Clinical chemistry and laboratory medicine最新文献

Objectives: The Fourth Universal Definition of Myocardial Infarction recommends high-sensitivity cardiac troponin (hs-cTn) as the preferred biomarker for diagnosing myocardial infarction. This study evaluated the analytical and clinical performance of a novel hs-cTnT chemiluminescence immunoassay (CLIA) developed by Mindray.

Methods: Analytical performance characteristics including precision, sensitivity (limit of detection [LoD] and limit of quantification [LoQ]), imprecision profile, linearity, sample type comparison, method comparison, and potential interferences were assessed. Sex-specific 99th percentile upper reference limits (URLs) were established in 895 healthy individuals. Clinical diagnostic performance was evaluated in 559 patients with suspected acute myocardial infarction and compared with the Roche hs-cTnT assay.

Results: The Mindray assay showed excellent precision (repeatability CV≤1.99 %, within-laboratory precision CV≤6.11 %), superior sensitivity (LoD: 1.4 ng/L; LoQ: 2.4 ng/L), and linearity (r=0.9978), along with robust performance against common and immunological interferences. Using the manufacturer-claimed LoD of 2.0 ng/L, measurable values were found in 99.36 % of males, 83.26 % of females, and 91.48 % overall, meeting criteria for high-sensitivity assays. The derived sex-specific 99th percentiles were 18.6 ng/L (males), 9.6 ng/L (females), and 16.0 ng/L (overall). In the clinical cohort, the assay showed 100.0 % sensitivity, 83.3 % specificity, 80.0 % PPV, 100.0 % NPV, and an AUC of 0.988, comparable to the Roche Gen 5 hs-cTnT assay.

Conclusions: The Mindray hs-cTnT (CLIA) assay meets high-sensitivity assay criteria and demonstrates robust analytical and diagnostic performance, offering a reliable alternative to the Roche Gen 5 assay for clinical evaluation of myocardial injury.

Objectives: To maximize participation in the international standardization effort, this recommendation aims to update the international guidance of the Working Group on Laboratory Errors and Patient Safety of the International Federation of Clinical Chemistry and Laboratory Medicine by identifying a limited and globally applicable panel of Essential Quality Indicators (QIs) focused on patient safety, clinical outcomes, and harmonization across medical laboratories.

Methods: Through a consensus meeting, experts from multiple countries reviewed the IFCC Model of Quality Indicators (MQI) to identify high-priority indicators. Selection prioritized the probability of patient harm, ease of detection, and feasibility of data collection and implementation within national contexts.

Results: Six essential QIs covering the total testing process were identified and ratified: (1) rate of misidentified requests (Pre-MisR) and misidentified samples (Pre-MisS); (2) rate of sample rejections (Pre-RejS); (3) rate of hemolysis detected either by automated hemolysis index (Pre-HemI) or visual inspection (Pre-HemV); (4) rate of unacceptable results in External Quality Assessment/Proficiency Testing (Intra-Unac); (5) turnaround time of cardiac troponin at the 90th percentile for the emergency room (Post-TnTAT, Post-TnTAT clin); and (6) rate of incorrect laboratory reports (Post-RectRep). Recommendations on calculation, reporting frequency, and integration into IFCC and national comparison programs are provided.

Conclusions: The proposed essential QI panel provides a standardized and feasible framework to support its integration into national comparison programs and the IFCC MQI platform. Its implementation will facilitate data consolidation, strengthen the development of national and global quality specifications, and contribute to continuous improvement in patient safety.

Recreational nitrous oxide (N₂O) use has emerged as a growing public health concern, with increasing reports of neurological, psychiatric, and thrombotic complications. This position paper from the EFLM Committee on Biological Markers of Nitrous Oxide Abuse highlights the urgent need for clinical and laboratory awareness, alongside coordinated action from healthcare systems and the scientific community. Short-term recommendations focus on early clinical recognition, prompt biological testing, and structured patient management. Key clinical symptoms include unexplained sensory disturbances, gait instability, bladder and bowel complaints, sexual dysfunction, mood disorders, and thromboembolic events in young individuals. Plasma homocysteine (HCY) and plasma methylmalonic acid (MMA) are central to the diagnostic approach, with HCY serving as a sensitive marker of recent exposure and MMA indicating clinical severity. Vitamin B12 and folate measurements are also essential, though B12 levels may be falsely reassuring (often in the low-normal range). Given the rapid normalization of biomarkers, testing should be performed on admission, and vitamin B12 supplementation should begin without delay, with caution regarding biomarker kinetics and possible self-supplementation by patients. In addition, this paper outlines long-term goals, including the harmonization of biomarker assays, creation of international patient registries, and development of interdisciplinary expert networks. Notably, the international network PROTOSIDE (www.protoside.com) plays a key role in facilitating case discussion, expert collaboration, and dissemination of best practices in the management of N₂O-related complications. A continuous bibliographic watch and support for translational research are necessary to improve biomarker discovery and understanding of the underlying mechanisms of toxicity. By combining immediate clinical action with long-term scientific and policy development, this document lays the foundation for an international strategy to address the silent but expanding epidemic of nitrous oxide misuse.

Objectives: To prevent intoxication with 5-fluorouracil (5-FU) during chemotherapy, the initial measurement of plasma uracil levels has recently been recommended by the European Medicines Agency. Here we present and compare two new chromatographic methods for analysis of uracil in plasma. Two independent laboratories analyzed the same set of samples using in-house-developed analytical methods. The aim of this comparison is to demonstrate that our methods are harmonized, providing comparable concentrations and consistent clinical interpretations.

Methods: The approaches presented employ mass spectroscopic detection in negative ion mode but differ in sample preparation and chromatographic techniques. Method 1: Protein precipitation using acetonitrile, followed by injection of a small sample volume for hydrophilic interaction liquid chromatography (HILIC). Method 2: Protein precipitation with acetonitrile combined with filtration through a 96-well filter plate, followed by evaporation and reconstitution in the chromatographic mobile phase for C18 reverse-phase chromatography.

Results: Both methods are demonstrated robust and accurate quantification of uracil. Results obtained from patient samples (n=161) show a strong correlation between the two methods, with a relative mean deviation of 2 %. The same clinical interpretation is obtained for the majority of samples (150/161). The remaining samples (11/161) were close to the lower clinical decision limit (16 μg/L).

Conclusions: For the analysis of uracil, both presented methods, which are based on simplified sample preparation procedures, provide accurate results without significantly impacting the clinical interpretation. However, the results indicate a potential gray area of analytical imprecision from 14 to 20 μg/L, encompassing the lower clinical decision limit (16 μg/L).

Capillary blood sampling is gaining recognition as a patient-centered alternative to traditional venipuncture. Its main advantages are that it is less invasive, reduces patient discomfort, and potentially can be performed without the direct supervision of a healthcare professional. These features could facilitate access to healthcare, particularly for patients with limited access to clinical facilities or those requiring frequent testing, thereby supporting telemedicine, and improving participation in screening programs and clinical trials. However, its integration into routine clinical practice requires the development of standardized traceable processes and user-friendly collection kits that preserve sample quality and have preanalytical error rates comparable to those of venipuncture. Compliance with ISO 15189 and integration into existing laboratory workflows are essential. Moreover, device affordability and compatibility with analyzers will determine accessibility and scalability. Addressing logistical, regulatory, and technical challenges is key to fully realizing its potential as a patient-centric solution in modern healthcare, where the robustness of analytical data derived from capillary blood could be comparable to that obtained from venous blood. In this review, we analyze the potential role of capillary blood in routine clinical practice, highlighting its benefits and challenges and determining the conditions necessary for its successful implementation.

Objectives: As (a lack of) vitamin D has been linked to a wide variety of chronic diseases, there is growing interest in generating robust epidemiological data. Consequently, the need for large-scale biological sample collection has increased. In this context, dried blood spot (DBS) microsampling offers a minimally invasive alternative to venous sampling. However, to allow interpretation of DBS-based 25-hydroxyvitamin D (25-(OH)D) results, the set-up of a clinical validation study is essential to assess the agreement with the reference matrix, plasma.

Methods: Venous plasma and whole blood, venous DBS (vDBS) and capillary DBS (cDBS) were collected from 44 healthy volunteers to evaluate the agreement between the different sample types for 25-(OH)D quantification. To transform cDBS-based results to plasma concentrations, a hematocrit (Hct)-dependent conversion factor was applied and evaluated using four different Hct determination approaches. All samples were analysed using previously described validated LC-MS/MS methods.

Results: No clinically relevant methodological (vDBS vs. whole blood) or sampling-site related (cDBS vs. vDBS) issues were observed. Following Hct-dependent conversion, good agreement between the cDBS-derived and actually measured plasma results was obtained, as 90 % of the results lay within 20 % of the plasma result, independent of the Hct approach used. Additionally, weighted Cohen's kappa values of 0.83-0.85 were obtained across the different Hct approaches, indicating substantial to almost perfect agreement in vitamin D status classification.

Conclusions: Following Hct-dependent conversion, cDBS can be used as a reliable and practical alternative matrix to plasma for large-scale monitoring of vitamin D status in epidemiological and public health contexts.

Objectives: Procalcitonin (PCT) is increasingly used to support sepsis diagnosis, but its role in predicting outcomes remains uncertain, particularly in low-resource settings. We evaluated whether single and serial PCT measurements were associated with 28-day mortality in critically ill adults with suspected sepsis.

Methods: We conducted a retrospective study of adult intensive care unit (ICU) patients with suspected sepsis and at least one PCT measurement at a tertiary hospital in South Africa (August 2022-July 2023). Baseline PCT was analysed using multivariable logistic regression. Among patients with ≥2 PCT values, we examined the association between PCT slope (from patient-level linear regression) and mortality. Latent class mixed models (LCMM) were used to identify PCT trajectory subgroups.

Results: Of 371 patients, 119 (32 %) died within 28 days. Higher baseline log-PCT was independently associated with increased mortality (adjusted odds ratio [aOR] 1.58; 95 % CI 1.01-2.50). A rising PCT slope trended toward higher mortality (aOR 3.56 per unit/day; p=0.06). LCMM identified three trajectory classes with distinct mortality risks (class 2: aOR 4.53; class 3: aOR 4.35, vs. reference). These models were based entirely on laboratory data and did not assess clinical scoring systems.

Conclusions: Both baseline and serial PCT measurements predicted mortality in ICU patients with suspected sepsis. Modelling approaches based on routine laboratory data may offer scalable tools for early risk stratification in resource-limited settings.