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.”