Female Cases Research Articles

Macrophage activation syndrome in a patient with systemic lupus erythematous triggered by tuberculous meningitis

Background: Hemophagocytic lymphohistiocytosis (HLH), is characterized by systemic uncontrolled inflammation resulting from immune dysregulation secondary to various triggers, including genetics, infections, autoimmune diseases, and malignancies. Macrophage activation syndrome (MAS) is an immune dysregulation phenomenon, in which an underlying rheumatological disease is present. We report a rare, interesting case of a middle-aged female, with a systemic lupus erythematosus (SLE) flare complicated by macrophage activation syndrome (MAS), in which tuberculous meningitis (TBM) was the identified trigger. Case report: A 48-year-old female with an African ethnic background, diagnosed with SLE, presented with a 2-week history of high-grade fever, cough, and worsening arthralgia. She was initially admitted with suspected SLE flare secondary to community acquired pneumonia and was started on broad-spectrum antibiotics. Later during her hospital stay, she underwent extensive workup because of her clinical condition, as she had continuous spikes of fever, progressive cytopenia, accompanied with acute confusion state despite treatment. She was ultimately diagnosed with SLE flare complicated by MAS secondary to TBM in view of persistent fever, neuropsychiatric symptoms, hyperferritinemia and hypertriglyceridemia, supported by bone marrow aspiration findings, a tuberculosis (TB) positive contact and supporting cerebrospinal fluid analysis suggestive of TBM. She was immediately started on pulse doses of steroids and anti-tuberculosis medications in which significant clinical improvement was observed. She was discharged home, with continuity of care done at the outpatient department in addition to continuity of physical rehabilitation. Conclusion: Given the wide range of clinical presentations and similarities between SLE and the life-threatening MAS, it is essential to maintain a high level of suspicion to establish the diagnosis and promptly start the necessary treatment to ensure better clinical and survival outcomes.

Impact of GRM7 Gene Variations on Glioblastoma Risk in the Iranian Population

AIMThe metabotropic glutamate receptor, GRM7 is a gene in the neurotransmitters prognostic signatures. Downregulation of this gene is associated with the progression of glioma tumors and has a negative impact on the immune response. MethodsIn the present study, we aim to assess the associations between rs6782011 and rs779867 SNPs within this gene and risk of glioblastoma multiforme (GBM) in Iranian population. ResultsThere was a noteworthy difference in distribution of genotypes (P value=0.001) and alleles (P value= 0.0002) of rs779867 between total GBM cases (n=299) and total normal controls (n=302). In addition, the significant difference in genotypes and alleles distribution was observed for both male and female GBM cases vs. respective normal controls. For rs6782011 variant, the significant difference in genotypes distribution was observed between male GBM cases (n=187) vs. respective normal controls (n=156) (P value=0.004) and between total GBM cases (n=299) vs. total normal controls (n=302) (P value=0.02). However, there was no significant difference in genotypes distribution between female GBM cases and respective normal controls (P value= 0.1). Distribution of rs6782011 alleles was not different between total GBM cases and normal controls; and between male GBM cases and male normal controls. However, there was a significant difference in alleles distribution between female GBM cases and female normal controls. Conclusion: Taken together, the mentioned polymorphisms might affect risk of GBM in Iranian population. Future studies are needed to elaborate the underlying mechanism.

Drug-Resistant Tuberculosis in Rural Eastern Cape, South Africa: A Study of Patients’ Characteristics in Selected Healthcare Facilities

This study investigated the characteristics and outcomes of drug-resistant tuberculosis patients in selected rural healthcare facilities in the Eastern Cape, South Africa. A retrospective review of clinical records from 456 patients, covering the period from January 2018 to December 2020, revealed a statistically significant relationship between DR-TB types and age groups (Chi-square statistic: 30.74, p-value: 0.015). Younger adults (19–35 years) and middle-aged adults (36–50 years) are more frequently affected by RR-TB and MDR-TB, which are the most prevalent forms of DR-TB. Less common types, including Pre-XDR, XDR, and INH TB, were observed in smaller numbers. The study suggests that DR-TB imposes a heavy burden on the working age population. Gender analysis shows that while the frequency of DR-TB differs between males and females, the percentage distribution of DR-TB types is relatively equal. Both genders are predominantly affected by RR-TB and MDR-TB, which together account for nearly 90% of cases. Pre-XDR, XDR, and INH-resistant TB are much less common, comprising only a small percentage of cases in both males and females. High-risk behaviors such as smoking and drinking are linked to a wider diversity of DR-TB types, while occupations like mining and prison work show higher rates of RR-TB and MDR-TB. In HIV-positive individuals, DR-TB is more common, but the distribution of DR-TB types between HIV-positive and negative groups shows no statistically significant difference. However, HIV-positive individuals have a 20% lower survival rate (65%) compared to HIV-negative patients (85%). Financial stability and comorbidities also significantly influence outcomes, with patients having stable income and fewer high-risk comorbidities experiencing better survival and treatment outcomes. The findings underscore the importance of addressing socioeconomic disparities and strengthening healthcare infrastructure to improve DR-TB treatment outcomes in rural Eastern Cape.

Impact of non-pharmacological interventions on incidence of hand, foot and mouth disease during the COVID-19 pandemic: a large population-based observational study

BackgroundHand, foot, and mouth disease (HFMD) is a highly prevalent and contagious disease, particularly in children under five years old. Its transmission route resembles that of COVID-19. During the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) were implemented to curb viral spread, which may have concurrently reduced HFMD incidence.MethodsUtilizing HFMD surveillance data from the Anhui Provincial Center for Disease Control and Prevention (2015–2020) and varying levels of COVID-19 emergency measures, a Bayesian structural time series model predicted the counterfactual HFMD incidence and quantified the causal relationships with NPIs.ResultsDuring the implementation of NPIs, the 915 cases observed between weeks 4 and 20 of 2020 reflected a 94.9% reduction from the expected cases number (915 vs. 17,790), avoiding approximately 16,875 cases. The relative reduction of male cases (95.2%) was similar to that of female cases (94.3%). Different age groups the number of cases decline roughly similar were 93.1%, 95.3%, 97.8%, 94.9%.ConclusionDuring the COVID-19 pandemic, NPIs implemented in response to COVID-19 effectively reduced HFMD incidence. NPIs should be promoted for future control of enteric infectious diseases such as HFMD.

Drug induced reversible cardiomyopathy reported for liposomal amphotericine B: a rare documented adverse event

Liposomal amphotericin B (LAmB), lipid formulation of amphotericin B (AmB) is used in the treatment of fungal infections, including invasive disease and cryptococcal meningitis and is associated with fewer nephrotoxic and infusion-related adverse effects than conventional amphotericin B. Cardiac toxicity due to LAmB is a rarely reported adverse event in literature. Here we report a case of 53 years female known case of vitiligo, Diabetes mellitus Type 2 diagnosed as case of sinonasal mucormycosis and started on inj LAmB, developed chest pain on day 4 of inj LAmB. ECG and 2D ECHO showed VPBs and ventricular ectopics that were transient and completely recovered on reducing the dose of LAmB. As LV function has recovered on reducing Liposomal AMB, and patient was not on any other cardiotoxic drugs. It was concluded that the patient developed Transient Cardiomyopathy also known as Takotsubo Cardiomyopathy likely due to Liposomal AMB that improved on reducing dose of the drug LAmB. Although very rare but reversible cardiomyopathy also known as Takotsubo Cardiomyopathy due to LAmB is a documented adverse effect. Therefore, ECG monitoring or cardiac monitoring (2D ECHO) should be done when patient is started on LAmB and if at any point cardiotoxicity is suspected then drug should be stopped or reduced in dose immediately. These adverse effects are reversible which recovere on stopping or reducing the dose of LAmB.

Retrospective Study of Fine Needle Aspiration Cytology of Patients with Thyroid Nodule in Benghazi in the Period of (2021-2023)

Background: Thyroid nodules constitute a common endocrine disorder, these nodules could be solitary, multiple, cystic, or solid. Increasing age, female gender, iodine deficiency, and history of thyroid radiation all are high risk for thyroid nodules. FNAC representing the most cost-effective diagnostic tool used in the assessment of nodules of the thyroid. Objective of the study: The aim of this study is to evaluate the result of fine needle aspiration cytology (FNAC) and assess thyroid status using of thyroid hormone obtained from patients with thyroid nodules. Materials and methods: this is a retrospective study, includes collection of data from available cases of thyroid nodules underwent fine needle aspiration between 2021 to 2023, data regarding age, sex, TFT, USS, FNAC was collected from the archive of endocrine out patients clinic of Benghazi Medical Center and from endocrine clinic of Benghazi diabetic center. The analysis was done using the SPSS program. Result: A total of 60 cases were studied, Data was collected from 60 patient’s files for years between 2021 and 2023. The mean age of the patients with FNAC selected for this study was 49.65, and ranged from 21-80 years. The gender distribution shows female predominance in which female cases were 53 (98.33%) while only one case (1.67%) was reported among men. The size of nodules in our cases range from 1cm to 4.5 cm. The mean size of nodules is 1.89cm. In this study the largest group of nodules located in right lobe (21) cases then left lobe (20) cases then both (17) cases and in isthmus only 2 cases. Most of the cases thyroid function test result shows an euthyroid status (38) cases. FNAC of thyroid nodule showed that most of patient’s result diagnosed as benign nodules (47) cases. Conclusion: FNAC is a key tool in diagnosis of thyroid nodule as it has safe, minimally invasive and cost effective diagnostic role.

Modulation of miR-205 expression using a Cheiranthus cheiri phyto-nano hybrid as a potential therapeutic agent against breast cancer.

Breast cancer is the fifth major cause of fatalities associated with cancer worldwide and in Pakistan, 34 066 female breast cancer cases were recorded in 2018. This study was designed to understand extracts of Cheiranthus cheiri (C. cheiri) and to evaluate the epigenetic modulation of microRNA expression for breast cancer therapy using a selected phyto-nanohybrid treatment. The phytochemical screening revealed the presence of potential phytochemicals and antioxidant scavenging activity in the C. cheiri extracts with a DPPH (2-diphenyl-1-picryl-hydroxyl) assay giving an IC50 value of 20.63 μg mL-1. GC-MS (gas chromatography-mass spectroscopy) analysis of the C. cheiri n-hexane extract detected 42 phytocompounds. Titanium oxide (TiO2) nanoparticles were synthesized and characterized using XRD (X-ray diffraction), SEM (scanning electron microscopy) and EDX (energy dispersive X-ray spectrometry) to confirm the synthesis of anatase (tetragonal) TiO2. The prepared nanoparticles were conjugated with the selected plant i.e., C. cheiri. The resulting phyto-nanohybrid was used for the subsequent treatment of breast cancer induced in a female rat model. The treatment groups were as follows: doxorubicin as the standard treatment, C. cheiri, TiO2 and the phyto-nano hybrid treatment. After 8 weeks of treatment, the groups induced to exhibit breast cancer (with and without treatment) and the control groups were dissected and analysed for histopathological, haematological and microRNA expression. Histopathological examination revealed chronic inflammation in the dilated ducts and tumour embolus formation, thus confirming the presence of breast cancer in the DMBA-induced female rat model. MicroRNA expression analysis showed a statistically significant decrease in levels of miR-205 in the plasma of the breast cancer rat model compared to the control (p < 0.05). After treatment with the phyto-nano hybrid, a statistically significant increase in the expression of miR-205 was observed in the rat models induced to exhibit breast cancer compared to the rat model without any treatment (p < 0.05). The downregulation of miR-205 in the plasma of the breast cancer exhibiting model, as compared to the control, and its upregulation after treatment with the selected phyto-nano hybrid indicated its diagnostic and prognostic significance. It is concluded that the phyto-nano hybrid used in this study is effective against breast cancer induced female rat model. All the results support the finding that the selected phyto-nano hybrid has great potential as a possible therapeutic agent for the treatment of breast cancer.

Females at a Clear Disadvantage with Postoperative Myocardial Infarction Symptoms.

Cardiovascular disease remains the leading cause of death in women. Gender bias and blindness are coming into focus as relevant risk factors for patients. To date, there have been no studies that target surgeons' potential gender bias in recognizing postoperative myocardial infarction (MI). An online clinical vignette describing a patient with postoperative MI was randomized for gender. Possible diagnoses, the next steps in management, and questions on gender bias were assessed. A total of 205 surveys were analyzed. MI was recognized in 55.6% of the male case studies vs. 32.0% of the female case studies in the first question (p < 0.005). Cardiac diagnostics were initiated significantly more in male case studies (94% vs. 76%, p = 0.001). Female surgeons listed MI as the first diagnosis twice as often as male surgeons overall (43% vs. 23%, p = 0.027). Female surgeons were also more likely to mention MI across the survey at all compared to male surgeons (89% vs. 67%, p = 0.0002). Board-certified surgeons diagnosed MI by the end of the survey significantly more (88.2%) than residents (75.0%) and medical students (75.0%, p = 0.047). Overall, this study was able to demonstrate the presence of both gender bias and gender blindness in surgeons' assessment of postoperative myocardial infarction symptoms with a clear disadvantage for female patients and a superior awareness for female surgeons.

The macular microvascular changes in children with a history of retinopathy of prematurity treated with intravitreal Bevacizumab injection using optical coherence tomography angiography: a retrospective cohort.

Our study aims to evaluate and compare the macular microvascular condition of the intravitreal Bevacizumab (IVB)-treated retinopathy of prematurity (ROP) cases to the preterm cases without ROP and spontaneously regressed ROPs. It is a retrospective cohort of 50 premature neonates visited from 2016 to 2017 for ROP screening in Nikookari Eye Hospital and recalled for re-evaluation in 2022. These patients were classified into three groups based on their medical documents: 1. Preterm cases without ROP (PT), 2. Spontaneously regressed ROPs (SR), and 3. IVB-treated ROPs (IVB). All the included cases underwent a thorough ophthalmic exam, cyclo-refraction, Best-corrected visual acuity (BCVA) assessment, and macular optical coherence tomography angiography (OCTA). The foveal thickness, foveal avascular zone (FAZ) area, foveal, parafoveal, and perifoveal vascular density (VD) were evaluated as the quantitative variables. Twenty-five male and 25 female cases with a median age of 5.0 entered the study. Twenty-six eyes were evaluated in the PT group, 50 in the SR group, and 24 in the IVB group. The SR group consisted of 25 zone-2 and 25 zone-3 ROPs. In comparison, the IVB group consisted of 9 zone-1 and 15 zone-2 ROPs (p: < 001). Also, zone-2 cases were more advanced in the IVB group. The IVB-treated eyes demonstrated a significantly higher foveal superficial capillary plexus (SCP) VD than the others (28.5% vs. 23.1 and 22.9, respectively, in PT and SR, p:0.008). However, the parafoveal deep capillary plexus (DCP) VD was lower than the PT cases (48.5% vs. 53.4, p:0.034). The FAZ area was also smaller than the PT cases (0.113 vs.0.219 mm2, p:0.032). The FAZ area was significantly positively correlated with the foveal SCP and DCP VD and negatively correlated with parafoveal DCP VD (CC: -0.770, -0.719, 0.377, respectively, p: < 0.001). In the long term, although the IVB-treated ROP cases experience an excellent visual outcome comparable to those without ROP, they may show some macular microvascular changes. These changes might be related to the effect of IVB or the nature of more advanced stages of ROP.

Clustering of hepatitis C infection among family members in Aden, Yemen

BackgroundHepatitis C infection is a common cause of liver diseases such as cirrhosis and liver carcinoma. This study aims to determine the clustering of HCV infection among family members of HCV-positive patients (index cases) and the association between internal and external risk factors and HCV infection among these family members.MethodsThis cross-sectional study was conducted during a period from January to June 2024. One hundred and seventeen family members belonging to 26 index cases were enrolled in this study. Blood samples were collected from all family members, and then sera were separated and tested for anti-HCV antibodies by using a commercially available Cobas technique based on ECLIA.ResultsAmong 117 family members, the majority 55.6% were females. The clustering of HCV infection among family members was 7.7%. The highest rates were 9.6% among males and 11.8% among members who were in close contact with female-positive cases, 12.8% in the age group 20–29 years, and 27.3% among brothers, but there were no HCV-positive cases detected among fathers, daughters, and husbands. There was a significant association between HCV infection and some behaviors of family members such as sharing the same sleeping places, nail clippers, and towels with index cases and exposure to cupping (p = 0.0001, 0.002, 0.017, and 0.050), respectively.ConclusionThe HCV infection among family members in Aden, Yemen, was low in comparison with most studies globally. The highest rates were found among males, those in contact with female index cases, in the age group 20–29 years, and brothers as relatives, but there were no positive cases among fathers, husbands, daughters, and other relatives.

Multi-omic analyses of a twin pair with mirror image cleft lip identifies pathogenic variant in FGF20 modified by differential methylation upstream of ZFP57.

Disturbances in the intricate processes that control craniofacial morphogenesis can result in birth defects, most common of which are orofacial clefts (OFCs). Nonsyndromic cleft lip (nsCL), one of the phenotypic forms amongst OFCs, has a non-random laterality presentation with the left side being affected twice as often compared to the right side. This study investigates the etiology of nsCL and the factors contributing to its laterality using a pair of monozygotic twins with mirror-image cleft lip. We conducted whole-genome sequencing (WGS) analyses in a female twin pair with mirror image nsCL, their affected mother and unaffected father to identify etiopathogenic variants. Additionally, to identify possible cleft lip laterality modifiers, DNA-methylome analysis was conducted to test for differential methylation patterns between the mirror twins. Lastly, DNA methylation patterns were also analyzed on an independent cohort of female cases with unilateral cleft lip (left=22; right=17) for replication purposes. We identified a protein-altering variant in FGF20 (p.Ile79Val) within the fibroblast growth factor interacting family domain segregating with the nsCL in this family. Concurrently, DNA-methylome analysis identified differential methylation regions (DMRs) upstream of Zinc-finger transcription factor ZFP57 (Δβ > 5%). Replication of these results on an independent cohort, confirmed these DMRs, emphasizing their biological significance (p<0.05). Enrichment analysis indicated that these DMRs are involved in DNA methylation during early embryo development (FDR adjusted p-value = 1.3241E-13). Further bioinformatics analyses showed one of these DMRs acting as a binding site for transcription factor AP2A ( TFAP2A ), a key player in craniofacial development. Interactome analysis also suggested a potential role for ZFP57 in left/right axis specification, thus emphasizing its significance in cleft laterality. This study provides novel insights into the etiology of nsCL and its laterality, suggesting an interplay between etiopathogenic variants and DNA methylation in cleft laterality. Our findings elucidate the intricate mechanisms underlying OFCs development. Understanding these factors may offer new tools for prevention and management of OFCs, alleviating the burden on affected individuals, their families and global health.

Survey on the Prevalence of Buruli Ulcer in Patients with Chronic Wounds in Pointe-Noire

Background &amp; objective: Buruli Ulcer (BU) is a human skin infection caused by Mycobacterium ulcerans, an environmental mycobacterium. This pathology is most prevalent in humid tropical regions, particularly near swampy or flood-prone areas. In Pointe-Noire, a coastal city in the Republic of Congo, Buruli ulcer is a health threat requiring ongoing surveillance and awareness-raising efforts to control its spread. The aim of this study was to determine the prevalence of Buruli ulcers in patients consulting for chronic wounds in Pointe-Noire. Methods: This was a descriptive cross-sectional study conducted from June 10, 2023 to September 18, 2024. We recruited 69 patients with chronic wounds consulted at the Adolphe Sicé General Hospital, the Tié Tié Referral Hospital, and the Pointe Noire Operational Sector. Mycobacterium ulcerans was systematically detected using the qPCR technique targeting the M. ulcerans IS 2404 specific insertion element on swab samples. Results: 69 patients with suspected BU were enrolled, with 57% (39) male and 43% (30) female subjects. The mean age was 47.7 ± 18.5, ranging from 6 to 94 years, and the most represented age group was [30-60] (66.7%). The wounds observed in our patients were mainly ulcerative in 94.2% (65) and localized to the lower limbs in 97.1% (67). The overall prevalence of Mycobacterium ulcerans infection was 2.89%. The age group affected was &lt; 15 years, with 01 positive male case and [30-60], with 1 positive female case. Conclusion: The study carried out in Pointe-Noire revealed a Buruli ulcer prevalence of 2.86% among the 69 patients with chronic wounds tested, with 02 positive cases.

Abstract B072: Molecular targets of caffeine in breast cancer treatment: A network pharmacology approach

Abstract In Ghana, breast cancer leads in female cases (31.8%), demanding advanced treatments. Rising caffeine-filled energy drinks raise concerns. Yet, caffeine's role in breast cancer lacks understanding, urging more research. Our study uses network pharmacology and molecular docking to unravel the intricate molecular targets of caffeine in breast cancer, offering new therapies for this widespread disease We identified breast cancer-related targets from GEO datasets and TCGA databases, while caffeine targets were obtained from the SwissTarget Prediction database and literature. Common targets of both caffeine and breast cancer were considered using Venny software. PPI networks were generated using STRING and Cytoscape, identifying hub genes. Target proteins were annotated using the GO database, and pathway enrichment analysis was performed using KEGG. To investigate the binding affinity target proteins were retrieved from the Protein DataBank and docking studies were conducted using AutoDock Vina to explore the binding interactions between caffeine and potential target proteins identified. We identified 108 targets, and 6 common targets, including Cyclin-Dependent Kinase 1, Cyclin B1, Epidermal Growth Factor Receptor, Cyclin B2, Monoamine Oxidase A, and Carbonic Anhydrase 12 in relation to breast cancer. Gene Ontology (GO) and KEGG pathway enrichment analysis revealed their interactions in key pathways such as the P53 signaling pathway and Foxo signaling pathway, suggesting their critical roles in anti-breast cancer processes. Notably, caffeine exhibited the best overall binding affinity when interacting with CDK1, CCNB1, EGFR, and CCNB2 These findings provide valuable insights into the potential molecular targets and pathways associated with caffeine's anti-breast cancer effects, offering new strategies for therapeutic strategies. Citation Format: Kingsley A Osei, Justina S Owusu. Molecular targets of caffeine in breast cancer treatment: A network pharmacology approach [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B072.

Associations of radiotherapy receipt with lung cancer risk by histological subtype among breast cancer survivors in the United States.

Radiotherapy for breast cancer has been associated with an increased risk of secondary malignancies, including primary lung cancer. Whether this association varies by histological subtype of lung cancer remains unknown. Based on the data from 12 Surveillance, Epidemiology, and End Results registries, we examined the association between radiotherapy receipt and the risk of subtype-specific subsequent primary lung cancer (SPLC) among female first primary breast cancer cases diagnosed between ages 20 and 84 from 1992 to 2020. More than half (53%) of the 550,007 breast cancer survivors identified had undergone radiotherapy as part of their initial breast cancer treatment. Over an average follow-up of 9.7 years, 8014 survivors developed SPLCs. For small-cell carcinoma, the standardized incidence ratio (SIR) compared with the general population was higher for survivors who received radiotherapy (SIR = 1.15, 95% confidence interval [CI] = 1.06-1.25) but similar for those who did not receive radiotherapy (SIR = 1.00, 95% CI = 0.91-1.09), with the difference in SIRs being statistically significant (p = .003). Similar associations were found for squamous cell carcinoma (SIRyes = 1.16, 95% CI = 1.08-1.24 vs. SIRno/unknown = 1.06, 95% CI = 0.98-1.15; p = .07). The increased risks were confined to ipsilateral SPLC, with the greatest SIRs for small-cell carcinoma occurring 5-10 years since breast cancer diagnosis (SIR = 1.83, 95% CI = 1.53-2.19) and for squamous cell carcinoma with a latency of 10 years or more (SIR = 1.64, 95% CI = 1.42-1.88). In contrast, the risk of developing adenocarcinoma did not vary by radiotherapy receipt (SIRyes = 1.23, 95% CI = 1.18-1.28 vs. SIRno/unknown = 1.17, 95% CI = 1.12-1.22; p = .18), indicating additional risk factors in play. The findings suggest a distinct carcinogenic pathway of radiation-induced lung cancer across histological subtypes and may inform risk-stratified surveillance guidelines for SPLC.

Abstract 4137646: Transcriptomic Profiling of Human Myocardium at Sudden Death to Define Vulnerable Substrate for Lethal Arrhythmias

Background: While some chronic pathological substrates for sudden cardiac death (SCD) are well-known (e.g., coronary disease and left ventricular [LV] dysfunction), the vulnerable myocardial state predisposing to fatal arrhythmia remains a critical barrier to near-term SCD prevention. Hypothesis: Myocardium of autopsy-defined SCDs exhibit distinct expression profiles vs. non-cardiac sudden deaths and trauma deaths that reflect its acute vulnerable state in the hours to days before SCD, as expression arrests upon death. Goals/Aims: Define the vulnerable myocardial substrate for lethal arrhythmia by targeted RNA profiling. Methods: We used autopsy to adjudicate arrhythmic from non-arrhythmic causes in 1,265 sudden deaths in San Francisco from 2011-2018. We performed a transcriptomic evaluation of LV sampled at the time of SCD from 245 consented cases using a curated panel of 448 genes with known or hypothesized association with SCD. Results: Comparison between Arrhythmic (n=129) and Non-Arrhythmic (n=116) cohorts revealed 31 differentially upregulated and 36 downregulated genes (p-adj&lt;0.05), related to collagen-containing extracellular matrix (upregulation of FAP , FMOD , LTBP2 ), ion transport (upregulation of KCNA5 and KCNN3 , and downregulation of KCNJ8, KCNK1, KCNJ5 ), and contraction (downregulation of MYH6 ). Fibrosis-related genes showed the highest magnitude increased expression in Arrhythmic vs. Non-arrhythmic deaths and vs. published transcriptomes from end-stage heart failure. After molecular stratification by known markers for mature ( COL1A1, COL1A2, COL3A1) and active ( POSTN , MEOX1 ) fibrosis, cases with highest expression of both had the highest proportion of arrhythmic cause of death (27/36 [75%]) vs. cases with low expression of both (87/181 [38%], p=0.006) or vs. mature only (10/14 [71%]) or active only (5/14 [36%]). Activated fibroblast gene expression was enriched in Arrhythmic female vs. Arrhythmic male cases, among other sex-specific differences in ion channel and myosin (upregulation of SCN4B , SCN8A , KCNAB1 in females, KCNJ4 and MYH7B in males) expression. Conclusions: RNA profiling of myocardium at SCD identifies active fibrosis, undetectable by conventional clinical methods, in the presence of fixed scar and selected ion channel dysregulation (more pronounced among female cases) as an acute vulnerable substrate for fatal arrhythmias, and may identify patients at elevated near-term risk for SCD and novel pathways for intervention.

Abstract 4137945: A Tuscany regional screening program for juvenile sudden cardiac death in high schools: the JUST project

Background: Juvenile sudden cardiac death (SCD) has high impact on the family and society of the victim. While SCD screening programmes are effective in athletes, most (70-80%) young non-athletes individuals are not routinely screened. Research question: We hypothesized that a low-cost screening program may early identify subjects at risk of juvenile SCD, even in non-athletes. Goals: To evaluate the prevalence of SCD-related abnormal findings and, ultimately, to test the effectiveness of a screening programme in high schools. Methods: Between April 2023 and June 2024, high school individuals were enrolled in a screening programme in Tuscany (Pisa, Lucca and Livorno), based on a questionnaire investigating family history of juvenile SCD or diseases predisposing to SCD and symptoms (syncope, palpitations, chest pain), and digitally recorded electrocardiograms (ECGs). In case of abnormal findings, second-line investigations locally (echocardiography, Holter ECG monitoring and/or exercise testing) or third-line investigations at Fondazione Monasterio, Pisa, Italy (cardiac MRI, genetics or electrophysiological testing) were planned. Only preliminary results of the first-line screening are hereby reported. Results: We have currently enrolled 872 individuals (age 17.1±1.8 years, 481 [55%] males, 288 [33%] smokers, 102 [11.7%] recreational drugs users, and 645 [74%] non-competitive athletes). At questionnaires, 56 individuals (6.4%) had a family history of SCD, 32 (3.7%) a first-degree relative with cardiomyopathy, and 13 (1.5%) with channelopathy. As for symptoms, 21 participants (2.4%) reported chest pain or 26 (3%) syncope during exertion, while 90 (10.3%) paroxysmal palpitations. At ECG, we found 2 cases (0.2%) with a type-2 Brugada pattern, 1 female case (0.1%) with prolonged QTc interval (QTc 480 ms), 20 cases (2.3%) with V1-V3 T wave inversion (age &gt; 16 years), 18 cases (2%) of left ventricular hypertrophy (non-athletes), and 4 cases (0.5%) with atypical ventricular ectopy. After the first-line screening, 61 (7%) and 10 (1.2%) individuals were referred to second and third-line investigations, which are currently ongoing. Conclusions: We hereby propose a screening model in high schools that includes specific health questionnaires and digitally recorded ECGs. From preliminary analyses, this approach seems sensitive enough to be tested as a model to favour the early diagnosis of diseased conditions associated with juvenile SCD in the general population.

Analgesic Efficacy of Transversus Abdominis Plane block vs Local Infiltration of Lignocaine and Bupivacaine in Post-operative Patients

Objective: To compare the effectiveness of Transversus Abdominis Plane (TAP) block vs Local Infiltration for pain management techniques in patients undergoing laparoscopic lower abdominal surgeries. Methodology: This cross-sectional study was conducted at the Department of Surgery, Lahore General Hospital, from March to May, 2024. It involved a total of 110 patients, divided into two groups of 55 each, between the ages of 20 to 60 years, diagnosed with indirect inguinal hernia by ultrasound. Chronic smokers, drug addicts, intravenous drug abusers, patients with a history of previous surgeries, with known drug allergies and with complicated hernia were excluded from this cross-sectional study. The Numerical Rating Scale (NRS) was used to see the pain variation and effectiveness of both techniques at 6, 12, 18 and 24 hours. Results: The mean age in the TAP Block Group was 32.0 ± 9.92 years, and the mean age in the Local Wound Infiltration Group was 34.21 ± 10.01 years. There were 108 (98.18%) male and 2(1.81%) female cases with a higher male-to-female ratio. The results indicated that the TAP Block group consistently required fewer rescue analgesic doses than the local wound Infiltration group at all postoperative time points. At 6 hours, 23.63% of patients in the TAP Block group needed additional analgesia, compared to 38.18% in the Wound Infiltration group, though this difference was not statistically significant. However, at 12, 18, and 24 hours, the TAP Block group showed a significantly lower need for rescue analgesia, with p-values of 0.002, and 0.008, respectively. Conclusion: In managing postoperative pain of Inguinal Hernia Repair, TAP Block is superior to Wound Infiltration of local anesthetic agent. After TAP Block NRS remains fewer and a smaller number of rescue doses are needed as compared to Wound infiltration.

Image Features and Diagnostic Value of Contrast-Enhanced Ultrasound for Ductal Carcinoma In Situ of the Breast: Preliminary Findings.

To explore the image features and the diagnostic value of contrast-enhanced ultrasound (CEUS) for ductal carcinoma in situ (DCIS) of the breast. A total of 96 female patients with a solitary and histologically proven DCIS were analyzed retrospectively, and 100 female cases of invasive ductal carcinoma (IDC) lesions were used as the control group. The Breast Imaging Reporting and Data System (BI-RADS) category of breast lesions was assessed according to conventional ultrasound features. The DCIS lesions were classified into mass type and non-mass type. The CEUS characteristics of these breast lesions were retrospectively analyzed qualitatively and quantitatively. The final gold standard was biopsy or surgery with histo-pathological examination. Comparing the ultrasound images of DCIS with that of IDC, there were significant differences in echo pattern, calcification morphology, and calcification distribution (p < .05 for all). There was a significant difference between DCIS and IDC in enhancement intensity, perfusion defects, peripheral high enhancement, intratumoral vessels, and arrival time (AT) (p < .05 for all). In the logistic multivariate regression analysis, two indicators linked with DCIS were recognized: perfusion defects (p = .002) and peripheral high enhancement (p < .001). In forecasting DCIS, the logistic regression equation resulted in an AUC of 0.689, a specificity of 0.720, and a sensitivity of 0.563. CEUS showed differences in enhancement characteristics between DCIS and IDC, with perfusion defects and peripheral high enhancement being associated with DCIS.

A comprehensive epidemiological assessment of female rape in São Paulo State, Brazil: trends, patterns, and implications for public health.

Sexual violence against women remains a global challenge, with Brazil exemplifying persistent issues despite legislative advancements. This study examined sexual violence within São Paulo state, Brazil's largest and economically affluent state, focusing on prevalence, patterns, forensic evidence, and health consequences. We analyzed 40,757 medical reports of alleged cases of rape against women available from the São Paulo Medical Legal Institute from 2014 to 2017. An increase in female rape cases was observed, reflecting broader societal trends, but underreporting, prevalent due to fear and stigma, underscored the need for multifaceted interventions. We also explored correlations between rape prevalence and the Human Development Index, highlighting disparities between urban and rural areas. Additionally, the study revealed concerning proportions of cases involving vulnerable victims, emphasizing the imperative for tailored interventions and legislative reforms. Furthermore, we demonstrated that only a small portion of medicolegal examinations were able to find evidence of sexual violence or recent sexual acts, necessary for conducting the criminal investigation of the alleged act. Therefore, despite challenges in forensic evidence collection, efforts to enhance medical examination protocols and awareness among professionals are crucial. Moreover, findings underscored the significant health consequences of rape, including unwanted pregnancies and sexually transmitted infections, necessitating comprehensive healthcare services for survivors. In conclusion, we reinforced that addressing sexual violence demands coordinated action, including legislative reforms, community engagement, and survivor-centered approaches, to create safer and more resilient communities.

Polygenic Risk Score and Lung Adenocarcinoma Risk Among Never-Smokers by EGFR Mutation Status: A Brief Report

We assessed the association between a genome-wide polygenic risk score (PRS) developed for lung adenocarcinoma (LUAD) risk and mutation on the EGFR gene in 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4544 never-smoking controls using case-case and multinomial regression analyses. We found that the PRS was more strongly associated with EGFR-positive LUAD compared with EGFR-negative LUAD, where the association between the fourth quartile of the PRS and EGFR-positive LUAD (odds ratio = 8.63, 95% confidence interval: 5.67–13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR-negative LUAD (odds ratio = 3.50, 95% confidence interval: 2.44–5.00) (p-heterogeneity = 3.66 × 10−3). Our findings suggest that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients depending on the cancer's mutation status, which may have important public health and clinical implications.