Clinical chemistry and laboratory medicine最新文献

Objectives: Dehydroepiandrosterone (DHEA) is a steroid prohormone and important precursor for estrogen and testosterone biosynthesis. For differential diagnosis of sexual development disorders (e.g., polycystic ovary syndrome, congenital adrenal hyperplasia), accurate measurement of DHEA in clinical testing is essential. To address that need for high-quality, reproducible assays, an isotope dilution-liquid chromatography (LC)-tandem mass spectrometry (MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of DHEA was developed and validated.

Methods: A certified primary reference material from the National Measurement Institute of Australia (NMIA), was used for DHEA assay calibration and to ensure traceability to the International System of Units (SI). Two-dimensional heart-cut chromatography was employed for LC-MS/MS in combination with a solid phase extraction sample preparation protocol, to mitigate matrix effects and prevent interference coelution. Selectivity was evaluated by spiking either the analyte or internal standard with potential interferents, such as dehydroepiandrosterone-sulfate, testosterone, and similar steroid compounds. For the evaluation of matrix effects, standard line slopes of various matrices were compared. Precision and accuracy were assessed via a multi-day validation experiment, and variability components were estimated using variance component analysis. Measurement uncertainty was evaluated in compliance with current guidelines.

Results: This candidate RMP proved suitable for the analysis of DHEA in the measurement range of 0.0800-36.0 ng/mL (0.277-125 nmol/L). Predefined requirements for sensitivity and selectivity were fully met, and independence from matrix effects was demonstrated successfully. Across all tested concentration levels, intermediate precision was ≤1.5 % and repeatability was ≤1.0 %, while the relative mean bias ranged from -1.1 to 0.1 %. Regardless of DHEA concentration or sample type, the expanded measurement uncertainty for reference value assignment (n=6) was ≤1.7 %.

Conclusions: This isotope dilution-LC-MS/MS-based candidate RMP for DHEA in human serum and plasma met pre-defined analytical performance requirements such as precision, specificity and measurement uncertainty, and showed superior selectivity towards several potential interferents tested. It is suitable for application in clinical sample evaluation and routine assay standardization.

The Meeting on Science, Quality and Value of Laboratory Medicine was held on 11 December 2025 in Padua, immediately preceding the 7th European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Conference on the Preanalytical Phase. For organizational reasons, the meeting was structured in two parts, with the first held in December 2025 and the second scheduled for early 2026. The initiative, designed to better steer and promote the activities of all EFLM Committees and Divisions, represents a pivotal step toward overcoming fragmentation and silo-based cultures. By fostering a holistic vision that captures interactions among all EFLM Functional Units, the meeting supported the translation of value-based laboratory medicine principles into real-world practice. This collective opinion paper summarizes the lectures presented at the meeting, providing an overview of ongoing EFLM projects and future developments in value-based laboratory medicine. Importantly, the meeting also generated significant opportunities for collaboration and shared project development, underscoring the transition from isolated activities to a collaborative, value-driven approach.

Objectives: Multiplex arrays offer a high-throughput, cost-effective means for quantifying multiple analytes simultaneously, essential for large-scale biomarker research. However, the shared reactive environment in multiplex assays could lead to variations in results compared to single plex assays, potentially impacting outcomes. This study aimed to explore these differences by examining a "3-plex" cytokine panel vs. single plex assays for tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10).

Methods: Using the R&D Systems Luminex HS Cytokine Panel A, 72 serum samples were tested across several batches, including three "3-plex" and two "1-plex" batches each for IL-10 and TNF-α. We evaluated differences in cytokine values using paired t-tests, comparing within 1-plex, between 3-plex, and between 1-plex and 3-plex assays. Bland-Altman plots visually assessed absolute and percentage differences.

Results: IL-10 values were similar between 1-plex and 3-plex assays, showing an average difference of 4.2 fmol/L (10.7 %), which was less than the within plex differences. Conversely, TNF-α showed a 16.7 % difference in the between plex comparison, compared to a 12 % difference in the within plex comparisons. Statistically significant differences emerged mainly for IL-10 across all comparisons. Bland-Altman analyses indicated pronounced variability at low analyte concentrations.

Conclusions: While the multiplex assays demonstrated variation at low analyte levels, especially for IL-10, such differences might not substantially affect comparability when mixed with single plex assays, particularly in datasets dominated by low concentrations.

Laboratory medicine lies at the core of modern healthcare, enabling timely diagnosis, effective patient monitoring, and increasingly personalized therapeutic strategies. Over the past decades, automation has profoundly reshaped the role of clinical laboratories, substantially enhancing their contribution to clinical outcomes, operational efficiency, and the overall sustainability of healthcare systems. More recently, laboratory automation has emerged as a cornerstone of value-based laboratory medicine, representing not merely a technological upgrade but a strategic transformation of laboratory practice aimed at delivering measurable value to patients and healthcare stakeholders. Although automation has long been established in clinical chemistry and immunoassays, its scope is now expanding to molecular diagnostics and mass spectrometry - two disciplines that are central to precision medicine. Looking ahead, the convergence of automation, digitalization, and artificial intelligence is driving the emergence of hyperautomation in laboratory medicine. Within this paradigm, laboratories evolve from isolated testing units into integrated diagnostic hubs, in which results from multiple laboratory disciplines are harmonized and contextualized to effectively support clinical decision-making.

Objectives: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne pathogen that can cause a fatality rate as high as 12-50 %, posing a significant threat to public health. SFTSV is prevalent in mountainous and hilly regions with relatively poor medical conditions. Therefore, there is an urgent need to develop a new convenient, rapid and sensitive method for SFTSV detection in low-resource environments.

Methods: We developed a one-pot and visualized method for SFTSV detection using loop-mediated isothermal amplification assisted by CRISPR/Cas12b with G478A/K396A double mutations (LAC12b-2M). The specificity, sensitivity, accuracy and limit of detection (LOD) of LAC12b-2M were evaluated using clinical reverse transcription-quantitative PCR (RT-qPCR) as the reference method, with gradient dilutions of strong positive SFTSV RNA samples and 215 clinical serum samples from two cohorts.

Results: LAC12b-2M is sensitive to detect SFTSV with a LOD of 1 copy/μL at 61 °C within 30 min. Compared to clinical RT-qPCR, LAC12b-2M demonstrated a sensitivity of 98.8 % (82/83), a specificity of 100.0 % (96/96), and an accuracy of 99.4 % (178/179) in cohort 1 (n=179), and an accuracy of 100.0 % in cohort 2 (n=36).

Conclusions: Our LAC12b-2M method holds promise for point-of-care SFTSV testing in different healthcare settings, particularly in low-resource region where SFTSV is prevalent.

Background: Method-comparison studies in laboratory medicine are routinely interpreted using regression-based or Bland-Altman analyses. Although useful descriptively, these statistical procedures are frequently misapplied to infer "agreement", "equivalence", or "interchangeability". Such interpretations overlook essential metrological conditions - including the definition of the measurand, the traceability chain, and measurement uncertainty - leading to misconceptions with potential clinical consequences.

Content: This Opinion Paper clarifies the distinct meanings of four metrological concepts that are often treated as synonyms: comparability, compatibility, equivalence, and interchangeability. We explain why numerical similarity or statistical association does not establish metrological relatedness, and outline the specific requirements for each concept. Comparability requires a shared measurand and calibration hierarchy; compatibility requires differences smaller than the combined uncertainty; equivalence requires clinically irrelevant residual differences; and interchangeability requires stability of clinical decisions when substituting one measuring system for another. We also discuss familiar sources of misinterpretation, including ambiguous definitions of the measurand, incomplete traceability chains, and uncritical reliance on regression- or bias-based summaries.

Summary and outlook: Distinguishing among comparability, compatibility, equivalence, and interchangeability is essential for the metrological interpretation of method-comparison studies and for ensuring safe analytical and clinical decision-making. Integrating these concepts explicitly into study design, harmonisation strategies, and reporting practice will strengthen traceability implementation, prevent erroneous claims of "agreement", and support more reliable patient care.

Objectives: Evolution is difficult to predict for some patients at emergency department (ED). The soluble urokinase plasminogen activator receptor (suPAR) is a non-specific prognostic inflammatory blood biomarker with a high negative predictive value for pejorative outcomes. The aim of this study was to investigate the relationship between low levels of suPAR at ED admission and patient discharge following hospitalization in a short stay unit.

Methods: We carried out a single-center prospective observational study in the acute-care hospital ward of a university hospital center, including patients over 18 years old with an intermediate triage score.

Results: Overall, 202 acute medical patients were included, exhibiting a mean suPAR level of 7.43 ± 3.36 μg/L. Of these patients, 25 (12.4 %) displayed a suPAR dosage below 4 μg/L and 177 (87.6 %) a dosage ≥4 μg/L. At 24 h, 55 patients (27.2 %) were discharged, 139 (68.8 %) were hospitalized, and five (2.5 %) were either admitted to intensive care or died. In contrast to group with a high suPAR rate, those with suPAR <4 μg/L benefited from secure ED discharge (OR=5.68; CI 95 %=2.6-12.4). For predicting hospital discharge, patients with a suPAR value <4 μg/L had an AUC-ROC of 0.75. (95% CI 0.67-0.83).

Conclusions: Our study revealed that in patients with a high triage scale level and requiring a monitoring period, SuPAR levels under 4 μg/L could have enabled five times more patients to return home compared with those exhibiting a level ≥4 μg/L at emergency visit.

Objectives: To establish evidence-based analytical performance specifications (APS), specifically allowable total error (TE_a), for five fundamental semen analysis parameters (sperm concentration, progressive motility, total motility, morphology, and vitality) in China utilizing the state-of-the-art model, and to compare these specifications with existing international benchmarks.

Methods: We examined national external quality assessment (EQA) data from 2019 to 2025, encompassing 315 laboratories across 30 provinces in China. TE_a was calculated using the state-of-the-art model as half the 10th-90th percentile range of result deviations from assigned values. Given that the participant count was below 100 from 2019 to 2022, this study eventually utilized data from 2023 to 2025 for the calculation of TE_a. The pass rate of participating laboratories was evaluated against the established TE_a criteria.

Results: The established TE_a values as follows: sperm concentration, 34.3 %; progressive motility, 26.9 % (for assigned value ≤40 %) and 13.5 % (>40 %); total motility, 26.3 % (≤50 %) and 10.5 % (>50 %); morphology, 67.7 %; vitality, 24.6 % (≤60 %) and 7.9 % (>60 %). The pass rates for all parameters in recent EQA cycles were approximately 80 %, supporting the practical achievability of the proposed specifications. Comparisons showed that the derived TE_a values are generally consistent with or more refined than previous state-of-the-art and biological variation-based standards.

Conclusions: This study provides the first large-scale, evidence-based TE_a for semen analysis in China. The stratified TE_a for motility and vitality based on clinical thresholds, improves diagnostic accuracy. The proposed specifications are practical, achievable, and clinically relevant, providing a consistent foundation for quality assurance in reproductive medicine laboratories.