Clinical chemistry and laboratory medicine最新文献

Objectives: Clinical laboratory operations consume large amounts of electricity and water and generate considerable quantities of solid waste. In this study, we quantified and compared the estimated solid waste produced from performing one million basic metabolic panels (BMPs) across five major high-throughput chemistry analyzer systems commonly used in the United States. Additionally, we estimated the carbon emissions associated with the electricity and water usage of each analyzer to better understand their environmental impact.

Methods: Five academic medical centers each using a different clinical chemistry analyzer system, collected their respective annual vendor purchase data (January 2022-December 2022). Consumables including reagent cartridges, packaging boxes, inserts associated with reagents, calibrators, and QC materials were categorized and weighed separately. Solid waste estimates for one million BMPs were calculated based on institutional testing volumes. Water and electricity usage for the analyzer systems was obtained and estimated CO₂ emissions (CO₂e) were determined using standard emission factors and calculators.

Results: The study found that performing one million BMPs on wet chemistry analyzer platforms, Abbott, Beckman, Roche and Siemens generated 995 kg, 1,274 kg, 579 kg and 489 kg of solid waste respectively while the dry chemistry Ortho system produced 160,593 kg. The majority of waste across all platforms was plastic. Annualized CO₂e from electricity and water use totaled to 69,665 kg CO₂e.

Conclusions: Analysis of BMPs generates substantial amounts of solid waste and CO₂e across major diagnostic platforms. These findings emphasize the urgent need for sustainability strategies in diagnostic laboratories to address their environmental footprint.

Objectives: Detection of paraneoplastic anti-neuronal antibodies (PNS autoantibodies) aids in diagnosing the particular syndrome and guides the search for an underlying tumor. To identify opportunities for harmonization that could enhance diagnostic value, we assessed variability in autoimmune serological testing for PNS across laboratories.

Methods: The European Autoimmunity Standardisation Initiative (EASI) developed a questionnaire addressing testing methods, digital tools, interpretation, clinical context, and quality assurance. This was distributed through two external quality assessment (EQA) providers (UK NEQAS and IfQ Lübeck) to clinical labs routinely performing PNS autoantibody assays.

Results: Among 139 responding laboratories, 78 % perform both cerebellum indirect immunofluorescence (IIF) and line/dot blot assays on serum and cerebrospinal fluid (76 %). Alignment on sample dilution (61 %) and conjugate type (70 %) is variable. Differences in antigen composition and reporting strategies contribute to variability in line/dot blot testing. Digitization is widespread for line/dot blot data (87 %) but limited for cerebellum IIF (31 %). About 53 % use testing algorithms that vary by sample type and requested antibodies. Internal quality control is performed by 89 % (IIF) and 48 % (line/dot blot), mainly using commercial controls. Nearly half (43 %) participate in multiple EQA programs; 46 % (IIF) and 42 % (line/dot blot) have ISO15189 certification, with 20 % planning certification. Positivity rates are low (<6 % in 73 % of labs), indicating low pre-test probability. While only 46 % restrict testing by discipline, most labs access clinical context (84 %) and interact with clinicians (63 %).

Conclusions: Considerable variability exists in PNS autoantibody assay execution, reporting, and quality control. Introducing lab-specific recommendations may harmonize practices and improve diagnostic quality.

Objectives: Neuron-specific enolase (NSE) is a clinically relevant biomarker used in the assessment of neuronal damage and in the diagnosis and monitoring of certain cancers. Despite its diagnostic importance, paediatric-specific reference intervals (RIs) for NSE are currently lacking. This study aimed to establish paediatric RIs for NSE in serum and to evaluate the influence of preanalytical factors on NSE measurements.

Methods: Residual serum samples from routine allergy testing in 242 Danish children (aged 0.1-17.9 years) were analysed using the Roche Elecsys^® NSE assay on a Cobas platform. Both traditional non-parametric, age-partitioned RIs and continuous RIs derived via quantile regression were established. In addition, we assessed the impact of preanalytical variables, including haemolysis, and evaluated a previously proposed correction method for haemolysed samples within this cohort.

Results: Both the non-parametric and continuous approaches yielded consistent RIs, showing an age-dependent decline in serum NSE concentrations irrespective of sex. The traditional age-partitioned RI (95th percentile, one-sided) indicated upper limits of 36.9 μg/L and 32.0 μg/L for the age groups 0-5 and 6-17 years of age, based on samples with haemolysis <10 mg/dL haemoglobin.

Conclusions: This study defines age-specific paediatric RIs for serum NSE, demonstrating a physiological decline with age and highlighting higher NSE levels in healthy children compared to adults. Furthermore, within a limited range, a previously proposed simple linear correction method was validated for adjusting NSE values in mildly haemolysed samples using the newly established RIs.

Objectives: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is increasingly used in clinical laboratories due to its high analytical specificity and multiplexing capabilities. While the pre-analytical and analytical phases have seen significant advances in automation, the post-analytical phase remains a bottleneck with limited standardisation. This survey aimed to identify gaps, benchmark practices against guidelines, and inform recommendations for improving consistency and quality in post-analytical data handling.

Methods: A descriptive electronic survey with 53 questions was distributed via the IFCC mailing list and collaborating organisations from May to July 2024. Questions covered participant characteristics, post-analytical quality indicators (e.g., chromatograms, calibration curves, ion ratios), quality assurance, and data management. Responses were benchmarked against three LC-MS/MS guidelines.

Results: Of 311 initial responses, 203 valid submissions from 57 countries were analysed. Laboratories reported diverse throughput: low (<100 samples/week, n=50), medium (100-2,000 samples/week, n=125), and high (>2,000 samples/week, n=28). Key findings included inconsistent acceptance criteria (e.g., variable ion ratios and signal-to-noise thresholds), reliance on manual data transcription (38 % of laboratories), and continued use of in-house spreadsheets. Practices often deviated from guidelines, with opportunities identified for harmonisation and automation.

Conclusions: In collaboration with the clinical mass spectrometry community, the IFCC-ETD developed six key recommendations from this survey to address challenges and enhance consistency, quality, and efficiency in post-analytical data handling.

EU laws are usually evaluated after 10 years; in the case of the IVDR, the targeted evaluation was brought forward and stakeholders in laboratory diagnostics were invited to comment. The Association of the Scientific Medical Societies in Germany (AWMF; Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V.), recognises a relevant need to amend the IVDR with regard to in-vitro-diagnostic medical devices that are manufactured and used in healthcare facilities but are not placed on the EU market. Inadequate overregulation is recognised and should be corrected as part of the generally required reduction of bureaucracy.

Objectives: Regulatory guidelines recommend non-parametric Passing-Bablok regression for evaluating the agreement between two measurement methods in laboratory settings. However, concluding for the agreement if the 95 % CI of the slope and of the intercept include 1 and 0, respectively is incorrect since the agreement assessment must focus on a null hypothesis of not equivalence and an alternative hypothesis of equivalence.

Methods: We exhaustively simulated appropriate structural models with several values of slope, intercept and measurement error by keeping equal variances and means of the two methods. We calculated the slope and intercept bias of four regressions: non-parametric Passing-Bablok, Theil, Ordinary Least Squares and Deming. In addition, we calculated the percentages of the agreement according to the not shareable Passing-Bablok suggestion. Furthermore, we calculated the percentages of the 95 % CI of the slope and of the intercept included within sensible equivalence thresholds for assessing the agreement.

Results: Passing-Bablok procedure gives unbiased estimates, a little more and less biased than those from Deming's regression. The percentages of rejecting the hypothesis of no-agreement, according to the wrong Passing-Bablok's approach are correctly near to 0.05 Type I error under the agreement and also for 0.990≤slopes≤1.005. However, they are too low for slopes >1.05 and <0.950.

Conclusions: The Passing-Bablok 95 % CIs are too wide for being included in sensible agreement thresholds according to a population equivalence model and, finally, this approach cannot be considered under the best agreement model of the individual equivalence.

Objectives: High-sensitivity cardiac troponin T (hs-cTnT) is used in pediatric healthcare to diagnose and assess the prognosis of various cardiac diseases, such as acute myocarditis, congenital heart disease, dilated cardiomyopathy, and heart failure. However, the standardized age-related reference intervals, 99th percentile cut-offs, and clinical guidelines are currently unavailable, especially in newborns and infants, making interpreting this biomarker challenging.

Methods: Residual serum samples were collected from 1,047 pediatric subjects with no cardiovascular disease, including 145 neonates and 902 infants. The concentrations of hs-cTnT were analyzed using Roche's Elecsys Troponin T hs assay. The age-related 99th percentile cut-offs with 90 % confidence intervals (CIs) of hs-cTnT were established.

Results: Subjects were divided into age subgroups as follows: newborns (0-30 days, n=142), infants aged 1 month (31-60 days, n=223), 2 months (61-90 days, n=152), 3-4 months (91-150 days, n=211), 5-6 months (151-210 days, n=149), and 7 months-1 year (211-365 days, n=149). Serum hs-cTnT concentrations were highest during the first month of life and progressively declined in a year. The 99th percentile cut-offs of hs-cTnT concentration in each group were as follows: 114 (90 % CI: 114-114), 65.6 (63.7-66.1), 55.2 (54.4-55.2), 30.4 (29.1-30.9), 23.5 (22.1-23.5), 12.7 (12.4-12.7) ng/L. The 97.5th percentile cut-offs for each group were 109.4 (105.2-114), 62.5 (60.5-63.9), 52.3 (50.3-54.4), 29 (28.5-29.1), 20.5 (19.2-23.4), and 12 (12-12.1) ng/L.

Conclusions: This study aimed to provide reliable pediatric reference values for hs-cTnT based on a population of well-child children. These reference intervals and 99th percentile cut-offs will inform clinical decisions in the pediatric cardiology setting.

The definition of analytical performance specifications (APS) by the Milan model 1b is based on indirect approaches investigating the impact of analytical performance of the laboratory test on clinical classification and thereby on the probability of patient outcomes. As direct diagnostic outcome studies (Milan model 1a) for defining APS are now considered very difficult and costly to be performed in practice, expert groups have gathered to reach consensus on how to use available information and apply Milan model 1b to the definition of APS. They have highlighted three major aspects: a) the definition of the clinically acceptable misclassification rate(s); b) the influence of the clinical pathway and patient population and setting (disease prevalence) when diagnostic thresholds are defined, e.g., in guidelines; and c) the intended use of the test. The basic question calling for an answer is how to move forward and provide specific APS for certain measurands that are key in clinical decision making. Here, cardiac troponin testing is used as a practical example for the application of model 1b-derived APS. Proposals are made for moving to practice with the application of this model to APS definition.

Objectives: To investigate the staining and serological characteristics of AC-30 pattern.

Methods: A total of 184 participants were recruited from patients who underwent routine antinuclear antibody testing between 2022 and 2023 at Peking Union Medical College Hospital. Cohort 1 (n=47) showed the AC-30 pattern on HEp-2 indirect immunofluorescence assay, and cohort 2 (n=137) showed AC-2 pattern as control. Anti-DFS70 antibody detection and DFS70 antigen adsorption assays were conducted. Pattern simulation assays were performed by combining serum samples exhibiting classic AC-2 pattern with other common HEp-2 IIFA patterns.

Results: Anti-DFS70 antibodies were detected in 97 % of patients in cohort one and in all patients in cohort 2. The titers of the IIFA pattern showed a weak correlation with anti-DFS70 antibody levels in cohort 1 (r=0.35, p=0.0331). In DFS70 antigen adsorption assays, a higher proportion of homogeneous nuclear staining was observed in cohort 1 (79 %) than in cohort 2 (62 %) (p=0.037). Simulated samples mixed classic AC-2 with homogeneous pattern resembled those of AC-30 pattern in both interphase and mitotic cells. Especially, the staining characteristics of AC-2 became increasingly indistinct when mixed with higher-titer homogeneous patterns. Among samples exhibiting homogeneous patterns post-DFS70 immunoadsorption, non-autoimmune conditions were more common in cohort one than cohort two.

Conclusions: The presence of relatively lower anti-DFS70 antibodies levels or coexisting high-titer homogeneous patterns may contribute to the development of the AC-30 pattern rather than AC-2. This finding needs to be further confirmed in larger-scale studies.

Currently, there is no accepted standard practice for determining the frequency of EQA challenge. The challenge frequency has evolved based on history and local requirements. However, EQA frequency should be based on identifying patient risks caused by poorly performing laboratories, methods, or processes in any phase of the total testing cycle. The role of IQC is to ensure result consistency from day to day and to halt reporting of results if there is an analytical failure. Historically, both activities have been based on synthetic control material. With the development of patient-based approaches to IQC and EQA, it is possible to continuously monitor analytical systems using the same patient parameter, usually the mean or median. These techniques can provide laboratories with additional information to reduce patient risk. There are limitations of Patient-Based Quality Assurance (PBQA), fundamentally the lack of middleware and connection of the analyzers to the EQA provider. It cannot be used to monitor the success of harmonization/standardization of assays to a reference measurement procedure. But the use of patient-based approaches offers an opportunity to reconsider how EQA can be undertaken and the relationship between IQC and EQA. If PBRTQC and PBQA could be implemented to provide daily peer group comparisons, then method-specific bias could be identified quickly by a laboratory. If this could be supplemented with a commutable, reference value assigned EQA program, then monitoring harmonization/standardization of assays to a reference measurement procedure could be achieved.