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Machine learning (ML) algorithms may enhance outcomes prediction and help guide clinical decision making. This study aimed to develop and validate a ML model that predicts postoperative outcomes and costs after cardiac surgery.The Society of Thoracic Surgeons registry data from 4874 patients who underwent cardiac surgery (56% coronary artery bypass grafting, 42% valve surgery, 19% aortic surgery) at our institution were divided into training (80%) and testing (20%) datasets. The Extreme Gradient Boosting decision-tree ML algorithms were trained to predict three outcomes: operative mortality, major morbidity or mortality, and Medicare outlier high hospitalization cost. Algorithm performance was determined using accuracy, F1 score, and area under the precision-recall curve (AUC-PR). The ML algorithms were validated in index surgery cases with The Society of Thoracic Surgeons risk scores for mortality and major morbidities and with logistic regression and were then applied to nonindex cases.The ML algorithms with 25 input parameters predicted operative mortality (accuracy 95%; F1 0.31; AUC-PR 0.21), major morbidity or mortality (accuracy 71%, F1 0.47; AUC-PR 0.47), and high cost (accuracy 84%; F1 0.62; AUC-PR 0.65). Preoperative creatinine, complete blood count, patient height and weight, ventricular function, and liver dysfunction were important predictors for all outcomes. For patients undergoing nonindex cardiac operations, the ML model achieved an AUC-PR of 0.15 (95% CI, 0.05-0.32) for mortality and 0.59 (95% CI, 0.51-0.68) for major morbidity or mortality.The extreme gradient boosting ML algorithms can predict mortality, major morbidity, and high cost after cardiac surgery, including operations without established risk models. These ML algorithms may refine risk prediction after cardiac surgery for a wide range of procedures.

Machine learning may enhance prediction of outcomes after coronary artery bypass grafting (CABG). We sought to develop and validate a dynamic machine learning model to predict CABG outcomes at clinically relevant pre- and postoperative time points.The Society of Thoracic Surgeons (STS) registry data elements from 2086 isolated CABG patients were divided into training and testing datasets and input into Extreme Gradient Boosting decision-tree machine learning algorithms. Two prediction models were developed based on data from preoperative (80 parameters) and postoperative (125 parameters) phases of care. Outcomes included operative mortality, major morbidity or mortality, high cost, and 30-day readmission. Machine learning and STS model performance were assessed using accuracy and the area under the precision-recall curve (AUC-PR).Preoperative machine learning models predicted mortality (accuracy, 98%; AUC-PR = 0.16; F1 = 0.24), major morbidity or mortality (accuracy, 75%; AUC-PR = 0.33; F1 = 0.42), high cost (accuracy, 83%; AUC-PR = 0.51; F1 = 0.52), and 30-day readmission (accuracy, 70%; AUC-PR = 0.47; F1 = 0.49) with high accuracy. Preoperative machine learning models performed similarly to the STS for prediction of mortality (STS AUC-PR = 0.11; P = .409) and outperformed STS for prediction of mortality or major morbidity (STS AUC-PR = 0.28; P.001). Addition of intraoperative parameters further improved machine learning model performance for major morbidity or mortality (AUC-PR = 0.39; P.01) and high cost (AUC-PR = 0.64; P.01), with cross-clamp and bypass times emerging as important additive predictive parameters.Machine learning can predict mortality, major morbidity, high cost, and readmission after isolated CABG. Prediction based on the phase of care allows for dynamic risk assessment through the hospital course, which may benefit quality assessment and clinical decision-making.

Safety-net hospitals provide essential services to vulnerable patients with complex medical and socioeconomic circumstances. We hypothesized that matched patients at safety-net hospitals and non-safety-net hospitals would have comparable outcomes, costs, and readmission rates after isolated surgical aortic valve replacement (AVR) or mitral valve replacement (MVR).The National Readmissions Database was queried to identify patients who underwent isolated AVR (n = 109 744) or MVR (n = 31 475) from 2016 to 2018. Safety-net burden was defined as the percentage of patients who were uninsured or insured with Medicaid, with hospitals in the top quartile designated as safety-net hospitals. After propensity score matching, outcomes for AVR and MVR at safety-net hospitals vs non-safety-net hospitals were compared.Overall, 17 925 AVRs (16%) and 5516 MVRs (18%) were performed at safety-net hospitals, and these patients had higher comorbidity rates, had lower socioeconomic status, and more frequently required urgent surgery. Observed inhospital mortality was similar between safety-net hospitals and non-safety-net hospitals (AVR 2.2% vs 2.1%, P = .4; MVR 4.8% vs 4.3%, P = .1). After matching, rates of inhospital mortality, major morbidity, and readmission were similar; however, safety-net hospitals had longer length of stay after AVR (7 vs 6 days, P = .001) and higher total cost after AVR ($49 015 vs $42 473, P.001) and MVR ($59 253 vs $52 392, P.001).Isolated surgical AVR and MVR are both performed at safety-net hospitals with outcomes comparable to those at non-safety-net hospitals, supporting efforts to expand access to these procedures for underserved populations. Investment in care coordination resources to reduce length of stay and curtail cost at safety-net hospitals is warranted.

Recruiting and promoting women and racial/ethnic minorities could help enhance diversity and inclusion in the academic cardiothoracic (CT) surgery workforce. However, the demographics of trainees and faculty at US training programs have not yet been studied.Traditional, integrated (I-6), and fast-track (4+3) programs listed in the Accreditation Council for Graduate Medical Education (ACGME) public database were analyzed. Demographics of trainees and surgeons, including gender, race/ethnicity, subspecialty, and academic appointment (if applicable), were obtained from ACGME Data Resource Books, institutional websites, and public profiles. Chi-square and Cochran-Armitage trend tests were performed.In July 2020, 78 institutions had at least 1 CT surgery training program; 40 (51%) had only a traditional program, 20 (26%) traditional and I-6, 6 (8%) all 3 types of program, and 4 (5%) only I-6. The proportion of female trainees increased significantly from 2011 to 2019 (19% vs 24%, P.001), with female I-6 trainees outnumbering female traditional trainees since 2018. Significant increases by race/ethnicity were observed overall and by program type, notably for Asian and Hispanic individuals in I-6 programs and Black individuals in traditional programs. Finally, of the 1175 CT surgeons identified, 633 (54%) were adult cardiac surgeons, 360 (37%) assistant professors, 116 (10%) women, and 33 (3%) Black.The demographic landscape of CT surgery trainees and faculty across multiple training pathways reflects increasing representation by gender and race/ethnicity. However, we must continue to work toward equitable representation in the workforce to benefit the diverse patients we treat.

Purpose:IL2 immunotherapy has the potential to elicit immune-mediated tumor lysis via activation of effector immune cells, but clinical utility is limited due to pharmacokinetic challenges as well as vascular leak syndrome and other life-threatening toxicities experienced by patients. We developed a safe and clinically translatable localized IL2 delivery system to boost the potency of therapy while minimizing systemic cytokine exposure.Experimental Design:We evaluated the therapeutic efficacy of IL2 cytokine factories in a mouse model of malignant mesothelioma. Changes in immune populations were analyzed using time-of-flight mass cytometry (CyTOF), and the safety and translatability of the platform were evaluated using complete blood counts and serum chemistry analysis.Results:IL2 cytokine factories enabled 150× higher IL2 concentrations in the local compartment with limited leakage into the systemic circulation. AB1 tumor burden was reduced by 80% after 1 week of monotherapy treatment, and 7 of 7 of animals exhibited tumor eradication without recurrence when IL2 cytokine factories were combined with anti–programmed cell death protein 1 (aPD1). Furthermore, CyTOF analysis showed an increase in CD69+CD44+ and CD69−CD44+CD62L− T cells, reduction of CD86−PD-L1− M2-like macrophages, and a corresponding increase in CD86+PD-L1+ M1-like macrophages and MHC-II+ dendritic cells after treatment. Finally, blood chemistry ranges in rodents demonstrated the safety of cytokine factory treatment and reinforced its potential for clinical use.Conclusions:IL2 cytokine factories led to the eradication of aggressive mouse malignant mesothelioma tumors and protection from tumor recurrence, and increased the therapeutic efficacy of aPD1 checkpoint therapy. This study provides support for the clinical evaluation of this IL2-based delivery system.See related commentary by Palanki et al., p. 5010

Supplementary Figure from Activation of Adaptive and Innate Immune Cells via Localized IL2 Cytokine Factories Eradicates Mesothelioma Tumors

Investigations into readmissions after surgical repair of acute Stanford type A aortic dissection (TAAD) remain scarce. We analyzed potential risk factors for readmission after TAAD.The 2013 to 2014 US Nationwide Readmissions Database was queried for TAAD index hospitalizations and 90-day readmissions indicated by diagnostic and procedural codes. Multivariable analysis was completed to identify risk factors and the most common reasons for readmission.We identified 6975 patients (65% men; mean age, 60.0 ± 0.4 years) who underwent surgical repair for TAAD. Overall 2062 patients (29.6%) were readmitted within 90 days: 634 (30.7%) during the first 30 days and 1428 (69.3%) during days 31 through 90. Readmitted patients had a higher prevalence of chronic kidney disease at index admission (18.0% vs 11.6%, P = .002), greater overall index length of stay (17.8 ± 0.6 vs 15. 5 ± 0.4 days; P = .0003), and greater index hospitalization cost ($90,637 ± $2691 vs $80,082 ± $2091; P = .0003). Mortality during readmission was 3.6% (n = 74). Indications for readmission were most commonly cardiac (26.2%), infectious (17.8%), and pulmonary (11.7%). Multivariate analysis identified 2 independent risk factors for readmission: acute kidney injury (odds ratio, 1.49; 95% confidence interval, 1.24-1.78; P.0001) and an Elixhauser comorbidity index4 (odds ratio, 1.26; 95% confidence interval, 1.06-1.49; P = .009).After surgical repair of TAAD, approximately 30% of patients were readmitted within 90 days, two-thirds of them during the 31- to 90-day period. Targeted improvements in perioperative care and postdischarge follow-up of patients with multiple comorbidities could mitigate readmission rates. Efforts to reduce readmissions should be continued throughout the 90-day period.

This study evaluated outcomes and risk factors for surgical aortic valve replacement (SAVR) for aortic insufficiency (AI) in a national cohort. We analyzed the incidence, outcomes, and risk factors for SAVR for AI in the Society of Thoracic Surgeons Adult Cardiac Surgery Database.The national database was queried for patients with moderate or greater AI undergoing isolated SAVR between July 2011 and December 2018. Patients with moderate or greater aortic stenosis, acute dissection, active endocarditis, concomitant procedures, or emergent operation were excluded. AI was staged using guideline criteria based on symptoms and ventricular remodeling. Operative mortality and morbidity were compared between stages, and risk factors for operative death were identified.A total of 12,564 patients underwent isolated SAVR for AI from 2011 to 2018. Patients were most frequently AI stage D (7019 [57.5%]), compared with B (1405 [11.2%]), C1 (1128 [9.0%]), or C2 (1325 [10.5%]). Operative mortality was 1.1% overall, and increased between stage C1, C2, and D (0.4% vs 0.7% vs 1.6%, respectively, P.01), along with major morbidity (5.1% vs 7.5% vs 9.9%, respectively; P.01). Mortality was higher in patients with severe ventricular dilation and an ejection fraction of less than 0.30 (2.7% vs 1.0%, P.01). Risk factors for death were symptomatic AI, decreased ejection fraction, age, weight, body surface area, and dialysis.Operative mortality and morbidity for isolated SAVR for AI is very low in a national cohort, providing a benchmark for future transcatheter approaches. Operative risk increases with advanced ventricular remodeling. SAVR before development of ventricular remodeling may be appropriate in patients with severe AI.

OBJECTIVES: Safety-net hospitals (SNHs) provide essential services to predominantly underserved patients regardless of their ability to pay. We hypothesized that patients who underwent coronary artery bypass grafting (CABG) would have inferior observed outcomes at SNHs compared with non-SNHs but that matched cohorts would have comparable outcomes. METHODS: We queried the Nationwide Readmissions Database for patients who underwent isolated CABG from 2016 to 2018. We ranked hospitals by the percentage of all admissions in which the patient was uninsured or insured with Medicaid; hospitals in the top quartile were designated as SNHs. We used propensity-score matching to mitigate the effect of confounding factors and compare outcomes between SNHs and non-SNHs. RESULTS: A total of 525,179 patients underwent CABG, including 96,133 (18.3%) at SNHs, who had a greater burden of baseline comorbidities (median Elixhauser score 8 vs 7; P = .04) and more frequently required urgent surgery (57.1% vs 52.8%; P

Atrial fibrillation is associated with an increased risk of stroke secondary to thrombus formation in the left atrial appendage. Left atrial appendage occlusion (LAAO) is an effective method of reducing the risk of stroke in patients with atrial fibrillation. Although LAAO does not remove the requirement for anticoagulation, it reduces the risk of stroke when compared to anticoagulation alone. We critically analyze the data on LAAO in cardiac surgery. We also discuss the methods of LAAO, the risks of LAAO, and patient populations that could benefit from LAAO. We discuss high-level evidence that LAAO at the time of cardiac surgery reduces the risk of stroke in patients with a history of atrial fibrillation. In patients without a history of atrial fibrillation undergoing cardiac surgery, we suggest that LAAO should be considered in select patients at high risk of atrial fibrillation and stroke, when technically feasible.

Background Sternal wound infections (SWI) are a devastating complication of cardiac surgery. The majority of SWI are bacterial infections; however, Candida species are a less common cause and have not been well described. The purposes of this study were (1) to describe clinical characteristics, management and outcomes of Candida SWI and (2) to compare the risk factors and outcomes for Candida to bacterial SWI. Methods Our study reviewed medical records of 41 patients with Candida SWI after cardiac surgeries between 2013 - 2020 at our medical center, then compared them to 76 patients with bacterial SWI during the same timeframe via univariate analysis. We defined superficial SWI as positive culture isolates involving the skin or subcutaneous tissues, deep SWI as involving deep soft tissues or bone, and mediastinitis as involving the mediastinum. Results Of the 41 Candida SWI patients, relevant comorbidities included previous cardiac surgery (46.3%), heart failure (65.9%), and diabetes (58.5%). Candida SWI was diagnosed at an average of 123.6 days after cardiac surgery, with the majority being deep SWI (70.7%). Candida albicans was most common (70.7%). Bacterial co-infections were found in 53.7% (Table 1). Longer bypass and operative times for the initial cardiac surgery were found to be positively correlated to disease severity. Clinical cure rate after completion of antimicrobial treatment was 100% in superficial SWI, 72.4% in deep SWI and 25.0% in mediastinitis. Overall mortality was 29.3%: 25%, 24.1% and 50.0%, respectively. When compared to bacterial SWI, factors significantly associated with Candida SWI included: previous cardiac surgery (46.3% vs. 7.9%, odds ratio (OR): 5.9; 95% confidence interval (CI): 2.2-15.9), heart failure (65.9% vs. 11.8%, OR: 5.6; 95% CI: 2.4-12.9), and >48 hours of postoperative antibiotics (39.0% vs. 3.0%, OR: 9.9; 95% CI: 2.7-35.9). Mortality rates were higher with Candida than with bacterial infections (29.3% vs. 1.3%, OR: 22.2, 95% CI 2.8-177.2) (Table 2). Conclusion This study showed Candida SWI as a serious complication of extensive cardiac surgery with higher mortality rates. Prior history of cardiac surgery and heart failure, prolonged surgeries, and complicated postoperative course were significant risk factors for the development of Candida SWI. Disclosures Barbara Trautner, MD, PhD, Genetech: Advisor/Consultant.

Patients with postcardiotomy cardiogenic shock refractory to conventional support can be successfully supported with extracorporeal membrane oxygenation. Management considerations are discussed to aid clinicians caring for these patients.

Choosing between a bioprosthetic and a mechanical mitral valve is an important decision for both patients and surgeons. We compared patient outcomes and readmission rates after bioprosthetic mitral valve replacement (Bio-MVR) vs mechanical mitral valve replacement (Mech-MVR).The Nationwide Readmissions Database was queried to identify 31 474 patients who underwent isolated MVR (22 998 Bio-MVR, 8476 Mech-MVR) between January 1, 2016, and December 31, 2018. Propensity score matching by age, sex, elective status, and comorbidities was used to compare outcomes between matched cohorts by prosthesis type. Freedom from readmission within the first calendar year was estimated by Kaplan-Meier analysis and compared between matched cohorts.Bio-MVR patients were older (median age, 69 vs 57 years; P.001) and had more comorbidities (median Elixhauser score, 14 vs 11; P.001) compared with Mech-MVR patients. After propensity score matching (n = 15 549), Bio-MVR patients had similar operative mortality (3.5% vs 3.4%; P = .97) and costs ($50 958 vs $49 782; P = .16) but shorter lengths of stay (8 vs 9 days; P.001) and fewer 30-day (16.0% vs 18.1%; P = .04) and 90-day (23.8% vs 26.8%; P = .01) readmissions compared with Mech-MVR patients. The difference in readmissions persisted at 1 year (P = .045). Readmission for bleeding or coagulopathy complications was less common with Bio-MVR (5.7% vs 10.1%; P .001).Readmission was more common after Mech-MVR than after Bio-MVR. Identifying and closely observing patients at high risk for bleeding complications may bridge the readmissions gap between Bio-MVR and Mech-MVR.

Cellular therapy with mesenchymal stem cells (MSCs) shows promise for restoring function after myocardial infarction (MI). However, cellular therapy has yet to be clinically translated, in part because of difficulty in studying how MSCs interact with the post-MI scar microenvironment. This study aimed to design an in vitro model to study MSC behavior in the post-MI scar stiffness microenvironment. Using poly(ethylene glycol)-acrylate (PEG) conjugated to bioactive peptides, rat MSCs were encapsulated in hydrogels of varying stiffnesses and crosslinking densities. Cell viability was assessed through 14 days using calcein and ethidium homodimer staining. To simulate post-MI pro-fibrotic signaling, transforming growth factor-beta (TGFβ) was added to selected cultures. Immunofluorescence and qRT-PCR were used to assess changes in cardiac transdifferentiation or paracrine secretion, two proposed methods of MSCs in cellular therapy. Bioactivated PEG hydrogels with stiffnesses between 1.6 and 151.0 kPa were prepared. Rat MSCs demonstrated up to 71.6% viability after 3 days of encapsulated culture, and survived within the hydrogels up to 14 days. Encapsulation decreased MSC expression of cardiac troponin T and most growth factors, except interleukin-6. Meanwhile, TGFβ caused increased cardiac troponin T expression but decreased secreted factor expression. Varying hydrogel stiffness did not have an effect on cardiac troponin T or secreted factor expression. These findings suggest that a 3D microenvironment hinders two key mechanisms by which MSCs could improve cardiac function after post-MI scar formation, namely cardiac transdifferentiation and secreted factor production. Future studies incorporating MSCs other cell types should broaden understanding of the post-MI scar microenvironment.

Purpose: IL2 immunotherapy has the potential to elicit immune-mediated tumor lysis via activation of effector immune cells, but clinical utility is limited due to pharmacokinetic challenges as well as vascular leak syndrome and other life-threatening toxicities experienced by patients. We developed a safe and clinically translatable localized IL2 delivery system to boost the potency of therapy while minimizing systemic cytokine exposure. Experimental Design: We evaluated the therapeutic efficacy of IL2 cytokine factories in a mouse model of malignant mesothelioma. Changes in immune populations were analyzed using time-of-flight mass cytometry (CyTOF), and the safety and translatability of the platform were evaluated using complete blood counts and serum chemistry analysis. Results: IL2 cytokine factories enabled 150× higher IL2 concentrations in the local compartment with limited leakage into the systemic circulation. AB1 tumor burden was reduced by 80% after 1 week of monotherapy treatment, and 7 of 7 of animals exhibited tumor eradication without recurrence when IL2 cytokine factories were combined with anti–programmed cell death protein 1 (aPD1). Furthermore, CyTOF analysis showed an increase in CD69+CD44+ and CD69−CD44+CD62L− T cells, reduction of CD86−PD-L1− M2-like macrophages, and a corresponding increase in CD86+PD-L1+ M1-like macrophages and MHC-II+ dendritic cells after treatment. Finally, blood chemistry ranges in rodents demonstrated the safety of cytokine factory treatment and reinforced its potential for clinical use. Conclusions: IL2 cytokine factories led to the eradication of aggressive mouse malignant mesothelioma tumors and protection from tumor recurrence, and increased the therapeutic efficacy of aPD1 checkpoint therapy. This study provides support for the clinical evaluation of this IL2-based delivery system. See related commentary by Palanki et al., p. 5010

Acute kidney injury after cardiac surgery increases morbidity and mortality. Diagnosis relies on oliguria or increased serum creatinine, which develop 48 to 72 hours after injury. We hypothesized machine learning incorporating preoperative, operative, and intensive care unit data could dynamically predict acute kidney injury before conventional identification.Cardiac surgery patients at a tertiary hospital (2008-2019) were identified using electronic medical records in the Medical Information Mart for Intensive Care IV database. Preoperative and intraoperative parameters included demographics, Charlson Comorbidity subcategories, and operative details. Intensive care unit data included hemodynamics, medications, fluid intake/output, and laboratory results. Kidney Disease: Improving Global Outcomes creatinine criteria were used for acute kidney injury diagnosis. An ensemble machine learning model was trained for hourly predictions of future acute kidney injury within 48 hours. Performance was evaluated by area under the receiver operating characteristic curve and balanced accuracy.Within the cohort (n = 4267), there were approximately 7 million data points. Median baseline creatinine was 1.0 g/dL (interquartile range, 0.8-1.2), with 17% (735/4267) of patients having chronic kidney disease. Postoperative stage 1 acute kidney injury occurred in 50% (2129/4267), stage 2 occurred in 8% (324/4267), and stage 3 occurred in 4% (183/4267). For hourly prediction of any acute kidney injury over the next 48 hours, area under the receiver operating characteristic curve was 0.82, and balanced accuracy was 75%. For hourly prediction of stage 2 or greater acute kidney injury over the next 48 hours, area under the receiver operating characteristic curve was 0.95 and balanced accuracy was 86%. The model predicted acute kidney injury before clinical detection in 89% of cases.Ensemble machine learning models using electronic medical records data can dynamically predict acute kidney injury risk after cardiac surgery. Continuous postoperative risk assessment could facilitate interventions to limit or prevent renal injury.

OBJECTIVES Del Nido cardioplegia (DNC) has been shown to be safe in adults with normal coronary arteries who are undergoing valve surgery. This study compared the effects of DNC versus traditional blood-based cardioplegia on postoperative complications in patients who underwent coronary artery bypass grafting (CABG). METHODS A retrospective analysis was performed on 863 patients who underwent CABG with DNC (n = 420) or control cardioplegia (CC) (n = 443) between 2014 and 2017. The full cohort of DNC and CC recipients, as well as propensity score-matched pairs, was compared regarding preoperative risk variables and outcomes. RESULTS The DNC and CC groups showed no significant differences in mean cardiopulmonary bypass time (53.09 vs 52.10 min, P = 0.206) or aortic cross-clamp time (32.82 vs 33.28 min, P = 0.967). The groups also showed no difference in operative mortality (2.1% vs 2.5%, P = 0.734); however, DNC use resulted in lower rates of overall infections (1.7% vs 4.3%, P = 0.024), total sternal infections (0.9% vs 3.2%, P = 0.023), postoperative atrial fibrillation (23.8% vs 30.7%, P = 0.023) and postoperative ventricular tachycardia (0.5% vs 3.4%, P = 0.002). A propensity-matching analysis (n = 335 pairs) showed similar statistically significant decreases with DNC. CONCLUSIONS In this large cohort of CABG patients, DNC was shown as a safe alternative to CC and was associated with lower postoperative dysrhythmia and infection rates. These findings show that DNC is safe and effective in patients whose operative interventions may require only single-dosing cardioplegia; its use in longer cases should be further explored given its low complication rate.

Periodontitis (PD) is a polymicrobial dysbiotic immuno-inflammatory disease. It is more prevalent in males and has poorly understood pathogenic molecular mechanisms. Our primary objective was to characterize alterations in sex-specific microRNA (miRNA, miR) after periodontal bacterial infection. Using partial human mouth microbes (PAHMM) (Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) in an ecological time-sequential polybacterial periodontal infection (ETSPPI) mouse model, we evaluated differential mandibular miRNA profiles by using high-throughput Nanostring nCounter® miRNA expression panels. All PAHMM mice showed bacterial colonization (100%) in the gingival surface, an increase in alveolar bone resorption (p < 0.0001), and the induction of a specific immunoglobin G antibody immune response (p < 0.001). Sex-specific differences in distal organ bacterial dissemination were observed in the heart (82% male vs. 28% female) and lungs (2% male vs. 68% female). Moreover, sex-specific differential expression (DE) of miRNA was identified in PAHMM mice. Out of 378 differentially expressed miRNAs, we identified seven miRNAs (miR-9, miR-148a, miR-669a, miR-199a-3p, miR-1274a, miR-377, and miR-690) in both sexes that may be implicated in the pathogenesis of periodontitis. A strong relationship was found between male-specific miR-377 upregulation and bacterial dissemination to the heart. This study demonstrates sex-specific differences in bacterial dissemination and in miRNA differential expression. A novel PAHMM mouse and ETSPPI model that replicates human pathobiology can be used to identify miRNA biomarkers in periodontitis.

The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days.Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life.By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01).Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.

Objectives The study objectives were to describe the trends and outcomes of isolated coronary artery bypass grafting after ST-elevation myocardial infarction using a nationwide database. Methods We queried the 2002-2016 National Inpatient Sample database for hospitalized patients with ST-elevation myocardial infarction who underwent isolated coronary artery bypass grafting. We report temporal trends, predictors, and outcomes of coronary artery bypass grafting in the early (2002-2010) and recent (2011-2016) cohorts. Results Of 3,347,470 patients hospitalized for ST-elevation myocardial infarction, 7.7% underwent isolated coronary artery bypass grafting. The incidence of isolated coronary artery bypass grafting after ST-elevation myocardial infarction decreased over time (9.2% in 2002 vs 5.5% in 2016, Ptrend Conclusions In this nationwide analysis, there has been a decline in the use of isolated coronary artery bypass grafting after ST-elevation myocardial infarction. Isolated coronary artery bypass grafting on day 1 was performed in sicker patients and was associated with higher in-hospital mortality than coronary artery bypass grafting performed on day 3 or more. In the recent cohort, isolated coronary artery bypass grafting on day 2 had similar in-hospital mortality compared with day 3 or more.

Studies have noted racial/ethnic disparities in coronary artery disease intervention strategies. We investigated trends and outcomes of coronary artery disease treatment choice (coronary artery bypass grafting or percutaneous coronary intervention) stratified by race/ethnicity.We queried the National Inpatient Sample for patients who underwent isolated coronary artery bypass grafting or percutaneous coronary intervention (2002-2017). Outcomes were stratified by race/ethnicity (White, African American, Hispanic, Asian). Multivariable logistic regression evaluated associations between race/ethnicity and receiving coronary artery bypass grafting versus percutaneous coronary intervention, in-hospital mortality, and costs.Over the 15-year period, 2,426,917 isolated coronary artery bypass grafting surgeries and 7,184,515 percutaneous coronary interventions were performed. Compared with White patients, African American patients were younger (62 [interquartile range, 53-70] vs 66 [interquartile range, 57-75] years), were more likely to have Medicaid insurance (12.2% vs 4.4%), and had more comorbidities (Charlson-Deyo index, 1.9 ± 1.6 vs 1.7 ± 1.6) (all P .01). After adjustment for patient comorbidities, presence of acute myocardial infarction, insurance status, and geography, African Americans were the least likely of all racial/ethnic groups to undergo coronary artery bypass grafting (odds ratio, 0.76; P .01), a consistent trend throughout the study. African American patients had higher risk-adjusted mortality after coronary artery bypass grafting (odds ratio, 1.09; P .01). Race/ethnicity was not associated with increased mortality after percutaneous coronary intervention. African American patients had higher hospitalization costs for coronary artery bypass grafting (+$5816; P .01) and percutaneous coronary intervention (+$856; P .01) after controlling for confounders.In this contemporary national analysis, risk-adjusted frequency of coronary artery bypass grafting versus percutaneous coronary intervention for coronary artery disease differed by race/ethnicity. African American patients had lower odds of undergoing coronary artery bypass grafting and worse outcomes. Reasons for these differences merit further investigation to identify opportunities to reduce potential disparities.

Introduction There is paucity of data on the outcomes of hospitalization for bicuspid aortic valve (BAV)-related aortopathies. Methods We queried the NIS database (2012–2016) for hospitalizations for elective thoracic aortic repair or acute aortic syndrome (AAS) among those with BAV versus trileaflet aortic valve (TAV). Results Our analysis yielded 38,010 hospitalizations for elective aortic repair, of whom 34.4% had BAV, as well as 81,875 hospitalizations for thoracic AAS, of whom 1.1% had BAV. Hospitalizations for BAV were younger and had fewer comorbidities compared with their TAV counterparts. The number of hospitalizations for BAV during the observational period was unchanged. After propensity matching, elective aortic repair for BAV was associated with lower mortality (0.5% versus 1.7%, odds ratio = 0.28; 95% CI 1.5–0.50, p

Paracrine factors secreted by mesenchymal stem cells (MSCs) have been previously shown to improve cardiac function following acute myocardial infarction (MI). However, cell therapy activates the innate immune response, leading to the rapid elimination of transplanted cells and only short-term therapeutic delivery. Herein, we describe a new strategy to deliver sustained paracrine-mediated MSC therapy to ischemic myocardium. Using an immune evasive, small molecule modified alginate, we encapsulated rat MSC cells in a core-shell hydrogel capsule and implanted them in the pericardial sac of post-MI rats. Encapsulated cells allowed diffusion of reparative paracrine factors at levels similar to non-encapsulated cells in vitro. Encapsulation enabled sustained cell survival with localization over the heart for 2 weeks. The effect of the experimental group on ventricular function and fibrosis was compared with blank (cell free) capsules and unencapsulated MSCs injected into infarcted myocardium. MSC capsules improved post-MI ventricular function ∼2.5× greater than MSC injection. After 4 weeks, post-MI fibrosis was reduced ∼2/3 with MSC capsules, but unchanged with MSC injection. MSC encapsulation with alginate core-shell capsules sustains cell survival and potentiates efficacy of therapy.

Introduction: Preoperative frailty is an independent risk factor for postoperative complications across surgical specialties. Functional mobility such as gait, timed up and go (TUG), and 5 times sit-to-stand (5-STS) are popular preoperative frailty measurements but are not suitable for patients with severe mobility impairment. A wrist-worn sensor-derived frailty index based on an upper-extremity functional test (20-s repetitive elbow flexion-extension task; UEFI) was developed previously; however, its association with functional mobility remained unexplored. We aimed to investigate the predictive power of the UEFI in predicting functional mobility. Methods: We examined correlation between the UEFI and gait speed, TUG duration, and 5-STS duration in 100 older adults (≥ 65 years) using multivariate regression analysis. The UEFI was calculated using slowness, weakness, exhaustion, and flexibility of the sensor-based 20-s repetitive elbow flexion-extension task. Results: The UEFI was a significant predictor for gait speed and TUG duration and 5-STS duration (all R ≥ 0.60; all p < 0.001) with the variance (adjusted R2) of 35–37% for the dependent variables. The multivariate regression analysis revealed significant associations between the UEFI and gait speed (β = −0.84; 95% confidence interval [95% CI] = [−1.19, −0.50]; p < 0.001) and TUG duration (β = 16.2; 95% CI = [9.59, 22.8]; p < 0.001) and 5-STS duration (β = 33.3; 95% CI = [23.6, 43.2]; p < 0.001), found after accounting for confounding variables (e.g., age and fear of falling scale). Conclusions: Our findings suggest that the UEFI can be performed with a wrist-worn sensor and has been validated with other established measures of preoperative frailty. The UEFI can be applied in a wide variety of patients, regardless of mobility limitations, in an outpatient setting.

Background There is a paucity of data on the trends and outcomes of reoperative coronary artery bypass graft ( CABG ) surgery during the current decade in the United States. Methods and Results We queried the National Inpatient Sample database (2002–2016) for all hospitalizations with isolated CABG procedure. We reported the temporal trends and outcomes of reoperative CABG versus primary CABG procedures. The main outcome was in‐hospital mortality. Among 3 212 768 hospitalizations with CABG , 46 820 (1.5%) had reoperative CABG . Over the 15‐year study period, there were no changes in the proportion of reoperative CABG (1.8% in 2002 versus 2.2% in 2016, P tren =0.08), and the related in‐hospital mortality (3.7% in 2002 versus 2.7% in 2016, P trend =0.97). Reoperative CABG was performed in patients with increasingly higher risk profile. Compared with primary CABG , hospitalizations for reoperative CABG were associated with higher in‐hospital mortality (3.2% versus 1.9%, P CABG , the predictors of higher mortality included history of heart failure and chronic kidney disease. Conclusions In this 15‐year nationwide analysis, reoperative CABG procedures were increasingly performed in patients with higher risk profile. In‐hospital mortality rates were relatively low and did not change during the examined period. Compared with primary CABG , reoperative CABG is associated with higher in‐hospital mortality.

Cellular therapy with mesenchymal stem cells (MSCs) shows promise for restoring function after myocardial infarction (MI). However, cellular therapy has yet to be clinically translated, in part because of difficulty in studying how MSCs interact with the post-MI scar microenvironment. This study aimed to design an in vitro model to study MSC behavior in the post-MI scar stiffness microenvironment.Using poly(ethylene glycol)-acrylate (PEG) conjugated to bioactive peptides, rat MSCs were encapsulated in hydrogels of varying stiffnesses and crosslinking densities. Cell viability was assessed through 14 days using calcein and ethidium homodimer staining. To simulate post-MI pro-fibrotic signaling, transforming growth factor-beta (TGFβ) was added to selected cultures. Immunofluorescence and qRT-PCR were used to assess changes in cardiac transdifferentiation or paracrine secretion, two proposed methods of MSCs in cellular therapy.Bioactivated PEG hydrogels with stiffnesses between 1.6 and 151.0 kPa were prepared. Rat MSCs demonstrated up to 71.6% viability after 3 days of encapsulated culture, and survived within the hydrogels up to 14 days. Encapsulation decreased MSC expression of cardiac troponin T and most growth factors, except interleukin-6. Meanwhile, TGFβ caused increased cardiac troponin T expression but decreased secreted factor expression. Varying hydrogel stiffness did not have an effect on cardiac troponin T or secreted factor expression.These findings suggest that a 3D microenvironment hinders two key mechanisms by which MSCs could improve cardiac function after post-MI scar formation, namely cardiac transdifferentiation and secreted factor production. Future studies incorporating MSCs other cell types should broaden understanding of the post-MI scar microenvironment.