Unselected Population Research Articles

Fertility and age at childbirth in Polycystic Ovary Syndrome: Results from a longitudinal population-based cohort study.

There are few studies in unselected populations describing reproductive outcomes in women with polycystic ovary syndrome (PCOS) at the end of their reproductive years. To compare parity and maternal age at deliveries and explore factors associated with advanced maternal age in a large, unselected population-based cohort, followed prospectively for 25 years. Women randomly selected from the general population and included in the prospective Australian Longitudinal Study on Women´s Health were assessed approximately every third year from 1996 (age 18 - 23 years) to 2021 (age 43 - 48 years). Women with and without self-reported PCOS diagnosis ((n=981 and n=13 266, respectively) were compared. Overall 9.9% of women reported having PCOS and by 43 - 48 years. Compared to women without PCOS, those with PCOS had fewer births (1.7 ± 1.3 vs. 1.9 ± 1.2, p<0.001), and more were nulliparous (23% vs. 18%, p=0.003). Women with PCOS were older at their first and second childbirths (29.5 ± 5.5 vs. 28.8 ± 5.5 years and 32.1 ± 5.2 vs. 31.1 ± 5.0 years, p<0.001 for both). PCOS was associated with increased odds of advanced maternal age at first childbirth, adjusted odds ratio (aOR) 1.40 (95% confidence interval 1.10-1.80), and increased odds of gestational diabetes, aOR 3.90 (2.99-5.10). However, type 2 diabetes and hypertension were not associated with advanced maternal age (aOR 0.81 (0.43-1.50) and aOR 0.78 (0.59-1.03), respectively. Within the PCOS group, a late PCOS diagnosis was associated with increased odds of advanced maternal age, aOR 1.98 (1.22-3.22). Women with PCOS have lower parity and give birth at a later age compared to women without PCOS. PCOS is associated with advanced maternal age, with subsequent increased pregnancy complications. Later PCOS diagnosis is associated with double the rate of advanced maternal age at birth, emphasizing the importance of timely diagnosis.

Abstract 4138662: Mineralocorticoid receptor antagonist in patients with acute myocardial infarction: An updated systematic review and meta-analysis of randomized trials

Background: While mineralocorticoid antagonists (MRA) reduce mortality in patients developing heart failure post myocardial infarction (MI), it is unclear whether they are beneficial in an unselected post-MI population. Aims: Using a systematic review and meta-analysis, we aim to determine the effect of MRA treatment versus no MRA treatment on all-cause mortality in unselected post-MI patients from randomized data, simultaneously with the presentation of the largest randomized controlled trial on the topic, the CLEAR SYNERGY trial. Methods/Approach: We completed a systematic review of all randomized controlled trials comparing MRA treatment to no MRA treatment in post-MI patients. We will perform our primary analysis using fixed effects with the Peto odds ratio method and use random effects as a sensitivity analysis. The primary outcome will be all-cause mortality, and secondary outcomes will include cardiovascular mortality, new or worsening heart failure, recurrent myocardial infarction and stroke. Results/Data: Our systematic review of Pubmed, Embase, and CENTRAL from inception until April 30, 2024, yielded 456 records. A total of 11,199 participants from 11 randomized clinical trials will be included in addition to the late-breaking CLEAR SYNERGY trial. The CLEAR SYNERGY trial is a 2 x 2 factorial randomized controlled trial of low-dose colchicine 0.5mg daily versus placebo and spironolactone 25mg daily versus placebo in 7,062 post-MI patients who were within 72h of the index percutaneous coronary intervention. The results of the spironolactone factorial will be presented in the fall of 2024 with an expected median follow-up of 3.5 years. As the investigators of the CLEAR SYNERGY trial, we will combine our data with the other 11 trials for a total of 12 trials and 18,261 participants. Conclusions: CLEAR SYNERGY is the largest randomized controlled trial with the longest follow-up of spironolactone in the post-MI population. Our meta-analysis will provide updated effect estimates of post-MI MRA treatment, leveraging the late-breaking CLEAR SYNERGY data to reflect the totality of the evidence.

Abstract 4135923: Predictive Value of Supraventricular Tachycardia on Ambulatory ECG Monitoring for Recurrent Atrial Fibrillation Post-Catheter Ablation

Introduction: Established predictors of recurrent atrial fibrillation (AF) following catheter ablation (CA) have not incorporated findings on post-CA ambulatory ECG monitoring (AECG). Aims: This study examined the predictive value of supraventricular tachycardia (SVT) detected on 7–14-day AECG for recurrent AF within one year post-CA. Methods: This single-center retrospective study included a select subset of patients who underwent CA for AF between 2015 and 2023 and had AECG monitoring within the first year post-CA. SVT presence and characteristics on AECG were analyzed.Data on demographics, AF risk factors, and AF recurrences were extracted from electronic health records. ROC curves determined SVT episode thresholds. A multivariable regression model included established risk factors and SVT thresholds, and best subsets regression identified predictors of AF recurrence. Results: Of 7,481 patients undergoing CA for AF, 1,245 were monitored within one year post-CA. Among this subset, 439 (35.26 %) had recurrent AF during the first year post- CA. Of the 439 patients with recurrent AF, 99 had AECG monitoring before recurrence. These 99 patients were compared with the 672 patients with no AF recurrence. Average duration of AECG monitoring for the entire cohort was 11±2.7 days. Mean SVT episodes per day ≥4.6 and total number of SVT episodes ≥14.5 were significantly associated with recurrent AF (OR =1.99, P =0.030, and OR =2.77, P =0.019, respectively). Significant predictors of AF recurrence were female gender, heart failure, confirmed SVT, cardioversion before ablation, mean SVT episodes per day, and total SVT episodes on AECG. Conclusion: High burden of SVT on AECG monitoring (defined in this study to be ≥4.6 episode per day or ≥14.5 total episodes per monitoring period) was significantly associated with AF recurrence. Longitudinal studies in larger unselected populations are needed to confirm these results.

Cardiovascular sequelae in symptomatic SARS-CoV-2 infection survivors.

SARS-CoV-2 infection may lead to myocardial and endothelial damage. The present study sought to characterize the cardiovascular sequel in a large group of consecutive patients admitted for out-patient cardiovascular follow-up after a symptomatic COVID-19 infection. The aims of this study were as follows: to evaluate the presence of post-covid cardiovascular symptoms in an unselected population of outpatients referred to a post-COVID outpatient cardiology clinic and to characterize the long-term abnormalities associated with a more severe COVID-19 infection clinical course. A total of 914 patients were included in this single-center, observational, cross-sectional study, of which 163 were hospitalized and 149 required mechanical ventilation for COVID-19 pneumonia. Patients were analyzed at follow-up according to the care setting during the initial presentation. The median time to follow-up was 126 days. At that time, only 3.5% of patients reported no persistent dyspnea, chest pain, or fatigue on exertion. In a follow-up echocardiographic assessment, patients who required hospitalization showed slight alterations in the pulmonary acceleration time and the tricuspid regurgitation pressure gradient, as well as reduced exercise tolerance during treadmill exercise testing when compared to patients with a benign clinical course. 24-hour Holter EKG monitoring or 24-hour blood pressure monitoring did not identify significant differences between the analyzed subgroups. The current study reports on an association between COVID-19 severity and the presence of cardiovascular alterations at follow-up. A simple diagnostic protocol, comprising an exercise treadmill test and transthoracic echocardiography is useful in identifying patients who may benefit from regular, structured cardiovascular medical care.

Prevalence of Chagas disease among Latin American immigrants in non-endemic countries: an updated systematic review and meta-analysis

BackgroundChagas disease (CD), endemic in 21 Latin American countries, has gradually spread beyond its traditional borders due to migratory movements and emerging as a global health concern. We conducted a systematic review and meta-analysis of available data to establish updated prevalence estimates of CD in Latin American migrants residing in non-endemic countries. MethodsAa systematic search was conducted in MEDLINE/PubMed, Embase, Cochrane Library, Scopus, Web of Science, and LILACS via Virtual Health Library (Biblioteca Virtual em Saúde - BVS), including references published until November 1st, 2023. Pooled prevalence estimates and 95% confidence intervals (CI) were calculated using random effect models. Heterogeneity was assessed by the chi-square test and the I2 statistic. Subgroup analyses were performed to explore potential sources of heterogeneity among studies. The study was registered in the PROSPERO database (CRD42022354237). FindingsFrom a total of 1,474 articles screened, a total of 51 studies were included. Studies were conducted in eight non-endemic countries (most in Spain), between 2006 and 2023, and involving 82,369 screened individuals. The estimated pooled prevalence of CD in Latin American migrants living in non-endemic countries was 3.5% (95% CI: 2.5-4.7; I2: 97.7%), considering studies in which screening was indicated simply because the person was Latin American. Per subgroups, the pooled CD prevalence was 11.0% (95% CI: 7.7-15.5) in non-targeted screening (unselected population in reference centers) (27 studies); in blood donors (4 studies), the pooled prevalence was 0.8% (95% CI: 0.2-3.4); among people living with HIV Latin American immigrants (4 studies) 2.4% (95% CI: 1.4-4.3) and for Latin American pregnant and postpartum women (14 studies) 3.7% (95 CI: 2.4-5.6). The pooled proportion of congenital transmission was 4.4% (95% CI: 3.3-5.8). Regarding the participants’ country of origin, 7,964 were from Bolivia, of which 1,715 (21,5%) were diagnosed with CD, and 21,304 were from other Latin American countries of which 154 (0,72%) were affected. InterpretationCD poses a significant burden of disease in Latin American immigrants in non-endemic countries, suggesting that CD is no longer a problem limited to the American continent and must be considered as a global health challenge. FundingThis study was funded by the World Heart Federation, through a research collaboration with Novartis Pharma AG.

Decision analytical modelling of strategies for investigating suspected acute aortic syndrome.

Acute aortic syndrome (AAS) requires urgent diagnosis with computed tomographic angiography (CTA). Diagnostic strategies need to weigh the benefits of detecting AAS against the costs of using CTA with a low yield of AAS when the prevalence of AAS is low. We aimed to estimate the cost-effectiveness of diagnostic strategies using clinical probability scoring and D-dimer to select patients with potential symptoms of AAS for CTA. We developed a decision analytical model to simulate the management of patients attending hospital with possible AAS. We modelled diagnostic strategies that used the Aortic Dissection Detection Risk Score (ADD-RS) and D-dimer to select patients for CTA. We used estimates from our meta-analysis, existing literature and clinical experts to model the consequences of diagnostic strategies on survival, health utility, and health and social care costs. We estimated the incremental cost per quality-adjusted life-years gained by each strategy compared with the next most effective alternative on the efficiency frontier. A strategy based on the Canadian guideline (CTA if ADD-RS>1 or ADD-RS=1 with D-dimer >500 ng/mL) is cost-effective but would result in high rates of CTA if applied to an unselected population (AAS prevalence 0.26%). The strategy is also cost-effective and would result in lower rates of CTA if applied to a more selected population, such as those with a non-zero clinical suspicion of AAS (prevalence 0.61%). For patients currently receiving CTA, using ADD-RS>1 or D-dimer >500 ng/mL to select patients for CTA is cost-effective. A strategy using ADD-RS>1 or ADD-RS=1 with D-dimer >500 ng/mL to select patients for CTA appears cost-effective but primary research is required to evaluate this strategy in practice and determine how suspicion of AAS is identified.

Safety and efficacy of simultaneous liver transplantation and sleeve gastrectomy in morbid obese end-stage liver disease patients: The LT-SG study.

In obese patients, metabolic dysfunction-associated steatotic liver disease is becoming a leading aetiology of end-stage liver disease and hepatocellular carcinoma. Simultaneous liver transplantation and sleeve gastrectomy (LT-SG) has been proposed in the US, but the safety and efficacy of the procedure have not been widely explored in Europe. Between January 2016 and December 2022, morbidly obese patients listed for LT at Tor Vergata University were enrolled in the LT-SG study. Primary outcomes were: i) safety expressed as 30- and 90-days overall survival (OS) and ii) major postoperative complications (Clavien-Dindo > IIIa). The secondary outcome was efficacy expressed as a 3-year %excess BMI loss(%EBMIL). Eleven patients were enrolled in the study. The median BMI at transplantation was 42 (IQR 38-48). Indications to LT-SG were HCC (63.6%) and cirrhosis (36.4%). In 54% of cases, donors had high-risk characteristics (ET-DRI>1.6). The 30 and 90-day OS were 63.6% and 54.5%, respectively. All deaths occurred in patients with p-SOFT>15 or in patients who had at least three of the following characteristics: >60 years, BMI >45, metabolic syndrome, MELD>25 or ET-DRI >1.6. The six months, 1, 2 and 3 years %excess BMI loss was 73%, 60%, 50% and 43%, respectively. LT-SG is a complex procedure thatmay carry excess risk in an unselected population. It should be considered only in highly selected patients. Standard donors are recommended and prioritization of severely obese patients on the waiting list should be considered.

Diabetes and sudden cardiac death in a nationwide, unselected population

Abstract Background and purpose Sudden cardiac death (SCD) remains a prominent cause of mortality, with individuals afflicted by diabetes mellitus (DM) bearing a heightened risk of ventricular arrhythmias and SCD. However, comprehensive investigations in a nationwide, unselected context are lacking. Therefore, this study aimed to compare the incidence rates (IR) of SCD among individuals with Type 1 Diabetes Mellitus (T1DM) and Type 2 Diabetes Mellitus (T2DM) to the general population. Methods The study included the entire Danish population (approximately 5.5 million individuals) in 2010. SCD cases were identified through the detailed Danish death certificates and discharge summaries, yielding 6851 cases of SCD. The Danish Register of Medicinal Product Statistics, containing comprehensive prescription data from Danish pharmacies, facilitated the identification of individuals with T1DM and T2DM. Loss of life years was estimated for both T1DM and T2DM patients. Results Among the identified 6851 SCD cases, 272 (4%) were diagnosed with T1DM, and 833 (12%) with T2DM. Incidence rates of SCD were consistently elevated across all age groups for individuals with diabetes, compared to the general population (Figure 1). Patients with T1DM exhibited higher incidence rates than patients with T2DM (Figure 1). Notably, individuals aged 30-40 years with DM showed the greatest differences in incidence rates of SCD compared to the general population, with incidence rate ratios of 20.0 (95% confidence interval: 11.8-80.0) and 5.6 (95% confidence interval: 2.7-14.0) for T1DM and T2DM, respectively. On average, each 30-year-old patient with either T1DM or T2DM experiences a reduction of 3.7 and 3 life-years, respectively, due to the increased risk of SCD in these groups (Figure 2). Conclusion This nationwide study examines the incidence rates of SCD among individuals with and without a history of DM across all age brackets. Notably, patients with DM display consistently elevated incidence rates across age groups, with a particularly pronounced risk observed in those with T1DM. For both T1DM and T2DM, SCD is an important contributing factor to their shorter life expectancy compared to the general population. The heightened risk among individuals with DM underscores the importance of improved risk stratification for these patients.Incidence rates of SCDStacked cumulative incidence curves

The prognostic interplay of heart failure and chronic kidney disease in atrial fibrillation, focus on cardiorenal outcomes

Abstract Background Heart failure (HF) and chronic kidney disease (CKD) create a mutually reinforcing cycle, escalating disease development, and increasing morbidity and mortality rates. Both are common comorbidities promoting atrial fibrillation (AF) and contributing to heightened symptom burden and poorer outcomes in AF. Purpose To investigate the relationship of HF and CKD with cardiorenal outcomes in patients with AF. Methods For this analysis we included patients with known AF, treated at a tertiary centre between 01/2005 and 07/2019. The primary endpoint was a composite of cardiovascular (CV) death and hospitalization for HF (HHF). Secondary outcomes were renal death and dialysis. The multivariate model has been adjusted for age, sex, body mass index, HF, diabetes mellitus, CKD, coronary artery disease, previous myocardial infarction, and C-reactive protein. Results We included in total 7412 patients (median age 70 years, 39.7% female) with AF and followed them over a median of 4.5 years. A total of 1668 patients (22.5%) were diagnosed with HF, 806 (10.9%) with CKD and 372 (5.0%) were suffering from both conditions. Both CKD (adjusted HR 1.87, 95% CI 1.55-2.25) and HF (adjusted HR 2.57, 95% CI 2.22-2.98) were significantly associated with the composite of CV death/ HHF after multivariable adjustment. There was a significant stepwise increase in 5-year’s event rates of CV death/ HHF (no CKD &amp; no HF: 23%, HF: 61%, CKD: 63%, CKD &amp; HF: 82%; P-logrank &amp;lt;0.001). These results remained significant in the multivariate analysis, showing the highest increase in risk in patients with both HF and CKD with an adjusted HR of 3.96 (95% CI 3.34-4.68), followed by patients with only HF (adjusted HR 2.53, 95% CI 2.26 to 2.84) and only CKD (adjusted HR 2.22, 95% CI 1.87-2.63, p-value of &amp;lt;0.001, respectively). Regarding renal death/ dialysis we could observe a similar distribution of the 5-year’s event rates (no CKD &amp; no HF: 1.5%, HF: 4.0%, CKD: 11.8%, CKD &amp; HF: 17.7%; P-logrank &amp;lt;0.001). Both conditions, CKD and HF, remained independently associated with the combined endpoint of renal death/ dialysis after multivariable adjustment (only HF: adjusted HR of 2.80, 95% CI 1.84 to 4.25; only CKD: adjusted HR of 5.31, 95% CI 3.22 to 8.76; CKD &amp; HF: adjusted HR of 7.47, 95% CI 4.70 to 11.87; Figure 1). Conclusions Both CKD and HF significantly increase the risk of CV death and HHF, as well as renal death and dialysis in patients with AF. Risk assessment should expand beyond stroke and bleeding to cardiorenal complications including HHF, CV and renal death, as well as kidney failure in an unselected AF patient population.

Artificial intelligence-enhanced electrocardiography predicts 10-year risk of atherosclerotic cardiovascular disease

Abstract Background The ACC/AHA pooled cohort equations (PCE) calculates the 10-year primary risk of atherosclerotic cardiovascular disease (ASCVD), an indication to initiate primary prevention statin therapy in international guidelines. The validity of PCE is limited by its overestimation of risk in high-risk cohorts and an ethnic heterogeneity. Electrocardiography (ECG) has not been incorporated in current ASCVD risk estimation tools. Artificial Intelligence (AI)-based models are capable to capture patterns that are informative for cardiovascular prognosis. Purpose We explored the predictive value of a discrete-time survival model in 10-year ASCVD risk in comparison to PCE. Methods We developed an AI-ECG model to predict the 10-year ASCVD risk in an unselected secondary care population from the USA comprised of 1,163,401 ECGs from 189,539 patients. Data was split into training/validation and hold-out test sets by patient ID. Our AI-ECG model uses deep learning with a residual convolutional neural network with a discrete-time survival loss function to output subject-specific survival curves, accounting for both time to event and censorship (i.e., loss to follow up). We compared the performance of out AI-ECG model using a subset of outpatient data (n=4590) of the BIDMC dataset to PCE and ASCVD risk factors including systolic blood pressure, total cholesterol, HDL cholesterol, hypertension, smoking history, diabetes mellitus, and ethnicity. Performances were evaluated using cox survival analysis. Our AI-ECG model was externally validated in the UKB Biobank (UKB), where we compared the performance of our AI-ECG model to predictions of existing AI-ECG models such as the Stanford Estimator of Electrocardiogram Risk (SEER) model. Results Our AI-ECG successfully predicted future ASCVD events in individuals (C-index 0.721 (0.719-0.723), 5-year AUC 0.761 (0.758-0.763), and differentiated between high and low risk group with an adjusted HR of 2.33 (2.26-2.41). Upon internal validation our AI-ECG model showed a superior performance (C-index 0.679 (0.651-0.708)) than PCE (0.605 (0.577-0.634)) and all risk factors combined (C index 0.642 (0.613-0.672)). When combining AI-ECG predictions with all risk factors, the model showed additional predictive value (0.686 (0.657-0.715)) (Figure 1). Our AI-ECG model showed modest predictive value within the UKB dataset (C-index 0.655 (0.637-0.673)), but significantly outperformed the SEER model (C-index 0.547 (0.527-0.567), p &amp;lt;0.0001 for comparison with AIRE). Conclusion We have shown the potential of AI-ECG models in predicting future ASCVD risks. AI-ECG models demonstrated accurate discrete time survival prediction and good classification performance superior to that of the SEER model, as well as PCE and ASCVD risk factors. . Accurate risk assessment of ASCVD may help prevent adverse events in high risk subjects and save unnecessary pharmacological interventios in low risk subjects.Figure 1

Real-world evidence for patient phenotypes in heart failure with preserved ejection fraction

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) presents a high mortality risk due to its heterogeneous and multifactorial nature, coupled with limited treatment options. The incompletely understood pathophysiology is influenced by various comorbidities, resulting in different clinical phenotypes. Identifying these could be crucial for tailored HFpEF treatments. While previous studies focused on small, well-characterized patient populations, electronic health records (EHRs) offer the potential to unveil HFpEF phenotypes in larger real-world patient groups. Purpose We aimed to establish a sizable, unselected HFpEF patient population using real-world data. Employing cluster analysis, we intended to uncover distinct groups with varied disease aetiology and medical needs based on comorbidity profiles and prognoses. Methods From EHRs of n = 1,610,101 HF patients, we identified an HFpEF cohort of n = 32,009 patients, by applying thresholds for the LVEF and data availability, and by excluding confounding conditions. Clustering by the relative frequency of common comorbidities aimed to reveal patient populations with unique prognoses, comorbidity profiles, and clinical and demographic characteristics. Results Six clusters of different sizes, comorbidity prevalence, clinical presentation, and all-cause mortality were identified. About 50% of patients (n = 15,445) were predominantly hypertensive, with varying extents of coronary heart disease and diabetes mellitus (DM), and a 5-year mortality of about 30%. Around 22% (n = 7,089) exhibited a cardiometabolic comorbidity profile, with an increased prevalence of obesity and sleep apnea, but also DM and hypertension, and a 5-year mortality of 22.5%. Over 15% of patients (n = 5,298) had a 5-year mortality rate of 45.0%, marked by highest rates of anaemia and chronic kidney disease (CKD) but also DM, elevated N-terminal prohormone of brain natriuretic peptide levels, and a reduced estimated glomerular filtration rate. Conclusion Despite the favourable prognosis, a significant proportion of patients represent a cardiometabolic HFpEF phenotype with notable unmet medical needs regarding cohort size and multimorbidity. Patients simultaneously suffering from CKD, anaemia, and the highest mortality rates may represent a previously underrecognized phenotype. Our study demonstrates that distinct medical needs can be identified in a large, unselected real-world HFpEF cohort. In contrast to clinical trials, this approach enabled access to a broader patient population, revealing novel phenotypes to be targeted by precision medicine in the future.

Nonlinear correlation between serum vitamin D levels and the incidence of endometrial polyps in infertile women.

Are serum vitamin D levels associated with the incidence of endometrial polyps (EPs) in infertile patients? Serum 25(OH)D levels were nonlinearly correlated with the incidence of EPs in infertile women. EPs are a common condition that may affect the receptivity of the endometrium in women of reproductive age. Vitamin D regulates cell proliferation and differentiation, apoptosis, angiogenesis, anti-inflammation, and immunomodulation, in addition to its well-known functions in balancing calcium and phosphorus. Previous studies have shown that vitamin D concentrations are associated with reproductive outcomes, and that low vitamin D levels are associated with the incidence of colorectal polyps and nasal polyps. There is little evidence regarding the relationship between EPs and serum vitamin D levels. We conducted a cross-sectional study using data from Guangdong Women and Children Hospital from January 2019 to October 2023, enrolling 3107 patients. A total of 3107 infertile patients who underwent hysteroscopy were included in this study; 642 patients had endometrial polyps and 2465 had a normal uterine cavity. Hysteroscopy findings included risk of EPs, polyp size, percentage of multiple polyps, and incidence of chronic endometritis (CE). Serum vitamin D were assessed by measuring total 25(OH)D using chemiluminescence. According to international guideline recommendations for vitamin D deficiency, patients were divided into two groups: the <50 nmol/l group and the ≥50 nmol/l group. Univariable and multivariable logistic regression models, stratified analyses, and smooth curve fitting were used to examine the relationship between serum 25(OH)D levels and risk of EPs. Of all patients, 23.8% (740/3107) were vitamin D deficient (<50 nmol/l). The incidence of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group (24.9% vs 19.3%; P = 0.001). However, there were no differences in polyp size, proportion of multiple polyps, and presence of CE between the two groups. After controlling for confounders, 25(OH)D ≥ 50 nmol/l (compared with <50 nmol/l) was negatively associated with risk of EPs (adjusted OR, 0.733; 95% CI, 0.598-0.898). Other variables that had an impact on polyp incidence included BMI, type of infertility, CA125, and CD138-positive plasma cells. In addition, a linear regression model between age and serum 25(OH)D levels showed a positive linear association. Subgroup analyses were performed for different age groups, and the risk of EPs was significantly higher in the 25(OH)D < 50 nmol/l group than in the ≥50 nmol/l group, both in the younger subgroup (23.8% vs 19.1%) and in the older subgroup (28.0% vs 19.9%). The smooth curve fitting model showed a nonlinear correlation between 25(OH)D levels and risk of EPs (nonlinear P-value = 0.020), with an optimal threshold of 51.8 nmol/l for 25(OH)D levels. Moreover, subgroup smooth curve fitting models showed a nonlinear correlation between 25(OH)D levels and polyp risk in patients aged <35 years (nonlinear P-value = 0.010), whereas a linear correlation between 25(OH)D levels and polyp risk was found in patients aged ≥35 years (nonlinear P-value = 0.682). Caution should be exercised in interpreting our findings as this is a correlational study and causality cannot be inferred from our results. In addition, because of strict inclusion and exclusion criteria, our results may not be generalizable to unselected populations, including premenopausal women or women of other races. This study demonstrated for the first time that vitamin D deficiency is an independent risk factor for the incidence of EPs in infertile patients. Identifying modifiable risk factors (e.g. vitamin D deficiency) can help in the development of new strategies for treating polyps or to protect against polyp development. Further clinical intervention trials and laboratory studies are needed to evaluate the effect of vitamin D on the development of EPs and to elucidate the mechanisms. The study was funded by the National Natural Science Foundation of China (82101718) and Natural Science Foundation of Guangdong Province, China (2022A1515010776). No competing interest was involved in this study. N/A.

Prognostic role of ECG patterns in Anderson Fabry disease

Abstract Background Anderson Fabry disease (AFD) is an X-linked lysosomal storage disorder leading to a deficiency in α-galactosidase A and globotriasylceramide (Gb3) deposition in different organs. Cardiac involvement is extremely common. It has been shown that the ECG abnormalities are directly correlated with the progressive accumulation of glycosphingolipids in the myocardium and cardiac conduction system. However, it is still unclear whether the ECG alterations are correlated with clinical events. Purpose To evaluate the prognostic role of ECG patterns in an unselected population of patients with AFD. Methods We conducted a retrospective multicenter study enrolling 215 consecutive patients. Based on the baseline ECG the study population was divided into the following five groups: 1) normal ECG or minimal alterations; 2) left ventricular hypertrophy (LVH) without signs of overload; 3) isolated negative T waves in the inferior and/or lateral leads; 4) LVH with signs of overload with or without incomplete right bundle branch block (RBBB); 5) complete RBBB. The primary endpoint was the composite of sudden cardiac death, resuscitated cardiac arrest, sustained ventricular tachycardia, and heart failure. Results Median age of study population was 45 years (32-57), and 86 patients (40%) were men. The rate of classic phenotype was 68%. Patients with ECG patterns 3 and 4 were older at baseline, more frequently affected by arterial hypertension, mostly male and showed greater left ventricular thickening, At a median follow up of 60 months (25-83) the overall Kaplan-Meier survival free from the primary endpoint was 57%: the Kaplan-Meier survival estimates of ECG groups were 66%, 75%, 68%, 27% e 52% respectively (log Rank 0.0026). On multivariable analysis patients belonging to either 3 or 4 group showed an increased risk of primary endpoint (HR= 2.45; 95% CI 1.04-5.78, p=0.040) compared to other groups. Conclusion ECG at baseline may be a useful tool to predict the risk of cardiovascular events in Anderson-Fabry Disease. Future studies should investigate if ECG may be useful also to evaluate the clinical response to specific therapy.

A novel 12-lead standard ECG derived scoring system for risk stratification in the emergency department

Abstract Background/Aims The ECG represents a routinely used diagnostic tool in the assessment of patients in the emergency department. Beside specific alterations within the ECG indicative of underlying pathologies, such as ST-elevation in myocardial infarction, several other parameters have been developed over the past decades that proofed themselves as strong and independent predictors of worsened outcome independent of a specific underlying pathology. These include basic metrics such as heart rate and QRS duration, but also more advanced biomarkers such as QRS microfragmentation (QRSµf) [1] and total cosine R to T (TCRT) [2] . In this work, we aimed to summarize all these markers derived from 12-lead standard ECGs into one novel risk score and evaluate its performance as mortality predictor in the emergency department. Methods We retrospectively collected 10- second 12- lead ECG recordings unselected patients presenting to the emergency department of a large university hospital between September 2019 and June 2022. For each patient a risk score was calculated from the first retrieved ECG using the criteria displayed in Figure 1. Calculation of all parameters was done as previously published. Patients with a total score of 0-1 points, 2-3 points, 4-6 points and 7 points were considered as low, intermediate, high and very high risk, respectively. The performance of the risk score was evaluated using Cox regression analysis and Kaplan-Meier curves with all-cause mortality within one year as primary endpoint. Results In total, 10 781 patients were included in our analyses. Median age was 69 (IQR 54-80) years, 5 588 (52%) were male and 5 193 (48%) were female. 6 966 (65%) patients were considered as low risk, 2 656 (25%) patients as intermediate risk, 1 098 (10%) patients as high risk and 61 (1%) patients as very high risk according to the ECG risk score with one year mortality rates of 8%, 17%, 26% and 43%, respectively (p &amp;lt; 0.001 for difference). In cox regression analysis the novel ECG risk score was a strong and independent predictor of one-year all-cause mortality with a hazard ratio of 1.35 (95% CI 1.31-1.39, p &amp;lt; 0.001). Kaplan-Meier survival curves for different risk categories are displayed in Figure 2. Conclusion In an unselected population of patients presenting to the emergency department of a large university hospital a novel risk score calculated from standard 12-lead ECGs recorded during clinical routine was a strong and independent mortality predictor. Further studies are needed to evaluate how incorporation of the novel score into existing triage systems can improve patient care.Figure 1:Calculation of ECG risk scoreFigure 2:Kaplan-Meier survival curves

Albumin creatinine index added to the grace score increases its discriminative capacity for mortality at 12 years of follow-up in patients with acute coronary syndrome

Abstract introduction There is currently no information on the prognostic value of the GRACE score with the additional addition of the albumin-creatinine index (ABI) for the prediction of very long-term mortality in unselected populations of acute coronary syndromes (ACS). Objectives To evaluate the additive value of the albumin-creatinine index in spontaneous urine sample to the GRACE score for the prediction of 12-year mortality from all causes in an unselected cohort of patients with acute coronary syndrome. Material and methods A prospective cohort study was carried out, which included patients admitted to a Community Hospital with a diagnosis of ACS. These patients had their IAC measured in a single spontaneous urine sample based on the principle of immunoturbidimetry in the first 24 hours of admission. The end point of the analysis was all-cause mortality at follow-up. The GRACE 2.0 score was calculated for all patients in the study. The scores were compared according to the following metrics: their power to discriminate between events and non-events (ROC Areas), calibration or goodness of fit, evaluating the agreement between the proportion of events and non-events expected by both scores observed by Hosmer Lemeshow Test. The comparison between the areas under the ROC Curves was carried out using De Long's test with the MEDCALC program version 19.1.7. The net reclassification index and its 95% CI (GRACE score + IAC/GRACE score) were evaluated. Results 600 patients with ACS were analyzed, with an average age of 64 years. The GRACE score risk subgroups were divided by the established cut-off values: low risk (0 to 108), intermediate (109 to 139) and high risk (greater than 139). The area under the curve of the Grace score for mortality during follow-up was 0.79 (95% CI 0.69-0.89), while the area under the ROC curve of the GRACE + IAC score was 0.81 (95% CI 0.74-0.87). ). Comparing the two areas by the De Long test, the difference was statistically significant (P &amp;lt; 0.0001; 95% CI 0.07- 0.015). On the other hand, contingency tables were developed and the Hosmer Lemeshow Test (goodness of fit) was performed on the GRACE score and the GRACE + IAC score, observing agreement between expected events and non-events, throughout all subgroups of risk. In addition, reclassifications were made into deceased and survivors by applying the GRACE + IAC score on the GRACE score. The net reclassification rate was 28% (95% CI 21-35). The chi square of its Mc Nemar Test was 3.69 p &amp;lt; 0.0002. The absolute comprehensive discriminatory improvement was 0.01 (95% CI 0.009-0.02) and the corresponding relative value was 8.2% (95% CI 7.9-8.5). Conclusions In this unselected ACS cohort, the albumin-creatinine index added to the GRACE score significantly increases its ability to discriminate mortality from all causes in a 12-year follow-up.Comparison between ROC curvesHosmer Lemeshow test

Effect of Chlorantraniliprole on Life History Traits and Relative Fitness of Laboratory-Selected Resistant and Susceptible Populations of Spodoptera litura (Lepidoptera: Noctuidae).

Insecticides are widely used to control pests and improve agricultural yield. The use of indiscriminate amounts and persistent pesticides has not only resulted in insect pest resistance challenges but has also harmed non-target organisms and contaminated the environment. We assessed the cost-effectiveness of Spodoptera litura (Fabricius) resistance to chlorantraniliprole (CTPR) as part of insect resistance control programs. S. litura larvae were collected from the fields and treated with chlorantraniliprole for 15 generations. Compared to the unselected population (Unsel-Lab), the chlorantraniliprole-selected population (CTPR-Sel) of S. litura exhibited a resistance level of 98.23 times. The findings demonstrated that the chlorantraniliprole-resistant genotype had lower egg-to-adult survivability, longer egg-to-adult developing times, and lower fecundity than the chlorantraniliprole-susceptible genotype. Compared to the Unsel-Lab population, the CTPR-Sel population of S. litura had a poorer relative fitness (0.44) at LC30 and shorter male/female longevity. Demographic parameters, including net reproductive rate (R0) and intrinsic (rm) and finite rate of increase (λ), were lower in the CTPR-Sel strain than in Unsel-Lab S. litura. These findings demonstrate that chlorantraniliprole resistance in S. litura has fitness costs at the individual and population levels, implying that removing the selecting agent from the environment might result in less resistance and opportunities for susceptibility restoration. As a result, the current work could help to determine effective management strategies to prevent chlorantraniliprole resistance in S. litura.

The Value of Androgen Measures for Diagnosing Polycystic Ovary Syndrome (PCOS) in an Unselected Population.

Polycystic Ovary Syndrome (PCOS) is diagnosed by a combination of three features: hyperandrogenism (biochemical and/or clinical), ovulatory dysfunction, and polycystic ovarian morphology, usually detected by ultrasonography. Our study aimed to determine the need for androgen measurements by using hirsutism to establish hyperandrogenism for diagnosing PCOS in a medically unbiased population. We utilized a pre-existing cohort of unselected (medically unbiased) females aged 18-45years. All underwent a history and physical, including a modified Ferriman-Gallwey (mFG) hirsutism score. Subjects were categorized clinically as eumenorrheic non-hirsute (CONTROLS), menstrual dysfunction only (OLIGO-ONLY), hirsutism only (HIRSUTE-ONLY), or menstrual dysfunction and hirsutism (OLIGO + HIRSUTE). All subjects underwent measurements of androgens using high-quality assays. CONTROLS established the upper normal limit for androgen levels. We defined PCOS using the NIH 1990 criteria. Of 462 individuals with complete evaluations, 311 (67.3%) were CONTROLS, 71 (15.4%) were OLIGO-ONLY, 64 (13.9%) were HIRSUTE-ONLY, and 16 (3.5%) were OLIGO + HIRSUTE. Neither HIRSUTE-ONLY nor OLIGO-HIRSUTE women required androgen measures to demonstrate hyperandrogenism. Among OLIGO-ONLY, 19 (26.8%) demonstrated hyperandrogenemia without hirsutism, with White women significantly more likely than Black women to demonstrate this. In our study of medically unbiased reproductive-aged women using the NIH 1990 criteria for PCOS, only 15.4% of women evaluated (those with menstrual dysfunction only) required androgen measurements. In these women only one-quarter demonstrated hyperandrogenemia. These data provide a strategy to minimize the need for androgen assays, including firstly categorizing subjects by clinical presentation and then assessing circulating androgens in the subgroup with menstrual dysfunction only.

Unlocking the potential of immunotherapy in platinum-resistant ovarian cancer: rationale, challenges, and novel strategies.

Ovarian cancer is a significant global health challenge, with cytoreductive surgery and platinum-based chemotherapy serving as established primary treatments. Unfortunately, most patients relapse and ultimately become platinum-resistant, at which point there are limited effective treatment options. Given the success of immunotherapy in inducing durable treatment responses in several other cancers, its potential in platinum-resistant ovarian cancer (PROC) is currently being investigated. However, in unselected advanced ovarian cancer populations, researchers have reported low response rates to immune checkpoint inhibition, and thus far, no validated biomarkers are predictive of response. Understanding the intricate interplay between platinum resistance, immune recognition, and the tumour microenvironment (TME) is crucial. In this review, we examine the research challenges encountered thus far, the biological rationale for immunotherapy, the underlying mechanisms of immune resistance, and new strategies to overcome resistance.

8582 THE PREVALENCE OF POLYCYSTIC OVARY SYNDROME IN ADULT WOMEN: THE IMPACT OF GEOGRAPHIC REGION

Abstract Disclosure: M. Amiri: None. S. Hatoum: None. R.P. Buyalos: None. A. Sheidaei: None. R. Azziz: Consulting Fee; Self; Spruce Biosciences, May Health, Core Access Surgical Technologies, Acacia Bio, Fortress Biotech, and Rani Therapeutics. Stock Owner; Self; Martin Imaging. Background: Polycystic ovary syndrome (PCOS) is a common hormonal disorder that affects women of reproductive age and is associated with various health complications. The reported prevalence of PCOS varies widely. However, variations in PCOS prevalence by geographic region are unclear. Objectives: This systematic review and meta-analysis aimed to compare PCOS prevalence in adults across World Health Organization (WHO) regions. Materials and methods: A search of PubMed and Embase was conducted for studies on PCOS prevalence in unselected populations published from inception to July 2023 using various diagnostic criteria. Studies were categorized according to: a) PCOS criteria (NIH 1990 [PCOS phenotypes A&amp;B], AE-PCOS 2006 [PCOS phenotypes A-C], Rotterdam 2003 [PCOS phenotypes A-D], and ‘other/self-reported’ criteria); b) subject assessment type (direct assessment, survey/indirect assessment, or mixed assessment); and c) study quality, assessed using the PCOS Epidemiology and Phenotype (PEP) quality assessment tool. Meta-analyses were performed using fixed-effects or random-effects models depending on the heterogeneity among the studies. Publication bias was assessed using the Egger’s regression test and funnel plots. Subgroup analyses were conducted based on PCOS criteria, assessment types, study quality, and WHO region. Results: Of 6,644 records, 50 studies with including a total of 70,146 adult women (age ≥18 years) were included. The overall pooled prevalence of PCOS was 9.7% (95% CI: 8.25, 11.38) with a pooled PCOS prevalence by criteria of NIH 7.7% (95% CI: 6, 9.83), Rotterdam 11.83% (95% CI: 9.15, 15.17), AE-PCOS 11.48% (95% CI: 7.5, 17.18), and other/self-report 10.05% (95% CI: 6.63, 14.96). High-quality studies reported lower prevalences for Rotterdam and NIH criteria than low-qualities (6.99% vs 10.07% for NIH and 11.07% vs 20.97% for Rotterdam), with all studies using AE-PCOS being high-quality and all studies using other/self-report criteria being low-quality. Among high-quality studies using direct/mixed assessments, PCOS prevalence by NIH was highest in Western Pacific Region (8.19%) and lowest in Europe (6.47%), whereas by Rotterdam, it was highest in Europe (21.30%) and lowest in Western Pacific Region (7.67%). We also observed that highest PCOS prevalence based on AE-PCOS criteria was in Europe (16.09%) and lowest in Western Pacific Region (7.43%). Publication bias was not significant (Egger’s coefficient = 1.2, 95% CI: -1.49, 3.9, p = 0.38), and funnel plot showed a nearly symmetrical distribution of studies around the estimated effect size. Conclusions: This meta-analysis revealed that the reported PCOS prevalence in adults varies widely by WHO geographic region. Study quality, assessment type and diagnostic criteria for PCOS impact the assessment, with low-quality studies overestimating PCOS prevalence. Presentation: 6/2/2024

Prevalence and accurate diagnosis of polycystic ovary syndrome in adolescents across world regions: a systematic review and meta-analysis.

To examine the global prevalence of polycystic ovary syndrome (PCOS) among adolescents across world regions, comparing the 2003 Rotterdam consensus criteria with the current International Evidence-based PCOS Guideline criteria which omits polycystic ovarian morphology (PCOM). Systematic review and meta-analysis, Prospero CRD42022372029. OVID MEDLINE, All EBM, PsycInfo, EMBASE, and CINAHL were searched from 1990 to November 2023 for studies assessing the prevalence of PCOS in unselected adolescent populations. Overall, 15 708 articles were identified. After removal of duplicates, 11 868 titles and abstracts and 445 full texts were assessed. Of these, 24 articles reporting on 23 studies from five world regions were included. In meta-analysis of 20 studies (n = 14 010 adolescents), global prevalence was 9.8% (95% CI 7.2, 12.3) according to original Rotterdam criteria, and 6.3% (95% CI 3.9, 8.8) according to International Evidence-based Guideline criteria. Global PCOS prevalence based on self-report was 9.8% (95% CI 5.5, 14.1). Grouped by WHO region, prevalence ranged from 2.9% (95% CI 2.0, 3.9) in the Western Pacific region to 11.4% (95% CI 7.1, 15.7) in the South-East Asia region according to guideline criteria. This paramount global meta-analysis on adolescent PCOS diagnosis directly informed the 2023 International PCOS Guideline. Guideline criteria generated a global PCOS prevalence of 6.3%, compared with 9.8% on Rotterdam criteria (including PCOM). Excluding PCOM, which overlaps with normal pubertal transition, is expected to deter over-diagnosis. To avoid under-diagnosis, the Guideline recommends identifying those with either irregular cycles or hyperandrogenism as being "at risk"; this group should undergo longitudinal serial evaluations until adulthood.