Gender differences in obesity hypoventilation syndrome.

Sleep-disordered breathing (SDB) is a group of sleep-related breathing disorders which includes obstructive sleep apnea (OSA), central sleep apnea (CSA), and obesity hypoventilation syndrome (OHS). OHS is characterized by a combination of obesity, daytime hypercapnia and hypoxemia, and sleep-disordered breathing without other known hypoventilation causes, such as severe obstructive or restrictive parenchymal lung disease, kyphoscoliosis, severe hypothyroidism, neuromuscular disease, or congenital central hypoventilation syndrome. Four hundred ninety potentially eligible references were identified; of these, 462 abstracts or full texts were excluded because they did not fulfil inclusion criteria. We reviewed the full text of the remaining 38 papers which fulfilled the inclusion criteria. The role of gender in SDB and particularly in OHS is not well known. In general, the diseases are under-recognized in women and only a few studies have reported the impact of gender on clinical presentation and treatment outcome. On the other hand, there is often a delay in diagnosing these diseases in women as compared to men; therefore, they are often more advanced when diagnosed in women. Better understanding and clinical awareness of the higher OHS prevalence in postmenopausal women may lead to earlier diagnosis and a more timely and appropriate treatment. Further studies are needed to assess the prevalence of OHS in women, the effect of menopause on OHS, and the increased risk of OHS, which will hopefully lead to optimizing OHS patient care.

Awareness of sex and gender dimensions among physicians: the European federation of internal medicine assessment of gender differences in Europe (EFIM-IMAGINE) survey.

Sociocultural gender is a complex construct encompassing different aspects of individuals' life, whereas sex refers to biological factors. These terms are often misused, although they impact differently on individuals' health. Recognizing the role of sex and gender on health status is fundamental in the pursuit of a personalized medicine. Aim of the current study was to investigate the awareness in approaching clinical and research questions on the impact of sex and gender on health among European internists. Clinicians affiliated with the European Federation of Internal Medicine from 33 countries participated to the study on a voluntary basis between January 1st, 2018 and July 31st, 2019. Internists' awareness and knowledge on sex and gender issues in clinical medicine were measured by an online anonymized 7-item survey. A total of 1323 European internists responded to the survey of which 57% were women, mostly young or middle-aged (78%), and practicing in public general medicine services (74.5%). The majority (79%) recognized that sex and gender are not interchangeable terms, though a wide discrepancy exists on what clinicians think sex and gender concepts incorporate. Biological sex and sociocultural gender were recognized as determinants of health mainly in cardiovascular and autoimmune/rheumatic diseases. Up to 80% of respondents acknowledged the low participation of female individuals in trials and more than 60% the lack of sex-specific clinical guidelines. Internists also express the willingness of getting more knowledge on the impact of sex and gender in cerebrovascular/cognitive and inflammatory bowel diseases. Biological sex and sociocultural gender are factors influencing health and disease. Although awareness and knowledge remain suboptimal across European internists, most acknowledge the underrepresentation of female subjects in trials, the lack of sex-specific guidelines and the need of being more informed on sex and gender-based differences in diseases.

Gender differences in vaccine therapy: where are we in COVID-19 pandemic?

Vaccination is one of the greatest achievements of public health. Vaccination programs have contributed to the decline in mortality and morbidity of various infectious diseases. This review aims to investigate the impact of sex/gender on the vaccine acceptance, responses, and outcomes. The studies were identified by using PubMed, until 30th June 2020. The search was performed by using the following keywords: SARS-CoV-2, COVID-19, gender, sex, vaccine, adverse reaction. Clinical trials, retrospective and prospective studies were included. Studies written in languages other than English were excluded. Studies were included if gender differences in response to vaccination trials were reported. All selected studies were qualitatively analyzed. Innate recognition and response to viruses, as well as, adaptive immune responses during viral infections, differ between females and males. Unfortunately, a majority of vaccine trials have focused on healthy people, with ages between 18 to 65 years, excluding the elderly, pregnant women, post-menopausal female and children. In conclusion, it is apparent that the design of vaccines and vaccine strategies should be sex-specific, to reduce adverse reactions in females and increase immunogenicity in males. It should be mandatory to examine sex-related variables in pre-clinical and clinical vaccine trials, such as their crucial role for successful prevention of pandemic COVID-19.

Gender differences in treatment of Coronavirus Disease-2019.

Coronavirus Disease-2019 (COVID-19) is the worst worldwide pandemic with more than 12,000,000 cases and 560,000 deaths until 14th July 2020. Men were more infected by COVID-19 than women, and male subjects with underlying conditions, including diabetes, hypertension, and cardiovascular diseases developed a severe form of the affection, with increased mortality rate. Many factors can contribute to the disparity in disease outcomes, such as hormone-specific reaction and activity of X-linked genes, which modulate the innate and adaptive immune response to virus infection. Until now, only the Remdesivir was approved by FDA (Food Drug Administration) for COVID-19 treatment, although several clinical trials are ongoing worldwide also on other drugs. In this review, we analyzed published studies on several drugs (chloroquine or hydroxychloroquine, remdesivir, favipiravir, lopinavir-ritonavir in combination, tocilizumab, plasma, and immunoglobulins) with some efficacy to COVID-19 in humans, and evaluated if there were a gender analysis of the available data. In our opinion, it is essential to report data about COVID-19 disaggregated by sex, age, and race, because the knowledge of gender differences is fundamental to identify effective and customized treatments to reduce hospitalizations, admissions to intensive care units, and mortality.

Gender differences in patients with COVID-19: a narrative review.

In December 2019 a novel coronavirus emerged in Wuhan, China causing many cases of severe pneumonia. World Health Organization (WHO) named this disease Coronavirus Disease 2019 (COVID-19). The infection has rapidly spread across China to many other countries, and on March 12, 2020 the WHO declared pandemic outbreak of COVID-19. As of May 16, 2020, COVID-19 has been diagnosed in more than 4,490,000 patients, associated to 305,976 deaths worldwide; in Italy 224,760 COVID-19 cases have been reported with 31,763 deaths. The main routes of transmission are respiratory droplets and direct contact with infected people, so numerous prevention strategies are employed to mitigate the spread of disease, including social distancing and isolation. The aim of this narrative review is to underline gender differences in epidemiology, etiopathogenesis, risk factors, clinical presentation, diagnosis, prognosis and mortality of patients infected with SARS-CoV-2. Currently data on the sex indicators for admitted or deceased patients are only available, but there is no analysis about other gender indicators. The data considered in our study are the only currently available in the literature, but it is appropriate to implement a specific analysis with all gender indicators to identify appropriate strategies. Moreover, the evaluation of a health service efficiency is a key element to define gender outcomes. Knowing the gender differences in COVID-19 outbreak would be a fundamental tool to understand the effects of a health emergency on individuals and communities as well as to carry out effective and equitable policies, public health measures and targeted solutions.

Gender Differences and Quality of Life in Parkinson's Disease.

Parkinson's disease has been found to significantly affect health-related quality of life. The gender differences of the health-related quality of life of subjects with Parkinson's disease have been observed in a number of studies. These differences have been reported in terms of the age at onset, clinical manifestations, and response to therapy. In general, women with Parkinson's disease showed more positive disease outcomes with regard to emotion processing, non-motor symptoms, and cognitive functions, although women report more Parkinson's disease-related clinical manifestations. Female gender predicted poor physical functioning and socioemotional health-related quality of life, while male gender predicted the cognitive domain of health-related quality of life. Some studies reported gender differences in the association between health-related quality of life and non-motor symptoms. Depression and fatigue were the main causes of poorer health-related quality of life in women, even in the early stages of Parkinson's disease. The aim of this review was to collect the best available evidence on gender differences in the development of Parkinson's disease symptoms and health-related quality of life.

Educational level, marital status and sex as social gender discharge determinants in chronic obstructive pulmonary disease exacerbations: a time-to-event analysis.

The aim of this study is to evaluate, in patients hospitalized for COPD exacerbation, how educational level, marital status and sex (social gender indicators) affect the prognosis (main effects) and how interact with each other in affecting prognosis (effect modification). Data for all patients discharged with a principal diagnosis of COPD with exacerbation (ICD-9 491.21) by Apulian facilities between 2013 and 2017 were retrieved from the National Hospital Discharge Register Database. A multivariable multi-stratified frailty cox proportional-hazard regression with interaction terms was fitted in order to assess the effect of sex, educational level and marital status on the time-to-event for home discharge through the estimation of hazard ratios. Adjusting for several hospitalization characteristics and for healthcare facilities, low educational level (<8 years of schooling) seems to be a risk factor in both sexes and in all marital status categories (HR 0.92, 95%CI 0.87-0.97, p=0.0020). Female sex seems to be a risk factor only in married patients (HR 0.83, 95%CI 0.78-0.88, p<0.0001). Marital status different from married seems to be a risk factor only in male patients, in particular single patients (HR 0.82, 95%CI 0.74-0.92, p=0.0009), separated or divorced patients (HR 0.71, 95%CI 0.58-0.86, p=0.0005) and widowed patients (HR 0.87, 95%CI 0.80-0.95, p=0.0018). Differently from findings about protective effect of education, the evidence of different effects of sex among civil statuses and of different effect of civil status among sexes is supposed to be a proxy for social gender health and healthcare inequalities.

The potential impact of multidimesional geriatric assessment in the social security system.

AIM: To evaluate the efficacy of multidimensional geriatric assessment (MGA/CGA) in patients over 65 years old in predicting the release of the accompaniment allowance (AA) indemnity by a Local Medico-Legal Committee (MLC-NHS) and by the National Institute of Social Security Committee (MLC-INPS). METHODS: In a longitudinal observational study, 200 Italian elder citizens requesting AA were first evaluated by MLC-NHS and later by MLC-INPS. Only MLC-INPS performed a MGA/CGA (including SPMSQ, Barthel Index, GDS-SF, and CIRS). This report was written according to the STROBE guidelines. RESULTS: The data analysis was performed on January 2016. The evaluation by the MLC-NHS and by the MLC-INPS was in agreement in 66% of cases. In the 28%, the AA benefit was recognized by the MLC-NHS, but not by the MLC-INPS. By the multivariate analysis, the best predictors of the AA release, by the MLC-NHS, were represented by gender and the Barthel Index score. The presence of carcinoma, the Barthel Index score, and the SPMQ score were the best predictors for the AA release by MLC-INPS. CONCLUSIONS: MGA/CGA could be useful in saving financial resources reducing the risk of incorrect indemnity release. It can improve the accuracy of the impairment assessment in social security system.

Role of surgery for colorectal cancer in the elderly.

The prevalence of subjects with colorectal cancer is expected to grow in the next future decades and surgery represents the most successful treatment modality for these patients. Anyway, currently elderly subjects undergo less elective surgical procedures than younger patients mainly due to the high rates of postoperative morbidity and mortality. Some authors suggest extensive surgery, including multistage procedures, as carried out in younger patients while others promote less aggressive surgery. In older patients, laparoscopic-assisted colectomy showed a number of advantages compared to conventional open surgery that include lower stress, higher rate of independency after surgery, quicker return to prior activities and a decrease in costs. The recent advances in chemotherapy and the introduction of new surgical procedures such as the endoluminal stenting, suggest the need for a revisitation of surgical practice patterns and the role of palliative surgery, mainly for patients with advanced disease. In this article, we discuss the current role of surgery for elderly patients with colorectal cancer.

Innate immune activity in plaque of patients with untreated and L-thyroxine-treated subclinical hypothyroidism.

CONTEXT: A strong association between subclinical hypothyroidism (SCH) and atherosclerotic diseases, independent of the traditional risk factors, was noted. OBJECTIVE: The objective of the study was to evaluate the association between SCH and the inflammatory potential of atherosclerotic plaques as well as the role of L-T(4) replacement therapy (LTR) on regulation of plaque inflammation. EXPERIMENTAL DESIGN AND MAIN OUTCOME MEASURES: We examined the differences in macrophage content, proinflammatory cytokine infiltration, and oxidative stress between asymptomatic carotid plaques of patients with and without SCH and LTR. SETTING AND PARTICIPANTS: Plaques were obtained from 23 SCH patients with LTR (treated), 34 untreated SCH patients, and 30 control patients without SCH enlisted to undergo carotid endarterectomy for extracranial high-grade (>70%) internal carotid artery stenosis. Plaques were analyzed for macrophages, T lymphocytes, human leukocyte antigen (HLA)-DR(+) cells, nuclear factor-κB (NF-κB), inhibitory-κBß (IκBß), TNF-α, nitrotyrosine, matrix metalloproteinase-9 (MMP-9), and collagen content (immunohistochemistry and ELISA). RESULTS: Compared with control plaques, SCH plaques had more macrophages, T lymphocytes, and HLA-DR(+) cells, TNF-α, NF-κB, markers of oxidative stress (nitrotyrosine and O(2-) production), and MMP-9 (P < 0.01, for all), along with a lesser collagen content and IκBß levels (P < 0.001). Compared with plaques from treated patients, plaques from untreated patients had more macrophages, T lymphocytes, HLA-DR(+) cells, TNF-α, NF-κB (P < 0.001), nitrotyrosine, O(2-) production, and MMP-9 (P < 0.01, for all), along with a lesser collagen content and IκBß levels (P<0.001). CONCLUSIONS: These data suggest a potential interplay between SCH and inflammatory activity in atherosclerotic plaque progression toward instability. Moreover, LTR might contribute to plaque stabilization by inhibiting the innate immunity-dependent plaque rupture in patients with SCH.

Potential role of TCF7L2 gene variants on cardiac sympathetic/parasympathetic activity.

Variants in transcription factor 7-like 2 (266096218TCF7L2266096218USuser266096218Gene names have been italicized per house style. Please check and confirm whether there are other instances that need to be italicized or instances where italics have been inappropriately applied.) gene have been found strongly associated with an increased risk of type 2 diabetes, as well as with an impairment of glucagon-like peptide-1 (GLP-1) signalling chain. In rats, stimulation of central GLP-1 receptors increases heart rate and activates autonomic regulatory neurons. We aimed to evaluate the potential role of TCF7L2 gene polymorphisms on sympathovagal response in relation to changes in plasma insulin and/or GLP-1 concentration after glucose ingestion. Genotyping was performed for rs12255372 and rs7903146 TCF7L2 gene variants in 250 non-related healthy volunteers (mean age 27±3 years). Consistent with previous reports, both single-nucleotide polymorphisms were in strong linkage disequilibrium (D'=0.87, r(2)=0.76). A subset of 167 patients underwent an oral glucose tolerance test while a continuous recording of heart rate variability was performed. At baseline, no differences in fasting plasma insulin, in GLP-1 levels and in LF/HF (low frequency/high frequency) ratio between the three genotypes were found. Along with glucose ingestion TT subjects had lower INS(AUC) (insulin area under curve), as well as higher LF/HF(AUC) (LF/HF area under curve) values. No difference in GLP-1(AUC) (GLP-1 area under curve) between TCF7L2 gene variants was found. A multivariate analysis including multiple covariates showed that only INS(AUC,) GLP-1(AUC) and TCF7L2 gene variants were independently associated with LF/HF(AUC). In conclusion, TT genotype of rs12255372 and rs7903146 TCF7L2 gene variants is associated with lower insulin secretion and higher cardiosympathetic activity. Moreover, such effect is independent of GLP-1 and insulin plasma concentrations suggesting a potential role of such gene variants in increasing cardiovascular risk through enhanced sympathetic nervous system activity.

Use of a non-specific immunomodulation therapy as a therapeutic vasculogenesis strategy in no-option critical limb ischemia patients.

BACKGROUND/AIMS: Inflammatory mediators contribute to the impairment of vasculogenesis by reducing endothelial progenitor cells (EPCs) mobilization in atherosclerotic vasculopathy. We tested the hypothesis that administration of an oxygen/ozone mixture (IMT) might counteract this pathophysiological mechanism and enhance limb tissue perfusion in patients with critical limb ischemia (CLI). METHODS: Randomized patients with rest pain or ischemic ulcers and transcutaneous oxygen tension (TcPO(2)) <40 mmHg and/or toe pressure <50 mmHg received placebo (n=74) or a non-specific immunomodulation therapy (IMT) (n=77), autologous blood exposed to oxygen/ozone gas mixture by intragluteal injection, on day 1, 2, 7, and once a week thereafter for at least 22 weeks. Patients were evaluated for changes in TcPO(2), levels of circulating EPCs (CD34/KDR-positive cells) and inflammation (tumor necrosis factor-alpha-TNF-alpha). RESULTS: TcPO(2) and CD34/CD133-positive cells increased at 22 weeks in IMT group (P<0.01) whereas no changes were observed in placebo group. TNF-alpha levels decreased at 6 months in IMT group (P<0.001) whereas no changes were observed in placebo group. There was a strong positive correlation between CD34/KDR-positive cells and TcPO(2) (r=0.56, P<0.01). Moreover, there was an inverse correlation between CD34/KDR-positive cells and TNF-alpha (r=-0.51, P<0.01). CONCLUSIONS: Intramuscular injection of IMT may improve wound healing and limb salvage in patients with CLI.