Clinical chemistry and laboratory medicine最新文献

{"title":"Impact of dried blood spot diameter and transit time on analyte concentrations and cut-off classification in routine newborn screening.","authors":"Nick Flynn, Sarah Hogg, Stuart J Moat","doi":"10.1515/cclm-2026-0976","DOIUrl":"https://doi.org/10.1515/cclm-2026-0976","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the effect of dried blood spot (DBS) diameter and specimen transit time on newborn screening (NBS) analyte concentrations and classification against cut-off values (CoV) using routine NBS data.</p><p><strong>Methods: </strong>DBS size and quality were assessed using a validated computer vision algorithm. Ordinary least squares analysis assessed associations between differences in DBS diameter and differences in within-batch duplicate thyroid stimulating hormone (TSH, n=1,101) and immunoreactive trypsinogen (IRT, n=2,581) results, and between specimen transit time and initial TSH (n=175,774), IRT (n=225,602), amino acids and acylcarnitine (n=227,032) results. The impact of pre-analytical factors on classification against CoVs was modelled using routine NBS data (n=256,554).</p><p><strong>Results: </strong>Differences in DBS diameter were positively associated with percentage concentration differences for both TSH (3.03 % per mm, 95 % CI: 1.87-4.19) and IRT (3.05 % per mm, 95 % CI: 1.96-4.15). Methionine and TSH decreased by 3.79 % (95 % CI: 3.67-3.91) and 2.53 % (95 % CI: 2.24-2.82) respectively, per additional day in transit. Methionine instability showed seasonal variation, with greater declines during wetter months. DBS diameter and transit time were estimated to influence classification against CoVs in 636 (95 % CI: 507-843) UK results annually. Reclassification risk increased for DBS specimens outside the recommended diameter range (8-14 mm; IRT risk ratio: 3.7, 95 % CI: 1.8-7.5) and for transit times ≥7 days (methionine risk ratio 48.6, 95 % CI: 16.9-139.8).</p><p><strong>Conclusions: </strong>DBS size and transit time affect analyte concentrations and classification against screening CoVs. Pre-analytical quality should be optimised to reduce its impact on NBS result classification.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"False-positive fentanyl colorimetric urine screening caused by risperidone: a diagnostic pitfall.","authors":"Annagiulia Di Trana, Adele Di Stefano, Manuela Pellegrini, Simona Pichini","doi":"10.1515/cclm-2026-1260","DOIUrl":"https://doi.org/10.1515/cclm-2026-1260","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biogenic amines as neuroendocrine tumor markers: limitations and future perspectives.","authors":"Maria Mellova, Ales Vicha, Richard Prusa, Tomas Zima, Eva Klapkova","doi":"10.1515/cclm-2026-0955","DOIUrl":"https://doi.org/10.1515/cclm-2026-0955","url":null,"abstract":"<p><p>Biogenic amines and their metabolites are central biochemical markers in the diagnosis and management of catecholamine-producing neuroendocrine tumors, including pheochromocytoma, paraganglioma, and neuroblastoma. Despite decades of clinical use, their wider implementation remains limited by substantial physiological variability, pre-analytical influences, and methodological heterogeneity across laboratories. The transition from colorimetric and immunoassay-based techniques to liquid chromatography-tandem mass spectrometry has markedly improved analytical sensitivity and specificity. The multiplexing capacity of modern mass spectrometric platforms has enabled comprehensive quantification of biogenic amine profiles, thereby increasing diagnostic sensitivity in tumor subtypes in which individual biomarkers exhibit limited performance. Increasing attention has been given to dopamine derived metabolites, especially 3-methoxytyramine, which is associated with MYCN-related tumor biology and unfavorable clinical outcomes in neuroblastoma and selected paraganglioma subtypes. However, the analytical complexity of mass spectrometric approaches, together with the absence of full metrological traceability, continues to limit inter-laboratory comparability. In this review, we critically evaluate the analytical evolution of biogenic amine testing, the principal pre-analytical and methodological determinants that influence the interpretation of results, and current efforts to improve harmonization. Particular emphasis is placed on the potential of biogenic amines as prognostic biomarkers and on the need to integrate expanded biogenic amine profiling into clinically robust, comparable diagnostic approaches that may advance precision oncology.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collaborating with AI for procurement drafting in laboratory medicine.","authors":"Andrea Bartolini, Margherita Scapaticci, Rita Mancini","doi":"10.1515/cclm-2026-1518","DOIUrl":"https://doi.org/10.1515/cclm-2026-1518","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An age-stratified semiquantitative urine ACR triage strategy for quantitative confirmation: a retrospective diagnostic accuracy study with temporal validation.","authors":"Marina Núñez Pérez, Rufino Mondéjar, Margarita Garcés Santos, María Del Mar Viloria Peñas","doi":"10.1515/cclm-2026-1298","DOIUrl":"https://doi.org/10.1515/cclm-2026-1298","url":null,"abstract":"<p><strong>Objectives: </strong>Early detection of albuminuria is important for identifying individuals at risk of chronic kidney disease (CKD) progression. Semiquantitative urine albumin-to-creatinine ratio (ACR) strips may serve as an initial laboratory screening or triage tool. However, screening strategies generally apply a single fixed threshold, regardless of patient age. Because CKD prevalence increases with age, a single cut-off does not account for differences in pre-test probability across age groups, potentially resulting in different trade-offs between quantitative confirmation and false-negative classification. We evaluated an age-adjusted threshold approach to improve diagnostic safety while reducing the number of quantitative ACR confirmations required.</p><p><strong>Methods: </strong>Semiquantitative ACR strip results (UC-3500, Sysmex) and quantitative ACR values (Alinity c, Abbott) were collected and analyzed. Diagnostic performance indicators for ACR strip testing were evaluated across different decision thresholds in the overall population and among age groups (18-44, 45-64 and ≥65 years), using quantitative ACR measurement as the reference standard.</p><p><strong>Results: </strong>Selected thresholds were 30, 30, and 15 mg/g creatinine for the 18-44, 45-64, and ≥65-year age groups with false omission rates (FOR) of 1.36 %, 3.97 % and 4.47 %, respectively. Overall, the age-stratified strategy yielded a sensitivity of 85.60 %, a NPV of 96.44 % and a FOR of 3.56 %, while avoiding 65.16 % of quantitative ACR measurements.</p><p><strong>Conclusions: </strong>In this retrospective simulation, an age-stratified reflex-testing strategy provided a balance between reducing quantitative ACR measurements and limiting the residual probability of ACR ≥30 mg/g creatinine following a negative semiquantitative result. The strategy used more sensitive thresholds in older patients, in whom albuminuria prevalence was higher, while allowing a greater reduction in quantitative testing in younger groups. These findings were reproducible in a temporal internal validation cohort but require external and local validation before implementation in other laboratories.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Routine laboratory data are decoupled from symptom phenotype and prognosis in Long COVID: within-cohort variation is dominated by age.","authors":"Viola Oberhauser, Thomas Perkmann, Patrick Mucher, Peter Quehenberger, Monika Fritzer-Szekeres, Thomas Szekeres, Rodrig Marculescu-Ferrari, Ena Hasimbegovic, Antonia Domanig, Kevin Hamzaraj, Laura Poschenreithner, Lisbona Kastrati, Dominika Lukovic, Emilie Han, Jutta Bergler-Klein, Oswald F Wagner, Mariann Gyöngyösi, Helmuth Haslacher","doi":"10.1515/cclm-2026-1238","DOIUrl":"https://doi.org/10.1515/cclm-2026-1238","url":null,"abstract":"<p><strong>Objectives: </strong>Long COVID is defined by persistent multi-organ symptoms without an alternative diagnosis. This study evaluated whether routine laboratory data collected under real-world conditions differentiate symptom-defined subgroups within an outpatient cohort and predict the course.</p><p><strong>Methods: </strong>In this single-center cohort study of 564 Long COVID patients (1,452 visits), symptom phenotypes were derived by latent class analysis of 19 organ-system domains at baseline. Structure in 89 routine analytes was sought by k-means clustering, confirmed with alternative algorithms, and repeated after age residualization. Analytes were compared across phenotypes using Kruskal-Wallis tests with false-discovery-rate control and adjustment for confounders. Equivalence testing was performed against reference change values. The course was modeled by count models. Prediction of improvement used a nested cross-validated elastic net with a baseline-independent endpoint.</p><p><strong>Results: </strong>Clustering showed no convincing structure (silhouette ≤0.09, two to eight clusters); the weak split tracked age (50.5 vs. 38 years) and vanished after residualization. Three age-independent phenotypes (n=503) had no laboratory correlate: none of 89 analytes survived FDR correction, with or without adjustment, or across 50 pseudo-class draws. Equivalence held for 86/89 analytes within ±0.5 SD and 63/70 within the reference change value. Symptom burden declined (median 4 to 2 organ systems, p=2.5 × 10^-19); however, no analyte predicted the course (AUC 0.46).</p><p><strong>Conclusions: </strong>Routine laboratory variation in this cohort was dominated by age and decoupled from symptom phenotype in both directions. Routine testing in a real-world setting could not provide an age-independent diagnostic, subtyping, or prognostic signature in a cohort of patients suffering from Long COVID.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A preanalytical quality indicator framework for automated extracellular vesicle separation.","authors":"Anna Maria Zimbo, Valentina Crapella, Selena Mimmi, Elisabetta Pingitore, Anna Maria Tolomeo, Khushboo Fatima, Annarita Scardamaglia, Costanza Maria Cristiani, Giovanni Di Salvo, Domenico Maisano, Mario Plebani, Kenneth W Witwer, Andrea Quattrone, Aldo Quattrone, Enrico Iaccino","doi":"10.1515/cclm-2026-1230","DOIUrl":"https://doi.org/10.1515/cclm-2026-1230","url":null,"abstract":"<p><strong>Objectives: </strong>Clinical translation of extracellular vesicle (EV)-based diagnostics is constrained by preanalytical variability in separation workflows. We developed a preanalytical quality indicator framework for automated EV separation, anchored to IFCC, EFLM, and MISEV2023 standards. This proof-of-concept study establishes analytical prerequisites; validation in disease cohorts is required before clinical implementation.</p><p><strong>Methods: </strong>Paired serum and plasma from 10 healthy controls were processed by EXODUS, Summit, and manual SEC. Endpoints included NTA yield, particle-to-protein ratio (PPR), intra-matrix reproducibility (CV%), and tetraspanin preservation (CD9, CD63, CD81) by SP-IRIS.</p><p><strong>Results: </strong>EXODUS achieved the highest particle concentration and PPR, exceeding SEC-based methods by 5- to 10-fold. Summit showed the lowest process variation (CV% <20 %) in serum (18.9 %) and plasma (16.5 %), satisfying IFCC-EFLM robustness criteria. Manual SEC showed the highest variability (serum: 55.3 %; plasma: 45.5 %). SP-IRIS revealed comparable tetraspanin detection across EXODUS and Summit, with qEV showing lower intensity. Summit confirmed superior scalability (4-48 samples/run, 10-15 min hands-on time).</p><p><strong>Conclusions: </strong>This proof-of-concept framework establishes analytical prerequisites. No single platform optimizes all parameters; selection should be driven by intended application: EXODUS for sensitivity-limited discovery, Summit for analytical standardization, manual SEC for morphological reference. Validation in disease cohorts is required before clinical implementation.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low PaO₂ with normal saturation: beyond leukocyte-mediated hypoxemia.","authors":"Gerald S Zavorsky, Kaila A Labrador","doi":"10.1515/cclm-2026-1313","DOIUrl":"https://doi.org/10.1515/cclm-2026-1313","url":null,"abstract":"<p><strong>Objectives: </strong>Spurious hypoxemia - a low PaO₂ with preserved, directly measured oxyhemoglobin saturation (sO₂) - is traditionally attributed to extreme leukocytosis or thrombocytosis (\"leukocyte larceny\"). We assessed how often it instead reflects PaO₂ temperature reporting or neonatal fetal-hemoglobin physiology.</p><p><strong>Methods: </strong>We retrospectively analyzed 7,473 arterial blood-gas specimens from 2,647 patients (September 2020-January 2026) with co-oximetry-derived sO₂, complete blood count, and metabolic panel data; regression analyses used the 7,431 specimens reported within 80 min of collection. Spurious hypoxemia was defined as PaO₂<60 torr (8.0 kPa) referenced to 37 °C at measured pH, with sO₂≥92 %. Firth logistic regression, Kaplan-Meier analysis, and receiver-operating-characteristic curves evaluated temperature correction, neonatal status, and extreme leukocytosis (≥50 × 10⁹/L) or thrombocytosis (≥500 × 10⁹/L).</p><p><strong>Results: </strong>Spurious hypoxemia affected 74 specimens (1.0 %). Among hypothermic specimens, the apparent rate fell from 3.5 % with PaO₂ reported at patient temperature to 0.9 % when referenced to 37 °C. Rates were higher in normothermic infants than adults (5.4 vs. 0.3 %), consistent with fetal hemoglobin. Extreme leukocytosis was associated with the outcome (adjusted odds ratio 20.2; 95 % confidence interval 5.6-60.9), but all four events occurred in neonates. Longer collection-to-reporting time was modestly associated (odds ratio 1.45 per 10 min), mainly in neonates. No non-neonatal specimen with a white-cell count ≥30 × 10⁹/L met the outcome (0/139), and extreme thrombocytosis showed no association (0/126).</p><p><strong>Conclusions: </strong>Apparent spurious hypoxemia was more often explained by temperature reporting and fetal hemoglobin than oxygen metabolism by leukocytes; the leukocytosis signal could not be separated from neonatal physiology. Laboratories should identify the PaO₂ reporting temperature, and clinicians should consider fetal-hemoglobin physiology before invoking leukocyte-mediated hypoxemia in neonates.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring serum bile acid variability: population-based concentration ranges and impact of lifestyle factors in an adult population.","authors":"Ida Erngren, Morgan Lundgren, Aina Vaivade, Henrik Carlsson, Asma Al-Grety, Anna Karin Hedström, Ingrid Kockum, Lars Alfredsson, Anders Larsson, Joachim Burman, Torbjörn Åkerfeldt, Peter Ridefelt, Kim Kultima","doi":"10.1515/cclm-2026-0809","DOIUrl":"https://doi.org/10.1515/cclm-2026-0809","url":null,"abstract":"<p><strong>Objectives: </strong>Bile acids (BAs) play crucial roles in digestion and metabolic regulation, and their composition is increasingly recognised as relevant to health and disease. This study aimed to establish population-based concentration ranges (2.5th-97.5th percentiles) for 24 individual serum BAs and assess the influence of demographic and lifestyle factors in a large cohort of Swedish adults.</p><p><strong>Methods: </strong>Serum samples from 931 Swedish adults were analysed using liquid chromatography-high-resolution mass spectrometry. Population-based concentration ranges were calculated for individual BAs, and associations with sex, age, BMI, sampling time, smoking, Swedish snuff use, serum cotinine, alcohol consumption, and ancestry were evaluated.</p><p><strong>Results: </strong>We found extensive interindividual variability in BA concentrations. The most abundant BAs were glycine-conjugated forms, while primary unconjugated BAs exhibited the largest concentration ranges, differing by over 1,000-fold between individuals. Sex-specific patterns emerged, with men showing significantly higher levels of unconjugated BAs. Age and BMI were negatively associated with taurine-conjugated BAs, and weak time-of-day variations were observed for several conjugated BAs. Lifestyle factors such as smoking, assessed through self-report and serum cotinine, showed stronger associations with BA levels than alcohol or ancestry, notably with increased murideoxycholic acid (MDCA) and reduced conjugated BA levels among nicotine users.</p><p><strong>Conclusions: </strong>These findings provide robust serum concentration ranges and highlight key variables that may confound BA biomarker interpretations, emphasising the need to consider sex, age, BMI, and lifestyle in future clinical and epidemiological applications.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrotroponin I interference with point-of-care high sensitivity assays: findings from a preliminary analytical verification study of three methods.","authors":"Marcela P Nascimento, Matthew Nguyen, Aloha Villadiego, Rhonalyn Hernandez, Catherine Woods, Marie Salib","doi":"10.1515/cclm-2026-0563","DOIUrl":"https://doi.org/10.1515/cclm-2026-0563","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}