Diagnostic Accuracy of Procalcitonin for Early Aspiration Pneumonia in Critically Ill Patients with Coma: A Prospective Study.

BACKGROUND: Early diagnostic orientation for differentiating pneumonia from pneumonitis at the early stage after aspiration would be valuable to avoid unnecessary antibiotic therapy. We assessed the accuracy of procalcitonin (PCT) in diagnosing aspiration pneumonia (AP) in intensive care unit (ICU) patients requiring mechanical ventilation after out-of-hospital coma. METHODS: Prospective observational 2-year cohort study in a medical-surgical ICU. PCT, C-reactive protein (CRP) and white blood cell count (WBC) were measured at admission (H0) and 6 h (H), H12, H24, H48, H96, and H120 after inclusion. Lower respiratory tract microbiological investigations performed routinely in patients with aspiration syndrome were the reference standard for diagnosing AP. Performance of PCT, CRP, and WBC up to H48 in diagnosing AP was compared based on the areas under the ROC curves (AUC) and likelihood ratios (LR+ and LR-) computed for the best cutoff values. RESULTS: Of 103 patients with coma, 45 (44%) had AP. Repeated PCT assays demonstrated a significant increase in patients with AP versus without AP from H0 to H120. Among the three biomarkers, PCT showed the earliest change. ROC-AUC values were poor for all three biomarkers. Best ROC-AUC values for diagnosing AP were for CRP at H24 [0.73 (95%CI 0.61-0.84)] and PCT at H48 [0.73 (95%CI 0.61-0.84)]. LR+ was best for PCT at H24 (3.5) and LR- for CRP and WBC at H24 (0.4 and 0.4, respectively). CONCLUSIONS: Early and repeated assays of PCT, CRP, and WBC demonstrated significant increases in all three biomarkers in patients with versus without AP. All three biomarkers had poor diagnostic performance for ruling out AP. Whereas PCT had the fastest kinetics, PCT assays within 48 h after ICU admission do not help to diagnose AP in ICU patients with coma.

Wide-range CRP versus high-sensitivity CRP on Roche analyzers: focus on low-grade inflammation ranges and high-sensitivity cardiac troponin T levels.

Wide-range C-reactive protein (wr-CRP) has been proposed as an economical alternative to high-sensitivity C-reactive protein (hs-CRP) for the evaluation of low-grade inflammation-associated cardiovascular risk (LGI-CVR). Concomitant values of serum hs-CRP and plasma wr-CRP ≤5 mg/L, and high-sensitivity cardiac troponin T (hs-cTnT), all assayed on Roche Diagnostics analyzers over a 1.8-year period, were extracted from a hospital laboratory database. Hs-CRP and wr-CRP values were compared (Bland-Altman method; Deming's correlation), then separately classified into low (<1 mg/L), moderate (1-3 mg/L) and high (>3 mg/L) LGI-CVR ranges for agreement test (κ), assessed before and after Deming's regression-based adjustment of wr-CRP (Adj-wr-CRP). Wr-CRP and hs-CRP values were strongly correlated, with linearity, whether below 5 mg/L (n = 744; τ = 0.933; p < .001) or below 1 mg/L (n = 283; τ = 0.823; p < .001). Overall, wr-CRP values were lower than hs-CRP (mean bias: -0.11 ± 0.17 mg/L). Agreement was good, with 8.1% of wr-CRP values misclassified compared to hs-CRP (κ: 0.874), and weakly improved after regression-based adjustment (7.7% reclassified values; κ: 0.881). Lowering the Adj-wr-CRP cutoff of the moderate LGI-CVR subrange from 1.0 to 0.9 mg/L resulted in an almost perfect agreement (3.2% reclassified data; κ: 0.950). Hs-cTnT concentration was positively associated with hs-CRP, wr-CRP, and Adj-wr-CRP (p < .001). Within each LGI-CVR subrange, hs-cTnT medians were similar regardless of the hs-CRP, wr-CRP or Adj-wr-CRP used for risk classification. Based on hs-cTnT, this study supports the use of wr-CRP as a low-cost alternative to hs-CRP for cardiovascular risk evaluation.

Comparison between B·R·A·H·M·S PCT direct, a new sensitive point-of-care testing device for rapid quantification of procalcitonin in emergency department patients and established reference methods - a prospective multinational trial.

BACKGROUND: Procalcitonin (PCT) is increasingly being used for the diagnostic and prognostic work up of patients with suspected infections in the emergency department (ED). Recently, B·R·A·H·M·S PCT direct, the first high sensitive point-of-care test (POCT), has been developed for fast PCT measurement on capillary or venous blood samples. METHODS: This is a prospective, international comparison study conducted in three European EDs. Consecutive patients with suspicion of bacterial infection were included. Duplicate determination of PCT was performed in capillary (fingertip) and venous whole blood (EDTA), and compared to the reference method. The diagnostic accuracy was evaluated by correlation and concordance analyses. RESULTS: Three hundred and three patients were included over a 6-month period (60.4% male, median age 65.2 years). The correlation between capillary or venous whole blood and the reference method was excellent: r2=0.96 and 0.97, sensitivity 88.1% and 93.0%, specificity 96.5% and 96.8%, concordance 93% and 95%, respectively at a 0.25 µg/L threshold. No significant bias was observed (-0.04 and -0.02 for capillary and venous whole blood) although there were 6.8% and 5.1% outliers, respectively. B·R·A·H·M·S PCT direct had a shorter time to result as compared to the reference method (25 vs. 144 min, difference 119 min, 95% CI 110-134 min, p<0.0001). CONCLUSIONS: This study found a high diagnostic accuracy and a faster time to result of B·R·A·H·M·S PCT direct in the ED setting, allowing shortening time to therapy and a more wide-spread use of PCT.

Comparison of LUMIPULSE(®) G1200 With Kryptor and Modular E170 for the Measurement of Seven Tumor Markers.

BACKGROUND: Tumor marker measurements are becoming essential for prognosis and follow-up of patients in oncology. In this context, we aimed to compare a new analyzer, Lumipulse(®) G1200 (Fujirebio group, distributed in Europe by the Innogenetics group) with Kryptor(®) (Thermo Fisher Scientific B.R.A.H.M.S, Asnières, France) and Modular(®) Elecsys E170 (Roche Diagnostics, Meylan, France) for the measurement of seven tumor markers: PSA, AFP, CEA, CA 15-3, CA 125, CA 19-9, and Cyfra 21-1. METHODS: A total of 471 serum samples from patients with elevated tumor markers and 100 serum from healthy patients were analyzed with Lumipulse(®) G1200 and either Kryptor(®) (for AFP) or Modular(®) (for the six other markers). RESULTS: The good precision of Lumipulse(®) G1200 assays was confirmed with CVs < 2.5% and < 5.0%, obtained, respectively, for within-run imprecision and intermediate imprecision (except for Cyfra 21-1: CV < 13%). For all markers, Lumipulse results were well correlated with Modular or Kryptor results (r ≥ 0.94). Concordance of results interpretation was > 95% and tumor marker kinetics were all similar. CONCLUSION: We confirmed the analytical performances of Lumipulse(®) tumor marker assays except for the CYFRA 21-1 assay for which performances were poor in this study. We noticed a few discrepancies for the CEA assay. Besides, values obtained for CA 19-9 were higher with Lumipulse leading to a bias (slope = 1.5). But for the four other tumor markers assays (PSA, AFP, CA 125, CA 15-3), the results were directly transferable between Lumipulse and Kryptor or Modular, thus facilitating an eventual substitution of one system by another.

Biomarkers from distinct biological pathways improve early risk stratification in medical emergency patients: the multinational, prospective, observational TRIAGE study.

INTRODUCTION: Early risk stratification in the emergency department (ED) is vital to reduce time to effective treatment in high-risk patients and to improve patient flow. Yet, there is a lack of investigations evaluating the incremental usefulness of multiple biomarkers measured upon admission from distinct biological pathways for predicting fatal outcome and high initial treatment urgency in unselected ED patients in a multicenter and multinational setting. METHOD: We included consecutive, adult, medical patients seeking ED care into this observational, cohort study in Switzerland, France and the USA. We recorded initial clinical parameters and batch-measured prognostic biomarkers of inflammation (pro-adrenomedullin [ProADM]), stress (copeptin) and infection (procalcitonin). RESULTS: During a 30-day follow-up, 331 of 7132 (4.6 %) participants reached the primary endpoint of death within 30 days. In logistic regression models adjusted for conventional risk factors available at ED admission, all three biomarkers strongly predicted the risk of death (AUC 0.83, 0.78 and 0.75), ICU admission (AUC 0.67, 0.69 and 0.62) and high initial triage priority (0.67, 0.66 and 0.58). For the prediction of death, ProADM significantly improved regression models including (a) clinical information available at ED admission (AUC increase from 0.79 to 0.84), (b) full clinical information at ED discharge (AUC increase from 0.85 to 0.88), and (c) triage information (AUC increase from 0.67 to 0.83) (p <0.01 for each comparison). Similarly, ProADM also improved clinical models for prediction of ICU admission and high initial treatment urgency. Results were robust in regard to predefined patient subgroups by center, main diagnosis, presenting symptoms, age and gender. CONCLUSIONS: Combination of clinical information with results of blood biomarkers measured upon ED admission allows early and more adequate risk stratification in individual unselected medical ED patients. A randomized trial is needed to answer the question whether biomarker-guided initial patient triage reduces time to initial treatment of high-risk patients in the ED and thereby improves patient flow and clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01768494 . Registered January 9, 2013.

Combined screening for open spina bifida at 11-13 weeks using fetal biparietal diameter and maternal serum markers.

OBJECTIVE: Screening at 11-13 weeks with ultrasound biparietal diameter (BPD) can detect half of open spina bifida cases. Maternal serum α-fetoprotein (AFP) levels at 15-19 weeks are increased 3- to 4-fold, in open spina bifida. We assessed whether combined screening using BPD, AFP, and other serum markers at 11-13 weeks would increase detection. STUDY DESIGN: Maternal AFP levels were measured on serum stored at 11-13 weeks in 44 open spina bifida and 182 unaffected pregnancies, and results were expressed in multiples of the median (MoM) for gestational age. All samples had been measured for free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein (PAPP)-A. A multivariate Gaussian model was used to predict screening performance from the serum data and BPD measurements on 80 cases, including 36 previously published. RESULTS: The median AFP level in cases was 1.201 MoM, significantly higher than in unaffected pregnancies (P < .01, 1 tail). The median free ß-hCG was significantly reduced to 0.820 MoM (P < .02), but the median PAPP-A was similar in cases and controls. Modeling predicted the following: BPD alone would detect 50% of cases for a 5% false-positive rate or 63% for 10%; adding AFP increases detection by 2%; and a combined test with BPD, AFP, and free ß-hCG detects 58% for 5% or 70% for 10%. CONCLUSION: Combining AFP and BPD with free ß-hCG as part of first-trimester aneuploidy screening would also allow early detection about two-thirds of cases with open spina bifida.

Serum lactate and procalcitonin measurements in emergency room for the diagnosis and risk-stratification of patients with suspected infection.

OBJECTIVE: To study the contribution of lactate and procalcitonin (PCT) serum measurements for the diagnosis and the risk-stratification of patients with suspected infection presenting to the ED. METHODS: Single-center one year observational study on 462 consecutive patients. Multivariate analysis to assess variables associated with sepsis, severe sepsis, septic shock and severe outcome. RESULTS: Multivariate analysis (Odds ratio [95% CI]), showed that PCT was the best independent variable to identify sepsis (3.98 [2.60-6.10]), while lactate was the best to diagnose severe sepsis (10.88 [6.51-18.19]). Patients with both lactate above 2 mmol·L(-1) and PCT above 0.8 ng·mL(-1) had an enhanced risk of severe outcome. CONCLUSIONS: the dosages of lactate and PCT are complementary for the diagnosis and risk-stratification of patients evaluated in the ED for suspected infection.

Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial.

BACKGROUND: Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting. METHODS: In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667. FINDINGS: Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21.2% [65/307] vs 20.4% [64/314]; absolute difference 0.8%, 90% CI -4.6 to 6.2) and day 60 (30.0% [92/307] vs 26.1% [82/314]; 3.8%, -2.1 to 9.7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14.3 days [SD 9.1] vs 11.6 days [SD 8.2]; absolute difference 2.7 days, 95% CI 1.4 to 4.1, p<0.0001). INTERPRETATION: A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes. FUNDING: Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.

[Potential value of CA125 kinetic monitoring in the initial management of advanced epithelial ovarian cancer]. / Intérêt potentiel du suivi de cinétique du CA125 dans la prise en charge initiale des cancers épithéliaux de l'ovaire de stade avancé

Ovarian carcinoma is account for 4% of all women cancer deaths because of late diagnosis at advanced stage. During chemotherapy, survey includes repeated assays of antigen carbohydrate 125 (CA125), which is a membrane glycoprotein belonging to the mucin family and secreted by 80% of the serous ovarian tumours. The aim of this study was to analyze the clinical relevance of a follow-up of CA125 kinetics of five ovarian carcinoma patients at advanced stages and under neoadjuvant chemotherapy. CA125 was assayed on a Kryptor(®) (Thermo-Fisher BRAHMS) and CA125 kinetics on semi-logarithmic curve with the software "Cinetic System". This software calculates the half-life and the doubling time between two points and can detect a line of tendency. It can also point out the nadir value. Kinetics are followed during 1 or 2 years. For all patients, we observe a very good agreement between kinetics, clinical and radiological issues (tumor size reduction). For three patients, after the first chemotherapy, the lines of tendency are decreasing. In one case with peritoneal carcinomatosis, the retrospective study of the pattern showed a biphasic curve anticipating the radiological modifications. For the two other patients, the normalisation of the CA125 is never obtained with no possible surgery. A greatest study could confirm the interest of associating this graphic approach to the clinical and radiological elements in order to optimize the medico-surgical assumption of responsibility of these patients with ovarian carcinoma at advanced stages, under first adjuvant treatment.

Procalcitonin measurement in routine emergency medicine practice: comparison between two immunoassays.

BACKGROUND: Accurate identification of bacterial infections in patients presenting at the emergency department is crucial for early and rational antibiotic treatment. In this situation, using a cut-off of 0.25 microg/L for procalcitonin allows for carefully monitoring of febrile patients. Most previous studies have been performed with the reference B.R.A.H.M.S PCT KRYPTOR assay. The goal of this study was to compare this test with the VIDAS B.R.A.H.M.S PCT((R)) assay and to validate clinically relevant cut-off thresholds. METHODS: This prospective study was conducted in adults presenting to the emergency departments of a tertiary hospital. We included 305 consecutive patients that had procalcitonin requested. Procalcitonin was measured first with the KRYPTOR, then with the VIDAS systems. Statistical analysis consisted in Passing and Bablok and Bland-Altman plots. RESULTS: In the overall cohort, 176 patients had procalcitonin concentrations measured using both methods and were well correlated. The Bland-Altman plot exhibited a bias of 0.108 [95% confidence interval: -0.044 to 0.260]. The concordance at different procalcitonin cut-off thresholds, respectively of 0.1, 0.25, 0.5 and 2 microg/L, indicated that above 0.25 microg/L, the kappa coefficient was >0.80. CONCLUSIONS: A highly significant correlation was observed between the two automated assays. Procalcitonin concentrations obtained from both methods led to the same clinical interpretation.

[Importance of hemolysis on neuron-specific enolase measurement]. / Importance de l'hémolyse sur le dosage de l'énolase neurospécifique (NSE).

The aim of this work is to establish a pre-analytical approach suitable for the neuron-specific enolase (NSE) measurement. This enzyme which is synthesized by neurons and neuroendocrine cells, is a marker useful for the diagnosis and the monitoring of patients with neuroendocrine tumors (neuroblastoma, small cell lung cancer) and during stroke to assess neuronal damage. This NSE measurement is very sensitive to hemolysis due to the abundance of the enzyme in red blood cells. Two methods of evaluation of hemolysis have been compared: the determination of free haemoglobin (Hb) by spectrophotometry and the indirect measurement of an hemolytic index with a multiparameter analyzer, the Modular (Roche Diagnostics). The correlation between these 2 methods on 42 samples is very satisfactory: Y (free Hb) = 12.337 X (index) + 31.743 r = 0.997. The NSE assay is based on TRACE (Time Resolved Amplified Cryptate Emission) technology, on a Kryptor (BRAHMS). The influence of hemolysis on the determination of NSE was confirmed by overloading with hemoglobin (hemolysate) 3 pools of serum with NSE concentrations close to the threeshold decision. The determination of NSE shows an increase in concentration parallely to the hemolytic index (about 150% for an hemolytic index of 10). Consequently, in our laboratory the NSE determination is realized only for samples presenting an hemolytic index < or = 10, this allowing a good monitoring of kinetics of this marker.

Mid-regional proatrial natriuretic peptide for predicting prognosis in hypertrophic cardiomyopathy.

OBJECTIVES: N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM. METHODS: We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion. RESULTS: Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10-4) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1-2 vs 3-4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001). CONCLUSIONS: MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.

Impact of antiphospholipid biology in maternal Down syndrome screening.

OBJECTIVE: Women with antiphospholipid (aPL) biology present obstetric complications. The alpha-fetoprotein (AFP) serum levels of these patients are higher than in general population. Because AFP is involved in the calculation of the risk of trisomy 21 (T21), we studied the effect of AFP variations in the presence of aPL during T21 screening. METHODS: The study group (aPL group) was comprised of 64 pregnancies in women with aPL antibodies. The control group was comprised of 21 655 pregnancies included in the national program for routine Down syndrome (DS) screening by maternal serum markers [human chorionic gonadotrophin (hCG) and AFP] between 14 + 0 and 18 + 6 weeks of gestation. RESULTS: AFP values, converted in logarithm of multiples of the median (MoM), were significantly higher in the aPL group (0.03 vs 0.10; p = 0.018). After a matricial transformation of AFP MoM and hCG MoM in the aPL group, new T21 risks presented a median of one in 1665 versus one in 2574 (p < 0.0001 with a rank-sign test). CONCLUSION: Our results highlight the fact that in the presence of aPL antibodies, the calculated risk of T21 is underestimated. Therefore, clinicians should interpret the screening borderline results in aPL patients with caution.

Copeptin as a prognostic biomarker in acute myocardial infarction.

BACKGROUND: Copeptin - the C-terminal section of vasopressin precursor - is a novel biomarker, that has been shown to be a useful prognostic factor in heart failure, ischemic stroke and in acute myocardial infarction (MI) but with restricted population and follow-up in ST-segment elevation MI (STEMI) setting. We evaluated in this study the hypothesis that copeptin measured on admission is an independent predictor of one-year all-cause mortality after a STEMI. METHODS: Copeptin was measured immediately on arrival in the catheterization laboratory in a cohort of unselected STEMI patients and was compared to the peak of cardiac troponin I as a prognosis marker. One-year follow-up was performed. RESULTS: We included 401 STEMI patients (77% of men, mean age 64 ±â€¯14 years) treated by primary percutaneous coronary intervention. Copeptin on admission was significantly higher in patients who died during the one-year follow-up than in survivors (154.8 pmol/L; IQR [63.9-304.8] vs 30.3 pmol/L; IQR [10.8-93.5]); p < 0.0001). There was an increase in mortality at one year from the lowest to the highest quartile of copeptin. After Cox regression analysis, copeptin was an independent predictor of death at one year (adjHR 3.1, 95% CI [1.5-6.2], p = 0.001). When compared to the peak value of cardiac troponin I, copeptin measured on admission had a better prognostic value to predict one-year mortality (AUC of 0.74 vs 0.60, p = 0.022). CONCLUSION: Copeptin measured on admission is a reliable and independent prognostic biomarker of one-year mortality in acute myocardial infarction patients.

Screening for liver fibrosis by using a noninvasive biomarker in patients with diabetes.

BACKGROUND & AIMS: Patients with diabetes are at risk for nonalcoholic fatty liver disease leading to advanced fibrosis, cirrhosis, and liver cancer. We examined the efficacy of a screening strategy with a noninvasive fibrosis biomarker (FibroTest) in patients with diabetes. METHODS: We prospectively studied 1131 consecutive patients without a history of liver disease seen for diabetes. The biomarker data were obtained, and patients with presumed advanced fibrosis were reinvestigated by a hepatologist using elastography and, if necessary, ultrasonography, endoscopy, or liver biopsy. RESULTS: The biomarker predicted advanced fibrosis in 63 of 1131 (5.6%) patients. A total of 45 patients was reinvestigated, and advanced fibrosis was confirmed in 32 patients, a 2.8% (32/1131) prevalence of confirmed advanced fibrosis, 5 cases of cirrhosis, and 4 cases of hepatocellular carcinoma. In the population with type 2 diabetes who were 45 years or older, the prevalence of confirmed advanced fibrosis was 4.3% (30/696), and hepatocellular carcinoma was 5.7 of 1000 (4/696). CONCLUSIONS: The fibrosis biomarker might be used for the detection of advanced fibrosis in patients with type 2 diabetes.

Influence of renal dysfunction on the accuracy of procalcitonin for the diagnosis of postoperative infection after vascular surgery.

OBJECTIVE: Procalcitonin has been advocated as a specific biomarker for bacterial infection. We performed this study to determine whether accuracy of procalcitonin for diagnosis of postoperative bacterial infection is affected by renal function after aortic surgery. DESIGN: Single-center prospective study. SETTING: University hospital. PATIENTS: Two hundred seventy-six patients scheduled for elective major aortic surgery. INTERVENTIONS: Blood samples were taken before surgery and each day over the 5-day postoperative period, and measurement of serum procalcitonin was performed. Diagnosis of infection was performed by a blinded expert panel. Renal function was assessed using an estimate of creatinine clearance with the Cockcroft formulas. Renal dysfunction was defined as a creatinine clearance <50 mL x min(-1). MEASUREMENTS AND MAIN RESULTS: Infection was diagnosed in 67 patients. Seventy five patients (27%) had postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, with a peak reached at the fourth postoperative day, but it was significantly higher in patients with impaired renal function in both control and infected patients. The optimal threshold of procalcitonin markedly differed in patients with renal dysfunction compared with patients without renal dysfunction (2.57 vs. 0.80 ng x mL(-1), p < .05). The diagnostic accuracy of procalcitonin significantly increased (0.74 vs. 0.70, p < .05) when the threshold of procalcitonin was adapted to the renal function. The elevation of procalcitonin occurred 2 days before the medical team was able to diagnose infection. CONCLUSIONS: Procalcitonin is a valuable marker of bacterial infections after major aortic surgery, but renal function is a major determinant of procalcitonin levels and thus different thresholds should be applied according to renal function impairment.

Is procalcitonin a marker of critical illness in heatstroke?

OBJECTIVE: To study the effect of non-exertional heatstroke on serum procalcitonin (PCT) levels. DESIGN: Cohort study. SETTING: The emergency and intensive care departments of two academic tertiary-care hospitals, Paris, France PATIENTS: A total of 53 patients with defined heatstroke attending the emergency department and/or the intensive care unit during the August 2003 heat wave in France. INTERVENTIONS: None. MEASUREMENTS: Serum PCT measurement using a sensitive assay and vital and routine biological variables on arrival of patients presenting with classic heatstroke. Thirty-day mortality was recorded. RESULTS: Among the 53 patients included, 14 (26%) were admitted to an intensive care unit (ICU). At 30 days, 24 patients (45%) had died. Median PCT value was 0.58 microg/l (95% confidence interval 0.16-1.61) and 31 (58%) patients had PCT above 0.2 microg/l (PCT+). Temperature above or equal to 40 degrees C was the only variable significantly associated with fatal outcome. Median PCT values were 1.4 microg/l (0.16-4.71) and 0.18 microg/l (0.12-1.61) in the group of deceased and surviving patients respectively (p = 0.22). All patients admitted in ICU had elevated PCT values. Patients PCT+ initially presented with a more pronounced systemic inflammatory response. Microbiologically or clinically documented infection was not more frequent in PCT+ group. CONCLUSION: High serum PCT levels can be observed in heatstroke without any concomitant documented bacterial infection. The PCT is not a valid mortality predictor in heatstroke but could be an indicator of the severity of illness. Heatstroke could represent a model of a "non-septic" pathway of PCT synthesis.

Usefulness of procalcitonin for the diagnosis of ventilator-associated pneumonia.

OBJECTIVE: To assess the predictive capacity for the diagnosis of ventilator-associated pneumonia (VAP) of serum procalcitonin levels before and on the day it is suspected. DESIGN AND SETTING: Single-center observational study in the intensive care unit of a teaching hospital. PATIENTS AND PARTICIPANTS: Consecutive patients whose serum procalcitonin levels were available on the day that VAP was clinically suspected (day 1) and at some time within the preceding 5 days ("before"). MEASUREMENTS AND RESULTS: Serum procalcitonin levels were determined on day 1 and "before". Among the 73 suspected episodes VAP was confirmed by quantitative bronchoalveolar lavage cultures in 32 and refuted in 41. Respective median "before" procalcitonin levels were 1.89 ng/ml (interquartile range 0.18-6.01) and 2.14 (0.76-5.75) in patients with and without VAP, but their respective median day-1 procalcitonin levels did not differ: 1.07 ng/ml (0.39-6.57) vs. 1.40 (0.67-3.39). On day 1 a 0.5 ng/ml procalcitonin threshold had 72% sensitivity but only 24% specificity for diagnosing VAP. Between "before" and day 1, procalcitonin increased in 41% and 15% of patients with and without VAP, respectively. Thus a procalcitonin rise on day 1, compared to its "before" level, had 41% sensitivity and 85% specificity for diagnosing VAP, with respective positive and negative predictive values of 68% and 65%. CONCLUSIONS: Crude values and procalcitonin rise had poor diagnostic value for VAP in this particular setting and thus should not be used to initiate antibiotics when VAP is clinically suspected.

Procalcitonin in liver transplantation: are high levels due to donors or recipients?

INTRODUCTION: To date, a specific marker to evaluate and predict the clinical course or complication of the liver-transplanted patient is not available in clinical practice. Increased procalcitonin (PCT) levels have been found in infectious inflammation; poor organ perfusion and high PCT levels in the cardiac donor appeared to predict early graft failure. We evaluated PCT as a predictor of early graft dysfunction and postoperative complications. METHODS: PCT serum concentrations were measured in samples collected before organ retrieval from 67 consecutive brain-dead donors and in corresponding recipients from day 0, before liver transplantation, up to day 7 after liver transplantation. The following parameters were recorded in donors: amount of vasopressive drug doses, cardiac arrest history 24 hours before retrieval, number of days in the intensive care unit, age of donor, and infection in donor, and the following parameters were recorded in recipients: cold and warm ischemia time, veno-venous bypass, transfusion amount during orthotopic liver transplantation (OLT), and occurrence of postoperative complication or hepatic dysfunction. RESULTS: In the donor, the preoperative level of PCT was associated with cardiac arrest and high doses of catecholamines before organ retrieval. In the recipient, elevated PCT levels were observed early after OLT, with a peak at day 1 or 2 after OLT, then a decrease until day 7. A postoperative peak of PCT levels was associated neither with preoperative PCT levels in the donor or the recipients nor with hepatic post-OLT dysfunction or other postoperative complications, but with two donor parameters: infection and cardiac arrest. CONCLUSION: PCT level in the donor and early PCT peak in the recipient are not predictive of post-OLT hepatic dysfunction or other complications. Cardiac arrest and infection in the donor, but not PCT level in the donor, are associated with high post-OLT PCT levels in the recipient.

Cell adhesion and integrin expression are modulated by oxidative stress in EA.hy 926 cells.

The effects of oxidative stress on integrin-mediated cell adhesion to the extracellular matrix (ECM) and related apoptosis were investigated using the EA.hy926 endothelial cells treated (or not) with two oxidants: the hypoxanthine/xanthine oxidase system (HX/XO) or the tert-butyl hydroperoxide (t-BHP) which both increased cell apoptosis. Cell adhesion onto vitronectin (Vn) and fibronectin (Fn) was increased at low concentrations of HX/XO (up to 5 mU/ml) or t-BHP (up to 125 microM) and prevented ROS-induced apoptosis. Flow cytometry analysis of integrin expression showed that the expression of integrin alphav and alpha5 subunits was, respectively, increased and decreased. Cell adhesion inhibition experiments using function-blocking monoclonal antibodies against integrin subunits indicated that alphavbeta1 and alphavbeta3 integrins were involved in adhesion of cells to Vn, and alphavbeta3 integrin played a major role in oxidant-treated cells. For adhesion to Fn, alpha5beta1 and alphavbeta1 integrins were required for oxidant-treated cells. Taken together, the results suggest that reactive oxygen species (ROS) produced either by HX/XO or t-BHP could affect expression and/or activation of specific integrins in the interaction of EA.hy926 cells with ECM.