Gabriele Savioli

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.

Sepsis is a complex and potentially life-threatening syndrome characterized by an abnormal immune response to an infection, which can lead to organ dysfunction, septic shock, and death. Early diagnosis is crucial to improving prognosis and reducing hospital management costs. This narrative review aims to summarize and evaluate the current literature on the role of monocyte distribution width (MDW) as a diagnostic biomarker for sepsis, highlighting its advantages, limitations, and potential clinical applications. MDW measures the volumetric distribution width of monocytes, reflecting monocytic anisocytosis, and is detected using advanced hematological analyzers. In 2019, it was approved by the FDA as a biomarker for sepsis due to its ability to identify systemic inflammatory response at an early stage. Thirty-one studies analyzed by us have shown that an increased MDW value is associated with a higher risk of sepsis and that its combination with clinical parameters (such as qSOFA) and other biomarkers (CRP, PCT) can enhance diagnostic sensitivity and risk stratification capacity. Despite its high sensitivity, MDW has lower specificity compared to more established biomarkers such as procalcitonin, thus requiring a multimodal integration for an accurate diagnosis. The use of MDW in emergency and intensive care settings represents an opportunity to improve early sepsis diagnosis and critical patient management, particularly when combined with other markers and clinical tools. However, further studies are needed to define a universal cut-off and confirm its validity in different clinical contexts and pathological scenarios.

Background: Chest pain is a prevalent reason for emergency room referrals and presents diagnostic challenges. The physician must carefully differentiate between cardiac and noncardiac causes, including various vascular and extracardiovascular conditions. However, it is crucial not to overlook serious conditions such as acute coronary syndrome (ACS). Diagnosis of acute myocardial infarction (AMI) and early discharge management become difficult when traditional clinical criteria, ECG, and troponin values are insufficient. Recently, the focus has shifted to a “multi-marker” approach to improve diagnostic accuracy and prognosis in patients with chest pain. Methods: This observational, prospective, single-center study involved, with informed consent, 360 patients presenting to the emergency department with typical chest pain and included a control group of 120 healthy subjects. In addition to routine examinations, including tests for hsTnI (Siemens TNIH kit), according to the 0–1 h algorithm, biochemical markers sST2 (tumorigenicity suppression-2) and suPAR (soluble urokinase plasminogen activator receptor) were also evaluated for each patient. A 12-month follow-up was conducted to monitor outcomes and adverse events. Results: We identified two groups of patients: a positive one (112 patients) with high levels of hsTnI, sST2 > 24.19 ng/mL, and suPAR > 2.9 ng/mL, diagnosed with ACS; and a negative one (136 patients) with low levels of hsTnI, suPAR < 2.9 ng/mL, and sST2 < 24.19 ng/mL. During the 12-month follow-up, no adverse events were observed in the negative group. In the intermediate group, patients with hsTnI between 6 ng/L and the ischemic limit, sST2 > 29.1 ng/mL and suPAR > 2.9 ng/mL, showed the highest probability of adverse events during follow-up, while those with sST2 < 24.19 ng/mL and suPAR < 2.9 ng/mL had a better outcome with no adverse events at 12 months. Conclusion: Our data suggest that sST2 and suPAR, together with hsTnI, may be useful in the prognosis of cardiovascular patients with ACS, providing additional information on endothelial damage. These biomarkers could guide the clinical decision on further diagnostic investigations. In addition, suPAR and sST2 emerge as promising for event prediction in patients with chest pain. Their integration into the standard approach in PS could facilitate more efficient patient management, allowing safe release or timely admission based on individual risk.