Biomarker combinations in predicting sepsis in hospitalized children with fever.

Sepsis is among the leading causes of critical illness worldwide. It includes physiologic, pathologic, and biochemical abnormalities, induced by infection. Novel methods for recognizing a dysregulated inflammatory response and predicting associated mortality must be developed. Our aim was to investigate biomarkers that characterize a pro-inflammatory and anti-inflammatory response in patients with fever by comparing predictive validity for sepsis. 165 patients with fever were enrolled in this study, 55 of them had sepsis according to pSOFA criteria. All patients had blood samples drawn at the time of inclusion and after 24 h. CRP, PCT and also IL-6, IL-8 and sFAS levels were significantly higher in patients with sepsis. The AUC of CRP to predict sepsis was 0.799, all the other biomarkers had AUC's lower than that. Cytokines, when used as a single marker, did not show a significant diagnostic performance We analyzed various models of biomarker combinations. CRP combined with sFAS showed increase in sensitivity in predicting sepsis (88% vs. 83%). The highest AUC was achieved, when CRP, IL-6, sFAS and sVCAM-1 markers were combined 0.830 (95% CI 0.762-0.884) with a sensitivity of 70% and specificity of 84%. vs. 0.799 for CRP alone.

Assessment of ADAMTS-13 Level in Hospitalized Children with Serious Bacterial Infections as a Possible Prognostic Marker.

Background and objectives: In children, acute infection is the most common cause of visits in the primary care or emergency department. In 2002, criteria for diagnostics of pediatric sepsis were published, and then revised in 2016 as "life-threatening organ dysfunction due to a dysregulated host response to infection". In the pathophysiology of sepsis endothelial dysfunction plays a very important role. Deficient proteolysis of von Willebrand factor, due to reduced ADAMTS-13 activity, results in disseminated platelet-rich thrombi in the microcirculation. ADAMTS-13 deficiency has been detected in systemic inflammation. The clinical relevance of ADAMTS-13 during sepsis is still unclear. We aimed to investigate the possible use of ADAMTS-13 as a prognostic marker in children with serious bacterial infection (SBI). Materials and Methods: Inclusion criteria were hospitalized children with SBI, aged from 1 month to 17 years. SBI was defined based on available clinical, imaging, and later also on microbiological data. Sepsis was diagnosed using criteria by The International Consensus Conference. In all the patients, the levels of ADAMTS-13 were measured at the time of inclusion. Results: Data from 71 patients were analyzed. A total of 47.9% (34) had sepsis, 21.1% (15) were admitted to the ICU, 8.5% (6) had mechanical ventilator support, and 4.2% (3) patients had a positive blood culture. The median level of ADAMTS-13 in this study population was 689.43 ng/mL. Patients with sepsis, patients admitted to the Intensive Care Unit, and patients in need of mechanical ventilator support had significantly lower levels of ADAMTS-13. None of the patients had ADAMTS-13 deficiency. In patients with SBI, the area under the curve (AUC) to predict sepsis was 0.67. A cut-off ADAMTS-13 level of ≤730.49 had 82% sensitivity and 60% specificity for sepsis in patients with SBI. Conclusions: ADATMS-13 levels were lower in patients with SBI and sepsis, but AUC and sensitivity were too low to accept it as a prognostic marker.

Inflammatory Cytokine and Chemokine Patterns in Paediatric Patients with Suspected Serious Bacterial Infection.

Background and objectives: In children, acute infection is the most common cause of visits to the emergency department. Although most of them are self-limiting, mortality due to severe bacterial infections (SBI) in developed countries is still high. When the risk of serious bacterial infection is too high to ignore, yet too low to justify admission and hospital observation, clinicians try to improve diagnostic accuracy by performing various laboratory tests. The aim of the study was to investigate whether an early inflammatory cytokine and chemokine panel can add information in diagnostics of SBI and assessment of efficacy of early therapies in hospitalized children with fever. Methods: This study included 51 children with febrile infections that were admitted to the emergency department (ED). Clinical examination and microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (1) patients with SBI (n = 21); (2) patients without SBI (n = 30). Inflammatory cytokine and chemokine panels were analyzed from the first routine blood samples at hospital admission and after 24 h. Results: Out of 12 cytokines and chemokines, only Eotaxin and granulocyte colony-stimulating factor (G-CSF) had statistically significant differences between groups at the time of inclusion. Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.679 for G-CSF. Conclusions: Analysis of inflammatory cytokine profiles may provide additional information in early diagnostics of SBI.

Association of ARID5B Genetic Variants with Risk of Childhood B Cell Precursor Acute Lymphoblastic Leukaemia in Latvia

Background: Acute lymphoblastic leukaemia (ALL) is the most common malignancy in childhood. Despite numerous investigations very little is still known about its aetiology. However, in one genome wide association study conducted to identify the possible genetic risk factors, two allelic variations rs10821936 and rs10994982 in the 3rd intron of the ARID5B gene were identified as possible ALL risk alleles. Association between ARID5B gene variants and ALL risk was also been confirmed for different ethnic groups. Materials and Methods: Eight genetic variants in the gene ARID5B were genotyped - rs10994982, rs7908445, rs7923074, rs10821936, rs10821937, rs7896246, rs10821938 and rs7089424 in 77 ALL patients in remission and in 122 age and gender matched controls; parental samples were also genotyped in 50 cases. Results: Six out of the eight (rs7908445, rs7923074, rs10821936, rs10821937, rs7896246 and rs7089424) analysed allelic variations were identified in the case-control analysis as statistically significant risk alleles for ALL development. In the family study and using hybrid analysis, all allelic variations were significantly associated with ALL. During the study, risk haplotype was identified rs10994982/rs7908445/rs7923074/ rs10821936/ rs10821937/rs7896246/rs10821938/rs7089424 ­ ATACCAAG ­ with a frequency in cases of 0.17 and in the control group at 0.29 (chi square = 6.69, p value = 0.009). In the family association study the same haplotype showed statistical significance (chi squared = 10.3, p value = 0.001). Conclusions: Results of the study replicate and extend previously published findings for ARID5B localized allelic variants, but do not explain the mechanism of action related to the pathogenesis of ALL.