Background and Objectives: Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Early recognition is crucial to improve outcomes, but conventional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) show limited diagnostic accuracy. Materials and Methods: We performed a narrative review of the literature on sepsis biomarkers, with a focus on their biological role, diagnostic performance, clinical applicability, and limitations. Particular attention was given to presepsin (P-SEP) and monocyte distribution width (MDW), which have recently gained relevance. Results: Several novel biomarkers—including lipopolysaccharide-binding protein (LBP), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), mid-regional pro-adrenomedullin (MR-proADM), neutrophil gelatinase-associated lipocalin (NGAL), Proenkephalin (PENK), and circulating microRNAs—have been studied, though most remain investigational. Among them, P-SEP shows rapid kinetics and correlation with disease severity, while MDW, derived from routine complete blood count, offers encouraging sensitivity and cost-effectiveness in emergency settings. Both biomarkers appear practical and potentially valuable for early sepsis detection. Conclusions: P-SEP and MDW emerge as the most promising biomarkers for timely sepsis recognition and risk stratification. Further validation and standardization are required to include them into routine clinical practice.

Objectives: The soluble urokinase plasminogen activator receptor (suPAR) is a well-established biomarker of immune activation, reflecting the severity of systemic inflammation. Recent evidence showed increasing interest in suPAR as a prognostic marker, with elevated levels consistently associated with greater disease severity and mortality, in different clinical settings. Methods: In this retrospective study, suPAR levels were assayed at Emergency Department admission in patients who received a diagnosis of sepsis or systemic infection during their initial clinical workup, using an automated turbidimetric assay (suPARnostic ViroGates kit on Atellica CH analyzer Siemens). The primary endpoint of this study was to evaluate the association between baseline suPAR levels and mortality, while the secondary endpoint aimed to explore their potential as indicators of clinical severity and predictors of patient outcomes. Results: suPAR levels were elevated in all patients (median 6.99 μg/L) consistent with the severity of their clinical condition. A threshold of 10.2 μg/L was strongly associated with mortality, while a cut-off of 5.96 μg/L identified patients with severe disease and prolonged hospital stays. Conclusions: suPAR seems to be a reliable, rapid, and clinically useful prognostic biomarker in the Emergency Department in patients with sepsis or systemic infections. Its early measurement by turbidimetric immunoassay in automation can support risk stratification, improve triage decisions, and enhance the management of these patients.

Background: Vitamin B12 is an essential water-soluble vitamin required for critical biological processes such as DNA synthesis, erythrocyte maturation, and maintenance of nervous system integrity. Deficiency of vitamin B12 can lead to serious clinical outcomes, including megaloblastic anemia and potentially irreversible neurological damage. Conversely, hypercobalaminemia may be associated with severe disorders, including solid neoplasms and hematological malignancies, or may result from inappropriate supplementation or immunoglobulin–B12 macrocomplexes. Current guidelines recommend total serum vitamin B12 and holotranscobalamin (holoTC) as first-line biomarkers for assessing cobalamin status. Content: Despite guideline recommendations, total serum vitamin B12 remains the most widely used test in routine clinical practice. However, holoTC represents the biologically active fraction of vitamin B12 available for receptor-mediated cellular uptake and may therefore provide a more reliable assessment of cobalamin status, particularly in specific clinical settings. Compared with total vitamin B12 measurement, holoTC is evaluated using a more limited number of analytical methods, and most commercially available assays are traceable to the WHO reference standard, improving interassay harmonization. This review examines the role of vitamin B12 and holoTC, focusing on analytical challenges and clinical interpretation. Summary: The available evidence suggests that holoTC may offer important advantages over total serum vitamin B12 in the evaluation of B12 status. Its biological relevance and improved analytical harmonization support its potential utility as a more reliable biomarker in selected clinical contexts.