Impact Of Sex Differences Research Articles

Abstract 13561: Sex-Based Differences in Outcomes for Transcatheter Based Intervention: Insight From the National Inpatient Sample

Introduction: Transcatheter aortic valve replacement (TAVR) is now firmly established as an alternative to surgical aortic valve replacement in the treatment of aortic stenosis in all risk groups. Sex differences may influence procedural outcomes. Our study aims to contribute further data on the impact of sex differences on patients who underwent TAVR using a nationally representative sample. Methods: Data were obtained from the combined National Inpatient Sample (NIS) 2016 and 2018. The NIS was searched for hospitalization for TAVR procedure using the ICD-10 PCS codes. Patients undergoing the TAVR procedure were then stratified by sex into male and female sex. Outcomes of interest include in-patient mortality, length of stay (LOS), Total hospital charge (THC), Post procedural complication, pacemaker implantation, cardiogenic shock, ischemic stroke, intra-aortic balloon pump insertion, post-procedural infection, and post-procedural kidney disease. Multivariate logistic and linear regression analysis was used accordingly to adjust for possible confounders. Results: There were over 105 million discharges in the combined 2016-2018 NIS database. The database contained hospitalizations for adult patients (aged ≥ 18 years) who were hospitalized for the TAVR procedure. Females had more TAVR procedures compared to men (54.1% vs 45.9%, P<0.0001 and were older than men who underwent TAVR. There was similar in-patient mortality in both group (1.7% vs 1.2%, AOR: 1.21, P=0.072, 95% CI 0.98- 1.51). Women had lower rate of cardiogenic shock (AOR: 0.78, P=0.009, 95% CI 0.65-0.94), pacemaker implantation (AOR: 0.84, P=0.001, 95% CI 0.76-0.93) compared to men. Women had higher odds of post-procedural complications compared to men (AOR: 1.18, P=0.001, 95% CI: 1.07-1.29. There were similar rates of ischemic stroke (AOR: 1.23, P=0.502, 95% CI 0.66-2.31), postprocedural kidney injury (AOR: 1.65, P=0.278, 95% CI 0.66-4.12) in women compared to men. In addition, there was no difference in total charge and length of hospital stay. Conclusions: Women had increased post-procedural complications compared to men in regard to TAVR, however, mortality is similar in both groups. There was no difference in resource utilization and length of stay between both sexes.

Vascular contributions to cognitive impairment/dementia in diabetes: role of endothelial cells and pericytes.

Vascular contributions to cognitive impairment/dementia (VCID) are a leading cause of dementia, a known neurodegenerative disorder characterized by progressive cognitive decline. Although diabetes increases the risks of stroke and the development of cerebrovascular disease, the cellular and vascular mechanisms that lead to VCID in diabetes are yet to be determined. A growing body of research has identified that cerebrovascular cells within the neurovascular complex display an array of cellular responses that impact their survival and reparative properties, which plays a significant role in VCID development. Specifically, endothelial cells and pericytes are the primary cell types that have gained much attention in dementia-related studies due to their molecular and phenotypic heterogeneity. In this review, we will discuss the various morphological subclasses of endothelial cells and pericytes as well as their relative distribution throughout the cerebrovasculature. Furthermore, the use of diabetic and stroke animal models in preclinical studies has provided more insight into the impact of sex differences on cerebral vascularization in progressive VCID. Understanding how cellular responses and sex differences contribute to endothelial cell and pericyte survival and function will set the stage for the development of potential preventive therapies for dementia-related disorders in diabetes.

Ultrasonic Vocalizations in Adult C57BL/6J Mice: The Role of Sex Differences and Repeated Testing.

Ultrasonic vocalizations (USVs) are a major tool for assessing social communication in laboratory mice during their entire lifespan. At adulthood, male mice preferentially emit USVs toward a female conspecific, while females mostly produce ultrasonic calls when facing an adult intruder of the same sex. Recent studies have developed several sophisticated tools to analyze adult mouse USVs, especially in males, because of the increasing relevance of adult communication for behavioral phenotyping of mouse models of autism spectrum disorder (ASD). Little attention has been instead devoted to adult female USVs and impact of sex differences on the quantitative and qualitative characteristics of mouse USVs. Most of the studies have also focused on a single testing session, often without concomitant assessment of other social behaviors (e.g., sniffing), so little is still known about the link between USVs and other aspects of social interaction and their stability/variations across multiple encounters. Here, we evaluated the USVs emitted by adult male and female mice during 3 repeated encounters with an unfamiliar female, with equal or different pre-testing isolation periods between sexes. We demonstrated clear sex differences in several USVs' characteristics and other social behaviors, and these were mostly stable across the encounters and independent of pre-testing isolation. The estrous cycle of the tested females exerted quantitative effects on their vocal and non-vocal behaviors, although it did not affect the qualitative composition of ultrasonic calls. Our findings obtained in B6 mice, i.e., the strain most widely used for engineering of transgenic mouse lines, contribute to provide new guidelines for assessing ultrasonic communication in male and female adult mice.

Impact of gender differences on hemostasis in patients after coronary artery bypass grafts surgeries in the context of tranexamic acid administration

BackgroundSex differences present in the blood management of patients after coronary artery bypass grafts (CABG) surgeries. Tranexamic acid (TXA) performed well in maintaining hemostasis during and after surgeries. However, the impact of sex differences on blood control after CABG in patients who received TXA was not investigated.MethodsOverall, 29,536 patients undergoing CABG with TXA administration from 2009 to 2019 in our hospital were included. Propensity score matching was performed. Finally, 6808 males and 6808 females were matched based on 23 covariates.ResultsFemale patients had a 0.36-fold lower incidence of reoperations due to major hemorrhage or cardiac tamponade compared to males (1.3% vs. 2.0%, p = 0.001, OR = 0.64, 95%CI = 0.49–0.84). Females had a median of 100 ml less blood loss in 24 h (median 360 vs. 460 ml, p < 0.0001), 150 ml less in 48 h (median 580 vs. 730 ml, p < 0.0001), and 180 ml less in total (median 760 vs. 940 ml, p < 0.0001) than male patients. The red blood cell (RBC) transfusion rate in female was 1.53-fold higher than that in male (33.0% vs. 21.6%, OR = 1.53, 95% CI = 1.43–1.63, p < 0.0001). Females also had higher morbidities than males after CABGs.ConclusionsFemales had less blood loss than males after CABG with the TXA treatment. Females still had a higher RBC transfusion rate after surgery. Morbidities in women were also higher than that in men.

Sex differences in prehospital analgesia in patients presenting with acute coronary syndromes and their association with clinical outcomes.

This study examined if sex differences in prehospital pain scores, opioid administration, and clinical outcomes exist in acute coronary syndrome (ACS) patients. Sex differences persist in ACSpresentation, management, and outcomes. The impact of sex differences on prehospital pain management of ACS with opioids is unknown. Patients presenting with ACS via ambulance (2014-2018) that underwent percutaneous coronary intervention (PCI) were prospectively collected via the Victorian Cardiac Outcomes Registry and Melbourne Interventional Group, linked to the Ambulance Victoria database. The primary outcome was 30-day major adverse cardiac events (MACE). Secondary outcomes were descriptive analyses of prehospital pain score, intravenous morphine equivalent analgesic dosing, plus predictors of MACE and thrombolysis in myocardial infarction (TIMI) 0-1 flow pre-PCI. A total of 10,547 patients were included (female: 2775 [26%]). Opioids were administered to 1585 (57%) females, 5068 (65%) males (p < 0.001). Adjusted 30-day MACE was similar between opioid groups in both sexes (female: odds ratio [OR]: 1.21, confidence interval [CI] 0.82-1.79, p = 0.34; male: OR: 0.89, CI: 0.68-1.16, p = 0.40). Median pain score at presentation was 6 (interquartile range [IQR]: 4, 8) for both sexes. Median opioid dose was 2.5 mg (IQR: 0, 10) in females and 5 mg (IQR: 0, 10) in males (p < 0.001), with similar pain relief achieved. Adjusted rates of TIMI 0-1 pre-PCI were higher in patients administered opioids (female: OR 2.9, CI: 2.07-4.07, p < 0.001; male: OR: 2.67, CI: 2.19-3.25, p < 0.001). Female patients undergoing PCI received less opioid analgesia, but no sex differences in prehospital pain scores were seen. Opioid administration was associated with impaired antegrade flow in the culprit artery in both sexes, but not short-term MACE. Trials evaluating nonopioid analgesics in ACS are needed.

SDC: An integrated database for sex differences in cancer

Sex differences are evident in the incidence and mortality of diverse cancers. With the development of personalized approaches in cancer treatment, the impact of sex differences has not been systematically incorporated into preclinical and clinical cancer research. The molecular mechanisms underlying sex differences in cancer have not been elucidated. Here, we developed the first database of Sex Differences in Cancer (SDC), a web-based public database that integrates resources from multiple databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UCSC Xena, Broad Institute Cancer Cell Line Encyclopedia (CCLE), Genomics of Drug Sensitivity in Cancer (GDSC). SDC contains 27 types of cancers, 6 types of molecular data, more than 10,000 donors, 977 cancer cell lines were used to analyze sex differences among cancers. It provides five main modules: Survival and phenotype, Molecular differences, Signatures and pathways, Therapy response, Download. Users can download the all the visualized results and raw data after analysis. Collectively, SDC is the first integrated database to analyze sex differences in cancer on the web server, which will strengthen our understanding of the role of sex in cancers. It is implemented in Shiny-server and freely available for public use at http://sdc.anticancer.xyz.

Sex-dependent sensitivity to positive allosteric modulation of GABA action in an APP knock-in mouse model of Alzheimer's disease: Potential epigenetic regulation

Conflicting evidence suggest that perturbations of GABAergic neurotransmission play crucial roles in disrupting cortical neuronal network oscillations, memory, and cognitive deficits in Alzheimer's disease (AD). However, the role and impact of sex differences on GABAergic transmission in AD are not well understood. Using an APP knock-in mouse model of AD, APPNLGF mice, we studied the effects of acute diazepam administration on memory and anxiety-like behavior to unveil sex-dependent dysregulation of GABAergic neurotransmission. We also examined sex differences in GABAA receptor subunit mRNA and protein expression and the role of epigenetic regulation in hippocampus of APPNLGF mice. We found that diazepam elicited dose-dependent suppression of locomotion in wildtype and APPNLGF mice. However, a low dose, which had no significant effect in both male and female wildtype as well as female APPNLGF mice, significantly suppressed locomotion in male APPNLGF mice. Furthermore, this low dose of diazepam was more efficacious at eliciting anxiolytic-like effects in male than female APPNLGF mice. The same low dose of diazepam disrupted recognition memory exclusively in male APPNLGF mice. Biochemical analyses revealed that hippocampal α1 and α5 GABAA receptor subunits mRNA and protein expression were significantly higher in male than female APPNLGF mice and were regulated by histone H3 tri-methylation (H3K4me3) but not histone H3 acetylation. The higher sensitivity of APPNLGF males to diazepam-induced behavioral effects may potentially be due to epigenetic-dependent upregulation of hippocampal α1 and α5 GABAA receptor subunits expression compared to female APPNLGF mice. These findings suggest that dysregulation of GABAergic neurotransmission plays a significant role in memory and affective behavior, particularly in male APPNLGF mice.

Prognostic Significance of Prolonged Corrected QT Interval in Acute Ischemic Stroke.

Background and Purpose: The aim of this study was to determine the relationship between the heart rate-corrected QT (QTc) interval and the risk of incident long-term mortality in patients with acute ischemic stroke (AIS), considering the impact of sex differences on clinical characteristics, outcomes, and QTc intervals.Methods: We analyzed prospectively registered data included patients with AIS who visited the emergency room within 24 h of stroke onset and underwent routine cardiac testing, such as measurements of cardiac enzymes and 12-lead ECG. QTc interval was corrected for heart rate using Fridericia's formula and was stratified by sex-specific quartiles. Cox proportional hazards models were used to examine the association between baseline QTc interval and incident all-cause death.Results: A total of 1,668 patients with 1,018 (61.0%) men and mean age 66.0 ± 12.4 years were deemed eligible. Based on the categorized quartiles of the QTc interval, cardiovascular risk profile, and stroke severity increased with prolonged QTc interval, and the risk of long-term mortality increased over a median follow-up of 33 months. Cox proportional hazard model analysis showed that the highest quartile of QTc interval (≥479 msec in men and ≥498 msec in women; hazard ratio [HR]: 1.49, 95% confidence interval [CI]: 1.07–2.08) was associated with all-cause death. Furthermore, dichotomized QTc interval prolongation, defined by the highest septile of the QTc interval (≥501 ms in men and ≥517 m in women: HR: 1.33, 95% CI: 1.00–1.80) was significantly associated with all-cause mortality after adjusting for all clinically relevant variables, such as stroke severity.Conclusions: Prolonged QTc interval was associated with increased risk of long-term mortality, in parallel with the increasing trend of prevalence of cardiovascular risk profiles and stroke severity, across sex differences in AIS patients.

Sex-specific associations between traumatic experiences and resting-state functional connectivity in the Philadelphia Neurodevelopmental Cohort.

Traumatic experiences during childhood or adolescence are a significant risk factor for multiple psychiatric disorders and adversely affect multiple cognitive functions. Resting-state functional magnetic resonance imaging has been used to investigate the effects of traumatic experiences on functional connectivity, but the impact of sex differences has not been well documented. This study investigated sex-specific associations between resting-state functional connectivity (rsFC) and traumatic experiences in typically developing youth. The sample comprised 1395 participants, aged 8-21 years, from the Philadelphia Neurodevelopmental Cohort. Traumatic experiences were assessed based on the structured psychiatric evaluation. Sex, the number of traumatic events, and their interaction were regressed onto voxel-wise intrinsic connectivity distribution parameter values derived from resting-state functional magnetic resonance imaging. Brain regions that passed cluster correction were used as seeds to define resting-state networks. After quality control, the final sample had 914 participants with mean (SD) age 14.6 (3.3) years; 529 (57.8%) females; 437 (47.8%) experienced at least one kind of traumatic event. Four discrete anatomical clusters showed decreased functional connectivity as the number of traumatic events increased. The resting-state networks defined by using these four clusters as seeds corresponded with the somatomotor network. Sex-specific associations were identified in another three clusters for which males showed increased connectivity, and females showed decreased connectivity as the number of traumatic events increased. The resting-state networks defined by the three sex-specific clusters corresponded with the default mode network (DMN). In youth without psychiatric diagnoses, traumatic experiences are associated with an alteration of rsFC in brain regions corresponding with the somatomotor network. Associations differ in direction between males and females in brain regions corresponding with the DMN, suggesting sex-specific responses to early exposure to trauma.

Sex differences in pre-hospital analgesia and outcomes in patients presenting with acute coronary syndromes

Abstract Background Opioid analgesia remains the mainstay of pain management in acute coronary syndromes (ACS). Significant sex differences persist in ACS presentation, management and outcomes, but the impact of sex-differences on pre-hospital pain management of ACS with opioids is unknown. There is increasing awareness of the importance of pre-hospital factors in ACS, as well as emerging concerns with opioid use impairing the gastrointestinal absorption of oral P2Y12 inhibitors. Purpose This study examined if sex-differences in pre-hospital pain scores, opioid administration and clinical outcomes exist in ACS patients. Methods Patients presenting with ACS via ambulance (2014–2018) that underwent percutaneous coronary intervention (PCI) were prospectively collected via the Victorian Cardiac Outcomes Registry (VCOR), the Melbourne Interventional Group (MIG), and linked to the Ambulance Victoria database. The primary outcome was 30-day major adverse cardiac events (MACE). Secondary outcomes were descriptive analyses of pre-hospital pain score, intravenous morphine equivalent analgesic dosing, plus predictors of MACE and Thrombolysis In Myocardial Infarction (TIMI) 0–1 flow pre-PCI using logistic regression. Results 10,547 patients were included (female: 2,775 [26.3%]). Opioids were administered to 1,585 (57%) females and 5,068 (65%) males (p&amp;lt;0.001). Adjusted 30-day MACE was similar between opioid groups in both sexes (female: OR 1.21, CI 0.82–1.79, p=0.34; male: OR 0.89, 0.68–1.16, p=0.40). Median pain score at presentation was 6 (IQR 4,8) for both sexes. Median opioid dose was 2.5 mg (IQR 0,10) in females and 5 mg (IQR 0,10) in males (p&amp;lt;0.001), with similar pain relief achieved. Adjusted rates of TIMI 0–1 pre-PCI were higher in patients administered opioids (female: OR 2.83, CI 2.14–3.56, p&amp;lt;0.001; male: OR 2.95, CI 2.49–3.49, p&amp;lt;0.001). Conclusions Female patients undergoing PCI received less opioid analgesia, but no sex-differences in pre-hospital pain scores were seen. Opioid administration was associated with impaired antegrade flow in the culprit artery in both sexes, but not short-term MACE. Randomised trials evaluating the clinical implications of opioid administration in ACS with sex subgroup analyses are needed to guide clinical practice. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Melbourne Interventional GroupVictorian Cardiac Outcomes Registry

Impact of sex differences on thrombin-induced hydrocephalus and white matter injury: the role of neutrophils

BackgroundThrombin has been implicated in playing a role in hydrocephalus development following intraventricular hemorrhage (IVH). However, the mechanisms underlying the sex differences to the detrimental effects of thrombin post-IVH remain elusive.MethodThree-month old male and female Sprague-Dawley rats underwent unilateral intracerebroventricular (ICV) injections of 3U or 5U thrombin, or saline, to examine differences in thrombin-induced hydrocephalus and white matter injury. Mortality, and lateral ventricle volume and white matter injury were measured on magnetic resonance imaging evaluation at 24 h post-injection. In addition, male rats were pretreated with 17-β estradiol (E2, 5 mg/kg) or vehicle at 24 and 2 h prior to ICV injection of 3U thrombin. All rats were euthanized at 24 h post-injection for histology and immunohistochemistry.ResultsICV injection of 5U thrombin caused 100 and 0% mortality in female and male rats, respectively. 3U of thrombin resulted in significant ventricular dilation and white matter damage at 24 h in both male and female rats, but both were worse in females (p < 0.05). Furthermore, neutrophil infiltration into choroid plexus and periventricular white matter was enhanced in female rats and may play a critical role in the sex difference in brain injury. Pre-treating male rats with E2, increased thrombin (3U)-induced hydrocephalus, periventricular white matter injury and neutrophil infiltration into the choroid plexus and white matter.ConclusionsICV thrombin injection induced more severe ventricular dilation and white matter damage in female rats compared to males. Estrogen appears to contribute to this difference which may involve greater neutrophil infiltration in females. Understanding sex differences in thrombin-induced brain injury may shed light on future interventions for hemorrhagic stroke.

B-PO05-074 SEX DIFFERENCES IN ATRIAL FIBRILLATION ABLATION OUTCOMES: A THREE YEAR RETROSPECTIVE SINGLE CENTER STUDY

The impact of sex differences on the outcomes of catheter ablation (CA) of AF is controversial. Moreover, data are still lacking for persistent AF, due to women under-representation in this category. To investigate gender differences in the outcome of CA of AF. We performed a retrospective observational study of pts referred for first AF ablation between 2017-2019. All pts underwent pulmonary vein (PV) isolation with either radiofrequency or cryo-energy. Two groups were identified according to the sex. The primary outcome was AF recurrence-free survival. A total of 1102 pts was enrolled: 287 (26%) female. The two groups were balanced for baseline characteristics (age, type of AF, BMI, left atrial volume, and CHA2DS2-VASC). Pts with persistent AF were 38% (309). The primary outcome was seen in 76% (77) of men and 70% (175) of woman (p=0,029). When stratified according to AF sub-type, 73% (55) of patients with paroxysmal AF in the female group were free of AF versus 79% (106) of patients in the male group (p=0.068). In the late persistent AF group, only 38% of the women and 61% of the men were free of AF (p=0,014). At multivariate analysis female sex was an independent predictor of arrhythmia recurrences (p=0,035). Time from symptoms occurrence to diagnosis was significantly longer in female: 5,4 mm (SD 24.8) vs 2,5 mm (SD 21.3) (p=0004). Female gender is independently and strongly associated with a worse outcome in pts referred to CA of AF, especially in persistent cases. A longer time from symptoms to diagnosis may partially explain these results. Further studies are required to investigate the role of a more advanced disease stage or Non PV triggers in women.

Vulnerability factors for mephedrone-induced conditioned place preference in rats\u2014the impact of sex differences, social-conditioning and stress

RationaleMephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood.ObjectivesThe aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats.MethodsThe rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively.ResultsMephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus.ConclusionsAltogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.

Impact of Sex Difference on Interaction between Adiponectin Gene Single Nucleotide Polymorphisms rs2241766, rs17300539 and rs1501299 w Environment Risk Factors of Type 2 Diabetes among the Ardabil Population in Iran

Impact of Sex Difference on Interaction between Adiponectin Gene Single Nucleotide Polymorphisms rs2241766, rs17300539 and rs1501299 w Environment Risk Factors of Type 2 Diabetes among the Ardabil Population in Iran

Impact of Sex Differences on Mortality in Patients With Sepsis After Trauma: A Nationwide Cohort Study.

ObjectiveSepsis is the leading cause of death in intensive care units, and sepsis after trauma is associated with increased mortality rates. However, the characteristics of sepsis after trauma remain unknown, and the influence of sex on mortality remains controversial. This study aimed to assess the role of sex in in-hospital mortality in patients with sepsis after trauma.MethodsWe performed a retrospective cohort study involving several emergency hospitals (n=288) in Japan. The data of patients with trauma who developed sepsis after admission from 2004 to 2019 were obtained from the Japan Trauma Data Bank. We divided the patients into two groups according to sex and compared their in-hospital mortality. We also performed subgroup analysis limited to the elderly population (age ≥ 65 years) and evaluated in-hospital mortality between men and women.ResultsA total of 1935 patients met the inclusion criteria during the study period. Of these, 1204 (62.2%) were allocated to the male group and 731 (37.8%) to the female group. Multivariable Cox proportional-hazards analysis showed a significantly lower risk of in-hospital mortality in the female group than in the male group (hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.62–0.89; p=0.001). In the subgroup analysis, multivariable Cox proportional hazards still showed significantly lower risks of in-hospital mortality in the female group than in the male group (HR: 0.72, 95% CI: 0.58–0.88; p=0.002).ConclusionThe present study shows a significantly increased survival in the female group when compared to that in the male group of patients with sepsis after trauma. The underlying mechanism remains unclear, and further investigations are required.

Women with Subclinical Hypothyroidism are at Higher Prevalence of Metabolic Syndrome and Its Components Compared to Men in an Older Chinese Population

ABSTRACT Purpose: This study investigated the impact of sex differences on the relationship of subclinical hypothyroidism (SCH) with the prevalence of metabolic syndrome (MetS) and its components in an older Chinese population. Methods: The study included 1842 older Chinese individuals aged 65 years or older who received annual health checkups. The impact of sex differences on the relationship of SCH with the prevalence of MetS and its components was investigated by multivariate logistic regression analysis. Interaction effect between sex and SCH on the prevalence of MetS and its components were evaluated using a multivariate logistic regression model which includes interaction terms (sex-SCH). Results: The study comprised 1701 (92.3%) individuals with euthyroidism and 141 (7.7%) with SCH. In men, SCH was not associated with MetS or any components of the MetS. In women, the SCH group had higher prevalence of MetS [odds ratio (OR), 1.870; 95% confidence interval (CI), 1.136–3.079], abdominal obesity (OR, 1.693; 95% CI, 1.043–2.748), hypertriglyceridemia (OR, 1.711; 95% CI, 1.054–2.775) and low high-density lipoprotein cholesterol (HDL-C) (OR, 3.039; 95% CI, 1.576–5.861). There was an interaction between sex and SCH in terms of the effect on the prevalence of MetS and its components, including abdominal obesity and hypertriglyceridemia (P < .01 for all), and with a trend for low HDL-C (P = .098). Conclusion: There were sex differences in the correlation of SCH with the prevalence of MetS and its components in the older Chinese population. An interaction effect between sex and SCH on the prevalence of MetS and its components was found.

The role of sex as a biological variable in the efficacy and toxicity of therapeutic nanomedicine.

Males and females have physiological, hormonal, and genetic differences that can cause different responses to medicinal treatments. The role of sex in the pharmacokinetics and pharmacodynamics of drugs is well established in the literature. However, researchers have yet to robustly and consistently consider the impact of sex differences on the pharmacokinetics and pharmacodynamics of nanomedicine formulations when designing nanomedicine therapeutics and/or constructing clinical trials. In this review, we highlight the physiological and anatomical differences between sexes and discuss how these differences can influence the therapeutic efficacy, side effects, and drug delivery safety of nanomedicine products. A deep understanding of the effects of sex on nano-based drug delivery agents will robustly improve the risk assessment process, resulting in safer formulations, successful clinical translation, and improved therapeutic efficacies for both sexes.

A multimethod approach to assessing motor skills in boys and girls with autism spectrum disorder

Motor peculiarities are often reported in children with autism spectrum disorder and may predict subsequent adaptive functioning and quality of life. Although the sex bias in the prevalence of the disorder is well documented, little is known about differences in motor profile in males and females with autism spectrum disorder. Our goal was to study differences in motor functioning of boys and girls with autism spectrum disorder aged 3-11 years compared with typically developing children. Their motor performances were evaluated using a multimethod approach, including standardized motor tests, caregiver reports, and a detailed motion capture analysis of a simple reach-to-drop movement. We found that, irrespective of sex, children with autism spectrum disorder had worse scores than typically developing children on standardized tests and on caregiver reports. Interestingly, girls with autism spectrum disorder, but not boys, presented altered motor anticipation in reach-to-drop. Our findings emphasize the need for more sex-specific assessment of motor function in autism spectrum disorder.

Impact of sex differences on outcomes in patients with non-valvular atrial fibrillation undergoing left atrial appendage closure: A single-center experience.

Female patients affected by non-valvular atrial fibrillation (NVAF) have a higher risk of stroke compared with male patients. Left atrial appendage (LAA) closure has been demonstrated as a reasonable alternative to warfarin therapy for stroke prevention in patients with NVAF. However, the impact of sex-related differences on outcomes in patients undergoing LAA closure (LAAC) remains unclear. Our study investigated the differences in LAAC efficacy and safety endpoints between sexes. 387 consecutive patients undergoing WATCHMAN device implantation were enrolled and stratified by sex. Baseline clinical characteristics, procedural data, severe peri-procedural complications and long-term outcomes were compared between men and women. Measurements of LAA width and depth, device implantation success rate, and the frequency of severe peri-procedural complications were comparable between the two groups. After an average follow-up length of two years post LAAC, no significant differences were observed in the risks for composite thromboembolic events (P = 0.096), major bleeding (P = 0.129), and combined primary (co-primary) efficacy events (P = 0.231) between sexes, but the risk of all-cause death decreased significantly in women compared with men (P = 0.045). After performing propensity matching adjustment for residual confounders, the sex-related differences in the cumulative ratio of freedom from all-cause death did not reach statistical significance (P = 0.062), as was also observed with the cumulative ratio of freedom from composite thromboembolic events (P = 0.104), major bleeding (P = 0.134), and co-primary efficacy events (P = 0.241). The observed annual rate of thromboembolic events was significantly decreased by 67.1% (P < 0.01) and 52.5% (P < 0.05) and the observed annual rate of bleeding was reduced by 33.6% (P < 0.05) and 43.5% (P < 0.05) in men and women when compared with the predicted risk based on CHA2DS2VASc score and HAS-BLED score, respectively. LAAC can be considered as an effective and safe strategy in preventing thromboembolic events and decreasing bleeding risks in NVAF patients, regardless of sex. LAAC appears to normalize the sex-specific differences in NVAF patients both in terms of safety and efficacy.

Sex Differences in Pre-hospital Analgesia and Outcomes in Patients Presenting with Acute Coronary Syndromes

Sex-differences persist in acute coronary syndrome (ACS) presentation, management, and outcomes. The impact of sex-differences on pre-hospital pain management of ACS with opioids is unknown. This study examined if sex-differences in pre-hospital pain scores, opioid administration and clinical outcomes exist in ACS patients.