undergoing urgent TAVR when compared to elective TAVR have not been well studied. METHODS All patients that underwent TAVR from 2011 to 2018 were included. Primary outcomes included operative (30-day), 1-, and 5-year survival and readmissions. RESULTS The total patient population undergoing TAVR was divided into urgent (n = 247) and elective (n = 946) cohorts. Thirty days mortality (6.5% vs. 2.3%; p = .001), acute kidney injury (2.8% vs. 0.6%; p = .003), and length of stay (12 vs. 3 days; p

Background Patients with acute type A aortic dissection (ATAAD) present with heterogeneous involvement of the aortic root complex. Despite this variation, the aortic root can usually be preserved the majority of the time by Teflon (WL Gore, Newark, DE) inlay patch reconstruction of the dissected sinuses of Valsalva (SOV). In this study, we report the long term anatomic, functional, and clinical outcomes associated with the preserved SOV after surgery for ATAAD. Methods From 2002-2017, of 776 emergency ATAAD operations at a single institution, 558 (71.9%) underwent valve resuspension with SOV preservation. Echocardiography reports were reviewed to obtain postoperative SOV dimensions. Cumulative incidence of SOV dilation ≥ 4 5mm was calculated using the Fine-Gray method with death as a competing risk. Repeated-measures linear mixed effects model was used to determine risk factors for SOV growth over time. Results During the follow-up period, 62 of 558 (11.1%) patients developed SOV diameter ≥ 45 mm. Cumulative incidence of SOV dilation ≥ 45 mm at 1, 5, and 10 years was 5.5%, 12.4%, and 18.9% respectively. In a multivariable Cox regression model, preoperative SOV diameter ≥ 45 mm was associated with a hazard ratio of 14.11 (95% confidence interval 7.03-31.62) for postoperative SOV dilation ≥ 45 mm. In a repeated-measures linear mixed effects model, preoperative and discharge SOV diameter were significant predictors of SOV dilation. Postoperative time course was also identified as significant indicating growth over time. Conclusions The preserved sinuses of Valsalva after surgery for ATAAD may be prone to progressive dilatation over time. Closer echocardiographic surveillance may be warranted in these patients.

Background Data on primary cardiac malignancies are limited to small single-center studies. Objectives The aim of the current study was to provide detailed outcomes for treatment of primary cardiac malignancies from a multi-institutional database. Methods Outcomes were acquired from the National Cancer Database for all solid primary cardiac malignancies from 2004 to 2016. The primary outcome was long-term survival. Logistic regression was used to determine factors associated with mortality. Results A total of 100,317 cardiac tumors were identified, of which 826 (0.8%) were primary malignant tumors. After exclusion criteria, the cohort consisted of 747 patients (median age 53 years, 47.5% women). Most tumors were primary sarcomas (88.5%), the majority of which were hemangiosarcoma (40.4%). A total of 136 patients received no therapy, 113 received just chemotherapy, and 20 received just radiation. Surgery was performed in 442 (59.2%) patients including 255 patients undergoing multimodal therapy (surgery with chemotherapy, radiation, or chemoradiation). With surgery alone, 90-day mortality was 29.4%. Overall 30-day, 1-year, and 5-year survival rates were 81.2%, 45.3%, and 11.5%, respectively. The surgery group as compared with the no surgery groups had significantly better long-term survival (p Conclusions Primary cardiac malignancies are rare cancers with dismal long-term survival despite mode of treatment. Patients who underwent surgery and those with stage III disease who received peri-operative chemotherapy had better survival compared with those who did not. However, there was likely a significant selection bias in patients chosen for surgical or medical therapy.

Objective: There is a paucity of clinical data on critically ill patients with COVID-19 requiring extracorporeal life support. Methods: A statewide multi-institutional collaborative for COVID-19 patients was utilized to obtain clinical data on the first 10 critically ill COVID-19 patients who required extracorporeal membrane oxygenation (ECMO). Results: Of the first 10 patients that required ECMO for COVID-19, the age ranged from 31 to 62 years with the majority (70%) being men. Seven (70%) had comorbidities. The majority (80%) of patients had known sick contact and exposure to COVID-19 positive patients or traveled to pandemic areas inside the United States within the 2 weeks before symptom onset. None of the patients were healthcare workers. The most common symptoms leading to the presentation were high fever ≥103°F (90%), cough (80%) and dyspnea (70%), followed by fatigue and gastrointestinal symptoms (both 30%), myalgia, loss of taste, pleuritic chest pain, and confusion (all 10%). All patients had bilateral infiltrates on chest X-rays suggestive of interstitial viral pneumonia. All patients were cannulated in the venovenous configuration. Two (20%) patients were successfully liberated from ECMO support after 7 and 10 days, respectively, and one (10%) patient is currently on a weaning course. One patient (10%) died after 9 days on ECMO from multiorgan dysfunction. Conclusions: These preliminary multi-institutional data from a statewide collaborative offer insight into the clinical characteristics of the first 10 patients requiring ECMO for COVID-19 and their initial clinical course. Greater morbidity and mortality is likely to be seen in these critically ill patients with longer follow-up.

Prior single-center studies suggest that kidney and liver allografts are immunoprotective toward transplanted hearts. The broader effects of the simultaneous transplantation of kidney or liver on protection from rejection are unclear.The United Network for Organ Sharing database for heart transplantation was queried from 1987 to 2015 and stratified into patients undergoing heart-liver transplantation (HLT) (n = 192), heart-kidney transplantation (HKT) (n = 1,174), and heart-only transplantation (HT) (n = 61,471). Perioperative and follow-up data were compared between HT versus HLT and HT versus HKT groups using analysis of variance (continuous), chi-square test (categorical), and Kaplan-Meier curves (survival).HKT patients were older (51.2 ± 13.4 years of age) compared with HT patients (45.6 ± 19.2 years of age; p0.0001), with higher rate of diabetes (33.8% versus 14.8%; p0.0001) and dialysis (49.7% versus 2.1%; p0.0001). HKT (46.2%) and HLT (49.5%) patients had more urgent need for transplantation (status 1A) compared with HT patients (32%; p0.0001). Acute rejection episodes before discharge were lower in the HLT group (7.1% versus 3.1%; p = 0.03). Ten-year patient survivals were similar for HT (53.6%) versus HKT (56.7%) (p = 0.13) versus HLT (60.4%) (p = 0.09). Treatment for rejection during the first posttransplant year was lower in HLT (2.1%) and HKT (8.4%) compared with HT (17.4%) (p0.0001 for both). Cox multivariate analysis showed that cardiac allograft survival was improved in HKT (odds ratio, 0.58; 95% confidence interval [CI], 0.49 to 0.70; p0.0001). Additionally, HKT (hazard ratio, 0.52; 95% CI, 0.45 to 0.60; p0.0001) and HLT (hazard ratio, 0.24; 95% CI, 0.15 to 0.39; p0.0001) were associated with improved freedom from rejection.Nationally, HKT and HLT have equivalent postoperative outcomes as HT. Simultaneous kidney or liver transplantation confers an improved clinical and immunologic outcome.

Background Unlike coronary artery bypass and aortic and mitral valve procedures, there is no predictive risk model for aortic root replacement procedures. As a first step toward development of a risk model, this study analyzed The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database to determine factors predictive of mortality and morbidity in patients undergoing elective aortic root replacement (ARR). Methods The STS database was queried (from July 2011 to June 2016) for elective ARR with the following exclusion criteria: urgent or salvage cases, endocarditis, redo cardiac surgery, circulatory arrest, and aortic arch surgery. Adjusted multivariate logistic regression models for outcomes of mortality and composite STS morbidity were performed using covariates of the STS aortic valve risk set (expressed as odds ratios [ORs]). Results Of 24,244 patients undergoing ARR, 8,807 (77.6% male) met inclusion criteria in 808 centers; 33.7% (n = 2,965) had a bicuspid aortic valve, and 3.7% (n = 327) had Marfan syndrome. The median age was 58.0 years (interquartile range, 49 to 67 years). Median intensive care unit and hospital stays were 46 hours and 6 days, respectively. Significant predictors for mortality included: atrial fibrillation (OR, 2.06), body surface area (OR, 0.14), chronic obstructive pulmonary disease (OR, 1.2), New York Heart Association class IV (OR, 2.53), diabetes (OR, 2.48), coronary artery bypass grafting (OR, 2.77), mitral valve surgery (OR, ≥2.18), and Bentall operation (OR, 2.08). Regression analysis for risk factors for STS morbidity yielded 14 significant factors. A glomerular filtration rate increase of 20 units was predictive of improved mortality (OR, 0.85) and morbidity (OR, 0.91). Conclusions Elective ARR is performed with excellent postoperative outcomes. Analysis of the STS database reveals several significant risk factors that are independently associated with increased mortality and morbidity. The investigators anticipate that future studies inclusive of the nonelective ARR cases in the database will facilitate development of a risk model for root replacement procedures.

PURPOSE The incidence and management of sternal wound complications in patients undergoing orthotopic heart transplantation (OHT) is not well studied. We report outcomes in heart transplant patients who developed sternal infections requiring reoperations. METHODS From 2004 to 2013, 437 patients underwent OHT at a single institution. In a retrospective review, patients who developed sternal infections (Infection group, n = 27) were compared with those without (Control group, n = 410). RESULTS Sternal infection rate was 6.2% (n = 27). Demographics were similar (Table 1). Infection group had higher rates of COPD 25% vs 13%, P = 0.03, and previous cardiac surgery via median sternotomy 28% vs 15%, P = 0.03. Infection group had a greater incidence of prolonged ventilation, 44% vs 31%, P = 0.2, renal failure 56% vs 24%, P = 0.001, dialysis requirement 30% vs 10%, P = 0.006, permanent stroke 11% vs 2%, P = 0.02, perioperative myocardial infarction 4% vs 0.2%, P = 0.09. The infection group had a longer ICU stay (524 + 410 vs 187 + 355 hours, P = 0.001) and hospitalization (59 + 28 vs 0.29 + 43 days, P = 0.001). In-hospital/30-day mortality was 30% vs 19%, P = 0.2. The mean time for sternal reoperation at 44 + 50 days. Deep wound infection (41%) and sternal dehiscence (22%) were common presentations. Causative organisms were Enterobacter (22%), Klebsiella (15%), and Pseudomonas (15%). Vancomycin (44%), 4th generation cephalosporin (37%), and fluoroquinolones (30%) were the most commonly used antibiotics. Surgical treatment included sternal debridement with pectoralis muscle flap (52%), primary closure (18%), and omental flap (11%). CONCLUSION Sternal wound infections impart a significant burden on patients with OHT. Causative organisms are predominantly virulent gram-negative bacteria. Therefore, a high index of suspicion must be maintained for early detection and treatment.

Background The opioid epidemic has seen a drastic increase in the incidence of drug-associated infective endocarditis (IE). No clinical tool exists to predict operative morbidity and mortality in patients undergoing surgery. Methods A multi-institutional database was reviewed between 2011 and 2018. Multivariate logistic regression was fitted in an automated stepwise fashion. The STratification risk analysis in OPerative management of drug-associated IE (STOP) score was constructed. Morbidity was defined as reintubation, prolonged ventilation, pneumonia, renal failure, dialysis, stroke, reoperation for bleeding, and a permanent pacemaker. Cross-validation provided an unbiased estimate of out-of-sample performance. Results A total of 1181 patients underwent surgery for drug-associated IE (median age, 39; interquartile range [IQR], 30-54, 386 women [32.7%], 341 reoperations for prosthetic valve endocarditis [28.9%], 316 patients with multivalve disease [26.8%]). Operative morbidity and mortality were 41.1% and 5.9%, respectively. Predictors of morbidity were dialysis (95% confidence interval [CI], 1.16-2.82), emergent intervention (1.83-4.73), multivalve procedure (1.01-1.98), causative organisms other than Streptococcus (1.09-2.02), and type of valve procedure performed [aortic valve procedure (1.07-2.15), mitral valve replacement (1.03-2.05), tricuspid valve replacement (1.21-2.60)]. Predictors of mortality were dialysis (1.29-5.74), active endocarditis (1.32-83), lung disease (1.25-5.43), emergent intervention (1.69-6.60), prosthetic valve endocarditis (1.24-3.69), aortic valve procedure (1.49-5.92) and multivalve disease (1.00-2.95). Variables maximizing explanatory power were translated into a scoring system. Each point increased odds of morbidity and mortality by 22.0% and 22.4% with an accuracy of 94.0% and 94.1%, respectively. Conclusion Drug-related IE is associated with significant morbidity and mortality. An easily-applied risk stratification score may aid in clinical decision-making.

Introduction: Aortic body tumors are rare intrathoracic tumors. The majority of existing literature for aortic body tumors exists as case reports or a limited series. Our aim was to analyze a large national database, providing a contemporary view of this cancer. Methods: The national cancer database, which includes data from 1,500 cancer centers was queried to retrospectively review all aortic body tumors between 2004 and 2015. The cohort was divided into patients who underwent surgery versus those who were treated with chemotherapy or radiation. Cohorts were assigned a year range based on when they were diagnosed. Survival between these cohorts were compared using Kaplan-Meier survival estimates. Cox multivariable analysis was performed using baseline variables (age, year range, metastasis, surgery, radiation, and chemotherapy). Overall survival of the cohort was analyzed via Kaplan-Meier survival estimates. Results: A total of 87 patients who were diagnosed with an aortic body tumor were identified. The mean age was 51 ± 15.7 years and the majority of patients were female (51.7%). Most patients were treated at an academic/research center (62.7%) or a comprehensive community cancer program (25.4%). A significant portion of patients (19.5%) had metastatic disease on diagnosis. The treatment modalities utilized were surgery (54%), radiation (44.8%), and chemotherapy (20.7%). Long-term survival was 35.5% with a median survival of 8.25 years (Figure 1A) . Overall survival was significantly higher in the surgery cohort (p(Figure 1B) . On Cox multivariable analysis (Figure 1C) , surgery (HR 0.32, p=0.01) was associated with increased survival. An independent predictor of mortality was having a metastasis on diagnosis (HR 8.49, p=0.001). Conclusion: The overall prognosis of aortic body tumors is poor, with metastasis on presentation significantly increasing mortality. Surgery provides a substantial benefit to these patients; however, this may be a result of selection bias. Aggressive surveillance in predisposed populations may be warranted given the grave prognosis once metastasis occurs.

Introduction: Carotid body tumors represent the most common site for extra-adrenal paragangliomas. Surgical resection is the treatment of choice as a low percentage of these tumors are malignant. Here we present long-term outcomes of a contemporary cohort of patients with a carotid body tumor. Methods: The national cancer database was quired for all cases of a carotid body tumor between 2004-2015. All baseline variables were gathered from the database. Kaplan-Meier curves were generated for the entire cohort to assess overall survival. The group was split into surgical and non-surgical cohorts. Survival was assessed via Kaplan-Meier estimates. Patients that underwent surgery were divided based on isolated surgical therapy or multimodal therapy (surgery with radiation or chemotherapy). Cox multivariable analysis was used to determine independent predictors for mortality. Results: The search returned 130 patients with a carotid body tumor. The average age of this cohort was 47 years and the majority were women (58.5%). A small proportion (9.2%) of the cohort had a metastasis at the time of diagnosis. Most patients underwent surgery (80%) followed by radiation (44.6%). The overall survival of the cohort was 81.5% at 10 years (Figure 1A) . Long-Term survival was higher in the surgical cohort (P=0.001) (Figure 1B) . Patients with multimodal therapy survived longer than those that underwent surgery alone (P=0.007) (Figure 1C). On Cox multivariable analysis (Figure 1D) , only radiation was a predictor for survival (HR 0.25, P=0.008). Having a metastasis on the time of diagnosis was a predictor for worse outcomes (HR 4.45, P=0.03). Conclusions: While surgery had a survival benefit on Kaplan-Meier analysis, when risk adjusting for other variables, radiation was the only treatment that conferred a survival benefit; an interesting finding given the historical standard of surgical management. Despite improvements in therapeutic modalities, metastasis on diagnosis carries an increased mortality, favoring aggressive treatment.

Background Redo cardiac surgery carries an inherent risk for adverse short-term outcomes and worse long-term survival. Strategies to mitigate these risks have been numerous, including initiation of cardiopulmonary bypass via peripheral cannulation before resternotomy. This study evaluated the impact of central versus peripheral cannulation on long-term survival after redo cardiac surgery. Methods This was an observational study of open cardiac surgeries between 2010 and 2018. Patients undergoing open cardiac surgery that utilized cardiopulmonary bypass, who also had more than equal to 1 prior cardiac surgery, were identified. Kaplan-Meier survival estimation and multivariable Cox regression analysis were performed to assess the impact of peripheral cannulation on survival. To isolate long-term survival, patients with operative mortality were excluded and survival time was counted from the date of discharge until the date of death. Results Of the 1660 patients with more than equal to 1 prior cardiac surgery, 91 (5.5%) received peripheral cannulation. After excluding patients with operative mortality and after multivariable risk-adjustment, the peripheral cannulation group had significantly increased hazard of death, as compared to the central cannulation group (HR 1.53, 95% CI: 1.01, 2.30, P = .044). Yet, there were no relevant differences for other postoperative outcomes, including blood product requirement, prolonged ventilation (>24 hours), pneumonia, reoperation for bleeding, stroke, sepsis, and new dialysis requirement. Conclusions This is the first study reporting the long-term impact of peripheral cannulation for redo cardiac surgery after excluding patients with operative mortality. These data suggest that central cannulation may to be the preferred approach to redo cardiac surgery whenever safe and possible.

As percutaneous coronary intervention (PCI) continues to evolve, comparative outcomes for PCI vs coronary artery bypass grafting (CABG) remain relevant in diabetic patients. All revascularization procedures in patients with coronary artery disease and diabetes mellitus from 2010 to 2018 were included. Propensity matching was used to identify equivalent cohorts to compare revascularization strategies. Primary outcomes included 30-day, 1-year, and 5-year mortality. Multivariable analysis was used to define factors associated with major adverse cardiovascular and cerebrovascular events (MACCE). A total of 2869 patients with diabetes were divided into PCI (n = 653) and CABG (n = 2216) cohorts. Propensity matching yielded a 1:1 match consisting of 552 patients in each cohort (CABG vs PCI). Total median follow-up was 3.28 years (range: 1.83-5.00). Following propensity matching in patients with no prior PCI (1:1; n = 279), mortality remained significantly higher in the PCI cohort at 1 year (13.98% vs 7.53%; P = 0.014) and 5 years (26.88% vs 16.85%; P0.004). Hospital readmissions were higher for PCI patients at 1 year (16.49% vs 9.32%; P0.0122) and 5 years (19.71% vs 11.83%; P = 0.011). MACCE occurred more frequently in the PCI cohort (32.97% vs 21.51%; P = 0.002). Need for subsequent revascularization (6.45% vs 2.51%; P = 0.024) were significantly higher in the PCI cohort, and time interval to revascularization was significantly longer in the CABG cohort (3.48 [2.11-5.17] vs 2.62 [1.33-4.25] years; P0.001). The current study reports improved survival, fewer long-term hospital readmissions, and reduced MACCE and need for repeat revascularization in the CABG cohort. Given these data, patients with diabetes mellitus and coronary artery disease may fare better with surgical revascularization, compared to PCI.

INTRODUCTION Stentless porcine xenografts are versatile bioprosthetic valves with the advantage of improved hemodynamics that mimic the function of the native aortic valve. However, these bioprostheses are challenging to implant in the subcoronary position. METHODS All consecutive patients who underwent a bioprosthetic aortic valve replacement (AVR) were included from our institutional database. Cox regression analysis was preformed to determine significant predictors for mid term mortality as well as all cause, cardiac, and heart failure readmission. RESULTS Patients in the subcoronary stentless group were older and more likely to be female and were likely to have a higher Society of Thoracic Surgery risk of mortality. Survival was superior in the stented AVR cohort at 30-days (96.4% vs 90.5%; P

Preeclampsia is the most common placental pathology in pregnant females, with increased morbidity and mortality incurred on the mother and the fetus. There is a need for improved biomarkers for diagnosis and monitoring of this condition. Placental syncytiotrophoblasts at the maternal-fetal interface release nanoparticles, including extracellular microvesicles, into the maternal blood during pregnancy. Syncytiotrophoblast extracellular microvesicles (STEVs) are being studied for their diagnostic potential and for their potential physiologic role in preeclampsia. We hypothesized that STEV profiles in maternal circulation would be altered under conditions of preeclampsia compared to normal pregnancy. Extracellular vesicles (EVs) released by BeWo cells in vitro showed high expression of syncytin-1, but no plac1 expression, demonstrating that trophoblast cell EVs express syncytin-1 on their surface. Placental alkaline phosphatase also showed high expression on BeWo EVs, but due to concern for cross reactivity to highly prevalent isoforms of intestinal and bone alkaline phosphatase, we utilized syncytin-1 as a marker for STEVs. In vivo, syncytin-1 protein expression was confirmed in maternal plasma EVs from Control and Preeclampsia subjects by Western blot, and overall, lower expression was noted in samples from patients with preeclampsia (n = 8). By nanoparticle analysis, EV profiles from Control and Preeclampsia groups showed similar total plasma EV quantities (p = 0.313) and size distribution (p = 0.415), but STEV quantitative signal, marked by syncytin-1 specific EVs, was significantly decreased in the Preeclampsia group (p = 2.8 × 10−11). Receiver operating characteristic curve demonstrated that STEV signal threshold cut-off of

Background Transcatheter aortic valve replacement (TAVR) continues to gain momentum with current-generation balloon-expandable (BE) Edwards SAPIEN 3 (Edwards Lifesciences, Irvine, CA) and self-expandable (SE) Medtronic Evolut valves (Medtronic, Minneapolis, MN). Safety and efficacy of each device has been studied independently but head-to-head comparisons remain limited. Methods The institutional database was used to identify patients undergoing TAVR with BE and SE systems through transfemoral access between 2015 and 2018. Patients with an alternative access were excluded. Multivariable logistic and Cox proportional hazards regression was used to compare baseline risk-adjusted 30-day Valve Academic Research Consortium-2 variables and midterm outcomes, including survival, stroke, and readmission rates. Results A total of 294 BE (52.2%) and 269 SE (47.8%) valves were implanted. BE cohort was predominantly male (59.9% vs 33.1%, P Conclusions Midterm outcomes of both valve types were comparable despite a higher risk of short-term stroke for the SE cohort. Select patients may benefit from one valve type over another based on clinical and anatomic risk factors.

The aim of this study was to evaluate comparative outcomes for percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with reduced ejection fraction.All patients from the University of Pittsburgh Medical Center from 2011 to 2018 who had reduced preoperative ejection fraction (50%) and underwent CABG or PCI for coronary revascularization were included in this study. Patients were risk-adjusted with propensity matching (1:1) and primary outcomes included long-term survival, readmission, and major adverse cardiac and cerebrovascular events (MACCE).A total of 2000 patients were included in the current study, consisting of CABG (n = 1553) and PCI (n = 447) cohorts with a mean ejection fraction of 35% ± 9.53%. Propensity matching yielded a 1:1 match with 324 patients in each cohort, controlling for all baseline characteristics. Thirty-day mortality was similar for PCI versus CABG (6.2% vs 4.9%; P = .49). Overall mortality over the study follow-up period (median, 3.23 years; range, 1.83-4.98 years) was significantly higher for the PCI cohort (37.4% vs 21.3%; P .001). Total hospital readmissions (24.1% vs 12.9%; P = .001), cardiac readmissions (20.4% vs 11.1%; P = .001), myocardial infarction event (7.7% vs 1.8%; P = .001), MACCE (41.4% vs 23.8%; P .001), and repeat revascularization (6.5% vs 2.6%; P = .02) occurred more frequently in the PCI cohort. Freedom from MACCE at 1 year (74.4% vs 87.0%; P .001) and 5 years (54.5% vs 74.0%; P .001) was significantly lower for the PCI cohort. On multivariable cox regression analysis, CABG (hazard ratio, 0.57; 95% confidence interval, 0.44-0.73; P .001) was significantly associated with improved survival. Prior liver disease, dialysis, diabetes, and peripheral artery disease were the most significant predictors of mortality. The cumulative incidence of hospital readmission was lower for the CABG cohort (hazard ratio, 0.51; 95% confidence interval, 0.37-0.71; P .001). Multivariable cox regression for MACCE (hazard ratio, 0.48; 95% confidence interval, 0.39-0.58; P .001) showed significantly fewer events for the CABG cohort.Patients with reduced ejection fraction who underwent CABG had significantly improved survival, lower MACCE, and fewer repeat revascularization procedures compared with patients who underwent PCI.

Data on primary cardiac malignancies are limited to small single-center studies.The aim of the current study was to provide detailed outcomes for treatment of primary cardiac malignancies from a multi-institutional database.Outcomes were acquired from the National Cancer Database for all solid primary cardiac malignancies from 2004 to 2016. The primary outcome was long-term survival. Logistic regression was used to determine factors associated with mortality.A total of 100,317 cardiac tumors were identified, of which 826 (0.8%) were primary malignant tumors. After exclusion criteria, the cohort consisted of 747 patients (median age 53 years, 47.5% women). Most tumors were primary sarcomas (88.5%), the majority of which were hemangiosarcoma (40.4%). A total of 136 patients received no therapy, 113 received just chemotherapy, and 20 received just radiation. Surgery was performed in 442 (59.2%) patients including 255 patients undergoing multimodal therapy (surgery with chemotherapy, radiation, or chemoradiation). With surgery alone, 90-day mortality was 29.4%. Overall 30-day, 1-year, and 5-year survival rates were 81.2%, 45.3%, and 11.5%, respectively. The surgery group as compared with the no surgery groups had significantly better long-term survival (p 0.0001). For stage III disease, there was a statistically significant improvement in survival with the addition of chemotherapy to surgery.Primary cardiac malignancies are rare cancers with dismal long-term survival despite mode of treatment. Patients who underwent surgery and those with stage III disease who received peri-operative chemotherapy had better survival compared with those who did not. However, there was likely a significant selection bias in patients chosen for surgical or medical therapy.

Transcatheter aortic valve replacement (TAVR) has emerged as the preferred alternative to surgical aortic valve replacement in elderly patients. However, the long-term outcomes of nonagenarians undergoing TAVR are unknown.Octogenarian and nonagenarian patients undergoing TAVR from 2011 to 2018 were identified from a prospectively maintained institutional database. Cox proportional hazards regression was used for baseline-adjusted outcome comparison and risk prediction. Survival was compared with age and gender-matched population from the Social Security Actuarial Life Table.A total of 649 (54.4%) octogenarians and 157 (13.2%) nonagenarians underwent TAVR. Nonagenarians had a lower body mass index (P.001), smaller BSA (P.001), and a lower prevalence of chronic obstructive pulmonary disease (P = .023) but a higher Society of Thoracic Surgeons score (P.001). The majority of nonagenarians and octogenarians were treated using self-expandable valves (60.3% vs 60.9%; P = .888) via transfemoral access (86.0% vs 81.0%; P = .148). At 30 days, 1 year, and 4 years, there was no difference in survival (95.5%, 80.3%, and 51.2% vs 96.9%, 87.4, and 57.6%, respectively) (adjusted hazard ratio [HR], 0.8; P = .205) and hospital readmissions for cardiac causes (7.9%, 25.7%, and 53.7% vs 10.3%, 27.9%, and 52.0%, respectively) (adjusted HR, 0.9; P = .488). Further, nonagenarians had a survival comparable to an age-matched and sex-matched U.S. population (P = .540). Post-TAVR paravalvular leak (HRs: 3.23 [P = .042] vs 2.66 [P = .032]) and anemia (HRs: 0.64 [P = .002] vs 0.80 [P = .004]) were associated with worse outcomes at 1 year.TAVR can be performed safely in nonagenarians, with comparable outcomes to younger patients approximating natural life expectancy. This age paradox should strengthen the role of TAVR in well selected nonagenarians by the heart team.

Objective The incidence of elderly patients with acute type A aortic dissection is increasing. A recent analysis of the International Registry of Acute Aortic Dissection failed to show a mortality benefit with surgery compared with medical management in octogenarians. Therefore, we compared our institutional outcomes of emergency surgery for acute type A aortic dissection in octogenarians versus septuagenarians to understand the outcomes of surgical intervention in elderly patients. Methods From 2002 to 2017, 70 octogenarians (aged ≥80 years) and 165 septuagenarians (70-79 years) underwent surgery for acute type A aortic dissection (N = 235, total). Quality of life was assessed by the RAND Short Form-36 quality of life survey. Midterm clinical and functional data were obtained retrospectively. Results At baseline, septuagenarians had a higher prevalence of diabetes (20.6% vs 5.7%, P = .01). The prevalence of cardiopulmonary resuscitation was 4.8% versus 10.0% (P = .24) in septuagenarians and octogenarians. The prevalence of cardiogenic shock was 18.2% versus 27.1% (P = .17). Thirty-day/in-hospital mortality was 21.2% versus 28.6% (P = .29). Multivariable logistic regression identified cardiogenic shock as an independent risk factor for in-hospital mortality (odds ratio, 10.07; 95% confidence interval, 2.30-44.03) in octogenarians. Survival at 5 years was 49.7% (42.1%-58.6%) versus 34.2% (23.9%-48.8%) in septuagenarians and octogenarians, respectively. Responses to the quality of life survey were no different between septuagenarians and octogenarians across all 8 quality of life categories. Conclusions Clinical outcomes after surgery for acute type A aortic dissection are similar in octogenarians and septuagenarians. For discharged survivors, quality of life remains favorable and does not differ between the 2 groups.

In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet–kidney (IK) model previously described by our laboratory was utilized. Three experimental donor animals underwent total pancreatectomy and autologous islet transplantation underneath the renal capsule to prepare an IK at a load of ≤1,000 islet equivalents (IE)/kg donor weight, leading to a chronic diabetic state during the engraftment period (fasting blood glucose >250 mg/dL). Three control donor animals underwent partial pancreatectomy (sufficient to maintain normoglycemia during islet engraftment period) and IK preparation. As in vivo functional readout for islet engraftment, the IKs were transplanted across an immunologic minor or class I mismatch barrier into diabetic, nephrectomized recipients at an islet load of ∼4,500 IE/kg recipient weight. A 12-d course of cyclosporine was administered for tolerance induction. All experimental donors became diabetic and showed signs of end organ injury, while control donors maintained normoglycemia. All recipients of IK from both experimental and control donors achieved glycemic control over long-term follow-up, with reversal of diabetic nephropathy and with similar glucose tolerance tests. In this preclinical, large animal model, neither islet engraftment nor subsequent long-term islet function after transplantation appear to be affected by the diabetic state.

Objective Patients with acute type A aortic dissection demonstrate a wide range of aortic insufficiency. Outcomes after valve resuspension and root repair are not well studied in the long term. We evaluated the long-term effects of preoperative aortic insufficiency in patients undergoing emergency root-preserving surgery for acute type A aortic dissection. Methods From 2002 to 2017, 558 of 776 patients with acute type A aortic dissection underwent native aortic valve resuspension and root reconstruction. Patients were stratified into 4 groups by preoperative aortic insufficiency grade (n = 539): aortic insufficiency less than 2+ (n = 348), aortic insufficiency = 2+ (n = 72), aortic insufficiency = 3+ (n = 49), and aortic insufficiency = 4+ (n = 70). Multivariable ordinal longitudinal mixed effects and multi-state transition models were used to assess risk factors for recurrent aortic insufficiency. Results The prevalence of cardiogenic shock in patients presenting with preoperative aortic insufficiency less than 2+, 2+, 3+, and 4+ was 53 of 348 (15.2%), 12 of 72 (16.7%), 10 of 49 (20.4%), and 24 of 70 (34.3%), respectively (P = .002). Postoperatively, 94.0% of patients had aortic insufficiency 1+ or less at discharge. Operative mortality was 34 of 348 (9.8%), 10 of 72 (13.9%), 6 of 49 (12.2%), and 12 of 70 (17.1%) (P = .303). In an ordinal mixed effects model, preoperative aortic insufficiency was associated with more severe postoperative aortic insufficiency. The multi-state transition model demonstrated that severe aortic insufficiency was associated with progression from no to mild aortic insufficiency (hazard ratio, 2.14; 95% confidence interval, 1.35-3.38), and progression from mild to moderate aortic insufficiency (hazard ratio, 5.70; 95% confidence interval, 1.88-17.30). Conclusions Preoperative aortic insufficiency is an important predictor of recurrent aortic insufficiency in patients undergoing valve resuspension with root reconstruction for emergency acute type A aortic dissection repair. Increased echocardiographic surveillance for recurrent aortic insufficiency may be warranted in this cohort.

Background and Aim Concomitant endovascular stent grafting of the descending thoracic aorta during open repair for acute DeBakey I aortic dissection can be performed in patients with extensive dissection and malperfusion. We analyzed the effects of this strategy on distal aortic remodeling. Methods From 2006-2014, acute DeBakey I dissection patients without primary aortic arch tear undergoing open distal hemiarch reconstruction (Standard group) versus those undergoing hemiarch with descending thoracic aorta (DTA) thoracic endovascular aortic repair (TEVAR group) were retrospectively reviewed. We studied aortic remodeling only in patients with three-dimensional computed tomography scans available at 1 and 12 months following surgery (Standard group n = 26; Stent group n = 21). Results At 1 month, abdominal aortic diameters were similar, but true lumen (TL) and true lumen to total diameter ratios (TL index [TLI]) in the DTA were significantly improved in the TEVAR group (P

Objective In patients presenting with aortic valvulopathy with concomitant ascending aortic aneurysm, surgical management of the sinus of Valsalva segment remains undefined, especially for moderately dilated aortic roots. In patients with this pathology undergoing aortic valve replacement with supracoronary ascending aorta replacement, we assessed the fate of the remnant preserved sinus of Valsalva segment stratified by aortic valve morphology and pathology. Methods From 2002 to 2015, 428 patients underwent elective aortic valve replacement with supracoronary ascending aorta replacement. Patients were stratified on the basis of valvular morphology (bicuspid aortic valve [n = 254] and tricuspid aortic valve [n = 174]), valvular pathology (bicuspid aortic valve with aortic stenosis [n = 178], bicuspid aortic valve with aortic insufficiency [n = 76], tricuspid aortic valve with aortic stenosis [n = 61], tricuspid aortic valve with aortic insufficiency [n = 113]), and preoperative sinus of Valsalva dimensions ( 45 mm). Results Kaplan–Meier analysis revealed no significant difference in freedom from reoperation in tricuspid aortic valve versus bicuspid aortic valve ( P = .576). Multivariable Cox regression model performed with sinus of Valsalva dimensions at baseline and follow-up as time-varying covariates did not adversely affect survival. A repeated-measure, mixed-effects model constructed to assess longitudinal sinus of Valsalva trends revealed that the retained sinus of Valsalva dimensions remain stable over long-term follow-up (discharge to ≥10 years), irrespective of valvular morphology/pathology (bicuspid aortic valve with aortic insufficiency, tricuspid aortic valve with aortic insufficiency, tricuspid aortic valve with aortic stenosis) and preoperative sinus of Valsalva groups ( 45 mm). Conclusions In patients with nonaneurysmal sinuses of Valsalva undergoing aortic valve replacement with supracoronary ascending aorta replacement, the sinus segment can be preserved irrespective of the type of valvular pathology (aortic stenosis vs aortic insufficiency) or valvular morphology (bicuspid aortic valve vs tricuspid aortic valve). Aortic valve replacement with supracoronary ascending aorta replacement may have a stabilizing effect on the sinus segment over long-term follow-up in patients with tricuspid aortic valves or bicuspid aortic valves.

Background Extracellular microvesicles (EVs) are being increasingly studied for their diagnostic potential. We investigated the feasibility of studying the kinetics and tissue-specific profiles of pulmonary EVs in the context of ex vivo lung perfusion (EVLP) used for salvaging marginal lungs for transplantation. Methods Perfusate from six marginal donor lungs placed on EVLP was collected at the following time points: 0, 10, and 60 minutes after and after perfusate exchange with Steen Solution; 120 and 180 minutes. Three lungs were successfully recovered for transplantation (transplant group), and three were not recoverable (nontransplant group). Perfusate EVs were isolated using methods of size exclusion chromatography, ultrafiltration, and ultracentrifugation. EVs were analyzed on NanoSight nanoparticle detector for quantity, size distribution, and surface expression of pulmonary tissue-specific markers. EV cargoes were profiled using mass spectrometry, reverse transcription polymerase chain reaction (RT-PCR), and Western blot analysis. Results Time course analysis showed EV presence by 10-minute time point. EV median size was smaller in the transplant group (165 nm versus 212 nm, p = 0.04). EV cargo analysis on Western blot analysis, RT-PCR, and NanoSight showed contribution from monocytes (CD14), endothelium (platelet endothelial cell adhesion molecule 1), and pulmonary parenchyma (epithelial cell adhesion molecule) into the perfusate total EV pool. Mass spectrometry showed differences in the EV protein cargoes of the transplant group versus the nontransplant group. Conclusions EVLP system provides a platform to understand the kinetics of pulmonary EVs in an isolated fashion. Donor lung recovery may be associated with changes in EV size distribution and proteomic profiles. Pulmonary tissue-specific EV profiling using the EVLP system may provide insights into EV contribution to pulmonary pathologic processes.

Transcatheter aortic valve replacement (TAVR) has evolved as an alternative therapy to open aortic valve replacement in most patients with aortic stenosis. Stroke associated with TAVR can be a devastating complication in the short term; however, little is known regarding midterm outcomes.All patients undergoing TAVR at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania from 2011 to 2018 were included. Modified Rankin Scale values as a measurement of stroke-related disability were extracted for patients who had neurologic deficits.Neurologic events (NEs) developed in 51 (4.3%) of the 1193 patients during the study period (32 [2.7%] had disabling strokes; 19 [1.6%] had nondisabling strokes, including 5 [0.4%] transient ischemic attacks). Patients who had TAVR-related NEs were older (85.8 ± 4.2 years vs 81.5 ± 7.9 years; P.001) and predominantly female (68.6% vs 31.4%; P = .007), but they were comparable in terms of The Society of Thoracic Surgeons predicted mortality score and vascular access. Patients with NEs had increased short term and midterm mortality (15.7% vs 2.6%, 29.4% vs 13.9%, and 47.1% vs 35.7% at 30 days, 1 year, and 3 years, respectively). Severity of disability, determined by the modified Rankin Scale, was a risk factor for 30-day mortality (HR, 5.8; P = .003), 1-year mortality (HR, 2.1; P.001) and 3-year mortality (HR, 1.8; P.001). Predictors of TAVR NEs were older age (odds ratio [OR] per year of age, 1.11; P = .001), low body surface area (OR per mStroke increases short-term and midterm mortality after TAVR. Risk prediction for neurologic events in TAVR could aid the framework for patient selection and further improve outcomes.

No clinically validated tool exists to predict in-hospital mortality in patients requiring extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation. We generated a quantitative risk assessment tool for these patients.Of 822 patients in the United Network for Organ Sharing (UNOS) database who required ECMO as bridge to lung transplant between 2004 and 2018, 630 were included in the analysis after exclusion for age18 years, prior transplant, or treatment before 2004. Recipient-specific variables associated with posttransplant in-hospital mortality were incorporated into a multivariable logistic regression model in an automated stepwise fashion. Linear prediction was used to construct the Recipient Stratification Risk Analysis in Bridging Patients to Lung Transplant on ECMO (STABLE) score. K-fold cross-validation provided an unbiased estimate of out-of-sample performance. After further exclusion for University of Pennsylvania patients, the remaining cohort was used for external score validation. An iOS application was developed to aid clinical use.Six recipient-specific, pretransplant variables were translated into a 24-point score. STABLE scores in the United Network for Organ Sharing (UNOS) database ranged from 0 to 21, and each point increased the odds of in-hospital mortality by 22.0% (95% confidence interval, 1.14-1.29, P.001). K-fold cross-validation yielded a receiver operating characteristic area under the curve of 86.2%. Validation of the STABLE score using our institutional database yielded an area under the curve of 89%.The STABLE score is a novel, internally cross-validated tool for risk stratification of patients on ECMO as a bridge to transplant. Its predictive power and accuracy may aid clinical decision-making and improve posttransplant outcomes.

The durability of root repair for acute type A aortic dissection is not well studied in the context of aortic insufficiency and stability of the sinuses of Valsalva. We compared clinical and functional outcomes in patients undergoing root repair and replacement for acute type A aortic dissection.Of 716 patients undergoing surgery for acute type A aortic dissection, 585 (81.7%) underwent root repair and 131 (18.3%) underwent root replacement. Survival, cumulative incidence of reoperation, aortic insufficiency, and sinuses of Valsalva dilation were compared between the 2 groups.Survival at 1, 5, and 10 years was 84.1% versus 77.3%, 70.8% versus 69.2%, 57.6% versus 58.0% in the root repair and replacement groups, respectively (P = .69). Cumulative incidence of reoperation at 1, 5, and 10 years was 0.0% versus 0.8%, 1.4% versus 3.8%, and 3.4% versus 8.6% in the root repair and root replacement groups, respectively (P = .011). Multivariable Cox regression identified sinuses of Valsalva diameter 45 mm or more as a risk factor for proximal aortic reoperation (hazard ratio, 9.06; 95% confidence interval, 1.26-65.24). In a repeated-measures, linear, mixed-effects model, root replacement was associated with smaller follow-up of sinuses of Valsalva dimensions (β = -0.66, P .001). In an ordinal longitudinal mixed model, root replacement was associated with lower severity of postoperative aortic insufficiency (β = -3.10, P .001).Survival is similar, but the incidence of aortic insufficiency and root dilation may be greater after root repair compared with root replacement for acute type A aortic dissection.

The stem cell field is hindered by its inability to noninvasively monitor transplanted cells within the target organ in a repeatable, time-sensitive, and condition-specific manner. We hypothesized that quantifying and characterizing transplanted cell–derived exosomes in the recipient plasma would enable reliable, noninvasive surveillance of the conditional activity of the transplanted cells. To test this hypothesis, we used a human-into-rat xenogeneic myocardial infarction model comparing two well-studied progenitor cell types: cardiosphere-derived cells (CDCs) and c-kit(+) cardiac progenitor cells (CPCs), both derived from the right atrial appendage of adults undergoing cardio-pulmonary bypass. CPCs outperformed the CDCs in cell-based and in vivo regenerative assays. To noninvasively monitor the activity of transplanted CDCs or CPCs in vivo, we purified progenitor cell–specific exosomes from recipient total plasma exosomes. Seven days after transplantation, the concentration of plasma CPC-specific exosomes increased about twofold compared to CDC-specific exosomes. Computational pathway analysis failed to link CPC or CDC cellular messenger RNA (mRNA) with observed myocardial recovery, although recovery was linked to the microRNA (miRNA) cargo of CPC exosomes purified from recipient plasma. We further identified mechanistic pathways governing specific outcomes related to myocardial recovery associated with transplanted CPCs. Collectively, these findings demonstrate the potential of circulating progenitor cell–specific exosomes as a liquid biopsy that provides a noninvasive window into the conditional state of the transplanted cells. These data implicate the surveillance potential of cell-specific exosomes for allogeneic cell therapies.

Rationale: Endothelial colony forming cells (ECFCs) or late blood outgrowth endothelial cells can be isolated from human cord or peripheral blood, display properties of endothelial progenitors, home into ischemic tissues and support neovascularization in ischemic disease models. Objective: To assess the functions of CYTL1 (cytokine-like 1), a factor we found preferentially produced by ECFCs, in regard of vessel formation. Methods and Results: We show by transcriptomic analysis that ECFCs are distinguished from endothelial cells of the vessel wall by production of high amounts of CYTL1. Modulation of expression demonstrates that the factor confers increased angiogenic sprouting capabilities to ECFCs and can also trigger sprouting of mature endothelial cells. The data further display that CYTL1 can be induced by hypoxia and that it functions largely independent of VEGF-A (vascular endothelial growth factor-A). By recombinant production of CYTL1 we confirm that the peptide is indeed a strong proangiogenic factor and induces sprouting in cellular assays and functional vessel formation in animal models comparable to VEGF-A. Mass spectroscopy corroborates that CYTL1 is specifically O-glycosylated on 2 neighboring threonines in the C-terminal part and this modification is important for its proangiogenic bioactivity. Further analyses show that the factor does not upregulate proinflammatory genes and strongly induces several metallothionein genes encoding anti-inflammatory and antiapoptotic proteins. Conclusions: We conclude that CYTL1 can mediate proangiogenic functions ascribed to endothelial progenitors such as ECFCs in vivo and may be a candidate to support vessel formation and tissue regeneration in ischemic pathologies.

Islet cell transplantation is curative therapy for patients with complicated autoimmune type 1 diabetes (T1D). We report the diagnostic potential of circulating transplant islet-specific exosomes to noninvasively distinguish pancreatic β cell injury secondary to recurrent autoimmunity vs immunologic rejection. A T1D patient with hypoglycemic unawareness underwent islet transplantation and maintained normoglycemia until posttransplant day 1098 before requiring exogenous insulin. Plasma analysis showed decreased donor islet exosome quantities on day 1001, before hyperglycemia onset. This drop in islet exosome quantity signified islet injury, but did not distinguish injury type. However, analysis of purified transplant islet exosome cargoes showed decrease in insulin-containing exosomes, but not glucagon-containing exosomes, indicating selective destruction of transplanted β cells secondary to recurrent T1D autoimmunity. Furthermore, donor islet exosome cargo analysis showed time-specific increase in islet autoantigen, glutamic acid decarboxylase 65 (GAD65), implicated in T1D autoimmunity. Time-matched analysis of plasma transplant islet exosomes in 3 control subjects undergoing islet cell transplantation failed to show changes in islet exosome quantities or intraexosomal cargo expression of insulin, glucagon, and GAD65. This is the first report of noninvasive diagnosis of recurrent autoimmunity after islet cell transplantation, suggesting that transplant tissue exosome platform may serve as a biomarker in islet transplant diagnostics.