Background: Most patients presenting to the emergency department (ED) with suspected acute coronary syndrome (ACS) undergo noninvasive cardiac testing with a low diagnostic yield. We determined whether a combination of high-sensitivity cardiac troponin I (hs-cTnI) and cardiovascular risk factors might improve selection of patients for cardiac testing.
Methods: We included patients from the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) I and II trials who presented to the ED with acute chest pain and were referred for cardiac testing. Read More
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN;
Background: A number of lipoprotein(a) [Lp(a)] analytical techniques are available that quantify distinct particle components, yet their clinical efficacy has not been comprehensively evaluated. This study determined whether Lp(a) mass [Lp(a)-M], Lp(a) cholesterol content [Lp(a)-C], and particle concentration [Lp(a)-P] differentially discriminated risk of calcific aortic valve disease (CAVD) or incident coronary heart disease (CHD) among 4679 participants of the Multi-Ethnic Study of Atherosclerosis (MESA).
Methods: Lp(a)-M, Lp(a)-C, and Lp(a)-P were measured in individuals without clinical evidence of CHD at baseline. Read More
Background: Plasma cell-free RNA (cfRNA) encompasses a broad spectrum of RNA species that can be derived from both human cells and microbes. Because cfRNA is fragmented and of low concentration, it has been challenging to profile its transcriptome using standard RNA-seq methods.
Methods: We assessed several recently developed RNA-seq methods on cfRNA samples. Read More
Background: Adrenocortical carcinoma (ACC) is a rare malignancy, with an annual incidence of 1 or 2 cases per million. Biochemical diagnosis is challenging because up to two-thirds of the carcinomas are biochemically silent, resulting from de facto enzyme deficiencies in steroid hormone biosynthesis. Urine steroid profiling by GC-MS is an effective diagnostic test for ACC because of its capacity to detect and quantify the increased metabolites of steroid pathway synthetic intermediates. Read More
Background: High blood pressure (BP) is associated with an increased rate of cardiovascular events and mortality. Cardiovascular biomarkers are able to predict long-term risk in the general population, particularly in diseased cohorts. We undertook an investigation of the effect of 2 different antihypertensive treatments on cardiovascular biomarkers in a randomized trial. Read More
Background: The physiological role of lipoprotein(a) is unclear; however, lipoprotein(a) may play a role in hemostasis and wound healing. We tested the hypothesis that high lipoprotein(a) concentrations are associated with low risk of major bleeding in the brain and airways both observationally and causally (from human genetics).
Methods: We examined 109169 individuals from the Copenhagen City Heart Study and the Copenhagen General Population study, 2 similar prospective studies conducted in the Danish general population. Read More
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT.
Background: Morphologic profiling of the erythrocyte population is a widely used and clinically valuable diagnostic modality, but one that relies on a slow manual process associated with significant labor cost and limited reproducibility. Automated profiling of erythrocytes from digital images by capable machine learning approaches would augment the throughput and value of morphologic analysis. To this end, we sought to evaluate the performance of leading implementation strategies for convolutional neural networks (CNNs) when applied to classification of erythrocytes based on morphology. Read More
Background: In 2014, 2 novel synthetic cannabinoids, MN-18 and its 5-fluoro analog, 5F-MN-18, were first identified in an ongoing survey of novel psychoactive substances in Japan. In vitro pharmacological assays revealed that MN-18 and 5F-MN-18 displayed high binding affinities to human CB1 and CB2 receptors, with Ki being 1.65-3. Read More
Background: High-resolution DNA melting analysis of small amplicons is a simple and inexpensive technique for genotyping. Microfluidics allows precise and rapid control of temperature during melting.
Methods: Using a microfluidic platform for serial PCR and melting analysis, 4 targets containing single nucleotide variants were amplified and then melted at different rates over a 250-fold range from 0. Read More
Background: Steroid profiling is a promising diagnostic tool for those with adrenal tumors, Cushing syndrome (CS), and disorders of steroidogenesis. Our objective was to develop a multiple-steroid assay using liquid-chromatography, high-resolution, accurate-mass mass spectrometry (HRAM LC-MS) and to validate the assay in patients with various adrenal disorders.
Methods: We collected 24-h urine samples from 114 controls and 71 patients with adrenal diseases. Read More
Background: Identification, enumeration, and characterization of extracellular vesicles (EVs) are hampered by the small size of EVs, a low refractive index, and low numbers of antigens on their surface.
Methods: We investigated the potential of a 48-multiplex surface plasmon resonance imaging (SPRi) system to perform EV phenotyping. Antigen surface density of 11 antigens was measured on the human breast cancer cell lines HS578T, MCF7, and SKBR3 and their EVs by use of both SPRi and the widely used flow cytometry (FCM). Read More
Background: There is much interest in the tissue of origin of circulating DNA in plasma. Data generated using DNA methylation markers have suggested that hematopoietic cells of white cell lineages are important contributors to the circulating DNA pool. However, it is not known whether cells of the erythroid lineage would also release DNA into the plasma. Read More
Background: Circulating tumor cells (CTC) are thought to be an ideal surrogate marker to monitor disease progression in metastatic breast cancer (MBC). We investigated the prediction of treatment response in CTC of MBC patients on the basis of the expression of 46 genes.
Methods: From 45 MBC patients and 20 healthy donors (HD), 2 × 5 mL of blood was collected at the time of disease progression (TP0) and at 2 consecutive clinical staging time points (TP1 and TP2) to proceed with the AdnaTest EMT-2/StemCellSelect™ (QIAGEN). Read More
Department of Medicine, Harvard Medical School, Division of Endocrinology, Diabetes, and Metabolism, Carl J. Shapiro Institute for Education and Research, Beth Israel Deaconess Medical Center, Boston, MA.
Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Australia;
Background: False-positive EGFR T790M mutations have been reported in formalin-fixed lung tumors, but the cause of the false positives has not been identified. The T790M mutation results from a C>T change at the cytosine of a CpG dinucleotide. The presence or absence of methylation at this cytosine has different consequences following deamination, resulting in a thymine or uracil, respectively, both of which however result in an artifactual change. Read More
Background: The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined biological variation (BV) indices. EuBIVAS determined BV for serum creatinine using the enzymatic and alkaline picrate measurement methods.
Method: In total, 91 healthy individuals (38 males, 53 females; age range, 21-69 years) were bled for 10 consecutive weeks at 6 European laboratories. Read More
Background: Gut microbiota, the collective community of microorganisms inhabiting the intestine, have been shown to provide many beneficial functions for the host. Recent advances in next-generation sequencing and advanced molecular biology approaches have allowed researchers to identify gut microbiota signatures associated with disease processes and, in some cases, establish causality and elucidate underlying mechanisms.
Content: This report reviews 3 commonly used methods for studying the gut microbiota and microbiome (the collective genomes of the gut microorganisms): 16S rRNA gene sequencing, bacterial group or species-specific quantitative polymerase chain reaction (qPCR), and metagenomic shotgun sequencing (MSS). Read More
Background: The IFCC Committee for Standardization of Thyroid Function Tests intended to standardize free thyroxine (FT4) immunoassays. We developed a Système International d'Unités traceable conventional reference measurement procedure (RMP) based on equilibrium dialysis and mass spectrometry. We describe here the latest studies intended to recalibrate against the RMP and supply a proof of concept, which should allow continued standardization efforts. Read More
Background: Detection of somatic genomic alterations in tumor-derived cell-free DNA (cfDNA) in the plasma is challenging owing to the low concentrations of cfDNA, variable detection methods, and complex workflows. Moreover, no proper quality control materials are available currently.
Methods: We developed a set of synthetic cfDNA quality control materials (SCQCMs) containing spike-in cfDNA on the basis of micrococcal nuclease digestion carrying somatic mutations as simulated cfDNA and matched genomic DNA as genetic background to emulate paired tumor-normal samples in real clinical tests. Read More
Background: We examined the diagnostic performance of high-sensitivity cardiac troponin I (hs-cTnI) vs contemporary cTnI with use of the 99th percentile alone and with a normal electrocardiogram (ECG) to rule out acute myocardial infarction (MI) and serial changes (deltas) to rule in MI.
Methods: We included consecutive patients presenting to a US emergency department with serial cTnI on clinical indication (NCT02060760). Diagnostic performance for acute MI, including MI subtypes, and 30-day outcomes were examined. Read More