Sex-based Differences Research Articles

Sex-Based Effects on Muscle Oxygenation During Repeated Maximal Intermittent Handgrip Exercise

Background: This investigation aimed to examine sex-based differences in deoxy[heme] (HHb), tissue saturation (StO2), and force-deoxygenation ratio (FD) of the forearm flexor muscles during a maximal-effort intermittent fatiguing handgrip protocol. Methods: Thirty-three healthy males (n = 15) and females (n = 18) completed a fatiguing handgrip protocol consisting of 60 4 s contractions separated by a 1 s rest. Near-infrared spectroscopy was used to measure muscle oxygenation before, during, and after the protocol. Results: Sex differences in HHb (p = 0.033) and StO2 (p = 0.021) were observed with significantly greater values for females (HHb: 110.204 ± 12.626% of baseline; StO2: 72.091 ± 5.812%) in comparison to males (HHb: 101.153 ± 12.847% of baseline; StO2: 66.978 ± 7.799%). Females (0.199 ± 0.081 AU) also demonstrated significantly (p = 0.001) lower FD in comparison to males (0.216 ± 0.094 AU). However, males (b = −0.023 ± 0.008 AU) demonstrated a significantly (p < 0.001) greater rate of decline in FD in comparison to females (b = −0.017 ± 0.006 AU). Conclusions: Prior to, during, and after a maximal-effort intermittent fatiguing handgrip fatiguing protocol, males demonstrate significantly lower StO2 than females and a faster rate of decline in FD. Moreover, females demonstrate greater HHb values than males when assessed relative to a resting baseline.

Sex-based differences in the long-term fate of hippocampal neurons born after a traumatic brain injury

IntroductionModerate-to-severe traumatic brain injury (TBI) results in an early loss of immature hippocampal granule cells and the activation of typically quiescent neural stem cells (NSCs) in the dentate gyrus. Activation of NSCs leads to a robust increase in proliferation and generation of neural progenitor cells (NPCs), supporting restoration of the immature neuron population of over a period of 1–2 weeks. However, it is unclear if neurons born early after injury develop normally, survive long-term and functionally integrate into the hippocampal network. Although adult hippocampal neurogenesis is regulated in a sex-dependent manner, the majority of pre-clinical TBI studies lack the inclusion of both sexes. The goal of this study was to examine sex differences in hippocampal neurogenesis in response to a moderate controlled cortical impact brain injury.MethodsIn-vivo labeling of NPCs and tracking of their morphological development into a granule cell was achieved using an inducible Cre recombinase driven by the Ascl1 promoter in a CAG-floxStopTom reporter mouse. Ascl1 is a basic helix-loop-helix transcription factor transiently expressed in NPCs and activated NSCs in the dentate gyrus of the adult mammalian brain. To specifically label NPCs born acutely after TBI, tamoxifen was delivered to mice on days 2 and 3 postinjury. Mice survived to 6 weeks after TBI to allow for full neuronal maturation of tdTomato-labeled NPCs.ResultsAt 6 weeks postinjury, numbers of tdTomato-positive granule cells were significantly reduced in the ipsilateral hippocampus of brain-injured mice compared to controls, with a more pronounced decrease in males. Further, posttrauma-born neurons in males, but not females, exhibited impaired dendritic development. Neurons born after injury extended axons which formed synaptic terminals within the CA3 region. Numbers of mossy fiber boutons were significantly decreased in injured males compared to naïve males or to injured females. Potential forms of plasticity were observed in brain-injured females, including increased neurogenesis in the contralateral hippocampus and increased mossy fiber bouton volume. Together these data suggest a neurogenic advantage in females after injury.DiscussionThis study is the first to report sex differences in posttraumatic hippocampal neurogenesis and to demonstrate modification of synaptic terminals formed by neurons born after TBI.

Sex Differences in Patients Presenting With ST-Segment Elevation Myocardial Infarction and Nonobstructive Coronary Arteries.

Sex differences in ST-segment elevation myocardial infarction (STEMI) due to obstructive coronary artery disease (CAD) are well-established, but limited research exists on sex differences in STEMI patients with nonobstructive coronary arteries (MINOCA) and MINOCA mimickers. We analyzed 8560 consecutive STEMI patients, enrolled in the Midwest STEMI Consortium from 2003 to 2020. Patients with non-obstructive CAD were classified into MINOCA (defined as < 50% coronary artery stenosis and confirmed or suspected coronary artery plaque disruption, epicardial coronary spasm, or coronary embolism/thrombosis) and MINOCA mimickers (takotsubo cardiomyopathy, myocarditis, or non-ischemic cardiomyopathy). The primary outcome was 5-year all-cause mortality. Of the 8560 patients, 409 (4.8%) had non-obstructive CAD, including 120 (1.4%) MINOCA and 289 (3.4%) MINOCA mimickers. Females were more likely to have MINOCA and MINOCA mimickers (49.2% and 56.4%, respectively). There were no significant sex differences in in-hospital or 5-year mortality in MINOCA, but females with MINOCA mimickers had higher unadjusted 5-year mortality (HR 2.90, 95% CI 1.53-5.53). After adjusting for age and comorbidities, the long-term mortality risk was similar between sexes (adjusted HR 1.16, 95% CI: 0.61-2.24). Females with obstructive CAD had higher 5-year mortality in unadjusted models (HR 1.66, 95% CI 1.48, 1.86), but the difference was not significant after adjustment (adjusted HR 1.1, 95% CI: 0.98-1.24). Our findings highlight important sex-based differences in the prevalence, treatment, and long-term outcomes of STEMI patients with MINOCA, MINOCA mimickers, and obstructive CAD. Despite clinical disparities, mortality risks were similar across sexes after adjusting for comorbidities.

Neuronal properties in the Lateral Habenula and adult-newborn interactions in virgin female and male mice.

The behavioral interactions between adults and newborns are decisive for the fitness and the survival of offsprings across the animal kingdom. In laboratory mice, while virgin females display caregiving behaviors, virgin males are rather neglectful or aggressive towards pups. Despite the importance of these behavioral variations, the underlying neural mechanisms remain poorly understood. Brain regions encoding these behaviors may exhibit sex-dependent functional differences at baseline. Additionally, these structures might undergo sex-specific plasticity after adults interact with the offspring.Emerging evidence suggests sex-based differences in input connectivity, genetics and receptor expression of the epithalamic Lateral Habenula (LHb). Moreover, LHb neuronal activity is instrumental for adult-newborn interactions. However, whether LHb neuronal function varies between sexes and/or undergoes adaptations following interactions with pups has not been fully investigated.In this study, we used in vivo and ex vivo single-cell electrophysiology to examine the basal LHb neuronal activity of virgin female and male mice. In a second set of experiments, we exposed mice to pups and recapitulated sex-based divergent behaviors. Recordings in acute slices showed no alterations in LHb firing properties, regardless of sex or pup exposure. These findings suggest that, although the LHb participates in adult behaviors towards pups, this is not mediated by sex-dependent functional differences or adaptations in the neuronal firing properties. Thus, this study provides new insights into the neural basis of sex-specific adult-newborn behaviors and the role of the LHb in these processes.Significance Statement Previous studies highlight the importance of the lateral habenula (LHb) in guiding parental behaviors. Virgin female and male mice differ in their behavior towards pups: while females are parental, males neglect or attack pups. We investigated whether LHb neuronal activity or its plasticity after pup exposure presented sex differences in virgin mice. Our findings reveal that LHb activity does not differ between naïve females and males, and it remains unchanged after pup exposure. This suggests a decoupling between sex-dimorphic behaviors towards newborns and activity of the LHb.

Triangular notch morphology in young males linked to increased risk of non-contact anterior cruciate ligament tears

Objectives: The knee joint, critical for human mobility, faces a heightened risk of injuries, with non-contact anterior cruciate ligament (ACL) tears occurring at a notable rate. This study aims to investigate the relationship between femoral intercondylar notch (ICN) morphometry, assessed through magnetic resonance imaging (MRI), and non-contact ACL tears. Given the anatomical intricacies of the femoral ICN, understanding its morphometry becomes imperative. The study also considers sex-based differences, the influence of individual height, and various notch shapes, including triangular, “U,” and omega configurations. Materials and Methods: A cross-sectional study involving 100 patients undergoing knee MRI examinations was conducted. Inclusion criteria encompassed patients over 18 years with a history of trauma and clinical evidence of knee joint instability. Measurements of femoral ICN were made using a 3 Tesla MRI scanner, with parameters such as notch depth, width, ICN width index (ICNWI), notch angle, and alpha angle (AA) being evaluated in axial and coronal planes. Results: Among 100 cases of non-contact ACL injuries, MRI examination revealed distinct ICN shapes: 24% triangular, 34% omega-shaped, and 42% U shaped. Triangular notches were more prevalent in young adults, with a mean age of approximately 25 years. Analysis of femoral ICN dimensions showed no significant associations for notch depth, width, ICNWI, notch angle, and AA. However, a significant difference in age was noted for the triangular-shaped ICN. Conclusion: Our study suggests a notable association between a triangular-shaped ICN, young age, and male individuals with a higher prevalence of non-contact ACL tears.

Sex Differences in the In-Hospital Outcomes of Left Ventricular Assist Device Implantation: A Population-Based National Inpatient Sample Study From 2015 to 2021.

Left ventricular assist device (LVAD) implantation can be used to manage advanced heart failure. Debates over sex differences in postoperative outcomes of LVAD implantation remain contentious; there is limited evidence available from the continuous-flow era, particularly following the introduction of third-generation devices. This study aimed to conduct a comprehensive, contemporary, and population-based analysis of the sex difference in the in-hospital outcomes following LVAD implantations. Patients who underwent LVAD implantation were selected from National Inpatient Sample from Q4 2015-2021. Multivariable logistic regression was used to compare in-hospital outcomes between females and males, where demographics, socioeconomic status, primary payer status, hospital characteristics, comorbidities, and transfer/admission status were adjusted. There were 1201 (23.6%) female and 3881 (76.4%) male patients who underwent LVAD implantation. Females and males had comparable in-hospital mortality, MACE, and stroke. However, females had higher diaphragmatic paralysis (aOR = 7.94, 95 CI = 1.46-43.48, p = 0.02). Meanwhile, females had lower cardiogenic shock (aOR = 0.85, 95 CI = 0.73-0.98, p = 0.02), renal complications (aOR = 0.72, 95 CI = 0.62-0.84, p < 0.01), and infection (aOR = 0.70, 95 CI = 0.58-0.86, p < 0.01). Females also had longer hospital length of stay (44.1 ± 40.0 vs. 38.8 ± 30.6 days, p = 0.01) and higher total hospital charges (1293779.0 ± 1182139.0 vs. 1172780.0 ± 917544.0 US dollars, p = 0.04). In the contemporary era with the introduction of third-generation devices, in-hospital mortality and stroke after LVAD implantation continued to decrease and were comparable in both sexes. However, there are still notable sex-based differences in the complications of LVAD implantation, which underscores the need for sex-specific preoperative risk assessments and tailored perioperative management.

Receipt of respiratory vaccines among patients with heart failure in a multicenter health system registry.

Heart failure affects people of all ages and is a leading cause of death for both men and women in most racial and ethnic groups in the United States. Infections are common causes of hospitalizations in heart failure, with respiratory infections as the most frequent diagnosis. Vaccinations provide significant protection against preventable respiratory infections. Despite being an easily accessible intervention, prior studies suggest vaccines are underused in patients with heart failure. An observational study of 5089 adults with heart failure was conducted using data from an integrated, multicenter, academic health system in Southern California from 2019 to 2022. Logistic regression models were used to determine the rates of influenza, pneumococcal, and COVID-19 vaccination among a population of patients with heart failure (heart failure preserved ejection fraction [HFpEF], heart failure mildly reduced ejection fraction [HFmrEF], and heart failure reduced ejection fraction [HFrEF], and identify whether heart failure phenotype is associated with vaccination status. Vaccination rates varied between influenza, pneumococcal, and COVID-19 vaccines. Of the three respiratory vaccines, 58.0% of patients had received an influenza vaccine, 76.2% had received a pneumococcal vaccine, and 83.3% had received a COVID-19 vaccine. There were no sex-based differences by vaccination status. Differences were seen within age, race/ethnicity, insurance type, whether the patient was a member of an Accountable Care Organization (ACO), primary language, Social Vulnerability Index (SVI) score, clinician type, and number of comorbidities. Patients with HFpEF and HFmrEF had higher vaccination rates than HFrEF. In adjusted models, patients with HFrEF had lower odds of being vaccinated for influenza (aOR=0.75, 95% CI=0.66-0.86), pneumococcal (aOR=0.65, 95% CI=0.55-0.75), and COVID (aOR=0.74, 95% CI=0.62-0.89) compared to patients with HFpEF. Patients with HFrEF had the lowest levels of respiratory vaccination compared to other specified heart failure categories. Interventions are needed to increase vaccination education and offerings, especially to patients with HFrEF.

Sex Differences in the Safety and Efficacy of Different Durations of DAPT After PCI.

Randomized controlled trials (RCTs) have examined the clinical impact of abbreviating the duration of dual antiplatelet therapy (DAPT) and have reported outcomes in men and women. The authors examined the safety and efficacy of different durations of DAPT following percutaneous coronary intervention (PCI) in men and women. We searched Cochrane, Embase, MEDLINE, PubMed, Scopus, and Web of Science databases for RCTs that compared any 2 of 1, 3, 6, or 12months of DAPT after PCI and reported outcomes in men and women. We performed a systematic review and network meta-analysis to examine sex-based differences in net adverse clinical events (NACE), major adverse cardiovascular events (MACE), and bleeding. Fifteen RCTs were included, comprising 44,610 men (74.7%) and 15,132 women (25.3%). No difference in NACE or MACE was observed between 1, 3, 6, or 12months of DAPT in both sexes. In both men and women, 1 and 3months of DAPT were each associated with lower risk of bleeding compared with 12months of DAPT. In women, 3months of DAPT was associated with a lower risk of bleeding compared with 6months. Similar results were found in sensitivity analysis of acute coronary syndrome-only trials. No significant sex-based differences in NACE or MACE were observed with different durations of DAPT after PCI, while a lower bleeding risk was observed with shorter DAPT (1-3months) among both sexes. This suggests that shorter DAPT may be preferred in both sexes following PCI, especially in those with high bleeding risk.

Shoulder pain among type 2 diabetes mellitus patients: A cross-sectional study in Chilean population.

This study aimed determine the prevalence of shoulder pain among Chilean patients with type 2 DM and to characterize their pain intensity and associated disabilities, including an analysis of sex-based differences. A total of 151 participants with type 2 DM, aged 18-79, from family health centers in Talca, Chile, were included. Data were collected via telephone interview, capturing demographic details and information about current shoulder pain, including its duration, intensity, using a Numerical Rating Scale (NRS), and disability using the Shoulder Pain and Disability Index (SPADI). Statistical analysis was performed using frequency measures, Chi-squared tests, binary logistic regression, and Student's t-tests with SPSS version 21.0. Out of 1662 eligible patients, 151 participated. The overall prevalence of shoulder pain was 53.6 % (95 % CI: 53.8-53.4), with women showing a higher prevalence (63 %; 95 % CI: 63.2-62.8) compared to men (37 %; 95 % CI: 37.2-36.8), a difference that was statistically significant (chi-square=13.5; p ≤ 0.001). The results showed that neither BMI nor sex was significantly associated with the presence of pain. No significant differences were found between sexes regarding pain intensity and disability (p ≥ 0.05). Shoulder pain is highly prevalent among patients with type 2 DM, with a higher prevalence in women. Future research should explore the impact of this condition on patients and develop targeted musculoskeletal rehabilitation programs.

Patient-centered adverse event reporting in clinical trials: A novel approach using ECOG-ACRIN E2211.

658 Background: The Common Terminology Criteria for Adverse Events (CTCAE) classifies adverse events (AEs) in clinical trials but traditionally limits the analysis to a single occurrence per patient and grade 3-4 AEs, overlooking frequent and lower grade AEs. We propose a new approach of AE reporting that captures both the safety profile and patient experience. Methods: We analyzed related AEs collected in the ECOG-ACRIN E2211 [Phase II capecitabine + temozolomide (Arm A) vs. temozolomide (Arm B) in advanced pancreatic neuroendocrine neoplasms] by CTCAE v4.0 and limited to hematologic and gastrointestinal (GI) categories for this exploratory analysis. We calculated AE burden, defined as the average occurrence of AE per patient experiencing the AE, measured by total occurrence of AEs, and divided by number of patients who developed the AE. We then compared burden of grade 3-4 AEs vs. grades 1-4 AEs. Sex differences were evaluated using t-tests. Results: For hematologic AEs, 72 patients reported 426 occurrences across grades 1-4 and 24 patients reported 39 occurrences for grades 3-4, resulting in AE burdens of 5.9 (grades 1-4) versus 1.6 (grades 3-4). For GI AEs, 108 patients reported 997 grade 1-4 events, and 13 patients reported 22 grade 3-4 events, resulting in AE burdens of 9.23 versus 1.69, respectively. Sex differences in AE burden are tabulated below (Table). For example, in Arm B, anemia burden was 4.8 (males) vs 2.7 (females) [p=0.068] for grades 1-4 and 0 (males) vs 1 (females) for grades 3 and 4. Conclusions: This AE reporting approach, accounting for the burden across grade 1-4, offers a different and more patient-centered assessment of AEs in clinical trials and may help better identify sex-based differences. Burden of AEs by treatment arm and sex distribution. Burden of Related AEs Categories of AEs Arm A (N=65) Arm B (N=68) Grade 1-Grade 4 Grade 3-Grade 4 Grade 1-Grade 4 Grade 3-Grade 4 Male Female p-value Male Female p-value Male Female p-value Male Female p-value Hematologic Anemia 2.9 3 0.937 0 0 4.8 2.7 0.068 0 1* Neutropenia 1.7 2.2 0.686 1 1* 1.2 2.3 0.064 1 1.1 0.356 Thrombocytopenia 4.3 2.6 0.241 1* 1.2 3.6 3.3 0.781 1 1 ** Gastrointestinal Abdominal pain 2.5 2.2 0.835 0 0 3.1 3 0.955 0 1* Constipation 4.1 3.2 0.515 1* 0 4.9 3.3 0.169 0 0 Diarrhea 1.8 3.6 0.158 0 0 2.6 2.5 0.940 1.25 1 0.390 Nausea 4.2 4.9 0.619 0 0 4.4 4.2 0.893 1 1** ** Vomiting 2.2 1.9 0.703 0 0 1.8 2.8 0.241 1 1 ** *Only 1 patient in each group **No variance within each group.

P-1453. Disparities in PrEP utilization

Abstract Background In October 2023, the CDC released data regarding PrEP uptake in the United States. The data indicated that in 2022, for the first time, more than one-third of individuals who could benefit from PrEP had been prescribed it. While this advancement is certainly significant, as PrEP coverage is one of the cornerstones in ending the HIV epidemic, the report also highlighted substantial disparities. According to the report, while 94% of White individuals who could benefit from PrEP had been prescribed it, only 13% of Black and 24% of Hispanic/Latino individuals who could benefit had received prescriptions for PrEP. Another notable disparity was observed regarding sex at birth, with 40% of males who could benefit from PrEP being prescribed it, compared to only 15% of females. Methods We aimed to determine if such a magnitude of disparity existed within our patient population receiving care at the infectious disease clinic. We identified 99 patients who had been prescribed PrEP at the ID clinic. These individuals were categorized based on their self-identified race/ethnicity and sex assigned at birth. Results Of the 99 individuals prescribed PrEP, 86 were males, while only 13 were females. Regarding race/ethnicity, there were 65 White or Caucasian patients, 24 Black or African American patients, 5 Hispanic or Latino patients, and 5 others. Conclusion Compared to national data published by the CDC, our data shows similar disparities. While the PrEP-to-need ratio would be a better indicator of the true disparity, our data still highlights the trend in racial and sex-based differences among users of PrEP prescriptions. Disclosures All Authors: No reported disclosures

P-1399. Impact of Positive Chlamydia and Gonorrhea Testing Among Male Military Trainees

Abstract Background All females trainees entering the U.S. Air Force basic military training (BMT) are tested for chlamydia (CT) and gonorrhea (GC) and account for the vast majority of cases in this population. Recent studies have demonstrated that, when universally tested, BMT males had similar overall rates of CT and GC as compared to females, as most cases are asymptomatic. This study evaluates the incidence of CT and GC in male BMT trainees and follow-up. Methods Over 30,000 BMT recruits train at Joint Base San Antonio-Lackland each year. This study included all male trainees who tested positive for CT or GC during their 8-week training period between 2017-2023. Information was obtained regarding patient’s age, indication for testing, facility-type performing testing, date of test, follow-up testing, and occurrence of STIs within three years of diagnosis. Male trainees were then matched with female trainees based on age, date of diagnosis, and pathogen type to determine sex-based differences in follow-up. Results 50 (0.03%) of the 182,726 males who attended BMT between 2017-2023 tested positive for CT or GC during their training. Most cases (88%) were detected in primary care and the median time in training until diagnosis was 12.5 [IQR: 8-27] days. (56%) of male trainees had symptoms on presentation for STI testing, with dysuria (40%) and penile discharge (35%) being the most common. When compared to matched-females, male trainees had significantly less follow-up testing within one year as compared to female trainees (56% vs. 75%, p=0.05). Despite the difference in follow-up testing, there was no difference in STIs diagnosed in the next three years (18% vs. 24%, p=0.5). Conclusion Despite universal access to care, only slightly more than half of male BMT trainees with CT or GC received guideline-directed follow-up within one year. Additionally, approximately one in five men who tested positive for CT or GC during BMT developed a subsequent STI in the next three years, at rates similar to women who tested positive, despite less frequent testing. More work is needed to improve follow-up testing services for those who test positive for CT or GC. Disclosures All Authors: No reported disclosures

Sex differences in delivery and neonatal characteristics of new-borns from the “MAMI-MED” cohort

IntroductionExploring modifiable and non-modifiable determinants—like sex of new-borns, maternal characteristics, and lifestyle—of maternal and child health is a priority in Public Health. Understanding these sex-based differences is essential for tailored care and informed public health policies.MethodsThe present study aimed to delineate sex disparities in delivery and neonatal characteristics within the “MAMI MED” cohort, an ongoing prospective study involving mother–child pairs from Catania, Italy. The analysis included 1,090 mother–child pairs.ResultsThe comparison of birth weight and birth length distribution showed some differences between sexes, confirmed by higher birth weight (β = 0.121; 95% CI = 0.071–0.172) and greater birth length (β = 0.659; 95% CI = 0.360–0.958) in males compared to females. However, the comparison of small and adequate for gestational age (SGA vs. AGA) revealed that the likelihood of being SGA was higher in males than in females (OR = 1.592; 95% CI = 1.005–2.563).DiscussionThus, the focus should be on improving the assessment of gender-based differences in diagnostic criteria and incorporating gender-specific aspects into existing preventive guidelines to deeply understand the effect of gender disparities and risk factors on maternal-child health.

Automated 3D Quantitative Analysis of Intrapulmonary Vessel Volume on Noncontrast CT in Healthy Individuals

Objective: This study aimed to compare automated three-dimensional Intrapulmonary Vessel Volume (IPVV) differences between lung and mediastinal windows in healthy individuals using quantitative measurements obtained from chest Computed Tomography (CT) plain scans. Methods: A total of 258 participants (aged 21–83 years) with negative chest CT scans from routine physical examinations conducted between January to November 2023 were retrospectively enrolled. For each healthy participant, an algorithm was used to automatically extract total lung IPVVs as well as IPVVs for vessels of specific diameter. Differences in IPVVs were then compared between those extracted using the lung window and those extracted using the mediastinal window. Results: The IPVVs for the entire lung, intrapulmonary arteries, intrapulmonary veins, and small pulmonary vessels (categorized by different diameters) extracted from the lung window were significantly higher than those extracted from the mediastinal window (p&lt;0.01). No significant sex-based differences in IPVV were observed for pulmonary arteries and veins with diameters between 0.8 and 1.6 mm, as well as pulmonary veins with diameters between 2.4 and 3.2 mm. However, in pulmonary arteries and veins with diameters between 1.6 and 2.4 mm, females had significantly higher IPVVs than males. In all other cases, IPVVs were larger in males than in females. Conclusion: This method of automatic IPVV extraction and quantitative assessment has been proven to be feasible. Automated IPVV expression effectively identified morphological characteristics of intrapulmonary vessels. The study has concluded IPVVs extracted from the lung window to be generally larger than those extracted from the mediastinal window.

Cross-species comparisons between pigs and mice reveal conserved sex-specific intraspinal inflammatory responses after spinal cord injury

ObjectiveTherapeutic translation is challenging in spinal cord injury (SCI) and large animal models with high clinical relevance may accelerate therapeutic development. Pigs have important anatomical and physiological similarities to humans. Intraspinal inflammation mediates SCI pathophysiology. The purpose of this study was to evaluate the effect of sex on inflammation and outcomes in a pig thoracic contusion/compression SCI model.MethodsAdult (gonad-intact) male and female Yucatan miniature swine were subjected to either SCI or sham (laminectomy-only) injury.ResultsSCI caused locomotor dysfunction (measured with the Porcine Thoracic Injury Behavior Score) with some recovery over 6 weeks and limited tissue sparing at 6 weeks with no difference between sexes. Immunohistological evaluations of spinal cord tissue at 2 days and 6 weeks post-injury revealed intraspinal microglia/macrophage (IBA-1, CD68) and lymphocyte responses (T-cells (CD3) and B-cells (CD79a)) consistent with observations in rodents and humans. Astrocyte (GFAP) immunoreactivity was observed within the lesion core at 6 weeks in contrast to observations in rodents. No differences were seen for astrocytes, microglia, macrophages, B-cells, and neutrophil infiltration between males and females. Intraspinal CD3 + T-cell counts and T-cell microclusters were significantly higher in females compared to males 6 weeks post-injury. Interestingly, we observed a similar significant increase in intraspinal CD3 + T-cell accumulation in female vs. male mice at 6 weeks post-thoracic contusion SCI.InterpretationOur observations indicate that sex is a potential biological variable for T-cell infiltration and may contribute to sex-based differences in SCI pathophysiology and recovery outcomes.

Sex differences in patients with working diagnosis of myocardial infarction with nonobstructive coronary arteries (MINOCA)

Myocardial infarction with nonobstructive coronary arteries (MINOCA) constitutes 3–15% of all acute myocardial infarctions. Women are more frequently diagnosed with MINOCA, although the influence of sex on long-term outcomes is still unclear. In this study we aimed to compare sex-based differences in baseline characteristics and clinical outcomes in patients with suspected MINOCA. We have retrospectively analyzed 6063 patients diagnosed with MINOCA (3220 females and 2843 male patients) from combined 3 large polish registries (PL-ACS, SILCARD and AMI-PL). Male patients were significantly younger (63 (55–74) vs. 71 (61–79) years, p < 0.05) and less frequently diabetic (20.1% vs. 24.1%, p < 0.05). Mortality was significantly higher in male population (11.8% vs. 10.2%, p < 0.05 at 1 year and 17.6% vs. 15.0%, p < 0.05 at 3 years). Male sex was an independent predictor of both mortality (HR = 1.29; CI 1.11–1.51; p < 0.05) and myocardial infarction (HR = 1.39; CI 1.1–1.75, p < 0.05) at 3 years follow-up. All-cause readmission rates were similar in male and female patients both at 1 year (46.0% vs. 44.4, p = 0.2) and 3 years follow-up (56.4% vs. 56.5%, p = 0.93). However, cardiovascular readmissions were more prevalent in male patients at both timepoints (33.9% vs. 29.10%, p < 0.05 at 1 year, and 41.0% vs. 37.6%, p < 0.05 at 3 years). This large-scale registry-based analysis demonstrated higher 3 years rates of adverse events, including death and MI among male patients with suspected MINOCA.

The Usability and Effect of a Novel Intelligent Rehabilitation Exergame System on Quality of Life in Frail Older Adults: Prospective Cohort Study.

Aging in older adults results in a decline in physical function and quality of daily life. Due to the COVID-19 pandemic, the exercise frequency among older adults decreased, further contributing to frailty. Traditional rehabilitation using repetitive movements tends not to attract older adults to perform independently. Intelligent Rehabilitation Exergame System (IRES), a novel retro interactive exergame that incorporates real-time surface electromyography, was developed and evaluated. Frail older adults were invited to use the IRES for rehabilitation using lower limb training twice per week for 4 weeks. Participants were required to have no mobility or communication difficulties and be willing to complete the 4-week study. The enrolled cohort had baseline scores ranging from 1 to 5 on the Clinical Frailty Scale, as described by Rockwood et al. Three major lower limb movements (knee extension, plantar flexion, and dorsiflexion) were performed 20 times for each leg within 30 minutes. The surface electromyography collected and analyzed muscle potential signals for review by health care professionals to customize the protocol for the next training. The System Usability Scale (SUS) and Taiwanese version of the EuroQol-5 Dimensions (EQ-5D) were administered after completing the first (week 1, baseline) and last training (week 4, one-month follow-up) to evaluate the usability of the IRES and its effects on the quality of life of participants. A total of 49 frail older adults (mean age 74.6 years) were included in the analysis. The usability of the IRES improved according to the mean SUS score, from 82.09 (good) at baseline to 87.14 (good+) at 1-month follow-up. The willingness to use (t96=-4.51; P<.001), learnability (t96=-4.83; P<.001), and confidence (t96=-2.27; P=.02) in working with the IRES increased. After using the IRES for 1 month, significant improvements were observed in the ease of use (t47=2.05; P=.04) and confidence (t47=2.68; P<.001) among participants without previous rehabilitation experience. No sex-based differences in the SUS scores were found at baseline or 1-month follow-up. The quality of life, as assessed by the EQ-5D, improved significantly after 1 month of IRES training compared to that at baseline (t96=6.03; P<.001). The novel IRES proposed in this study received positive feedback from frail older adults. Integrating retro-style exergame training into rehabilitation not only improved their rehabilitation motivation but also increased their learning, system operability, and willingness to continue rehabilitation. The IRES provides an essential tool for the new eHealth care service in the post-COVID-19 era.

Sex-Based Differences in the Arthroscopic Treatment of Femoroacetabular Impingement Syndrome: 10-Year Outcomes With a Nested Propensity-Matched Comparison

Background: Sex has been associated with different pathologic characteristics in painful hips undergoing hip arthroscopic surgery. Purpose: To compare minimum 10-year patient-reported outcomes (PROs) and survivorship in patients who underwent primary hip arthroscopic surgery for femoroacetabular impingement syndrome and labral tears according to sex. Study Design: Cohort study; Level of evidence, 3. Methods: Data from patients who underwent primary hip arthroscopic surgery between March 2009 and May 2011 were reviewed. Patients with minimum 10-year PROs for the modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score–Sports-Specific Subscale (HOS-SSS), and visual analog scale (VAS) for pain were eligible. Exclusion criteria included previous ipsilateral hip conditions or surgical procedures, Tönnis grade >1, or dysplasia (lateral center-edge angle <25°). In the subanalysis, female patients were matched to male patients using a 1:1 ratio by age, sex, and body mass index. Results: A total of 375 hips had a minimum 10-year follow-up. There were 249 female (mean age, 36.8 ± 13.1 years) and 126 male (mean age, 38.9 ± 13.1 years) hips. Survivorship was defined as no conversion to total hip arthroplasty. Female and male hips exhibited similarly high rates of survivorship (80.3% vs 72.2%, respectively; P = .076). Female hips underwent secondary arthroscopic surgery at a statistically higher rate of 14.5% (P = .021) and had higher rates of capsular repair and iliopsoas fractional lengthening (P < .0001 and P < .001, respectively). Male hips had a significantly higher rate of acetabular labrum articular disruption/Outerbridge grade 3 and 4 damage at 54.0% compared with female hips (both P < .001) and underwent femoroplasty and acetabular microfracture at significantly higher rates of 88.1% versus 51.0%, respectively, and 16.7% versus 4.8%, respectively (both P < .001). In the subanalysis, both groups showed significant improvements in all PROs from baseline (all P < .001). Even though female patients demonstrated a higher rate of secondary arthroscopic surgery, they had a higher self-reported mean satisfaction score of 9.0 compared with 8.4 (P = .003) and a greater magnitude of improvement in 10-year PROs (ΔmHHS: 29.3 ± 17.5 vs 23.1 ± 19.8, respectively [P = .036]; ΔNAHS: 33.2 ± 21.3 vs 25.1 ± 19.5, respectively [P = .012]; ΔHOS-SSS: 47.0 ± 32.0 vs 32.7 ± 31.9, respectively [P = .008]; and ΔVAS: –4.6 ± 2.7 vs −3.5 ± 2.0, respectively [P = .009]). However, all PROs at a minimum 10-year follow-up were similar between the groups. Conclusion: After undergoing hip arthroscopic surgery for femoroacetabular impingement syndrome, both female and male patients reported significant improvements in all PROs at a minimum 10-year follow-up and high patient satisfaction, with similar final functional scores. Even though female patients demonstrated a higher rate of secondary arthroscopic surgery, they had a higher satisfaction score and a greater magnitude of improvement in PROs postoperatively.

Long-term pulse pressure trajectories and risk of incident atrial fibrillation: the Tromsø Study.

Sex-based differences in the association of long-term trends in pulse pressure with future risk of atrial fibrillation (AF) have been explored using data from the population-based Tromsø Study 1986-2016. Women (n = 8331) and men (n = 7638) aged ≥20 years who attended at least two of the three Tromsø Study surveys conducted between 1986 and 2001 (the exposure period) were followed up for incident AF throughout 2016 (the follow-up period). Pulse pressure ≥60 mmHg was considered elevated. Group-based trajectory modelling and Cox regression were used for statistical analyses. Three long-term trajectory groups for pulse pressure were identified: Group 1 had normal pulse pressure throughout the exposure period, Group 2 had normal pulse pressure at the beginning and elevated pulse pressure at the end of the exposure period, and Group 3 had elevated pulse pressure throughout. Over the follow-up period, 568 (6.8%) women and 798 (10.5%) men developed AF. After adjustment for potential confounders at baseline, the long-term trajectory groups for elevated pulse pressure were associated with increased risk of AF in women, but not in men. In women, the adjusted hazard ratios of AF were 1.60 (95% confidence interval: 1.23, 2.09) for trajectory Group 2 and 2.78 (1.93, 4.02) for trajectory Group 3, compared with Group 1. Long-term elevated pulse pressure trajectories were independently associated with increased risk of AF in women, but not in men. Our findings call for further investigations to understand the mechanisms behind these sex-based differences.

Expression Rates of Sex Hormone Receptors with Their Clinical Correlates in Gastric Cancer Patients and Normal Controls.

Sex hormones affect development and prognosis of gastric cancer (GC). This study aimed to compare the sex hormone receptor expression between control and GC, and to evaluate its correlation with patient characteristics. 110 patients (74 with GC, 36 controls) underwent immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) for estrogen receptors (ERs) α and β and androgen receptor (AR). The effect of ERs and AR on the clinicopathological and tumor characteristics were analyzed. The positive rate of ERα, ERβ, and AR in GC tissue was 64.9%, 78.4%, and 60.8% by IHC and 41.4%, 27.6%, and 48.3% in RT-PCR respectively. In control, the positive rate of those was 16.7%, 80.6%, and 38.9% by IHC and 22.2%, 58.3%, and 19.4% in RT-PCR respectively. The IHC and RT-PCR results showed concordance with each other, and ERα and AR expressions were positively correlated with cancer, while ERβ showed the opposite pattern. ERα expression was correlated with Helicobacter pylori negativity (p<0.001), diffuse or mixed-type histology (p=0.014), and undifferentiated histology (p<0.001), and AR expression was related to H. pylori negativity (p<0.001), cardiac cancer (p=0.040), and undifferentiated histology (p<0.001). The higher expression rate of ERα in males and that of AR in females seemed to be related with cancer, showing sex differences. The expression rates of ERα, ERβ, and AR were different depending on sex, histologic type and H. pylori infection status, which may explain sex-based differences in GC.