Clinical chemistry and laboratory medicine最新文献

Objectives: The clinical utility of serum bone turnover markers (BTMs) in managing osteoporosis in the elderly is constrained by the absence of personalized reference intervals (prRI) based on biological variation (BV).

Methods: This longitudinal study tracked monthly serum levels of β-CTX, PINP, OC, PTH, and 25(OH)D over six months in 40 healthy elderly participants aged 60-75 years (16 males and 24 females). The study calculated estimates of within-subject BV (CV_I), between-subject BV (CV_G), within-person BV (CV_P), analytical variation (CV_A), and reference change values (RCVs).These parameters were subsequently used to establish the personalized reference interval (prRI).

Results: Considerable variability in CV_I, CV_P, and CV_G was observed for BTMs in older adults. Gender differences in baseline concentrations were observed for PINP, OC, and 25(OH)D (p<0.05), but no significant differences were found in BV parameters. Among the markers, OC exhibited the lowest CV_I (7.9 %), while β-CTX had the highest (14.8 %). Other markers had CV_I values ranging from 11.0 to 14.2 %. RCVs ranged from -19.8 to -33.7 % and 24.6 to 50.8 %. For all five BTMs, the CV_I-based prRI ranges were narrower than the popRI, whereas the CV_P-based prRIs showed wide inter-individual variation, reflecting substantial heterogeneity in prRIs among older adults.

Conclusions: This study establishes BV-based prRI for BTMs in older adults, which offers a more clinically relevant interpretation of individual-level data than popRI and facilitates more accurate clinical decision-making.

Objectives: This study presents a candidate reference measurement procedure (RMP) for testosterone quantification in human serum and plasma, utilizing isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC MS/MS).

Methods: The developed LC-MS/MS method employs a two-dimensional heart-cut LC approach combined with solid-phase extraction (SPE) for sample clean-up, ensuring accurate testosterone analysis in human serum and plasma. Traceability to SI units was achieved by using a primary reference material listed by the Joint Committee on Traceability in Laboratory Medicine (JCTLM). An alternative quantification approach using qNMR content determination is also described. Assay validation followed current guidelines, assessing selectivity and specificity with spiked serum samples. Matrix effects were evaluated through post-column infusion experiments and comparison of standard line slopes. Precision, accuracy, and trueness were determined through an extensive 5-day protocol. Measurement uncertainty for reference value assignment was evaluated as per the Guide to the Expression of Uncertainty in Measurement (GUM), with three individual sample preparations performed on at least two different days.

Results: The RMP facilitated testosterone quantification in the range of 27.7 pmol/L (8.00 pg/mL) to 62.4 nmol/L (18.0 ng/mL) without interference from structurally-related compounds or matrix effects. Intermediate precision was ≤3.1 % and repeatability ranged from 1.4 to 1.9 % across all analyte concentrations. The bias ranged from -1.2 to 3.0 % for all levels and matrices. Expanded measurement uncertainties (k=2) for single measurements (n=1) ranged from 3.4 to 6.4 %. Measurement uncertainties for target value assignment (n=6) were ≤1.5 %, with expanded uncertainties ≤2.9 % (k=2) for all levels. Specific assessment at the LLMI yielded an expanded uncertainty (k=2) of 4.4 % for target value assignments (n=6), confirming the method's suitability for accurate and precise quantification over the entire measuring range.

Conclusions: The RMP demonstrated high analytical performance for testosterone quantification in human serum and plasma, making it suitable for routine assay standardization and clinical sample evaluation.

Objectives: Clinical intent for laboratory testing ("indication") is rarely recorded in structured form, limiting contextual interpretation, auditability, and utilization stewardship. We developed a comprehensive, and clinically applicable framework that standardizes laboratory test indications and links them to indication-dependent utilization and interpretation.

Methods: A structured literature review on utilization, appropriateness, and request rationale informed an iterative, consensus-based process with a multidisciplinary expert panel to develop and operationalize an indication taxonomy and attribute schema. Structural coherence was assessed by comparing semantic distance hierarchies derived from indication labels alone with an enriched multi-layer ("layered prototype") representation incorporating these attributes. Use cases were applied to assess feasibility of indication-to-interpretation mapping.

Results: We defined 19 distinct indication types, grouped into five clusters across the clinical course: Initial Detection and Diagnostic Clarification, Disease Characterization and Prognosis, Therapy Guidance and Safety, Longitudinal Management and Reassessment, and Analytical and External Requirements. Each is specified with structured attributes and examples to support implementation. Semantic distance analyses supported a coherent hierarchy. Layered prototypes yielded more informative organization than labels alone, enabling context-dependent consolidation and guided deployment.

Conclusions: By providing explicit indication-to-interpretation mapping/logic, the framework closes a key gap in the total testing process between order entry and post-analytical interpretation. It supports context-specific decision limits, reporting logic, and stewardship analytics, and is amenable to formalization as a machine-readable ontology for interoperable implementation.

Objectives: This stability study aimed to evaluate the stability of 48 biochemical analytes in pooled serum samples derived from leftover sera over 14 days at room temperature (RT) and at 2-10 °C, and to assess the consistency of storage effects across independent pools. The goal was to determine the suitability of such materials for external quality assessment (EQA) schemes.

Methods: A total of 110 residual serum samples were derived from Greiner Bio-One Vacuette tubes (with or without separator gel) and randomly assigned to 10 pools. Aliquots were stored at RT or 2-10 °C and analysed on days 0, 1, 2, 3, 4, 7, and 14 using Roche Cobas and DiaSorin Liaison platforms. Percent deviations from baseline (PD%) were compared against maximum permissible differences (MPDs) derived from reference change values. Inter-pool variability was assessed by linear regression of standard deviations of PD%-values over storage time.

Results: Under refrigerated conditions, six analytes exceeded stability limits, with only alanine aminotransferase (ALAT), lactate dehydrogenase (LDH), and 1,25(OH)₂ vitamin D showing instability within seven days and the others not before day 14. At RT, 38/48 parameters remained stable for at least 4 days. Inter-pool variability increased significantly for only three parameters at 2-10 °C and nine at RT, with most slopes below 0.35 %/day, indicating largely matrix-independent degradation patterns.

Conclusions: The majority of analytes in pooled leftover sera demonstrated acceptable stability, particularly under refrigerated conditions. Storage effects occurred consistently across pools, supporting reproducibility. These findings indicate that pooled sera from diagnostic leftovers represent a practical resource for EQA when analysed within defined timeframes.

Objectives: Clinical laboratories play a vital role in healthcare but are also among the most resource-intensive hospital units. High energy and water consumption, extensive use of single-use plastics, and the generation of non-recyclable biomedical waste present major environmental challenges. This study aimed to quantify the environmental and economic burden associated with common and avoidable practices in clinical laboratory medicine, including: excessive blood collection, inappropriate test ordering, and unnecessary tube duplication in pre-analytical workflows.

Methods: Real-world data from the Clinical Biochemistry Laboratory of the AOU Maggiore della Carità (Novara, Italy) for the year 2024 were analysed to quantify the environmental and economic impact of inappropriate test ordering based on minimum retesting intervals, as well as pre-analytical practices, including redundant sample tube collection and excessive blood volumes relative to analytical requirements.

Results: Inappropriate retesting of selected biomarkers resulted in 2,931 unnecessary tubes, generating over 26.7 kg of avoidable waste. Redundant EDTA tubes for complete blood count, glycated haemoglobin, erythrocyte sedimentation rate, and haemoglobin electrophoresis led to 356.14 kg of excess waste, which could be eliminated through sample consolidation. In haematology, 264,834 CBC tests generated 2.62 tonnes of biological waste. For biochemistry, 3 million tests produced 36.98 tonnes of waste.

Conclusions: Excessive blood collection and unnecessary test repetition contribute to significant but avoidable environmental and financial burdens. Pre-analytical interventions, such as reducing tube volume and consolidating tests, could prevent over 40 tonnes of waste and save more than € 60,800 annually in a single laboratory.

Objectives: Despite growing interest in artificial intelligence (AI) and machine learning (ML), many laboratory professionals lack experience with developing in-house AI systems or implementing those supplied by external providers. The IFCC Committee on AI in Laboratory Medicine (C-AILM) conducted a survey to collect the status of AI/ML applications, challenges, and expert perspectives on key technical considerations.

Methods: An 20-item survey was distributed to laboratory professionals experienced in AI. It covered application status (in-house or provider-supplied, with or without regulatory approval); essential information to request from AI system providers; validation or verification practices; monitoring strategies; and perceived implementation challenges.

Results: Fifty complete responses from global experts were received. AI implementation in clinical laboratories was limited and heterogeneous. Most respondents agreed that AI systems provided externally, regardless of regulatory approval status, require local verification. Key information needed from providers included performance metrics from original and external datasets, and demographics of the training/test populations. For both approved and non-approved models, high-priority verification studies were local performance analysis, confirmation of intended-use alignment, and verification of privacy and security safeguards. Top monitoring strategies were regular accuracy checks and comparison against human decision-making. Leading challenges were insufficient IT infrastructure and lack of practical implementation guidelines.

Conclusions: Although many challenges remain, clinical laboratories demonstrate strong enthusiasm for AI, particularly with the growing prevalence of commercial AI products. The timely expert insights from our survey and C-AILM recommendations for both AI system providers and clinical laboratories on essential information, verification requirements, and monitoring strategies will inform standardized guideline development.

Objectives: Antiphosphatidylserine/prothrombin (aPS/PT) antibodies are promising non-criteria aPLs associated with antiphospholipid syndrome (APS) manifestations. Their influence on long-term outcomes and damage remains uncertain. To assess aPS/PT antibodies association with accrual damage and severe APS disease phenotypes, focusing on their potential for risk stratification.

Methods: This single-centre cohort study involved 163 patients who fulfilled the 2023 ACR/EULAR APS criteria. IgG/IgM aPS/PT, aCL, and anti-β2GPI antibodies were measured by commercial ELISA. Lupus anticoagulant (LA) was detected in accordance with the ISTH-SSC recommendation. Clinical data covered macrovascular, microvascular, obstetric, and hematologic manifestations. Damage was assessed using DIAPS.

Results: aPS/PT IgG and IgM were positive in 46.0 % and 65.6 %, respectively. aPS/PT IgG positivity was linked to microvascular involvement (58.7 % vs. 34.1 %, p=0.002), obstetric APS (57.4 % vs. 24.6 %, p<0.0001), valvular disease (17.3 % vs. 4.6 %, p=0.008), and thrombocytopenia (37.3 % vs. 12.5 %, p<0.0001). aPS/PT IgM positivity was also associated with microvascular APS (p=0.006), obstetric morbidity (p=0.02), and thrombocytopenia (p=0.01). In multivariable analysis, quadruple aPL positivity (LA + aCL + anti-β2GPI + aPS/PT) was independently linked to damage (OR 4.3, 95 % CI 1.3-14.5; p=0.02), with no other factors remaining significant.

Conclusions: Both IgG and IgM aPS/PT antibodies are associated with severe APS features, including microvascular and obstetric issues, as well as overall organ damage. Adding aPS/PT to standard aPL tests finds a subgroup of quadruple-positive APS patients at higher risk of damage. These results could help guide personalized APS management.

Recent advances in blood-based biomarkers for neurodegenerative diseases present promising opportunities for earlier diagnosis and more effective disease monitoring. However, challenges in standardizing sample collection, processing protocols, and data reporting continue to hinder reproducibility, limit cross-study comparability, and delay clinical adoption. As efforts toward harmonization progress (supported by technological innovation and integration into multimodal diagnostic strategies), blood biomarkers are expected to transition from research settings to routine clinical use, bringing precision medicine closer to individuals affected by these disorders.