Clinical Chemistry Podcast

In a 2009 study in Clinical Chemistry, Dr. Erna Lenters and Dr. Robbert Slingerland evaluated eight different points of care instruments measuring hemoglobin A1c and came to the conclusion that six of the eight did not meet generally accepted analytical performance criteria.

MicroRNAs measured in blood samples are promising, minimally invasive biomarker candidates that have recently been the target of many case control studies. However, the influence of age and gender is confounding variables and MicroRNAs remain largely unknown.

The cover of the September 2014 issue of Clinical Chemistry tells it all: one million downloads! That's the number of Clinical Chemistry podcasts that have been downloaded since the feature was initiated in 2009. It's a relatively new feature in the 60 years of publication of the journal, and the word podcast itself is only been in the vernacular for about 10 years.

Analysis of circulating RNA in the plasma of pregnant women can be a powerful tool for noninvasive prenatal testing and research. However, unbiased and high throughput detection of circulating RNA in plasma is a technical challenge.

Performing measurements that are comparable over time and location and across assays is essential for insuring appropriate clinical and public health practice. One step toward achieving this goal is using assays that are traceable to a higher-order reference measurement system or harmonized by using internationally recognized procedures.

Analysis of Human Chorionic Gonadotropin or hCG is usually associated with monitoring or detecting pregnancy. It is also a protein tumor marker for some cancers. In males, hCG stimulates testosterone production and has the potential to be abused by athletes in an attempt to enhance performance in sports.

There are few scientific papers that do not include the use of the P value to evaluate the statistical significance of results. However, use of this statistic may be misleading, as noted by a recent paper by Regina Nuzzo in the journal Nature. That paper served as a basis for commentary with additional examples by Drs. Jim Boyd and Tom Annesley in the July 2014 issue of Clinical Chemistry.

Chronic kidney disease is an important risk factor for cardiovascular morbidity and mortality. This risk is all the more important for patients undergoing hemodialysis. In the presence of clinical signs of an acute myocardial infarction, the universal definition includes the finding of a serum cardiac troponin concentration above the 99 percentile as defined by healthy individuals, together with time dependant changes in serum and troponin concentrations. But in contrast to individuals with normal kidney function the troponin concentrations in patients with chronic kidney disease, but no myocardial infarction, may already be at concentrations higher than the 99 percentile of a healthy population.

Central nervous system infections, including diseases like meningitis and encephalitis, are important public heath concerns across the globe, as they occur commonly and/or associated with high rates of mortality and morbidity. Measurement of biomarkers provide objective indicators of normal function or pathology, and can present information that may assist diagnosis, assessment of health condition, and evaluation of treatment safety and efficacy.

Early detection of acute myocardial infarction is crucial for deciding the course of treatment to preserve and prevent further damage to the myocardial tissue. During the last several years there has been a burgeoning interest in circulating microRNAs as potential novel biomarkers for acute myocardial infarction.

The universal definition of myocardial infarction requires both an increase in cardiac troponin concentrations and changes in values over serial measurements. However, exact criteria regarding the magnitude of change in troponin remain elusive. In the June 2014 issue of Clinical Chemistry, two studies on biological variation of serum troponins helped shed further light on the kinetics of this important cardiac marker.!

Laboratory test results are used to aid decisions in the diagnosis and treatment of disease. Consistent and comparable results from different measurement procedures are important for developing clinical practice guidelines, and for those guidelines to be applied to decisions about patient care. Yet results for many analytes are neither consistent nor comparable when measured using different clinical laboratory procedures.

One of the largest direct consumer genetic testing facilities, 23andMe, was ordered by the US Food and Drug Administration to cease marketing its Personal Genome Service test in late 2013. This occurred after 23andMe failed to respond to questions that the FDA had about the analytical and clinical validity of this test. While some support the FDA's actions because of the test potential for harm to consumers, some advocates of the technology fault the FDA for being overly paternalistic and impeding medical advances.

The clinical utility of molecular genetic testing relies on an accurate and comprehensive knowledge about the relationships between genes and variants, and diseases. Correctly interpreting the clinical significance of variants that may be detected continues to be a constant challenge for molecular diagnostic practice. This challenge has become substantially enlarged as next generation sequencing-based testing becomes rapidly integrated into routine clinical practice.

In the May issue of Clinical Chemistry, researchers involved in the Copenhagen City Heart Study found that lower nonfasting, circulating triglyceride concentrations are associated with lower all-cause mortality.

Increased nonfasting plasma triglycerides indicating increase amounts of cholesterol in remnant liver proteins and are important risk factors for cardiovascular disease. In the May issue of Clinical Chemistry, researchers involved in the Copenhagen City Heart Study found that lower circulating triglyceride concentrations are associated with lower all-cause mortality.

This is a podcast from Clinical Chemistry, sponsored by the Department of Laboratory Medicine at Boston Children's Hospital.

In well-resourced countries with a low incidence of tuberculosis, a major focus of TB control efforts is the detection and treatment of latent TB infection to prevent reactivation to active TB disease. This approach is particularly relevant for healthcare workers. Interferon Gamma Release Assays are used to detect the release of interferon from T cells stimulated by tuberculosis specific antigens. However, these tests differ in cost and complexity than the conventional tuberculin skin test.

In well-resourced countries with a low incidence of tuberculosis, a major focus of TB control efforts is the detection and treatment of latent TB infection to prevent reactivation to active TB disease. This approach is particularly relevant for healthcare workers. Interferon Gamma Release Assays are used to detect the release of interferon from T cells stimulated by tuberculosis specific antigens. However, these tests differ in cost and complexity than the conventional tuberculin skin test.

Recent studies have demonstrated that a variety of cells release exosomes or microvesicles into nearby biological fluids such as blood and saliva. During the exocytic process various proteins' messenger RNA and micro RNA are included in these exosomes.

Tacrolimus or FK506 is a macrocyclic lactone that is commonly used along with other immunosuppressant drugs to reduce graft rejection in organ transplantation by suppressing the immune system. Because of its narrow therapeutic window, it is critical to accurately monitor blood concentrations of this drug for optimal efficacy.

Platelet function testing has traditionally been used to diagnose inherited qualitative and quantitative defects in platelet function, such as Von Willebrand disease, but with the increased use of anti-platelet agents to prevent arterial thrombosis and the interest in identifying patients at risk for thrombosis despite anti-platelet therapy, the use of platelet function testing to monitory response to anti-platelet therapy, for example, aspirin, has become a hot topic.

Over the past several years, investigations have shown that many clinical studies remain unpublished and even among published studies the results are often presented selectively.

Pregnancy tests such as the ones used to test urine in hospitals have been shown to give false-negative results in certain patients.

In the February 2014 issue of Clinical Chemistry, the influence of PCR reagents on DNA polymerase extension rates were studied by examining nucleotide incorporation with DNA dyes. We are joined by one of the authors of that study, Dr. Carl Wittwer. He is Professor of Pathology at the University of Utah Health Sciences Center and is also affiliated with ARUP Laboratories, BioFire Diagnostics, and is an Associate Editor of Clinical Chemistry.

Type 1 diabetes is a chronic progressive autoimmune disorder with complex, polygenic susceptibility. Environmental factors which are poorly defined also contribute to the pathogenesis. This disease is characterized by lymphocyte infiltration into the islets of Langerhans in the pancreas, leading to inflammation and selective destruction of the insulin-producing beta cells resulting in hyperglycemia.

The latest incarnation of polymerase chain reaction, Digital PCR, takes three decades of development in enzyme chemistry and assay design and applies them with formidable precision and sensitivity.

Hemoglobin A1C is one of the analytes most commonly measured in clinical laboratories in patients with diabetes mellitus. Physicians use Hemoglobin A1C to monitor long-term glycemic control, adjust therapy, and predict complications of diabetes. It was recently added as a criterion for diagnosis of diabetes.

Although standardization of barcodes and label formats has lowered the number of mislabeled specimens in clinical laboratories, it remains a potential source of pre-analytical error. Published error rates of mislabeled specimens range up to as high as just over 1 percent.

Gestational diabetes mellitus is often defined as any degree of glucose intolerance during pregnancy. Fetal complications and adverse outcomes for both the fetus and the mother are important concerns in gestational diabetes.

Acute kidney injury is an important health problem. Patients who develop acute kidney injury have increased in-hospital mortality, and if they do survive, they still suffer long-term increased morbidity and mortality. For that reason there has been great interest in the development of biomarkers that could identify kidney injury in its earliest stages, at a time when interventions might be more successful.

Acute kidney injury is an important health problem. Patients who develop acute kidney injury have increased in-hospital mortality, and if they do survive, they still suffer long-term increased morbidity and mortality. For that reason there has been great interest in the development of biomarkers that could identify kidney injury in its earliest stages, at a time when interventions might be more successful.

The discovery phase of proteomics is essential for the identification of suitable markers for exploration and validation of promising new clinical tests. But can researchers be certain if what they believe they are measuring is in fact what they are actually measuring?

The January 2014 issue of Clinical Chemistry is devoted to the area of women's health. It includes a multi-center report on the application of measuring the circulating products of the proteolytic enzyme carboxypeptidase-N for the early detection of breast cancer. Accompanying that paper was an editorial by Eleftherios Diamandis on the tumor microenvironment and if released peptides could form the basis for early diagnosis breast cancer tests.

The development of in vitro fertilization in the 1970s has revolutionized the treatment of infertility. The ability to culture embryos has allowed for the development of the preimplantation genetic diagnosis. This involves removing a cell from the developing embryos for genetic testing before choosing one to implant. Just like prenatal diagnosis, it is used to screen for various genetic diseases before birth. For women of advanced maternal age or couples with known genetic mutations, the ability to screen of embryos free of certain genetic mutations is reassuring.

Women who present with acute coronary events are less frequently to be properly diagnosed and often have worse outcomes than men. Part of the problem may be that women are less apt to manifest increased biomarkers or often receive less aggressive guideline-mandated care. Women also have lower reference values for biomarkers of cardiac injury that are rarely taken into account.

Until recently, much of the research in medical literature used primarily male populations. Slowly we've come to appreciate the importance of studying female populations due to the differences in normal physiology as well as disease pathology between men and women.

Gestational diabetes mellitus is becoming more common as the epidemic of obesity and type 2 diabetes continues. Newly proposed diagnostic criteria will, if adopted universally, further increase the prevalence of this condition.

In making the diagnosis of diabetes, there are several advantages using determinations of hemoglobin A1c rather than glucose measurements. These include the pre-analytics stability of hemoglobin A1c in the sample, a low within-subject biological variation, as well as being free from the dietary restrictions associated with measuring glucose.

Cell free DNA from transplanted organs in the circulation of transplant recipients is a potential biomarker of rejection. But most of these methods entail high costs, long turnaround times and the need for donor DNA.

Multiplex digital PCR can be used for the sensitive detection of circulating tumor DNA with performance unachievable by other current molecular detection approaches.