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1.  Serum procalcitonin for the early recognition of nosocomial infection in the critically ill patients: a preliminary report 
The usefulness of procalcitonin (PCT) measurement in critically ill medical patients with suspected nosocomial infection is unclear. The aim of the study was to assess PCT value for the early diagnosis of bacterial nosocomial infection in selected critically ill patients.
An observational cohort study in a 15-bed intensive care unit was performed. Seventy patients with either proven (n = 47) or clinically suspected but not confirmed (n = 23) nosocomial infection were included. Procalcitonin measurements were obtained the day when the infection was suspected (D0) and at least one time within the 3 previous days (D-3 to D0). Patients with proven infection were compared to those without. The diagnostic value of PCT on D0 was determined through the construction of the corresponding receiver operating characteristic (ROC) curve. In addition, the predictive value of PCT variations preceding the clinical suspicion of infection was assessed.
PCT on D0 was the best predictor of proven infection in this population of ICU patients with a clinical suspicion of infection (AUROCC = 0.80; 95% CI, 0.68–0.91). Thus, a cut-off value of 0.44 ng/mL provides sensitivity and specificity of 65.2% and 83.0%, respectively. Procalcitonin variation between D-1 and D0 was calculated in 45 patients and was also found to be predictive of nosocomial infection (AUROCC = 0.89; 95% CI, 0.79–0.98) with a 100% positive predictive value if the +0.26 ng/mL threshold value was applied. Comparable results were obtained when PCT variation between D-2 and D0, or D-3 and D0 were considered. In contrast, CRP elevation, leukocyte count and fever had a poor predictive value in our population.
PCT monitoring could be helpful in the early diagnosis of nosocomial infection in the ICU. Both absolute values and variations should be considered and evaluated in further studies.
PMCID: PMC2679028  PMID: 19386110
2.  Procalcitonin kinetics within the first days of sepsis: relationship with the appropriateness of antibiotic therapy and the outcome 
Critical Care  2009;13(2):R38.
Management of the early stage of sepsis is a critical issue. As part of it, infection control including appropriate antibiotic therapy administration should be prompt. However, microbiological findings, if any, are generally obtained late during the course of the disease. The potential interest of procalcitonin (PCT) as a way to assess the clinical efficacy of the empirical antibiotic therapy was addressed in the present study.
An observational cohort study including 180 patients with documented sepsis was conducted in our 15-bed medical intensive care unit (ICU). Procalcitonin measurement was obtained daily over a 4-day period following the onset of sepsis (day 1 (D1) to D4). The PCT time course was analyzed according to the appropriateness of the first-line empirical antibiotic therapy as well as according to the patient outcome.
Appropriate first-line empirical antibiotic therapy (n = 135) was associated with a significantly greater decrease in PCT between D2 and D3 (ΔPCT D2–D3) (-3.9 (35.9) vs. +5.0 (29.7), respectively; P < 0.01). In addition, ΔPCT D2–D3 was found to be an independent predictor of first-line empirical antibiotic therapy appropriateness. In addition, a trend toward a greater rise in PCT between D1 and D2 was observed in patients with inappropriate antibiotics as compared with those with appropriate therapy (+5.2 (47.4) and +1.7 (35.0), respectively; P = 0.20). The D1 PCT level failed to predict outcome, but higher levels were measured in the nonsurvivors (n = 51) when compared with the survivors (n = 121) as early as D3 (40.8 (85.7) and 21.3 (41.0), respectively; P = 0.04). Moreover, PCT kinetics between D2 and D3 were also found to be significantly different, since a decrease ≥ 30% was expected in the survivors (log-rank test, P = 0.04), and was found to be an independent predictor of survival (odds ratio = 2.94; 95% confidence interval 1.22 to 7.09; P = 0.02).
In our study in an ICU, appropriateness of the empirical antibiotic therapy and the overall survival were associated with a greater decline in PCT between D2 and D3. Further studies are needed to assess the utility of the daily monitoring of PCT in addition to clinical evaluation during the early management of sepsis.
PMCID: PMC2689475  PMID: 19291325
3.  Performance of N-terminal-pro-B-type natriuretic peptide in critically ill patients: a prospective observational cohort study 
Critical Care  2008;12(6):R137.
The purpose of this study was to assess the accuracy of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) as a diagnostic tool to recognize acute respiratory failure of cardiac origin in an unselected cohort of critically ill patients.
We conducted a prospective observational study of medical ICU patients. NT-proBNP was measured at ICU admission, and diagnosis of cardiac dysfunction relied on the patient's clinical presentation and echocardiography.
Of the 198 patients included in this study, 102 (51.5%) had evidence of cardiac dysfunction. Median NT-proBNP concentrations were 5,720 ng/L (1,430 to 15,698) and 854 ng/L (190 to 3,560) in patients with and without cardiac dysfunction, respectively (P < 0.0001). In addition, NT-proBNP concentrations were correlated with age (ρ = 0.43, P < 0.0001) and inversely correlated with creatinine clearance (ρ = -0.58, P < 0.0001). When evaluating the performance of NT-proBNP concentrations to detect cardiac dysfunction, the area under the receiver operating characteristic (ROC) curve was 0.76 (95% confidence interval (CI) 0.69 to 0.83). In addition, a stepwise logistic regression model revealed that NT-proBNP (odds ratio (OR) = 1.01 per 100 ng/L, 95% CI 1.002 to 1.02), electrocardiogram modifications (OR = 11.03, 95% CI 5.19 to 23.41), and severity assessed by organ system failure score (OR = 1.63 per point, 95% CI 1.17 to 2.41) adequately predicted cardiac dysfunction. The area under the ROC curve of this model was 0.83 (95% CI 0.77 to 0.90).
NT-proBNP measured at ICU admission might represent a useful marker to exclude cardiac dysfunction in critically ill patients.
PMCID: PMC2646347  PMID: 18990203
4.  Serum procalcitonin elevation in critically ill patients at the onset of bacteremia caused by either gram negative or gram positive bacteria 
In the ICU, bacteremia is a life-threatening infection whose prognosis is highly dependent on early recognition and treatment with appropriate antibiotics. Procalcitonin levels have been shown to distinguish between bacteremia and noninfectious inflammatory states accurately and quickly in critically ill patients. However, we still do not know to what extent the magnitude of PCT elevation at the onset of bacteremia varies according to the Gram stain result.
Review of the medical records of every patient treated between May, 2004 and December, 2006 who had bacteremia caused by either Gram positive (GP) or Gram negative (GN) bacteria, and whose PCT dosage at the onset of infection was available.
97 episodes of either GN bacteremia (n = 52) or GP bacteremia (n = 45) were included. Procalcitonin levels were found to be markedly higher in patients with GN bacteremia than in those with GP bacteremia, whereas the SOFA score value in the two groups was similar. Moreover, in the study population, a high PCT value was found to be independently associated with GN bacteremia. A PCT level of 16.0 ng/mL yielded an 83.0% positive predictive value and a 74.0% negative predictive value for GN-related bacteremia in the study cohort (AUROCC = 0.79; 95% CI, 0.71–0.88).
In a critically ill patient with clinical sepsis, GN bacteremia could be associated with higher PCT values than those found in GP bacteremia, regardless of the severity of the disease.
PMCID: PMC2289831  PMID: 18366777
5.  Is There a Correlation between Vitamin C Status and Catecholamines Concentrations in Hemodialysis Patients? 
It is well established that there is a high incidence of cardiovascular diseases in hemodialysis patients, and involvement of oxidative stress has been hypothesised in these phenomena. Plasma norepinephrine is an independent predictor of many causes of mortality in general, and high norepinephrine levels predict cardiovascular complications in end stage renal disease. The aim of our study was to evaluate the potential link between vitamin C status, a marker of oxidative stress, and catecholamine concentrations before and after hemodialysis sessions. In a prospective study of 16 chronic hemodialysis patients, ascorbyl free radical levels were directly measured using electron spin resonance spectroscopy. These values were expressed with respect to vitamin C concentrations to obtain a direct index of oxidative stress. Vitamin C, epinephrine and norepinephrine were measured by high performance liquid chromatography. The data were examined for correlations between these compounds and clinical parameters including blood pressure and heart rates. In hemodialysis patients, ascorbyl free radical/vitamin C ratios increased significantly after dialysis. No differences were observed for catecholamine concentrations during hemodialysis sessions. In multivariate analysis, the ascorbyl free radical/vitamin C ratio did not correlate with epinephrine or norepinephrine levels. In our study, plasma norepinephrine and ascorbyl free radical/vitamin C ratios were not related among patients with end-stage renal disease. From these findings, we conclude that although these two factors are likely to be involved in the same causal pathway leading to cardiovascular events, it is likely that they seem to be independent.
PMCID: PMC3614698  PMID: 23675078
ascorbyl free radical; catecholamines; haemodialysis; oxidative stress; vitamin C
6.  Impact of previous sepsis on the accuracy of procalcitonin for the early diagnosis of blood stream infection in critically ill patients 
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.
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.
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).
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.
PMCID: PMC2614426  PMID: 19055740

Results 1-6 (6)