Sex-dependent effects in the aged melanoma tumor microenvironment influence invasion and resistance to targeted therapy.

There is documented sex disparity in cutaneous melanoma incidence and mortality, increasing disproportionately with age and in the male sex. However, the underlying mechanisms remain unclear. While biological sex differences and inherent immune response variability have been assessed in tumor cells, the role of the tumor-surrounding microenvironment, contextually in aging, has been overlooked. Here, we show that skin fibroblasts undergo age-mediated, sex-dependent changes in their proliferation, senescence, ROS levels, and stress response. We find that aged male fibroblasts selectively drive an invasive, therapy-resistant phenotype in melanoma cells and promote metastasis in aged male mice by increasing AXL expression. Intrinsic aging in male fibroblasts mediated by EZH2 decline increases BMP2 secretion, which in turn drives the slower-cycling, highly invasive, and therapy-resistant melanoma cell phenotype, characteristic of the aged male TME. Inhibition of BMP2 activity blocks the emergence of invasive phenotypes and sensitizes melanoma cells to BRAF/MEK inhibition.

Patient-physician sex concordance and outcomes in cardiovascular disease: a systematic review.

The sex disparity in outcomes of patients with cardiovascular disease is well-described and has persisted across recent decades. While there have been several proposed mechanisms to explain this disparity, there are limited data on female patient-physician sex concordance and its association with outcomes. The authors review the existing literature on the relationship between patient-physician sex concordance and clinical outcomes in patients with cardiovascular disease, the evidence of a benefit in clinical outcomes with female patient-physician sex concordance, and the possible drivers of such a benefit and highlight directions for future study.

Sex disparity in liver allocation within Eurotransplant.

In Eurotransplant, relatively more females than males die while waiting for liver transplantation, and relatively fewer females undergo transplantation. With adult liver transplantation candidates listed between 2007 and 2019 (n = 21 170), we study whether sex disparity is inherent to the model for end-stage liver disease (MELD) scoring system, or the indirect result of a small candidate body size limiting access to transplantation. Cox proportional hazard models are used to quantify the direct effect of sex on waitlist mortality, independent of the effect of sex through MELD scores, and the direct effect of sex on the transplantation rate, independent of the effect of sex through MELD and candidate body size. Adjusted waitlist mortality hazard ratios (HRs) for female sex are insignificant (HR: 1.03, 95% CI: 0.88-1.20). We thus lack evidence that MELD systematically underestimates waitlist mortality rates for females. Transplantation rates are 25% lower for females than males in unadjusted analyses (HR: 0.74, 95% CI: 0.71-0.77), but HRs become insignificant with adjustment for mediators (HR: 0.98, 95% CI: 0.93-1.04), most importantly candidate body size. Sex disparity in Eurotransplant thus appears to be largely a consequence of lower transplantation rates for females, which are explained by sex differences in body size.

Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a higher incidence in males, but the association of sex with survival remains controversial. This study aimed to examine the effect of sex on HCC survival and its association with age. METHODS: Among 33,238 patients with HCC from 12 Chinese tertiary hospitals, 4175 patients who underwent curative-intent hepatectomy or ablation were analyzed. Cancer-specific survival (CSS) was analyzed using Cox regression and Kaplan-Meier methods. Two propensity score methods and multiple mediation analysis were applied to mitigate confounding. To explore the effect of estrogen, a candidate sex-specific factor that changes with age, female participants' history of estrogen use, and survival were analyzed. RESULTS: There were 3321 males and 854 females included. A sex-related disparity of CSS was present and showed a typical age-dependent pattern: a female survival advantage over males appeared at the perimenopausal age of 45 to 54 years (hazard risk [HR], 0.77; 5-year CSS, 85.7% vs 70.6%; P = .018), peaked at the early postmenopausal age of 55 to 59 years (HR, 0.57; 5-year CSS, 89.8% vs 73.5%; P = .015), and was not present in the premenopausal (<45 y) and late postmenopausal groups (≥60 y). Consistent patterns were observed in patients after either ablation or hepatectomy. These results were sustained with propensity score analyses. Confounding or mediation effects accounted for only 19.5% of sex survival disparity. Female estrogen users had significantly longer CSS than nonusers (HR, 0.74; 5-year CSS, 79.6% vs 72.5%; P = .038). CONCLUSIONS: A female survival advantage in HCC depends on age, and this may be associated with age-dependent, sex-specific factors.

TIPARP as a prognostic biomarker and potential immunotherapeutic target in male papillary thyroid carcinoma.

BACKGROUND: Male patients with papillary thyroid carcinoma (PTC) tend to have poorer prognosis compared to females, partially attributable to a higher rate of lymph node metastasis (LNM). Developing a precise predictive model for LNM occurrence in male PTC patients is imperative. While preliminary predictive models exist, there is room to improve accuracy. Further research is needed to create optimized prognostic models specific to LNM prediction in male PTC cases. METHODS: We conducted a comprehensive search of publicly available microarray datasets to identify candidate genes continuously upregulated or downregulated during PTC progression in male patients only. Univariate Cox analysis and lasso regression were utilized to construct an 11-gene signature predictive of LNM. TIPARP emerged as a key candidate gene, which we validated at the protein level using immunohistochemical staining. A prognostic nomogram incorporating the signature and clinical factors was developed based on the TCGA cohort. RESULTS: The 11-gene signature demonstrated good discriminative performance for LNM prediction in training and validation datasets. High TIPARP expression associated with advanced stage, high T stage, and presence of LNM. A prognostic nomogram integrating the signature and clinical variables reliably stratified male PTC patients into high and low recurrence risk groups. CONCLUSIONS: We identified a robust 11-gene signature and prognostic nomogram for predicting LNM occurrence in male PTC patients. We propose TIPARP as a potential contributor to inferior outcomes in males, warranting further exploration as a prognostic biomarker and immunotherapeutic target. Our study provides insights into the molecular basis for gender disparities in PTC.

Sex disparity, prediagnosis lifestyle factors, and long-term survival of gastric cancer: a multi-center cohort study from China.

BACKGROUND: This multi-center cohort study aimed to investigate whether sex and prediagnosis lifestyle affect the prognosis of gastric cancer. METHODS: Patients with gastric cancer were from four gastric cancer cohorts of the National Cancer Center of China, The First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Provincial Cancer Hospital. Prediagnosis lifestyle factors in our study included body mass index (BMI) at diagnosis, usual BMI, weight loss, the history of Helicobacter pylori (Hp) infection, and the status of smoking and drinking. RESULTS: Four gastric cancer cohorts with 29,779 gastric cancer patients were included. In total patients, female patients had a better prognosis than male patients (HR = 0.938, 95%CI: 0.881-0.999, P = 0.046). For prediagnosis lifestyle factors, BMI at diagnosis, usual BMI and the amount of smoking were statistically associated with the prognosis of gastric cancer patients. Female patients with smoking history had a poorer survival than non-smoking females (HR = 0.782, 95%CI: 0.616-0.993, P = 0.044). Tobacco consumption > 40 cigarettes per day (HR = 1.182, 95%CI: 1.035-1.350, P = 0.013) was independent adverse prognostic factors in male patients. Obesity paradox was observed only in male patients (BMI < 18.5, HR = 1.145, 95%CI: 1.019-1.286, P = 0.023; BMI: 23-27.4, HR = 0.875, 95%CI: 0.824-0.930, P < 0.001; BMI ≥ 27.5, HR = 0.807, 95%CI: 0.735-0.886, P < 0.001). CONCLUSIONS: Sex and some prediagnosis lifestyle factors, including BMI at diagnosis, usual BMI and the amount of smoking, were associated with the prognosis of gastric cancer.

Gastric emptying is slower in women than men with type 2 diabetes and impacts on postprandial glycaemia.

AIM: To evaluate sex differences in gastric emptying and the glycaemic response to a glucose drink and a high carbohydrate meal in type 2 diabetes (T2D). METHODS: In cohort 1, 70 newly diagnosed, treatment-naïve Chinese patients with T2D (44 men) recruited from a diabetes outpatient clinic ingested a 75-g glucose drink containing 150 mg 13C-acetate. In cohort 2, 101 Australian patients with T2D (67 male) recruited from the community, managed by diet and/or metformin monotherapy, ingested a semi-solid mashed potato meal, labelled with 100 µl 13C-octanoic acid. Breath samples were collected over 3 and 4 h, respectively, for assessment of gastric emptying, and venous blood was sampled for evaluation of glycaemia (with and without adjustment for each participant's estimated total blood volume). RESULTS: Gastric emptying was slower in female than male subjects in both cohorts (both p < .01). Multiple linear regression analyses revealed that gastric emptying was independently associated with sex (both p < .05). Without adjustment for blood volume, the glycaemic responses to oral glucose and the mixed meal were greater in female subjects (both p < .001). However, after adjustment for blood volume, the glycaemic responses were greater in men (both p < .05). CONCLUSIONS: Gastric emptying is slower in women than men with T2D, associated with a reduced blood volume-adjusted glycaemic response to oral glucose and a mixed meal in women. These observations highlight the sex difference in postprandial glucose handling, which is relevant to the personalized management of postprandial glycaemia in T2D.

Sex-specific implications of inflammation in covert cerebral small vessel disease.

BACKGROUND: The relationship between inflammation and covert cerebral small vessel disease (SVD) with regards to sex difference has received limited attention in research. We aim to unravel the intricate associations between inflammation and covert SVD, while also scrutinizing potential sex-based differences in these connections. METHODS: Non-stroke/dementia-free study population was from the I-Lan longitudinal Aging Study. Severity and etiology of SVD were assessed by 3T-MRI in each participant. Systemic and vascular inflammatory-status was determined by the circulatory levels of high-sensitivity C-reactive protein (hsCRP) and homocysteine, respectively. Sex-specific multivariate logistic regression to calculate odds ratios (ORs) and interaction models to scrutinize women-to-men ratios of ORs (RORs) were used to evaluate the potential impact of sex on the associations between inflammatory factors and SVD. RESULTS: Overall, 708 participants (62.19 ± 8.51 years; 392 women) were included. Only women had significant associations between homocysteine levels and covert SVD, particularly in arteriosclerosis/lipohyalinosis SVD (ORs[95%CI]: 1.14[1.03-1.27] and 1.15[1.05-1.27] for more severe and arteriosclerosis/lipohyalinosis SVD, respectively). Furthermore, higher circulatory levels of homocysteine were associated with a greater risk of covert SVD in women compared to men, as evidenced by the RORs [95%CI]: 1.14[1.01-1.29] and 1.14[1.02-1.28] for more severe and arteriosclerosis/lipohyalinosis SVD, respectively. No significant associations were found between circulatory hsCRP levels and SVD in either sex. CONCLUSION: Circulatory homocysteine is associated with covert SVD of arteriosclerosis/lipohyalinosis solely in women. The intricacies underlying the sex-specific effects of homocysteine on SVD at the preclinical stage warrant further investigations, potentially leading to personalized/tailored managements. TRIAL REGISTRATION: Not applicable.

An MRI Study of Morphology, Asymmetry, and Sex Differences of Inferior Precentral Sulcus.

Numerous studies utilizing magnetic resonance imaging (MRI) have observed sex and interhemispheric disparities in sulcal morphology, which could potentially underpin certain functional disparities in the human brain. Most of the existing research examines the precentral sulcus comprehensively, with a rare focus on its subsections. To explore the morphology, asymmetry, and sex disparities within the inferior precentral sulcus (IPCS), we acquired 3.0T magnetic resonance images from 92 right-handed Chinese adolescents. Brainvisa was used to reconstruct the IPCS structure and calculate its mean depth (MD). Based on the morphological patterns of IPCS, it was categorized into five distinct types. Additionally, we analyzed four different types of spatial relationships between IPCS and inferior frontal sulcus (IFS). There was a statistically significant sex disparity in the MD of IPCS, primarily observed in the right hemisphere. Females exhibited significantly greater asymmetry in the MD of IPCS compared to males. No statistically significant sex or hemispheric variations were identified in sulcal patterns. Our findings expand the comprehension of inconsistencies in sulcal structure, while also delivering an anatomical foundation for the study of related regions' function.

Sex disparities in global burden of gallbladder and biliary tract cancer: analysis of Global Burden of Disease study from 2010 to 2019.

BACKGROUND AND AIM: The global burden of gallbladder and biliary tract cancer (GBTC) has been on the rise, making it a major public health concern. We aim to comprehensively analyze sex disparities in the temporal trends of GBTC incidence, mortality, and disability-adjusted life years (DALYs) regionally and globally from 2010 to 2019. METHODS: Age-standardized rates of GBTC incidence, death, and DALYs were analyzed utilizing the Global Burden of Disease study 2019. RESULTS: From 2010 to 2019, the estimated annual percent change (APC) of the age-standardized incidence rates (ASIRs) and age-standardized disability-adjusted life years (ASDALYs) due to GBTC globally decreased in both sexes (males, APC: -0.80%; APC: -1.00%) and (females, APC: -0.89%; APC: -0.96%). At the same time, age-standardized death rates (ASDRs) decreased only in males (APC: -0.82%) and remained stable in females. By regions, ASIRs and ASDR increased in both sexes only in Southeast Asia (SEA) but decreased in the other regions. All regions had decreased ASDALYs except for an increase in ASDALYs for females only in the SEA region (APC: 0.41%), and males have a stable trend. CONCLUSIONS: Our study reveals substantial geographic variance in the burden of GBTC, specifically in the SEA region. Therefore, localized interventional methodologies must be undertaken to effectively address this global burden from GBTC.

Australian males and females have similar rates of presentation for symptomatic and advanced thyroid cancer: Retrospective analysis of the Australian New Zealand Thyroid Cancer Registry.

INTRODUCTION: Thyroid cancer is more commonly diagnosed in females, however recent research has challenged whether this finding is due to a true difference in biology or rates of diagnosis, with concerns that over-diagnosis may be a factor in differences. The rates of symptomatic versus incidental diagnosis by males and females is not well known. This study used the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) to explore whether symptomatic presentation varies between sexes. MATERIALS AND METHODS: Retrospective analysis on ANZTCR data between 2017 and 2022 was performed. Symptomatic cases were those with thyroid compressing symptoms, toxic goiter, Graves' disease, or abnormal laryngoscopy. Cases with asymptomatic goiter or surgeries for a thyroid nodule were classified as incidental. RESULTS: Among 1082 patients with differentiated thyroid cancer, 32% of males and 38% of females presented with symptomatic thyroid disease (p = 0.06). A similar rate of presentation of advanced thyroid cancer (T3/4) was seen with male and female patients (n = 70, 47% vs. n = 79, 53%). Females exhibited a higher prevalence of low-risk relapse cancers according to American Thyroid Association stratification (66.3% vs. 50.4%), whereas males exhibited a higher prevalence of high-risk relapse cancers compared to females (27.3% vs. 15.3%, p < 0.001). Regression showed symptoms were associated with more advanced T stage (OR = 1.62, p = 0.02). DISCUSSION: Symptomatic presentation was similar between males and females, but symptomatic presentation was associated with larger cancers. CONCLUSION: This study highlights comparable rates of symptomatic detection between males and females with DTCs and symptomatic presentations were responsible for less than 40% of presentations.

Association between physical activity and cardiovascular parameters in 7-year-old children: a Chinese cross-sectional study.

INTRODUCTION: Physical activity (PA) is believed to play an important part in many aspects during childhood and adolescence, especially cardiorespiratory fitness and cardiometabolic health. However, whether different levels of PA in daily life influence the structure or function of heart in school-aged children remains unknown. We aimed to investigate the association between PA and cardiovascular parameters in 7-year-old children. METHODS: Follow-up data from the Shanghai Prenatal Cohort Study and the Shanghai Birth Cohort was analyzed. Perinatal information including both maternal and offspring datum was recorded. A refined questionnaire was used to evaluate the frequency and duration of children's PA levels. Blood pressure, echocardiography, and anthropometry assessment were conducted during the follow-up of 7-year-old children. RESULTS: Overall, high PA level was associated with higher left ventricle posterior wall thickness in diastole (LVPWd, ß coefficient: 0.36, 95% CI: 0.12, 0.61), higher left ventricle mass index (LVMI, ß = 0.28, 95% CI: 0.07, 0.48), mitral E/a ratio (ß = 0.47, 95% CI: 0.22, 0.71) and slower heart rate (ß = -0.32, 95% CI: -0.57, -0.07), compared to low PA level. Medium PA level was associated with lower diastolic blood pressure (DBP, ß = -0.18, 95% CI: -0.35, -0.01). In subgroup analysis, increased relative wall thickness (RWT) was found in high PA level boys (ß = 0.36, 95% CI: 0.05, 0.67), and systolic blood pressure (SBP) showed a significant decrease in high PA level girls (ß = -0.42, 95% CI: -0.78, -0.06). CONCLUSIONS: This study suggested non-athlete children having higher PA level were associated with thicker left ventricle (LV) walls and better LV diastolic function, as well as slower heart rate and DBP at the age of 7. Furthermore, disparity in the association between PA level with morphological heart patterns and blood pressure existed in different sex category.

Trend and heterogeneity in forced vital capacity among Chinese students during 1985-2019: results from Chinese National Survey on Students' Constitution and Health.

BACKGROUND: Forced vital capacity (FVC) reflects respiratory health, but the long-term trend and heterogeneity in FVC of Chinese students were understudied. METHODS: Data were from Chinese National Survey on Students' Constitution and Health 1985-2019. Super Imposition by Translation and Rotation model was used to draw FVC growth curves. Sex-, region-, and nationality-heterogeneity in FVC was evaluated. Spearman correlation and generalized additive model was used to reveal influencing factors for FVC. RESULTS: Compared to 1985, age at peak FVC velocity was 1.09, 3.17, 0.74, and 1.87 years earlier for urban male, urban female, rural male, and rural female in 2019, respectively. Peak FVC velocity first decreased and then increased during 1985-2019, only male rebounded to larger than 1985 level. FVC declined from 1985 to 2005 and then raised. Males consistently had higher FVC than females, with disparities increasing in the 13-15 age group. Urban students also had higher FVC than rural students. In 2019, FVC difference between 30 Chinese provinces and the national average showed four scenarios: consistently above national average; less than national average until age 18, then above; greater than national average until age 18, then this advantage reversed; less than national average in almost all the age. Most Chinese ethnic minority students had lower FVC levels compared to Han students. Spearman correlation and generalized additive model showed that age, sex, and height were the leading influencing factors of FVC, followed by socioeconomic and environmental factors. CONCLUSIONS: Chinese students experienced advanced FVC spurt, and there was sex-, region- and nationality-heterogeneity in FVC. Routine measurement of FVC is necessary in less developed areas of China.

Sex-differences in the association of interleukin-10 and interleukin-12 variants with the progression of hepatitis B virus infection in Caucasians.

AIM: Interleukin (IL)-10 and IL-12 contribute to immune responses against hepatitis B virus (HBV) infection. Polymorphisms in the IL-10 and IL-12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL-10 rs1800896 and rs3024490, and IL-12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population. METHOD: A total of 636 white European patients with chronic HBV infection, 239 individuals with spontaneous HBV surface antigen seroclearance, and 254 healthy controls were enrolled. The chronic HBV infection group included patients with hepatitis B envelope antigen (HBeAg) negative chronic hepatitis B (n = 255), with HBeAg positive chronic hepatitis B (n = 99) and with HBeAg negative HBV infection (n = 228). A total of 104 chronically infected patients were diagnosed with liver cirrhosis. Serum levels of cytokines were measured in patients with HBV infection (n = 195) and in healthy controls (n = 160). RESULTS: In adjusted multivariate analysis, the IL-10 rs1800896 AG/GG genotypes were significantly associated with an increased probability of HBV surface antigen seroclearance (OR = 1.75, 95% CI 1.04-2.94, p = 0.034), with an increased likelihood of HBeAg negative chronic infection (OR = 1.93, 95% CI 1.05-3.54, p = 0.034) and with increased serum cytokines levels in female patients. In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis, with an OR of 1.90 (95% CI 1.07-3.39, p = 0.029) in male patients. CONCLUSION: The current study shows a sex-related association of the IL-10 single-nucleotide polymorphism rs1800896 and IL-12A single-nucleotide polymorphism rs568408 with different stages of HBV infection and with HBV-related liver cirrhosis in white European patients.

Sex-disparities in chest pain workup: a retrospective cohort review of a university based clinical decision pathway.

BACKGROUND: Females have historically lower rates of cardiovascular testing when compared to males. Clinical decision pathways (CDP) that utilize standardized risk-stratification methods may balance this disparity. We sought to determine whether clinical decision pathways could minimize sex-based differences in the non-invasive workup of chest pain in the emergency department (ED). Moreover, we evaluated whether the HEART score would minimize sex-based differences in risk-stratification. METHODS: We conducted a retrospective cohort review of adult ED encounters for chest pain where CDP was employed. Primary outcome was any occurrence of non-invasive imaging (coronary CTA, stress imaging), invasive testing, intervention (PCI or CABG), or death. Secondary outcomes were 30-day major adverse cardiac events (MACE). We stratified HEART scores and primary/secondary outcomes by sex. RESULTS: A total of 1078 charts met criteria for review. Mean age at presentation was 59 years. Females represented 47% of the population. Low, intermediate, and high-risk patients as determined by the HEART score were 17%, 65%, and 18% of the population, respectively, without any significant differences between males and females. Non-invasive testing was similar between males and females when stratified by risk. Males categorized as high risk underwent more coronary angiogram (33% vs. 16%, p = 0.01) and PCI (18% vs. 8%, p = 0.04) than high risk females, but this was not seen in patients categorized as low or intermediate risk. Males experienced more MACE than females (8% vs. 3%, p = 0.001). CONCLUSIONS: We identified no sex-based differences in risk-stratification or non-invasive testing when the CDP was used. High risk males, however, underwent more coronary angiogram and PCI than high risk females, and consequently males experienced more overall MACE than females. This disparity may be explained by sex-based differences in the pathophysiology driving each patient's presentation.

Pediatric males receiving hematopoietic stem cell transplant lose their male disadvantage in disease risk after the procedure: A retrospective observational study.

Sex differences play a relevant role in cancer susceptibility, incidence and survival. Exploring such differences is difficult because of the close interplay of genetic, epigenetic and hormonal factors. However, a better understanding of the role of such disparities in cancer mechanisms could improve its prevention and therapy. Our study explores how sex differences in pediatric outcomes vary after undergoing first and advanced-line therapy for hematological malignancies. The primary goal was to evaluate if sex differences in pediatric outcomes after first-line therapy persist after allogeneic hematopoietic stem cell transplantation (HSCT). The secondary goal was to analyze sex differences in disease risk at onset and pediatric outcomes after first-line therapy to compare our results with the literature's reported results. Among a total of 485 patients (280 males, 205 females) admitted for hematological malignancies, disease risk at the onset was significantly higher in males (P < .05). One hundred and seventy-four patients (111 males and 63 females) had a high-risk disease requiring HSCT. Before HSCT, all patients underwent myeloablative conditioning, which substantially impaired gonadal function. Although the number of boys undergoing HSCT was almost double that of girls, there were no sex-related differences in overall survival, cancer relapse and complications after HSCT exposure (P > .05). These findings suggest that the existing sex differences in cancer risk ab initio can be somehow flattened by a conditioning regimen, shedding new light on the role of hormonal factors in cancer mechanism and management.

Female sex portends increased risk of major amputation following surgical repair of symptomatic popliteal artery aneurysms.

OBJECTIVE: Popliteal artery aneurysms (PAAs) are rare in women, with only ∼5% of all PAAs occurring in women. The aim of the present study was to investigate whether sex disparities exist for patients treated with open PAA repair. METHODS: We reviewed all patients with PAAs who had undergone open PAA repair in the Vascular Quality Initiative from January 2010 to July 2021. Univariate analyses and multivariable logistic or Cox regression analyses controlling for potential confounders were performed. The study outcomes included primary patency, major amputation, overall survival, and amputation-free survival at 1 year. RESULTS: The study included 3807 adult patients, of whom 160 were women (4.2%). The female patients were younger (age, 66.1 years vs 68.3 years; P = .012) and less likely to have coronary artery disease (14.5% vs 23.4%; P = .009). However, the women were more likely to be taking aspirin (69.2% vs 60.4%; P = .019) and statins (67.8% vs 60.4%; P < .001) and to undergo repair for symptomatic disease (77.5% vs 64.1%; P = .001). No difference was found between the women and men in primary patency (95.2% vs 90.8%; P = .230) and overall survival (94.3% vs 96.1%; P = .270). Amputation-free survival was lower for women than for men (91.4% vs 95.3%; P = .033). This finding resulted from by lower freedom from major amputation for women (96.1% vs 98.9%; P = .010). After adjustment for confounders, no differences were found between the women and men regarding the loss of primary patency and all-cause mortality. For symptomatic PAAs, the risk of major amputation was threefold greater for women (adjusted hazard ratio, 3.09; 95% confidence interval, 1.05-9.06; P = .040), and the risk of the composite end point of major amputation or death was twofold higher for women than for men (adjusted hazard ratio, 1.97; 95% confidence interval, 1.02-3.79; P = .043). CONCLUSIONS: In our large national study of patients with PAAs, women were more likely to be treated for symptomatic PAAs. The risk of 1-year major amputation was threefold greater for women with symptomatic PAAs than for men with a similar presentation. Early recognition and treatment of PAAs in women before the PAAs have become symptomatic could optimize limb salvage outcomes in women.

Prevalence of abdominal aortic aneurysms in patients with lung cancer.

OBJECTIVE: Concomitance of abdominal aortic aneurysm (AAA) and primary lung cancer (LC) is not uncommon due to several shared risk factors. To evaluate the incidence of this association, analysis of the National Inpatient Sample database was utilized. METHODS: A retrospective analysis of the National Inpatient Sample database between 2014 and 2018 for all patients diagnosed with primary LC was performed. The differences in the reported findings between the LC and control groups were assessed using the Pearson χ2, Fisher exact, Student t, and/or Mann-Whitney U tests where appropriate. Multivariable logistic regression analysis was conducted to determine independent predictors of the presence of documented AAA. RESULTS: A total of 158,904 patients were identified. Of these, 2430 patients (1.53%) were diagnosed with AAA and 156,474 (98.47%) without AAA. In the multivariable model, LC patients had higher odds of AAA compared with the general population (odds ratio, 1.43; 95% confidence interval, 1.35-1.51). In all age groups, female smokers had a higher rate of AAA compared with female nonsmokers (age <60 years, 0.13% vs 0.04%; 60-69 years, 0.77% vs 0.34%; 70-79 years, 1.65% vs 0.69%; and >80 years, 2.63% vs 1.31%; all P < .001). CONCLUSIONS: LC and AAA share similar risk factors, which may explain the higher AAA prevalence among patients with LC. Given the higher prevalence of AAA in smokers compared with nonsmokers across all age groups in both male and female patients with LC, further sex-based studies investigating the overall mortality and morbidity benefits of AAA screening among patients with LC are highly warranted. This consideration would potentially address the sex disparity in outcomes for AAA management.

Association of severity and mortality of Covid-19 cases among acute kidney injury and sexual dimorphism.

INTRODUCTION: The outbreak of coronavirus disease 2019 (Covid-19) severely impacted global health and economic status. The native receptor-ligand interaction of Angiotensin-converting enzyme 2 (ACE2) and S protein induces host cell pathogenesis via immunosuppression. MATERIAL AND METHODS: The emerging evidence reports the sex disparity in Covid-19 induced mortality rate which affects abundantly men population. Although the biological interaction of Covid-19 with receptor upregulates the viral genome protein interactions and initiates the predictive multiorgan failure followed by acute kidney injury (AKI) in Covid-19 infected male population. CONCLUSION: Besides, the knowledge and lessons learned from the study depict that cellular and molecular links may explain the risk and severity of Covid-19 and AKI in the male population and lead to management of Covid-19 induced AKI. Therefore, this review explored the pathways associated with the pathogenesis of two diseased conditions with sex disparity.

Sex-Specific Associations Between Diabetes Mellitus and Hearing Loss in the Middle-Aged and Elderly Individuals: A National Cohort Study of Chinese Adults.

OBJECTIVE: To examine the association between diabetes and hearing loss and whether the association varied by sex. METHODS: This cohort study based on nationally representative data from the China Health and Retirement Longitudinal Study included 16 140 Chinese adults aged >45 years between 2011 and 2018. Diabetes was identified by blood glucose levels, HbA1c levels, and a self-reported diagnosis at baseline. The main outcome was self-reported incident hearing loss. Cox proportional hazards regression models were performed to estimate the risk of hearing loss. RESULTS: We documented 2388 cases of hearing loss during a median 6.9 years of follow-up. The incidence rates were 29.64 (95% CI, 28.07-31.29) per 1000 person-years in women and 25.23 (95% CI, 23.77-26.78) per 1000 person-years in men. After adjustment, the hazard ratios of hearing loss associated with diabetes were 1.20 (95% CI, 1.01-1.42) for women and 0.97 (95% CI, 0.78-1.19) for men. Compared with poor control of the blood sugar levels, the odds ratio for hearing loss for women with good glycemic control was reduced from 5.08 (95% CI, 1.31-19.66) to 1.26 (95% CI, 0.69-2.28), and the corresponding odds ratio for men was 1.65 (95% CI, 0.61-4.44) to 0.50 (95% CI, 0.18-1.38). CONCLUSION: In conclusion, we identified a differential effect of sex on hearing loss risk with more pronounced effects for women. Our data suggest that good blood glucose level control is helpful to prevent hearing loss.