Comprehensive Brain MRI Segmentation in High Risk Preterm Newborns

Most extremely preterm newborns exhibit cerebral atrophy/growth disturbances and white matter signal abnormalities on MRI at term-equivalent age. MRI brain volumes could serve as biomarkers for evaluating the effects of neonatal intensive care and predicting neurodevelopmental outcomes. This requires detailed, accurate, and reliable brain MRI segmentation methods. We describe our efforts to develop such methods in high risk newborns using a combination of manual and automated segmentation tools. After intensive efforts to accurately define structural boundaries, two trained raters independently performed manual segmentation of nine subcortical structures using axial T2-weighted MRI scans from 20 randomly selected extremely preterm infants. All scans were re-segmented by both raters to assess reliability. High intra-rater reliability was achieved, as assessed by repeatability and intra-class correlation coefficients (ICC range: 0.97 to 0.99) for all manually segmented regions. Inter-rater reliability was slightly lower (ICC range: 0.93 to 0.99). A semi-automated segmentation approach was developed that combined the parametric strengths of the Hidden Markov Random Field Expectation Maximization algorithm with non-parametric Parzen window classifier resulting in accurate white matter, gray matter, and CSF segmentation. Final manual correction of misclassification errors improved accuracy (similarity index range: 0.87 to 0.89) and facilitated objective quantification of white matter signal abnormalities. The semi-automated and manual methods were seamlessly integrated to generate full brain segmentation within two hours. This comprehensive approach can facilitate the evaluation of large cohorts to rigorously evaluate the utility of regional brain volumes as biomarkers of neonatal care and surrogate endpoints for neurodevelopmental outcomes

Reproductive Factors and Serum Uric Acid Levels in Females from the General Population: The KORA F4 Study

Hyperuricemia is associated with an increased risk of metabolic and cardiovascular diseases. There are pronounced sex differences in the levels of uric acid. It is largely unknown whether or not reproductive parameters which induce hormonal changes are responsible for this. We examined if there are associations between reproductive parameters and uric acid levels in a female population-based sample. In this cross-sectional analysis, data of 1530 women aged 32 to 81 years participating in the KORA F4 study, conducted between 2006 and 2008 in Southern Germany were used. Reproductive parameters were obtained by standardized interviews. Uric acid levels were tested by the uricase method. The whole study sample and stratified in pre- and postmenopausal women was analyzed. Menopausal status and earlier age at menarche were associated with higher serum uric acid levels (age-adjusted: p-values 0.003, <0.001 respectively; after multivariable adjustment, including BMI: p-values 0.002, 0.036). A history of oral contraceptive use showed an association with uric acid levels only after multivariable adjustment (p-value 0.009). Hot flushes showed an association with uric acid levels only after age-adjustment (p-value 0.038), but lost significance after adding other confounders. Other reproductive factors, including parity, current or ever use of hormone replacement therapy, current use of oral contraceptives, hysterectomy, bilateral oophorectomy, or depressive mood related to menopausal transition were not associated with uric acid levels. Postmenopausal status, earlier age at menarche and a history of oral contraceptive use were independently associated with higher serum uric acid concentrations in women from the general population. Further studies, especially longitudinal population-based studies investigating the relationship of female reproductive parameters with uric acid levels are necessary to confirm our findings

Clinical Features of Cardio-Renal Syndrome in a Cohort of Consecutive Patients Admitted to an Internal Medicine Ward

Introduction: Cardiorenal syndrome (CRS) is a disorder of the heart and kidney whereby interactions between the 2 organs can occur. We recorded the clinical features of CRS in patients consecutively admitted to an Internal Medicine ward. Patients and Methods: We retrospectively analyzed the anthropometric, history, clinical, biochemical and treatment characteristics in 438 out of 2,998 subjects (14.6%) admitted to our unit (from June 2007 to December 2009), diagnosed with CRS, according to Acute Dialysis Quality Initiative (ADQI) recommendations. Estimated glomerular filtration (eGFR) was calculated using several equations: MDRD (Modification of Diet in Renal Disease; 2 variations GFRMDRD186, GFRMDRD175), Mayo, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockroft-Gault. Results: Mean age was 80±8 years, 222 (50.6%) were males, 321 (73.2%) were smokers, 229 (52.2%) were diabetic, 207 (47.2%) had a history of acute myocardial infarction, 167 (38.1%) had angina, 135 (30.8%) were affected by cerebrovascular disease, 339 (77.3%) had peripheral arterial disease. CRS was type 1 in 211 cases (48.2%), type 2 in 96 (21.9%), type 3 in 88 (20.1%), type 4 in 29 (6.6%) and type 5 in 14 (3.2%). eGFR, calculated by different formulae, ranged between 31 and 36 ml/min/1.73 m2. GFR was lower in CRS type 3 than in the other types, and the values ranged between 24 and 27 ml/min/1.73 m2. Mean hospital length-of-stay (LOS) was 9.8±6.3 days. Diuretics were the most prescribed medication (78.7%); only 5 patients underwent haemodialysis. Conclusions: CRS is common, especially in the elderly. CRS Type 1 was the prevalent subset and patients had stage 3-4 renal insufficiency. Results obtained from the GFR equations were similar although the Mayo equation tended to overestimate the eGFR

Does lumbar spinal degeneration begin with the anterior structures? A study of the observed epidemiology in a community-based population

<p>Abstract</p> <p>Background-</p> <p>Prior studies that have concluded that disk degeneration uniformly precedes facet degeneration have been based on convenience samples of individuals with low back pain. We conducted a study to examine whether the view that spinal degeneration begins with the anterior spinal structures is supported by epidemiologic observations of degeneration in a community-based population.</p> <p>Methods-</p> <p>361 participants from the Framingham Heart Study were included in this study. The prevalences of anterior vertebral structure degeneration (disk height loss) and posterior vertebral structure degeneration (facet joint osteoarthritis) were characterized by CT imaging. The cohort was divided into the structural subgroups of participants with 1) no degeneration, 2) isolated anterior degeneration (without posterior degeneration), 3) combined anterior and posterior degeneration, and 4) isolated posterior degeneration (without anterior structure degeneration). We determined the prevalence of each degeneration pattern by age group < 45, 45-54, 55-64, ≥65. In multivariate analyses we examined the association between disk height loss and the response variable of facet joint osteoarthritis, while adjusting for age, sex, BMI, and smoking.</p> <p>Results-</p> <p>As the prevalence of the no degeneration and isolated anterior degeneration patterns decreased with increasing age group, the prevalence of the combined anterior/posterior degeneration pattern increased. 22% of individuals demonstrated isolated posterior degeneration, without an increase in prevalence by age group. Isolated posterior degeneration was most common at the L5-S1 and L4-L5 spinal levels. In multivariate analyses, disk height loss was independently associated with facet joint osteoarthritis, as were increased age (years), female sex, and increased BMI (kg/m²), but not smoking.</p> <p>Conclusions-</p> <p>The observed epidemiology of lumbar spinal degeneration in the community-based population is consistent with an ordered progression beginning in the anterior structures, for the majority of individuals. However, some individuals demonstrate atypical patterns of degeneration, beginning in the posterior joints. Increased age and BMI, and female sex may be related to the occurrence of isolated posterior degeneration in these individuals.</p

Paternal and Maternal History of Myocardial Infarction and Cardiovascular Diseases Incidence in a Dutch Cohort of Middle-Aged Persons

Background - A positive parental history of myocardial infarction (MI) is an independent risk factor for cardiovascular diseases (CVD). However, different definitions of parental history have been used. We evaluated the impact of parental gender and age of onset of MI on CVD incidence. Methods - Baseline data were collected between 1993 and 1997 in 10¿524 respondents aged 40–65 years. CVD events were obtained from the National Hospital Discharge Register and Statistics Netherlands. We used proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for CVD incidence and adjusted for lifestyle and biological risk factors. Results - At baseline, 36% had a parental history of MI. During 10-year follow-up, 914 CVD events occurred. The age and gender adjusted HR was 1.3 (95% CI 1.1–1.5) for those with a paternal MI, 1.5 (1.2–1.8) for those with a maternal MI and 1.6 (1.2–2.2) for those with both parents with an MI. With decreasing parental age of MI, HR increased from 1.2 (1.0–1.6) for age =70 years to 1.5 (1.2–1.8) for ag

Distribution, size, shape, growth potential and extent of abdominal aortic calcified deposits predict mortality in postmenopausal women

Background: Aortic calcification is a major risk factor for death from cardiovascular disease. We investigated the relationship between mortality and the composite markers of number, size, morphology and distribution of calcified plaques in the lumbar aorta.Methods: 308 postmenopausal women aged 48-76 were followed for 8.3 ± 0.3 years, with deaths related to cardiovascular disease, cancer, or other causes being recorded. From lumbar X-rays at baseline the number (NCD), size, morphology and distribution of aortic calcification lesions were scored and combined into one Morphological Atherosclerotic Calcification Distribution (MACD) index. The hazard ratio for mortality was calculated for the MACD and for three other commonly used predictors: the EU SCORE card, the Framingham Coronary Heart Disease Risk Score (Framingham score), and the gold standard Aortic Calcification Severity score (AC24) developed from the Framingham Heart Study cohorts.Results: All four scoring systems showed increasing age, smoking, and raised triglyceride levels were the main predictors of mortality after adjustment for all other metabolic and physical parameters. The SCORE card and the Framingham score resulted in a mortality hazard ratio increase per standard deviation (HR/SD) of 1.8 (1.51-2.13) and 2.6 (1.87-3.71), respectively. Of the morphological x-ray based measures, NCD revealed a HR/SD >2 adjusted for SCORE/Framingham. The MACD index scoring the distribution, size, morphology and number of lesions revealed the best predictive power for identification of patients at risk of mortality, with a hazard ratio of 15.6 (p < 0.001) for the 10% at greatest risk of death.Conclusions: This study shows that it is not just the extent of aortic calcification that predicts risk of mortality, but also the distribution, shape and size of calcified lesions. The MACD index may provide a more sensitive predictor of mortality from aortic calcification than the commonly used AC24 and SCORE/Framingham point card systems

Suboptimal blood pressure control in chronic kidney disease stage 3: baseline data from a cohort study in primary care

BACKGROUND: Poorly controlled hypertension is independently associated with mortality, cardiovascular risk and disease progression in chronic kidney disease (CKD). In the UK, CKD stage 3 is principally managed in primary care, including blood pressure (BP) management. Controlling BP is key to improving outcomes in CKD. This study aimed to investigate associations of BP control in people with CKD stage 3. METHODS: 1,741 patients with CKD 3 recruited from 32 general practices for the Renal Risk in Derby Study underwent medical history, clinical assessment and biochemistry testing. BP control was assessed by three standards: National Institute for Health and Clinical Excellence (NICE), National Kidney Foundation Kidney Disease Outcome Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Descriptive statistics were used to compare characteristics of people achieving and not achieving BP control. Univariate and multivariate logistic regression was used to identify factors associated with BP control. RESULTS: The prevalence of hypertension was 88%. Among people with hypertension, 829/1426 (58.1%) achieved NICE BP targets, 512/1426 (35.9%) KDOQI targets and 859/1426 (60.2%) KDIGO targets. Smaller proportions of people with diabetes and/or albuminuria achieved hypertension targets. 615/1426 (43.1%) were only taking one antihypertensive agent. On multivariable analysis, BP control (NICE and KDIGO) was negatively associated with age (NICE odds ratio (OR) 0.27; 95% confidence interval (95% CI) 0.17-0.43) 70–79 compared to <60), diabetes (OR 0.32; 95% CI 0.25-0.43)), and albuminuria (OR 0.56; 95% CI 0.42-0.74)). For the KDOQI target, there was also association with males (OR 0.76; 95% CI 0.60-0.96)) but not diabetes (target not diabetes specific). Older people were less likely to achieve systolic targets (NICE target OR 0.17 (95% CI 0.09,0.32) p < 0.001) and more likely to achieve diastolic targets (OR 2.35 (95% CI 1.11,4.96) p < 0.001) for people >80 compared to < 60). CONCLUSIONS: Suboptimal BP control was common in CKD patients with hypertension in this study, particularly those at highest risk of adverse outcomes due to diabetes and or albuminuria. This study suggests there is scope for improving BP control in people with CKD by using more antihypertensive agents in combination while considering issues of adherence and potential side effects

Genome-wide association study for renal traits in the Framingham Heart and Atherosclerosis Risk in Communities Studies

Background: The Framingham Heart Study (FHS) recently obtained initial results from the first genome-wide association scan for renal traits. The study of 70,987 single nucleotide polymorphisms (SNPs) in 1,010 FHS participants provides a list of SNPs showing the strongest associations with renal traits which need to be verified in independent study samples. Methods: Sixteen SNPs were selected for replication based on the most promising associations with chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), and serum cystatin C in FHS. These SNPs were genotyped in 15,747 participants of the Atherosclerosis in Communities (ARIC) Study and evaluated for association using multivariable adjusted regression analyses. Primary outcomes in ARIC were CKD and eGFR. Secondary prospective analyses were conducted for association with kidney disease progression using multivariable adjusted Cox proportional hazards regression. The definition of the outcomes, all covariates, and the use of an additive genetic model was consistent with the original analyses in FHS. Results: The intronic SNP rs6495446 in the gene MTHFS was significantly associated with CKD among white ARIC participants at visit 4: the odds ratio per each C allele was 1.24 (95% CI 1.09–1.41, p = 0.001). Borderline significant associations of rs6495446 were observed with CKD at study visit 1 (p = 0.024), eGFR at study visits 1 (p = 0.073) and 4 (lower mean eGFR per C allele by 0.6 ml/min/1.73 $\text{m}^2$, p = 0.043) and kidney disease progression (hazard ratio 1.13 per each C allele, 95% CI 1.00–1.26, p = 0.041). Another SNP, rs3779748 in EYA1, was significantly associated with CKD at ARIC visit 1 (odds ratio per each T allele 1.22, p = 0.01), but only with eGFR and cystatin C in FHS. Conclusion: This genome-wide association study provides unbiased information implicating MTHFS as a candidate gene for kidney disease. Our findings highlight the importance of replication to identify common SNPs associated with renal traits

Incidences of obesity and extreme obesity among US adults: findings from the 2009 Behavioral Risk Factor Surveillance System

<p>Abstract</p> <p>Background</p> <p>No recent national studies have provided incidence data for obesity, nor have they examined the association between incidence and selected risk factors. The purpose of this study is to examine the incidence of obesity (body mass index [BMI] ≥ 30.0 kg/m²) and extreme obesity (BMI ≥ 40.0 kg/m²) among US adults and to determine variations across socio-demographic characteristics and behavioral factors.</p> <p>Methods</p> <p>We used a weighted sample of 401,587 US adults from the 2009 Behavioral Risk Factor Surveillance System. Incidence calculations were based on respondent's height and current and previous weights. Logistic regression was used to examine associations between incidence and selected socio-demographic characteristics and behavioral factors.</p> <p>Results</p> <p>The overall crude incidences of obesity and extreme obesity in 2009 were 4% and 0.7% per year, respectively. In our multivariable analyses that controlled for baseline body mass index, the incidences of obesity and extreme obesity decreased significantly with increasing levels of education. Incidences were significantly higher among young adults, women, and adults who did not participate in any leisure-time physical activity. Incidence was lowest among non-Hispanic whites.</p> <p>Conclusions</p> <p>The high incidence of obesity underscores the importance of implementing effective policy and environmental strategies in the general population. Given the significant variations in incidence within the subgroups, public health officials should prioritize younger adults, women, minorities, and adults with lower education as the targets for these efforts.</p