Risk Of Syndrome Research Articles

Association of Zinc Intake, Tobacco Smoke Exposure, With Metabolic Syndrome: Evidence from NHANES 2007-2018.

The objective was to explore the effect modification of zinc (Zn) intake levels on the relationship of tobacco smoke exposure and risk of metabolic syndrome (MetS) in children and adolescents. We used data from 2007-2018 National Health and Nutrition Examination Survey (N = 3701). MetS was considered as main endpoint. Weighted multivariable logistic regression models showed that high cotinine level (≥ 0.05ng/mL) was associated with increased odds of MetS [odds ratio = 1.54, 95% confidence interval: 1.01, 2.36], and the association between Zn intake levels and MetS did not demonstrate statistical significance. Importantly, the multiplicative interaction term between low Zn intake (≤ 4.89mg/1000kcal) and high cotinine level was related to higher odds of MetS (p-value for interaction 0.018). For the group with low Zn intake, high cotinine level was associated with increased odds of MetS. However, there was no significant relationship between cotinine levels and MetS risk in the group with high Zn intake. The effect modification by Zn intake on the relationship of tobacco smoke exposure and risk of MetS is significant in individuals who had a sedentary time of ≥ 6h, identified as non-Hispanic White, or resided in households with smokers. In short, low Zn intake may potentiate the association of tobacco smoke exposure and MetS risk in children and adolescents.

Pharmacokinetics of Tarlatamab, a Delta-Like Ligand-3 (DLL3) Targeted Half-Life Extended Bispecific T-Cell Engager (BiTE®) Immunotherapy in Adult Patients with Previously Treated Small-Cell Lung Cancer: Results from DeLLphi-300, a Phase I Multiple-Dose-Escalation Study.

Tarlatamab binds to delta-like ligand 3 on cancer cells and cluster of differentiation-3 on T cells, leading to T-cell-mediated tumor lysis, and has demonstrated a promising safety and efficacy profile in patients with previously treated small-cell lung cancer (SCLC). Here, we present pharmacokinetic results from DeLLphi-300 (NCT03319940), an ongoing international, open-label, first-in-human study in previously treated adult patients with SCLC. Multiple escalating doses of tarlatamab were administered every 2 weeks (Q2W; 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mg) in a 28-day cycle. To reduce the risk of cytokine-release syndrome, starting at the 3 mg dose level, a step dose regimen was employed consisting of a 1 mg infusion on cycle 1 day 1 (C1D1), followed by the target dose on C1D8, C1D15, and Q2W thereafter. All doses were infused over 1 h. Other tarlatamab dosing regimens were also explored, either for patient convenience (every 3 weeks) or to mitigate cytokine-release syndrome (extended intravenous infusion over a period of 3 days). Intensive pharmacokinetic samples were collected during cycles 1 and 2, and additional samples for pharmacokinetic and immunogenicity measurement were collected at regular intervals in later cycles. Pharmacokinetic data were analyzed using noncompartmental analysis, and antidrug antibody (ADA) incidence, including any effect on tarlatamab pharmacokinetic parameters, was summarized. Pharmacokinetic data were available from 203 patients. The median age was 62 years (range 32-80), and 55.7% (n = 113) of patients were male, 78.3% (n = 159) were white, and 8.3% (n = 17) were of Japanese descent. Following intravenous infusion, serum tarlatamab concentrations declined with time in a biphasic manner. Serum exposures increased in an approximately dose-proportional manner across the evaluated target dose range with a mean (standard deviation) estimated terminal phase elimination half-life of 5.8 (1.6) days, and steady state achieved by approximately C2D15. Of the 183 evaluable patients, 12 (6.6%) developed treatment-emergent ADAs; the distribution of dose-normalized serum concentrations were similar between patients who were ADA positive and ADA negative. In addition, the distribution of exposures was comparable in Japanese and non-Japanese patients. In patients with previously treated SCLC, tarlatamab demonstrated dose-proportional pharmacokinetic and extended half-life characteristics that support a Q2W dosing interval. Neither Japanese race nor ADA had a clinically relevant impact on exposures.

The Association between Rheumatic Diseases and the Risk of Polycystic Ovary Syndrome: A Two-Sample Mendelian Randomization Analysis

Aims/Background The association between rheumatic immune diseases and polycystic ovary syndrome (PCOS) remains elusive. The purpose of this study was to investigate the causal relationship between rheumatic immune diseases and the risk of PCOS through a two-sample Mendelian randomization (MR) analysis. Methods In the assessment of exposure variables, we chose systemic lupus erythematosus (SLE), polymyositis (PM), and rheumatoid arthritis (RA) as representative rheumatic immune diseases, while PCOS was designated as the outcome of interest. All data utilized in this investigation were obtained from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) database. A two-sample MR analysis was conducted using summary statistics for both the exposure and outcome variables, which were gathered from the genome-wide association study (GWAS) datasets. Single nucleotide polymorphisms (SNPs) significantly associated with rheumatic diseases were selected as instrumental variables (IVs) to estimate the causal effects on PCOS. The final results were analyzed using five MR analysis methods, namely MR-Egger, inverse variance weighted (IVW), weighted median (WM), simple mode, and weighted mode. Causal estimation of MR was primarily obtained using the IVW method. Sensitivity analyses were also conducted to evaluate pleiotropy and heterogeneity. Results In this two-sample MR analysis, a total of 1,000,246 participants were included. Among them, there were 647 cases of SLE, 44 cases of PM, 5539 cases of RA, and 797 cases of PCOS. The IVW approach indicated a causal relationship between RA and an increased risk of PCOS (odds ratio [OR] = 1.069, 95% confidence interval [CI] = 1.007–1.134, p = 0.041). The MR-Egger intercept and Cochran’s Q test (p > 0.005) further verified the stability of the MR results. However, no significant correlation was observed between the other two rheumatic immune diseases (PM and SLE) and the risk of developing PCOS (both p > 0.05). Conclusion This study suggests a potential causal association between RA and PCOS, while SLE and PM do not exhibit a causal association with PCOS, enhancing our comprehension of the etiological factors of PCOS and shedding light on prevention strategies for the disease. Additional research is required to elucidate the underlying biological mechanisms by which RA contributes to the progression of PCOS.

Associations Between Cardiorespiratory Fitness and Metabolic Syndrome in Adolescents: A Systematic Review and Meta-Analysis.

Introduction: Low levels of cardiorespiratory fitness (CRF) are associated with a greater risk of metabolic syndrome (MetS) in adolescence. In this sense, it is important to verify the strength of this association and the certainty that this evidence can be recommended. Objective: The objective of this paper is to summarize, through a systematic review and meta-analysis, the evidence available to verify the association between CRF and MetS in adolescents. Methods: PubMed, Embase, CINAHL, SPORTDiscus, LILACS, and Web of Science were searched until 20 August 2024. The risk of bias in each study was assessed via the AXIS tool, and the certainty of the evidence was assessed via the GRADE system. For the meta-analysis, the odds ratio (OR) was calculated with a 95% confidence interval. Results: Nine studies (7077 participants), all with a low risk of bias, were included in the systematic review. There was a high certainty of evidence that adolescents with low CRF have significantly greater odds of developing MetS (OR = 3.63 [CI 95%, 2.54 to 5.20]). The odds increase for low vs. moderate (OR = 4.23 [CI 95%, 2.64 to 6.78]) and low vs. high (OR = 8.03 [CI 95%, 3.20 to 20.18]) CRF are considered separately. The effect does not change according to the type of test used to assess CRF (p = 0.51). Conclusions: There is high certainty of evidence that adolescents with low CRF levels have significantly greater odds of developing MetS; therefore, it is essential that intervention strategies be designed to increase CRF in this population.

Clinical Relevance of Intensive Laboratory Monitoring With Standard Venetoclax Ramp-Up for Chronic Lymphocytic Leukemia: A Real-World Experience

PURPOSE Venetoclax is the standard of care for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) but requires intensive monitoring for optimal safety. Clinical relevance of intensive monitoring in practice is unknown, especially for patients with low or intermediate risk for tumor lysis syndrome (TLS). PATIENTS AND METHODS A retrospective review was conducted to determine clinical significance of monitoring for TLS during standard ramp-up for patients with CLL/SLL. Patients receiving abbreviated ramp-up, clinical trials, or concurrent Bruton tyrosine kinase inhibitors were excluded. The primary end point was TLS incidence, with secondary end points describing associated clinical interventions. RESULTS Fifty-five patients met study criteria. The majority of patients received venetoclax as first-line therapy (58%), with anti-CD20 antibody therapy (82%), and were at low risk of TLS (75%). No clinical TLS events occurred, whereas laboratory TLS occurred in only 1.8% of patients. No patients required antihyperuricemic therapy, and few interventions for hyperphosphatemia or hypocalcemia (3.6% of patients) were required. Additional intravenous fluids were uncommonly required (1.8% of patients), and no unplanned hospitalizations were required. CONCLUSION These findings support efforts to reduce intensive monitoring requirements during venetoclax ramp-up for patients with CLL, potentially increasing accessibility of venetoclax.

The association between metabolic syndrome and lung cancer risk: a Mendelian randomization study

Metabolic syndrome (MetS) is closely linked to cancer development, with emerging evidence suggesting its association with pulmonary carcinoma. However, causal relationships remain unclear due to observational study limitations. Employing Mendelian randomization, we investigated the causal link between MetS and lung cancer (LC) susceptibility. The data utilized in this study were obtained from the publicly available genetic variation summary database. The causal relationship was assessed using the inverse variance weighting method (IVW), weighted median method, and MR-Egger regression. A sensitivity analysis was carried out to confirm the robustness of the findings. Furthermore, risk factor analyses were conducted to explore potential mediators. Utilizing various analyses, MetS demonstrated a significant positive association with LC (OR, 1.22; 95% CI, 1.09–1.37, p = 7.57 × 10− 4), lung squamous cell carcinoma (LUSC) (OR, 1.47; 95%, 1.23–1.75, p = 2.22 × 10− 5), and small cell lung cancer (SCLC) (OR, 1.76; 95% CI, 1.37–2.26, p = 8.20 × 10− 6) but not lung adenocarcinoma (LUAD) (OR, 1.08; 95% CI, 0.94–1.24, p = 0.28). Risk factor analyses indicated that smoking, alcohol, body mass index, education, and type 2 diabetes might mediate the association. This study genetically validates and reinforces the evidence of MetS increasing the incidence of LC, including both LUSC) and SCLC, especially among individuals with abdominal obesity. It provides valuable insights for the development of lung cancer prevention strategies and directions for future research.

A pedicled anterolateral thigh flap decreased the risk of empty pelvis syndrome following total pelvic exenteration.

Total pelvic exenteration (TPE) can be complicated by empty pelvis syndrome (EPS), and none of the currently available procedures completely mitigate this problem. The aim of this study was to evaluate the feasibility and effectiveness of a pedicled anterolateral thigh (p-ALT) flap for preventing EPS. All cases of TPE at the National Cancer Center Hospital in Tokyo between 2008 and 2022 were retrospectively reviewed. The main indication for TPE was colorectal cancer, with some other malignancies. Background factors, surgical outcomes and postoperative complications were compared between patients who underwent primary suture closure (the PC group) and those who underwent p-ALT flap reconstruction (the flap group). A total of 114 patients underwent TPE during the study period. Twenty patients in whom a different procedure was performed or a different flap was used for reconstruction were excluded, leaving 94 for analysis (PC group, n = 54; flap group, n = 40). There was no significant between-group difference in patient characteristics. Severe pelvic abscess developed in 12 patients (22.2%) in the PC group and 2 (5%) in the flap group. Multivariable analysis identified a significantly lower risk of severe pelvic abscess in the p-ALT flap reconstruction (OR 0.07, 95% CI 0.01-0.58, p = 0.01). EPS-related readmissions were more common in the PC group [37.0% (20/54) vs. 25% (10/40)]. The risk of severe pelvic abscesses and readmission for EPS was significantly lower after perineal reconstruction with a p-ALT flap. Perineal reconstruction with this flap is a feasible and effective method in TPE.

The Role of Vitamin D3 Deficiency and Colonization of the Oral Mucosa by Candida Yeast-like Fungi in the Pathomechanism of Psoriasis.

Psoriasis is a chronic inflammatory skin disease with complex pathogenesis and variable severity. Performed studies have indicated the impact of vitamin D3 deficiency on the pathogenesis of psoriasis and its severity. However, there is no clear evidence of the influence of the mucosal microbiome on the onset and progression of psoriasis. This review aims to present the current evidence on the role of vitamin D3 and colonization of the oral mucosa by Candida yeast-like fungi in the pathogenesis of psoriasis. Candida albicans is a common yeast that can colonize the skin and mucosal surfaces, particularly in individuals with weakened immune systems or compromised skin barriers. In psoriasis, the skin's barrier function is disrupted, potentially making patients more susceptible to fungal infections such as Candida. Since patients with psoriasis are at increased risk of metabolic syndrome, they may experience the vicious circle effect in which chronic inflammation leads to obesity. Vitamin D3 deficiency is also associated with microbiological imbalance, which may promote excessive growth of Candida fungi. Under normal conditions, the intestinal and oral microflora support the immune system. Vitamin D3 deficiency, however, leads to disruption of this balance, which allows Candida to overgrow and develop infections.

Clinical analysis of systemic juvenile idiopathic arthritis with Kawasaki disease-like symptoms

Objective: To analyze the clinical characteristic of systemic juvenile idiopathic arthritis (sJIA) patients with Kawasaki disease like onset symptom. Methods: A retrospective case-control study was performed. A total of 24 patients with sJIA with Kawasaki disease-like symptoms in the Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University from January 2018 to August 2024 were selected as the Kawasaki disease combined with sJIA group. A total of 96 patients with Kawasaki disease as the Kawasaki disease group and 83 patients with sJIA were selected as the sJIA group. The general information, clinical manifestations, laboratory examinations and complications of the patients were compared between the three groups. Differences between groups were assessed by Mann-Whitney U test, Kruskal-Wallis H test and Chi-square test was used for counting data. Results: There were significant differences in age and fever course between Kawasaki disease combined with sJIA groups, Kawasaki disease groups, and sJIA groups (3.4 (2.5, 7.3) vs. 3.4 (1.9, 4.8) vs. 8.8 (5.1, 11.7) years, 24.5 (18.0, 37.3) vs. 23.0 (18.0, 31.0) vs. 7.0 (6.0, 8.0) d, Z=67.09, 138.24, both P<0.05). Among the 24 cases of Kawasaki disease combined with sJIA, 20 cases (83%) had joint symptoms and 9 cases (38%) had conjunctival congestion. There were significant differences in the incidence of coronary artery injury between Kawasaki disease combined with sJIA group, Kawasaki disease group and sJIA group (58% (14/24) vs. 44% (42/96) vs. 6% (5/83), χ2=40.50, P<0.05). There were significant differences in the risk of macrophage activation syndrome between Kawasaki disease combined with sJIA group, sJIA group and Kawasaki disease group (17% (4/24) vs. 10% (8/83) vs. 0 , χ2=16.91, P<0.05). In the Kawasaki disease combined with sJIA group, 11 cases (46%) did not respond after 2 courses of intravenous immunoglobulin (IVIG) treatment, and 21 cases (88%) used glucocorticoids. The use rate of high-dose hormones in the Kawasaki disease combined with sJIA group was higher than that in the sJIA group (29% (7/24) vs. 5% (4/83), χ2=12.95, P<0.05). In the Kawasaki disease combined with sJIA group, 17 cases (71%) used biological agents, 1 case used adalimumab, and 16 cases received tocilizumab treatment, of which 4 cases (25%) were allergic to tocilizumab. In the group of Kawasaki disease combined with sJIA, 11 patients (46%) treated with tocilizumab were followed up regularly for 1 month, and 10 patients were effective. Conclusions: Children with sJIA who present with Kawasaki disease-like clinical symptoms have clinical features of Kawasaki disease and sJIA. Children with Kawasaki disease who present at a young age, have a long fever course, are accompanied by joint symptoms, and are IVIG-resistant need to be alert to the possibility of sJIA and receive timely treatment with hormones and biological agents.

Relationship of Body Fat Distribution and Anthropometric Status with Lipid Profiles in Ethnic Minang Adult Women

Background The prevalence of metabolic syndrome is increasing, and it is a risk factor for cardiovascular disease. One of the indicators of metabolic syndrome is dyslipidemia. Objective This study analyzes adult women's body fat distribution, anthropometric status, and lipid profiles. Methods This study used a cross-sectional design with simple random sampling. A total of 159 adult women aged 25-44 living in the Pesisir Selatan district participated in the study. Ethical approval was obtained, and the respondents were not taking cholesterol-lowering drugs. Body fat distribution, anthropometric status, and lipid profile data were assessed using standard procedures and compared with the categories recommended for Indonesian women. Results The average age of respondents was 36.6 years. 45.3% of the respondents suffered from dyslipidemia. Most of them were obese based on BMI and had central obesity based on WC. Additionally, 76% had an above-normal fat mass. Lipid profile data showed that some (45.3%) had high total cholesterol, 44% had high LDL, 8% had high TG, and a small proportion (15%) had low HDL levels. There was a significant relationship (p &lt; 0.01) between body fat distribution and anthropometric status with lipid profiles, except for total cholesterol (p &lt; 0.05). A negative correlation was found between body fat percentage, BMI, and WC with HDL, while a positive correlation existed between body fat percentage, BMI, and WC with TG and LDL levels. Conclusions Obesity is found to be higher, and dyslipidemia begins to occur in women at a younger age, increasing the risk of metabolic syndrome. Education and routine screening are necessary to prevent non-communicable diseases.

OPTIMIZING THE DELIVERY METHOD FOR EXTREMELY PREMATURE BIRTHS

The contemporary classifi cation of premature birth is predicated on the condition of the newborn, encompassing the severity of respiratory disorders, morpho- functional immaturity, prognosis for survival, and long-term consequences. In accordance with these criteria, newborns with a gestational age of up to 28 weeks are classifi ed as extremely premature, given the inherently challenging nature of their weaning process. This article presents the dynamics of early neonatal mortality and lethality indicators in cases of vaginal and abdominal delivery. This article presents an analysis of contemporary global trends in the selection of delivery methods for premature births and extremely premature pregnancies.The aim of the study. To propose a modifi ed approach to the choice of delivery method in pregnant women in the gestational period of 24-28 weeks.Research materials and methods. The analysis was conducted on 350 cases of extremely premature singleton births (within 24-28 weeks) that occurred at the Perinatal Center of Kyiv between 2019 and 2023. A comparison of the early neonatal mortality rate of newborns with a gestational age of 24-28 weeks was conducted, stratifi ed by the method of delivery. The relative risk of mortality during the fi rst seven days and throughout the fi rst year of life, contingent on the method of delivery, was calculated. Furthermore, the frequency of the most common complications of the neonatal period in newborns with extremely low body weight was analyzed, and the relative risk of their development was calculated depending on the method of delivery. The Foster- Stewart test was employed to substantiate the statistical reliability of the obtained results. The two average indicators are then compared with one another using the Student’s test. A value of ≤0.05 indicates statistically signifi cant changes in the indicator’s dynamics. The research was carried out within the framework of the implementation of scientifi c topics of the Department of Obstetrics and Gynecology No. 1 of the Bogomolets National Medical University: Research work «Preservation and restoration of women’s reproductive health in conditions of rapid medical and social changes» implementation period 01.01.2023-12.2024. Research results and their discussion. An analysis of the dynamics of early neonatal mortality in the category of 24-28 gestationalweeks from 2019 to 2023 was conducted, identifying several factors. These included the active implementation of intranatal magnesium therapy and improvements in the quality of neonatal care at the technical level. As evidenced by the data, the rate of early neonatal mortality in very early premature births reached 43.3 % in 2019, declining to 25.5 % by 2022. In the 2019-2020 period, 50 % of neonatal deaths occurring within the fi rst seven days were infants born by caesarean section. The ratio of vaginal births to births by caesarean section in gestational periods up to 28 weeks is approximately 2:1. In addition to the observed reduction in the rate of early neonatal mortality, a two-fold decrease was noted in the rate among children born by caesarean section. The mortality rate of extremely premature infants, despite a gradual decline, remains relatively high, at approximately 34.2 % in 2023. Our fi ndings, based on the expansion of indications for caesarean section rather than its routine use in preterm birth, indicate that the relative risk of neonatal death before seven days for vaginal delivery compared with caesarean section, calculated with a 95 % confi dence interval, was 2.65. Similarly, the calculated riskof mortality during the fi rst year of life is 1.34. With regard to intraventricular hemorrhage, the relative risk was 3.12, indicating that the route of delivery in this cohort of newborns exerts an infl uence on the frequency of the complication. The risk of hemorrhagic syndrome is 0.97, which does not provide suffi cient evidence to suggest that it can be prevented by selecting an abdominal delivery. The proportion of abdominal deliveries at the Perinatal Center has remained relatively stable since the expansion of indications for premature births, with a slight increase from 14.2 % in 2019 to 15.2 % in 2023. This was accomplished through a logical and evidence- based approach to caesarean section in full-term pregnancies.Conclusions. 1.From 2019 to 2023, a notable decline was observed in the incidence of early neonatal mortality (from 43.3 to 23.6 %) and child mortality (from 61.3 % to 34.2 %) among newborns with a gestational age of up to 28 weeks. 2. The incidence of early neonatal mortality up to 28 weeks is lower among newborns delivered by caesarean section than among those delivered vaginally. 3. The optimization of perinatal indicators is contingent upon an individualized approach to the selection of a delivery method for pregnant women with premature rupture of the membranes up to 28 weeks.

Abstract 4142793: Development of an Angiography-Based Multimodal AI Model for Predicting the risk of In-Stent Restenosis

Background: Despite advances in Second-generation drug-eluting stents (DES), 5-10% of patients still experience in-stent restenosis (ISR) after percutaneous coronary intervention (PCI), which generates significant financial burden and elevates the risk of acute coronary syndrome (ACS) and rehospitalization. Thus, early identification of patients at high risk for ISR is crucial for guiding clinical stratification and early intervention. Aims: To develop and validate a multimodal artificial intelligence (AI) model based on coronary angiography images for predicting ISR risk in patients post-DES implantation. Methods: To establish an accurate predictive model, our approach begins with the pre-training on 100,000 angiographic images to enhance the model’s capability in recognizing image features. Subsequently, we employ the DenseNet architecture as the primary deep learning model, incorporating angiographic images from 2,000 cases of DES-treated de novo lesions—1,000 from patients who did not experience ISR within two years and 1,000 from those who did. A multivariate logistic regression analysis, including radiomic features, clinical baselines, and functional information, constructs the predictive model. Additionally, a separate prospective cohort of 300 cases was assembled for validation to simulate real-world application and to verify the model's reliability and accuracy. Results: Our study successfully developed an AI prediction model for ISR, utilizing a large cohort of coronary angiography images, which effectively predicts ISR with high accuracy. Leveraging the DenseNet architecture and finely tuned machine learning algorithms, the model achieved a sensitivity and specificity of 90% in the validation cohort. The ROC curve from the test phase demonstrated an AUC above 0.90, underscoring the model’s exceptional diagnostic capabilities. Furthermore, the implementation of this model in a prospective cohort confirmed its reliability and practical utility in real-world clinical settings. Conclusions: This study introduces the first multimodal AI model using angiographic imaging to predict ISR. By demonstrating high diagnostic accuracy and reliability in real-world settings, this model serves as an essential tool for early ISR detection and intervention, ultimately helping to reduce the incidence of major adverse cardiac events (MACEs) and mortality.

Depression and the risk of fibromyalgia syndrome: a two-sample Mendelian randomization study.

Fibromyalgia (FM) is a common illness with a wide range of symptoms, mainly manifested by unexplained chronic systemic musculoskeletal pain, sleep disorders and fatigue, sometimes accompanied by cognitive impairment, psychiatric symptoms and autonomic dysfunction. Previous studies have indicated a correlation between depression and the risk of FM; however, it remains uncertain whether this association reflects a causal relationship. We evaluated the etiological association between the genetically predicted depression and the risk of developing FM by conducting a two-sample Mendelian Randomization (MR) study. The data on single nucleotide polymorphisms (SNPs) related to depression were obtained from the UK Biobank (UKB) and the Psychiatric Genomics Consortium (PGC) of White British European ancestry, and the data for FM were from the 5th release of the FinnGen study. We adopted the Inverse Variance Weighted (IVW) approach as the principal standard. In order to detect the existence of horizontal pleiotropy and heterogeneity, we adopted the MR-Egger approach as the sensitivity analysis. In our MR analysis, 42 depression-related variants were identified as valid instrumental variables (IVs). The IVW approach's results manifest that there is no etiologic causality between genetically predicted depression and the risk of FM (odds ratio [OR]: 1.673, 95% confidence interval [CI]: 0.852-3.287, P = 0.135). The study did not find any significant heterogeneities or horizontal pleiotropies (P > 0.05). Our results suggest that there is no significant genetic evidence linking depression to an increased risk of FM. However, further research is necessary to investigate the potential relationship and underlying mechanisms between depression and the risk of FM.

Gestational Diabetes Mellitus: Unveiling Maternal Health Dynamics from Pregnancy Through Postpartum Perspectives

Gestational Diabetes Mellitus (GDM) is the most frequent pregnancy-related medical issue and presents significant risks to both maternal and foetal health, requiring monitoring and management during pregnancy. The prevalence of GDM has surged globally in recent years, mirroring the rise in diabetes and obesity rates. Estimated to affect from 5% to 25% of pregnancies, GDM impacts approximately 21 million live births annually, according to the International Diabetes Federation (IDF). However, consensus on diagnostic approaches remains elusive, with varying recommendations from international organizations, which makes the comparison between research complicated. Compounding concerns are the short-term and long-term complications stemming from GDM for mothers and offspring. Maternal outcomes include heightened cardiovascular risks and a notable 70% risk of developing Type 2 Diabetes Mellitus (T2DM) within a decade postpartum. Despite this, research into the metabolic profiles associated with a previous GDM predisposing women to T2D remains limited. While genetic biomarkers have been identified, indicating the multifaceted nature of GDM involving hormonal changes, insulin resistance, and impaired insulin secretion, there remains a dearth of exploration into the enduring health implications for both mothers and their children. Furthermore, offspring born to mothers with GDM have been shown to face an increased risk of obesity and metabolic syndrome during childhood and adolescence, with studies indicating a heightened risk ranging from 20% to 50%. This comprehensive review aims to critically assess the current landscape of Gestational Diabetes Mellitus (GDM) research, focusing on its prevalence, diagnostic challenges, and health impacts on mothers and offspring. By examining state-of-the-art knowledge and identifying key knowledge gaps in the scientific literature, this review aims to highlight the multifaceted factors that have hindered a deeper understanding of GDM and its long-term consequences. Ultimately, this scholarly exploration seeks to promote further investigation into this critical area, improving health outcomes for mothers and their children.

Abstract 4137770: Development of a User-Friendly Self-Screening Tool for Assessing Metabolic Syndrome Risk in young adults from economically challenged regions

Background: Metabolic syndrome is a cluster of conditions that increase the risk of heart disease and diabetes. Early identification and management are crucial, particularly in economically challenged regions where access to healthcare may be limited. Research Questions/Hypothesis: User-friendly self-report data accurately predict metabolic outcomes. Aims: To develop and validate nomograms for individualized estimation of metabolic syndrome risk. Methods: Data from 521 college students (60.1% aged 17-20 years; 68.7% female; 28.0% white) were collected in 2022/2023 from two Brazilian cities. These cities are located in the country's poorest states, with Gini indices of 0.56 and 0.43. The potential predictors include demographic and economic variables, school-related factors, behaviors, and body weight. Based on predictors for abdominal obesity identified through multilevel logistic regression, we created a nomogram model. We performed the Hosmer-Lemeshow test to assess model calibration and used a bootstrapping approach (B = 150) for internal validation. To evaluate external validity, we assessed metabolic syndrome in a subset of 375 students. The area under the receiver operating characteristic curve (AUROC), with a threshold of 0.70, was used to evaluate the model's discrimination accuracy. Results: We identified 114 (23.0%) college students who were abdominally obese. We found ten variables associated with the primary outcome: age, biological sex, physical education facilities, enrollment in sports competition (during elementary school); grade retention, preferred subject, physical education classes per week; enrollment in sports training (during secondary school); adherence of 24-hour movement behaviors and body weight. The proposed nomogram showed acceptable performance in the AUROC (0.94 [95% CI: 0.92-0.96). The calibration assessment indicated reasonable consistency of our model (p &gt; 0.05). In the internal validation, we observed a decreased predictive capability (AUROC = 0.86). Conclusion: The 24h-MESYN risk score offers an effective self-screening tool for college students from diverse racial and ethnic backgrounds in economically challenged regions to assess their risk of developing metabolic syndrome.

Prenatal diagnosis of a fetus with mosaicism ring chromosome 2

To explore the genetic basis for a fetus with increased risk for Down syndrome and cardiac anomalies discovered by prenatal ultrasonography. A pregnant woman presented at the Women and Children's Hospital of Ningbo University on August 21, 2023 were selected as the study subject. Clinical data were retrospectively analyzed. Maternal peripheral blood sample was collected for non-invasive prenatal testing (NIPT) based on fetal free DNA. Amniotic fluid sample was collected for G-banded chromosomal karyotyping analysis. Trio-whole exome sequencing (WES) was also carried out on the amniotic fluid sample and peripheral blood samples from the couple. Copy number variation (CNV) identified by the WES was validated by real-time fluorescent quantitative PCR (qPCR). Chromosomal karyotyping was also carried out for the couple. This study has been approved by the Medical Ethics Committee of Women and Children's Hospital of Ningbo University (No. EC2020-048). Ultrasound examination at 22+6 gestational weeks had indicated intrauterine growth retardation (IUGR). The fetus was also found to have ventricular septal defect, overriding aorta and pulmonary stenosis. NIPT indicated a low risk for aneuploidy of chromosomes 13, 18 and 21. G-banding analysis revealed that the fetus had a karyotype of 45,XY,-2[5]/46,XY,r(2)(p25q37)[55]. WES has identified a deletion of approximately 1 614.28 kb in the 2p25.3 region, namely seq[hg38]del(2)(p25.3p25.3)chr2: g.10500_1624775del. The same deletion was found in neither parent, suggesting a de novo origin. qPCR results confirmed the expression of target genes in the fetal sample to be significantly reduced, whilst no similar anomaly was found in either parent. The mosaicism ring chromosome 2 probably underlay the IUGR and cardiovascular malformations in this fetus.

Metabolic syndrome is associated with poorer outcomes in people with osteoarthritis participating in a rehabilitation program: an observational study

Purpose To determine the prevalence of metabolic syndrome and explore its association with clinical outcomes (pain, quality of life, and physical function) in adults participating in an education and exercise program (GLA:D®). Methods An observational study of adults with hip and/or knee osteoarthritis who participated in GLA:D® between 2019 and 2022. Metabolic syndrome status was determined through self-report. Differences in clinical outcomes among people with, at risk of (1–2 risk factors), or without metabolic syndrome were compared at baseline, 3-, and 12-months using linear mixed models (age, sex, and baseline outcomes as covariates). Results Of 6846 participants (aged 65(SD 9) years), 20% (n = 1337) had, and 68% (n = 4632) were at risk of metabolic syndrome. Adults with metabolic syndrome reported higher pain (0–100 VAS: 7.3, 95% CI 5.4–9.1), lower health-related quality of life (EQ5D 0–100, VAS: −8.6, 95% CI −10.2 to −7.0), and slower gait speed (−0.26 m/s, 95%CI -0.3 to −0.23) at baseline compared to those with no metabolic risk factors. Differences remained at 3- and 12-months for pain and quality of life. Conclusions Metabolic syndrome risk factors were common in adults with osteoarthritis. Clinical outcomes remain impaired in people with metabolic syndrome compared to those without after education and exercise, suggesting further intervention may be required.

Circulating mtNFPs Are Associated with ARDS after CPB and Regulate Endothelial Barrier through FPR2.

Cardiopulmonary bypass (CPB) increases the risk of acute respiratory distress syndrome (ARDS) due to endothelial cell (EC) barrier dysfunction. However, the specific role of mitochondrial N-formyl peptides (mtNFPs) in ARDS following CPB remains unexplored. Here, we investigated the differential expression of circulating mtNFPs in patients after CPB, focusing on the novel role of FPR2 in ECs. Levels of circulating mtNFPs were assessed using enzyme-linked immunosorbent assay (ELISA). Several mtNFPs (ND4, ND5, ND6, and Cox1) were significantly upregulated in patients with ARDS at day 1 post-CPB compared to patients without ARDS. Higher levels of ND6 were correlated with worst PaO2/FiO2 (r=-0.2219 and P<0.0001) and cardiac Troponin T (r=2.107 and P<0.0001). Utilizing patient-derived serum and a rat lung ischemia reperfusion injury (LIRI) model, we observed a positive correlation between serum ND6 concentration and ARDS, which is also associated with EC barrier dysfunction. In vitro experiments, using trans-endothelial electric resistance (TEER) measurements and fluorescence microscopy with FITC-labeled VE-cadherin, demonstrated that ND6 disrupts the EC barrier through FPR2. Furthermore, FPR2 controls the release of ND6 out of mitochondria and cytoplasm under hypoxia reoxygenation (HR). Activated FPR2 leads to upregulation of nuclear transcription factor-kappa B (NF-κB) by inducing IκBα phosphorylation, promoting ICAM1 and VCAM1 expression, thereby compromising EC barrier integrity. Circulating pro-inflammatory and barrier-disruptive mtNFPs, particularly ND6, are associated with ARDS in patients undergoing CPB. The novel ND6-FPR2 axis regulates inflammation and EC permeability through the NF-κB pathway.

Lipid Accumulation Product and Cardiometabolic Index as Effective Tools for the Identification of Athletes at Risk for Metabolic Syndrome.

Metabolic syndrome (MS) is a growing global public health concern that is associated with increased risk for cardiovascular events, even in athletes. The lipid accumulation product (LAP) index and cardiometabolic index (CMI) have been shown to be efficient markers of MS in the general population; its applicability in athletes has not been discussed yet. We aimed to assess the role of LAP and CMI in predicting MS in athletes. We retrospectively enrolled 793 Olympic athletes practicing different sporting disciplines (power, skill, endurance, and mixed), classified arbitrarily into no risk (NR), low risk (LR), high risk (HR), or MS if they had 0, 1, 2, or 3 criteria for MS, respectively. Evaluations included a calculation of the LAP index, CMI, anthropometric measurements, and clinical and laboratorial variables. Among our population, only 0.8% reached the criteria for MS, 9.1% were at HR for MS, 37.8% were defined as LR, and 52.3% had NR. Significant differences in anthropometric parameters and the principal components of MS criteria (blood pressure, lipidic profile, glycemia) were reported predominantly in HR athletes and those with MS (p < 0.0001). LAP and CMI presented linearly increasing values from individuals with NR to those with MS (p < 0.0001). In addition, HR and MS athletes were classified as "likely MS" (9.8%) and LR and NR athletes as "unlikely MS" (90.2%). After adjusting for potential confounders, LAP ≥ 34.66 and CMI ≥ 0.776 emerged as independent predictors for MS in the overall cohort (Hazar Ratio (HR) 7.22 [3.75-13.89], p < 0.0001, and HR 5.37 [2.96-9.73], p < 0.0001, respectively). The ROC curve revealed that these cut-offs in the general population predict MS with an area under the curve (AUC) of 0.80 and 0.79, respectively, for LAP and CMI. However, gender-related cut-offs seem to be more precise in predicting MS (LAP ≥ 38.79 for male, LAP ≥ 14.16 for female, and CMI ≥ 0.881 for male and ≥0.965 for female). The ROC curve analyses of LAP and CMI showed good diagnostic accuracy in predicting MS among athletes, despite the low prevalence of MS in our sample. Thus, these indexes may be used to promote screening for primary prevention and early detection of athletes at risk for MS to establish an early prevention strategy. Larger prospective studies are necessary to validate their benefit in the general population.

Associations of schizophrenia with arrhythmic disorders and electrocardiogram traits: genetic exploration of population samples.

An important contributor to the decreased life expectancy of individuals with schizophrenia is sudden cardiac death. Arrhythmic disorders may play an important role herein, but the nature of the relationship between schizophrenia and arrhythmia is unclear. To assess shared genetic liability and potential causal effects between schizophrenia and arrhythmic disorders and electrocardiogram (ECG) traits. We leveraged summary-level data of large-scale genome-wide association studies of schizophrenia (53 386 cases, 77 258 controls), arrhythmic disorders (atrial fibrillation, 55 114 cases, 482 295 controls; Brugada syndrome, 2820 cases, 10 001 controls) and ECG traits (heart rate (variability), PR interval, QT interval, JT interval and QRS duration, n = 46 952-293 051). We examined shared genetic liability by assessing global and local genetic correlations and conducting functional annotation. Bidirectional causal relations between schizophrenia and arrhythmic disorders and ECG traits were explored using Mendelian randomisation. There was no evidence for global genetic correlation, except between schizophrenia and Brugada syndrome (rg = 0.14, 95% CIs = 0.06-0.22, P = 4.0E-04). In contrast, strong positive and negative local correlations between schizophrenia and all cardiac traits were found across the genome. In the most strongly associated regions, genes related to immune and viral response mechanisms were overrepresented. Mendelian randomisation indicated that liability to schizophrenia causally increases Brugada syndrome risk (beta = 0.14, CIs = 0.03-0.25, P = 0.009) and heart rate during activity (beta = 0.25, CIs = 0.05-0.45, P = 0.015). Despite little evidence for global genetic correlation, specific genomic regions and biological pathways emerged that are important for both schizophrenia and arrhythmia. The putative causal effect of liability to schizophrenia on Brugada syndrome warrants increased cardiac monitoring and early medical intervention in people with schizophrenia.