Journal of Applied Laboratory Medicine最新文献

Background: The role of high-sensitivity cardiac troponin (cTn) assays for children and young adults is uncertain, and no guidance is available on diagnostic thresholds. This study evaluates the effect of applying pediatric compared to adult upper reference limits (URLs) for cTn.

Methods: We carried out a retrospective multicenter international cohort study of consecutive children and young adults (1 day to 18 years) undergoing cTn I or T testing at 4 tertiary care hospitals in Norway and Scotland, United Kingdom, from 2013 to 2023. Myocardial injury was classified using the adult sex-specific 99th percentile URL, a pediatric sex-specific 99th percentile, and a pediatric sex-specific 97.5th percentile. Diagnoses of myocarditis were obtained from the Norwegian Patient Register and the Scottish Morbidity Record.

Results: In total, 9833 (46.6% female) children and young adults underwent cTn testing. Applying the adult sex-specific 99th percentile, 1771 (18.0% [95% CI, 17.3%-18.8%]) had myocardial injury compared with 1762 (17.9% [95% CI, 17.2%-18.7%]) using a pediatric 99th percentile. In contrast, applying a pediatric sex-specific 97.5th percentile would identify 2261 (23.0% [95% CI, 22.2%-23.8%]) with myocardial injury (a 28% relative increase). Infants had a higher frequency of myocardial injury than those 1-18 years old (1035/1104; 93.8% [95% CI, 92.2%-95.1%] vs 1226/8729; 14.0% [95% CI, 13.3%-14.8%] using pediatric sex-specific 97.5th percentile, P < 0.001). Testing for cTn increased over the study period (τ = 0.42, P < 0.001).

Conclusions: The use of pediatric-specific 97.5th percentile URLs for cTn would increase classification of myocardial injury in children and young adults. The clinical implications of this are uncertain and require further study given cTn testing has increased over the last decade.

Background: Historically, 25-hydroxyvitamin D (25OHD) assays have under- or over-recovered 25-hydroxyvitamin D2 (25OHD2), but assay manufacturers have modified their reagents to address this problem. In this study, we compared the second- and third-generation Roche assays as well as two contemporary offerings from Diasorin and Beckman against liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Methods: We identified 50 remnant serum samples with 25OHD concentrations from across the analytical range of the second-generation Roche assay. To increase 25OHD2 representation, we identified 25 additional samples from individuals prescribed high-dose vitamin D2 supplements. We tested samples on Roche assays and circulated to laboratories performing Beckman and Diasorin 25OHD assays. We tested samples by LC-MS/MS to obtain concentrations for 25OHD2 and 25-hydroxyvitamin D3.

Results: Mean overall bias for each assay was 5.1 ng/mL or less against the LC-MS/MS measurement; mean proportional bias was 8.7% to 12.1%. Some individual specimens had much larger bias. 25OHD2 was under-recovered on average, but the bias for the third-generation Roche assay represents a significant improvement over the previous assay, and mean bias for current generation assays was no worse than -3.2 ng/mL. In most cases, clinical classification by automated assay values agreed with clinical classification by LC-MS/MS; where present, disagreements occurred near classification thresholds.

Conclusions: Automated 25OHD assays continue to improve, and 25OHD2 recovery no longer appears to be a significant concern for the assays evaluated here. All assays evaluated were adequate for clinical classification of vitamin D nutritional status and are suitable for routine use, including in patients prescribed high-dose vitamin D2.

Background: Measurement of serum free light chains (FLC) including kappa FLC, lambda FLC, and calculated kappa to lambda FLC ratio play a vital role in the diagnosis, prognosis, and monitoring of plasma cell disorders. Recent concerns regarding upward drift in The Binding Site's kappa FLC measurements have prompted a reformulation of the kappa FLC calibrator by the manufacturer. This study aims to assess the impact of the reformulated/new kappa FLC calibrator on both the kappa FLC reference interval (RI) and the FLC ratio diagnostic range.

Methods: Healthy volunteers (n = 124) from 3 tertiary care medical centers had FLCs measured using both the new and the prior lot of kappa FLC calibrators on an Optilite analyzer (The Binding Site). All samples were screened for monoclonal proteins using capillary electrophoresis. Creatinine was measured to confirm renal function.

Results: Comparison of kappa FLC values from the new vs prior calibrator demonstrated minimal differences. Neither calibrator was able to verify manufacturer-suggested RI in our study population. The proportion of samples that had FLC ratios within the manufacturer's claimed diagnostic range was equivalent between calibrators, with roughly 6% to 7% of study participants falling above the diagnostic range of 0.26 to 1.65.

Conclusion: The new reformulated kappa FLC calibrator from The Binding Site does not support verification of the manufacturer's claimed kappa FLC RI or improve the number of healthy patients falling within the FLC ratio diagnostic range. Both the kappa FLC RI and diagnostic range for FLC ratio should be reevaluated and updated in consensus guidelines.

Background: Cancer immunotherapy research, immune microenvironment exploration, and biomarker discovery are key application areas of immune checkpoint analysis. PD-1 and CD28 are crucial receptors expressed on the surface of T cells, playing vital roles in regulating T cell activation and immune response. Accurate detection of these immune checkpoints, such as PD-1 and CD28 on lymphocytes, is essential for understanding immune responses, particularly in clinical contexts such as cancer immunotherapy. Flow cytometry offers a precise approach to detect these markers in whole blood samples.

Methods: This study developed and optimized a flow cytometry-based detection method utilizing the CYTEK NL-CLC flow cytometer to quantitatively assess the expression of PD-1 and CD28 on lymphocytes. A detailed protocol was established and validated, focusing on key performance parameters.

Results: Our method showed high sensitivity and specificity, providing a powerful tool for immune monitoring and treatment decision-making. Validation results, including precision, dilution linearity, fluorescence stability, reference interval, and accuracy, all met acceptable criteria and have been reviewed and approved for clinical testing.

Conclusions: The CYTEK NL-CLC flow cytometer is positioned as a reliable and effective platform for immune checkpoint analysis in both clinical and research settings, supporting its integration into cancer immunotherapy workflows and personalized medicine strategies.

Background: Increases in obesity and hypertriglyceridemia worldwide, together with lower LDL cholesterol (LDL-c) values from new lipid-lowering agents, prompted the development of new estimation formulas including Martin (M-LDL-c), extended Martin (ME-LDL-c), and Sampson (S-LDL-c) equations. These require validation in different populations.

Methods: Lipid profiles with direct LDL-c (D-LDL-c) by homogeneous assay were collected from 22 748 patients in Argentina. Friedewald (F-LDL-c), S-LDL-c, M-LDL-c, and ME-LDL-c were calculated. Patients were classified into treatment categories using both D-LDL-c and each formula independently. Datasets were subdivided by triglycerides (TG). Lipid ratio plot (LRP) provided indirect comparison to beta quantification (BQ). Passing-Bablok, Bland-Altman, and clinical concordance (kappa index) analyses assessed formula performance against D-LDL-c.

Results: LRP analysis showed S-LDL-c had the closest agreement with BQ surrogate line, followed by D-LDL-c. All formulas showed good correlation with D-LDL-c (r > 0.95) and moderate concordance (kappa > 0.6). M-LDL-c and ME-LDL-c demonstrated the best clinical concordance with D-LDL-c overall. Performance decreased with increasing TG for all formulas. F-LDL-c deteriorated from 200 mg/dL (2.28 mmol/L) TG, while S-LDL-c, M-LDL-c, and ME-LDL-c maintained acceptable performance up to 400 mg/dL (4.56 mmol/L) TG.

Conclusion: S-LDL-c, M-LDL-c, and ME-LDL-c showed better agreement with D-LDL-c than F-LDL-c in this South American population. LRP analysis suggests S-LDL-c may provide most accurate estimation vs gold standard BQ, particularly in hypertriglyceridemia. These findings support the adoption of newer equations in clinical practice.

Background: Acute graft-versus-host disease (aGVHD) is a common complication of allogenic hematopoietic cell transplantation (HCT). The aGVHD presymptomatic algorithm is comprised of 2 serum biomarkers, suppression of tumorigenicity 2 and regenerating islet-derived 3-alpha. This test was developed to predict severe aGVHD and 6-month nonrelapse mortality (NRM) in allogeneic HCT recipients.

Methods: The medical records of 223 patients tested with the aGVHD presymptomatic algorithm between January 2020 and June 2024 were retrospectively reviewed. Sensitivity and specificity for the prediction of severe aGVHD (grade III or IV) and 6-month NRM were determined. Logistic regression modeling was used to assess the odds ratios of risk factors for severe aGVHD and 6-month NRM. The likelihood ratio test was used to evaluate whether the addition of the aGVHD presymptomatic algorithm improved model fit.

Results: Severe aGVHD occurred in 8.5% of patients, and 6-month NRM was 7.2%. The aGVHD presymptomatic algorithm demonstrated a sensitivity of 21.1% (95% CI, 8.0%-43.9%) and specificity of 83.3% (95% CI, 77.6%-87.9%) for severe aGVHD and a sensitivity of 43.8% (95% CI, 23.1%-66.8%) and specificity of 85.0% (95% CI, 79.5%-89.3%) for 6-month NRM. The addition of results from the aGVHD presymptomatic algorithm to conventional risk factors did not improve prediction of aGVHD but improved prediction of 6-month NRM.

Conclusions: The aGVHD presymptomatic algorithm was suboptimal for routine clinical use. Further development of predictive aGVHD biomarkers may be required to aid in the management of allogeneic HCT recipients.

Background: Health literacy and numeracy are broad terms that relate to a patient's understanding of their health information. While there is a substantial amount of research on this topic in a general sense as well as in relation to how deficiencies in these skills impact patients' understanding of laboratory results, little is known regarding the extent to which underlying factors, which are impacted by health literacy/numeracy, affect how patients interpret their results. This literature review attempts to shed light on the current literature on this more focused and narrow issue, including recommendations to address these barriers.

Content: To perform this review, the key terms "health literacy AND numeracy," "health literacy AND laboratory results," and "patient understanding of laboratory test results" were searched in the PubMed Central, Health Source: Nursing/Academic Edition, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. After reviewing articles for inclusion and exclusion criteria, a total of 16 articles were included. Major themes from the articles utilized were (a) the impact of the laboratory, (b) factors that affect health literacy and numeracy of laboratory data, and (c) recommendations to improve patient understanding and comprehension of their test results.

Summary: Many factors affect patients' comprehension of laboratory data, such as access to this information, data presentation, and holistic influences. Recommendations for improving patient health numeracy of laboratory information are to improve how data is presented to patients and to increase access to supplemental resources via patient portals.

Background: Rapid, accurate diagnosis in acute and emergent care remains a major challenge, with delays directly impacting patient outcomes. Extracellular vesicles (EVs), nanoscale membranous particles secreted by all cell types and found in virtually all biological fluids, have the potential to transform acute diagnostics as minimally invasive biomarkers. As key intercellular messengers and carriers of biological cargo, EVs reflect the physiological and pathological states of their parent cells. While EV research has largely focused on chronic diseases such as cancer and neurodegeneration, their role in acute pathologies remains under-investigated.

Content: This review describes the current landscape of EVs in laboratory medicine, with a focus on their potential for acute and emergent conditions, including sepsis, stroke, traumatic brain injury, and myocardial infarction. We examine advances in EV isolation and characterization techniques and discuss the unique challenges of implementing these approaches in a clinical setting. In particular, we highlight emerging technologies that aim to address existing barriers, including lack of standardization, long processing times, and limited clinical scalability.

Summary: By summarizing existing knowledge and identifying critical research gaps, this review intends to refocus attention toward EV applications for acute care. As EV-based diagnostics continue to advance, their successful integration into clinical work flows has the potential to significantly transform healthcare delivery, enabling real-time, personalized diagnostics and improving health outcomes across a wide range of settings.