Sex-specific Outcomes Research Articles

Volumetric body composition analysis of the Cancer Genome Atlas reveals novel body composition traits and molecular markers Associated with Renal Carcinoma outcomes

Clinically, the body mass index remains the most frequently used metric of overall obesity, although it is flawed by its inability to account for different adipose (i.e., visceral, subcutaneous, and inter/intramuscular) compartments, as well as muscle mass. Numerous prior studies have demonstrated linkages between specific adipose or muscle compartments to outcomes of multiple diseases. Although there are no universally accepted standards for body composition measurement, many studies use a single slice at the L3 vertebral level. In this study, we use computed tomography (CT) studies from patients in The Cancer Genome Atlas (TCGA) to compare current L3-based techniques with volumetric techniques, demonstrating potential limitations with level-based approaches for assessing outcomes. In addition, we identify gene expression signatures in normal kidney that correlate with fat and muscle body composition traits that can be used to predict sex-specific outcomes in renal cell carcinoma.

Long-term clinical outcomes and healthcare resource utilization in male and female patients following hospitalization for heart failure.

Heart failure (HF) is a leading cause of hospitalization, and sex differences in care have been described. We assessed sex-specific clinical outcomes and healthcare resource utilization following hospitalization for HF. This was an exploratory analysis of patients hospitalized for HF across 10 Canadian hospitals in the Patient-Centered Care Transitions in HF (PACT-HF) cluster-randomized trial. The primary outcome was all-cause mortality. Secondary outcomes included all-cause readmissions, HF readmissions, emergency department (ED) visits, and healthcare resource utilization. Outcomes were obtained via linkages with administrative datasets. Among 4441 patients discharged alive, 50.7% were female. By 5 years, 63.6% and 65.5% of male and female patients, respectively, had died (p = 0.19); 85.4% and 84.4%, respectively, were readmitted (p = 0.35); and 72.2% and 70.9%, respectively, received ED care without hospitalization (p = 0.34). There were no sex differences in mean [SD] number of all-cause readmissions (males, 2.8 [7.8] and females, 3.0 [8.4], p = 0.54), HF readmissions (males, 0.9 [3.6] and females, 0.9 [4.5], p = 0.80), or ED visits (males, 1.8 [11.3] and females, 1.5 [6.0], p = 0.24) per person. There were no sex differences in mean [SD] annual direct healthcare cost per patient (males, $80 334 [116 762] versus females, $81 010 [112 625], p = 0.90), but males received more specialist, multidisciplinary HF clinic, haemodialysis, and day surgical care, and females received more home visits, continuing/convalescent care, and long-term care. Annualized clinical events were highest in first year following index discharge in both males and females. Among people discharged alive after hospitalization for HF, there were no sex differences in total and annual deaths, readmissions, and ED visits, or in total direct healthcare costs. Despite similar risk profiles, males received relatively more specialist care and day surgical procedures, and females received more supportive care. ClinicalTrials.gov NCT02112227.

Sex-specific clinical outcomes and healthcare resource utilization in the 5 years following hospitalization for heart failure

Abstract Background Heart failure (HF) a leading cause of hospitalization, and sex differences in care have been described. Purpose We assessed sex-specific clinical outcomes and healthcare resource utilization following hospitalization for HF. Methods This was an exploratory analysis of patients hospitalized for HF across 10 Canadian hospitals enrolled in the Patient-Centred Care Transitions in HF pragmatic cluster-randomized trial. Primary outcome was all-cause mortality. Secondary outcomes included all-cause readmissions, HF readmissions, emergency department (ED) visits, and healthcare resource utilization. Outcomes were obtained via linkages with administrative datasets. Results The 4441 patients (50.7% female) had high event rates. At 5 years of follow-up, 63.6% male and 65.5% of male and female patients, respectively, had died (p=0.19); 85.4% and 84.4% of male and female patients, respectively, were readmitted with no sex differences in mean [SD] all-cause readmissions (males, 2.8 [7.8] and females, 3.0 [8.4], p=0.54) or HF readmissions (males, 0.9 [3.6] and females, 0.9 [4.5], p=0.80) per person. The mean (SD) annual total healthcare costs per patient was $80334 (116762) for males and $81010 (112625) for females, with no sex difference (p=0.90); however, there were sex differences in cost breakdown: males incurred greater costs from specialist, hemodialysis, and day surgical care, and females incurred greater costs from home visits and long-term care. Conclusions Males and females were at similarly high risk of mortality and readmissions, and had similar total healthcare costs following hospitalized for HF. Notwithstanding similar risks, males received relatively more specialist and invasive care, and females received relatively more supportive care.

Visual pathways functioning in healthy pre-term adolescents: Sex but not gestational age effect.

Visuo-spatial and visuo-perceptual functioning is widely studied in preterm child and is strongly sex-specific. However, little to no data is available regarding male-female differences in preterm children and adolescents and about the interaction effect between sex and preterm birth. We studied 30 adolescents born preterm with normal cognitive and clinical neurological outcomes and 34 age-matched controls to investigate the interaction between levels of prematurity and sex in predicting the outcome of visual pathways functioning and to explore the relation between psychophysiological perceptive processing and neuropsychological performance. In the presence of prematurity, a greater female vulnerability in central visuo-cognitive processing (Form Coherence Task), but not in neuropsychological accuracy (Street Completion Test and Visual Object and Space Perception battery), seems to be more evident. Moreover, the psychophysical threshold is correlated to neuropsychological accuracy only in preterm females and not in males. These results support the idea that the male vulnerability in cognitive functioning described in prematurity-related developmental conditions is negligible during school age in children-adolescents with normal cognitive and clinical neurological outcomes. Visuo-perceptual functioning is widely studied in prematurity. However, few data are available about the interaction effect between sex and preterm birth in predicting visuo-perceptual functioning. We evidenced that in females born preterm with preserved cognitive abilities, the efficiency of the psychophysical visuo-perceptual threshold is reduced, but not related to the neuropsychological performance. Females may implement compensation strategies to achieve good performance regardless of the perceptual threshold. The present study addresses an important gap in literature, suggesting possible sex-specific outcomes in visuo-perceptual ability among preterm children and adolescents with normal intelligence and neurological outcomes.

TCT-497 Sex-Specific Clinical Outcomes After Treatment of In-Stent Restenosis With the AGENT Paclitaxel-Coated Balloon: A Subgroup Analysis of the AGENT IDE Randomized Trial

TCT-497 Sex-Specific Clinical Outcomes After Treatment of In-Stent Restenosis With the AGENT Paclitaxel-Coated Balloon: A Subgroup Analysis of the AGENT IDE Randomized Trial

TCT-627 Sex-Specific Outcomes of Transcatheter Edge-to-Edge Repair in Degenerative Mitral Regurgitation: Results From the CLASP IID Trial

TCT-627 Sex-Specific Outcomes of Transcatheter Edge-to-Edge Repair in Degenerative Mitral Regurgitation: Results From the CLASP IID Trial

Maternal Folic Acid and Dietary Folate Intake in Relation to Sex Ratio at Birth and Sex-Specific Birth Weight in China.

It is well-established that prenatal folic acid supplements can reduce neural tube defects. However, the associations between folic acid supplementation, dietary folate intake, and overall folate intake with sex-specific birth outcomes are not yet fully understood. This study aims to investigate the association of periconceptional folic acid supplement, dietary folate, and total folate intake with the sex ratio at birth and sex-specific birth weight. Data were sourced from a cross-sectional survey conducted between August and December 2013 in Northwest China, involving 7318 infants and their mothers, recruited using a stratified multistage random sampling method. Folic acid supplements (400 μg/d) were ascertained via a retrospective in-person interview. Dietary folate was evaluated using a validated food frequency questionnaire. Birth outcomes, including sex and weight at birth, were obtained from the Medical Certificate of Birth. Generalized linear models were employed to calculate relative risks (RRs) or differences with 95% confidence intervals (CIs). No association or dose-response relationship was observed between folic acid supplement, dietary folate, and total folate intake during periconception and the likelihood of male births. However, women who took folic acid supplements during pre- and post-conception were associated with an increased male birth weight by 52.8 (8.1 to 97.5) g. Additionally, the total folate intake during periconception was associated with birth weight for males (upper vs. lower tertile: β = 38.8, 95%CI: 5.0 to 72.5 g, p-trend = 0.024) and females (upper vs. lower tertile: β = 42.4, 95%CI: 6.7 to 78.1; p-trend = 0.022). Our findings indicate that periconceptional total folate intake does not correlate with sex ratio at birth but was positively linked to infant birth weights, regardless of gender. These findings offer novel insights into potential benefits of total folate intake, beyond the prevention of neural tube defects, for policymakers and public health.

Sex-Specific Behavioral and Molecular Responses to Maternal Lipopolysaccharide-Induced Immune Activation in a Murine Model: Implications for Neurodevelopmental Disorders.

Maternal immune activation (MIA) during pregnancy has been increasingly recognized as a critical factor in the development of neurodevelopmental disorders, with potential sex-specific impacts that are not yet fully understood. In this study, we utilized a murine model to explore the behavioral and molecular consequences of MIA induced by lipopolysaccharide (LPS) administration on embryonic day 12.5. Our findings indicate that male offspring exposed to LPS exhibited significant increases in anxiety-like and depression-like behaviors, while female offspring did not show comparable changes. Molecular analyses revealed alterations in pro-inflammatory cytokine levels and synaptic gene expression in male offspring, suggesting that these molecular disruptions may underlie the observed behavioral differences. These results emphasize the importance of considering sex as a biological variable in studies of neurodevelopmental disorders and highlight the need for further molecular investigations to understand the mechanisms driving these sex-specific outcomes. Our study contributes to the growing evidence that prenatal immune challenges play a pivotal role in the etiology of neurodevelopmental disorders and underscores the potential for sex-specific preventative approaches of MIA.

1223P Sex specific efficacy and safety outcomes in operable stage III non-small cell lung cancer (NSCLC): Pooled analysis of the SAKK trials 16/96, 16/00, 16/01, 16/08 and 16/14

1223P Sex specific efficacy and safety outcomes in operable stage III non-small cell lung cancer (NSCLC): Pooled analysis of the SAKK trials 16/96, 16/00, 16/01, 16/08 and 16/14

Acetate enhances spatial memory in females via sex- and brain region-specific epigenetic and transcriptional remodeling.

Metabolic control of chromatin and gene expression is emerging as a key, but largely unexplored aspect of gene regulation. In the brain, metabolic-epigenetic interactions can influence critical neuronal functions. Here, we use a combination of behavioral, proteomic and genomic approaches to demonstrate that the intermediary metabolite acetate enhances memory in a brain region- and sex-specific manner. We show that acetate facilitates the formation of dorsal hippocampus-dependent spatial memories in female but not in male mice, while having no effect on cortex-dependent non-spatial memories in either sex. Acetate-enhanced spatial memory is driven by increased acetylation of histone variant H2A.Z, and upregulation of genes implicated in spatial learning in the dorsal hippocampus of female mice. In line with the sex-specific behavioral outcomes, the effect of acetate on dorsal hippocampal histone modifications and gene expression shows marked differences between the sexes during critical windows of memory formation (consolidation and recall). Overall, our findings elucidate a novel role for acetate, a ubiquitous and abundant metabolite, in regulating dorsal hippocampal chromatin, gene expression and learning, and outline acetate exposure as a promising new approach to enhance memory formation.

Sex-Specific Outcomes After Anterior Cruciate Ligament Reconstruction Using an All–Soft Tissue Quadriceps Tendon Autograft in a Young Active Population

Background: The ideal graft for anterior cruciate ligament (ACL) reconstruction (ACLR) in young athletes has a high return-to-sport (RTS) rate and a low reinjury rate. Quadriceps tendon autografts are being used with increasing frequency for ACLR in this population, despite a paucity of evidence to support their use. Purpose: To report the RTS rate, ipsilateral reinjury rate, and contralateral ACL injury rate in a young athletic population undergoing primary ACLR using an all–soft tissue quadriceps tendon (ASTQT) autograft. Study Design: Cases series; Level of evidence, 4. Methods: Patients aged 14 to 22 years who underwent primary ACLR using an ASTQT autograft by a single surgeon between January 1, 2005, and April 30, 2020, were identified via electronic medical records and contacted ≥24 months after ACLR to complete a survey regarding subsequent ipsilateral or contralateral ACL injuries and RTS. Patients who had undergone previous ACLR (ipsilateral or contralateral) were excluded. Results: A total of 656 patients (330 male, 326 female; mean age, 17.9 years) were identified, and 395 patients completed the survey (60.2%; 174 male, 221 female; mean age, 17.8 years) with a mean follow-up of 73 ± 29 months (range, 24-139 months). The RTS rate was high (male: 87.7%; female: 82.8%; P = .19). Male and female patients had similar rates of revision ACLR (male: 12.6%; female: 10.0%; P = .40) and contralateral ACL injuries (male: 13.8%; female: 11.3%; P = .46). Conclusion: A high RTS rate and similar rates of ipsilateral and contralateral ACL injuries were found for male and female patients in a young athletic population undergoing primary ACLR using an ASTQT autograft. These results help one to better understand the utility of ASTQT grafts to support successful ACLR in young athletic populations, for which ASTQT grafts appear to yield favorable outcomes.

Longitudinal sex-specific impacts of high-fat diet on dopaminergic dysregulation and behavior from periadolescence to late adulthood

ABSTRACT Objectives: Obesity is recognized for its adverse impact on brain health and related behaviors; however, the specific longitudinal effects of a high-fat diet (HFD) from juvenile stages of development through late adulthood remain poorly understood, particularly sex-specific outcomes. This study aimed to determine how prolonged exposure to HFD, commencing during periadolescence, would differentially predispose male and female mice to an elevated risk of dopaminergic dysregulation and associated behavioral deficits. Methods: One-month-old C57BL/6J male and female mice were subjected to either a control diet or an HFD for 5 and 9 months. Muscle strength, motor skills, sensorimotor integration, and anxiety-like behaviors were assessed at the end of the 5th and 8th months. Key dopaminergic molecules, including dopamine (DA), dopamine receptor D2 (DRD2), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2), were quantified at the end of the 5th or 9th months. Results: Behaviorally, male mice exposed to HFD exhibited more pronounced alterations in sensorimotor integration, anxiety-like behavior, and muscle strength after the 5th month of dietary exposure. In contrast, female mice displayed most behavioral differences after the 8th month of HFD exposure. Physiologically, there were notable sex-specific variations in the dopaminergic pathway response to HFD. Male mice exposed to HFD exhibited elevated tissue levels of VMAT2 and DRD2, whereas female mice showed reduced levels of DRD2 and DAT compared to control groups. Discussion: These findings indicate a general trend of altered time course susceptibility in male mice to chronic HFD consumption compared to their female counterparts, with male mice impacted earlier than females.

Sex-specific comparative outcomes between oral anticoagulants in patients with atrial fibrillation: a systematic review and meta-analysis

AimsWomen with atrial fibrillation (AF) are under-represented in randomised controlled trials (RCTs) of direct oral anticoagulants (DOACs). This systematic review and meta-analysis of RCTs and observational studies examined sex-specific outcomes...

Sex-specific outcomes and left atrial remodeling following catheter ablation of persistent atrial fibrillation: results from the DECAAF II trial

Sex-specific outcomes and left atrial remodeling following catheter ablation of persistent atrial fibrillation: results from the DECAAF II trial

Sex-specific associations of adolescent motherhood with cognitive function, behavioral problems, and autistic-like traits in offspring and the mediating roles of family conflict and altered brain structure

BackgroundPrevious studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear.MethodsThis study included 6952 children aged 9–11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20–35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations.ResultsOur results revealed that children of adolescent mothers had significantly lower cognitive scores (β, − 2.11, 95% CI, − 2.90 to − 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study.ConclusionsOur results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.

Sex-Specific Analysis of Mid-Term Outcomes of Atherectomy-Assisted Endovascular Treatment in Severe Peripheral Arterial Disease.

Background: Endovascular treatment of lower-extremity peripheral disease (PAD) is associated with higher complication rates and suboptimal outcomes in women. Atherectomy has shown favourable outcomes in calcified lesions, minimising the incidence of stent placement caused by recoil or flow-limiting dissection. To date, there are no published mid-term outcomes evaluating the performance of atherectomy differentiated by sex. This study aims to evaluate sex-specific outcomes and prognostic factors affecting the results of atherectomy-assisted endovascular treatment in severe PAD. Methods: A retrospective analysis was conducted at a single centre in Germany, initiated by physicians and not sponsored by industry, on patients presenting with Rutherford categories ranging from III to V and featuring de novo occlusive or stenotic lesions of the superficial femoral (SFA) and/or popliteal arteries. The intervention involved rotational atherectomy-assisted angioplasty utilising the Jetstream (Boston, US®) device. The point of interest of this study was postinterventional clinical improvement as well as mid-term outcomes, including primary patency, over a targeted 2-year follow-up period. Statistical analysis utilised Cox regression (survival analysis) to calculate hazard ratios according to sex category. Comparative survival analysis was performed using the log-rank test and visually represented through Kaplan-Meier curves. Risk factors associated with absence of clinical improvement were examined across both sex groups utilising the chi-square or Fisher exact test, as appropriate. Results: A total of 98 patients (103 limbs) were initially included, with >75% having moderate-to-severe lesion calcification (>50%). A total of 84 patients (97 limbs, 62 male and 35 female) proceeded to a 2-year follow-up (mean 16.4 months for males and 16.1 for females) after a successful index procedure. Age distribution, Rutherford class, diabetes, chronic kidney disease (CKD), target vessel, lesion type, and length were balanced among both groups. Similar primary patency rates, of 89% among female and 91% among male limbs, were observed (p = 0.471). Female patients exhibited a lower rate of clinical improvement based on the Rutherford scale in comparison to males (80.6% vs. 94.5%, p = 0.048). CDK was the only significant prognostic factor across pooled data (odds ratio for CKD: 15.15, p < 0.001). Conclusions: Rotational atherectomy showed comparably high rates of mid-term primary patency, with low rates of bailout stent placement. These findings highlight the beneficial use of atherectomy in female patients who are per se at risk for higher rates of complications during and after endovascular interventions.

Mathematical Modeling Suggests That Monocyte Activity May Drive Sex Disparities during Influenza Infection.

In humans, females of reproductive age often experience a more severe disease during influenza A virus infection, which may be due to differences in their innate immune response. Sex-specific outcomes to influenza infection have been recapitulated in mice, enabling researchers to study viral and immune dynamics in vivo in order to identify immune mechanisms that are differently regulated between the sexes. This study is based on the hypothesis that sex-specific outcomes emerge due to differences in the rates/speeds that select immune components respond. Using publicly available sex-specific murine data, we utilized dynamic mathematical models of the innate immune response to identify candidate mechanisms that may lead to increased disease severity in female mice. We implemented a large computational screen using the Bayesian information criterion (BIC), wherein the goodness of fit of the competing model scenarios is balanced against complexity (i.e., the number of parameters). Our results suggest that having sex-specific rates for proinflammatory monocyte induction by interferon and monocyte inhibition of virus replication provides the simplest (lowest BIC) explanation for the difference observed in the male and female immune responses. Markov-chain Monte Carlo (MCMC) analysis and global sensitivity analysis of the top performing scenario were performed to provide rigorous estimates of the sex-specific parameter distributions and to provide insight into which parameters most affect innate immune responses. Simulations using the top-performing model suggest that monocyte activity could be a key target to reduce influenza disease severity in females. Overall, our Bayesian statistical and dynamic modeling approach suggests that monocyte activity and induction parameters are sex-specific and may explain sex-differences in influenza disease immune dynamics.

Implications of Prenatal Exposure to Endocrine-Disrupting Chemicals in Offspring Development: A Narrative Review.

During the last decades, endocrine-disrupting chemicals (EDCs) have attracted the attention of the scientific community, as a result of a deepened understanding of their effects on human health. These compounds, which can reach populations through the food chain and a number of daily life products, are known to modify the activity of the endocrine system. Regarding vulnerable groups like pregnant mothers, the potential damage they can cause increases their importance, since it is the health of two lives that is at risk. EDCs can affect the gestation process, altering fetal development, and eventually inducing the appearance of many disorders in their childhood and/or adulthood. Because of this, several of these substances have been studied to clarify the influence of their prenatal exposure on the cognitive and psychomotor development of the newborn, together with the appearance of non-communicable diseases and other disorders. The most novel research on the subject has been gathered in this narrative review, with the aim of clarifying the current knowledge on the subject. EDCs have shown, through different studies involving both animal and human investigation, a detrimental effect on the development of children exposed to the during pregnancy, sometimes with sex-specific outcomes. However, some other studies have failed to find these associations, which highlights the need for deeper and more rigorous research, that will provide an even more solid foundation for the establishment of policies against the extended use of these chemicals.

Epidemiology and outcome of out-of-hospital cardiac arrest in Salt Lake City: Sex-based investigations.

Prior research indicates sex disparities in the incidence and outcomes of out-of-hospital cardiac arrest (OHCA). This study investigates the presence of such differences in Salt Lake City, Utah. We analyzed data from the Salt Lake City Fire Department (2008‒2023). We included adults with non-traumatic OHCA. We calculated the annual incidence of OHCA and examined sex-specific survival outcomes using multivariable logistic regression, adjusting for OHCA characteristics known to be associated with survival. The annual incidence of OHCA was 76 per 100,000 person-years. Among the 894 OHCA cases included in the analysis, 67.5% were males, 37.3% achieved return of spontaneous circulation (ROSC), and 13.6% survived hospital discharge. Unadjusted analysis revealed that males had significantly higher OHCA in public locations (43.9%vs. 28.6%), witnessed arrests (54.5%vs. 47.8%), and shockable rhythms (33.3%vs. 22.9%). Males also showed higher rates of ROSC (37.5%vs. 36.9%), hospital discharge survival (14.5%vs. 11.7%), and neurologically intact survival. After adjusting for the OHCA characteristics, there was no significant differences between males and females in ROSC, survival to hospital discharge, and favorable neurological function with adjusted odds ratios (male vs. female) of 0.92 (95% confidence interval [CI] 0.73‒1.16), 0.85 (95% CI 0.59‒1.22), and 0.92 (95% CI 0.62‒1.40), respectively. Approximately, 128 adults suffer OHCA in Salt Lake City annually. Males initially showed higher crude survival rates, but after adjusting for OHCA characteristics, no significant sex differences in survival outcomes were found. Enhancing OHCA characteristics could benefit both sexes. Investigations into the relationship between sex- and region-specific factors influencing OHCA outcomes are needed.

Sex-specific Outcomes and Predictors of Mortality in Blunt Thoracic Aortic Injury

Sex-specific Outcomes and Predictors of Mortality in Blunt Thoracic Aortic Injury