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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. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) [Lp(a)]-cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2–10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20–100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds. [ABSTRACT FROM AUTHOR]

Background: Biomarker discovery studies often claim 'promising' findings, motivating further studies and marketing as medical tests. Unfortunately, the patient benefits promised are often inadequately explained to guide further evaluation, and few biomarkers have translated to improved patient care. We present a practical guide for setting minimum clinical performance specifications to strengthen clinical performance study design and interpretation. Methods: We developed a step-by-step approach using test evaluation and decision-analytic frameworks and present with illustrative examples. Results: We define clinical performance specifications as a set of criteria that quantify the clinical performance a new test must attain to allow better health outcomes than current practice. We classify the proposed patient benefits of a new test into three broad groups and describe how to set minimum clinical performance at the level where the potential harm of false-positive and false-negative results does not outweigh the benefits. (1) For add-on tests proposed to improve disease outcomes by improving detection, define an acceptable trade-off for false-positive versus true-positive results; (2) for triage tests proposed to reduce unnecessary tests and treatment by ruling out disease, define an acceptable risk of false-negatives as a safety threshold; (3) for replacement tests proposed to provide other benefits, or reduce costs, without compromising accuracy, use existing tests to benchmark minimum accuracy levels. Conclusions: Researchers can follow these guidelines to focus their study objectives and to define statistical hypotheses and sample size requirements. This way, clinical performance studies will allow conclusions about whether test performance is sufficient for intended use. [ABSTRACT FROM AUTHOR]

The article information on the requirement of a reference measurement system for the tissue factor-induced coagulation time. Topics discussed include information on the prothrombin time test influence not only by the prothrombin but also by the coagulation factor and the fibrinogen; discussions on the international normalized ratio; and the World Health Organization's International Standards for thromboplastin.

Introduction: The current way to assess the risk of cardiovascular disease (CVD) is to measure conventional lipid and lipoprotein cholesterol fractions. Despite the success of statin treatment, residual cardiovascular risk remains high. Therefore, the value of extensive serum apolipoprotein (apo) profiling to assess the risk of ST-segment elevation myocardial infarction (STEMI) and of major adverse cardiac events (MACE) in patients with STEMI was investigated in a case–control design. Methods and results: Serum apo levels were measured using liquid chromatography and mass spectrometry in 299 healthy individuals and 220 patients with STEMI. First, the association of apo profiles in baseline samples with risk of STEMI was examined, and second, the association of apo profiles at baseline with risk of recurrent MACE in patients with STEMI in a longitudinal study design was studied. High baseline (> 1.25 g/L) apoA1 levels were associated with a decreased risk of STEMI [odds ratio (OR) 0.17; 95% CI 0.11–0.26], whereas high apoB (> 1.00 g/L) levels (OR 2.17; 95% CI 1.40–3.36) and apoB/apoA1 ratio (OR per 1 SD (OR/SD): 2.16; 95% CI 1.76–2.65) were associated with an increased risk. Very-low-density-lipoprotein (VLDL)-associated apos gave conflicting results. Neither conventional lipid levels nor apo levels were associated with MACE in the STEMI group. Conclusion: In conclusion, apoA1, apoB, and apoB/apoA1 were strongly associated with risk of STEMI. No clear relation between VLDL-associated apos and the risk of STEMI was found. Neither baseline serum apos nor lipids predicted MACE in statin-treated patients during long-term follow-up after a first STEMI. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a frequent complication in hospitalised patients and is diagnosed by urinary output and serum creatinine. Serum creatinine is an indirect marker for renal glomerular filtration, but lacks specificity for damage to kidney tissue and the relatively late response to injury precludes early recognition of AKI. Timely diagnosis of kidney injury using biomarkers that provide information about the aetiology of kidney injury is an unmet clinical need.To overcome the suboptimal performance of serum creatinine, injury biomarkers have been proposed that predict AKI in diverse clinical settings. The clinical performance of these markers is considered moderate due to the lack of specificity for kidney tissue or the underlying injury mechanisms, poor test specificity and confounding by interventions or comorbidities. Hence, it is not unequivocally beneficial to implement current kidney injury biomarkers in the clinical laboratory for diagnostic purposes. In this article we review biomarkers that might fulfil AKI-related unmet clinical needs in the academic hospital setting. [ABSTRACT FROM AUTHOR]

Background: External quality assessment (EQA) programs for general chemistry tests have evolved from between laboratory comparison programs to trueness verification surveys. In the Netherlands, the implementation of such programs has reduced inter-laboratory variation for electrolytes, substrates and enzymes. This allows for national and metrological traceable reference intervals, but these are still lacking. We have initiated a national endeavor named NUMBER (Nederlandse UniforMe Beslisgrenzen En Referentie-intervallen) to set up a sustainable system for the determination of standardized reference intervals in the Netherlands. Methods: We used an evidence-based 'big-data' approach to deduce reference intervals using millions of test results from patients visiting general practitioners from clinical laboratory databases. We selected 21 medical tests which are either traceable to SI or have Joint Committee for Traceability in Laboratory Medicine (JCTLM)-listed reference materials and/or reference methods. Per laboratory, per test, outliers were excluded, data were transformed to a normal distribution (if necessary), and means and standard deviations (SDs) were calculated. Then, average means and SDs per test were calculated to generate pooled (mean±2 SD) reference intervals. Results were discussed in expert meetings. Results: Sixteen carefully selected clinical laboratories across the country provided anonymous test results (n=7,574,327). During three expert meetings, participants found consensus about calculated reference intervals for 18 tests and necessary partitioning in subcategories, based on sex, age, matrix and/or method. For two tests further evaluation of the reference interval and the study population were considered necessary. For glucose, the working group advised to adopt the clinical decision limit. Conclusions: Using a 'big-data' approach we were able to determine traceable reference intervals for 18 general chemistry tests. Nationwide implementation of these established reference intervals has the potential to improve unequivocal interpretation of test results, thereby reducing patient harm. [ABSTRACT FROM AUTHOR]

This was a cross-sectional study on the correlation between abdominal aortic calcification (AAC) and Modic changes (MC). Little is known regarding the etiology of MC in the lumbar spine. Currently, insufficient vascularization of the endplate has been proposed to contribute to the appearance of MC. Our objective was to investigate whether AAC, a marker for a poor vascular status, is associated with MC in patients suffering from degenerative disc disease. Radiologic images of patients (n = 130) suffering from degenerative lumbar disc disease were reviewed. Type and severity of MC were assessed using magnetic resonance images, and severity of AAC was evaluated using computed tomography images or fluoroscopy. Both items were dichotomized into minimal and relevant grades. The correlation between them was studied using Spearman's correlation test, with age as a covariate. Of the patients, 113 (87%) demonstrated MC (31% type I, 63% type II, and 6% type III) (55% relevant grade), and 68% had AAC (44% relevant grade). Spearman statistical analysis revealed that AAC was correlated with age (P < 0.001), whereas MC were not (P = 0.142). AAC severity was significantly correlated with MC, remaining so after age adjustment (P < 0.05). While MC type I lacked correlation with AAC, MC type II were significantly correlated with AAC (0.288, P = 0.015); however, this association lost significance after adjusting for age (P = 0.057). AAC and MC (mainly MC type II) are associated, indicating that reduced blood supply or even a poor systemic vascularization status due to atherosclerotic disease may play a role in the formation of MC. Future studies focusing on the etiology of MC should pay more attention to patients' vascular status and determinants of abdominal aorta calcification. [ABSTRACT FROM AUTHOR]