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Table 9 Other biomarkers identified in the literature search (with some selected references)

From: Sepsis biomarkers: a review

Sepsis marker

Evaluated in experimental studies

Evaluated in clinical studies

Evaluated as a prognostic factor

Comment

Alpha2 macroglobulin [196, 208]

√

   

Albumin [209]

√

   

Anti-endotoxin core antibodies (EndoCab) [210]

 

A

√

Distinguished between survivors and non-survivors at 28 days

Apolipoprotein CI [211–213]

 

C

√

Distinguished between survivors and non-survivors at 28 days

Bcl-2 [214]

 

A

√

Distinguished between survivors and non-survivors at 28 days

Beta-thromboglobulin [215]

 

B

√

Predicted response to therapy

Caspase-1 [216]

 

A

 

Increased in septic shock compared with healthy controls

Ceramide [217]

 

B

√**

Predicted development of MOF

Cholesterol [218]

 

C

√

Distinguished between survivors and non-survivors at 28 days in patients with severe sepsis

Complement (C3, C4, C5a levels) [219, 220]

 

B(m)

√

Distinguished between survivors and non-survivors at 28 days

Terminal complement complex [221]

√

   

Dendritic cell [222, 223]

√

B

√

Distinguished between survivors and non-survivors at 28 days, correlated with SOFA score

Dipeptidylpeptidase [224]

 

B

 

Decreased in sepsis compared with healthy controls

Diiodotyrosine (DIT) [225]

 

C

√

Increased in sepsis compared with non-septic critically ill

Eicosanoid [226, 227]

√

A(s)

√

Correlated with SAPS score, predicted response to therapy

Elastase [228, 229]

√

C(s)

√

Predicted response to therapy in patients with joint infections

Elastase-a1-antitrypsin complex [230, 231]

 

C

√

Predicted response to therapy

Erythropoietin [232]

 

A

√

Distinguished between survivors and non-survivors at 28 days in patients with septic shock, correlated with lactate levels

F2 isoprostanes [233]

 

B(m)

√

Increased in infected diabetic patients compared with non-infected diabetics

Fatty acid amide hydrolase [234]

 

A

√

Decreased in sepsis compared with healthy controls

Free DNA [235]

 

B

√*

Distinguished between survivors and non-survivors at 28 days

G-CSF and GM-CSF [236, 237]

 

B

√**

Distinguished between survivors and non-survivors at 28 days

Gelsolin [238]

 

B(s)

√

Distinguished between survivors and non-survivors at 28 days

Ghrelin [239, 240]

√

   

Growth arrest specific protein (Gas) 6 [241]

 

B

√

Correlated with APACHE II score in patients with severe sepsis

Heat shock protein (HSP)70, 72, 73, 90 and 32 [242–245]

√

C(s)

 

Increased in sepsis compared with healthy controls

HDL cholesterol

 

C

√**

Distinguished between survivors and non-survivors at 28 days, predicted polonged ICU length of stay

HLA-G5 protein (soluble) [246]

 

C(m)

√*

Distinguished between survivors and non-survivors at 28 days in patients with septic shock

H2S [247]

√

   

Hyaluronan [248, 249]

√

B

 

Distinguished between survivors and non-survivors at 28 days in patients with septic shock

Hydrolytic IgG antibodies [250]

 

B

√

Distinguished between survivors and non-survivors at 28 days, correlation with SAPS II score

Inter-alpha inhibitor proteins (IalphaIp) [251]

 

C

√

Predicted development of MOF

Intracellular nitric oxide in leukocyte [252]

 

B

√

Negatively correlated with SOFA score

IP-10 [30]

 

C

 

Increased in sepsis compared with healthy controls

Lactate [253, 254]

 

C

√

Distinguished between survivors and non-survivors at 28 days, predicted response to therapy

Lactoferrin [255, 256]

√

C(s)

 

Predicted response to therapy

Leptin [240, 257]

√

B

√

No prognostic value, higher in septic than in non-septic ICU patients

Serum lysozyme (enzyme activity) [258]

 

B(s)

 

Increased in sepsis compared with healthy controls

Matrix-metalloproteinase (MMP)-9 [259]

 

B

 

Increased in severe sepsis compared with healthy controls

Microparticles (cell derived) [252]

 

B

√

Distinguished between survivors and non-survivors at 28 days, correlation with SOFA score

Neurotensin [260]

√

   

Nitrate excretion (urinary and expired) [261]

√

   

Nociceptin/orphanin FQ (N/OFQ) [262]

 

A

√

Distinguished between survivors and non-survivors at 28 days

NF-κB (activity and expression) [263]

 

B

√**

Distinguished between survivors and non-survivors at 28 days in patients with severe sepsis, correlation with APACHE II score

Nucleosomes [264]

 

C

 

Distinguished between survivors and non-survivors at 28 days

Peptidoglycan [265]

 

B(s)

√

Increased in sepsis compared with healthy controls

PlGF [266]

√

   

Plasma amino acids [267–269]

 

A

√

Distinguished between survivors and non-survivors at 28 days, predicted development of MOF

Plasma fibronectin [270]

 

B

√

Increased in sepsis compared with healthy controls

Plasmin alpha2-antiplasmin complex [271]

 

C

 

Predicted development of MOF

Renin [272]

 

B

√

Correlation with lactate levels in patients with septic shock

Resistin [273]

 

C

√

Correlation with APACHE II score in patients with severe sepsis

Selenium [274]

 

C

√

Correlation with APACHE II in patients with severe sepsis

Selenoprotein P [275]

 

B

 

Decraesed in sepsis compared with healthy controls

Serum bicarbonate [276]

 

A(m)

√

Predicted development of septic shock in neutropenic patients

Sphingomyelinase (enzyme activity) [277]

 

A

 

Distinguished between survivors and non-survivors at 28 days in patients with severe sepsis

Sulfite [278]

√

B(m)

√

Predicted response to therapy

Transforming growth factor (TGF)-β1 [279, 280]

√

A(m)

 

Distinguished between survivors and non-survivors at 28 days

TIMP-1 and 2 [259]

 

B

√*

Distinguished between survivors and non-survivors at 28 days

TIMP-3 [281]

√

   

Uric acid [282]

 

C(s)

√

Decreased in postoperative patients with sepsis compared with those with no sepsis

Urinary 8-OhdG [283]

 

C

√

Distinguished between survivors and non-survivors at 28 days

Urinary bilirubin oxidative metabolites (BOMs) [284]

 

A

√

Correlation with APACHE II score

Annexin V binding [285]

√

B(s)

 

Increased in sepsis compared with healthy controls

Xanthine oxidase (activity) [286]

 

C

√

Distinguished between survivors and non-survivors at 28 days

  1. *sensitivity and specificity of less than 90%; **sensitivity of more than 90% but specificity of less than 90%; A, Clinical study with less than 20 patients; B, Clinical study with 20 to 50 patients; C, Clinical study with more than 50 patients; (s), surgical patients only; (m), medical patients only.
  2. APACHE: acute physiology and chronic health evalution; G-CSF: granulocyte colony-stimulating factor; GM-CSF: granulocyte-macrophage colony stimulating factor; MOF: multiple organ failure; NF-κB: nuclear factor kappa B; PlGF: placental growth factor; SAPS: simplified acute physiology score; SOFA: sequential organ failure assessment; TIMP: tissue inhibitor of metalloproteinase.