Sex-based Differences Research Articles

Sex-based differences in hamstrings stiffness assessment in football players using ultrasound shear wave elastography

Sex-based differences in hamstrings stiffness assessment in football players using ultrasound shear wave elastography

Sex-dependent interplay of phosphate and inflammation on muscle strength irrespective of muscle mass in middle-aged and older adults

BackgroundElevated circulatory phosphate levels are linked to age-related muscle dysfunction, yet the mechanisms remain unclear. This study investigated the hypothesis that inflammation plays a role in connecting elevated phosphate levels to muscular dysfunction in middle-aged and older individuals and explored potential sex-based differences in these associations. MethodsThe study, based on the I-Lan Longitudinal Aging Study Cohort, analyzed individuals' serum phosphate and hsCRP levels. Sex-specific analyses explored links between circulatory phosphate, inflammation, and muscle profiles (mass, handgrip strength, and walking speed). The study also examined potential mediation or synergistic effects of inflammation in the circulatory phosphate-muscle relationship. ResultsThe study included 2006 participants (mean age: 65.5 ± 6.5 years; 49.8 % men). Women exhibited higher circulatory phosphate levels than men. Linear analyses revealed that higher phosphate levels were significantly associated with weaker handgrip strength but not with reduced muscle mass in both men and women. In women, circulatory phosphate was not associated with inflammation (hsCRP levels), while in men, higher phosphate levels were significantly associated with higher hsCRP levels. In men, a synergistic effect was observed, where the combination of high hsCRP and elevated phosphate levels had a more pronounced impact on reducing handgrip strength than either factor alone. ConclusionsThis study highlights a sex-specific association of inflammation in the mechanisms of hyperphosphatemia-related muscle weakness. The findings emphasize the importance of managing both hyperphosphatemia and chronic inflammation to mitigate their collective impact on muscle function, particularly in older men. Addressing these factors is crucial for promoting muscle health in later life.

Circulating Galectin-3 distinguishes global aortic aging among older women

Abstract Background Traditional cardiovascular risk factors may underestimate age-associated cardiovascular risk, particularly in estimating discrepant risks between sexes. As a marker of adverse cardiovascular events, aortic stiffness may improve risk assessment, but the requirement for advanced imaging equipment restrict widespread translation of this paradigm. Conversely, circulating blood biomarkers may augment mechanistic understanding and distinguish sex-based differences in aortic stiffness. Purpose Hypothesizing that Galectin-3 (Gal-3) is associated with aortic aging among older adults, we examined sex-based differences between Gal-3 and global aortic stiffness as assessed by a novel cardiac magnetic resonance (CMR)-derived measurement of aortic global longitudinal strain (AOGLS). Methods Community older adults without cardiovascular disease underwent simultaneous CMR with serum Gal-3 quantification using chemiluminescent microparticle immunoassays. Poorer AOGLS was defined as values below the 75th percentile of AOGLS measurements. Multivariable regression models were used to assess the association of Gal-3 with AOGLS. Results Of 255 participants (mean age 70.8 ±9.1 years, LVEF 66.3 ±8.3%), 44.3% were women. Poorer AOGLS was characterized by higher Gal-3 (B coefficient = -0.101, 95%CI [-0.167, -0.034], p = 0.003), mean age (B = -0.126, 95%CI [-0.154, -0.098], p <0.001), male sex (B = -0.991, 95%CI [-0.409, -1.572], p = 0.001), history of hypertension (B = -0.777, 95%CI [-1.364, -0.189], p = 0.010), diabetes mellitus (B = -0.888, 95%CI [-1.617,-0.158], p = 0.017), smoking (B = -1.346, 95%CI [-2.15, -0.542], p=0.001), pulse rate (B = -0.032, 95%CI [-0.055, -0.01], p = 0.005), systolic BP (B = -0.014, 95%CI [-0.025, -0.004], p = 0.009), and diastolic BP (B = -0.033, 95%CI [-0.06, -0.006], p = 0.018) on univariable linear regressions; no associations were observed with urine albumin-to-creatinine ratio, serum NT-ProBNP, or hs-Troponin I. After multivariable adjustments for sex, age, significant cardiovascular risk factors (hypertension, diabetes, smoking), and pulse rate, the inverse relationship between Gal-3 and AOGLS (Figure 1) persisted (B = -0.071 95%CI [-0.135, -0.008], adj. p = 0.028, R2 = 0.217). The association between Gal-3 and AOGLS was more marked among women (Figure 2), compared to men. Among women, higher Gal-3 characterized women with poorer AOGLS (17.04 ±3.73 ng/mL vs 15.48 ±3.55 ng/mL p = 0.040) (B = -0.120, OR 0.887, 95% CI [0.787, 0.999], adj. p = 0.048), independent of age. Conclusions Galectin-3 was adversely associated with novel CMR-derived AOGLS. Among these older adults with age-associated observations in AOGLS, Gal-3 highlighted sex-based differences in AOGLS and differentiated women with poorer AOGLS from women with better AOGLS. Serum Gal-3 measurements may be useful for detecting adverse patterns of aortic aging, particularly as an early approach in community older adults.

Sex-based differences in anatomical and hemodynamic parameters and outcomes in patients with hypertrophic cardiomyopathy undergoing alcohol septal ablation

Abstract Background This study aimed to assess sex differences in anatomical and hemodynamic parameters, and in procedure related outcomes, in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing alcohol septal ablation (ASA). Methods 154 patients that underwent ASA in at our university hospital, between 2009 and 2021, were retrospectively included. Anatomical and hemodynamic parameters were collected from invasive catheterization before and during ASA, and from echocardiography (ECHO) examinations at maximum one week before ASA. Follow-up was conducted one year after ASA. The parameters analyzed were left ventricular (LV) volume, basal septal wall thickness (BSWT), anterior (AML) and posterior mitral leaflet (PML) length, minimal left ventricle outflow tract (LVOT) diameter, and LVOT pressure gradient at rest, prior to ASA, and prevalence of atrioventricular block after ASA. Linear and logistic regression models were used to assess the sex differences between the parameters. Results 50% of the patients were women. At the time of ASA, women were significantly older, had lower LV volume indexed for BSA in end-diastole (44 vs. 54 ml, p<0.001) and end-systole (18 vs. 23 ml, p=0.021), longer AML length indexed for BSA (13.7 vs. 11.6 mm, p<0.001) and PML length indexed for BSA (8.8 vs. 8.1 mm, p=0.018), smaller minimal LVOT diameter (4.6 vs. 4.9 mm, p=0.042), and higher LVOT pressure gradient at rest (49.3 vs. 32.5 mmHg, p=0.014), compared with men. The median follow-up was 364 days. Atrioventricular block (II or III) was more common among women (n=20, 26%) compared with men (n=10, 13%, p=0.045). Conclusions ECHO and invasive catheterization prior to ASA showed that women with HOCM presented with less favorable anatomical and hemodynamic pre-conditions, compared with men. At follow-up, women had a greater incidence of atrioventricular block after ASA. This strongly emphasizes the need for a sex-specific approach to optimize care and improve outcomes in patients with HOCM.

Sex differences in cancer incidence amongst people with cardiovascular disease: a large British population study

Abstract Background Studies have shown that patients with cardiovascular disease (CVD) have an incremental risk of death due to noncardiac causes. This is especially attributable to cancer developments during long term follow up. The two diseases share pathophysiological mechanisms that extend beyond traditional risk factors. With well-established sex disparities in CVD, it becomes imperative to investigate whether similar sex-based differences exist in both the incidence of cancer and cancer-related mortality, in participants with CVD vs those without CVD. Purpose We aim to analyse the sex differences in incident cancer and cancer-related mortality between people with and without CVD. Methods Participants were drawn from a large British population based prospective cohort study and followed up for a median of 26.2 years. Participants were stratified by sex and whether they developed CVD over the study follow-up. The cumulative incidence of cancer, excluding non-melanoma skin cancers were calculated. Sex-specific lifetime risks were determined accounting for competing risks of death. Cause-specific hazard ratios were determined using Royston-Parmar models. Models were adjusted for ethnicity and time-updated covaries, including material deprivation, CV risk factors, lifestyle factors, comorbidities, and medication. Participants’ CVD status was time-updated over the study follow-up as this was diagnosed. Results Out of a total of 22, 534 participants, free of cancer at baseline, 53.7% were women. Mean (standard deviation) age was 58.6 (9.3) for women and 59.5 (9.3) for men, at baseline. Men were older and had more comorbidities. Hypertension and obesity were risk factors more prevalent amongst men, while women were more likely to be smokers at baseline. Participants with CVD had more comorbidities, were more likely to smoke, have higher HbA1cs and be obese than those without CVD. The adjusted lifetime risks of incident cancer in participants with CVD at age 75 were higher in men (13.9%) compared to women (10.1%). This translates into a cause-specific hazard ratio (cHR) (99% confidence interval) for incident cancer (men vs. women) of 1.41 (1.27 - 1.55). Similar findings were demonstrated in participants with no CVD (10.2% for men and 8.2% for women), corresponding to a cHR of 1.27 (1.15 - 1.40). Furthermore, men had a higher risk of cancer-related mortality compared to women in participants with CVD 1.54 (1.33 - 1.78), as well as among participants without CVD 1.34 (1.17 - 1.53). Conclusion Our study showed an association between CVD and the lifetime cancer risk in both sexes after extensive adjustment. Furthermore, we show that men have a higher risk of cancer incidence and cancer-related mortality than women, regardless of comorbid CVD. However, these associations, were stronger in participants with CVD. It is vital to identify driving forces of such disparities to achieve health equity.

Outcomes of CT- or CMR-guided TAVR according to sex: a secondary analysis of the randomized TAVR-CMR trial

Abstract Background Previous studies have reported sex differences in pre-procedural imaging characteristics of patients undergoing transcatheter aortic valve replacement (TAVR) evaluation. Whether these differences affect the outcome of computed tomography (CT)-guided or cardiac magnetic resonance (CMR)-guided TAVR has not been studied. Objectives This analysis aimed to evaluate sex-based differences in imaging findings and outcomes in patients undergoing TAVR for severe aortic valve stenosis. Methods This was a secondary analysis of the TAVR-CMR trial, a randomized clinical trial comparing TAVR planning by CT or CMR. Outcomes (based on the Valve Academic Research Consortium (VARC)–2 definition) with each imaging strategy were compared according to sex. Results Of 380 patient randomized into the TAVR-CMR trial, 194 (51.1%) were female and 186 (48.9%) were male. Of these, 267 patients eventually underwent TAVR (133 women (49.8%) and 134 men (50.2%), p=0.457). Imaging findings differed between the sexes for both imaging modalities. The comparison between CT and CMR to assess the access route and landing zone showed no difference in both women and men (all p>0.05). Implantation success was not significantly different between imaging strategies for both women (84.7% (CT group) vs. 93.2% (CMR group), p=0.11) and men (95.7% (CT group) vs. 93.8% (CMR group), p=0.61). All-cause mortality at 6 months was not significantly different between imaging strategies for both women (10.2% (CT group) vs. 8.1% (CMR group), p=0.68) and men (4.3% (CT group) vs. 9.4% (CMR group), p=0.24). Conclusions This secondary analysis has confirmed sex-related differences in pre-procedural imaging characteristics, with no influence of the imaging modality used. Similar outcomes were observed in both female and male patients when the TAVR was guided by either a CMR or a CT scan.

Enhancing Equity in Clinical Research: A Multifaceted Proposal for Spondyloarthritis.

Clinical research advances medical knowledge and improves healthcare outcomes. However, disparities in research participation hinder progress. The Unmet Research Needs in Spondyloarthritis Conference IV highlighted critical insights and strategies to enhance equity in clinical research. Talks focused on engaging underrepresented communities and addressing disparities in rheumatic diseases, particularly spondyloarthritis (SpA), to ensure research results are generalizable and inclusive. Disparities in SpA management, such as greater back pain severity among Black and Hispanic Americans and sex-based differences in pain management, emphasize the need for equitable research. Dr. Elizabeth Ferucci discussed the racial disparities in rheumatologic care, highlighting the importance of early access to rheumatologists and culturally informed primary care to improve outcomes. Dr. Hani El-Gabalawy's talk on engaging Indigenous communities stressed the importance of community consent and reciprocal benefits. Dr. Sarfaraz Hasni's presentation on mitigating disparities in research participation underscored the need for inclusive practices and strategies to promote diverse representation. Finally, Dr. Edith Williams emphasized institutional approaches to fostering equity, including diverse recruitment practices and institutional review board alignment with diversity priorities. Strategies to enhance equity in clinical research include community engagement, addressing logistical barriers to participation, and ensuring diverse research teams. These approaches can dismantle barriers for underrepresented communities, making research more accessible and reflective of the broader population. The SpA research community must commit to creating structures that foster inclusivity, ensuring medical advancements benefit all populations, especially historically underrepresented groups. The principles and strategies proposed serve as a roadmap for achieving equity in SpA research.

Sex Differences in Colonoscopy Indications and Findings: Results from a Large Multicenter Database.

Background: Sex-based differences are common among diseases. We aimed to investigate the differences in colonoscopy indications and its findings between males and females. Methods: A large, multi-center, cross-sectional, retrospective study included all colonoscopies performed between 2016 and 2021 in seven endoscopy departments. The indications and findings of the procedures were compared between males and females. Results: A total of 151,411 (52.6%) women and 136,519 (47.4%) men were included, aged 56.54 ± 12.9 years and 56.59 ± 12.7. Cecal intubation was similar (95.6% vs 95.5%, p = 0.251). More females had excellent or good bowel preparation compared to males (71.4% vs 65.6%). Colonoscopy due to abdominal pain, constipation, diarrhea, and anemia was higher in females compared to males (15% vs 9.9%, 3.9% vs 2.2%, and 7.6% vs 4.9%, p < 0.001, respectively), while positive FOBT, rectal bleeding and post-polypectomy surveillance and screening were more common indications among males (9.5% vs 7.8%, 10.7% vs 7.8%, and 10.8% vs 7.1%, respectively). On colonoscopy, males were found to have significantly higher colorectal cancer and polyps (0.5% vs 0.4% and 35.1% vs 24.6%). Polyp detection rates were lower in females across all indications, whereas diverticulosis rates were higher in males. However, a clinically significant difference regarding diverticulosis was observed only in patients with anemia as the indication. Conclusions: Notable differences exist between males and females in terms of the indications and findings on colonoscopy. This highlights the need for identifying the factors contributing to these differences and the developing sex-specific approaches for the diagnosis and management of gastrointestinal diseases.

Gender and violent crime modify associations between greenspace and cardiovascular disease mortality in Philadelphia, PA

Few studies have explored variability of associations between greenspace and cardiovascular (CVD) mortality according to demographic or neighborhood contextual factors. We estimated overall and sex-stratified associations between greenspace and CVD mortality rates in Philadelphia, PA, and quantified effect modification of the sex-stratified associations by neighborhood violent crime rates. Sex- and age-stratified census tract CVD mortality rates (years 2008–2015) were linked with proportion tree canopy cover, grass/shrub cover, and total vegetation cover, and proportion of adult residents reporting access to a park. We used multivariable negative binomial models to estimate overall and sex-stratified associations between neighborhood greenspace and CVD mortality rates, and quantified effect modification by tract-level rates of violent crime. Higher proportion tree canopy cover and higher proportion adults reporting access to parks were associated with modestly lower rates of CVD mortality, with more pronounced estimates in males than females. In tracts with higher rates of crime, higher tree canopy coverage and perceived park access were associated with lower CVD mortality rates. We did not observe strong evidence of sex-based differences in interaction between neighborhood crime rates and greenspace. Results from this study reveal variability of associations between greenspace and CVD mortality rates according to sex categories, and according to neighborhood social environments. There is a need for further research exploring the extent to which differences in perceived safety explain gender-based differences in associations between greenspace and cardiovascular outcomes.

Effectiveness of high-frequency vibration, cotton rolls and elastomeric wafers in alleviating debonding pain of orthodontic metal brackets: a randomized clinical trial

This study aimed to evaluate the effectiveness of different pain mitigation methods during orthodontic debonding and to evaluate pain sensitivity across various regions of the dentition. A total of 144 participants (50 males and 94 females) with metal brackets were randomly assigned to one of four groups: High-Frequency Vibration (V), Cotton Roll (CR), Elastomeric Wafer (EW), and Open Mouth group (OM). Pain levels were measured using the Visual Analog Scale (VAS) across different sextants of the dentition. The Kruskal-Wallis test and post hoc analyses were conducted to compare VAS scores between groups. The Mann-Whitney test was used to analyse sex-based differences. The V group, utilizing high-frequency vibration, had the lowest total VAS score, indicating superior pain relief compared to CR, EW, and OM groups. No significant difference was observed between the CR and EW groups. Median VAS scores were highest in the lower front sextant, followed by the upper front sextants, and lowest in the posterior regions, indicating greater pain sensitivity in the anterior regions during debonding. High-frequency vibration was the most effective method for reducing pain during orthodontic debonding, particularly in the anterior dental regions. Both CR and EW methods were also effective but to a lesser extent. These findings suggest that high-frequency vibration could significantly improve patient comfort during orthodontic procedures. Utilizing high-frequency vibration for orthodontic debonding can enhance patient comfort, especially in the more sensitive anterior dental regions, thereby potentially improving treatment compliance and experience.Trial registration: NCT05904587.

Bacteriophage–derived double-stranded RNA (larifan) exerts variable effects on human blood monocytes depending on age and sex of donors

To date, great attention is paid to sex and age differences in the therapeutic effectiveness of drugs, including those that impact the immune system. Bacteriophage-derived dsRNA is the main component of the medicinal product Larifan, which exhibits interferonogenic activity. This study aimed to estimate the effect of Larifan on the activation status of human peripheral blood monocytes collected from donors of different ages and sex. Blood samples were obtained from the healthy volunteers, divided into 4 groups: young men and young women aged from 20 to 39 years, aged men and aged women from 54 to 69 years old. EDTA-anticoagulated blood samples were exposed to 200 μg/ml Larifan for 30 min, cells were washed and treated to study phagocytic index, ROS generation and expression of phenotypic markers. Only live monocytes selected by flow cytometry were included in the analysis. It was shown that monocytes from young as well as from aged females turned out to be quite inert to the treatment with Larifan. Monocytes from young males after the treatment demonstrated a minor decrease in phagocytic activity and significant down-regulation of ROS generation. Monocytes from aged adults showed clear sex-based differences in the basal cell phenotype. Thus, compared to monocytes from women, the monocytes from men over 50 after the treatment with Larifan showed decreased phagocytic activity and CD86 expression along with increased CD206 expression. Taken together, these results indicate the need for further studies of Larifan focused on developing personalized treatment depending on the age and sex of an individual. Keywords: double-stranded RNA, Larifan, monocytes, phagocytosis, reactive oxygen species, sex and age differences

Mouse Corneal Immune Cell Heterogeneity Revealed by Single-Cell RNA Sequencing.

This study aimed to define the heterogeneity, spatial localization, and functional roles of immune cells in the mouse cornea using single-cell RNA sequencing (scRNA-seq) and immunofluorescent staining. Enriched mouse corneal immune cells (C57BL/6 strain, age 16-20 weeks) underwent single-cell RNA sequencing library preparation, sequencing, and analysis with Seurat, Monocle 3, and CellChat packages in R. Pathway analysis used Qiagen Ingenuity Pathway Analysis software. Immunostaining confirmed cell distribution. We identified 14 distinct immune cell clusters (56% myeloid and 44% lymphoid). Myeloid populations included resident macrophages, conventional dendritic cells (cDC2s), Langerhans cells, neutrophils, monocytes, and mast cells. Additionally, lymphocyte subsets (B, CD8, CD4, γδT, natural killer, natural killer T, and group 2 innate lymphoid cells) were found. We also found three new subtypes of resident macrophages in the cornea. Trajectory analysis suggested a differentiation pathway from monocytes to conventional dendritic cells, resident macrophages, and LCs. Intercellular communication network analysis using cord diagram identified amyloid precursor protein, chemokine (C-C motif) ligands (2, 3, 4, 6, 7, 9, and 12), Cxcl2, Mif, Tnf, Tgfb1, Igf1, and Il10 as prominent ligands involved in these interactions. Sexually dimorphic gene expression patterns were observed, with male myeloid cells expressing genes linked to immune regulation (Egr1, Foxp1, Mrc1, and Il1rn) and females showing higher expression of antigen presentation genes (Clic1, Psmb8, and Psmb9). Finally, immunostaining confirmed the spatial distribution of these cell populations within the cornea. This study unveils a diverse immune landscape in the mouse cornea, with evidence for cell differentiation and sex-based differences. Immunostaining validates the spatial distribution of these populations, furthering our knowledge of corneal immune function.

Morphometry of Typical Cervical Vertebrae on Magnetic Resonance Imaging in Adult Bangladeshi People: A Cross-sectional Analytical Study

Background: Accurate knowledge of cervical vertebral morphometry is crucial for diagnosing pathological conditions and planning surgical interventions. However, data specific to the Bangladeshi population is lacking. Objectives: To determine the morphometric measurements of typical cervical vertebrae (C3-C6) on Magnetic Resonance Imaging (MRI) in adult Bangladeshi people and to analyze potential sex-based differences. Methods: This cross-sectional analytical study was conducted on 70 MRI scans (35 male, 35 female) of typical cervical vertebrae from adult Bangladeshi individuals. Various morphometric parameters were measured using 'Radiant DICOM Viewer' software. Statistical analysis was performed using SPSS version 22.0. Results: The sagittal diameter of the vertebral body was significantly larger in males compared to females for all measured vertebrae (p&lt;0.001). No significant differences were found between sexes in the height and transverse length of the vertebral body, anteroposterior and transverse lengths of the vertebral foramen, dimensions of foramen transversarium, superior articular facets, lamina, pedicle, and spinous process length (p&gt;0.05 for all). Conclusion: This study provides baseline morphometric data for typical cervical vertebrae in adult Bangladeshi individuals. The observed sexual dimorphism in sagittal vertebral body diameter and the lack of significant differences in other parameters contribute to our understanding of population-specific cervical spine anatomy. These findings may have implications for optimizing surgical techniques and implant designs for the Bangladeshi population.

Sex Differences in Management, Time to Intervention, and In-Hospital Mortality of Acute Myocardial Infarction and Non-Myocardial Infarction Related Cardiogenic Shock.

Limited data are available on sex differences in the time to treatment of cardiogenic shock (CS) with and without acute myocardial infarction (AMI). For this retrospective cohort study, we used nationally representative hospital survey data from the National Inpatient Sample (years 2016-2021) to assess sex differences in interventions, time to treatment (within versus after 24 hours of admission), and in-hospital mortality for AMI-CS and non-AMI-CS, adjusting for age, race, income, insurance, comorbidities, and prior cardiac interventions. We identified 1,052,360 weighted CS hospitalizations (60% non-AMI-CS; 40% AMI-CS). Women with CS had significantly lower rates of all interventions. For AMI-CS, women had a higher likelihood of in-hospital mortality after: revascularization (adjusted odds ratio (aOR) 1.15 [95% CI 1.09-1.22]), mechanical circulatory support (MCS) (1.15 [1.08-1.22]), right heart catheterization (RHC) (1.10 [1.02-1.19]) (all p<0.001). Similar trends were found for the non-AMI-CS group. Women with AMI-CS were less likely to receive early (within 24 hours of admission) revascularization (0.93 [0.89-0.96]), MCS (0.76 [0.73-0.80]), or RHC (0.89 [0.84-0.95]) than men; women with non-AMI-CS were less likely to receive early revascularization (0.78 [0.73-0.84]), IABP (0.85 [0.78-0.94]), pLVAD (0.88 [0.77-0.99]) or RHC (0.83 [0.79-0.88]) than men (all p<0.001). For both types of CS, in-hospital mortality was not significantly different between men and women receiving early ECMO, pLVAD, or PCI. Sex disparities in the frequency of treatment of CS persist on a national scale, with women being more likely to die following treatment and less likely to receive early treatment. However, when comparing patients who received early treatment, in-hospital mortality does not differ significantly when men and women are treated equally within 24 hours of admission. Early intervention if clinically indicated could mitigate sex-based differences in CS outcomes and should be made a priority in the management of CS. What is new?Women have increased in-hospital mortality with cardiogenic shock and have lower odds of early intervention (within 24 hours of admission) compared to men.When men and women with cardiogenic shock are treated equally in terms of early intervention within 24 hours of admission, sex differences in in-hospital mortality disappear.What are the clinical implications?Sex-based disparities are present in the utilization of treatment and time to intervention for patients with cardiogenic shock.Early recognition and intervention for cardiogenic shock among women should be considered to improve clinical outcomes.

Gray matter volume differences based on sex in first-episode drug-naive patients with major depressive disorder and its molecular analysis.

This study analyzed whether gray matter volume (GMV) differences exist between the sexes in patients with major depressive disorder (MDD) and explored the relationships between these differences and neurotransmitter systems. This study enrolled 190 first-episode drug-naive patients with MDD and 293 healthy controls. All participants underwent T1-weighted high-resolution MRI. The interaction between the diagnosis (healthy controls vs. MDD) and sex (male vs. female) regarding GMV alterations was analyzed. The JuSpace toolbox, which covers a wide range of neurotransmitter systems, was used to identify the relationship between MDD-induced and sex-induced GMV alterations and specific receptor/transporter proteins in the brain. Sex-specific GMV differences were observed in the healthy controls but not in MDD patients. Male healthy controls had a larger GMV in the bilateral parahippocampal, lingual, inferior occipital, fusiform, cerebellar subregions, and left inferior temporal than female healthy controls, but several subregions of the thalamus had a larger GMV in female healthy controls than in male healthy controls. Sex-induced GMV alterations were associated with 5-hydroxytryptamine receptor subtype 1a, cannabinoid receptor, and dopamine receptor (P < 0.01, false discovery rate corrected). GMV differences were not detected in the main effect of diagnosis and the interaction of diagnosis and sex. Sex-specific GMV differences are associated with the spatial distribution of serotonin, dopamine, and cannabinoid neurotransmitter receptor systems. Sex-based physiological differences in the GMV may account for male and female susceptibility to and differences in the clinical symptoms of MDD.

Physiological influences on neurovascular coupling: A systematic review of multimodal imaging approaches and recommendations for future study designs.

In this review, we have amalgamated the literature, taking a multimodal neuroimaging approach to quantify the relationship between neuronal firing and haemodynamics during a task paradigm (i.e., neurovascular coupling response), while considering confounding physiological influences. Original research articles that used concurrent neuronal and haemodynamic quantification in humans (n ≥ 10) during a task paradigm were included from PubMed, Scopus, Web of Science, EMBASE and PsychINFO. Articles published before 31 July 2023 were considered for eligibility. Rapid screening was completed by the first author. Two authors completed the title/abstract and full-text screening. Article quality was assessed using a modified version of the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. A total of 364 articles were included following title/abstract and full-text screening. The most common combination was EEG/functional MRI (68.7%), with cognitive (48.1%) and visual (27.5%) tasks being the most common. The majority of studies displayed an absence/minimal control of blood pressure, arterial gas concentrations and/or heart rate (92.9%), and only 1.3% monitored these factors. A minority of studies restricted or collected data pertaining to caffeine (7.4%), exercise (0.8%), food (0.5%), nicotine (2.7%), the menstrual cycle (0.3%) or cardiorespiratory fitness levels (0.5%). The cerebrovasculature is sensitive to numerous factors; thus, to understand the neurovascular coupling response fully, better control for confounding physiological influences of blood pressure and respiratory metrics is imperative during study-design formulation. Moreover, further work should continue to examine sex-based differences, the influence of sex steroid hormone concentrations and cardiorespiratory fitness.

Propofol and Fentanyl Pharmacokinetics and Pharmacodynamics in Extracorporeal Membrane Oxygenation.

Despite the potential risks associated with sedation, there is a paucity of pharmacokinetic/pharmacodynamic (PK/PD) data for propofol and fentanyl in patients supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO). Describe propofol and fentanyl PK/PD profiles in V-V ECMO patients. Prospective, single-center, open-label PK/PD study at the Toronto General Hospital ICU between July 2022 and January 2023. Using high-performance liquid chromatography-tandem mass spectrometry, propofol and fentanyl total concentrations were measured during V-V ECMO. Sequential PK/PD modeling, using sex as a covariate, was conducted with processed electroencephalography (PSI) for sedation, and expiratory occlusion pressure (Pocc), and airway occlusion pressure during the first 0.1 seconds (P0.1) for respiratory effort. Eleven patients underwent 106 evaluations over a median (IQR) follow-up of 146 (116-146) hours. Patient's average (±SD) age was 43 (±13) years, and 55% were female. Propofol and fentanyl PK were best described by a two-compartment model. Propofol-PSI PD was described using an effect compartment, with a coefficient of determination (ρ2) of 0.78. There was a significant increase in propofol (p=0.01) and fentanyl (p=0.03) clearance within 10 minutes of ECMO initiation, plateauing after 8 hours of ECMO support. Despite this, patient over-sedation (PSI<40) occurred in 74% of the observations. Females exhibited higher sedative central volume of distribution and lower propofol clearance. ECMO initiation resulted in a time-limited increased sedative clearance. PSI accurately described sedative PD, but variable respiratory effort was observed irrespective of sedative plasma concentrations. Sex-based differences were found in sedative PK/PD parameters.

Differences between women and men in prolonged weaning

BackgroundIn recent years, the importance of sex as a factor influencing medical care has received increasing attention in the field of intensive care medicine. The objective of this study was to examine the influence of sex in prolonged weaning.MethodsA retrospective analysis of patients undergoing prolonged weaning at Thoraxklinik, University Hospital Heidelberg between 12/08 and 12/23 was conducted. Patients with neuromuscular diseases were excluded from the analyses. The risk factors for weaning failure in men and women were identified through stepwise cox-regression analyses.ResultsA total of 785 patients were included, of whom 313 (39.9%) were women. 77.9% of the women and 75.4% of the men were successfully weaned from invasive ventilation. In group comparisons and multivariable analyses, sex was not found to be a risk factor for weaning failure. Cox regression analyses were performed separately for both sexes on the outcome of weaning failure, adjusting for relevant covariates. The results indicated that age ≥ 65 years (HR 2.38, p < 0.001) and the duration of IMV before transfer to the weaning centre (HR 1.01/day, p < 0.001) were independent risk factors in men. In women, however, the duration of IMV before transfer (HR 1.01, p < 0.001), previous non-invasive ventilation (HR 2.9, p 0.005), the presence of critical illness polyneuropathy (HR 1.82; p = 0.040) and delirium (HR 2.50, p = 0.017) were identified as relevant risk factors. In contrast delirium was associated with a favourable weaning outcome in men (HR 0.38, p = 0.020) and nosocomial pneumonia as a reason for prolonged weaning in women (HR 0.43; p = 0.032).ConclusionThe analyses indicate that there are sex-based differences in the risk factors associated with weaning failure. Further studies, ideally prospective, should confirm these findings to assess whether sex is a factor that should be taken into account to improve weaning outcomes.

Sex-Based Differences in Polytraumatized Patients between 1995 and 2020: Experiences from a Level I Trauma Center.

Background/Objectives: The aim of this study was to examine sex-related differences in the outcomes of polytraumatized patients admitted to a level I trauma center. Methods: This was a retrospective data analysis of 980 consecutive polytraumatized patients admitted to a single level I trauma center between January 1995 and December 2020. Results: Among all patients, about 30% were female, with a significantly higher age and significantly higher rates of suicidal attempts. No sex-related differences regarding injury severity or trauma mechanisms could be seen, but female patients had significantly higher overall in-hospital mortality rates compared to male patients. Even in the elderly group of patients, elderly female patients were significantly older compared to elderly male patients, with significantly increased lengths of hospital stay. In the elderly group of patients, no sex-related differences regarding injury severity, trauma mechanisms or mortality could be detected. Multivariate analysis revealed suicidal attempt, severe head injury and age > 54 years as independent prognostic factors in the survival of polytraumatized patients. Conclusions: Distinctive sex-related differences can be found, with female polytraumatized patients being significantly older and having higher overall mortality rates with significantly increased LOS. Our study suggests a strong sex-independent influence of age, suicidal attempt and severe head injury on the outcomes of polytraumatized patients.

No Sex-based Differences in Self-reported Empathy between Patients with Schizophrenia and Control Subjects.

Schizophrenia, one of the most disabling disorders worldwide, is characterized by impaired empathy, which appears to be more common in women. This study aimed to compare empathy levels between control subjects and patients with schizophrenia by sex. We compared sixty-two patients with schizophrenia and 166 control subjects. All participants completed the Empathy Quotient (EQ) questionnaire. A multivariate analysis of variance model was performed with the EQ as the outcome criterion, and group and sex as fixed factors to test for interaction effects. Overall, patients obtained lower scores in the cognitive, emotional reactivity and social skills domains of empathy (p < 0.001). No differences between men and women were found and no interaction effect was identified between sex and group (schizophrenia vs. control) (p > 0.05). This study adds to the evidence on differences in social cognition between people with and without a mental illness such as schizophrenia. It also identifies the absence of sex differences between men and women, observed in both the group of patients and control subjects, which warrants further exploration.