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The temporal kinetics of circulating angiopoietin levels in children with sepsis.

ABSTRACT: Capillary integrity continues to challenge critical care physicians worldwide when treating children with sepsis. Vascular growth factors, specifically angiopoietin-1 and angiopoietin-2, play opposing roles in capillary stabilization in patients with sepsis. We aim to determine whether pediatric patients with severe sepsis/shock have persistently high angiopoietin-2/1 ratios when compared with nonseptic PICU patients over a 7-day period.Prospective observational study. Patients were classified within 24 hours of admission into non-systemic inflammatory response syndrome, systemic inflammatory response syndrome/sepsis, or severe sepsis/shock. Plasma levels of angiopoietin-1 and angiopoietin-2 were measured via enzyme-linked immunosorbent assay. The angiopoietin-2/1 ratio was graphically plotted and determined whether patients fell into "constant" or "variable" patterns.Tertiary care center PICU.Critically ill pediatric patients with varying sepsis severity.None.Forty-five patients were enrolled (nine non-systemic inflammatory response syndrome, 19 systemic inflammatory response syndrome/sepsis, and 17 severe sepsis/shock). Gender, age, weight, comorbidities, and PICU length of stay were not significantly different between the groups. Admission pediatric risk stratification scores and net fluid ins/outs were significantly elevated in the severe sepsis/shock group when compared (all p < 0.05). Admission angiopoietin-2 levels and angiopoietin-2/1 ratios were significantly different in the severe sepsis/shock group when all groups were compared (both p < 0.05). Additionally, the latter were significantly elevated in the severe sepsis/shock group at multiple time points (all p ? 0.05) with the peak occurring on day 2 of illness. In a separate analysis, 32% of systemic inflammatory response syndrome/sepsis and 82% of severe sepsis/shock had variable angiopoietin-2/1 ratio patterns compared with none in the control group (p < 0.001).Pediatric patients with severe sepsis and septic shock possess significantly elevated angiopoietin-2/1 ratios during their first 3 days of illness, which peak at day 2 of illness. A subset of these patients demonstrated variable angiopoietin-2/1 ratio patterns.

SUBMITTER: Giuliano JS

PROVIDER: S-EPMC3947338 | biostudies-other | 2014 Jan

REPOSITORIES: biostudies-other

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The temporal kinetics of circulating angiopoietin levels in children with sepsis.

Giuliano John S JS Tran Kevin K Li Fang-Yong FY Shabanova Veronika V Tala Joana A JA Bhandari Vineet V

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 20140101 1

<h4>Objective</h4>Capillary integrity continues to challenge critical care physicians worldwide when treating children with sepsis. Vascular growth factors, specifically angiopoietin-1 and angiopoietin-2, play opposing roles in capillary stabilization in patients with sepsis. We aim to determine whether pediatric patients with severe sepsis/shock have persistently high angiopoietin-2/1 ratios when compared with nonseptic PICU patients over a 7-day period.<h4>Design</h4>Prospective observational ...[more]

PMID: 24141659

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Project description:PurposeThoracic aortic dissection (TAD) is characterized by an inflammatory response. Angiopoietin-like protein 8 (ANGPTL8) is a hormone involved in the regulation of lipid metabolism and inflammation. However, the relationship between ANGPTL8 and TAD remains unknown.MethodsThis case-control study included 78 TAD patients and 72 controls. The aortic diameter was evaluated by computed tomography and used to assess TAD severity. Circulating ANGPTL8 levels were measured by enzyme-linked immunosorbent assay. Associations of ANGPTL8 with TAD were determined by multivariate logistic regression.ResultsSerum ANGPTL8 levels were significantly higher in TAD patients compared with controls (562.50 ± 20.84 vs. 419.70 ± 22.65 pg/mL, respectively; P < 0.001). After adjusting for confounding factors, circulating ANGPTL8 levels were an independent risk factor for TAD (odds ratio = 1.587/100 pg ANGPTL8, 95% confidence interval [CI] = 1.121-2.247, P < 0.001) and positively associated with diameter (β = 1.081/100 pg ANGPTL8, 95% CI = 0.075-2.086, P = 0.035) and high-sensitivity C-reactive protein (hs-CRP) (β = 0.845/100 pg ANGPTL8, 95% CI = 0.020-1.480, P = 0.009). The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8, hs-CRP, and D-dimer was 0.927, and the specificity and sensitivity were 98.46% and 79.49%, respectively. ANGPTL8 was significantly increased in TAD tissue compared with controls. In vitro, ANGPTL8 was increased in angiotensin II (AngII)-treated macrophages and vascular smooth muscle cells (VSMCs), while ANGPTL8 siRNA-mediated knockdown decreased inflammatory factors in AngII-treated macrophages and decreased apoptosis in AngII-treated VSMCs.ConclusionANGPTL8 is associated with TAD occurrence and development, which may involve pro-inflammatory effects on macrophages. ANGPTL8 combined with D-dimer and hs-CRP might be a useful clinical predictor of TAD.Trial registrationChiCTR-COC-17010792 http://www.chictr.org.cn/showproj.aspx?proj=18288.

Project description:Background:The endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet. Methods:Serum levels of the main endocannabinoids, N-arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age = 13.1 ± 4.1, range 6-21; 79% boys) and 93 age- and gender-matched neurotypical children (age = 11.8 ± 4.3, range 5.5-21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2). Results:Children with ASD had lower levels (pmol/mL, mean ± SEM) of AEA (0.722 ± 0.045 vs. 1.252 ± 0.072, P < 0.0001, effect size 0.91), OEA (17.3 ± 0.80 vs. 27.8 ± 1.44, P < 0.0001, effect size 0.94), and PEA (4.93 ± 0.32 vs. 7.15 ± 0.37, P < 0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons. Conclusions:We found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid "tone" in the brain, as found in animal models of ASD.

Dataset Information

The temporal kinetics of circulating angiopoietin levels in children with sepsis.

Publications

The temporal kinetics of circulating angiopoietin levels in children with sepsis.

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