JALM Talk Podcast: Recent Episodes
Association for Diagnostics and Laboratory Medicine
Podcast interviews with authors of articles published in The Journal of Applied Laboratory Medicine, a publication of the Association for Diagnostics and Laboratory Medicine.
Clinical chemistry assays are widely impacted by inherent interferences in patient blood samples such as hemolysis, icterus, and lipemia. These interferences can cause inaccurate laboratory results and may even prevent the laboratory from releasing test results to ordering health care providers. In particular, the interference of bilirubin in various creatinine assays is common. Inaccurately reported creatinine, or the inability to report creatinine, can have adverse implications in the management of patients. Accurate creatinine results are important for assessing kidney function in many clinical contexts such as imaging procedures and the dosing of therapeutic drugs. Therefore, mechanisms to overcome bilirubin interference and creatinine assays would be beneficial to patient care. The November 2019 issue of The Journal of Applied Laboratory Medicine includes a Laboratory Reflections article entitled, “A Practical Approach to Eliminate Bilirubin Interference in Icteric Samples for Creatinine Measurement.”
An original research article published in the September 2019 issue of the Journal of Applied Laboratory Medicine describes a study which investigated whether laboratory tests were being properly utilized for hospitalized patients aged 80 years and older.
An original research article published in the September 2019 issue of the Journal of Applied Laboratory Medicine describes the validation of a clinical chemistry score which incorporates high sensitivity troponin with other laboratory results of glucose and estimated glomerular filtration rate as an alternative assessment strategy for emergency room patients with possible myocardial infarction.
An original research article published in the July 2019 issue of the Journal of Applied Laboratory Medicine, describes a proof-of-concept study which tested the possibility of using artificial plasma matrix spiked with fragmented genomic DNA from immortalized cell lines to produce reference material for noninvasive prenatal testing assays.
Serum protein electrophoresis and immunofixation electrophoresis are critical laboratory assays in the identification of monoclonal proteins. Monoclonal proteins, also called “M spikes” or “paraproteins,” may be due to monoclonal gammopathy of undetermined significance, but they may also indicate malignant diagnoses such as multiple myeloma or lymphoplasmacytic lymphoma.
Protein electrophoresis separates the proteins in a patient sample by their size and charge and allows for the detection of abnormal monoclonal proteins. Immunofixation electrophoresis is used to determine the type of monoclonal protein present. Both methods are technically challenging and require interpretation by a qualified laboratory professional.
Occasionally, anomaly such as immunoglobulin complexes or temperature sensitive cryoglobulins distort the protein separation and prevent accurate interpretation of test results.
A case study published in the July 2019 issue of the Journal of Applied Laboratory Medicine describes a patient whose monoclonal protein was not identifiable by routine protein electrophoresis and immunofixation methods. The Case Report suggests steps that laboratories may take to reduce artifacts and identify monoclonal proteins accurately.
Venous thromboembolism, or VTE, is a serious medical condition characterized by a blood clot in a vein, also known as deep vein thrombosis. If the clot breaks free from the vein, it can cause a life-threatening pulmonary embolism by blocking blood supply to the lungs. Over 100,000 Americans may die from VTE per year. If recognized quickly, VTE may be effectively treated with anticoagulant therapy; however, it can be difficult to detect when VTE is occurring and when treatment is warranted, thus the clinical laboratory plays an important role in performing diagnostic tests for VTE.
Cardiac troponin is the supreme biomarker for the diagnosis of acute myocardial infarction. The ability of the clinical laboratory to provide rapid and reliable troponin results is critical for patient management in the emergency room. In clinics and environments far from a laboratory, point-of-care troponin testing may be necessary for timely results and patient triage. However, questions remain about the concordance among point of care and laboratory-based methods and whether the same result cut-offs should be used for clinical decision making. A study published in the March 2019 issue of The Journal of Applied Laboratory Medicine investigates the analytical concordance of three point-of-care cardiac troponin I assays against the added high sensitivity troponin I assay.
Clinical laboratories play a crucial role in emergency medicine through toxicology and drug testing. The type of testing provided is often a balance between laboratory resources and the patient population served. Each approach to drug screening comes with advantages and disadvantages depending upon the specific drug exposure or illicit drug suspected. A “Case of Sudden Acute Coma Followed by Spontaneous Recovery” was published in the November 2018 issue of The Journal of Applied Laboratory Medicine. The Case Study details the presentation and resolution for an unresponsive patient admitted to the hospital with a history of drug and alcohol abuse with a negative urine drug screen.
Measuring vancomycin levels has long been an important component of laboratory therapeutic drug monitoring. Such measurements are important for obtaining optimal targets serum concentrations for drug dosing, while avoiding vancomycin induced nephrotoxicity. “AUC-Based Monitoring of Vancomycin: Closing the Therapeutic Window” was published in the January 2019 issue of The Journal of Applied Laboratory Medicine. This review evaluates shifting the conventional therapeutic drug monitoring approach of vancomycin from trough monitoring, to an area under the curve approach for more appropriate drug dosing.
“Clinical Effect of Expedited Pathogen Identification and Susceptibility Testing for Gram-Negative Bacteremia and Candidemia by Use of the Accelerate PhenoTM System” was published in the January 2019 issue of The Journal of Applied Laboratory Medicine. This work evaluates the clinical impact on a new device for pathogen identification and antimicrobial susceptibility testing.
The gold standard for identification of fat malabsorption has conventionally been 72h fecal fat analysis. Despite its long use, fecal fat analysis poses both preanalytical and analytical challenges for both the patient and the laboratory. Implementing changes to well-established tests can be difficult in healthcare systems. “Elimination of 72-Hour Quantitative Fecal Fat Testing by Restriction, Laboratory Consultation, and Evaluation of Specimen Weight and Fat Globules” was published in the November 2018 issue of The Journal of Applied Laboratory Medicine. The study details intervention efforts to reduce unnecessary quantitative fecal fat analysis and the use of historical data to support specimen weight and fat globules as alternatives for evaluation of malabsorption.
Ovarian cancer is the fifth most common cause of cancer death among women in the U.S. The high rate of mortality for ovarian cancer is multifactorial, but it is estimated that more than 60% of cases have already metastasized at the time of diagnosis. Despite more invasive surgical treatments and targeted chemotherapies, ovarian cancer survival rates have remained similar over time. “Algorithms Used in Ovarian Cancer Detection: A Minireview on Current and Future Applications” was published in the September 2018 issue of the Journal of Applied Laboratory Medicine. The review outlined some of the challenges associated with the diagnosis of ovarian cancer and highlights how our understanding of the biology of ovarian cancer has changed.
The potential benefits of maintaining sufficient vitamin D levels has led to a steady increase in testing of vitamin D status in the general population. This increase has impacted laboratories in a variety of ways, as organizations adapt to growing demand while striving for accuracy and test standardization.The potential benefits of maintaining sufficient vitamin D levels has led to a steady increase in testing of vitamin D status in the general population. This increase has impacted laboratories in a variety of ways, as organizations adapt to growing demand while striving for accuracy and test standardization. “The (Sun)Light and Dark of 25-Hydroxyvitamin D Testing” was published in the November 2018 issue of the Journal of Applied Laboratory Medicine. The Review details some of the analytical issues surrounding vitamin D in laboratory testing.
The November 2018 issue of the Journal of Applied Laboratory Medicine published a Special Report by Drs. Ann Gronowski and Carey-Ann Burnham at the Washington University School of Medicine in St. Louis that discussed the formation of a professional development group for women in the pathology department of a major medical school. Dr. Gronowski, who is Professor in the departments of pathology and immunology, and obstetrics and gynecology, joins us in this podcast.
Diagnostic errors in medicine continue to be a large problem for effective healthcare delivery. As a result, moderate and severe consequences from the errors, including death, account for 75% of diagnostic errors in the United States. “Interventions That Can Help Reduce Diagnostic Errors” was published in the July 2018 issue of The Journal of Applied Laboratory Medicine. The editorial discusses the associated JALM Review “The Definition and Scope of Diagnostic Error in the US and How Diagnostic Error is Enabled” by Dr. Michael Laposata. The authors of the editorial are Dr. Michael Astion and Dr. Jane Dickerson.
Conventional approaches to drug testing rely on a primary screening step followed by a secondary confirmation. Best practice dictates that the secondary confirmation step utilize a separate methodology than the initial screening step and have improved sensitivity and specificity. This approach is widely utilized in clinical, pre-employment, and forensic settings. Despite the standard adoption of this approach, issues can occur that impact the accuracy of results.
“False Positive Carbamazepine Results by Gas-Chromatography Mass Spectrometry and VITROS 5600 Following a Massive Oxcarbazepine Ingestion” was published in the July 2018 issue of The Journal of Applied Laboratory Medicine. The case study highlights unique circumstances that affected both screening and confirmatory methods for urine drug testing.
The rapid rise in the prevalence of fentanyl and fentanyl analogs has contributed significantly to an increase in overdose death rates in North America. Laboratories, healthcare providers, and government agencies struggle to effectively detect and reduce negative outcomes associated with fentanyl use in the absence of accurate data on prevalence and use.
“Keeping Up with Fentanyl: Failure to Do So Is Not an Option” was published in the July 2018 issue of The Journal of Applied Laboratory Medicine. This manuscript surveys the current landscape of available laboratory testing for detection of fentanyl and fentanyl analogs. Additionally, point-of-care testing of fentanyl and its analogs for the treatment of substance abuse disorder is discussed.
Laboratory automation holds the promise of enhanced workflows, improved efficiency, and decreased turnaround time while mitigating an environment of rising costs, constrained resources, and staffing shortages. Many publications tout improved outcomes from laboratory automation but realizing these results may not come easily.
Automated Laboratories: When Technology Needs a Human Touch was published in the May 2018 issue of the Journal of Applied Laboratory Medicine. This work reflects on one lab’s experience with a challenging implementation of laboratory automation. Several unanticipate outcomes were encountered that required investigation to improve laboratory turnaround time.
“Thrombophilia: Women-Specific Reference Ranges Can Prevent Misdiagnosis in Women” was published in the March 2018 issue of The Journal of Applied Laboratory Medicine. This work presents the establishment and impact of female-specific reference intervals for a variety of coagulation markers during pregnancy.
A high throughput LC-MS/MS method for the determination of phosphatidylethanol (PEth) in clinical samples using a simple automated extraction procedure was published in the May 2018 issue of The Journal of Applied Laboratory Medicine. This work describes an improved automated approach to analysis of the alcohol marker phosphatidylethanol that uses liquid chromatography mass spectrometry instead of conventional HPLC.
“Genotype–Phenotype Correlations of Glucose-6-Phosphate–Deficient Variants Throughout an Activity Distribution” was published in the May 2018 issue of The Journal of Applied Laboratory Medicine. This work examines G6PD mutations across a range of enzyme activities and seeks to establish enzyme activity cutoffs that could be implemented to rule out G6PD deficiency.
Recently, a method was described that combines the sensitivity of single-molecule counting with the convenience of dried spot collection. The study evaluates three conventional protein analytes routinely measured in the clinical lab: Troponin I, Prostate Specific Antigen (PSA), and C-reaction protein. The authors detailed the assay method that incorporates spot-scanning to account for dried blood spot variability followed by analysis with single-molecule counting. “Expanding the Utility of High-Sensitivity Dried Blood Spot Immunoassay Testing with Single Molecule Counting” was published in the March 2018 issue of The Journal of Applied Laboratory Medicine.
Cell-free DNA analysis, also called non-invasive prenatal screening and IPS, has emerged as an alternative to the conventional analysis of maternal serum markers. Modern molecular techniques have now achieved sensitivity for the direct detection and analysis of placental DNA fragments that circulate in the maternal bloodstream and serve as a proxy for fetal aneuploidy. This technology is transforming the field of prenatal screening and has significant implications for laboratories, patients, and physicians.
The rise in opioid prescribing and subsequent growth of opioid abuse has led to increased oversight and challenges for clinicians who prescribe opioids to their patients. Recommendations and guidance documents vary when recommending approaches to monitor patients receiving controlled substances. In this podcast, we will explore drug testing for pain management from the prescriber’s perspective. A Laboratory Reflection “Reflections of Two Pain Medicine Clinicians in the Era of the Opioid Crisis” was published in the January 2018 special issue of JALM on Laboratory Support of Pain Management.
Opioids are frequently prescribed for pain management but there is large inter-individual variation in opioid-induced pain relief. These compounds are metabolized by enzymes leading to active and inactive metabolites, and there are differences in the quantity or presence of these metabolites between individuals.
This complicates the interpretation by clinicians of urine drug tests that are often administered to patients prescribed opioids. Further, although opioid addiction is a worldwide problem, only some of the individuals exposed to these drugs become addicted to them.
A mini-review titled “The Pharmacogenetics of Opioid Use and Implications for Pain Management” published in the January 2018 special issue of JALM on Laboratory Support of Pain Management discusses these complex topics.
Laboratory Medicine Practice Guidelines, published by the American Association for Clinical Chemistry, recommend best practices for clinical laboratories in a number of different areas of patient testing. These guidelines are formed via a systematic review of published literature and the consensus of experts in the field with the goal of optimizing patient care. Recently, a review of the pain management literature was undertaken in order to produce laboratory practice guidelines in this subject area.
Donor-derived cell-free DNA measurement in the circulating blood of transplant recipients is thought to have utility for clinical monitoring of tissue injury and therefore transplant rejection in heart, lung, liver, and kidney transplants, as increased levels of this biomarker are seen during acute rejection.
However, the normal concentration of donor-derived cell-free DNA in successful kidney transplant patients has not been determined. An article titled “Biological Variation of Donor-Derived Cell-Free DNA in Renal Transplant Recipients: Clinical Implications” published in the November 2017 issue of JALM, determined the biological variation and reference intervals of this biomarker in this patient population to aid in discrimination between rejection versus no rejection in kidney transplant patients
A Technical Tips article titled “The Importance of Verifying Reference Intervals for Calculated Results” published in the November 2017 issue of JALM, discusses the common ways in which laboratories establish reference intervals for calculated results. Further, it contains recommendations as to the best practice for verifying these reference intervals in the patient population that they serve. The first author of this article is Dr. Rajeevan Selvaratnam, clinical chemist in the Department of Laboratory Services at BayCare Health System in Clearwater, Florida, and he is our guest for today’s podcast.