Prospective Study Research Articles

Impact of fetal sex on neonatal outcomes in women with gestational diabetes mellitus: a systematic review and meta-analysis

BackgroundResearch on the relationship between fetal sex and neonatal outcomes in pregnant women with gestational diabetes mellitus (GDM) is limited, and existing findings have yielded inconsistent results. Therefore, the aim of our study was to investigate the impact of fetal sex on neonatal outcomes in mothers with GDM.MethodsWe conducted a systematic search of six database) PubMed, Cochrane Library, Scopus, Web of Science, SID (Persian database), and Embase (up to January 1, 2025. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Subgroup analyses differentiated between retrospective and prospective cohorts for the primary outcomes. Sensitivity analyses were performed using the leave-one-out approach to evaluate the robustness of the pooled results. Additionally, a meta-regression analysis was conducted, considering maternal age, gestational weight gain, and BMI for both male and female infants.ResultsFrom 702 studies screened, twelve observational studies were included in the analysis. The results revealed a significant increase in the rates of macrosomia (RR 1.47, 95% CI 1.23 to 1.77, 6 studies, 121,230 neonates; p < 0.0001), cesarean delivery (RR 1.05, 95% CI 1.03 to 1.06, 6 studies, 127,704 neonates; p < 0.0001), large for gestational age (LGA) (RR 1.21, 95% CI 1.08 to 1.36, 6 studies, 16,863 neonates; p < 0.0001), small for gestational age (SGA) (RR 1.14, 95% CI 1.05–1.25, 6 studies, 16,863 neonates; p = 0.002), and a 5-minute Apgar score of less than 7 (RR 1.26, 95% CI 1.11 to 1.43, 2 studies, 104,881 neonates; p = 0.0003) in male neonates compared to female neonates. However, there were no significant differences in the rates of preterm delivery (p = 0.86), jaundice (p = 0.75), and a 1-minute Apgar score of less than 7 (p = 0.08) between male and female neonates in women with GDM.ConclusionThe findings suggest that male infants are at a greater risk of experiencing specific adverse outcomes in the context of GDM. Further research is needed to establish tailored interventions and guidelines to improve the care and management of women with GDM and their infants.

Ear Problems Are Associated With Traumatic Dental Injuries Among Australian-Indigenous-Children.

The association between ear problems and traumatic dental injuries (TDIs) has not been examined in longitudinal cohort studies. The study aimed to estimate the effect of ear problems on TDIs in primary and permanent teeth among Australian Indigenous children. The Longitudinal Study of Indigenous Children is a study of two representative cohorts of Indigenous Australian children, aged from 6 months to 2 years (baby cohort) or from 3.5 to 5 years (child cohort) at baseline (2008). The children's mother/primary carer undertook a face-to-face interview in 2008, repeated annually for the next 9 years. Ear problems included runny ears, perforated eardrum, total deafness, deaf in one ear, hearing loss/partially deaf, and other ear problems. TDIs were teeth and oral soft and hard tissue injuries. Multivariate survival analysis using Cox proportional regression models estimated hazards ratio (HR) were used in the analysis. A total of 870 from baby cohort and 668 from child cohort Indigenous children, who had no TDIs at baseline were included in the analysis. The prevalence of TDIs was 9.2%, 11.1%, and 6.6% in the total, baby, and child cohorts, respectively. Multivariable models for TDIs indicate children with ear problems had nearly four times (total: HR = 3.72, 95% CI: 1.82-6.77), five times (baby cohort: HR = 4.76, 95% CI: 1.59-11.63), and more than 15 times (child cohort: HR = 16.2, 95% CI: 4.78-49.28) the average hazard over time, than those without ear problems. After adjusting for all covariates, children with ear problems had more than 22 times (HR = 22.03, 95% CI: 4.50-87.07) TDIs than those without ear problems in the child cohort. Mothers/primary carers with lower educational level was positively associated with the incidence of TDIs. Ear problems were a risk indicator for the increased incidence of TDIs in two large cohorts of Indigenous Australian children. Mothers/primary carers' educational level was a significant risk factor for TDIs.

Association between poor oral health and deterioration of appetite in older age: results from longitudinal analyses of two prospective cohorts from the UK and USA

ObjectiveThis study investigated the association of poor oral health with appetite loss and deterioration in appetite longitudinally in older adults.DesignCross-sectional and longitudinal observational study.SettingData came from two population-based cohorts of...

Gestational exposure to environmental chemical mixtures and cognitive abilities in children: A pooled analysis of two North American birth cohorts.

Gestational exposures to single toxic chemicals have been associated with cognitive deficits in children, but few studies have explored chemical mixtures. To evaluate the associations between gestational chemical biomarker mixtures and cognitive abilities in children from two prospective cohorts. This study includes 617 birthing parent-child pairs from the Health Outcomes and Measures of the Environment (HOME) and Maternal-Infant Research on Environmental Chemicals (MIREC) Studies. We measured 29 chemical biomarkers (metals, persistent organic pollutants, perfluoroalkyl substances, organophosphate esters, phenols, phthalates, organophosphate pesticides, and parabens) in pregnant individuals during early pregnancy and their children's cognitive abilities at ages 3 to 5years using Wechsler Intelligence Scales. We assessed linear associations using quantile g-computation and non-linear associations using Bayesian Kernel Machine Regression (BKMR) methods, adjusted for covariates. Using quantile g-computation, we observed overall null associations between the chemical biomarker mixture and cognitive outcomes among preschool-age children. Although statistical significance was not attained for child sex as an effect modifier, our stratified analysis unveiled a moderate divergence in association trends. We noted a marginal inverse trend between the chemical biomarker mixture and cognitive scores [Full-Scale Intelligence Quotient (FSIQ) & Performance Intelligence Quotient (PIQ)] among males. Using quantile g-computation and BKMR methods, we observed that PBDE47, PFHxS, and di-ethyl organophosphates commonly contributed towards a decline in FSIQ scores in males. Among males, a quartile increase in the chemical biomarker mixture was associated with a 0.64-point decrease (95% CI: -2.59, 1.31) in the FSIQ score and a 1.59-point decrease (95% CI: -3.72, 0.54) in the PIQ score. In this study, we observed a weak negative trend between the gestational chemical biomarker mixture and cognitive scores (FSIQ/PIQ) among males. Further studies are needed to confirm the findings between the longitudinal chemical biomarkers and child cognitive scores at school ages.

Abstract TP106: Cognitive Impairment in Young Adult Ischaemic Stroke Survivors: a Systematic Review And Meta-analysis

Background: Post-stroke cognitive impairment is especially devastating for young adult patients, who are in their most productive years. Despite its significant impact, this remains under-studied in this growing and clinically distinct patient group. Methods: We systematically searched PubMed, Embase, Scopus, and Cochrane CENTRAL for studies including ischemic stroke patients aged 18-50 years from January 2000 to July 2024. This meta-analysis evaluated the pooled prevalence of post-stroke cognitive impairment (CogI) and specific cognitive domains, as well as the associations between baseline characteristics and CogI. Results: A total of 4 studies with 1060 patients were included in this systematic review and meta-analysis. Overall, 35.9% (95% CI 27.2-45.5; Figure 1) of patients experienced post-stroke CogI with a mean follow-up time of 11.7 months (95% CI 8.00-15.4). One study was not included in the meta-analysis of proportions of overall cognition as this information was not available. The prevalence for individual domains was: visuospatial construction (23.1%; 95% CI 14.7-34.4), episodic memory (18.5%; 95% CI 9.7- 32.5), delayed memory (16.0%; 95% CI 13.5-18.9), working memory (18.8%; 95%CI 11.8-28.6), and attention (9.3%; 95%CI 3.2-24.0) with a mean follow-up time of 8.11 months (95% CI 3.50-12.7). Male patients had significantly higher odds of CogI (OR 1.58, 95% CI 1.05-2.38, p=0.030; Figure 2). Hypertension, diabetes mellitus, current smoking and dyslipidaemia were not significantly associated with CogI. Conclusions: A significant proportion of young adult ischemic stroke survivors experience CogI. Longitudinal prospective cohort studies are needed to better characterise the post-stroke cognitive trajectory in this important group of patients.

Study of the application prospects of film detectors for estimation of α-radiation density

Study of the application prospects of film detectors for estimation of α-radiation density

Patterns of physical activity, sedentary behavior, and sleep across pregnancy before and during two COVID pandemic years.

Physical activity is recommended during pregnancy, and high sedentary behavior and poor sleep may increase the risk of pregnancy complications. Activity patterns and sleep were negatively impacted by the COVID pandemic in many segments of the population, but the impact of the pandemic on pregnant people is understudied. We aimed to compare patterns of physical activity, sedentary time, and sleep during pregnancy between a pre-COVID and a COVID-era cohort. Physical activity, sedentary time, and sleep in each trimester of pregnancy were compared between two parallel prospective observational cohorts using identical collection methods. Pre-COVID participants (n=111) were recruited in 2017-2019 and COVID-era participants (n=117) from 2021-2023. Physical activity and sedentary time were measured using the activPAL3 micro accelerometer, and sleep duration was self-reported. Between-cohort comparisons were conducted using linear regression for each behavior in each trimester. Within-COVID-era cohort linear regression analyses assessed whether activity patterns differed as pandemic-era restrictions were eased. Participant demographics were similar between cohorts except for self-reported income. Adjusted mean moderate-to-vigorous physical activity was 57-77 min/week higher in each trimester in pre-COVID compared to COVID-era participants (p<0.001); adjusted mean sedentary time was 0.77-1.13 hours/day lower in each trimester (p<0.01) and sleep duration was 0.8 hours/day lower in the third trimester in the pre-COVID compared to COVID-era cohort (p<0.05). Within the COVID-era cohort, no significant within-trimester differences were detected across the pandemic years. Pregnant participants during the COVID pandemic were less active and more sedentary than their pre-pandemic counterparts, and this trend was still detected years after the pandemic began. A more sedentary lifestyle during pregnancy may have health implications, and prenatal care providers should help pregnant people identify strategies to adopt an active lifestyle in the context of pandemic-era barriers.

Association between Mediterranean diet adherence and Parkinson's disease: a systematic review and meta-analysis.

Parkinson's disease (PD) is a chronic neurodegenerative disorder, and past research suggests that adherence to the Mediterranean diet (MD) may influence the risk of PD. However, there are varying conclusions among different studies regarding the correlation between long-term adherence to the MD and the occurrence of PD. This meta-analysis aimed to investigate the association between MD adherence and PD incidence. This meta-analysis was registered on PROSPERO (CRD42024520410). We searched PubMed, Embase, Web of Science, and Cochrane databases to identify observational studies, including prospective cohorts, case-control, and cross-sectional studies, up to February 2024. Studies reported on MD adherence were included, with MD adherence categorized through a quantifying score or index. The pool odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the highest versus the lowest categories of MD score in relation to PD risk, using random-effects models. Additionally, bias assessment, heterogeneity assessment, sensitivity analysis, and subgroup analysis were performed. A total of 12 studies were included in the meta-analysis. The overall effect size of PD risk was as follows: compared to the lowest adherence to the MD, the highest adherence to MD showed a significant negative correlation with the incidence of PD, with an overall OR of 0.75 (95% CI: 0.66, 0.84). Specifically, in studies diagnosing PD, the overall OR was 0.83 (95% CI: 0.74, 0.94), while in studies diagnosing prodromal Parkinson's disease (pPD), the overall OR was 0.67 (95%CI: 0.59, 0.76). For individuals aged <60 years, the overall OR was 0.70 (95%CI: 0.62, 0.78), whereas, for those aged ≥60 years, the overall OR was 0.86 (95%CI: 0.74, 0.99). The evidence from this meta-analysis demonstrates a significant negative correlation between adherence to MD patterns and the risk of PD, suggesting that the MD may serve as a protective factor for PD. This dietary pattern may be particularly beneficial in reducing the risk of pPD.

Impact of duration of treatments with metformin and sulfonylureas, individually or in combination, on diabetic retinopathy among newly diagnosed type 2 diabetic patients: a pooled cohort’s analysis

BackgroundThis study aimed to evaluate the effect of metformin and sulfonylurea (SUs) medication time on Diabetic retinopathy (DR) among newly diagnosed patients with type 2 diabetes (T2DM) using a pooled analysis. This study aimed to evaluate the effect of metformin and SUs’ medication time on DR among newly diagnosed T2DM using a pooled analysis.MethodsThe data of 4,068 newly diagnosed DM individuals(mean age, 60.2 ± 0.85 years) from three prospective cohorts of Tehran Sugar and Lipid Study (TLGS), Multi-Ethnic Study of Atherosclerosis (MESA), and Atherosclerosis Risk in Communities (ARIC) with a mean age of 59.6 ± 08 years were pooled. The cumulative exposure to metformin, SUs, aspirin, statin, and anti-hypertensive medication was also determined using the same approach. The Cox proportional hazards (CPH) model was used to calculate the hazard ratio (HR) (95% CI) for the outcomes while adjusting for confounding factors such as fasting Blood Sugar (FBS), age, statin, aspirin, and anti-hypertensive medications.ResultsDuring follow-up, DR occurred in 519 DM. Metformin alone, SUs alone, and the combination of both reduced the hazard of DR by 10%, 7%, and 11% for each year of use, respectively (p < 0.05). The protective effect of metformin and SUs, individually or in combination, on DR started approximately five years after the initial treatment and continued until approximately 15 years after the initial treatment and then reached a plato.ConclusionLong-term treatment with metformin and SUs, individually and in combination, was associated with a reduced risk of DR in people with newly diagnosed diabetes for up to a decade compared with no treatment. These findings highlight the protective role of metformin and sulfonylureas as inexpensive and readily available drugs to prevent DR in people with newly diagnosed diabetes.

P-769. A chromosome 4p14 locus associates with higher protection from Leprosy in close family contacts of Lepromatous Leprosy cases in endemic regions

Abstract Background Leprosy presents as an infectious disease with intricate genetic and immunological underpinnings. Genetic variations affecting cytokine genes and immune receptors, such as Toll-like receptor 1 (TLR1), may influence disease susceptibility. Close family contacts of individuals with slit skin positive lepromatous leprosy face a notably heightened risk of transmission. It is crucial to implement rigorous screening and early intervention protocols to promptly identify and manage latent infections, thereby curtailing potential disease dissemination within households and communities. Methods We conducted a genome-wide association study involving close family contacts of individuals with positive slit skin smears for Mycobacterium leprae. Our study comprised 131 lepromatous leprosy patients from prospective cohorts in an endemic region. Genotyping was performed using real-time polymerase chain reaction (RT-PCR) on the 7500 Real Time PCR System, employing SNP genotyping assays for pre-selected SNPs (rs7842033 and rs4167826) with specific primers and probes corresponding to the SNP of interest. Results Two-locus analyses of association of variants near rs7842033 showed a haplotype comprised of rs977477 and an IL9 missense variant, rs943138945, had the most significant association (p = 1.26x10-12).Our results showed no association between the SNP rs4052176 in NOD2 and leprosy in this population. Conclusion Situated on chromosome four (4p14), the TLR1 gene encodes a receptor that identifies glycolipids and lipopolysaccharides of M. leprae, stimulating the transcription factor nuclear factor-kappa B (NF-kβ) and enhancing the expression of pro-inflammatory genes. This gene may confer a degree of protection to close contacts against Leprosy. Disclosures All Authors: No reported disclosures

Optimization of Well Locations and Trajectories: Comparing Sub-Vertical, Sub-Horizontal and Multi-Lateral Well Concepts for Marginal Geothermal Reservoir in The Netherlands

Scaling up the direct use of geothermal heat in urban areas comes with the challenge of enabling the development of projects in geological settings where geothermal reservoir flow properties may be poor, resulting in low well flow performance. Cost-effective field development strategies and well designs tailored to such reservoirs can ensure the deliverability of geothermal energy in economic terms. This study presents a framework based on computer-assisted optimization to support practitioners in selecting the most suitable well concept for the exploitation of such marginal geothermal reservoirs. The proposed methodology is illustrated in a real-life case study of a geothermal development prospect in an urban area in The Netherlands, where the performance of sub-vertical, sub-horizontal and multi-lateral wells is compared. The obtained results indicate that the techno-economic performance of the geothermal doublet can be significantly improved by optimization, for all considered well concepts, and that, despite the importance of selecting the well concept, well location is still the main determinant of an effective field development strategy. The sub-horizontal and multi-lateral well concepts appear to be the most suitable for the target case study, outperforming the sub-vertical doublets, with a higher expected net present value and a lower economic variability risk for the multi-lateral solution.

P-164. Comparing long-term cardiovascular, neuropsychiatric, and autoimmune complications following dengue infection versus SARS-CoV-2 infection

Abstract Background While persistence of chronic symptoms following dengue infection has been documented in small prospective cohorts, population-based studies are limited. The post-acute risk of new-incident multi-systemic complications following dengue infection was evaluated and contrasted against that following SARS-CoV-2 infection in a multi-ethnic adult Asian population Methods National testing and healthcare claims databases in Singapore were utilised to build a retrospective population-based adult cohort with laboratory-confirmed infection during overlapping waves of SARS-CoV-2 and dengue transmission (1 Jul 2021-31 Oct 2022). Risks of new-incident cardiovascular/neuropsychiatric/autoimmune complications 31-300 days post-dengue infection, contrasted with SARS-CoV-2 infection were estimated using Cox regression with overlap weights. Risks were reported in terms of adjusted-hazard-ratio (aHR) and excess-burden (EB) per-1000-persons. Results 11,960 dengue-infected individuals and 1,265,329 contemporaneous COVID-19 cases were included; the majority had mild initial infection not requiring hospitalisation. Amongst dengue-infected individuals, there was 50% (aHR=1.50 [1.25–1.81]) increased risk of any sequelae (EB=1.51[1.40-4.42]), with 90% (aHR=1.90 [1.44–2.52]) increased risk of cardiovascular sequelae (EB=1.64[0.09-3.37]). Specifically, increased risk of ischemic-heart-disease (aHR=1.88[1.31-2.70]), other cardiac disorders (aHR=2.87[1.74-4.74]) and thrombotic disorders (aHR=4.56[2.37-8.75]) was noted. Elevated risk of individual neurological sequelae, including cerebrovascular disorders (aHR=2.05[1.29-3.25]) and cognition/memory disorders (aHR=2.31[1.40-3.84]) was observed in dengue-infected individuals compared to COVID-19 cases. Elevated risks of post-acute sequelae in dengue survivors were observed when contrasted against COVID-19 survivors infected during Delta/Omicron predominance, as well as across vaccination strata. Conclusion Increased risk of post-acute cardiovascular/neurological complications was observed in dengue survivors, when contrasted against COVID-19 survivors infected during Delta/Omicron predominance. Disclosures All Authors: No reported disclosures

Improving predictive accuracy of early recurrence in pancreatic ductal adenocarcinoma: Role of postoperative serum tumor markers.

In a recent study by He et al, the nomogram integrates postoperative serum tumor markers such as carbohydrate antigen 19-9 and carcinoembryonic antigen, thereby improving the accuracy of identifying high-risk patients compared to relying solely on preoperative markers, which has significant implications for customizing adjuvant therapy and potentially improving outcomes for this aggressive form of cancer. However, the study's single-center design and short follow-up period may limit the generalizability of its findings and potentially introduce reporting bias. Future studies could consider additional confounding factors, such as adjuvant chemotherapy and variations in surgical techniques, to improve the model's accuracy. Furthermore, it would be valuable to validate the nomogram in broader, prospective cohorts and explore the inclusion of additional markers like circulating tumor DNA to refine further its predictive power and applicability across diverse patient populations.

Novel Insights into the Pathogenesis of Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs), encompassing Crohn’s disease and ulcerative colitis, are complex chronic disorders characterized by an intricate interplay between genetic predisposition, immune dysregulation, gut microbiota alterations, and environmental exposures. This review aims to synthesize recent advances in IBD pathogenesis, exploring key mechanisms and potential avenues for prevention and personalized therapy. A comprehensive literature search was conducted across major bibliographic databases, selecting the most recent and impactful studies on IBD pathogenesis. The review integrates findings from multi-omics analyses, single-cell transcriptomics, and longitudinal cohort studies, focusing on immune regulation, gut microbiota dynamics, and environmental factors influencing disease onset and progression. Immune dysregulation, including macrophage polarization (M1 vs. M2) and Th17 activation, emerges as a cornerstone of IBD pathogenesis. Dysbiosis, as a result of reduced alpha and beta diversity and overgrowth of harmful taxa, is one of the main contributing factors in causing inflammation in IBD. Environmental factors, including air and water pollutants, maternal smoking, and antibiotic exposure during pregnancy and infancy, significantly modulate IBD risk through epigenetic and microbiota-mediated mechanisms. While recent advances have supported the development of new therapeutic strategies, deeply understanding the complex dynamics of IBD pathogenesis remains challenging. Future efforts should aim to reduce the burden of disease with precise, personalized treatments and lower the incidence of IBD through early-life prevention and targeted interventions addressing modifiable risk factors.

Potato Consumption and Risk of Cardiovascular Disease in a Harmonized Analysis of Seven Prospective Cohorts

Background/Objectives: While previous study results have suggested an elevated risk of type 2 diabetes with potato consumption, limited and inconsistent results are available on the association of potato consumption with the risk of cardiovascular disease (CVD) and hypertension (HTN). We assessed the associations of (i) total potato consumption with the risk of CVD and HTN as the primary aim and (ii) fried potatoes and combined baked, boiled, and mashed potatoes with the risk of CVD and HTN as the secondary aim. Methods: We conducted a meta-analysis using data from seven cohorts for CVD (n = 110,063) and five cohorts for HTN (n = 67,146). Cox regression was used to estimate multivariable adjusted hazard ratios separately in each cohort and the cohort-specific results were meta-analyzed using an inverse-variance weighted method. Results: The mean age ranged from 25 to 72 years, 65% of the respondents were women, and the mean consumption of total potatoes ranged from 1.9 to 4.3 times per week. In the primary analysis, total potato intake was not associated with the risk of either CVD or HTN: multivariable adjusted HR (95% CI) comparing 5+ servings/week to no potato intake: 0.96 (0.89–1.04) for CVD and 1.04 (0.99–1.08) for HTN. In secondary analyses, the consumption of combined baked, boiled, and mashed potatoes was not associated with CVD or HTN; while fried potato consumption was not associated with CVD risk, there was a 10% higher risk of HTN (95% CI: 4% to 17%) comparing 1+ servings/week to no fried potato intake. Conclusions: While the consumption of total potato was not associated with the risk of CVD or HTN risk, a modest elevated risk of HTN but not CVD was observed only with fried potato consumption.

Associations of Global Burden of Diseases study-derived dietary scores with mortality and chronic disease risk: a comprehensive analysis from the prospective NutriNet-Santé study.

The Global Burden of Diseases (GBD) network has proposed theoretical minimum risk exposure level (TMREL) for leading risk factors associated with diet that minimize the risk of morbimortality from chronic diseases. TMREL can be applied to develop follow-up or evaluation indicators in individual studies. The validity of these scores can be tested by assessing associations with health outcomes in prospective cohorts. In this study conducted within the NutriNet-Santé cohort, four dietary scores (TMREL-Risk Score, TMREL-Probability of adequacy, TMREL-standardized distance, and TMREL dietary score) using different scoring methods were developed, with higher scores reflecting less healthy diets. Associations of these scores with the risk of type 2 diabetes, cancer, cardiovascular diseases (CVD) and mortality were estimated using multivariable Cox proportional hazards models, adjusted for a wide range of covariates. Counterfactual and marginal structural models were used to infer causality. Analyses were conducted in a sample of up to103,324 participants ((78.3% women, mean age of 43.6 years old (y) (SD = 14.6)), followed for a median of 8.47 (IQR = 14.7) years (2009-2024). The association with dietary scores (for 1SD-increase) varied in magnitude for each health outcome. For mortality, HR varied from 1.12 (95%CI = 1.07-1.18, ) to 1.18 (95%CI = 1.12-1.24) for TMREL-Stdis and TMREL-DI, for overall cancer from 1.07 (95%CI = 1.03-1.12) to 1.09 (1.04-1.13) for TMREL-RS and TMREL-PA, for CVD from 1.07 (95%CI = 1.00-1.16) to 1.12 (95%CI = 1.04-1.20) for TMREL-PA and TMREL-RS, and for type 2 diabetes from 1.33 (95%CI = 1.23-1.43) to 1.47 (95%CI = 1.36-1.59) for TMREL-DI and TMREL-PA. Marginal structural Cox models strengthened all associations compared to classical analyses. Standardized survival curves showed clear associations, especially for the risk of cancer and type 2 diabetes. Dietary scores based on GBD TMREL can serve as key indicators for characterizing diet quality in relation to long-term health, and using different scoring systems helped evaluate the robustness of these associations.

Machine Learning to Predict Mortality in Older Patients With Cancer: Development and External Validation of the Geriatric Cancer Scoring System Using Two Large French Cohorts.

Establishing an accurate prognosis remains challenging in older patients with cancer because of the population's heterogeneity and the current predictive models' reduced ability to capture the complex interactions between oncologic and geriatric predictors. We aim to develop and externally validate a new predictive score (the Geriatric Cancer Scoring System [GCSS]) to refine individualized prognosis for older patients with cancer during the first year after a geriatric assessment (GA). Data were collected from two French prospective multicenter cohorts of patients with cancer 70 years and older, referred for GA: ELCAPA (training set January 2007-March 2016) and ONCODAGE (validation set August 2008-March 2010). Candidate predictors included baseline oncologic and geriatric factors and routine biomarkers. We built predictive models using Cox regression, single decision tree (DT), and random survival forest (RSF) methods, comparing their predictive performance for 3-, 6-, and 12-month mortalities by computing time-dependent area under the receiver operator curve (tAUC). A total of 2,012 and 1,397 patients were included in the training and validation set, respectively (mean age: 81 ± 6 years/78 ± 5 years; women: 47%/70%; metastatic cancer: 50%/34%; 12-month mortality: 43%/16%). Tumor site/metastatic status, cancer treatment, weight loss, ≥five prescription drugs, impaired functional status and mobility, abnormal G-8 score, low creatinine clearance, and elevated C-reactive protein (CRP)/albumin were identified as relevant predictors in the Cox model. DT and RSF identified more complex combinations of features, with G-8 score, tumor site/metastatic status, and CRP/albumin ratio contributing most to the predictions. The RSF approach gave the highest tAUC (12 months: 0.87 [RSF], 0.82 [Cox], 0.82 [DT]) and was retained as the final model. The GCSS on the basis of a machine learning approach applied to two large French cohorts gave an accurate externally validated mortality prediction. The GCSS might improve decision making and counseling in older patients with cancer referred for pretherapeutic GA. GCSS's generalizability must now be confirmed in an international setting.

Reproductive and Hormonal Factors and Thyroid Cancer Risk: Pooled Analysis of Prospective Cohort Studies in the Asia Cohort Consortium.

Given the female predominance of thyroid cancer (TC), particularly in the reproductive age range, female sex hormones have been proposed as an aetiology; however, previous epidemiological studies have shown conflicting results. We conducted a pooled analysis using individual data from 9 prospective cohorts in the Asia Cohort Consortium, to explore the association between 10 female reproductive and hormonal factors and TC risk. Using Cox proportional hazards models, cohort-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated and then pooled using a random-effects model. Analyses were stratified by country, birth years, smoking status, body mass index, and TC risk based on age of diagnosis was also examined. Among 259,649 women followed for a mean 17.2 years, 1,353 incident TC cases were identified, 88% (n=1,140) being papillary TC. Older age at first delivery (≥26 vs 21-25 years) was associated with increased TC risk (p-trend=0.003, HR=1.16, 95% CI:1.03-1.31), particularly when diagnosed later in life (≥55 vs <55 years) [p-trend=0.003; HR=1.19, 95% CI:1.02-1.39]. Among younger birth cohorts, women with more number of deliveries showed an increased TC risk [p-trend=0.0001, HR=2.40, 95% CI:1.12-5.18 (≥5 vs 1-2 children)], and there was no substantial trend in older cohorts. Distinct patterns were observed for the number of deliveries and TC risk across countries, with a significant positive association for Korea [p-trend=0.0008, HR=1.89, 95% CI:1.21-2.94 (≥5 vs 1-2 children)], and non-significant inverse associations for China and Japan. Contextual and macrosocial changes in reproductive factors in Asian countries may influence thyroid cancer risk.

P0296 Comparison of clinical characteristics of Montreal classification group A3 patients with Crohn’s disease in Korea: Results from the Prospective and Retrospective CONNECT Study

Abstract Background The CONNECT study, a nationwide multicenter cohort study of Crohn’s disease (CD) in Korea, was designed to investigate the clinical characteristics and long-term prognosis of CD patients. Starting in 2009, the study enrolled patients in both a prospective cohort (patients diagnosed since 2009) and a retrospective cohort (patients diagnosed before 2009). Recent trends show an increase in elderly-onset CD (EOCD) in Korea, alongside cases in younger individuals; however, research focusing specifically on EOCD patients remains limited. This study aims to evaluate the clinical characteristics and long-term outcomes of EOCD patients using data from this nationwide, multicenter cohort in Korea. Methods We analyzed data both the prospective and retrospective CONNECT cohorts, which included 2,399 CD patients diagnosed between 1982 and 2019 (retrospective cohort of 1,224 patients, prospective cohort of 1,175 patients). Of these, 244 patients were identified as having Montreal classification A3 at diagnosis. Fifty-six EOCD patients (diagnosed at age 60 or older) were compared with 188 adult-onset CD patients (diagnosed at age 40-59) in aspects of baseline characteristics, medication use, and bowel resection rates. Results EOCD patients had a higher proportion of females (55.4%) compared to the adult-onset CD group (31.5%). Ileal involvement was the most common location of disease at diagnosis in EOCD patients (51.8%). Previous use of anti-tuberculosis medication was more frequent in EOCD patients than in the adult-onset CD group (29.6% vs. 16.3%, p = 0.047). Although there were no significant differences in disease behavior at diagnosis or ever use of medication between the groups, EOCD patients showed a significantly lower risk of bowel resection (p = 0.008). Conclusion EOCD patients in Korea appear to present with distinct clinical features and have a more favorable prognosis, as evidenced by a reduced need for bowel resection compared with adult-onset CD patients. Further research is essential to better understand the unique needs of EOCD patients, including the development of tailored therapeutic guidelines that address the complexities associated with aging and the management of CD.

P1220 Circulating Metabolite Signatures Linking Physical Activity to Inflammatory Bowel Disease Risk and Interactions with Genetic Susceptibility

Abstract Background Recent studies have demonstrated the protective effect of physical activity on incident IBD, but the underlying mechanism remain unclear. Here, large-scale circulating metabolomics data was used to identify a metabolic signature reflecting moderate-to-vigorous physical activity (MVPA). We then investigated whether this signature mediated the association between MVPA and inflammatory bowel diseases (IBD) risk and how genetic susceptibility to IBD played roles in the association. Methods The present study was conducted in two prospective cohorts: the UK Biobank (n=194,292 for prospective analysis, n=12,766 for identification of the metabolic signature) and the Whitehall II study (n=5,925 for validation of the metabolic signature). MVPA in minutes per day was assessed by questionnaires and the circulating metabolome was profiled using a high-throughput nuclear magnetic resonance (NMR)-based platform. Associations between MVPA and individual metabolites were assessed using multivariable linear models and the MVPA-related metabolic signature was identified using elastic net regression. The primary analyses evaluated the prospective associations between MVPA/metabolic signature and incident IBD using multivariable Cox proportional hazards regression, and further examined the mediation role of the metabolic signature and the interaction with genetic susceptibility to IBD. Results We identified 100 metabolites significantly associated with MVPA, with a combination of 25 metabolites selected comprising the metabolic signature. During a mean follow-up of 13.3 years, 1,259 incident IBD cases were documented. Both MVPA and metabolic signature were associated with reduced incident IBD, with hazard ratio [HR] of 0.77 (95%CI, 0.66-0.90) and 0.60 (95%CI, 0.51- 0.71) for highest quartile vs. lowest quartile, respectively. The MVPA-related metabolic signature mediated 15.2% of the inverse association between MVPA and IBD risk. Participants with low MVPA/ metabolic signature and high genetic risk showed the highest IBD incidence, with both additive and multiplicative interactions observed. Conclusion The identified metabolic signature reflecting MVPA was found to mediate the inverse association between MPVA and incident IBD. Measuring a specific set of metabolites representative of MVPA, together with genetic susceptibility, may identify individuals with higher risk of IBD.