Michal Fedora

Hyperphosphorylated neurofilament NF-H as a predictor of mortality after brain injury in children

Objective: The aim of the study was to determine whether serum levels of hyperphosphorylated neurofilament NF-H correlate with severity of brain injury in children. Methods: Forty-nine patients with traumatic brain injury (TBI) were enrolled into the prospective study. Venous blood samples were taken after admission and every 24 h for a maximum of 6 consecutive days. Serum NF-H concentrations were quantified by enzyme-linked immunosorbent assay. The outcome was evaluated 6 months after TBI using Glasgow Outcome Scale (GOS) in all patients. Results: The quantitative level of pNF-H remained significantly higher in patients with poor outcome (GOS = 1) in comparison with the other patients for the 2nd–4th day (p = 0.027; p = 0.019; p = 0.01). Levels of pNF-H were significantly higher in patients with diffuse axonal injury on initial CT scan (p = 0.004). Normal levels pNF-H in the paediatric population are unknown. Objective ROC analysis was identification of optimal cut-offs of proteins for prediction of GOS = 1. Conclusions: Although further, prospective study is warranted, these findings suggest that levels of hyperphosphorylated neurofilament NF-H correlate with mortality and may be useful as predictors of outcome in children with TBI.

Dynamics of glial fibrillary acidic protein during traumatic brain injury in children.

BACKGROUNDS Glial fibrillary acidic protein (GFAP) is a monomeric intermediate filament protein found in the astroglial cytoskeleton and is not found outside the central nervous system. It is a brain-specific protein that is released after traumatic brain injury (TBI). METHODS This prospective study enrolled 59 children who had TBI, as verified by computed tomography. Daily GFAP measurement began at admission (<12 hours after trauma) and continued for 6 days. Blood samples were analyzed for GFAP by enzyme-linked immunosorbent assay. Outcome was assessed using the Glasgow Outcome Scale (GOS) at 6 months after injury. RESULTS The median serum levels of GFAP at admission were 7.47 ng/mL in patients who died, compared with 0.12 ng/mL in patients who survived (p=0.002). GFAP levels were significantly higher in patients who had a poor outcome 6 months after injury than in those who were alive or had good outcome (p<0.001). The area under the receiver operating characteristic curve for GFAP was 0.833 for day 0 and 0.884 for day 2. CONCLUSIONS These results suggest that determination of serum levels of GFAP may add to the clinical assessment of the primary damage and prediction of outcome after severe TBI.

Modeling effect of the septic condition and trauma on C-reactive protein levels in children with sepsis: a retrospective study.

IntroductionSepsis is the main cause of morbidity and mortality in intensive care units and its early diagnosis is not straightforward. Many studies have evaluated the usefulness of various markers of infection, including C-reactive protein (CRP), which is the most accessible and widely used. CRP is of weak diagnostic value because of its low specificity; a better understanding of patterns of CRP levels associated with a particular form of infection may improve its usefulness as a sepsis marker. In the present article, we apply multilevel modeling techniques and mixed linear models to CRP-related data to assess the time course of CRP blood levels in association with clinical outcome in children with different septic conditions.MethodsWe performed a retrospective analysis of 99 patients with systemic inflammatory response syndrome, sepsis, or septic shock who were admitted to the Pediatric Critical Care Unit at the University Hospital, Brno. CRP blood levels were monitored for 10 days following the onset of the septic condition. The effect of different septic conditions and of the surgical or nonsurgical diagnosis on CRP blood levels was statistically analyzed using mixed linear models with a multilevel modeling approach.ResultsA significant effect of septic condition and diagnosis on the course of CRP levels was identified. In patients who did not progress to septic shock, CRP blood levels decreased rapidly after reaching peak values – in contrast to the values in patients with septic shock in whom CRP protein levels decreased slowly. Moreover, CRP levels in patients with a surgical diagnosis were higher than in patients with a nonsurgical condition. The magnitude of this additional elevation in surgical patients did not depend on the septic condition.ConclusionUnderstanding the pattern of change in levels of CRP associated with a particular condition may improve its diagnostic and prognostic value in children with sepsis.

Multiple gene-to-gene interactions in children with sepsis: a combination of five gene variants predicts outcome of life-threatening sepsis

IntroductionThe aim of the study was to identify the dependency structure of genetic variants that can influence the outcome for paediatric patients with sepsis.MethodsWe evaluated the role of single nucleotide polymorphisms for five genes: bactericidal permeability increasing protein (BPI; rs5743507), lipopolysaccharide-binding protein (LBP; rs2232618), toll-like receptor 4 (TLR4; rs4986790), heat shock protein 70 (HSP 70; rs2227956), and interleukin 6 (IL-6; rs1800795) in 598 children aged 0 to 19 years that were admitted to a paediatric intensive care unit with fever, systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, or multiple organ dysfunction syndrome. A control group of 529 healthy individuals was included. Multi-way contingency tables were constructed and statistically evaluated using log-linear models. Typical gene combinations were found for both study groups.ResultsDetailed analyses of the five studied gene profiles revealed significant differences in sepsis survival. Stratification into high-risk, intermediate-risk, and low-risk groups of paediatric patients can predict the severity of sepsis.ConclusionsAnalysis of single nucleotide polymorphisms for five genes can be used as a predictor of sepsis outcome in children.

Pancreatic stone protein - a possible biomarker of multiorgan failure and mortality in children sepsis.

Pancreatic stone protein (PSP)/regenerating protein 1-alpha (reg) is associated with inflammation, infection, and other disease-related stimuli. The prognostic value of PSP/reg among critically ill pediatric patients is unknown. The aim of this pilot study was to evaluate PSP/reg in children with systemic inflammatory response syndrome or sepsis. Prospective observational study, a five day evaluation period in children 0-19years old with systemic inflammatory response syndrome or septic state. Blood tests to determine levels of PSP/reg were obtained as long as the patient met the criteria for systemic inflammatory response syndrome or sepsis. PSP/reg levels did not differ between patients with systemic inflammatory response syndrome and septic condition until organ dysfunction signs were present. PSP/reg levels were significantly higher in patients with a PELOD score of 12 or higher or in those with MODS. Patients who died tended to have higher PSP/reg levels.

Trefoil factor 3 as a marker of intestinal cell damage during sepsis

Abstract Objective: Gastrointestinal dysfunction or gut failure frequently occurs in seriously ill patients and can be responsible for multi-organ failure. Trefoil factor 3 (TFF3) was characterized for its role in reconstitution of an epithelial barrier after mucosal injury in the jejunum. The aims of our study was an analysis of TFF3 levels dynamics in patients with sepsis and the correlation of TFF3 with severity of sepsis and mortality. Methods: Prospective observational study, a ten days evaluation period in children aged 0-19 years with systemic inflammatory response syndrome or septic state. Blood tests to determine levels of TFF3 were obtained as long as the patient met the criteria for systemic inflammatory response syndrome or sepsis. Results: Analysis of dynamics revealed steady levels of TFF3 during the 10 day period evaluated. TFF3 levels could not differentiate between various septic conditions in patients until a marked organ dysfunction developed. Higher Area Under Curve was noticed between control group and patients with sepsis. We could not make any strong conclusions based on mortality model. Conclusions: Levels of TFF3 are elevated in paediatric patients with sepsis through organ dysfunction.

Trefoil factor 2 expression and its significance as a predictor of severity of sepsis in children.

Intestinal injury significantly contributes to critical illness, sepsis and multiorgan failure. TFF2 (Trefoil Factor 2) is expressed and secreted preferentially by gastric mucous neck cells. TFF2 gene expression is promptly increased after gut injury, and its expression profile broadens to include the regenerative epithelia of virtually the entire gastrointestinal tract. The first objective of our study was an analysis of TFF2 levels dynamics in patients with Systemic Inflammatory Response Syndrome (SIRS) or septic condition during a 5-day period after admission. The second objective was to determine optimal cut-off value and quantify diagnostic characteristics of TFF2 between controls and patients with various septic states. The study included 57 children aged 0-19 years, with expected or proven SIRS and septic condition. The degree of severity was evaluated according to PELOD Score (Pediatric Logistic Organ Dysfunction). Blood samples to determine levels of TFF2 factor were taken during the time patient met the criteria of SIRS or sepsis. Control group samples to determine the serum levels of TFF2 were taken from patients undergoing elective surgery. Analysis of TFF2 levels dynamics revealed that TFF2 levels kept steady state during the 5-day period. Significantly higher levels of TFF2 were in patients with Multiple Organ Dysfunction Syndrome (MODS). The difference was noticed also in ROC analysis.

Trefoil Factor 1 as a marker of mucosal damage of the gastrointestinal tract in children with sepsis

Abstract Intestinal ischemia and reperfusion is a common pathway for many diseases in children. The objective of our study was an analysis of Trefoil factor 1 levels dynamics in patients with SIRS or septic condition during a 5-day period. Analysis of TFF1 levels dynamics revealed that TFF1 levels kept steady state during the 5-day period. TFF1 levels were similar in patients with SIRS, sepsis and severe sepsis. Significantly higher levels of TFF1 were in patients with septic shock and MODS.

1843 High Frequency Oscillation and Prone Position in the Experimental Model of Ards - Changes of Pressure Hemodynamic Parameters

Background and Aims High frequency oscillation (HFO) and prone position ventilation have their places in the treatment of an inhomogeneous pulmonary pathology of ARDS. Possible benefits of early used HFO include improved ventilation and oxygenation, reduced risk of ventilator induced lung injury development, lower plasmatic levels of pro-inflammatory cytokines, and therefore reduced mortality of ARDS patients. Prone position ventilation improves oxygenation, but without an impact on mortality or length of hospitalization. Aim of this study was to compare the pressure hemodynamic parameters in experimental models of ARDS ventilated in prone position or by HFO. Methods Total of 16 experimental piglets were randomised into 2 groups of 8 piglets: PP group ventilated conventionally in prone (18 hours) and supine (6 hours) position, HFO group ventilated 24 hours in supine position with HFO. Mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (mPAP) and pulmonary capillary wedged pressure (PCWP) were measured invasively, indexed systemic (SVRI) and pulmonary (PVRI) vascular resistances were calculated. Results MAP is lower in HFO group than in PP (3 hours: p=0,001; 6 hours: p=0,016; 9 hours: 0,007; 12 hours: 0,041). mPAP is higher in PP group (3 hours: p=0,001), as well as PVRI (1 hour: p=0,003) and SVRI (9 hours: 0,027). CVP and PCWP values show no differences between groups. Conclusions Early used HFO lowers PVRI in first hours of ARDS, PP has milder impact on systemic pressures - combination of both procedures can be beneficial. Grant Acknowledgment IGA MZčR NS 11100–4