Journal of Applied Laboratory Medicine最新文献

Background: Tacrolimus therapeutic drug monitoring is a routine and critical assay for managing transplant patients. Tacrolimus can be measured from whole blood samples via liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay (IA). LC-MS/MS provides accurate parent drug quantification with minimal metabolite interference but requires expensive analyzers, highly trained staff, and is often a very manual process. Immunoassays offer faster, simpler workflows, but historically have been prone to significant cross-reaction with the drug's metabolites or other therapeutic drugs, leading to a falsely elevated result. Newer immunoassays show promising improvements in specificity.

Methods: Using 73 residual patient samples, we compared our in-house LC-MS/MS tacrolimus assay to the Roche Elecsys® tacrolimus electrochemiluminescence immunoassay on the cobas® e801 analyzer. Comparative analysis was done with Deming regression and Bland-Altman comparison. Linearity, within-individual imprecision, and total imprecision post immunoassay implementation were also evaluated, along with changes and improvements to workflow and turnaround times (TAT).

Results: The Roche Elecsys tacrolimus assay correlated well with our LC-MS/MS method (Deming regression equation: y = 1.004x + 0.4848). The bias was 0.52 ng/mL (an average of 8.1%) as determined by Bland-Altman comparison. When switching to the immunoassay we observed a 42%-51% improvement in TAT across the median, 75th percentile, and 90th percentile.

Conclusions: We observed excellent correlation between the Roche Elecsys tacrolimus assay on an e801 analyzer vs our in-house LC-MS/MS assay, with good precision and linearity across reportable ranges. Changing from mass spectrometry to tacrolimus immunoassay substantially improved our TAT and workflow.

Background: The rise of synthetic cathinones (SC), and in particular 3,4-MDPHP (3,4-methylenedioxy-α-pyrrolidinohexanophenone), is a concerning health threat. This paper represents the most extensive case series on 3,4-MDPHP suspected intoxications to date, offering a detailed analysis of its impact.

Methods: This study presents the analytical findings for 108 hospitalized patients who tested positive for 3,4-MDPHP, out of a total of 465 subjects admitted for suspected new psychoactive substances (NPS) intoxication. Analyses were performed by GC-MS and LC-MS/MS. The potential cross-reactivity of 3,4-MDPHP with the Syva EMIT II Plus urine ecstasy immunoassay is also investigated.

Results: 3,4-MDPHP was detected in 56% of NPS positive cases. A wide range of 3,4-MDPHP concentrations was observed in both blood (1-257 ng/mL) and urine (2-32 250 ng/mL). 3,4-MDPHP was the sole detected substance in 73.1% of cases, while 26.9% involved co-consumption with other drugs of abuse, primarily cocaine. Investigations about 3,4-MDPHP cross-reactivity with Syva EMIT II Plus urine ecstasy demonstrated that unmodified 3,4-MDPHP does not trigger a positive result, but its metabolites seem to be involved in a positive cross-reaction.

Conclusion: This study confirms the high prevalence (108/465) of 3,4-MDPHP in NPS related intoxication cases in our cohort. It is essential for clinical laboratories and emergency departments to be aware of the potential cross-reactivity in ecstasy immunoassay, as this may lead to significant diagnostic errors and misinterpretation of results.

Toxicology testing for drugs associated with scenarios such as recreational use or substance use disorder can be performed in support of the emergency department (ED) for specific patient populations such as pediatrics and trauma. These compounds were historically referred to as drugs of abuse (DOA); although the word "abuse" is recognized as potentially stigmatizing, no replacement terminology for DOA has emerged in current guidelines. This document refers to these compounds as drugs or substances of misuse, and acknowledges the need for less-stigmatizing language that more fully encompasses the range of uses for these drugs. This literature-driven, consensus guidance document provides recommendations primarily targeted to US hospital-based laboratories performing urine drug testing (UDT) in support of the ED. Indications for ordering UDT and related testing in both pediatric and adult populations are summarized. Further, recommendations are made for testing that should be available at all facilities with rapid turnaround, and how to perform and report testing. The advantages and disadvantages of immunoassays and mass spectrometry, as well as common challenges, are reviewed. Indications for mass-spectrometry assays and more extensive testing (e.g., novel psychoactive substances) are also provided. Future directions for improvements in laboratory technology to improve the utility of this testing are outlined. All laboratories should collaborate with ED leadership, medical toxicologists and poison control centers to optimize and update test menus to reflect local drug use patterns, ensure test methodologies and results meet clinical needs, and educate clinical staff regarding assay limitations and accurate test interpretation.

Background: Analytical interferences are very common in clinical laboratories, so professionals must develop strategies for their detection, avoiding incorrect results that can lead to inappropriate diagnoses and treatments.

Methods: An isolated 1040 error (absorbance-related) in the Alanine Aminotransferase2 (ALT2) assay performed on the Abbott Alinity c that occurred in 158 samples over 7 months was investigated. Highly lipemic or hemolyzed samples were excluded, and an error due to an increased concentration of total proteins was ruled out, all of which are documented analytical interferences.

Results: We isolated immunoglobulin (Ig) with an increased concentration (monoclonal components: 149 IgM, 7 IgG, and 2 IgA) from all analyzed samples, so the presence of this error solely in the alanine aminotransferase (ALT) assay had a 100% positive predictive value for monoclonal gammopathy. Serum viscosity was elevated in all cases, which is the reason for the detected interference. Treatment of IgM samples with dithiothreitol confirmed that dissociation of the pentamers eliminates the error in ALT determination.

Conclusions: The detection of this interference in samples from patients without recent immunoglobulin determinations indicates the presence of a significant and isolated increase in the concentration of one of them, potentially leading to the diagnosis of a previously unknown monoclonal gammopathy.

Background: In vitro diagnostic (IVD) devices are essential for disease detection and clinical decision-making. India's IVD market has grown rapidly, but regulatory oversight has lagged. Although the Indian Medical Device Rules introduced a risk-based framework in 2017, persistent gaps in enforcement, quality standards, and post-market surveillance undermine diagnostic reliability.

Content: This review examines India's IVD regulatory framework, focusing on device classification, approval pathways, quality management requirements, and post-market mechanisms. Particular attention is given to challenges such as enforcement issues, inconsistent compliance among small and medium enterprises, adoption barriers for national/international standards, weak post-market surveillance systems, and the absence of transparent public databases. Comparative analysis highlights India's shortfalls relative to the European and US systems, especially in mandatory clinical evidence, structured post-market surveillance, and stakeholder engagement.

Summary: Despite progress, India's IVD ecosystem remains constrained by fragmented oversight and weak harmonization with global standards. Strengthening regulatory capacity, mandating evidence-based evaluation, and fostering digital health readiness are critical to ensure patient safety and global competitiveness.