BackgroundAlterations in extracellular vesicles (EVs), including exosomes and microparticles, contribute to cardiovascular disease. We hypothesized that obesity could favour enhanced release of EVs from adipose tissue, and thereby contribute to cardiovascular risk via obesity-induced metabolic complications. The objectives of this study were: 1) to investigate the relation between the quantity, distribution and (dys) function of adipose tissue and plasma concentrations of atherothrombotic EV-markers; 2) to determine the relation between these EV-markers and the prevalence of the metabolic syndrome; and 3) to assess the contribution of EV markers to the risk of incident type 2 diabetes.MethodsIn 1012 patients with clinically manifest vascular disease, subcutaneous and visceral fat thickness was measured ultrasonographically. Plasma EVs were isolated and levels of cystatin C, serpin G1, serpin F2 and CD14 were measured, as well as fasting metabolic parameters, hsCRP and adiponectin. The association between adiposity, EV-markers, and metabolic syndrome was tested by multivariable linear and logistic regression analyses. As sex influences body fat distribution, sex-stratified analyses between adipose tissue distribution and EV-markers were performed. The relation between EV-markers and type 2 diabetes was assessed with Cox regression analyses.ResultsHigher levels of hsCRP (β 5.59; 95% CI 3.00–8.18) and lower HDL-cholesterol levels (β-11.26; 95% CI −18.39 – -4.13) were related to increased EV-cystatin C levels, and EV-cystatin C levels were associated with a 57% higher odds of having the metabolic syndrome (OR 1.57; 95% CI 1.19–2.27). HDL-cholesterol levels were positively related to EV-CD14 levels (β 5.04; 95% CI 0.07–10.0), and EV-CD14 levels were associated with a relative risk reduction of 16% for development of type 2 diabetes (HR 0.84, 95% CI 0.75–0.94), during a median follow up of 6.5 years in which 42 patients developed type 2 diabetes.ConclusionsIn patients with clinically manifest vascular disease, EV-cystatin C levels were positively related, and EV-CD14 levels were negatively related to metabolic complications of obesity.

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The plasma concentration of adiponectin, an adipokine that has anti-inflammatory, anti-atherogenic and insulin sensitizing properties, is lower in obese subjects and could therefore be a target for therapy. In order to review and meta-analyse prospective cohort studies investigating adiponectin concentration and the risk for incident coronary heart disease (CHD) or stroke, a systematic search of MEDLINE, EMBASE and Cochrane databases was performed. Two independent reviewers selected prospective cohort studies investigating the relationship between adiponectin level and incident CHD or stroke using 'adiponectin' and 'cardiovascular disease' or 'stroke' and their synonyms, excluding patients with clinically manifest vascular disease. Random-effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI). Generalized least squares regression was used to assess dose-response relationships for adiponectin concentrations from studies that provided RRs solely based upon categorical data regression. In total, 16 prospective cohort studies, comprising 23,919 patients and 6,870 CHD or stroke outcome events, were included in the meta-analyses. An increase of 1 standard deviation in log-transformed adiponectin did not lower the risk for CHD (RR 0.97; 95% CI 0.86-1.09). A 10 μg mL(-1) increase in adiponectin conferred a RR of 0.91 (95% CI 0.80-1.03) for CHD and a RR 1.01 (95% CI 0.97-1.06) for stroke. In conclusion, plasma adiponectin is not related to the risk for incident CHD or stroke.

ObjectivesExtracellular vesicles (EVs) and their protein levels have been identified as a potential risk marker for the development of vascular disease. In the present study, we assessed whether levels of four previously identified EV proteins (cystatin C, serpin G1, serpin F2 and CD14) are associated with cerebral white matter lesions (WMLs) and brain atrophy.DesignCohort study; cross-sectional and prospective.SettingSingle centre, secondary and tertiary setting.Participants1309 patients with manifest vascular disease from the Second Manifestations of ARTerial disease-MR (SMART-MR) study, of which 994 had successful brain MRI and EV protein level measurements.OutcomesWML and brain parenchymal fraction (BPF), as parameter for brain atrophy, at baseline and follow-up.Statistical methodsThe relationship between EV protein levels and WML volume (expressed as log transformed percentage of intracranial volume) and BPF (expressed percentage of intracranial volume) on 1.5 T brain MRI was assessed with multivariable linear regression modelling. Subsequently, the relationship between baseline EV protein levels and progression of atrophy and WML was analysed in 534 patients, in whom a follow-up MRI was obtained after 4 years.ResultsHigher EV-cystatin C and EV-CD14 were significantly associated with larger WML volume (linear regression coefficient (95% CI) 0.10 log %/SD (0.04 to 0.17) and 0.14 log %/SD (0.07 to 0.20), respectively. Higher EV-CD14 was associated with more brain atrophy (–0.14%/SD; –0.27 to –0.01). Baseline EV-CD14 was significantly associated with increase of WMLs (0.11 log %/SD (0.04 to 0.18)). No relationship with EV-serpins was observed at baseline or at follow-up.ConclusionsEV proteins cystatin C and CD14 are related to cerebral WMLs and the progression of brain atrophy in patients with manifest vascular disease, potentially identifying EVs in the aetiology of structural brain changes.

BackgroundBlunt head trauma is a common presentation to emergency departments (EDs). Identifying skull fractures in children is important as they are known factor of risk for traumatic brain injury (TBI). Currently, CT is the reference standard for diagnosing skull fractures and TBIs in children. Identifying skull fractures with point-of-care ultrasound (POCUS) may help risk-stratify children for TBI following blunt trauma. The purpose of this study is to evaluate the sensitivity, specificity, positive predictive value and negative predictive value of POCUS in identifying skull fractures in children.MethodsA systematic search was performed on 17 July 2020 in Ovid Medline, Cochrane Library, Google Scholar, Web of Science and Embase. Prospective studies reporting skull fractures diagnosed with ultrasound in children younger than 18 years due to blunt head injury were included. Studies that did not confirm the fracture with CT were excluded. The quality of studies was evaluated using the QUADAS-2 tool. Data were extracted from the eligible studies to calculate outcomes such as sensitivity and specificity; when possible overall outcomes were calculated.ResultsSeven studies were included. All eligible studies included patients for whom the decision to perform a CT scan was made in advance. Overall, the included studies demonstrated low risk of bias or had minor concerns regarding risk of bias. The pooled data (n=925) demonstrated a sensitivity of 91%, specificity of 96%, positive predictive value of 88% and negative predictive value of 97%.ConclusionThe included studies demonstrate minor methodological limitations. Overall, the evidence suggests that POCUS is a valid option for diagnosing skull fractures in children visiting the ED after blunt head injury.