Risk In Female Patients Research Articles

Correlation between vascular endothelial function and bone mineral density in type 2 diabetes mellitus patients with MAFLD

Objective The relationship between vascular endothelial function and bone mineral density (BMD) in T2DM patients with metabolic dysfunction associated fatty liver (MAFLD) is still unclear. This study aims to analyse the correlation between vascular endothelial function and BMD or fracture risk in T2DM patients with MAFLD. Methods A total of 872 T2DM patients aged ≥50 years were enrolled and divided into two groups according to the diagnostic criteria of MAFLD: MAFLD (+) and MAFLD (−). Flow-mediated dilation (FMD) was measured by high-resolution ultrasound to reflect vascular endothelial function. BMD was measured by dual-energy X-ray bone densitometry, and FRAX scores were calculated for 10-year hip fracture risk (HF1) and major osteoporotic fracture risk (MOF). Results After multivariate adjustment, there was no significant correlation between FMD and BMD in MAFLD (−) group (p > 0.05). In MAFLD (+) and FMD < 4% group, FMD was positively correlated with WB, LS, and FN BMD, while FMD was negatively correlated with fracture risk and osteoporotic fracture history, and this correlation was only observed in female patients. However, FMD was not correlated with BMD and fracture risk and osteoporotic fracture history in 4%≤FMD ≤ 7% and FMD > 7% groups. Conclusions The association of FMD with BMD in T2DM patients with MAFLD varies according to FMD level. The decrease of FMD is associated with reduced BMD and increased fracture risk in female patients with FMD < 4% group. FMD may be an influential factor for the occurrence and development of osteoporosis, and has some clinical value in early diagnosis of osteoporosis in T2DM patients with MAFLD.

Alzheimer's disease risk associated with changes in Epstein-Barr virus nuclear antigen 1-specific epitope targeting antibody levels

BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder influenced by age, sex, genetic factors, immune alterations, and infections. Multiple lines of evidence suggest that changes in antibody response are linked to AD pathology. MethodsTo elucidate the mechanisms underlying AD development, we investigated antibodies that target autoimmune epitopes using high-resolution epitope microarrays. Our study compared two groups: individuals with AD (n = 19) and non-demented (ND) controls (n = 19). To validate the results, we measured antibody levels in plasma samples from AD patients (n = 96), mild cognitive impairment (MCI; n = 91), and ND controls (n = 97). To further explore the invlovement of EBV, we performed epitope masking immunofluorescence microscopy analysis and tests to induce lytic replication using the B95–8 cell line. ResultsIn this study, we analyzed high-resolution epitope-specific serum antibody levels in AD, revealing significant disparities in antibodies targeting multiple epitopes between the AD and control groups. Particularly noteworthy was the significant down-regulation of antibody (anti-DG#29) targeting an epitope of Epstein-Barr virus nuclear antigen 1 (EBNA1). This down-regulation increased AD risk in female patients (odds ratio up to 6.6), but not in male patients. Our investigation further revealed that the down-regulation of the antibody (anti-DG#29) is associated with EBV reactivation in AD, as indicated by the analysis of EBV VCA IgG or IgM levels. Additionally, our data demonstrated that the epitope region on EBNA1 for the antibody is hidden during the EBV lytic reactivation of B95–8 cells. ConclusionOur findings suggest a potential relationship of EBV in the development of AD in female. Moreover, we propose that antibodies targeting the epitope (DG#29) of EBNA1 could serve as valuable indicators of AD risk in female.

Decade-long Trends in Incidence of Slipped Capital Femoral Epiphysis in the United States: A Nationwide Database Analysis of Over 33 Million Patients.

Slipped capital femoral epiphysis (SCFE) is a prevalent pediatric hip disorder linked to severe complications, with childhood obesity as a crucial risk factor. Despite the rising obesity rates, contemporary data on SCFE's epidemiology remain scarce in the United States. This study examined SCFE incidence trends and demographic risk factors in the United States over a decade. A decade-long (2011 to 2020) retrospective cohort study was undertaken using the Healthcare Cost and Utilization Project National Inpatient Sample. Patients aged younger than 18 years were identified and further analyzed if diagnosed with SCFE through ICD-9 or ICD-10 codes. Key metrics included demographics variables, with multivariate regression assessing demographic factors tied to SCFE, and yearly incidence calculated. Of 33,180,028 pediatric patients, 11,738 (0.04%) were diagnosed with SCFE. The incidence escalated from 2.46 to 5.96 per 10,000 children, from 2011 to 2020, mirroring childhood obesity trends. Lower socioeconomic status children were predominantly affected. Multivariate analysis revealed reduced SCFE risk in female patients, while Black and Hispanic ethnicities, alongside the Western geographic location, had an increased risk. This study underscores a twofold increase in SCFE incidence over the past decade, aligning with childhood obesity upsurge. Moreover, SCFE disproportionately affects lower SES children, with male sex, Black and Hispanic ethnicities amplifying the risk. This calls for targeted interventions to mitigate SCFE's effect, especially amidst the vulnerable populations.

Relationship Between Overactive Bladder and Bone Fracture Risk in Female Patients.

Overactive bladder (OAB) has recently been recognized as an independent risk factor for falls and fractures. This study aimed to predict fracture risk in female patients with OAB symptoms. We assessed and compared the fracture risk in newly diagnosed female patients with OAB to those without OAB using the Fracture Risk Assessment Tool (FRAX), and investigated the relationship between fracture risk and OAB severity. The present single-center, cross-sectional study included 177 female participants (79 with OAB, 98 without OAB). The OAB group was older (p=0.033) and shorter (p=0.010) compared to the non-OAB group. Compared to the non-OAB group, the OAB group had more patients with hypertension (p<0.001) and diabetes mellitus (p=0.011), as well as higher risks for major fractures (non-OAB group: 15.2±13.2%; OAB group: 23.6±14.1%; p<0.001) and hip fractures (non-OAB group: 6.3±11.0%; OAB group: 10.6±10.0%; p=0.007). In addition, those with moderate/severe OAB had the most significantly elevated risks for both major fractures (non-OAB group: 15.2±13.2%, mild-OAB: 17.6±12.5%, moderate/sever-OAB: 26.4±14.0%; p<0.001) and hip fractures (non-OAB group: 6.3±11.0%, mild-OAB: 6.5±7.6%, moderate/sever-OAB: 12.5±10.4%; p<0.001). Among the OAB symptoms, nocturia had the strongest correlation with fracture risk (major fracture, ρ=0.534; hip fracture, ρ=0.449; all p<0.001). Patients with severe OAB, and particularly severe nocturia, should be closely monitored with timely and aggressive symptom management; however, an interventional study incorporating the management of OAB symptoms is required to confirm whether the proactive management of OAB symptoms reduces the risk of fractures in older females.

USE OF PSYCHIATRIC RISK FACTORS IN PREDICTING 10 YEAR CARDIOVASCULAR RISK FOR CHINESE PATIENTS WITH SCHIZOPHRENIA

Abstract Patients with schizophrenia are known to have excessive cardiovascular morbidity. Traditional Framingham risk prediction models do not consider additional risk attributable to factors related to psychiatric illness and treatment. The Framingham risk scores also tend to over-estimate cardiovascular risk in Chinese cohorts. This study aimed to develop a 10-year cardiovascular risk prediction model using routine clinical data from an electronic health database in Hong Kong. We identified a cohort of 39,449 patients who were diagnosed with schizophrenia between Year 2005 and 2015 and had no history of cardiovascular disease (CVD). Cox proportional hazards regression models were employed to determine psychiatric and clinical risk factors influencing the timing of incident CVD over 10 years. Psychiatric variables of interest included comorbid psychiatric disorders, duration of schizophrenia, use of antidepressant, use of first- or second-generation antipsychotics (FGA &amp; SGA) at baseline and duration of exposure to FGA and SGA. The main analysis showed that comorbid substance use-related disorders (HR = 1.52; 95% CI 1.22 – 1.90; P &amp;lt; 0.001) increased CVD risk and each year of cumulative exposure to FGA increased CVD risk by 2% (HR = 1.02; 95% CI 1.01 – 1.04; P = 0.001). The use of antidepressant predicted a higher CVD risk in female patients (HR 1.19; 95% CI 1.02 – 1.38; P = 0.028). Our risk model predicted that 20.6% of patients had a CVD risk ≥ 20% over 10 years. Our risk models may offer an accessible clinical tool to help monitor cardiovascular risk in patients with schizophrenia.

Comparative Risk of Type 2 Diabetes after Gastrectomy and Endoscopic Resection for Gastric Cancer: A Nationwide Cohort Study.

Patients with gastric cancer (GC) experience 2 characteristic treatment modalities (gastrectomy or endoscopic resection), which may induce heterogeneity in the risk of post-cancer treatment type 2 diabetes (T2D). We investigated differences in the risk for T2D development in survivors of GC according to the 2 treatment methods. This retrospective nationwide population-based cohort study included 14,646 patients with GC who underwent gastrectomy (n = 12,918) or endoscopic resection (n = 1,728). We enrolled patients who survived for at least 5 years after gastrectomy or endoscopic resection, had no history of diabetes, and had not received adjuvant chemotherapy. T2D risk was evaluated using Cox regression for the gastrectomy group and compared to that of the endoscopic resection group. Because of the competing risks of incident T2D and death, a competing risk regression was performed. After a median follow-up duration of 8.1 years, the incidence rates of T2D in the endoscopic resection group and gastrectomy group were 7.58 and 6.98 per 1,000 person-years, respectively. Patients undergoing gastrectomy showed a significantly higher risk for developing T2D than patients undergoing endoscopic resection (hazard ratio [HR], 1.37; 95% CI 1.18 to 1.58; p < 0.0001). In subgroup analyses, gastrectomy was associated with increased T2D risk in female patients (HR, 1.72; 95% CI 1.22 to 2.43; p = 0.030 for interaction). Among GC survivors, patients undergoing gastrectomy showed a 37% increased risk of T2D development compared to patients undergoing endoscopic resection. Subgroup analyses showed that T2D risk increased by up to 72% in female patients. These results provide insights for establishing screening and preventive strategies for GC survivors to prevent T2D according to different treatment modalities.

Asymptomatic pyuria and bacteriuria are not risk factors for urinary tract infection in women with type 2 diabetes mellitus initiated SGLT2 inhibitors.

Asymptomatic pyuria and bacteriuria are more prevalent in diabetic patients and may be associated with urinary tract infection (UTI). The aim of this study is to investigate the association between asymptomatic pyuria/bacteriuria at the initiation of SGLT2 inhibitor and UTI risk in female patients with type 2 diabetes. The study was designed as a practical, single-center, prospective, cohort study. The female outpatients with type 2 diabetes initiated SGLT2 inhibitor were included. Patients who were symptomatic or treated in the past 3months for urinary or genital tract infection, had a high risk for UTI were excluded. Hospitalization/antibiotic use for indications other than UTI were exclusion criteria during follow-up. All patients were followed up for 3months. Pyuria and bacteriuria were exposure and, UTI was the outcome. Cumulative incidence and relative risk of UTI were analyzed for pyuria and bacteriuria. 143 female patients were included among 1132 female type 2 diabetic patients. 13 patients were excluded during follow-up. 41.5% of the patients (n = 54) had pyuria and 28.5% (n = 37) had bacteriuria. The cumulative incidence of UTI was 20% in the whole cohort, 25,9% (n = 14/54) in the pyuria group and 18.9% (n = 7/37) in the bacteriuria group. The relative risk of UTI was 1.64 (95% CI: 0.82-3.26, p = 0.15) for pyuria, 0.92 (95% CI: 0.42-2.01, p = 0.84) for bacteriuria, and 1.2 (95% CI: 0.47-3.08, p = 0.69) for pyuria plus bacteriuria. Adjusted odd ratios revealed similar results. Asymptomatic pyuria/bacteriuria at the initiation of SGLT2 inhibitors are not risk factors for UTI in women with type 2 diabetes.

Increased 10-year cardiovascular disease risk in depressed patients with coexisting subclinical hypothyroidism.

The prevalence of depressive disorder (DD) and subclinical hypothyroidism (SH) was almost twofold higher in women compared with men, both of which are confirmed to be related to cardiovascular disease (CVD) risk. The current study aimed to identify the prevalence of CVD risk factors and evaluate the 10-year CVD risk in female depressed patients with and without comorbid SH. We recruited 1744 female inpatients with a diagnosis of DD. Venous blood samples were taken from all patients for lipid and thyroid hormones. Framingham Risk Score (FRS) was used to estimate the 10-year CVD risk. Female depressed patients with SH had increased BMI, higher Hamilton Anxiety Scale (HAMA) scores, higher LDL-C, TC, UA, and a higher 10-year CVD risk than euthyroid DD groups. Serum TSH levels and HAMA scores were critical predictive variables for 10-year CVD risk in female depressed patients with comorbid SH. Our study suggests that female depressed patients with SH have a high 10-year CVD risk. Serum TSH levels and HAMA scores may be helpful to predict cardiovascular risk in female patients with SH. The increased CVD risk in female depressed patients with comorbid SH requires more attention from researchers and clinicians.

Bleeding risk in female patients undergoing intravesical injection of onabotulinumtoxinA for overactive bladder: a Danish retrospective cohort study

Introduction and hypothesisWe aimed to examine the risk of bleeding in female patients undergoing intravesical onabotulinumtoxinA (BTX-A) treatments and provide clinical recommendations for the perioperative management of patients on antithrombotic therapy prior to BTX-A treatments.MethodsThis was a retrospective cohort of Danish female patients, who had their first BTX-A treatment because of an overactive bladder at the Department of Gynecology and Obstetrics, Herlev and Gentofte University Hospital, between January 2015 and December 2020. Data extraction was from an electronic medical journal system. BTX-A, Botox® Allergan was injected in the detrusor at 10–20 sites. Significant bleeding during or after a BTX-A treatment was defined as persistent macroscopic hematuria. Bleeding reporting was based on information obtained from journal notes.ResultsWe included 400 female patients, who had a total of 1,059 BTX-A treatments. Median age at first BTX-A treatment was 70 years (IQR 21), and median number of BTX-A treatments was 2 (range 1–11). In total, 27.8% (n=111) received antithrombotic therapy. Within this group, 30.6% and 69.4% were on anticoagulant and antiplatelet therapy. No cases of hematuria were reported in our cohort. We found that no patients stopped their antithrombotic therapy, were bridged, or monitored by International Normalized Ration (INR) levels.ConclusionsWe suggest that BTX-A treatments might be classified as low-risk procedures. Discontinuation of antithrombotic therapy is not required in the perioperative management of this patient group.

Propensity Matched Outcomes of Minimally Invasive Mitral Surgery: Does a Heart-Team Approach Eliminate Female Gender as an Independent Risk Factor?

There is increasing evidence that female gender is an independent risk factor for cardiac surgery. Minimally invasive mitral surgery (MIV) has proven to have excellent long-term results, but little is known about gender-dependent outcomes. The aim of our study was to analyze our heart team's decision-based MIV-specialized cohort. In-hospital and follow-up data were retrospectively collected. The cohort was divided into gender groups and propensity-matched groups. Between 22 July 2013 and 31 December 2022, 302 consecutive patients underwent MIV. Before matching, the total cohort showed that women were older, had a higher EuroSCORE II, were more symptomatic, and had more complex valve pathology and tricuspid regurgitation resulting in more valve replacements and tricuspid repairs. Intensive and hospital stays were longer. In-hospital deaths (n = 3, all women) were comparable, with more atrial fibrillation in women. The median follow-up time was 3.44 (0.008-8.9) years. The ejection fraction, NYHA, and recurrent regurgitation were low and comparable and atrial fibrillation more frequent in women. The calculated 5-year survival and freedom from re-intervention were comparable (p = 0.9 and p = 0.2). Propensity matching compared 101 well-balanced pairs; women still had fewer resections and more atrial fibrillation. During the follow-up, women had a better ejection fraction. The calculated 5-year survival and freedom from re-intervention were comparable (p = 0.3 and p = 0.3). Despite women being older and sicker, with more complex valve pathology and subsequent replacement, early and mid-term mortality and the need for reoperation were low and comparable before and after propensity matching, which might be the result of the MIV setting combined with our patient-tailored decision-making. We believe that a multidisciplinary heart team approach is crucial to optimize patient outcomes in MIV, and it might also reduce the widely reported increased surgical risk in female patients. Further studies are needed to prove our findings.

Sex-based differences in risk of ischaemic stroke or systemic embolism after BNT162b2 or CoronaVac COVID-19 vaccination in patients with atrial fibrillation: a self-controlled case series and nested case-control study.

Patients with atrial fibrillation (AF) have a higher risk of ischaemic stroke or systemic embolism, with a greater risk for female patients. This study aims to evaluate the risk of ischaemic stroke or systemic embolism and bleeding following COVID-19 vaccination in patients with AF and the sex differences. Self-controlled case series (SCCS) analysis was conducted to evaluate the risk of ischaemic stroke or systemic embolism and bleeding following BNT162b2 or CoronaVac in patients with AF, using the territory-wide electronic medical records from the Hospital Authority and vaccination records from the Department of Health in Hong Kong. Patients with a primary diagnosis of ischaemic stroke, systemic embolism, or bleeding in the inpatient setting between 23 February 2021 and 31 March 2022 were included. A nested case-control analysis was also conducted with each case randomly matched with 10 controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Conditional Poisson regression was used in the SCCS analysis, and conditional logistic regression was used in the nested case-control analysis to assess the risks, and all analyses were stratified by sex and type of vaccines. Among 51 158 patients with AF, we identified an increased risk of ischaemic stroke or systemic embolism after the first dose of BNT162b2 in SCCS analysis during 0-13 days [incidence rate ratio 6.60, 95% confidence interval (CI) 1.51-28.77] and 14-27 days (6.53, 95% CI 1.31-32.51), and nested case-control analysis during 0-13 days (adjusted odds ratio 6.21, 95% CI 1.14-33.91) and 14-27 days (5.52, 95% CI 1.12-27.26) only in female patients. The increased risk in female patients following the first dose of CoronaVac was only detected during 0-13 days (3.88, 95% CI 1.67-9.03) in the nested case-control analysis. No increased risk of ischaemic stroke or systemic embolism was identified in male patients, and no increased risk of bleeding was detected in all patients with AF for both vaccines. An increased risk of ischaemic stroke or systemic embolism after COVID-19 was also observed in both females (17.42, 95% CI 5.08-59.73) and males (6.63, 95% CI 2.02-21.79). The risk of ischaemic stroke or systemic embolism after COVID-19 vaccination was only increased in female patients with AF. However, as the risk after COVID-19 was even higher, proactive uptake of COVID-19 vaccines is recommended to prevent the potential severe outcomes after infection.

Sexual Dysfunction and Associated Factors in Women with Psoriasis.

Psoriasis, a chronic inflammatory skin disease, may negatively affect sexual function; however, data on the sexual health of female patients with psoriasis in Vietnam are lacking. To assess the risk of sexual dysfunction (SD) and its associated factors in female patients with psoriasis who visited the Ho Chi Minh City Hospital of Dermato-Venereology from April 2020 to October 2020. Cross-sectional study. A total of 302 female patients with psoriasis aged 18 to 49 years were recruited. The Female Sexual Function Index (FSFI) was used to assess the risk of SD (cut-off value at 26). The risk of SD accounted for 79.1% of the study population and was not associated with age, comorbidities, weight, or trigger factors. Urban dwellers had greater odds of SD risk than non-urban dwellers (OR = 2.63). Similar trends were observed in terms of higher education than grade 12, less than once a week of physical activities, and psychological stress as a trigger factor (OR = 1.89, 2.65, and 3.41, respectively). Female psoriasis patients with SD risk had a lower age of onset and higher weight, BMI, waist circumference, and PASI than patients who did not (P < 0.05). Psychological stress and high PASI were independent risk factors of SD risk in female patients with psoriasis (P < 0.05). Factors with negative impacts on psoriasis may also increase the risk of SD in female patients; among these factors, psychological stress and high PASI were the strongest predictors of SD in female patients with psoriasis.

Clinicopathologic Features and Prognosis of Female Early Breast Cancer With HER2 Low Expression: A Propensity Score Matched Analysis.

Metastatic breast cancer (MBC) patients with low expression of human epidermal growth factor 2 (HER2) have been proven to benefit from HER2 targeted therapy. We aimed to determine how HER2-low status affected survival and metastatic risk as well as how it affected pathological complete response (pCR) in neoadjuvant chemotherapy (NAC) patients. According to the results of immunohistochemistry (IHC) and in situ hybridization (ISH) testing, 321 female patients were sorted into HER2-low (IHC 1+/2+ with ISH negative) and HER2-zero (IHC 0) groups using propensity score matching (PSM). Overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS) were compared for both groups, while pCR was only analyzed for NAC patients. In total, 97 patients in each group after PSM were included. We discovered that pCR was not associated with HER2 expression status in 45 patients who underwent NAC. Five-year OS in the HER2-low group was significantly higher (98.99%) than in the HER2-zero group (95.87%, P = .044); however, this difference was not reflected in the 5-year DFS (90.61 vs 90.52%, P = .868) and 5-year DDFS (93.67 vs 91.53%, P = .757). Meanwhile, multivariate analysis revealed that HER2-low expression could indicate better OS (P = .047, hazard ratios [HRs] = 16.121, 95% confidence interval [CI] = 1.035-251.046), but it had no prognostic value for DFS or DDFS. When compared with HER2-zero expression, HER2-low expression was not connected to pCR and could not modify metastasis risk in female patients with early-stage breast cancer (BC), but it may prolong patient survival.

Risk of Cardiovascular Diseases Associated With Medications Used in Attention-Deficit/Hyperactivity Disorder

Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety. To provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs). PubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022. Observational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD. Independent reviewers extracted data and assessed study quality using the Good Research for Comparative Effectiveness (GRACE) checklist. Data were pooled using random-effects models. This study is reported according to the Meta-analyses of Observational Studies in Epidemiology guideline. The outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest. Nineteen studies (with 3 931 532 participants including children, adolescents, and adults; 60.9% male), of which 14 were cohort studies, from 6 countries or regions were included in the meta-analysis. Median follow-up time ranged from 0.25 to 9.5 years (median, 1.5 years). Pooled adjusted relative risk (RR) did not show a statistically significant association between ADHD medication use and any CVD among children and adolescents (RR, 1.18; 95% CI, 0.91-1.53), young or middle-aged adults (RR, 1.04; 95% CI, 0.43-2.48), or older adults (RR, 1.59; 95% CI, 0.62-4.05). No significant associations for stimulants (RR, 1.24; 95% CI, 0.84-1.83) or nonstimulants (RR, 1.22; 95% CI, 0.25-5.97) were observed. For specific cardiovascular outcomes, no statistically significant association was found in relation to cardiac arrest or arrhythmias (RR, 1.60; 95% CI, 0.94-2.72), cerebrovascular diseases (RR, 0.91; 95% CI, 0.72-1.15), or myocardial infarction (RR, 1.06; 95% CI, 0.68-1.65). There was no associations with any CVD in female patients (RR, 1.88; 95% CI, 0.43-8.24) and in those with preexisting CVD (RR, 1.31; 95% CI, 0.80-2.16). Heterogeneity between studies was high and significant except for the analysis on cerebrovascular diseases. This meta-analysis suggests no statistically significant association between ADHD medications and the risk of CVD across age groups, although a modest risk increase could not be ruled out, especially for the risk of cardiac arrest or tachyarrhythmias. Further investigation is warranted for the cardiovascular risk in female patients and patients with preexisting CVD as well as long-term risks associated with ADHD medication use.

Diabetes associated with HPV infection in women aged over 50 years: A cross-sectional study from China's largest academic woman's hospital.

Metabolic disturbances and immune alterations caused by diabetes are not just bystanders of HPV infection, but the conclusion that diabetes increases the risk of HPV infection requires more clinical epidemiological evidence to confirm. Our aim was to evaluate the association of diabetes with HPV infection risk in female patients aged over 50 years in the cervical clinic. We conducted a cross-sectional study of 6402 women aged over 50 years in the cervical clinic between May 2019 and March 2022 from China's largest academic woman's hospital. The quantitative-effect relationship between diabetes and HPV infection was observed by dose-response graph. Segmented multivariate logistic regression analysis was conducted to estimate the relative risk of HPV infection in diabetes patients. Multivariable predicted marginal proportions from logistic regression models were used to compute adjusted risk ratios. There is a nonlinear relationship between HbA1c and the risk of HPV infection. When the HbA1c exceeds 5.7%, there is a saturation effect. After adjustment for confounders, the risk ratio for HPV infection in women with prediabetes was 1.09 (95% CI: 1.00-1.18) compared with women with HbA1c <5.7%, and the risk ratio for HPV infection in women with diabetes was 1.18 (95%). CI: 1.04-1.33). Sensitivity analysis showed that the risk ratio for HPV infection was 1.47 (95% CL: 1.07-1.91) when diabetes was associated with vaginitis. E-value analysis suggested robustness to unmeasured confounding. Diabetes and prediabetes are at increased risk of coinfection with HPV in female patients aged over 50 years in the cervical clinic.

Sex hormones and the risk of cardiovascular disease and mortality in male and female patients with chronic kidney disease: A systematic review and meta-analysis.

Patients with chronic kidney disease (CKD) commonly experience sex hormone disturbances, which may be associated with the risk of cardiovascular disease (CVD) and mortality. This review aimed to systematically evaluate current findings on the association of sex hormone levels with the risk of CVD events and mortality (CVD and all-cause) in the CKD population. Articles were systematically searched in CINAHL, Cochrane, and PubMed. A total of 1739 articles were independently screened by two reviewers and 17 prospective cohort studies were included. The clinical conditions of the patients were those with non-dialysis CKD [mean/median estimated glomerular filtration rate (eGFR) between 15-51 ml/min/1.73 m2 ] and those on chronic dialysis (mean/median vintage between 6-125 months). The sample size ranged from 111 to 2419 and the mean/median age of subjects ranged from 52 to 72 years. The sex hormones studied were testosterone, estradiol, prolactin, dehydroepiandrosterone sulfate, and relaxin. A random-effects model was used to generate a pooled hazard ratio (HR) to evaluate the association of total testosterone levels with the risk of CVD and all-cause mortality. Most studies examined total testosterone levels (11 out of 17 studies) and studied only male patients (12 out of 17 studies). A lower total testosterone level was associated with a higher risk of CVD mortality [HR 4.37 (95% CI 1.40-13.65)] and all-cause mortality [1.96 (1.35-2.83)] in males with CKD. To conclude, there is a strong need for additional studies examining the association of sex hormones with cardiovascular and mortality risk in female patients with CKD.

Sex-specific evaluation and redevelopment of the GRACE score in non-ST-segment elevation acute coronary syndromes in populations from the UK and Switzerland: a multinational analysis with external cohort validation

The Global Registry of Acute Coronary Events (GRACE) 2.0 score was developed and validated in predominantly male patient populations. We aimed to assess its sex-specific performance in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and to develop an improved score (GRACE 3.0) that accounts for sex differences in disease characteristics. We evaluated the GRACE 2.0 score in 420 781 consecutive patients with NSTE-ACS in contemporary nationwide cohorts from the UK and Switzerland. Machine learning models to predict in-hospital mortality were informed by the GRACE variables and developed in sex-disaggregated data from 386 591 patients from England, Wales, and Northern Ireland (split into a training cohort of 309 083 [80·0%] patients and a validation cohort of 77 508 [20·0%] patients). External validation of the GRACE 3.0 score was done in 20 727 patients from Switzerland. Between Jan 1, 2005, and Aug 27, 2020, 400 054 patients with NSTE-ACS in the UK and 20 727 patients with NSTE-ACS in Switzerland were included in the study. Discrimination of in-hospital death by the GRACE 2.0 score was good in male patients (area under the receiver operating characteristic curve [AUC] 0·86, 95% CI 0·86-0·86) and notably lower in female patients (0·82, 95% CI 0·81-0·82; p<0·0001). The GRACE 2.0 score underestimated in-hospital mortality risk in female patients, favouring their incorrect stratification to the low-to-intermediate risk group, for which the score does not indicate early invasive treatment. Accounting for sex differences, GRACE 3.0 showed superior discrimination and good calibration with an AUC of 0·91 (95% CI 0·89-0·92) in male patients and 0·87 (95% CI 0·84-0·89) in female patients in an external cohort validation. GRACE 3·0 led to a clinically relevant reclassification of female patients to the high-risk group. The GRACE 2.0 score has limited discriminatory performance and underestimates in-hospital mortality in female patients with NSTE-ACS. The GRACE 3.0 score performs better in men and women and reduces sex inequalities in risk stratification. Swiss National Science Foundation, Swiss Heart Foundation, Lindenhof Foundation, Foundation for Cardiovascular Research, and Theodor-Ida-Herzog-Egli Foundation.

Sex-specific analysis in Behçet's disease reveals higher genetic risk in male patients

ObjectivesBehçet's disease tends to be more severe in men than women. This study was undertaken to investigate sex-specific genetic effects in Behçet's disease. MethodsA total of 1762 male and 1216 female patients with Behçet's disease from six diverse populations were studied, with the majority of patients of Turkish origin. Genotyping was performed using an Infinium ImmunoArray-24 BeadChip, or extracted from available genotyping data. Following imputation and extensive quality control measures, genome-wide association analysis was performed comparing male to female patients in the Turkish cohort, followed by a meta-analysis of significant results in all six populations. In addition, a weighted genetic risk score for Behçet's disease was calculated and compared between male and female patients. ResultsGenetic association analysis comparing male to female patients with Behçet's disease from Turkey revealed an association with male sex in HLA-B/MICA within the HLA region with a GWAS level of significance (rs2848712, OR = 1.46, P = 1.22 × 10−8). Meta-analysis of the effect in rs2848712 across six populations confirmed these results. Genetic risk score for Behçet's disease was significantly higher in male compared to female patients from Turkey. Higher genetic risk for Behçet's disease was observed in male patients in HLA-B/MICA (rs116799036, OR = 1.45, P = 1.95 × 10−8), HLA-C (rs12525170, OR = 1.46, P = 5.66 × 10−7), and KLRC4 (rs2617170, OR = 1.20, P = 0.019). In contrast, IFNGR1 (rs4896243, OR = 0.86, P = 0.011) was shown to confer higher genetic risk in female patients. ConclusionsMale patients with Behçet's disease are characterized by higher genetic risk compared to female patients. This genetic difference, primarily derived from our Turkish cohort, is largely explained by risk within the HLA region. These data suggest that genetic factors might contribute to differences in disease presentation between men and women with Behçet's disease.

FOXP3 Gene Variants in Patients with Systemic Lupus Erythematosus: Association with Disease Susceptibility in Men and Relationship with Abortion in Women.

FOXP3, an important transcription factor of regulatory T cells has shown a contribution to the development of various autoimmune diseases. To investigate the influence of FOXP3 polymorphisms (rs3761548 and rs2294021) on systemic lupus erythematosus (SLE) susceptibility and patients' characteristics. Genotyping was performed on 265 patients with SLE and 404 healthy controls using PCR-RFLP. Patients' demographic, laboratory, and clinical information were all documented. The relationship between the SNPs and patients' characteristics was statistically analyzed. The frequency of C/- genotype in male patients was significantly higher than in the healthy male controls, whereas the frequency of A/- genotype was lower (OR=0.53; 95% CI=0.28-1.00, p=.05). Analysis of the correlation between these SNPs and the patients' characteristics showed a longer disease duration in the rs3761548 C/- carriers and a correlation with arthralgia in both SNPs. In the females, there was a significant association between CC haplotype and disease susceptibility (OR=0.6, CI=0.38-0.94, p=.027). A significant association of both SNPs with the history of abortion was also detected. The frequencies of the rs3761548 AA (p=.006) and the rs2294021 CC genotypes (p=.038) and AC/AC combination (p=.033) were higher in women who had an abortion. We found a correlation between the rs3761548 AC genotype and the decreased C4 level and cardiovascular involvement, and the rs2294021 CC genotype with ESR, neurological involvement, and photosensitivity. FOXP3 rs3761548 C/- genotype association with disease susceptibility in male patients, an association of both SNPs with the abortion risk in female patients, and the correlation between these SNPs and several clinical features of the patients suggest their association with the disease development and pathology.

Pioglitazone and breast cancer risk in female patients with type 2 diabetes mellitus: a retrospective cohort analysis

BackgroundWhether pioglitazone may affect breast cancer risk in female diabetes patients is not conclusive and has not been investigated in the Asian populations.MethodsThe reimbursement database of Taiwan’s National Health Insurance was used to enroll an unmatched cohort and a propensity score-matched cohort of ever users and never users of pioglitazone in female patients with newly diagnosed type 2 diabetes during 1999–2008. The patients were alive on January 1, 2009 and were followed up for breast cancer incidence until December 31, 2011. Cox regression was used to estimate hazard ratios for ever users and tertiles of cumulative duration of pioglitazone therapy versus never users, and for cumulative duration of pioglitazone therapy treated as a continuous variable. Three models were created for the unmatched cohort and the matched cohort, respectively: 1) without adjustment for covariates; 2) after adjustment for covariates that differed with statistical significance (P-value < 0.05) between ever users and never users; and 3) after adjustment for all covariates.ResultsThere were 174,233 never users and 6926 ever users in the unmatched cohort; and 6926 never users and 6926 ever users in the matched cohort. After a median follow-up of 2.8 years, the numbers of incident breast cancer were 1044 in never users and 35 in ever users in the unmatched cohort and were 41 and 35, respectively, in the matched cohort. Hazard ratios suggested a null association between pioglitazone and breast cancer in all three models in either the unmatched cohort or the matched cohort. The overall hazard ratio after adjustment for all covariates was 0.758 (95% confidence interval: 0.539–1.065) in the unmatched cohort and was 0.824 (95% confidence interval: 0.524–1.296) in the matched cohort. None of the hazard ratios for the tertiles of cumulative duration of pioglitazone therapy and for the cumulative duration being treated as a continuous variable were statistically significant.ConclusionsThis study suggests a null association between pioglitazone and breast cancer risk in female patients with type 2 diabetes mellitus. However, because of the small breast cancer cases and the limited follow-up time, further studies are warranted to confirm our findings.