Clinical chemistry and laboratory medicine最新文献

Objectives: Accurate measurement of 17α-hydroxyprogesterone (17-OHP) in human serum and plasma is required for steroid profiling, to ensure the appropriate diagnosis of congenital adrenal hyperplasia. Therefore, an isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) to quantify 17-OHP in human serum and plasma has been developed.

Methods: A two-dimensional heart-cut LC approach was used to minimize matrix effects and prevent co-elution of interferences. A post-column infusion experiment was conducted to assess the potential impact of different matrices on ion suppression or enhancement effects. A multi-day validation experiment assessed precision, trueness and accuracy. Measurement uncertainty was evaluated in compliance with current guidelines.

Results: The working range of this RMP was 0.0200-60.0 ng/mL (0.0605-182 nmol/L) and the method proved to be matrix-independent. The intermediate precision coefficient of variation (CV) ranged from 1.5 % to 2.1 % and repeatability CV from 1.3 % to 1.9 %, across all concentration levels. The relative mean bias ranged from -4.0 % to 2.0 %, regardless of the matrix and concentration level. The measurement process for single measurements showed an expanded uncertainty (k=2) between 3.6 % and 4.5 %. This uncertainty was further reduced performing the target value assignment (n=6), resulting in a range of 2.0-2.5 %. Equivalence between the candidate RMP and the Joint Committee on Traceability in Laboratory Medicine-listed RMPs was established through participation in the External Quality Assessment scheme for reference Laboratories in Laboratory Medicine (RELA) ring trial.

Conclusions: The performance of this procedure enables the evaluation and standardization of routine assays, and the evaluation of patient samples, to ensure traceability of individual patient results.

Clinical endocrinology relies critically on high-quality biochemical data for diagnosis, therapeutic decisions, and long-term patient monitoring. As endocrine diagnostics grow more complex due to expanding test menus, technological advances, and changing patient populations, the need for a strong, structured partnership between clinicians and Laboratory Medicine professionals has never been greater. This joint opinion paper, developed by young professionals from the EFLM Committee Young Scientists (EFLM-C:YS), the IFCC Task Force Young Scientists (IFCC TF-YS), and the European Young Endocrinologists and Scientists (ESE-EYES), explores clinicians' expectations of modern Endocrine Laboratory Medicine (ELM) and proposes actionable strategies to meet them. Using a clinician-laboratory question-and-answer framework, we address five key domains: procedural harmonization, analytical reliability, interpretability and contextualization of results, consultative partnership, and innovation in service delivery. We highlight the central role of laboratory medicine professionals throughout the total testing process, from test selection to post-analytical interpretation of laboratory results. Particular emphasis is placed on the harmonization of endocrine dynamic function tests, adoption of high-specificity analytical platforms such as liquid chromatography-tandem mass spectrometry, development of personalized reference intervals, and implementation of diagnostic management teams. Emerging challenges, including transgender care, endocrine disruptors, digital health technologies, and artificial intelligence, are discussed as opportunities for laboratories to assume leadership in precision and preventive endocrinology. We conclude that the future of endocrine diagnostics depends on transforming laboratory data from a technical endpoint into a strategic clinical partner, ensuring diagnostic excellence through continuous dialogue, shared accountability, and innovation.

Objectives: The quantification of linezolid in serum and plasma matrices is crucial for therapeutic drug monitoring and pharmacokinetic studies. A reference measurement procedure (RMP) was developed and validated to provide accurate, precise, and reliable measurements, fit for its intended use while ensuring suitability for clinical and laboratory settings.

Methods: Linezolid quantification was achieved using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with specific ion transitions monitored for the analyte and its stable isotope-labeled internal standard (ISTD). The RMP validation process encompassed key performance parameters including selectivity, matrix effects (MEs), linearity, precision, accuracy, and stability. MEs were assessed by comparing slopes and correlation coefficients (r) across neat solution, analyte-free serum, native serum, and various plasma matrices. Precision and accuracy were quantified through multiday experiments and by analyzing spiked samples across multiple concentrations. Measurement uncertainties were calculated by determining standard uncertainties as well as expanded uncertainties for the entire concentration range.

Results: The described method provides robust quantification of linezolid in human serum and plasma across a concentration range of 0.0800-48.0 μg/mL, demonstrating high specificity and no significant matrix effects. A comprehensive five-day validation study (n=60) demonstrated the method's strong performance, with intermediate precision coefficients of variation (CVs) ≤2.1 % and repeatability CVs≤2.0 %. At the lower limit of the measuring interval (LLMI), the method maintained reliability, achieving an intermediate precision CV of 3.7 % and a repeatability of 1.7 % (n=20). Mean relative biases ranged from -2.0 to 2.9 %. Measurement uncertainty (MU) analysis further supported these results, with standard MUs (k=1) determined to be 1.6-3.8 % for single measurements and 0.8-1.4 % for target value assignments (n=6). Specific assessment at the LLMI yielded an expanded uncertainty (k=2) of 7.6 and 2.8 % for single measurements and target value assignments (n=6), respectively. These results confirm the method's suitability for accurate and precise quantification across the entire measuring range.

Conclusions: This LC-MS/MS-based candidate RMP accurately quantifies linezolid in human serum and plasma. Its robust performance makes it suitable for standardization of routine analytical assays and for analysis of individual patient samples, ensuring analytical reliability and traceability.

A challenge in the implementation of rapid risk-stratification algorithms for patients with suspected acute coronary syndrome is the turnaround time for cardiac troponin (cTn) from blood sampling to reporting of results. Measurement of cTn in whole blood using point of care (POC) offers a solution. There is lack of consensus on how these instruments should be assessed and deployed when implemented into routine practice. A pragmatic strategy is needed to balance the requirement for appropriate evaluation, validation and local verification of POC high sensitivity (hs) cTn assays whilst avoiding unnecessary duplication of previously conducted work using central laboratory assays. The International Federation of Clinical Chemistry and Laboratory Medicine Committee on Clinical Application of Cardiac Bio-Markers (IFCC C-CB) has developed an educational document to provide practical suggestions as to how hs-cTn POC assays may be implemented in acute health care settings and networks. The objective of this document is to provide a pragmatic framework for implementation of such systems. The article describes the validation and verification procedures and outlines what should be the responsibility of the manufacturers and provides recommendations on how a local verification may be undertaken before instruments are implemented into routine clinical practice.

Objectives: To determine the prevalence and clinical associations of rare HEp 2 indirect immunofluorescence ANA patterns and to evaluate their relationships with disease categories, ANA titers, and expression form.

Methods: We retrospectively analyzed 366,524 ANA tests performed between 2018 and 2024 using pattern definitions based on the 2018 ICAP update. Rare patterns were defined as those occurring in less than 1 % of ANA positive cases and represented by more than 30 samples. Clinical diagnoses were categorized as autoimmune, metabolic, infectious, neoplastic, or unclassified.

Results: Among 81,860 ANA positive cases (22.3 %), 1,769 (2.2 %) showed rare patterns. The most frequent rare patterns were AC-22 (0.7 %), AC-23 (0.41 %), AC-25 (0.25 %), AC-26 (0.23 %) and AC-29 (0.16 %). AC-29 was largely confined to autoimmune diseases, particularly systemic sclerosis, and was often observed at high titers. For AC-26, higher titers were more frequently observed among autoimmune disease cases, suggesting titer dependent enrichment. By contrast, AC-22 and AC-23 were more frequently observed in metabolic or infectious diseases and were mainly characterized by low titers (≤1:320). Cytoplasmic and mitotic patterns more commonly appeared as mixed patterns and showed broader distributions across disease categories. Among patients with systemic sclerosis exhibiting the AC-29 pattern, 96.2 % were positive for anti-Scl-70 antibodies.

Conclusions: Rare ANA patterns show distinct disease and titer profiles. Recognition of these patterns may enhance diagnostic accuracy when interpreted in conjunction with clinical and serological findings.

Hemophilia A and B are X-linked hemorrhagic disorders, characterized by low/dysfunctional factor (F)VIII or FIX, respectively. The history of hemophilia treatment has evolved remarkably over time from the introduction of cryoprecipitate in the 1960s to plasma-derived factors in the 1970s. The 1980s brought a tragic chapter, as many plasma-derived products were contaminated with blood-borne viruses. In response to ongoing safety concerns, recombinant factors were developed in the 1990s. However, coagulation factors had a relatively short half-life upon infusion. As technology progressed, extended half-life factors were introduced in the 2010s. More recently, the development of non-transfusional therapies such as emicizumab has revolutionized prophylaxis. Additionally, gene therapy is emerging as a potentially curative approach. Despite these advances, discrepancies in laboratory assays have emerged as a significant challenge. Treatments employing extended half-life products and/or gene therapy, may yield variable results depending on the type of assays used, typically one-stage clotting vs. chromogenic assays. These discrepancies can lead to confusion in monitoring factor levels and assessing treatment outcome. This article aims to review the current situation on results discrepancies recorded when measuring post infusion extended half-life factors with different methods and to provide guidance on options that may be adopted to minimize discrepancies.

Objectives: We evaluated the diagnostic performance of the Atellica HEMA 580 hematology analyzer for complete blood count (CBC) parameters compared with the ADVIA 2120i and assessed its capability to flag abnormal cells, and determined optimal cut-offs for immature myeloid cell detection.

Methods: A total of 400 K₂EDTA blood samples were analyzed. Peripheral blood smears were independently reviewed by two clinical pathologists, each performing a 200-cell differential count. Analytical correlation, regression, Bland-Altman, and receiver operating characteristic (ROC) curve analyses were used to assess performance. Optimal cut-offs for immature myeloid cell (IMC) detection were determined using ROC analysis and the Youden index.

Results: Manual microscopy identified 23 samples with blasts (≥0.5 %), 177 with immature myeloid cells, and 61 with nucleated red blood cells (NRBCs). ROC analysis showed good accuracy for IMC detection using the IMG (immature granulocytes) parameter (AUC=0.81). An IMG cut-off >0.8 provided the best balance between sensitivity (40.7 %) and specificity (96.9 %), while large immature cells (LICs) >0.9 yielded higher sensitivity (60.5 %) at the expense of specificity (82.5 %). The Atellica HEMA 580 also demonstrated superior NRBC detection compared to ADVIA 2120i.

Conclusions: The Atellica HEMA 580 provided reliable performance in detecting immature myeloid cells and NRBCs. The IMG cut-off >0.8, determined through ROC optimization, supports its implementation for enhancing laboratory workflow efficiency while maintaining diagnostic accuracy. These findings support the clinical implementation of the Atellica HEMA 580 for routine hematology laboratories, particularly for enhanced detection of clinically significant immature myeloid populations.