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Table 2 Sepsis biomarkers, except for C-reactive protein (CRP) and procalcitonin (PCT), that have been evaluated for their prognostic value in clinical studies with more than 300 subjects

From: Biomarkers of sepsis: time for a reappraisal

Biomarker [ref]

No. of patients

Sepsis definition

Study population

Main finding

Sensitivity/specificity (%)

AUC

Urokinase plasminogen activator receptor (uPAR) [19]

1914

International Sepsis Definitions Conference 2001

Critically ill patients and patients hospitalized in internal medicine ward

Levels ≥ 12 ng/mL predicted fatal outcome within 30 days

NR/> 70%

0.708

0.83 (when combined with APACHE II score)

Plasminogen activator inhibitor (PAI) 1 [20]

1790

ACCP 1992

Septic patients with disseminated intravascular coagulation (DIC)

Levels > 90 ng/mL predict fatal outcome within 30 days

NR (Kaplan-Meier survival functions)

NR

Interleukin (IL)-12 [21]

1444

Proven peritonitis or mediastinitis and systemic inflammation signs

Surgical patients

Pre-surgery IL-12-synthesizing capability was low in patients who had fatal sepsis after operation

NR

0.72

Thrombomodulin [22]

1103

ACCP 1992

Critically ill patients with sepsis

Levels > 14 ng/mL can predict circulatory failure or death—gray zone between 7 and 14 ng/mL

NR (logistic regression analysis)

NR

Syndecan-1 [22]

1103

ACCP 1992

Critically ill patients with sepsis

Levels > 240 ng/mL can predict circulatory failure or death—gray zone between 70 and 240 ng/mL

NR (logistic regression analysis)

NR

Fibrinogen [23]

1103

ACCP 1992

Critically ill patients with sepsis

Levels < 200 mg/dL related to increased risk of fatal outcome

NR (logistic regression analysis)

NR

Antithrombin activity [23]

1103

ACCP 1992

Critically ill patients with sepsis

Decrease in activity > 50% related to increased risk of fatal outcome

NR (logistic regression analysis)

NR

Brain natriuretic peptide (BNP) [24]

1000

International Sepsis Definition Conference 2001

ED patients

Levels > 113 pg/mL can predict fatal outcome within 28 days

86/55

0.73

Angiopoietin-2 [25]

931

NR

Critically ill patients with ARDS

Persistently increased levels related to fatal outcome within 90 days

NR (logistic regression analysis)

NR

Prothrombin time (PT) [26]

840

Suspected infection plus ≥ 3 signs of systematic inflammatory response

Critically ill patients with sepsis

Increase in PT time within first 7 days of sepsis was higher in patients who died within 28 days

NR (no test)

NR

Adrenomedullin [27]

837

International Sepsis Definitions Conference 2001

ED patients sepsis

Levels < 34.4 ng/L predicted fatal outcome within 30 days

86/61

0.77

0.81 (when combined with Mortality in Emergency Department Sepsis (MEDS) score)

Pro-adrenomedullin [28]

896

Clinical suspicion of infection

ED patients with sepsis

Levels ≥ 1.6 nmol/L predicted fatal outcome within 28 days

75/92

0.89

Heparin-binding protein [29]

759

Suspected infection and at least one clinical sign of systematic inflammatory response

ED patients with sepsis

Levels > 30 ng/mL predicted any organ dysfunction development within 72 h

78/76 (cross-tabulation analysis)

NR

D-dimer [30]

684

International Sepsis Definitions Conference 2001

Emergency department patients with sepsis

Higher in non-survivors than survivors within 28 days

NR

0.68

Troponin [31]

598

ACCP 1992

Critically ill patients

Levels > 0.06 ng/mL independent prognostic marker for 28-day mortality

NR (logistic regression analysis)

NR

YKL-40 [32]

502

ACCP 1992

Critically ill patients

Levels ≤ 505 ng/mL predicted survival in 90 days

53/76

0.64

CD64 [13]

468

International Sepsis Definition Conference 2001

Critically ill patients

Sustained elevated levels were related to non-appropriate antibiotic therapy

93/48

0.74

Cell-free DNA [33]

481

International Sepsis Definitions Conference 2001

ED patients

Levels > 1.6 μg/mL predicted short-term fatal outcome

70/76

0.77

  1. ARDS acute respiratory distress syndrome, NR not reported, IL interleukin, SOFA sequential organ failure assessment, AUC area under the receiver operating characteristic curve