Clinical Chemistry Podcast

Measurement of hemoglobin A1c in blood is essential for the management of patients with diabetes mellitus. Hemoglobin A1c reflects the average blood glucose concentration over the proceeding 8 to 12 weeks. While the clinical value of hemoglobin A1c was initially limited by large differences in results among various methods, the investment of considerable effort to implement standardization has brought about a marked improvement in analysis. In the July 2019 issue of Clinical Chemistry, a Review article chronicles the substantial progress that has been achieved in enhancing the accuracy of these measurements and the role of the National Glycohemoglobin Standardization Program in those efforts.

Bladder cancer is the ninth most common cancer worldwide. The current diagnosis and monitoring of bladder cancer is still heavily reliant on cystoscopy, an invasive procedure where the tumor is directly visualized. However, a paper appearing in the July 2019 issue of Clinical Chemistry from Dr. Dennis Lo's laboratory in Hong Kong reports that bladder cancer can be detected noninvasively in urinary cell-free DNA by methylomic and copy number analysis. Such analyses could be used as a liquid biopsy to aid in the diagnosis and monitoring of bladder cancer.

High-density lipoprotein or HDL is one of the most important of the lipoproteins in most species and there is evidence that points towards a role of HDL in normal immune function. A paper appearing in the May 2019 issue of Clinical Chemistry tested the hypothesis that concentrations of HLD cholesterol are associated with risk of autoimmune disease. That study from the Copenhagen General Population Study and the Copenhagen City Heart Study included over 100,000 individuals. We are pleased to have the senior author of that paper with us today, Dr. Borge Nordestgaard.

In 2014, the U.S. Congress passed the Protecting Access to Medicare Act (PAMA) which required CMS, the Centers for Medicare & Medicaid Services, to revise the clinical laboratory fee schedule to reflect private sector payment rates. Many in the laboratory community believed that the cuts are too deep and have urged CMS to recalculate fees to more accurately reflect the spectrum of laboratories that provide testing for patients. To gain greater insight on the potential impact of PAMA, a Q&A feature in the June 2019 issue of Clinical Chemistry asked six experts with different roles in this field to give their opinions on several of the key issues pertaining to the new reimbursement rates, particularly its potential impact on the laboratory marketplace and patient care.

The standard course for academic promotion has primarily been based on the number and quality of peer-reviewed papers published and the number of peer-reviewed grants received. Other academic activities such as teaching, book editing, mentoring, and service to scientific organizations have also been considered. But this process often falls short for those whose interests are in biomedical education or in translational and clinical applications. In the June 2019 issue of Clinical Chemistry, Nader Rifai, Brian Smith, and Maureen Connelly published an editorial titled, "A Message to Medical School Promotion Committees: Proper Credit for Peer-Reviewed Online Educational Materials."

Non-invasive prenatal testing based on cell-free DNA is now a widely used technique. However, quality control materials that have properties identical to clinical samples and that are applicable to a wide range of procedures are not available to support assay development, internal or external quality control, and proficiency testing. The June 2019 issue of Clinical Chemistry includes a study describing the development of such quality control materials that comprise simulated human plasma and mixtures of mother cell line derived cell-free DNA based on DNA fragmentation factor digestion.

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.