Large Epidemiological Studies Research Articles

Effects of Concurrent Administration of Spironolactone in Veterans with Metastatic Prostate Cancer Receiving Abiraterone: A Real-World Retrospective Study.

Prostate cancer is the most common cancer in men in the United States with low survival rates once metastasized. Abiraterone is approved for use in castrate-sensitive and castrate-resistant prostate cancer and is used extensively in the Veterans Affairs (VA) healthcare system. Spironolactone, a diuretic used to treat heart failure, edema, ascites, and hypertension, may increase androgen levels and reduce effectiveness of abiraterone when used concurrently to treat prostate cancer patients. While previous case studies support this, no large epidemiology studies have been conducted. The current study utilizes the large, VA prostate cancer data core and evaluates the effect of concomitant spironolactone on efficacy of abiraterone treatment in metastatic prostate cancer patients. The study selected 18,943 veterans with metastatic prostate cancer on abiraterone treatment. Of these, 581 patients (3.1%) were also on concomitant spironolactone. The concomitant treatment group, abiraterone + spironolactone, significantly differed from the abiraterone-only group in body mass index, prevalence rates of heart failure and liver disease, and being previously treated with docetaxel. A 1:1 propensity score matching method was used to balance sample sizes and baseline traits between the two treatment groups, abiraterone versus abiraterone + spironolactone. Kaplan-Meier curves and Cox proportional hazard model were used to compare 5-year overall survival and all-cause mortality outcomes, respectively, between the two groups. After propensity score matched, the abiraterone + spironolactone group was treated with abiraterone significantly longer than the abiraterone-only group (mean ± standard deviation days 549.0 ± 552.3 vs. 435.5 ± 474.1; p = 0.0002) and had a higher 5-year overall survival rate (44% vs. 37%; p = 0.0116). Veterans with metastatic prostate cancer treated with abiraterone + spironolactone also had a lower 5-year all-cause mortality compared to those only on abiraterone (hazard ratio 0.80, 95% confidence intervals 0.61-0.96; p = 0.012). This large VA observational study suggests that concomitant use of spironolactone does not compromise cancer control or survival of metastatic prostate cancer patients treated with abiraterone.

Patient reported outcomes, control of hypertension and dyslipidemia: results of two epidemiological studies in Romania, conducted during pandemia (Snapshot-1) and post-pandemic (Snapshot-2)

Abstract Background Coexistence of hypertension and dyslipidemia is commonly found in daily practice. Patient reported outcomes (PRO) are increasingly used to guide clinical decision-making, as well as public reporting of health system performance. Purpose To assess patient reported outcomes (PRO: socio-economic factors, depression level, and treatment adherence) and control of blood pressure (BP) and LDL-cholesterol (LDL-C) during pandemia and in the post-pandemic period. Methods Two real-world, cross-sectional, multicentre, observational studies, with a similar design, were conducted in Romania during pandemia, in June 2021 (SnapShot-1), and post-pandemic, in June 2022 (SnapShot-2). They included 5004 consecutive outpatients diagnosed with both hypertension and dyslipidemia, addressing cardiologists, diabetologists, and general practitioners: 2469 in SnapShot-1 and 2535 in SnapShot-2. Patients completed a three-part questionnaire including: (1) questions on socio-economic factors; (2) Patient Health Questionnaire (PHQ-9) (Depression scale); and (3) Hill-Bone Medication Adherence Scale (HBMAS) for hypertension and dyslipidemia. Results Characteristics of patients were similar between studies: 65.0±10.0 years and 40.9% men (SnapShot-1), 63.6±10.7 years and 43.3% men (SnapShot-2). Most of the patients declared themselves as "adherent" to the prescribed treatment: 91.8% (SnapShot-1) and 93.0% (SnapShot-2) adherent to antihypertensive treatment; 89.6% (SnapShot-1) and 90.9% (SnapShot-2) adherent to lipid lowering treatment. Socio-economic factors were similar between studies, except education, with higher education rates in SnapShot-2 (Table 1). Compared to SnapShot-1, depression scores evaluated by PHQ-9 scale were lower in SnapShot-2, conducted post-pandemic: 5.9±4.9 for SnapShot-1, suggesting a "mild" depression level, vs. 4.9±4.6 for SnapShot-2, which is below the "mild" depression threshold. Similarly, the adherence scores measured by HBMAS were lower in SnapShot-1 vs. SnapShot-2: 33.8±3.0 vs. 34.0±2.9 for antihypertensive medication, and 33.5±3.5 vs. 33.7±3.4 for lipid lowering treatment (Table 2). Conclusion Data collected from two large epidemiological studies in Romania showed an improvement of post-pandemic depression rates, as well as an improvement of adherence scores. Use of PRO assessment in routine clinical practice could support identification of patients on risk for uncontrolled BP or LDL-C, in need of more intense medical care.

6651 A Traceable Clinical Free Thyroxine Assay Based on Equilibrium Dialysis ID-LC/MS/MS

Abstract Disclosure: D. Spector: None. L. Zhang: None. A. Ribera: None. A. Doty: None. C. Tse: None. O. Sugahara: None. N. Vazquez: None. U. Danilenko: None. H.W. Vesper: None. Accurate diagnosis and effective treatment of thyroid diseases rely on reliable thyroid function tests. Serum free thyroxine (FT4) immunoassays (IAs) are most commonly used for FT4 measurements in clinical practice. However, FT4 IAs have not been standardized with large variations between different assay platforms. A reference measurement procedure (RMP) for FT4 based on well-defined equilibrium dialysis (ED) of serum has been established for CDC standardization program to support the standardization of clinical assays for patient care. In the current study, we aim to develop a routine clinical FT4 assay based on ED-LC/MS/MS that is traceable to the RMP. ED-LC/MS/MS analysis was performed using a commercially available micro-ED plate. FT4 in dialysate was extracted with a 96-well C18 SPE plate. FT4 in the samples was quantitated by using LC/MS/MS in positive ion mode. The assay was calibrated with the certified primary reference material. By using RMP as a reference, we compared the analysis of 40 single donor sera between the ED-LC/MS/MS assay and FT4 IA on Roche e401platform. ED-LC/MS/MS assay could resolve T4, T3, reverse triiodothyronine (rT3), and other interferences in the samples with C18 chromatography in 4 min. The linear range of the routine FT4 assay was from 0.5-100 pg/mL covering clinically relevant FT4 concentrations including hypo-, hyperthyroid patient samples. The intra and inter-run CV% of the assay in 20 days was 3.72 and 5.25%, respectively. The effect of minor changes to the method conditions was studied. It was determined that serum/buffer ratios from 1:1 to 1:2 in the ED inserts, speeds of shaker for ED, and ED incubation time, did not influence the FT4 measurement. However, elevated ED temperature at 38°C could result in a more than 10% increase in FT4 values. A microplate format for the procedures of ED and SPE is amiable to the application of an automation system which significantly improves the throughput of the procedure. Method comparison showed good agreement between ED-LC/MS/MS assay and RMP in Deming regression analysis with a slope close to 1, while there was significant bias of IA from RMP. ED-LC/MS/MS assay was also applied for pregnancy serum samples with minimal difference on the FT4 measurement from RMP. We have developed a routine clinical FT4 assay that is traceable to RMP. The accuracy, precision, and sensitivity of the assay are suitable for high-throughput FT4 measurements in clinical laboratories and large epidemiologic studies. We demonstrate that the developed method can provide accurate FT4 measurements in patients including pregnant women. Presentation: 6/3/2024

Lipoprotein(a) and risk-weighted apolipoprotein B: a novel metric for atherogenic risk

BackgroundRetention of apolipoprotein B (apoB)-containing lipoproteins within the arterial wall plays a major causal role in atherosclerotic cardiovascular disease (ASCVD). There is a single apoB molecule in all apoB-containing lipoproteins. Therefore, quantitation of apoB directly estimates the number of atherogenic particles in plasma. ApoB is the preferred measurement to refine the estimate of ASCVD risk. Low-density lipoprotein (LDL) particles are by far the most abundant apoB-containing particles. In patients with elevated lipoprotein(a) (Lp(a)), apoB may considerably underestimate risk because Mendelian randomization studies have shown that the atherogenicity of Lp(a) is approximately 7-fold greater than that of LDL on a per apoB particle basis. In subjects with increased Lp(a), the association between LDL-cholesterol and incident CHD (coronary heart disease) is increased, but the association between apoB and incident CHD is diminished or even lost. Thus, there is a need to understand the mechanisms of Lp(a), LDL-cholesterol and apoB-related CHD risk and to provide clinicians with a simple practical tool to address these complex and variable relationships. How can we understand a patient’s overall lipid-driven atherogenic risk? What proportion of this risk does apoB capture? What proportion of this risk do Lp(a) particles carry? To answer these questions, we created a novel metric of atherogenic risk: risk-weighted apolipoprotein B.MethodsIn nmol/L: Risk-weighted apoB = apoB - Lp(a) + Lp(a) x 7 = apoB + Lp(a) x 6. Proportion of risk captured by apoB = apoB divided by risk-weighted apoB. Proportion of risk carried by Lp(a) = Lp(a) × 7 divided by risk-weighted apoB.ResultsRisk-weighted apoB agrees with risk estimation from large epidemiological studies and from several Mendelian randomization studies.ConclusionsApoB considerably underestimates risk in individuals with high Lp(a) levels. The association between apoB and incident CHD is diminished or even lost. These phenomena can be overcome and explained by risk-weighted apoB.

Utility of an Archival Dried Blood Spot (DBS) Collection from HIV-Infected Individuals with and without Cancer in a Resource-Limited Setting.

The frequency of virus-associated cancers is growing worldwide, especially in resource-limited settings. One of the biggest challenges in cancer research among people living with HIV (PLWH) has been understanding how infection with both HIV and Kaposi sarcoma-associated herpesvirus (KSHV) promotes the pathogenesis of Kaposi sarcoma (KS), the most common cancer among PLWH worldwide and a significant public health problem in regions with high prevalence of HIV such as Sub-Saharan Africa (SSA). The AIDS and Cancer Specimen Resource (ACSR) provides samples for research, including dried blood spots (DBS) that were collected from large clinical epidemiology studies of KSHV and KS in PLWH conducted more than a decade ago in SSA. Here, we validated the quality of DNA derived from DBS samples from SSA studies and provided evidence of quantitative recovery of inflammatory cytokines using these DBS samples through comparison with paired frozen plasma. Significant differences in DNA, protein yields, and inflammatory biomarker levels were also observed between PLWH with/without KS. Establishing the fitness of DBS samples for studies of KS pathogenesis extends the number of projects that can be supported by these ACSR special collections and provides evidence that DBS collection for future KS research is a practical option in resource-limited settings.

Iron Overdose in Pregnant Women and its Treatment

During pregnancy, Iron requirements increase significantly to support the growth of the foetus and placenta, as well as maternal erythropoietic expansion. Iron supplementation is universally recommended for a viable pregnancy, irrespective of maternal Iron status. A food fortification strategy delivering about 10mg Iron per day lowers the proportion of women under risk of Iron deficiency to the range of 6 per cent to 39 per cent in many states. Combining fortification with weekly supplementation would lower the risk to between 1 per cent and 5 per cent. Food fortification and supplementation would expose many women to Iron levels that exceed the tolerable upper level of 45mg per day, producing Iron overload which can be prove to be toxic. Large epidemiological studies show a U-shaped association between maternal ferritin, a marker of Iron stores, and risk of adverse outcomes of pregnancy such as low birthweight, stillbirth, preterm birth (<37 weeks), very preterm birth (<32 weeks’ gestation), and neonatal asphyxia.

Correlation between Bronchopulmonary Dysplasia and Cerebral Palsy in Children: A Comprehensive Analysis Using the National Inpatient Sample Dataset.

Background: The existing literature lacks conclusive evidence regarding the relationship between bronchopulmonary dysplasia (BPD) and cerebral palsy (CP). This large epidemiological study aimed to explore the co-occurrence of BPD and CP among children. Methods: This retrospective cohort analysis utilized the National Inpatient Sample (NIS) dataset from 2016 to 2019, investigating pediatric patients with BPD and CP diagnoses. Descriptive and inferential statistics, including univariate and multivariate regression analyses, were conducted to explore the association between BPD and CP. Results: Overall, 3,951,039 patients were analyzed. Among them, 28,880 patients had CP (n = 796 with BPD and n = 28,084 without BPD). The rates of intraventricular hemorrhage grade 3 and 4, central nervous system anomalies, chromosomal disorders, retinopathy of prematurity (≥grade 3), periventricular leukomalacia, prematurity, and low birth weight were significantly higher in the CP-with-BPD arm contrasted to the CP-without-BPD arm. Univariate regression demonstrated a significant BPD-CP association (odds ratio [OR] = 7.78, 95% confidence interval [CI]: 7.24-8.37, p < 0.0001). Multivariate analysis, adjusting for various confounders, reinforced this association (OR = 5.70, 95% CI: 5.17-6.28, p < 0.0001). We observed a significant association between increasing prematurity in neonates with BPD and an elevated risk of CP. Conclusions: This nationwide study identified a strong correlation between the co-occurrence of BPD and CP, though it does not establish causality. Rigorous adjustments revealed that patients with BPD appear to have a six-fold increased likelihood of being diagnosed with CP later on, compared to those without BPD. While aligned with the existing literature, this study represents the largest sample size with recommendations for targeted preventive strategies to mitigate the burden of CP.

Per-and polyfluoroalkyl substances and disrupted sleep: mediating roles of proteins

BackgroundPer-and polyfluoroalkyl substances (PFAS) contamination may disrupt sleep through disrupted metabolic and immune functions. The study aims to investigate the association and potential mechanism between PFAS and sleep. MethodsWe included 136 young adults recruited between 2014-2018 and 76 were re-assessed between 2020-2022. Additional 8 participants only had complete data between 2020-2022. Plasma PFAS (PFOS, PFOA, PFHxS, PFHpS, PFPeS, PFNA, PFDA) were measured at both visits using liquid-chromatography high-resolution mass spectrometry. Plasma proteins were measured by Olink® Explore 384 Cardiometabolic and Inflammation Panel I. Sleep duration was self-reported at both visits along with follow-up sleep disturbance and sleep-related impairment using validated instruments. We utilized multiple linear regression to explore the association between individual PFAS (in tertile) and these sleep outcomes. PFAS associated with sleep outcomes were subjected to computational toxicology analysis using the Comparative Toxicogenomics Database and Toxicology in the 21st Century database to identify potential genetic links between them. Mediation analysis using proteomic data was then performed to confirm the findings from computational toxicology analysis. ResultsAt baseline, one tertile increase in PFDA was associated with 0.39 (95 % CI: 0.05, 0.73) hours of shorter nightly sleep duration, and, at follow-up, PFHxS and PFOA were associated with 0.39 (95 % CI: 0.05, 0.72) and 0.32 (95 % CI: 0.01, 0.63) hours shorter sleep duration, respectively. One tertile increase in PFOS exposure was associated with a 2.99-point increase in sleep disturbance scores (95 % CI: 0.67, 5.31) and a 3.35-point increase in sleep-related impairment scores (95 % CI: 0.51, 6.20). Computational toxicology and mediation analyses identified potential mediating roles for several proteins in the PFAS-sleep associations, including 11-beta-dehydrogenase isozyme 1 (HSD11B1), cathepsin B (CTSB) and several immune system-related proteins. ConclusionFuture large scale epidemiological and mechanistic studies should confirm our findings and test effect measure modification of the associations by age.

Biological monitoring of exposure to benzene in water pipe smokers of rural Western Uttar Pradesh (India)

Aim: Present study was performed to investigate the possible human exposure to benzene through water pipe smoking, if any, in the selected rural population of Western Uttar Pradesh. Methodology: Urine samples from water pipe smokers of both the sexes were collected and analyzed for urinary concentration of phenol, creatinine and malondialdehyde employing standard methods. Results: The results showed that tobacco used by selected rural population contained traces of benzene in the range of 2.75 to 9.682µl ml-1. Analysis of urine samples for phenol, a major metabolite of benzene, showed its increased concentrations in water pipe smokers than non smokers. Further, the effects of age and gender differences on the excretion of phenol were also recorded. Female water pipe smokers were found to be more vulnerable to benzene exposure than male smokers. Intriguingly, alcoholic water pipe smokers were less vulnerable than the non-alcoholic smokers. Interpretation: It is concluded that respiratory, cardiac and haematological disorders caused by water pipe smoking might be attributed to long term benzene exposure amongst water pipe smokers. Large scale epidemiological studies are warranted in Indian rural population considering WHO (Framework Convention on Tobacco Control) regulations of water pipe smoking and tobacco products. Key words: Biological monitoring, Benzene, Oxidative stress, Phenol, Tobacco, Waterpipe smoking

A large epidemiological study on human papillomavirus vaccine post-vaccination symptoms and healthy vaccinee bias

Objective This study aimed to examine the existence of healthy vaccinee bias, a source of distortion in the evaluation of vaccine efficacy, through analysis without random assignment using real data on post-vaccination symptoms from the Nagoya Study, a large epidemiological study of human papillomavirus (HPV) vaccine post-vaccination symptoms.Methods For three school years of individuals born in 1997, 1998, and 1999, as the HPV vaccine had a 2-year target period, 3,246 were first vaccinated at age 14 years and 3,961 were unvaccinated. The proportion of symptom onset in these 7,207 individuals during the unvaccinated period at age 13 years was compared by birth year to examine the presence of a healthy vaccinee bias.Results Only four symptoms were significantly higher among unvaccinated participants, such as the proportion of "severe headache," which occurred in 2010 among those born in 1997, "hyperventilation," which occurred in 2011 among those born in 1998, "fatigue" and "sudden vision loss," which occurred in 2012 among those born in 1999. Healthy vaccinee biases are rarely observed.Conclusion Underestimation of the odds ratio of HPV vaccination due to healthy vaccinee bias is limited, and the claim that the supposedly high odds ratio in the Nagoya Study was masked by a healthy vaccinee bias is invalid.

Proportion of patients with prosthetic joint infection eligible for adjuvant phage therapy: a French single-centre retrospective study

BackgroundBone and joint infections represent a major public health issue due to their increasing prevalence, their functional prognosis and their cost to society. Phage therapy has valuable anti-biofilm properties against prosthetic joint infections (PJI). The aim of this study was to establish the proportion of patients eligible for phage therapy and to assess their clinical outcome judged against all patients presenting with PJI.Method. Patients admitted for periprosthetic joint infection (PJI) at a French general hospital between 2015 and 2019 were retrospectively included. Eligibility for phage therapy was determined based on French recommendations, with polymicrobial infections serving as exclusion criteria. Patients were categorized into two groups: those eligible and those ineligible for phage therapy. We analyzed their characteristics and outcomes, including severe adverse events, duration of intravenous antibiotic therapy, length of hospitalization, and relapse rates.Results. In this study, 96 patients with PJI were considered in multidisciplinary medical meetings. Of these, 44% patients (42/96) were eligible for additional phage therapy. This group of patients had a longer duration of intravenous therapy (17 days vs. 10 days, p = 0.02), more severe adverse events (11 vs. 3, p = 0.08) and had a longer hospital stay (43 days vs. 18 days, p < 0.01).Conclusion. A large number of patients met eligibility criteria for phage therapy and treatment and follow-up is more complex. A larger epidemiological study would more accurately describe the prognosis of eligible patients.

54098 Higher Incidence of Precocious Puberty in Pediatric Patients with Hidradenitis Suppurativa: A large database epidemiological study

54098 Higher Incidence of Precocious Puberty in Pediatric Patients with Hidradenitis Suppurativa: A large database epidemiological study

PREVALENCE OF LYMPHEDEMA USING LARGE DATA SETS; AN EPIDEMIOLOGICAL ANALYSIS IN THE UNITED STATES AND IN ITALY

There is a lack of large epidemiological studies focusing on the prevalence of lymphedema. Vital registration data from the United States (US) (1999-2020) and Veneto, Italy (2008-2021) were analyzed. Lymphedema-related deaths were identified using disease-specific ICD-10 codes and served to estimate the burden of disease in the general population. We studied (i) the lymphedema-specific proportionate mortality as a proxy of the disease-specific prevalence, (ii) the prevalence of lymphedema in key patient subgroups, and (iii) age and sex-specific mortality rates. The prevalence of lymphedema increased over the last two decades with marked sex-specific differences: in the US, the estimated prevalence of lymphedema was 2.7 per 10,000 deaths for women and 1.5 per 10,000 deaths for men. In Veneto, the prevalence was 3.0 per 10,000 deaths for women and 1.1 per 10,000 deaths for men. The prevalence of lymphedema was 2- to 20-times in specific subgroups of patients, including those with obesity, skin infections, hypertension, diabetes mellitus, breast/gynecological cancers, and venous thromboembolism. The estimated prevalence of lymphedema is 2- to 3- times higher than previously thought and has been increasing for the past two decades. These results will serve as a reference for future research in this field.

Saliva-derived DNA is suitable for the detection of clonal haematopoiesis of indeterminate potential

Clonal haematopoiesis of indeterminate potential (CHIP) has been associated with many adverse health outcomes. However, further research is required to understand the critical genes and pathways relevant to CHIP subtypes, evaluate how CHIP clones evolve with time, and further advance functional characterisation and therapeutic studies. Large epidemiological studies are well placed to address these questions but often collect saliva rather than blood from participants. Paired saliva- and blood-derived DNA samples from 94 study participants were sequenced using a targeted CHIP-gene panel. The ten genes most frequently identified to carry CHIP-associated variants were analysed. Fourteen unique variants associated with CHIP, ten in DNMT3A, two in TP53 and two in TET2, were identified with a variant allele fraction (VAF) between 0.02 and 0.2 and variant depth ≥ 5 reads. Eleven of these CHIP-associated variants were detected in both the blood- and saliva-derived DNA sample. Three variants were detected in blood with a VAF > 0.02 but fell below this threshold in the paired saliva sample (VAF 0.008—0.013). Saliva-derived DNA is suitable for detecting CHIP-associated variants. Saliva can offer a cost-effective biospecimen that could both advance CHIP research and facilitate clinical translation into settings such as risk prediction, precision prevention, and treatment monitoring.

53 Associations between body composition, ClearCode34, and clinical outcomes in localized clear cell renal cell carcinoma

Abstract Background Emerging evidence suggests that pre-surgical body composition is a prognostic factor for cancer outcomes. Lower skeletal muscle quantity and radiodensity have been associated with renal cell carcinoma (RCC) outcomes in other studies, while reports of the relationship between visceral adipose tissue and RCC outcomes have been inconsistent. Mechanisms underlying these associations are unclear but may relate to tumor biology. We leveraged a large molecular epidemiology study of localized clear cell renal cell carcinoma (ccRCC) patients to examine how pre-surgical body composition features were associated with survival post-nephrectomy as well as ClearCode34 status, a previously validated prognostic gene expression signature. Methods The RESOLVE study at Memorial Sloan Kettering Cancer Center is a retrospective study of 1,239 patients with stage I-III ccRCC undergoing nephrectomy without systemic therapy. Pre-surgical CT scans at the third lumbar vertebrae were segmented for the cross-sectional areas and radiodensities of skeletal muscle, subcutaneous adipose and visceral adipose tissues using Automatica software. Formalin-fixed, paraffin-embedded tumor tissue samples were available for 929 patients, which were sent to the University of North Carolina at Chapel Hill and assayed for gene expression. RNA was extracted from these samples and analyzed using the Nanostring nCounter system on a custom panel of 356 genes, including the 34 genes used in the ClearCode34 assay. Of the 929 patients with tumor tissue available, gene expression data from 837 patients (90.1%) passed RNA extraction and data QC. Samples were classified into either ccA or ccB ClearCode34 classes using a reference data set and PAM (prediction analysis of microarrays) centroid-based classification. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) within five years of diagnosis using Cox proportional hazards models for both body composition variables and ClearCode34 subtype. We also estimated odds ratios (ORs) and 95% CIs for associations between ClearCode34 subtype and body composition with logistic regression. All multivariable models were adjusted for age, sex, and all body composition variables. Results Of the 837 patients in our analytic sample, 219 (26%) had ccB tumors. Men, patients with high stage or grade tumors, and patients with chronic kidney disease prior to nephrectomy were more likely to present with ccB tumors. Lower skeletal muscle density (SMD) was significantly associated with lower five-year DFS [HR (95% CI) per 10 HU decrease in SMD: 1.7 (1.2, 2.3)]. While no other body composition features were significantly associated, we also observed non-significantly increased HRs for VATI and VATD [HR (95% CIs): 1.3 (0.8, 2.0) and 1.5 (0.9, 2.7), respectively]. ClearCode34 subtype was significantly associated with five-year DFS, where patients with ccB tumors had poorer DFS [HR (95% CI): 1.7 (1.1, 2.5)] compared to patients with ccA tumors. Notably, we observed no significant associations between any body composition feature and ClearCode34 in univariable analyses. However, in multivariable models that accounted for all body composition variables simultaneously as well as age and sex, lower SMD emerged as significantly associated with ccB subtype [OR (95% CI) per 10 HU decrease in SMD: 1.3 (1.0, 1.7)]. Conclusions Our findings suggest that the associations observed between body composition features and clinical outcomes in ccRCC may be related to tumor biology. Lower pre-surgical SMD, which may represent myosteatosis and metabolic dysregulation in ccRCC patients, was associated with both decreased five-year DFS and an increased likelihood of presenting with a more aggressive ccB tumor. Future studies should investigate body composition features related to ccRCC prognosis and additional markers of tumor biology, such as immune-related gene expression patterns, to extend these findings.

Let's talk about radiation dose and radiation protection in children.

Children are more sensitive to ionizing radiation than adults. Even though the risk is very low, exposure from radiological examinations can possibly cause them long-term side effects. Recent large epidemiological studies involving children and young adults have added evidence suggesting that even small doses of radiation, such as those from computed tomography scans, might slightly increase the risk of developing cancer later in life. Therefore, even though radiologic studies are essential for an accurate diagnosis and management of various conditions, it is crucial to minimize radiation exposure. This article addresses radiation protection for children in the medical use of ionizing radiation and it is set in the context of the European legislative framework regarding radiation protection. It advocates for a holistic approach to paediatric radiological tests. This approach includes the key principles of radiation protection, such as the justification of imaging procedures supported by referral guidelines, as well as the optimization of techniques (according to the ALARA principle) and effective communication with parents about the benefits and the risks of radiologic procedures. Protecting children from unnecessary radiation is not only a technical challenge, but also a moral obligation and a legal requirement.

Differences in self-reported disruptions in mental health treatment during COVID-19 in a national household sample: impact of severity of functional impairment.

This report uses data from Mental Disorders Prevalence Study (MDPS), a large epidemiologic study that provided national prevalence estimates of seven mental disorders based on the Structured Clinical Interview for DSM-5 (SCID), to assess the odds of treatment disruption during COVID for SMI and non-SMI groups. This cross-sectional study conducted from 2020 to 2022 included 2,810 household participants with any lifetime mental health treatment. Weighted logistic regressions estimated the odds of reporting disruptions in access to mental health care or psychotropic prescriptions due to COVID. SMI was broadly defined as having an MDP diagnosis and serious functional impairment (GAF ≤50, a validated and widely used cutoff). Non-SMI groups were a mental diagnosis without serious impairment (MDPS diagnosis, GAF >50) and any lifetime treatment and no serious impairment (no MDPS diagnosis, GAF >50). The SMI and mental disorder without serious impairment groups had approximately 6.4- and 2.4-greater odds, respectively, of reporting inability to access mental health care and 4- and 3- greater odds, respectively, of having prescriptions delayed, relative to the group with any lifetime treatment. Among those with serious mental illness, having Medicare insurance increased the odds of reporting inability to access mental health care. Individuals with SMI were much more likely to experience treatment disruptions throughout the pandemic than non-SMI groups.

Mitochondrial DNA abundance in blood is associated with Alzheimer's disease- and dementia-risk.

The mitochondrial cascade hypothesis of Alzheimer's disease (AD) has been portrayed through molecular, cellular, and animal studies; however large epidemiological studies are lacking. This study aimed to explore the association of mitochondrial DNA copy number (mtDNAcn), a marker representative of mtDNA abundance per cell, with risk of incident all-cause dementia, AD, and vascular dementia diagnosis within 17 years and dementia-related blood biomarkers (P-tau181, GFAP, and NfL). Additionally, sex-stratified analyses were completed. In this German population-based cohort study (ESTHER), 9940 participants aged 50-75 years were enrolled by general practitioners and followed for 17 years. Participants were included in this study if information on dementia status and blood-based mtDNAcn measured via real-time polymerase chain reaction were available. In a nested case-control approach, a subsample of participants additionally had measurements of P-tau181, GFAP, and NfL in blood samples taken at baseline. Of 4913 participants eligible for analyses, 386 were diagnosed with incident all-cause dementia, including 130 AD and 143 vascular dementia cases, while 4527 participants remained without dementia diagnosis within 17 years. Participants with low mtDNAcn (lowest 10%) experienced 45% and 65% percent increased risk of incident all-cause dementia and AD after adjusting for age and sex (all-cause dementia: HRadj, 95%CI:1.45, 1.08-1.94; AD: HRadj, 95%CI: 1.65, 1.01-2.68). MtDNAcn was not associated to vascular dementia diagnosis and was more strongly associated with all-cause dementia among women. In the nested case-control study (n = 790), mtDNAcn was not significantly associated with the dementia-related blood biomarkers (P-tau181, GFAP, and NfL) levels in blood from baseline before dementia diagnosis. This study provides novel epidemiological evidence connecting mtDNA abundance, measured via mtDNAcn, to incident dementia and AD at the population-based level. Reduced mitochondrial abundance may play a role in pathogenesis, especially among women.

How pre-analytical conditions impact glucose measurement and (gestational) diabetes diagnosis: A real-world stability study and a call for harmonization

Background and aimsSince 2023, guidelines of the AACC/ADA recommend the use of citrate buffer-containing tubes as a first option for glucose measurement. This study aims to assess the pre-analytical stability of glucose under various conditions (room temperature (RT) or at 4 °C) and the potential real-world impact of introducing these tubes on (gestational) diabetes and IFG prevalence. Materials and Methods25 healthy volunteers were sampled to assess glucose stability across time, at 4 °C and at RT, before and following centrifugation. 701 patients undergoing fasting plasma glucose analysis and 109 women having OGTT were collected according to current procedures (NaFl K2C2O4 (NaFl) tubes) as well as with citrate-containing tubes (FC Mix). ResultsThe mean glucose concentration bias between FC Mix and NaFl tubes when centrifugation occurred within 5 min was 0.53 % and this difference raised slowly to reach 2.3 %, six-hours post-centrifugation. When centrifugation was delayed, a rapid decrease in glucose concentrations was observed for NaFl tubes (4.9 % at 30 min) and this trend was only partially reduced by placing samples at 4 °C (3.1 %). The decrease reached 10.8 % (RT) and 7.8 % (4 °C) at 2 h, before reaching a plateau. Samples collected on citrate remained stable during 24 h. In real-life conditions, the mean bias between FC Mix and NaFl tubes increased progressively over time and reached 8.59 % for samples centrifuged between two- and four-hours following sampling. Compared to widespread practices, the use of citrate-containing tubes increased IFG, DM and GDM prevalences by 84.0 %, 36.7 % and 150 %, respectively. ConclusionsGlucose concentrations rapidly decrease in NaFl tubes following collection and placing samples at 4 °C reduces only marginally the decay. Citrate-containing tubes offer a valuable solution for direct and long-lasting glucose stabilization but, before wider adoption, large epidemiologic studies should confirm or redefine current diabetes diagnostic thresholds.

Epidemiology of childhood interstitial lung disease in France: the RespiRare cohort

IntroductionInterstitial lung disease in children (chILD) are rare and mostly severe lung diseases. Very few epidemiological data are available in limited series of patients. The aim of this study was...