Implementation of high sensitivity troponin into routine clinical practice - results of the extended CARdiac MArkers guideline uptake in Europe group (CARMAGUE) survey.

Background: Measurement of cardiac troponin (cTn) by a high sensitivity method is now the recommended strategy for the detection of myocardial injury. An international survey was undertaken to assess how this has been implemented.

Methods: A questionnaire based around 14 domains on cardiac biomarkers was distributed electronically with the aid of professional societies accessed by a web link within the invitation.

The multidimensional value of natriuretic peptides in heart failure, integrating laboratory and clinical aspects.

Natriuretic peptides (NP) play an essential role in heart failure (HF) regulation, and their measurement has improved diagnostic and prognostic accuracy. Clinical symptoms and objective measurements, such as NP levels, should be included in the HF definition to render it more reliable and consistent among observers, hospitals, and healthcare systems. BNP and NT-proBNP are reasonable surrogates for cardiac disease, and their measurement is critical to early diagnosis and risk stratification of HF patients.

Construction of Fusion Protein for Enhanced Small RNA Loading to Extracellular Vesicles.

Extracellular vesicles (EVs) naturally carry cargo from producer cells, such as RNA and protein, and can transfer these messengers to other cells and tissue. This ability provides an interesting opportunity for using EVs as delivery vehicles for therapeutic agents, such as for gene therapy. However, endogenous loading of cargo, such as microRNAs (miRNAs), is not very efficient as the copy number of miRNAs per EV is quite low.

Nuclear microRNA-466c regulates Vegfa expression in response to hypoxia.

MicroRNAs are well characterized in their role in silencing gene expression by targeting 3´-UTR of mRNAs in cytoplasm. However, recent studies have shown that miRNAs have a role in the regulation of genes in the nucleus, where they are abundantly located. We show here that in mouse endothelial cell line (C166), nuclear microRNA miR-466c participates in the regulation of vascular endothelial growth factor a (Vegfa) gene expression in hypoxia.

Rats bred for low intrinsic aerobic exercise capacity link obesity with brain inflammation and reduced structural plasticity of the hippocampus.

Background: Increasing evidence shows obesity and poor metabolic health are associated with cognitive deficits, but the mechanistic connections have yet to be resolved. We studied rats selectively bred for low and high intrinsic aerobic capacity in order to test the association between low physical fitness, a genetic predisposition for obesity, and brain health. We hypothesized that low-capacity runner (LCR) rats with concurrently greater levels of adiposity would have increased hippocampal inflammation and reduced plasticity compared to the more physically fit high-capacity runner (HCR) rats.

How Well Do Laboratories Adhere to Recommended Guidelines for Cardiac Biomarkers Management in Europe? The CArdiac MARker Guideline Uptake in Europe (CAMARGUE) Study of the European Federation of Laboratory Medicine Task Group on Cardiac Markers.

Background: The CARdiac MARker Guideline Uptake in Europe (CAMARGUE) program is a multi-country audit of the use of cardiac biomarkers in routine clinical practice.

Methods: An email link to a web-based questionnaire of 30 multiple-choice questions was distributed via the professional societies in Europe.

Results: 374 questionnaires were returned from 39 countries, the majority of which were in northern Europe with a response rate of 8.

Update on current practice in laboratory medicine in respect of natriuretic peptide testing for heart failure diagnosis and management in Europe. The CARdiac MArker guideline Uptake in Europe (CARMAGUE) study.

Background: The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) initiated the CArdiac MARker Guidelines Uptake in Europe (CAMARGUE) Study to survey if current biomarker testing for heart failure (HF) in Europe is in accordance with up-dated guidelines.

Methods: A web-based questionnaire was distributed to clinical laboratories via European biochemical societies in 2019. Questions covered the type of natriuretic peptide (NP) assays performed, decision limits for HF, and opinion concerning requirement of different thresholds in patients with renal failure or obesity.

How well do laboratories adhere to recommended guidelines for dyslipidaemia management in Europe? The CArdiac MARker Guideline Uptake in Europe (CAMARGUE) study.

Background: The CArdiac MARker Guidelines Uptake in Europe Study (CAMARGUE) initiated by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) aims to survey the current use of evidence-based guidelines for dyslipidemia testing in Europe.

Methods: In 2019 a web-based questionnaire was distributed via EFLM National Societies to clinical laboratories in Europe. Questions covered pre-analytics, analytical methods, measurement units, flagging of decision thresholds, and use of decision-enhancing comments.

Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM.

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol (=total - HDL cholesterol) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDL cholesterol is the primary target of lipid-lowering therapies.

Quantifying atherogenic lipoproteins for lipid-lowering strategies: consensus-based recommendations from EAS and EFLM.

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total - HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipid-lowering therapies.

Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress.

MicroRNAs (miRNAs) are small non-coding RNAs that have well-characterized roles in cytoplasmic gene regulation, where they act by binding to mRNA transcripts and inhibiting their translation (i.e. post-transcriptional gene silencing, PTGS).

Activating the Chromatin by Noncoding RNAs.

Significance: The extent and breadth of transcription have recently been uncovered and this has revealed an extensive array of noncoding RNAs (ncRNAs). The biological role and significance of these ncRNAs have been realized and to date it appears that ncRNAs may have many important regulatory functions. ncRNAs are multifaceted and they induce a complexity of different types of transcriptional and posttranscriptional regulation, including gene activation.

Are Heart Failure Management Recommendations and Guidelines Followed in Laboratory Medicine in Europe and North America? The Cardiac Marker Guideline Uptake in Europe (CARMAGUE) Study.

Background: The aim of this survey was to investigate how well heart failure (HF) guidelines for use of natriuretic peptides (NPs) have been implemented in laboratory practice in Europe and North America.

Methods: In 2013 and 2014, a web-based questionnaire was distributed via North American and European biochemical societies. Questions covered assay performed, reason for method choice, decision limits for HF, and laboratory accreditation status.

How Well Do Laboratories Adhere to Recommended Clinical Guidelines for the Management of Myocardial Infarction: The CARdiac MArker Guidelines Uptake in Europe Study (CARMAGUE).

Background: We undertook an assessment of current use of evidence-based guidelines for the use of cardiac biomarkers in Europe (EU) and North America (NA).

Methods: In 2013-2014 a web-based questionnaire was distributed via NA and EU biochemical societies. Questions covered cardiac biomarkers measured, analytical methods used, decision thresholds, and use of decision-making protocols.

First-trimester maternal serum ADAM12-s and PAPP-A levels are altered in pregnancies conceived after assisted reproduction techniques (ART).

Objective: The objective of this article is to estimate whether the maternal serum levels of A disintegrin and metalloprotease domain 12 (ADAM12-s), pregnancy-associated plasma protein-A (PAPP-A), and free beta human chorionic gonadotrophin (fβ-hCG) are altered in assisted reproduction techniques (ART) pregnancies.

Method: A retrospective cohort study with a control group was performed. Two hundred eighty-three ART pregnancies and 1008 controls were studied.

Combined first-trimester screening in northern Finland: experiences of the first ten years.

Objective: To evaluate the efficacy of first trimester combined screening for Down's syndrome in Northern Finland during the first 10 years of practice.

Methods: During 1 January 2002 to 31 December 2011, 47,896 women participated voluntarily in combined screening during first trimester. The risk cutoff was 1:250.

Extremely large nuchal translucency measurement predicts adverse pregnancy outcome.

A prospective study was conducted to determine the outcome of pregnancies with 1st trimester nuchal translucency measurement of ≥ 6.5 mm. The risk of fetal abnormalities increases with enlarging nuchal translucency, being around 45% with a measurement of ≥ 6.

Novel sensitive cardiac troponin I immunoassay free from troponin I-specific autoantibody interference.

Background: Cardiac troponins (cTnI and cTnT) are the recommended biomarkers of myocardial infarction. As cTn-specific autoantibodies (cTnAAb) can interfere with the cTn detection by state-of-the-art cTnI assays, our objective was to develop a sensitive cTnI immunoassay free from this analytical interference.

Methods: The assay used antibody-coated spots containing three capture Mabs/Fabs directed against the N-terminus, midfragment and C-terminus of cTnI and a europium chelate-labeled tracer Mab against the C-terminus.

Clinical impact of direct HDLc and LDLc method bias in hypertriglyceridemia. A simulation study of the EAS-EFLM Collaborative Project Group.

Background: Despite international standardization programs for LDLc and HDLc measurements, results vary significantly with methods from different manufacturers. We aimed to simulate the impact of analytical error and hypertriglyceridemia on HDLc- and LDLc-based cardiovascular risk classification.

Methods: From the Dutch National EQA-2012 external quality assessment of 200 clinical laboratories, we examined data from normotriglyceridemic (∼ 1 mmol/l) and hypertriglyceridemic (∼ 7 mmol/l) serum pools with lipid target values assigned by the Lipid Reference Laboratory in Rotterdam.

Extension of dynamic range of sensitive nanoparticle-based immunoassays.

Nanoparticles have successfully been employed in immunometric assays that require high sensitivity. Certain analytes, however, require dynamic ranges (DRs) around a predetermined cut-off value. Here, we have studied the effects that antibody orientation and addition of free solid-phase and detection antibodies have on assay sensitivity and DR in traditional sandwich-type immunoassays.

Four automated 25-OH total vitamin D immunoassays and commercial liquid chromatography tandem-mass spectrometry in Finnish population.

Background: Comparing four fully automated 25-OH-D immunoassays to a commercially available liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with human serum samples from Finnish population.

Methods: 400 samples were analyzed with the Liaison Total Vitamin D, the IDS-iSYS 25-Hydroxy Vitamin D, the ARCHITECT 25-OH Vitamin D, the ADVIA Centaur Vitamin D Total, and a commercially available LC-MS/MS 25-OH D (PerkinElmer) method.

Results: The Liaison method mean value (95% confidence intervals) was 65.

Comparison of combined, biochemical and nuchal translucency screening for Down syndrome in first trimester in Northern Finland.

Objective: To compare the efficacy of fetal nuchal translucency screening, maternal serum screening and combined screening for Down syndrome.

Design: A prospective study.

Setting: University hospital and its public health care district in Northern Finland.

Do laboratories follow heart failure recommendations and guidelines and did we improve? The CARdiac MArker Guideline Uptake in Europe (CARMAGUE).

Background: Natriuretic peptides (NP) are well-established markers of heart failure (HF). During the past 5 years, analytical and clinical recommendations for measurement of these biomarkers have been published in guidelines. The aim of this follow-up survey was to investigate how well these guidelines for measurement of NP have been implemented in laboratory practice in Europe.

Comparison of automated 25-OH vitamin D immunoassays with liquid chromatography isotope dilution tandem mass spectrometry.

Background: Comparing two fully automated 25-OH-D immunoassays with a validated liquid chromatography isotope dilution tandem mass spectrometry (LC-IDMS/MS) method in human serum samples.

Methods: 180 samples were analyzed with the Liaison TOTAL Vitamin D, the IDS-iSYS 25-Hydroxy Vitamin D, and a validated LC-IDMS/MS 25-OH D method.

Results: The Liaison method mean +/- standard deviation (SD) was 64.