Gender-Related Aspects of Laryngeal Squamous Cell Carcinoma: A Retrospective Cohort Study.

OBJECTIVES: Laryngeal squamous cell carcinoma (SCC) is a predominantly male illness. Although the rate of female patients increased, a knowledge gap exists in the medical literature regarding gender-based differences. DESIGN: Retrospective cohort study. SETTING: Adult patients treated for laryngeal SCC in a tertiary medical centre between 2006 and 2020. Data were collected on demographics, clinical presentation, treatment modalities, disease recurrence and survival status. PARTICIPANTS: Two hundred ninety-one patients with laryngeal SCC, 50 (17.2%) females and 241 (82.8%) males. MAIN OUTCOME MEASURES: Disease-specific survival (DSS), overall survival (OS) and disease-free survival (DFS), as well as differences in disease characteristics and treatment modalities. RESULTS: Tumour subsites differed significantly between females and males (36% vs. 19.5% supraglottic, 62% vs. 80.5% glottic and 2% vs. 0% subglottic, respectively; p = 0.006). Females were diagnosed at younger ages (61.7 ± 10.58 vs. 65.87 ± 11.11 years, p = 0.016) and advanced-stage disease (58% vs. 39.4%, p = 0.018). Females were treated with combined modalities at higher rates (36% vs. 54.8% for single modality, p = 0.031). DSS rates did not differ between genders (log-rank p = 0.12). Despite being diagnosed at more advanced disease stages, females demonstrated prolonged median OS compared to males (130.17 vs. 106.17 months, log-rank p = 0.017). No significant differences in DFS were observed (log-rank p = 0.32). In a multivariate Cox proportional hazards model, male gender remained an independent negative OS predictor (HR = 2.08; CI, 1.10-3.96; p = 0.025), along with increasing age (HR = 1.06; CI, 1.04-1.09; p < 0.001) and advanced disease stage (HR = 1.7; CI, 1.08-2.67; p = 0.023). CONCLUSIONS: Our findings suggest the importance of considering gender-specific factors in the management of laryngeal SCC.

[Sex differences in hepatobiliary and transplantation surgery]. / Geschlechtsunterschiede in der hepatobiliären und Transplantationschirurgie.

Gender-specific differences in hepatobiliary and transplantation surgery are decisive for the diagnosis, treatment and long-term outcomes. Men exhibit a higher risk of late recurrences and cancer-specific death after liver cancer resection. The emphasis on screening recommendations and ensuring equal access to treatment options are vital to minimize disparities. In kidney and liver transplantations, women are less frequently listed and endure longer waiting times, while men dominate the waiting list. Gender-specific disparities in drug compatibility necessitate differentiated dosing. Further studies are needed to ensure equity in transplantation treatment. Individualized treatment considering these differences can enhance treatment outcomes and the quality of life of patients.

[Sex differences in pancreatic cancer]. / Geschlechtsunterschiede beim Pankreaskarzinom.

This review article discusses the currently available evidence on the importance of biological and social sex in pancreatic cancer in the context of the operative, perioperative and multimodal treatment. In pancreatic cancer there are gender differences with respect to the incidence, treatment response and prognosis. Sex significantly influences both innate and adaptive immune responses, thereby affecting treatment response and survival rates. Women are less likely to receive systemic treatment and tend to wait longer for surgery but have better perioperative outcomes after pancreatic resection. Overall, female pancreatic cancer patients seem to have longer survival under treatment; however, they report a subjectively lower quality of life and higher disease burden.

Incorrect and Sex-Inconsistent Mapping of Disorders: Identification of Sex Biases in the ICD-10, ICD-11 and SNOMED CT and How to Work Around Them.

In the international classifications ICD-10-WHO and ICD-11-WHO, many sex-specific diseases have incomplete coding. It is possible to further enhance semantic interoperability using SNOMED CT additionally to ICD. Part of the analysis of semantic interoperability of diagnoses in the ICD are Sexual Dysfunctions, Postpartum Depression, Sexual Assault, Premenstrual Tension Syndrome and Premenstrual Dysphoric Disorder, Female Genital Mutilation and Cutting, Gender Incongruence and Disorders of Breast. Labeling biases have been identified in all diagnoses, either in SNOMED CT or ICD. For mental disorders associated with pregnancy, gender incongruence and sexual violence the use of the GPS of SNOMED CT can help enhance semantic interoperability additionally to ICD.

Reproductive life factors and estro-progestin exposure in women with early-onset Parkinson's disease compared to late-onset disease and controls: A retrospective cohort study.

BACKGROUND: Parkinson's disease (PD) is more common in men than women. Although hormonal factors may partially explain this difference, there are no studies evaluating reproductive life factors and exogenous estroprogestin exposure in women with Early Onset Parkinson Disease (EOPD). OBJECTIVE: To compare reproductive life factors and exogenous estroprogestin exposure among female patients with EOPD, late-onset Parkinson's disease (LOPD), and EOPD-matched unaffected controls. METHODS: We identified female patients with EOPD from 1989 to 2021, defining EOPD as PD with motor-symptoms onset before age 50 and LOPD as PD with motor onset after 50. We paired EOPD patients to age-matched, unaffected controls. We reviewed medical records to determine demographic characteristics, clinical history, and reported reproductive menopausal history (reviewing medical records). RESULTS: We included 87 EOPD patients, 84 LOPD patients, and 91 unaffected controls with information about reproductive life factors and exogenous estroprogestin exposure in their medical records. There were no significant differences in race, ethnicity, or BMI between the three groups. EOPD patients were more likely to have used hormonal contraception than LOPD patients (23/49 (47 %) vs 0/84 (0 %), p < 0.001). LOPD patients had higher numbers of pelvic surgeries (48/84 [57 %] in LOPD, 23/87 [26 %] in EOPD, p < 0.001) and higher usage of perimenopausal hormonal therapy (52/84 [62 %] in LOPD, 10/87 [11 %] in EOPD, p < 0.001) in LOPD than EOPD. CONCLUSIONS: Our study reports no significant difference in reproductive life factors and exogenous estroprogestin exposure between controls and EOPD patients, except for higher exposure to hormonal contraception in EOPD. There was no apparent difference in reproductive life factors and exogenous estroprogestin exposure between EOPD and LOPD patients. Our findings therefore do not observe that hormonal exposure is different between earlier onset of female EOPD compared to female LOPD patients, or between female EOPD patients and unaffected female controls.

Gender-Specific Medicine in the European Society of Cardiology Guidelines from 2018 to 2023: Where Are We Going?

Background/Objectives: Evidence-based medicine (EBM) shapes most clinical guidelines. Although the advent of EBM marked a significant advancement, failure to include sex differences in the study design and analysis of most trials leads to an under-representation of gender-specific medicine (GM) in EBM-directed guidelines. In this review, we evaluated how the topic of GM was developed in the guidelines produced by the European Society of Cardiology (ESC) from 2018 to 2023. Methods: Two independent reviewers evaluated 24 ESC guidelines. Significant mentions of GM were counted and divided between epidemiology, diagnosis, and therapeutics. The qualitative and semi-quantitative analysis of information relating to GM was performed. Data on the number of citations of papers with a title concerning GM and the prevalence and role of women in guidelines' authorship were also analyzed. Results: Less than 50% of guidelines had a section dedicated to GM. Only nine guidelines were led by a woman, and 144/567 authors were female. In the most recent guidelines and in those with at least 30% of female authors, there was an increased mention of GM. On average, guidelines had four significant mentions of GM regarding epidemiology, two regarding diagnosis, and one regarding therapy. Articles with titles concerning GM made up, on average, 1.5% of the total number of citations. Conclusions: Although sex differences play a significant role in most clinical scenarios, ESC guidelines still do not sufficiently account for this. The problem does not seem to solely lie in the guidelines, but in the lack of attention to GM in research needed for their preparation.

The Cardiovascular Risk Awareness and Health Lifestyle of Italian Women.

Background: Cardiovascular (CV) disease is the leading cause of death in women, but few of them are aware of the CV risks (CVRs). Most women are not aware of all the CV risk factorsand their knowledge often still does not improve their lifestyle. Methods: The Carin Women is a survey conducted among Italian women by filling out a questionnaire in the waiting rooms of clinics. The aim was to determine the level of awareness of women's cardiovascular risk, knowledge of risk factors, and lifestyle. A total of 5590 questionnaires were completed in two different periods. Results: Median age was 56 (IQR 46-65); BMI was 25 (IQR 22-29). Schooling, marital status, and rate of risk conditions were assessed; 311 women (5.57%) had already suffered a cardiovascular event. The relationship between the CV events and the number of traditional risk factors was significant. A similar curve, but without significant differences, was reported for non-traditional risk factors. From the total number of women, 23% with a high CVR and 62% with a very high CVR underestimated thei risk regardless of their level of education. Up to 43% of women underestimated female CV risk compared to male risk. Women showed a good knowledge of traditional risk factors, but only a few of them had a healthy lifestyle: 21.86% were smokers, only 45.88% performed sufficient physical activity, 27.55% did not recognize they were overweight, and only 30.4% consumed more than two daily portions of fruit and vegetables. Most women (86%) need more information about CVR. Conclusions: Italian women underestimate female CVRs and their own CVR.

Infections and gender: clues for diagnosis of adrenal insufficiency-a case report and a review of the literature.

The clinical presentation of adrenal insufficiency, a condition causing adrenal hormone deficiency, is characterised by non-specific symptoms and signs: consequently, an important diagnostic delay is often evident which correlates with an increased mortality. This case report shows how the clustering of some symptoms and signs may hamper the diagnostic suspicion for this condition: serum electrolyte alterations and weight loss, when associated to recurrent infections and, in female patients, an empty sella may further guide the clinician towards a diagnosis of adrenal insufficiency. Accordingly, a clinical approach taking into account gender medicine could improve the diagnostic workup.

Maternal-fetal dyad beyond the phenomenology of pregnancy: from primordial cardiovascular prevention on out, do not miss this boat!

Pregnancy represents a stress test for every woman's cardiovascular (CV) system, and a pre-existing maternal unfavorable cardio-metabolic phenotype can uncover both adverse pregnancy outcomes and the subsequent development of cardiovascular disease (CVD) risk factors during and after pregnancy. Moreover, the maternal cardiac and extracardiac environment can affect offspring's cardiovascular health through a complex mechanism called developmental programming, in which fetal growth can be influenced by maternal conditions. This interaction continues later in life, as adverse developmental programming, along with lifestyle risk factors and genetic predisposition, can exacerbate and accelerate the development of CV risk factors and CVD in childhood and adolescence. The aim of this narrative review is to summarize the latest evidences regarding maternal-fetal dyad and its role on primordial, primary and secondary CV prevention.

Sex differences in the use of mechanical ventilation in a neurointensive care population: a retrospective study.

BACKGROUND: In the general intensive care unit (ICU) women receive invasive mechanical ventilation (IMV) less frequently than men. We investigated whether sex differences in the use of IMV also exist in the neurocritical care unit (NCCU), where patients are intubated not only due to respiratory failure but also due to neurological impairment. METHODS: This retrospective single-centre study included adults admitted to the NCCU of the University Hospital Zurich between January 2018 and August 2021 with neurological or neurosurgical main diagnosis. We collected data on demographics, intubation, re-intubation, tracheotomy, and duration of IMV or other forms of respiratory support from the Swiss ICU registry or the medical records. A descriptive statistics was performed. Baseline and outcome characteristics were compared by sex in the whole population and in subgroup analysis. RESULTS: Overall, 963 patients were included. No differences between sexes in the use and duration of IMV, frequency of emergency or planned intubations, tracheostomy were found. The duration of oxygen support was longer in women (men 2 [2, 4] vs. women 3 [1, 6] days, p = 0.018), who were more often admitted due to subarachnoid hemorrhage (SAH). No difference could be found after correction for age, diagnosis of admission and severity of disease. CONCLUSION: In this NCCU population and differently from the general ICU population, we found no difference by sex in the frequency and duration of IMV, intubation, reintubation, tracheotomy and non-invasive ventilation support. These results suggest that the differences in provision of care by sex reported in the general ICU population may be diagnosis-dependent. The difference in duration of oxygen supplementation observed in our population can be explained by the higher prevalence of SAH in women, where we aim for higher oxygenation targets due to the specific risk of vasospasm.

PD-L1 expression in patients with non-small-cell lung cancer is associated with sex and genetic alterations: A retrospective study within the Caucasian population.

BACKGROUND: Programmed cell death-ligand 1 (PD-L1) expression is a well-established biomarker for predicting responses to immune checkpoint inhibitors and certain targeted therapies. As a result, treatment strategies for patients vary based on their PD-L1 expression status. Understanding the clinical features of patients with distinct PD-L1 levels is crucial for personalized treatment approaches. METHODS: Demographic and clinicopathological characteristics of 227 patients (54% male, mean age 67 ± 9.9 years) newly diagnosed with non-small-cell lung cancer (NSCLC) between April 2020 and December 2022 were retrospectively compared among three groups based on the PD-L1 expression: PD-L1 Tumor Proportion Score (TPS) negative, 1-50%, and ≥50%. Logistic regression analysis was performed to evaluate predictors for high PD-L1 expression ≥50%. RESULTS: PD-L1 expression levels were distributed as follows: negative in 29% of patients, between 1% and 50% in 41%, and greater than 50% (high) in 29%. In comparison to negative PD-L1 expression, low and high PD-L1 expression was associated with female sex (32.9% vs. 52.7% vs. 50.7%, p = 0.031), with the absence of epidermal growth factor receptor (EGFR) mutations (83.6% vs. 91.1% vs. 98.1% p = 0.029), and with the absence of ERBB2 (HER2) tyrosine kinase mutations (90.9% vs. 100% vs. 98.1% p = 0.007), respectively. Age, smoking status, histological subtype, and disease stage showed no significant differences among the three patient groups. In the univariate logistic regression, EGFR mutation appeared to be the only predictor for PD-L1 expression, although it did not reach statistical significance (p = 0.06). CONCLUSION: Although sex and genomic alterations are associated with PD-L1 expression in patients with NSCLC, no clinical characteristics seem to predict PD-L1 expression significantly.

Sex and Gender-related Disparities in Clinical Characteristics and Outcomes in Heart Transplantation.

PURPOSE OF REVIEW: Limited research has been conducted on sex disparities in heart transplant (HT). The aim of this review is to analyse the available evidence on the influence of sex and gender-related determinants in the entire HT process, as well as to identify areas for further investigation. RECENT FINDINGS: Although women make up half of the population affected by heart failure and related mortality, they account for less than a third of HT recipients. Reasons for this inequality include differences in disease course, psychosocial factors, concerns about allosensitisation, and selection or referral bias in female patients. Women are more often listed for HT due to non-ischaemic cardiomyopathy and have a lower burden of cardiovascular risk factors. Although long-term prognosis appears to be similar for both sexes, there are significant disparities in post-HT morbidity and causes of mortality (noting a higher incidence of rejection in women and of malignancy and cardiac allograft vasculopathy in men). Additional research is required to gain a better understanding of the reasons behind gender disparities in eligibility and outcomes following HT. This would enable the fair allocation of resources and enhance patient care.

Poor adherence during adolescence is a risk factor for becoming lost-to-follow-up in patients with phenylketonuria.

Purpose: A high rate of lost to follow-up (LTFU) in patients with phenylketonuria (PKU) represents a main challenge. In this study, we investigated potential risk factors for becoming LTFU related to adolescence as a critical period of life. Methods: We retrospectively analyzed longitudinal data collected from 1993 to 2019 of patients diagnosed with classic PKU that were followed at our center during adolescence (14-18 y) and at least once in adulthood (>18 y). Patients who interrupted their contact with our center after the 18th birthday for at least 2 years were classified as LTFU. We performed a multivariate regression analysis to investigate following potential risk factors for becoming LTFU in adult life: sex, dietary compliance during adolescence assessed through the mean of the annual medians of phenylalanine plasma values, average number of contacts with the center during adolescence and age at first visit after the 18th birthday. Results: 93 patients (52 males, 41 females) were included in the study. 58% became LTFU during adulthood. The mean age at the last visit before becoming LTFU was 26.2 ± 5.1 years. In the multivariate Cox regression analysis we found that poor dietary compliance during adolescence was significantly associated with a higher risk of becoming LTFU during adulthood (p-value = 0.028). Discussion: Adult patients who displayed poor treatment adherence during adolescence should be identified and carefully monitored to prevent loss of contact.

Physically demanding occupations among females and sex-related differences to develop osteoarthritis of the hip: a systematic review and meta-analysis.

BACKGROUND: Hip osteoarthritis (HOA) is a leading cause of disability increasing with age and is more prevalent in women and in various physically demanding occupations. This systematic review identifies and summarises occupational exposures for women in physically demanding occupations and discusses sex differences and consequences. METHODS: In this systematic review, we searched various electronic databases for reports published between date of database inception and October 2022. We included cohort studies and case-control studies that assessed the association between exposure to physically demanding occupations and the development of HOA. We then assessed the methodological quality of selected studies, extracted relative effects, compared the risk for women and men and meta-analytically reviewed the effects of physically demanding occupations. All steps were based on a study protocol published in PROSPERO (CRD42015016894). RESULTS: We included six cohort studies and two case-control studies in this systematic review. These studies showed a considerably increased risk of developing HOA in both sexes. Women working in traditionally female-dominated occupations such as cleaning, sales, catering, childcare and hairdressing that are physically demanding, have a higher risk of developing HOA than men in similarly physically demanding occupations. Conversely, in traditionally male-dominated occupations with a high heterogeneity of work activities, such as agriculture, crafts, construction, as well as in low-skilled occupations, the risk was higher for men. One exception are health occupations, which are grouped together with a wide range of other technical occupations, making it difficult to draw conclusions. CONCLUSIONS: Existing studies indicate an association between various occupations with a high physical workload and an increased risk of developing HOA. Occupational prevention and individual health promotion strategies should focus on reducing the effects of heavy physical workloads at work. The aforementioned as well as early detection should be specifically offered to women in female-dominated occupations and to people working in elementary occupations.

MicroRNA in cardiometabolic health and disease: The perspectives of sex, gender and personalised medicine.

BACKGROUND: Personalized medicine represents a novel and integrative approach that focuses on an individual's genetics and epigenetics, precision medicine, lifestyle and exposures as key players of health status and disease phenotypes. METHODS: In this narrative review, we aim to carefully discuss the current knowledge on gender disparities in cardiometabolic diseases, and we consider the sex- specific expression of miRNAs and their role as promising tool in precision medicine. RESULTS: Personalised medicine overcomes the restricted care of patient based on a binomial sex approach, by enriching itself with a holistic and dynamic gender integration. Recognized as a major worldwide health emergency, cardiometabolic disorders continue to rise, impacting on health systems and requiring more effective and targeted strategies. Several sex and gender drivers might affect the onset and progression of cardiometabolic disorders in males and females at multiple levels. In this respect, distinct contribution of genetic and epigenetic mechanisms, molecular and physiological pathways, sex hormones, visceral fat and subcutaneous fat and lifestyle lead to differences in disease burden and outcomes in males and females. CONCLUSIONS: Sex and gender play a pivotal role in precision medicine because the influence the physiology of each individual and the way they interact with environment from intrauterine life.

Sex and sex steroids as determinants of cardiovascular risk.

There are considerable sex differences regarding the risk of cardiovascular disease (CVD), including arterial hypertension, coronary artery disease (CAD) and stroke, as well as chronic renal disease. Women are largely protected from these conditions prior to menopause, and the risk increases following cessation of endogenous estrogen production or after surgical menopause. Cardiovascular diseases in women generally begin to occur at a later age than in men (on average with a delay of 10 years). Cessation of estrogen production also impacts metabolism, increasing the risk of developing obesity and diabetes. In middle-aged individuals, hypertension develops earlier and faster in women than in men, and smoking increases cardiovascular risk to a greater degree in women than it does in men. It is not only estrogen that affects female cardiovascular health and plays a protective role until menopause: other sex hormones such as progesterone and androgen hormones generate a complex balance that differentiates heart and blood vessel function in women compared to men. Estrogens improve vasodilation of epicardial coronary arteries and the coronary microvasculature by augmenting the release of vasodilating factors such as nitric oxide and prostacyclin, which are mechanisms of coronary vasodilatation that are more pronounced in women compared to men. Estrogens are also powerful inhibitors of inflammation, which in part explains their protective effects on CVD and chronic renal disease. Emerging evidence suggests that sex chromosomes also play a significant role in shaping cardiovascular risk. The cardiovascular protection conferred by endogenous estrogens may be extended by hormone therapy, especially using bioidentical hormones and starting treatment early after menopause.

Palpitations in puerperium-a self-recorded smart watch ECG gives the hint to hormone-induced ventricular arrhythmia: case report.

Background: Gender-related aspects in cardiac arrhythmias have gained increasing attention, still the understanding of peripartum electrical disorders remains vague. Case summary: A 28-year-old woman developed palpitations and presyncopes during the post-partum period after her second pregnancy. Palpitations remained unclear until a self-recorded single-lead smartwatch ECG revealed a complete episode of a fast broad complex tachycardia (260 b.p.m.) that led to hospital admission. Echocardiography, cardiac magnetic resonance imaging, and exercise testing, showed no relevant abnormalities. Recording the tachycardia in a 12-lead-ECG could eventually be achieved revealing an inferior axis and positive concordance in the precordial leads. Episodes of ventricular tachycardia (VT) could be provoked by breast feeding and mental stress, but not induced in two electrophysiological studies. Genetic testing was normal. The patient continued to experience repeated, self-terminating VT episodes, lasting between 10 and 40 s, leading to presyncopes and a syncope with a fall. The beginning of symptoms subsequent to child birth and frequent premature ventricular contractions in her first pregnancy made hormone-induced arrhythmia a tentative diagnosis. Heart rate-corrected QT (QTc) intervals showed significant variability corresponding to the frequency of episodes in a retrospective evaluation. The cessation of breastfeeding led to a termination of arrhythmias. The patient was temporarily equipped with a wearable cardioverter defibrillator vest, an implantable cardioverter defibrillator (ICD) was not implanted. Discussion: The case report highlights the potential of self-recorded, patient-activated ECG monitoring in diagnosing recurrent palpitations, and the dilemma of timing for implanting ICDs in young patients with ventricular arrythmias (VTs). Additionally, it underlines the role of post-partum hormones in the susceptibility to ventricular arrhythmias, calling for further research of gender-specific, and pregnancy-associated arrhythmias.

Gender differences in the relationship between serum uric acid and the long-term prognosis in heart failure: a nationwide study.

BACKGROUND: Serum uric acid (SUA) is an important pathogenetic and prognostic factor for heart failure (HF). Gender differences are apparent in HF. Furthermore, gender differences also exist in the association between SUA and prognosis in various cardiovascular diseases. However, the gender difference for SUA in the prediction of long-term prognosis in HF is still ambiguous. METHODS: A total of 1593 HF patients (897 men, 696 women) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 cycle were enrolled in our final analysis. Participants were categorized according to gender-specific SUA tertile. We assessed the association between SUA and long-term prognosis of HF patients, defined as all-cause mortality and cardiovascular mortality, in different genders via Kaplan-Meier curve analysis, Cox proportional hazard model, and Fine-Gray competing risk model. The restricted cubic spline (RCS) was performed to investigate the dose-response relationship between SUA and outcomes. RESULTS: Gender differences exist in demographic characteristics, clinical parameters, laboratory tests, and medication of HF patients. After a median follow-up of 127 months (95% CI 120-134 months), there were 853 all-cause deaths (493 events in men, 360 events in women) and 361 cardiovascular deaths (206 events in men, 155 events in women). Kaplan-Meier analysis showed that SUA had gender difference in the prediction of cardiovascular mortality (Log-rank p < 0.001, for male, Log-rank p = 0.150, for female), but not in all-cause mortality. Multivariate Cox regression analysis revealed that elevated SUA levels were associated with higher all-cause mortality and cardiovascular mortality in men (HR 1.11, 95% CI 1.05-1.18, p < 0.001, for all-cause death; HR 1.18, 95% CI 1.09-1.28, p < 0.001, for cardiovascular death), but not in women (HR 1.05, 95% CI 0.98-1.12, p = 0.186, for all-cause death; HR 1.01, 95% CI 0.91-1.12, p = 0.902, for cardiovascular death). Even using non-cardiovascular death as a competitive risk, adjusted Fine-Gray model also illustrated that SUA was an independent predictor of cardiovascular death in men (SHR 1.17, 95% CI 1.08-1.27, p < 0.001), but not in women (SHR 0.98, 95% CI 0.87 - 1.10, p = 0.690). CONCLUSIONS: Gender differences in the association between SUA and long-term prognosis of HF existed. SUA was an independent prognostic predictor for long-term outcomes of HF in men, but not in women.