Daniela I. Gerova

Background: Pediatric sepsis is a life-threatening emergency and remains complex to diagnose promptly due to the absence of universally reliable biomarkers. C-reactive protein (CRP) and procalcitonin (PCT) are widely used but have limited effectiveness. We evaluated the diagnostic reliability of presepsin and soluble mannose receptor (sMR) and identified optimal biomarker combinations for distinguishing sepsis from non-infectious systemic inflammatory response syndrome (SIRS) in children. Methods: A total of 80 children were enrolled in this prospective study, including 53 consecutive admissions to the pediatric intensive care unit (PICU) (sepsis, n = 42; non-infectious SIRS, n = 11) and 27 healthy controls. The serum levels of new biomarkers presepsin and soluble mannose receptor (sMR) levels were quantified by ELISA methods and their diagnostic reliability (both individually and combined with CRP and PCT) was assessed using receiver operating characteristic (ROC) curves and multivariate logistic regression. Results: Significantly higher concentrations of all measured markers were found both in septic and other critically ill patients than in healthy controls (p < 0.05). No single biomarker reliably differentiated sepsis from non-infectious SIRS. The sMR + CRP + PCT combination demonstrated the highest diagnostic accuracy (AUC = 0.78, p = 0.0007), surpassing the CRP + PCT model (AUC = 0.71, p = 0.0087). Conclusions: The addition of sMR to the established markers CRP and PCT improves the diagnostic effectiveness in pediatric sepsis. Larger multicenter studies are warranted to confirm clinical utility.

Endothelial dysfunction is one of the major factors in the pathogenesis of metabolic syndrome (MetS), and its molecular mechanisms are not completely understood. The present study aimed to examine the connection between nuclear factor2-related factor2 (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), heme oxygenase 1 (HO-1), and plasma asymmetric dimethylarginine (ADMA) and malondialdehyde (MDA) in people with MetS. Participants in the study were as follows: with MetS (n = 30) and without MetS (Control) (n = 14). Expression of Nrf2, NF-kB, and HO-1 was measured in peripheral blood mononuclear cells (PBMCs). Plasma ADMA was determined using the ELISA technique and MDA via the thiobarbituric acid method. Our study showed that mRNA of NF-kB, Nrf2, and HO-1 levels in PBMCs in the MetS group were significantly higher than in the controls by 53%, 130%, and 185% (p < 0.05), respectively. Similarly, elevated levels of MDA (by 78%, p < 0.001) and ADMA (by 18.7%, p < 0.001) were established in the MetS group. Our findings show the importance of transcription factor Nrf2, playing an integral role in the protection of the endothelium, and of NF-κB, a transcription factor mediating the inflammatory response in MetS. Knowledge of complex cellular–molecular mechanisms would allow the use of biomarkers such as Nrf2, NF-kB, HO-1, and ADMA for the assessment of endothelial dysfunction in clinical practice.