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1.  Dynamic changes of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) reflect sepsis severity and can predict prognosis: a prospective study 
Background
We examined the utility of serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for the diagnoses, severity assessments, and predicting the prognoses of patients with sepsis and compared sTREM-1 values with those of C-reactive protein (CRP) and procalcitonin (PCT).
Methods
Fifty-two patients with sepsis were included: 15 sepsis cases and 37 severe sepsis cases (severe sepsis + septic shock). Serum levels of sTREM-1, CRP, and PCT were determined on days 1, 3, 5, 7, 10, and 14 after admission to an ICU.
Results
Serum sTREM-1 levels of patients with severe sepsis were significantly higher than for those with sepsis on day 1 (240.6 pg/ml vs. 118.3 pg/ml; P < 0.01), but CRP and PCT levels were not significantly different between the two groups. The area under an ROC curve for sTREM-1 for severe sepsis patients was 0.823 (95% confidence interval: 0.690-0.957). Using 222.5 pg/ml of sTREM-1 as the cut-off value, the sensitivity was 59.5%, the specificity was 93.3%, the positive predictive value was 95.6%, the negative predictive value was 48.3%, the positive likelihood ratio was 8.92, and the negative likelihood ratio was 0.434. Based on 28-day survivals, sTREM-1 levels in the surviving group showed a tendency to decrease over time, while they tended to gradually increase in the non-surviving group. sTREM-1 levels in the non-surviving group were higher than those in the surviving group at all time points, whereas CRP and PCT levels showed a tendency to decrease over time in both groups. sTREM-1 levels and Sequential Organ Failure Assessment (SOFA) scores were positively correlated (r = 0.443; P < 0.001), and this correlation coefficient was greater than the correlation coefficients for both CRP and PCT.
Conclusions
Serum sTREM-1 levels reflected the severity of sepsis more accurately than those of CRP and PCT and were more sensitive for dynamic evaluations of sepsis prognosis.
Trial Registration
Current controlled trials ChiCTR-OCH-09000745
doi:10.1186/1471-2334-11-53
PMCID: PMC3056794  PMID: 21356122
2.  In Critically Ill Patients, Serum Procalcitonin Is More Useful in Differentiating between Sepsis and SIRS than CRP, Il-6, or LBP 
We studied the usefulness of serum procalcitonin (PCT), interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) levels and C-reactive protein (CRP) levels, in differentiating between systemic inflammatory response syndrome (SIRS) and sepsis in critically ill patients. Methods. In this single centre prospective observational study we included all consecutive patients admitted with SIRS or sepsis to the ICU. Blood samples for measuring CRP, PCT, IL-6 and LBP were taken every day until ICU discharge. Results. A total of 76 patients were included, 32 with sepsis and 44 with SIRS. Patients with sepsis were sicker on admission and had a higher mortality. CRP, PCT, IL-6 and LBP levels were significantly higher in patients with sepsis as compared to SIRS. With PCT levels in the first 24 hours after ICU admission <2 ng/mL, sepsis was virtually excluded (negative predictive value 97%). With PCT >10 ng/mL, sepsis with bacterial infection was very likely (positive predictive value 88%). PCT was best at discriminating between SIRS and sepsis with the highest area under the ROC curve (0.95, 95% CI 0.90–0.99). Discussion. This study showed that PCT is more useful than LBP, CRP and IL-6 in differentiating sepsis from SIRS.
doi:10.1155/2011/594645
PMCID: PMC3113363  PMID: 21687569
3.  Diagnostic value of urine sTREM-1 for sepsis and relevant acute kidney injuries: a prospective study 
Critical Care  2011;15(5):R250.
Introduction
We explored the diagnostic value of a urine soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for early sepsis identification, severity and prognosis assessment, and for secondary acute kidney injury (AKI). We compared this with white blood cell (WBC) counts, serum C-reactive protein (CRP), serum procalcitonin (PCT), urine output, creatinine clearance (CCr), serum creatinine (SCr), and blood urea nitrogen (BUN).
Methods
We enrolled 104 subjects admitted to the ICU: 16 cases with systemic inflammatory response syndrome (SIRS); 35 with sepsis and 53 with severe sepsis. Results for urine sTREM-1, WBC, serum CRP and serum PCT were recorded on days 1, 3, 5, 7, 10, and 14. For 17 sepsis cases diagnosed with secondary AKI, comparisons between their urine sTREM-1, urine output, CCr, SCr and BUN at diagnosis and 48 h before diagnosis were made.
Results
On the day of admission to the ICU, and compared with the SIRS group, the sepsis group exhibited higher levels of urine sTREM-1 and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) scores (P < 0.05). Areas under the curve (AUC) shaped by the scores were 0.797 (95% CI 0.711 to 0.884) and 0.722 (95% CI 0.586 to 0.858), respectively. On days 1, 3, 5, 7, 10, and 14, urine sTREM-1, serum PCT and WBC levels registered higher in the severe sepsis group in contrast to the sepsis group (P < 0.05). Urine sTREM-1 and serum PCT levels continuously increased among non-survivors, while WBC and serum CRP levels in both groups declined. For 17 patients with AKI, urine sTREM-1, SCr and BUN levels at 48 h before AKI diagnosis were higher, and CCr level was lower than those for non-AKI subjects (P < 0.05). AUC for urine sTREM-1 was 0.922 (95% CI 0.850 to 0.995), the sensitivity was 0.941, and the specificity was 0.76 (based on a cut-off point of 69.04 pg/ml). Logistic regression analysis showed that urine sTREM-1 and severity were risk factors related to AKI occurrence.
Conclusions
Besides being non-invasive, urine sTREM-1 testing is more sensitive than testing WBC, serum CRP, and serum PCT for the early diagnosis of sepsis, as well as for dynamic assessments of severity and prognosis. It can also provide an early warning of possible secondary AKI in sepsis patients.
Trial Registration
ClinicalTrial.gov identifier NCT01333657
doi:10.1186/cc10508
PMCID: PMC3334801  PMID: 22023777
urine; soluble triggering receptor expressed on myeloid cells-1(sTREM-1); sepsis; severity; prognosis; acute kidney injury (AKI); sensitivity; specificity
4.  The Value of Procalcitonin and the SAPS II and APACHE III Scores in the Differentiation of Infectious and Non-infectious Fever in the ICU: A Prospective, Cohort Study 
Journal of Korean Medical Science  2010;25(11):1633-1637.
Early and accurate differentiation between infectious and non-infectious fever is vitally important in the intensive care unit (ICU). In the present study, patients admitted to the medical ICU were screened daily from August 2008 to February 2009. Within 24 hr after the development of fever (>38.3℃), serum was collected for the measurement of the procalcitonin (PCT) and high mobility group B 1 levels. Simplified Acute Physiology Score (SAPS) II and Acute Physiology And Chronic Health Evaluation (APACHE) III scores were also analyzed. Sixty-three patients developed fever among 448 consecutive patients (14.1%). Fever was caused by either infectious (84.1%) or non-infectious processes (15.9%). Patients with fever due to infectious causes showed higher values of serum PCT (7.8±10.2 vs 0.5±0.2 ng/mL, P=0.026), SAPS II (12.0±3.8 vs 7.6±2.7, P=0.006), and APACHE III (48±20 vs 28.7±13.3, P=0.039) than those with non-infectious fever. In receiver operating characteristic curve analysis, the area under the curve was 0.726 (95% CI; 0.587-0.865) for PCT, 0.759 (95% CI; 0.597-0.922) for SAPS II, and 0.715 (95% CI; 0.550-0.880) for APACHE III. Serum PCT, SAPS II, and APACHE III are useful in the differentiation between infectious and non-infectious fever in the ICU.
doi:10.3346/jkms.2010.25.11.1633
PMCID: PMC2967001  PMID: 21060753
Fever; Intensive Care Units; Procalcitonin; SAPS II; APACHE III
5.  Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study 
Critical Care  2007;11(2):R38.
Introduction
Accurate and timely diagnosis of community-acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared the diagnostic characteristics of novel and routinely used biomarkers of sepsis alone and in combination.
Methods
This prospective cohort study included patients with systemic inflammatory response syndrome who were suspected of having community-acquired infections. It was conducted in a medical emergency department and department of infectious diseases at a university hospital. A multiplex immunoassay measuring soluble urokinase-type plasminogen activator (suPAR) and soluble triggering receptor expressed on myeloid cells (sTREM)-1 and macrophage migration inhibitory factor (MIF) was used in parallel with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed – one including a linear combination of the three best performing markers and another including all six – and the area under the receiver operating characteristic curve (AUC) was used to compare their performance and those of the individual markers.
Results
A total of 151 patients were eligible for analysis. Of these, 96 had bacterial infections. The AUCs for detection of a bacterial cause of inflammation were 0.50 (95% confidence interval [CI] 0.40 to 0.60) for suPAR, 0.61 (95% CI 0.52 to 0.71) for sTREM-1, 0.63 (95% CI 0.53 to 0.72) for MIF, 0.72 (95% CI 0.63 to 0.79) for PCT, 0.74 (95% CI 0.66 to 0.81) for neutrophil count, 0.81 (95% CI 0.73 to 0.86) for CRP, 0.84 (95% CI 0.71 to 0.91) for the composite three-marker test, and 0.88 (95% CI 0.81 to 0.92) for the composite six-marker test. The AUC of the six-marker test was significantly greater than that of the single markers.
Conclusion
Combining information from several markers improves diagnostic accuracy in detecting bacterial versus nonbacterial causes of inflammation. Measurements of suPAR, sTREM-1 and MIF had limited value as single markers, whereas PCT and CRP exhibited acceptable diagnostic characteristics.
Trial registration
NCT 00389337
doi:10.1186/cc5723
PMCID: PMC2206456  PMID: 17362525
6.  Procalcitonin and C-reactive protein during systemic inflammatory response syndrome, sepsis and organ dysfunction 
Critical Care  2004;8(4):R234-R242.
Introduction
Both C-reactive protein (CRP) and procalcitonin (PCT) are accepted sepsis markers. However, there is still some debate concerning the correlation between their serum concentrations and sepsis severity. We hypothesised that PCT and CRP concentrations are different in patients with infection or with no infection at a similar severity of organ dysfunction or of systemic inflammatory response.
Patients and methods
One hundred and fifty adult intensive care unit patients were observed consecutively over a period of 10 days. PCT, CRP and infection parameters were compared among the following groups: no systemic inflammatory response syndrome (SIRS) (n = 15), SIRS (n = 15), sepsis/SS (n = 71) (including sepsis, severe sepsis and septic shock [n = 34, n = 22 and n = 15]), and trauma patients (n = 49, no infection).
Results
PCT and CRP concentrations were higher in patients in whom infection was diagnosed at comparable levels of organ dysfunction (infected patients, regression of median [ng/ml] PCT = -0.848 + 1.526 sequential organ failure assessment [SOFA] score, median [mg/l] CRP = 105.58 + 0.72 SOFA score; non-infected patients, PCT = 0.27 + 0.02 SOFA score, P < 0.0001; CRP = 84.53 - 0.19 SOFA score, P < 0.005), although correlation with the SOFA score was weak (R = 0.254, P < 0.001 for PCT, and R = 0.292, P < 0.001 for CRP). CRP levels were near their maximum already during lower SOFA scores, whereas maximum PCT concentrations were found at higher score levels (SOFA score > 12).
PCT and CRP concentrations were 1.58 ng/ml and 150 mg/l in patients with sepsis, 0.38 ng/ml and 51 mg/l in the SIRS patients (P < 0.05, Mann–Whitney U-test), and 0.14 ng/ml and 72 mg/l in the patients with no SIRS (P < 0.05). The kinetics of both parameters were also different, and PCT concentrations reacted more quickly than CRP.
Conclusions
PCT and CRP levels are related to the severity of organ dysfunction, but concentrations are still higher during infection. Different sensitivities and kinetics indicate a different clinical use for both parameters.
doi:10.1186/cc2877
PMCID: PMC522844  PMID: 15312223
calcitonin; C-reactive protein; infection; procalcitonin; sepsis; sequential organ failure assessment score; systemic inflammatory response syndrome
7.  Procalcitonin and procalcitonin kinetics for diagnosis and prognosis of intravascular catheter-related bloodstream infections in selected critically ill patients: a prospective observational study 
BMC Infectious Diseases  2012;12:247.
Background
Procalcitonin (PCT) has emerged as a valuable marker of sepsis. The potential role of PCT in diagnosis and therapy monitoring of intravascular catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) is still unclear and was evaluated.
Methods
Forty-six patients were included in the study, provided they were free of infection upon admission and presented the first episode of suspected CRBSI during their ICU stay. Patients who had developed any other infection were excluded. PCT was measured daily during the ICU hospitalization. Primary endpoint was proven CRBSI. Therapy monitoring as according to infection control was also evaluated.
Results
Among the 46 patients, 26 were diagnosed with CRBSI. Median PCT on the day of infection suspicion (D0) was 7.70 and 0.10 ng/ml for patients with and without proven CRBSI, respectively (p < 0.001). The area under the curve (AUC) for PCT was 0.990 (95% CI; 0.972 – 1.000), whereas a cut-off value of 0.70 ng/ml provided sensitivity and specificity of 92.3 and 100% respectively. In contrast, the AUC for white blood cells (WBC) was 0.539 (95% CI; 0.369 – 0.709), and for C-reactive protein (CRP), 0.603 (95% CI; 0.438 – 0.768). PCT was the best predictor of proven infection. Moreover, an increase >0.20 ng/ml of PCT between the D0 and any of the 4 preceding days was associated with a positive predictive value exceeding 96%. PCT concentrations from the D2 to D6 after suspected infection tended to decrease in controlled patients, whereas remained stable in non-controlled subjects. A PCT concentration exceeding 1.5 ng/ml during D3 was associated with lack of responsiveness to therapy (p = 0.028).
Conclusions
We suggest that PCT could be a helpful diagnostic and prognostic marker of CRBSI in critically ill patients. Both absolute values and variations should be considered.
doi:10.1186/1471-2334-12-247
PMCID: PMC3502591  PMID: 23043618
8.  Soluble Triggering Receptor Expressed on Myeloid Cells-1 Is an Early Marker of Infection in the Surgical Intensive Care Unit 
Surgical Infections  2009;10(5):435-439.
Abstract
Background
To determine the value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in early differentiation of systemic inflammatory response syndrome (SIRS) from infection in patients in a surgical intensive care unit (ICU).
Methods
Patients were enrolled if there was clinical suspicion of infection and they fulfilled at least two criteria of SIRS at the time of admission to the ICU. The patients were classified as having SIRS (no infection; n = 37) or infection (n = 56) on the basis of the decision of the treating physician and bacteriological evidence of infection. The plasma concentrations of sTREM-1 in the two groups were compared.
Results
Patients with infection had significantly higher sTREM-1 concentrations than patients with SIRS: Median 398 pg/mL (interquartile range [IQR] 302, 552) vs. 78 pg/mL (IQR 28, 150), respectively (p < 0.0001). At a cut-off of 230 pg/mL, sTREM-1 correctly identified patients suffering from infection with 96% sensitivity and 91% specificity.
Conclusions
In the present study, sTREM-1 was an accurate tool for differentiating SIRS from infection in patients in the surgical ICU.
doi:10.1089/sur.2009.030
PMCID: PMC2956524  PMID: 19792836
9.  Procalcitonin as an adjunctive biomarker in sepsis 
Indian Journal of Anaesthesia  2011;55(3):266-270.
Sepsis can sometimes be difficult to substantiate, and its distinction from non-infectious conditions in critically ill patients is often a challenge. Serum procalcitonin (PCT) assay is one of the biomarkers of sepsis. The present study was aimed to assess the usefulness of PCT assay in critically ill patients with suspected sepsis. The study included 40 patients from the intensive care unit with suspected sepsis. Sepsis was confirmed clinically and/or by positive blood culture. Serum PCT was assayed semi-quantitatively by rapid immunochromatographic technique (within 2 hours of sample receipt). Among 40 critically ill patients, 21 had clinically confirmed sepsis. There were 12 patients with serum PCT ≥10 ng/ml (8, blood culture positive; 1, rickettsia; 2, post-antibiotic blood culture sterile; and 1, non-sepsis); 7 patients with PCT 2-10 ng/ml (4, blood culture positive; 1, falciparum malaria; 2, post-antibiotic blood culture sterile); 3 patients with PCT of 0.5 to 2 ng/ml (sepsis in 1 patient); and 18 patients with PCT < 0.5 ng/ml (sepsis in 2 patients). Patients with PCT ≥ 2 ng/ml had statistically significant correlation with the presence of sepsis (P<0.0001). The PCT assay revealed moderate sensitivity (86%) and high specificity (95%) at a cut-off ≥ 2 ng/ml. The PCT assay was found to be a useful biomarker of sepsis in this study. The assay could be performed and reported rapidly and provided valuable information before availability of culture results. This might assist in avoiding unwarranted antibiotic usage.
doi:10.4103/0019-5049.82676
PMCID: PMC3141151  PMID: 21808399
Blood culture; immunochromatographic assay ; procalcitonin; sepsis
10.  Can serum procalcitonin and C-reactive protein as nosocomial infection markers in hospitalized patients without localizing signs?* 
BACKGROUND:
Early diagnosis of infection with the use of valuable markers leads to decreased mortality and morbidity. The aim of this study was to evaluate the value of procalcitonin (PCT) and C-reactive protein (CRP) for detecting nosocomial infection in hospitalized patients without localizing signs.
METHODS:
We conducted a prospective observational study on 150 hospitalized patients with fever > 38°C emerging 48-72 hours after their admission at Alzahra Hospital, Isfahan, Iran. The subjects did not have any localizing sign of infection. PCT and CRP values were determined using rapid tests and were compared with results of blood culture as the standard test. The sensitivity, specificity, positive and negative predictive values (PV) and likelihood ratios (LRs) were calculated for both PCT and CRP. Receiver operating characteristic (ROC) curves were also used to evaluate the diagnostic value of the PCT and CRP for detecting nosocomial infections. Finally, the areas under the resulting curves were compared.
RESULTS:
PCT had a sensitivity of 57.1%, a specificity of 89.1%, a positive PV of 46.2%, and a negative PV of 92.7% while the corresponding percentages for CRP test were 76.2%, 48%, 19.3%, and 92.5%. PCT marker also had a higher positive LR and lower negative LR than did CRP marker. The observed areas under the ROC curves were 0.73 for CRP (95% CI, 0.63-0.82; p = 0.023) and 0.80 for PCT (95% CI, 0.68-0.91; p = 0.001). The optimal cut-off values (best diagnostic accuracy) were 39 mg/L for CRP and 7.5 ng/mL for PCT.
CONCLUSIONS:
Determination of PCT and CRP is a valuable tool for identifying nosocomial infections. PCT showed better specificity, negative and positive PV. However CRP showed significantly better sensitivity compared with PCT. Therefore, these tests should be considered as part of initial work-up for patients with unknown source of infection.
PMCID: PMC3430017  PMID: 22973321
Nosocomial Infection; Blood Culture; Procalcitonin; C-Reactive Protein
11.  Use of Procalcitonin in Patients on Chronic Hemodialysis: Procalcitonin Is Not Related with Increased Serum Calcitonin 
ISRN Urology  2012;2012:431859.
Objectives. To investigate whether procalcitonin (PCT) could be useful for detecting bacterial infections in patients on hemodialysis (HD) and with increased calcitonin (CT). Methods. This prospective study included 42 males and 34 females on HD. The infection group consisted of 15 patients with proven bacterial infections; the other 61 patients were designated as the noninfection group. Serum C-reactive protein (CRP), interleukin (IL)-6, white blood cell (WBC) count, immature and total neutrophil (I/T) ratio, and CT were measured at the beginning of HD, and serum PCT levels at the beginning of HD and after HD. Results. The mean CT level in the both groups was apparently higher than that of nonchronic kidney disease. Significantly higher values between the infection and noninfection groups were seen for CRP, IL-6, WBC, I/T ratio, PCT, and CT. The PCT value of the area under the receiver operating characteristic curve was 0.921, which was significantly higher than the values for CRP (0.853; P < 0.01), IL-6 (0.739; P < 0.01), WBC (0.692; P < 0.01), and I/T ratio (0.584; P < 0.01). Conclusions. PCT was useful marker of bacterial infection in patients on HD and with increased CT. PCT levels should be determined before HD.
doi:10.5402/2012/431859
PMCID: PMC3363985  PMID: 22685675
12.  Procalcitonin does discriminate between sepsis and systemic inflammatory response syndrome 
Archives of Disease in Childhood  2005;91(2):117-120.
Aims
To evaluate whether procalcitonin (PCT) and C reactive protein (CRP) are able to discriminate between sepsis and systemic inflammatory response syndrome (SIRS) in critically ill children.
Methods
Prospective, observational study in a paediatric intensive care unit. Kinetics of PCT and CRP were studied in patients undergoing open heart surgery with cardiopulmonary bypass (CPB) (SIRS model; group I1) and patients with confirmed bacterial sepsis (group II).
Results
In group I, PCT median concentration was 0.24 ng/ml (reference value <2.0 ng/ml). There was an increment of PCT concentrations which peaked immediately after CPB (median 0.58 ng/ml), then decreased to 0.47 ng/ml at 24 h; 0.33 ng/ml at 48 h, and 0.22 ng/ml at 72 h. CRP median concentrations remained high on POD1 (36.6 mg/l) and POD2 (13.0 mg/l). In group II, PCT concentrations were high at admission (median 9.15 ng/ml) and subsequently decreased in 11/14 patients who progressed favourably (median 0.31 ng/ml). CRP levels were high in only 11/14 patients at admission. CRP remained high in 13/14 patients at 24 h; in 12/14 at 48 h; and in 10/14 patients at 72 h. Median values were 95.0, 50.9, 86.0, and 20.3 mg/l, respectively. The area under the ROC curve was 0.99 for PCT and 0.54 for CRP. Cut off concentrations to differentiate SIRS from sepsis were >2 ng/ml for PCT and >79 mg/l for CRP.
Conclusion
PCT is able to differentiate between SIRS and sepsis while CRP is not. Moreover, unlike CRP, PCT concentrations varied with the evolution of sepsis.
doi:10.1136/adc.2005.077446
PMCID: PMC2082702  PMID: 16326799
procalcitonin (PCT); C reactive protein (CRP); cardiopulmonary bypass (CPB); systemic inflammatory response syndrome (SIRS); sepsis
13.  Diagnostic implications of soluble triggering receptor expressed on myeloid cells-1 in patients with acute respiratory distress syndrome and abdominal diseases: a preliminary observational study 
Critical Care  2011;15(1):R50.
Introduction
Patients admitted to the intensive care unit (ICU) because of acute or decompensated chronic abdominal disease and acute respiratory failure need to have the potential infection diagnosed as well as its site (pulmonary or abdominal). For this purpose, we measured soluble triggering receptor expression on myeloid cells-1 (sTREM-1) in alveolar and peritoneal fluid.
Methods
Consecutive patients (n = 21) with acute or decompensated chronic abdominal disease and acute respiratory failure were included. sTREM was measured in alveolar (A-sTREM) and peritoneal (P-sTREM) fluids.
Results
An infection was diagnosed in all patients. Nine patients had a lung infection (without abdominal infection), 5 had an abdominal infection (without lung infection) and seven had both infections. A-sTREM was higher in the patients with pneumonia compared to those without pneumonia (1963 ng/ml (1010-3129) vs. 862 ng/ml (333-1011); P 0.019). Patients with abdominal infection had an increase in the P-sTREM compared to patients without abdominal infection (1941 ng/ml (1088-3370) vs. 305 ng/ml (288-459); P < 0.001). A cut-off point of 900 pg/ml of A-sTREM-1 had a sensitivity of 81% and a specificity of 80% (NPV 57%; PPV 93%, AUC 0.775) for the diagnosis of pneumonia. In abdominal infections, a cut-off point for P-sTREM of 900 pg/ml had the best results (sensitivity 92%; specificity 100%; NPV 90%, PPV 100%, AUC = 0.903).
Conclusions
sTREM-1 measured in alveolar and peritoneal fluids is useful in assessing pulmonary and peritoneal infection in critical-state patients-A-sTREM having the capacity to discriminate between a pulmonary and an extra-pulmonary infection in the context of acute respiratory failure.
doi:10.1186/cc10015
PMCID: PMC3221980  PMID: 21294874
14.  Utility of Procalcitonin as an Early Diagnostic Marker of Bacteremia in Patients with Acute Fever 
Yonsei Medical Journal  2011;52(2):276-281.
Purpose
Procalcitonin (PCT) is a current, frequently used marker for severe bacterial infection. The aim of this study was to assess the ability of PCT levels to differentiate bacteremic from nonbacteremic patients with fever. We assessed whether PCT level could be used to accurately rule out a diagnosis of bacteremia.
Materials and Methods
Serum samples and blood culture were obtained from patients with fever between August 2008 and April 2009. PCT was analyzed using a VIDAS® B.R.A.H.M.S PCT assay. We reviewed the final diagnosis and patient histories, including clinical presentation and antibiotic treatment.
Results
A total of 300 patients with fevers were enrolled in this study: 58 with bacteremia (positive blood culture) (group I); 137 with local infection (group II); 90 with other diseases (group III); and 15 with fevers of unknown origin (group IV). PCT levels were significantly higher in patients with bacteremia than in those with non-bacteremia (11.9 ± 25.1 and 2.5 ± 14.7 ng/mL, respectively, p < 0.001). The sensitivity and specificity were 74.2% and 70.1%, respectively, at a cut-off value of 0.5 ng/mL. A serum PCT level of < 0.4 ng/mL accurately rules out diagnosis of bacteremia.
Conclusion
In febrile patients, elevated PCT may help predict bacteremia; furthermore, low PCT levels were helpful for ruling out bacteremia as a diagnosis. Therefore, PCT assessment could help physicians limit the number of prescriptions for antibiotics.
doi:10.3349/ymj.2011.52.2.276
PMCID: PMC3051230  PMID: 21319346
Bacteremia; procalcitonin; infection
15.  A Prospective Bicenter Study Investigating the Diagnostic Value of Procalcitonin in Patients with Acute Appendicitis 
Background
Procalcitonin (PCT) is an established laboratory marker for disease severity in patients with infection and sepsis. In addition, PCT has been shown to be an effective marker for a limited number of localized infections. However, whether or not PCT has any diagnostic value for acute appendicitis, still remains unclear. The purpose of this prospective bicenter study was, therefore, to determine whether or not the PCT levels in the serum of patients with acute appendicitis have any diagnostic value.
Methods
This prospective study included 103 patients who received an appendectomy, based on the clinical diagnosis of acute appendicitis, in a surgical department of an academic teaching hospital in Germany or in a county hospital in Spain. White blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT) values were determined preoperatively. All appendectomy specimens were sent for routine histopathological evaluation. Based on this information, the patients were assigned to 1 of 5 groups that reflected the severity of the appendicitis.
Results
Of the 103 patients who were included in the study, 98 had appendicitis. Fourteen (14.3%) showed an increase in PCT values. Of those 14, 4 had a serum PCT >0.5 ng/ml, 9 had a PCT value >2–10 ng/ml and 1 had a PCT value >10 ng/ml. The sensitivity of PCT was calculated to be 0.14. The mean WBC value was 13.0/nl (± 5.2, 3.4–31), and for CRP it was 8.8 mg/dl (± 13, 0–60.2). The values of CRP, WBC and PCT increased with the severity of the appendicitis.
Conclusions
PCT is potentially increased in rare cases of severe inflammation and, in particular, after appendiceal perforation or gangrenous appendicitis. However, its remarkably low sensitivity prohibits its routine use for the diagnosis of appendicitis.
doi:10.1159/000232939
PMCID: PMC2790741  PMID: 19672084
Procalcitonin; Appendicitis; Diagnostic
16.  Diagnostic Value of Simultaneous Measurement of Procalcitonin, Interleukin-6 and hs-CRP in Prediction of Early-Onset Neonatal Sepsis 
Neonatal sepsis is a major cause of morbidities and mortalities mostly remarkable in the third world nations.We aimed to assess the value of simultaneous measurement of procalcitonin (PCT) and interleukin-6 (IL-6) in association with high sensitive- C reactive protein(hs-CRP) in prediction of early neonatal sepsis.
A follow-up study was performed on 95 neonates who were below 12 hours (h) of age and had clinical signs of sepsis or maternal risk factors for sepsis. Neonates were assigned to 4 groups including “proven early-onset sepsis”, “clinical early-onset sepsis”, “negative infectious status”, and “uncertain infectious status”. Blood samples were obtained within the first 12 h of birth repeated between 24 hours and 36 hours of age for determination of serum levels of PCT, IL-6, hs-CRP, and white blood cell (WBC) count.
On admission, neonates with sepsis had a higher WBC count, IL-6, PCT, and hs-CRP levels compared with those neonates without sepsis. This remained significant even after 12–24 hours of admission. Also, patients with clinical evidences of sepsis had a higher serum level of PCT and IL-6 within 12–24 hours after admission compared to the patients with uncertain sepsis.
The combination of PCT and IL-6 yielded had a sensitivity of 88% and PCT and CRP (using the cutoff value of 8 mg/L) a sensitivity of 82%.The areas under the ROC curve for the two periods were 0.801, and 0.819 respectively.
In final The combination of IL-6, hs-CRP, and PCT seems to be predictive in diagnosis of early onset neonatal sepsis.
doi:10.4084/MJHID.2012.028
PMCID: PMC3375671  PMID: 22708043
17.  Usefulness of procalcitonin for diagnosis of sepsis in the intensive care unit 
Critical Care  2002;7(1):85-90.
Introduction
The diagnosis of sepsis in critically ill patients is challenging because traditional markers of infection are often misleading. The present study was conducted to determine the procalcitonin level at early diagnosis (and differentiation) in patients with systemic inflammatory response syndrome (SIRS) and sepsis, in comparison with C-reactive protein, IL-2, IL-6, IL-8 and tumour necrosis factor-α.
Method
Thirty-three intensive care unit patients were diagnosed with SIRS, sepsis or septic shock, in accordance with the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria. Blood samples were taken at the first and second day of hospitalization, and on the day of discharge or on the day of death. For multiple group comparisons one-way analysis of variance was applied, with post hoc comparison. Sensitivity, specificity and predictive values of PCT and each cytokine studied were calculated.
Results
PCT, IL-2 and IL-8 levels increased in parallel with the severity of the clinical condition of the patient. PCT exhibited a greatest sensitivity (85%) and specificity (91%) in differentiating patients with SIRS from those with sepsis. With respect to positive and negative predictive values, PCT markedly exceeded other variables.
Discussion
In the present study PCT was found to be a more accurate diagnostic parameter for differentiating SIRS and sepsis, and therefore daily determinations of PCT may be helpful in the follow up of critically ill patients.
doi:10.1186/cc1843
PMCID: PMC154110  PMID: 12617745
C-reactive protein; cytokine; diagnosis; procalcitonin; sepsis
18.  Impact of previous sepsis on the accuracy of procalcitonin for the early diagnosis of blood stream infection in critically ill patients 
Background
Blood stream infections (BSI) are life-threatening infections in intensive care units (ICU), and prognosis is highly dependent on early detection. Procalcitonin levels have been shown to accurately and quickly distinguish between BSI and noninfectious inflammatory states in critically ill patients. It is, however, unknown to what extent a recent history of sepsis (namely, secondary sepsis) can affect diagnosis of BSI using PCT.
Methods
review of the medical records of every patient with BSI in whom PCT dosage at the onset of sepsis was available between 1st September, 2006 and 31st July, 2007.
Results
179 episodes of either primary (n = 117) or secondary (n = 62) sepsis were included. Procalcitonin levels were found to be markedly lower in patients with secondary sepsis than in those without (6.4 [9.5] vs. 55.6 [99.0] ng/mL, respectively; p < 0.001), whereas the SOFA score was similar in the two groups. Although patients in the former group were more likely to have received steroids and effective antibiotic therapy prior to the BSI episode, and despite a higher proportion of candidemia in this group, a low PCT value was found to be independently associated with secondary sepsis (Odd Ratio = 0.33, 95% Confidence Interval: 0.16–0.70; p = 0.004). Additional patients with suspected but unconfirmed sepsis were used as controls (n = 23). Thus, diagnostic accuracy of PCT as assessed by the area under the receiver-operating characteristic curves (AUROCC) measurement was decreased in the patients with secondary sepsis compared to those without (AUROCC = 0.805, 95% CI: 0.699–0.879, vs. 0.934, 95% CI: 0.881–0.970, respectively; p < 0.050).
Conclusion
In a critically ill patient with BSI, PCT elevation and diagnosis accuracy could be lower if sepsis is secondary than in those with a first episode of infection.
doi:10.1186/1471-2334-8-163
PMCID: PMC2614426  PMID: 19055740
19.  Procalcitonin: A Reliable Marker for the Diagnosis of Neonatal Sepsis 
Objective(s)
In the last few years, serum procalcitonin has been proposed as an early marker of infections in neonates, with varying results. In this study, we aimed to investigate the value of procalcitonin, and C- reactive protein in establishing the diagnosis of neonatal sepsis.
Materials and Methods
Blood samples were collected at admission from 69 neonates with suspected infection (admitted to the Neonatal Intensive Care Units at Alzahra and Dr Beheshti Hospital in and Fatema-Zahra in Najafabad from May 2005 to April 2006). Patients were categorized in different groups according to clinical symptoms of sepsis, bacteriological and laboratory results. Group I consisted of 20 newborns with positive blood cultures and other biological tests which suggested infection. Group II consisted of 49 neonates with negative blood cultures but had two or three of clinical signs of sepsis. The control group included 18 healthy neonates with physiological hyperbilirubinemia and no clinical and biological data of infection, referred to the hospital for bilirubin determination. Procalcitonin and C-reactive protein (CRP) were determined by immunoluminometric assay and nephlometry method respectively.
Results
Mean levels of procalcitonin and CRP in septic neonates (group I) were significantly higher than the other two groups (P< 0.005). Sensitivity, specificity, positive predictive value and negative predictive value were determined for all markers and compared with each other.
Conclusion
We conclude that procalcitonin is a better marker than CRP in the diagnosis of neonatal sepsis.
PMCID: PMC3586883  PMID: 23493845
C-reactive protein; Neonatal sepsis; Procalcitonin
20.  Procalcitonin levels in acute exacerbation of COPD admitted in ICU: a prospective cohort study 
Background
Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU). Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population.
Methods
We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006. Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses. PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay.
Results
Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission. The median [25%–75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 μg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 μg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 μg/L [IQR, 0.088 to 0.252] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 μg/L in 14/35 (40%) patients and more than 0.25 μg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively. Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients. Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 μg/L and three had a PCTmax less than 0.1 μg/L. The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 μg/L. The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 μg/L respectively, P = 0.80).
Conclusion
The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 μg/L) suggesting a possible inappropriate use of antibiotics. Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.
doi:10.1186/1471-2334-8-145
PMCID: PMC2577677  PMID: 18947382
21.  Predictive value of procalcitonin decrease in patients with severe sepsis: a prospective observational study 
Critical Care  2010;14(6):R205.
Introduction
This prospective study investigated the predictive value of procalcitonin (PCT) for survival in 242 adult patients with severe sepsis and septic shock treated in intensive care.
Methods
PCT was analyzed from blood samples of all patients at baseline, and 155 patients 72 hours later.
Results
The median PCT serum concentration on day 0 was 5.0 ng/ml (interquartile range (IQR) 1.0 and 20.1 ng/ml) and 1.3 ng/ml (IQR 0.5 and 5.8 ng/ml) 72 hours later. Hospital mortality was 25.6% (62/242). Median PCT concentrations in patients with community-acquired infections were higher than with nosocomial infections (P = 0.001). Blood cultures were positive in 28.5% of patients (n = 69), and severe sepsis with positive blood cultures was associated with higher PCT levels than with negative cultures (P = < 0.001). Patients with septic shock had higher PCT concentrations than patients without (P = 0.02). PCT concentrations did not differ between hospital survivors and nonsurvivors (P = 0.64 and P = 0.99, respectively), but mortality was lower in patients whose PCT concentration decreased > 50% (by 72 hours) compared to those with a < 50% decrease (12.2% vs. 29.8%, P = 0.007).
Conclusions
PCT concentrations were higher in more severe forms of severe sepsis, but a substantial concentration decrease was more important for survival than absolute values.
doi:10.1186/cc9327
PMCID: PMC3219988  PMID: 21078153
22.  Procalcitonin Predicts Real-Time PCR Results in Blood Samples from Patients with Suspected Sepsis 
PLoS ONE  2012;7(12):e53279.
Background
Early diagnosis and rapid bacterial identification are of primary importance for outcome of septic patients. SeptiFast® (SF) real-time PCR assay is of potential utility in the etiological diagnosis of sepsis, but it cannot replace blood culture (BC) for routine use in clinical laboratory. Procalcitonin (PCT) is a marker of sepsis and can predict bacteremia in septic patients. The aim of the present study was to investigate whether PCT serum levels could predict SF results, and could help screening febrile patients in which a SF assay can improve the etiological diagnosis of sepsis.
Methods
From 1009 febrile patients with suspected sepsis, 1009 samples for BC, SF real-time PCR, and PCT determination were obtained simultaneously, and results were compared and statistically analysed. Receiver operating characteristic (ROC) curves were generated to determine the area under the curve and to identify which cut-off of PCT value produced the best sensitivity to detect SF results.
Results
Mean PCT values of sera drawn simultaneously with samples SF positive (35.42±61.03 ng/ml) or BC positive (23.14±51.56 ng/ml) for a pathogen were statistically higher than those drawn simultaneously with SF negative (0.84±1.67 ng/ml) or BC negative (2.79±16.64 ng/ml) samples (p<0.0001). For SF, ROC analysis showed an area under the curve of 0.927 (95% confidence interval: 0.899–0.955, p<0.0001). The PCT cut-off value of 0.37 ng/ml showed a negative predictive value of 99%, reducing the number of SF assays of 53.9%, still identifying the 96.4% of the pathogens.
Conclusion
PCT can be used in febrile patients with suspected sepsis to predict SF positive or negative results. A cut-off value of 0.37 ng/ml can be considered for optimal sensitivity, so that, in the routine laboratory activity, SF assay should not be used for diagnosis of sepsis in an unselected patient population with a PCT value <0.37 ng/ml.
doi:10.1371/journal.pone.0053279
PMCID: PMC3531374  PMID: 23300907
23.  DIAGNOSTIC UTILITY OF SERUM PROCALCITONIN LEVELS IN PULMONARY ASPIRATION SYNDROMES 
Critical care medicine  2011;39(6):1251-1256.
Objective
To assess the predictive accuracy of serum procalcitonin (PCT) in distinguishing bacterial aspiration pneumonia from aspiration pneumonitis.
Design
Prospective observational study.
Setting
Intensive care unit of a University-affiliated hospital.
Patients
Sixty five consecutive patients admitted with pulmonary aspiration and 7 controls intubated for airway protection.
Interventions and results
Quantitative cultures from bronchoalveolar lavage (BAL) fluid were conducted on all participants at the time of admission. Serial serum PCT levels were measured on day 1 and day 3 using the PCT enzyme-linked fluorescent assay. There were no differences in the median serum concentrations of PCT between patients with positive BAL cultures (n=32) and patients with negative BAL cultures (n=33) on either day 1 or day 3 post admission. The areas under the ROC curves were 0.59 (95% CI 0.47–0.72) and 0.63 (95% CI 0.5–0.75), respectively (p=0.74). However, duration of mechanical ventilation and antibiotic therapy were shorter in those who had a decrease in their PCT levels on day 3 from baseline compared to those who did not (6.7±7.1 days and 11.1±13.5 days, p=0.03; and 8.2±2.6 days versus 12.8±4.6 days; p<0.001, respectively). Hospital mortality was associated with radiographic multilobar disease (adjusted odds ratio (AOR) 1.14; 95% CI 1.01 to 1.31; p=0.04) and increasing procalcitonin levels (AOR 5.63; 95% CI 1.56 to 20.29; p= 0.008).
Conclusion
Serum PCT levels had poor diagnostic value in separating bacterial aspiration pneumonia from aspiration pneumonitis based on quantitative BAL culture. However, serial measurements of serum PCT may be helpful in predicting survival from pulmonary aspiration.
doi:10.1097/CCM.0b013e31820a942c
PMCID: PMC3102149  PMID: 21283001
procalcitonin; aspiration pneumonia; aspiration pneumonitis; outcome; intensive care unit
24.  Soluble Triggering Receptor Expressed on Myeloid cells-1 in bronchoalveolar lavage fluid is not predictive for ventilator-associated pneumonia 
Intensive Care Medicine  2009;35(7):1265-1270.
Purpose
Soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1) has proven to be a good biomarker for sepsis. For the diagnosis ventilator-associated pneumonia (VAP), however, there have only been a few, relatively small, studies on the role of this receptor. The aim of the study was to evaluate the usefulness of sTREM-1 in bronchoalveolar lavage fluid (BALF) from Intensive Care Unit patients as rapid diagnostic test for VAP.
Methods
The concentration of sTREM-1 in 240 BALF samples was measured using a quantitative sandwich enzyme immunoassay. Two researchers who were blind to the assay results determined whether a VAP was present or not. Clinical suspicion of a VAP was confirmed by the presence of ≥2% cells containing intracellular organisms and/or a quantitative culture result of ≥104 colony forming units per millilitre BALF.
Results
The mean concentration of sTREM-1 was significantly higher in the BALF of patients with confirmed VAP than in that of patients without confirmed VAP. However, the area under the receiver-operating characteristic curve was 0.58 (95% confidence interval 0.50–0.65, P = 0.04).
Conclusions
The results imply that the sTREM-1 assay in BALF may not be discriminative for VAP.
doi:10.1007/s00134-009-1463-y
PMCID: PMC2698974  PMID: 19343323
Artificial respiration; Biological marker; Early diagnosis; Enzyme-linked immunosorbent assay; Intensive care; Respiratory tract infections
25.  Can procalcitonin measurement help in differentiating between bacterial infection and other kinds of inflammatory processes? 
Annals of the Rheumatic Diseases  2003;62(4):337-340.
Objective: To study the levels of procalcitonin (PCT) in various inflammatory states seen in an internal medicine department and to evaluate the possible discriminative role of PCT in differentiating bacterial infection from other inflammatory processes.
Methods: PCT, C reactive protein (CRP), and white blood cell count (WBC) were measured in patients admitted to the department for fever or biological inflammatory syndrome, or both. The serum of 173 consecutive patients was analysed according to the aetiological diagnosis. The patients were divided into two groups: group I (n=60) with documented bacterial or fungal infection; group II (n=113) with abacterial inflammatory disease.
Results: PCT levels were >0.5 ng/ml in 39/60 (65%) patients in group I. In group II, three patients with a viral infection had slightly increased PCT levels (0.7, 0.8, and 1.1 ng/ml) as did two others, one with crystal arthritis and the other with vasculitis (0.7 ng/ml in both cases). All other patients in group II had PCT levels <0.5 ng/ml. In this study a value of PCT >0.5 ng/ml was taken as the marker of bacterial infection (sensitivity 65%, specificity 96%). PCT values were more discriminative than WBC and CRP in distinguishing a bacterial infection from another inflammatory process.
Conclusion: PCT levels only rose significantly during bacterial infections. In this study PCT levels >1.2 ng/ml were always evidence of bacterial infection and the cue for starting antibiotic treatment.
doi:10.1136/ard.62.4.337
PMCID: PMC1754509  PMID: 12634233

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