Biomarkers In Sepsis And The Winner Is…

Sumit Ray

Chairperson

Critical Care Medicine

Artemis Hospital

Delhi NCR

India

PERFORMANCE OF BIOMARKERS IN SEPSIS

Diagnosing sepsis → differentiating from SIRS →

Diagnosing HAIs

Prognosticating sepsis & tracking response to

therapy

Antibiotic stewardship → Initiating & stopping

antibiotics

Round 1

Round 2

Round 3

CONFLICT OF INTEREST &CONFESSIONS!

Conducted clinical trials with funding from

Indian Council of Medical Research on PCT &

cytokines in sepsis

Skeptical of industry sponsored studies!

Results:

1.Research funded by drug companies with negative

results were less likely to be published than research

funded by other sources.

2.Studies sponsored by pharmaceutical companies

were more likely to have outcomes favouring the

sponsor than were studies with non-industry sponsors

(odds ratio 4.05; 95%CI 2.98 to 5.51)

WHAT IS A BIOMARKER & WHY DO WE NEED THEM?

A biomarker is “. . . a characteristic that is objectively

measured and evaluated as an indicator of normal biological

processes, pathogenic processes, or pharmacologic

responses to a therapeutic intervention”

Or more simply, as a “quantifiable measurement(s) of

biological homeostasis that define(s) what is „normal,‟

therefore providing a frame of reference for predicting or

detecting what is „abnormal‟…”

Biomarkers Definitions Working Group: Clin Pharmacol Ther 2001; 69:89–95 Dalton et al; Science 2006;312:1165-1168

“the ability to accurately distinguish between SIRS and

sepsis has become one of the holy grails of medicine.”

THE CONTENDERS -- BIOMARKERS

o CRP (C reactive Protein)

o PCT (Procalcitonin)

o Presepsin (sCD14-ST)

o MR-proADM (Mid-regional proadrenomedullin)

o suPAR (soluble urokinase-type plasminogen activator receptor)

o Pro-AVP (Pro-vasopressin)

o Histidine-Rich Glycoprotein

o Heparin Binding Protein

THE CONTENDERS:

1.Procalcitonin (PCT):

Precursor of the hormone calcitonin.

In bacterial infection ↑of pro inflammatory cytokines → PCT is synthesized

in extrathyroidal tissues

Detectable at 4 hrs in sepsis → maintaining a plateau through 8- 24 hrs

Viral infections do not cause an ↑, as interferons may suppress PCT release

Clearance effected in renal failure

2.Presepsin (sCD14-ST): is a soluble N-terminal fragment of the cluster of

differentiation (CD) marker protein CD14

Released into the circulation during monocyte activation upon the

recognition of LPS from infectious agents

Levels rise rapidly→ detectable within 2 hrs of infection.

Clearance effected by liver failure.

THE CONTENDERS: 3.MR-proADM (Mid-regional proAdrenomedullin):

ADM belongs to the calcitonin gene peptide superfamily.

Cytokines (TNF-α/β, IL-1-α/β & LPS) stimulate the production & release of

ADM → MR-proADM is a fragment which splits from the final proADM

Widely synthesised → bone, adrenals, kidney, lung, blood vessels, heart,

pituitary, thalamus & hypothalamus

Released to stabilize the microcirculation & reduce endothelial permeability

Clearance in the pulmonary circulation

4. suPAR (soluble urokinase-type plasminogen activator receptor)

uPA (Urokinase-type plasminogen activator) is secreted by PMN cells &

macrophages → uPA binds to uPAR (receptor) → suPAR is cleaved from

uPAR.

suPAR is expressed on macrophages monocytes, endothelial cells &

neutrophils → role in regulating cytokines responses

ROUND 1- TO DIAGNOSE SEPSIS

Single center, 33 patients of SIRS, Sepsis & Septic Shock(SSh)

Conclusion: “Procalcitonin is a useful marker to rule out sepsis

and systemic inflammation in the ED.” (NPV=98.2%)

Single center – 367 blood cultures

AUROC = 0.79

Enrolled patients 208 → 46 SIRS, 90 culture-negative sepsis, and 72 culture-positive sepsis

Excluded: Postoperative, immunocompromised & malignancies.

Bilateral pneumonia (suspected viral infection) and diagnosed tropical

diseases such as malaria, dengue, Leptospira, and rickettesiae

SIRS pts were recent onset (within last 24 hrs) pancreatitis & trauma patients

☆ Funded by the Indian Council of Medical Research, New Delhi, India, through project no. 52/10/08.

TO DIAGNOSE SEPSIS

Uzzan et al, Crit Care Med 2006; 34:(7) 1996-2003

33 studies 3,943 pts →1825 Sepsis/SS/SSh, 1,545 SIRS

ROC for PCT= 0.78(0.71-0.84)

ROC for CRP =0.71(0.64-0.76)

OR for diagnosis of infection

complicated by SIRS were:

PCT =15.7 (CI =7.12-30.27)

CRP = 5.4 (CI =3.19-9.23)

PCT cut-off range = 0.6- 5 ng/mL

CRP cut off range = 39 – 180mg/L

Conclusions: “Procalcitonin represents

a good biological diagnostic marker for

sepsis, severe sepsis, or septic shock,

a difficult diagnoses in critically ill pts.

Procalcitonin is superior to CRP.”

TO DIAGNOSE SEPSIS Tang et al, Lancet Infect Dis 2007:7;210-17

18 Studies, 2097 pts

The diagnostic performance of PCT was low →

sAUROC = 0·78

sSensitivity= 73%

sSpecificity = 73%

Diagnostic OR= 7.79 Cut offs= 0.2-20 ng/ml

Conclusion: “Procalcitonin cannot

reliably differentiate sepsis from other

non-infectious causes of SIRS.”

“We are concerned about the authors‟ search strategy, which yielded only 18

studies eligible out of more than 600, and surprisingly omitted some well

performed studies….authors did not include the widely accepted terms

“severe sepsis” and “septic shock” in their search strategy.” Konrad Reinhart

TO DIAGNOSE SEPSIS

30 studies,3244 patients

sSensitivity of 0·77 (CI 0·72- 0·81) specificity of 0·79 (CI 0·74–0·84).

sAUROC was 0.85 (95% CI 0·81–0·88).

PLR (Positive Likelyhood Ratio) = 4 & NLR 0.29

Cut offs for PCT= 1.1ng/ml (IQR 0.5-2)(Range 0.5-9.7)

Interpretation: “Procalcitonin is a helpful biomarker for early diagnosis

of sepsis in critically ill patients. Nevertheless, the results of the test

must be interpreted carefully in the context of medical history, physical examination and microbiological assessment.”

“For situations of greatest clinical uncertainty, procalcitonin does not

offer good enough negative predictive value to justify withholding

antibiotic treatment.” Arash Afshari

Meta-analysis 10 diagnostic studies that evaluated 1144 patients and 435 bacterial

infection episodes (32.1%)

PCT

Sensitivity = 0.79

Specificity = 0.89

AUROC = 0.92 (CI-.89-.94)

PLR= 7.38 (CI- 4.70–11.58)

NLR= 0.23 (CI- 0.13–0.41)

CRP

Sensitivity = 0.77

Specificity= 0.85

AUROC= 0.87(CI-.84-.90)

PLR = 5.12 (CI-3.04- 8.54)

NLR = 0.26 (CI-.18-.38)

Conclusion: “….The overall accuracy between PCT and CRP in differentiating

bacterial infections from other noninfectious causes of systemic inflammation

in cirrhotic patients is nearly comparable.

PCT has slightly better rule-in and rule-out value than CRP.”

• Systematic review, included 1418 critically immunosuppressed pts

• CRP was showed a sensitivity of 0.69 (0.53–0.60), specificity of 0.76

(0.71–0.76) & sAUROC of 0.77 for the detection of bacterial infections.

• In immunocompetent → Sensitivity 75% [CI: 62–84%], Specificity 67%

[CI: 56–77%] and AUROC = 0.82 [CI: 0.79–0.84])

• In cirrhotic patients, CRP performed poorly → Sensitivity of 0.57 (CI: 0.31–0.80) Specificity of 0.75 (CI: 0.59–0.86) sAUROC (0.74)

Single center, 72 pts of Sepsis, 23 of SIRS & 20 Healthy volunteers

Conclusion: Presepsin was a promising biomarker for initially diagnosis

and risk stratification of sepsis

Single Center, 92 pts with Blood culture & Blood RT-PCR positive

Conclusion: In patients with suspected sepsis, presepsin and PCT

showed a good diagnostic accuracy in predicting both bacteraemia

and bacterial DNAaemia, superior to CRP.

Diagnostic value

in Sepsis

Diagnostic value

in CAP

2 Hospital, 144 pts→ 100 SS/SShock, 29 SIRS & 15 Non-SIRS

sAUROC= 0.88 (0.84-0.90)

s Sen = 0.83 (0.77-0.88)

s Spec= 0.78 (0.72-0.83)

PLR = 3.9

NLR = 0.21

The cut-off values ranged from 317 to 729

pg/mL

AUROC ranged from 0.70 to 1.00

Sensitivity ranged from 0.70 to 1.00

Specificity ranged from 0.62 to 0.93.

11 studies→ 4 with High Risk of bias, 4 moderate risk & 3 unknown → 1630 pts/

1422 controls

Conclusion: “We conclude that

presepsin cannot always confirm or rule out sepsis when used alone, and

its results should be interpreted within

the clinical context.”

Summary AUROC = 0.89(0.86-0.92) Sensitivity = 0.86(0.79-0.91)

Specificity = 0.78(0.68-0.85) PLR = 3.8 NLR = 0.18

8 Studies, 1815 pts

Conclusion: “Presepsin exhibits very good diagnostic accuracy (AUC=0.89)

for diagnosising sepsis. Nevertheless, an overall assessment of all the clinical

indexes for sepsis diagnosis and re-evaluation of presepsin during the course

of the disease are needed.”

Presepsin sAUROC = 0.88, PLR=3.4, NLR=0.22

Conflict of Interest

AUROC curves:

PCT= 0.7132

proADM= 0.7028

CRP= 0.5261

Procalcitonin and mid-regional pro-adrenomedullin test combination in

sepsis diagnosis. Silvia Angeletti, Fabrizio Battistoi, Marta Fioravanti, Sergio Bernardin

Clinical Chemistry and Laboratory Medicine (CCLM) doi.org/10.1515/cclm-2012-0595

200 septic patients, 90 patients with SIRS and 30 healthy individuals

• Results: Healthy controls and non-infectious SIRS were clearly

distinguished from sepsis patients using the cut-off values: 0.30

ng/mL for PCT and 1 nmol/L for MR-proADM.

• 200 sepsis pts → AUCs for PCT & MR-proADM were 0.921& 0.977

• There was a statistically significant difference between the two

AUC 0.0563 (p=0.0002)

• The combined use of PCT and MR-proADM gave a post-test

probability of 0.998 in the cohort of all septic patients.

Review of 9 studies→ >1000 pts

AUROC for diagnosing

sepsis= 0.62

• Systemic levels of suPAR were

significantly higher in patients with blood culture-positive bacteremia

compared to healthy controls

• suPAR seemed to have no value in

discriminating patients with bacterial infection from patients

with viral or parasitic infections

• Compared to other frequently used

biological markers…..including

CRP, PCT,….suPAR added little to the diagnostic process

TO DIAGNOSE HAI’S

PCT levels on any day upto 3 days before suspected infection

PCT levels after day of infection

Single center, 70 pts→ 47 with HAI & 23 without HAI

ROLE OF PCT & CRP IN DETECTING SECONDARY

BACTERIAL INFECTION

For PCT a cut-off of 0.8 ug/l , the sensitivity and specificity for distinguishing

isolated viral from mixed pneumonia were 91% & 68%, with a NPV of 91%

PCT cut off 0.8ug/L → ROC=0.90

CRP cut off 230mg/dL → ROC = 0.82

THE FAVOURITES TO DIAGNOSE SEPSIS:

Round 1Scores:

CRP = 6.5

PCT = 8

Presepsin = 8

Pro-ADM = 7

suPAR = 6.5

1.PCT AUROC’s between 0.7-0.85

Better negative predictive value to rule out (R/O) sepsis

Cut offs are a problem → Anywhere between < 0.5 ng to R/O sepsis to >1.5 ng/ml

to R/I sepsis

2.Presepsin= AUROC’s of 0.8 -0.9

In head to head comparision with PCT & Pro-ADM = 0.7-0.8

Cut-offs between 300-700 pg/ml

3.MRpro-ADM- AUROC’s between 0.7 -0.8. Relatively fewer studies.

Cut-offs below 1-1.4 ng/ml to R/O sepsis

4.suPAR-- AUROC’s 06-0.7. Cut offs= >10 ng/ml to R/I sepsis

5.CRP-- AUROC’s 0.55-0.8 to R/I sepsis. Wide-range of cut-offs=40-200 mg

ROUND 2- PROGNOSTICATION IN SEPSIS &

TRACKING RESPONSE TO THERAPY

The prognostic markers of sepsis → AUROC of

APACHE II = 0.75 [95% (CI) 0.67–0.83],

SAPS II= 0.82 (95% CI 0.75– 0.89),

SOFA= 0.8 (95% CI 0.72–0.88),

CRP= 0.55 (95% CI 0.45–0.65),

The ICU mortality rate of septic patients with CRP< 10, 10–20, 20–30, 30–40

and >40 mg/dL was 20, 34, 30.8, 42.3 and 39.1%, respectively (P = 0.7)

No correlation was found between CRP concentrations and severity of sepsis.

Crit Care Med 2006; 34:2596–2602

Single center, 472 pts →

PCT values were categorized as:

alert values or non-alert values.

Alert values → all values >1.0 ng/mL with

an increase daily

Non-alert values → ↓on the 1st day after

exceeding 1.0 ng/mL & additionally all

values >1.0 ng/mL that were not

succeeded by values >1.0 ng/mL.

Single center, 130 pts→ PCT at T-0, T-24 & T-48hrs & SOFA at T0 & T-48hrs

Analysed PCT-c (clearance) at 24 hrs & 48 hrs and ∆SOFA at 48 hrs

AUROC

0.68(CI 0.56-79) 0.76(CI 0.66-86)

0.76(CI 0.66-.86)

Conclusions: The 48-hour Δ SOFA score and the clearance of 24- and 48-

hour PCT are useful markers of prognosis in patients with severe sepsis and

septic shock.

A reduced PCT clearance at 24 hours of treatment should prompt the

reassessment of the appropriateness and adequacy of treatment

Only RCTs testing PCT-guided decisions in at least one of the comparison arms for adults with sepsis, severe sepsis or septic shock were considered → 10 RCTS -1215 pts

7/10 studies had high

risk of bias

Results: • Presepsin concentration at baseline (946[492–1,887] ng/L) → ↑ed

with the SOFA score & the no. of organ dysfunctions/failures

• The concentrations of Presepsin ↓ed over 7 days in pts with –ve blood

cultures & in +ve blood cultures on appropriate antibiotic therapy

• ↑ with inappropriate antibiotic therapy (p = 0.0009).

• Baseline presepsin was independently associated with the risk of ICU and 90-day mortality.

• ↑ing concentrations of presepsin from day 1 to day 2 predicted

higher ICU and 90-day mortality (p <0.0001 and 0.01 respectively)

Secondary analysis of the randomized, Placebo-Controlled Trial of Sodium Selenite and

Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT)→1089 patients

Results: “….Patients with ↓ed PCT

concentrations of either ≥ 20%

(baseline to day 1) or ≥ 50%

(baseline to day 4) but

continuously high MR-proADM

concentrations had a significantly

increased mortality risk- HR : 19.1

(CI; 8.0–45.9) & 43.1 (CI;10.1–

184.0)).”

Review of 9 studies→ >1000 pts.

Prognostic ability of suPAR to predict mortality in ICU pts

Prognostic ability of suPAR

to predict mortality in sepsis

SCORES FOR BIOMARKERS FOR PROGNOSTICATION IN SEPSIS

1.PCT trends and clearance has better prognostic value than initial values

Reduction of >80% in levels over 4 days or >50%-over 48 to 72 hrs are

indicators of better survival → AUROC’s of 0.75-0.8

Head to Head comparisons of PCT with Presepsin, pro-ADM, suPAR, though

show lower AUROC’s → 0.5 – 0.6

2. Presepsin ↓ing trends predict survival, while ↑ing trends predict mortality

→ AUROCs of 0.65-0.85

3. MRproADM initial values had AUROC’s ≈ 0.75 to predict mortality.

In head to head RCT’s & Meta-analysis it performed better than PCT/CRP/suPAR

Mortality in one large trial remained high if proADM levels remained high,

inspite of a ↓ PCT

4.suPAR had AUROC’s at ≈ 0.6 to predict mortality.

In head to head comparisions it performed worse than proADM & PCT

5.CRP levels & trends performed poorly in predicting mortality→AUROC’s ≈ 0.50

SCORES: PCT= 7.5, Presepsin= 7,MR proADM = 7.5, suPAR = 6, CRP = 5

ROUND 3- ANTIBIOTIC STEWARDSHIP

Bouadma et al,Lancet 2010;375:463-474

of 621 pts

Bouadma et al,Lancet 2010;375:463-474

PASS Trial → 9 hospital → 1200 pts →604 PCT & 596 Control group

Jensen et al, Crit Care Med 2011;39:2048-2058

“Alert procalcitonin” was defined as a PCT ≥ 1.0 ng/mL and not ↓ing by at

least 10% from the previous day.

At baseline, a single PCT of ≥1.0 ng/mL was considered to be “alert PCT.”

Jensen et al, Crit Care Med 2011;39:2048-2058

No difference in mortality=31.5% vs 32%

Significantly Higher use of antibiotics in the PCT arm

LOS in the ICU ↑ed by 1 day (p .004) in the PCT arm.

The rate of Mech Vent per day in the ICU ↑ed by 4.9% (CI, 3.0–6.7%)

in the PCT arm

The RR of days with estimated GFR <60 mL/min was 1.21 (CI1.15-1.27)

ProACT study→14 US Hospitals→1656 pts

Antibiotic prescription in emergency department, by procalcitonin tier

There was no significant difference between the procalcitonin

group and the usual-care group in antibiotic-days (mean, 4.2 and

4.3 days,respectively; difference, −0.05 day;CI, −0.6 to 0.5; P = 0.87)

OR the proportion of patients with adverse outcomes (11.7% [96

patients] and 13.1% [109 patients]

Individual pt data was studied for 6708 pts from 26 trials in 12 countries.

Conclusion: “….use of procalcitonin to guide initiation and duration of

antibiotic treatment results in lower risks of mortality, lower antibiotic

consumption, and lower risk for antibiotic-related side effects, in ARI‟s ……thus

supporting the use of procalcitonin in the contextof antibiotic stewardship in

people with ARIs.”

SCORES FOR BIOMARKERS FOR ANTIBIOTIC STEWARDSHIP

Major RCT’s & meta-analysis for antibiotic stewardship

have been done only for PCT

PCT ↓ of 20-25% over 24 hrs or >50% over 48-72 hrs or

≥80% over 4 days OR levels ≤ 0.5 ng/ml would decide if

antibiotics need to be changed or stopped

Scores: PCT=7.5, All the rest→ ???

AND THE WINNER IS ???!!!

PCT!!! Close fight vs proADM

for prognostication.

Close fight vs Presepsin

for diagnosis

Won because of:

1.Experience (1st mover advantage)

2.Volume of punches (No. of studies)

3.Promoters (Study funding)

Thank you!

EOSINOPENIA AS MARKER FOR SEPSIS?

AUROC 0.89

AUROC 0.77

AUROC=0.82 Survivors vs Non-survivors AEC ≤ 40/mm3

HR 1.85; 95% (CI), 1.01–

3.42; P = 0.046],

Date of download: 9/15/2018 Copyright 2018 American Medical Association.

All Rights Reserved.

From: Development and Validation of a Prediction Model for Mortality and Adverse

Outcomes Among Patients With Peripheral Eosinopenia on Admission for Clostridium

difficile Infection

JAMA Surg. Published online September 12, 2018. doi:10.1001/jamasurg.2018.3174

Comparisons of Primary and Secondary Outcomes Between the Eosinophil Count Groups

Two-sided univariate χ2 tests were used to compare outcomes of patients with an eosinophil count > 0 cells/μL (n = 610) and patients with an eosinophil count of 0 cells/μL

(n = 454). For all 4 outcomes, P < .05 between groups. Error bars represent 95% CIs.

Figure Legend:

BIOMARKERS-ROLE IN TROPICAL DISEASES

Hesslink et al, Malaria Journal 2009;8:206

PCT in Malaria

WHY DO WE NEED BIOMARKERS?

“the ability to accurately distinguish between SIRS and sepsis has become one of the holy grails of medicine.”

To be clinically useful, a sepsis biomarker needs to provide information quickly and more accurately than existing ones → like CRP, TLC etc.

Kibi et al, J Antimicrob Chemother 2011;66 suppl2:ii33-ii40

Conclusion: “Although it was useful for the diagnosis of infection (AUROC

>80%), the positive predictive value of PCT decreased significantly with

increasing severity of heart failure (P < 0.05), and the cut-off value of PCT

concentrations for infection complicated by classes II, III and IV heart failure

were 0.086, 0.192 and 0.657 μg/L, respectively.”

0.97 0.82

0.77

AUROC

Single center, 70 SIRS, 9 Non-SIRS & 16 Healthy Volunteers

Conflict of Interest

Jensen et al, Crit Care Med 2006;34:2596-2602

Prospective observational cohort, single center study on 472 patients

Jensen et al, Crit Care Med 2006;34:2596-2602

2.PCT levels are directly associated with organ dysfunction in sepsis as

assessed by SOFA score. The significant positive correlation was observed

only in the survivor group

Results: 1.PCT levels significantly decreased (p<0.001) in 89.3 % of surviving

patients, whereas, in 60 % non surviving patients the PCT level increased

significantly (p<0.001)

PCT levels were measured at 0, 24, 72 h and 7th day and sequential organ

failure assessment score (SOFA) scores were calculated.

Measured the PCT level on the day they suspected VAP and compared it

with any PCT levels in the previous 5 days → confirmatory BAL .

Intensive Care Med 2008;34:1434-1440

Antibiotic duration

LOS

Mortality

PCT Cut off 0.8ug/L → ROC =0.88

CRP Cut off >200mg/dL → ROC=0.97

PCT = 100% sensitivity/62% specificity

CRP = 100% sensitivity/ 87.5% specificity

PCT + CRP = 100% sensitivity/ 94% specificity

NPV= 100%/ PPV= 90%

Schuetz et al, Clinical Infectious Diseases 2012;55(5):651-662

Stop Antibiotics on Procalcitonin guidance Study (SAPS)

15 Hospital in Netherlands →RCT of 1575 pts

PCT-guided group, a non-binding advice to discontinue antibiotics was

provided if PCT levels ↓ed by ≥80% of its peak value or to ≤0.5 μg/L.

OTHER MARKERS FOR DIAGNOSING SEPSIS

IN THE CRITICALLY ILL?

PCT-guided patients had shorter antibiotics duration(7.35 vs. 8.85 d; WMD, –

1.49 d; 95% CI, –2.27 to –0.71; p < 0.001).

PCT use had no adverse impact on mortality (RR=0.90,CI, 0.79–1.03; p =

0.114) and length of ICU stay (11.09 d vs. 11.91 d)

AUROC for Culture –ve vs SIRS AUROC for Culture +ve vs SIRS

PCT

AUROC= 0.892

Cut-off=1.43

IL6

AUROC = 0.636

Cut-off=219

PCT

AUROC = 0.959

Cut-off=2.49

IL6

AUROC = 0.784

Cut-off=432

Conclusions: “Our results suggest that a protocol based on serial PCT

measurement allows reducing antibiotic treatment duration and exposure in

patients with severe sepsis and septic shock without apparent harm.”

THANK YOU!

Causes of immunodepression were hematological disorders (64 pts 53.8%),

HIV infection (31 patients, 26%) & solid cancers (26 patients, 21.8%).

Bacterial sepsis was diagnosed in 58 pts & nonbacterial infections in 9 pts

(7.6%); 52 pts(43.7%) had no infection

TO DIAGNOSE HAI IN CRITICALLY PATIENTS

Critical Care 2006,10:R145

For prediction of infection

34 studies & 1384 pts

TO DIAGNOSE HAI IN CRITICALLY PATIENTS

Sponholz et al,Critical Care 2006,10:R145

Causes of immunodepression were hematological disorders, HIV infections

& solid cancers

Bacterial sepsis was diagnosed in 58 pts & nonbacterial infections in 9 pts ;

52 pts(43.7%) had no infection

2 centers, 326 pts of sepsis/SS. Biomarkers =MR-proADM, PCT, CRP, Lactate

measured at within 12 hrs of ICU admission

All patients with MR-proADM concentrations ≤0.88 nmol/L survived up to 28 days

137 pts of sepsis → Compared suPAR, proADM, PCT & CRP and APACHE II

Conclusions: “suPAR and, to a lesser extent, proADM levels on ICU admission

were better tools in prognosticating in-hospital mortality than CRP or PCT.

However, neither of the two new biomarkers has been demonstrated to be

excessively useful in the current setting.”