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A vaccine for bovine tuberculosis is urgently needed. The BCG vaccine (the Bacille Calmette-Guérin), currently the only licensed vaccine for tuberculosis in humans, offers variable protection in cattle. However, BCG is a highly safe vaccine, and any alternative vaccine must not only offer greater protection than BCG but also match and improve its safety profile. Mice are the most widely used animal models in tuberculosis research, particularly for pre-clinical vaccine evaluation. In these animal models, the key indicator of infection or vaccine efficacy is the mycobacteria load in the lungs. In this study, we evaluated the long-term protection conferred by vaccinating BALB/c mice with a Mycobacterium bovis triple mutant lacking the virulence genes phoP, esxA, and esxB. Our findings showed that the triple mutant protected the lungs of mice against M. bovis challenge for up to one-year post-vaccination. However, the bacterial load in the spleens predominantly comprised the vaccine strain, and the lungs also contained some of these bacteria. These results suggest that the vaccine strain persisted in the mouse organs for at least one year, which raised concerns about its potential safety for animal vaccination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To evaluate survival and reoperation after repair of transposition of the great arteries (TGA) by linking to administrative databases., Methods: Demographic, diagnostic, and surgical data were retrieved from a surgical database for children born between 1990 and 2019 who underwent TGA repair at a single institution and were linked to administrative databases. TGA repair was performed in 838 patients, among whom 791 (94%) had an arterial switch operation (ASO), 25 a Rastelli, 10 Mustard, and 9 repaired by aortic translocation., Results: Follow-up was complete to December 2023 in 828 (98.8%) patients. In-hospital death was 3.8%. Survival probability at 30 years was 92%, not different between ASO versus other repairs. Freedom from cardiac reoperation was 82% at 30 years postrepair. Reoperation rates among patients who underwent ASO were greatest within the first 2 years after the initial repair (cumulative incidence function increase 0.85%/year), followed by 18 years of lower risk (0.25%/year), and then a late increase >20 years (0.48%/year). Coronary reoperations occurred early (median 3.3 months). Single coronary pattern from sinus 2 occurred in 56 patients with an in-hospital mortality of 10.7%. Contemporary operative risk was <2% for 93% of coronary artery patterns but persistently 7 times greater for 2LRCx and intramural pattern. Reoperation for neoaortic valve and root problems occurred late (17.7 years)., Conclusions: Patient survival was excellent 3 decades after TGA repair. We found disconcerting evidence of a late increase in neoaortic valve reoperations >17-years post-ASO attributable to enlarging neoaortic roots and/or neoaortic valve insufficiency. Future improvement after ASO hinges on better strategies for the subset of <7% with high-risk coronary artery patterns and avoiding neoaortic root distortion., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background/Objectives : Vaccines may improve the control and eradication of bovine tuberculosis. However, the evaluation of experimental candidates requires the assessment of the protection, excretion, transmission and biosafety. A natural transmission trial among likely infected animals was conducted. Methods : Seventy-four male heifers were randomly distributed (five groups) and vaccinated subcutaneously with attenuated strains ( M. bovis Δmce2 or M. bovis Δmce2 - phoP ), a recombinant M. bovis BCG Pasteur (BCGr) or M. bovis BCG Pasteur. Then, they cohoused with a naturally infected bTB cohort under field conditions exposed to the infection. Results : A 23% of transmission of wild-type strains was confirmed (non-vaccinated group). Strikingly, first vaccination did not induce immune response (caudal fold test and IFN-gamma release assay). However, after 74 days of exposure to bTB, animals were re-vaccinated. Although their sensitization increased throughout the trial, the vaccines did not confer significant protection, when compared to the non-vaccinated group, as demonstrated by pathology progression of lesions and confirmatory tools. Besides, the likelihood of acquiring the infection was similar in all groups compared to the non-vaccinated group ( p > 0.076). Respiratory and digestive excretion of viable vaccine candidates was undetectable. To note, the group vaccinated with M. bovis Δmce2-phoP exhibited the highest proportion of animals without macroscopic lesions, compared to the one vaccinated with BCG, although this was not statistically supported. Conclusions : This highlights that further evaluation of these vaccines would not guarantee better protection. The limitations detected during the trial are discussed regarding the transmission rate of M. bovis wild-type, the imperfect test for studying sensitization, the need for a DIVA diagnosis and management conditions of the trials performed under routine husbandry conditions. Re-vaccination of likely infected bovines did not highlight a conclusive result, even suggesting a detrimental effect on those vaccinated with M. bovis BCG.

Proper monitoring of rotating machines is responsible for the efficiency in detecting, diagnosing, or even prognosing failures. Effective monitoring can lead to increased economic viability of any equipment, as it may reduce costly repairs, decrease downtime, and increase safety. Knowing the behaviour of a machine promotes better monitoring of its operation and maintenance. Data-driven algorithms have been widely used to identify failures and predict the behaviour of machines and systems. The difficulty in obtaining reliable data to test strategies or methods for this purpose is well known. Our contribution is a set of electrical current data (time series data) from a rotating machine that generates electrical energy, generically called a power generator, in a laboratory. In this machine we have the possibility of, besides monitoring its healthy behaviour, causing internal defects that can reduce its efficiency and remaining useful life. We highlight three key lines of study with the data available here: it is possible to apply data processing tools to make discoveries not evidenced in studies; test and compare new data-driven algorithms using public and reliable data; engineering lectures can use the dataset regarding the study of electrical machines and data driving methods. The dataset contains information mainly about the voltage and current of generators when they are subject to internal faults. These faults include short circuits between turns of winding, short circuits between windings of the same phase, and short circuits between different phases. This dataset has a wide variety of bench configurations. The dataset comes from real generators and allows the study of phenomena that are difficult to reproduce through analytical or computational models. The time series of electrical currents are raw, no preprocessing has been done. In fact, the signals contain natural noise from an industrial environment. In this context, the main contribution of this work is to provide a public and reliable database, which helps to speed up the development of more efficient techniques for monitoring, diagnosis, and prognostics of the behaviour of rotating electrical machines., (© 2024 The Authors.)

Objective: Few have examined the influence of early adverse events after coronary artery bypass grafting (CABG) on long-term survival. We sought to determine if the occurrence of nonfatal major adverse cardiac and cerebrovascular events (MACCE) during the first 5 years after CABG influences survival and adverse events at 10 years., Methods: All patients who underwent isolated CABG from 1990 to 2014 at a single center in Ontario, Canada, were included. Primary end point was all-cause mortality. The secondary end point of interest was MACCE, a composite of mortality, nonfatal myocardial infarction, stroke, and repeat revascularization., Results: A total of 20,444 cases of elective primary isolated CABG were identified as being alive at 5 years, with 11% of patients developing nonfatal MACCE within the first 5 years after CABG (MACCE group) and the remaining 89% were alive without a MACCE event at 5 years (non-MACCE group). Following propensity score matching, 2167 patient-pairs were formed. Among the MACCE group, 972 out of 2167 (44.9%) developed a myocardial infarction, 519 out of 2167 (24.0%) had a stroke, and 946 out of 2167 (43.7%) required a repeat revascularization within the first 5 years after CABG. Non-MACCE was associated with better overall survival (hazard ratio, 1.42; 95% CI, 1.25-1.63; P < .01) and freedom from MACCE (hazard ratio, 1.61; 95% CI, 1.45-1.79; P < .01) up to 10 years after CABG compared with MACCE cases., Conclusions: Patients who experienced nonfatal MACCE during the first 5 years after CABG experienced worse survival and more MACCE at 10 years. Prevention of major adverse events during the first 5 years after surgical revascularization may be an important strategy to improve late outcomes., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: The optimal revascularization strategy in patients with diabetes and multivessel disease in the setting of a non-ST-segment elevation myocardial infarction (NSTEMI) is unknown., Objectives: The purpose of this study was to compare all-cause mortality between coronary artery bypass grafting (CABG) and multivessel percutaneous coronary intervention (PCI) among patients with diabetes and NSTEMI., Methods: All patients with diabetes and multivessel disease admitted for NSTEMI in Ontario, Canada, between April 2009 and March 2020 were included. Those with previous CABG, PCI in the previous 90 days, or shock were excluded. The primary outcome was all-cause mortality. Propensity score matching was used to account for confounding. Patients who had a cardiac surgeon consultation and then received PCI were classified as being potentially ineligible for CABG., Results: The cohort included 4,649 CABG and 6,760 PCI patients (mean age: 67.8 ± 11.5 years; 70.4% males), resulting in 2,385 matched pairs. CABG was associated with reduced all-cause mortality compared to PCI over a median follow-up of 5.5 years (5-year estimates: 23.4% vs 26.5%; HR: 0.89; 95% CI: 0.80-0.98; P  = 0.021). However, no significant differences in mortality were observed between CABG and PCI patients without a surgical consultation (2,130 pairs; HR: 0.97; 95% CI: 0.86-1.08), while CABG was associated with reduced mortality when compared against PCI patients who had received a surgical consultation (388 pairs; HR: 0.72; 95% CI: 0.58-0.88; P  = 0.002)., Conclusions: While CABG was associated with reduced all-cause mortality compared to multivessel PCI in patients with diabetes and NSTEMI, CABG benefit was seen only against PCI patients potentially ineligible for CABG after receiving a preprocedure surgical consultation., Competing Interests: This study is funded in part by a Foundation Grant (FDN 154333) from the 10.13039/501100000024Canadian Institutes of Health Research (CIHR). This study was supported by ICES, which is funded by an annual grant from the Ontario 10.13039/100009647Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). Dr Godoy receives the Frederick Banting and Charles Best Canada Graduate Scholarship (Doctoral Research Award) from the Canadian Institutes of Health Research. Dr Farkouh has received research grants from 10.13039/100002429Amgen, 10.13039/100004325AstraZeneca, 10.13039/501100004191Novo Nordisk, and 10.13039/100004336Novartis; and serves as a consultant to Otitopic. Dr Shah is supported by the 10.13039/501100004191Novo Nordisk Research Chair in Equitable Care of Diabetes and Related Conditions from the University of Toronto. Dr Nicolau has received research grants from 10.13039/100002429Amgen, 10.13039/100004325AstraZeneca, 10.13039/100004326Bayer, 10.13039/100008322CSL Behring, 10.13039/501100022274Daiichi Sankyo, Dalcor, 10.13039/501100022336Esperion, 10.13039/100014554Janssen, 10.13039/100004336Novartis, 10.13039/501100004191Novo Nordisk, 10.13039/100004339Sanofi, Vifor; and a scholarship from the Brazilian National Council for Scientific and Technological Development (CNPq #303448/2021/0). Dr Fremes has received research support from AMGEN, Boston Scientific, Medtronics, the Canadian Institutes of Health Research and the National Institutes of Health. Dr Lawler has received unrelated royalties from McGraw-Hill Publishing; and is supported by the Fonds de Recherche du Quebec. Dr Wijeysundera is supported by a Canada Research Chair in Structural Heart Disease Policy and Outcomes. Dr Gaudino has received research grants from the 10.13039/100000002National Institutes of Health and the 10.13039/501100000024Canadian Institutes of Health Research. Dr Ko is supported by the Jack Tu Research Chair in Cardiovascular Outcomes Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Bovine tuberculosis (bTB) represents a threat to livestock production. Mycobacterium bovis is the main causative agent of bTB and a pathogen capable of infecting wildlife and humans. Eradication programs based on surveillance in slaughterhouses with mandatory testing and culling of reactive cattle have failed to eradicate bTB in many regions worldwide. Therefore, developing effective tools to control this disease is crucial. Using a computational tool, we identified proteins in the M. bovis proteome that carry predictive binding peptides to BoLADRB3.2 and selected Mb0309, Mb1090, Mb1810 and Mb3810 from all the identified proteins. The expression of these proteins in a baculovirus-insect cell expression system was successful only for Mb0309 and Mb3810. In parallel, we expressed the ESAT-6 family proteins EsxG and EsxH in this system. Among the recombinant proteins, Mb0309 and EsxG exhibited moderate performance in distinguishing between cattle that test positive and negative to bTB using the official test, the intradermal tuberculin test (IDT), when used to stimulate interferon-gamma production in blood samples from cattle. However, when combined as a protein cocktail, Mb0309 and EsxG were reactive in 50 % of positive cattle. Further assessments in cattle that evade the IDT (false negative) and cattle infected with Mycobacterium avium paratuberculosis are necessary to determine the potential utility of this cocktail as an additional tool to assist the accurate diagnosis of bTB., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Recent reports on sex differences in long-term outcomes after surgery for acute type A aortic dissection (ATAAD) are conflicting. We aimed to aggregate updated data on long-term survival and reoperation stratified by sex., Methods: A literature search was conducted using Medline, Embase, and Cochrane Central. Studies reporting sex-stratified long-term survival and/or reoperation following surgery for ATAAD between January 1, 2000, to March 15, 2023 were included. Preoperative characteristics, intraoperative variables, and early perioperative outcomes were meta-analyzed using a random effects model and pooled risk ratio (RR) with men as the reference group. Individual patient-level data for long-term outcomes was reconstructed to generate sex-specific pooled Kaplan-Meier curves to assess long-term survival and freedom from reoperation., Results: A total of 15 studies with 7,608 male and 3,989 female patients were included in this analysis. Female patients were older, had higher rates of hypertension, and had less previous cardiac surgery. Intraoperatively, women received less extensive repairs with lower rates of aortic valve replacement and total arch replacement, and higher rates of hemiarch replacement. There were no sex differences for in-hospital/30-day mortality [risk ratio (RR), 1.18; 95% confidence interval (CI): 0.96, 1.45; P=0.12], stroke (RR, 1.07; 95% CI: 0.90, 1.28; P=0.46), and early reoperation (RR, 0.90; 95% CI: 0.75, 1.09; P=0.28). Female patients had lower long-term survival overall (P<0.001) and amongst survivors at 1-year (P=0.014). Overall survival at 5-year was 82.4% in men and 78.1% in women, and at 10-year was 68.1% for men and 63.4% in women. Male patients had higher rates of long-term reoperation (P<0.001). Freedom for reoperation at 5-year was 88.4% in men vs. 93.1% in women., Conclusions: Though perioperative early outcomes have equalized between the sexes following surgery for ATAAD, differences remain in long-term survival and reoperation., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2023 Annals of Cardiothoracic Surgery. All rights reserved.)

Objective: We sought to compare the long-term outcomes of multiarterial graft (MAG) coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DES) to treat stable multivessel coronary artery disease., Methods: This study was a multicenter population-based retrospective analysis of all residents of Ontario, Canada, from January 1, 2011, to December 31, 2019. We identified 3600 cases of elective primary isolated CABG with MAG and 2187 cases of PCI with second-generation DES., Results: After the application of propensity score-weighting using overlap weights, MAG was associated with better survival over 5 years compared with DES (96.8% vs 94.5%; hazard ratio [HR], 0.56; 95% CI, 0.37-0.85). MAG was also associated with better secondary outcomes including a composite of death, myocardial infarction, and stroke (94.3% vs 88.5%; HR, 0.49; 95% CI, 0.36-0.65). The rate of death, stroke, myocardial infarction, and repeat revascularization (91.2% vs 70.7%; HR, 0.24; 95% CI, 0.20-0.30), and the individual end points of myocardial infarction (1.4% vs 6.9%; HR, 0.22; 95% CI, 0.13-0.35), and repeat revascularization (4.1% vs 24.2%; HR, 0.14; 95% CI, 0.10-0.18) were lower with MAG. PCI with second-generation DES was associated with a lower rate of stroke up to 5 years (0.6% vs 1.8%; HR, 3.97; 95% CI, 1.45-10.88)., Conclusions: CABG with MAG was associated with better survival and fewer major cardiac adverse events compared with second-generation DES and might be considered the treatment of choice for patients with stable multivessel coronary artery disease. Further randomized controlled trials are needed to confirm this hypothesis., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Randomized trials have compared percutaneous coronary intervention and coronary artery bypass grafting (CABG) in patients with left main coronary artery disease undergoing nonemergent revascularization. However, there is a paucity of real-world contemporary observational studies comparing percutaneous coronary intervention (PCI) and CABG., Objectives: The purpose of this study was to compare the long-term clinical outcomes of CABG versus PCI in patients with left main coronary disease., Methods: Clinical and administrative databases for Ontario, Canada, were linked to obtain records of all patients with angiographic evidence of left main coronary artery disease (≥50% stenosis) treated with either isolated CABG or PCI from 2008 to 2020. Emergent, cardiogenic shock, and ST-segment elevation myocardial infarction patients were excluded. Baseline characteristics of patients were compared and 1:1 propensity score matching was performed. Late mortality and major adverse cardiac and cerebrovascular events were compared between the matched groups using a Cox proportional hazard model., Results: After exclusions, 1,299 and 21,287 patients underwent PCI and CABG, respectively. Prior to matching, PCI patients were older (age 75.2 vs 68.0 years) and more likely to be women (34.6% vs 20.1%), although they had less CAD burden. Propensity score matching on 25 baseline covariates yielded 1,128 well-matched pairs. There was no difference in early mortality between PCI and CABG (5.5% vs 3.9%; P = 0.075). Over 7-year follow-up, all-cause mortality (53.6% vs 35.2%; HR: 1.63; 95% CI: 1.42-1.87; P < 0.001) and major adverse cardiac and cerebrovascular events (66.8% vs 48.6%; HR: 1.77; 95% CI: 1.57-2.00) were significantly higher with PCI than CABG., Conclusions: CABG was the most common revascularization strategy in this real-world registry. Patients undergoing PCI were much older and of higher risk at baseline. After matching, there was no difference in early mortality but improved late survival and freedom from major adverse cardiac and cerebrovascular events with CABG., Competing Interests: Funding Support and Author Disclosures This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. This study also received funding from a Foundation grant from the Canadian Institutes of Health Research (grant FDN 148446) and the Ted Rogers Centre for Heart Research. The authors acknowledge that the clinical registry data used in this analysis are from participating hospitals through CorHealth Ontario, which serves as an advisory body to the Ontario Ministry of Health, is funded by the MOH, and is dedicated to improving the quality, efficiency, access, and equity in the delivery of the continuum of adult cardiac and stroke care in Ontario, Canada. Dr Lee has served as the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Objective: We sought to determine the risk factors associated with late mortality or complications (thoracoabdominal aortic aneurysm [TAAA] life-altering events [TALE]: a composite of mortality, permanent paraplegia, permanent dialysis, and stroke) for patients who had undergone endovascular or open TAAA repair., Methods: We performed a population-based study of patients who had undergone TAAA repair in Ontario, Canada, from 2006 to 2017. The association of baseline risk factors with mortality and complications after repair was examined using Cox hazards models with hospital-specific random effects. The survival of patients who had undergone TAAA repair was compared with that of controls without TAAAs. The two groups were matched by age, sex, area of residence, and average annual household income. The type of repair (endovascular vs open) was included in all models., Results: We identified 664 adults (mean age, 69.3 ± 10.6 years; 71% men) who had undergone TAAA repair. At 5 and 8 years, survival was 55.0% (95% confidence interval [CI], 49.8%-60.1%) and 44.6% (95% CI, 40.4%-49.6%) for patients who had undergone TAAA repair vs 85.6% (95% CI, 83.9%-87.1%) and 76.3% (95% CI, 73.8%-78.8%) for the control population, respectively (hazard ratio [HR], 1.97; 95% CI, 1.67-2.32; P < .01). For the TAAA group, freedom from TALE was 49.2% (95% CI, 44.7%-53.7%) and 37.3% (95% CI, 33.1%-42.4%) at 5 and 8 years of follow-up, respectively. On multivariable analysis, the risk factors associated with mortality during follow-up included older age (HR, 1.21 per 5-year increase; 95% CI, 1.13-1.28), peripheral artery disease (HR, 1.46; 95% CI, 1.03-2.09), hypertension (HR, 1.58; 95% CI, 1.03-2.43), congestive heart failure (HR, 1.78; 95% CI, 1.34-2.36), and urgent procedures (HR, 2.27; 95% CI, 1.74-3.00). A lower rate of death was observed for those with previous coronary revascularization (HR, 0.63; 95% CI, 0.41-0.96) and those who had undergone repair at high-volume institutions (>60 TAAA repairs during the study period; HR, 0.71; 95% CI, 0.55-0.91). Older age, chronic kidney disease, congestive heart failure, and urgent procedures were associated with a higher rate of TALE. The type of repair (endovascular vs open) was not associated with mortality or TALE., Conclusions: TAAA repair was associated with reduced long-term survival compared with the general population, regardless of the mode of treatment. Urgent or emergent repair was the most profound risk factor for late adverse events. The type of repair (endovascular vs open) was not a predictor of long-term death or complications. Previous coronary revascularization and treatment performed at a high-volume institution were associated with improved late outcomes for patients undergoing TAAA repair., (Copyright © 2021 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background The degree of hospital-level variation in the ratio of percutaneous coronary interventions to coronary artery bypass grafting procedures (PCI:CABG) and the association of the PCI:CABG ratio with clinical outcome are unknown. Methods and Results In a multicenter population-based study conducted in Ontario, Canada, we identified 44 288 patients from 19 institutions who had nonemergent diagnostic angiograms indicating severe multivessel coronary artery disease (2013-2017) and underwent a coronary revascularization procedure within 90 days. Hospitals were divided into tertiles according to their adjusted PCI:CABG ratio into low (0.70-0.85, n=17 487), medium (1.01-1.17, n=15 275), and high (1.18-1.29, n=11 526) ratio institutions. Compared with low PCI:CABG ratio hospitals, hazard ratios (HRs) for major adverse cardiac and cerebrovascular events were higher at medium (HR, 1.19; 95% CI, 1.14-1.25) and high ratio (HR, 1.21; 95% CI, 1.15-1.27) hospitals during a median 3.3 (interquartile range 2.1-4.6) years follow-up. When interventional cardiologists performed the diagnostic angiogram, the odds of the patient receiving PCI was higher (odds ratio, 1.37; 95% CI, 1.23-1.52) than when it was performed by noninterventional cardiologists, after accounting for patient characteristics. Having the diagnostic angiogram at an institution without cardiac surgical capabilities was independently associated with a higher risk of major adverse cardiac and cerebrovascular events (HR, 1.07; 95% CI, 1.02-1.11), death (HR, 1.09; 95% CI, 1.02-1.18), and myocardial infarction (HR, 1.10; 95% CI, 1.03-1.17). Conclusions Patients undergoing diagnostic angiography in hospitals with higher PCI:CABG ratio had higher rates of adverse outcomes, including major adverse cardiac and cerebrovascular events, myocardial infarction, and repeat revascularization. Presence of on-site cardiac surgery was associated with better survival and lower major adverse cardiac and cerebrovascular events.

Introduction: Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) are cytokines widely used in ex vivo monocyte differentiation experiments, vaccine formulations and disease treatment. The aim of this study was to produce recombinant bovine GM-CSF and IL-4 in an episomal expression system that conserves the postransductional modification of the native proteins and to use the products to differentiate bovine monocytes into dendritic cells., Material and Methods: The recombinant proteins rGM-CSF and rIL-4 were expressed in PEAKrapid CRL-2828 human kidney cells, ATCC CRL-2828. The functional activity of the recombinant cytokines was monitored by registering morphological changes in bovine monocytes and assessing the expression of CD14 upon incubation with them., Results: Both recombinant proteins were detected in the cell culture supernatant of transfected cells. Culture supernatants of transfected cells induced in bovine monocytes morphological changes that resemble macrophages or dendritic cells. In addition, bovine cells treated with rGM-CSF and rIL-4 showed reduced expression of the macrophage surface marker CD14 compared with untreated cells. This effect indicates the expected differentiation. The expression of the cytokines was stable after many successive cell passages and a freeze/thaw cycle., Conclusions: The semi-stable mammalian episomal expression system used in this study allowed us to easily produce functional bovine rGM-CSF and rIL-4 without the need for protein purification steps., Competing Interests: Conflict of Interest Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2021 F.C. Blanco et al. published by Sciendo.)

Objective: Multiple arterial grafting (MAG) in coronary artery bypass grafting (CABG) is associated with higher survival and freedom from major adverse cardiac and cerebrovascular events (MACCEs) in observational studies of mostly men. It is not known whether MAG is beneficial in women. Our objectives were to compare the long-term clinical outcomes of MAG versus single arterial grafting (SAG) in women undergoing CABG for multivessel disease., Methods: Clinical and administrative databases for Ontario, Canada, were linked to obtain all women with angiographic evidence of left main, triple or double vessel disease undergoing isolated non-emergent primary CABG from 2008 to 2019. 1:1 propensity score matching was performed. Late mortality and MACCE (composite of stroke, myocardial infarction, repeat revascularisation and death) were compared between the matched groups with a stratified log-rank test and Cox proportional-hazards model., Results: 2961 and 7954 women underwent CABG with MAG and SAG, respectively, for multivessel disease. Prior to propensity-score matching, compared with SAG, those who underwent MAG were younger (66.0 vs 68.9 years) and had less comorbidities. After propensity-score matching, in 2446 well-matched pairs, there was no significant difference in 30-day mortality (1.6% vs 1.8%, p=0.43) between MAG and SAG. Over a median and maximum follow-up of 5.0 and 11.0 years, respectively, MAG was associated with greater survival (HR 0.85, 95% CI 0.75 to 0.98) and freedom from MACCE (HR 0.85, 95% CI 0.76 to 0.95)., Conclusions: MAG was associated with greater survival and freedom from MACCE and should be considered for women with good life expectancy requiring CABG., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare 1-year health care costs between endovascular and open thoracoabdominal aortic aneurysm (TAAA)., Methods: Population-based administrative health databases were used to capture TAAA repairs performed in Ontario, Canada, between January 2006 and February 2017. All health care costs incurred by the Ministry of Health from a single-payer universal health care system were included. Costs of the aortic endografts and ancillary devices for the index procedure were estimated as C$44,000 per endovascular case vs C$1000 for open cases, based on previous reports. Costs (2017 Canadian dollars) were calculated in phases (1, 1-3, 3-6, and 6-12 months from surgery) with censoring for death. For each phase, propensity score matching of endovascular and open cases based on preoperative patient and hospital characteristics was used. The association between preoperative characteristics (including repair approach) and the first month postprocedure cost was characterized through multivariable analysis., Results: Overall 664 TAAA repairs were identified (open, n = 361 [54.5%] and endovascular, n = 303 [45.6%]). At 1 month, the median cost was higher for endovascular TAAA repair in the prematching cohort (C$64,892 vs C$36,647; P < .01). Similarly, in 241 well-balanced endovascular/open patient pairs after propensity score matching, the median health care costs were higher in endovascular TAAA cases during the first month (C$62,802 vs C$33,605; P < .01). The 1- to 3-month median cost was not statistically different between endovascular and open TAAA cases either before matching (C$2781 vs C$2618; P = .71) or after matching (C$2762 vs C$2092; P = .58). Likewise, in the 3- to 6-month and 6- to 12-month postprocedure intervals, there were no significant differences in the median health care costs between groups. On multivariable analysis, older age (5-year increments) (relative change [RC] in mean cost, 1.05; 95% confidence interval [CI], 1.04-1.06; P = .01), urgent procedures (RC, 1.29; 95% CI, 1.10-1.52; P < .01), and history of stroke (RC, 1.34; 95% CI, 1.00-1.78; P = .05) were associated with higher costs in the first postoperative month, whereas open relative to endovascular TAAA repair was associated with a decreased 1-month cost (RC, 0.65; 95% CI, 0.56-0.74; P < .01)., Conclusions: TAAA repair is expensive regardless of technique. Compared with open TAAA repair, endovascular repair was associated with a higher early cost, owing to the upfront cost of the endograft and aortic ancillary devices. There was no difference in cost from 1 to 12 months after repair. A decrease in the cost of endovascular devices might allow equivalent costs between endovascular and open TAAA repair., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: We sought to determine the early and late outcomes of endovascular versus open thoracoabdominal aortic aneurysm repair., Methods: We performed a multicenter population-based study across the province of Ontario, Canada, from 2006 to 2017. The primary end point was mortality. Secondary end points were time to first event of a composite of mortality, permanent spinal cord injury, permanent dialysis, and stroke, the individual end points of the composite, patient disposition at discharge, hospital length of stay, myocardial infarction, and secondary procedures at follow-up., Results: A total of 664 adults undergoing surgical repair of a thoracoabdominal aortic aneurysm (endovascular: n = 303 [45.5%] vs open: n = 361 [54.5%]) were identified using an algorithm of administrative codes validated against the operative records. Propensity score matching resulted in 241 patient pairs. Endovascular repairs increased during the study and currently comprise more than 50% of total repairs. In the matched sample, open repair was associated with a higher incidence of in-hospital death (17.4% vs 10.8%, P = .04), complications (26.1% vs 17.4%, P = .02), discharge to rehabilitation facilities (18.7% vs 10.0%, P = .02), and longer length of stay (12 [7-21] vs 6 [3-13] days, P < .01). Long-term mortality was not significantly different (hazard ratio, 1.09; 95% confidence interval, 0.78-1.50), nor were the other secondary end points, with the exception of secondary procedures, which were higher in the endovascular group (hazard ratio, 2.64; 95% confidence interval, 1.54-4.55). At 8 years, overall survival was 41.3% versus 44.6% after endovascular and open repair (P = .62)., Conclusions: Endovascular repair was associated with improved early outcomes but higher rates of secondary procedures after discharge. Long-term survival after thoracoabdominal aortic aneurysm repair is poor and independent of repair technique., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The safety and efficacy of aortic root enlargement (ARE) at the time of aortic valve replacement (AVR) remains unknown. The objective of this multicenter study was to compare AVR with ARE to AVR for early and late mortality and secondary safety outcomes., Methods: Clinical and administrative databases in Ontario, Canada, were linked to obtain patients undergoing AVR with or without ARE from 2008 to 2017. Baseline characteristics were compared and 1:1 propensity score matching was performed to account for differences in baseline characteristics. Early outcomes were compared in the matched groups. Late mortality was compared using Kaplan-Meier survival curves and a Cox-proportional hazard model., Results: Sixteen thousand six hundred fifty-six patients undergoing AVR in 11 Ontario institutions were reviewed. Patients who underwent ARE were younger, nonurgent, more likely to be men and had lower rates of hypertension, ischemic heart disease, and congestive heart failure. Propensity score matching yielded similar groups for comparison, with 809 pairs for AVR versus AVR with ARE. There was no difference in 30-day mortality between AVR with ARE versus AVR (2.0% vs 2.1%; P = 1.00). Rates of chest reopening for bleeding, permanent pacemaker implantation, and blood transfusions were similar. Late mortality over 8 years was similar between AVR with ARE and AVR (P = .45). In a sensitivity analysis, results were similar in 525 pairs comparing AVR with coronary artery bypass grafting and ARE to AVR with coronary artery bypass grafting, except that chest reopening for bleeding was higher with AVR with coronary artery bypass grafting and ARE (7.2% vs 3.2%; P = .006)., Conclusions: The addition of ARE to isolated AVR can be safely performed to increase implanted prosthesis size without compromising early mortality. Additional studies with longer follow-up are necessary., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Aortic valve-sparing operations theoretically have fewer stroke and bleeding complications but may increase late reoperation risk versus composite valve grafts., Methods: We meta-analyzed all studies comparing aortic valve-sparing (reimplantation and remodelling) and composite valve-grafting (bioprosthetic and mechanical) procedures. Early outcomes were all-cause mortality, reoperation for bleeding, myocardial infarction, and thromboembolism/stroke. Long-term outcomes included all-cause mortality, reintervention, bleeding, and thromboembolism/stroke. Studies exclusively investigating dissection or pediatric populations were excluded., Results: A total of 3794 patients who underwent composite valve grafting and 2424 who underwent aortic valve-sparing procedures were included from 9 adjusted and 17 unadjusted observational studies. Mean follow-up was 5.8 ± 3.0 years. Aortic valve sparing was not associated with any difference in early mortality, bleeding, myocardial infarction, or thromboembolic complications. Late mortality was significantly lower after valve sparing (incident risk ratio, 0.68; 95% confidence interval [CI], 0.54-0.87; P < .01). Late thromboembolism/stroke (incident rate ratio, 0.36; 95% CI, 0.22-0.60; P < .01) and bleeding (incident rate ratio, 0.21; 95% CI, 0.11-0.42; P < .01) risks were lower after valve sparing. Procedure type did not affect late reintervention., Conclusions: Aortic valve sparing appears to be safe and associated with reduced late mortality, thromboembolism/stroke, and bleeding compared with composite valve grafting. Late durability is equivalent. Aortic valve sparing should be considered in patients with favorable aortic valve morphology., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Importance: The optimal conduits for coronary artery bypass grafting (CABG) remain controversial in multivessel coronary artery disease., Objective: To compare the long-term clinical outcomes of total arterial revascularization (TAR) vs non-TAR (CABG with at least 1 arterial and 1 saphenous vein graft) in a multicenter population-based study., Design, Setting, and Participants: This multicenter population-based cohort study using propensity score matching took place from October 2008 to March 2017 in Ontario, Canada, with a mean and maximum follow-up of 4.6 and 9.0 years, respectively. Individuals with primary isolated CABG were identified, with at least 1 arterial graft. Exclusion criteria were individuals from out of province and younger than 18 years. Patients undergoing a cardiac reoperation or those in cardiogenic shock were also excluded because these conditions would potentially bias the surgeon toward not performing TAR. Analysis began April 2019., Exposures: Total arterial revascularization., Main Outcomes and Measures: Primary outcome was time to first event of a composite of death, myocardial infarction, stroke, or repeated revascularization (major adverse cardiac and cerebrovascular events). Secondary outcomes included the individual components of the primary outcome., Results: Of 49 404 individuals with primary isolated CABG, 2433 (4.9%) received TAR, with the total number of bypasses being 2, 3, and 4 or more vessels in 1521 (62.5%), 865 (35.6%), and 47 individuals (1.9%), respectively. The mean (SD) age was 61.2 (10.4) years and 1983 (81.5%) were men. After propensity score matching, 2132 patient pairs were formed, with equal total number of bypasses (mean [SD], 2.4 [0.5]) but with more arterial grafts in the TAR group (mean [SD], 2.4 [0.5] vs 1.2 [0.4]; P < .01). In-hospital death (15 [0.7%] vs 21 [1.0%]; P = .32) did not differ between TAR vs non-TAR groups after propensity score matching. Throughout 8 years, TAR was associated with improved freedom from major adverse cardiac and cerebrovascular events (hazard ratio, 0.78; 95% CI, 0.68-0.89), death (hazard ratio, 0.80; 95% CI, 0.66-0.97), and myocardial infarction (hazard ratio, 0.69; 95% CI, 0.51-0.92). There was no difference in stroke and repeated revascularization., Conclusions and Relevance: Total arterial revascularization was associated with improved long-term freedom from major adverse cardiac and cerebrovascular events, death, and myocardial infarction and may be the procedure of choice for patients with reasonable life expectancy requiring CABG.

Objectives: Off-pump coronary artery bypass (OPCAB) may benefit select high-risk patients. We sought to analyze the long-term outcomes of OPCAB versus on-pump coronary artery bypass (ONCAB) in patients with moderate renal failure., Methods: A retrospective cohort analysis of primary isolated CAB surgery performed in Ontario, Canada, from October 2008 to March 2016 in the CorHealth Ontario Cardiac Registry identified 50,115 cases. Of these, 7782 (15.5%) had estimated glomerular filtration rate (eGFR) of 30 to 59 mL/min/1.73 m 2 . OPCAB was compared to ONCAB after propensity score matching., Results: Following propensity score matching, 1578 patient pairs were formed. Total number of bypass grafts was higher in ONCAB (3.31 ± 1.01 vs 3.12 ± 1.14; P < .01) and more arterial grafts were used in OPCAB (1.55 ± 0.71 vs 1.14 ± 0.58; P < .01). OPCAB was associated with lower rate of in-hospital stroke (0.7% vs 2.2%; P < .01), renal failure requiring dialysis (1.2% vs 2.9%; P < .01), and blood transfusion (52.4% vs 69.3%; P < .01). There was no difference in perioperative mortality (2.4% vs 3.0%; P = .36) between OPCAB and ONCAB, respectively. At 8-year follow-up, survival probability was not different when comparing OPCAB versus ONCAB: 62% versus 65%, respectively (hazard ratio, 0.98; 95% confidence interval, 0.84-1.13; P = .38). Cumulative incidence of permanent dialysis did not differ at 8-year follow-up: 7% versus 7%, respectively (hazard ratio, 1.01; 95% confidence interval, 0.72-1.43; P = .74., Conclusions: OPCAB is associated with improved in-hospital renal outcomes, but is not associated with changes in short- or long-term mortality, or with the long-term cumulative incidence of end-stage renal failure requiring permanent dialysis in patients with moderate renal failure., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of the study was to provide a systematic review of the literature reporting the contemporary early outcomes after endovascular and open repair of thoracoabdominal aortic aneurysms (TAAAs)., Methods: MEDLINE and Embase were searched for studies from January 2006 to March 2018 that reported either endovascular (using branched or fenestrated endografts) or open repair of TAAA in at least 10 patients. Outcomes of interest included perioperative mortality, spinal cord injury (SCI), renal failure requiring dialysis, and stroke. Pooled proportions were determined using a random-effects model., Results: The analysis included 71 studies, of which 24 and 47 reported outcomes after endovascular and open TAAA repair, respectively. Endovascular cohort patients were older and had higher rates of coronary artery disease, chronic obstructive pulmonary disease, and diabetes. Endovascular repair was associated with higher rates of SCI (13.5%; 95% confidence interval [CI], 10.5%-16.7%) compared with open repair (7.4%; 95% CI, 6.2%-8.7%; P < .01) but similar rates of permanent paralysis (5.2% [95% CI, 3.8%-6.7%] vs 4.4% [95% CI, 3.3%-5.6%]; P = .39), lower rates of postoperative dialysis (6.4% [95% CI, 3.2%-9.5%] vs 12.0% [95% CI, 8.2%-16.3%]; P = .03) but similar rates of being discharged on permanent dialysis (3.7% [95% CI, 2.0%-5.9%] vs 3.8% [95% CI, 2.9%-5.3%]; P = .93), a trend to lower stroke (2.7% [95% CI, 1.9%-3.6%] vs 3.9% [95% CI, 3.0%-4.9%]; P = .06), and similar perioperative mortality (7.4% [95% CI, 5.9%-9.1%] vs 8.9% [95% CI, 7.2%-10.9%]; P = .21)., Conclusions: This systematic review summarizes the contemporary literature results of endovascular and open TAAA repair. Endovascular repair studies included patients with more comorbidities and were associated with higher rates of SCI but similar rates of permanent paraplegia, whereas open repair studies had higher rates of postoperative dialysis but similar rates of being discharged on permanent dialysis. Perioperative mortality rates were similar. Universally adopted reporting standards for patient characteristics, outcomes, and the conduct of contemporary comparative studies will allow better assessment and comparisons of the risks associated with the two surgical treatment options for TAAA., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to compare early and late outcomes between redo surgical aortic valve replacement (AVR) and valve-in-valve (ViV) transcatheter AVR., Background: Published studies to date comparing redo surgical AVR (RS) with ViV transcatheter AVR for failed biological prostheses have been small and limited to early outcomes., Methods: Clinical and administrative databases for Ontario, Canada's most populous province, were linked to obtain patients undergoing ViV and RS for failed previous biological prostheses. Propensity score matching was performed to account for differences in baseline characteristics. Early outcomes were compared using the McNemar test. Late mortality was compared between the matched groups using a Cox proportional hazards model., Results: A total of 558 patients undergoing intervention for failed biological prostheses between March 31, 2008, and September 30, 2017, at 11 Ontario institutions (ViV, n = 214; RS, n = 344) were included. Patients who underwent ViV were older and had more comorbidities. Propensity matching on 27 variables yielded similar groups for comparison (n = 131 pairs). Mean time from initial AVR to RS or ViV was 8.6 ± 4.4 years and 11.3 ± 4.5 years, respectively. Thirty-day mortality was significantly lower with ViV compared with RS (absolute risk difference: -7.5%; 95% confidence interval: -12.6% to -2.3%). The rates of permanent pacemaker implantation and blood transfusions were also lower with ViV, as was length of stay. Survival at 5 years was higher with ViV (76.8% vs. 66.8%; hazard ratio: 0.55; 95% confidence interval: 0.30 to 0.99; p = 0.04)., Conclusions: ViV TAVR was associated with lower early mortality, morbidity, and length of hospital stay and with increased survival compared with RS and may be the preferred approach for the treatment of failed biological prostheses., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: Time trends in surgical valve selection have not been explored in detail in the era of transcatheter aortic valve replacement (TAVR) in nationally representative data. Herein, we explore valve selection trends in the TAVR era using the Society of Thoracic Surgeons Adult Cardiac Surgery Database., Methods: Isolated first-time biological or mechanical aortic valve replacements (AVR) from 2004 to 2016 in the Society of Thoracic Surgeons Adult Cardiac Surgery Database were included. Patient characteristics were examined in the pre-TAVR era (2004-2007) and the post-TAVR era (2008-2016) using the year 2007 as the cut-point. Using a piece-wise regression analysis to model the relationship between time and type of valve used, a change-point analysis was performed to empirically determine the time of change in practice, both overall and in age-specific subgroups (≤60 years and >60 years)., Results: In total, 214,390 patients underwent isolated primary mechanical or biological AVR from 2004 to 2016. The patients' mean age increased slightly between the 2 eras (67.1 vs 68.6 years, P < .001), whereas the proportion of mechanical AVRs decreased (24.8% vs 12.2%, P < .001). Piece-wise regression demonstrated that the proportion of mechanical valves decreased over time. An empirically estimated slope change-point was found after the first quarter 2010; from 2004 to 2009, the overall proportion of mechanical valves was decreasing quickly (-2.81%/year, 95% confidence interval [95% CI], -3.03% to -2.60%), compared with 2010 to 2016. The early decline was steeper for younger patients (-4.21%/year, 95% CI, -4.74 to -3.69) compared with older patients (-1.44%/year, 95% CI -1.64 to -1.23)., Conclusions: Use of mechanical AVR declined significantly from 2004 to 2016 and was decreasing before the introduction or the approval of TAVR in the United States., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Aim of the Study: We compared early and late outcomes of surgical aortic valve replacement (SAVR) in patients with aortic stenosis (AS) and pulmonary hypertension (PHT)., Methods: We searched MEDLINE and EMBASE databases until July 2018 for studies comparing patients with AS and none, mild-moderate, or severe PHT undergoing SAVR. Random-effects meta-analysis was performed., Results: There were 12 observational studies with 70 676 patients with median follow-up 4.0 years (interquartile range, 2.6-4 years). Compared to patients with no PHT, patients with any PHT undergoing SAVR were older (mean difference [MD], 2.31 years; 95% confidence interval [CI], 1.38-3.23 years; P < .01), with greater comorbidities and reduced ejection fraction (MD, -4.36; 95%CI, -5.94 to -2.78; P < .01). Patients with any PHT had higher unadjusted (5.2% vs 2.4%; risk ratio [RR], 2.27; 95%CI, 2.04-2.53; P < .01) and adjusted (RR, 1.65; 95%CI, 1.28-2.14; P < .01) in-hospital mortality compared with no PHT. Severe (RR, 3.53; 95%CI, 1.46-8.54; P < .01) and mild-moderate PHT (RR, 2.13; 95%CI, 1.28-3.55; P < .01) were associated with higher unadjusted in-hospital mortality compared with no PHT. Any PHT was associated with a higher unadjusted risk of stroke (RR, 1.64; 95%CI, 1.42-1.90; P < .01), acute kidney injury (RR, 2.02; 95%CI, 1.50-2.72; P < .01), prolonged ventilation (RR, 1.62; 95%CI, 1.04-2.52; P = .03), and longer hospital stay (MD, 1.76 days; 95%CI, 0.57-2.95; P < .01). Severe (HR, 2.44; 95%CI, 1.60-3.72; P < .01) but not mild-moderate PHT (HR, 2.25; 95%CI, 0.91-5.59; P = .08) was associated with higher adjusted long-term mortality compared with no PHT., Conclusions: Patients with severe AS and severe PHT had a significant increase in operative mortality and more than double the risk of long-term mortality following SAVR compared with patients with no PHT. Such patients may benefit from a less invasive transcatheter aortic valve intervention., (© 2019 Wiley Periodicals, Inc.)

In this study, we characterized the role of Rv2617c in the virulence of Mycobacterium tuberculosis . Rv2617c is a protein of unknown function unique to M. tuberculosis complex (MTC) and Mycobacterium leprae. In vitro , this protein interacts with the virulence factor P36 (also named Erp) and KdpF, a protein linked to nitrosative stress. Here, we showed that knockout of the Rv2617c gene in M. tuberculosis CDC1551 reduced the replication of the pathogen in a mouse model of infection and favored the trafficking of mycobacteria to phagolysosomes. We also demonstrated that Rv2617c and P36 are required for resistance to in vitro hydrogen peroxide treatment in M. tuberculosis and Mycobacterium bovis , respectively. These findings indicate Rv2617c and P36 act in concert to prevent bacterial damage upon oxidative stress.

Purpose: The positive predictive value (PPV) of endovascular and open thoracoabdominal aortic aneurysm (TAAA) repair coding was assessed in Ontario health administrative databases., Methods: Between 1 January 2006 and 31 March 2016, a random sample of 192 patients was identified using Canadian Classification of Health Intervention (CCI) procedure codes and Ontario Health Insurance Plan (OHIP) billing codes from administrative data. Blinded chart reviews were conducted at two cardiovascular centers to assess the level of agreement between the administrative records and the corresponding patients' hospital charts. The PPV was calculated with 95% confidence intervals using hospital charts as the gold standard., Results: The PPV for the single endovascular TAAA repair code, 1ID80GQNRN, was 0.90 (0.78, 0.97). A combination of all nine CCI open TAAA repair codes was performed, with a PPV of 0.62 (0.47, 0.76). The combination of any one of the nine CCI codes AND the single OHIP code for open TAAA repair (R803) rendered a PPV of 0.98 (0.90, 1.00)., Conclusions: Endovascular TAAA repair may be identified using a single CCI code (1ID80GQNRN). Open TAAA repair may be identified using a combination of CCI and OHIP codes. Researchers may therefore use administrative data to conduct population-based studies of endovascular and open repair of TAAA.

Background: Aortic root enlargement (ARE) may be an important adjunct to aortic valve replacement (AVR) to prevent patient-prosthesis mismatch and facilitate future valve-in-valve transcatheter AVR (TAVR). However, the early safety and late benefits of adding surgical ARE to AVR remain controversial., Methods: MEDLINE and EMBASE were searched from 1946 to 2018 for articles comparing patients undergoing AVR+ARE with those undergoing AVR alone. A random-effects meta-analysis was performed to compare early and late clinical outcomes., Results: A total of 2570 AVR+ARE and 5,991 AVR patients were included from 9 observational studies. There was no difference in early mortality (relative risk [RR] 1.21; 95% confidence interval [CI], 0.94-1.54; P = 0.13). Both cardiopulmonary bypass (mean difference [MD] 20 minutes; 95% CI, 15-25; P < 0.01) and aortic cross-clamp time (MD 14 minutes; 95% CI, 11-17, P < 0.01) were higher following AVR+ARE. There was no difference in the risk of permanent pacemaker implantation (RR 1.02; 95% CI, 0.83-1.25; P = 0.86), reoperation for bleeding (RR 1.05; 95% CI, 0.84-1.32; P = 0.64), or stroke (RR 0.93; 95% CI, 0.68-1.27; P = 0.65). The risk of moderate (indexed effective orifice area [iEOA] < 0.85 cm 2 /m 2 ) and severe (iEOA < 0.65 cm 2 /m 2 ) patient-prosthesis mismatch (PPM) was lower with AVR+ARE (RR 0.65; 95% CI, 0.51-0.83; P < 0.01) and RR 0.36; 95% CI, 0.16-0.82; P = 0.01, respectively). There was no difference in late mortality (incidence rate ratio [IRR] 1.05; 95% CI, 0.87-1.27; P = 0.59) at mean 7.8-year follow-up in 5 studies., Conclusions: Surgical ARE is a safe adjunct to AVR in selected patients that does not increase early adverse events and results in less patient-prosthesis mismatch. This strategy allows for a larger valve size at the time of implantation, an important consideration for potential future valve-in-valve procedures in the era of TAVR., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: We report our 10-year experience of a multicenter hemoglobin optimization program with the aim to reduce red blood cell transfusion in patients undergoing coronary artery bypass grafting (CABG)., Methods: From 2006 to 2016, patients undergoing CABG at 10 centers in Ontario were referred to the Ontario Transfusion Coordinators (ONTraC) program. Of these, we present data on the first 60 consecutive patients per center, per year (n = 6,145)., Results: Overall, 45.7% patients were assessed <14 days preoperatively, 16.4% were assessed ≥14 days preoperatively, and 37.9% were not assessed by ONTraC preoperatively. Transfusion rates fell from 40.1% in 2006 to 26.2% in 2016 (p < 0.01). Patients undergoing assessment were more likely to be older (p < 0.01), female (p < 0.01), and anemic (p < 0.01) versus nonassessed patients. Those patients assessed were more likely to be treated with iron (p < 0.01) and erythropoietin (p < 0.01) preoperatively versus nonassessed patients. Transfusion rates were 26%, 28%, and 28% for patients undergoing assessment ≥14 days prior to operation, <14 days prior to operation, or not at all. After baseline covariate adjustment, patients assessed ≥14 days preoperatively had shorter length of stay (effect -0.83, 95% confidence interval [CI] -1.41 to -0.25; p < 0.01) and a trend towards lower risk of red blood cell transfusion (odds ratio [OR] 0.83, 95% CI 0.68 to 1.00; p = 0.06). Blood transfusion was independently associated with an increased risk of death (OR 1.49, 95% CI 1.37 to 1.60; p < 0.01), infection (OR 1.24, 95% CI 1.18 to 1.30; p < 0.01), and longer hospital length of stay (effect 1.49, 95% CI 1.35 to 1.62; p < 0.01)., Conclusions: The results of this study suggest that preoperative hemoglobin optimization may be effective in reducing red blood cell transfusion after CABG, particularly for patients assessed ≥14 days preoperatively., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Bovine tuberculosis (bTB) is a disease produced by Mycobacterium bovis that affects livestock, wild animals, and humans. The classical diagnostic method to detect bTB is measuring the response induced with the intradermal injection of purified protein derivative of M. bovis (PPDb). Another ancillary bTB test detects IFN-γ produced in whole blood upon stimulation with PPDb, protein/peptide cocktails, or individual antigens. Among the most used M. bovis antigens in IFN-γ assays are the secreted proteins ESAT-6 and CFP-10, which together with antigen Rv3615c improve the sensitivity of the test in comparison to PPDb. Protein reagents for immune stimulation are generally obtained from Escherichia coli, because this bacterium produces a high level of recombinant proteins. However, E. coli recombinant antigens are in general contaminated with lipopolysaccharides and other components that produce non-specific IFN-γ secretion in in vitro assays. In this work, we produced the relevant ESAT-6, CFP-10, and Rv3615c M. bovis antigens as fusions to the polyhedrin protein from the baculovirus AcMNPV. We obtained chimeric proteins effectively incorporated to the occlusion bodies and easily purified the recombinant polyhedra with no reactive contaminants. In an IFN-γ assay, these fusion proteins showed equivalent sensibility but better specificity than the same M. bovis proteins produced in E. coli., (© 2020 S. Karger AG, Basel.)

Objective: The objective of this study was to compare the early results of endovascular vs open thoracoabdominal aortic aneurysm (TAAA) repair., Methods: MEDLINE and Embase were searched for studies from January 2006 to March 2018 that compared endovascular vs open repair of TAAA using branched or fenestrated endografts. Data were subjected to a meta-analysis using a random-effects model. The outcomes of interest included early mortality, spinal cord injury, renal failure requiring dialysis, stroke, and hospital length of stay., Results: Eight comparative studies met inclusion criteria. There were two retrospective propensity-matched studies, two unadjusted single-center retrospective studies, and four unadjusted national population-based studies. Mortality in the matched studies was equivalent in both groups. Pooled analysis of all unmatched observational studies revealed a survival benefit for endovascular over open repair (relative risk [RR], 0.63; 95% confidence interval [CI],0.45-0.87); P < .01, I 2  = 47%). Endovascular repair was also associated with lower incidence of spinal cord injury (RR, 0.65; 95% CI, 0.42-1.01; P = .05; I 2  = 28%). For unmatched studies, pooled RR of renal failure requiring dialysis significantly favored endovascular repair (RR, 0.44; 95% CI, 0.23-0.85; P = .01; I 2  = 0%), although in the adjusted cohort, risk of dialysis was not different (RR, 1.00; 95% CI, 0.06-15.65; P = 1.00). Postoperative stroke rate was reported in three unadjusted studies and was not different between groups (RR, 0.81; 95% CI, 0.28-2.40; P = .71; I 2  = 77%). Hospital length of stay was reported in four studies and was shorter in the endovascular group (mean difference, -4.4 days; 95% CI, -6.6 to -1.7; P < .01; I 2  = 73%)., Conclusions: There are few reports comparing endovascular vs open repair of TAAAs. Short-term outcomes may be improved in patients undergoing endovascular treatment of TAAA on the basis of a limited number of studies with high risk of bias. These findings highlight the need for larger comparative studies with standardization of reporting., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Observational studies have shown better survival in patients undergoing coronary artery bypass grafting (CABG) with 2 arterial grafts compared with 1. However, whether a third arterial graft is associated with incremental benefit remains uncertain. We sought to analyze the outcomes of 3 versus 2 arterial grafts during CABG. As a secondary objective, we compared CABG with 2 or 3 arterial grafts (multiple arterial grafts [MAG]) with CABG using a single arterial graft (SAG)., Methods: Retrospective cohort analyses of all patients undergoing primary isolated CABG in Ontario, Canada, from October 2008 to March 2016. Propensity score matching was performed between patients with 3 arterial grafts (3Art group) versus 2 (2Art group). The primary outcome was time to first event of a composite of death, myocardial infarction, stroke, and repeat revascularization (major adverse cardiac and cerebrovascular events). Additional analyses were performed to evaluate the association between MAG versus SAG and long-term outcomes using propensity score matching., Results: Fifty thousand, two hundred thirty patients underwent isolated CABG during our study period; 3044 (6.1%) and 8253 (16.4%) patients had 3 and 2 arterial grafts, respectively, resulting in 2789 propensity score matching pairs for the primary analyses. Mean and maximum follow-up was 4.2 and 8.5 years, respectively. Radial artery grafting was more common in the 3Art versus 2Art group (79.3% versus 65.6%, P<0.01). In-hospital outcomes were not significantly different, including death (3Art 0.8% versus 2Art 0.5%, P=0.26). Up to 8 years, there were no differences in major adverse cardiac and cerebrovascular events (3Art 27%, 95% confidence interval [CI], 24% to 30% versus 2Art 25%, 95% CI, 22% to 28%; hazard ratio [HR], 1.08, 95% CI, 0.94-1.25), death (HR, 1.08; 95% CI, 0.90-1.29), myocardial infarction (HR, 1.15; 95% CI, 0.87-1.51), stroke (HR, 1.39; 95% CI, 0.95-2.06), or repeat revascularization (HR, 1.04; 95% CI, 0.82-1.32). When evaluating MAG versus SAG, 8629 patient pairs were formed using propensity score matching. At 8 years, cumulative incidences of major adverse cardiac and cerebrovascular events (HR, 0.82, 95% CI, 0.77-0.88), survival (HR, 0.80; 95% CI, 0.73-0.88), repeat revascularization (HR, 0.79; 95% CI, 0.69-0.90), and myocardial infarction (HR, 0.83; 95% CI, 0.72-0.97) were superior in the MAG group., Conclusions: CABG with 3 arterial grafts was not associated with increased in-hospital death nor with better clinical outcomes at 8-year follow-up, compared with CABG with 2 arterial grafts. MAG was associated with superior outcomes compared with SAG.

Importance: The ideal aortic valve substitute in young and middle-aged adults remains unknown., Objective: To compare long-term outcomes between the Ross procedure and mechanical aortic valve replacement in adults., Data Sources: The Ovid versions of MEDLINE and EMBASE classic (January 1, 1967, to April 26, 2018; search performed on April 27, 2018) were screened for relevant studies using the following text word search in the title or abstract: ("Ross" OR "autograft") AND ("aortic" OR "mechanical")., Study Selection: All randomized clinical trials and observational studies comparing the Ross procedure to the use of mechanical prostheses in adults undergoing aortic valve replacement were included. Studies were included if they reported any of the prespecified primary or secondary outcomes. Studies were excluded if no clinical outcomes were reported or if data were published only as an abstract. Citations were screened in duplicate by 2 of the authors, and disagreements regarding inclusion were reconciled via consensus., Data Extraction and Synthesis: This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines. Data were independently abstracted by 3 reviewers and pooled using a random-effects model., Main Outcomes and Measures: The prespecified primary outcome was all-cause mortality., Results: The search identified 2919 reports, of which 18 studies (3516 patients) met inclusion criteria, including 1 randomized clinical trial and 17 observational studies, with a median average follow-up of 5.8 (interquartile range, 3.4-9.2) years. Analysis of the primary outcome showed a 46% lower all-cause mortality in patients undergoing the Ross procedure compared with mechanical aortic valve replacement (incidence rate ratio [IRR], 0.54; 95% CI, 0.35-0.82; P = .004; I2 = 28%). The Ross procedure was also associated with lower rates of stroke (IRR, 0.26; 95% CI, 0.09-0.80; P = .02; I2 = 8%) and major bleeding (IRR, 0.17; 95% CI, 0.07-0.40; P < .001; I2 = 0%) but higher rates of reintervention (IRR, 1.76; 95% CI, 1.16-2.65; P = .007; I2 = 0%)., Conclusions and Relevance: Data from primarily observational studies suggest that the Ross procedure is associated with lower all-cause mortality compared with mechanical aortic valve replacement. These findings highlight the need for a large, prospective randomized clinical trial comparing long-term outcomes between these 2 interventions.

Mycobacterium bovis is the causative agent of bovine tuberculosis and is a member of Mycobacterium tuberculosis complex, which causes tuberculosis in a number of mammals including humans. Previous studies have shown that the genes encoding the two-component system PhoPR, which regulates several genes involved in the virulence of M. tuberculosis, are polymorphic in M. bovis, when compared to M. tuberculosis, which results in a dysfunctional two-component system. In this study we investigated the role of PhoPR in two M. bovis strains with differing degrees of virulence. We found that the deletion of phoP in an M. bovis isolate reduced its capacity of inducing phagosomal arrest in bovine macrophages. By gene expression analysis, we demonstrated that, in both M. bovis strains, PhoP regulates the expression of a putative lipid desaturase Mb1404-Mb1405, a protein involved in redox stress AhpC, the sulfolipid transporter Mmpl8 and the secreted antigen ESAT-6. Furthermore, the lack of PhoP increased the sensitivity to acidic stress and alteration of the biofilm/pellicle formation of M. bovis. Both these phenotypes are connected to bacterial redox homeostasis. Therefore, the results of this study suggest a role of PhoPR in M. bovis to be linked to the mechanisms that mycobacteria display to maintain their redox balance., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Primary cardiac adipose tumors are rare. There are two distinct pathologically defined entities that represent this tumor type: lipoma and lipomatous hypertrophy of the interatrial septum (LHIS). We present a single-center experience with these tumors and demonstrate that the location may not correspond to the pathologic diagnosis., Methods: A retrospective review of a prospectively collected cardiac surgery database from January 1990 to July 2016 identified 254 cases of surgically treated primary cardiac tumors at our Institution. Of these, 06/254 (2%) were primary adipose tumors., Results: In 3/6 (50%) cases, patients were asymptomatic or had symptoms referable to other known intracardiac lesions. Five patients (83%) had preserved ventricular function. In 4/6 cases (67%), the tumor was identified preoperatively. All patients presented in New York Heart Association functional class ≤2. Pathologic diagnosis of LHIS was made in 5/6 cases (83%), with 2/5 LHIS (40%) located in the interatrial septum. A bovine pericardial patch was utilized for reconstruction following tumor resection in 3/6 cases (50%). Mean cardiopulmonary bypass time was 88 ± 43 min. All the patients tolerated the procedure well without any postoperative complications., Conclusions: Primary cardiac adipose tumors are responsible for a small portion of all primary heart tumors. Surgical resection provided excellent outcomes, and did not affect cardiac performance, in spite of the need for extensive resections. LHIS was identified in locations other than the interatrial septum and was usually symptomatic., (© 2018 Wiley Periodicals, Inc.)

Background: Surgical aortic root enlargement (ARE) during aortic valve replacement (AVR) allows for larger prosthesis implantation and may be an important adjunct to surgical AVR in the transcatheter valve-in-valve era. The incremental operative risk of adding ARE to AVR has not been established. We aimed to evaluate the early outcomes of patients undergoing AVR with or without ARE., Methods: From January 1990 to August 2014, 7039 patients underwent AVR (AVR+ARE, n=1854; AVR, n=5185) at a single institution. Patients with aortic dissection and active endocarditis were excluded. Mean age was 65±14 years and 63% were male. Logistic regression and propensity score matching were used to adjust for unbalanced variables in group comparisons., Results: Patients undergoing AVR+ARE were more likely to be female (46% versus 34%, P <0.001) and had higher rates of previous cardiac surgery (18% versus 12%, P <0.001), chronic obstructive pulmonary disease (5% versus 3%, P =0.004), urgent/emergent status (6% versus 4%, P =0.01), and worse New York Heart Association status ( P <0.001). Most patients received bioprosthetic valves (AVR+ARE: 73.4% versus AVR: 73.3%, P =0.98) and also underwent concomitant cardiac procedures (AVR+ARE: 68% versus AVR: 67%, P =0.31). Mean prosthesis size implanted was slightly smaller in patients requiring AVR+ARE versus AVR (23.4±2.1 versus 24.1±2.3, P <0.001). In-hospital mortality was higher after AVR+ARE (4.3% versus 3.0%, P =0.008), although when the cohort was restricted to patients undergoing isolated aortic valve replacement with or without root enlargement, mortality was not statistically different (AVR+ARE: 1.7% versus AVR: 1.1%, P =0.29). After adjustment for baseline characteristics, AVR+ARE was not associated with an increased risk of in-hospital mortality when compared with AVR (odds ratio, 1.03; 95% confidence interval, 0.75-1.41; P =0.85). Furthermore, AVR+ARE was not associated with an increased risk of postoperative adverse events. Results were similar if propensity matching was used instead of multivariable adjustments for baseline characteristics., Conclusions: In the largest analysis to date, ARE was not associated with increased risk of mortality or adverse events. Surgical ARE is a safe adjunct to AVR in the modern era., (© 2017 American Heart Association, Inc.)