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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Mario Plebani
Edited by: Ronda Greaves , Dina N. Greene , Karl J. Lackner , Giuseppe Lippi , Bohuslav Melichar , Shiyang Pan and Peter Schlattmann

Language: English

First published: January 1, 1963

Publication Frequency: 12 issues per year

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Objective
Clinical Chemistry and Laboratory Medicine (CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. It is focused on basic and applied research and cutting-edge clinical laboratory medicine. CCLM is one of the leading international journals in the field of clinical laboratory sciences and drives progress in the field. CCLM is led by a multi-institutional editorial board.
CCLM is a hybrid journal published monthly in print and online. All contributions submitted for publication in JPEM are subject to single-anonymized peer review by at least two experts in the field, selected and invited by the Editor-in-Chief and a dedicated Editorial Team. CCLM publishes only English-language articles.
Letters to the Editor and Congress Abstracts are published online only.

CCLM is the official journal of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM).

Topics

Clinical Biochemistry // Clinical Genomics and Molecular Biology // Clinical Hematology and Hemostasis // Clinical Immunology and Autoimmunity // Clinical Microbiology // Drug Monitoring and Analysis // Evaluation of Diagnostic Biomarkers // Disease-Oriented Topics (Cardiovascular Disease, Cancer Diagnostics, Diabetes) // Clinical Evaluation of New Reagents, Instrumentation and Technologies // Innovative and/or Disruptive Analytical Techniques // Reference Materials and Methods // Reference Values and Decision Limits // Candidate Reference Measurement Procedures and Materials // Quality and Safety in Laboratory Medicine // Laboratory-Related Errors and Patient Safety // Standardization/Harmonization of Laboratory Assays // Translational Laboratory Medicine // Clinical Metrology

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Research Articles, Reviews, Mini Reviews, Opinion Papers Point/Counterpoint Articles, Perspectives, Guidelines and Recommendations, Letters to the Editor, Editorials

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Open Access
Measurement of lipoprotein(a) via a novel point of care approach with comparison to established laboratory assays

January 6, 2026

Caroline A.E. Bachmeier, Greg J. Ward, Andrew J. Kassianos, Alex Dechavez, Chantelle Ebersohn, Andrew Liu, Karam M. Kostner

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Objectives Lipoprotein(a) is an atherogenic particle causative of atherosclerotic cardiovascular disease. Novel treatments have been developed that lower lipoprotein(a) to unprecedented levels with cardiovascular outcomes trials ongoing. Many guidelines recommend testing once in the lifetime of everyone, but testing rates remain low. In this study we compare a lipoprotein(a) point of care testing device to laboratory analysers and assess its performance. Methods Lipoprotein(a) concentrations on residual patient samples measured on the Randox and Roche assays were compared to a novel point of care device, iProtin. Furthermore, assessment of iProtin performance characteristics were performed, including intra- and inter-assay coefficient of variation and dilutional studies. Results Lipoprotein(a) concentrations measured on the Randox and Roche assays showed strong correlation with iProtin. Regression analysis using Passing-Bablock showed the best fits for iProtin based on 58 serum samples were: 1.15 × Randox + 7.28 nmol/L and 1.02 × Roche + 17.54 nmol/L. The R 2 values for Randox/iProtin and Roche/iProtin were 0.906 and 0.912 respectively. Correlation between Roche and Randox showed Roche=1.15 × Randox − 13.33 nmol/L with an R 2 value of 0.973. Inter-assay coefficient of variation of the iProtin device showed a day-to-day imprecision over 5 days of 15.5 % (low concentration quality control) and 6.2 % (high concentration quality control). Within day imprecision was 13.2 % (lower concentration patient sample) and 14.3 % (higher concentration patient sample). Conclusions Point of care testing could be a complimentary option to laboratory testing of lipoprotein(a), especially in remote areas. It may help (re-)stratify cardiovascular risk and help tailor treatment decisions.
Publicly Available
Retraction of: External Quality Assessment Programs in the US with an emphasis on urinary sediment testing: the College of American Pathologists experience

May 23, 2018

Eric F. Glassy, David J. Blomberg

Article number: 20180453

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Open Access
An isotope dilution-liquid-chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of total and free valproic acid in human serum and plasma

November 4, 2025

Tobias Schierscher, Linda Salzmann, Neeraj Singh, Sandra Fleischer, Carina Schäfer, Julia Hoop, Friederike Bauland, Andrea Geistanger, Lorenz Risch, Christoph Seger, Judith Taibon

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Objectives An isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (cRMP) was developed and validated to measure serum and plasma concentrations of the total and free form of valproic acid. Methods Quantitative nuclear magnetic resonance spectroscopic methodology was used to determine the absolute content (g/g) of the reference material, ensuring traceability to SI units. Separation of valproic acid from potential unknown interferences was achieved with reversed-phase chromatography. A protein precipitation protocol was established for sample preparation for total valproic acid, while the free form was separated by ultrafiltration. Assay validations and measurement uncertainties were aligned with guidelines from the Clinical and Laboratory Standards Institute, the International Conference on Harmonization, and the Guide to the Expression of Uncertainty in Measurement. Results The cRMPs were highly selective and specific with no evidence of matrix effects, allowing quantifying total and free valproic acid in a range of 2.40–145 μg/mL and 1.60–42.0 μg/mL, respectively. Intermediate precision was <4.0 % and repeatability CV ranged from 0.9 to 3.5% for all concentrations of free and total valproic acid. The relative mean bias ranged from −0.4 to 4.1 % for native serum and from −0.3 to 3.5 % for Li-heparin plasma levels for total valproic acid. Free valproic acid showed mean biases between −2.9 and 4.0 % for native serum and ultrafiltrates. Measurement uncertainties for single measurements and target value assignment ranged from 1.7 to 3.4 % and 0.9–1.3 %, respectively, for total valproic acid. Free valproic acid ranged from 2.0 to 4.1 % and from 0.8 to 1.5 % for single measurements and target value assignment, respectively. Conclusions We present novel ID-LC-MS/MS-based cRMPs for total and free valproic acid in human serum and plasma which provides a traceable and reliable platform for the standardization of routine assays and evaluation of clinically relevant samples.
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Falsely elevated serum estradiol levels measured by Abbott estradiol immunoassay in women taking abemaciclib

January 21, 2026

Ivana Lapić, Saša Kralik Oguić, Tajana Silovski, Dragana Šegulja, Sanja Kačkov, Fran Smaić, Ksenija Kukuruzović Živković, Lovorka Đerek, Dunja Rogić

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Publicly Available
Automation in value-based laboratory medicine: driving precision, capacity, and better outcomes

January 15, 2026

Damien Gruson, Tomáš Zima, Mario Plebani

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Laboratory medicine lies at the core of modern healthcare, enabling timely diagnosis, effective patient monitoring, and increasingly personalized therapeutic strategies. Over the past decades, automation has profoundly reshaped the role of clinical laboratories, substantially enhancing their contribution to clinical outcomes, operational efficiency, and the overall sustainability of healthcare systems. More recently, laboratory automation has emerged as a cornerstone of value-based laboratory medicine, representing not merely a technological upgrade but a strategic transformation of laboratory practice aimed at delivering measurable value to patients and healthcare stakeholders. Although automation has long been established in clinical chemistry and immunoassays, its scope is now expanding to molecular diagnostics and mass spectrometry – two disciplines that are central to precision medicine. Looking ahead, the convergence of automation, digitalization, and artificial intelligence is driving the emergence of hyperautomation in laboratory medicine. Within this paradigm, laboratories evolve from isolated testing units into integrated diagnostic hubs, in which results from multiple laboratory disciplines are harmonized and contextualized to effectively support clinical decision-making.
Open Access
Laboratory solution to diagnose and monitor atypical IgG4-mediated anti-GBM disease

February 2, 2026

Joannes F.M. Jacobs, Annechien J.A. Lambeck, Rosa G.M. Lammerts, Anne-Els van de Logt, Jan-Stephan Sanders, Mark Lenssen, Mark Eijgelsheim, Ingeborg Bajema, Eric J. Steenbergen, Wibe Hoefsloot, Wilbert A.G. van der Meijden, Renate G. van der Molen

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Objectives Diagnosing atypical IgG4-mediated anti-glomerular basement membrane (anti-GBM) disease is challenging because conventional serological assays poorly detect IgG4 antibodies. Here we study which commercial assays are affected and we describe proof-of-concept of improved IgG4 anti-GBM detection. Methods To investigate the scope of the diagnostic dilemma detecting IgG4 anti-GBM antibodies, serum from a patient with atypical IgG4-mediated anti-GBM was distributed to 36 laboratories participating in the Dutch External Quality Assessment (EQA) program. To improve IgG4 anti-GBM detection in the fluorescent enzyme immunoassay (FEIA), the standard anti-IgG conjugate was replaced with anti-IgG4 conjugate. Results We report the diagnostic delay of a patient with atypical anti-GBM disease who presented with an indolent disease course. Histopathology comprised hallmarks of classic anti-GBM disease including bright linear IgG deposits along the GBM but without the typical findings of diffuse crescentic and necrotizing glomerulonephritis. IgG anti-GBM test results were repeatedly negative. Histopathological subclass analysis demonstrated that the linear IgG deposits were predominantly IgG4. All 36 Dutch EQA-participants reported negative anti-GBM test results, demonstrating that the diagnostic challenge of detecting IgG4 anti-GBM is broadly applicable across multiple diagnostic assays. A minor modification to the manufacturer’s standard protocol of the FEIA anti-GBM dramatically improved the assay’s performance for measuring antibodies of the IgG4 isotype. Using the modified IgG4-GBM test, we were able to diagnose and monitor one more patient with atypical IgG4-mediated anti-GBM disease. Conclusions Here we demonstrate proof-of-concept of a modified IgG4 anti-GBM blood test allowing serological confirmation of atypical anti-GBM disease and sensitive monitoring of therapy response.
Publicly Available
Addressing the silent epidemic of recreational nitrous oxide use: a position, call to action and recommendations by the European Federation of Clinical Chemistry and Laboratory Medicine Committee on Biological Markers of Nitrous Oxide Abuse

November 20, 2025

Guillaume Grzych, Graham R. Lee, Medine Alpdemir, Emeline Gernez, Kurt Anseeuw, Anne-Lise Bjorke-Monsen, Kathleen Croes, Joe M. El-Khoury, Jasmin Hamzic, Alastair J. Noyce, Sanja Stankovic, Benjamin Rolland, Jorgen Bramness, Pieter Vermeersch, Etienne Cavalier

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Recreational nitrous oxide (N 2 O) 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 N 2 O-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.
Open Access
An isotope dilution-liquid-chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of mycophenolic acid in human serum and plasma

October 20, 2025

Tobias Schierscher, Linda Salzmann, Neeraj Singh, Carina Schäfer, Luc Sungauer, Friederike Bauland, Andrea Geistanger, Lorenz Risch, Christian Geletneky, Christoph Seger, Judith Taibon

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Objectives A candidate reference measurement procedure (RMP) based on isotope dilution (ID) liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated to accurately measure serum and plasma concentrations of mycophenolic acid (MPA). Methods Quantitative nuclear magnetic resonance (qNMR) spectroscopy was utilized for determining the absolute content of the reference material, guaranteeing its traceability to SI units. Separation of MPA from potential interferences, whether known or unknown, was accomplished by using a C18 column. For sample preparation, a protocol for protein precipitation followed by a high dilution step was established. Assay validation and measurement uncertainty determination were conducted following the Clinical and Laboratory Standards Institute, the International Conference on Harmonization, and the Guide to the Expression of Uncertainty in Measurement guidelines. Results The RMP demonstrated high selectivity and specificity without any indication of a matrix effect, enabling the quantification of MPA in the range between 0.240 and 18.0 mg/L. The intermediate precision and repeatability (n=60, measurements) were found to be <3.7 % and <3.0 %, respectively, across all concentration levels and independent from the matrix. The relative mean bias ranged from −1.9 to 2.1 % for serum and from −0.5 to 1.8 % for Li-heparin plasma levels. The measurement uncertainties for single measurements and target value assignment were found to be <6.4 % and <3.0 % (k=2), respectively. Conclusions We are pleased to present a new LC-MS/MS-based candidate RMP for MPA in human serum and plasma which offers a traceable and reliable platform for the standardization of routine assays and evaluation of clinically relevant samples.
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Clinical validation of a DBS-based LC-MS/MS method for 25-hydroxyvitamin D: from lab sampling to home sampling

November 13, 2025

Liesl Heughebaert, Rosalie Ghesquière, Christophe P. Stove

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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.
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Holiday-associated biochemical patterns of pancreatitis: a 16-year retrospective analysis of ambulatory laboratory data (2009–2024)

January 13, 2026

Marlene Hollenstein, Van Lin Nguyen, Thomas Szekeres, Helmuth Haslacher, Klaus G. Schmetterer

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Open Access
Biological variation and inter-relation between key calcium homeostasis biomarkers

January 26, 2026

Nora Alicia Guldhaug, Eirik Åsen Røys, Kristin Viste, Bashir Alaour, Marit Sverresdotter Sylte, Janniche Torsvik, Heidi Strand, Michael Marber, Torbjørn Omland, Kristin Moberg Aakre

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Objectives This study aims to explore the biological variability of calcium homeostasis biomarkers, including calcium, phosphate, magnesium, 25-OH vitamin D, 1,25-OH vitamin D, and parathyroid hormone (PTH), and to develop a model that predicts PTH concentrations based on these parameters. Methods Thirty healthy volunteers were sampled on a weekly basis over a period of 10 weeks. Each sample was analyzed in duplicate. Statistical methods included estimating within- and between-subject biological variation (CV I , CV G ) using ANOVA with outlier removal and a Bayesian model. A linear mixed-effects model (LMM) was used to estimate 95 % prediction intervals for PTH as a function of calcium, phosphate, and 25-OH vitamin D in healthy participants. The effect of applying this prediction model in routine practice was estimated using data from the Laboratory Information System. Results Estimated CV I from ANOVA and the Bayesian model was: PTH, 18.0 % and 17.4 %; calcium, 1.7 % and 1.6 %; phosphate, 9.3 % and 9.3 %; 25-OH vitamin D, 4.7 % and 7.2 %; and 1,25-OH vitamin D, 16.2 % and 17.1 %. The LMM indicated the best 95 % prediction interval for PTH included calcium (PTH (pmol/L)=exp(3.46−2.67·ln(Ca (mmol/L)) ± Z·0.29)) and did not improve with phosphate and/or 25-OH vitamin D. Compared with conventional reference intervals, this model flagged 56 % vs. 41.6 % of routine PTH/calcium results, respectively. Conclusions Similar CV I data were obtained using two different methods. A predictive model can be used to predict concentrations for co-regulated biomarkers, potentially enhancing sensitivity in identifying non-physiological results and facilitating clinicians’ awareness of conditions affecting calcium homeostasis.
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Predicting congenital hypothyroidism in newborns with complex risk profiles by using thyroid-stimulating hormone variations across serial dried blood spots

January 28, 2026

Laura Cappelletti, Amy Gaviglio, Sara Moggia, Simona Lucchi, Luca Lalli, Sabrina Fede, Lorenza Cannella, Maria Cristina Vigone, Gianvincenzo Zuccotti, Antonella Zambon, Cristina Cereda, Simona Ferraro

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Objectives Newborn screening for congenital hypothyroidism (CH) relies on thyroid-stimulating hormone (TSH) levels from dried blood spots (DBS). We investigated whether incorporating TSH variation across serial DBS could improve prediction of CH in term and preterm infants with complex risk profiles. Methods Among 207,895 newborns screened, 272 (0.13 %) were diagnosed with CH. TSH variations across 3 serial DBS were analyzed in 6,146 healthy infants (2.96 %). Predictive algorithms were developed using linear mixed-effects models in 1,968 term and 1,387 preterm infants with ≥2 and ≥3 DBS, respectively. Average DBS collection times were 58, 260, and 478 h for term and 63, 350, and 664 h for preterm infants. TSH was measured by GSP neonatal hTSH assay (Revvity). Results Daily TSH variation was influenced by the initial DBS1 value. For DBS1 >5.2 and <1.7 mUI/L, increase and decrease, respectively, in TSH level on DBS2 is detectable, and this particularly occurs in preterm infants. In preterms, CH could be excluded when TSH remained <5 mUI/L on DBS1, <6 mUI/L on DBS2, <4 mUI/L on DBS3, and with daily variation <12 % from DBS1 to DBS3 (sensitivity 100 %; specificity 77.85 %). Term infants with TSH <11 mUI/L on DBS1, <4.5 mUI/L on DBS2, and daily variation <13 % from DBS1 to DBS2 may be ruled out for CH (sensitivity 96.5 %; specificity 66.6 %). Conclusions Distinct predictive algorithms for term and preterm newborns, incorporating TSH variations as daily percentage changes, may improve CH rule out in children with complex risk profiles.
Publicly Available
Implementation of AI systems in the clinical laboratory: insights from an expert survey and recommendations for best practice

February 3, 2026

He S. Yang, Hikmet Can Çubukçu, Fabio Del Ben, Xincen Duan, Jennifer Feng, Glynis Frans, Damien Gruson, Michael King, Javier Nieto-Moragas, Beili Wang, Fei Wang

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Objectives Despite growing interest in artificial intelligence (AI) and machine learning (ML), many laboratory professionals lack experience with developing in-house AI systems or implementing those supplied by external providers. The IFCC Committee on AI in Laboratory Medicine (C-AILM) conducted a survey to collect the status of AI/ML applications, challenges, and expert perspectives on key technical considerations. Methods An 20-item survey was distributed to laboratory professionals experienced in AI. It covered application status (in-house or provider-supplied, with or without regulatory approval); essential information to request from AI system providers; validation or verification practices; monitoring strategies; and perceived implementation challenges. Results Fifty complete responses from global experts were received. AI implementation in clinical laboratories was limited and heterogeneous. Most respondents agreed that AI systems provided externally, regardless of regulatory approval status, require local verification. Key information needed from providers included performance metrics from original and external datasets, and demographics of the training/test populations. For both approved and non-approved models, high-priority verification studies were local performance analysis, confirmation of intended-use alignment, and verification of privacy and security safeguards. Top monitoring strategies were regular accuracy checks and comparison against human decision-making. Leading challenges were insufficient IT infrastructure and lack of practical implementation guidelines. Conclusions Although many challenges remain, clinical laboratories demonstrate strong enthusiasm for AI, particularly with the growing prevalence of commercial AI products. The timely expert insights from our survey and C-AILM recommendations for both AI system providers and clinical laboratories on essential information, verification requirements, and monitoring strategies will inform standardized guideline development.
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Kappa Index predicts disease activity and transition to high-efficacy therapies in multiple sclerosis

December 29, 2025

Simone Marcheselli, Federica Galota, Patrizia Natali, Francesco Corrado, Alessia Fiore, Francesca Vitetta, Krzysztof Smolik, Giulia De Napoli, Martina Cardi, Diana Ferraro

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Objectives The Kappa Index has proven its diagnostic value for multiple sclerosis (MS), while its prognostic potential remains to be fully explored. The objective of this study is thus to investigate the value of the Kappa Index at disease onset in predicting disease activity and high-efficacy therapy (HET) initiation. Methods We enrolled MS patients with available Kappa Index values at disease onset and a follow-up of at least two years. Primary outcome was the time to loss of NEDA3 (no evidence of disease activity-3) defined as the absence of relapses, MRI activity, and disability progression. Secondary outcome was the time to HET initiation. Results Of 120 enrolled patients (36 M, 84 F, mean age: 35 ± 11 years), NEDA3 loss occurred in 89 (74 %) by the end of the follow-up period. A total of 98 (82 %) initiated a moderate efficacy therapy (MET); of these, 34 (28 %) transitioned to a HET during follow-up. Kappa Index values above the maximally selected log-rank statistic-derived cut-off of 38 were independent risk factors for NEDA3 loss (HR 1.75, 95 % CI: 1.09–2.80, p=0.021) and HET initiation (3.25, 95 % CI: 1.54–6.87, p=0.002) and also independently predicted HET following MET failure (2.54, 95 % CI: 1.17–5.51, p=0.018). Conclusions Elevated Kappa Index values at diagnosis predict disease activity, MET failure and HET initiation and may be a valuable adjunctive tool in identifying patients in need of prompt HET initiation.
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Cryoproteins: a rare cryofibrinogenemia case

January 7, 2026

Ann Amvuyele Maseti, Jerry George, Jaco Louw, Saiesha Dindayal, Rachelle Nossel, Ngalulawa Kone

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Open Access
Science, Quality and Value of Laboratory Medicine

January 22, 2026

Mario Plebani, Michel Langlois, Alexander von Meyer, Pieter Vermeersch, Martina Zaninotto, Ruben L. Smeets, Andrea Padoan, Hikmet Can Cubukcu, Phillip J. Monaghan, Abdurrahman Coşkun, Matthias Orth, Marc Thelen

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The Meeting on Science, Quality and Value of Laboratory Medicine was held on 11 December 2025 in Padua, immediately preceding the 7th European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Conference on the Preanalytical Phase. For organizational reasons, the meeting was structured in two parts, with the first held in December 2025 and the second scheduled for early 2026. The initiative, designed to better steer and promote the activities of all EFLM Committees and Divisions, represents a pivotal step toward overcoming fragmentation and silo-based cultures. By fostering a holistic vision that captures interactions among all EFLM Functional Units, the meeting supported the translation of value-based laboratory medicine principles into real-world practice. This collective opinion paper summarizes the lectures presented at the meeting, providing an overview of ongoing EFLM projects and future developments in value-based laboratory medicine. Importantly, the meeting also generated significant opportunities for collaboration and shared project development, underscoring the transition from isolated activities to a collaborative, value-driven approach.
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Contribution of SuPAR for patients in a situation of uncertainty downstream of emergencies

January 9, 2026

Marina Brailova, Dorian Teissandier, Bruno Pereira, Ando Rajemisa, Jean-Baptiste Bouillon-Minois, Jeannot Schmidt, Vincent Sapin, Farès Moustafa

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Objectives Evolution is difficult to predict for some patients at emergency department (ED). The soluble urokinase plasminogen activator receptor (suPAR ) is a non-specific prognostic inflammatory blood biomarker with a high negative predictive value for pejorative outcomes. The aim of this study was to investigate the relationship between low levels of suPAR at ED admission and patient discharge following hospitalization in a short stay unit. Methods We carried out a single-center prospective observational study in the acute-care hospital ward of a university hospital center, including patients over 18 years old with an intermediate triage score. Results Overall, 202 acute medical patients were included, exhibiting a mean suPAR level of 7.43 ± 3.36 μg/L. Of these patients, 25 (12.4 %) displayed a suPAR dosage below 4 μg/L and 177 (87.6 %) a dosage ≥4 μg/L. At 24 h, 55 patients (27.2 %) were discharged, 139 (68.8 %) were hospitalized, and five (2.5 %) were either admitted to intensive care or died. In contrast to group with a high suPAR rate, those with suPAR <4 μg/L benefited from secure ED discharge (OR=5.68; CI 95 %=2.6–12.4). For predicting hospital discharge, patients with a suPAR value <4 μg/L had an AUC-ROC of 0.75. (95% CI 0.67–0.83). Conclusions Our study revealed that in patients with a high triage scale level and requiring a monitoring period, SuPAR levels under 4 μg/L could have enabled five times more patients to return home compared with those exhibiting a level ≥4 μg/L at emergency visit.
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Moving to practice with the application of Milan model 1b-based analytical performance specifications

September 25, 2025

Mauro Panteghini

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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.
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Reimagining External Quality Assessment for precision medicine: a perspective from biochemistry laboratories

November 10, 2025

Stanford Chigaro, Maria Mvere

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External Quality Assessment (EQA) is central to quality assurance in laboratory medicine, providing independent measures of tests trueness, and inter-laboratory comparability. Traditional EQA schemes, designed around stable and well-characterised measurands, have been successful in routine analytes such as electrolytes and liver enzymes. However, the rise of precision medicine presents new challenges that extend beyond the scope of traditional EQA models. Advances in genomics, proteomics and metabolomics require quality systems capable of evaluating complex and context-specific biomarkers which may lack reference materials or established targets values. This creates a paradox: while EQA depends on standardisation, precision medicine is individualised. To remain relevant, EQA must evolve from static, one-size-fits-all models into adaptive, technology-driven, and clinically contextualised systems. In our view, the evolution of EQA must be immediate and decisive. Adaptive program design, cloud-based digital integration, AI-assisted analytics, and hybrid models provide a roadmap towards more flexible and clinically relevant systems. Together, these approaches offer a template for ensuring that EQA continues to safeguard quality while supporting innovation in personalised diagnostics.
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Spun citrate samples as a suitable alternative for platelet measurement. Is recollection necessary? A preliminary study

November 11, 2025

Ana Nikler, Brankica Šimac, Vanja Radišić Biljak

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A specific-neonatal hemolysis correction model for accurate potassium assessment in blood samples with in vitro hemolysis

December 10, 2025

Jinmei Li, Hua Liu, Yushan Li, Ting Wei, Bing Zhang, Qiang Wang

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Objectives Accurate determination of blood potassium levels in neonates presents significant clinical challenges, primarily attributable to technical difficulties in phlebotomy procedures and the elevated susceptibility of neonatal blood samples to hemolysis. This study aimed to develop and validate a hemoglobin-based mathematical model to correct for hemolysis-induced pseudohyperkalemia in neonatal blood samples. Methods This prospective study analyzed 134 neonatal blood specimens (postnatal age ≤7 days). Controlled hemolysis induction established the potassium-hemoglobin relationship, with specimens allocated to model development (n=101) and validation (n=33) cohorts. The model utilized direct hemoglobin quantification and multivariate regression, with statistical analyses performed using SPSS 26.0. Results Analysis of the training cohort established a neonatal-specific potassium release coefficient (ΔK + /ΔHb=0.28 ± 0.03 mmol/L per g Hb) and revealed a strong linear correlation between hemoglobin concentration and potassium elevation (Y=0.2834X, r 2 =0.8606, p<0.0001). Method validation showed strong agreement between constant correction and model-predicted values (p=0.887). Independent validation confirmed clinical utility, demonstrating comparable corrected and baseline potassium concentrations (p=0.0693) with excellent correlation (r=0.8845, p<0.0001). The model improved hypokalemia detection from 8.9% to 26.7 %, effectively resolving pseudo-normalization artifacts. Conclusions The developed hemoglobin-driven correction model provides a validated and accurate method for hemolysis interference in neonatal potassium measurement, offering significant clinical value for managing irreplaceable specimens in neonatal intensive care settings.
Open Access
Shift happens: the utility of external quality assessment data in evaluating folate lot changes

December 11, 2025

Rachel Marrington, Sarah L. Davies, Finlay MacKenzie

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Reshaping laboratory medicine through technological advances

January 5, 2026

Giuseppe Lippi, Mario Plebani

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Open Access
Validation study of the Helena V8 UltraCE capillary elecrophoresis analyser

January 5, 2026

Joris R. Delanghe, Maaike Godefroid, Thomas Maenhout

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Objectives Serum protein electrophoresis is one of the keystone investigations for screening for monoclonal proteins and assessing the serum protein profile. The newly released Helena V8ultra capillary electrophoresis system has been evaluated. Methods In total, 164 serum samples were assessed on the Helena V8 UltraCE system and compared with the Sebia Capillarys™ instrument. Abnormalities suggestive of monoclonal proteins were confirmed by immunosubtraction. Imprecision studies intervals were determined. Special attention was paid to complement C3 polymorphism. Results The imprecision of the Helena V8ultra was inferior or equal from 0.73 % (albumin) to 4.32 % (alpha 2 globulin). The mean bias of Helena V8ultraCE vs. Sebia Capillarys was about −0.225 % for albumin; −0.791 % for alpha 1 globulins; 1.353 % for alpha 2 globulins; −2.317 % for beta globulins; 0.066 % for gamma globulins. Among the 6 samples with monoclonal proteins confirmed by immunofixation, all were seen on both methods, with only 1 discordant result. The theoretical plate number (albumin fraction) was 2,371 ± 718 (Helena V8UltraCE) vs. 445 ± 115 (Sebia Capillarys 2). The high resolution also allows to distinguish Complement C3 phenotypes. CV values for the various fractions were low, ranging from 0.47 % (albumin) to 0.89 % (gamma globulins). IgG, IgA and IgM M-proteins could be detected in the electropherogram with an excellent sensitivity (<0.1 g/L). Conclusions Our evaluation confirms the good analytical performance of the Helena V8 analyzer as a suitable alternative to the Sebia Capillarys instrument. The high resolution allows detailed analysis of individual protein fractions which is an excellent basis for studying microheterogeneity.
Open Access
Blood biomarkers in neurodegenerative diseases: pre-analytical, analytical, and post-analytical challenges

February 3, 2026

Constance Delaby, Sylvain Lehmann

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Recent advances in blood-based biomarkers for neurodegenerative diseases present promising opportunities for earlier diagnosis and more effective disease monitoring. However, challenges in standardizing sample collection, processing protocols, and data reporting continue to hinder reproducibility, limit cross-study comparability, and delay clinical adoption. As efforts toward harmonization progress (supported by technological innovation and integration into multimodal diagnostic strategies), blood biomarkers are expected to transition from research settings to routine clinical use, bringing precision medicine closer to individuals affected by these disorders.
Open Access
Serial measurements of neuron specific enolase, glial fibrillary acidic protein and neurofilament light for mortality prediction in patients with severe acute brain injury in the ICU

December 17, 2025

Wolmet E. Haksteen, Lynn Boonkamp, Lisa Vermunt, Daan C. Velseboer, Sefanja Achterberg, Peter van Vliet, Cornelia Hoedemaekers, Charlotte E. Teunissen, Janneke Horn

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Objectives Prognostication in patients with severe acute brain injury (SABI) in the Intensive Care Unit (ICU) is complex, often requiring early decisions on life-sustaining therapy. Serum biomarkers such as neurofilament light (NFL), glial fibrillary acidic protein (GFAP) and neuron specific enolase (NSE) may aid in predicting outcomes. This study investigated the association between biomarker concentrations and hospital mortality in ICU patients with SABI. Methods In this prospective multi-center study, 103 adult ICU patients with SABI were enrolled within 24 h of injury. Serum concentrations (NFL, GFAP, NSE) were measured at 24 h, 72 h, 7 days, and 14 days post-injury. Biomarker concentrations between hospital survivors and non-survivors were compared using a linear mixed-effects model and ROC curves. Results GFAP concentrations peaked on day 1, while NSE and NFL concentrations peaked on day 14. Higher concentrations were observed in non-survivors for all biomarkers on day 3, a 1,4 fold increase for NSE (p=0.034) and approximately 2-fold increase for GFAP (p=0.041) and NFL (p=0.018). Distinct temporal patterns were observed for all biomarkers, although biomarker trajectories did not significantly differ between survivors and non-survivors. Prognostic accuracy was moderate when biomarkers were combined with established mortality predictors (AUC 0.749) on day 3. Conclusions NSE, GFAP and NFL show distinct temporal trajectories in SABI patients. Concentrations were higher in non-survivors during the early phase of admission. While individual biomarkers showed limited prognostic accuracy, in combination with other predictors mortality prediction improved. Serum biomarkers may still be valuable in a multimodal prognostication framework for SABI patients.
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Innovative closed tube protocol reveals a super critical early preanalytical phase of whole blood glucose stability in routine matrices

November 12, 2025

Guillaume Grzych, Arnaud Pinsart, Inès Defauwes, Manon Campas, Elodie Grifnée, Pascal de Tullio, Etienne Cavalier

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Cortisol measurement challenges in managing ectopic Cushing’s syndrome with etomidate

December 15, 2025

Pauline Brouwers, Pauline Delannoy, Laurence Lousberg, Etienne Cavalier, Patrick Petrossians, Caroline Le Goff

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Extended verification of an automated MALDI-TOF mass spectrometry system for high throughput serum M-protein measurement

December 3, 2025

Louis Nevejan, Jan Van Droogenbroeck, Emile Van Hecke, Alexander Schauwvlieghe, Michel R. Langlois, Xavier Bossuyt, Martine Vercammen

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Objectives This study aimed to perform an extended analytical verification of the Immunoglobulin Isotypes (GAM) for the EXENT ® Analyzer (EXENT ® -GAM) assay, a MALDI-TOF mass spectrometry-based method for detecting and quantifying serum M-proteins in patients with plasma cell dyscrasias, and to compare it with conventional serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (sIFE) and serum free light chains (sFLC) assays. Methods Imprecision, linearity, limit of quantification (LOQ), quantification comparison with SPEP, isotyping concordance with sIFE and sFLC, interference from therapeutic monoclonal antibodies (t-mAbs), sample stability, and reagent lot consistency were evaluated. Results EXENT ® -GAM demonstrated acceptable imprecision (CV ≤20 % for low and ≤15 % for high M-protein levels) and wide linear range (∼0.03–30 g/L). The polyclonal immunoglobulin background negatively influenced the assays LOQ. M-proteins with mass-shifted light chains (i.e., glycosylated light chains) are prone to non-linearity and inferior LOQ. M-protein quantification by EXENT ® differed systematically and proportionally from quantification by SPEP, highlighting non-interchangeability. EXENT ® demonstrated 97 % concordance with sIFE for M-protein isotyping and identified numerous additional (low-level) M-proteins. Some proved to be clinically relevant (residual disease in sIFE-negative samples); others lacked correlation with sFLC result or clinical diagnosis. EXENT ® reliably distinguished endogenous M-proteins from t-mAbs, except talquetamab, which interfered with quantification and was partially misclassified. Conclusions EXENT ® -GAM enables sensitive and reproducible quantification and isotyping of M-proteins below the detection limit of SPEP and sIFE. Its ability to resolve analytical challenges posed by SPEP and sIFE represents a significant advancement. Further clinical studies are needed to confirm its potential in residual disease detection.
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External Quality Assessment Programs in the US with an emphasis on urinary sediment testing: the College of American Pathologists experience

August 11, 2015

Eric F. Glassy, David J. Blomberg

Article number: 20150658

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The College of American Pathologists (CAP) has maintained the highest standards for laboratory medicine through education, evaluation, and certification. One form of External Quality Assurance – proficiency testing (PT) – is the centerpiece of that mission. Over 500 medical and scientific experts oversee CAP PT programs which include more than 600 tests performed by 22,000 laboratories in over 100 countries. It is the most comprehensive laboratory peer-review comparison program in the world. The CAP offers four urine sediment PT products tailored to the needs of different laboratories. Each includes three or four digital images, shipped twice a year. The program is overseen by the Hematology and Clinical Microscopy Resource Committee. Images are graded if there is 80% or greater consensus of either referee or participant laboratories. Failing laboratories must analyze the reasons for the failure, report the results, and initiate corrective action. Over the years, there has been a progressive decline in the number of errors, demonstrating that education and regulatory oversight are major contributors to improved PT performance and, by extension, patient care. The PT urine sediment image databank is a unique resource, representing the consensus of many laboratories. Participant and referee responses identify which morphologic variants are unambiguous and which are more difficult to classify. The PT challenges include discussions of disease pathophysiology and key morphologic features. This teaching component is what helps to set the CAP’s program apart. The discussions formed the basis for the Color Atlas of Urinary Sediment published by the CAP in 2010.
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Impact of an autonomous delivery robot on sample turnaround time in a clinical laboratory: an early evaluation of first implementation

December 10, 2025

Jacopo Gervasoni, Davide Pedrazzini, Michela Cicchinelli, Silvia Persichilli, Silvia Baroni, Sandro Rocchetti, Giovanni Arcuri, Andrea Urbani

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Objectives The aim of this study was to evaluate the impact of introducing an autonomous courier in a clinical laboratory, focusing on specimen turnaround time (TAT). We assessed whether high-frequency robotic transport from the central accessioning area to analytical sections could reduce delays and variability compared with manual delivery. Methods We retrospectively analyzed routine lithium–heparin glucose specimens processed during the initial days of robot deployment (13–23 May 2025, weekdays, 08:00–16:00) and compared them with the same period in 2024 under manual transport. TAT was defined as the interval from check-in at accessioning to technical validation in the Laboratory Information System (LIS). Data were assessed globally and stratified by time of day, examining changes in central tendency, dispersion, and extreme delays. Results In total, 6,299 samples in 2024 and 5,759 in 2025 were analyzed, showing a leftward shift of the distribution with fewer delay. In 2025, the mean TAT decreased from 122.64 to 106.72 min, the median from 112 to 101 min, and dispersion tightened. Stratification by time of day also demonstrated consistent improvements. Conclusions Even in its earliest days of operation, the delivery robot reduced TAT and variability, converting specimen transport from batch runs into near-continuous flow. These findings highlight ease of adoption and the potential of robotic transport to improve speed, predictability, and safety in intralaboratory logistics. Further validation across longer periods and additional laboratory sections is warranted.
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Multi-analytical identification of the synthetic opioids cychlorphine and methiodone (IC-26) in drug seizures: first detection in Europe

January 12, 2026

Paméla Dugues, Tiphaine Robin, Marie Bellouard, Sevag Chenorhokian, Maxime Triguel, Gregory Pfau, Cindy Feng, Sabrina Cherki, Gaëtan Herbette, Jean Claude Alvarez, Islam Amine Larabi

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Objectives The rapid emergence of highly potent synthetic opioids represents a growing challenge for forensic and clinical laboratories. Methods We report the first identification in Europe of methiodone (IC-26) and the first detection in France of cychlorphine in drug samples collected by a drug-checking service in Paris. Results Preliminary screening by liquid chromatography with diode-array detection (LC-DAD) and gas chromatography coupled with mass spectrometry (GC-MS) revealed unknown peaks due to the lack of corresponding spectra in available spectral librairies. High-resolution mass spectrometry (LC-HRMS) provided accurate mass measurements consistent with the cychlorphine and Methiodone formulas. Structural confirmation was obtained by 1D/2D nuclear magnetic resonance (NMR) spectroscopy. Targeted LC-MS/MS quantified 5 % cychlorphine and 2 % methiodone, with no other psychoactive compounds detected. Conclusions These results highlight the limitations of library-based screening and the value of multi-platform strategies integrating LC-HRMS, LC-MS/MS, and NMR for the early detection of emerging drugs.
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From automation to agentic artificial intelligence in laboratory medicine: an opinion of the IFCC Division on Emerging Technologies

December 29, 2025

Damien Gruson, Bernard Gouget, Woochang Lee, Ronda Greaves, Yan Liu, Sven Ebert, He Sarina Yang, Swarup Shah

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Agentic artificial intelligence (AI) systems are distinguished by their ability to invoke multiple tools, compose command chains, and combine chain-of-thought reasoning with deep research to execute complex tasks and take actions. This represents a major evolution beyond machine learning and large language models (LLM), toward systems capable of planning, executing, and coordinating complex workflows. In contrast to traditional LLMs, which primarily focus on generating and classifying information, agentic AI introduces elements of autonomy, reasoning, and orchestration, while digital twins extend this concept to dynamic virtual representations of patients and laboratory processes, capable of continuous learning, simulation and adaptation. This transition has profound implications for laboratory medicine, a field characterized by high data complexity, multi-omics integration, and stringent operational demands. At the same time, laboratories face growing expectations regarding efficiency, resource stewardship, and value-based healthcare delivery. This article explores both the opportunities and limitations of agentic AI in laboratory medicine, highlighting its potential to move beyond static automation toward autonomous, outcome-driven innovation. It also examines the ethical, interpretability, and governance considerations that must accompany its implementation.
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Hierarchy of reference interval models: advancing laboratory data interpretation

October 29, 2025

Thomas Streichert, Mustafa Özçürümez, Jasmin Weninger, Ali Canbay, Abdurrahman Coskun

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Accurate interpretation of laboratory data is a critical step in clinical decision-making. This requires the availability of reliable reference data for comparison. Reference data can be derived from various sources, including hospital or laboratory databases, groups of reference individuals, or an individual’s own data, and can be estimated using different statistical approaches. In addition to the possible lack of standardization of measurement methods this diversity results in the availability of multiple reference intervals for a given measurand. However, selecting the most appropriate reference data is challenging and requires a systematic approach to identify the best available option for each measurand. In this opinion paper, we aim to develop a systematic approach for constructing a hierarchical structure encompassing all known reference interval (RI) models, to discuss the advantages and disadvantages of each, and to provide a framework for selecting the most appropriate RI for routine clinical practice. To illustrate the model visually, we constructed a hierarchical pyramid with the less reliable reference intervals positioned at the base, gradually increasing in reliability toward the top. Based on the data sources and the statistical approaches used to estimate RIs, we conclude that, at least from a theoretical perspective, the currently widespread model – discrete population-based RIs derived from hospital or laboratory data – occupies the lowest level, that is, it represents the ground of the hierarchical pyramid, whereas multivariate continuous personalized RIs reside at the top.
Open Access
An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of dehydroepiandrosterone sulfate in human serum and plasma

December 1, 2025

Sara Cheikh Ibrahim, Neeraj Singh, Katrin Gradl, Friederike Bauland, Daniel Köppl, Alexander Gaudl, Andrea Geistanger, Uta Ceglarek, Manfred Rauh, Christian Geletneky, Judith Taibon

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Objectives Dehydroepiandrosterone sulfate (DHEAS), the sulfate ester of dehydroepiandrosterone, is one of the most common steroid hormones in the human body and the precursor of several other androgens. It is primarily used as a diagnostic or prognostic indicator in adrenal and reproductive disorders. Present immunoassays for DHEAS lack sensitivity and specificity, being vulnerable to cross-reactivity with endogenous interferences. Therefore, an isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS)-based candidate reference measurement procedure (RMP) was developed to quantify DHEAS in human serum/plasma. Methods We ensured traceability to the International System of Units by using quantitative nuclear magnetic resonance to characterize a commercially available DHEAS reference material used for assay calibration. To mitigate matrix effects and prevent interference co-elution, a two-dimensional heart-cut LC method was employed for LC-MS/MS, in combination with a solid phase extraction sample preparation protocol. Selectivity was determined by spiking the prepared internal standard with the interferences testosterone, epi-testosterone, dehydroepiandrosterone, 5α-dihydrotestosterone, and estrone, in analyte free matrix. A post-column infusion experiment and comparison of standard line slopes were performed to evaluate matrix effects. Precision and accuracy were assessed via a multi-day validation experiment, and variability components estimated using analysis of variance-based variance-components analysis. Measurement uncertainty (MU) was evaluated in compliance with current guidelines. Results This RMP was suitable for analyzing DHEAS within the 0.800 to 8,400 ng/mL (2.17–22,800 nmol/L) range, demonstrating selectivity, sensitivity, and matrix-independence. Trueness and accuracy assessment revealed a relative bias (n=6) between −1.9 and 0.3 % for surrogate matrix samples (except for 5.9 % at the lowest level), −2.3 to 3.6 % for Li-heparin plasma samples and sample dilutions, and an overall bias between 0.7 and 1.8 % (n=60), indicating no statistically significant bias. The measurement process resulted in standard measurement uncertainties (MUs) ranging from 4.0 to 5.6 % for the low range and 3.5–4.2 % for the high range. At a 95 % confidence level (k=2), these uncertainties expanded to 7.9–11.1 % and 7.1–8.3 %, respectively. Reference values, determined from six measurements over multiple days (n=6), had standard MUs between 1.6 and 2.1 % for the low range and 0.9–1.7 % for the high range, with expanded MUs of 3.2–4.3 % and 1.9–3.5 %. Conclusions This RMP exhibited high analytical performance for DHEAS quantification and met requirements for measurement uncertainty. Additionally, it enabled differentiation between the DHEAS and other androgens. Consequently, this RMP is suitable for routine assay standardization and clinical sample evaluation.
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Development and validation of a candidate reference measurement procedure for free triiodothyronine and free thyroxine in human serum using equilibrium dialysis isotope-dilution liquid chromatography-tandem mass spectrometry

December 18, 2025

Min Zhan, Qiaoxuan Zhang, Zijia Ma, Liqiao Han, Jun Yan, Guangya Zheng, Wenxi Zhou, Weiyan Zhou, Xianzhang Huang

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Objectives Free triiodothyronine (FT3) and free thyroxine (FT4) are important diagnostic markers for assessing thyroid function. However, their accurate quantification remains challenging due to low serum concentrations. Significant variability exists among current assay methods for measuring FT3 and FT4. This study aims to establish a candidate Reference Measurement Procedure (cRMP) for simultaneous quantification of serum FT3 and FT4 based on isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) technology. Methods A convenient and reusable equilibrium dialysis (ED) device was utilized to separate free thyroid hormones from their protein-bound counterparts in serum. Key dialysis parameters, including temperature, pH, membrane type, and duration, were optimized to ensure consistent and reliable performance. The dialysate containing FT3 and FT4 was directly quantified by ID-LC-MS/MS. The method underwent systematic validation, comparative analysis with existing assays, and a comprehensive uncertainty assessment. Results The developed cRMP demonstrated limits of quantification (LoQ) of 1.54 pmol/L for FT3 and 3.22 pmol/L for FT4, and with an imprecision of less than 3 %. No interference from endogenous analogs was observed, and the method showed good consistency in interlaboratory comparison. In contrast, chemiluminescent immunoassay results exhibited poor agreement with and the cRMP. Conclusions This study developed a highly precise, accurate, specific, and sensitive ID-LC-MS/MS-based cRMP for the simultaneous measurement of FT3 and FT4 in human serum. This method provides a reliable tool for standardizing routine thyroid function tests.
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Experimental evaluation of colorimetric beverage drug tests: reliability and limitations

January 5, 2026

Annagiulia Di Trana, Maria Chiara David, Nunzia La Maida, Manuela Pellegrini, Simona Pichini

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Antiphosphatidylserine/prothrombin antibodies define a high-risk antiphospholipid syndrome profile associated with organ damage

February 3, 2026

Ariela Hoxha, Giovanni Gobbo, Sabrina Gavasso, Aldo Montagna, Francesca Sartorello, Marta Tonello, Patrizia Zerbinati, Roberta Ramonda, Paolo Simioni

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Objectives Antiphosphatidylserine/prothrombin (aPS/PT) antibodies are promising non-criteria aPLs associated with antiphospholipid syndrome (APS) manifestations. Their influence on long-term outcomes and damage remains uncertain. To assess aPS/PT antibodies association with accrual damage and severe APS disease phenotypes, focusing on their potential for risk stratification. Methods This single-centre cohort study involved 163 patients who fulfilled the 2023 ACR/EULAR APS criteria. IgG/IgM aPS/PT, aCL, and anti-β2GPI antibodies were measured by commercial ELISA. Lupus anticoagulant (LA) was detected in accordance with the ISTH-SSC recommendation. Clinical data covered macrovascular, microvascular, obstetric, and hematologic manifestations. Damage was assessed using DIAPS. Results aPS/PT IgG and IgM were positive in 46.0 % and 65.6 %, respectively. aPS/PT IgG positivity was linked to microvascular involvement (58.7 % vs. 34.1 %, p=0.002), obstetric APS (57.4 % vs. 24.6 %, p<0.0001), valvular disease (17.3 % vs. 4.6 %, p=0.008), and thrombocytopenia (37.3 % vs. 12.5 %, p<0.0001). aPS/PT IgM positivity was also associated with microvascular APS (p=0.006), obstetric morbidity (p=0.02), and thrombocytopenia (p=0.01). In multivariable analysis, quadruple aPL positivity (LA + aCL + anti-β2GPI + aPS/PT) was independently linked to damage (OR 4.3, 95 % CI 1.3–14.5; p=0.02), with no other factors remaining significant. Conclusions Both IgG and IgM aPS/PT antibodies are associated with severe APS features, including microvascular and obstetric issues, as well as overall organ damage. Adding aPS/PT to standard aPL tests finds a subgroup of quadruple-positive APS patients at higher risk of damage. These results could help guide personalized APS management.
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Impact of delayed centrifugation on the stability of 32 biochemical analytes in blood samples collected in serum gel tubes and stored at room temperature

January 28, 2026

María Sanz-Felisi, Paula Tauler-Quetglas, Teresa Escartín-Díez, Ariadna Arbiol-Roca, Dolors Dot-Bach

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Open Access
An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of voriconazole in human serum and plasma

January 26, 2026

Marie Kubicova, Anett Engel, Lena Ruhe, Friederike Bauland, Andrea Geistanger, Johannes Kolja Hegel, Judith Taibon

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Objectives Voriconazole is an antifungal agent measured in serum and plasma for therapeutic drug monitoring. This study aimed to develop a robust isotope-dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) reference measurement procedure (RMP) to ensure accurate and reliable quantification in compliance with metrological standards. Methods A commercially available voriconazole material, traceable to the International System of Units (SI), characterized by quantitative nuclear magnetic resonance spectroscopy (qNMR), served as the primary reference material. Chromatographic separation was achieved using a Raptor Biphenyl column, and isotope-labeled voriconazole was utilized as the internal standard. The candidate RMP was validated for selectivity, matrix effects, linearity, precision, accuracy, sample stability, and measurement uncertainty. Results The method’s selectivity was successfully demonstrated, with no interfering signals observed at the retention time of voriconazole. Assessment of matrix effects revealed no significant differences in slopes across native serum, analyte-free human serum, and Li-hep plasma, confirming the absence of matrix-derived interferences. Intermediate precision was ≤3.7 %, repeatability was ≤2.3 %, and accuracy showed a mean bias ranging from −0.7 to 2.7 % across all matrices and concentration levels. Relative bias for the lower limit of the measuring interval (LLMI) was 1.7 %, with a coefficient of variation (CV) for intermediate precision of 4.3 %. Expanded measurement uncertainties (k=2) for target value assignment (n=6) ranged from 1.4 to 3.4 %. Conclusions This validated ID-LC-MS/MS-based RMP proved to be selective, precise, accurate, and reliable for the quantification of voriconazole in human serum and plasma. The RMP demonstrated high accuracy and precision, along with suitable measurement uncertainty, meeting all relevant requirements for an RMP. These findings support the method’s suitability for use in establishing target values and ensuring accuracy in clinical laboratories.
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Utility of flow cytometric PAX5 protein detection for the diagnosis of B-cell acute lymphoblastic leukemia

January 28, 2026

Tanintorn Pootrakul, Burana Khiankaew, Paisarn Boonsakan, Karan Paisooksantivatana

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Objectives Accurate B-lineage assignment in acute leukemia is critical for therapeutic decisions. While nuclear expression of PAX5 protein (nPAX5) is a highly reliable marker for B-cell differentiation, its conventional assessment by time-consuming immunohistochemistry (IHC) is not ideal for rapid diagnosis. This study aimed to validate the utility of flow cytometric (FCM) detection of nPAX5 for the diagnosis of B-lymphoblastic leukemia (B-ALL), potentially enhancing diagnostic efficiency. Methods A retrospective study was conducted, comparing nPAX5 expression by FCM and IHC in 125 bone marrow biopsies (57 B-ALL, 12 T-ALL, 56 AML). Further diagnostic performance analysis, using ROC analysis of the geometric mean fluorescence intensity ratio (Blast/Normal T-cell), was performed for nPAX5, cCD22, and cCD79a across a larger cohort of 538 acute leukemia cases (123 B-ALL, 29 T-ALL, 386 AML). Results FCM and IHC for PAX5 expression showed 100 % concordance across the 125 cases (57/57 B-ALL positive; 0/12 T-ALL negative). The single PAX5-positive AML case harbored the t(8;21) translocation. ROC analysis demonstrated excellent diagnostic performance for both cCD79a (AUC 0.980) and nPAX5 (AUC 0.955). At optimal criteria, cCD79a achieved 100.00 % specificity and 91.06 % sensitivity. nPAX5 showed strong utility, matching the 91.06 % sensitivity with 89.45 % specificity (criterion >6.30). cCD22 exhibited moderate discriminatory power (AUC 0.807). Conclusions Flow cytometric nuclear PAX5 (nPAX5) demonstrated 100 % agreement with IHC and exhibited excellent diagnostic accuracy (AUC 0.955, 91.06 % sensitivity). These compelling results validate nPAX5 as a reliable and powerful FCM marker, supporting its immediate adoption for rapid and efficient B-lineage assignment in acute leukemia diagnostics.
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Hyperferritinemia and analytical challenges: can proteomics make the difference?

December 16, 2025

Victor Corasolla Carregari, Giulia Napoli, Simone Leggeri, Marco Teti, Andrea Urbani, Silvia Baroni

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Open Access
An isotope dilution-liquid chromatography tandem mass spectrometry-based candidate reference measurement procedure for the quantification of dehydroepiandrosterone in human serum and plasma

January 22, 2026

Lea Lewin, Michael Stadlmeier, Neeraj Singh, Friederike Bauland, Daniel Köppl, Alexander Gaudl, Andrea Geistanger, Uta Ceglarek, Manfred Rauh, Judith Taibon

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Objectives Dehydroepiandrosterone (DHEA) is a steroid prohormone and important precursor for estrogen and testosterone biosynthesis. For differential diagnosis of sexual development disorders (e.g., polycystic ovary syndrome, congenital adrenal hyperplasia), accurate measurement of DHEA in clinical testing is essential. To address that need for high-quality, reproducible assays, an isotope dilution-liquid chromatography (LC)-tandem mass spectrometry (MS/MS)-based candidate reference measurement procedure (RMP) for the quantification of DHEA was developed and validated. Methods A certified primary reference material from the National Measurement Institute of Australia (NMIA), was used for DHEA assay calibration and to ensure traceability to the International System of Units (SI). Two-dimensional heart-cut chromatography was employed for LC-MS/MS in combination with a solid phase extraction sample preparation protocol, to mitigate matrix effects and prevent interference coelution. Selectivity was evaluated by spiking either the analyte or internal standard with potential interferents, such as dehydroepiandrosterone-sulfate, testosterone, and similar steroid compounds. For the evaluation of matrix effects, standard line slopes of various matrices were compared. Precision and accuracy were assessed via a multi-day validation experiment, and variability components were estimated using variance component analysis. Measurement uncertainty was evaluated in compliance with current guidelines. Results This candidate RMP proved suitable for the analysis of DHEA in the measurement range of 0.0800–36.0 ng/mL (0.277–125 nmol/L). Predefined requirements for sensitivity and selectivity were fully met, and independence from matrix effects was demonstrated successfully. Across all tested concentration levels, intermediate precision was ≤1.5 % and repeatability was ≤1.0 %, while the relative mean bias ranged from −1.1 to 0.1 %. Regardless of DHEA concentration or sample type, the expanded measurement uncertainty for reference value assignment (n=6) was ≤1.7 %. Conclusions This isotope dilution-LC-MS/MS-based candidate RMP for DHEA in human serum and plasma met pre-defined analytical performance requirements such as precision, specificity and measurement uncertainty, and showed superior selectivity towards several potential interferents tested. It is suitable for application in clinical sample evaluation and routine assay standardization.
Open Access
Response to: Shift happens: The utility of external quality assessment data in evaluating folate lot changes. https://doi.org/10.1515/cclm-2025-1569

December 8, 2025

Anders Larsson, Johan Saldeen, Frida Duell

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The hook effect of an immunoassay results in a series of pediatric patients with elevated total immunoglobulin E: implications for dilution protocols and method comparison

December 1, 2025

Oleg Melnichuk, Ekaterina Brzhozovskaya, Maria Borodina, Nikolay Mayanskiy

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Open Access
Uracil in plasma: comparison of two in-house-developed LC-MS/MS methods

November 17, 2025

Svend H. Hansen, Eva Greibe

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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).
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The indispensable role of phenotypic screening in thalassemia diagnosis: a case of deception uncovered by inconsistent results

December 15, 2025

Youqiong Li, Ting Qin, Liang Liang, Lihong Zheng

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Open Access
Comparison of blood sample quality and test results between robotic and manual venipuncture: a pilot study

January 8, 2026

Rong Wang, Jiazheng Wang, Wenhan Wu, Dali Wang

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Objectives This study aimed to evaluate the feasibility of robotic venipuncture in clinical settings and compare its performance with manual venipuncture in terms of blood specimen quality and test results. Methods From March to April 2025, 63 participants (35 females, 28 males), aged 23–73 years, were recruited at Zoucheng People’s Hospital Medical Laboratory Center. Blood samples were collected using both robotic venipuncture and manual venipuncture on April 8, 2025. Specimen quality was assessed pre-testing, and coagulation/biochemical parameters were analyzed. Results Robotic venipuncture demonstrated advantages in reducing venipuncture pain and achieving more consistent blood sample mixing. Compared with manual venipuncture, the robotic system enables more precise control of blood collection volume and anticoagulant ratio. Statistically significant differences (p<0.05) were observed in fibrinogen (Fib), prothrombin time (PT), plasminogen activity (PTA), activated partial thromboplastin time (APTT), International Normalized Ratio (INR), thrombin time (TT), potassium (K + ), lactate dehydrogenase (LDH), α‐hydroxybutyrate dehydrogenase (HBDH) levels between the two methods. Conclusions Robotic venipuncture technology demonstrates clinical feasibility, offering more precise blood collection volumes and accurate anticoagulant-to-blood ratios compared to manual venipuncture, thereby enhancing specimen stability (Lippi G, Salvagno GL, Montagnana M, Lima-Oliveira G, Guidi GC, Favaloro EJ. Quality standards for sample collection in coagulation testing. Semin Thromb Hemost. 2012;38:565–75; Reneke J, Etzell J, Leslie S, Ng VL, Gottfried EL. Prolonged prothrombin time and activated partial thromboplastin time due to underfilled specimen tubes with 109 mmol/L (3.2 %) citrate anticoagulant. Am J Clin Pathol. 1998;109:754–7). However, challenges remain, including longer procedure times and initial user acceptance barriers.
Open Access
Laboratory findings in patients treated with complement factor C3 inhibitor pegcetacoplan

January 5, 2026

Saskia M.C. Langemeijer, Jeroen D. Langereis, Mendy ter Avest, Caroline Duineveld, Anne-Els van de Logt, Corrie M. De Kat Angelino, Amber van Deelen, Marloes A.H.M. Michels, Jolein Gloerich, Evelien G.G. Sprenkeler, Renate G. van der Molen, Nicole C.A.J. van de Kar, Joannes F.M. Jacobs

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Objectives Complement inhibitor pegcetacoplan binds to C3 and its activation product C3b. Pegcetacoplan has been approved for the treatment of paroxysmal nocturnal hemoglobinuria. Because pegcetacoplan exerts broad inhibition of the complement cascade its efficacy is also investigated in numerous other diseases caused by complement dysregulation, such as C3 glomerulopathy. Pegcetacoplan causes a number of counterintuitive changes in laboratory results. Methods In-depth complement analysis in two patients with PNH and three patients with C3 glomerulopathy, all treated with pegcetacoplan. Results C3 levels increase up to 300 % above reference levels. In vitro testing showed that this is not a turbidimetric artifact in the C3 immunoassay due to pegcetacoplan-C3 complex formation but appears to be caused by increased half-life of C3 bound to pegcetacoplan. Unbiased mass spectrometric plasma proteome analysis confirmed the dramatic pegcetacoplan-induced increase in circulating C3. Surprisingly, also a three-fold increase of properdin was observed during pegcetacoplan treatment. Serum protein electrophoresis showed an additional band in all patients after pegcetacoplan exposure. This C3-band does not migrate at its expected position because of changes in the mass and charge of C3 bound to pegcetacoplan and should therefore not be misinterpreted as an M-protein. Both in vitro experiments and real clinical practice laboratory results demonstrated that pegcetacoplan completely blocked the alternative complement pathway while the classical pathway is affected but remains largely intact. Conclusions Because of the increasing use of pegcetacoplan in routine clinical practice, it is important that both clinicians and laboratory specialists are aware of these unexpected therapy-induced laboratory findings.
Open Access
An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of 5-alpha-dihydrotestosterone in human serum and plasma

January 26, 2026

Lea Lewin, Michael Stadlmeier, Neeraj Singh, Friederike Bauland, Daniel Köppl, Alexander Gaudl, Andrea Geistanger, Uta Ceglarek, Manfred Rauh, Judith Taibon

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Objectives 5α-dihydrotestosterone (DHT) is a potent androgen, related to male sexual development and irreversibly synthesized from testosterone via 5α-reductase. Dysfunctions in the 5α-reductase system, locally or globally, can have substantial health impacts; measurement of both DHT levels and the testosterone-DHT ratio are thus important for diagnosis and treatment monitoring. For that reason, an isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC MS/MS)-based candidate reference measurement procedure (RMP) to quantify DHT in human serum/plasma was developed. Methods We utilized certified primary reference material for DHT provided by the National Measurement Institute of Australia (NMIA) to calibrate our assay and ensure SI (International System of Units) traceability. To mitigate matrix effects and prevent the co-elution of interferences, two-dimensional heart-cut chromatography was employed for LC-MS/MS, in combination with a solid phase extraction (SPE) sample preparation protocol. Selectivity was determined by spiking the prepared internal standard with possibly interfering substances such as the inactive isomer 5β-DHT and other similar compounds. Comparison of standard line slopes was performed to evaluate matrix effects. Precision and accuracy were assessed via a multi-day validation experiment, and variability components estimated using analysis of variance (ANOVA)-based variance component analysis (VCA). Measurement uncertainty (MU) was evaluated in compliance with current guidelines. Results This RMP was suitable for analyzing DHT within the range of 0.0160–2.76 ng/mL (0.0551 nmol/L–9.50 nmol/L), demonstrating selectivity, sensitivity and matrix-independence. Intermediate precision was ≤2.1 %, repeatability was ≤1.6 % across all concentration levels, and relative mean bias ranged from −2.2 to 2.5 %, across matrices and concentrations. Expanded MU for reference value assignment (n=6) was ≤2.8 %, irrespective of concentration or sample type. Conclusions This RMP exhibited high analytical performance for DHT quantification and met requirements for measurement uncertainty. Additionally, it enabled differentiation between the 5α-DHT and 5β-DHT isomers. Consequently, this RMP is suitable for routine assay standardization and clinical sample evaluation.
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Green laboratory through test ordering appropriateness and innovation

February 3, 2026

Sveva Stangalini, Sara Sacchetti, Paolo Tillio, Luca Giacomini, Valentina Zanotti, Chiara Puricelli, Umberto Dianzani, Roberta Rolla

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Objectives Clinical laboratories play a vital role in healthcare but are also among the most resource-intensive hospital units. High energy and water consumption, extensive use of single-use plastics, and the generation of non-recyclable biomedical waste present major environmental challenges. This study aimed to quantify the environmental and economic burden associated with common and avoidable practices in clinical laboratory medicine, including: excessive blood collection, inappropriate test ordering, and unnecessary tube duplication in pre-analytical workflows. Methods Real-world data from the Clinical Biochemistry Laboratory of the AOU Maggiore della Carità (Novara, Italy) for the year 2024 were analysed to quantify the environmental and economic impact of inappropriate test ordering based on minimum retesting intervals, as well as pre-analytical practices, including redundant sample tube collection and excessive blood volumes relative to analytical requirements. Results Inappropriate retesting of selected biomarkers resulted in 2,931 unnecessary tubes, generating over 26.7 kg of avoidable waste. Redundant EDTA tubes for complete blood count, glycated haemoglobin, erythrocyte sedimentation rate, and haemoglobin electrophoresis led to 356.14 kg of excess waste, which could be eliminated through sample consolidation. In haematology, 264,834 CBC tests generated 2.62 tonnes of biological waste. For biochemistry, 3 million tests produced 36.98 tonnes of waste. Conclusions Excessive blood collection and unnecessary test repetition contribute to significant but avoidable environmental and financial burdens. Pre-analytical interventions, such as reducing tube volume and consolidating tests, could prevent over 40 tonnes of waste and save more than € 60,800 annually in a single laboratory.
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Evaluation of the MAGLUMI non-competitive angiotensin I chemiluminescence immunoassay for measuring renin activity in human plasma

January 7, 2026

Lina Wu, Baohu Zhang, Yun Zhang, Shucai Yang, Chenyan Shi, Wenfeng Wang, Zhonggang Fang, Li Zhang, Xiaosong Qin

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Objectives Plasma renin activity (PRA) measures the rate of renin converting angiotensinogen to angiotensin I in circulation and reflects the function of renin-angiotensin-aldosterone system (RAAS). The study aimed to demonstrate the performance of the MAGLUMI Angiotensin I assay for the measurement of PRA. Methods The MAGLUMI Angiotensin I assay was evaluated for precision, linearity, limit of blank (LoB), limit of detection (LoD), limit of quantification (LoQ), interferences, cross-reactivity and reference intervals. It was compared to liquid chromatography tandem mass spectrometry (LC-MS/MS) using 54 samples, and impact of clinical factors was assessed in 181 samples. Results The assay demonstrated repeatability of 1.5 %, 1.85%, and 1.6 % across three different pool concentrations, with corresponding within-laboratory imprecision values of 2.0 %, 2.5%, and 1.9 %. The linear range was [0.10, 24.0] ng/mL. The LoB, the LoD, and the LoQ were 0.03 ng/mL, 0.07 ng/mL, and 0.10 ng/mL, respectively. The interferences and cross-reactivity met the criterion for acceptable cross-reactivity (CR) with <±10 %. Reference interval validation shows <10 % of a total of 40 healthy individuals’ plasma samples falling outside the established interval for standing and lying position. The MAGLUMI assay showed excellent agreement with LC-MS/MS for both angiotensin I (slope=1.076, intercept=0.109 ng/mL/h, r=0.987, p<0.001) and plasma renin activity (slope=1.131, intercept=−0.386 ng/mL/h, r=0.973, p<0.001). Conclusions The MAGLUMI Angiotensin I chemiluminescence immunoassay is a sensitive and reliable commercial kit for detecting plasma renin activity. The assay exhibited robust analytical performance and strong agreement with LC-MS/MS.
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Mass spectrometry reveals limitations of serum immunofixation electrophoresis in monitoring lambda light chain myeloma

December 11, 2025

Yu Chen, Min Yang, Haitao Meng, Hongyan Tong

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Capillary blood in core laboratories: current and future challenges

November 14, 2025

Álvaro González, Sara Deza, Julia Maroto-García, Nerea Varo

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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.
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Analytical and diagnostic evaluation of the Anvajo fluidlab 2 analyzer: a novel urine particle analyzer for clinical application using digital holographic microscopy?

January 2, 2026

Sigrid Deprez, Marijn Speeckaert, Joris Delanghe, Matthijs Oyaert

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Objectives The performance of a novel urine particle analyzer, fluidlab 2 (Anvajo GmbH, Dresden, Germany), was evaluated against phase-contrast visual microscopy according to the most recent EFLM European Urinalysis Guideline. Methods The fluidlab 2 device combines digital holographic microscopy with neural network-based object detection for particle classification. Its compact benchtop design is suitable for bedside use, reducing turnaround times. The analytical performance (imprecision, linearity, LoQ) was evaluated according to the 2023 EFLM Urinalysis Guideline. Method comparison involved the analysis of 450 urine samples, assessing RBC, WBC, and SEC counts against visual microscopy using Passing-Bablok regression and Spearman’s correlation. Bland-Altman plots were used to evaluate the agreement with clinical performance standards, while weighted Cohen’s kappa was used to measure diagnostic agreement on an ordinal scale. Results By applying Dahlberg’s procedure, a desirable relative coefficient of variation R(CV) ≤2.0 was obtained for RBC and WBC. Linearity of up to 7 × 10 6 /L and 6 × 10 6 /L was achieved. The estimated LoQ at CV=30 % reached 20 × 10 6 /L for RBC and 5 × 10 6 /L for WBC. Spearman’s correlation coefficient against visual microscopy was 0.86, 0.92 and 0.94 for RBC, WBC and SEC, respectively. Agreement with visual microscopy (Cohen’s weighted kappa) was 0.92 for RBC, 0.93 for WBC, 0.96 for SEC, 0.86 for casts, 0.82 for non-SEC, 0.33 for crystals and 0.51 for bacterial counts. Conclusions Fluidlab 2 provides desirable imprecision for RBC and WBC, and meets the criteria for linearity and LoQ. Cohen’s weighted kappa coefficients show an optimal comparison to visual microscopy for RBC, WBC and SEC and a minimum comparison for casts and non-SEC. This evaluation demonstrated promising results for the use of the fluidlab 2 analyzer in a clinical setting to detect kidney-related diseases based on urine particle analysis.
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Cytoplasmic crystalline inclusions in lymphocytes of B-cell lymphoproliferative disorders

January 5, 2026

Mirela Balan, Stefania Cione, Tiziana Lamacchia, Chiara Daverio, Alberto Giuseppe Passi

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Open Access
At-home blood collection for clinical chemistry analyses in a kidney transplant population: a feasibility study

January 5, 2026

Jorrit Hoekstra, Manon Wilpshaar, Stefan Berger, Joyce Doorn

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Objectives To investigate the feasibility of at-home collection of liquid capillary blood samples for clinical chemistry analyses. Methods Kidney transplant recipients performed a fingerprick to collect capillary blood samples. Samples were kept at room temperature for 24 h before further processing. Results were compared to results obtained from venipuncture samples using Passing-Bablok analysis and by calculating mean relative differences, which were compared to CLIA and TEa acceptance limits. In addition, transport times/temperatures and effects of postal handling were examined. Results Of 38 patients that performed a fingerprick, 29 properly filled 2 microtainers, 4 filled 1 microtainer and 5 were unable to fill any microtainer. Capillary samples were generally more hemolytic, but we found mean differences within CLIA/TEa for hemoglobin, leukocytes, hemoglobinA1c, creatinine, alanine transaminase, C-reactive protein, albumin, calcium and gamma-glutamyl transferase. For alkaline phosphatase and thrombocytes, we found a negative bias, but mean differences within CLIA/TEa. Mean differences for potassium, aspartate transaminase, hematocrit and mean corpuscular volume exceeded CLIA and/or total allowable error (TEa). For phosphate, individual samples showed large variation. Transport times did not exceed 24 h, but temperatures up to 10 °C above outside temperatures were observed. Transport of samples resulted in slight increases in H-index, lactate dehydrogenase (LDH) and aspartate transaminase (ASAT). Conclusions At-home capillary blood collection is feasible for many patients and samples are suitable for a subset of clinical chemistry analyses. Instruction, monitoring of transport time/temperature and knowledge of the pitfalls when interpreting results are key elements upon implementation in clinical practice.
Open Access
An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of cortisol in human urine

October 20, 2025

Myriam Ott, Friederike Bauland, Daniel Köppl, Alice Ayik, Andrea Geistanger, Manfred Rauh, Judith Taibon

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Objectives Precise and accurate determination of urinary cortisol is important for diagnosis and monitoring of cortisol excess and deficiency. To achieve this, a selective and specific, isotope-dilution two-dimensional heart-cut liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method was developed. Methods A novel, two-dimensional heart-cut LC-MS/MS method was developed using a Waters Acquity BEH C18 column and a Raptor Biphenyl column, with water (A1) and with 0.2 mM ammonium fluoride in water (A2) and methanol (B1+B2) as mobile phases. This approach was complemented by a supported liquid extraction (SLE) sample preparation protocol. Matrix effects were assessed through post-column infusion experiments and comparisons of standard line slopes across matrices. A multi-day validation study evaluated accuracy and precision of the candidate reference measurement procedure (RMP) and measurement uncertainty (MU) was estimated in compliance with current guidelines. Reproducibility was assessed by performing a method comparison study between two independent laboratories. Results In the first LC column dimension, cortisol and prednisolone were separated from cortisone, prednisone, and 20-beta-dihydrocortisone. Baseline separation of cortisol from prednisolone was achieved in the second dimension. No interfering signals were detected at the retention time for quantifier and internal standard transitions in any urine samples analysed. No significant matrix effect, ion suppression, or enhancement was observed. Linearity was successfully demonstrated (r≥0.999); residuals were randomly distributed in a quadratic model via linear regression with an 1/x weighting. The lower limit of the measuring interval was determined at 2.00 ng/mL (5.52 nmol/L), displaying a relative deviation of −0.1 %, a coefficient of variation (CV) of 2.9 %, and recoveries of 96–103 %. Intermediate precision ranged from 1.9–3.2 % and repeatability CV from 1.6–2.7 %. Relative mean bias ranged from −3.5–1.2 %, indicating method accuracy was unaffected by matrix variance. Measurement uncertainties (k=1) for cortisol were ≤3.4 % across different concentrations and sample types. The expanded uncertainty at a 95 % confidence level (k=2) was ≤6.8 %. An increased number of measurements (n=6) for target value assignment reduced the uncertainty to 0.8–1.3 % (k=1), yielding an expanded uncertainty (k=2) of 1.7–2.5 %. Conclusions The validation results confirm the robustness, accuracy, and reliability of this RMP for determination of cortisol in human urine within a working range of 2.00–220 ng/mL (5.52–552 nmol/L).
Open Access
Comparison of six serum analyte workflows using routine liquid chromatography-tandem mass spectrometry methods at multiple laboratories with the Cobas i 601 analyzer, an automated mass spectrometry system

January 26, 2026

Pieter Vermeersch, Robert de Jonge, Takamaro Miyazawa, Mads Nybo, Palle Fruekilde, Barry J. Toole, Philippe Metz, Eva Albrecht, Karl Slusarczyk, Michael Vogeser, Robert L. Fitzgerald

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Objectives Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers substantial analytical advantages over traditional immunoassay methods, including greater specificity and robustness. Conventional LC-MS/MS methods are labor-intensive, requiring highly trained, dedicated laboratory staff. The Cobas ® i 601 analyzer (Roche Diagnostics International Ltd., Rotkreuz, Switzerland) is an automated, random-access, mass spectrometry (MS) system designed to improve workflows and reduce turnaround times. This study evaluated turnaround times for analyses with the i 601 analyzer vs. routine LC-MS/MS using batch processing. Methods We performed a workflow analysis for six sets of analytes (mycophenolic acid, antibiotics, antiepileptics, voriconazole, testosterone, and 25-hydroxyvitamin D) in seven laboratories across Europe, North America, and Asia. We recorded batch size, result turnaround times, and hands-on times (including quality control) for 93 batches analyzed on routine LC-MS/MS. These were compared to equivalent measurements generated using the i 601 analyzer in batch mode as part of a prototype pilot study at Ludwig Maximilian University, Munich. Results Turnaround times were shorter with the i 601 analyzer vs. routine LC-MS/MS for all tested workflows, independent of batch size and analyte workflow. Median time from batch start to final result availability with the i 601 analyzer was 6.8-fold shorter vs. routine LC-MS/MS (1 h, 34 min vs. 10 h, 37 min, respectively). In addition, median total hands-on time was 19-fold shorter with the i 601 analyzer vs. routine LC-MS/MS (5 vs. 93 min). Conclusions Compared with routine LC-MS/MS methods, the i 601 analyzer substantially reduced turnaround and hands-on times for common analytes, regardless of batch size.
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The democratization of cancer screening, or a waste of valuable resources?

December 15, 2025

Miyo K. Chatanaka, Eleftherios P. Diamandis

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The discovery of circulating tumor DNA (ctDNA) prompted many scientists and companies to apply this new technology for cancer diagnostics. One valuable application of ctDNA is in the screening for cancer. This procedure has been coined “liquid biopsy” and unlike classical biopsy, is minimally invasive. This technology can be used to detect one, a few or several cancers, hopefully at an early, treatable stage. There is considerable debate on the ability of this technology to efficiently detect small, localized tumors since the amount of ctDNA in the circulation is miniscule, potentially leading to many false negatives. Additionally, the false positive rate is concerning, especially for low prevalence tumors. Here, we provide an update and underline important issues that need to be addressed before this technology enters the clinic. Due to substantial financial rewards of successful companies and the prospective large investment of public healthcare resources, scientists have the responsibility to thoroughly validate these technologies and make sure that these tests not only detect cancer, but they also trigger actionable interventions that improve patient survival and/or quality of life.
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Performance evaluation of a new high-sensitivity cardiac troponin T assay: hs-cTnT (CLIA) assay

November 26, 2025

Xin Shu, Chenbin Zhang, Ting Deng, Yisha Jing, Hui Wang, Xianzhi Li, Jiajia Zhu, Ling Li, Zhenlu Zhang, Litao Zhang

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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.
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Toward neonatal analytical stewardship: building on Cadamuro et al.’s minimum-volume framework

December 16, 2025

Mulavagili Vijayasimha

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Prognostic value of suPAR in sepsis: a potential tool to support patient management in the Emergency Department

December 15, 2025

Simone Leggeri, Giulia Napoli, Andrea Piccioni, Fabio Belvederi, Gloria Rozzi, Francesco Franceschi, Andrea Urbani, Silvia Baroni

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Objectives The soluble urokinase plasminogen activator receptor (suPAR) is a well-established biomarker of immune activation, reflecting the severity of systemic inflammation. Recent evidence showed increasing interest in suPAR as a prognostic marker, with elevated levels consistently associated with greater disease severity and mortality, in different clinical settings. Methods In this retrospective study, suPAR levels were assayed at Emergency Department admission in patients who received a diagnosis of sepsis or systemic infection during their initial clinical workup, using an automated turbidimetric assay (suPARnostic ViroGates kit on Atellica CH analyzer Siemens). The primary endpoint of this study was to evaluate the association between baseline suPAR levels and mortality, while the secondary endpoint aimed to explore their potential as indicators of clinical severity and predictors of patient outcomes. Results suPAR levels were elevated in all patients (median 6.99 μg/L) consistent with the severity of their clinical condition. A threshold of 10.2 μg/L was strongly associated with mortality, while a cut-off of 5.96 μg/L identified patients with severe disease and prolonged hospital stays. Conclusions suPAR seems to be a reliable, rapid, and clinically useful prognostic biomarker in the Emergency Department in patients with sepsis or systemic infections. Its early measurement by turbidimetric immunoassay in automation can support risk stratification, improve triage decisions, and enhance the management of these patients.
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Analytical verification and comparative assessment of the new Atellica IM high-sensitivity prostate specific antigen assay

December 23, 2025

Xavier Filella, Cristina González-Escribano, María Rodríguez-García, Núria Medina-Esteban, Esther Fernández-Galan

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Objectives Despite standardization efforts, significant inter-assay variability persists among prostate-specific antigen (PSA) tests, impacting prostate cancer (PCa) diagnosis and monitoring. We aimed to evaluate the analytical and clinical performance of the newly developed Atellica IM high-sensitivity PSA (hsPSA Atellica) assay compared with established PSA assays. Methods A total of 236 serum samples from healthy individuals and patients with or without PCa were analyzed using the hsPSA Atellica assay and four FDA-approved PSA assays: Hybritech Access, Architect, Atellica, and Cobas. Analytical performance included limit of detection (LOD), limit of quantification (LOQ), linearity, inter-assay precision, and hook effect. Method comparison was performed using Passing-Bablok regression, Bland-Altman analysis, and kappa index concordance. Results The hsPSA Atellica assay demonstrated a LOD of 0.01 μg/L and LOQ of 0.028 μg/L (CV: 3.2 %, accuracy: 115 %). Precision was maintained across concentrations, with CVs of 4.2 %, 3.8 %, and 2.4 % at low, medium, and high levels of PSA. Strong agreement was observed with the compared tests, particularly with Cobas and Hybritech PSA assays. Diagnostic sensitivity and specificity at the 4 μg/L clinical decision threshold were 98 % and 35 %, respectively. In 87 samples between 3 and 10 μg/L, concordance between hsPSA Atellica and Hybritech reached 96.6 % (κ=0.82). The assay remained accurate up to PSA concentrations of 13,311 μg/L, showing minimal hook effect. Conclusions The hsPSA Atellica assay shows excellent analytical sensitivity and strong agreement with established assays. To our knowledge, this is the first published evaluation of this assay, supporting its clinical utility in both PCa diagnosis and follow-up.
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From venipuncture to self-sampling dried blood spots: a shift in monitoring testosterone levels

January 5, 2026

Anouk Olthof, Jacquelien J. Hillebrand, Lysette H.A. van Deursen-Nagel, Anita Boelen, Andreas Meißner, Annemieke C. Heijboer

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Objectives Dried blood spot (DBS) sampling enables convenient at-home blood collection, suitable for patients needing regular check-ups, such as those receiving testosterone replacement therapy (TRT). This study assessed the feasibility and reliability of DBS sampling for monitoring testosterone concentrations in patients undergoing TRT, aiming to provide a convenient at-home alternative to venipuncture. Methods Twenty healthy volunteers (12F/8M) and 56 male patients (n=59 samples) receiving TRT were included. Blood was collected parallel by venipuncture (reference) and patient-performed finger prick (DBS) following instruction materials and additional verbal guidance from the andrology consultant. Feasibility and patients’ experience were evaluated through questionnaires. Testosterone concentrations in both serum and DBS were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results In healthy volunteers, serum and DBS testosterone concentrations were highly correlated (y=−0.021 + 0.66x; r=0.99). For patients receiving intramuscular testosterone undecanoate, this correlation was strong (y=1.3 + 0.54x; r=0.87). However, DBS samples from patients using testosterone gel showed extremely elevated testosterone levels compared to serum, likely due to local contamination. Most healthy volunteers and in general all patients preferred at-home DBS-sampling over venipuncture at the hospital when regular check-ups are necessary, citing convenience and reduced travel time. Conclusions At-home DBS sampling is a feasible and reliable method for monitoring testosterone in patients treated with intramuscular testosterone undecanoate, improving patient comfort and convenience. However, DBS sampling at-home is currently unsuitable for patients using testosterone gel, likely due to contamination issues. Comprehensive patient education on collection of DBS samples is crucial to ensure high-quality DBS and accurate testosterone quantification.
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One copy in one-pot for rapid and accurate SFTSV testing by LAC12b-2M

January 14, 2026

Ya Pang, Yongwei Duan, Yuehua Sun, Tong Zhou, Anling Li, Ruoxi Ran, Hongyan Hou, Song-Mei Liu

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Objectives Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne pathogen that can cause a fatality rate as high as 12–50 %, posing a significant threat to public health. SFTSV is prevalent in mountainous and hilly regions with relatively poor medical conditions. Therefore, there is an urgent need to develop a new convenient, rapid and sensitive method for SFTSV detection in low-resource environments. Methods We developed a one-pot and visualized method for SFTSV detection using loop-mediated isothermal amplification assisted by CRISPR/Cas12b with G478A/K396A double mutations (LAC12b-2M). The specificity, sensitivity, accuracy and limit of detection (LOD) of LAC12b-2M were evaluated using clinical reverse transcription-quantitative PCR (RT-qPCR) as the reference method, with gradient dilutions of strong positive SFTSV RNA samples and 215 clinical serum samples from two cohorts. Results LAC12b-2M is sensitive to detect SFTSV with a LOD of 1 copy/μL at 61 °C within 30 min. Compared to clinical RT-qPCR, LAC12b-2M demonstrated a sensitivity of 98.8 % (82/83), a specificity of 100.0 % (96/96), and an accuracy of 99.4 % (178/179) in cohort 1 (n=179), and an accuracy of 100.0 % in cohort 2 (n=36). Conclusions Our LAC12b-2M method holds promise for point-of-care SFTSV testing in different healthcare settings, particularly in low-resource region where SFTSV is prevalent.
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Comparability, compatibility, equivalence and interchangeability: metrological concepts widely misunderstood in laboratory medicine

January 12, 2026

Raúl Rigo-Bonnin, Sofía Durán-Espín, Míriam Valbuena-Asensio, Virgínia Mas-Bosch, Aurora Blanco-Font

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Background Method-comparison studies in laboratory medicine are routinely interpreted using regression-based or Bland–Altman analyses. Although useful descriptively, these statistical procedures are frequently misapplied to infer “agreement”, “equivalence”, or “interchangeability”. Such interpretations overlook essential metrological conditions – including the definition of the measurand, the traceability chain, and measurement uncertainty – leading to misconceptions with potential clinical consequences. Content This Opinion Paper clarifies the distinct meanings of four metrological concepts that are often treated as synonyms: comparability , compatibility , equivalence , and interchangeability . We explain why numerical similarity or statistical association does not establish metrological relatedness, and outline the specific requirements for each concept. Comparability requires a shared measurand and calibration hierarchy; compatibility requires differences smaller than the combined uncertainty; equivalence requires clinically irrelevant residual differences; and interchangeability requires stability of clinical decisions when substituting one measuring system for another. We also discuss familiar sources of misinterpretation, including ambiguous definitions of the measurand, incomplete traceability chains, and uncritical reliance on regression- or bias-based summaries. Summary and outlook Distinguishing among comparability, compatibility, equivalence, and interchangeability is essential for the metrological interpretation of method-comparison studies and for ensuring safe analytical and clinical decision-making. Integrating these concepts explicitly into study design, harmonisation strategies, and reporting practice will strengthen traceability implementation, prevent erroneous claims of “agreement”, and support more reliable patient care.
Open Access
Assessment for potential bias in multiplexed IL-10 and TNF-α from plex count

January 19, 2026

Wade M. Sanders, Carrie A. Karvonen-Gutierrez, Daniel S. McConnell

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Objectives Multiplex arrays offer a high-throughput, cost-effective means for quantifying multiple analytes simultaneously, essential for large-scale biomarker research. However, the shared reactive environment in multiplex assays could lead to variations in results compared to single plex assays, potentially impacting outcomes. This study aimed to explore these differences by examining a “3-plex” cytokine panel vs. single plex assays for tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10). Methods Using the R&D Systems Luminex HS Cytokine Panel A, 72 serum samples were tested across several batches, including three “3-plex” and two “1-plex” batches each for IL-10 and TNF-α. We evaluated differences in cytokine values using paired t-tests, comparing within 1-plex, between 3-plex, and between 1-plex and 3-plex assays. Bland-Altman plots visually assessed absolute and percentage differences. Results IL-10 values were similar between 1-plex and 3-plex assays, showing an average difference of 4.2 fmol/L (10.7 %), which was less than the within plex differences. Conversely, TNF-α showed a 16.7 % difference in the between plex comparison, compared to a 12 % difference in the within plex comparisons. Statistically significant differences emerged mainly for IL-10 across all comparisons. Bland-Altman analyses indicated pronounced variability at low analyte concentrations. Conclusions While the multiplex assays demonstrated variation at low analyte levels, especially for IL-10, such differences might not substantially affect comparability when mixed with single plex assays, particularly in datasets dominated by low concentrations.
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Response to Lenters-Westra, Erna, et al. “Limitations of glycated albumin standardization when applied to the assessment of diabetes patients” Clin Chem Lab Med doi.org/10.1515/cclm-2024-0591

December 18, 2025

Julie Sherfan, Rana Suilman, Tony Badrick

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Comparative analysis of three platforms for serum NfL quantification in healthy controls and MS patients

December 18, 2025

Justina Dargvainiene, Antje Torge, Klaus-Peter Wandinger, Ralf Junker, Robert Markewitz, Pascal Benkert, Eline Willemse, Aleksandra Maleska, Sven Ole Schuster, Malte Ziemann, Cansu Tafrali, Maria Martinez-Serrat, Michael Khalil, Jens Kuhle, Frank Leypoldt

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Objectives Neurofilament light chain (NfL) is a biomarker of neuroaxonal damage in various neurological conditions, including multiple sclerosis (MS). With new analytical platforms entering the market, standardization of serum NfL (sNfL) measurement is essential. This study compared sNfL levels across three assays – NF-light Advantage V2/Plus (Quanterix), Lumipulse G NfL blood (FujiRebio), and Elecsys NfL (Roche Diagnostics) – and derived conversion formulas for harmonization. Methods Serum samples from three cohorts including healthy donors (n=303) and MS patients (n=181) were analyzed across three platforms. Passing-Bablok regression and correlation analyses assessed inter-platform agreement and potential systematic differences. Assays were further evaluated for their ability to detect MS disease activity. Results All platforms showed strong correlations (Pearson>0.98; Spearman>0.90, p<0.001). Absolute values from Elecsys were ∼6-fold lower than the other assays. Fourteen of 484 samples (2.90 %) showed substantial, retest-stable deviations (>4 SD) on at least one platform. After excluding outliers, conversion formulas were derived to transform the values to the NF-light Advantage V2/Plus scale: NfL=6.31 × [Elecsys NfL] + 2.33 ng/L; NfL=0.94 × [Lumipulse G NfL] + 1.30 ng/L. In MS patients, all platforms detected significant differences between relapse and remission (p<0.001). Age-adjusted Z scores from converted values yielded the highest effect sizes (Cohen’s d: 0.84 for NF-light Advantage, 1.11 for Elecsys, 0.93 for Lumipulse). Conclusions The three platforms demonstrated high correlation and comparable performance in sNfL quantification. About 3 % of samples showed strong deviations, highlighting the need for vigilance and further harmonization. Age-adjusted Z scores may enhance clinical and research utility.
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Assessment of drone transport for biological samples: a real-world experience at a tertiary hospital

January 6, 2026

Paula Calomarde-Pastor, Álvaro Piedra-Aguilera, Arnau Pulido-Gracia, Carla Fernández-Prendes, Marta Álvarez-Álvarez, Silvia Martínez-Couselo, María Martínez-Bujidos, María Antonia Huertas-Contreras, María Carmen García-Martín, Laura Jiménez-Añón, Jennifer Rodríguez-Domínguez, Vanessa García-Bayarri, Berta Llebot-Casajuana, Núria Abdón-Giménez, Núria Sánchez-Mercader, Sara Iglesias-Lorente, Yolanda García-González, Ignacio Blanco-Guillermo, Cristian Morales-Indiano, Susana Malumbres-Serrano

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Objectives Our aim is to determine whether drone transport introduces relevant variability in analytical results and to assess its suitability for integration into routine hospital laboratory operations. Methods A two-phase study was conducted. The stability phase involved three sets of samples from 31 healthy volunteers transported by drone, by road, and processed without transport. The pilot phase included paired samples from 104 primary care patients transported by drone and by road. A broad panel of 53 biochemical, hematological and urinary analytes was assessed. Analytical performance was evaluated using mean bias, comparison with reference change values (RCVs) and hemolysis grading. Results Most analytes showed minimal differences between transport methods. In the stability study, glucose and MCH in road-transported samples, and lactate dehydrogenase (LDH) and mean corpuscular hemoglobin (MCH) in drone-transported samples, exceeded their respective RCVs, with LDH likely affected by mild hemolysis. In the pilot study, statistically significant differences were observed between transport methods for potassium, exhibiting a bias of −1.7 % (−2.6 to −0.8 %). Hemolysis was slightly more frequent in drone samples during the stability study but comparable in the pilot study. Conclusions Drone transport preserved the analytical integrity of a comprehensive test panel and has the potential to reduce logistical constraints. These findings support its implementation as a reliable and sustainable alternative to conventional transport in clinical laboratory settings.
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Establishment of allowable total error for semen analysis based on the state of the art in China

January 9, 2026

Yan Zheng, Lin Yu, Yingbi Wu, Yelin Jia, Shasha Liu, Jiao Qin, Jintao Yuan, Yuan Liu, Fuping Li

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Objectives To establish evidence-based analytical performance specifications (APS), specifically allowable total error (TE a ), for five fundamental semen analysis parameters (sperm concentration, progressive motility, total motility, morphology, and vitality) in China utilizing the state-of-the-art model, and to compare these specifications with existing international benchmarks. Methods We examined national external quality assessment (EQA) data from 2019 to 2025, encompassing 315 laboratories across 30 provinces in China. TE a was calculated using the state-of-the-art model as half the 10th–90th percentile range of result deviations from assigned values. Given that the participant count was below 100 from 2019 to 2022, this study eventually utilized data from 2023 to 2025 for the calculation of TE a . The pass rate of participating laboratories was evaluated against the established TE a criteria. Results The established TE a values as follows: sperm concentration, 34.3 %; progressive motility, 26.9 % (for assigned value ≤40 %) and 13.5 % (>40 %); total motility, 26.3 % (≤50 %) and 10.5 % (>50 %); morphology, 67.7 %; vitality, 24.6 % (≤60 %) and 7.9 % (>60 %). The pass rates for all parameters in recent EQA cycles were approximately 80 %, supporting the practical achievability of the proposed specifications. Comparisons showed that the derived TE a values are generally consistent with or more refined than previous state-of-the-art and biological variation-based standards. Conclusions This study provides the first large-scale, evidence-based TE a for semen analysis in China. The stratified TE a for motility and vitality based on clinical thresholds, improves diagnostic accuracy. The proposed specifications are practical, achievable, and clinically relevant, providing a consistent foundation for quality assurance in reproductive medicine laboratories.
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Recommendations from the IFCC Working Group on Laboratory Errors and Patient Safety for the Global Adoption of an Essential Quality Indicators Panel in Laboratory Medicine

November 20, 2025

Vincent De Guire, Cesar Alex Oliveira Galoro, Mercedes Ibarz, Agnes Ivanov, Giuseppe Lippi, Rui Zhou, Laura Sciacovelli, Sohini Sengupta Neogi, Julie Shaw, Wilson Shcolnik, Ruben L. Smeets, Zorica Sumarac, Pieter Vermeersch, Alexander Von Meyer, Mario Plebani

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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.
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Hook effect for ferritin immunoassays: implications for clinical practice

December 17, 2025

Meshach Asare-Werehene, Qiu Yi Shao, Felix Leung, Davor Brinc, Annie Ren, Peter A. Kavsak, Daniel R. Beriault, Saranya Arnoldo

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Combining the calibrator uncertainty and the long-term measurement uncertainty? A comment to the ISO/TS 20914 guideline

November 26, 2025

Arne Åsberg, Øyvind Skadberg

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Artificial intelligence and machine learning in thrombosis and hemostasis: a scoping review of clinical and laboratory applications, challenges, and future directions

December 17, 2025

Mohammad A. Altememi, Emmanuel J. Favaloro, Md Zahid Islam, Abishek. B. Santhakumar

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This scoping review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines to systematically map the current landscape of artificial intelligence (AI) and machine learning (ML) applications in the field of thrombosis and hemostasis (T&H), specifically targeting diagnostic enhancements in clinical and laboratory settings. Utilizing comprehensive searches across MEDLINE, EMBASE, Web of Science, and Scopus (2020–2025), 107 original studies met inclusion criteria and were analyzed. Clinical applications predominantly focused on predictive modelling for venous thromboembolism (VTE), pulmonary embolism (PE), deep vein thrombosis (DVT), anticoagulant management, and disease risk stratification, employing algorithms including neural networks, random forests, and gradient boosting. Laboratory-based AI implementations, though fewer, provided automated quality control, clot detection, and assay interpretation enhancements for potential better decision-making. Significant limitations addressed by the include studies include reliance on retrospective, single-center, small-sample datasets, limited external validation, model interpretability concerns, and integration challenges into clinical workflows. Persistent interdisciplinary disconnect between hemostasis domain experts and AI-ML specialists, compounded by regulatory hurdles, fragmented data, and labor-intensive data labelling processes, was highlighted as a major barrier to broader adoption. Recommendations for future research include developing large, externally validated multicenter datasets, transparent and interpretable ML models, prospective clinical validations, and user-centered integration strategies. Enhancing collaboration between laboratory scientists and AI-ML experts, establishing structured education programs, and creating regulatory frameworks are essential next steps to fully realize the potential of AI for significantly improving diagnostic accuracy, clinical decision-making, and patient management in T&H.
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Cardiac troponin T measurement following cardiac surgery in children with congenital heart defects predicts adverse outcomes

January 28, 2026

Giuseppe Isgrò, Alessandro Giamberti, Elena Costa, Savina Mannarino, Claudia Chillemi, Vittoria Garella, Francesca Magrì, Martina Anguissola, Alessandro Barbaria, Martina Evangelista, Benedetta Rampoldi, Mariano Lanna, Gianvincenzo Zuccotti, Peter Kavsak, Marco Ranucci, Simona Ferraro

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Objectives Testing for high-sensitivity cardiac troponin (hs-cTn) often occurs following pediatric cardiac surgery, although evidence regarding its utility remains heterogeneous. This study aimed to assess the prognostic value of postoperative hs-cTnT patterns detected within 48 h after cardiac surgery. Methods Serum hs-cTnT (Roche Diagnostics, 5th generation assay) concentrations were measured post-operatively at three time points: upon pediatric intensive care unit (PICU) admission (T1), 13 h after admission (T2), and 24 h after T2 (T3). Surgical and postoperative variables were recorded. The outcome was a composite of 30-day mortality and/or PICU stay >10 days. Multivariable logistic regression and model discrimination were evaluated. Results Over 15 months, 154 patients (56.5 % male) with a median age of 3.8 (25th–75th percentile: 1.2–7.8) months and a median Risk Assessment for Congenital Heart Surgery score of 2, were included in this study. The outcome occurred in 24 % of the population (with the 30-day mortality rate being 7.8 %). The time point of the highest recorded hs-cTnT concentration, and not the concentration, was significantly associated with the outcome (p=0.001). Patients, whose peak hs-cTnT concentration occurred later after surgery had a sixfold higher risk of the adverse outcome. Urgent/emergent procedures were associated with a 3.6-fold increase in relative risk, and each additional minute of cardiopulmonary bypass (CPB) time conferred a 1.6 % incremental increase in risk. The multivariate model including time to troponin peak, CPB duration, need for urgent/emergent procedures showed a good discriminatory ability (c-statistic=0.84; 95 %CI: 0.78–0.90). Conclusions Timing of hs-cTnT elevation post cardiac surgery is a valuable prognostic marker in children.
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A study of the performance of different methods for measuring serum lithium

November 17, 2025

Xiaoyu Fan, Chenyun Huang, Jingqi Xu, Ping Hu, Xin Huang

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An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of progesterone in human serum and plasma

December 1, 2025

Sara Cheikh Ibrahim, Tobias Santner, Neeraj Singh, Friederike Bauland, Daniel Köppl, Marie Kubicova, Alexander Gaudl, Andrea Geistanger, Uta Ceglarek, Manfred Rauh, Christian Geletneky, Judith Taibon

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Objectives Progesterone regulates reproductive processes and is used clinically to monitor ovarian function in people experiencing fertility problems. Measuring serum progesterone is challenging as it is highly protein-bound and exists at very low physiological levels. An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate RMP to quantify progesterone in human serum/plasma has been developed. Methods To ensure traceability to the SI Units, this RMP utilized primary reference material from the NMIJ. For the determination of progesterone, two-dimensional heart-cut chromatography, in combination with a straightforward protein precipitation protocol, was employed to minimize matrix effects and the coelution of isobaric interferences. Accuracy and precision of the candidate RMP was assessed in a multi-day validation experiment using certified secondary reference materials, spiked serum and plasma samples; measurement uncertainty was evaluated according to the GUM. Equivalence to JCTLM-listed RMPs was determined using leftover samples from the RELA scheme. Results The candidate RMP was highly selective for progesterone within a measurement range of 0.0400–72.5 ng/mL (0.127–231 nmol/L) and matrix independent. Intermediate precision was ≤3.3 %, and repeatability ranged from 1.4 to 2.7 % across all concentration levels. The mean bias ranged from 0.1 to 0.7 % for secondary certified reference materials, from −1.6 % to −0.2 % for serum samples, and from −2.3 to 4.0 % for plasma samples. Expanded measurement uncertainty (k=2) for target value assignment (n=6) was found to be ≤3.7 %. Equivalence to JCTLM-listed RMPs demonstrated a relative bias of −2.4 to 2.2 %, all within the measurement uncertainty of the respective RMP. Conclusions A candidate RMP based on ID-LC-MS/MS for progesterone quantification is presented, providing metrological traceability, target value assignment, routine test standardization, and the analysis of clinical samples comprising human serum and plasma to ensure the accuracy and traceability of individual patient results.
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Quantitative analysis of phylloquinone (vitamin K1) and menaquinone (vitamin K2) in serum of Russians by liquid chromatography-tandem mass spectrometry

December 16, 2025

Mikhail Vokuev, Anastasia Frolova, Stepan Makarkin, Daria Prosuntsova, Timur Baygildiev, Lidia Nefedova, Oleg Klychnikov, Igor Rodin

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Objectives Vitamin K homologues are essential to human health, and their concentrations in biological samples serve as valuable diagnostic biomarkers. This study was aimed to develop a method for determining vitamins K1 (phylloquinone, VK1) and K2 (menaquinone, MK-4) in human serum. The proposed method was validated and applied to the serum of a cohort of 20 Russian individuals. Methods High-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was used to analyse the content of VK1 and MK-4 in serum. Atmospheric pressure chemical ionisation (APCI) in negative mode was applied to ionise VK1 and MK-4. Protein precipitation and solid-phase extraction (SPE) on polystyrene-divinylbenzene resin were combined to isolate and preconcentrate the analytes from serum. Results The HPLC-MSMS method was developed and validated for the determination of vitamins VK1 and MK-4 in human serum. The method demonstrated a lower limit of quantification (LLOQ) of 0.05 μg/L, with more than 71 % recoveries and precision within 17 %. To demonstrate the applicability of the method to real samples, serum from 20 healthy adults was analyzed. VK1 was detected in four individuals (0.094–0.96 μg/L), whereas MK-4 concentrations were below 0.22 μg/L in all cases. Conclusions The validated HPLC-MS/MS workflow provides a reliable and sensitive approach for the quantification of VK1 and MK-4 in minimal serum volumes. The method demonstrates robustness, reproducibility, and suitability for large-scale analytical applications. The proposed LC-MS/MS protocol successfully applied to native human serum samples, illustrating its applicability for future clinical and biochemical studies involving vitamin K.
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Implementation of an automated alert system of critical results in hospitalized and emergency patients

November 24, 2025

Angela García-de la Torre, Francisco J. Sánchez-Lora, Maria C. Navarrete-Ortiz, Paloma Trillo López, Carmen Ortiz-García, Gonzalo Méndez Alarcón, Marina Buforn-Jiménez, Andres Cobos-Diaz, Maria V. De la Torre-Prados

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Objectives The accurate and timely identification and notification of critical results (CR) are crucial to ensure patient safety and is an integral part of the process of medical validation of laboratory results. The objective of the study was to evaluate whether the implementation of an automated alert system care process based on CR from emergency department and inpatient units, could reduce the average length of stay and mortality. Methods A 2-year case-control study, where we compared the process of reporting CR by telephone with reporting via secure text messaging, in which the CR was directly communicated to the provider on their smartphone device. Results During the study, a total of 1,242 CR were included in the control group and 1,185 CR in the intervention group. Comparing pre- and post-implementation data, a significant improvement was observed in CR notification efficiency, with a marked reduction in turnaround time when using secure text messaging. Additionally, there was a significant decrease in the delay to first therapeutic intervention, average length of stay, and mortality. Conclusions Secure text messaging has facilitated the reporting of CR to targeted physicians to provide more effective care to their patients and to facilitate rapid and timely intervention.
Open Access
Comparative analysis of plasma p-tau217 immunoassays: challenges for standardization and harmonization

November 10, 2025

Burak Arslan, Johan Gobom, Ulf Andreasson, Fernando Gonzalez-Ortiz, Nicholas J. Ashton, Henrik Zetterberg, Hlin Kvartsberg

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From conventional to personalized reference intervals and decision limits: addressing latent errors in the post-post analytical phase

November 28, 2025

Abdurrahman Coskun, Jasmin Weninger, Ali Canbay, Mustafa Özcürümez

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Laboratory errors are an important component of medical errors and are predominantly associated with the extra-analytical phases of the total testing process, particularly the pre-pre-analytical and post-post-analytical phases, which are largely dependent on clinical activities but also require laboratory support. The post-post-analytical phase is the stage in which clinicians interpret patients’ laboratory data using population-based reference data, such as population-based reference intervals (popRIs) and population-based decision limits (popDLs), typically provided by the laboratory. To minimize errors in this phase, it is essential that more accurate tools – such as personalized reference intervals (prRIs) and personalized decision limits (prDLs) – are made available to clinicians. However, population-based references are still widely used, whereas their personalized counterparts have not yet been implemented in routine practice. The discrepancy between inadequate population-based references and more appropriate personalized references can introduce systematic yet latent errors in the interpretation of patients’ laboratory data, potentially compromising patient safety even when clinicians are highly competent in data interpretation. In this opinion paper, we (1) summarize the limitations of popRIs and popDLs, (2) develop the concept of latent errors, and (3) discuss how personalized RIs and personalized DLs can be used to reduce latent errors and enable more accurate interpretation of patient laboratory data.
Open Access
An isotope dilution-liquid chromatography-tandem mass spectrometry-based candidate reference measurement procedure for the quantification of mycophenolic acid glucuronide in human serum and plasma

November 10, 2025

Tobias Schierscher, Janik Wild, Neeraj Singh, Martina Bachmann, Julia Hoop, Friederike Bauland, Andrea Geistanger, Lorenz Risch, Christoph Seger, Judith Taibon

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Objectives A candidate reference measurement procedure (RMP) based on isotope dilution (ID) liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated to accurately measure serum and plasma concentrations of mycophenolic acid glucuronide (MPAG). Methods Quantitative nuclear magnetic resonance (qNMR) spectroscopy was utilized for determining the absolute content (mass fraction; g/g) of the reference material, thereby, establishing the traceability to SI units. Separation of MPAG from potential interferences, whether known or unknown, was accomplished by using a Phenomenex Luna C18(2) column. For sample preparation, a protocol based on protein precipitation followed by a high-dilution step was established. A multi-day validation experiment evaluated precision and accuracy. Reproducibility was determined by comparing the results of the procedure between two independent laboratories. Measurement uncertainty (MU) was assessed in accordance with current guidelines. Results The RMP demonstrated high selectivity and specificity enabling the quantification of MPAG in the range between 0.750 and 600 μg/mL. The intermediate precision and repeatability (n=60, measurements) were found to be in the range from 0.9 to 3.7 % for serum samples and from 1.2 to 4.6 % for plasma samples. The repeatability was less than 3.5 % for serum samples and less than 4.0 % for plasma samples. The relative mean bias ranged from −0.9 to 3.2 % for serum samples and from −0.3 to 2.9 % for plasma samples. The expanded measurement uncertainties (k=2) for single measurements ranged between 2.4 and 7.7 % and were further reduced performing a target value assignment (n=6) resulting in expanded measurement uncertainties between 1.8 and 3.3 % (k=2), respectively. Conclusions We herein present a new LC-MS/MS-based candidate RMP for MPAG in human serum and plasma which offers a traceable and reliable platform for the standardization of routine assays and evaluation of clinically relevant samples.
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Defining non-diabetic hypoglycemia: is there an appropriate plasma glucose threshold?

December 17, 2025

Tomás González-Vidal, Elías Delgado, Edelmiro Menéndez-Torre

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Serum GFAP as a biomarker for progression in multiple sclerosis: assay comparison and a large reference database of healthy controls

December 29, 2025

Eline A.J. Willemse, Sofia Sandgren, Pascal Benkert, Sabine Schaedelin, Aleksandra Maleska Maceski, Johanna Oechtering, Nafiye Genc, Klaus Berger, Marco Hermesdorf, Stefanie Müller, Sebastian Finkener, Juan F. Vilchez Gomez, Amar Zadic, Giulio Disanto, Marcus D’Souza, Cristina Granziera, Caroline Pot, Chiara Zecca, Patrice H. Lalive, Robert Hoepner, Patrick Roth, Marina Herwerth, Claudio Gobbi, David Leppert, Maximilian Einsiedler, Jens Kuhle

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Objectives Compare Elecsys (Roche) and Simoa (Quanterix) immunoassays for serum glial fibrillary acidic protein (GFAP) using our reference database and Z scores, and evaluate their prognostic value for progression independent of relapse activity (PIRA) in multiple sclerosis (MS). Methods Platform correlation was assessed in 612 samples from healthy controls (n=188; median [interquartile range, IQR] age 45.1 [36.4–61.7] years) and people with MS (n=424; 45.3 [35.2–53.9] years). Elecsys values were converted to Z scores via Passing-Bablok-derived regression and validated in fingolimod (n=414), and B-cell depleting therapy (BCDT; n=353) cohorts. Z scores and hazard ratios (HRs) for time-to-PIRA were compared using Cox regression. Results GFAP Simoa and GFAP Elecsys measurements were correlated (r=0.94), with Elecsys values ∼54 % lower (GFAP Elecsys , ng/L=2.847 [95 % confidence interval, CI: 1.335 – 4.98] + 0.457 [0.434 – 0.478] * GFAP Simoa , ng/L). In univariable Cox models, GFAP Simoa and GFAP Elecsys Z scores were associated with time-to-PIRA in both validation cohorts. In multivariable Cox models, higher GFAP Simoa Z scores were associated with shorter time-to-PIRA in fingolimod cohort (HR: 1.27 [95 % CI 1.08 – 1.50], p=0.0031) and trended toward significance in BCDT (1.18 [0.99 – 1.41, p=0.0693). In contrast, GFAP Elecsys Z scores were associated with time-to-PIRA in both cohorts (fingolimod: 1.27 [1.09 – 1.48], p=0.0023; BCDT: (1.19 [1.00 – 1.40], p=0.0487). Conclusions Serum GFAP measured by Elecsys shows a comparable association with time-to-PIRA as Simoa, and GFAP Simoa Z scores can be successfully bridged to GFAP Elecsys Z scores, supporting Elecsys`s potential for clinical implementation.
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Applying the Implementation Science to the harmonization of laboratory test results in the changing landscape

January 6, 2026

Mauro Panteghini

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Nowadays, we are facing major changes in the landscape of test harmonization through metrological traceability approach, all expected to promote equivalence of reported laboratory results. However, having traceability tools in place does not automatically mean that metrological traceability is correctly implemented. As concepts that are poorly implemented do not produce expected benefits, it is time to move from just discussing the effectiveness of traceability theory to how correctly implement it and effectively monitor its effects. In particular, considering the implementation outcomes, there is still a limited knowledge about the actual harmonization status of laboratory test results. We need to increase the information about the expected outcome by assessing result uniformity across different in vitro diagnostic medical devices (IVD-MDs) through an approach providing an ongoing robust evidence of standardization effectiveness. External Quality Assessment (EQA) programs have an irreplaceable role in this IVD traceability surveillance providing that they fulfill specific requirements. i.e., the use of commutable materials with target values assigned by reference measurement procedure (RMP) or strictly controlled procedures, if RMP does not exist, and with validation of results in relation to fit-for-purpose analytical performance specifications. If adequately designed, EQA programs can create evidence about intrinsic standardization status and equivalence of the examined IVD-MDs, serving as management tool for the medical laboratory and IVD manufacturers, and forcing them to investigate and eventually fix the identified problems. In this way, major stumbling blocks opposing the correct implementation of metrological traceability and the obtaining of harmonized laboratory results can be identified and removed.
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Effect of storage conditions on NSE, S100, and B2M stability in cerebrospinal fluid and serum

January 28, 2026

Natalia García-Sancha, Juan Valencia, Simón Gundín, María Martín, María Miranda, Anna Valls, Sara Calvo-Simal, Juan Arnáez

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Objectives The reliability of cerebrospinal fluid (CSF) and serum biomarkers depends on sample integrity, which is strongly influenced by storage conditions. While −80 °C is considered the gold standard for long-term preservation, it requires specialized infrastructure, whereas −20 °C is more accessible but may compromise protein stability. This study aimed to evaluate the stability of three clinically relevant biomarkers – neuron-specific enolase (NSE), S100, and β-2 microglobulin (B2M), associated with neuronal injury and neuroinflammation – in CSF and serum samples stored at −20 °C and −80 °C over different time periods. Methods A total of 63 CSF and 56 serum samples from pediatric patients were analyzed. Samples were stored at −20 °C (24 h and 6 months) and −80 °C (6 and 12 months). NSE and S100 were measured by electrochemiluminescence immunoassays and B2M by turbidimetric immunoassay. Biomarker variability was expressed as relative percentage change from baseline. A maximum permissible error of ±15 % for CSF and ±10 % for serum was selected. Results NSE and S100 were highly unstable at −20 °C. In CSF, after 6 months, NSE decreased by ∼74 % and S100 by ∼71 %; in serum, NSE declined by ∼54 % and S100 by ∼13 %. Remarkably, after only 24 h at −20 °C, CSF NSE dropped by 61 %. Storage at −80 °C largely preserved these two biomarkers, with declines below ∼15 % over 12 months. B2M levels remained stable under all conditions. The reduction in CSF NSE at −20 °C was strongly correlated with baseline concentrations. Conclusions CSF biomarkers NSE and S100 are highly susceptible to degradation at −20 °C, whereas B2M remains relatively stable. Strict adherence to −80 °C storage protocols is essential to ensure the reliability of biomarker-based diagnostics and research.

Journal Impact Factor	3.7	2024, Journal Citation Reports (Clarivate, 2025)
5-year Journal Impact Factor	3.8	2024, Journal Citation Reports (Clarivate, 2025)
Journal Citation Indicator	1.53	2024, Journal Citation Reports (Clarivate, 2025)
CiteScore	6.9	2024, Scopus (Elsevier B.V., 2025)
SCImago Journal Rank	0.952	2024, SJR (Scimago Lab, 2025; Data Source: Scopus)
Source Normalized Impact per Paper	1.306	2024, CWTS Journal Indicators (CWTS B.V., 2025; Data Source: Scopus)

Clinical Chemistry and Laboratory Medicine (CCLM)

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