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BACKGROUND: The extent of the association between vitamin D deficiency and knee osteoarthritis remains inadequately understood. OBJECTIVE: This study aimed to elucidate the relationship between vitamin D levels and knee osteoarthritis through a cross-sectional analysis. METHODS: This retrospective study involved an analysis of knee radiographs and serum 25-hydroxyvitamin D3 (25-(OH) vitamin D3) levels in a cohort of 3424 individuals (2901 women and 523 men). Knee osteoarthritis severity was evaluated using the Kellgren-Lawrence radiological scoring system. RESULTS: Of the participants, 49.2% (n = 1,683) were diagnosed with knee osteoarthritis. Among these patients, the levels of adjusted 25-(OH) vitamin D3 were significantly lower (p < 0.001). Regression analysis revealed a significant association between vitamin D deficiency and knee osteoarthritis, with an adjusted odds ratio (OR) of 1.7 (95% CI: 1.5–2.0; p < 0.001). Notably, a stronger association was observed between vitamin D deficiency and knee osteoarthritis in women under 65 compared to those aged 65 and above. CONCLUSIONS: The findings of this study indicate a higher prevalence of vitamin D deficiency in patients with knee osteoarthritis. Maintaining adequate serum 25-(OH) vitamin D3 levels may prevent knee osteoarthritis, especially in women below 65. [ABSTRACT FROM AUTHOR]

Purpose: Reporting gender-related outcomes for symptomatic carotid lesion revascularization after both endarterectomy (CEA) and carotid artery stenting (CAS) procedures in an unselected group of patients treated by Italian Vascular Specialists. Material and Methods: A retrospective study was conducted on patients presenting with recently symptomatic carotid stenosis treated by CAS and by CEA. The primary endpoint was the 30 days any stroke occurrence rate; secondary endpoints were technical success, occurrence of transient ischemic attack (TIA), acute myocardial infarction (AMI) and death. Demographic, clinical and procedural data were all noted in order to identify the outcome's determining factor. Results: A total of 265 patients (193 males and 72 females) were enrolled, and of these 134 (50.5%) underwent CEA and 131 CAS (49.5%). At 30 days, the overall new stroke rate was 3.4% (one fatal), and no TIA, AMI or deaths were observed. Among strokes, seven major and two minor strokes were reported, with six after CEA and three after CAS (p = 0.32; OR: 2; CI95%: 0.48–8.17). The timing of revascularization has been found to be slightly associated with new stroke occurrence: seven out nine strokes were observed in patients treated within 14 days from symptom onset (5.5% vs. 1.4%; p = 0.08, OR: 3.8, CI95%: 0.77–18.56). Lastly, female patients presented a significantly higher risk of post-operative stroke compared to male patients: 6.9% vs. 2.1% (p: 0.05; OR: 3.52; CI95%: 0.91–13.52). Conclusions: Our experience seems to suggest that both CEA and CAS provide safe and effective results in treating patients presenting with symptomatic carotid stenosis. Regardless of the type of revascularization, female sex is an independent risk factor for stroke recurrence after treatment. [ABSTRACT FROM AUTHOR]

Abstract Introduction Surgical site infection after saphenous vein harvest is common, with reported leg wound infection rates ranging from 2 to 24%. There have been few investigations into sex-related differences in complication rates. Moreover, varied effects of smoking have been reported. The aim of this study was to investigate risk factors such as gender and smoking, associated with surgical site infection after vein graft harvesting in coronary artery bypass grafting surgery. Methods We included 2,188 consecutive patients who underwent coronary artery bypass grafting surgery with at least one vein graft at our centre from 2009 to 2018. All patients were followed up postoperatively. Risk factors for leg wound infection requiring antibiotic treatment and surgical revision were analysed using logistic regression analysis. Results In total, 374 patients (17.1%) received antibiotic treatment and 154 (7.0%) underwent surgical revision for leg wound infection at the harvest site. Female sex, high body mass index, diabetes mellitus, longer operation time, peripheral vascular disease and direct oral anticoagulants were independently associated with any leg wound infection at the harvest site. Among surgically revised patients, female sex and insulin or oral treatment for diabetes mellitus as well as longer operation time were independent risk factors. Smoking was not associated with leg wound infection. Conclusion Female sex is associated with increased risk of leg wound infection. The underlying mechanism is unknown. In the current population, previous or current smoking was not associated with an increased risk of leg wound infection.

Abstract To detect environmental factors, which may be possible risk factors in the disease course of Fuchs’ endothelial corneal dystrophy (FECD). Evaluation of patients with FECD registered in the FECD genetics database of the Center for Ophthalmology, University Hospital Cologne. For the evaluation, disease onset, central corneal thickness, best spectacle corrected visual acuity (BSCVA, logMAR), and modified Krachmer grading (grades 1–6) were correlated with the presence of diabetes mellitus (DM), body mass index (BMI), and smoking behavior. To put the age-related increase in Krachmer grading into perspective, a correction of grading were formed. Depending on the variables studied, differences between groups were examined by Mann–Whitney U test and chi-square test. The significance level was 5%. 403 patients with FECD were included in the analysis. The mean age of the patients was 70.0 ± 10.32 (range 28–96) years. The mean age at diagnosis of those patients was 63.1 ± 13.2 years. The female-to-male ratio was 1.46:1. Patients with a BMI > 30.0 kg/m2 developed FECD significantly earlier than patients with a BMI 30.0 kg/m2 (p = 0.012). In addition to smoking and DM our study shows for the first time that obesity may have a negative impact on the development of FECD. Whether dietary interventions and hormones can influence the development or progression of the disease needs to be investigated in future studies.

Background and Aims Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes. Methods In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up. Results At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27–1.65), P <.001] but was higher in females [SMR 2.00 (1.67–2.38), P <.001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04–1.61), P =.02], cardiovascular mortality [adjusted HR 1.58 (1.14–2.18), P =.007], and heart failure [adjusted HR 1.36 (1.02–1.81), P =.04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P <.001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥.09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16–1.47), P <.001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85–0.99), P =.036]. Conclusions Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management. [ABSTRACT FROM AUTHOR]

Idiopathic intracranial hypertension is a neurological condition characterized by a raised intracranial pressure and papilledema, leading to chronic headaches and visual disturbances. By recognizing modifiable risk factors and deploying evidence-based interventions, healthcare providers have the potential to mitigate the burden of the disease and improve patient outcomes. It is well known that the condition occurs in predominantly pre-menopausal females who live with obesity particularly in the context of recent weight gain. This review discusses what risk factors may contribute to the metabolic underpinnings of cerebrospinal fluid dysregulation. There are a number of disease associations that are important to screen for as they can alter management. There is emerging evidence to suggest that idiopathic intracranial hypertension is a systemic metabolic disease and it is unknown what are all the risk factors are that precipitate the condition. Targeting certain hardwired risk factors is unachievable. However, as recent weight gain has been identified as a predominant risk factor for the development of the disease and relapse, modification of body weight should be the primary aim of management. Insightful research into the involvement of the neuroendocrine axis driving cerebrospinal fluid dysregulation now has the potential for the development of therapeutic targets. [ABSTRACT FROM AUTHOR]

Gardner, Laurel, Linda E. Keyes, Caleb Phillips, Elan Small, Tejaswi Adhikari, Nathan Barott, Ken Zafren, Rony Maharjan, and James Marvel. Women at altitude: Menstrual-cycle phase, menopause, and exogenous progesterone are not associated with acute mountain sickness. High Alt Med Biol. 00:000–000, 2024. Background: Elevated progesterone levels in women may protect against acute mountain sickness (AMS). The impact of hormonal contraception (HC) on AMS is unknown. We examined the effect of natural and exogenous progesterone on the occurrence of AMS. Methods: We conducted a prospective observational convenience study of female trekkers in Lobuche (4,940 m) and Manang (3,519 m). We collected data on last menstrual period, use of exogenous hormones, and development of AMS. Results: There were 1,161 trekkers who met inclusion criteria, of whom 307 (26%) had AMS. There was no significant difference in occurrence of AMS between women in the follicular (28%) and the luteal (25%) phases of menstruation (p = 0.48). The proportion of premenopausal (25%) versus postmenopausal women (30%) with AMS did not differ (p = 0.33). The use of HC did not influence the occurrence of AMS (HC 23% vs. no HC 26%, p = 0.47), nor did hormonal replacement therapy (HRT) (HRT 11% vs. no HRT 31%, p = 0.13). Conclusion: We found no relationship between menstrual-cycle phase, menopausal status, or use of exogenous progesterone and the occurrence of AMS in trekkers and conclude that hormonal status is not a risk factor for AMS. Furthermore, women should not be excluded from future AMS studies based on hormonal status. [ABSTRACT FROM AUTHOR]

Sex-specific outcomes after catheter ablation (CA) for atrial fibrillation (AF) have reported conflicting findings. We examined the impact of female sex on outcomes in patients with persistent AF (PsAF) from the Catheter Ablation for Persistent Atrial Fibrillation: A Multicentre Randomized Trial of Pulmonary Vein Isolation vs PVI with Posterior Left Atrial Wall Isolation (CAPLA) randomized trial. A total of 338 patients with PsAF were randomized to pulmonary vein isolation (PVI) or PVI with posterior wall isolation (PWI). The primary outcome was arrhythmia recurrence at 12 months. Clinical and electroanatomical characteristics, arrhythmia recurrence, and quality of life were compared between women and men. Seventy-nine women (23.4%; PVI 37; PVI + PWI 42) and 259 men (76.6%; PVI 131; PVI + PWI 128) underwent AF ablation. Women were older {median age 70.4 (interquartile range [IQR] 64.8–74.6) years vs 64.0 (IQR 56.7–69.7) years; P <.001} and had more advanced left atrial electroanatomical remodeling. At 12 months, arrhythmia-free survival was lower in women (44.3% vs 56.8% in men; hazard ratio 1.44; 95% confidence interval 1.02–2.04; log-rank, P =.036). PWI did not improve arrhythmia-free survival at 12 months (hazard ratio 1.02; 95% confidence interval 0.74–1.40; log-rank, P =.711). The median AF burden was 0% in both groups (women: IQR 0.0%–2.2% vs men: IQR 0.0%–2.8%; P =.804). Health care utilization was comparable between women (36.7%) and men (30.1%) (P =.241); however, women were more likely to undergo a repeat procedure (17.7% vs 6.9%; P =.007). Women reported more severe baseline anxiety (average Hospital Anxiety and Depression Scale [HADS] anxiety score 7.5 ± 4.9 vs 6.3 ± 4.3 in men; P =.035) and AF-related symptoms (baseline Atrial Fibrillation Effect on Quality-of-Life Questionnaire [AFEQT] score 46.7 ± 20.7 vs 55.9 ± 23.0 in men; P =.002), with comparable improvements in psychological symptoms (change in HADS anxiety score −3.8 ± 4.6 vs −3.0 ± 4.5; P =.152 (change in HADS depression score −2.9 ± 5.0 vs −2.6 ± 4.0; P =.542) and greater improvement in AFEQT score compared with men at 12 months (change in AFEQT score +45.9 ± 23.1 vs +39.2 ± 24.8; P =.048). Women undergoing CA for PsAF report more significant symptoms and poorer quality of life at baseline than men. Despite higher arrhythmia recurrence and repeat procedures in women, the AF burden was comparably low, resulting in significant improvements in quality of life and psychological well-being after CA in both sexes. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review is to provide an overview of recent evidence on female-specific risk factors related to reproductive status or pregnancy. Recent Findings: Pregnancy-related factors, including hypertensive disorders and gestational diabetes, increase the risk of heart failure in women, while breastfeeding and hormone therapy may offer protection. Summary: Hypertensive disorders of pregnancy, gestational diabetes, polycystic ovarian syndrome, placental abruption, younger maternal age at first live birth, younger maternal age at last live birth, number of stillbirths, number of pregnancies, onset of menstruation before 12 years of age, shorter reproductive age, ovariectomy, and prolonged absence of ovarian hormones may increase the risk of heart failure in women. Conversely, breastfeeding status and hormone therapy (for menopause or contraception) may serve as protective factors, while fertility treatments have no discernible effect on the risk of heart failure. [ABSTRACT FROM AUTHOR]

Introduction: Surgical site infection after saphenous vein harvest is common, with reported leg wound infection rates ranging from 2 to 24%. There have been few investigations into sex-related differences in complication rates. Moreover, varied effects of smoking have been reported. The aim of this study was to investigate risk factors such as gender and smoking, associated with surgical site infection after vein graft harvesting in coronary artery bypass grafting surgery. Methods: We included 2,188 consecutive patients who underwent coronary artery bypass grafting surgery with at least one vein graft at our centre from 2009 to 2018. All patients were followed up postoperatively. Risk factors for leg wound infection requiring antibiotic treatment and surgical revision were analysed using logistic regression analysis. Results: In total, 374 patients (17.1%) received antibiotic treatment and 154 (7.0%) underwent surgical revision for leg wound infection at the harvest site. Female sex, high body mass index, diabetes mellitus, longer operation time, peripheral vascular disease and direct oral anticoagulants were independently associated with any leg wound infection at the harvest site. Among surgically revised patients, female sex and insulin or oral treatment for diabetes mellitus as well as longer operation time were independent risk factors. Smoking was not associated with leg wound infection. Conclusion: Female sex is associated with increased risk of leg wound infection. The underlying mechanism is unknown. In the current population, previous or current smoking was not associated with an increased risk of leg wound infection. [ABSTRACT FROM AUTHOR]

To detect environmental factors, which may be possible risk factors in the disease course of Fuchs' endothelial corneal dystrophy (FECD). Evaluation of patients with FECD registered in the FECD genetics database of the Center for Ophthalmology, University Hospital Cologne. For the evaluation, disease onset, central corneal thickness, best spectacle corrected visual acuity (BSCVA, logMAR), and modified Krachmer grading (grades 1–6) were correlated with the presence of diabetes mellitus (DM), body mass index (BMI), and smoking behavior. To put the age-related increase in Krachmer grading into perspective, a correction of grading were formed. Depending on the variables studied, differences between groups were examined by Mann–Whitney U test and chi-square test. The significance level was 5%. 403 patients with FECD were included in the analysis. The mean age of the patients was 70.0 ± 10.32 (range 28–96) years. The mean age at diagnosis of those patients was 63.1 ± 13.2 years. The female-to-male ratio was 1.46:1. Patients with a BMI > 30.0 kg/m2 developed FECD significantly earlier than patients with a BMI < 30 kg/m2, p = 0.001. Patients with DM showed significantly more often an Krachmer grade of 5, p = 0.015. Smoking had a negative effect on Krachmer grading (p = 0.024). Using the mediation analysis, the presence of DM correlated Krachmer Grade 5 (p = 0.015), and the presence of DM correlated with BMI > 30.0 kg/m2 (p = 0.012). In addition to smoking and DM our study shows for the first time that obesity may have a negative impact on the development of FECD. Whether dietary interventions and hormones can influence the development or progression of the disease needs to be investigated in future studies. [ABSTRACT FROM AUTHOR]

Background and Aims Female sex has been linked with higher risk of ischaemic stroke (IS) in atrial fibrillation (AF), but no prior study has examined temporal trends in the IS risk associated with female sex. Methods The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study included all patients with AF in Finland from 2007 to 2018. Ischaemic stroke rates and rate ratios were computed. Results Overall, 229 565 patients with new-onset AF were identified (50.0% women; mean age 72.7 years). The crude IS incidence was higher in women than in men across the entire study period (21.1 vs. 14.9 events per 1000 patient-years, P <.001), and the incidence decreased both in men and women. In 2007–08, female sex was independently associated with a 20%–30% higher IS rate in the adjusted analyses, but this association attenuated and became statistically non-significant by the end of the observation period. Similar trends were observed when time with and without oral anticoagulant (OAC) treatment was analysed, as well as when only time without OAC use was considered. The decrease in IS rate was driven by patients with high IS risk, whereas in patients with low or moderate IS risk, female sex was not associated with a higher IS rate. Conclusions The association between female sex and IS rate has decreased and become non-significant over the course of the study period from 2007 to 2018, suggesting that female sex could be omitted as a factor when estimating expected IS rates and the need for OAC therapy in patients with AF. [ABSTRACT FROM AUTHOR]

Objective: The significance of the onset of seizure based on the medical and social aspects of epilepsy. The aim of this study was to investigate the age of seizure onset based on the specific characteristics of each age of seizure onset in many epilepsy syndromes to make an appropriate diagnosis. Methods: The age at epilepsy was retrospectively studied in 155 women aged between 16 and 45 years with a verified diagnosis of epilepsy. The epidemiological method revealed the age at epilepsy onset, and females were divided into three groups: pre-puberty (10-11 years old), puberty (10-18 years old), and post-puberty (18+ years old). A correlation study of the frequency of onset with the periods of formation and function of the female reproductive tract was conducted. Results: A statistically significant quantitative predominance of females with epilepsy onset during puberty (p

Abstract Background Amidst the COVID-19 pandemic, vaccination has been a crucial strategy for mitigating transmission and disease severity. However, vaccine-effectiveness may be influenced by various factors, including booster vaccination, as well as personal factors such as age, sex, BMI, smoking, and comorbidities. To investigate the potential effects of these factors on SARS-CoV-2 infection and disease severity, we analyzed data from the third round of the Cologne Corona Surveillance (CoCoS) project, a large cross-sectional survey. Methods The study was conducted mid-February to mid-March 2022 in Cologne, Germany. A random sample of 10,000 residents aged 18 years and older were invited to participate in an online survey. Information on participants’ demographics (age, sex), SARS-CoV-2 infections, vaccination status, smoking, and preexisting medical conditions were collected. The outcomes of the study were: (1) the occurrence of SARS-CoV-2 infection despite vaccination (breakthrough infection) and (2) the occurrence of moderate-to-severe disease as a result of a breakthrough infection. Cox proportional-hazards regression was used to investigate possible associations between the presence/absence of booster vaccination, personal factors and the occurrence of SARS-CoV-2 infection. Associations with moderate-to-severe infection were analyzed using the Fine and Gray subdistribution hazard model. Results A sample of 2,991 residents responded to the questionnaire. A total of 2,623 primary immunized participants were included in the analysis of breakthrough infection and 2,618 in the analysis of SARS-CoV-2 infection severity after exclusions due to incomplete data. The multivariable results show that booster vaccination (HR = 0.613, 95%CI 0.415–0.823) and older age (HR = 0.974, 95%CI 0.966–0.981) were associated with a reduced hazard of breakthrough infection. Regarding the severity of breakthrough infection, older age was associated with a lower risk of moderate-to-severe breakthrough infection (HR = 0.962, 95%CI0.949–0.977). Female sex (HR = 2.570, 95%CI1.435–4.603), smoking (HR = 1.965, 95%CI1.147–3.367) and the presence of chronic lung disease (HR = 2.826, 95%CI1.465–5.450) were associated with an increased hazard of moderate-to-severe breakthrough infection. Conclusion The results provide a first indication of which factors may be associated with SARS-CoV-2 breakthrough infection and moderate-to-severe course of infection despite vaccination. However, the retrospective nature of the study and risk of bias in the reporting of breakthrough infection severity limit the strength of the results. Trial registration DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Purpose: Whether blood volume (BV) primarily determines the synchronous nature of the myocardium remains unknown. This study determined the impact of standard blood withdrawal on left ventricular mechanical dyssynchrony (LVMD) in women. Methods: Transthoracic speckle-tracking echocardiography and central hemodynamic measurements were performed at rest and during moderate- to high-intensity exercise in healthy women (n = 24, age = 53.6 ± 16.3 year). LVMD was determined via the time to peak standard deviation (TPSD) of longitudinal and transverse strain and strain rates (LSR, TSR). Measurements were repeated within a week period immediately after a 10% reduction of BV. Results: With intact BV, all individuals presented cardiac structure and function variables within normative values of the study population. Blood withdrawal decreased BV (5.3 ± 0.7 L) by 0.5 ± 0.1 L. Resting left ventricular (LV) end-diastolic volume (− 8%, P = 0.040) and passive filling (− 16%, P = 0.001) were reduced after blood withdrawal. No effect of blood withdrawal was observed for any measure of LVMD at rest (P ≥ 0.225). During exercise at a fixed submaximal workload (100 W), LVMD of myocardial longitudinal strain (LS TPSD) was increased after blood withdrawal (36%, P = 0.047). At peak effort, blood withdrawal led to increased LVMD of myocardial transverse strain rate (TSR TPSD) (31%, P = 0.002). The effect of blood withdrawal on TSR TPSD at peak effort was associated with LV concentric remodeling (r = 0.59, P = 0.003). Conclusion: Marked impairments in the mechanical synchrony of the myocardium are elicited by moderate blood withdrawal in healthy women during moderate and high intensity exercise. [ABSTRACT FROM AUTHOR]

AbstractStudies about violence by women with severe mental disorders are rare. The aim of this paper is to analyse the sample of women diagnosed with Schizophrenia Spectrum Disorders (SSD) from the EU-VIORMED study who had offended violently and were admitted to forensic facilities (cases), and compare them to women with SSD who never exhibited violent behaviour (controls). Cases and controls matched for age and diagnosis were compared for sociodemographic, clinical, neuropsychological, and treatment-related characteristics using a standardised assessment. When compared to 36 controls, the 26 cases were significantly older, with longer duration of illness, had fewer years of education, were less likely to have children, and were more likely to have a comorbid personality disorder. Cases were less functionally impaired and scored lower on cognitive domains. There were no differences between the groups in exposure to childhood or adult violence, but a greater proportion of cases reported more frequently being witness to and victims of violence and more frequently reported being beaten, kicked, or punched. Results suggest that the emergence of violent behaviour in women with SSD might be shaped by various factors including violent victimisation, personality factors, soft cognitive impairment and perhaps as a result a more extended duration of illness. [ABSTRACT FROM AUTHOR]

Background: Amidst the COVID-19 pandemic, vaccination has been a crucial strategy for mitigating transmission and disease severity. However, vaccine-effectiveness may be influenced by various factors, including booster vaccination, as well as personal factors such as age, sex, BMI, smoking, and comorbidities. To investigate the potential effects of these factors on SARS-CoV-2 infection and disease severity, we analyzed data from the third round of the Cologne Corona Surveillance (CoCoS) project, a large cross-sectional survey. Methods: The study was conducted mid-February to mid-March 2022 in Cologne, Germany. A random sample of 10,000 residents aged 18 years and older were invited to participate in an online survey. Information on participants' demographics (age, sex), SARS-CoV-2 infections, vaccination status, smoking, and preexisting medical conditions were collected. The outcomes of the study were: (1) the occurrence of SARS-CoV-2 infection despite vaccination (breakthrough infection) and (2) the occurrence of moderate-to-severe disease as a result of a breakthrough infection. Cox proportional-hazards regression was used to investigate possible associations between the presence/absence of booster vaccination, personal factors and the occurrence of SARS-CoV-2 infection. Associations with moderate-to-severe infection were analyzed using the Fine and Gray subdistribution hazard model. Results: A sample of 2,991 residents responded to the questionnaire. A total of 2,623 primary immunized participants were included in the analysis of breakthrough infection and 2,618 in the analysis of SARS-CoV-2 infection severity after exclusions due to incomplete data. The multivariable results show that booster vaccination (HR = 0.613, 95%CI 0.415–0.823) and older age (HR = 0.974, 95%CI 0.966–0.981) were associated with a reduced hazard of breakthrough infection. Regarding the severity of breakthrough infection, older age was associated with a lower risk of moderate-to-severe breakthrough infection (HR = 0.962, 95%CI0.949–0.977). Female sex (HR = 2.570, 95%CI1.435–4.603), smoking (HR = 1.965, 95%CI1.147–3.367) and the presence of chronic lung disease (HR = 2.826, 95%CI1.465–5.450) were associated with an increased hazard of moderate-to-severe breakthrough infection. Conclusion: The results provide a first indication of which factors may be associated with SARS-CoV-2 breakthrough infection and moderate-to-severe course of infection despite vaccination. However, the retrospective nature of the study and risk of bias in the reporting of breakthrough infection severity limit the strength of the results. Trial registration: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021. [ABSTRACT FROM AUTHOR]

Martin Marinsek,1,&ast; David Šuran,2,&ast; Andreja Sinkovic1,3,&ast; 1Department of Medical Intensive Care, University Clinical Centre Maribor, Maribor, 2000, Slovenia; 2Department of Cardiology, University Clinical Centre Maribor, Maribor, 2000, Slovenia; 3Medical Faculty of University Maribor, Maribor, 2000, Slovenia&ast;These authors contributed equally to this workCorrespondence: Andreja Sinkovic, Department of medical intensive care, University clinical centre Maribor, Ljubljanska 5, Maribor, 2000, Slovenia, Tel +38641337822, Email andreja.sinkovic@guest.arnes.siPurpose: There are well-known gender differences in mortality of patients with ST-elevation myocardial infarction (STEMI). Our purpose was to assess factors of hospital mortality separately for men and women with STEMI, which are less well known.Patients and Methods: In 2018– 2019, 485 men and 214 women with STEMI underwent treatment with primary percutaneous coronary intervention (PCI). We retrospectively compared baseline characteristics, treatments and hospital complications between men and women, as well as between nonsurviving and surviving men and women with STEMI.Results: Primary PCI was performed in 94% of men and 91.1% of women with STEMI, respectively. The in-hospital mortality was significantly higher in women than in men (14% vs 8%, p=0.019). Hospital mortality in both genders was associated significantly to older age, heart failure, prior resuscitation, acute kidney injury, to less likely performed and less successful primary PCI and additionally in men to hospital infection and in women to bleeding. In men and women ≥ 65 years, mortality was similar (13.3% vs 17.8%, p = 0.293).Conclusion: Factors of hospital mortality were similar in men and women with STEMI, except bleeding was more likely observed in nonsurviving women and infection in nonsurviving men.Keywords: ST-elevation myocardial infarction, female sex, male sex, sex differences, hospital mortality, 30-day survival, 6-month survival

Background and aims Female sex is associated with higher rates of stroke in atrial fibrillation (AF) after adjustment for other CHA2DS2-VASc factors. This study aimed to describe sex differences in age and cardiovascular care to examine their relationship with stroke hazard in AF. Methods Population-based cohort study using administrative datasets of people aged ≥66 years diagnosed with AF in Ontario between 2007 and 2019. Cause-specific hazard regression was used to estimate the adjusted hazard ratio (HR) for stroke associated with female sex over a 2-year follow-up. Model 1 included CHA2DS2-VASc factors, with age modelled as 66–74 vs. ≥ 75 years. Model 2 treated age as a continuous variable and included an age–sex interaction term. Model 3 further accounted for multimorbidity and markers of cardiovascular care. Results The cohort consisted of 354 254 individuals with AF (median age 78 years, 49.2% female). Females were more likely to be diagnosed in emergency departments and less likely to receive cardiologist assessments, statins, or LDL-C testing, with higher LDL-C levels among females than males. In Model 1, the adjusted HR for stroke associated with female sex was 1.27 (95% confidence interval 1.21–1.32). Model 2 revealed a significant age–sex interaction, such that female sex was only associated with increased stroke hazard at age >70 years. Adjusting for markers of cardiovascular care and multimorbidity further decreased the HR, so that female sex was not associated with increased stroke hazard at age ≤80 years. Conclusion Older age and inequities in cardiovascular care may partly explain higher stroke rates in females with AF. [ABSTRACT FROM AUTHOR]

Objective: The significance of the onset of seizure based on the medical and social aspects of epilepsy. The aim of this study was to investigate the age of seizure onset based on the specific characteristics of each age of seizure onset in many epilepsy syndromes to make an appropriate diagnosis. Methods: The age at epilepsy was retrospectively studied in 155 women aged between 16 and 45 years with a verified diagnosis of epilepsy. The epidemiological method revealed the age at epilepsy onset, and females were divided into three groups: pre-puberty (10-11 years old), puberty (10-18 years old), and postpuberty (18+ years old). A correlation study of the frequency of onset with the periods of formation and function of the female reproductive tract was conducted. Results: A statistically significant quantitative predominance of females with epilepsy onset during puberty (p<0.001) was identified. Statistically valid was the prevalence of epilepsy onset in the combined age range of 12 to16 (p<0.001). A direct link between menarche and epilepsy onset was detected in the general cohort in 13% of females, which is among the risk factors for catamenial seizure onset. Conclusion: Epilepsy onset in females of reproductive age dominates during childhood development. In more than half of the cases, the epilepsy onset occurs in the puberty period. Epilepsy onset most often occurs between the ages of 12 and 16. Seizure onset occurs at the ages of 12-16 years during menstrual bleeding and ovulatory cycle development due to the proconvulsive effects of estrogens. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is known to be linked with metabolic associated fatty liver disease and type 2 diabetes, but few studies assessed this relationship in prediabetes, especially among women, who are at greater risk of CVD. We aimed to evaluate cardiac alterations and its relationship with hepatic lipid metabolism in prediabetic female rats submitted to high-fat-high-sucrose diet (HFS). Wistar female rats were divided into 2 groups fed for 5 months with standard or HFS diet. We analyzed cardiac morphology, function, perfusion and fibrosis by Magnetic Resonance Imaging. Hepatic lipid contents along with inflammation and lipid metabolism gene expression were assessed. Five months of HFS diet induced glucose intolerance (p < 0.05), cardiac remodeling characterized by increased left-ventricular volume, wall thickness and mass (p < 0.05). No significant differences were found in left-ventricular ejection fraction and cardiac fibrosis but increased myocardial perfusion (p < 0.01) and reduced cardiac index (p < 0.05) were shown. HFS diet induced hepatic lipid accumulation with increased total lipid mass (p < 0.001) and triglyceride contents (p < 0.05), but also increased mitochondrial (CPT1a, MCAD; (p < 0.001; p < 0.05) and peroxisomal (ACO, LCAD; (p < 0.05; p < 0.001) β-oxidation gene expression. Myocardial wall thickness and perfusion were correlated with hepatic β-oxidation genes expression. Furthermore, myocardial perfusion was also correlated with hepatic lipid content and glucose intolerance. This study brings new insights on the relationship between cardiac sub-clinical alterations and hepatic metabolism in female prediabetic rats. Further studies are warranted to explore its involvement in the higher CVD risk observed among prediabetic women. • Early cardiac remodeling and perfusion alteration in HFS prediabetic female rats. • Hepatic steatosis in HFS prediabetic female rats. • Increased hepatic β-oxidation genes expression in HFS prediabetic female rats. • Cardiac defects correlation with liver lipid metabolism in prediabetic female rats. [ABSTRACT FROM AUTHOR]

Purpose of Review: Females outnumber males among long-term cancer survivors, primarily as a result of the prevalence of breast cancer. Late cardiovascular effects of cancer develop over several decades, which for many women, may overlap with reproductive and lifecycle events. Thus, women require longitudinal cardio-oncology care that anticipates and responds to their evolving cardiovascular risk. Recent Findings: Women may experience greater cardiotoxicity from cancer treatments compared to men and a range of treatment-associated hormonal changes that increase cardiometabolic risk. Biological changes at critical life stages, including menarche, pregnancy, and menopause, put female cancer patients and survivors at a unique risk of cardiovascular disease. Women also face distinct psychosocial and physical barriers to accessing cardiovascular care. Summary: We describe the need for a lifespan-based approach to cardio-oncology for women. Cardio-oncology care tailored to women should rigorously consider cancer treatment/outcomes and concurrent reproductive/hormonal changes, which collectively shape quality of life and cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Background: Existing data on the impact of sex differences on transvenous lead extraction (TLE) outcomes in cardiac device patients are limited. Objective: The purpose of this study was to evaluate the safety and efficacy of mechanical TLE in female patients. Methods: A retrospective evaluation was performed on 3051 TLE patients (group 1: female; group 2: male) from a single tertiary referral center. All individuals received treatment using single sheath mechanical dilation and various venous approaches as required. Results: Our analysis included 3051 patients (group 1: 750; group 2: 2301), with a total of 5515 leads handled with removal. Female patients were younger, had a higher left ventricular ejection fraction, and lower prevalences of coronary artery disease and diabetes mellitus. Infection was more common in male patients, whereas lead malfunction or abandonment were more frequent in female patients. Radiologic success was lower in female patients (95.8% vs 97.5%; P = .003), but there was no significant difference in clinical success between groups (97.2% vs 97.5%; P = .872). However, major complications (1.33% vs 0.60%; P

Abstract Background Post-COVID-19 syndromes have associated with female sex, but the pathophysiological basis is uncertain. Aim There are sex differences in myocardial inflammation identified using cardiac magnetic resonance (CMR) in post-COVID-19 patients, and in patient reported health outcomes following COVID-19 infection. Design This prospective study investigated the time-course of multiorgan injury in survivors of COVID-19 during convalescence. Methods Clinical information, blood biomarkers, and patient reported outcome measures were prospectively acquired at enrolment (visit 1) and 28–60 days post-discharge (visit 2). Chest computed tomography (CT) and CMR were performed at visit 2. Follow-up was carried out for serious adverse events, including death and rehospitalization. Results Sixty-nine (43%) of 159 patients recruited were female. During the index admission, females had a lower peak C-reactive protein (74 mg/l (21,163) versus 123 mg/l (70, 192) p = 0.008) and peak ferritin (229 μg/l (103, 551) versus 514 μg/l (228, 1122) p

The effect of a high glycemic diet (HGD) on brain microvasculature is a crucial, yet understudied research topic, especially in females. This study aimed to determine the transcriptomic changes in female brain hippocampal microvasculature induced by a HGD and characterize the response to a soluble epoxide hydrolase inhibitor (sEHI) as a mechanism for increased epoxyeicosatrienoic acids (EETs) levels shown to be protective in prior models of brain injury. We fed mice a HGD or a low glycemic diet (LGD), with/without the sEHI (t-AUCB), for 12 weeks. Using microarray, we assessed differentially expressed protein-coding and noncoding genes, functional pathways, and transcription factors from laser-captured hippocampal microvessels. We demonstrated for the first time in females that the HGD had an opposite gene expression profile compared to the LGD and differentially expressed 506 genes, primarily downregulated, with functions related to cell signaling, cell adhesion, cellular metabolism, and neurodegenerative diseases. The sEHI modified the transcriptome of female mice consuming the LGD more than the HGD by modulating genes involved in metabolic pathways that synthesize neuroprotective EETs and associated with a higher EETs/dihydroxyeicosatrienoic acids (DHETs) ratio. Our findings have implications for sEHIs as promising therapeutic targets for the microvascular dysfunction that accompanies vascular dementia.

Background: APOE genotype is the greatest genetic risk factor for sporadic Alzheimer's disease (AD). APOE4 increases AD risk up to 12-fold compared to APOE3, an effect that is greater in females. Evidence suggests that one-way APOE could modulate AD risk and progression through neuroinflammation. Indeed, APOE4 is associated with higher glial activation and cytokine levels in AD patients and mice. Therefore, identifying pathways that contribute to APOE4-associated neuroinflammation is an important approach for understanding and treating AD. Human and in vivo evidence suggests that TLR4, one of the key receptors involved in the innate immune system, could be involved in APOE-modulated neuroinflammation. Consistent with that idea, we previously demonstrated that the TLR4 antagonist IAXO-101 can reduce LPS- and Aβ-induced cytokine secretion in APOE4 glial cultures. Therefore, the goal of this study was to advance these findings and determine whether IAXO-101 can modulate neuroinflammation, Aβ pathology, and behavior in mice that express APOE4. Methods: We used mice that express five familial AD mutations and human APOE3 (E3FAD) or APOE4 (E4FAD). Female and male E4FAD mice and female E3FAD mice were treated with vehicle or IAXO-101 in two treatment paradigms: prevention from 4 to 6 months of age or reversal from 6 to 7 months of age. Learning and memory were assessed by modified Morris water maze. Aβ deposition, fibrillar amyloid deposition, astrogliosis, and microgliosis were assessed by immunohistochemistry. Soluble levels of Aβ and apoE, insoluble levels of apoE and Aβ, and IL-1β were measured by ELISA. Results: IAXO-101 treatment resulted in lower Iba-1 coverage, lower number of reactive microglia, and improved memory in female E4FAD mice in both prevention and reversal paradigms. IAXO-101-treated male E4FAD mice also had lower Iba-1 coverage and reactivity in the RVS paradigm, but there was no effect on behavior. There was also no effect of IAXO-101 treatment on neuroinflammation and behavior in female E3FAD mice. Conclusion: Our data supports that TLR4 is a potential mechanistic therapeutic target for modulating neuroinflammation and cognition in APOE4 females. [ABSTRACT FROM AUTHOR]

The association of biological female sex with outcome in patients with Staphylococcus aureus bacteraemia remains unresolved. The aim of this study was to determine the independent association of female sex with management and mortality in patients with S. aureus bacteraemia. This is a post hoc analysis of prospectively collected data from the S. aureus Bacteraemia Group Prospective Cohort Study. Adult patients with monomicrobial S. aureus bacteraemia at Duke University Medical Center were enrolled from 1994 to 2020. Univariable and multivariable Cox regression analyses were performed to assess differences in management and mortality between females and males. Among 3384 patients with S. aureus bacteraemia, 1431 (42%) were women. Women were, as compared with men, more often Black (581/1431 [41%] vs. 620/1953 [32%], p < 0.001), haemodialysis dependent (309/1424 [22%] vs. 334/1940 [17%], p 0.001) and more likely to be infected with methicillin-resistant S. aureus (MRSA) (697/1410 [49%] MRSA in women vs. 840/1925 [44%] MRSA in men, p 0.001). Women received shorter durations of antimicrobial treatment (median 24 [interquartile range 14–42] vs. 28 [interquartile range 14–45] days, p 0.005), and were less likely to undergo transesophageal echocardiography as compared with men (495/1430 [35%] vs. 802/1952 [41%], p < 0.001). Despite these differences, female sex was not associated with 90-day mortality in either univariable (388/1431 [27%] in women vs. 491/1953 [25%] in men, p 0.204) or multivariable analysis (adjusted hazard ratio for women 0.98 [95% CI, 0.85–1.13]). Despite significant differences in patient characteristics, disease characteristics, and management, women and men with S. aureus bacteraemia have a similar mortality risk. [ABSTRACT FROM AUTHOR]

Background: Post-COVID-19 syndromes have associated with female sex, but the pathophysiological basis is uncertain. Aim: There are sex differences in myocardial inflammation identified using cardiac magnetic resonance (CMR) in post-COVID-19 patients, and in patient reported health outcomes following COVID-19 infection. Design: This prospective study investigated the time-course of multiorgan injury in survivors of COVID-19 during convalescence. Methods: Clinical information, blood biomarkers, and patient reported outcome measures were prospectively acquired at enrolment (visit 1) and 28–60 days post-discharge (visit 2). Chest computed tomography (CT) and CMR were performed at visit 2. Follow-up was carried out for serious adverse events, including death and rehospitalization. Results: Sixty-nine (43%) of 159 patients recruited were female. During the index admission, females had a lower peak C-reactive protein (74 mg/l (21,163) versus 123 mg/l (70, 192) p = 0.008) and peak ferritin (229 μg/l (103, 551) versus 514 μg/l (228, 1122) p < 0.001). Using the Modified Lake-Louise criteria, females were more likely to have definite evidence of myocardial inflammation (54% (37/68) versus 33% (30/90) p = 0.003). At enrolment and 28–60 days post-discharge, enhanced illness perception, higher levels of anxiety and depression and lower predicted maximal oxygen utilization occurred more commonly in women. The mean (SD, range) duration of follow-up after hospital discharge was 450 (88) days (range 290, 627 days). Compared to men, women had lower rates of cardiovascular hospitalization (0% versus 8% (7/90); p = 0.018). Conclusions: Women demonstrated worse patient reported outcome measures at index admission and 28–60 days follow-up though cardiovascular hospitalization was lower. [ABSTRACT FROM AUTHOR]

• Although clinical trial methods and conduct are well established, efforts are needed to optimize consistent monitoring of harm outcomes of trials. • Work done in the cystic fibrosis clinical trials space have focused on rates and characteristics of adverse events. • Attribution of adverse events to the intervention is more likely in the active drug group than in the placebo group. • Females were less likely to have attribution of the adverse event to the assigned treatment highlighting the need to develop improved processes in clinical trial monitoring. Although work to date in cystic fibrosis (CF) has elucidated frequencies and characteristics of adverse events, the accuracy of attribution of relatedness to study drug by investigators has not been assessed. We aimed to determine whether there was an association of attribution by group allocation in CF clinical trials. We conducted a secondary analysis from 4 CF trials of all persons who experienced an AE. Our primary outcome was the odds of an AE related to active study drug and predictor of interest was the treatment allocation. We constructed a multivariable generalized estimating equation model allowing for repeated measures. A total of 785 subjects (47.5% female, mean age 12 years) had 11,974 AEs, of which 430 were serious. AE attribution was greater with receipt of active study drug as compared to placebo but did not reach statistical significance (OR 1.38, 95% CI 0.98–1.82). Significantly associated factors included female sex (OR 0.58, 95% 0.39–0.87), age (OR 1.24, 95% CI 1.06–1.46) and baseline lung function (per 10%, OR 1.16, 95% CI 1.05–1.28). In our large study, there was a non-significant but greater odds of AE attribution (a key element of clinical trial reporting) to active study drug based on assigned treatment to study drug or control which suggests that there is a trend in physicians to attribute blinded safety data to the active drug. Interestingly, females were less likely to have AE attribution to study drug and warrants further work in development and validation of monitoring guidelines and processes. [ABSTRACT FROM AUTHOR]

HIV-associated neurocognitive disorders (HAND) remain a major challenge for people with HIV in the antiretroviral therapy era. Cocaine use may trigger/exacerbate HAND among African American (AA) adults, especially women. Between 2018 and 2019, 922 adults, predominantly AAs, with/without HIV and with/without cocaine use in Baltimore, Maryland, were enrolled in a study investigating the association of HIV and cocaine use with neurocognitive impairment (NCI). Neurocognitive performance was assessed with the NIH Toolbox Cognition Battery (NIHTB-CB). NCI was considered to be present if the fully adjusted standard score for at least two cognitive domains was 1.0 standard deviation below the mean. Although the overall analysis showed HIV and female sex were associated with NCI, the associations were dependent on cocaine use. Neither HIV [adj prevalence ratio (PR): 1.12, confidence interval (95% CI): 0.77–1.64] nor female sex (adj PR: 1.07, 95% CI: 0.71–1.61) was associated with NCI among cocaine nonusers, while both HIV (adj PR: 1.39, 95% CI: 1.06–1.81) and female sex (adj PR: 1.53, 95% CI: 1.18–1.98) were associated with NCI in cocaine users. HIV was associated with two NIHTB-CB measures overall. In addition, HIV was associated with a lower dimensional change card sort score (an executive function measure) in cocaine users and not in nonusers. Cognitive performance was poorer in female than in male cocaine users. The adverse effect of HIV on cognitive performance predominantly affected cocaine users. However, cocaine use may moderate the impact of HIV and female sex on cognitive performance, highlighting the importance of reducing cocaine use in NCI prevention among the AA population. [ABSTRACT FROM AUTHOR]

The regulation of erythropoiesis via hemodynamic stimuli such as reduced central blood volume (CBV) remains uncertain in women and elderly individuals. This study assessed the acute effects of lower body negative pressure (LBNP) on key endocrine biomarkers regulating erythropoiesis, that is, erythropoietin (EPO) and copeptin, in young and older women and men (n = 87). Transthoracic echocardiography and hemodynamics were assessed throughout incremental LBNP levels for 1 hour, or until presyncope, with established methods. Venous blood samples were collected at baseline and immediately after termination of the orthostatic tolerance (OT) test for subsequent hormone analyses. The average age of young women and men (33.1 ± 6.0 vs. 29.5 ± 6.9 yr) and older women and men (63.8 ± 8.0 vs. 65.3 ± 8.9 yr) as well as their physical activity levels were matched within each age and sex group. CBV, as determined by right atrial volume, was reduced in all individuals at the end of the OT test (p < 0.001). The average OT time ranged from 50.1 to 58.1 min in all individuals. LBNP increased circulating EPO in young women (p = 0.023) but not in young men or older individuals. Copeptin was increased in all individuals with LBNP but was exclusively associated with EPO in men (r = 0.39, p = 0.013). The present study indicates that the acute hemodynamic regulation of EPO production is both sex‐ and age‐dependent. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases show a gender bias, as reported for several other immune-mediated diseases. Female-specific differences influence disease presentation and activity, leading to a different progression between males and females. Women show a genetic predisposition to develop inflammatory bowel disease related to the X chromosome. Female hormone fluctuation influences gastrointestinal symptoms, pain perception, and the state of active disease at the time of conception could negatively affect the pregnancy. Women with inflammatory bowel disease report a worse quality of life, higher psychological distress, and reduced sexual activity than male patients. This narrative review aims to resume the current knowledge of female-related features in clinical manifestations, development, and therapy, as well as sexual and psychological implications related to inflammatory bowel disease. The final attempt is to provide gastroenterologists with a roadmap of female-specific differences, to improve patients' diagnosis, management, and treatment. [ABSTRACT FROM AUTHOR]

This study determined whether an intervention combining hematological and exercise stimuli may overcome the prevailing limitations to improve the cardiac phenotype and orthostatic tolerance (OT) of females with advanced age. Healthy females (n = 15) and males (n = 14) matched by age (63.7 ± 7.0 vs. 63.6 ± 8.7 yr) and moderate physical activity were recruited. OT, transthoracic echocardiography, and central hemodynamics were assessed during incremental lower body negative pressure (LBNP) levels (up to −50 mmHg) for 1 h or until presyncope, prior to and after an intervention comprising standard (10%) blood withdrawal and an 8-wk exercise training program designed to maximize central hemodynamic adaptations. OT time was lower in females compared with males (48.1 ± 10.6 vs. 57.0 ± 4.8 min, P = 0.008) before the intervention. Improved OT time (+11%) in females (48.1 ± 10.6 vs. 53.5 ± 6.1 min, P = 0.021) but not in males (57.0 ± 4.8 vs. 56.7 ± 5.6 min, P = 0.868) was found following the intervention, resulting in similar OT time between females and males (P = 0.156). The intervention induced improvements in left ventricular (LV) diastolic function (+13% for myocardial e′) along with increased LV mass (+13%) in females (P ≤ 0.039) but not in males (P ≥ 0.257). During the initial LBNP stages (0 to −20 mmHg), LV stroke volume and cardiac output were exclusively increased in females after the intervention (P ≤ 0.034). In conclusion, the cardiac phenotype of females with advanced age can be structurally and functionally modified in parallel to improved OT via short-term hematological and central hemodynamic stimuli. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with an increased thromboembolic risk. The impact of the female sex as an independent risk factor for thromboembolic events in AF is still debated. Background and Objectives: The aim of this review is to evaluate the gender-related differences in cardioembolic risk and response to anticoagulants among AF patients. Materials and Methods: The PubMed database is used to review the reports about gender differences and thromboembolic risk in atrial fibrillation. Results: Non-vitamin K oral anticoagulants (NOACs) represent the gold standard for thromboembolic risk prevention in patients with non-valvular atrial fibrillation (NVAF). Despite a similar rate of stroke and systemic embolism (SE) among men and women in NOACs or vitamin K antagonists (VKAs) treatment, the use of NOACs in AF women is associated with a lower risk of intracranial bleeding, major bleeding, and all-cause mortality than in men. Conclusions: The female sex can be defined as a stroke risk modifier rather than a stroke risk factor since it mainly increases the thromboembolic risk in the presence of other risk factors. Further studies about the efficacy and safety profile of NOACs according to sex are needed to support clinicians in performing the most appropriate and tailored anticoagulant therapy, either in male or female AF patients. [ABSTRACT FROM AUTHOR]

Abstract Background Sex disparities in blood pressure and anthropometry may account for differences in cardiovascular (CV) risk burden with advancing age; modulated by ethnic variability. We explored trajectories of blood pressures (BPs) and anthropometric indices with age on the basis of sex in an urban Nigerian population. Methods We conducted a secondary analysis on data from 5135 participants (aged 16–92 years; 2671(52%) females) from our population-based cross-sectional study of BP profiles. We utilized the WHO STEPS and standardized methods for documenting BPs, body mass index (BMI) and waist circumference (WC). Data was analyzed using Analysis of variance (ANOVA), Spearman correlation analysis and mean difference in variables (with 95% confidence interval). We explored the influence of age and sex on BP profiles and specific anthropometric indices using generalized regression analysis. Results In those aged 15–44 years, males had significantly higher systolic BP (SBP) and pulse pressure (PP). However, mean SBP and PP rose more steeply in females from 25 to 34 years, intersected with that of males from 45 to 54 years and remained consistently higher. Difference in mean BPs (95% Confidence Interval) (comparing 45 years) was higher in females compared to males for SBP (17.4 (15.8 to 19.0) v. 9.2 (7.7 to 10.7), DBP (9.0 (7.9 to 10.1) v. 7.8 (6.7 to 8.9)), and PP (8.4 (7.3 to 9.5) v. 1.4 (0.3 to 2.5)). Females had significantly higher BMI and WC across all age groups (p

Background: Whether the synchronous nature of the myocardium is sex-dependent or affected by the aging process remains unknown. This study aimed to determine the influence of sex and age on cardiac mechanical synchrony during controlled hemodynamic stress. Methods: Transthoracic speckle-tracking echocardiography analyses and central hemodynamics were assessed at rest and during moderate- to high-intensity exercise in healthy young ( 0.05). The rate pressure product, an index of myocardial work, did not differ between sex and age groups at rest and during exercise at a given percentage of peak heart rate (P > 0.05). A consistent age effect was observed for transverse LVMD (P-for-age ≤ 0.011). Specifically, older women presented with marked increments (≥42 %) in TSR TPSD at all exercise levels compared with younger women (P ≤ 0.005). Sex per se did not generally affect LVMD. Conclusion: A prevailing impairment of cardiac mechanical synchrony in the transverse axis of the left ventricle is revealed during conditions of elevated hemodynamic stress in women with advanced age.

Background: Sex is a significant determinant of survival and functional outcome after stroke. Long-term cognitive outcome after acute lacunar stroke in the context of sex differences has been rarely reported. Methods: A cohort of small vessel disease (SVD) patients presenting with first-ever acute lacunar stroke and normal cognitive status has been evaluated 4 years after the qualifying event for the presence of cognitive impairment (CI) with a comprehensive neuropsychological battery. Differences in baseline clinical and neuroimaging characteristics were compared between sexes in relation to cognitive status. Results: A total of 124 female and 150 male patients were analyzed. No difference was detected between the groups regarding age (p = 0.932) or frequency of common vascular risk factors (p > 0.1 for all). At the baseline assessment, women had more disabilities compared to men with a mean modified Rankin scale (mRS) score of 2.5 (1.5 in men, p < 0.0001). Scores of white matter hyperintensities (WMH) of presumed vascular origin and a total number of lacunes of presumed vascular origin on brain MRI were higher in women compared to men (p < 0.0001 for all). As many as 64.6% of patients had CI of any severity on follow-up, women more frequently (77.4%) than men (54.0%; p < 0.0001). Univariate logistic regression analysis showed that female sex, higher NIHSS and mRS scores, presence of depression, and increasing WMH severity were associated with an increased risk for CI. Multivariate regression analysis indicated that only depression (OR 1.74, 95%CI 1.25–2.44; p = 0.001) and WMH severity (OR 1.10, 95%CI 1.03–1.17; p = 0.004) were independently associated with the CI. Conclusion: At the long-term follow-up, women lacunar stroke survivors, compared to men, more frequently had CI in the presence of more severe vascular brain lesions, but this association was dependent on the occurrence of depression and severity of WMH, and could not be explained by differences in common vascular risk factors. [ABSTRACT FROM AUTHOR]

Background: Women and men with chronic coronary syndrome (CCS) have different clinical features and management, and studies on mid-term prognosis have reported conflicting results. Our objective was to investigate the impact of the female sex in the prognosis of the disease in the very long term. Methods and Results: We investigated differential features and very long-term prognosis in 1268 consecutive outpatients with CCS (337 [27%] women and 931 [73%] men). Women were older than men, more likely to have hypertension, diabetes, angina, and atrial fibrillation, and less likely to be exsmoker/active smoker and to have been treated with coronary revascularization (p < 0.05 for all). The prescription of statins, antiplatelets, and betablockers was similar in both groups. After up to 17 years of follow-up (median = 11 years, interquartile range = 4–15 years), cumulative incidences of acute myocardial infarction (10.2% vs. 11.8%) or stroke (11% vs. 10%) at median follow-up were similar, but the risks of major cardiovascular events (acute myocardial infarction, stroke, or cardiovascular death, 41.2% vs. 33.6%), hospital admission for heart failure (20.9% vs. 11.9%), or cardiovascular death (32.3% vs. 22.1%) were significantly higher for women (p < 0.0005), with a nonsignificant trend to higher overall mortality (45.2% vs. 39.1%, p = 0.07). However, after multivariate adjustment, all these differences disappeared. Conclusion: Although women and men with CCS presented a different clinical profile, and crude rates of major cardiovascular events, heart failure and cardiovascular death were higher in women, female sex was not an independent prognostic factor in this study with up to 17 years of follow-up. [ABSTRACT FROM AUTHOR]

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Abstract Background Whether the fundamental hematological and cardiac variables determining cardiorespiratory fitness and their intrinsic relationships are modulated by major constitutional factors, such as sex and age remains unresolved. Methods Transthoracic echocardiography, central hemodynamics and pulmonary oxygen (O2) uptake were assessed in controlled conditions during submaximal and peak exercise (cycle ergometry) in 85 healthy young (20–44 year) and older (50–77) women and men matched by age-status and moderate-to-vigorous physical activity (MVPA) levels. Main outcomes such as peak left ventricular end-diastolic volume (LVEDVpeak), stroke volume (SVpeak), cardiac output (Q peak) and O2 uptake (VO2peak), as well as blood volume (BV), BV–LVEDVpeak and LVEDVpeak–SVpeak relationships were determined with established methods. Results All individuals were non-smokers and non-obese, and MVPA levels were similar between sex and age groups (P ≥ 0.140). BV per kg of body weight did not differ between sexes (P ≥ 0.118), but was reduced with older age in men (P = 0.018). Key cardiac parameters normalized by body size (LVEDVpeak, SVpeak, Q peak) were decreased in women compared with men irrespective of age (P ≤ 0.046). Older age per se curtailed Q peak (P ≤ 0.022) due to lower heart rate (P

Introduction: Globally, nine million people are injured due to fire, heat and hot substances every year with a mortality rate of 1.34%. Research shows conflicting reports regarding sex as a risk factor for mortality in patient with burns. We analysed whether sex is a risk factor for in-hospital mortality in patients admitted with burns in urban India. Methods: A subgroup analysis of patients with burns as mechanism of injury was done from a multi-centre prospective observational study ‘Towards Improved Trauma Care Outcomes (TITCO)’ in India conducted in October 2013 to December 2015. Results: 1209 patients were identified as having suffered burns from the TITCO study. The mean age was 23 years with 58.9% females. The overall 30 day in-hospital mortality was 574 (48.5%). Among patients who succumbed, 72% were females and 27% were males. We conducted a multivariable logistic regression and found that females were at a significantly higher odds of death compared with males (OR = 1.73 95%CI = 1.06–2.80, p value = 0.02). After performing a sex and age stratified analysis, females in the age group of 15–44 years had a significantly higher number of deaths compared to males in that group. Conclusion: In this multi-center study from urban Indian university hospitals, sex was identified as an independent risk factor of mortality in patients admitted with burns. Females have an increased odds of mortality from burns.

BackgroundSex is a significant determinant of survival and functional outcome after stroke. Long-term cognitive outcome after acute lacunar stroke in the context of sex differences has been rarely reported.MethodsA cohort of small vessel disease (SVD) patients presenting with first-ever acute lacunar stroke and normal cognitive status has been evaluated 4 years after the qualifying event for the presence of cognitive impairment (CI) with a comprehensive neuropsychological battery. Differences in baseline clinical and neuroimaging characteristics were compared between sexes in relation to cognitive status.ResultsA total of 124 female and 150 male patients were analyzed. No difference was detected between the groups regarding age (p = 0.932) or frequency of common vascular risk factors (p > 0.1 for all). At the baseline assessment, women had more disabilities compared to men with a mean modified Rankin scale (mRS) score of 2.5 (1.5 in men, p < 0.0001). Scores of white matter hyperintensities (WMH) of presumed vascular origin and a total number of lacunes of presumed vascular origin on brain MRI were higher in women compared to men (p < 0.0001 for all). As many as 64.6% of patients had CI of any severity on follow-up, women more frequently (77.4%) than men (54.0%; p < 0.0001). Univariate logistic regression analysis showed that female sex, higher NIHSS and mRS scores, presence of depression, and increasing WMH severity were associated with an increased risk for CI. Multivariate regression analysis indicated that only depression (OR 1.74, 95%CI 1.25–2.44; p = 0.001) and WMH severity (OR 1.10, 95%CI 1.03–1.17; p = 0.004) were independently associated with the CI.ConclusionAt the long-term follow-up, women lacunar stroke survivors, compared to men, more frequently had CI in the presence of more severe vascular brain lesions, but this association was dependent on the occurrence of depression and severity of WMH, and could not be explained by differences in common vascular risk factors.

IntroductionSexual dimorphism has been reported in non-alcoholic fatty liver disease (NAFLD), similar to the sex differences evident with cardiovascular disease. Type 2 diabetes mellitus (T2D) significantly increases the risk and severity of NAFLD, but there is scarce information on whether T2D or altered glucose metabolism can modify the prevalence of NAFLD in men and women of reproductive age.PurposeTo investigate the relationship between age, sex and NAFLD in subjects with and without dysglycemia.Materials and methodsWe analyzed 2,790 patients. NAFLD was characterized using established diagnostic criteria: one or more positive results on the fatty liver index and hepatic ultrasound. Liver fibrosis (liver stiffness measurement [LSM] ≥8.0 kPa) was assessed by Fibroscan®. For analysis purposes, we included both T2D and prediabetes under the predefined condition of dysglycemia.ResultsThe global prevalence of NAFLD was higher in men than in women (50% and 34%; P

BackgroundTreatment burden (TB) is defined as the patient’s workload of healthcare and its impact on patient functioning and wellbeing. High TB can lead to non-adherence, a higher risk of adverse outcomes and lower quality of life (QoL). We have previously reported a higher TB in patients with atrial fibrillation (AF) vs. those with other chronic conditions. In this analysis, we explored sex-related differences in self-reported TB in AF patients.Materials and methodsA single-center, prospective study included consecutive patients with AF under drug treatment for at least 6 months before enrollment from April to June 2019. Patients were asked to voluntarily and anonymously answer the Treatment Burden Questionnaire (TBQ). All patients signed the written consent for participation.ResultsOf 331 patients (mean age 65.4 ± 10.3 years, mean total AF history 6.41 ± 6.62 years), 127 (38.4%) were females. The mean TB was significantly higher in females compared to males (53.7 vs. 42.6 out of 170 points, p < 0.001), and females more frequently reported TB ≥ 59 points than males (37.8% vs. 20.6%, p = 0.001). In females, on multivariable analysis of the highest TB quartile (TB ≥ 59), non-vitamin K Antagonist Oral Anticoagulant (NOAC) use [Odds Ratio (OR) 0.319; 95% Confidence Interval (CI) 0.12–0.83, P = 0.019], while in males, catheter ablation and/or ECV of AF (OR 0.383; 95% CI 0.18–0.81, P = 0.012) were negatively associated with the highest TB quartile.ConclusionOur study was the first to explore the sex-specific determinants of TB in AF patients. Females had significantly higher TB compared with males. Approximately 2 in 5 females and 1 in 5 males reported TB ≥ 59 points, previously shown to be an unacceptable burden of treatment for patients. Using a NOAC rather than vitamin K antagonist (VKA) in females and a rhythm control strategy in males could decrease TB to acceptable values.

Background: Atrial fibrillation is more common in men, but in the presence of ischemic heart disease, this arrhythmia is more frequent in women. However, like in coronary heart disease, women with atrial fibrillation are suboptimally treated. Methods: To identify particularities of ablation, in women with atrial fibrillation and ischemic heart disease. Results: 29 women and 26 men, with documented ischemic heart disease and atrial fibrillation, who underwent catheter ablation, were admitted in the study. No significant differences were registered regarding the heart rate control treatment. Electrical cardioversion was significantly higher in men, while pharmacological cardioversion was predominantly recommended in women. The ablation was performed later in women, after 2.55 ± 1.84 years versus 1.80 ± 1.05 in men (p = 0.05). The time elapsed until the ablation was performed was statistically correlated with atypical symptomatology and with the number of antiarrhythmics used prior to the ablation. There were no significant differences for the relapse of atrial fibrillation at 3 months. Quality of life at 3 months after ablation was increased in both groups. Conclusion: Catheter ablation is performed much later in women, and the causes responsible for this delay would be more atypical symptoms and a greater number of antiarrhythmics tried before the ablation. [ABSTRACT FROM AUTHOR]

Background Studies from high income countries suggest improved survival for females as compared to males following trauma. However, data regarding differences in trauma outcomes between females and males is severely lacking from low- and middle-income countries. The objective of this study was to determine the association between sex and clinical outcomes amongst Indian trauma patients using the Australia-India Trauma Systems Collaboration database. Methods A prospective multicentre cohort study was performed across four urban public hospitals in India April 2016 through February 2018. Bivariate analyses compared admission physiological parameters and mechanism of injury. Logistic regression assessed association of sex with the primary outcomes of 30-day and 24-hour in-hospital mortality. Secondary outcomes included ICU admission, ICU length of stay, ventilator requirement, and time on a ventilator. Results Of 8,605 patients, 1,574 (18.3%) were females. The most common mechanism of injury was falls for females (52.0%) and road traffic injury for males (49.5%). On unadjusted analysis, there was no difference in 30-day in-hospital mortality between females (11.6%) and males (12.6%, p = 0.323). However, females demonstrated a lower mortality at 24-hours (1.1% vs males 2.1%, p = 0.011) on unadjusted analysis. Females were also less likely to require a ventilator (17.3% vs 21.0% males, p = 0.001) or ICU admission (34.4% vs 37.5%, p = 0.028). Stratification by age or by ISS demonstrated no difference in 30-day in-hospital mortality for males vs females across age and ISS categories. On multivariable regression analysis, sex was not associated significantly with 30-day or 24-hour in-hospital mortality. Conclusion This study did not demonstrate a significant difference in the 30-day trauma mortality or 24-hour trauma mortality between female and male trauma patients in India on adjusted analyses. A more granular data is needed to understand the interplay of injury severity, immediate post-traumatic hormonal and immunological alterations, and the impact of gender-based disparities in acute care settings. [ABSTRACT FROM AUTHOR]

Background: Transradial access (TRA) is now the default access site for PPCI, but technically is a more challenging approach mostly due to anatomic challenges connected to the RA., Aims: To assess the differences according to sex in radial artery (RA) access site characteristics during primary percutaneous coronary intervention (PPCI) for ST segment elevation myocardial infarction (STEMI)., Material and Methods: All 5092 consecutive STEMI patients from our center in the period from March 2011 until December 2017 were examined. The right proximal radial was the "intention-to-treat" access in all patients. Preprocedural RA angiography was performed in all patients. Clinical and procedure characteristics, type of radial anatomy variants, need to use another arterial access sites (the primary endpoint for this study), and procedure time were analyzed by sex. Using logistic regression, we selected predictors of radial crossover. Access site bleeding complications and vascular complications were also recorded., Results: The STEMI population in this period included 1326 females and 3766 male patients. Females were older (65 ± 11 years) than males (59 ± 11 years, p < 0.0001). Among standard risk factors, hypertension and diabetes mellitus were more common in women and smoking less common. RA anomalies were more frequent in the females (8.8% vs. 6.5%, p < 0.0001), with complex RA loop and tortuous RA twice as frequent in women. Failure of TRA access as the initially chosen site occurred in 4.6% (61) of females versus 2.5% (97) of male STEMI patients (p = 0.0003). The most common subsequent access site was right ulnar access in both groups (57 and 61% respectively). Access site bleeding complications were more common in women 4.4% versus 3.2%, mirrored in hematomas with EASY score III to V. Clinical RA spasm (RAS) was significantly more frequent in females (5.7% vs. 2.2%, p < 0.0001). Multiple regression analysis identified 5 independent predictors for TRA access crossover: previous TRA, anomalous RA, RAS, along with female sex and diabetes., Conclusion: Female sex is a significant predictor of more complex TRA in STEMI. Understanding sex differences and predictors for TRA crossover will strengthen the use of different procedural modalities that can help in preserving a successful wrist access in female STEMI patients., (© 2024 Wiley Periodicals LLC.)

Background: Significant knowledge gaps remain regarding the heterogeneity of heart failure (HF) phenotypes, particularly among patients with preserved or mildly reduced left ventricular ejection fraction (HFp/mrEF). Our aim was to identify HF subtypes within the HFp/mrEF population., Methods: K-prototypes clustering algorithm was used to identify different HF phenotypes in a cohort of 2 570 patients diagnosed with HFmrEF or HFpEF. This algorithm employs the k-means algorithm for quantitative variables and k-modes for qualitative variables., Results: We identified three distinct phenotypic clusters: Cluster A (n = 850, 33.1%), characterized by a predominance of women with low comorbidity burden; Cluster B (n = 830, 32.3%), mainly women with diabetes mellitus and high comorbidity; and Cluster C (n = 890, 34.5%), primarily men with a history of active smoking and respiratory comorbidities. Significant differences were observed in baseline characteristics and one-year mortality rates across the clusters: 18% for Cluster A, 33% for Cluster B, and 26.4% for Cluster C (P < 0.001). Cluster B had the shortest median time to death (90 days), followed by Clusters C (99 days) and A (144 days) (P < 0.001). Stratified Cox regression analysis identified age, cancer, respiratory failure, and laboratory parameters as predictors of mortality., Conclusion: Cluster analysis identified three distinct phenotypes within the HFp/mrEF population, highlighting significant heterogeneity in clinical profiles and prognostic implications. Women were classified into two distinct phenotypes: low-risk women and diabetic women with high mortality rates, while men had a more uniform profile with a higher prevalence of respiratory disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Sex disparities in blood pressure and anthropometry may account for differences in cardiovascular (CV) risk burden with advancing age; modulated by ethnic variability. We explored trajectories of blood pressures (BPs) and anthropometric indices with age on the basis of sex in an urban Nigerian population.Methods: We conducted a secondary analysis on data from 5135 participants (aged 16-92 years; 2671(52%) females) from our population-based cross-sectional study of BP profiles. We utilized the WHO STEPS and standardized methods for documenting BPs, body mass index (BMI) and waist circumference (WC). Data was analyzed using Analysis of variance (ANOVA), Spearman correlation analysis and mean difference in variables (with 95% confidence interval). We explored the influence of age and sex on BP profiles and specific anthropometric indices using generalized regression analysis.Results: In those aged 15-44 years, males had significantly higher systolic BP (SBP) and pulse pressure (PP). However, mean SBP and PP rose more steeply in females from 25 to 34 years, intersected with that of males from 45 to 54 years and remained consistently higher. Difference in mean BPs (95% Confidence Interval) (comparing < and > 45 years) was higher in females compared to males for SBP (17.4 (15.8 to 19.0) v. 9.2 (7.7 to 10.7), DBP (9.0 (7.9 to 10.1) v. 7.8 (6.7 to 8.9)), and PP (8.4 (7.3 to 9.5) v. 1.4 (0.3 to 2.5)). Females had significantly higher BMI and WC across all age groups (p < 0.001). Age more significantly correlated with BPs, BMI and WC in females. Interaction models revealed that SBP was significantly predicted by age category in females from (15-54 years), while DBP was only significantly predicted by age in the 15-34-year category (p < 0.01). BMI and WC were significantly predicted by age only in the 25-34-year category in females, (p < 0.01).Conclusions: Our population demonstrates sex disparity in trajectories of SBP, PP, BMI and WC with age; with steeper rise in females. There is a need to focus on CV risk reduction in females, starting before, or during early adulthood. [ABSTRACT FROM AUTHOR]