Association of TP53 Mutation Status and Sex with Clinical Outcome in NSCLC Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non-small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of TCGA and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in disease control rate per the TP53 mutation status (p=0.503); however, female patients with TP53 mutated (MT) had a significantly prolonged median progression-free survival (PFS) compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). PD-L1 high (≥50%) expression was significantly enriched in female patients with TP53 MT (p=0.001). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p<0.001). In TCGA analysis, expression of immune-related genes, and TMB score in TP53 MT females were higher than in males without TP53 MT. Conclusion: Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Deciphering the Sex gap in global life expectancy: the impact of female-specific cancers 1990-2019.

BACKGROUND: Females live longer than males, which results in a sex gap in life expectancy. This study examines the contribution of female cancers to this differential by world region and country 1990-2019 with special focus to the 15-69 age group. METHODS: Cause-specific mortality data for 30 cancers, including four female-specific cancers from 238 countries and territories was retrieved from the Global Burden of Disease Study 2019. Using life table techniques and demographic decomposition analysis, we estimated the contribution of cancer deaths to the sex gap in life expectancy by age and calendar period. RESULTS: At ages 15-69, females had a higher life expectancy than males in 2019. Countries with the largest sex gaps or the largest female advantage in life expectancy were in Eastern Europe and Northern Asia, Latin America and Southern Africa. In contrast, countries with the smallest sex gaps were mainly located in Northern Africa, Northern America, and Northern Europe. The contribution of female-specific cancers to sex gaps in life expectancy were largely negative, ranging from -0.15 years in the Western Pacific to -0.26 years in the Eastern Mediterranean Region, implying that the disproportionately higher premature cancer mortality among females contributed to a reduction in the female life expectancy advantage. CONCLUSION: Female-specific cancers are important determinants of sex gaps in life expectancy. Their negative impact on life expectancy at working and reproductive age groups has far-reaching consequences for society. Increasing the availability and access to prevention, screening, timely diagnosis, and effective treatment can reduce this gap.

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.

A Review of the Role of Estrogens in Olfaction, Sleep and Glymphatic Functionality in Relation to Sex Disparity in Alzheimer's Disease.

Several risk factors contribute to the development of Alzheimer's disease (AD), including genetics, metabolic health, cardiovascular history, and diet. It has been observed that women appear to face a higher risk of developing AD. Among the various hypotheses surrounding the gender disparity in AD, one pertains to the potential neuroprotective properties of estrogen. Compared to men, women are believed to be more susceptible to neuropathology due to the significant decline in circulating estrogen levels following menopause. Studies have shown, however, that estrogen replacement therapies in post-menopausal women do not consistently reduce the risk of AD. While menopause and estrogen levels are potential factors in the elevated incidence rates of AD among women, this review highlights the possible roles estrogen has in other pathways that may also contribute to the sex disparity observed in AD such as olfaction, sleep, and glymphatic functionality.

Study of sex-biased differences in genomic profiles in East Asian hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is characterized by a notable sex disparity in incidence and tumor aggressiveness. Revealing differences in genetic landscapes between male and female HCCs may expand the understanding of sexual disparities mechanisms and assist the development of precision medicine. Although reports on the sex disparity of HCC are accumulated, studies focusing on sex-related biomarkers among Asian populations remain limited. Here, we conducted a comprehensive genomic profiling analysis to explore differences between male and female patients within a cohort of 195 Taiwanese HCC patients. We did not detect any sex-biased genomic alterations. However, when our investigation extended to the TCGA dataset, we found higher frequencies of gene copy gains in CCNE2 and mutations in CTNNB1 and TP53 among male patients. Besides, we further evaluated the associations between genomic alterations and patients' prognosis by sex. The results showed that female patients harboring tumors with STAT3 gain and alterations in the JAK-STAT pathway displayed a poor prognosis. These two factors remained independently associated with unfavorable prognosis even after adjusting for the patient's age and stage characteristics (Hazard ratio = 10.434, 95% CI 3.331-32.677, P < 0.001; Hazard ratio = 2.547, 95% CI 1.195-5.432, P = 0.016, respectively). In summary, this study provides valuable insights into understanding sex disparity in HCC in the East Asian population. Validation through larger cohorts and extensive sequencing efforts is warranted.

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.

Sex differences in the plasma glucagon responses to a high carbohydrate meal and a glucose drink in type 2 diabetes.

Elevated fasting glucagon concentrations and/or attenuated postprandial glucagon suppression are characteristics of type 2 diabetes (T2D) and contribute to hyperglycaemia. This study shows that hyperglucagonaemia is more prominent in males than females after a nutrient load in T2D, adding insights into sex differences in relation to the pathophysiology of 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.

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 Disparity in the Association of Metabolic Syndrome with Cognitive Impairment.

Background/Objectives: Metabolic syndrome (MS) is a constellation of several cardiometabolic risk factors. We investigated sex disparity in the associations between MS and cognitive impairment using cross-sectional data from Taiwan Biobank. Methods: We determined the associations of MS and its five components with cognitive impairment (mini-mental state examination, MMSE < 24) and the five domains of MMSE using logistic regression analyses. Results: A total of 7399 men and 11,546 women were included, and MS was significantly associated with cognitive impairment only in women (adjusted OR 1.48, 95% CI 1.29-1.71, p = 0.001) (p for interaction 0.005). In women, the association with MS was significant in orientation (adjusted OR 1.21, 95% CI 1.07-1.37, p = 0.003), memory (adjusted OR 1.12, 95% CI 1.01-1.25, p = 0.034) and design copying (adjusted OR 1.41, 95% CI 1.23-1.62, p = 0.001) (p value for interaction 0.039, 0.023, and 0.093, respectively). Among the components of MS, a large waist circumference (adjusted OR 1.25, 95% CI 1.08-1.46, p = 0.003), high fasting glucose (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.046), and low HDL cholesterol (adjusted OR 1.16, 95% CI 1.00-1.34, p = 0.049) were significantly associated with cognitive impairment in women. Conclusions: Our findings suggest that sex has a significant influence on the association between MS and cognitive dysfunction, especially in orientation and memory.

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.

The Disproportionate Rise in Pancreatic Cancer in Younger Women Is Due to a Rise in Adenocarcinoma and Not Neuroendocrine Tumors: A Nationwide Time-Trend Analysis Using 2001-2018 United States Cancer Statistics Databases.

In previous studies, a significant increase in the incidence of pancreatic cancer among younger women compared to men in the United States was noted. However, the specific histopathologic characteristics were not delineated. This population-based study aimed to assess whether this disproportionate rise in pancreatic cancer in younger women was contributed by pancreatic ductal adenocarcinoma (PDAC) or pancreatic neuroendocrine tumors (PanNET). The United States Cancer Statistics (USCS) database was used to identify patients with pancreatic cancer between 2001 and 2018. The results showed that, in younger adults, the incidence of PDAC has increased in women [average annual percentage change (AAPC) = 0.62%], while it has remained stable in men (AAPC = -0.09%). The PDAC incidence rate among women increased at a greater rate compared to men with a statistically significant difference in AAPC (p < 0.001), with neither identical nor parallel trends. In contrast, cases of PanNET did not demonstrate a statistically significant sex-specific AAPC difference. In conclusion, this study demonstrated that the dramatic increase in the incidence rate of PDAC explains the disproportionate rise in pancreatic cancer incidence in younger women. This prompts further prospective studies to investigate the underlying reasons for these sex-specific disparities in PDAC.

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.

Association between sex and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis.

Aim: To explore the association between sex and immune checkpoint inhibitors (ICIs). Materials & methods: We assessed the difference in survival outcomes from ICIs between sexes using an interaction test. Results: 108 studies representing 70,243 patients were included. In the first-line setting, the pooled interaction HR was 0.97 (95% CI: 0.91-1.04). In the subsequent-line setting, the pooled interaction HR was 0.85 (95% CI: 0.77-0.95). When ICIs were given as perioperative therapy or as systemic therapy in patients with positive PD-L1 expression, both men and women obtained equal survival benefits. Conclusion: Both sex, line of therapy, cancer (sub)type and PD-L1 status should be taken into account in the assessment of risk versus benefit when deciding to offer ICIs to patients.

There are many differences between men and women, and whether these differences also affect the efficacy of immune checkpoint inhibitors is important because immune checkpoint inhibitors have been widely accepted as standardized treatments for patients with malignant tumors. Previous studies have reported conflicting results. This research was conducted to reassess this sex disparity with additional available reports. We found that both men and women can benefit from immune checkpoint inhibitors, while sex should be taken into account when deciding to offer immune checkpoint inhibitors to patients who have already been heavily treated.

Sex Bias in Treatment Abandonment of Childhood Cancer in India.

OBJECTIVES: To explore the magnitude of sex bias and determinants of treatment abandonment (TA) in childhood cancer in India. METHODS: Individual data of children (0-19 y) registered between January 1, 2017 and July 31, 2022, was compiled. TA was defined as defaulting curative intent treatment ≥4 wk. Defaulting treatment irrespective of intent ≥4 wk was defined as Treatment Default (TD). The primary outcome was the proportion of male-to-female children with TA. Secondary outcomes included the proportion of male-to-female children with upfront TA, TA at relapse, TD, TD-p (TD only in the palliative setting). The impact of clinico-demographic factors on TA was analysed using multivariable regression and propensity score matching (PSM). RESULTS: Three thousand two hundred eighty four patients were analysed. The overall male-to-female ratio (MFR) was 2.08 (95% CI 1.94-2.24). Of 2906 patients treated with curative intent, 415 (14·3%) abandoned treatment. TA was higher in females than males (16·4% vs. 13·3%; p = 0·022) with adjusted MFR of 0·81 (0·66-0·98). The adjusted MFR of TA for treatment-naïve and relapsed patients and TD were 0·73 (0·59-0·91), 1·13 (0·65-1·96) and 0·84 (0·71-1·00) respectively. Sex independently predicted TA on multivariable analysis. However, on PSM analysis including socio-economic variables, lower maternal education predicted higher TA in children with cancer (10·1% vs. 6%, p = 0·015). CONCLUSIONS: Child sex predicted TA in childhood cancer in India with more females abandoning treatment. Maternal education is a more crucial factor predicting TA over child sex, when socio-economic factors were considered. Hence, policies promoting female education and gender equality may mitigate sex-based gaps in childhood cancer care.

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.

Sexual dimorphism in medullary thyroid cancer aggressiveness.

Thyroid cancer is the only nonreproductive cancer with striking female predominance, although men with thyroid cancer develop more aggressive disease. This study aimed to quantify sex-specific differences in medullary thyroid cancer (MTC) spread after controlling for primary thyroid tumor size. Included in this retrospective analysis were all patients with unilateral solitary MTC who underwent initial neck surgery at a tertiary referral center. A total of 565 patients, 255 men and 310 women, were identified, of whom 467 had sporadic and 98 hereditary MTC. When stratified by sex, and after correction for multiple testing, men had higher preoperative basal calcitonin levels (medians of 655 vs 181 pg/mL; P < 0.001), more frequent extrathyroid extension (25 vs 9%; P < 0.001) and node metastasis (53 vs 27%; P < 0.001) with more involved nodes (medians of 2 vs 0 nodes; P < 0.001) than women but achieved less often biochemical cure (53 vs 74%; P < 0.001). Although absent in patients with very small (≤5 mm) thyroid tumors, sex disparities were immediately apparent in patients with 5.1-40 mm (node metastasis and biochemical cure) and 10.1-40 mm (extrathyroid extension) large thyroid tumors but were lost in patients with thyroid tumors >40 mm as women caught up. Sex disparities were strongest for node metastasis with a 27-41% (overall 24.0%) point difference, followed by biochemical cure with a -15-35% (overall -20.3%) point difference and extrathyroid extension with a 17-24% (14.2% overall) point difference. These findings indicate that the male predominance in MTC aggressiveness is largely biologically driven, warranting further research.

Sex-specific disparities in COVID-19 outcomes.

Objectives: Sex-specific disparities in morbidity and mortality of COVID-19 illness are not well understood. Neutralizing antibodies (Ab) may protect against severe COVID-19 illness. We investigated the association of sex with disease progression and SARS-CoV-2 Ab response. Methods: In this exploratory analysis of the phase 3, multicenter, randomized, placebo-controlled Convalescent Plasma in Outpatients (C3PO) trial, we examined whether sex was associated with progression to severe illness, defined as a composite of all-cause hospitalization, emergency/urgent care visit, or death within 15 days from study enrollment. Patients had a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test, symptom onset within 7 days, stable condition for emergency department discharge, and were either ≥50 years old or had at least one high-risk feature for disease progression. Patients received blinded convalescent plasma or placebo in a 1:1 fashion and were evaluated on days 15 and 30 after infusion. Blood samples were collected on day 0 (pre-/post-infusion), 15, and 30 to measure Ab levels with the Broad Institute using the Plaque Reduction Neutralization Test assay. Results: Of 511 patients enrolled (median age 54 [Iinterquartile range 41-62] years, 46% male, 66% white, 20% black, 3.5% Asian), disease progression occurred in 36.7% of males and 25.9% of females (unadjusted risk difference 10.8%, 95% confidence interval [CI], 2.8-18.8%). Sex-disparities did not persist when adjusted for treatment group, age, viremic status, symptom onset, and tobacco use (adjusted risk difference 5.6%, 95% confidence interval [CI], -2.2% to 13.4%), but were present in the subgroup presenting 3 or more days after symptom onset (adjusted risk difference 12.6%, 95% CI, 3.4% to 21.9%). Mean baseline Ab levels (log scale) available for 367 patients were similar between sexes (difference 0.19 log units, 95% CI, -0.08 to 0.46). The log-scale mean increase from baseline to day 15 after adjusting for treatment assignment and baseline levels was larger in males than females (3.26 vs. 2.67). A similar difference was noted when the groups were subdivided by outcome. Conclusions: Progression of COVID-19 was similar in males and females when adjusted for age, tobacco use, and viremia status in this study. However, in the cohort presenting 3 or more days after symptom onset, COVID-19 outcomes were worse in males than females. Neutralizing Ab levels increased more in males but did not correlate with sex differences in outcomes.

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.

Sex disparities in adverse outcomes after surgically managed isolated traumatic spinal injury.

BACKGROUND: Traumatic spinal injury (TSI) encompasses a wide range of injuries affecting the spinal cord, nerve roots, bones, and soft tissues that result in pain, impaired mobility, paralysis, and death. There is some evidence suggesting that women may have different physiological responses to traumatic injury compared to men; therefore, this study aimed to investigate if there are any associations between sex and adverse outcomes following surgically managed isolated TSI. METHODS: Using the 2013-2019 TQIP database, all adult patients with isolated TSI, defined as a spine AIS ≥ 2 with an AIS ≤ 1 in all other body regions, resulting from blunt force trauma requiring spinal surgery, were eligible for inclusion in the study. The association between the sex and in-hospital mortality as well as cardiopulmonary and venothromboembolic complications was determined by calculating the risk ratio (RR) after adjusting for potential confounding using inverse probability weighting. RESULTS: A total of 43,756 patients were included. After adjusting for potential confounders, female sex was associated with a 37% lower risk of in-hospital mortality [adjusted RR (95% CI): 0.63 (0.57-0.69), p < 0.001], a 27% lower risk of myocardial infarction [adjusted RR (95% CI): 0.73 (0.56-0.95), p = 0.021], a 37% lower risk of cardiac arrest [adjusted RR (95% CI): 0.63 (0.55-0.72), p < 0.001], a 34% lower risk of deep vein thrombosis [adjusted RR (95% CI): 0.66 (0.59-0.74), p < 0.001], a 45% lower risk of pulmonary embolism [adjusted RR (95% CI): 0.55 (0.46-0.65), p < 0.001], a 36% lower risk of acute respiratory distress syndrome [adjusted RR (95% CI): 0.64 (0.54-0.76), p < 0.001], a 34% lower risk of pneumonia [adjusted RR (95% CI): 0.66 (0.60-0.72), p < 0.001], and a 22% lower risk of surgical site infection [adjusted RR (95% CI): 0.78 (0.62-0.98), p < 0.032], compared to male sex. CONCLUSION: Female sex is associated with a significantly decreased risk of in-hospital mortality as well as cardiopulmonary and venothromboembolic complications following surgical management of traumatic spinal injuries. Further studies are needed to elucidate the cause of these differences.