Male Patients Research Articles

Abstract Su602: Categorizing Witnessed Out-of-Hospital Cardiac Arrest by Bystander Type

Witnessed out-of-hospital cardiac arrests (OHCA) are associated with improved outcomes with increased likelihood of rapid activation of the emergency response system thus decreasing no-flow or low-flow times. Current literature has largely treated witnessed cardiac arrest as binary (i.e. was a cardiac arrest witnessed Yes/No). We hypothesize there is a need to further delineate and categorize distinct bystander types; these differences may have important downstream contributions to outcomes and survival and targets for improving training and recognition. For example, a bystander who is a healthcare provider with formal training or has experience performing resuscitation may be associated with better outcomes than a non-medical layperson. We examined a national-level database of emergency medical services (EMS) activations in the United States (NEMSIS). Inclusion criteria were any adult (18+ years) cardiac arrest activation between January 2022 and December 2023. Cardiac arrests taking place after EMS arrival (EMS-witnessed) were excluded. Witnessed status was described as unwitnessed, witnessed by healthcare provider, witnessed by family member, or witnessed by bystander. Across basic demographic variables, we compared overall witnessed rates, family member witnessed rates, and healthcare worker witnessed rates. A total of 791,217 cardiac arrests met inclusion criteria. Overall, 62.5% of arrests were unwitnessed, 22.8% were witnessed by a family member, and 6.3% were witnessed by a healthcare provider. Across sex, cardiac arrests in male patients were more likely to be witnessed, however, cardiac arrests in female patients were more likely to be witnessed by a family member or healthcare provider (p<0.05). Significant differences in witnessed status were also seen across race/ethnicity. For instance, cardiac arrests in Black/African American patients were less likely to be witnessed by family members and cardiac arrests in Hispanic/Latino patients were less likely to be witnessed by healthcare workers (p<0.05). Our analysis of a large and nationally-representative database of cardiac arrest suggests differences in rates of witnessed cardiac arrest and – perhaps, more importantly – the existence of different types of bystanders. Moreover, when considering these differences, there is heterogeneity among demographic variables. Future research is needed to understand whether these differences in bystander type may contribute to differences in outcomes.

Systemic Coagulation Derangement as an Early Sign of Oxygenator Failure in Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) Without Anticoagulation

Background and Clinical Significance: Veno-venous extracorporeal membrane oxygenation (VV ECMO) has become a widely accepted supportive treatment for severe acute respiratory distress syndrome (ARDS) in intensive care units (ICUs). Although it has gained popularity, some of its aspects, including optimal anticoagulation management and the best means of monitoring hemostasis, remain unresolved. Thrombosis and bleeding are still important complications of ECMO. Case Presentation: A 44-year-old male patient, with no underlying conditions, was diagnosed with severe acute respiratory distress syndrome (ARDS) due to AH1N1 influenza. He presented severe hypoxemia despite the use of mechanical ventilation, neuromuscular blocking agent infusion and prone position. VV ECMO was used, and coagulation was stopped on ECLS day 6 due to severe pulmonary hemorrhage. The systemic hemostatic disorders found in this patient were difficult to differentiate from disseminated intravascular coagulation (DIC) or sepsis-induced coagulopathy (SIC), improved transiently after circuit exchange, and resolved only after discontinuation of ECMO. The patient was discharged fully conscious and cooperative, with no apparent neurological deficit. Conclusions: Systemic hemostatic abnormalities may precede oxygenator failure and mimic DIC or SIC. Timely oxygenator exchange may therefore be considered. However, it is a high-risk procedure, especially in fully ECLS-dependent patients.

Abstract 4138593: Sex-, Age-and Racial- specific disparities, echocardiographic myocardial mechanics and biomarkers, and 1-year survival among patients with heart failure.

Background: Heart failure with reduced ejection fraction (HFrEF) is a global health burden affecting millions worldwide, particularly among resource constrained communities. Information is limited regarding addative prognostic relations of sex -, age- and racial- differences, myocardial mechanics and biomarkers, in HFrEF. Aim: Assess prognostic implications of sex-, age- and racial- related disparity in HFrEF; and additive prognostic implications of these parameters to other markers including echocardiography (myocardial mechanics). Methodology: The HFrEF patients’ data were prospectively evaluated during the initial assessment and those hospitalized, and subseguently followed for at least 12months. Patients' KCCQ and EQ-5D-5L Questionnaires were assessed during the initial evaluation and follow-up. Sex, age and racial/ethnic disparities, in-hospital management, follow-ups, health status and 1year mortality were assessed. These parameters were further assessed in addition to biomakers and echocardiographic parameters including LV and RV systolic and distolic strain. Multivariable Cox regression models were fitted to investigate additive prognostic differences. Results: The study population consisted mainly of blacks and major factors were hypertension, diabetes, mitral valve disease, and older age (p<0.0001). Of the initial 2642 screened, only 1883 completed the 1year follow-up visit (mean LVEF 38%). Women were likely to have hypertension, atrial fibrillation and diabetes (p<.001). Rheumatic or valvular heart diseases were more commonly identified among younger, black ethnicity, and males patients. No demonstrated sex differences in functional class and biomarkers including NT-proBNP levels. Men demonstrated significant risk for one-year mortality than women, as was black ethnicity and older age. Impaired strain parameters (RV>LV systolic) were independent risk factors for poor survival, more so when added to sex, racial ethnicity, age and biomarkers i.e. the NT-proBNP levels. Conclusion: The prevalence of HFrEF was higher than anticipated. Men, black ethnicity and older age were associated with a high one-year mortality. Impaired strain (RV>LV systolic) parameters were independent risk factors for poor survival, with additive prognostic implications to sex, racial ethnicity, age and traditional biomarkers. These parameters should be assessed routunely to risk stratify HFrEF patients earlier during their disease course.

Abstract 4138397: Gender Difference in Prevalence and Survival of Pulmonary Hypertension: A Prospective Cohort Study of 502,173 UK Biobank Participants

Background: Research into pulmonary hypertension (PH) reveals significant sex-based disparities in long-term survival rates. Notably, women, despite being more susceptible to PH, often experience better survival outcomes than men—a phenomenon possibly linked to the "estrogen paradox." This study leverages the comprehensive UK Biobank to examine the role of sex in influencing these outcomes. By exploring differences in PH incidence and survival rates across genders, our research aims to provide a deeper understanding of the mechanisms at play and inform more effective, gender-specific analysis. Methods: This prospective cohort study utilized data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until November 30, 2023, for England and Scotland, and May 31, 2022, for Wales. Through diagnostic codes, medical records, and imaging studies, 3,296 PH cases and 497,580 cases without PH were identified . We followed them for the mortality rates over a period of 10 years. Survival analysis was conducted using Kaplan-Meier curves and Cox proportional hazards models to assess sex-specific survival differences, adjusting for confounders like age, BMI, ethnic, menopause, smoking status, and comorbidities. Results: During 7,978,349 person-years of follow-up, of 502,173 participants in this prospective cohort, 3,296 were diagnosed with PH, while 497,580 did not receive the PH diagnosis. The prevalence of PH in the male cohort and the female cohort were 0.76% (1743 of 228,991 men) and 0.57% (1553 of 273,182 women), respectively, with significant difference between the two groups (p<0.001). In the PH cohort, the mortality rates of patients were 47.06%. In the male patients with PH, the mortality rate was significantly higher than the female PH patients (51.78% vs. 41.53%, p<0.001). After stratifying women into menopause and no-menopause group, Kaplan-Meier curves showed that even the age of male group was significantly younger than the menopause group (p<0.001), the male still had worse survival situation. Conclusion: To conclude, the prevalence of PH in the male participants was significantly higher than the female participants. While the mortality rate in the male participants was also significantly higher than the female participants.

Abstract 4138486: Unplanned Readmissions Due to Post-Acute Myocardial Infarction Complications: Insights from the Nationwide Readmission Database

Introduction: Acute myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Despite advances in treatment, readmissions within 30 days remain a significant concern, impacting both patient outcomes and healthcare costs. This study aims to analyze trends in 30-day readmission rates (30-dr) for patients discharged after an acute MI. Methods: We analyzed the 2016-2020 Nationwide Readmission Database for patients aged ≥ 18 years with initial admission of acute MI and were readmitted within 30 days. Variables were identified using ICD-10 codes. The primary outcome was trends in 30-dr; secondary outcomes included trends in complications, mortality rate, length of stay (LOS), and healthcare costs. Multivariate and descriptive bivariate analyses were conducted, with p-values <0.05 considered statistically significant. Results: There was a notable decrease in the acute MI index admissions total number from 507,608 in 2016 to 471,292, p trend < 0.01. The index admission mean age throughout the study years was 66.9 ± 13.5 years, with 62.7% male patient. Index admission inpatient mortality dropped reaching OR 0.92 (CI 0.88-0.96) by 2020 with a drop of 0.08 OR from 2016 with (p trend < 0.01) using logistic regression. The index admission LOS remained consistent with allover average 4.64 days (p trend = 0.25). The mean healthcare costs saw a significant increase from $22,456 in 2016 to $27,249 in 2020 (p trend < 0.01). The 30-dr trend decreased from 9.41% in 2016 to 7.8% in 2020 (p trend < 0.01). The top five readmission reasons in order included heart failure (14.94%of total readmission), myocardial reinfarction (13.59%), sepsis (4.49%), Acute kidney injury(2.4%), and chest pain(2.1%). The risk of readmission went up 1% for each year increase of age and 12% for female gender (using OR,logistic regression), despite initial admission was more male dominant. Conclusion: Our study demonstrates a declining initial admission, its mortality rate,and 30-dr. There was readmission healthcare costs increase. We noticed four top complications-driven readmission falling under cardiovascular diseases category with the top one as heart failure and myocardial reinfarction. This study tries to highlight relevant data to target interventions to reduce readmissions and complications, ultimately improving patient outcomes and reducing the healthcare economic burden.

Isofraxidin alleviated radiation-induced testicular damage via the Nrf2/HO-1-NLRP3/ASC Axis

OBJECTIVE: Radiotherapy is used to treat patients with tumors; however, radiation (IR)-induced testicular injury, which has no effective treatment approved in clinical practice, significantly influences their prognosis and quality of life. The protective effects and underlying mechanisms of action of isofraxidin (IF) against IR-induced testicular injury were investigated. Methods: A mouse testis injury model was established using 5 Gy irradiation. H&E staining, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to measure DNA damage, apoptosis, inflammatory reactions, and oxidative stress in the testes of mice after irradiation. The effectiveness of IF irradiation on testicular injury was evaluated, and the mechanisms of the related oxidative stress and inflammatory response pathways are discussed. Results: IF can improve IR-induced testicular injury by inhibiting the increased levels of DNA damage, apoptosis rate, oxidative stress, and inflammatory factors. The radioprotective effects of IF on testicular injury are mediated by the stimulation of Nrf2/HO-1 or suppression of NLRP3 inflammasome signaling pathways. In addition, crosstalk between the Nrf2/HO-1 and NLRP3 inflammasome signaling pathways was elucidated, in which the inhibition of the NLRP3 inflammasome was mediated by the activation of Nrf2 signaling with IF upon IR exposure. Conclusion: IF can be a potent radioprotective agent to mitigate testicular damage, and may provide a new therapeutic option to alleviate the side effects of radiotherapy in male patients with tumors.

Abstract 4122035: The Distinct Natural History, Phenotype Spectrum, Familial Penetrance and Clinical Outcomes in Desmin ( DES )-Associated Cardiomyopathy

Background: Pathogenic/likely pathogenic variants (P/LP) in the desmin ( DES ) gene cause heterogeneous cardiomyopathy and skeletal myopathy phenotypes. Research Questions: Limited data suggest that patients with P/LP DES variants have a high incidence of major adverse cardiac events (MACEs), including cardiac conduction disease requiring pacemaker implantation (CCD-PM), sustained ventricular arrhythmias (VA), and heart failure (HF) events (HF hospitalization, heart transplant, HF-related death). However, small cohort sizes have limited full clinical characterization. Aims: We aimed to describe the natural history, phenotype spectrum, familial penetrance and MACE in patients with P/LP DES variants identified via clinical genetic testing. Methods: We conducted a systematic review and individual patient data meta-analysis of cardiac and skeletal myopathy phenotypes and MACE (CCD-PM, VA and HF events) in patients with P/LP DES variants by retrieving publications from Medline (PubMed) and Embase. Diagnosis of cardiomyopathy or MACE were both considered evidence of cardiac involvement. Results: Out of 4,212 screened records, 72 met inclusion criteria. In total, 230 patients were included (52.6% male, 52.2% probands, median age: 31 years at first evaluation [22.0; 42.8]). Eighty-five (37.0%) patients showed isolated cardiac involvement, 89 (38.7%) cardiac and skeletal muscle involvement, 39 (17.0%) only skeletal muscle involvement, and 17 (7.4%) had neither phenotype. Overall, 130 (56.5%) patients were diagnosed with a cardiomyopathy and 134 (57.4%) patients developed MACE (96 [41.7%] had CCD-PM, 36 [15.7%] sustained VA, and 43 [18.7%] HF events). Familial cardiac disease penetrance was 69.1% (76/110) in relatives with P/LP DES variants. Out of 40 patients who presented with isolated CCD-PM phenotype, 18 (45.0%) were diagnosed with a cardiomyopathy after 6 [2.0; 16.0] years of follow-up. In multivariable analysis, male sex and non-missense variants were associated with higher risk of sustained VA (HR 2.71, p=0.008, and HR 4.62, p<0.001, respectively) and HF events (HR 2.63, p=0.005, and HR 2.79, p=0.015). Conclusions: DES cardiomyopathy demonstrates a distinct natural history, characterized by high familial penetrance and a high MACE burden. Male patients and those carrying non-missense variants are at higher risk for sustained VA events and may benefit from primary preventive ICD implantation even in the absence of severe LV systolic dysfunction.

Abstract 4116975: Safety signals with SGLT2 inhibitor use in diabetic males with erythrocytosis, but not in females: Findings from the CANVAS Program and CREDENCE trial

Backgrounds: Mediation analyses have shown that an increase in hematocrit (Hct) levels significantly contributes to the cardiorenal benefits of SGLT2 inhibitors (SGLT2i). However, given the link between erythrocytosis and poor prognosis, concerns remain about whether SGLT2i-induced erythropoiesis in patients with erythrocytosis may increase thromboembolic events (TE) including myocardial infarction (MI). Methods: We conducted a pooled analysis utilizing individual participant data from the CANVAS Program and the CREDENCE trial, both aimed to evaluate the efficacy and safety of canagliflozin versus placebo in diabetic patients. The primary outcome was a composite of MI, stroke, or any other TE. Sex-specific Cox analyses were performed to assess effect modifications by baseline Hct levels, treated as categorical (anemia, normal, and erythrocytosis) or continuous variable. Results: Of the participants for whom baseline Hct values were available (98.5% [14,321/14,543]), 35% were female. Canagliflozin significantly increased the percentage of erythrocytosis from baseline to 1 year in males (5.6% to 16.9%) and females (1.9% to 5.2%), unlike placebo. Overall, canagliflozin did not alter the risk of the primary outcome for either male (HR 0.97; 95% CI, 0.86–1.10) or female (HR 0.95; 95% CI, 0.78–1.15). In males, baseline Hct levels modified treatment effect on the primary outcome, whether treated as categorical or continuous variables (Pinteraction <0.05), with benefits in anemic patients and harm in those with erythrocytosis (Figure). Meanwhile, no effect modifications were noted in females. In analyses for each component of the primary outcome, canagliflozin consistently reduced the risk of MI, stroke, and any TE in anemic male patients (HR 0.53, 0.49, and 0.71, respectively). However, mixed results were observed in those with erythrocytosis (HR 1.77, 0.62, and 1.11, respectively), suggesting detrimental effects on the primary outcome in these patients were primarily driven by MI. No heterogeneity by Hct was found for heart failure hospitalization or kidney outcome in both sexes. Conclusion: Canagliflozin may pose a safety concern regarding the risk of TE in diabetic male patients with erythrocytosis.

Possibly more favorable short‐term outcomes with minimally invasive surgery than with open surgery in total gastrectomy for locally advanced gastric cancer: A single high‐volume center study

AbstractBackgroundMinimally invasive total gastrectomy (MTG) requires advanced surgical skills and is still associated with a higher rate of postoperative complications than other types of gastrectomy. Additionally, the short‐term outcomes of MTG compared to open total gastrectomy (OTG) for locally advanced gastric cancer have yet to be demonstrated.MethodsWe retrospectively compared short‐term outcomes between MTG and OTG for locally advanced gastric and esophago‐gastric junctional cancer, performed at the Cancer Institute Hospital, Tokyo, during the period from January 2017 to March 2024. Propensity score matching (PSM) was conducted to adjust for potential confounders.ResultsIn total, 359 patients were included, with 190 remaining after PSM, resulting in 95 in each group. The MTG group experienced a significantly lower incidence of postoperative complications of Clavien–Dindo classification (C‐D) ≥3 than the OTG group (3.2% vs. 11.6%, p = 0.026). Moreover, the rate of postoperative intra‐abdominal infectious complications (IAIC) was significantly lower in the MTG than in the OTG group (C‐D ≥ 2; 7.4% vs. 17.9%, p = 0.029 and C‐D ≥ 3; 2.1% vs. 9.5%, p = 0.030, respectively). Subgroup analyses showed the odds ratios for IAIC with C‐D ≥ 2 to be more favorable for the MTG than the OTG group in male patients, those ≥70 years of age, patients without esophageal invasion, those without neoadjuvant chemotherapy, those diagnosed with cT≥3, and patients not undergoing combined resection of other organs except for the gallbladder or spleen.ConclusionsMTG for locally advanced gastric cancer may provide improved short‐term outcomes compared to OTG, when performed or supervised by surgeons with high proficiency in laparoscopic techniques.

Abstract 4122350: Most Diabetes Mellitus Patients Had Right Lower Pulmonary Vein Thrombi; Additionally, Many Patients Had Extended Large Rod-Like Thrombi in the Left Atrium

Background: Retrieved thrombus studies have shown that retrieved thrombi have calcifications, indicating that the thrombi are old. Left atrium diverticula (LADs) are common; however, the mechanisms of LAD formation are poorly understood. Pulmonary vein thrombi (PVTs) are common and are underestimated. In 2022, we reported that 98.6% of senior patients with age-related diseases such as hypertension, dyslipidemia and atrial fibrillation had PVTs, as estimated by cardiac computed tomography (CT) and transesophageal echocardiography (TEE). Additionally, we reported a case in which a malignant lymphoma patient had ATs in the right lower pulmonary vein, in which extended large rod-like thrombi in the left atrium (LA) were found, as determined by TEE. Patients with type 2 diabetes mellitus (T2DM) must have PVTs. The characteristics of extended LA thrombi in patients with T2DM are unclear. Methods: Thirty-one patients with T2DM (73.5 +/- 8.9 y.o., from 50 y.o. to 88 y.o.; male, 24) were examined for PVTs, as estimated via TEE and cardiac CT. Results: Thirty (97%) patients with T2DM had PVTs in the right lower pulmonary vein (RLPV) and connected LA thrombi, as estimated using TEE. Among them, 27 (87%) patients had large white rod-like LA thrombi extending from RLPV thrombi, and the diameter of the thin part of the rod-like LA thrombi was approximately 5 mm. The end of the LA thrombi was mainly attached to the left side of the anterior wall or the posterior side of left side wall of the LA. Additionally, there were left atrium diverticula (LADs) around the attachment regions. Three patients had RLPV thrombi and connected shorter LA thrombi. A 79-year-old male patient did not have detectable PVTs. The patient had taken apixaban (2.5 mg, twice daily) for six years due to atrial fibrillation and stroke. Conclusions: Most (97%) elderly T2DM patients had RLPV thrombi. Additionally, many (87%) patients had extended large rod-like thrombi in the LA. The diameter of the thin part of the large rod-like LA thrombi was approximately 5 mm. There were LADs around the attachment regions where the ends of the LA thrombi from the RLPV thrombi were attached.

Clinicopathological Characteristics of Neutrophil-Rich Hepatocellular Carcinoma: An Uncommon Subtype of Primary Liver Cancer.

Introduction. Neutrophil-rich hepatocellular carcinoma (HCC) is an extremely uncommon subtype of HCC with an overall incidence of <1%. Neutrophil-rich HCC shows poor cellular differentiation and sarcomatoid transformation in most patients. There is prominent neutrophilic inflammatory cell infiltration in the tumor. These tumors are associated with poor prognosis, high rate of recurrence, and metastasis. Methods. Herein, we investigated 4 patients with neutrophil-rich HCC reported at our center. Clinical, radiological, and pathological findings were reviewed. Immunophenotypic characterization of the tumors were done. Granulocyte colony-stimulating factor (G-CSF), programmed cell death ligand 1 (PD-L1), and mismatch repair immunostains were performed in all 4 tumors. Results. We report 4 neutrophil-rich HCCs in 3 male patients and one female patient with an age range of 43 to 64 years. Three underwent living donor liver transplantation and one underwent right hepatectomy. Tumor measured 0.5 cm to 12 cm in maximum dimension. Histologically, tumors demonstrated moderate to marked cellular pleomorphism. Spindle cell transformation was noted in 3 tumors. Three tumors showed vascular invasion, and one tumor showed bile duct invasion. Immunopositivity for Hep Par-1, arginase-1, and glypican-3 was present in all tumors. Tumors also expressed stemness markers including KRT19 and EpCAM. Cytoplasmic positivity for G-CSF and immunoexpression of PD-L1 was demonstrated. We also report proficient mismatch repair by immunohistochemistry in all tumors. Conclusion. Neutrophil-rich HCC is an aggressive primary liver cancer which demonstrates stemness-related features. Programmed cell death ligand 1 expression in tumor cells suggests distinct immunogenic features and potential role of anti-PD-L1 therapies in inoperable disease.

A rare primary cutaneous myoepithelial carcinoma in the axilla accompanied by lymph node metastasis: A case report.

Primary cutaneous myoepithelial carcinoma is an extremely rare tumor, and to the best of our knowledge, it has never been reported to occur in the axilla. Furthermore, the pathological and clinical factors of cutaneous myoepithelial carcinoma are poorly understood and may considerably affect prognosis and treatment. Here, we report a case of a 44-year-old male patient who was diagnosed with primary cutaneous myoepithelial carcinoma in the axilla accompanied by extensive lymph node metastasis. After an enlarged resection of the left axillary mass, axillary lymph node dissection, and the administration of postoperative chemotherapy and local radiotherapy, there were no signs of tumor recurrence or metastasis. At the time of manuscript preparation, the patient was recurrence-free. This case may contribute to the clinical management, diagnosis, and treatment of primary cutaneous myoepithelial carcinoma.

Abstract 4143265: Unveiling Gender Disparities in Chagas Disease patients with cardiac involvement: Insights from the NIS Database

Background: Chagas disease (CD) is caused by a protozoan named Trypanosoma cruzi, in its chronic stage it may present with organ involvement, including the heart. Previous studies suggest that being a male is associated with increased mortality in CD. Understanding gender disparities associated with this condition is imperative for better patient management. Hypothesis: Gender has an impact on the outcome of CD with cardiac involvement. Aim: To investigate if gender has an impact on the clinical outcomes of CD with cardiac involvement. Methods: We examined the National Inpatient Sample data from 2016-2020, and conducted a retrospective descriptive study. We included all patients 18 years and older, male and female, diagnosed with CD with cardiac involvement. We excluded patients who were younger than 18 years of age. Baseline socio-demographic characteristics, comorbidities, and outcomes of the two groups were described. Hypothesis testing for categorical variables was performed using Chi-Square. Continuous variables were tested with a Student t-test. Statistical significance was defined as a two-tailed p-value of &lt;0.0001. Results: A total of 135 patients had CD with cardiac involvement. The prevalence of CD with cardiac involvement was notably lower (33.33%) among male patients than among females (66.67%).There was zero in-hospital mortality in these patients. The average hospital stay was 11.37 days, and the average total charges were $227,041.9. Gender did not significantly impact hospital length of stay and total charge in these patients. Most patients were categorized as Hispanic (85.2%). Main comorbidities included diabetes mellitus 2, heart failure, hypertension, obesity, with no significant gender difference. Conclusion: CD with cardiac involvement was more prevalent in Hispanic females, but gender did not impact hospital length of stay and total charges.

Investigation of GPM6B as a novel therapeutic target in Osteoarthritis.

Osteoarthritis (OA) is the most common motor system disease in older people, characterized by a high incidence and significant social and economic burden. Women have a higher risk of OA, more severe clinical symptoms, and a higher rate of disabilities than men. However, the pathogenesis of OA remains unclear. Therefore, we screened for differentially expressed genes (DEGs) in OA patients of different sex and searched for new targets that may be involved in regulating the development of OA. The study compared the expression of DEGs in synovial fluid exosomes between male and female patients with OA through RNA sequencing combined with bioinformatics analysis using public data. To evaluate the screened DEGs, synovial tissue and fluid samples were obtained from patients with OA who underwent joint replacement surgery. SiRNA-mediated knockdown in vitro experiments were performed to investigate the role of glycoprotein membrane 6B (GPM6B). Meanwhile, GPM6B gene knockout mice were used to assess the in vivo pathological roles of GPM6B in OA. The results revealed that GPM6B is a potential target associated with OA. Immunofluorescence staining demonstrated that GPM6B was expressed in fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes in patients with OA. In vitro experiments confirmed that GPM6B knockdown can reduce the expression of inflammatory factors in primary FLS from patients with OA. Under inflammatory conditions, GPM6B knockdown can reduce the expression of matrix metalloproteinases as well as proliferation of FLS. In addition, using a destabilization of the medial meniscus-induced OA model, we revealed that GPM6B is associated with OA progression in mice. Thus, we provided evidence that GPM6B act as a new target associated with OA.

Abstract 4143217: Gender Disparities in Clinical Outcomes Following Transcatheter Aortic Valve Replacement: Insights from the National Inpatient Sample

Background: Transcatheter aortic valve replacement (TAVR) has revolutionized the management of aortic stenosis, offering a less invasive alternative to surgical valve replacement, particularly for high-risk patients. While TAVR has demonstrated efficacy and safety in various patient populations, there is growing recognition of gender-specific differences in clinical outcomes post-procedure.Understanding gender-related variations in TAVR outcomes is crucial for optimizing patient care and ensuring equitable access to this life-saving therapy. Methods: Using the National Inpatient Sample (2017-2020), we analyzed the characteristics and comorbidities of male and female patients undergoing TAVR. We then assessed the incidence of clinical outcomes between genders, including in-hospital mortality, mechanical ventilation, length of stay, hospital charges, vasopressor requirement, heart block, pacemaker insertion, stroke, acute kidney injury (AKI), vascular complications, and discharge disposition. Multivariate analysis was performed to evaluate mortality risk among congestive heart failure (CHF) patients. Results: Among 234,860 total admissions, females comprised 44.5% (104,365) of the population. Females were slightly older (mean age 79.4 vs. 78.5 years, p &lt; 0.001) and had a lower mean Charlson Comorbidity Index (2.8 vs. 3.1, p &lt; 0.001) compared to males. After adjusting for confounding factors, females had a higher odds ratio for in-hospital mortality (OR 1.48, 95% CI 1.37-1.60, p &lt; 0.001), mechanical ventilation (OR 1.14, 95% CI 1.07-1.20, p &lt; 0.001), stroke (OR 1.55, 95% CI 1.46-1.65, p &lt; 0.001), and vascular complications (OR 1.24, 95% CI 1.19-1.31, p &lt; 0.001). Length of stay (mean difference 0.37 days, 95% CI 0.32-0.42, p &lt; 0.001) and hospital charges (mean difference $3,795, 95% CI 2,488-5,102, p &lt; 0.001) were also significantly higher in females (p &lt; 0.001 for both). Conclusion: The divergent clinical profile and poorer outcomes observed among females undergoing TAVR, characterized by elevated in-hospital mortality, stroke, and vascular complications compared to males, may emphasize the need for gender-specific approaches in TAVR management.

Abstract 4137845: A single-cell lung atlas of human pulmonary arterial hypertension

Introduction: Pulmonary arterial hypertension (PAH) is a disaster disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients. Hypothesis: We hypothesis that single-cell RNA sequencing analysis can help understand the cellular and molecular mechanisms that drive the disease initiation and progression. Methods: 10 healthy donors, 10 idiopathic PAH, 10 drug and toxin induced PAH, 10 systemic and pulmonary shunting induced PAH patients from both male and female, and different ethical groups and races, and ages were obtained from PHBI. Lung tissue specimens were processed for fixed scRNA-seq. The cell proportion change, gene expression, and pathway analysis were evaluated between different disease subclasses, sex, age on different cell types. Results: Our analysis reveals 317,414 cells, 33 clusters and 9 major cell types, including endothelial cells (ECs), alveolar cells, fibroblast, smooth muscle cells (SMCs), pericytes, myeloid cells, lymphocytes, airway epithelial cells, platelet. Cell proportion analysis demonstrated an increase in the proportions of venous ECs, adventitial fibroblasts and myofibroblasts, alveolar macrophages, B cells, plasma cells and a reduction in capillary ECs 2 and pericytes in PAH lungs. KEGG Pathway analysis showed that upregulated pathways related Herpes simplex virus 1 infection, ECM-receptor interaction, Complement and coagulation cascades, Hedgehog signaling, TGF-beta signaling pathway, and downregulated pathways related to IL-17 signaling, TNF signaling, MAPK signaling pathway were enriched in the PAH patients. Female PAH patients exhibit an increase of myofibroblasts and platelets proportion compared to male PAH patients. MsigDB Hallmark Pathway analysis showed that p53 pathway was upregulated, whereas Inflammatory Response, Hypoxia, Epithelial Mesenchymal Transition were downregulated in female PAH patients. PAH patients older than 21 years exhibit an increase in the cell proportion of Platelet, SMCs, Arterial ECs and Venous ECs, and alveolar macrophages and a reduction of B cells and plasma cells. Conclusions: Our integrated analysis of human PAH lung atlas dataset provides a comprehensive understanding of lung cell populations and molecular signature in PAH patients with different sex, age and subclasses

Abstract 4132875: Living Address Environmental Biotope Affects the Risk of Coronary Obstruction and Myocardial Ischemia Detected by Coronary Computed Tomography

Background: Several studies reported positive associations between air and noise pollution exposure and coronary artery calcification, but environmental effects on coronary obstruction and flow remain largely unknown. Hypothesis: Distance to road and airport, air pollution, and residential green space are linked to coronary artery obstruction and myocardial ischemia. Low CV-risk patients develop coronary obstruction due to environmental factors, while high-risk patients are more prone to develop myocardial ischemia. Methods: Consecutive patients screened by coronary CT angiography for stable chest pain between 01/01/2019 and 31/12/2020 were included in a registry. Distance to airport and major road, and exposure to PM2.5, NO 2 and normalized difference vegetation index (NDVI) were modelled at patients’ living address. Risk of obstructive coronary artery disease (OCAD, stenosis ≥50%) and abnormal fractional flow reserve (FFR CT &lt;80%) was assessed using propensity score (PS)-adjusted logistic regression. Subgroup analysis was performed according to gender and Framingham CV-risk categories. Results: We enrolled 2620 patients, including 420 (16%) FFR CT analyses. OCAD was reported in 518 (20%) patients and abnormal FFR CT in 276 (11%). People with OCAD lived closer to the airport (10.841 [7.869-19.022] km vs. 12.297 [8.691-22.843] km, p&lt;0.001). Distance to airport decreased OCAD risk (OR 0.983, 95%CI 0.974-0.992, per 1 km) in univariate analysis, with the association present in male, female, and low-risk patients. After PS-adjustment, a trend of association was present between airport distance and abnormal FFR CT risk (OR 0.986, 95%CI 0.969-1.003, per 1 km). Road distance tended to decrease OCAD risk in univariate and PS-adjusted analysis, in the general (OR 0.928, 95%CI 0.808-1.309; and OR 0.928, 95%CI 0.840-1.021, per 1 km) and high-risk population. NO 2 exposure tended to increase OCAD risk in univariate analysis (OR 1.012, 95%CI 0.997-1.027, per 1 µg/m 3 ), with the association only present in female patients, and disappearance after PS-adjustment. PM2.5 exposure showed no associations, while NDVI tended to increase OCAD risk in low-risk patients after PS-adjustment. Conclusion: Residential distance to airport is the major risk component compared to other urban exposome factors studied in this epidemiological observation. Green space tends to exert a cardioprotective effect in low-risk patients, whereas living close to major road worsens the risk in high-risk patients

Abstract 4146315: Complications Associated With the 4798 Attain Stability Active Fixation Coronary Sinus Lead: Insights from the MAUDE Registry

Background: The Attain Stability Quad 4798 [Medtronic, Minneapolis, MN] lead was recently developed with a mechanism for active fixation into the venous wall, allowing for precise and secure placement in coronary venous branches. However, real-world data regarding complication rates are limited. Research Question: What are the real-world complications of the Medtronic 4798 lead? Goals: We reviewed the United States Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database for adverse events associated with the 4798 lead. Methods: We reviewed the MAUDE database on November 15, 2023, for all reported complications due to the 4798 lead from January 1, 2018 – a year before the lead was approved by the FDA – to the present. Results: A total of 2011 reports of adverse events occurred in mostly males (67.9%) patients with an average age of 70.86±12.1 years. Leads were used most frequently in 2023 (32.3%) for initial use (65.5%) but events commonly occurred intra-procedurally (73.7%). Device malfunction occurred in 43.4% of cases and included but was not limited to adverse events without an identified device problem (33.9%), device dislodgment (24.1%), infection (21.1%), and failure to capture (18.4%). In several cases, the guidewire was stuck (10.7%), or lead dislodgement (27.9%) occurred, resulting in direct helix damage (10.1%). Malfunctions resulted in injury and death in 55.8% and 1.1% of cases, respectively. Conclusions: The use of an active fixation CS lead has been associated with a significant incidence of intraprocedural helix mechanism malfunction. Further real-world surveillance and registry data can help clarify the true incidence of lead failure.

Abstract 4144559: Sex Differences in Vascular Remodeling in Pulmonary Hypertension are mediated by Endothelin-2

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial vascular remodelingleading to increased pulmonary artery pressure causing right ventricular hypertrophy, failure anddeath. The incidence of PAH is much higher in female patients, indicating that males may have aprotective factor that could help elucidate the pathogenesis of PAH. We have recently demonstratedthat the Y chromosome gene UTY protects against PH development in mice, however the fulldownstream mechanisms remains unknown. By integrating RNA-Seq on whole lung tissues fromUty-KO and WT male mice with a publically available male and female PAH lung microarraydataset, we found increased expression of Endothelin 2 (ET-2) in the lungs of Uty-KO compared toWT mice with PH as well as in the lungs of female patients compared to males with PAH. The roleof ET-1 is known in PAH, and Endothelin receptor antagonists are a common PAH therapy to whichfemale patients are more responsive. However, ET-2 has yet to be investigated in this context. Wevalidated that ET-2 expression is significantly increased in lung tissue from PAH female patientscompared to males. Plasma ET-2 concentration is also significantly higher in PAH patients versuscontrols. Interestingly, plasma ET-2 negatively correlates with pulmonary vascular resistance (PVR)and mean pulmonary arterial pressure (mPAP) in male PAH patients, whereas plasma ET-2significantly positively correlates with PVR and mPAP in female PAH patients. Functionally, wefound that recombinant ET-2 significantly inhibits proliferation of male pulmonary artery endothelialcells (PAECs), but significantly promotes proliferation in female PAECs. Similarly, ET-2 significantlyincreased proliferation of female pulmonary artery smooth muscle cells (PASMC), but not malePASMC. Together, we show that increased ET-2 expression may contribute to worsening PH bypromoting vascular remodeling in the lung and that elevated ET2 in females may at least partiallyexplain the higher incidence of female PAH patients

Abstract 4135938: Angiopoeitin-2 and Mortality in an End-Stage Renal Disease, Heart Failure Population

Introduction: Angiopoeitin-2 (Ang2) is a vascular growth factor involved in regulating angiogenesis and endothelial remodeling. Higher Ang2 levels have been associated with mortality in the general population and among male hemodialysis patients, but its effects on concomitant heart failure with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD) are unknown. Methods: Plasma samples from 73 ESRD patients and 40 normal healthy patients (NHP) were analyzed for Ang2 concentrations using ELISA. Patient groups were stratified into those with or without HFrEF (EF &lt; 50%). At two years following sample collection, the medical record was reviewed for mortality. The optimal cut-off value for Ang2 to predict all-cause mortality was 1715 pg/mL (AUC 0.706) based on the regression analysis. Statistical analyses included Mann–Whitney U tests, Cox proportional hazards model, and Log-rank (Mantel-Cox) test. Results: Multiple comorbidities were present; coronary artery disease 46%, diabetes 69%, hypertension 97%, and smoking 49%. Patients with one-year mortality had higher Ang2 (Figure 1). Ang2 levels above the optimal cut-off are associated with mortality, both within the entire ESRD sample and within the group with both ESRD and HFrEF (Figures 2-3). In the Cox proportional hazards analysis, Ang2 levels were associated with mortality within the larger ESRD sample (HR=1.001) but not in the group with ESRD and HFrEF. Discussion: Ang2 has potential as a biomarker for prognostication in patients with chronic disease given its association with mortality. Future research should be conducted with larger samples to evaluate if it has prognostic value in individuals with HFrEF without ESRD.