Clinical biochemistry最新文献

Introduction: Vancomycin is a critical antibiotic for treating severe Gram-positive infections. Due to its narrow therapeutic window, reliable plasma concentration measurements are essential for dose adjustment and avoiding toxicity. However, method-dependent analytical variability between immunoassay platforms may compromise result comparability.

Methods: Data from 78 external quality assurance (EQA) samples distributed between 2016 and 2025 by Labquality (Helsinki, Finland) and Equalis (Uppsala, Sweden) were analyzed. Results from laboratories using immunoassays from Abbott Laboratories (n = 1391), Beckman Coulter (n = 172), Roche Diagnostics (n = 3584), Ortho Clinical Diagnostics (n = 78), Siemens Healthineers (n = 1670), Thermo Fisher (n = 152), and ARK Diagnostics (n = 33) were included (total = 7104). The mean consensus value for each sample was used as reference.

Results: Across the study period, Abbott Laboratories (+4.7%), Thermo Fisher (+12%), Ortho Clinical Diagnostics (-4.6%), and Siemens Healthineers (-4.9%) showed systematic biases relative to the consensus mean, whereas Beckman Coulter (-0.3%), Roche Diagnostics (<0.1%), and ARK Diagnostics (-2.4%) displayed good agreement. Temporal trends indicated method-specific drifts, most notably for Beckman Coulter (-20.2%) and Siemens Healthineers (+12.5%). Coefficients of variation ranged from 0.9% (ARK Diagnostics) to 12.1% (Beckman Coulter).

Conclusion: Considerable intermethod bias and temporal drift exist among commonly used vancomycin immunoassays, underscoring the need for improved calibration harmonization and traceability to ensure consistent therapeutic drug monitoring.

Objective: To evaluate thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC), tissue-plasminogen activator-inhibitor complex (t-PAIC), and D-dimer for diagnosing heparin-induced thrombocytopenia (HIT) and stratifying thrombosis risk.

Methods: A total of 221 patients with suspected HIT were classified as HIT-positive (HIT+) or HIT-negative (HIT-), with HIT+ further stratified by thrombosis (HITT+/HITT - ). We collected clinical variables and identified HIT risk factors using multivariable logistic regression. Group differences in TM, TAT, PIC, t-PAIC, and D-dimer were assessed, diagnostic performance was examined using receiver operating characteristic (ROC) curves, and correlations were tested with Spearman's rank correlation. Kaplan-Meier analysis estimated the 15-day cumulative incidence of thrombosis in HIT patients stratified by TAT.

Results: Elevated 4 T scores and HIT antibody levels were independent risk factors for HIT. TM, TAT, and D-dimer levels were higher in HIT+ versus HIT-. Only TAT was elevated in HITT+ versus HITT-, correlating positively with HIT antibodies. For diagnosing HIT, the areas under the curve (AUCs) for TM, TAT, and D-dimer were 0.712, 0.735, and 0.721, respectively. The combination of these three markers yielded the highest efficacy (AUC = 0.807). TAT showed predictive value for thrombosis among HIT patients; a threshold of 12.11 µg/L yielded the best performance. Kaplan-Meier analysis demonstrated a significantly higher 15-day thrombosis risk for patients with TAT ≥ 12.11 µg/L vs. < 12.11 µg/L.

Conclusion: TM, TAT, and D-dimer can serve as auxiliary biomarkers for HIT diagnosis, with combined use improving accuracy. Notably, TAT may be useful in guiding risk-stratified anticoagulation therapy based on thrombotic risk.

Neuromuscular autoantibody testing is an essential component in the diagnosis and management of autoimmune neuromuscular disorders. These immune-mediated diseases target antigens found in nerves, muscles, and neuromuscular junctions, and may occasionally involve the central nervous system, resulting in complex clinical presentations. Developments in antibody identification and validation have provided clinically relevant biomarkers for diagnostic, therapeutic, and prognostic purposes. Among antibody-associated neuromuscular disorders, paraneoplastic onconeural autoantibodies are of particular significance, as their presence may direct search for specific underlying malignancies. Appropriate ordering and interpretation of these tests should be integrated with clinical and electrodiagnostic (CEDX) findings. Given that these disorders are often rare, estimating an optimal pre-test probability is important to improve test accuracy and reduce false positive outcomes. Online clinical calculators are available to help clinicians determine appropriate testing strategies for some disorders. This review summarizes principal neuromuscular antibodies, current testing approaches, and the influence of laboratory data on patient care.

Background: Reagent stability is a significant determinant of analytical reliability in clinical laboratories. Post-expiry reagent use is often discouraged due to the potential risk of systematic bias; however, empirical data supporting or refuting such restrictions are limited.

Methods: This study evaluated the post-expiry performance of free T3 (FT3) and free T4 (FT4) immunoassays on the Abbott Architect i1000SR analyzer using an integrated framework combining three complementary approaches: (i) a simulation-optimized moving average (MA) model based on real patient data (ii) Westgard Sigma rules quality control, and (iii) Clinical and Laboratory Standards Institute EP25-A drift analysis. The MA was optimised via Monte Carlo simulations using a step-shift bias model, which defined the optimal window size (N) for 90% detection power and 0% false rejection rate. Stability was then assessed across three reagent lots per analyte, spanning both pre- and post-expiration phases.

Results: Westgard rules provided the earliest analytical alerts, while EP25 confirmed sustained drift relative to allowable total error. The MA detected progressive instability, showing strong concordance with EP25 after lag correction (N × cadence). FT4 indicated extended stability of up to 19 months post-expiry, while FT3 showed limited stability (<4 months). These differences reflected distinct assay robustness and kinetics.

Conclusions: The combination of Westgard sigma rules, EP25, and simulation-optimized MA provides a reproducible, data-driven framework for post-expiry reagent stability assessment. Optimizing MA with real patient data enhances detection performance, bridging theoretical quality-control design and routine laboratory application. This integrated approach enables laboratories to make scientifically justified, cost-effective decisions regarding reagent reuse beyond manufacturer expiry dates.

Seed amplification assays have shown promise in research for accurate diagnosis of synucleinopathies. In consideration of clinical implementation, gaps in the literature include that performance data are frequently determined using clinically unrelated controls (e.g., healthy controls or phenotypically unrelated conditions [UC]), and a lack of emphasis on methodological variability, including required replicates and positivity thresholds. A review and meta-analysis were performed to assess the methodological parameters and diagnostic performance of seed amplification assays for detecting synucleinopathies and, where necessary, cohorts were adjusted to be more representative of the populations in which the testing would be deployed in clinical practice. A search was conducted for α-synuclein seed amplification assay studies on Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, for matrices including cerebrospinal fluid (CSF), skin, and olfactory mucosa (OM). Assay methodological details were extracted, as were diagnostic performance data. For the latter, negative controls were divided into two distinct groups: disease mimics (DM) and UC. A total of 55 studies met the inclusion/exclusion criteria. Methodological parameters varied including the concentration, sequence and source of the assay substrate, as well as required assay replicates and determination of the positivity threshold. Median sensitivities and specificities relative to DM groups for CSF were 0.92 (95% confidence interval: 0.88-0.96) and 0.90 (0.89-0.96), for skin were 0.94 (0.79-1.0) and 0.86 (0.83-1.0), and for OM were 0.69 (0.33-1.0) and 0.94 (0.83-1.0), respectively. Although diagnostic performance was slightly reduced when adjusting for clinically relevant populations, it remained encouragingly high. Towards broader clinical implementation, valuable research directions include further streamlining of analytical workflows, and characterizing diagnostic performance by stage of disease and co-pathologies.

This article reflects on the relationship between Planetary Health and healthcare workers in 2025. As clinical chemistry specialists working within the healthcare system, attention to the health of the patients who utilize our portion of the healthcare system now extends beyond provision of information. How we provide that information, how often we provide this information, and how extensive the information is that we do provide impacts Planetary Health - the major determinant of health for our patients born this year and thereafter. We summarize the importance of looking at this broader view of health as lab specialists have agency in effecting how clinical labs operate in the remainder of this century. Our position is that this agency should be in alliance with Planetary Health for the benefit of our patient's health in the next generations. We recognize the patient born today, a 50 year old in 2075, as a Patient Advocate Virtual (PAV) who could symbolically be present in decision making in the clinical lab - and throughout the healthcare system - to remind us of the importance of caring for Planetary health tomorrow while we care for patients today.