Reference intervals: past, present, and future.

Clinical laboratory test results alone are of little value in diagnosing, treating, and monitoring health conditions; as such, a clinically actionable cutoff or reference interval is required to provide context for result interpretation. Healthcare practitioners base their diagnoses, follow-up treatments, and subsequent testing on these reference points. However, they may not be aware of inherent limitations related to the definition and derivation of reference intervals.

Artificial Intelligence Applications in Clinical Chemistry.

Artificial intelligence (AI) applications are an area of active investigation in clinical chemistry. Numerous publications have demonstrated the promise of AI across all phases of testing including preanalytic, analytic, and postanalytic phases; this includes novel methods for detecting common specimen collection errors, predicting laboratory results and diagnoses, and enhancing autoverification workflows. Although AI applications pose several ethical and operational challenges, these technologies are expected to transform the practice of the clinical chemistry laboratory in the near future.

Quantitation of non-derivatized free amino acids for detecting inborn errors of metabolism by incorporating mixed-mode chromatography with tandem mass spectrometry.

Introduction: Amino acids are critical biomarkers for many inborn errors of metabolism, but amino acid analysis is challenging due to the range of chemical properties inherent in these small molecules. Techniques are available for amino acid analysis, but they can suffer from long run times, laborious derivatization, and/or poor resolution of isobaric compounds.

Objective: To develop and validate a method for the quantitation of a non-derivatized free amino acid profile in both plasma and urine samples using mixed-mode chromatography and tandem mass spectrometry.

Indirect reference intervals using an R pipeline.

Background: Indirect reference intervals require robust statistical approaches to separate the pathological and healthy values. This can be achieved with a data pipeline created in R, a freely available statistical programming language.

Methods: A data pipeline was created to ingest, partition, normalize, remove outliers, and identify reference intervals for testosterone (Testo; n  = 7,207) and aspartate aminotransferase (AST; n  = 5,882) using data sets from NHANES.

Preterm to term infant postmenstrual age reference intervals for thyroid-stimulating hormone and free thyroxine.

Background: Infants born preterm are affected by a hypothalamic-pituitary-thyroid axis that is immature and still developing as they progress closer to corrected term gestation. Multiple risk factors place preterm infants at risk for a hypothyroid state. However, there is variability in thyroid-stimulating hormone cutoff values and limited data on free thyroxine reference intervals to guide clinicians.

First- and Second-Trimester Reference Intervals for Thyroid Function Testing in a US Population.

Objectives: Thyroid dysfunction in pregnancy is associated with increased risk of adverse outcomes to mother and child. Trimester-specific reference intervals for thyroid function tests are not routinely provided by clinical laboratories. In this study, we present first- and second-trimester-specific reference intervals in a US population for thyroid-stimulating hormone (TSH), free thyroxine (FT4), total thyroxine (T4), and total triiodothyronine (T3) measured on Roche analyzers.

Urinary cannabinoid mass spectrometry profiles differentiate dronabinol from cannabis use.

Background: Dronabinol is used to treat a variety of conditions, including loss of appetite in people with AIDS and severe nausea and vomiting caused by cancer chemotherapy. Its therapeutic potential for pain management is now being explored in specific populations. Monitoring dronabinol compliance is challenging because its active ingredient, Δ-9-tetrahydrocannabinol (THC), is also present in cannabis.

The 2018 AACC/SYCL PhD Clinical Chemist Compensation Survey.

Background: Doctoral level board-certified clinical chemists play an invaluable role in many facets of laboratory medicine and healthcare. However, information concerning their total compensation is sparse.

Content: A confidential self-reported compensation survey was conducted by the American Association for Clinical Chemistry's Society for Young Clinical Laboratorians (AACC SYCL) Core Committee from April 1 to April 17, 2018.

Health Care and Precision Medicine Research: Analysis of a Scalable Data Science Platform.

Background: Health care data are increasing in volume and complexity. Storing and analyzing these data to implement precision medicine initiatives and data-driven research has exceeded the capabilities of traditional computer systems. Modern big data platforms must be adapted to the specific demands of health care and designed for scalability and growth.

Quantitation of Benzodiazepines and Metabolites in Urine by Liquid Chromatography-Tandem Mass Spectrometry.

Background: Benzodiazepines (BZDs) are central nervous system depressants that are prescribed to prevent seizures, manage anxiety, or help sleep. When misused, BZDs can lead to addiction and sometimes cause death. Measurement of BZDs in urine is used to identify their use, especially in pain management settings.

Investigation of transition ion ratio variation for liquid chromatography-tandem mass spectrometry: A case study approach.

Background: A transition ion ratio (TIR) is the ratio of one fragment over another from the same precursor and is frequently monitored in liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for analyte identification. The Clinical and Laboratory Standards Institute (CLSI) C50-A guidelines give a static percent allowable TIR deviation based on the TIR level. Anecdotally, we observed failures of these rules for some of our LC-MS/MS assays.

Whole blood selenium determination by inductively coupled plasma mass spectrometry.

Objective: To develop a sensitive method for accurately measuring whole blood selenium and determining an appropriate reference interval for the local Cleveland population.

Design And Methods: The assay was developed and validated on an inductively coupled plasma mass spectrometry (ICP-MS) with a collision cell. Whole blood trace element free EDTA tubes were used to collect samples for the reference interval study (n=50).

Comparison of symmetric dimethylarginine with creatinine, cystatin C and their eGFR equations as markers of kidney function.

Objectives: Symmetric dimethylarginine (SDMA) is a catabolic product of arginine-methylated proteins and is an emerging biomarker for kidney function. A limited number of studies in selected populations have shown good correlation between SDMA and a few known markers of glomerular filtration rate (GFR). However, a comprehensive comparison of SDMA with all existing serum endogenous markers in a population with varied kidney function and against measured GFR is lacking.

Therapeutic drug monitoring of immunosuppressants by liquid chromatography-mass spectrometry.

Immunosuppressant medications allow the transplantation of tens of thousands of allografts per year and consequently have great potential to decrease patient morbidity and mortality. However, some medications have great risk associated with over- and under-dosing leading to adverse effects or allograft rejection, respectively. This necessitates immunosuppressant therapeutic drug monitoring accomplished by immunoassay or liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).

Quantification of 1,25-Dihydroxyvitamin D2 and D3 in Serum Using Liquid Chromatography-Tandem Mass Spectrometry.

1,25-Dihydroxyvitamin D is the active form of vitamin D and plays a critical role in the maintenance of calcium and phosphorous metabolism of the human body. Measurement of 1,25-dihydroxyvitamin D in serum can aid in clinical diagnosis and/or management of renal disease, sarcoidosis, and rare inherited diseases. We present here an effective and accurate method for measuring 1,25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D2 by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) after immunoaffinity extraction.

Fast, simple, and sensitive high-performance liquid chromatography method for measuring vitamins A and E in human blood plasma.

Vitamins A and E are fat-soluble vitamins that play important roles in several physiological processes. Monitoring their concentrations is needed to detect deficiency and guide therapy. In this study, we developed a high-performance liquid chromatography method to measure the major forms of vitamin A (retinol) and vitamin E (α-tocopherol and γ-tocopherol) in human blood plasma.