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Background and Objectives: This is a propensity-matched, single-center study of limited versus extended resection for type A acute aortic dissection (AAAD). Materials and Methods : This study collected retrospective data for 440 patients with acute type A aortic dissection repairs (limited resection, LR-215; extended resection, ER-225), of which 109 pairs were propensity-matched to LR versus ER. Multivariate analysis was performed for inpatient death, long-term survival and the composite outcome of inpatient death/TIA/stroke. Kaplan-Meier survival curves were compared at 1, 3, 5, 10 and 15 years using the log-rank test. Results : Mean age was 66.9 ± 13 years and mean follow-up was 5.3 ± 4.7 years. A total of 48.9% had LR. In-hospital mortality was 10% (LR: 6% vs. ER: 13.8%, p < 0.01). ER, NYHA class, salvage surgery and additional procedures were predictors of increased mortality in unmatched data. Propensity-matched data showed no difference in TIA/stroke rates, LOS, inpatient mortality or composite outcomes. LR had better survival (LR: 77.1% vs. ER: 51.4%, p < 0.001). ER (OR: 1.97, 95% CI: 1.27, 3.08, p = 0.003) was a significant predictor of worse long-term survival. At 15 years, aortic re-operation was 17% and freedom from re-operation and death was 42%. Conclusions : Type A aortic dissection repair has high mortality and morbidity, although results have improved over two decades. ER was a predictor of worse perioperative results and long-term survival.

Pneumonia is a worldwide threat, making discovery of novel means to combat lower respiratory tract infection an urgent need. Manipulating the lungs' intrinsic host defenses by therapeutic delivery of certain pathogen-associated molecular patterns protects mice against pneumonia in a reactive oxygen species (ROS)-dependent manner. Here we show that antimicrobial ROS are induced from lung epithelial cells by interactions of CpG oligodeoxynucleotides (ODN) with mitochondrial voltage-dependent anion channel 1 (VDAC1). The ODN-VDAC1 interaction alters cellular ATP/ADP/AMP localization, increases delivery of electrons to the electron transport chain (ETC), increases mitochondrial membrane potential (ΔΨm), differentially modulates ETC complex activities and consequently results in leak of electrons from ETC complex III and superoxide formation. The ODN-induced mitochondrial ROS yield protective antibacterial effects. Together, these studies identify a therapeutic metabolic manipulation strategy to broadly protect against pneumonia without reliance on antibiotics., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MJT and SEE are authors on U.S. patent 8,883,174, “Stimulation of Innate Resistance of the Lungs to Infection with Synthetic Ligands.” MJT and SEE own stock in Pulmotect, Inc. All other authors declare that no conflicts of interest exist., (Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marro, Leiva-Juárez, D’Ovidio, Chan, Van Raemdonck, Ceulemans, Moreno, Kindelan, Krueger, Koutsokera, Ehrsam, Inci, Yazicioglu, Yekeler, Boffini, Brioude, Thomas, Pizanis, Aigner, Schiavon, Rea, Anile, Venuta and Keshavjee.)

Background: This retrospective propensity matched study investigated the impact of age on the survival benefit from a second arterial conduit to the left-sided circulation., Methods: Data for isolated coronary artery bypass surgery were collected from October 2004 to March 2014. All patients with an internal mammary artery graft to left anterior descending artery and additional arterial or venous graft to the circumflex circulation were included. Propensity matching was used to balance co-variates and generate odds of death for each observation. Odds ratios (venous vs. arterial) were charted against age., Results: The in-hospital mortality rate was 1.12% (arterial) vs. 1.24% (venous) (p = 0.77). The overall 10-year survival was 74.6% (venous) vs. 82.6% (arterial) (p = 0.001). A total of 1226 patients were successfully matched to the venous or arterial (second conduit to circumflex territory after left internal mammary artery to left anterior descending artery) cohorts. Odds ratio for death (venous to arterial) showed a linear decremental overall survival benefit for the second arterial graft to circumflex circulation with increasing age., Conclusions: The survival benefit of a second arterial graft persists through all age groups with a gradual decline with increasing age over the decades. Elderly patients should not be denied a second arterial graft to the circumflex circulation based on age criterion alone.

Introduction: Gastroesophageal reflux and aspiration are risk factors for chronic lung allograft dysfunction in lung transplant recipients. Patients with systemic sclerosis are at an increased risk of aspiration due to esophageal dysmotility and an ineffective lower esophageal sphincter. The aim of this study is to understand the effect of fundoplication on outcomes in systemic sclerosis recipients., Methods: Between 2001 and 2019, 168 systemic sclerosis patients were referred for lung transplantation-51 (30.3%) were listed and 36 (21.4%) were transplanted. Recipients were stratified whether they underwent a fundoplication (n = 10, 27.8%) or not (n = 26, 72.2%). Freedom from chronic lung allograft dysfunction and survival were analyzed using log-rank test. Multivariable analysis for known risk factors was performed using a Cox-proportional hazards model., Results: Median time to fundoplication after transplantation was 16.4 months (interquartile range: 9.6-25.1) and all were laparoscopic (Dor 50%, Nissen 40%, Toupet 10%). There were no differences in acute rejection ⩾ A1 (26.9% vs 30%), or primary graft dysfunction grades 2-3 at 72 h (42.3% vs 40%) between groups. Recipients with fundoplication had an increased freedom from chronic lung allograft dysfunction (p = 0.035) and overall survival (p = 0.01). Fundoplication was associated with a reduced risk of mortality adjusting for other comorbidities (hazard ratio = 0.13; 95% confidence interval = 0.02-0.65; p = 0.014). Double and single lung transplant did not have different post-transplant survival., Conclusion: Fundoplication in systemic sclerosis lung transplant recipients is associated with greater freedom from chronic lung allograft dysfunction and overall survival. Screening for reflux and aspiration followed by early fundoplication may delay graft deterioration in this population., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Introduction: Duodeno-gastroesophageal reflux aspiration is associated with chronic lung allograft dysfunction (CLAD). Reflux aspirate can contain bile acids (BA), functional molecules in the gastro-intestinal tract with emulsifying properties. We sought to determine and quantify the various BA species in airways of the lung transplant recipients to better understand the various effects of aspirated BA that contribute to post-transplantation outcomes., Methods: Bronchial washings (BW) were prospectively collected from lung transplant recipients and subsequently assayed by liquid chromatography-mass spectrometry for 13 BA and 25 lipid families. Patients were monitored for CLAD, rejection, inflammation and airway infections., Results: Detectable BA were present in 45/50 patients (90%) at 3 months after transplant. Elevated BA and predominance of conjugated species were independent predictors of CLAD (hazard ratio 7.9; 95% confidence interval 2.7-23.6; p < 0.001 and 7.3; 2.4-22; p < 0.001, respectively) and mortality (hazard ratio 4.4; 1.5-12.7; p = 0.007 and 4.8; 1.4-15.8; p = 0.01, respectively). High BA associated with increased positive bacterial cultures (60% vs 25%, p = 0.02). Primary conjugated species independently correlated with the rate of bacterial cultures during the first-year post-transplant (Beta coefficient: 0.77; 0.28-1.26; p = 0.003) and changes in airway lipidome and cytokines., Conclusions: Higher BA levels and predominance of conjugated BA are independent predictors of chronic lung allograft dysfunction, mortality and bacterial infections. Primary conjugated BA are related to distinct changes in airway lipidome and inflammatory cytokines. This elucidates novel evidence into the mechanism following BA aspiration and proposes novel markers for prediction of adverse post-transplant outcomes., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Transfemoral aortic valve replacement (TAVR) has been studied extensively in patients with improving safety and efficacy in high to intermediate-risk patients with aortic stenosis. TAVR has been now approved for patients with low surgical risk., Objective: The purpose of this study is to integrate the evidence from randomized controlled trials (RCT) and large registry data comparing TAVR to surgical aortic valve repair (SAVR)., Methods: Seven studies (three RCTs, one post hoc study of a RCT, and three registries) were included. Incidence rate ratios (IRR) of outcomes of interest (overall mortality, 30-day mortality, cardiovascular death, stroke, pacemaker implantation [PPMI], myocardial infarction, moderate-severe paravalvular leak [PVL], and re-intervention) were compared using a random-effects model., Results: The pooled analysis included 24 819 patients (TAVR, 8227 and SAVR, 16 592). 2,952 (11.9%) patients were from RCTs and 21 867 (88.1%) were registry patients. Thirty-day mortality was lower in TAVR (logIRR, -0.43; 95% CI. -0.61 to -0.25; P < .001), whereas the rate of moderate-severe PVL (logIRR, 1.44; 95% CI, 0.58-2.3; P < .001) and PPMI (logIRR, 1.13; 95% CI, 1.02-1.24; P < .001) were higher. There were no significant differences in the rates of overall mortality, reintervention, cardiovascular death, myocardial infarction, or stroke between SAVR and TAVR., Conclusions: Early mortality is higher in SAVR while rates of PVL and PPMI are substantially higher in TAVR. There is no significant advantage with TAVR for overall survival, cardiovascular death, stroke, MI, and re-intervention rates., (© 2020 Wiley Periodicals LLC.)

Background: Ex vivo lung perfusion (EVLP) allows for a reassessment of lung grafts initially deemed unsuitable for transplantation, increasing the available donor pool; however, this requires a pre- and post-EVLP period of cold ischemic time (CIT). Paucity of data exists on how the sequence of cold normothermic-cold preservations affect outcomes., Methods: A total of 110 patients were retrospectively analyzed. Duration of 3 preservation phases was measured: cold pre-EVLP, EVLP, and cold post-EVLP. The donor and recipient clinical data were collected. Primary graft dysfunction (PGD) and survival were monitored. Risk of mortality or PGD was calculated using Cox proportional hazards and logistic regression models to adjust for baseline characteristics., Results: Using the highest quartile, patients were stratified into extended vs non-extended pre-EVLP (<264 vs ≥264 minutes) and post-EVLP (<287 vs ≥287 minutes) CIT. The rates of 1-year mortality (8.4% vs 29.6%, p = 0.013), PGD 2-3 (20.5% vs 52%, p = 0.002), and PGD 3 (8.4% vs 29.6%, p = 0.005) at 72 hours were increased in the extended post-EVLP CIT group. After adjusting for baseline risk factors, the extended group remained an independent predictor of PGD ≥2 (odd ratio: 6.18, 95% CI: 1.88-20.3, p = 0.003) and PGD 3 (odd ratio: 20.4, 95% CI: 2.56-161.9, p = 0.004) at 72 hours and 1-year mortality (hazard ratio: 17.9, 95% CI: 3.36-95.3, p = 0.001). Cold pre-EVLP was not a significant predictor of primary outcomes., Conclusions: Extended cold post-EVLP preservation is associated with a risk for PGD and 1-year mortality. Pre-EVLP CIT does not increase mortality or high-grade PGD. These findings from a multicenter trial should caution on the implementation of extended cold preservation after EVLP., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

There is conflicting evidence for adverse outcomes after coronary artery bypass surgery (CABG) with prior percutaneous intervention (PCI). A literature search was performed from 1998 to 2017 and articles with primary or secondary outcomes of survival, major adverse cardiovascular events (MACE), and myocardial infarction in CABG patients with prior PCI were included. Forest plots were generated from odds ratios for survival, MACE, and myocardial infarction for unmatched and propensity-matched data. Heterogeneity between studies was assessed for all outcomes using I 2 . Funnel plots were generated for early survival, survival at 5 years, survival at >5 years, and MACE. Thirty-one studies were included over 18 years with 194,544 patients without PCI prior to CABG and 23,519 patients (12.09%) with prior PCI. Prior PCI did not adversely affect survival among the included studies (inverse rate ratio: 1.12, 95% confidence interval: 0.98-1.27, P = 0.110. MACE was significantly worse for those with prior PCI (odds ratio: 1.26, confidence interval: 1.02-1.55, P = 0.03). The relative risk of mortality associated with prior PCI has decreased significantly over the last 2 decades. Studies with higher percentage of prior PCI patients had higher relative mortalities. There was significant heterogeneity between studies for the treatment effects. PCI prior to CABG in recent times does not adversely affect survival despite adverse early and late MACE rates. However, high institutional rates of prior PCI may be associated with increasing mortality after CABG., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The long-term benefits of a third arterial conduit to the right circulation in triple-vessel disease remain debatable. This retrospective, single-center, propensity-matched study investigates the impact of a third arterial conduit to the right circulation on early and intermediate survival after coronary artery bypass grafting., Methods: Data were retrospectively collected from 2004 to 2014 for all surgical revascularizations for triple-vessel disease with at least 2 arterial conduits to the left circulation and a third arterial or venous conduit to the right circulation. A total of 167 pairs were propensity matched to arterial versus venous third conduit to right circulation. Hazard functions were obtained with Cox multivariate regression and Kaplan-Meier survival curves were compared between the matched cohorts., Results: Extracardiac arteriopathy, logistic euroSCORE, and left main stem disease were significant predictors of adverse survival. A third arterial conduit to the right circulation was not a significant predictor of improved survival in multivariate analysis (HR, 0.72; 95% CI, 0.34-1.55; P = .411). 30-day mortality was 0.6% in both groups. There was no significant difference in early or intermediate survival in the propensity-matched groups (venous vs arterial, 99.2% vs 99.2%; P = 1.000 at 1 year; 85.2% vs 88.8%; P = .248 at 5 years and 69.2% vs 88.8%; P = .297 at 7 years) CONCLUSIONS: The use of a third arterial versus a venous conduit to the right circulation does not improve early or intermediate survival up to 7 years in triple-vessel coronary artery disease in this study. Longer follow-up and larger cohorts may be needed for differences to emerge., (Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.)

Objectives: Conventional coronary artery bypass surgery involves the use of a single left internal mammary artery to the left anterior descending artery and saphenous vein grafts reserved for other sites. This retrospective propensity-matched study investigated the impact of a second arterial conduit to the left-sided circulation on early and long-term survival after coronary artery bypass surgery., Methods: Data were retrospectively collected from 2004 to 2014 for all revascularizations with at least 1 arterial and/or 1 venous graft to the circumflex circulation, in addition to an internal mammary artery to the left anterior descending artery. Propensity-matched groups were created based on baseline characteristics. Hazard functions were estimated using Cox multivariable regression, and the Kaplan-Meier survival curves were compared between the matched cohorts., Results: A total of 1226 patients with a venous conduit to the left-sided circulation were successfully matched to an equal number of patients with an arterial conduit. Regression analysis identified a second arterial conduit, logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE), pulmonary disease, left ventricular ejection fraction, New York Heart Association (NYHA) Class and previous myocardial infarction as significant predictors of survival. A second arterial graft to the left circumflex circulation was a predictor of improved survival (hazard ratio 0.64, 95% confidence interval 0.51-0.80; P < 0.001). There were significant early and late survival benefits (arterial vs venous: 98.2% vs 96.3%, P = 0.003 at 1 year; 82.4% vs 62.2%, P < 0.001 at 10 years) from a second arterial conduit to the circumflex circulation., Conclusions: There are significant early and late incremental survival benefits from a second arterial conduit to the circumflex circulation., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Lung epithelial cells are increasingly recognized to be active effectors of microbial defense, contributing to both innate and adaptive immune function in the lower respiratory tract. As immune sentinels, lung epithelial cells detect diverse pathogens through an ample repertoire of membrane-bound, endosomal, and cytosolic pattern-recognition receptors (PRRs). The highly plastic epithelial barrier responds to detected threats via modulation of paracellular flux, intercellular communications, mucin production, and periciliary fluid composition. Epithelial PRR stimulation also induces production of cytokines that recruit and sculpt leukocyte-mediated responses, and promotes epithelial generation of antimicrobial effector molecules that are directly microbicidal. The epithelium can alternately enhance tolerance to pathogens, preventing tissue damage through PRR-induced inhibitory signals, opsonization of pathogen-associated molecular patterns, and attenuation of injurious leukocyte responses. The inducibility of these protective responses has prompted attempts to therapeutically harness epithelial defense mechanisms to protect against pneumonias. Recent reports describe successful strategies for manipulation of epithelial defenses to protect against a wide range of respiratory pathogens. The lung epithelium is capable of both significant antimicrobial responses that reduce pathogen burdens and tolerance mechanisms that attenuate immunopathology. This manuscript reviews inducible lung epithelial defense mechanisms that offer opportunities for therapeutic manipulation to protect vulnerable populations against pneumonia.

Background: This retrospective propensity-matched study investigated the impact of prior percutaneous coronary intervention (PCI) on short-term and long-term survival after coronary artery bypass graft surgery (CABG)., Methods: A total of 4,634 patients underwent isolated first-time CABG between April 2004 and March 2014. Among these, 424 (9.2%) had PCI. Propensity score analysis yielded 1:1 risk-adjusted matched groups: PCI (330 patients) and non-PCI (330 patients). A Cox proportional hazards model was used among the matched groups to assess the impact of prior PCI among other variables. Kaplan-Meier survival curves were compared at 1, 2, 3, 5, 7, and 10 years using the log-rank test to assess differences in survival., Results: In-hospital 30-day mortality was 1.1% (non-PCI) versus 0.9% (prior PCI; p = 0.66). Overall survival at 10 years was 77.5% (non-PCI) versus 82.71% (prior PCI; p = 0.4). Cox regression analysis identified European System for Cardiac Operative Risk Evaluation, nonsinus rhythm, age, pulmonary disease, and urgent surgery as risk factors for increased mortality. Prior PCI was not an independent predictor for mortality (hazard ratio, 0.55; 95% confidence interval, 0.25 to 1.18; p = 0.123). Overall survival in matched cohorts, non-PCI versus prior PCI, was 96.02% versus 97.13% (p = 0.08) at 1 year, 92.64% versus 96.36% (p = 0.08) at 3 years, 90.01% versus 93.47% (p = 0.02) at 5 years, 83.33% versus 90.37% (p = 0.01) at 7 years, and 73.56% versus 90.27% (p = 0.004) at 10 years., Conclusions: The survival in matched cohorts did not show adverse outcomes with prior PCI at 1, 3, 5, 7, and 10 years. Prior PCI does not adversely impact survival after CABG., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Despite widespread infection prevention efforts, pneumonia remains the leading cause of death among patients with acute leukemia, due to complex disease- and treatment-dependent immune defects. We have reported that a single inhaled treatment with a synergistic combination of Toll-like receptor 2/6 (TLR 2/6) and TLR9 agonists (Pam2-ODN) induces protective mucosal defenses in mice against a broad range of pathogens. As Pam2-ODN-induced protection persists despite depletion of several leukocyte populations, we tested whether it could prevent pneumonia in a mouse model of acute myeloid leukemia (AML) remission induction therapy. Pam2-ODN prevented death due to pneumonia caused by Pseudomonas aeruginosa, Streptococcus pneumoniae, and Aspergillus fumigatus when mice were heavily engrafted with leukemia cells, had severe chemotherapy-induced neutropenia or both. Pam2-ODN also extended survival of pneumonia in NSG mice engrafted with primary human AML cells. Protection was associated with rapid pathogen killing in the lungs at the time of infection and with reduced pathogen burdens at distant sites at the end of observation. Pathogen killing was inducible directly from isolated lung epithelial cells and was not abrogated by the presence of leukemia cells or cytotoxic agents. Pam2-ODN had no discernible effect on replication rate, total tumor population, or killing by chemotherapy of mouse or human leukemia cells, either in vitro or in vivo. Taken together, we report that therapeutic stimulation of lung epithelial defenses robustly protects against otherwise lethal pneumonias despite the profound immune dysfunction associated with acute leukemia and its treatment. These findings may suggest an opportunity to protect this population during periods of peak vulnerability., (© 2016 by The American Society of Hematology.)

Diabetes mellitus is a significant risk modifier for stable coronary artery disease, causing patients to have more extensive and diffuse lesions. Opposing treatment strategies remain a matter of debate. A multiple database search was conducted and outcomes, lesion, and patient characteristics were compared. Overall mortality, cardiac death, major adverse cardiovascular and cerebrovascular events, and need for revascularization were higher with percutaneous coronary intervention than with coronary artery bypass graft surgery. Multivessel disease and high Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) scores were associated with better outcomes for coronary artery bypass graft surgery., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)