Clinical Chemistry

BACKGROUND: Measuring parathyroid hormone-related peptide (PTHrP) helps diagnose the humoral hypercalcemia of malignancy, but is often ordered for patients with low pretest probability, resulting in poor test utilization. Manual review of results to identify inappropriate PTHrP orders is a cumbersome process. METHODS: Using a dataset of 1330 patients from a single institute, we developed a machine learning (ML) model to predict abnormal PTHrP results. We then evaluated the performance of the model on two external datasets...

BACKGROUND: Using broad range cell-free DNA sequencing (BRcfDNA-Seq), a nontargeted next-generation sequencing (NGS) methodology, we previously identified a novel class of approximately 50 nt ultrashort single-stranded cell-free DNA (uscfDNA) in plasma that is distinctly different from 167 bp mononucleosomal cell-free DNA (mncfDNA). We hypothesize that uscfDNA possesses characteristics that are useful for disease detection. METHODS: Using BRcfDNA-Seq, we examined both cfDNA populations in the plasma of 18 noncancer controls and 14 patients with late-stage nonsmall cell lung carcinoma (NSCLC)...

BACKGROUND: Disrupted pre-mRNA splicing is a frequent deleterious mechanism in hereditary cancer. We aimed to functionally analyze candidate spliceogenic variants of the breast cancer susceptibility gene CHEK2 by splicing reporter minigenes. METHODS: A total of 128 CHEK2 splice-site variants identified in the Breast Cancer After Diagnostic Gene Sequencing (BRIDGES) project (https://cordis.europa.eu/project/id/634935) were analyzed with MaxEntScan and subsetted to 52 variants predicted to impact splicing...

BACKGROUND: Development of validated biomarkers to detect early Alzheimer disease (AD) neuropathology is needed for therapeutic AD trials. Abnormal concentrations of "core" AD biomarkers, cerebrospinal fluid (CSF) amyloid beta1-42, total tau, and phosphorylated tau correlate well with neuroimaging biomarkers and autopsy findings. Nevertheless, given the limitations of established CSF and neuroimaging biomarkers, accelerated development of blood-based AD biomarkers is underway. CONTENT: Here we describe the clinical significance of CSF and plasma AD biomarkers to detect disease pathology throughout the Alzheimer continuum and correlate with imaging biomarkers...

It is important for external quality assessment materials (EQAMs) to be commutable with clinical samples; i.e., they should behave like clinical samples when measured using end-user clinical laboratory in vitro diagnostic medical devices (IVD-MDs). Using commutable EQAMs makes it possible to evaluate metrological traceability and/or equivalence of results between IVD-MDs. The criterion for assessing commutability of an EQAM between 2 IVD-MDs is that its result should be within the prediction interval limits based on the statistical distribution of the clinical sample results from the 2 IVD-MDs being compared...

BACKGROUND: Cell-type specific DNA methylation (DNAm) can be employed to determine the numbers of leukocyte subsets in blood. In contrast to conventional methods for leukocyte counts, which are based on cellular morphology or surface marker protein expression, the cellular deconvolution based on DNAm levels is applicable for frozen or dried blood. Here, we further enhanced targeted DNAm assays for leukocyte counts in clinical application. METHODS: DNAm profiles of 40 different studies were compiled to identify CG dinucleotides (CpGs) with cell-type specific DNAm using a computational framework, CimpleG...

BACKGROUND: Artificial intelligence (AI) has emerged as a promising and transformative tool in the field of urinalysis, offering substantial potential for advancements in disease diagnosis and the development of predictive models for monitoring medical treatment responses. CONTENT: Through an extensive examination of relevant literature, this narrative review illustrates the significance and applicability of AI models across the diverse application area of urinalysis...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and intrinsic factor secretion, leading to iron deficiency and pernicious anemia as a consequence of iron and cobalamin malabsorption. Positivity toward parietal cell (PCA) and intrinsic factor (IFA) autoantibodies is very common. AAG may remain asymptomatic for many years, thus making its diagnosis complex and often delayed...

BACKGROUND: Artificial intelligence (AI) conversational agents, or chatbots, are computer programs designed to simulate human conversations using natural language processing. They offer diverse functions and applications across an expanding range of healthcare domains. However, their roles in laboratory medicine remain unclear, as their accuracy, repeatability, and ability to interpret complex laboratory data have yet to be rigorously evaluated. CONTENT: This review provides an overview of the history of chatbots, two major chatbot development approaches, and their respective advantages and limitations...

No abstract text is available yet for this article.

BACKGROUND: The standard lipid panel forms the backbone of atherosclerotic cardiovascular disease risk assessment. Suboptimal analytical performance, along with biological variability, could lead to erroneous risk assessment and management decisions. The current National Cholesterol Education Program (NCEP) performance recommendations have remained unchanged for almost 3 decades despite improvements in assay technology. We investigated the potential extent of risk misclassification when the current recommendations are met and explored the impact of improving analytical performance goals...

No abstract text is available yet for this article.

BACKGROUND: Molecular brain tumor diagnosis is usually dependent on tissue biopsies or resections. This can pose several risks associated with anesthesia or neurosurgery, especially for lesions in the brain stem or other difficult-to-reach anatomical sites. Apart from initial diagnosis, tumor progression, recurrence, or the acquisition of novel genetic alterations can only be proven by re-biopsies. METHODS: We employed Nanopore sequencing on cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) and analyzed copy number variations (CNV) and global DNA methylation using a random forest classifier...

BACKGROUND: The quantification of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine are the first-line tests for diagnosis and monitoring of acute hepatic porphyrias (AHP). Ion-exchange chromatography (IEC), which is time- and staff-consuming and limited to urine, is still the preferred method in many specialized laboratories, despite the development of mass spectrometry-based methods. METHODS: We describe a new LC-MS method that allows for rapid and simple quantification of ALA and PBG in urine and plasma with an affordable instrument that was used to analyze 2260 urine samples and 309 blood samples collected in 2 years of routine activity...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Despite clinically demonstrated accuracy in next generation sequencing (NGS) data, many clinical laboratories continue to confirm variants with Sanger sequencing, which increases cost of testing and turnaround time. Several studies have assessed the accuracy of NGS in detecting single nucleotide variants; however, less has been reported about insertion, deletion, and deletion-insertion variants (indels). METHODS: We performed a retrospective analysis from 2015-2022 of indel results from a subset of NGS targeted gene panel tests offered through the Mayo Clinic Genomics Laboratories...