Association between inflammation, glycocalyx biomarkers, and endothelial function in children with hypercholesterolemia.

INTRODUCTION: Hypercholesterolemia is a risk factor for premature arteriosclerosis. Inflammation and oxidative stress are thought to contribute to endothelial dysfunction preceding vasculopathy. We investigated the association between inflammation, glycocalyx biomarkers, endothelial function and vascular parameters in children with hypercholesterolemia. METHODS: In 22 patients (LDL-cholesterol > 130 mg/dl; median age [IQR]: 13 [2.3] years) and 22 controls (13 [2.5] years) tumor necrosis factor-alpha (TNF-α), oxidized cholesterol (oxLDL), and glycocalyx biomarkers (Syndecan-1, Hyaluronan) were measured using immunoassays. Endothelial function was assessed by peripheral arterial tonometry, sublingual glycocalyx and microcirculation by videomicroscopy and carotid intima media thickness by ultrasound. RESULTS: OxLDL was significantly higher in patients (78.9 [38.2] vs. 50.3 [16.6] U/l, p=0.002), whereas all other experimental parameters were comparable between groups. Multivariate analysis revealed a significant association of Syndecan-1 with TNF-α (ß=0.75, p<0.001) and with hypercholesterolemia (ß=0.31, p=0.030). The interaction term combining TNF-α and hypercholesterolemia showed a significant effect (p=0.034). Sex was an independent predictor of endothelial function. CONCLUSION: The combined effect of hypercholesterolemia and inflammation on glycocalyx perturbation and the impact of sex in the premature development of arteriosclerosis deserve further evaluation. Therapeutic approaches tackling low grade systemic inflammation-may offer potential to prevent or delay progression of CVD and cardiovascular complications. .

Monitoring of the microcirculation in children undergoing major abdominal and thoracic surgery: A pilot study.

BACKGROUND: Monitoring of the macrocirculation during surgery provides limited information on the quality of organ perfusion. OBJECTIVE: We investigated the feasibility of perioperative microcirculatory measurements in children. METHODS: Sublingual microvessels were visualized by handheld videomicroscopy in 11 children (19 mo - 10 yrs) undergoing surgery > 120 min at four time points: T0) after induction of anesthesia; T1) before end of anesthesia, T2) 6 h post surgery and T3) 24 h post surgery. RESULTS: Measurements were feasible in all children at T0 and T1. At T2 and T3, imaging was restricted to 6 and 4 infants, respectively, due to respiratory compromise and missing cooperation. The capillary density was reduced at T1 compared to T0 (8.1 mm/mm2 [4.0-17.0] vs. 10.6 mm/mm2 [5.1-19.3]; p = 0.01), and inversely related to norepinephrine dose (Pearson r = -0.65; p = 0.04). Microvascular flow and serum glycocalyx makers Syndecan-1 and Hyaluronan increased significantly from T0 to T1. CONCLUSION: Perioperative microcirculatory monitoring in children requires a high amount of personal and logistic resources still limiting its routine use. Major surgery is associated with microvascular alterations and glycocalyx perturbation. The possible consequences on patient outcome need further evaluation. Efforts should concentrate on the development of next generation devices designed to facilitate microcirculatory monitoring in children.

Associations between circulating obesity-related biomarkers and prognosis in female breast cancer survivors: a systematic review of observational data in women enrolled in lifestyle intervention trials.

Obesity plays an important role in the development and progression of breast cancer via various oncogenic pathways. However, the biological mechanisms underlying this relationship are not fully understood. Moreover, it is unclear whether obesity-related and further associated biomarkers could be suitable targets for lifestyle interventions. This systematic review was conducted to examine relationships between obesity-related blood parameters and prognosis for breast cancer survivors enrolled in lifestyle intervention studies. A systematic, computerized literature search was conducted from inception through August 26th, 2020 in PubMed, EMBASE, and CENTRAL. The focus was on observational data from randomized controlled lifestyle intervention trials investigating associations between selected baseline biomarkers, measured in remission, and breast cancer recurrence, breast cancer mortality and/or all-cause mortality. Four studies with data from 5234 women met the inclusion criteria.Studies herein provide moderate evidence that bioavailable or serum testosterone may be positively linked to breast cancer recurrence and inversely linked to disease-free survival. Limited evidence suggests no associations with circulating estradiol or insulin levels on prognosis outcomes, whereas HDL cholesterol was inversely associated with breast cancer recurrence. For some other biomarkers, such as growth factors, adipokines, and CRP, the evidence for associations with disease prognosis was too weak to draw conclusions.Overall, despite potential candidates, there is insufficient evidence to confirm or refute that obesity-related biomarkers and sex hormones have a prognostic value for breast cancer survival. More longitudinal studies in breast cancer survivors to examine the clinical utility of obesity-related biomarkers are needed.

Rationale and feasibility of transcatheter pulmonary valve implantation in small conduits with the Edwards Sapien valves.

BACKGROUND: Conduit dilatation above 110% and TPVI in conduits <16 mm is not recommended. However, if we want to reach normal values for RVOT diameters and diminish reintervention rates, pushing these boundaries is essential. METHODS: Analysis of subsequent patients who underwent TPVI with Edwards Sapien valves in conduits ≤16 mm between 2010 and 2020. RESULTS: In n = 33 cases median age was 13 years (5-20 y) and median weight 47 kg (15-91 kg). Preexisting RVOT grafts were n = 28 Contegra® conduits and n = 5 homografts (12 mm n = 15; 14 mm n = 11; 16 mm n = 7). Implanted were the Sapien (n = 8), Sapien XT (n = 10) and Sapien 3 valve (n = 15) with 20 mm (n = 4), 23 mm (n = 19), 26 mm (n = 9) and 29 mm (n = 1). Mean minimal RVOT diameter after TPVI was 22,7 ± 2,3 mm (18-30 mm) which is 150% of the mean minimal RVOT diameter before TPVI (15,1 ± 4,3 mm). Covered stents were used in n = 10 cases. Contained conduit rupture occurred in n = 7 cases (21%). Residual RVOT gradients of 5,7 ± 4,9 mmHg (0-18 mmHg) showed adequate RV unloading. CONCLUSION: TPVI could be performed successfully in all patients. Dilatation above 150% and a valve/conduit diameter ratio up to 2,4 were well tolerated. There was a considerable amount of conduit rupture but all were confined without further need for intervention or surgery.

Sedentarism, Physical Activity, Steps, and Neurotrophic Factors in Obese Children.

PURPOSE: This study aimed to examine the associations of sedentary time, physical activity (PA) and step-related behaviors with neurotrophic growth factors. METHODS: A total of 97 children with overweight/obesity age 8 to 11 yr participated in this study. Sedentary time, PA, and steps were measured by GT3X+ accelerometers in hip and nondominant wrist. Estimates of light, moderate, vigorous, and moderate-to-vigorous PA (MVPA) were obtained. Steps per daytime, peak 60-, 30-, and 1-min cadence were computed. The time accumulated (min·d) in different cadence bands of steps was also computed from hip accelerometer. Plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin growth factor-1 (IGF-1) were determined by the XMap technology (Luminex IS 100/200 system, Luminex Corporation, Austin, TX). RESULTS: Light PA, moderate PA, MVPA, and the peak 60-min cadence were positively related with BDNF concentrations (all P < 0.05), and only light PA to VEGF (P = 0.048). No association was observed for IGF-1 (P > 0.05). The associations of light PA with BDNF and VEGF disappeared (all P > 0.05) after performing analyses with nondominant wrist-placement data. However, moderate PA and MVPA remained significantly associated with BDNF (both P < 0.05). The time accumulated in cadence bands of 40 to 59 steps per day and 60 to 79 steps per day (i.e., walking at slow pace) was positively associated with plasma BDNF (all P < 0.05). CONCLUSIONS: In conclusion, PA is positively related to plasma BDNF, whereas no relationship was observed for VEGF or IGF-1. Higher amounts of time spent in slow walking cadence bands could increment BDNF levels. Exercise-based randomized controlled trials in children with overweight/obesity should be carried out to better understand the influence of PA behaviors on the neurotrophic factors.

Are we close to defining a metabolomic signature of human obesity? A systematic review of metabolomics studies.

INTRODUCTION: Obesity is a disorder characterized by a disproportionate increase in body weight in relation to height, mainly due to the accumulation of fat, and is considered a pandemic of the present century by many international health institutions. It is associated with several non-communicable chronic diseases, namely, metabolic syndrome, type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), and cancer. Metabolomics is a useful tool to evaluate changes in metabolites due to being overweight and obesity at the body fluid and cellular levels and to ascertain metabolic changes in metabolically unhealthy overweight and obese individuals (MUHO) compared to metabolically healthy individuals (MHO). OBJECTIVES: We aimed to conduct a systematic review (SR) of human studies focused on identifying metabolomic signatures in obese individuals and obesity-related metabolic alterations, such as inflammation or oxidative stress. METHODS: We reviewed the literature to identify studies investigating the metabolomics profile of human obesity and that were published up to May 7th, 2019 in SCOPUS and PubMed through an SR. The quality of reporting was evaluated using an adapted of QUADOMICS. RESULTS: Thirty-three articles were included and classified according to four types of approaches. (i) studying the metabolic signature of obesity, (ii) studying the differential responses of obese and non-obese subjects to dietary challenges (iii) studies that used metabolomics to predict weight loss and aimed to assess the effects of weight loss interventions on the metabolomics profiles of overweight or obese human subjects (iv) articles that studied the effects of specific dietary patterns or dietary compounds on obesity-related metabolic alterations in humans. CONCLUSION: The present SR provides state-of-the-art information about the use of metabolomics as an approach to understanding the dynamics of metabolic processes involved in human obesity and emphasizes metabolic signatures related to obesity phenotypes.

A Systematic Review of the Efficacy of Bioactive Compounds in Cardiovascular Disease: Phenolic Compounds.

The prevalence of cardiovascular diseases (CVD) is rising and is the prime cause of death in all developed countries. Bioactive compounds (BAC) can have a role in CVD prevention and treatment. The aim of this work was to examine the scientific evidence supporting phenolic BAC efficacy in CVD prevention and treatment by a systematic review. Databases utilized were Medline, LILACS and EMBASE, and all randomized controlled trials (RCTs) with prospective, parallel or crossover designs in humans in which the effects of BAC were compared with that of placebo/control were included. Vascular homeostasis, blood pressure, endothelial function, oxidative stress and inflammatory biomarkers were considered as primary outcomes. Cohort, ecological or case-control studies were not included. We selected 72 articles and verified their quality based on the Scottish Intercollegiate Guidelines Network, establishing diverse quality levels of scientific evidence according to two features: the design and bias risk of a study. Moreover, a grade of recommendation was included, depending on evidence strength of antecedents. Evidence shows that certain polyphenols, such as flavonols can be helpful in decreasing CVD risk factors. However, further rigorous evidence is necessary to support the BAC effect on CVD prevention and treatment.