Female Patients Research Articles

ZNAČAJ DIGITALNE STEREOTAKSIJSKE BIOPSIJE U KORELACIJI SA PATOHISTOLOŠKIM POSTOPERATIVNIM NALAZIMA

Aim : This research was conducted with the aim of analyzing the accuracy and diagnostic value of digital stereotactic breast biopsy compared to the postoperative histopathological findings. Methods : A retrospective-prospective study was carried out over a period of 10 months, involving 30 female patients who underwent stereotactic breast biopsy. Data were collected on BI-RADS status, histopathological findings after stereotactic breast biopsy and after surgical excision, basic demographic and relevant medical history data. The patients were divided according to the degree of malignancy into three groups: patients with benign, patients with suspicious and patients with malignant pathohistological findings. The BIS and RIS systems were used for data collection, and the data were statistically analyzed using STATISTICA for Windows. Results : All patients had a radiological finding of BI-RADS 3 or higher. Histopathological results after stereotactic biopsy showed benign findings in 17 patients (B1 and B2), borderline malignant changes were present in 4 patients (B3), one patient had a lesion suspicious for malignancy (B4), and 8 had confirmed malignant lesions (B5). Out of the total 30 patients, 13 underwent surgical treatment. Postoperative histopathological findings in 4 patients showed benign changes, 6 patients had an invasive form of carcinoma, including 5 with invasive NST breast carcinoma and one characterized as invasive ductal breast carcinoma, while three patients had Ductal Carcinoma In Situ (DCIS). A correlation test was performed between the estimated degree of malignancy from the pathohistological findings after stereotaxic biopsy and after surgical operation. Spearman's ρ test showed a significant correlation between the two methods (p < 0.001). Conclusion : The results of histopathological analysis of samples obtained through the stereotactic biopsy method largely correlate with the postoperative histopathological diagnosis in patients who underwent surgical treatment. Keywords : digital stereotactic breast biopsy, PHD findings, BI-RADS, NST, Ductal Carcinoma In Situ.

Will a patient information brochure increase acceptance of Omani women with varicose veins to be examined by a male surgeon ?- A prospective randomized single blinded study.

Varicose veins are not uncommon among Omani women. As currently there are no female vascular surgeons, it has been noticed in our outpatient clinic that a number of them are reluctant to be examined by a male vascular surgeon, have a duplex ultrasound done and therefore a management plan cannot be made in this subset. This study is a first of its kind in Oman, looking at the impact of a patient information booklet about varicose veins etiology, symptoms, signs, assessment and management, on the attitude of a female patient's acceptance towards examination by a male surgeon in the presence of a chaperone.

Clinical Effectiveness of Viddha Karma in PCOS: A Case Report

ABSTRACT Polycystic ovary syndrome (PCOS) is a common hormonal disorder affecting women of reproductive age. Ayurveda, an ancient Indian medical system, offers a comprehensive approach to addressing PCOS, including treatments like Viddha Karma. In the case of PCOS, Viddha Karma aims to relieve symptoms and enhance overall well-being. A 27 -year-old unmarried female patient came with complaints of irregular and scanty menses for the past 3-4 years, along with severe abdominal pain during the first 1-3 days of menstruation. She was treated with Shaman Chikitsa and Viddha Karma for 8 months. The patient’s menstrual cycle become regular, the volume of bleeding increased to a normal level, and she experienced a weight reduction of 5 kg. The examination of Viddha Karma principles in the management of PCOS emphasizes its potential as a supplementary treatment that tackles the underlying causes and promotes overall well-being. However, further research and clinical trials are necessary to gain a comprehensive understanding of its effectiveness.

The assessment of psychosocial distress in hospitalized cancer patients during radio-oncological treatment: a monocentric experience study.

This study investigated the prevalence and determinants of psychosocial distress among hospitalized patients undergoing radiotherapy to identify opportunities for interventions to enhance patient well-being. Between January 2021 and May 2023, 137 hospitalized patients received radiotherapy treatment at the Department of Radiation Oncology of the Fondazione A. Gemelli IRCCS were recruited. Participants completed a questionnaire comprising the Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). The study revealed a significant correlation among anxiety, depression, total HADS scores, and Distress Thermometer scores (p < 0.001). Female patients exhibited higher total HADS scores and anxiety levels compared to males (p < 0.004, p < 0.010, respectively). Sleep disturbances were associated with increased anxiety, depression, and overall distress (p < 0.05). Younger patients (< 65years old) demonstrated elevated anxiety and depression levels, while no significant depressive tendency was observed among older participants (> 65years old). These findings underscore the intricate interplay between demographic variables, psychological distress, and treatment-related symptoms among patients during radiotherapy treatments. The study highlights the critical necessity of promptly identifying and addressing psychosocial distress in this population. It suggests that implementing a psychological therapeutic approach, particularly one focused on support, could effectively deter the onset of depression, especially among younger patients. Future research should focus on longitudinal studies to explore distress trajectories and interventions' effectiveness in mitigating distress, with collaborative efforts to translate research findings into evidence-based clinical practice for improved patient care.

Meningiomas: Sex-Specific Differences and Prognostic Implications of a Chromosome X Loss.

Meningiomas are the most common primary intracranial tumours in adults. Several studies proposed new stratification systems with a more accurate risk prediction than the WHO grading, e.g. based on methylation and copy number variations (CNVs). Yet, common shortcomings in these analyses are either a lack of stratification by sex of patients or excluding the gonososmes from CNV assessment. Within this study, DNA methylation array data from 7,424 meningioma samples as well as targeted sequencing, clinical annotations and morphology subtyping of 796 samples were examined for differences between females and males regarding mutations, methylation classes, copy number variations and histology. Meningiomas from females accounted for about 53 % of the malignant tumours and present a loss of one X chromosome in 57 % of these malignant cases. In the group of benign tumours, females comprised about 75 % of the patients. Therein, a loss of one X chromosome was detected in only about 10 % of the cases but was associated with a significantly worse progression free survival. Although genomic instability is a common feature of malignant meningiomas, particularly loss of the X chromosome in tumours of female patients in otherwise histologically and molecularly low-risk tumours confers higher risk. Hence, the gonosomal copy number status can be leveraged for increased diagnostic accuracy.

Hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer (CHIPOR): a randomised, open-label, phase 3 trial.

Hyperthermic intraperitoneal chemotherapy (HIPEC) at interval cytoreductive surgery for ovarian cancer improves overall survival but its role in recurrent disease is uncertain. We aimed to compare outcomes in patients treated with or without HIPEC during surgery for recurrent ovarian cancer. The multicentre, open-label, randomised, phase 3 CHIPOR trial was conducted at 31 sites in France, Belgium, Spain, and Canada, and enrolled patients with first relapse of epithelial ovarian cancer at least 6 months after completing platinum-based chemotherapy. Eligible patients were aged 18 years or older with WHO performance status of less than 2. After six cycles of platinum-based chemotherapy (and optional bevacizumab), patients amenable to complete cytoreductive surgery were randomly assigned centrally in a 1:1 ratio, using a web-based system and a minimisation procedure, during surgery to receive HIPEC (cisplatin 75 mg/m2 in 2 L/m2 of serum at 41±1°C for 60 min) or not, stratified by centre, completeness of cytoreduction score, platinum-free interval, and latterly, planned poly(ADP-ribose) polymerase inhibitor use. The primary endpoint was overall survival, analysed on an intention-to-treat basis in all randomly assigned patients. This ongoing trial is registered with ClinicalTrials.gov, NCT01376752. Between May 11, 2011, and May 14, 2021, 415 female patients were randomly assigned (207 HIPEC, 208 no HIPEC). At the primary analysis (median follow-up 6·2 years, IQR 4·1-8·1), 268 (65%) patients had died (126 [61%] of 207 in the HIPEC group; 142 [68%] of 208 in the no-HIPEC group). Overall survival was significantly improved with HIPEC (stratified hazard ratio 0·73, 95% CI 0·56-0·96; p=0·024). Median overall survival was 54·3 months (95% CI 41·9-61·7) with HIPEC versus 45·8 months (38·9-54·2) without. Grade 3 or worse adverse events within 60 days after surgery occurred in 102 (49%) of 207 patients receiving HIPEC versus 56 (27%) of 208 receiving no HIPEC, the most common being anaemia (47 [23%] vs 30 [14%]), hepatotoxicity (23 [11%] vs 18 [9%]), electrolyte disturbance (28 [14%] vs two [1%]), and renal failure (20 [10%] vs three [1%]). There were three deaths within 60 days of surgery, all in the no-HIPEC group. Adding HIPEC to cytoreductive surgery after response to platinum-based chemotherapy at first epithelial ovarian cancer recurrence significantly improved overall survival. When treating patients with late first relapse of high-grade serous or high-grade endometrioid ovarian cancer amenable to complete cytoreductive surgery at specialist centres, platinum-based HIPEC should be considered to extend overall survival. French National Cancer Institute and French League Against Cancer.

Effectiveness of ultrasound-guided vacuum-assisted excision for treating benign breast lesions.

Ultrasound‑guided vacuum-assisted excision (UGVAE) and breast biopsy are widely used for the diagnosis and treatment of both benign and suspicious breast lesions. In this retrospective study, we aimed to determine the safety of UGVAE for benign breast lesions and provide guidance for clinical practice. We analyzed clinical and pathological data of female patients who had undergone UGVAE between January 2015 and December 2017 at our institution. All breast lesions were categorized according to the Breast Imaging Reporting and Data System (BI-RADS) before performing UGVAE. In our study cohort, UGVAE was used to resect 10,378 breast lesions from 5789 patients, and selected clinical and histopathological data were analyzed. The most common adverse events were postoperative bleeding (0.24%) and skin hypersensitivity (0.67%). The residual lesion rate was 2.27%. Fibroadenomas accounted for most of the benign lesions (7932 of 10,193; 77.82%). Breast cancer was diagnosed in 150 lesions from 128 patients. Multivariable binary logistic regression analyses showed that older age (odds ratio [OR] = 2.034, 95% confidence interval [CI]: 1.668-2.480, p < 0.001), higher BI-RADS category (OR = 9.514, 95% CI: 6.790-13.332, p < 0.001), and larger legion size (OR = 1.048, 95% CI: 1.019-1.077, p = 0.001) were associated with an increased likelihood of breast cancer. Ninety-six patients with breast cancer had undergone follow-up treatment, achieving a 3-year disease-free survival rate of 97.2% and a 3-year overall survival rate of 100%. UGVAE is a safe and effective means of removing benign breast lesions, causing minimal postoperative trauma and fewer complications compared with open surgery. Moreover, UGVAE had little impact on the follow-up treatment and survival of patients diagnosed with breast cancer.

Missense variant Met119Val in ACTB in a patient with Baraitser-Winter syndrome type 1 and mild intellectual disability.

Here we report on a Brazilian female patient with striking dysmorphic craniofacial features of the Baraitser-Winter syndrome (BRWS), including coarse face with prominent metopic ridge, highly arched eyebrows, ocular hypertelorism, ptosis, long palpebral fissures, broad nasal tip, long philtrum, full cheeks, cleft lip and palate, and low-set ears with abnormal lobe. Other clinical signs included partial agenesis of the corpus callosum, asymptomatic pineal cyst, oligodontia, cervical cystic hygroma, pterygium colli, axillary pterygium, duplicated left hallux and seizures. Sanger sequencing of the ACTB gene showed a heterozygous missense variation NM_001101.5 (ACTB):c.355A&gt;G (p.Met119Val). This variant is located very close to the ACTB variant Thr120Ile, which results in the severe BRWS phenotype with severe intellectual disability and absence of speech, firstly described as Fryns-Aftimos syndrome. Despite this, our patient had mild developmental delay, without impairment of speech, and with moderated learning difficulties.

Changes in Physical Function After Long Corrective Fusion to the Ilium for Adult Spinal Deformity

Study Design. Prospective cohort study. Objective. To investigate longitudinal changes in physical functional status after long corrective fusion in patients with adult spinal deformity (ASD) during 2 years of follow-up. Summary of Background Data. In ASD surgery, reports assessing physical functional status in long-term observations for more than a year are lacking. Assessing whether patients maintain significant improvements in their physical status with a longer follow-up duration is crucial. Methods. A total of 70 female patients with ASD who underwent long corrective fusion of ≥ 7 segments between June 2016 and June 2022 were included in this study. Preoperative and postoperative assessments (at 6 months, 1 year, and 2 years) included radiographic spinopelvic parameters, health-related quality of life (HRQOL) using the Scoliosis Research Society Outcome Instrument-22 (SRS-22) questionnaire, and physical function tests conducted by a physical therapist. Results. All domains of the SRS-22 improved the most in the first 6 months after surgery (P &lt;0.0001); however, the Pain and Function domains continued to improve gradually until 2 years postoperatively. Regarding trunk dynamic balance, the timed up-and-go test score improved gradually until 2 years postoperatively (P &lt;0.0001). Regarding gait performance, gait speed and the 6-minute walking test improved the most in the first 6 months after surgery (P &lt;0.01) and almost reached a plateau 1 year postoperatively. Conclusions. Long corrective fusion for ASD significantly enhanced physical function and HRQOL within 2 years, with the greatest improvement in the first 6 months after surgery. These findings underscore the importance of increasing activities of daily living through early exercise instruction, as well as preventive measures to avoid early surgery-related complications. Level of Evidence. 3

Primary dedifferentiated liposarcoma of the gallbladder: a case report and literature review

BackgroundLiposarcoma (LPS) is a kind of malignancy of soft tissue usually found in the retroperitoneal, limb, or neck region, and some may be detected with delayed symptoms (pain or palpable mass), and less frequently occurs in organs of the digestive system. In contrast, Dedifferentiated liposarcoma (DDLPS) is a common histological subtype of LPS. The present study reported a case of dedifferentiated liposarcoma originating in the gallbladder. Differentiated liposarcoma originating from the gallbladder is rarely reported.Case descriptionA 64-year-old female patient presented to our hospital with a painless abdominal mass. Abdominal computed tomography (CT) showed that the gallbladder had lost its normal shape, and a 9.1 cm × 7.1 cm × 12.1 cm mass was seen in the area of the gallbladder fossa and the right upper abdomen below it, which had an irregular morphology, inhomogeneous density, and nodular calcification, with marked inhomogeneous enhancement on enhancement scan. Preoperative tumor markers and liver function indicators were not abnormal. With suspicion of a giant malignant tumor of the gallbladder, she underwent a cholecystectomy combined with abdominal mass resection. After surgery, the tumor and gallbladder, were completely resected, and postoperative pathological results confirmed the diagnosis of dedifferentiated liposarcoma deriving from gallbladder. After surgery, the patient and his family refused to continue treatment. After 15 months follow-up, the patient remains asymptomatic and does not show any signs of recurrence. And she is now under continued follow - up.ConclusionsTreatment of dedifferentiated liposarcoma is still at exploratory stage, and a lack of clinical evidence for this condition might hinder access to clinical trials and studies. Currently, the treatment of choice for dedifferentiated liposarcoma remains radical resection. In the available clinical studies, there are no robust data to support clinical use of neoadjuvant and adjuvant radiochemotherapy. As with other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential future treatment.

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 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 4140149: Differences in Interventional Treatment Outcomes of Peripheral Arterial Disease between African American Females, African American Males, and Caucasian Females

Introduction: Several recent publications demonstrated worse outcomes of interventional treatment of peripheral arterial disease (PAD) in patients of African American (AA) descent compared to Caucasians (C), and in female patients compared to male patients. However, studies addressing sex differences in outcomes, included predominantly white female patients. To our knowledge, there are no published studies specifically addressing outcomes of interventional treatment of PAD in female patients of African American descent. Aims: 1. To determine if the outcomes of interventional treatment of PAD in female patients of African American (FAA) descent differ from male African American patients (MAA), and Caucasian female patients (FC). If such differences exist, to identify factors associated with it. Methods: This study has a cross-sectional design with systematically retrospective data collection by the National Vascular Quality Initiative. Included in this study was data on patients treated with endovascular and open surgical options for symptomatic PAD. Statistical analysis was done using IBM Statistic SPSS V25. Results: 447,263 unique cases containing required data were available in the VQI database. Among them, 171,250 were female patients, of which 32,966 were FAA, 126,519 FC, and 39,461 MAA. This race and gender distribution is not significantly different from the US population structure (US Census Bureau 2023). 1 However, female to male ratio was higher in AA (0.83) compared to C (0.58, p&lt;0.0001). FAA were younger (65.143+/-9.59) compared to FC (69.16+/-10.32, P&lt;0.00001). Comparison of comorbidities, smoking rates, pre-interventional medications and post-interventional outcomes are listed in Table 1. Multivariate analysis confirmed higher amputation rate among FAA compared to FC and to MAA and showed no significant difference in mortality. Conclusions: FAA patients who require interventional treatment for PAD have significantly higher rate of hypertension and diabetes compared to FC and MAA patients and have higher amputation rates. It appears that differences in clinical outcomes of PAD treatment in FAA are related mostly if not entirely to poorly managed comorbidities existed prior to intervention.

Abstract 4138731: Clonal Hematopoiesis of Indeterminant Potential is Associated with Pulmonary Arterial Hypertension

Background: Pulmonary Arterial Hypertension (PAH) is a fatal cardiopulmonary disorder characterized by adverse vascular remodelling of small pulmonary arteries, which increases resistance and demand on the right ventricle (RV), ultimately leading to RV fibrosis and failure. Emerging evidence suggests that inflammation plays a crucial role in PAH pathogenesis. Here, we study Clonal Hematopoiesis of Indeterminate Potential (CHIP), a disorder characterized by somatic mutations in genes such as DNMT3A and TET2 , that promotes an inflammatory phenotype, in the development of PAH. Methods: We performed deep, targeted panel sequencing on 1659 PAH patients from the PAH Biobank and 3644 controls (3401 Vanderbilt University Biorepository patients and 243 participants recruited by the Queen’s Genomics Centre at Ongwanada). Variants in known CHIP genes expressed at a variant allele frequency (VAF) &gt; 2% were classified as CHIP. Genes with a VAF &gt; 25% and &lt;50% were considered CHIP if located in reported CHIP hotspot regions. The prevalence of CHIP mutations was compared between controls and PAH patients. Logistic regression was used for statistical analysis. Results: We identified 242 CHIP variants in the 1659 PAH patients. DNMT3A was the most mutated gene (116/242 = 48%), followed by TET2 (46/242=19%). After adjusting for age and sex, we identified a significant association between all CHIP variants combined and PAH (OR: 23.35 [7.67, 71.03]; p&lt;0.0001). Further, DNMT3A CHIP (OR: 25.44 [5.37, 120.40]; p&lt;0.0001), non- DNMT3A CHIP (OR: 26.80 [5.56, 129.23]; p&lt;0.0001) and TET2 CHIP (OR: 13.69 [1.29, 145.30]; p=0.03) were all associated with PAH. A higher proportion of PAH patients under the age of 70 were found to have CHIP variants compared to controls and this was significant for individuals between 60-69 years of age (p=0.037). While there was a 3.8:1 female-to-male ratio of PAH patients, there was a 5.8:1 female-to-male preponderance of DNMT3A variants (p=0.039) (4.3:1 for all CHIP; p=ns), suggesting DNMT3A variants are more common in female patients. The presence of CHIP variants had no significant effect on PAH patient 10-year survival. Conclusion: This research reveals a significant association between CHIP variants, specifically in DNMT3A and TET2, and PAH. The prevalence of CHIP is higher in PAH patients aged 40 to 70 compared to controls and is more common in female patients. These findings suggest that CHIP is a significant risk factor for the development of PAH.

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

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.

Unusual Foreign Body in the Middle Ear: Surgical Removal of a Live Ant Entering the Tympanic Cavity Through an Ear Drum Perforation

This case report details the unusual occurrence of a live ant invading the middle ear cavity through a pre-existing perforation in the tympanic membrane of a 42-year-old female patient. She presented to an outpatient clinic with symptoms of sudden-onset tinnitus (“ringing”) and a foreign body sensation in her left ear. Otomicroscopy revealed an oval-shaped perforation in the posterior part of the left tympanic membrane, through which a dark, moving foreign object was observed in the middle ear. The object was identified as a live ant. Initial attempts to remove the insect under local anesthesia were unsuccessful, necessitating the patient’s admission for surgery. Under general anesthesia, an endoscopic tympanotomy was performed, and the ant was successfully removed without complications. The patient recovered and was discharged the following day. At her follow-up appointment, she remained symptom-free. This case highlights the rare yet possible occurrence of live foreign bodies entering the middle ear through tympanic perforations and the need for timely surgical intervention to prevent complications.

Abstract 4122024: Fibroblasts Are the Primary Contributors to a Disrupted Micro-Environment in End-Stage Pediatric Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in pediatric patients. This represents a vulnerable population who often require heart transplantation. Here, we examine the transcriptome in ventricular tissue to identify underlying cellular processes unique to pediatric HCM (pHCM). Methods: We performed single-nucleus RNA sequencing on explanted hearts at transplant in female patients with end-stage pHCM (n=3) and compared findings to pediatric control (n=2) and adult HCM (n=5; Figure 1A-1B). Results: We generated 91,682 single-cell transcriptomes from 8 tissue samples. Principal component analysis exhibited the largest source of transcriptional variation separated pHCM and controls (Figure 1C). We identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells in pHCM. pHCM was enriched in cardiomyocytes with stressed signatures and pathways associated with hypertrophy (Figure 1D); we noted depletion of tissue-resident macrophages (Figure 1D) and increased vascular remodeling in endothelial cells in pHCM. Fibroblasts exhibited activation signatures and compared to adult HCM, showed heightened fibrotic processes and a unique pro-fibrotic cluster with increased metabolic stress, mitochondrial turnover, and anti-apoptotic properties (Figure 2). In cell-to-cell communication, the differential number and weight of interactions were higher in pHCM compared to controls and fibroblasts had the highest strength of outgoing interactions. Conclusions: Our analysis provides the first single-nuclei analysis focused on pHCM. Fibroblast-mediated cellular processes contributed most to the disrupted micro-tissue environment; they had more downstream processes associated with fibrosis and may respond to metabolic stress differently compared to adult HCM. This advances our understanding of the early presentation of pHCM, providing a crucial steppingstone toward improved patient outcomes.

Abstract 4115542: Female patients with Andersen-Tawil Syndrome are more prone to develop cardiac arrest.

Background: Andersen-Tawil Syndrome (ATS) is an autosomal dominant disorder characterized by a triad of dysmorphic features, periodic muscular weakness, and ventricular arrhythmias. We presented a meta-analysis of cardiologic-affected ATS patients. Objective: This study sought to compare the characteristic features of ATS according to their gender with a special focus on the cardiologic anomalies. Methods: To enable a meta-analysis, we searched literature reviews of reported cases or cohort studies with ATS between 1994 and 2024. Cases were selected if they presented a cardiologic affection alone or combined with morphologic features, periodic paralysis, or both. A gender comparison was made using the available information. Each variable was calculated using the validated percentage. Numerical variables are expressed as mean or median and SD. Categorical variables are expressed as percentages. Student’s t-test was used for numerical variables. Categorical variables were analyzed using chi-square. The results were expressed as an odds ratio (OR) with a 95% confidence interval (CI). Values of p &lt;0.05 were considered statistically significant. Results: The studied population consisted of 243 cardiologic-affected patients with ATS, 163 females, and 80 Males. Compared to males, females are less likely to present periodic paralysis (p = 0.03, OR = 0.54, 95% CI = 0.30-0.98). Analyzing cardiologic features, females had more syncope episodes than males (73% (n=52) vs. 22.4% (n=15). Only 45% of cases had a prolonged QTc. A longer QTc measure was reported in females (453 ± 52) compared to males (427 ± 55) (p = 0.004). Premature ventricular contractions (PVCs) were the most commonly reported arrhythmia, and bigeminy was the most common type of presentation. Polymorphic PVCs were more prevalent in females than males (p = 0.009, OR = 2.49, 95%CI = 1.24-4.99). Females reported more Ventricular tachycardias (VT) episodes than males, especially Bidirectional (p = 0.01, OR = 2.10, 95%CI = 1.17-3.78). Thirty-five patients had an episode of cardiac arrest, either non-fatal, fatal or in some cases non-fatal, followed by SCD after years. Females were more prone to develop cardiac arrest compared to males (n=29 vs. n=6, respectively; p = 0.03, OR = 2.66, 95%CI = 1.06-6.72). Conclusion: ATS females with cardiologic affection may require a closer follow-up due to the higher risk of developing life-threatening arrhythmias and cardiac arrest than males.

Abstract 4137939: Mosaic loss of Y chromosome is associated with increased all-cause mortality in patients with ST-segment elevation myocardial infarction

Introduction: Mosaic loss of Y chromosome (LOY), a common subtype of somatic mosaicism, is characterized as loss of the entire Y chromosome in a mosaic manner and increases with age. Accumulating evidence has manifested the positive link between LOY and shorter life expectations in elderly men as well as common age-associated diseases, such as cancer and cardiovascular diseases. Experimental studies also demonstrated that hematopoietic LOY in mice induced cardiac fibrosis and led to increased mortality. However, little is known about LOY and prognosis of ST-segment elevation myocardial infarction (STEMI). Hypothesis: We hypothesized that LOY may be associated with lower survival rate of patients with STEMI. Aims: Investigating the impact of LOY in peripheral blood cells on prognosis of patients with STEMI. Methods: This study prospectively enrolled 928 males and 272 females undergoing primary percutaneous coronary intervention for STEMI. LOY was measured in 928 males using droplet digital polymerase chain reaction technique. Results: During a median follow-up of 3.99 years, 93 males (10.0%) and 45 females (16.5%) died. After adjusting for traditional cardiovascular risk factors, the risk of all-cause mortality in males with LOY ≥ 18% (the 90th percentile of LOY) increased to 2.45 (95% confidence intervals [CI]: 1.16–5.15, P = 0.018), 2.11 (95% CI: 1.11–4.01, P = 0.024), and 1.88 (95% CI: 1.02–3.45, P = 0.043) times during 1-, 2-, and 3-year follow-up, respectively, compared to males with LOY &lt; 18%. Among males without prior MI, those with LOY ≥ 18% had an increased risk of all-cause mortality compared to those with LOY &lt; 18% (adjusted hazard ratio 1.93, 95% CI: 1.01–3.67; P = 0.045); this was not observed for males with prior MI. Female patients had a 1.71-fold (95%CI: 1.04–2.81; P = 0.035) increased risk of all-cause mortality than males with LOY &lt; 18%, whereas the risk was similar to males with LOY ≥ 18%. Conclusion: LOY was associated with an increased risk of all-cause mortality in male STEMI patients, particularly in those without prior MI. Detecting LOY in STEMI patients could help further refine sex differences in prognosis and assist in identifying male patients with better prognoses.