COVID-19 in Pediatric Intensive Care Units in Poland, PAPITCO-19 Study (Polish Analysis of PICU Trends during COVID-19).

BACKGROUND: Children suffering from COVID-19 constitute about 10% of the entire population infected with the virus. In most of them, we observe asymptomatic or mild courses; however, about 1% of affected children require a stay in a paediatric intensive care unit (PICU) due to the course of the disease becoming severely life-threatening. The risk of respiratory failure, as with adults, is associated with the coexistence of concomitant diseases. The aim of our study was to analyse patients admitted to PICUs due to the severe course of their SARS-CoV-2 infection. We studied epidemiological and laboratory parameters, as well as the endpoint (survival or death). METHODS: A retrospective multi-centre study, the analysis covered all children with a confirmed diagnosis of SARS-CoV-2 virus infection who were admitted to PICUs in the period from November 2020 to August 2021. We studied epidemiological and laboratory parameters, as well as the endpoint (survival or death). RESULTS: The study analysed 45 patients (0.075% of all children hospitalised in Poland due to COVID-19 at that time). Mortality calculated in the entire study group was 40% (n = 18). Statistically significant differences between the compared groups (survived and died) concerned the parameters of the respiratory system. Lung Injury Score and the Paediatric Sequential Organ Failure Assessment were used. A significant correlation between disease severity and the patient's prognosis was shown by the liver function parameter AST (p = 0.028). During the analysis of patients requiring mechanical ventilation and assuming survival as the primary outcome, a significantly higher oxygen index on the first day of hospitalisation, lower pSOFA scores and lower AST levels (p: 0.007; 0.043; 0.020; 0.005; 0.039, respectively) were found. CONCLUSIONS: As with adults, children with comorbidities are most frequently at risk of severe SARS-CoV-2 infection. Increasing symptoms of respiratory failure, the need for mechanical ventilation and persistently high values of aspartate aminotransferase are indicators of poor prognosis.

Selected Factors of Vascular Changes: The Potential Pathological Processes Underlying Primary Headaches in Children.

BACKGROUND: The prevalence, social consequences and complicated pathogenesis make headaches in children a significant clinical issue. Studies in adults suggest that primary headaches could be the first sign of atherosclerosis and platelet aggregation. AIM: To analyze the blood levels of selected biomarkers of vascular changes potentially associated with a higher risk of atherosclerosis in children with primary headaches. METHODS: The medical family history, brain-derived neurotrophic factor (BDNF), soluble CD40 ligands (sCD40L), endothelial plasminogen activator inhibitor (PAI I), vascular endothelial growth factor (VEGF) and intima-media thickness (IMT) measurements were performed in the 83 children (52 with primary headaches, 31 controls). Selected factors were compared with basic laboratory parameters that are potentially related to atherosclerosis: C-reactive protein (CRP) and lipid concentration. RESULTS: There were no significant differences in biomarkers of vascular changes in the study group and controls in general. In the study group, boys had a higher BDNF level than girls (p = 0.046). Normal-weight migraine patients had significantly higher PAI-I levels than controls (p = 0.034). A positive correlation between PAI-1 and triglycerides (TG) was observed. IMT did not differ between children with primary headaches and controls; however, IMT showed a positive correlation with BMI z-score and TG. Children with headaches had, more often, a positive family history of cardiovascular disease (p = 0.049). CONCLUSIONS: There were no clear clinical changes indicative of atherosclerosis in the study population. However, some trends are visible. Primary headaches are more often related to a family history of cardiovascular diseases. IMT is associated with TG levels and BMI z-score. The measured biomarkers of vascular changes show mutual relations.

Levels of Lipid Parameters in Children with Arterial Ischemic Stroke and Headache: Case-Control Study and Meta-Analysis.

Background: Abnormalities in levels of lipid parameters are one of the main causes of cardiovascular and cerebrovascular disease in adults. There are limited data on the role of disturbances of lipid metabolism in the etiopathogenesis of arterial ischemic stroke (AIS) in children and the results provided are ambiguous. The aim of the study was to compare the levels of lipid parameters (total cholesterol [TC], triglycerides [TG], high-density lipoprotein [HDL] and low-density lipoprotein [LDL]) between children with AIS, children with headache and healthy children. In addition, we performed meta-analysis of available data on lipid parameters in young patients with AIS. Methods: We retrospectively analyzed 218 children hospitalized between 2002 and 2018 in the Upper-Silesian Child's Health Center (n = 82 children with AIS, n = 45 children with headache, n = 91 healthy children) with available data on lipid levels, i.e., TC, TG, and HDL. The levels of LDL, non-HDL cholesterol, and a very-low density lipoprotein (VLDL) were calculated. The ratios of TC/HDL, TG/HDL and LDL/HDL were also assessed. Data between cases and controls were analyzed using STATISTICA 13.0 whereas meta-analysis was performed with RevMan version 5.4 software. Results: Children with headache were significantly older than children with AIS (p = 0.001). Ten percent of children with AIS had posterior stroke. The mean TC level was significantly higher in the AIS children than in controls or in children with headache. Mean TG and VLDL levels were significantly different between all groups (p < 0.001 each). The hypertriglyceridemia was more prevalent in AIS children than in children with headache (39% vs. 13%, OR = 4.16 95% CI 1.58-10.94, p = 0.004). Similarly, the frequency of dyslipidemia was higher in children with AIS compared to children with headache (38% vs. 22%, OR = 2.13 95% CI 0.93-4.89, p = 0.078). The meta-analysis was conducted based on data from 4 studies (3 studies published previously plus the results we obtained in the present case-control analysis) with total number of 236 young patients with AIS and 272 healthy controls. Significant Standard Mean Difference (SMD) was found in triglycerides level between young patients with AIS and controls (0.78 95%CI 0.30-1.26 p = 0.002). Conclusions: Lipid abnormalities, especially levels of triglycerides, seem to be of particular importance in children with AIS, as confirmed in meta-analysis. The results of the present study may be a significant contribution to the further research on the role of lipid metabolism disorders in the development of childhood stroke.

Headache in Children: Selected Factors of Vascular Changes Involved in Underlying Processes of Idiopathic Headaches.

Headaches are common complaints in children. The International Classification of Headache Disorders, 3rd edition (beta version), defines more than 280 types of headaches. Primary headaches refer to independent conditions that cause pain and include migraine, tension-type headaches (TTH), and trigeminal autonomic cephalalgias (TACs). Several agents are involved in the pathogenesis of headaches. The factors associated with predisposition to atherosclerosis seem to be particularly important from the clinical point of view. The influence of obesity on the incidence of headaches has been well established. Moreover, idiopathic headaches, especially migraine, are thought to be one of the first signs of disorders in lipid metabolism and atherosclerosis. The risk of migraine increases with increasing obesity in children. Another factor that seems to be involved in both obesity and headaches is the adiponectin level. Recent data also suggest new potential risk factors for atherosclerosis and platelet aggregation such as brain-derived neurotrophic factor (BDNF), sCD40L (soluble CD40 ligand), serpin E1/PAI I (endothelial plasminogen activator inhibitor), and vascular endothelial growth factor (VEGF). However, their role is controversial because the results of clinical studies are often inconsistent. This review presents the current knowledge on the potential markers of atherosclerosis and platelet aggregation, which may be associated with primary headaches.

Lipid levels and selected biomarkers of vascular changes in children with idiopathic headaches - a preliminary report.

INTRODUCTION: Elevated lipid concentrations were observed in adults with headaches. However, studies in children are scarce. Recent data suggest new potential risk factors for atherosclerosis, which may be associated with headaches. The aim of the study was to analyse the blood levels of lipids and new markers of atherosclerosis in children with idiopathic headaches. MATERIAL AND METHODS: The study population comprised 65 children (39 with idiopathic headaches and 26 healthy children). Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol and triacylglycerol (TG) levels were measured in every patient. Brain-derived neurotrophic factor (BDNF), soluble CD40 ligand (sCD40L), endothelial plasminogen activator inhibitor (serpin E1/PAI I) and vascular endothelial growth factor (VEGF) blood level measurements were performed in 34 children. RESULTS: Children with headaches had higher BMI z-scores (0.2 vs. -1.14; p = 0.006). TC level was lower in patients with headaches (121.04 mg/dl vs. 146.87 mg/dl, p = 0.019). No differences in concentrations of TG, HDL or LDL were found. BDNF was significantly higher in the studied group (171.57 pg/ml vs. 64.04 pg/ml, p = 0.012). The VEGF was higher in boys with headaches than in girls (368.27 pg/ml vs. 142.86 pg/ml, p = 0.011). There were no differences in levels of VEGF, sCD40L or PAI-1 between groups. CONCLUSIONS: Children with headaches have lower total cholesterol and higher BDNF levels than controls. No significant difference in levels of triacylglycerols, HDL cholesterol, LDL cholesterol, VEGF, sCD40L or PAI-1 was found between children with headaches and controls.

Association Between the 20210G>A Prothrombin Gene Polymorphism and Arterial Ischemic Stroke in Children and Young Adults-Two Meta-analyses of 3586 Cases and 6440 Control Subjects in Total.

BACKGROUND: Previous data have shown that the 20210G>A polymorphism of the Factor II gene is related to an increased prothrombin level, which may in turn lead to a procoagulant state. The heterogeneous and multifactorial character of arterial ischemic stroke often results in contradictory reports describing the association between the 20210G>A polymorphism and arterial ischemic stroke in different populations. We performed a meta-analysis of available data addressing the relation between the FII 20210G>A polymorphism and arterial ischemic stroke, both in young adults and children. METHODS: We searched PubMed using appropriate keywords. The inclusion criteria for the study were as follows: case-control study, study population consisting of children, study population consisting of young adults, arterial ischemic stroke confirmed by magnetic resonance imaging or computed tomography, and English language. The exclusion criteria included lack of genotype or allele frequencies, study design other than a case-control study, outcome definition other than arterial ischemic stroke, and previously overlapped patient groups. Finally, 30 case-control studies (14 in children and 16 in young adults) were included. Statistical analyses were conducted using R software. Heterogeneity between the studies was evaluated using the Dersimonian and Laird's Q test. In the case of significant between-studies heterogeneity, the pooled odds ratio was estimated with a random-effects model, otherwise a fixed-effects model was used. RESULTS: The pooled analysis showed that carriers of 20210A allele (GA+AA genotypes) of the prothrombin gene are more common in arterial ischemic stroke patients, both in children and young adults, than in control subjects (P = 0.006; odds ratio, 1.83; 95% confidence interval, 1.19 to 2.80 and P = 0.001; odds ratio, 1.69; 95% confidence interval, 1.25 to 2.28, respectively). CONCLUSIONS: The results of the present meta-analysis have proven that the FII 20210G>A polymorphism is associated with arterial ischemic stroke in both pediatric and young adult patients.

The role of genetic risk factors in arterial ischemic stroke in pediatric and adult patients: a critical review.

The incidence of arterial ischemic stroke (AIS) in childhood (about 2-13 per 100,000 children a year) is much lower than the incidence in the adult population. Still, adverse outcomes of acute brain ischemia in childhood include death (10% of AIS children), neurological sequel, epileptic seizures (over 50%) and recurrence (over 20%). The knowledge of childhood stroke etiopathogenesis is still insufficient and the diagnostic and therapeutic procedures--controversial. Risk factors for childhood stroke differ from those observed in adults due to differing exposure to external risk factors. The most frequently reported risk factors for pediatric ischemic stroke are cerebral arteriopathies and vascular malformations, cardiac diseases, infections, traumas and metabolic diseases. Because of its multifactorial etiology pediatric AIS probably has a multigenic inheritance pattern. The genetic susceptibility to AIS may be determined by specific polymorphic variants encoding markers of hemostasis regulation and they are some of the most important targets in searching for genetic determinants in pediatric AIS. The authors have reviewed the recent literature on risk factors of childhood ischemic stroke with the focus on genetic factors like polymorphisms of genes encoding coagulation factors II, V, VII and XIII, MTHFR, fibrinogen beta, and compared them with the results performed in adult patients.