Citations

Cardiovascular disease remains the leading cause of morbidity and mortality for women in United States and worldwide. One in 3 women dies from cardiovascular disease, and 45% of women >20 years old have some form of CVD. Historically, women have had higher morbidity and mortality after cardiac surgery. Sex influences pathogenesis, pathophysiology, presentation, postoperative complications, surgical outcomes, and survival. This review summarizes current cardiovascular surgery outcomes as they pertain to women. Specifically, this article seeks to address whether sex disparities in research, surgical referral, and outcomes still exist and to provide strategies to close these gaps. In addition, with the growing population of women of reproductive age with cardiovascular disease and cardiovascular risk factors, indications for cardiac surgery arise in pregnant women. The current review will also address the unique issues associated with this special population.

Background: In Alzheimer’s disease and related disorders (ADRD) research, common outcome measures include cognitive and functional impairment, as well as persons with mild cognitive impairment (pwMCI) and care partner self-reported mood and quality of life. Studies commonly analyze these measures separately, which potentially leads to issues of multiple comparisons and/or multicollinearity among measures while ignoring the latent constructs they may be measuring. Objective: This study sought to examine the latent factor structure of a battery of 12-13 measures of domains mentioned above, used in a multicomponent behavioral intervention (The HABIT® program) for pwMCI and their partners. Methods: Exploratory factor analysis (EFA) involved 214 pwMCI-partner pairs. Subsequent Confirmatory factor analyses (CFA) used 730 pairs in both pre- and post-intervention conditions. Results: EFA generated a three-factor model. Factors could be characterized as partner adjustment (29.9%), pwMCI adjustment (18.1%), and pwMCI impairment (12.8%). The subsequent CFA confirmed our findings, and the goodness-of-fit for this model was adequate in both the pre- (CFI = 0.937; RMSEA = 0.057, p = 0.089) and post-intervention (CFI = 0.942; RMSEA = 0.051, p = 0.430) groups. Conclusion: Results demonstrated a stable factor structure across cohorts and intervention conditions suggesting that three broad factors may provide a straightforward and meaningful model to assess intervention outcome, at least during the MCI phase of ADRD.

Background: The Kansas City Cardiomyopathy Questionnaire (KCCQ) has been psychometrically evaluated in multiple heart failure (HF) populations, but the comparability of its psychometric properties between men and women is unknown. Methods: Data from 3 clinical trials (1 in stable HF with preserved ejection fraction, 1 each in stable and acute HF with reduced ejection fraction) and 1 prospective cohort study (stable HF with reduced ejection fraction), incorporating 6773 men and 3612 women with HF, were used to compare the construct validity, internal and test-retest reliability, ability to detect change, predict mortality and hospitalizations and minimally important differences between the 2 sexes. Interactions of the KCCQ overall summary and subdomain scores by sex were independently examined. Results: The KCCQ-Overall Summary score correlated well with New York Heart Association functional class in both sexes across patients with stable (correlation coefficient: −0.40 in men versus −0.49 in women) and acute (−0.37 in men versus −0.34 in women) HF. All KCCQ subdomains demonstrated concordant relationships with relevant comparison standards with no significant interactions by sex in 19 of 21 of these construct validity analyses. All KCCQ scores were equally predictive and other psychometric evaluations showed similar results by sex: test-retest reliability (intraclass correlation coefficient 0.94 in men versus 0.92 in women), responsive to change (standardized response mean 1.01 in both sexes), as were the minimally important differences and internal reliability. Conclusions: The psychometric properties of the KCCQ, in terms of validity, prognosis, reliability, and sensitivity to change, are comparable in men and women with HF with preserved ejection fraction and HF with reduced ejection fraction.

AbstractThe National Football League Scouting Combine is an annual event held to evaluate football players. The results of the combine are used to identify talent and player potential. Our study aims to examine the relationship between combine drill performance (e.g., speed, power, agility, explosiveness) and career longevity. We performed a retrospective review of The National Football League combine test results for all defensive players from 2005–2015 to determine the association of each player’s combine test results with career longevity. The position that had the most significant associations for 1-year status was linebackers, with weight, 10-yard dash, 20-yard dash, 40-yard dash, broad jump, 3-cone drill, and shuttle being significantly associated with 1-year roster status. The position that had the most significant associations for 5-year status was cornerbacks, with weight, 10-yard dash, 20-yard dash, 40-yard dash, 3-cone drill, and shuttle being significantly associated with 1-year roster status. The least number of significant associations was found for safeties, with no drill being associated with 1-year roster status and only height and shuttle time significantly associated with 5-year career longevity. Our study demonstrates the utility of the combine results to help estimate the career longevity of NFL defensive players.

Objectives: Determine relationships between calcification and cognitive function. Background: Dementia affects over 5.4 million Americans; prevalence will quadruple in the next 50 years. Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, may affect cognitive function through microvascular brain effects. Abdominal aortoiliac calcification (AAC) generally precedes CAC and may provide earlier risk determination. Effects of calcification on cognition have not been studied in African Americans (AA). Methods: The 2008-2011 GENOA CAC cohort consists of AA sibships (n=657, mean age 69 [range 40-98], 74% women, 82% hypertensive) enriched with hypertension from Jackson, MS with computed tomography (CT) Agatston calcification measures. Cognition was assessed in 4 domains: global cognitive function (Mini-Mental State Examination); processing speed (Digit Symbol Substitution and Trail Making A); memory (RAVLT and WAIS-III Incidental Learning); and executive function (Trail Making B). Relationships of cognition (standardized) and calcification (log base 2 scale accounting for skewness) were examined using linear regressions with GEE to account for sibship clustering, adjusting parsimoniously for age, sex, and education. Results: Doublings of CAC were significantly associated with poorer processing speed (ß=-0.049 [-0.072, -0.025] p=0.000) and executive function (ß=-0.037 [-0.070, -0.003] p=0.031) in younger subjects and with poorer global function (ß=-0.0648 [-0.096, -0.020] p=0.000), memory (ß=-0.034 [-0.060, -0.007] p=0.013), and processing speed (ß=-0.051 [-0.076, -0.025] p=0.000) in older subjects. Doublings of AAC were significantly associated with poorer processing speed (ß=-0.0381 [-0.056, -0.020] p=0.000) and executive function (ß=-0.045 [-0.070, -0.020] p=0.000) in younger subjects and poorer processing speed (ß=-0.050 [-0.075, -0.025] p=0.000) in older subjects. Conclusions: Calcification is associated with processing speed in young and old AA with prevalent cardiovascular risk factors and may be differentially associated with other cognitive domains by age. Processing speed in particular may be a domain affected early in the calcification process, warranting further study. This supports existing literature addressing the relationship between calcification and cognitive function in ethnically diverse cohorts. Further studies can focus on the temporal and causal relationships between calcification and cognition across age in AA samples enriched for hypertension to identify predictive factors associated with future cognitive decline.

Dementia affects approximately 5 million people in the United States and cost $183 billion in 2011, with African Americans (AA) experiencing a disproportionate burden of dementia compared to European Americans (EA). Inflammation is considered by many to be a potential mediator in the development of cognitive dysfunction. High sensitivity C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α), increasingly measured by the soluble TNF receptors 1 & 2 (sTNFRI1, sTNFR2), are among the most frequently cited inflammatory markers associated with dementia and are also elevated in vascular disease. Few studies have compared associations of inflammatory markers with cognitive function in EA and AA. We examined the association of CRP, sTNFR1 and sTNFR2 with cognitive function using detailed neuropsychological assessments in the Genetic Epidemiology Network of Arteriopathy (GENOA)-Genetics of Microangiopathic Brain Injury (GMBI) participants, a cohort considered at high risk of vascular disease due to family history (> 2 individuals in sibships with hypertension at age <60 years) and high prevalence rates of hypertension (74%), diabetes (27%), and obesity (51%). Cognitive function was measured across 5 cognitive domains: global cognitive function, processing speed, language, memory, and executive function. In AA, higher sTNFR2 was associated with poorer performance across all five domains. Higher sTNFR1 and CRP were associated with slower processing speed. In EA, higher sTNFR1 was associated with slower processing speed. CRP and sTNFR2 were not associated with cognitive function in EA. Inflammatory markers in this cohort were associated differentially across cognitive domains in AA and EA, and may reflect racial differences in vascular responses to inflammation.

The immune system consists of two broad branches: innate and adaptive. In the innate branch of the immune system, one will find natural killer (NK) cells, which are responsible for recognizing and killing virally infected or cancerous cells within the human body. Numerous immunodeficiency syndromes arise from mutations in genes that encode proteins essential to NK cells including those involved in NK cell development and effector functions. Among the most important NK cell effector functions is cell‐mediated cytotoxicity. Our lab has been interested in understanding the molecular machinery that regulates this process, in particular those regulated by the small GTP‐binding proteins of the Rho family. With this in mind, the ArhGAP12 protein, which functions as a GTPase activating protein for members of the Rho family, was tested in NK cells to see if it had an effect on cytotoxicity. Significantly, knockdown of ArhGAP12 in NK cells resulted in diminished NK cell‐mediated cytotoxicity. In addition, we found that ArhGAP12 is tyrosine phosphorylated following stimulation through the NKG2D+2B4 activating receptors, indicating that it is linked to this important signaling pathway. As ArhGAP12 is a multi‐modular signaling protein containing a src‐homology 3 (SH3), WW, pleckstrin homology (PH), and GAP domains, we performed proteomics to identify potential interacting partners using the SH3 domain as bait. We found that ArhGAP12 interacts strongly with multiple regulators of F‐actin dynamics including WAVE2, WASP, Evl and VASP. Taken together, these results suggest that ArhGAP12 is linked to activating receptors on NK cells, associates with F‐actin regulators, and is involved in NK cell‐mediated cytotoxicity. Support or Funding Information Mayo Clinic Graduate School of Biomedical Sciences SURF Program and the R01 grant AI120949 to D.D.B. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Drug interactions are common and can affect patient outcomes. Drugs that undergo emergency approval have less preapproval drug testing to identify potential interactions. Tramadol is an effective pain medication prodrug with a complex mechanism of action that requires extensive metabolism. Remdesivir is an antiviral medication given emergency approval to treat hospitalized patients with COVID-19 infections. Remdesivir is also a nucleotide analogue prodrug that undergoes intracellular metabolic conversions to its active metabolite. We discuss the case of a hospitalized patient in the United States diagnosed with COVID-19 pneumonia who developed acute pain crisis secondary to a drug–drug interaction between tramadol and remdesivir, and we propose a possible mechanism of interaction.