Clinical Chemistry Podcast

Inborn errors of metabolism are rare diseases in which a single gene defect causes a clinically significant block in a metabolic pathway resulting either in an accumulation of substrate behind the block or a lack or deficiency of the product. Profiling metabolites in the pathway could allow for accurate and timely identification of patients who have these diseases and help physicians to devise effective treatment. Congenital disorders of glycosylation represent one of the largest groups of such metabolic disorders. In May 2019, Clinical Chemistry published a study on the development and validation of a plasma protein N-glycan assay using a flow injection-electrospray ionization-quadrupole time-of-flight mass spectrometry.

For about the past 15 years, the public has become aware that genetic testing can provide medical diagnosis and inform specific medical therapies. In addition to being used for medical purposes, genetics has also become a popular recreational tool for genealogy and general wellness. The number of customers for direct-to-consumer genetic testing has now grown to greater than 12 million and continues to rise. In the May 2019 issue of Clinical Chemistry, a Q&A feature titled "Privacy in Direct-to-Consumer Genetic Testing" asked four experts with different roles in this field to discuss the current state of genomics and privacy.

Hospital pneumatic tube systems provide rapid transportation of patient samples to the laboratory. However, it is known that the physical movement through a pneumatic tube system can agitate blood samples and sometimes cause cells to break open and leak intracellular components. As a result, multiple laboratory results are susceptible to error. The May 2019 issue of Clinical Chemistry published a paper by Dr. Ann Gronowski and Dr. Christopher Farnsworth and their colleagues at the Washington University School of Medicine in St. Louis that describes parameters for evaluating a hospital pneumatic tube system.

Mendelian randomization is a genetic epidemiological approach that is made substantial inroads into our understanding of the causes and consequences of disease, but can that same technique be run in reverse? In the March 2019 issue of Clinical Chemistry, a paper investigated potential blood markers of early chronic kidney disease which are caused by loss of kidney function, using an innovative reverse Mendelian randomization approach. That same issue included an editorial that was authored by Dr. Michael Holmes from the University of Oxford and by Dr. George Davey Smith from the University of Bristol, both from the United Kingdom and both are our guests in this podcast.

Polycystic ovary syndrome is a complex endocrine-mediated disorder in women with an estimated prevalence of about 10%. Women with PCOS typically present with heterogeneous clinical signs and symptoms such as excess hair growth, irregular menstrual cycles, infertility and metabolic issues. Currently, there are no universal criteria for diagnosis of this condition and as a result, women with the disorder often reports significant delays in diagnosis and poor follow-up care. A Q&A feature in the March 2019 issue of Clinical Chemistry asked five experts with different roles in this field to discuss recent advances and ongoing challenges surrounding the current diagnostic criteria, available biomarkers, and the timely diagnosis and management of women with polycystic ovary syndrome.

Identifying markers of chronic kidney disease that occur early in the disease process and are specific to loss of kidney function may allow timely more accurate identification of patients who will eventually develop the disease. In the March 2019 issue of Clinical Chemistry, a paper investigated potential blood markers of early chronic kidney disease which are caused by loss of kidney function using an innovative reverse Mendelian randomization approach.

Glomerular filtration rate, or GFR, is generally accepted as the best overall index of kidney function, and a decrease in GFR has important implications for prognosis in patient management. GFR is most commonly estimated by calculation, using the serum concentration of an endogenous filtration marker such as creatinine and demographic variables such as age, sex, and race. In the March 2019 issue of Clinical Chemistry, a paper investigated the possibility of developing a more accurate estimate of GFR, using a panel of metabolites measured by quantitative liquid chromatography, tandem mass spectrometry without creatinine, cystatin C, or demographic variables.

In the March 2019 issue of Clinical Chemistry, Professor Andrew Levey and others from a multinational consortium of institutions, published a study titled, "Validation of a Metabolite Panel for a More Accurate Estimation of Glomerular Filtration Rate Using Quantitative LC-MS-MS." In fact, we have another podcast from one of the authors of that paper available. But today, we're joined by Dr. Anders Berg, the Associate Medical Director of the Core Laboratories at Cedars-Sinai in Los Angeles, who co-authored an editorial that accompanied the paper. Dr. Berg is here to help us deconvolute the significance of this intriguing study and where this research might lead us in the future.

Acute abdominal pain is one of the most common presenting symptoms in emergency department patients and its differential diagnosis can be extensive and challenging. Rapid and accurate diagnosis of urgent causes of abdominal pain is essential for the early initiation of effective therapy and efficient patient flow. To see how the clinical laboratory can help in this process, a recent study that appeared in the February 2019 issue of Clinical Chemistry examined inflammatory biomarkers in the emergency diagnosis of urgent abdominal pain.

Cardiovascular risk is so high in type III hyperlipoproteinemia that is typically a "treat immediately on diagnosis" disorder. In the February 2019 issue of Clinical Chemistry, a paper presented the advantages of a non-high density lipoprotein cholesterol ratio with apolipoprotein B as a diagnostic tool for type III hyperlipoproteinemia. In the same issue, an accompanying editorial entitled "Type III Hyperlipoproteinemia: The Forgotten, Disregarded, Neglected, Overlooked, Ignored but Highly Atherogenic, and Highly Treatable Dyslipo-proteinemia" was also published. The author of that article is Dr. Allan Sniderman, the Edwards Professor of Cardiology at McGill University in Montreal, Quebec, Canada, and he is our guest in this podcast.

High-density lipoproteins, or HDLs, are macromolecular assemblies that play a key role in lipid transport, but also exert effects in endothelial function, thrombosis, and inflammation. A recent focus by several groups on HDL function rather than HDL cholesterol revealed that efflux capacity was inversely associated with coronary artery disease. Traditionally, cholesterol efflux is measured using a cell-based assay where cultured microphages are treated with radioactively-labeled cholesterol and subsequently exposed to a cholesterol acceptor. A recent study that appeared in the February 2019 issue of Clinical Chemistry took a completely different approach and assessed the lipoprotein proteome by using liquid chromatography and tandem mass spectrometry to measure 21 lipoprotein associated proteins.

Machine learning involves the study of algorithms and mathematical models so that computer systems can progressively improve their performance on solving a specific task. A recent application of machine learning through the interpretation of urine steroid profiles appears in the November 2018 issue of Clinical Chemistry.

A recent study appears in the September 2018 issue of Clinical Chemistry, an assessment of digital PCR as a primary reference measurement procedure to support advances in precision medicine.

In almost all high-income countries, the U.S. included, women live longer than men. As we enter a new era in which biomedical data are increasingly ubiquitous, current and future research may help us understand the fundamental issues that drive differences in longevity and other health outcomes between men and women. Our ability to measure the entire spectrum of information about the human biological, environmental, and behavioral condition will become both routine and relatively inexpensive from genes to genomics. From clinical data to the electronic health record in insurance claims. From digital information about behavior and social interaction to geospatial referencing. The January 2019 issue of Clinical Chemistry is devoted to topics of men's health and in that issue, an article examined differences in health outcomes between men and women and underlying biological, behavioral, and societal factors.