Presepsin is an early monitoring biomarker for predicting clinical outcome in patients with sepsis Fahmy T. Ali a , Mohamed A.M. Ali a, ⁎, Mostafa M. Elnakeeb b , Heba N.M. Bendary b a Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt b Microbiology and Immunology Department, El-Maadi Military Hospital, Cairo, Egypt abstract article info Article history: Received 9 May 2016 Received in revised form 23 June 2016 Accepted 24 June 2016 Available online 25 June 2016 Despite their undoubted helpfulness in diagnosing sepsis, increased blood C-reactive protein (CRP) and procalcitonin (PCT) levels have been described in many noninfectious conditions. Presepsin is a soluble fragment of the cluster of differentiation 14 involved in pathogen recognition by innate immunity. We aimed to investigate the diagnostic and prognostic performance of presepsin in comparison to PCT and CRP in patients presenting with systemic inflammatory response syndrome (SIRS) and suspected sepsis. Seventy-six subjects were enrolled in this study, including 51 patients with SIRS as well as 25 healthy subjects. Plasma presepsin, PCT and CRP levels were serially measured on admission and at days 1, 3, 7 and 15. Presepsin and PCT yielded similar diagnostic ac- curacy, whereas presepsin performed significantly better than CRP. Presepsin and PCT showed comparable per- formance for predicting 28-day mortality, and both biomarkers performed significantly better than CRP. In septic patients, presepsin revealed earlier concentration changes over time when compared to PCT and CRP. Presepsin and PCT could differentiate between septic and non-septic patients with comparable accuracy and both bio- markers showed similar performance for predicting 28-day mortality. Early changes in presepsin concentrations might reflect the appropriateness of the therapeutic modality and could be useful for making effective treatment decisions. © 2016 Elsevier B.V. All rights reserved. Keywords: Systemic inflammatory response syndrome Sepsis Presepsin Procalcitonin C-reactive protein 1. Introduction Sepsis, a major public health concern, is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Organ dysfunction is identified by an increase in the sequential [sepsis- related] organ failure assessment (SOFA) score of ≥ 2 points, which is as- sociated with an in-hospital mortality of N 10%. A new bedside clinical score termed quick SOFA (qSOFA) and incorporating altered mentation, systolic blood pressure of ≤ 100 mm Hg, and respiratory rate of ≥ 22/min, provides simple bedside criteria to identify adult patients with suspected infection who are likely to have poor outcomes. Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of ≥ 65 mm Hg and having a serum lactate level N 2 mmol/L (N 18 mg/dL) in the absence of hypovolemia, with hospital mortality rates of N 40% [1]. Although the true incidence of sepsis is unknown, conservative esti- mates indicate that sepsis is a leading cause of mortality and critical ill- ness worldwide [2]. Early diagnosis of sepsis prior to the onset of clinical deterioration is of particular interest because an early diagnosis increases chances for an early and specific treatment. Indeed, the time taken to initiate therapy seems to be crucial and represents the major determining factor for sur- viving sepsis. In clinical practice, sepsis can be difficult to distinguish from other non-infectious, systemic, inflammatory responses. Blood culture is frequently used as the “gold standard” diagnostic method for sepsis. However, it usually takes 3 to 7 days to obtain the results and frequently yields low positive results. Various biomarkers have been studied for diagnosing sepsis [3]. The state of the art in diagnosing and monitoring sepsis, severe sepsis and septic shock consists of the measurement of plasma C-reactive protein (CRP) and procalcitonin (PCT) at the onset and in the course of the disease [4]. CRP and PCT in combination are clinically significant in diagnosing and monitoring sep- sis [5]. Regardless of its usefulness in diagnosing sepsis, blood CRP levels Clinica Chimica Acta 460 (2016) 93–101 Abbreviations: APACHE II, acute physiology and chronic health evaluation II; AUC, area under the curve; CD14, cluster of differentiation 14; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; CVD, cardiovascular disease; EDTA, ethylenediaminetetraacetic acid; ICU, intensive care unit; LBPs, lipopolysaccharide- binding proteins; LPSs, lipopolysaccharides; NPV, Negative predictive value; PCT, procalcitonin; PPV, Positive predictive value; ROC, Receiver operating characteristic; SIRS, systemic inflammatory response syndrome; SOFA, sequential [sepsis-related] organ failure assessment; TLR4, toll-like receptor 4. ⁎ Corresponding author at: Department of Biochemistry, Faculty of Science, Ain Shams University, Abbassia, 11566 Cairo, Egypt. E-mail address: mohd_ali2@sci.asu.edu.eg (M.A.M. Ali). http://dx.doi.org/10.1016/j.cca.2016.06.030 0009-8981/© 2016 Elsevier B.V. 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