Family Medical History Research Articles

Additive interaction of family medical history of cardiovascular diseases with hypertension and diabetes on the diagnosis of cardiovascular diseases among older adults in India

IntroductionThe present study aimed to examine the additive interaction of family medical history of cardiovascular disease (CVD) and self-reported hypertension and diabetes on the diagnosis of CVD among older adults aged 45 years and above in India. A family medical history of CVD in individuals with hypertension and diabetes could identify a subpopulation with a higher risk of CVD.MethodsThe study used the data from the Longitudinal Ageing Study in India (LASI) Wave 1 (2017–2018). The total sample size for the study was 58,734 older adults aged 45 years and above. An additive model was applied to determine the additive interaction effect of the family medical history of CVD with hypertension and diabetes on the diagnosis of CVD by calculating three different measures of additive interaction: the relative excess risk due to interaction (RERI), attribution proportion due to interaction (AP), and synergy index (S).ResultsThe prevalence of CVD was higher among hypertensive individuals with a family medical history of CVD (18.6%) than individuals without the coexistence of family medical history of CVD and hypertension (4.7%), and hypertensive individuals without family medical history of CVD (11.3%). On the other hand, the prevalence of CVD was higher among individuals with diabetes and family history of CVD (20.5%) than individuals without the coexistence of family history of CVD and diabetes (5.0%). Individuals with parental and sibling medical history had two times higher odds of having chronic heart diseases and strokes, respectively than those without parental and sibling history. In the adjusted model, RERI, AP, and S for CVD were 2.30 (95% CI: 0.87–3.74), 35% (0.35; 95% CI: 0.20–0.51), and 1.71 (95% CI: 1.27–2.28) respectively, demonstrating significant positive interaction between family medical history and hypertension on the diagnosis of cardiovascular diseases.ConclusionsThe present study revealed that in the additive model, the interaction effects of family medical history and hypertension were significantly positive on cardiovascular diseases even after adjustment with potential confounding factors. Therefore, it is crucial to consider the presence of family medical history of CVD among individuals with hypertension and diabetes measured in research and clinical practice.

A comprehensive analysis and performance evaluation for osteoporosis prediction models

Medical data analysis is an expanding area of study that holds the promise of transforming the healthcare landscape. The use of available data by researchers gives guidelines to improve health practitioners’ decision-making capacity, thus enhancing patients’ lives. The study looks at using deep learning techniques to predict the onset of osteoporosis from the NHANES 2017–2020 dataset that was preprocessed and arranged into SpineOsteo and FemurOsteo datasets. Two feature selection methods, namely mutual information (MI) and recursive feature elimination (RFE), were applied to sequential deep neural network models, convolutional neural network models, and recurrent neural network models. It can be concluded from the models that the mutual information method achieved higher accuracy than recursive feature elimination, and the MI feature selection CNN model showed better performance by showing 99.15% accuracy for the SpineOsteo dataset and 99.94% classification accuracy for the FemurOsteo dataset. Key findings of this study include family medical history, cases of fractures in patients and parental hip fractures, and regular use of medications like prednisone or cortisone. The research underscores the potential for deep learning in medical data processing, which eventually opens the way for enhanced models for diagnosis and prognosis based on non-image medical data. The implications of the study shall then be important for healthcare providers to be more informed in their decision-making processes for patients’ outcomes.

Clinical diagnosis of the monogenic Ehlers-Danlos syndromes.

Monogenic Ehlers-Danlos syndromes (EDS) are a group of inherited connective tissue conditions that are clinically characterised by joint hypermobility, skin hyperextensibility and/or fragility, and generalised tissue fragility. Gene panel testing with massively parallel sequencing is currently gold standard to confirm diagnoses of the monogenic EDS types. We aim to report on the (combination of) clinical features of the monogenic EDS types through text and photographs, to aid clinical diagnosis as despite the significant progress in genetic testing possibilities, a thorough clinical assessment which includes medical history, family history and physical examination remains important in the diagnostic process. In addition, in those cases where no molecular diagnosis is possible, a clinical diagnosis can still guide management and surveillance.

Survival Stacking Ensemble Model for Lung Cancer Risk Prediction.

The most well-established risk factor for lung cancer (LC) is smoking, responsible for approximately 85% of cases. The Lung Cancer Risk Assessment Tool (LCRAT) is a key advancement in this field, which predicts individual risk based on factors like smoking habits, demographic details, personal and family medical history, and environmental exposures. This paper proposes a model with fewer features that improves state of the art performance, using a simplified stacking ensemble, making it more accessible and easier to implement in routine healthcare practice. The data used in this work were derived from two cohorts in the United States: The National Lung Screening Trial (NLST) and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Both our model and LCRAT achieve an AUC of 0.799 and 0.782 on test respectively. In terms of percentage of positives, in the 50% of the population, both detect 0.766 and 0.754 of the cases. The ensemble of different survival models enhances robustness by mitigating the weakness of individual models and directly impacts the efficiency of the model, increasing the efficiency and generalizability.

Social Demographic and Clinical Predictors of Time to Clinic Presentation After a Sport-Related Concussion.

To investigate the associations between clinical risk factors, social demographic and time to concussion clinic presentation after sports-related concussion in young athletes. Retrospective cohort study. Multidisciplinary regional concussion center. Athletes ages 12 to 18 years who sustained a SRC from November 2017 to April 2022. Independent variables included social demographic factors (ie, race, ethnicity, public vs private school, public vs private insurance), patient medical history, family medical history, acute concussion characteristics, and initial presentation elsewhere. Descriptive statistics were employed to assess for group differences. Mann-Whitney U tests, Spearman rank order correlations, and linear regressions were performed to explore associations between each independent variable and the main outcome, days to concussion clinic presentation. A total of 945 athletes we included (age 15.8 ± 1.61, 33.7% female). Hispanic/Latino background, (P = 0.009), public insurance status (U = 47 377.0, P = 0.002), amnesia (U = 57 738.0, P = 0.002) at time of injury, family psychiatric (U = 35 091.0, P < 0.001) or migraine (U = 59 594.5, P < 0.001) histories, and personal psychiatric (U = 30 798.0, P = 0.004) or migraine (U = 34 133.5, P = 0.011) histories were associated with longer time to concussion clinic presentation. A multivariable linear regression found that initial presentation elsewhere (β = 0.37, P < 0.001), family migraine history (β = 0.18, P < 0.001), public insurance status (β = 0.09, P = 0.024), and history of learning disability (β = 0.09, P = 0.032) were the only predictors of longer time to concussion clinic presentation. Variables that predicted longer time to concussion clinic presentation included initial presentation elsewhere, public insurance status, positive family migraine history, and history of learning disability. Further research is needed to elucidate these findings and determine how they impact concussion seeking behavior.

Risk of postpartum depression in women with allergic disorders: A nationwide cohort study involving 1,017,507 women

BackgroundAllergic symptoms and depression are prevalent ailments in childbearing age women. This study assessed the risk of maternal postpartum depression (PPD) associated with prenatal allergic disorders. MethodsFrom 1,017,507 eligible women of 20–49 years old with singleton live births and 20-week or more gestational age in the birth registry of Taiwan, from 2011 to 2020, we identified cohorts with and without allergic disorders matched by propensity score in the size of 457,826. Cumulative incident PPDs in one year after births were assessed from insurance claims data. Odds ratios (OR) of PPD were measured by each allergic type and multiple types, comparing with the controls. ResultsWith an overall cumulative PPD incidence 1.25-fold higher in the allergic cohort than in the controls (0.69 % versus 0.55 %), the rate was the highest in women with asthma: 0.94 % with an adjusted OR of 1.71 (95 % CI = 1.49–1.95), followed by those with allergic rhinitis, allergic conjunctivitis and atopic dermatitis. The rate increased from 0.65 % for those with one allergic disorder to 1.06 % for those with 4 or 5 disorders, and the corresponding adjusted OR increased from 1.17 (95 % CI = 1.10–1.24) to 1.92 (95 % CI = 1.36–2.69). LimitationThe claims data lack detailed information on socio-demographic status, lifestyle, laboratory result, physical activity, and family medical history. ConclusionsWomen with prenatal allergic disorder(s) are at an increased risk of PPD in addition to the impact of pregnancy. Prompt and efficient intervention for PPD prevention is needed for women with allergic disorders, particularly for those with asthma and multiple disorders.

Defining the Effect of Teachers’ Medical History on their Inclusive Teaching Practice: Analyzing Feelings of Competence and Knowledge in Inclusive Physical Education

Background. The process of including special students in the school system has prompted a comprehensive examination of strategies to ensure equity in school justice, the quality of learning, and the harmonious development of students’ potential. The efficacy of these strategies is contingent upon the life experiences and medical backgrounds of the educators in question. Objectives. The study aimed to evaluate the extent to which personal and family medical histories impact teachers’ sense of pedagogical competence (TSPC) and their knowledge (TK) of students’ physical activity management. Materials and Methods. The methodology entailed the distribution of an online questionnaire to 339 physical education and sports (PE) teachers, comprising 159 females and 180 males over the age of 21, employed in public schools at the high school and middle school levels. The measurement instrument consisted of four sections: socio-demographic characteristics, personal and family background, sense of pedagogical competence, and teacher knowledge. Results. The findings indicate a notable prevalence of diseases such as obesity and diabetes in males compared to females, with a significant predominance in older people. It is demonstrated that gender has a particular influence on TSPC and TK in managing hypertensive students. Furthermore, older teachers and those employed in urban settings tend to exhibit greater self-efficacy, despite the absence of a statistically significant association between their initial PES training and TSPC and knowledge outcomes. There is a positive correlation between TSPC and teacher knowledge. Conclusions. To sum it up, older teachers are more susceptible to developing illnesses such as diabetes, hypertension, and obesity. This medical history has a significant impact on the development of inclusive skills and knowledge of school-related pathologies.

Evaluation of Knowledge, Attitudes, and Practices towards Colorectal Cancer in a Community in Mexico City: A Cross-Sectional Study Based on Surveys.

Colorectal cancer (CRC) is one of the most common and deadly neoplasms worldwide, with a growing burden in low- and middle-income countries, such as Mexico. This study seeks to evaluate the knowledge, attitudes, and practices related to CRC in a community in Mexico City. A cross-sectional survey was conducted between March and April 2023 among adults aged 45 to 74 residing in six neighborhoods of the Tlalpan borough in Mexico City. The questionnaire included sections on sociodemographic characteristics, medical family history, lifestyle habits, knowledge about CRC, attitudes towards prevention, and willingness to undergo screening. Data were analyzed using logistic regression models to identify factors associated with greater knowledge, attitudes, and practices. A total of 349 people were surveyed. A total of 35.2% reported knowing what CRC is, with greater knowledge of CRC being associated with higher education levels and having a family history of cancer. A total of 23.8% showed positive attitudes towards CRC screening, influenced by having a tertiary level of education. A total of 80.8% of participants expressed willingness to undergo CRC screening if offered, with lower intention observed among men. Levels of knowledge about CRC within the studied community are low, especially among those with lower education levels and without a family history of cancer. Intervention strategies should improve CRC education and foster positive attitudes towards early detection, particularly in high-risk groups.

An exploratory study of perceptions and utilization of genetic information in the intended parent experience of oocyte donor selection.

Utilization of oocyte donation has become an increasingly common practice in assisted reproductive technology (ART). Since the introduction of larger carrier screening (CS) panels and extended family medical histories (EFMH), studies have not examined how this information factors into the oocyte donor selection process. This exploratory, qualitative study provides further insight into what role, if any, donors' available genetic information (e.g., larger CS panels and EFMH) plays in selecting an oocyte donor. An online screening survey was distributed to individuals who have undergone or are currently in the process of selecting an oocyte donor through the RESOLVE network and Mayo Clinic's Reproductive Endocrinology and Infertility clinic. From 13 survey respondents, six oocyte recipients subsequently participated in semi-structured telephone interviews and discussed their experiences as oocyte recipients including their perceptions of donors' available genetic information and process in choosing an oocyte donor. Genetic information was seen as valuable and reassuring for participants, particularly EFMH, but did not play a significant role in the selection process for these participants. Supplemental emergent themes provide context on the psychosocial complexities of the oocyte recipient experience and possible explanations for why genetic information is not a decisional priority. Participants indicated genetic information was not extensively discussed or fully explained by providers. Results demonstrate how genetic counselors can be more involved in the pre-selection process to discuss the utility and limitations of genetic information, as well as address psychosocial issues common to the oocyte recipient experience.

Systematic evaluation of multifactorial causal associations for Alzheimer's disease and an interactive platform MRAD developed based on Mendelian randomization analysis.

Alzheimer's disease (AD) is a complex degenerative disease of the central nervous system, and elucidating its pathogenesis remains challenging. In this study, we used the inverse-variance weighted (IVW) model as the major analysis method to perform hypothesis-free Mendelian randomization (MR) analysis on the data from MRC IEU OpenGWAS (18,097 exposure traits and 16 AD outcome traits), and conducted sensitivity analysis with six models, to assess the robustness of the IVW results, to identify various classes of risk or protective factors for AD, early-onset AD, and late-onset AD. We generated 400,274 data entries in total, among which the major analysis method of the IVW model consists of 73,129 records with 4840 exposure traits, which fall into 10 categories: Disease, Medical laboratory science, Imaging, Anthropometric, Treatment, Molecular trait, Gut microbiota, Past history, Family history, and Lifestyle trait. More importantly, a freely accessed online platform called MRAD (https://gwasmrad.com/mrad/) has been developed using the Shiny package with MR analysis results. Additionally, novel potential AD therapeutic targets (CD33, TBCA, VPS29, GNAI3, PSME1) are identified, among which CD33 was positively associated with the main outcome traits of AD, as well as with both EOAD and LOAD. TBCA and VPS29 were negatively associated with the main outcome traits of AD, as well as with both EOAD and LOAD. GNAI3 and PSME1 were negatively associated with the main outcome traits of AD, as well as with LOAD, but had no significant causal association with EOAD. The findings of our research advance our understanding of the etiology of AD.

Systematic evaluation of multifactorial causal associations for Alzheimer’s disease and an interactive platform MRAD developed based on Mendelian randomization analysis

Alzheimer’s disease (AD) is a complex degenerative disease of the central nervous system, and elucidating its pathogenesis remains challenging. In this study, we used the inverse-variance weighted (IVW) model as the major analysis method to perform hypothesis-free Mendelian randomization (MR) analysis on the data from MRC IEU OpenGWAS (18,097 exposure traits and 16 AD outcome traits), and conducted sensitivity analysis with six models, to assess the robustness of the IVW results, to identify various classes of risk or protective factors for AD, early-onset AD, and late-onset AD. We generated 400,274 data entries in total, among which the major analysis method of the IVW model consists of 73,129 records with 4840 exposure traits, which fall into 10 categories: Disease, Medical laboratory science, Imaging, Anthropometric, Treatment, Molecular trait, Gut microbiota, Past history, Family history, and Lifestyle trait. More importantly, a freely accessed online platform called MRAD (https://gwasmrad.com/mrad/) has been developed using the Shiny package with MR analysis results. Additionally, novel potential AD therapeutic targets (CD33, TBCA, VPS29, GNAI3, PSME1) are identified, among which CD33 was positively associated with the main outcome traits of AD, as well as with both EOAD and LOAD. TBCA and VPS29 were negatively associated with the main outcome traits of AD, as well as with both EOAD and LOAD. GNAI3 and PSME1 were negatively associated with the main outcome traits of AD, as well as with LOAD, but had no significant causal association with EOAD. The findings of our research advance our understanding of the etiology of AD.

8401 Genetic Characterization of a Case of Primary Aldosteronism in an 11-Year-Old Girl carrying a Germline VUS of CACNA1H and a Somatic Mutation of CTNNB1

Abstract Disclosure: S. Parisien-La Salle: None. G. Van Vliet: None. G. Corbeil: None. M. Labrecque: None. M. Tétreault: None. I. Bourdeau: None. Introduction: Primary aldosteronism is a frequent cause of secondary hypertension in adults but is rare in children. We report the case and genetic studies of an 11 yo girl presenting with primary aldosteronism at puberty. Case presentation: An 11-year-old female patient was referred to the pediatric endocrinology clinic for hypertension (166/118). Her past medical history and family history were unremarkable. She reported polyuria, polydipsia and occasional headaches and abdominal pain. Her Tanner stage indicated that puberty was initiated (P2M2). An abdominal CT revealed a 9x10x11cm right adrenal mass with calcifications and a necrotic zone. On [1]8F-FDG PET/CT, the mass had an uptake of 2.9 SUVmax. Laboratory results revealed hypokalemia (K: 2.6 mmol/L [N: 3.5-4.5]) and elevated aldosterone (1712.8 pmol/L [N: 110-1330]) with suppressed renin (0.2 ng/ml/h [N: &amp;lt;5.3]). Her urinary aldosterone level was elevated (114 nmol/day [N: &amp;lt;67]). The rest of the biochemical adrenal panel was normal. Patient underwent a right adrenalectomy by laparotomy. The pathology report showed an adrenal tumor without capsular or vascular invasion. The only malignancy criterion was an area of necrosis and the ki-67% proliferation index was &amp;lt; 1%. Genetic investigations: After informed consent, the patient underwent germline analysis for the chimeric gene CYP11B2/CYP11B1 (Ruhr University Bochum, Germany) and a multigene panel including KCNJ5, CACNA1D, CACNA1H and CLCN2 genes (Fulgent, CA), which were both negative except for a variant of unknown significance (VUS) that was identified in CACNA1H (c.3868G&amp;gt;A, p.Val1290Ile) with a minor allele frequency of 3.291E-5 (GnomAD). Tumor DNA was extracted after adrenalectomy from fresh frozen tissues. Somatic genetic analysis of GNAS, CTNNB1, KCNJ5, ATP1A1, ATP2B3 and CACNA1D was performed using direct Sanger Sequencing (Genome Quebec Innovation Centre) and revealed a heterozygous missence pathogenic variant in the CTNNB1 gene (c.121 A&amp;gt;G p.Thr41Ala). This mutation was absent in leukocyte DNA of the patient. Immunohistochemistry of the adrenal tumor disclosed strong cytoplasmic β-catenin staining in most tumor cells (monoclonal anti-β-catenin antibody; BD Transduction Laboratories). RNA-sequencing of patient tumor RNA was performed (Research Center CHU Québec) and compared to human adrenal total RNA (Clontech, Mountain View, CA). Pathway enrichment analysis showed activation of the Wnt signaling pathway. No variant was identified in GNAQ or GNA11 genes. However, GNRHR was upregulated compared to the control sample with a log2 fold change of 3.96 (p=0.000074). Conclusion: We present a rare pediatric case of an aldosterone producing adenoma harbouring a somatic β-catenin pathogenic variant with upregulation of GNRHR. The implication of the germline CACNA1H VUS still needs to be clarified. Presentation: 6/3/2024

Unusual gastrointestinal bleeding - Small intestinal venous ectasias.

A 34-year-old man presented to our emergency department with a 6-day history of bloody stools. He had no complaints of alteration in bowel habits in the stool. He did not consume alcohol and was a non-smoker. The patient had no any previous notable medical history or family history of similar complaints. Physical examination was unremarkable. In the local hospital, laboratory studies showed a hemoglobin level of 6.0g per deciliter (normal range, 11.5 to 15.5). After blood transfusion, an upper gastrointestinal endoscopy and complete colonoscopy did not reveal any bleeding lesion. In our hospital, the patient underwent abdominal contrast-enhanced CT, small intestinal venous ectasias were detected. The selective angiography was performed, but no aneurysm or arteriovenous fistula was found. The gastrointestinal tract bleeding still occurred for an unknown reason. Subsequently, single-balloon enteroscopy was carried out. By oral approach enteroscopy, obvious jejunum venous ectasias were detected.

Indication-based use of low molecular weight heparin during pregnancy: A retrospective study in Northern Greece

Introduction: Venous thromboembolism (VTE) is a condition with high morbidity and mortality rates and presents as the third leading cause of cardiovascular deaths, globally. During the antenatal period, the risk of VTE occurrence increases, therefore, in pregnant women at high-risk for VTE, the use of low molecular weight heparin (LMWH) is recommended. This study aimed to investigate the indication-based administration of LMWH in pregnancy. Material and methods: This was a retrospective cohort study (2019-2022) conducted at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece. All pregnant women at the first trimester of pregnancy were eligible. Their physical characteristics were recorded and information about their personal, familial, gynecological and obstetrical medical history was collected. By utilizing the above characteristics, a score of the risk of developing VTE during pregnancy was calculated for each woman, using the algorithm recommended by the Royal College of Obstetricians &amp; Gynecologists. Results: In total, 2,716 pregnant women were included in the study. Of these, 149 (5.5%) received LMWH throughout their pregnancy with only 2 of them (0.1%) having appropriate indications. Of the women not prescribed LMWH, 2,567 (94.5%), none had an indication for LMWH administration. Notably, 495 (19.3%) women had a history of at least one miscarriage and 89 (59.7%) of them used LMWH, regardless of whether they had an indication or not. Conclusion: There was a high percentage of women with no indication for LMWH who, in fact, received this medication. Physicians should refrain their use following evaluation based on appropriate risk factors.

An Epidemiological Perspective on New Pediatric Cases of Type 1 Diabetes and Vitamin D Deficiency in South-East Romania: A Retrospective Study.

The aim of this study is to analyze the epidemiological characteristics and the biological profile of children from the southeast of Romania who have been newly diagnosed with type 1 diabetes (T1DM) and to investigate the potential relationships between vitamin D deficiency and the onset of this disease, especially in the context of the COVID-19 pandemic. This is a retrospective study that included 79 children under the age of 18 who were diagnosed with T1DM at the St. Ioan Galati Children's Emergency Clinical Hospital between 2018 and 2023. Their demographic data (age, sex, and home environment), medical history (family medical history, birth weight, Apgar score, and type of nutrition), and biological parameters, including glycemia, HbA1C, and vitamin D level, were collected. We used advanced statistical methods to compare the levels of vitamin D in the children with T1DM with a control group of nondiabetic children. The demographic characteristics of new T1DM are a median age of 9 and female/male sex ratio of 1:3, with 50.6% living in urban areas, 59.5% with a normal body mass index, and 74.6% presenting with ketoacidosis. Vitamin D deficiency was found in 52% of diabetic cases compared to 2.53% in the nondiabetic controls. There is an increasing incidence of pediatric T1DM. Diabetic ketoacidosis was frequently diagnosed as an initial manifestation and has frequently accompanied lower levels of vitamin D. Children with T1DM showed significant vitamin D deficiencies compared to the control group, highlighting the need for the monitoring and supplementation of this vitamin.

Use and feasibility of a Lynch Syndrome predictive model for inherited colorectal and endometrial cancer in a low-middle income country.

While universal tumor testing for Lynch Syndrome (LS) is recommended in all new diagnoses of colorectal cancer (CC) and endometrial cancer (EC), the cost and availability of this test in low-resource settings poses challenges. The PREdiction Model for gene Mutations (PREMM5) is a clinical algorithm designed to assess the risk of an individual carrying estimates one's risk of carrying a LS mutation. This study aims to assess the feasibility of using PREMM5 to screen for LS risk in Guatemala. This cross-sectional pilot study enrolled 50 patients with colorectal or endometrial cancer receiving treatment at LIGA-INCAN, a cancer hospital in Guatemala City, between June 2022-July 2022. Patients were contacted by phone and administered the PREMM5 survey, followed by an additional feasibility questionnaire. Of the 50 participants, 62% of patients had a PREMM5 predicted probability of ≥ 2.5%, the threshold above which genetic testing is recommended. Almost all patients found the survey easy to complete (98%), were able to easily recall personal (90%) and family (88%) medical history, understood its purpose (94%), and reported an interest in (96%) and ability to (98%) act on the results if applicable. Our study shows the role of the PREMM5 as a feasible tool for identifying individuals at risk of carrying mutations associated with LS in this low-resource setting. By implementing the PREMM5 model, high risk individuals can be identified early, enabling timely interventions and improving outcomes in this at-risk population.

Abstract B025: Surveillance outcome in individuals at high risk of pancreatic cancer

Abstract INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate. PDAC surveillance is recommended in high-risk individuals (HRIs) with strong PDAC family history or a pathogenic germline variant (PGV) in a PDAC susceptibility gene. We aimed to explore a potential correlation between genetic status, extent of family history, pancreatic findings, and surveillance implications in heterogeneous PDAC HRIs. METHODS: from January 2015 up to date, a total of 340 HRIs from 291 families visited our pancreatic cancer high-risk clinic. Surveillance included annual clinic visits, EUS/MRI imaging, genetic and laboratory blood testing. Participants completed a questionnaire that included personal and familial medical history, dietary habits, daily activities with emphasis on smoking habits, alcohol use, and physical activity. RESULTS: Our cohort was divided into 3 groups: familial pancreatic cancer that include individuals with family history of 2 or more first degree family (FDR) with PDAC (FPC; 96 individuals), familial non-FPC, families with at least 2 biological relatives with PDAC and not meeting FPC criteria, (119 individuals), and hereditary pancreatic cancer (PC), individuals with PGV in a PC susceptibility gene and a family member with PDAC carrying the same PGV (124 individuals). The cohort average age at first visit was 54 years with 44% male and 56% female ratio. Seventy percent of the cohort was of Jewish Ashkenazi decent. Genetic testing was performed in several steps, first BRCA1/2 founder mutations was performed in all individuals followed by genetic panels and whole exome sequencing (WES). PGVs were detected in 36.4% of all families. There was no significant difference in the genetic finding between the FPC and non-FPC groups (11% and 9.6% respectively). Of the study cohort 35% were screened by EUS and 8% by MRI/MRCP. Pancreatic lesions detected included 11 cases of new PDAC (3.2%), 69 cystic lesions (20.3%), 43 cases early chronic pancreatitis (12.6%) and 11 cases of main pancreatic duct dilation (3.2%). To better understand the risk of PDAC development in HRIs we recently added a novel cell-free chromatin blood test for early cancer detection (in collaboration with SENSEERA, Israel) and compared it to EUS imaging results. The test provides multidimensional epigenetic information that sheds light on the identity and the transcriptional state of the cells that are dying in the body of the patient. Our preliminary results show nice separation between the healthy control and PC groups. PC HRIs show slight increase in score compared to the general population while individuals with worrisome features show substantial increase compared to HRIs with no EUS findings. DISCUSSION: Surveillance seems effective for detection of early-stage PDAC and precursor lesions. However, screening strategy can be improved by adding newer modalities like chromatin-based tests that might help to further define the risk of cancer development in HRIs. Citation Format: Merav Ben Yehoyada, Erez Scapa, Oren Shibolet, Guy Rosner. Surveillance outcome in individuals at high risk of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B025.

Treacher Collins Syndrome 2 caused by a novel pathogenic variant in PLOR1D: clinical report and literature review

Objective: To investigate the clinical features, molecular etiology, and treatment of a family with Treacher Collins Syndrome 2 (TCS2). Methods: Information of the proband (female, 8 years old) including medical history and family history was collected. Physical examination and examinations concerning laboratory, audiology, and radiology were performed on the proband. Physical examination was also performed on the family members. Genomic DNA of proband was extracted for whole exome sequencing, and then the genomic DNA of family members was extracted for Sanger sequencing. POLR1D and TCS2 related literatures published before August 31,2023 were searched and sifted in PubMed and CKNI databases. The clinical characteristics of TCS2 were summarized. Results: The proband had poor hearing since childhood, with pure tone audiometry indicating conductive hearing loss. She had a smaller jaw, bilateral preauricular fistulas and cup-shaped ear deformities. Temporal bone CT scan revealed deformities in the left external ear canal, bilateral middle ear and inner ear. A bone-conduction hearing aid device was surgically implanted, resulting in restoration of almost normal hearing levels. The proband's mother also had a slightly smaller jaw. Genetic analysis revealed a novel heterozygous variant NM_015972.4:c.38_47del in the POLR1D gene in the proband, which was inherited from her mother. A review of the literature revealed no clear evidence of genotype-phenotype correlation in TCS2. Conclusions: Molecular diagnosis plays a vital role in the diagnosis of TCS2. Patients with normal facial phenotype may be carriers of pathogenic variants in the POLR1D gene and have the risk of passing it to the offsprings with complete penetrance. Proper bone conductive hearing devices can improve the quality of life of TCS2 patients.

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Peripheral artery disease is a considered as one of the major macrovascular complications in diabetes mellitus type 2. It is chronic arteriosclerotic illness that mainly affects the lower limbs and is presented as narrowed or blocked blood vessels. The prevalence increases with the age, it affects 15-20% of persons older than 70 years age, 10-15% of the general population. Smoking and high cholesterol levels increase the risk for PAD progression in large blood vessels such as legs, while diabetes increases the risk for PAD in small blood vessels such as the feet. Critical ischemia, its most severe form can lead to limb amputation and the patient’s death, and even its asymptomatic forms are associated with a high risk of cardiovascular morbidity and mortality. Approximately more than half of all patients are asymptomatic and preventive therapy reduces the risk of complications and death, so it’s important to recognize the subclinical forms in time and to control risk factors of disease. The risk factors that can be modified are tobacco use, hypertension, hyperlipidemia, diabetes mellitus, obesity and some of them cannot be modified such as age, sex or family medical history. Diabetes mellitus type 2 is considered as the most important risk factor for development of peripheral artery disease. The experts suggest that is necessary to establish an HBA1C therapeutic target below 8% in patient with DM and PAD.

Cardiovascular Risk Factors in Socioeconomically Disadvantaged Populations in a Suburb of the Largest City in Western Romania.

Background and Objectives: Cardiovascular disease (CVD) remains a major public health issue worldwide, disproportionately affecting socioeconomically disadvantaged populations due to the social determinants of health (SDOHs). In Western Romania, these populations are particularly vulnerable to CVD. This study aims to investigate the prevalence and impact of cardiovascular risk factors (CVRFs) among socioeconomically disadvantaged individuals in Western Romania and identify the primary CVRFs contributing to the high incidence of CVD within this population. Materials and Methods: A retrospective observational design was employed, utilizing data from the medical records of 1433 eligible individuals. The inclusion criteria were based on Eurostat's EU-SILC benchmarks, focusing on severe material deprivation, at-risk-of-poverty rates, and low work intensity. Data on demographics, familial and personal medical history, smoking status, blood pressure, glucose, cholesterol, triglycerides, and HbA1c levels were collected. Results: Of the 1433 subjects, 34.75% were male, with a median age of 52 years. Significant conditions included diabetes (7.39%), coronary disease (3.83%), arterial hypertension (35.58%), and dyslipidemia (21.28%). Median ages were higher for those with diabetes (65 vs. 51 years, p < 0.0001), coronary disease (64 vs. 51 years, p < 0.0001), arterial hypertension (65 vs. 43 years, p < 0.0001), and dyslipidemia (66 vs. 47 years, p < 0.0001). BMI (Body Mass Index) classifications showed 33.77% were overweight, 21.21% obese, and 15.07% morbidly obese. Smokers were younger than non-smokers (48 vs. 54 years, p < 0.0001). Conclusions: The findings highlight the significant prevalence of CVRFs among socioeconomically disadvantaged populations in Western Romania. Socioeconomically disadvantaged populations exhibit a significantly higher prevalence of cardiovascular risk factors such as diabetes, impaired glucose regulation, hypertension, and dyslipidemia compared to their before known status.