Sex-based Differences In Clinical Outcomes Research Articles

Abstract 265: Sex-Based Differences in Clinical Outcomes of Out-of-Hospital Cardiac Arrest Patients

Introduction: Historically, studies have shown lower overall survival rates for women following out of hospital cardiac arrests (OHCA). Despite advancements in resuscitation care over recent years, it is not clear if sex-based differences in inpatient mortality and postresuscitation outcomes have improved. Aims: We aim to investigate if gender disparities still exist in the clinical outcomes of OHCA patients. Methods: A national cohort of patients primarily hospitalized for cardiac arrest was identified using the 2019 National Inpatient Sample database. The study cohort was divided into male and female populations. The primary outcome was inpatient mortality. Secondary endpoints assessed length of stay and discharge to home rates (as a surrogate to functional status on discharge). Results: A total of 28,890 admissions were identified during the study period. Of them, 63.6% (n = 18,365) were males and 36.4% (n = 10,510) were females. The overall unadjusted inpatient mortality rate was 52.2% (n = 15,065) and was lower in females than males [48% (n = 5,040) vs 54.6% (n = 10,025), p < 0.001]. However, after adjusting for potential confounders in Table 1, the female sex was associated with higher adjusted inpatient mortality (aOR 1.085, 95% CI 1.023-1.150, p = 0.007). The average LOS for those who survived to hospital discharge was 5.0 days (IQR 2-10) and was similar between both groups (p = 0.703). Of those who survived to hospital discharge, disposition to home was significantly higher in males (49.3%, n = 4,940) than in females (41.3%, n = 2,080), (p < 0.001). Conclusions: Female sex remains an independent predictor of inpatient mortality in patients admitted with OHCA. Discharge to home after successful resuscitation was lower in females than males, suggestive of worsened functional status on discharge.

Sex Differences in the Clinical Outcomes of Patients With Takotsubo Stress Cardiomyopathy: A Meta-Analysis of Observational Studies

BackgroundThe incidence of takotsubo stress cardiomyopathy (TSCM) in males is low compared to females. Sex-based differences in clinical outcomes of TSCM are not well characterized. The aim of this meta-analysis was to analyze whether sex-based differences are observed in TSCM clinical outcomes. MethodA comprehensive literature search of Pubmed, Embase, Cochrane Library database, and Web of Science was performed from inception to June 20, 2022, for studies comparing the clinical outcomes between males versus females in TSCM. The primary outcome of interest was in-hospital all-cause mortality and cardiogenic shock. The secondary outcomes were cardiovascular mortality, receipt of mechanical ventilation, intra-aortic balloon pump, and occurrence of ventricular arrhythmia, and left ventricular thrombus. A random-effects model was used to calculate the risk ratios (RR) and confidence intervals (CI). Heterogenicity was assessed using the Higgins I2 index. ResultsTwelve observational studies involving 51,213 patients (4,869 males, and 46,344 females) were included in the meta-analysis. Male sex was associated with statistically significant higher in-hospital all-cause mortality when compared to females in patients with TSCM (RR 2.17; 95% CI 1.77–2.67; P < 0.001) The rate of cardiogenic shock was significantly higher in males with TSCM as compared to females (RR 1.66; 95% CI 1.29-2.12; P < 0.001). ConclusionOur meta-analysis showed a difference in the clinical outcomes of TSCM between men and women. Males sex was associated with a two-fold greater in-hospital all-cause mortality risk compared to female sex. The higher mortality risk associated with male sex deserves further study, and particularly whether it represents later recognition of the condition and disparities in treatments.

Gender disparities in patients with aortoiliac disease requiring open operative intervention

ObjectivePeripheral artery disease is known to affect males and females in different proportions. Disparate surgical outcomes have been quantified after endovascular aortic aneurysm repair, arteriovenous fistula creation, and treatment of critical limb ischemia. The aim of this study is to objectively quantify the sex differences in outcomes in patients undergoing open surgical intervention for aortoiliac occlusive disease. MethodsPatients were identified in the aortoiliac occlusive disease Vascular Quality Initiative database who underwent aorto-bifemoral bypass or aortic thromboendarterectomy as determined by Current Procedural Terminology codes between 2012 and 2019. Patients with a minimum of 1-year follow-up were included. Risk differences (RDs) by sex were calculated using a binomial regression model in 30-day and 1-year incidence of mortality and limb salvage. Additionally, incidence of surgical complications including prolonged length of stay (>10 days), reoperation, and change in renal function (>0.5 mg/dl rise from baseline), were recorded. Inverse probability weighting was used to standardize demographic and medical history characteristics. Multivariate logistic regression models were employed to conduct analyses of the before mentioned clinical outcomes, controlling for known confounders. ResultsOf 16,218 eligible patients from the VQI data during the study period, 6538 (40.3%) were female. The mean age, body mass index, and race were not statistically different between sexes. Although there was no statistically significant difference detected in mortality between males and females at 30 days postoperatively, females had an increased crude 1-year mortality with an RD of 0.014 (95% confidence interval, 0.01-0.02; P value < .001. Males had a higher rate of a postoperative change in renal function with an RD of −0.02 (95% confidence interval, −0.03 to −0.01; P < .001). ConclusionsAlthough there was no sex-based mortality difference at 30 days, there was a statistically significant increase in mortality in females after open aortoiliac intervention at 1 year based on our weighted model. Male patients are statistically significantly more likely to have a decline in renal function after their procedures when compared with females. Postoperative complications including prolonged hospital stay, reoperation, and wound disruption were similar among the sexes, as was limb preservation rates at 1 year. Further studies should focus on elucidating the underlying factors contributing to sex-based differences in clinical outcomes following aortoiliac interventions.

Sex-Based Differences in Clinical Outcomes of Stroke Related to LVAD

<h3>Purpose</h3> Sex-based differences among patients with left ventricular assist devices (LVAD) having stroke are uncertain. We aimed to compare demographic and clinical characteristics, inpatient outcomes, and measures of health care utilization among men and women who had stroke while undergoing LVAD implantation. <h3>Methods</h3> We analyzed the National Inpatient Sample from 2009 and 2019) to identify patients with stroke while on LVAD utilizing ICD Codes. The data were weighted to reflect national estimates. Outcomes of interest include inpatient mortality, clinical complications, length of stay (LOS), and inflation-adjusted care costs among men vs. women. <h3>Results</h3> A total of 2192 hospitalizations (556 females and 1636 males) were included in this analysis. Most strokes occurred in men vs. women (75% vs. 25%). Women patients were younger (51 y vs. 59 yr); Black women had a higher likelihood of stroke than Black men (32.4% vs. 15.6%). Men had a higher burden of cardiometabolic comorbidities (hypertension, diabetes, ischemic heart disease) than women. While there were no significant differences regarding ischemic stroke, women had higher odds of hemorrhagic stroke than men (1.49 [CI: 1.02-2.18]). Between 2010 and 2019, stroke rates have significantly increased among men, while the trend remained stable in women (<b>Figure</b>). There was no significant difference in all-cause mortality or clinical complications (cardiac arrest, invasive mechanical ventilation, pressors, dialysis). <h3>Conclusion</h3> In this national analysis, men had a higher comorbidity burden, translating into worsening stroke trends over the last 10 years than women with LVAD and stroke. In contrast, women were younger, exhibited racial disparities, and had a higher risk of hemorrhagic stroke. A deeper understanding of factors influencing sex-related outcomes may explain diverging trends among men and women.

Sex differences in high-risk but indicated coronary interventions (CHiP): National report from British Cardiovascular Intervention Society Registry.

To assess sex-based differences in clinical outcomes following complex and high-risk but indicated percutaneous coronary intervention (CHiP). CHiP is increasingly common in contemporary percutaneous coronary intervention (PCI) practice. Data on sex differences in the type of CHiP procedures undertaken or their associated clinical outcomes are limited. Patients with stable coronary artery disease who underwent CHiP between January 1, 2006, and December 31, 2017, were included. All procedures were stratified by sex. Multivariate logistic regression analyses were performed to investigate the sex-specific adjusted odds ratios (aOR) of in-hospital outcomes. Out of 424,290 PCI procedures, 141,610 (33.37%) were CHiP procedures. Overall, 32,129 (23%) of CHiP were undertaken in females. Females were older than males (median: 74.8vs. 69.1 years). Males had a higher prevalence of previous myocardial infarction (MI) (44.6% vs. 35.6%) and previous PCI (40% vs. 32.5%). The most common variable observed in female patients undergoing CHiP was age >80 (35.4%), followed by prior coronary artery bypass graft (CABG) (24.3%) and severe coronary calcification (22.6%). In contrast, the most common variable in male patients was prior CABG (36%), followed by chronic thrombus occlusion (CTO) PCI (34.4%) and severe coronary calcification (22%). Females had higher odds (aOR) for mortality (aOR: 1.78, 95% CI: [1.4, 2.2]), bleeding (aOR: 1.99, 95% CI: [1.72, 3.2]), and major adverse cardiovascular and cerebral events (aOR: 1.23, 95% CI: [1.09, 1.38])compared to males. In this national analysis of CHiP procedures over 12 years, there were significant sex differences in the type of CHiP procedures undertaken, with females at increased odds for mortality and in-hospital adverse outcomes.

PATH-16. EVALUATION OF SEX-BASED DIFFERENCES IN CLINICAL OUTCOMES AND TUMOR GENOMICS IN PATIENTS WITH NEWLY DIAGNOSED IDH-WILDTYPE GLIOBLASTOMA RECEIVING CHEMORADIATION

Abstract BACKGROUND We evaluated sex-based differences in clinical outcomes and tumor genomics in patients with newly-diagnosed GBM. METHODS We reviewed 665 IDH-wild type GBM patients with Karnofsky Performance Status (KPS) ≥60 treated at our institution from 2010-2019 including; 585 patients with targeted exome sequencing of 447 cancer associated genes (OncoPanel). Deleterious mutations were defined as homozygous deletions or loss of function mutations of known tumor suppressors (as reported in TCGA, ≥ 3 times in the COSMIC database, or predicted as “damaging” in SIFT and/or “probably damaging” in Polyphen 2) or known oncogenic mutations in proto-oncogenes (reported in TCGA or ≥ 3 times in COSMIC). RESULTS There were 384 (57.7%) males and 281 (42.3%) females. Median OS was 22.5 months for females and 19.3 months for males (hazard ratio [HR] 0.81, 95% CI 1.03-1.48, p = 0.02). On multivariable analysis adjusted for age, KPS ≥90, extent of resection, and MGMT methylation status, female sex (adjusted hazard ratio 0.78, 95% CI [0.64-0.95], p = 0.015) was associated with improved OS. Superior OS in females was observed in MGMT-unmethylated patients (HR 0.69, 95% CI [0.54-0.90], p = 0.005) but not MGMT-methylated patients. Thirteen genes were deleteriously altered in ≥5% of our cohort: CDK4 (12.1% male vs. 7.8% female), CDKN2A (46.5% vs. 45.7%), CDKN2B (41.8% vs. 43.3%), EGFR (34.7% vs. 40.0%, MTAP (18.2% vs. 18.8%), NF1 (11.5% vs. 9.4%), PTEN (28.2% vs. 29.8%), TP53 (28.2% vs. 30.2%), RB1 (5.6% vs. 6.5%), MDM4 (6.2% vs. 5.7%), ATM (5.9% vs. 3.7%), MDM2 (7.4% vs. 4.1%), PIK3R1 (6.2% vs. 4.1%). There were no differences in frequency of mutations in these individual genes between males and females (χ 2 [1, N=585] = 0.05-2.86, p = 0.09-0.86). CONCLUSIONS Female sex is associated with improved survival. We did not identify sex-based differences in deleterious genomic alterations amongst commonly altered genes in GBM.

Evaluation of Sex-Based Differences in Patient Characteristics, Tumor-Related Factors, and Clinical Outcomes in Patients With Newly Diagnosed IDH-Wildtype Glioblastoma Receiving Chemoradiation

While glioblastoma (GBM) is known to have increased incidence in males, recent work has identified possible sex-specific molecular differences that could be associated with improved clinical outcomes for female GBM patients. We evaluated sex-based differences in patient and tumor characteristics, and clinical outcomes in newly diagnosed GBM patients.We reviewed 665 newly diagnosed adult IDH-wild type GBM patients with Karnofsky Performance Status (KPS) ≥60 who were treated at our institution from January 1, 2010 to May 30, 2019. Patient, tumor and treatment details were obtained from the electronic medical record. An unpaired t-test, Fisher's exact test and univariable/multivariable Cox proportional hazards modeling were used to evaluate associations, including progression free survival (PFS) and overall survival (OS).In our GBM cohort, 384 (57.7%) were male and 281 (42.3%) were female. There were no significant differences in age (60.6 years in males vs. 60.0 years in females, P = 0.16), KPS (KPS ≥90 in 46.1% in males vs. 43.4% in females, P = 0.53), extent of resection (gross total resection in 44.8% in males vs. 47.7% in females, P = 0.48), or prevalence of MGMT methylation (37.8% in males vs. 43.4% in females, P = 0.11). There were also no differences in receipt of temozolomide (95.1% of males vs. 95.7% of females, P = 0.71), radiation dose (≥59.4 Gy in 85.2% in males vs. 87.5% in females, P = 0.43), or clinical trial enrollment (24.7% males vs. 21.0% females, P = 0.27). Median OS was 22.5 months for females and 19.3 months for males (hazard ratio [HR] 0.81, 95% CI 1.03-1.48, P = 0.02). On multivariable analysis adjusted for age (adjusted hazard ratio [AHR] 1.04, 95% CI [1.03-1.05], P < 0.001), KPS ≥90 (AHR 0.73, 95% CI [0.60-0.89], P = 0.002), extent of resection (AHR 1.12, 95% CI 0.92-1.37, P = 0.26), and MGMT methylation status (AHR 0.38, 95% CI [0.31-0.47], P < 0.001), female sex (AHR 0.78, 95% CI [0.64-0.95], P = 0.015) was associated with improved OS. Superior OS in females was observed in MGMT unmethylated patients (HR 0.69, 95% CI [0.54-0.90], P = 0.005) but not in MGMT methylated patients (HR 0.85, 95% CI [0.64-1.14], P = 0.28). While age (AHR 1.02, 95% CI [1.02-1.03], P < 0.001), KPS ≥90 (AHR 0.79, 95% CI [0.66-0.95], P = 0.01), and MGMT methylation (AHR 0.40, 95% CI [0.33-0.49], P < 0.001) were associated with PFS, biologic sex was not associated with PFS (AHR 0.94, 95% CI [0.78-1.12], P = 0.49).Female sex was associated with improved survival after adjustment of known clinical covariates in newly diagnosed GBM patients. Further study is necessary to understand biologic mechanism for sex-based differences in clinical outcome given implications for therapy development and clinical trial design.D.D. Shi: None. M. Lim-Fat: None. G.C. Youssef: None. S. Whorral: None. M. Allen: None. D.N. Cagney: None. S. Tanguturi: None. D. Haas-Kogan: Research Grant; Novartis; Cellworks. A.A. Aizer: Research Grant; Varian. Consultant; Novartis. Advisory Board; Seattle Genetics. J. McFaline-Figueroa: None. U.N. Chukwueke: None. E.Q. Lee: None. D.A. Reardon: Research Grant; Celldex, Inovio, Midatech. Consultant; Amgen. Speaker's Bureau; Merck/Schering, Roche/Genentech. Advisory Board; AbbVie, Bristol Myers Squibb, Cavion, Celldex, EMD Serono, Juno Pharmaceuticals, Momenta Pharmaceuticals, Novartis, Novocure, Oxigene, Regeneron, Roche/Genentech, Stemline. L. Nayak: None. W.L. Bi: Research Grant; The Leukemia and Lymphoma Society, NIH/NCI.R. Beroukhim: Independent Contractor; Scorpion Therapeutics. Stock; Scorpion Therapeutics. K.L. Ligon: None. B.M. Alexander: Research Grant; Puma Biotechnology, Eli Lily, Celgene. Stock; Hoffman-La Roche. P.Y. Wen: None. R. Rahman: Research Grant; Project Data Sphere, LLC.

Sex-based differences in clinical outcomes and resource utilization of type 2 myocardial infarction

Abstract Background Sex-based differences in clinical outcomes have been previously well described in type 1 myocardial infarction (MI). However, type 2 MI is common in contemporary practice with scarce data regarding sex-based differences of clinical outcomes and resource utilization. Purpose To examine the association of sex category with clinical outcomes and resource utilization in hospitalizations with type 2 MI. Methods The Nationwide Readmission Database 2018 was queried for hospitalizations within the United States with type 2 MI using The International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code I21.A1. Comorbidities and outcomes were identified using the corresponding ICD-10 codes. Complex samples multivariable logistic and linear regression models were used to determine the association between type 2 MI and outcomes (in-hospital mortality, index length of stay [LOS], hospital costs, discharge to nursing facility, and 30-day all-cause readmissions) in females compared to males with type 2 MI. Results A total of 252,641 hospitalizations [119,783 (47.4%) females and 132,858 (52.6%) males] were included in this analysis. Females with type 2 MI were more likely to be older (72.8 years vs. 69.7 years; P&amp;lt;0.001), admitted on the weekend (26.5% vs. 25.9%; P=0.02), and have a higher prevalence of chronic pulmonary disease (35.6% vs. 32.0%; P&amp;lt;0.001), obesity (17.9% vs. 15.7%; P&amp;lt;0.001), neurological disorders (22.9% vs. 22.3%; P=0.02), deficiency anemias (7.5% vs. 6.6%; P&amp;lt;0.001), and hypothyroidism (22.1% vs. 10.1%; P&amp;lt;0.001) compared to males with type 2 MI. Female with type 2 MI was associated with lower in-hospital mortality, shorter LOS, less hospital costs, and increased nursing home discharge compared to males with type 2 MI. Females and males with type 2 MI had similar rates of 30-day all-cause readmission [Table 1]. Conclusion Among type 2 MI hospitalizations, females have lower in-hospital mortality, less hospitalization cost, shorter LOS, but increased rates of nursing home discharge compared to males. Thirty-day all-cause readmission was similar between males and females with type 2 MI. Funding Acknowledgement Type of funding sources: None.

Sex-based differences in clinical outcomes and resource utilization of type 2 myocardial infarction

BackgroundSex-based differences in clinical outcomes have been previously well described in type 1 myocardial infarction (T1MI). However, type 2 myocardial infarction (T2MI) is more common in contemporary practice, with scarce data regarding sex-based differences of outcomes. MethodsThe Nationwide Readmission Database 2018 was queried for hospitalizations with T2MI as a primary or secondary diagnosis. Complex samples multivariable logistic and linear regression models were used to determine the association between T2MI and outcomes (in-hospital mortality, index length of stay [LOS], hospital costs, discharge to nursing facility, and 30-day all-cause readmissions) in females compared to males with T2MI. ResultsA total of 252,641 hospitalizations [119,783 (47.4%) females and 132,858 (52.6%) males] were included in this analysis. Females with T2MI was associated with lower in-hospital mortality (adjusted odds ratio [aOR] 0.92; 95% confidence interval [CI] 0.88–0.96; P < 0.001), shorter LOS (adjusted parameter estimate [aPE] −0.28; 95% CI −0.38–0.17; P < 0.001), less hospital costs (aPE -1510.70; 95% CI −1916.04–1105.37; P < 0.001), and increased nursing home discharges (aOR 1.08; 95% CI 1.05–1.12; P < 0.001) compared to males with T2MI. Females and males with T2MI had similar rates of 30-day all-cause readmission (aOR 1.00; 95% CI 0.97–1.04; P = 0.841). ConclusionAmong T2MI hospitalizations, females have lower in-hospital mortality, hospitalization costs, shorter LOS, and increased rates of nursing home discharge compared to males. Although statistically significant, the clinical significance of these small differences are unknown and require future studies.

Sex-Based Differences in Clinical Outcomes After Arthroscopic Anterior Shoulder Stabilization: Results at 5-Year Follow-up.

Background:The influence of patient sex on clinical outcomes after arthroscopic anterior shoulder stabilization is unclear.Purpose:To investigate sex-based differences in clinical outcomes after arthroscopic anterior shoulder stabilization.Study Design:Cohort study; Level of evidence, 3.Methods:A retrospective study was conducted among 76 patients who underwent arthroscopic anterior shoulder stabilization from February 2010 to December 2017. The patients were grouped by sex. The recurrence rate of instability was compared, as were pre- and postoperative pain scores, functional outcome scores, and active range of motion (ROM). Postoperative magnetic resonance imaging (MRI) was also performed for structural assessment of the glenohumeral joint.Results:No significant difference was found in the recurrence rate between female and male patients (13.3% vs 14.8%; P ≥ .999; risk ratio, 1.107 [95% CI, 0.266-4.597]). Compared with male patients, female patients had a significantly lower preoperative Constant score (94.4 ± 6.4 vs 85.4 ± 11.1; P = .002), forward flexion (173.8° ± 10.7° vs 154.0° ± 33.8°; P = .011), abduction (171.0° ± 18.4° vs 142.7° ± 39.9°; P = .001), and external rotation (76.6° ± 21.6° vs 67.7° ± 20.4°; P = .037). Postoperatively, female patients had a significantly lower Simple Shoulder Test score compared with men (8.8 ± 1.9 vs 10.3 ± 1.6; P = .005). The mean changes from pre- to postoperative Rowe score (43.6 ± 21.4 vs 31.5 ± 19.8; P = .044), Constant score (9.9 ± 8.9 vs 0.8 ± 8.1; P = .002), forward flexion (24.0 ± 36.2 vs 4.2 ± 10.9; P = .013), abduction (36.0 ± 38.3 vs 7.6 ± 18.4; P < .001), and external rotation (19.7 ± 21.3 vs 6.7 ± 26.2; P = .023) in female patients were significantly higher than those in the men. There were no sex-based differences on any MRI parameter measured.Conclusion:Female patients had a similar recurrence rate as that of male patients after arthroscopic anterior shoulder stabilization. Most postoperative clinical outcome measures showed no significant difference between the sexes. Despite worse preoperative values, more significant improvements in postoperative shoulder function and active ROM were seen in women.

Sex Differences in Clinical Outcomes Following Surgical Treatment of Femoroacetabular Impingement.

Sex-based differences in clinical outcomes following surgical treatment of femoroacetabular impingement remain largely uncharacterized; this prospective, multicenter study evaluated these differences both directly and adjusted for covariates. Hips undergoing surgical treatment of symptomatic femoroacetabular impingement were prospectively enrolled in a multicenter cohort. Patient demographics, radiographic parameters, intraoperatively assessed disease severity, and history of surgical procedures, as well as patient-reported outcome measures, were collected preoperatively and at a mean follow-up of 4.3 years. A total of 621 (81.6%) of 761 enrolled hips met the minimum 1 year of follow-up and were included in the analysis; 56.7% of analyzed hips were female. Univariate and multivariable statistics were utilized to assess the direct and adjusted differences in outcomes, respectively. Male hips had greater body mass index and larger α angles. Female hips had significantly lower preoperative and postoperative scores across most patient-reported outcome measures, but also had greater improvement from preoperatively to postoperatively. The preoperative differences between sexes exceeded the threshold for the minimal clinically important difference of the modified Harris hip score (mHHS) and all Hip disability and Osteoarthritis Outcome Score (HOOS) domains except quality of life. Preoperative sex differences in mHHS, all HOOS domains, and Short Form-12 Health Survey physical function component score were greater than the postoperative differences. A greater proportion of female hips achieved the minimal clinically important difference for the mHHS, but male hips were more likely to meet the patient acceptable symptom state for this outcome. After adjusting for relevant covariates with use of multiple regression analysis, sex was not identified as an independent predictor of any outcome. Preoperative patient-reported outcome scores were a strong and highly significant predictor of all outcomes. Significant differences in clinical outcomes were observed between sexes in a large cohort of hips undergoing surgical treatment of femoroacetabular impingement. Despite female hips exhibiting lower baseline scores, sex was not an independent predictor of outcome or reoperation. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Trends in sex-based differences in outcomes following coronary artery bypass grafting in the United States between 2004 and 2015

BackgroundThe present study sought to examine the trends of sex-based differences in clinical outcomes after coronary artery bypass grafting (CABG), an area in which the current evidence remains limited. MethodsAll US adults hospitalized for first-time isolated CABG in the National Inpatient Sample database between 2004 and 2015 were included, stratified by sex. Multivariable regression analysis examined the adjusted odds ratios (OR) of postoperative in-hospital complications in females versus males. Trend analyses of sex-based differences in in-hospital post-operative complications over the study period were performed. ResultsOverall, 2,537,767 CABG procedures were analyzed, including 27.9% (n = 708,459) females. Female sex was associated with an increase in adjusted odds of all-cause mortality (OR 1.43 95% CI 1.40, 1.45), stroke (OR 1.34 95% CI 1.32, 1.37) and thoracic complications (OR 1.28 95% CI 1.27, 1.29) and lower odds of all-cause bleeding (OR 0.87 95% CI 0.86, 0.89) compared to males. Trend analysis revealed these sex differences to be persistent for mortality, stroke and thoracic complications (ptrend = non-significant) but eliminated for bleeding over the study period (ptrend < 0.001). ConclusionDespite technical advances over the 12-year period, worse post-operative outcomes including death, stroke, and thoracic complications have persisted in female patients after CABG. These findings are concerning and underscore the need for risk reduction strategies to address this disparity gap.

105. Sex-based differential response in rhBMP-2-mediated spinal fusion in vivo

BACKGROUND CONTEXT Sex-based differences in clinical outcomes for spinal fusion have been investigated with conflicting results. Estrogen is well known to have a major influence on bone and interacts with the recombinant human bone morphogenetic protein-2 (rhBMP-2) pathway, yet literature investigating the potential but unsubstantiated sex-dependent differential response to rhBMP-2 spine fusion is scarce. Clarifying whethera sex-based differential bone regenerative response could improve and personalize patient care in the setting of spine and other orthopedic procedures requiring bone healing. Herein, we investigated whether there is a sex-dependent bone regenerative response to rhBMP-2 in a rat spinal fusion model. PURPOSE The purpose of this study was to assess and validate the presence and extent of the sex differences in bone response to rhBMP-2 in vivo. STUDY DESIGN/SETTING Pre-clinical. PATIENT SAMPLE Male and female Sprague-Dawley rats, ages 12-16 weeks. OUTCOME MEASURES Radiography, fusion scoring, microCT. METHODS Twenty-eight Sprague-Dawley male and female rats underwent L4-L5 posterolateral fusion with bilateral placement of an absorbable collagen sponge loaded with 10 μg of rhBMP-2/animal (INFUSE™; 5 μg/implant; N=14/group). Bone regenerative response and fusion were assessed eight weeks postoperatively via radiography and blinded manual palpation, where each specimen was assigned a score of 0 (unfused, no bridging bone), 1 (unilaterally fused, L4-L5 bridging), or 2 (bilaterally fused). MicroCT imaging (N=3/group) was used for microarchitectural analysis to evaluate new bone, the bone volume fraction, and trabecular thickness. RESULTS As expected at this dose, radiography and manual palpation showed 100% fusion rates for both sexes. Fusion scores, though, were significantly different with females having a lower fusion score (female: 1.26±0.31 vs males: 1.55±0.33, *p=0.001). Radiography showed noticeably smaller fusion mass volumes in females vs males, but the fusion mass was found to be less compressible on manual palpation in females relative to males. MicroCT evaluation showed significant differences in females vs males, with females having significantly lower new bone volumes (female: 26.591±3.871 mm3 vs male: 37.595±11.174 mm3, *p=0.046), but a significantly higher bone volume fraction (female: 0.266±0.116 vs male: 0.126±0.064, *p=0.028) and significantly greater trabecular thickness (female: 0.198±0.016 mm vs male: 0.178±0.014 mm, *p=0.041). CONCLUSIONS This study shows that there may indeed be a sex-based difference in bone regeneration induced by rhBMP-2. We showed that female rats have higher quality, but less volume of new bone formation compared to males. Future work will evaluate the extent of this distinction, especially at sub-therapeutic doses of the growth factor, and will investigate the interplay between the BMP-2 pathway and sex hormones in bone regenerative outcomes. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.

SEX DIFFERENCES IN QUADRICEPS STRENGTH AMONG ADOLESCENTS WITHIN 1 YEAR OF ACL RECONSTRUCTION

Background Female patients with ACLR are 40% less likely to return to preinjury levels of sport after subsequent ACLR when compared to their male counterparts. Additionally, 24-30% of young female athletes who do return to sport will go on to experience a second ACL injury to the ipsilateral or contralateral knee within 2 years of ACLR. Despite these findings, sex-based differences in clinical outcomes following ACLR are not currently well understood within the adolescent population. Involved limb knee extension weakness, contralateral limb knee extension weakness, and between limb strength asymmetry persist months to years following ACLR among adolescent patients. Improvements in unilateral and symmetry-based measures of knee extension strength during and after the rehabilitation process have been linked to improved patient-reported knee related function, lower extremity functional performance, and decreased risk of subsequent ACL injury among individuals with recent ACLR. Currently, there is a lack of evidence describing the role that sex plays in persistent quadriceps weakness. Therefore, the purpose of this study was to investigate the effects of patient sex on unilateral and symmetry-based measures of knee extension strength, and patient-reported knee function among adolescent individuals with ACL reconstruction (ACLR) within the first year after surgery. Methods: Fifty-two male participants (age = 16.8±1.3 years, BMI = 25.6±5.6 kg/m2, time since surgery = 6.3±1.4 months) and 66 female participants (age = 16.7±1.4 years, BMI = 23.9±3.9kg/m2, time since surgery = 6.8±1.7 months) with unilateral ACLR, 4-12 months prior to enrollment were recruited for this multi-site cross-sectional study. Participants completed bilateral knee extension maximal voluntary isometric contraction (MVIC) torque assessments using a multimodal dynamometer with continuous verbal encouragement from the tester and visual feedback on a nearby monitor. Peak knee extension MVIC torque was identified for each of 3 trials and was normalized to body mass (Nm/kg). Limb symmetry indices were also calculated by dividing the MVIC torque obtained for the involved limb by the MVIC torque obtained for the contralateral limb. Participants also completed the International Knee Documentation Committee (IKDC) Subjective Knee Form to assess patient-reported knee function. Sex-based comparisons of quadriceps strength outcomes and IKDC score were made using separate ANCOVAs where time since surgery was utilized as a covariate. Cohen’s d effect sizes and 95% confidence intervals (CI95) were calculated to assess the magnitude of sex difference for all outcome measures. Odds ratios and CI95 were also calculated to assess the odds of an adolescent female achieving clinical threshold for acceptable involved limb quadriceps strength (MVIC = 3.0 Nm/kg), quadriceps limb symmetry (LSI = 90.0%), and patient-reported knee function (IKDC = 90.0). Results: The involved limb (male = 2.08±0.95 Nm/kg, female = 1.69±0.63 Nm/kg, p = 0.01, d = -0.50, CI95 = -0.13 to -0.87) and contralateral limbs (male = 2.75±0.75 Nm/kg, female = 2.31±0.64 Nm/kg, p = 0.001, d = -0.64, CI95 = -0.26 to -1.01) of male participants were stronger when compared to female participants but limb symmetry (male = 74.7±22.6%, female = 74.7±24.6%, p = 0.95, d = 0.00, CI95 = 0.36 to -0.36) and IKDC score (male = 84.4±16.1, female = 79.4±13.7, p = 0.08, d = -0.34, CI95 = 0.03 to -0.71) was not significantly different between the sexes. Male participants were 5.66 times (CI95 = 1.46 to 21.87) more likely to meet the clinical threshold for acceptable involved limb quadriceps strength and 3.52 times (CI95 = 1.54 to 8.05) more likely to report acceptable knee related function. The likelihood of achieving clinically acceptable limb symmetry was not significantly different between the sexes (OR = 1.17, CI95 = 0.48 to 2.83). Conclusion/Significance: Adolescent female patients may experience significantly worse involved limb and contralateral quadriceps weakness when compared to adolescent male patients despite displaying equally poor limb symmetry and patient-reported knee function during the first 12 month following surgery. Given the importance of involved limb quadriceps strength as a predictor of patient-reported function and movement quality, clinicians should incorporate patient education regarding the importance of quadriceps function and recommend progressive lower extremity loading when implementing patient-centered rehabilitation plans that promote safe return to healthy levels of physical activity following ACLR.

Gender-related differences in antiplatelet treatment patterns and outcome: Insights from the GReekAntiPlatElet Registry.

Data on the clinical impact of gender in "real-life" patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), receiving clopidogrel, prasugrel, or ticagrelor are limited. We aimed to investigate sex-based differences in clinical outcome of those patients. In a prospective, observational, multicenter, cohort study, 2047 patients were recruited into the GReekAntiPlatElet (GRAPE) Registry and were followed up until 1year for major adverse cardiovascular events (MACE, composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and bleeding events (Bleeding Academic Research Consortium [BARC] classification). Women (n=360, 17.6%) were more frequently administered clopidogrel (rather than novel P2Y12 receptor antagonists) at PCI hospital and at discharge. MACE occurred in 9.2% and 8.1% of women and men, respectively and did not differ significantly by gender. Rate of observed bleeding BARC any type was 57.2% and 44.4% in women and men, respectively. Following adjustment, only differences in BARC any type and BARC type 1 events remained significant, with higher rates observed between women: hazard ratio (95% confidence interval) 1.51 (1.23-1.85) and 1.58 (1.27-1.96), respectively, P<.001 for both. In a contemporary "real-life" cohort of patients with ACS treated with PCI and focusing on antiplatelet treatment 1-year ischemic outcome does not differ by gender, while women do present more frequently not actionable bleeding events.