Interleukin-6 Receptor Gene, Plasma C-Reactive Protein, and Diabetes Risk in Women

OBJECTIVE—Recent genome-wide association studies (GWASs) related common variants in the interleukin-6 (Il-6) receptor (IL6R) gene to plasma C-reactive protein (CRP) concentrations. Because IL6R variants were previously associated with IL-6 levels, we tested whether the associations with CRP were independent of IL-6 and the interactions between IL6R variants and CRP in relation to diabetes risk

Body fatness and sex steroid hormone concentrations in US men: results from NHANES III

Objective: Obesity is associated with a variety of chronic diseases, including cancer, which may partly be explained by its influence on sex steroid hormone concentrations. Whether different measures of obesity, i.e., body mass index (BMI), waist circumference, and percent body fat were differentially associated with circulating levels of sex steroid hormones was examined in 1,265 men, aged 20-90+years old, attending the morning examination session of the Third National Health and Nutrition Examination Survey (NHANES III). Materials and methods: Serum hormones were measured by immunoassay. Weight, height, and waist circumference were measured by trained staff. Percent body fat was estimated from bioelectrical impedance. Multivariate linear regression was used to estimate associations between body fatness measures and hormone levels. Results: Total and free testosterone and sex hormone binding globulin concentrations decreased, whereas total and free estradiol increased with increasing BMI, waist circumference, and percent body fat (all p trend<0.05). The magnitude of change in these hormones was similar for a one-quartile increase in each body fatness measure. Conclusion: Measured BMI, waist circumference, and percent body fat led to similar inferences about their association with hormone levels in me

Racial variation in vitamin D cord blood concentration in white and black male neonates

Aim: The aim of this study is to evaluate racial variation in umbilical cord blood concentration of vitamin D and to explore its correlation with markers of the insulin-like growth factor axis (IGFs) and sex steroid hormones in white and black male neonates. Methods: In 2004-2005, venous umbilical cord blood samples were collected from 75 black and 38 white male neonates, along with maternal and birth characteristics from two hospitals in Maryland, United States. 25-Hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured by radioimmunoassay and testosterone, estradiol, and sex hormone-binding globulin (SHBG) by immunoassay and IGF-1, IGF-2, and IGF-binding protein-3 by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed. Results: Mean 25(OH)D levels were lower in black than in white neonates (11.44; 95% CI 10.10-12.95ng/mL vs. 18.24; 95% CI 15.32-21.72ng/mL; p<0.0001). Black neonates were at higher risk of suboptimal vitamin D levels [25(OH)D<20ng/mL] than whites (84 vs. 63%). 25(OH)D concentrations varied by season in whites but not in blacks and were significantly inversely correlated with mother's parity (number of live births) in blacks but not in whites. Mean concentration of 1,25(OH)2D did not differ by race. 25(OH)D and 1,25(OH)2D did not correlate with IGFs, sex steroid hormones, and SHBG. Conclusions: Suboptimal vitamin D levels were prevalent especially in blacks and influenced by mother's parity and by season. The observed vitamin D differences between black and white neonates warrant further evaluation of the etiology of the disparity in chronic diseases in adulthoo

Genomic Newborn Screening for Pediatric Cancer Predisposition Syndromes: A Holistic Approach

As next-generation sequencing (NGS) has become more widely used, germline and rare genetic variations responsible for inherited illnesses, including cancer predisposition syndromes (CPSs) that account for up to 10% of childhood malignancies, have been found. The CPSs are a group of germline genetic disorders that have been identified as risk factors for pediatric cancer development. Excluding a few “classic” CPSs, there is no agreement regarding when and how to conduct germline genetic diagnostic studies in children with cancer due to the constant evolution of knowledge in NGS technologies. Various clinical screening tools have been suggested to aid in the identification of individuals who are at greater risk, using diverse strategies and with varied outcomes. We present here an overview of the primary clinical and molecular characteristics of various CPSs and summarize the existing clinical genomics data on the prevalence of CPSs in pediatric cancer patients. Additionally, we discuss several ethical issues, challenges, limitations, cost-effectiveness, and integration of genomic newborn screening for CPSs into a healthcare system. Furthermore, we assess the effectiveness of commonly utilized decision-support tools in identifying patients who may benefit from genetic counseling and/or direct genetic testing. This investigation highlights a tailored and systematic approach utilizing medical newborn screening tools such as the genome sequencing of high-risk newborns for CPSs, which could be a practical and cost-effective strategy in pediatric cancer care

The prognostic value of serum myoglobin in patients with non–ST-segment elevation acute coronary syndromes Results from the TIMI 11B and TACTICS-TIMI 18 studies

AbstractObjectivesThe goal of this study was to define the prognostic value of serum myoglobin in patients with non–ST-elevation acute coronary syndromes (ACS).BackgroundWhile myoglobin is useful for the early diagnosis of myocardial infarction (MI), its role in the early risk-stratification of patients with ACS has not been established.MethodsMyoglobin, creatine kinase-MB subfraction (CK-MB) and troponin I (cTnI) were measured at randomization in 616 patients from the Thrombolysis In Myocardial Ischemia/Infarction (TIMI) 11B study and 1,841 patients from the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Therapy-Thrombolysis In Myocardial Ischemia/Infarction (TACTICS-TIMI) 18 study. The risks for death and nonfatal MI through six months of follow-up were compared between patients with and without myoglobin elevation (>110 μg/l) in each study and in a dataset combining all eligible patients from both studies (n = 2,457).ResultsIn a multivariate model adjusting for baseline characteristics, ST changes and CK-MB and cTnI levels, an elevated baseline myoglobin was associated with increased six-month mortality in TIMI 11B (adjusted odds ratio [OR] 2.9 [95% confidence interval {CI} 1.2 to 7.1]), TACTICS-TIMI 18 (adjusted OR 3.0 [95% CI 1.5 to 5.9]) and the combined dataset (adjusted OR 3.0 [95% CI 1.8 to 5.0]). In contrast, there was no significant association between myoglobin elevation and nonfatal MI (combined dataset adjusted OR 1.55, 95% CI 0.9 to 2.6). In TACTICS-TIMI 18, patients with versus those without myoglobin elevation were more likely to have an occluded culprit artery (28% vs. 10%; p < 0.0001) and visible thrombus (49% vs. 34%; p = 0.006) and less likely to have TIMI 3 flow (53% vs. 68%; p = 0.009).ConclusionsA serum concentration of myoglobin above the MI detection threshold (>110 μg/l) is associated with an increased risk of six-month mortality, independent of baseline clinical characteristics, electrocardiographic changes and elevation in CK-MB and cTnI. These findings suggest that myoglobin may be a useful addition to cardiac biomarker panels for early risk-stratification in ACS

Growth differentiation factor 15 and cardiovascular risk: individual patient meta-analysis

AIMS: Levels of growth differentiation factor 15 (GDF-15), a cytokine secreted in response to cellular stress and inflammation, have been associated with multiple types of cardiovascular (CV) events. However, its comparative prognostic performance across different presentations of atherosclerotic cardiovascular disease (ASCVD) remains unknown. METHODS AND RESULTS: An individual patient meta-analysis was performed using data pooled from eight trials including 53 486 patients. Baseline GDF-15 concentration was analyzed as a continuous variable and using established cutpoints ( 1800 ng/L) to evaluate its prognostic performance for CV death/hospitalization for heart failure (HHF), major adverse cardiovascular events (MACE), and their components using Cox models adjusted for clinical variables and established CV biomarkers. Analyses were further stratified on ASCVD status: acute coronary syndrome (ACS), stabilized after recent ACS, and stable ASCVD. Overall, higher GDF-15 concentration was significantly and independently associated with an increased rate of CV death/HHF and MACE (P < 0.001 for each). However, while GDF-15 showed a robust and consistent independent association with CV death and HHF across all presentations of ASCVD, its prognostic association with future myocardial infarction (MI) and stroke only remained significant in patients stabilized after recent ACS or with stable ASCVD [hazard ratio (HR): 1.24, 95% confidence interval (CI): 1.17-1.31 and HR: 1.16, 95% CI: 1.05-1.28 for MI and stroke, respectively] and not in ACS (HR: 0.98, 95% CI: 0.90-1.06 and HR: 0.87, 95% CI: 0.39-1.92, respectively). CONCLUSION: Growth differentiation factor 15 consistently adds prognostic information for CV death and HHF across the spectrum of ASCVD. GDF-15 also adds prognostic information for MI and stroke beyond clinical risk factors and cardiac biomarkers but not in the setting of ACS

Incidence, risk factors, and feto-maternal outcomes of inappropriate birth weight for gestational age among singleton live births in Qatar : a population-based study

Background Abnormal fetal growth can be associated with factors during pregnancy and at postpartum. Objective In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes associated with small-for-gestational age (SGA) and large-for-gestational age (LGA) infants. Methods We performed a population-based retrospective study on 14,641 singleton live births registered in the PEARL-Peristat Study between April 2017 and March 2018 in Qatar. We estimated the incidence and examined the risk factors and outcomes using univariate and multivariate analysis. Results SGA and LGA incidence rates were 6.0% and 15.6%, respectively. In-hospital mortality among SGA and LGA infants was 2.5% and 0.3%, respectively, while for NICU admission or death in labor room and operation theatre was 28.9% and 14.9% respectively. Preterm babies were more likely to be born SGA (aRR, 2.31; 95% CI, 1.45–3.57) but male infants (aRR, 0.57; 95% CI, 0.4–0.81), those born to parous (aRR 0.66; 95% CI, 0.45–0.93), or overweight (aRR, 0.64; 95% CI, 0.42–0.97) mothers were less likely to be born SGA. On the other hand, males (aRR, 1.82; 95% CI, 1.49–2.19), infants born to parous mothers (aRR 2.16; 95% CI, 1.63–2.82), or to mothers with gestational diabetes mellitus (aRR 1.36; 95% CI, 1.11–1.66), or pre-gestational diabetes mellitus (aRR 2.58; 95% CI, 1.8–3.47) were significantly more likely to be LGA. SGA infants were at high risk of in-hospital mortality (aRR, 226.56; 95% CI, 3.47–318.22), neonatal intensive care unit admission or death in labor room or operation theatre (aRR, 2.14 (1.36–3.22). Conclusion Monitoring should be coordinated to alleviate the risks of inappropriate fetal growth and the associated adverse consequences.The PEARL-Peristat study was funded by Qatar National Research Fund (Grant no NPRP 6-238-3-059) and was sponsored by the Medical Research Centre, Hamad Medical Corporation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Incidence, Risk Factors, and Outcomes of Preterm and Early Term Births: A Population-Based Register Study

Preterm birth (PTB) and early term birth (ETB) are associated with high risks of perinatal mortality and morbidity. While extreme to very PTBs have been extensively studied, studies on infants born at later stages of pregnancy, particularly late PTBs and ETBs, are lacking. In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes of PTB and ETB births in Qatar. We examined 15,865 singleton live births using 12-month retrospective registry data from the PEARL-Peristat Study. PTB and ETB incidence rates were 8.8% and 33.7%, respectively. PTB and ETB in-hospital mortality rates were 16.9% and 0.2%, respectively. Advanced maternal age, pre-gestational diabetes mellitus (PGDM), assisted pregnancies, and preterm history independently predicted both PTB and ETB, whereas chromosomal and congenital abnormalities were found to be independent predictors of PTB but not ETB. All groups of PTB and ETB were significantly associated with low birth weight (LBW), large for gestational age (LGA) births, caesarean delivery, and neonatal intensive care unit (NICU)/or death of neonate in labor room (LR)/operation theatre (OT). On the other hand, all or some groups of PTB were significantly associated with small for gestational age (SGA) births, Apgar <7 at 1 and 5 minutes and in-hospital mortality. The findings of this study may serve as a basis for taking better clinical decisions with accurate assessment of risk factors, complications, and predictions of PTB and ETB.The study was approved by the Hamad Medical Corporation Institutional Review Board, with a waiver of consent. It was funded by Qatar National Research Fund (Grant no NPRP 6-238-3-059) and was sponsored by the Medical Research Centre, Hamad Medical Corporation. The authors want to thank their respective institutions for their continued support. The publication of this article is funded by the Qatar National Library, Doha, Qatar