Relevant Sex Differences Research Articles

Sex differences in sleep and sleep-disordered breathing.

There is increasing evidence for relevant sex differences in pathophysiology, symptom presentation and outcomes in obstructive sleep apnoea (OSA). However, research on sex differences and sex-specific phenotypes in sleep-disordered breathing (SDB) is still in its infancy and data on sex differences in other SDB is still very scarce. While OSA is more common in men than in premenopausal women, the prevalence of OSA doubles postmenopausally and becomes comparable to that of men. Women have a lower collapsibility of the upper airway and a lower arousal threshold. In addition, the rapid eye movement (REM)-apnoea-hypopnoea index (AHI) is typically higher in women than in men, but the non-REM-AHI and thus the total AHI is often lower. Women are often symptomatic at lower AHI and present more frequently with symptoms of sleep fragmentation and poor sleep quality. Both certain forms of OSA (e.g. REM-OSA) and certain phenotypes (e.g. COMISA) are more common in women. Men have a higher risk of high loop gain central sleep apnoea. For a better understanding of sex-typical phenotypes with the aim of a more targeted treatment approach of SDB, adequately powered studies on sex differences in SDB should be conducted.

Sex-specific structural and functional cardiac remodeling during healthy aging assessed by cardiovascular magnetic resonance.

Aging as a major non-modifiable cardiac risk factor challenges future cardiovascular medicine and economic demands, which requires further assessments addressing physiological age-associated cardiac changes. Using cardiovascular magnetic resonance (CMR), this study aims to characterize sex-specific ventricular adaptations during healthy aging. The population included healthy volunteers who underwent CMR at 1.5 or 3 Tesla scanners applying cine-imaging with a short-axis coverage of the left (LV) and right (RV) ventricle. The cohort was divided by sex (female and male) and age (subgroups in years): 1 (19-29), 2 (30-39), 3 (40-49), and 4 (≥50). Cardiac adaptations were quantitatively assessed by CMR indices. After the exclusion of missing or poor-quality CMR datasets or diagnosed disease, 140 of 203 volunteers were part of the final analysis. Women generally had smaller ventricular dimensions and LV mass, but higher biventricular systolic function. There was a significant age-associated decrease in ventricular dimensions as well as a significant increase in LV mass-to-volume ratio (LV-MVR, concentricity) in both sexes (LV-MVR in g/ml: age group 1 vs. 4: females 0.50 vs. 0.57, p=0.016, males 0.56 vs. 0.67, p=0.024). LV stroke volume index decreased significantly with age in both sexes, but stronger for men than for women (in ml/m2: agegroup 1 vs. 4: females 51.76 vs. 41.94, p<0.001, males 55.31 vs. 40.78, p<0.001). Ventricular proportions (RV-to-LV-volume ratio) were constant between the age groups in both sexes. In both sexes, healthy aging was associated with an increase in concentricity and a decline in ventricular dimensions. Furthermore, relevant age-related sex differences in systolic LV performance were observed.

Deep learning models reveal replicable, generalizable, and behaviorally relevant sex differences in human functional brain organization

Sex plays a crucial role in human brain development, aging, and the manifestation of psychiatric and neurological disorders. However, our understanding of sex differences in human functional brain organization and their behavioral consequences has been hindered by inconsistent findings and a lack of replication. Here, we address these challenges using a spatiotemporal deep neural network (stDNN) model to uncover latent functional brain dynamics that distinguish male and female brains. Our stDNN model accurately differentiated male and female brains, demonstrating consistently high cross-validation accuracy (>90%), replicability, and generalizability across multisession data from the same individuals and three independent cohorts (N ~ 1,500 young adults aged 20 to 35). Explainable AI (XAI) analysis revealed that brain features associated with the default mode network, striatum, and limbic network consistently exhibited significant sex differences (effect sizes > 1.5) across sessions and independent cohorts. Furthermore, XAI-derived brain features accurately predicted sex-specific cognitive profiles, a finding that was also independently replicated. Our results demonstrate that sex differences in functional brain dynamics are not only highly replicable and generalizable but also behaviorally relevant, challenging the notion of a continuum in male-female brain organization. Our findings underscore the crucial role of sex as a biological determinant in human brain organization, have significant implications for developing personalized sex-specific biomarkers in psychiatric and neurological disorders, and provide innovative AI-based computational tools for future research.

Sex Differences in Presentation, Treatment, and Survival in Patients Receiving Palliative (Chemo)Radiotherapy for Non-Small Cell Lung Cancer.

The aim of this study was to analyze sex differences in a real-world cohort of patients who received palliative thoracic radiotherapy or chemoradiotherapy for non-small cell lung cancer. Retrospectively, baseline, treatment, toxicity, and survival data from a single institution were analyzed. The study included 181 patients (82 females, 99 males). Despite borderline significant differences in disease presentation (T and N stage), final assignment to stage II, III or IV was similar. The same was true for target volume size. Neither radiotherapy parameters nor systemic treatment approaches were significantly different. Toxicity profiles and survival were similar too. Less than 1 out of 3 patients experienced high-grade toxicity, largely esophagitis. Median survival was 8.1 (males) versus 7.8 months (females) and the corresponding 2-year survival rates were 16 and 15%, respectively (p=0.78). Relevant sex differences were not observed in this study of common radiotherapy regimes such as 10 fractions of 3 Gy or 15 fractions of 2.8 Gy, the latter often combined with carboplatin/vinorelbine chemotherapy.

Sex-Specific Disparities in Outcomes of Transcatheter Edge-to-Edge Repair for Mitral Regurgitation: A Multicenter “Real-World” Analysis

Background: mitral regurgitation (mr) is the most common valvular heart disease (vhd) in the elderly and tends to be more prevalent in women. while relevant sex differences in outcomes are evident in surgically treated collectives, there are very limited and conflicting sex-specific data for the growing cohort of patients undergoing transcatheter edge-to-edge repair (teer). Objective: to investigate whether sex impacts procedural safety and efficacy, and in-hospital- and long-term outcomes, after teer for mr. Methods: in a multicenter observational cohort study, patients who underwent teer were stratified by sex and relevant outcome measures, and analyzed using multivariable cox regression and propensity score matching (psm). Results: a total of 821 patients were analyzed, of whom 37.4% (307/821) were female. compared to male patients, females were significantly older (77 ± 8.5 vs. 80.4 ± 6.7 years, p = 0.03), and had less coronary artery disease (cad, 67.7% vs. 53.1%, p &lt; 0.0001) and a higher proportion of preserved left ventricular function (lvef &gt; 50%, 32.5% vs. 50.5%, p &gt; 0.0001). safety and efficacy of the teer procedure and in-hospital mortality did not differ between the sexes. after psm, women showed significantly better survival 3 years after teer compared to men (60.7% vs. 54.2%, p = 0.04) and a lower risk of all-cause death according to multiple cox regression (hr 0.8, 95% ci 0.6–0.9, p = 0.02). after sex-specific stratification for concomitant atrial fibrillation (af), the most common comorbidity in the present collective, women with af experience significantly worse adjusted survival compared to women without af (53.9% vs. 75.1%, p = 0.042) three years after teer and lose the survival advantage over men. Conclusions: female patients are older and less comorbid than males undergoing TEER. The TEER procedure is equally safe and effective in both sexes. While in-hospital mortality did not differ, female patients experienced a significantly better adjusted long-term survival compared to male patients. Concomitant AF offsets the prognostic advantage of females over males and, in contrast to males, significantly impairs long-term survival in women undergoing TEER. Further research is warranted to elucidate underlying causes for the observed sex disparities and to develop sex-tailored treatment recommendations.

A nation-wide analysis of socioeconomic and geographical disparities in the prevalence of obesity and excess weight in children and adolescents in Spain: Results from the ENE-COVID study.

To estimate national and provincial prevalence of obesity and excess weight in the child and adolescent population in Spain by sex and sociodemographic characteristics, and to explore sources of inequalities in their distribution, and their geographical patterns. ENE-COVID is a nationwide representative seroepidemiological survey (68 287 participants) stratified by province and municipality size (April-June 2020). Participants answered a questionnaire which collected self-reported weight and height, that allowed estimating crude and model-based standardized prevalences of obesity and excess weight in the 10 543 child and adolescent participants aged 2-17 years. Crude prevalences (WHO growth reference) were higher in boys than in girls (obesity: 13.4% vs. 7.9%; excess weight: 33.7% vs. 26.0%; severe obesity: 2.9% vs. 1.2%). These prevalences varied with age, increased with the presence of any adult with excess weight in the household, while they decreased with higher adult educational and census tract average income levels. Obesity by province ranged 1.8%-30.5% in boys and 0%-17.6% in girls; excess weight ranged 15.2%-49.9% in boys and 10.8%-40.8% in girls. The lowest prevalences of obesity and excess weight were found in provinces in the northern half of Spain. Sociodemographic characteristics only partially explained the observed geographical variability (33.6% obesity; 44.2% excess weight). Childhood and adolescent obesity and excess weight are highly prevalent in Spain, with relevant sex, sociodemographic and geographical differences. The geographic variability explained by sociodemographic variables indicates that there are other potentially modifiable factors on which to focus interventions at different geographic levels to fight this problem.

Quantitative and qualitative sex difference in habenula-induced inhibition of midbrain dopamine neurons in the rat.

Clinically relevant sex differences have been noted in a number of affective, behavioral, cognitive, and neurological health disorders. Midbrain dopamine neurons are implicated in several of these same disorders and consequently are under investigation for their potential role in the manifestation of these sex differences. The lateral habenula exerts significant inhibitory control over dopamine neuronal firing, yet little is known about sex differences in this particular neurocircuit. We performed in vivo, single unit, extracellular recordings of dopamine neurons in female and male anesthetized rats in response to single pulse stimulation of the lateral habenula. In addition, we assessed baseline firing properties of lateral habenula neurons and, by immunochemical means, assessed the distribution of estrogen receptor alpha cells in the lateral habenula. Habenula-induced inhibition of dopamine neuronal firing is reduced in female rats relative to male rats. In addition, male rats had a higher prevalence of rebound excitation. Furthermore, the firing pattern of lateral habenula neurons was less variable in female rats, and female rats had a higher density of estrogen receptor alpha positive cells in the lateral habenula. We found that the dopamine neuronal response to habenular stimulation is both qualitatively and quantitatively different in female and male rats. These novel findings together with reports in the contemporary literature lead us to posit that the sex difference in dopamine inhibition seen here relate to differential firing properties of lateral habenula neurons resulting from the presence of sex hormones. Further work is needed to test this hypothesis, which may have implications for understanding the etiology of several mental health disorders including depression, schizophrenia, and addiction.

Heart rate variability measures indicating sex differences in autonomic regulation during anxiety-like behavior in rats.

Mental health conditions remain a substantial and costly challenge to society, especially in women since they have nearly twice the prevalence of anxiety disorders. However, critical mechanisms underlying sex differences remain incompletely understood. Measures of cardiac function, including heart rate (HR) and HR variability (HRV), reflect balance between sympathetic (SNS) and parasympathetic (PNS) systems and are potential biomarkers for pathological states. To better understand sex differences in anxiety-related autonomic mechanisms, we examined HR/HRV telemetry in food-restricted adult rats during novelty suppression of feeding (NSF), with conflict between food under bright light in the arena center. To assess HRV, we calculated the SDNN (reflective of both SNS and PNS contribution) and rMSSD (reflective of PNS contribution) and compared these metrics to behaviors within the anxiety task. Females had greater HR and lower SNS indicators at baseline, as in humans. Further, females (but not males) with higher basal HR carried this state into NSF, delaying first approach to center. In contrast, males with lower SNS measures approached and spent more time in the brightly-lit center. Further, females with lower SNS indicators consumed significantly more food. In males, a high-SNS subpopulation consumed no food. Among consumers, males with greater SNS ate more food. Together, these are congruent with human findings suggesting women engage PNS more, and men SNS more. Our previous behavior-only work also observed female differences from males during initial movement and food intake. Thus, high basal SNS in females reduced behavior early in NSF, while subsequent reduced SNS allowed greater food intake. In males, lower SNS increased engagement with arena center, but greater SNS predicted higher consumption. Our findings show novel and likely clinically relevant sex differences in HRV-behavior relationships.

"Tranq-dope" overdose and mortality: lethality induced by fentanyl and xylazine.

Introduction: The recreational use of fentanyl in combination with xylazine (i.e., "tranq-dope") represents a rapidly emerging public health threat characterized by significant toxicity and mortality. This study quantified the interactions between these drugs on lethality and examined the effectiveness of potential rescue medications to prevent a lethal overdose. Methods: Male and female mice were administered acute doses of fentanyl, xylazine, or their combination via intraperitoneal injection, and lethality was determined 0.5, 1.0, 1.5, 2.0, and 24 h after administration. Both fentanyl and xylazine produced dose-dependent increases in lethality when administered alone. Results: A nonlethal dose of fentanyl (56 mg/kg) produced an approximately 5-fold decrease in the estimated LD50 for xylazine (i.e., the dose estimated to produce lethality in 50% of the population). Notably, a nonlethal dose of xylazine (100 mg/kg) produced an approximately 100-fold decrease in the estimated LD50 for fentanyl. Both drug combinations produced a synergistic interaction as determined via isobolographic analysis. The opioid receptor antagonist, naloxone (3 mg/kg), but not the alpha-2 adrenergic receptor antagonist, yohimbine (3 mg/kg), significantly decreased the lethality of a fentanyl-xylazine combination. Lethality was rapid, with death occurring within 10 min after a high dose combination and generally within 30 min at lower dose combinations. Males were more sensitive to the lethal effects of fentanyl-xylazine combinations under some conditions suggesting biologically relevant sex differences in sensitivity to fentanyl-xylazine lethality. Discussion: These data provide the first quantification of the lethal effects of "tranq-dope" and suggest that rapid administration of naloxone may be effective at preventing death following overdose.

Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach

BackgroundDiabetes mellitus (DM) accelerates the progression of aortic stenosis (AS), but how their underlying molecular mechanisms interact is not clear. Moreover, whether DM contributes to clinically relevant sex-differences in AS is unknown. In this work we aim to characterize the sex-specific profile of major pathological mechanisms fundamental to aortic valve (AV) degeneration in AS patients with or without concomitant DM.Methods283 patients with severe AS undergoing surgical valve replacement (27.6% DM, 59.4% men) were recruited. Expression of pathological markers related to AS were thoroughly assessed in AVs and valve interstitial cells (VICs) according to sex and presence of DM. Complementary in vitro experiments in VICs in the presence of high-glucose levels (25 mM) for 24, 48 and 72 h were performed.ResultsOxidative stress and metabolic dysfunction markers were increased in AVs from diabetic AS patients compared to non-diabetic patients in both sexes. However, disbalanced oxidative stress and enhanced inflammation were more predominant in AVs from male AS diabetic patients. Osteogenic markers were exclusively increased in the AVs of diabetic women. Basal characterization of VICs confirmed that oxidative stress, inflammation, calcification, and metabolic alteration profiles were increased in diabetic VICs with sex-specific differences. VICs cultured in hyperglycemic-like conditions triggered inflammatory responses in men, whereas in women rapid and higher production of pro-osteogenic molecules.ConclusionsDM produces sex-specific pathological phenotypes in AV of AS patients. Importantly, women with diabetes are more prone to develop AV calcification. DM should be considered as a risk factor in AS especially in women.

Impact of Baseline Anemia in Patients Undergoing Transcatheter Aortic Valve Replacement: A Prognostic Systematic Review and Meta-Analysis.

Transcatheter aortic valve replacement (TAVR) is currently the treatment of choice for patients aged ≥75 years with severe aortic stenosis. Preoperative anemia is present in a large proportion of patients and may increase the risk of post-procedural complications. The purpose of this prognostic systematic review was to analyze the impact of baseline anemia on short- and mid-term outcomes following TAVR. A computerized search was performed on PubMed and Web of Science databases for studies published between January 2013 and December 2022. Primary outcomes were 30-day need for transfusion, acute renal failure, 30-day and mid-term mortality, and readmission during the first year post-TAVR. Data were analyzed via random effects model using inverse variance method with 95% confidence intervals. Eleven observational studies met our eligibility criteria and included a total of 12,588 patients. The prevalence of baseline anemia ranged between 39% and 72%, with no relevant sex differences. Patients with preprocedural anemia received more blood transfusions [OR: 2.95 (2.13-4.09)]), and exhibited increased rates of acute kidney injury [OR:1.74 (1.45-2.10)], short-term mortality [OR: 1.47 (1.07-2.01], and mid-term [OR: 1.89 (1.58-2.25)] mortality following TAVR compared with those without anemia. Baseline anemia determined an increased risk for blood transfusion, acute kidney injury, and short/mid-term mortality among TAVR recipients.

A roadmap for sex- and gender-disaggregated health research

Sex and gender are fundamental aspects of health and wellbeing. Yet many research studies fail to consider sex or gender differences, and even when they do this is often limited to merely cataloguing such differences in the makeup of study populations. The evidence on sex and gender differences is thus incomplete in most areas of medicine. This article presents a roadmap for the systematic conduct of sex- and gender-disaggregated health research. We distinguish three phases: the exploration of sex and gender differences in disease risk, presentation, diagnosis, treatment, and outcomes; explaining any found differences by revealing the underlying mechanisms; and translation of the implications of such differences to policy and practice. For each phase, we provide critical methodological considerations and practical examples are provided, taken primarily from the field of cardiovascular disease. We also discuss key overarching themes and terminology that are at the essence of any study evaluating the relevance of sex and gender in health. Here, we limit ourselves to binary sex and gender in order to produce a coherent, succinct narrative. Further disaggregation by sex and gender separately and which recognises intersex, non-binary, and gender-diverse identities, as well as other aspects of intersectionality, can build on this basic minimum level of disaggregation. We envision that uptake of this roadmap, together with wider policy and educational activities, will aid researchers to systematically explore and explain relevant sex and gender differences in health and will aid educators, clinicians, and policymakers to translate the outcomes of research in the most effective and meaningful way, for the benefit of all.

Sex-specific differences of special tumor diseases

Numerous data show that sex and gender have gained increasing importance in precision medicine as relevant modulators of specific oncological and hematological diseases. The purpose of this article is to provide asummary of the current state of knowledge on sex differences in the incidence and outcome of specific malignancies and to further elucidate possible underlying causes. Evaluation and discussion of basic research studies, meta-analyses, and clinical trials. There are significant sex-specific differences in the incidence, response rates, and mortality for avariety of oncological diseases. For the most part, men have poorer outcomes, whereas women have higher treatment-associated toxicities and distinct presentations at younger ages. Hormonal, immunological, and pharmacological causes are suspected. Advanced patient-individualized treatment in oncology and hematology will be measured in the future by the implementation of the existing relevant sex differences in the clinical practice and further investigations on underlying mechanisms in studies in order to guarantee and to optimize the best possible treatment for oncological patients in the future.

Population-based reference values for 4D flow MRI derived aortic blood flow parameters

Objective. This study assesses age-related differences of thoracic aorta blood flow profiles and provides age- and sex-specific reference values using 4D flow cardiovascular magnetic resonance (CMR) data. Approach. 126 volunteers (age 20–80 years, female 51%) underwent 4D flow CMR and 12 perpendicular analysis planes in the thoracic aorta were specified. For these planes the following parameters were evaluated: body surface area-adjusted aortic area (A′), normalized flow displacement (NFD), the degree of wall parallelism (WPD), the minimal relative cross-sectional area through which 80% of the volume flow passes (A80) and the angle between flow direction and centerline (α). Main results. Age-related differences in blood flow parameters were seen in the ascending aorta with higher values for NFD and angle and lower values for WPD and A80 in older subjects. All parameters describing blood flow patterns correlated with the cross-sectional area in the ascending aorta. No relevant sex-differences regarding blood flow profiles were found. Significance. These age- and sex-specific reference values for quantitative parameters describing blood flow within the aorta might help to study the clinical relevance of flow profiles in the future.

Deep proteome profiling reveals signatures of age and sex differences in paw skin and sciatic nerve of naïve mice.

The age and sex of studied animals profoundly impact experimental outcomes in biomedical research. However, most preclinical studies in mice use a wide-spanning age range from 4 to 20 weeks and do not assess male and female mice in parallel. This raises concerns regarding reproducibility and neglects potentially relevant age and sex differences, which are largely unknown at the molecular level in naïve mice. Here, we employed an optimized quantitative proteomics workflow in order to deeply profile mouse paw skin and sciatic nerves (SCN) - two tissues implicated in nociception and pain as well as diseases linked to inflammation, injury, and demyelination. Remarkably, we uncovered significant differences when comparing male and female mice at adolescent (4 weeks) and adult (14 weeks) age. Our analysis deciphered protein subsets and networks that were correlated with the age and/or sex of mice. Notably, among these were proteins/biological pathways with known (patho)physiological relevance, e.g., homeostasis and epidermal signaling in skin, and, in SCN, multiple myelin proteins and regulators of neuronal development. Extensive comparisons with available databases revealed that various proteins associated with distinct skin diseases and pain exhibited significant abundance changes in dependence on age and/or sex. Taken together, our study uncovers hitherto unknown sex and age differences at the level of proteins and protein networks. Overall, we provide a unique proteome resource that facilitates mechanistic insights into somatosensory and skin biology, and integrates age and sex as biological variables - a prerequisite for successful preclinical studies in mouse disease models.

Abstract 14219: Are There Sex Differences in the Imaging Modalities and Early Use of Echocardiography in Elderly Patients With Pulmonary Embolism?

Background: Sex differences in symptoms of acute pulmonary embolism (PE) in older adults (aged ≥65 years) may correlate with differences in the imaging modality used for confirming PE. It is also unknown if sex disparities exist in early use of echocardiography for prognostication. Methods: Using data from RIETE, a prospective multinational registry of patients with venous thromboembolism, we included older adults with acute PE. We compared the diagnostic modalities that were used in women vs men to confirm PE. We assessed the presenting symptoms/signs, thrombus location in patients diagnosed with computed tomography pulmonary angiography (CTPA), and evaluated PE severity according to the simplified Pulmonary Embolism Severity Index (sPESI) and the European Society of Cardiology (ESC) categories. We investigated the use of echocardiography within 3 days of PE diagnosis by sex. Results: REITE had 33,462 PE patients ≥65 years old including 19,294 women (mean age: 78.6±7.4 years) and 14,168 men (mean age: 76.1±7.2 years). CTPA was the dominant modality for PE diagnosis in both sexes, although a slightly smaller proportion of women were diagnosed with CTPA (77.1 vs 79.4, P&lt;0.001). There were no sex differences in the proportion of patients presenting with isolated subsegmental PE (5.0%; 99% CI, 4.6-5.5% vs 5.5% 99% CI, 5.0-6.0%). There were no clinically relevant sex differences according to sPESI or the ESC risk categories (Table). Women were not less likely, indeed slightly more likely, than men to undergo echocardiography within 3 days of PE diagnosis (51.1%; 99% CI, 50.3-51.9% vs 48.9%; 99% CI, 48.0-49.8%). Conclusions: Slightly greater use of CTPA for diagnosing PE in men compared to women may reflect more chest pain and hemoptysis on presentation in men. However, there is similar illness severity in elderly men and women and minimal disparity in early use of echocardiography after diagnosis for prognostication.

Sex Disparities in Outcome of Patients with Alcohol-Related Liver Cirrhosis within the Eurotransplant Network-A Competing Risk Analysis.

Alcohol use disorder (AUD) is one of the most important risk factors for the development of alcohol-related liver cirrhosis (ALC). Importantly, psychiatrists are an integral part of the interdisciplinary care for patients with AUD and ALC. The aim of the current study was to investigate whether sex influences the outcome within this group of patients. For this purpose, data of all registrations for liver transplantations due to ALC within the Eurotransplant region from 2010 to 2019 were analyzed for sex disparities using competing risk models and in-between group comparisons. Relevant sex differences in registration numbers (24.8% female) and investigated outcomes were revealed. Risk ratios for a positive outcome, i.e., transplantation (0.74), and those of adverse outcomes, i.e., removal from waiting list (1.44) and death on waiting list (1.10), indicated a relative disadvantage for female patients with ALC. Further, women listed for liver transplantations were significantly younger than their male counterparts. Notably, sex disparities found in registration and outcome parameters were independent of differences found in the prevalence of AUD and liver transplantations. Further research is necessary to identify the underlying mechanisms and establish strategies to ensure equity and utility in liver transplantations due to ALC.

Are Women Really Different? Comparison of Men and Women in a Sample of Forensic Psychiatric Inpatients.

BackgroundWomen in detention remain a widely understudied group. Although the number of studies in women in prison has grown in the past decade, research on female forensic psychiatric inpatients has not increased, and women are in the minority in forensic psychiatry not only as patients but also as examinees. Consequently, most treatment manuals and risk assessments were developed in male samples and apply to male offenders. However, the same treatment and risk assessment rationale can be applied in male and female mentally ill offenders only if evidence shows that no relevant sex differences exist.AimsThe aim of the present study was to examine a sample of male and female forensic psychiatric inpatients with substance use disorders and to compare the socio-demographic, legal, and clinical characteristics between the sexes.MethodsThe sample included 115 male and 61 female patients. All patients were in mandatory inpatient forensic psychiatry treatment according to section 64 of the German penal code.ResultsWe found no significant differences between men and women in terms of educational status and vocational training. However, women were more often single and less likely to be employed full time, and they reported adverse childhood experiences more often than men. Regarding clinical variables, women appeared to be less likely to have a substance use disorder due to alcohol use and had more previous psychiatric treatments than men. Male patients were significantly younger on first conviction and detention, had more criminal records and served longer total penalties than female patients. Furthermore, men committed more violent crimes and women, more narcotics-related crimes.ConclusionsThe study identified sex-specific differences in forensic psychiatric patients that should be considered in the context of forensic therapy.

Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study

Objective Post-COVID syndrome (PCS) is a poorly known entity. An underlying chronic, low-grade inflammation (LGI) has been theorized as a pathophysiological mechanism. Available data on biomarkers in PCS show conflicting results. Our aim was to know whether subjects with PCS present higher levels of inflammatory markers, after a mild COVID-19. Methods Analytical cross-sectional study. Cases of mild COVID-19 in a community setting were included. We collected epidemiological data (age, sex, BMI, smoking, comorbidities), variables of the acute COVID-19 (duration, symptoms), and data at 3 months after the acute phase (symptoms and laboratory test). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase, ferritin, fibrinogen, and D-dimer levels were analysed. LGI was defined as CRP >0.3 and <1.0 mg/dL. A subject was classified as PCS + if presented signs and symptoms >12 weeks after an infection consistent with COVID-19. Five composite indices (C1–C5) were developed, combining the upper ranges of biomarkers distributions. Multivariate analyses were performed. Results We analysed 121 mild COVID-19 cases (mean age = 45.7 years, 56.2% women). Among the acute symptoms, women presented a higher frequency of fatigue (54.4% vs 30.2%; p = .008). PCS affected 35.8% of women and 20.8% of men (p = .07), and the most reported symptoms were fatigue (42.8%), anosmia (40%), ageusia (22.8%), dyspnea (17.1%) and myalgia (11.4%). Neutrophil count, NLR, CRP and fibrinogen showed the best correlations with PCS and were selected to develop the indices. In women PCS+, C1, C3 and C4 indices were more frequently met, while in men PCS+, C2, C5 and CRP were in the range of LGI. Anosmia, ageusia and fatigue were related to higher neutrophil counts, with sex differences. Fibrinogen levels were higher in persistent myalgia (510 ± 82 mg/dL vs 394 ± 87; p = .013). In multivariable analysis, a woman with a neutrophil count above the median, or with fibrinogen level or NLR in the highest tertile, had a 4–5-fold increased risk of prevalent PCS. A man with CRP in the range of LGI, or fibrinogen level or a neutrophil count in the highest tertile, had a 10–17-fold increased risk of prevalent PCS. Conclusions The data obtained in the present cross-sectional study seems to demonstrate a consistent association between PCS and upper ranges of the neutrophil count, NLR, fibrinogen, and CRP in the LGI range. Furthermore, composite indices appear useful in detecting relationships between slight elevations of biomarkers and PCS, and our study identifies relevant sex differences in symptoms and markers regarding the PCS.

Sex-specific lesion pattern of functional outcomes after stroke.

Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men – women) = −0.295 (90% highest posterior density interval = −0.556 to −0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.