How to Solve the Underestimated Problem of Overestimated Sodium Results in the Hypoproteinemic Patient.

OBJECTIVES: The availability of a fast and reliable sodium result is a prerequisite for the appropriate correction of a patient's fluid balance. Blood gas analyzers and core laboratory chemistry analyzers measure electrolytes via different ion-selective electrode methodology, that is, direct and indirect ion-selective electrodes, respectively. Sodium concentrations obtained via both methods are not always concordant. A comparison of results between both methods was performed, and the impact of the total protein concentration on the sodium concentration was investigated. Furthermore, we sought to develop an adjustment equation to correct between both ion-selective electrode methods. DESIGN: A model was developed using a pilot study cohort (n = 290) and a retrospective patient cohort (n = 690), which was validated using a prospective patient cohort (4,006 samples). SETTING: ICU and emergency department at Ghent University Hospital. PATIENTS: Patient selection was based on the concurrent availability of routine blood gas Na⁺(direct) as well as core laboratory Na⁺(indirect) results. INTERVENTIONS: In the pilot study, left-over blood gas syringes were collected for further laboratory analysis. MEASUREMENT AND MAIN RESULTS: There was a significant negative linear correlation between Na⁺(indirect) and Na⁺(direct) relative to changes in total protein concentration (Pearson r = -0.69; p < 0.0001). In our setting, for each change of 10 g/L in total protein concentration, a deviation of ~1.3 mmol/L is observed with the Na⁺(indirect) result. Validity of our adjustment equation protein-corrected Na⁺(indirect) = Na⁺(indirect) - 10.53 + (0.1316 × total protein) was demonstrated on a prospective patient cohort. CONCLUSIONS: As Na⁺(direct) measurements on a blood gas analyzer are not influenced by the total protein concentration in the sample, they should be preferentially used in patients with abnormal protein concentrations. However, as blood gas analyzers are not available at all clinical wards, the implementation of a protein-corrected sodium result might provide an acceptable alternative.

Influence of anticardiolipin and anti-ß2 glycoprotein I antibody cutoff values on antiphospholipid syndrome classification.

BACKGROUND: Anticardiolipin (aCL) and anti-ß2 glycoprotein I (aß2GPI) immunoglobulin (Ig) G/IgM antibodies are 2 of the 3 laboratory criteria for classification of antiphospholipid syndrome (APS). The threshold for clinically relevant levels of antiphospholipid antibodies (aPL) for the diagnosis of APS remains a matter of debate. The aim of this study was to evaluate the variation in cutoffs as determined in different clinical laboratories based on the results of a questionnaire as well as to determine the optimal method for cutoff establishment based on a clinical approach. METHODS: The study included samples from 114 patients with thrombotic APS, 138 patients with non-APS thrombosis, 138 patients with autoimmune disease, and 183 healthy controls. aCL and aß2GPI IgG/IgM antibodies were measured at 1 laboratory using 4 commercial assays. Assay-specific cutoff values for aPL were obtained by determining 95th and 99th percentiles of 120 compared to 200 normal controls by different statistical methods. RESULTS: Normal reference value data showed a nonparametric distribution. Higher cutoff values were found when calculated as 99th rather than 95th percentiles. These values also showed a stronger association with thrombosis. The use of 99th percentile cutoffs reduced the chance of false positivity but at the same time reduced sensitivity. The decrease in sensitivity was higher than the gain in specificity when 99th percentiles were calculated by methods wherein no outliers were eliminated. CONCLUSIONS: We present cutoff values for aPL determined by different statistical methods. The 99th percentile cutoff value seemed more specific. However, our findings indicate the need for standardized statistical criteria to calculate 99th percentile cutoff reference values.

Recommendations for enterovirus diagnostics and characterisation within and beyond Europe.

Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5'noncoding regions (5'NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5'NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden.