Promoting Health Equity Through Effective Laboratory Stewardship Strategies.

There is a close relationship between the goals of laboratory stewardship and efforts to improve health equity for vulnerable populations. Laboratory stewardship programs should evaluate their policies and interventions to ensure that they improve access to testing, test selection, and result interpretation and delivery for all populations. Specific solutions to consider are (1) to evaluate the benefits of point-of-care testing when it can decrease barriers to specimen collection, (2) to use standardized naming conventions to help providers select the best test, and (3) to partner with insurance processing departments to help reduce financial barriers for expensive testing.

Evaluation of the Visby medical COVID-19 point of care nucleic acid amplification test.

Rapid and widespread diagnostic testing is critical to providing timely patient care and reducing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recently, the Visby Medical COVID-19 point of care (POC) test was granted emergency use authorization (EUA) for qualitative detection of SARS-CoV-2 nucleic acid at the point of care. We evaluated its performance characteristics using residual specimens (n = 100) collected from Mayo Clinic patients using nasopharyngeal (NP) swabs and placed in viral transport media (VTM).

Analytical and Clinical Considerations in Implementing the Roche Elecsys Troponin T Gen 5 STAT Assay.

Objectives: To evaluate the analytical and clinical performance characteristics of the fifth-generation troponin T reagent.

Methods: Troponin T was measured in 2,332 paired serum and plasma samples from emergency department and hospital patients using the fourth- and fifth-generation reagents. Testing was repeated after recentrifugation to determine the frequency of analytical outliers and percentage of patients with elevated values for each assay.

Validation of a Commercial Reagent for the Depletion of Biotin from Serum/Plasma: A Rapid and Simple Tool to Detect Biotin Interference with Immunoassay Testing.

Background: It is important for clinical laboratories to have protocols for investigating suspected biotin interference in patient samples. VeraPrep Biotin™ is a commercial product used to rapidly deplete biotin from serum/plasma samples. The objectives of this study were to verify that VeraPrep Biotin™: (a) does not impact immunoassay analyte recovery in control samples and (b) can effectively deplete biotin from samples (both biotin-spiked and samples from donors who ingested biotin supplements).

The Negative Allosteric Modulator EU1794-4 Reduces Single-Channel Conductance and Ca Permeability of GluN1/GluN2A -Methyl-d-Aspartate Receptors.

NMDA receptors are ligand-gated ion channels that mediate a slow, Ca-permeable component of excitatory synaptic currents. These receptors are involved in several important brain functions, including learning and memory, and have also been implicated in neuropathological conditions and acute central nervous system injury, which has driven therapeutic interest in their modulation. The EU1794 series of positive and negative allosteric modulators of NMDA receptors has structural determinants of action near the preM1 helix that is involved in channel gating.

Test Utilization Proposal for Reflex Bilirubin Testing: Why Order Two Tests When One Will Do?

Background: Reflex testing algorithms are effective tools to reduce unnecessary laboratory testing. Direct (conjugated) bilirubin (DB) and total bilirubin (TB) are often ordered together at our institution. Therefore, the objective of our study was to evaluate the potential impact of performing reflex testing for DB when TB is elevated.

Is It Time to Remove Total Calcium from the Basic and Comprehensive Metabolic Panels? Assessing the Effects of American Medical Association-Approved Chemical Test Panels on Laboratory Utilization.

Background: The necessity of individual tests within the most commonly used disease-oriented test panels has not been well established. We evaluated test-ordering practices for total calcium, both before and after implementation of American Medical Association (AMA)-approved panels (basic metabolic panel [BMP] and comprehensive metabolic panel [CMP]) in our electronic ordering system.

Methods: We performed a retrospective review of all total calcium orders placed during April and June 2018, before and after implementation of the panels.

Unintended Consequence of High-Dose Vitamin C Therapy for an Oncology Patient: Evaluation of Ascorbic Acid Interference With Three Hospital-Use Glucose Meters.

The use of high-dose vitamin C in cancer care has offered promising results for some patients. However, the intravenous (IV) doses used for these patients can reach concentrations that interfere with some strip-based glucose meters. We characterized the impact of vitamin C interference, from standard to the very high doses used for some cancer protocols, using three different hospital-use glucose meters.

Estimating short- and long-term reference change values and index of individuality for tests of platelet function.

Background: In order to manage risks of bleeding and thrombosis after some surgical procedures, platelet function is often measured repeatedly over days or weeks using laboratory tests of platelet function. To interpret test results in the perioperative period, it is necessary to understand analytical, biological and between-person variation.

Methods: We collected three separate blood specimens from 16 healthy volunteers on the first study day, and one additional specimen from each volunteer 1, 2, and 3 months later.

Best practices in mitigating the risk of biotin interference with laboratory testing.

Dietary biotin intake does not typically result in blood biotin concentrations that exceed interference thresholds for in vitro diagnostic tests. However, recent trends of high-dose biotin supplements and clinical trials of very high biotin doses for patients with multiple sclerosis have increased concerns about biotin interference with immunoassays. Estimates of the prevalence of high biotin intake vary, and patients may be unaware that they are taking biotin.

Relationship between free hemoglobin (hemolysis), potassium and ionized calcium in lithium heparin blood gas samples collected intraoperatively.

Objective: Develop sample acceptability rules by determining the relationship between free hemoglobin level (hemolysis) and potassium or ionized calcium in blood gas samples collected intraoperatively.

Design And Methods: Hemolysis was assessed visually or by H index for lithium heparin blood gas samples collected intraoperatively. During periods one and three this was done using two different rules for visual assessment of centrifuged lithium heparin plasma.

Tetrahydroisoquinoline CXCR4 Antagonists Adopt a Hybrid Binding Mode within the Peptide Subpocket of the CXCR4 Receptor.

The rationale for the structural and mechanistic basis of a tetrahydroisoquinoline (THIQ) based series of CXCR4 antagonists is presented. Using the previously reported crystal structures which reveal two distinct binding sites of CXCR4 defined as the small molecule (IT1t or minor) binding pocket and peptide (CVX15 or major) binding pocket, we hypothesized our THIQ small molecule series could bind like either molecule in these respective receptor configurations (IT1t versus CVX15 based poses). To this end, a thorough investigation was performed through a combination of receptor mutation studies, medicinal chemistry, biological testing, conformational analysis, and flexible docking.

Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department.

Background: Several cases of biotin interference with laboratory testing have been reported in the literature. However, there are no publications discussing the extent of biotin use or plasma concentrations observed among the patient population. The objective of this study was to determine the prevalence of biotin consumption using two distinct methods: surveying the outpatient population using a questionnaire and quantifying biotin in plasma samples collected from patients presenting to the Emergency Department (ED).

An NMDAR positive and negative allosteric modulator series share a binding site and are interconverted by methyl groups.

N-methyl-d-aspartate receptors (NMDARs) are an important receptor in the brain and have been implicated in multiple neurological disorders. Many non-selective NMDAR-targeting drugs are poorly tolerated, leading to efforts to target NMDAR subtypes to improve the therapeutic index. We describe here a series of negative allosteric NMDAR modulators with submaximal inhibition at saturating concentrations.

Small molecule CXCR4 antagonists block the HIV-1 Nef/CXCR4 axis and selectively initiate the apoptotic program in breast cancer cells.

The chemokine receptor CXCR4 plays an integral role in the development of highly metastatic breast cancer and in the pathogenesis of chronic HIV infection. In this study, we compared the effects of CXCR4 antagonists on apoptosis induction in hematopoietic cells and in tumor cells. We incubated cells expressing CXCR4 with a series of CXCR4 antagonists and subsequently exposed the cultures to a pro-apoptotic peptide derived from the HIV-1 Nef protein (NefM1).

Discovery of Tetrahydroisoquinoline-Containing CXCR4 Antagonists with Improved in Vitro ADMET Properties.

CXCR4 is a seven-transmembrane receptor expressed by hematopoietic stem cells and progeny, as well as by ≥48 different cancers types. CXCL12, the only chemokine ligand of CXCR4, is secreted within the tumor microenvironment, providing sanctuary for CXCR4 tumor cells from immune surveillance and chemotherapeutic elimination by (1) stimulating prosurvival signaling and (2) recruiting CXCR4 immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract and support CXCR4 metastatic growths.

Evaluation of the CLSI EP26-A protocol for detection of reagent lot-to-lot differences.

Background: Verification of new reagent lots is a required laboratory task. The Clinical and Laboratory Standards Institute (CLSI) EP26-A guideline provides a lot-to-lot verification protocol to detect significant changes in test performance. The aim of this study was to compare the performance of EP26-A with our laboratory reagent lot verification protocol.

A novel class of negative allosteric modulators of NMDA receptor function.

NMDA receptors mediate a slow Ca(2+)-permeable component of excitatory synaptic transmission, and are involved in numerous normal brain functions including learning and memory. NMDA receptor over-activation can lead to cell death and abnormal excitation in ischemia associated with stroke, traumatic brain injury, and epilepsy. We have explored a series of novel noncompetitive allosteric modulators of NMDA receptor function characterized by an iminothiazolidinone ring.

Discovery of tetrahydroisoquinoline-based CXCR4 antagonists.

A de novo hit-to-lead effort involving the redesign of benzimidazole-containing antagonists of the CXCR4 receptor resulted in the discovery of a novel series of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogues. In general, this series of compounds show good potencies (3-650 nM) in assays involving CXCR4 function, including both inhibition of attachment of X4 HIV-1IIIB virus in MAGI-CCR5/CXCR4 cells and inhibition of calcium release in Chem-1 cells. Series profiling permitted the identification of TIQ-(R)-stereoisomer 15 as a potent and selective CXCR4 antagonist lead candidate with a promising in vitro profile.

Novel NMDA receptor modulators: an update.

Introduction: The NMDA receptor is a ligand-gated ion channel that plays a critical role in higher level brain processes and has been implicated in a range of neurological and psychiatric conditions. Although initial studies for the use of NMDA receptor antagonists in neuroprotection were unsuccessful, more recently, NMDA receptor antagonists have shown clinical promise in other indications such as Alzheimer's disease, Parkinson's disease, pain and depression. Based on the clinical observations and more recent insights into receptor pharmacology, new modulatory approaches are beginning to emerge, with potential therapeutic benefit.