Interlaboratory variation for NT-proBNP among Swedish laboratories in an external quality program 2011-2021.

OBJECTIVES: NT-proBNP is frequently used for ruling out heart failure. Different cut-offs are used depending on the clinical context, e.g. an acute or chronic condition. Medical decision limits have been suggested at 125 and 300 ng/L or 400 ng/L in international guidelines. However, there is limited standardization between NT-proBNP methods and using the same blood sample might cause different treatment of patients. METHODS: Data from the external quality assessment program for NT-proBNP from Equalis, Sweden, were extracted for the period 2011-2021, and categorized according to manufacturer. Manufacturer median NT-proBNP values were compared to total median values. CV% was calculated for each manufacturer and in comparison to different levels of NT-proBNP. RESULTS: Roche was the most common method, and its median results were closest to the median consensus results. When looking at the total CV at NT-proBNP levels in the range of 0-500 ng/L, the total CV varied from 4 to 27%. During 2019-2021, Siemens (Immulite, Centaur, Atellica) yielded results 16-20% above the consensus median depending on sample level. Similarly, Abbott was 5-7% above, while Roche and Siemens Stratus were 1% respectively 6-10% below the consensus median. CONCLUSIONS: The introduction of new manufacturers and methods in 2017 have caused the agreement between manufacturers to decline. This highlights the need for a common calibrator and reference materials, particularly since medical decision limits in guidelines, e.g. European Society of Cardiology 2021, which are mostly based on Roche methods, do not take these method differences into account.

Comparison of outcomes and complications between one- and two-level anterior cervical discectomy and fusion: a population-based study of 410 patients.

OBJECTIVE: The objective of this study was to compare outcomes and patient satisfaction, and secondly to compare complication rates between one- and two-level anterior cervical discectomy and fusion (ACDF) for cervical radiculopathy. METHODS: Data from patients receiving one- or two-level ACDF for cervical radiculopathy at two institutions were prospectively collected and retrospectively analysed. Patients were separated into one-level ACDF and two-level ACDF. Comparison analyses of patient-reported outcome measures (PROMs) comprising Visual Analogue Scale for neck pain (VAS-NP) and arm pain (VAS-AP), Neck Disability Index (NDI), and EQ-5D 3-level version (EQ-5D-3L) were performed between baseline and 1-year follow-up and between groups as well as achievement of minimal clinically important differences (MCID) in PROMs and satisfaction. Additionally, complications were compared between groups. RESULTS: A total of 410 patients (270 one-level and 140 two-level) were included. PROMs improved significantly from baseline to 1-year follow-up (p < 0.001) in both groups. When comparing PROMs between one- and two-level ACDF, a trend towards greater improvement was observed in patients undergoing one-level ACDF, notably in EQ-5D-3L (p = 0.073). Significantly more patients in the one-level group achieved MCID in VAS-NP compared to patients in the two-level group (56% vs 44%, p = 0.025). Two hundred and ninety-six (67%) patients reported to be satisfied, but the one-level group trended to be more satisfied (70% vs. 62%). One-level ACDF further demonstrated a trend of more favourable complication profiles; however, complication rates were low in both groups. The risk of intraoperative complications was 2.4%, postoperative complications in-hospital were 1.2%, and patient-reported postoperative events post-discharge 42%. CONCLUSIONS: One- and two-level ACDF are effective procedures for degenerative cervical nerve root compression. Yet, significantly more patients in the one-level group achieved MCID in neck pain compared to patients in the two-level group.

Evaluation of venous plasma glucose measured by point-of-care testing (Accu-Chek Inform II) and a hospital laboratory hexokinase method (Cobas c701) in oral glucose tolerance testing during pregnancy - a challenge in diagnostic accuracy.

To diagnose gestational diabetes mellitus (GDM), plasma glucose measurements during oral glucose tolerance test (OGTT) put high demands on the methods in terms of accuracy. The aim was to evaluate and compare diagnostic performance of a point-of-care test and a glucose hexokinase laboratory method. Using risk-based screening, 175 pregnant women were included. They underwent a 75 g OGTT in their 28th (median) week of gestation. Venous blood was collected in two different tubes. Plasma glucose was measured on Cobas c701 and in duplicates on AccuChek Inform II (both methods from Roche Diagnostics). Accuracy was assessed by participating in external control programs with reference method assigned values. The methods were compared for all samples (n = 512) by regression analysis; slope of 0.90 (95% CI: 0.89-0.92), intercept of 0.12 (95% CI: 0.011-0.22) and rs of 0.968. The average bias between AccuChek Inform II and Cobas c701 was -8%. The proportion of women diagnosed with GDM was 25% based on AccuChek Inform II versus 55% for Cobas c701. Results from the external control program showed a bias of approximately 5% for Cobas c701 and no significant bias for AccuChek Inform II. Cobas c701 showed a large bias both towards Accu-Chek Inform II and the reference method used in the external control program, clearly exceeding the desirable bias of <2.6%. The lack of accuracy has great implications on either over- or under-diagnosis of GDM.

Evaluating Commutability of Control Materials in Three Nordic External Quality Assessment Schemes for Lipoproteins.

BACKGROUND: The quality of control materials is crucial for evaluating external quality assessment (EQA) results. To detect method differences, the EQA material should behave the same as a patient sample, meaning the material must be commutable. Noncommutable materials may cause misinterpretations of EQA results. Here, we examined the commutability of EQA materials used in 3 Nordic EQA schemes for lipids. METHODS: The study was designed according to the procedures recommended for assessing commutability by the International Federation of Clinical Chemistry and Laboratory Medicine. Commutability was assessed based on the difference in bias between a control material (CM) and clinical samples (CS) consisting of human plasma using 2 different measurement procedures (MPs). Measurands: LDL-cholesterol (LDL-C), total cholesterol (TC), HDL-cholesterol (HDL-C), and triglycerides (TG). Four CMs (CM1-4) were assessed for commutability by using 40 CS and 3 MPs (Abbott Architect, Roche Cobas, and Siemens Atellica). RESULTS: Unmodified native CMs (CM1 and CM3), stored at -80 °C, were commutable for all included measurands, except for LDL-C that was indeterminate, when comparing MPs pairwise. Modified CM2 was noncommutable for HDL-C, LDL-C, non-HDL-C, and LDL-C calculations. Unmodified native CM4, stored at -20°C, was noncommutable for LDL-C. CONCLUSIONS: Unmodified serum samples stored at -80 °C were commutable for lipids on the evaluated MPs, and therefore suitable as CMs in EQA schemes. Moreover, the study demonstrated that minor modifications of samples may lead to noncommutability.

Handling of hemolyzed serum samples in clinical chemistry laboratories: the Nordic hemolysis project.

Background Some clinical chemistry measurement methods are vulnerable to interference if hemolyzed serum samples are used. The aims of this study were: (1) to obtain updated information about how hemolysis affects clinical chemistry test results on different instrument platforms used in Nordic laboratories, and (2) to obtain data on how test results from hemolyzed samples are reported in Nordic laboratories. Methods Four identical samples containing different degrees of hemolysis were prepared and distributed to 145 laboratories in the Nordic countries. The laboratories were asked to measure the concentration of cell-free hemoglobin (Hb), together with 15 clinical chemistry analytes. In addition, the laboratories completed a questionnaire about how hemolyzed samples are handled and reported. Results Automated detection of hemolysis in all routine patient samples was used by 63% of laboratories, and 88% had written procedures on how to handle hemolyzed samples. The different instrument platforms measured comparable mean Hb concentrations in the four samples. For most analytes, hemolysis caused a homogenous degree of interference regardless of the instrument platform used, except for alkaline phosphatase (ALP), bilirubin (total) and creatine kinase (CK). The recommended cut-off points for rejection of a result varied substantially between the manufacturers. The laboratories differed in how they reported test results, even when they used the same type of instrument. Conclusions Most of the analytes were homogeneously affected by hemolysis, regardless of the instrument used. There is large variation, however, between the laboratories on how they report test results from hemolyzed samples, even when they use the same type of instrument.

Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model.

Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure are hallmarks of the disease. The critical mechanisms causing chronic mucocutaneous candidiasis in APS-1 patients have not been identified although autoantibodies to cytokines are implicated in the pathogenesis. To investigate whether the Th reactivity to Candida albicans (C. albicans) and other stimuli was altered, we isolated PBMC from APS-1 patients and matched healthy controls. The Th17 pathway was upregulated in response to C. albicans in APS-1 patients, whereas the IL-22 secretion was reduced. Autoantibodies against IL-22, IL-17A and IL-17F were detected in sera from APS-1 patients by immunoprecipitation. In addition, Aire-deficient (Aire(0/0) ) mice were much more susceptible than Aire(+/+) mice to mucosal candidiasis and C. albicans-induced Th17- and Th1-cell responses were increased in Aire(0/0) mice. Thus an excessive IL-17A reactivity towards C. albicans was observed in APS-1 patients and Aire(0/0) mice.

Impaired autoimmune T helper 17 cell responses following DNA vaccination against rat experimental autoimmune encephalomyelitis.

BACKGROUND: We have previously shown that vaccination with DNA encoding the encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG)(91-108) (pMOG) suppresses MOG(91-108)-induced rat Experimental Autoimmune Encephalomyelitis (EAE), a model for human Multiple Sclerosis (MS). The suppressive effect of pMOG is dependent on inclusion of CpG DNA in the plasmid backbone and is associated with early induction of Interferon (IFN)-beta. PRINCIPAL FINDINGS: In this study we examined the mechanisms underlying pMOG-induced protection. We found that in the DNA vaccinated cohort proinflammatory Interleukin (IL)-17 and IL-21 responses were dramatically reduced compared to in the control group, but that the expression of Foxp3 and Tumor Growth Factor (TGF)-beta1, which are associated with regulatory T cells, was not enhanced. Moreover, genes associated with Type I IFNs were upregulated. To delineate the role of IFN-beta in the protective mechanism we employed short interfering RNA (siRNA) to IFN-beta in the DNA vaccine. SiRNA to IFN-beta completely abrogated the protective effects of the vaccine, demonstrating that a local early elaboration of IFN-beta is important for EAE protection. IL-17 responses comparable to those in control rats developed in rats injected with the IFN-beta-silencing DNA vaccine. CONCLUSIONS: We herein demonstrate that DNA vaccination protects from proinflammatory Th17 cell responses during induction of EAE. The mechanism involves IFN-beta as IL-17 responses are rescued by silencing of IFN-beta during DNA vaccination.