Search

Introduction:Women have historically been underrepresented in cardiothoracic (CT) surgery. Here, we delineate the current state of gender disparities in academic CT surgery.Methods:All CT surgery faculty at the 72 accredited U.S. CT surgery training programs in 2018 were included. Data regarding subspecialization, training, practice history, and publications were gathered from public sources including department websites, CTSNet, and Scopus.Results:In total, 952 surgeons (31.5% thoracic, 52.9% cardiac, 15.5% congenital) were identified. Women accounted for 8.9% of the study population (12.7% of thoracic, 6.9% of cardiac, 8.1% of congenital surgeons). The median number of CT surgeons per institution was 12 [IQR 9-15.8], with a median of 1 woman [IQR 0-2] (Fig. 1). Twenty-two programs had zero women on faculty. Among women faculty, 4.7% were Clinical Instructors, 49.4% were Assistant Professors, 25.8% were Associate Professors, and 16.4% were Full Professors (vs 1.7%, 35.5%, 25.3%, and 33.3% among men, p=0.006). Women and men who became Full Professors did so in a comparable amount of time (women 25.1?4.0 yrs from medical school matriculation, men 26.9?5.7 yrs, p=0.287). Women authored significantly fewer total (22 [7-56] vs 48 [18-120], p<0.001), first author (5 [1.5-15] vs 11 [4-25], p<0.001) and last author (2 [0-6.5] vs 6 [1-23], p<0.001) publications than men. The difference in first author publications was non-significant after the first 4 years of practice, while the difference in total and last author publications was significant until after 25 years of practice. H-index, a metric of research impact, did not differ significantly between men and women.Conclusions:Gender disparities persist in CT surgery, particularly in leadership and academic roles. The increased number of women in junior positions reflects a trend toward their better representation in the field. Efforts should be made to support women as they transition into senior academic roles.

Introduction:Current interventions of coronary artery disease do not address residual microvascular perfusion deficits after myocardial infarction, leading to ischemic cardiomyopathy. Stromal cell-derived factor 1-alpha (SDF) augments neo-vascularization by activating C-X-C chemokine receptor type 4 (CXCR4), mobilizing endothelial progenitor cells (EPC).Hypothesis:A custom-engineered CXCR4 agonist would result in chemotaxis of EPCs, increasing neovascularization, microvascular perfusion, and ventricular function.Methods:Native SDF:CXCR4 conformations were constructed using the relax protocol from Rosetta, the SDF N-terminal tail was rebuilt using RosettaRemodel. The converged structure was used as a template to create a library of 47,486 potential CXCR4 agonists using Schrodinger (v2019-2). Each CXCR4:peptide complex was then scored and ranked based on relative binding energies calculated using a Generalized Born Solvation method. Multivariate ranking was used to rank and select top peptides. Interactions with key receptor residues were studied for top peptides with 100ns molecular dynamics simulations (MD). A final peptide was then chosen and synthesized using solid phase protein synthesis. Modified Boyden assays were performed to assess chemokine response via EPC migration.Results:A 44-amino acid peptide (?-mutant 292) was found to have superior binding energy (?E) to CXCR4. MD confirmed binding to the same docking site on CXCR4, with similar conformations of the active peptide motifs as SDF:CXCR4. In vitroEPC migration assays showed that even at small concentrations, the novel peptide was supratherapeutic to SDF (p-values 0.004 and 0.008, respectively, at 0.625 nanomolar concentration; Figure 1).Conclusions:Computational protein modeling was used to successfully engineer a novel agonist to CXCR4, that was shown to be supratherapeutic compared to native SDF in activating EPCs, which is key to microvascular regeneration.