Prognosis Of Female Patients Research Articles

A novel classification of posterior pelvic exenteration to assess prognosis in female patients with locally advanced primary rectal cancer: a retrospective cohort study from China PelvEx collaborative

PurposeSurgical techniques and the prognosis of posterior pelvic exenteration for locally advanced primary rectal cancer in female patients pose challenges that need to be addressed. Therefore, we investigated the short-term and survival outcomes of posterior pelvic exenteration in female patients using a novel Peking classification.MethodsWe retrospectively analysed a prospective database from China PelvEx Collaborative across three tertiary referral centres. A total of 172 patients who underwent combined resection for locally advanced primary rectal cancer were classified based on four subtypes (PPE-I [64/172], PPE-II [68/172], PPE-III [21/172], and PPE-IV [19/172]) according to the Peking classification; perioperative characteristics and short-term and oncological outcomes were analysed.ResultsDifferences were significant among the four groups regarding colorectal reconstruction (p < 0.001), perineal reconstruction (p < 0.001), in-hospital complications (p < 0.05), and urinary retention (p < 0.05). The R0 resection rates for PPE-I, PPE-II, PPE-III, and PPE-IV were 90.6%, 89.7%, 90.5%, and 89.5%, respectively. The 5-year overall survival rates of the PPE-I, PPE-II, PPE-III, and PPE-IV groups were 73.4%, 68.8%, 54.7%, and 37.3%, respectively. Correspondingly, their 5-year disease-free survival rates were 76.0%, 62.5%, 57.7%, and 43.1%, respectively. Notably, the PPE-IV group demonstrated the lowest 5-year overall survival rate (p < 0.001) and 5-year disease-free survival rate (p < 0.001).ConclusionThe Peking classification can aid in determining suitable surgical techniques and conducting prognostic assessments in female patients with locally advanced primary rectal cancer.

Sex Alters the Effect of Perfusion Deficits on Functional Outcome in Patients with Acute Ischemic Stroke Undergoing Mechanical Thrombectomy

Introduction: The discourse surrounding differences in cerebral hemodynamics and clinical outcomes among male and female patients treated with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) remains unresolved. We aimed to elucidate these differences by employing computed tomography perfusion (CTP) imaging before MT and examining the influence of perfusion deficits on the 90-day functional outcome. Methods: This single-center retrospective analysis involved patients with anterior circulation AIS treated with MT at the Comprehensive Stroke Center, University Hospital, Krakow, from January 2019 to July 2023. We compared male and female patients in terms of baseline characteristics, CTP deficits, hypoperfusion intensity ratio (HIR, defined as T10max/T6max), and complications. The endpoints included the 90-day excellent functional outcome, defined as modified Rankin Score <2, and the 90-day mortality rate. Results: We included 794 patients, of whom 408 were female (51.4%). Female patients had a smaller early infarct volume (median [interquartile range]: 7 mL [0–24.8] vs. 10 mL [0–33], p = 0.004), smaller penumbra volume (77.5 mL [46–117] vs. 99.5 mL [59.8–140], p < 0.001), lower HIR (0.34 [0.16–0.5] vs. 0.37 [0.2–9.53], p = 0.043) and were less likely to achieve an excellent functional outcome (55.6% vs. 66.1%, p = 0.003). For every 10 mL increase in early infarct volume, the odds for achieving an excellent outcome were lower in females (odds ratio [OR]: 0.82 [95% confidence interval: 0.73–0.92]) compared to males (OR: 0.96 [0.88–1.04]), whereas the risk of death was higher for females (OR: 1.25 [1.13–1.39] than for males (OR: 1.05 [0.98–1.14]). Discussion: Despite more favorable cerebral hemodynamic profile, female AIS patients have worse outcomes than their male counterparts. This effect seems to be independently mediated by the more pronounced impact of early infarct volume on the prognosis in female patients. These findings underscore the possible explanatory power arising from sex-specific interpretation of early infarct volume in clinical practice.

Sex-specific impact of mild obesity on the prognosis of ST-segment elevation myocardial infarction

This study aimed to clarify the existence of the mild obesity paradox in patients with ST-segment elevation myocardial infarction (STEMI) and assess the impact of mild obesity on the prognosis of STEMI. A retrospective cohort study was conducted on STEMI patients who underwent percutaneous coronary intervention at Xiangtan Central Hospital from January 1, 2020 to July 31, 2022. After excluding individuals with a body mass index (BMI) of no less than 35 kg/m2, subjects were divided into the mildly obese group (BMI, 30–35 kg/m2) and non-obese group (BMI < 30 kg/m2). The cardiovascular events and death were deemed the composite endpoints and were employed as the outcome event. The study recruited 664 patients with STEMI, including 515 males and 149 females. The mildly obese group of male patients exhibited a lower incidence of composite endpoints than the non-obese group (22.4% vs. 41.3%, P < 0.001). For female patients, no significant difference was observed in the incidence of composite endpoints between the two groups (43.6% vs. 43.8%, P = 0.987). After adjusting for confounding factors, the multivariable Cox regression analysis revealed mild obesity as an independent protective factor for male patients [hazard ratio (HR) 0.47; 95% confidence interval (CI) 0.32–0.69; P < 0.001]. Nevertheless, mild obesity was not associated with the prognosis of female patients (HR 0.96; 95% CI 0.47–1.94; P = 0.9). In male STEMI patients, mild obesity presented a paradoxical effect in improving the prognosis and functioned as an independent protective factor for the prognosis of STEMI. However, no association between mild obesity and prognosis was found in female patients, possibly due to distinct physiological and metabolic characteristics between male and female patients, which deserved further investigation and validation.

Impact of Acute Myocardial Infarction Type on Prognosis in Female Patients With Cardiogenic Shock

There are limited data about mid-term prognosis according to acute myocardial infarction (AMI) type in female patients with AMI complicated by cardiogenic shock (CS). In this study, we evaluated the impact of AMI type on prognosis in female patients who underwent percutaneous coronary intervention (PCI) for AMI complicated by CS. A total of 184 female patients who underwent PCI for AMI complicated by CS were enrolled from 12 centers in the Republic of Korea. Patients were divided into 2 groups according to AMI type: the ST-segment elevation myocardial infarction (n=114) and the non-ST-segment elevation myocardial infarction (n=70) group. Primary outcome was a major adverse cardiac event (MACE) (defined as a composite of cardiac death, myocardial infarction, or repeat revascularization). Propensity-score matching analysis was performed to reduce selection bias and potential confounding factors. During 12-month follow-up, a total of 73 MACEs occurred (ST-segment elevation myocardial infarction group, 47 [41.2%] vs non-ST-segment elevation myocardial infarction group, 26 [37.1%], p=0.643). Multivariate analysis revealed no significant difference in the incidence of MACE at 12months between the 2 groups (adjusted hazard ratio 1.16, 95% confidence interval 0.70 to 2.37, p=0.646). After propensity-score matching, the incidence of MACE at 12months remained similar between the 2 groups (hazard ratio 1.31, 95% confidence interval 0.69 to 2.52, p=0.413). The similarity in MACEs between the 2 groups was consistent across a variety of subgroups. In conclusion, after adjusting for baseline differences, AMI clinical type did not appear to increase the risk of MACEs at 12months in female patients who underwent emergency PCI for AMI complicated by CS.

Integrated analysis of single-cell RNA-seq and bulk RNA-seq unveils heterogeneity and establishes a novel signature for prognosis and tumor immune microenvironment in ovarian cancer

Ovarian cancer is a highly heterogeneous gynecological malignancy that seriously affects the survival and prognosis of female patients. Single-cell sequencing and transcriptome analysis can effectively characterize tumor heterogeneity to better study the mechanism of occurrence and development. In this study, we identified differentially expressed genes with different differentiation outcomes of tumor cells by analyzing a single-cell dataset. Based on the differentially expressed genes, we explored the differences in function and tumor microenvironment among clusters via consensus clustering. Meanwhile, WGCNA was employed to obtain key genes related to ovarian cancer. On the basis of the TCGA and GEO datasets, we constructed a risk model consisting of 7 genes using the LASSO regression model, and successfully verified that the model was characterized as an independent prognostic factor, efficiently predicting the survival prognosis of patients. In addition, immune signature analysis showed that patients in the high-risk group exhibited lower anti-tumor immune cell infiltration and immunosuppressive status, and had poorer responsiveness to chemotherapeutic drugs and immunotherapy. In conclusion, our study provided a 7-gene prognostic model based on the heterogeneity of OC cells for ovarian cancer patients, which could effectively predict the prognosis of patients and identify the immune microenvironment status of patients.

Low skull bone density is associated with poor motor prognosis in women with Parkinson's disease.

Parkinson's disease (PD) and osteoporosis are degenerative diseases that have shared pathomechanisms. To investigate the associations of skull bone density with nigrostriatal dopaminergic degeneration and longitudinal motor prognosis in female patients with PD. We analyzed the data of 260 drug-naïve female PD patients aged ≥50 years old who were followed-up for ≥3 years after their first visit to the clinic with baseline dopamine transporter (DAT) imaging. We measured skull bone density as a surrogate marker for systemic bone loss by calculating the Hounsfield unit (HU) in computed tomography scans. A Cox proportional hazard model was built to compare the rates of levodopa-induced dyskinesia (LID) or wearing-off according to skull HU. Longitudinal changes in levodopa-equivalent dose (LED) during a 3-year follow-up were assessed using a linear mixed model. A lower skull HU was associated with lower baseline DAT availability in striatal subregions; however, this relationship was not significant after adjusting for age, disease duration, body mass index, and white matter hyperintensities. After adjusting for confounding factors, a lower skull HU was significantly associated with an increased risk of LID development (hazard ratio = 1.660 per 1 standard deviation decrease, p = 0.007) and wearing-off (hazard ratio = 1.613, p = 0.016) in younger (<67 years) but not in older patients. Furthermore, a lower skull HU was associated with a steeper increase in LED during follow-up in younger patients only (β = -21.99, p < 0.001). This study suggests that baseline skull bone density would be closely linked to motor prognosis in drug naïve women with PD.

Cancer-specific survival after diagnosis in men versus women: A pan-cancer analysis.

Comprehensive understanding of cancer‐specific survival differences in gender is critical for cancer prevention and treatment. Based on the Surveillance Epidemiology and End Results database, we included data from the most prevalent cancers (lung, esophageal, liver, pancreatic, stomach, colorectal, kidney, and bladder cancer). Cox proportional hazards regression models were constructed to estimate hazard ratios, simultaneously adjusting for demographic, clinical, and treatment factors. Overall, male patients had a worse cancer‐specific survival than female patients. After adjustment for cancer prevalence with 1:1 matching, gender remained a significant factor in cancer‐specific survival. Among the included cancer types, female patients showed survival benefit in lung, liver, colorectal, pancreatic, stomach, and esophageal cancer, and male patients showed better survival in bladder cancer. Except for kidney cancer, the gender disparity was consistent between cancer patients with nonmetastatic and metastatic disease. Overall, gender appears to be a significant factor influencing cancer‐specific survival, and the prognosis of female patients is better than male patients in most cancers. This work might inspire the development of strategies for gender‐specific precision cancer prevention and treatment.

Value of conventional ultrasound and shear wave elastography in assessing disease activity and prognosis in female patients with Sjögren's syndrome.

This study aimed to assess the diagnostic value of labial salivary gland changes in female patients with Sjögren's syndrome (SS) having different European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) and serological markers using conventional ultrasound and shear wave elastography (SWE). A total of 82 female inpatients diagnosed with SS were retrospectively examined at the First Affiliated Hospital of Soochow University from July 2020 to December 2021. The patients were divided into two groups based on the ESSDAI score: remission group (ESSDAI <5) and active group (ESSDAI ≥5). The prognosis of patients was assessed using serological markers. The ultrasound examination of bilateral labial glands was performed in all patients to analyse the quantity and area of the largest single labial gland per unit detection range (Smax). The SWE of labial glands was performed in different groups. The Smax and quantity of labial glands on both sides were correlated with patient age in 82 female patients with SS. Emin, Emean and Emax of the remission group based on ESSDAI were significantly lower than the active group (p<0.001), and the areas under the receiver operating characteristic (ROC) curve for these three in diagnosing were 0.720, 0.728 and 0.734, respectively. The differences in Emean, Emin and Emax values of labial glands between the two groups of immunoglobulin G (IgG) <16g/L and IgG ≥16g/L were statistically significant (p<0.05), and the area under the ROC curve (AUC) for the three values were 0.825, 0.830, and 0.815, respectively. There were statistically significant differences (p<0.05) in Emin, Emean, and Emax of labial glands between the hypocomplementaemic and non-hypocomplementaemic groups, and the AUC for the three values were 0.840, 0.843, and 0.819, respectively. Conventional ultrasound and SWE of the labial gland can reflect the disease activity and prognosis of patients with SS, and more conveniently assess the progression in the patients and provide imaging evidence.

Prognosis for Young Females with Pseudomyxoma Peritonei of Appendiceal Origin and Unilateral or Bilateral Ovaries Preserved During Cytoreductive Surgery.

ObjectiveTo determine prognosis for young female patients with peritoneal pseudomyxoma (PMP) of appendiceal origin and unilateral or bilateral ovaries preserved during cytoreductive surgery (CRS).MethodsClinical data of female patients treated with CRS with or without hyperthermic intraperitoneal chemotherapy (HIPEC) at the Aerospace Center Hospital, Beijing between January, 2009 and December, 2019 were retrospectively reviewed. Patients had no changes in the bilateral ovaries on gross pathological observations or biopsy during CRS, and normal ovarian function. The demographic and clinical characteristics and prognosis of women with ovaries preserved (ovarian preservation group) or resected (ovarian resection group) during CRS were compared. Independent prognostic factors for survival were identified using univariate and multivariate analysis.Results40 patients were included in the final analysis. 19 patients chose ovarian preservation while 21 patients underwent ovarian resection. Completeness of cytoreduction (CCR) scores were CCR-0/1. There were significant differences in age (<40 vs. ≥40), symptoms, intraoperative HIPEC (Y vs. N), and histopathologic subtype of PMP (low-grade vs. high-grade) (p < 0.001) between patients in the ovarian preservation and ovarian resection groups. In the ovarian preservation group, median overall survival (OS) was 59 months (range, 53–65 months), and the 5-year survival rate was 37.9%. Median disease-free survival (DFS) was 13 months (range, 9–17 months), and the 5-year recurrence rate was 87.4%. In the ovarian resection group, the 5-year survival rate was 87.7%, and the 5-year recurrence rate was 18.3%. Median OS and median DFS were not reached. In patients with low-grade PMP, median DFS was significantly longer in patients with ovarian resection compared to ovarian preservation (p < 0.001). Univariate analysis showed histopathologic subtype of PMP (low-grade vs. high-grade, p < 0.001) was significantly associated with OS and DFS. On multivariate analysis, high-grade histopathologic subtype of PMP was an independent predictor of poor prognosis (OS and DFS).ConclusionHistopathologic subtype of PMP represents an independent predictor of prognosis in female patients with PMP of appendiceal origin and unilateral or bilateral ovaries preserved during CRS. These findings imply that ovarian preservation is a more suitable option for young females with low-grade PMP compared to high-grade PMP. Further prospective studies should be done investigating the role of resection of uninvolved ovaries in PMP.

Effects of treatments on gender differences in patients with localized muscle-invasive bladder cancer

To explore the gender differences in survival under different treatments in localized muscle-invasive bladder cancer (MIBC), and to find clinical strategies to improve the poor prognosis of female with bladder cancer (BC). Patients with localized MIBC were collected in the SEER database from 2010 to 2016 to analyze the gender differences in clinical characteristics. Propensity score matching was used to balance the effects of confounding factors. Kaplan-Meier method and Cox proportional hazards regression model were performed to compare the overall survival (OS) and cancer-specific survival (CSS) of patients between different treatment subgroups. The entire cohort included 13,272 T2N0M0 MIBC patients, with a male-to-female incidence of 3:1. Compared with male patients, females had a higher age of onset and more blacks. There were more female patients undergoing bladder-sparing surgery (BSS) alone, and the OS and CSS were worse than those in males. The gender difference showed statistical significance in the BSS group, but not in the radical cystectomy (RC) group. The survival of localized MIBC patients can be affected by treatments. Multi-modality treatment and RC may improve the survival prognosis of female patients.

Short-Term Prognostic Predictive Evaluation in Female Patients With Ischemic Stroke: A Retrospective Cross-Sectional Study.

Introduction and AimStroke is a disease with high mortality and morbidity. Although studies are generally performed on all patients with stroke, it is known that gender has an effect on etiology and prognosis. This study aimed to determine the importance of clinical stroke scales and laboratory markers in determining the short-term prognosis of female patients with ischemic stroke of anterior circulation.Materials and MethodsThe study was planned as a retrospective and cross-sectional study. SEDAN score, the National Institutes of Health stroke scale (NIHSS), the Modified Rankin Scale (mRS), the Glasgow Coma Scale (GCS), and THRIVE score applied to the patients at the time of admission were recorded. Admission blood glucose, hemoglobin, leukocyte, urea, albumin, and blood lipid levels were evaluated. The relationship of all these parameters with in-hospital prognosis, mortality, and disability at discharge was examined. The relationship between groups and data was analyzed using the SPSS package program after the normality analysis.ResultsIn this study, there were 733 female patients with stroke with a mean age of 69.53 ± 14.51 years and 858 male patients with stroke with a mean age of 64.27 ± 13.29 years. Hospitalization time, length of stay in the intensive care unit, ventilation need rate, mortality, and dependency rate were higher in female patients (p = 0.001). The NIHSS, SEDAN, and THRIVE scores were higher in female patients who had in-hospital mortality, had a poor prognosis, and who were discharged as dependent (p = 0.001). GCS was lower in this patient group (p = 0.001). Blood glucose, creatinine, leukocytes, urea, and CRP levels were higher; the albumin and hemoglobin levels was lower in female patients who had fatal outcomes (p = 0.009, 0.001, 0.001, 0.001, 0.001, and 0.020; respectively). In female patients who were dependent at discharge, blood urea, glucose, and CRP levels were higher and the albumin levels were lower than those in female patients who achieved functional independence (p = 0.001, 0.016, 0.002, and 0.001, respectively).ConclusionOur study showed that the short-term prognosis is worse in female patients who had an ischemic stroke of anterior circulation. It also revealed some clinical and laboratory parameters that could predict this situation. More intensive monitoring may be needed to improve prognosis in female patients.

Combined Estrogen Alpha and Beta Receptor Expression Has a Prognostic Significance for Colorectal Cancer Patients.

We reported that high estrogen receptor beta (ERβ) expression is independently associated with better prognosis in female colorectal cancer (CRC) patients. However, estrogen receptor alpha (ERα) is expressed at very low levels in normal colon mucosa, and its prognostic role in CRC has not been explored. Herein, we investigated the combined role of ERα and ERβ expression in the prognosis of female patients with CRC, which, to the best of our knowledge, is the first study to investigate this topic. A total number of 306 primary CRCs were immunostained for ERα and ERβ expression. A Cox regression model was used to evaluate overall survival (OS) and disease-free survival (DFS). The combined expression of high ERβ + negative ERα correlates with longer OS (HR = 0.23; 95% CI: 0.11–0.45, P <0.0001) and DFS (HR = 0.10; 95% CI: 0.03–0.26, P < 0.0001) and a more favorable tumor outcome, as well as significantly higher expression of antitumorigenic proteins than combined expression of low ERβ + positive ERα. Importantly, we found that low ERβ expression was associated with local recurrence of CRC, whereas ERα expression was correlated with liver metastasis. Overall, our results show that the combined high ERβ + negative ERα expression correlated with a better prognosis for CRC patients. Our results suggest that the combined expression of ERα and ERβ could be used as a predictive combination marker for CRC patients, especially for predicting DFS.

Clinicopathological value of long non-coding RNA profiles in gastrointestinal stromal tumor.

BackgroundLong non-coding RNAs (lncRNAs) have been implicated in diagnosis and prognosis in various cancers. However, few lncRNA signatures have been established for prediction of gastrointestinal stromal tumors (GIST). We aimed to explore a lncRNA signature profile that associated with clinical relevance by mining data from Gene Expression Ominus (GEO) and Surveillance, Epidemiology, and End Results (SEER) Program.MethodsUsing a lncRNA-mining approach, we performed non-negative matrix factorization (NMF) consensus algorithm in Gastrointestinal stromal tumors (GISTs) cohorts (61 patients from GSE8167 and GSE17743) to cluster LncRNA expression profiles. Comparative markers selection, and Gene Set Enrichment Analysis (GSEA) algorithm were performed between distinct molecular subtypes of GIST. The survival rate of GIST patients from SEER stratified by gender were compared by Kaplan–Meier method and log-rank analysis. lncRNA-mRNA co-expression analysis was performed by Pearson correlation coefficients (PCC) using R package LINC. Somatic copy number alterations of GIST patients (GSE40966) were analyzed via web server GenePattern GISTIC2 algorithm.ResultsA total of four lncRNA molecular subtypes of GIST were identified with distinct biological pathways and clinical characteristics. LncRNA expression profiles well clustered the GIST samples into small size (<5 mm) and large size tumors (>5 mm), which is a fundamental index for GIST malignancy diagnosis. Several lncRNAs with abundant expression (LRRC75A-AS1, HYMAI, NEAT1, XIST and FTX) were closely associated with tumor size, which may suggest to be biomarkers for the GIST malignancy. Particularly, LRRC75A-AS1 was positively associated with tumor diameters and suggested an oncogene in GIST. Co-expression analysis suggested that chromosome region 17p11.2–p12 may contribute to the oncogenic process in malignant GIST. Interestingly, the gender had a strong influence on clustering by lncRNA expression profile. Data from the Surveillance, Epidemiology, and End Results (SEER) Program were further explored and 7983 patients who were diagnosed with GISTs from 1973 to 2014 were enrolled for analysis. The results also showed the favorable prognosis for female patients. The survival rate between male and female with GIST was statistically significant (P < 0.0001). Gene set enrichment analysis (GSEA) indicated distinct pathways between female and male, and malignant GIST was associated with several cancer metabolism and cell cycle associated pathways.ConclusionsThis lncRNAs-based classification for GISTs may provide a molecular classification applicable to individual GIST that has implications to influence lncRNA markers selection and prediction of tumor progression.

Gender differences in patients with structural heart disease undergoing VT ablation

This study sought to examine gender differences in patients with structural heart disease (SHD) referred for ablation of ventricular tachycardia (VT). Female patients are often underrepresented in large studies. Significant differences in the clinical presentation, treatment, and prognosis of female patients have been described in previous studies. We investigated 88 female patients with SHD undergoing VT ablation (mean age 59 years, 56% nonischemic cardiomyopathy, mean left ventricular ejection fraction 35%, 82% in electrical storm). A case-control study with 88 male patients was performed and the results regarding clinical and procedural characteristics, acute and long-term results of the two groups were compared. The female patients had more arrhythmogenic substrate, as they more commonly presented with electrical storm (p = .016) and had a higher number of inducible VT morphologies during the procedure (p = .018). Moreover, the female patients were less likely to have an optimized heart failure medical treatment at baseline (p = .030) and required more time from the first manifestation of the VT to ablation referral (p = .034). Although fewer epicardial ablations were performed in female patients (p = .019), the two groups showed similar results regarding VT noninducibility as ablation endpoint (p = .844), major procedure-related complications (p = .719) and freedom from VT during follow-up (p = .268). Moreover, the overall mortality in the two groups was similar (p = .176). Advanced NYHA class was associated with worse transplant and assist-device-free survival in the female group. Female patients presenting for VT ablation had more arrhythmogenic substrate and were less likely to have an optimized heart failure medical treatment. Nevertheless, the procedural acute and long-term outcomes between the two genders were similar.

Screening of Human Epidermal Growth Factor Receptor 2 (HER2) Extracellular Domain for Potential Epitopes by Using Immuno-informatics Tools

The human epidermal growth factor receptor 2 (HER2) is a well-studied oncoprotein that is overexpressed in a considerable proportion of breast cancer patients. The increased expression of this tyrosine kinase receptor is usually associated with poor clinical prognosis in female patients with breast cancer. In these patients, specific response of immune system against HER2 had been observed. This suggests that immunotherapy approaches can be employed for enhancing the response of tumor infiltrating lymphocytes against HER2 in susceptible tumor microenvironment. In this regard, peptide vaccines are considered one of the most affordable immunotherapy modalities due to their low production cost and long-term effect. For this purpose, we have screened the extracellular domain of HER2 crystal for potential B-cells and T-cells epitopes by using different immuno-informatics tools. The output peptides were then refined and filtered according to their antigenicity, allergenicity and vulnerability to selected proteases. Here, we present multiple B-cells and T-cells epitope candidates against HER2 extracellular domain with high antigenicity, low allergenicity and good resistance for selected proteolytic enzymes. These filtered epitopes can be used for design and construction of anti-HER2 peptide vaccine for potential use in HER2 positive breast cancer patients. Additionally, the sequence of linear B-cells epitopes can be used for the design of monoclonal antibody variable region against HER2 extracellular domain.

Nomogram for preoperative estimation of prognosis after retropubic tension free vaginal tape in female patients with stress urinary incontinence.

To identify risk factors by developing a nomogram for predicting surgical outcomes for female patients who underwent tension free vaginal tape (TVT) for stress urinary incontinence (SUI). Data on 365 patients with pure SUI who underwent TVT at the Shanghai General Hospital between February, 2017 and July, 2018, were retrospectively collected. Within this group, symptoms of patients who were found to have disappeared or have been improved (subjective success group) were compared with symptoms of those patients who were found to have no change or recurrence (subjective failure group). We evaluated the effect of treatment after TVT surgery on SUI patients based upon patient prognosis. During the study period, 327 women underwent TVT surgery and met the qualifications for inclusion in six-month follow-up consultations and 38 patients were lost. Multivariable logistic regression analysis of risk factors that were important in relation to the failure of surgery indicated two independent predictors: total cholesterol (TC) (P=0.005) and maximal urethral closure pressure (MUCP) (P=0.028). We developed a nomogram to predict prognosis after TVT in female patients with SUI using these parameters. We developed a predictive model for preoperative estimation of prognosis in female patients who underwent TVT based treatment for SUI. This model could select patients who were found to have successful postoperative outcomes, which can lead to a rational therapeutic choice.

Abstract P885: Sex-Based Differences of Cerebral Venous Sinus Thrombosis Patients in the Appalachian Region

Introduction: The majority of data describing Cerebral Venous Sinus Thrombosis (CVST) patients has been collected outside the United States (U.S.). Females are reported at higher incidence with more favorable outcomes. Available U.S. data have poor representation of the Appalachian region, which has a higher burden of chronic disease and lower socioeconomic level. The objective of this study was to examine the sex-based characteristics of an Appalachian CVST cohort. Methods: Data were collected in a retrospective cohort using the Kentucky Appalachian Stroke Registry (KApSR), from admissions in a comprehensive stroke center serving 554,300 from the Appalachian region. Patients 18 years and older diagnosed with CVST from 2010-2018 were retrieved via International Classification of Diseases 9 and 10 codes. Secondary analysis by review of patient records was performed to screen for inclusion criteria and acquire additional data points. Results: Fifty-eight patients met inclusion criteria and 35(60%) were female. Twenty-three (40%) (15F 8M) had Kentucky Medicaid as primary insurance. At least one comorbidity was documented in 44(76%) (26F 18M) and 32(55%) (17F 13M) had 2 or more comorbidities. Headache was the most common presenting complaint, present in 33(56%) (19F 14M) with 8 (5F 3M) absent symptoms other than headache. Those with headache were more likely to have multi-sinus involvement OR 7.9 (1.9-32.7). Abnormal neurological exam was documented at admission in 36(64%) (20F 16M). Infarct was present in 19(32%) (11F 8M) hemorrhage in 3(1F 2M). Those with infarct were more likely to have superior sagittal involvement OR 3.6 (1.1 - 12.0). The National Institutes of Health Stroke Scale (NIHSS) was administered to 43(25F 18M) patients. Median NIHSS was 2.0 at admission, 0.5 at discharge and 19 (13F 6M) recorded an NIHSS &gt;2 at admission. Median length of stay was 6 days. Thirty-nine patients (67%) (20F 19M) were routinely discharged to home vs hospice, skilled nursing facility, long term care or death. Female patients were less likely to be discharged to home OR 0.3 (0.1-0.9). Conclusion: The results suggest a high burden of comorbid disease among CVST patients in the Appalachian region. This may explain the worse prognosis of female patients in this cohort.

Sex Differences in Left Ventricular Remodeling and Outcomes in Chronic Aortic Regurgitation.

Background: Left ventricular (LV) dilatation is a key compensatory feature in patients with chronic aortic regurgitation (AR). However, sex-differences in LV remodeling and outcomes in chronic AR have been poorly investigated so far. Methods: We performed cardiovascular magnetic resonance imaging (CMR) including phase-contrast velocity-encoded imaging for the measurement of regurgitant fraction (RegF) at the sinotubular junction, in consecutive patients with at least mild AR on echocardiography. We assessed LV size (end-diastolic volume indexed to body surface area, LVEDV/BSA) and investigated sex differences between LV remodeling and increasing degrees of AR severity. Cox-regression models were used to test differences in outcomes between men and women using a composite of heart failure hospitalization, unscheduled AR intervention, and cardiovascular death. Results: 270 consecutive patients (59.6% male, 59.8 ± 20.8 y/o, 59.6% with at least moderate AR on echocardiography) were included. On CMR, mean RegF was 18.1 ± 17.9% and a total of 65 (24.1%) had a RegF ≥ 30%. LVEDV/BSA was markedly closer related with AR severity (RegF) in men compared to women. Each 1-SD increase in LVEDV/BSA (mL/m2) was associated with a 9.7% increase in RegF in men and 5.9% in women, respectively (p-value for sex-interaction < 0.001). Based on previously published reference values, women—in contrast to men—frequently had a normal LV size despite severe AR (e.g., for LVEDV/BSA on CMR: 35.3% versus 8.7%, p < 0.001). In a Cox-regression model adjusted for age, LVEDV/BSA and RegF, women were at significantly higher risk for the composite endpoint when compared to men (adj. HR 1.81 (95%CI 1.09–3.03), p = 0.022). Conclusion: In patients with chronic AR, LV remodeling is a hallmark feature in men but not in women. Severity of AR may be underdiagnosed in female patients in the absence of LV dilatation. Future studies need to address the dismal prognosis in female patients with chronic AR.

Myeloid-Derived Suppressor Cell Subsets Drive Glioblastoma Growth in a Sex-Specific Manner.

Myeloid-derived suppressor cells (MDSC) that block antitumor immunity are elevated in glioblastoma (GBM) patient blood and tumors. However, the distinct contributions of monocytic (mMDSC) versus granulocytic (gMDSC) subsets have yet to be determined. In mouse models of GBM, we observed that mMDSCs were enriched in the male tumors, whereas gMDSCs were elevated in the blood of females. Depletion of gMDSCs extended survival only in female mice. Using gene-expression signatures coupled with network medicine analysis, we demonstrated in preclinical models that mMDSCs could be targeted with antiproliferative agents in males, whereas gMDSC function could be inhibited by IL1β blockade in females. Analysis of patient data confirmed that proliferating mMDSCs were predominant in male tumors and that a high gMDSC/IL1β gene signature correlated with poor prognosis in female patients. These findings demonstrate that MDSC subsets differentially drive immune suppression in a sex-specific manner and can be leveraged for therapeutic intervention in GBM. SIGNIFICANCE: Sexual dimorphism at the level of MDSC subset prevalence, localization, and gene-expression profile constitutes a therapeutic opportunity. Our results indicate that chemotherapy can be used to target mMDSCs in males, whereas IL1 pathway inhibitors can provide benefit to females via inhibition of gMDSCs.See related commentary by Gabrilovich et al., p. 1100.This article is highlighted in the In This Issue feature, p. 1079.

Unique Genetic Characteristics and Clinical Prognosis of Female Patients with Lung Cancer Harboring RET Fusion Gene

Objectives: Since no report on the genetic characteristics of RET fusions in female patients with lung cancer is available, this study revealed the genetic and prognostic characteristics of female patients with lung cancer harboring RET fusion gene for the first time. Materials and Methods: The molecular portfolios of 1,652 patients with lung cancer who underwent targeted next-generation sequencing for screening candidate oncogenic drivers in their histological specimens from January 2016 to December 2018 were investigated in this study. Results: RET fusions were identified in 23 cases, 15 females [2.2% (15/685)] and eight males [0.9% (8/902)]. The most common fusions were KIF5B–RET in females [80% (12/15)] and CCDC6–RET in males [50% (4/8)], along with some rare RET fusions, including SLC39A8–RET, ITIH2–RET, FYCO1–RET and SLC25A36–RET in females, and MIR3924–RET, ZBTB41–RET and ITGA8–RET in males. Interestingly, the highly positive, moderate positive, and negative rates of PD–L1 staining in females were 33.3%, 8.3% and 58.3%, respectively; whereas those in males were 0%, 57.1% and 42.9%. Additionally, the progression-free survival (PFS) of stage IV patients was comparatively shorter in females, shown by the medians of 4.0 months in females and 6.0 months in males (P = 0.029). A 43-year-old female patient with metastatic lung adenocarcinoma, who harbored KIF5B–RET fusion and had highly positive PD–L1 staining, received nivolumab as second-line treatment. A partial response was achieved and remained for more than five months. Conclusion: Unique genetic characteristics and poor prognosis are found in female patients with lung cancer harboring RET fusion gene. Immune checkpoint inhibitors are a potential option for patients with high expression of PD–L1.