Harmonization status of procalcitonin measurements: what do comparison studies and EQA schemes tell us?

Sepsis represents a global health priority because of its high mortality and morbidity. The key to improving prognosis remains an early diagnosis to initiate appropriate antibiotic treatment. Procalcitonin (PCT) is a recognized biomarker for the early indication of bacterial infections and a valuable tool to guide and individualize antibiotic treatment. To meet the increasing demand for PCT testing, numerous PCT immunoassays have been developed and commercialized, but results have been questioned. Many comparison studies have been carried out to evaluate analytical performance and comparability of results provided by the different commercially available immunoassays for PCT, but results are conflicting. External Quality Assessment Schemes (EQAS) for PCT constitute another way to evaluate results comparability. However, when making this comparison, it must be taken into account that the variety of EQA materials consist of different matrices, the commutability of which has not yet been investigated. The present study gathers results from all published comparison studies and results from 137 EQAS surveys to describe the current state-of-the-art harmonization of PCT results. Comparison studies globally highlight a significant variability of measurement results that nonetheless seem to have a moderate impact on medical decision-making. For their part, EQAS for PCT provides highly discrepant estimates of the interlaboratory CV. Due to differences in commutability of the EQA materials, the results from different peer groups could not be compared. To improve the informative value of the EQA data, the existing limitations such as non-harmonized conditions and suboptimal and/or unknown commutability of the EQA materials have to be overcome. The study highlights the need for commutable reference materials that could be used to properly evaluate result comparability and possibly standardize calibration, if necessary. Such an initiative would further improve the safe use of PCT in clinical routine.

Mid-regional pro-atrial natriuretic peptide and pro-adrenomedullin testing for the diagnostic and prognostic evaluation of patients with acute dyspnoea.

AIMS: The aim of this study was to assess diagnostic and prognostic value of mid-regional pro-atrial natriuretic peptide (MR-proANP) and adrenomedullin (MR-proADM) for the evaluation of patients presenting to the emergency department with acute dyspnoea. METHODS AND RESULTS: A total of 560 patients from the pro-B type natriuretic peptide Investigation of Dyspnoea in the Emergency Department were evaluated; 180 had acutely decompensated heart failure (ADHF). Concentrations of amino-terminal pro-B type natriuretic peptide (NT-proBNP), MR-proADM, and MR-proANP were measured, and patients were followed to 4 years for survival. Logistic regression evaluated utility of MR-proANP in ADHF diagnosis. Area under the curve (AUC), multivariate Cox regression, net reclassification improvement, and Kaplan-Meier survival analyses were used for mortality analyses. Mid-regional pro-atrial natriuretic peptide was higher in patients with ADHF (median 329 vs. 58 pmol/L; P < 0.001), and remained an independent predictor of HF diagnosis even when NT-proBNP was included as a covariate (odds ratio = 4.34, 95% CI = 2.11-8.92; P < 0.001). In time-dependent analyses, MR-proADM had the highest AUC for death during the first year; after 1 year, MR-proANP and NT-proBNP had a higher AUC. Both mid-regional peptides were independently prognostic and reclassified risk at 1 year [MR-proANP, hazard ratio (HR) = 2.99, MR-proADM, HR = 2.70; both P < 0.001] and at 4 years (MR-proANP, HR = 3.12, P < 0.001; MR-proADM, HR = 1.51, P = 0.03) and in Kaplan-Meier curves both mid-regional peptides were associated with death out to 4 years, individually or in a multimarker strategy. CONCLUSION: Among patients with acute dyspnoea, MR-proANP is accurate for diagnosis of ADHF, while both MR-proANP and MR-proADM are independently prognostic to 4 years of the follow-up.

Detection of PAHs in seawater using surface-enhanced Raman scattering (SERS).

The laboratory characterization of a field-operable surface-enhanced Raman scattering sensor (SERS optode) is presented for the detection of aromatic hydrocarbons in seawater. The sensor has been developed for deployment with a robust underwater spectrograph. To meet the demands of the harsh seawater application, sol-gel derived SERS substrates were used. The calibration curves of six PAHs were determined to be of Langmuir adsorption isotherm type with limits of detection ranging from the microg l(-1) to ng l(-1) level. The experimentally determined adsorption constants varied strongly with the molecular weight of the analytes and correlated with their solubility. A mixture of five PAHs dissolved in seawater was investigated to demonstrate the utility of this method for screening. Emphasis was put on the interference from suspended particulate matter (SPM). The Raman measurement with backscattering configuration was shown to be immune against turbidities up to 1000 NTU. The physico-chemical interference arising from adsorption by the sediment was measured on-line by adding sediment to a PAH-spiked solution. According to the calibration curve, the PAH concentration decrease corresponded to more than 98% of the analyte being scavenged by the sediment.

The use of surface-enhanced Raman scattering (SERS) for detection of PAHs in the Gulf of Gdansk (Baltic Sea).

A field operable surface enhanced Raman scattering (SERS) sensor system was applied for the first time under real conditions for the detection of polycyclic aromatic hydrocarbons (PAHs) as markers for petroleum hydrocarbons in the Gulf of Gdansk (Baltic Sea). At six stations, seawater samples were taken, and the sensor system was applied in situ simultaneously. These measurements were compared to the results of conventional GC/MS laboratory analysis of the PAH concentrations in the seawater samples. For a PAH concentration above 150 ng(12PAH)l(-1), there was agreement between the SERS sensor and the GC/MS determinations. A standard addition experiment yielded a PAH concentration of 900 ng l(-1) at the Gdansk Harbor, which was of the same order as the GC/MS determinations of 12PAHs (200 ng(12PAH)l(-1)). The high SERS detection limit for seawater samples is explained by the competition for PAHs between the sensor membrane and particulate matter surfaces. Thus, the SERS sensor can be applied, e.g., as a non-quantitative alarm sensor for relatively high PAH concentrations in heavily polluted waters. The spectral unmixing procedure applied for Gdansk Harbor water confirmed the presence of phenanthrene at the highest concentration ([Phe]=140 ngl(-1)) and of Chr (2.7 ng l(-1)), but it did not detect the other PAHs present in the Gdansk Harbor water, as determined by GC/MS. When compared to the past literature and databases, the SERS spectra indicated the presence of a mixture of molecules consisting of carotenoids, n-alkanes, amines or fatty acids, and benzimidazoles at the coastal station ZN2. The spectra in the offshore direction indicated carboxylic acids. Interpretation of the farthest offshore in situ SERS measurements is difficult, principally due to the limited availability of reference spectra. The detection of the lower PAH concentrations commonly found in Baltic coastal water needs further research and development to obtain better sensitivity of the SERS sensor. However, the high analytical specificity of the SERS sensor also allows the detection of other chemical species that require the development of a SERS/Raman library for specific in situ spectral interpretation.

Acoustic tonometry: feasibility study of a new principle of intraocular pressure measurement.

PURPOSE: An accurate measurement of intraocular pressure (IOP) is still essential for detecting, following-up, and treating glaucoma. The objective of the interdisciplinary project GlauPhon was to prove a new noncontact tonometry principle that analyzes the acoustic oscillation of the eye. METHOD: Three enucleated porcine eyes were infused via the optic nerve with a saline solution. The IOP was adjusted by varying the height of the infusion bottle. A speaker closed one end of a cylindrical pressure chamber and an eye was fixed to the other side. A PC sound card induced the speaker to oscillate by generating a rectangular signal (20 Hz). A pressure sensor recorded the oscillating pressure within the chamber. For each IOP a calculation was performed that characterizes the attenuation profile. RESULTS: Each series of measurements revealed an evident dependency between the amplitude difference and the IOP. The highest signal belonged to low IOP levels and it decreased with increasing IOP. The correlation of the mean acoustical signal with the given IOP showed a highly significant correlation coefficient (r=-0.98). As a result, the measured oscillation parameters are strongly dependent on the exerted IOPs. CONCLUSIONS: The experiments verified the presumed relation between the acoustic oscillation of the eye and the IOP. Nevertheless, further developments are necessary for converting the oscillation parameters into reliable IOP values, to construct a tonometry device for clinical trials.