Volume 64, Issue 4

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.

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.

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.

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.

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.

Objectives To maximize participation in the international standardization effort, this recommendation aims to update the international guidance of the Working Group on Laboratory Errors and Patient Safety of the International Federation of Clinical Chemistry and Laboratory Medicine by identifying a limited and globally applicable panel of Essential Quality Indicators (QIs) focused on patient safety, clinical outcomes, and harmonization across medical laboratories. Methods Through a consensus meeting, experts from multiple countries reviewed the IFCC Model of Quality Indicators (MQI) to identify high-priority indicators. Selection prioritized the probability of patient harm, ease of detection, and feasibility of data collection and implementation within national contexts. Results Six essential QIs covering the total testing process were identified and ratified: (1) rate of misidentified requests (Pre-MisR) and misidentified samples (Pre-MisS); (2) rate of sample rejections (Pre-RejS); (3) rate of hemolysis detected either by automated hemolysis index (Pre-HemI) or visual inspection (Pre-HemV); (4) rate of unacceptable results in External Quality Assessment/Proficiency Testing (Intra-Unac); (5) turnaround time of cardiac troponin at the 90th percentile for the emergency room (Post-TnTAT, Post-TnTAT clin); and (6) rate of incorrect laboratory reports (Post-RectRep). Recommendations on calculation, reporting frequency, and integration into IFCC and national comparison programs are provided. Conclusions The proposed essential QI panel provides a standardized and feasible framework to support its integration into national comparison programs and the IFCC MQI platform. Its implementation will facilitate data consolidation, strengthen the development of national and global quality specifications, and contribute to continuous improvement in patient safety.

Recreational nitrous oxide (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.

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.

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.

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.

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.

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.

Objectives As (a lack of) vitamin D has been linked to a wide variety of chronic diseases, there is growing interest in generating robust epidemiological data. Consequently, the need for large-scale biological sample collection has increased. In this context, dried blood spot (DBS) microsampling offers a minimally invasive alternative to venous sampling. However, to allow interpretation of DBS-based 25-hydroxyvitamin D (25-(OH)D) results, the set-up of a clinical validation study is essential to assess the agreement with the reference matrix, plasma. Methods Venous plasma and whole blood, venous DBS (vDBS) and capillary DBS (cDBS) were collected from 44 healthy volunteers to evaluate the agreement between the different sample types for 25-(OH)D quantification. To transform cDBS-based results to plasma concentrations, a hematocrit (Hct)-dependent conversion factor was applied and evaluated using four different Hct determination approaches. All samples were analysed using previously described validated LC-MS/MS methods. Results No clinically relevant methodological (vDBS vs. whole blood) or sampling-site related (cDBS vs. vDBS) issues were observed. Following Hct-dependent conversion, good agreement between the cDBS-derived and actually measured plasma results was obtained, as 90 % of the results lay within 20 % of the plasma result, independent of the Hct approach used. Additionally, weighted Cohen’s kappa values of 0.83–0.85 were obtained across the different Hct approaches, indicating substantial to almost perfect agreement in vitamin D status classification. Conclusions Following Hct-dependent conversion, cDBS can be used as a reliable and practical alternative matrix to plasma for large-scale monitoring of vitamin D status in epidemiological and public health contexts.

Objectives 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.

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).

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.

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.

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.

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.

Objectives The Fourth Universal Definition of Myocardial Infarction recommends high-sensitivity cardiac troponin (hs-cTn) as the preferred biomarker for diagnosing myocardial infarction. This study evaluated the analytical and clinical performance of a novel hs-cTnT chemiluminescence immunoassay (CLIA) developed by Mindray. Methods Analytical performance characteristics including precision, sensitivity (limit of detection [LoD] and limit of quantification [LoQ]), imprecision profile, linearity, sample type comparison, method comparison, and potential interferences were assessed. Sex-specific 99th percentile upper reference limits (URLs) were established in 895 healthy individuals. Clinical diagnostic performance was evaluated in 559 patients with suspected acute myocardial infarction and compared with the Roche hs-cTnT assay. Results The Mindray assay showed excellent precision (repeatability CV≤1.99 %, within-laboratory precision CV≤6.11 %), superior sensitivity (LoD: 1.4 ng/L; LoQ: 2.4 ng/L), and linearity (r=0.9978), along with robust performance against common and immunological interferences. Using the manufacturer-claimed LoD of 2.0 ng/L, measurable values were found in 99.36 % of males, 83.26 % of females, and 91.48 % overall, meeting criteria for high-sensitivity assays. The derived sex-specific 99th percentiles were 18.6 ng/L (males), 9.6 ng/L (females), and 16.0 ng/L (overall). In the clinical cohort, the assay showed 100.0 % sensitivity, 83.3 % specificity, 80.0 % PPV, 100.0 % NPV, and an AUC of 0.988, comparable to the Roche Gen 5 hs-cTnT assay. Conclusions The Mindray hs-cTnT (CLIA) assay meets high-sensitivity assay criteria and demonstrates robust analytical and diagnostic performance, offering a reliable alternative to the Roche Gen 5 assay for clinical evaluation of myocardial injury.

Objectives 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.

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.

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.