Journal of Applied Laboratory Medicine最新文献

Background: Heart failure (HF) is a complex syndrome with high mortality. The Metabolic Vulnerability Index (MVX) is a novel multimarker score derived from inflammation and malnutrition markers that has demonstrated prognostic value in patients with HF; however, changes in MVX over time have not been characterized. The purpose of this study was to evaluate change between baseline and 12-month measurements of the MVX and its components in an HF clinical trial population.

Methods: Nuclear magnetic resonance spectroscopy (NMR) MetaboProfile analyses (Labcorp) were performed on paired EDTA baseline and 12-month plasma samples collected from 46 HF patients with preserved ejection fraction (HFpEF) enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) clinical trial to generate non-sex-specific MVX scores and component analytes. Paired t-tests were used to test the null hypothesis that the differences in paired population means between baseline and 12-months for MVX, or its components, were equal to 0. In sensitivity analyses, we evaluated whether differences in MVX or component values differed by drug status.

Results: In this sample, the mean (SD) age was 72.5 (9.2) years; 50% were female, and 89% were White. The prevalence of comorbidities was similar to the full TOPCAT population. MVX mean scores were not significantly different between baseline and 12-month measurements (mean difference = 1.52, 95% CI: -0.97 to 4.01, P = 0.225).

Conclusions: MVX scores appeared stable in this cohort over one year. Future studies should evaluate changes in serial measurements of MVX in a larger sample size.

Background: The clinical performance of the VITROS® Immunodiagnostic Products Syphilis Assay was evaluated by comparison with composite results obtained with widely used lipoidal antigen (nontreponemal) and T. pallidum (treponemal) tests.

Methods: Serum samples were tested from patients presenting for syphilis screening, and in relevant subpopulations including pregnant women, people living with HIV, known serologically positive for syphilis, and medically diagnosed with syphilis. Samples originated from 1710 and 113 patients in the United States and South America, respectively. Results were also compared for VITROS vs the Roche Elecsys® Syphilis immunoassay alone.

Results: Positive percentage agreement was ≥98.81% for VITROS and the comparator composite results within and across populations, with a 95% Wilson Score confidence interval of 98.01%-99.94% across the entire intended use population. Negative agreement was ≥90.63%, with 95% Wilson Score confidence interval of 96.93%-98.67% for the entire population. Method comparison between VITROS and Elecsys assays found 99.09% total agreement and a Cohen's kappa coefficient of 0.97. In separate analyses, nonreactivity was observed for VITROS in 197 of 201 (98%) apparently healthy individuals, and positive reactivity was observed in 151/151 (100%) serum samples preselected from patients with medically diagnosed syphilis, indicating high clinical sensitivity of the VITROS Syphilis assay. In addition, specimens preselected as serologically positive showed 100% reactivity with VITROS.

Conclusions: These findings support strong clinical performance of the VITROS Syphilis assay for aiding in diagnosis of syphilis, and excellent concordance with the well-established Elecsys Syphilis test.

Background: Measurement of β-hydroxybutyrate (BOHB) is a valuable tool for the assessment of metabolic acidoses. In this study we evaluated hemolysis, icterus, and lipemia interference thresholds for a commonly used BOHB assay, the Stanbio β-Hydroxybutyrate LiquiColor reagent, on 3 different Roche cobas analyzers.

Methods: Remnant patient samples were combined to generate pools with target BOHB concentrations of approximately 0.20, 3.00, and 7.00 mmol/L into which increasing amounts of hemolysate, bilirubin, or Intralipid® were added. Samples were measured in triplicate for both interferences and BOHB concentration on Roche cobas c502, c501, and c311 analyzers.

Results: We determined that the Stanbio β-Hydroxybutyrate LiquiColor reagent will tolerate hemolysis to a hemolysis index of 400 (approximately 400 mg/dL hemoglobin) for BOHB concentrations ≤1.00 mmol/L, or 1010 for BOHB concentrations of >1.00 mmol/L. For icterus, the assay was unaffected by bilirubin to an icterus index of 25 [approximately 25 mg/dL bilirubin (427 μmol/L)] for all concentrations tested. Using the most conservative data from our study, the lipemia index limit was set at 800.

Conclusions: Our studies across 3 laboratories running 3 different cobas modules allowed our health system to better define permissible limits of sample quality and these updated values will reduce the number of unnecessary cancelations as compared to the limits defined by the manufacturer. Our data also demonstrated heterogeneity of interference between analyzer models, which is an important consideration for those seeking to adopt the limits determined on analyzers other than those in their own laboratories.

Background: Accurate and precise pipetting is critical for reliable laboratory results, especially when handling small volumes or sensitive analytical techniques. Despite the common use of piston-operated pipettes, operator-dependent variability remains a major source of error. This study aimed to evaluate pipetting performance among laboratory personnel with varying levels of experience.

Methods: The study included 108 participants: 26 laboratory school students (first to third year), 10 PhD students, 10 clinical chemists, and 62 laboratory technicians. Technicians were stratified into 3 groups based on the extent of sensitive manual pipetting in their work: minimal (Group A), moderate (Group B), and high (Group C). Pipetting performance was evaluated using gravimetric replicates at 10 µL and 100 µL volumes, and a dilution task involving serial dilutions of 1 M copper sulfate. Accuracy and precision metrics were compared across groups.

Results: The median coefficient of variation (CV%) was lower for 100 µL replicates (0.3% to 0.8%) than for 10 µL replicates (1.4% to 5.9%). Laboratory students showed the greatest variability and longest task completion times, although performance improved with advancing school year. Ten percent of participants exceeded ISO-defined accuracy limits for 10 µL pipetting, and 22% for 100 µL. Imprecision limits were surpassed by 36% and 20% of participants for 10 µL and 100 µL, respectively. Group C technicians achieved optimal dilution performance (R2 = 1.00), while students showed the highest deviation.

Conclusions: Pipetting performance was significantly influenced by experience level and task sensitivity. Even experienced personnel occasionally failed to meet ISO standards, underscoring the need for ongoing training and performance assessment.

Application of the results provided by medical laboratories plays an essential role in medical decision-making. This is not limited to diagnosis and monitoring of disease but also involves its use in other phases of the health continuum, e.g., predisposition, risk stratification, screening, staging, prognosis, and surveillance. With the growing importance of precision medicine, the importance of requirements related to clinical performance, and consequently analytical performance of laboratory tests, also grows. To allow the community of laboratory medicine to translate clinical need into a test arsenal with adequate performance, the application of metrology concepts is essential. This paper summarizes, for all steps in the examination process from test development to clinical interpretation, why and how metrological traceability is a fundamental requirement for adequate medical decision-making and is critical for correct use of test results in algorithms and artificial intelligence-led approaches. This includes the importance of metrology concepts and their correct implementation for obtaining equivalence of test results upon cross-facility result exchange for primary or secondary use in healthcare and research. This is not limited to biochemistry and hematology but is also of importance to other areas of laboratory medicine, including microbiology. This paper provides an overview of the purposes of the underappreciated science of metrology in modern laboratory medicine and its importance to patients and caregivers.

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.