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Incidence, molecular presentation and outcome of acute myeloid leukaemia (AML) are influenced by sex, but little attention has been directed at untangling sex‐related molecular and phenotypic differences between female and male patients. While increased incidence and poor risk are generally associated with a male phenotype, the poor prognostic FLT3 internal tandem duplication (FLT3‐ITD) mutation and co‐mutations with NPM1 and DNMT3A are overrepresented in female AML. Here, we have investigated the relationship between sex and FLT3‐ITD mutation status by comparing clinical data, mutational profiles, gene expression and ex vivo drug sensitivity in four cohorts: Beat AML, LAML‐TCGA and two independent HOVON/SAKK cohorts, comprising 1755 AML patients in total. We found prevalent sex‐associated molecular differences. Co‐occurrence of FLT3‐ITD, NPM1 and DNMT3A mutations was overrepresented in females, while males with FLT3‐ITDs were characterized by additional mutations in RNA splicing and epigenetic modifier genes. We observed diverging expression of multiple leukaemia‐associated genes as well as discrepant ex vivo drug responses, suggestive of discrete functional properties. Importantly, significant prognostication was observed only in female FLT3‐ITD‐mutated AML. Thus, we suggest optimization of FLT3‐ITD mutation status as a clinical tool in a sex‐adjusted manner and hypothesize that prognostication, prediction and development of therapeutic strategies in AML could be improved by including sex‐specific considerations., Internal tandem duplications (ITDs) in the FMS‐like tyrosine kinase 3 (FLT3) gene are linked to poor prognosis in acute myeloid leukaemia (AML). Here, we investigated sex‐related differences in mutation, gene expression and drug sensitivity profiles in FLT3‐ITD‐mutated AML. We demonstrated significant sex‐associated molecular and functional differences, and surprisingly identified significant prognostication related to FLT3‐ITD only in female AML patients.

Objective: To investigate the impact of menopausal status on the prognosis for sex-classified Hepatocellular carcinoma (HCC) and to establish prognostic nomograms for patients after liver resection. Results: After propensity score matching (PSM), statistically significant differences in both overall survival (OS) and recurrence-free survival (RFS) were found between men and women HCC patients. Based on Cox regression analysis, these differences were evident in the normal menstruation (N) group expanded with male patients, but not in either the expanded postmenopausal (P) or intermediate (I) groups. Sex disparity was also apparent in the recurrence-free survival (RFS) of the total HCC patients. Integrated with independent factors, nomograms for the OS and RFS of the expanded N group showed higher C-indices of 0.773 and 0.724, respectively, than those of nomograms for the total patients and BCLC stage (P

The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health issue which has profound effects on most aspects of societal well-being, including physical and mental health. A plethora of studies globally have suggested the existence of a sex disparity in the severity and outcome of COVID-19 patients, mainly due to mechanisms of virus infection, immune response to the virus, development of systemic inflammation, and consequent systemic complications, particularly thromboembolism. Epidemiological data report a sex difference in the severity of COVID-19, with a more favorable course of the disease in women compared to men regardless of age, although the rate of SARS-CoV-2 infection seems to be similar in both sexes. Sex hormones, including androgens and estrogens, may not only impact virus entry and load, but also shape the clinical manifestations, complications, and ultimately the outcome of the disease. The current review comprehensively summarizes the current literature on sex disparities in susceptibility and outcome of COVID-19 as well as the literature underpinning the pathophysiological and molecular mechanisms, which may provide a rationale to a sex disparity. These mechanisms include sex hormone influence on factors that facilitate virus entry and priming, immune and inflammatory response, as well as coagulation and thrombosis diathesis. Based on present evidence, women appear to be relatively protected from COVID-19 because of a more effective immune response and a less pronounced systemic inflammation, with consequent moderate clinical manifestations of the disease, together with a lesser predisposition to thromboembolism. Conversely, men appear to be particularly susceptible to COVID-19 because of a less effective immune response with consequent severe clinical manifestations of the disease, together with a greater predisposition to thromboembolism. In the elderly, generally characterized by the phenomenon of inflammaging, sex disparities in overall mortality following SARS-CoV-2 infection are even more palpable as elderly men appear to be more prone to severe COVID-19 because of a greater predisposition to infections, a weaker immune defense, and an enhanced thrombotic state compared to women. The information revealed from the review highlights potential novel therapeutic approaches employing the administration of hormonal or antihormonal therapy in combination with antiviral drugs in COVID-19 patients.

BACKGROUND AND PURPOSE Unexpected stressful life events may alter immune function and affect susceptibility to autoimmune diseases including multiple sclerosis (MS). Current results from epidemiological investigations examining the role of stress in MS remain inconsistent. The aim was to conduct the hitherto largest population-based case-control study on this topic. METHODS Extensive questionnaire information collected on lifestyle environmental factors available for 2930 incident MS cases and 6170 controls were used to assess the association of 10 major life events that had occurred before disease onset with the risk of MS by unconditional logistic regressions, adjusting for potential confounders. Stratified analyses were also performed by sex and time. RESULTS Compelling evidence was found for a link between major life events and risk of MS - most events significantly increased disease risk by 17%-30%. It was further observed that women were affected to a greater extent than men under certain stressful scenarios, and that most events that happened recently (≤5 years prior to MS onset) had significant effects on MS, indicating a critical window in disease development. CONCLUSION Stressful life events may have an adverse effect on the risk of MS. Research into the mechanisms of this observation may give important clues to triggering pathogenetic events in MS.

Rationale: Men and postmenopausal women are more prone to developing non-alcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) than premenopausal women. However, the pathological links and underlying mechanisms of this disparity are still elusive. The sex-difference in hepatic very low-density lipoprotein (VLDL) assembly and secretion may contribute to NAFLD development. Estrogen-related receptor alpha (ERRα) is a key regulator of several metabolic processes. We hypothesized that ERRα plays a role contributing to the sex-difference in hepatic VLDL assembly and secretion. Methods: VLDL secretion and essential genes governing said process were assessed in male and female mice. Liver-specific ERRα-deficient (ERRαLKO) mice were generated to assess the rate of hepatic VLDL secretion and alteration in target gene expression. Overexpression of either microsomal triglyceride transfer protein (Mttp) or phospholipase A2 G12B (Pla2g12b) by adenovirus was performed to test if the fatty liver phenotype in male ERRαLKO mice was due to defects in hepatic VLDL secretion. Female ERRαLKO mice were put on a diet high in saturated fat, fructose and cholesterol (HFHC) to promote NASH development. Wild type female mice were either ovariectomized or treated with tamoxifen to induce a state of estrogen deficiency or disruption in estrogen signaling. Adenovirus was used to overexpress ERRα in these mice to test if ERRα was sufficient to rescue the suppressed VLDL secretion due to estrogen dysfunction. Finally, wild type male mice on a high-fat diet (HFD) were treated with an ERRα inverse agonist to assess if suppressing ERRα activity pharmacologically would lead to fatty liver development. Results: ERRα is an indispensable mediator modulating hepatic triglyceride-rich very low-density lipoprotein (VLDL-TG) assembly and secretion through coordinately controlling target genes apolipoprotein B (Apob), Mttp and Pla2g12b in a sex-different manner. Hepatic VLDL-TG secretion is blunted in ERRαLKO mice, leading to hepatosteatosis which exacerbates endoplasmic reticulum stress and inflammation paving ways for NASH development. Importantly, ERRα acts downstream of estrogen/ERα signaling in contributing to the sex-difference in hepatic VLDL secretion effecting hepatic lipid homeostasis. Conclusions: Our results highlight ERRα as a key mediator which contributes to the sex disparity in NAFLD development, suggesting that selectively restoring ERRα activity in the liver may be a novel strategy for treating NAFLD/NASH.

Background: Lifestyle contributors to frailty among the elderly were previously reported in the developed Western countries, while evidence from the less developed East Asian regions was still lacking. Due to the well-acknowledged sex-based disparity of frailty and sex-difference of socioeconomic status and lifestyle, it is worth investigating the sex-specific association between the social and behavioral contributors and the risk of frailty among the East Asian longevous population.Methods: The present study was an observational study based on the four waves of interviews of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008 to 2018. The participants aged ≥65 years and without frailty at baseline were included. Fried criteria (exhaustion, shrink, weakness, low mobility, and inactivity) were adopted to identify the incidence of frailty (≥3 domains) and pre-frailty (1–2 domains) during the follow-up. The sex-specific association between lifestyle (smoke status, drinking status, food intake, sleep, exercise, and physical activity) and the risk of incident pre-frailty and frailty was analyzed using the multinomial logistic regression models.Results: Altogether, 3,327 participants aged 81.2 ± 10.3 (range 65–116) years were included. In total, 964 (29.0%) and 1,249 (37.5%) participants were recognized as having incident pre-frailty and frailty, respectively. Older women were disproportionately uneducated, frequently did housework and labor work, but seldom did exercise. Men had diverse dietary and recreational activities but were frequently exposed to tobacco and alcohol. The protective effects of higher income, exercise, doing housework, and daily intake of fresh fruits/vegetables were found in both the sexes (P < 0.05). Sleep disorders (odds ratio [OR] = 2.16, 95% CI: 1.28–3.62) and labor work (OR = 2.18, 95% CI: 1.42–3.33) were associated with the increased risk of frailty among women. For men, diverse dietary (four types of food added: OR = 0.21, 95% CI: 0.09–0.50) showed a protective effect on the risk of frailty, but daily intake of pickled vegetables showed the opposite effect (OR = 1.86, 95% CI: 1.12–3.07).Conclusion: Socioeconomic status, lifestyle, and the association with the risk of frailty showed substantial difference between the sexes among the longevous population in China. To establish the individualized strategy of behavioral improvement for the frailty prevention should consider the sex disparity.

Various studies on oral anticoagulants (OAC) use among atrial fibrillation (AF) patients have shown high rates of undertreatment and the presence of sex disparity. This study used the ‘Geisinger Neuroscience Ischemic Stroke’ (GNSIS) database to examine sex differences in OAC treatment among ischemic stroke patients with the pre-event diagnosis of AF in rural Pennsylvania between 2004 and 2019. We examined sex disparities in OAC undertreatment and associated risks based on age group and ischemic stroke year. A total of 1062 patients were included in the study and 1015 patients (96%) had CHA2DS2-VASc score ≥ 2, of which 549 (54.1%) were women. Undertreatment rates were not statistically significant between men and women in the overall cohort (50.0% vs. 54.5%, p = 0.18), and male sex was not found to be a significant factor in undertreatment (OR 0.82, 95% CI 0.62–1.09, p = 0.17). The result persisted even when patients were divided into four age groups and two groups based on the study time period. The undertreatment rates in both sex groups remained consistent following the introduction of novel oral anticoagulants. In conclusion, there was no evidence of sex disparity with respect to OAC treatment, even after stratifying the cohort by age and ischemic stroke year.

Background Women remain relatively underrepresented in all subspecialties of academic medicine. While sex disparity is prevalent in a number of specialties, the association between academic productivity and sex in academic cardiology has not been assessed in the Canadian context. Methods Academic faculty of accredited Canadian Resident Matching Service (CaRMS) programs were included from cardiology division websites across 17 universities. Cardiology faculty members’ names, academic ranks, leadership positions, and sex were obtained from each institutions’ website. The Elsevier database Scopus© was used to extract the Hirsch index (H-index), years of active research, and number of publications of each faculty member. The H-index was used as a metric of academic output and research productivity. Univariate regression was run with the H-Index as the outcome of interest, and multiple linear regression analysis was used to determine factors associated with higher H-index. Results Sex was identified for 1,040 members, of whom 836 (80%) were male. Male members had higher numbers of publications (p

Simple Summary Primary liver cancer ranks amongst the top ten cancers in frequency and mortality, with its global prevalence continuing to increase. Chemotherapy response remains poor and many therapies result in adverse side effects. The use of transgenic animal models that have high disease reproducibility provides opportunities to study cancer events that are difficult to study in human patients. Other than well-established mouse models in cancer research, now there is an increasing interest in using zebrafish to model various cancers. This review summarises the various oncogene transgenic zebrafish models for hepatocellular carcinoma (HCC) our laboratory has established, and the subsequent findings about liver cancer biology by using these transgenic models. In particular, most of our transgenic models employed chemically induced oncogene expression, allowing for temporal control and study of tumour initiation and regression. Investigation into these models reveals activation of tumorigenic pathways, inflammation, male-bias severity and skeletal muscle-wasting, characteristic of human HCC. Some of the models are also useful in screening for novel anti-metastatic drugs and evaluating the tumorigenic ability of environmental toxicants. The findings presented here demonstrate the utility of the zebrafish models for the further investigation of cancer biology and the development of novel and improved therapies. Abstract Primary liver cancer is one of the most prevalent and deadly cancers, which incidence continues to increase while treatment response remains poor; thus, in-depth understanding of tumour events is necessary to develop more effective therapies. Animal models for liver cancer are powerful tools to reach this goal. Over the past decade, our laboratory has established multiple oncogene transgenic zebrafish lines that can be robustly induced to develop liver cancer. Histological, transcriptomic and molecular analyses validate the use of these transgenic zebrafish as experimental models for liver cancer. In this review, we provide a comprehensive summary of our findings with these inducible zebrafish liver cancer models in tumour initiation, oncogene addiction, tumour microenvironment, gender disparity, cancer cachexia, drug screening and others. Induced oncogene expression causes a rapid change of the tumour microenvironment such as inflammatory responses, increased vascularisation and rapid hepatic growth. In several models, histologically-proven carcinoma can be induced within one week of chemical inducer administration. Interestingly, the induced liver tumours show the ability to regress when the transgenic oncogene is suppressed by the withdrawal of the chemical inducer. Like human liver cancer, there is a strong bias of liver cancer severity in male zebrafish. After long-term tumour progression, liver cancer-bearing zebrafish also show symptoms of cancer cachexia such as muscle-wasting. In addition, the zebrafish models have been used to screen for anti-metastasis drugs as well as to evaluate environmental toxicants in carcinogenesis. These findings demonstrated that these inducible zebrafish liver cancer models provide rapid and convenient experimental tools for further investigation of fundamental cancer biology, with the potential for the discovery of new therapeutic approaches.

Methadone maintenance treatment (MMT) remains the cornerstone for the management of opiate abuse. However, MMT can be associated with complex factors, including complications during the tolerance phase, the inability of some patients to maintain treatment effects during the tapering or abstinence phases, and the development of methadone dependence. Previous studies have revealed a sex disparity in MMT efficacy, showing that women undergoing MMT experiencing an increase in psychological symptoms compared with men and suggesting a link between disparate responses and the effects of estrogen signaling on methadone metabolism. More specifically, estradiol levels are positively associated with MMT dosing, and the expression of a single-nucleotide polymorphism (SNP) associated with estrogen receptor (ER) regulation is also associated with MMT dosing. In addition to performing mechanistic dissections of estrogen signaling in the presence of methadone, past studies have also proposed the targeting of estrogen signaling during MMT. The present report provides an overview of the relevant literature regarding sex effects, including differences in sex hormones and their potential impacts on MMT regimens. Moreover, this article provides a pharmacological perspective on the targeting of estrogen signals through the use of selective ER modulators (SERMs) during MMT. Preliminary preclinical experiments were also performed to evaluate the potential effects of targeting estrogen signaling with tamoxifen on methadone metabolism.

Background Prior studies have shown that women have worse 3‐month survival after receiving a left ventricular assist device compared with men. Currently used prognostic scores, including the Heartmate II Risk Score, do not account for the increased residual risk in women. We used the IMACS (International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support) registry to create and validate a sex‐specific risk score for early mortality in left ventricular assist device recipients. Methods and Results Adult patients with a continuous‐flow LVAD from the IMACS registry were randomly divided into a derivation cohort (DC; n=9113; 21% female) and a validation cohort (VC; n=6074; 21% female). The IMACS Risk Score was developed in the DC to predict 3‐month mortality, from preoperative candidate predictors selected using the Akaike information criterion, or significant sex × variable interaction. In the DC, age, cardiogenic shock at implantation, body mass index, blood urea nitrogen, bilirubin, hemoglobin, albumin, platelet count, left ventricular end‐diastolic diameter, tricuspid regurgitation, dialysis, and major infection before implantation were retained as significant predictors of 3‐month mortality. There was significant ischemic heart failure × sex and platelet count × sex interaction. For each quartile increase in IMACS risk score, men (odds ratio [OR], 1.86; 95% CI, 1.74–2.00; P P P Conclusions A sex‐specific risk score provides excellent risk prediction in LVAD recipients.

There are many differences in cancer manifestation between men and women. New understanding of the origin of these point to fundamental distinctions in the genetic code and its demise. Tumour suppressor protein p53 is the chief operating officer of cancer defence and critically acts to safeguard against sustained DNA damaged. P53 cannot be ignored in cancer sex disparity. In this review we discuss the greater prevalence and associated death rates for non-reproductive cancers in males. The major tumour suppressor protein p53, encoded in the TP53 gene is our chosen context. It is fitting to ask why somatic TP53 mutation incidence is estimated to be disproportionately higher among males in the population for these types of cancers compared with females? We scrutinised the literature for evidence of predisposing genetic and epigenetic alterations that may explain this sex bias. Our second approach was to explore whether redox activity, either externally imposed or inherent to males and females, may define distinct risks that could contribute to the clear cancer sex disparities.

Medical academic research done in various specialties shows sex disparity in terms of academic and leadership rank. Research shows that in many medical academic research fields, there are a greater number of men with higher academic and leadership ranks, as well as higher research productivity. This begs the question: What is the case for medical academic research specifically in physiology departments throughout North America? Upon review of the literature, we found that a knowledge gap still exists in North America regarding sex differences among the faculty of physiology. Our rationale for this study is that if a sex disparity among the faculty of physiology in North American academia is found, steps can be taken to lower this disparity. The very first step is identifying that a problem exists. Scopus was used to obtain the h-index, years of active research, and the number of publications and citations of each faculty member. The h-index was used as a metric of academic output and scholarly productivity. Univariate regression was run with the h-index as the outcome of interest and multiple linear regression analysis was used to determine factors associated with a higher h-index. The analysis showed that while the overall number of females holding academic positions in physiology departments throughout North America has increased over the years, a large sex disparity still exists between males and females in the field. This disparity exists not only in academic and leadership rank but also in research productivity, a key predictor of success in the field. This finding warrants that further work be done to find what is causing this disparity and how it can be addressed.

Background: Several studies suggest women may be disproportionately affected by poorer stroke outcomes than men. This study aims to investigate whether women have a higher risk of all-cause mortality and recurrence after an ischemic stroke than men in a rural population in central Pennsylvania, United States. Methods: We analyzed consecutive ischemic stroke patients captured in the Geisinger NeuroScience Ischemic Stroke research database from 2004 to 2019. Kaplan–Meier (KM) estimator curves stratified by gender and age were used to plot survival probabilities and Cox Proportional Hazards Ratios were used to analyze outcomes of all-cause mortality and the composite outcome of ischemic stroke recurrence or death. Fine–Gray Competing Risk models were used for the outcome of recurrent ischemic stroke, with death as the competing risk. Two models were generated; Model 1 was adjusted by data-driven associated health factors, and Model 2 was adjusted by traditional vascular risk factors. Results: Among 8900 adult ischemic stroke patients [median age of 71.6 (interquartile range: 61.1–81.2) years and 48% women], women had a higher crude all-cause mortality. The KM curves demonstrated a 63.3% survival in women compared with a 65.7% survival in men ( p = 0.003) at 5 years; however, the survival difference was not present after controlling for covariates, including age, atrial fibrillation or flutter, myocardial infarction, diabetes mellitus, dyslipidemia, heart failure, chronic lung diseases, rheumatic disease, chronic kidney disease, neoplasm, peripheral vascular disease, past ischemic stroke, past hemorrhagic stroke, and depression. There was no adjusted or unadjusted sex difference in terms of recurrent ischemic stroke or composite outcome. Conclusion: Sex was not an independent risk factor for all-cause mortality and ischemic stroke recurrence in the rural population in central Pennsylvania.

To confirm whether a relationship exists between male sex and coronavirus disease 2019 (COVID-19) mortality and whether this relationship is age dependent.We queried the COVID-19 Research Network, a multinational database using the TriNetX network, to identify patients with confirmed COVID-19 infection. The main end point of the study was all-cause mortality.A total of 14,712 patients were included, of whom 6387 (43%) were men. Men were older (mean age, 55.0±17.7 years vs 51.1±17.9 years; P.001) and had a higher prevalence of hypertension, diabetes, coronary disease, obstructive pulmonary disease, nicotine dependence, and heart failure but a lower prevalence of obesity. Before propensity score matching (PSM), all-cause mortality rate was 8.8% in men and 4.3% in women (odds ratio, 2.15; 95% CI, 1.87 to 2.46; P.001) at a median follow-up duration of 34 and 32 days, respectively. In the Kaplan-Meier survival analysis, the cumulative probability of survival was significantly lower in men than in women (73% vs 86%; log-rank, P.001). After PSM, all-cause mortality remained significantly higher in men than in women (8.13% vs 4.60%; odds ratio, 1.81; 95% CI, 1.55 to 2.11; P.001). In the Kaplan-Meier survival analysis, the cumulative probability of survival remained significantly lower in men than in women (74% vs 86%; log-rank, P.001). The cumulative probability of survival remained significantly lower in propensity score-matched men than in women after excluding patients younger than 50 years and those who were taking angiotensin-converting enzyme inhibitor or angiotensin receptor blocker medications on admission.Among patients with COVID-19 infection, men had a significantly higher mortality than did women, and this difference was not completely explained by the higher prevalence of comorbidities in men.

Lung cancer poses the greatest cancer-related death risk and males have poorer outcomes than females, for unknown reasons. Patient sex is not a biological variable considered in lung cancer standard of care. Correlating patient genetics with outcomes is predicted to open avenues for improved management. Using a bioinformatics approach across non-small cell lung cancer (NSCLC) subtypes, we identified where patient sex, mutation of the major tumor suppressor gene, Tumour protein P53 (TP53), and immune signatures stratified outcomes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), among datasets of The Cancer Genome Atlas (TCGA). We exposed sex and TP53 gene mutations as prognostic for LUAD survival. Longest survival in LUAD occurred among females with wild-type (wt) TP53 genes, high levels of immune infiltration and enrichment for pathway signatures of Interferon Gamma (INF-&gamma, ), Tumour Necrosis Factor (TNF) and macrophages-monocytes. In contrast, poor survival in men with LUAD and wt TP53 genes corresponded with enrichment of Transforming Growth Factor Beta 1 (TGFB1, hereafter TGF-&beta, ) and wound healing signatures. In LUAD with wt TP53 genes, elevated gene expression of immune checkpoint CD274 (hereafter: PD-L1) and also protein 53 (p53) negative-regulators of the Mouse Double Minute (MDM)-family predict novel avenues for combined immunotherapies. LUSC is dominated by male smokers with TP53 gene mutations, while a minor population of TCGA LC patients with wt TP53 genes unexpectedly had the poorest survival, suggestive of a separate etiology. We conclude that advanced approaches to LUAD and LUSC therapy lie in the consideration of patient sex, TP53 gene mutation status and immune signatures.

Background: Female servicemembers sustain higher rates of lower extremity injuries as compared with their male counterparts. This can include intra-articular pathology in the hip. Female patients are considered to have worse outcomes after hip arthroscopy for femoroacetabular impingement and for hip labral repair. Purpose: To (1) compare published rates of hip arthroscopy between male and female military servicemembers and (2) determine if there are any sex-based differences in outcomes after hip arthroscopy in the military. Study Design: Systematic review; Level of evidence, 3. Methods: We reviewed the literature published from January 1, 2000, through December 31, 2020, to identify studies in which hip arthroscopy was performed in military personnel. Clinical trials and cohort studies were included. The proportion of women within each cohort was identified, and results of any between-sex analyses were reported. Results: Identified were 11 studies that met established criteria. Studies included 2481 patients, 970 (39.1%) of whom were women. Surgery occurred between January 1998 and March 2018. Despite women accounting for approximately 15% of the active-duty military force, they represented 39.1% (range, 25.7%-57.6%) of patients undergoing hip arthroscopy. In most cases, there were no differences in self-reported outcomes (pain, disability, and physical function), return to duty, or medical disability status based on sex. Conclusion: Women account for approximately 15% of the military, but they made up 40% of patients undergoing hip arthroscopy. Outcomes were not different between the sexes; however, definitive conclusions were limited by the heterogeneity of outcomes, missing data, lack of sex-specific subgroup analyses, and zero studies with sex differences as the primary outcome. A proper understanding of sex-specific outcomes after hip arthroscopy will require a paradigm shift in the design and reporting of trials in the military health system.

Background Chest pain is a frequent reason for calls in emergency medical communication centre (EMCC). Detecting a coronary origin by phone is a challenge. This is especially so as the presentations differ according to gender. We aimed to establish and validate a sex-based model to predict a coronary origin of chest pain in patients calling an EMCC. Methods This prospective cohort study enrolled patients at 18 years of age or older who called the EMCC because of non-traumatic chest pain. The main outcome was the diagnosis of acute coronary syndrome (ACS) determined by expert evaluation of patient files. Results During 18 months, 3727 patients were enrolled: 2097 (56%) men and 1630 (44%) women. ACS was diagnosed in 508 (24%) men and 139 (9%) women. For men, independent factors associated with an ACS diagnosis were age, tobacco use, severe and permanent pain; retrosternal, breathing non-related and radiating pain; and additional symptoms. The area under the receiver operating characteristic curve (AUC) was 0.76 (95% confidence interval [CI] 0.73–0.79) for predicting ACS. The accuracy of the male model to predict ACS was validated in a validation dataset (Hosmer-Lemeshow test: p = 0.554); the AUC was 0.77 (95%CI 0.73–0.80). For women, independent factors associated with an ACS diagnosis were age ≥ 60 years, personal history of coronary artery disease, and breathing non-related and radiating pain. The AUC was 0.79 (95%CI 0.75–0.83). The accuracy of the female model to predict ACS was not validated in the validation dataset (Hosmer-Lemeshow test: p = 0.035); the AUC was 0.67 (95%CI 0.60–0.74). Conclusions Predictors of an ACS diagnosis in patients calling an EMCC for chest pain differ between men and women. We developed an accurate predictive model for men, but for women, the accuracy was poor. Trial registration This study is registered with ClinicalTrials.gov (NCT02042209).

This study aimed to compare the clinicopathologic characteristics and oncologic outcomes of papillary thyroid cancer (PTC) patients according to sex. Then, we validated prognostic variables to determine whether sex is a significant prognostic factor for PTC. Between January 2007 and December 2010, 1232 men and 7276 women PTC patients underwent surgery. The patient characteristics and 5-year oncologic outcomes were compared. The stepwise Cox proportional hazards model determined the significance of survival variables. Men PTC patients had more lymph node (LN) metastases than women, both in the total (P

Background The objectives were to investigate the disparity in the prevalence of bone metastases (BM) between the sexes and to assess the effect of female sex on the development and prognosis of BM. Methods Cases of invasive non-sex-specific cancers diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) program were used. The prevalence of BM was calculated by combining the prevalence of BM among different cancers. Multivariable logistic regression and proportion hazard regression were conducted to investigate the effect of female sex, and the results were pooled by meta-analysis. Results The pooled prevalence of BM among male and female patients was 2.3% (95% CI: 1.6–3.2%) and 1.8% (95% CI: 1.2–2.6%), respectively. The pooled prevalence of BM dramatically decreased for patients aged 11–40 years old, plateaued for patients aged 41–90 years old and increased for patients aged > 90 years old in both male and female patients. Meta-analysis suggested that female sex had a protective effect on the development of BM (pooled OR = 0.80; 95% CI: 0.75–0.84; p p Conclusions Female sex was associated with fewer BM in various non-sex-specific cancers, and the effect was constant with changes in age. Female sex showed a protective effect exclusively on the prognosis of respiratory system cancers.

The incidence and mortality rates of lung cancers are different between females and males. Therefore, sex information should be an important part of how to train and optimize a diagnostic model. However, most of the existing studies do not fully utilize this information. This study carried out a comparative investigation between sex-specific models and sex-independent models. Three feature selection algorithms and five classifiers were utilized to evaluate the contribution of the sex information to the detection of early-stage lung cancers. Both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) showed that the sex-specific models outperformed the sex-independent detection of early-stage lung cancers. The Venn plots suggested that females and males shared only a few transcriptomic biomarkers of early-stage lung cancers. Our experimental data suggested that sex information should be included in optimizing disease diagnosis models.

Cancer represents a significant challenge for humankind, as early diagnosis and treatment are difficult to achieve. To systemically investigate the effect of sex, body mass index (BMI) and age on cancer incidence and prognosis, the data from 14,504 cases of cancer were downloaded from The Cancer Genome Atlas (TCGA). BMI was used to categorize each person as underweight, normal weight, overweight or obese. Two- and five-year survival rates were applied to estimate the prognosis for each cancer type. All data were statistically analyzed. We identified that males were more susceptible to lung, liver and skin cancer when compared with females, whereas females were more susceptible to thyroid, breast and adrenal cortex cancer. High BMI (>25) was positively associated with the occurrence of cancer, although patients with high BMI at the time of initial diagnosis had higher two/five-year survival rates. The survival rates for cancer were positively correlated with the age at initial pathologic diagnosis. Some types of cancer were associated with particularly young ages of onset, including adrenocortical carcinoma, cervical and endocervical cancers, brain lower grade glioma, pheochromocytoma and paraganglioma, testicular germ cell tumors and thyroid carcinoma. Hence, the early diagnosis and prognosis for these cancers need to be improved. In conclusion, sex, BMI and age are associated with the incidence and survival rates for cancers. These results could be used to supplement precision and personalized medicine.

Rationale & Objective In the general population, girls have lower mortality risk compared with boys. However, few studies have focused on sex differences in survival and in access to kidney transplantation among children with end-stage kidney disease. Study Design Retrospective cohort study. Setting & Participants Children aged 2 to 19 years registered in the US Renal Data System who started renal replacement therapy (RRT) between 1995 and 2011. Predictor Study participant sex. Outcome Time to death and time to kidney transplantation. Analytical Approach We used adjusted Cox models to examine the association between sex and all-cause mortality. We used Fine-Gray models to examine the association between sex and kidney transplantation accounting for the competing risk for death. Results We included 14,024 children, of whom 1,880 died during a median 7.1 years of follow-up. In adjusted analyses, the HR for death was higher for girls (HR, 1.36; 95% CI, 1.25-1.50) than boys. When we further adjusted our survival models for transplantation as a time-dependent covariate, the hazard rate of death in girls was partially attenuated but remained statistically significantly higher than that for boys (HR, 1.28; 95% CI, 1.17-1.41). Girls were also less likely to receive a kidney transplant than boys (adjusted subdistribution HR, 0.91; 95% CI, 0.88-0.95) in analyses treating death as a competing risk. Limitations Lack of data for disease course before the onset of RRT and observational study data. Conclusions The mortality rate was substantially higher for girls than for boys treated with RRT. Access to transplantation was lower for girls than boys, but differences in transplantation access accounted for only a small proportion of the survival differences by sex.

Background We examined the influence of sex, ethnicity, and time on competing cardiovascular and noncardiovascular causes of death following acute myocardial infarction in a multiethnic Asian cohort. Methods and Results For 12 years, we followed a prospective nationwide cohort of 15 151 patients (aged 22–101 years, median age 63 years; 72.3% male; 66.7% Chinese, 19.8% Malay, 13.5% Indian) who were hospitalized for acute myocardial infarction between 2000 and 2005. There were 6463 deaths (4534 cardiovascular, 1929 noncardiovascular). Compared with men, women had a higher risk of cardiovascular death (age‐adjusted hazard ratio [ HR ] 1.3, 95% CI 1.2–1.4) but a similar risk of noncardiovascular death ( HR 0.9, 95% CI 0.8–1.0). Sex differences in cardiovascular death varied by ethnicity, age, and time. Compared with Chinese women, Malay women had the greatest increased hazard of cardiovascular death ( HR 1.4, 95% CI 1.2–1.6) and a marked imbalance in death due to heart failure or cardiomyopathy ( HR 3.4 [95% CI 1.9–6.0] versus HR 1.5 [95% CI 0.6–3.6] for Indian women). Compared with same‐age Malay men, Malay women aged 22 to 49 years had a 2.5‐fold (95% CI 1.6–3.8) increased hazard of cardiovascular death. Sex disparities in cardiovascular death tapered over time, least among Chinese patients and most among Indian patients; the HR comparing cardiovascular death of Indian women and men decreased from 1.9 (95% CI 1.5–2.4) at 30 days to 0.9 (95% CI 0.5–1.6) at 10 years. Conclusion Age, ethnicity, and time strongly influence the association between sex and specific cardiovascular causes of mortality, suggesting that health care policy to reduce sex disparities in acute myocardial infarction outcomes must consider the complex interplay of these 3 major modifying factors.

Background: Women generally wait longer than men prior to seeking treatment for acute myocardial infarction (AMI). They are more likely to present with atypical symptoms, and are less likely to be admitted to coronary or intensive care units (CCU or ICU) compared to similarly-aged males. Women are more likely to die during hospital admission. Sex differences in the associations of delayed arrival, admitting ward, and mortality have not been thoroughly investigated. Methods: Focusing on presenting symptoms and time of presentation since symptom onset, we evaluated sex differences in in-hospital mortality following a first AMI in 4859 men and women presenting to three emergency departments (ED) from December 2008 to February 2014. Sex-specific risk of mortality associated with admission to either CCU/ICU or medical wards was calculated after adjusting for age, socioeconomic status, triage-assigned urgency of presentation, blood pressure, heart rate, presenting symptoms, timing of presentation since symptom onset, and treatment in the ED. Sex-specific age-adjusted attributable risks were calculated. Results: Compared to males, females waited longer before seeking treatment, presented more often with atypical symptoms, and were less likely to be admitted to CCU or ICU. Age-adjusted mortality in CCU/ICU or medical wards was higher among females (3.1 and 4.9 % respectively in CCU/ICU and medical wards in females compared to 2.6 and 3.2 % in males). However, after adjusting for variation in presenting symptoms, delayed arrival and other risk factors, risk of death was similar between males and females if they were admitted to CCU or ICU. This was in contrast to those admitted to medical wards. Females admitted to medical wards were 89 % more likely to die than their male counterparts. Arriving in the ED within 60 min of onset of symptoms was not associated with in-hospital mortality. Among males, 2.2 % of in-hospital mortality was attributed to being admitted to medical wards rather than CCU or ICU, while for females this age-adjusted attributable risk was 4.1 %. Conclusions: Our study stresses the need to reappraise decision making in patient selection for admission to specialised care units, whilst raising awareness of possible sex-related bias in management of patients diagnosed with an AMI.