Clinical Chemistry Podcast

B-type natriuretic peptides, or BNP, and N-terminal proBNP, or NT-proBNP, are peptides produced in the heart in response to increased wall stretch and volume overload. Their production and secretion increases in the heart with the progression of heart failure and they have emerged as useful heart failure biomarkers. Since the discovery of BNPs in the 1980s, much effort has been made to precisely determine the BNP and NT-proBNP levels via immunoassays for reliable heart failure diagnostics. Entresto™ is a new heart failure therapy that includes sacubitril as one of its components. Sacubitril is a specific inhibitor of neprilysin. This is a zinc-dependent metalloproteinase that cleaves various peptides including BNP. In fact, augmentation of circulating BNP due to neprilysin inhibition is considered as a possible mechanism of Entresto's positive effects. A paper appearing in the October 2019 issue of Clinical Chemistry examines the circulating products of BNP proteolysis by neprilysin and how they might reflect impact on the metabolism of active BNP.

In the August 2019 issue of Clinical Chemistry, a Q&A feature titled "Optimal Use of Biomarker for Chronic Kidney Disease" asked five experts in laboratory medicine and nephrology to examine laboratory ordering, testing, and reporting practices, and recommend how those practices should be optimized to better serve patients with CKD. In this podcast, Dr. Greg Miller from the Department of Pathology at Virginia Commonwealth University in Richmond who moderated the Q&A will summarize the expert advice from his colleagues.

Analyzing quality control specimens is a daily component of modern medical laboratories to help assure that correct results are reported for patient samples. That involves periodic analysis of materials with a known analyte concentration and estimating if measurement error is within acceptable criteria. The QC samples may be obtained commercially or prepared within the laboratory. However, how adequately do those samples represent authentic patient samples? What if we were to use the patient samples themselves as a source of quality control data? That's not as radical as one might think as implementation and application of moving averages of patient results was suggested as early as the 1960s, but the practice never really caught on. A Review paper appearing in the August 2019 issue of Clinical Chemistry re-examines this concept and perhaps newer software can provide such data in near real-time, or as the paper calls it, patient-based real-time quality control.

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.