Clinical chemistry and laboratory medicine最新文献

{"title":"Clinical vs. statistical significance: considerations for clinical laboratories.","authors":"Hamit Hakan Alp, Mai Thi Chi Tran, Corey Markus, Chung Shun Ho, Tze Ping Loh, Rosita Zakaria, Brian R Cooke, Elvar Theodorsson, Ronda F Greaves","doi":"10.1515/cclm-2025-0219","DOIUrl":"https://doi.org/10.1515/cclm-2025-0219","url":null,"abstract":"<p><p>Amongst the main perspectives when evaluating the results of medical studies are statistical significance (following formal statistical testing) and clinical significance. While statistical significance shows that a factor's observed effect on the study results is unlikely (for a given alpha) to be due to chance, effect size shows that the factor's effect is substantial enough to be clinically useful. The essence of statistical significance is \"negative\" - that the effect of a factor under study probably did not happen by chance. In contrast, effect size and clinical significance evaluate whether a clinically \"positive\" effect of a factor is effective and cost-effective. Medical diagnoses and treatments should never be based on the results of a single study. Results from numerous well-designed studies performed in different circumstances are needed, focusing on the magnitude of the effects observed and their relevance to the medical matters being studied rather than on the p-values. This paper discusses statistical inference and its relevance to clinical importance of quantitative testing in clinical laboratories. To achieve this, we first pose questions focusing on fundamental statistical concepts and their relationship to clinical significance. The paper also aims to provide examples of using the methodological approaches of superiority, equivalence, non-inferiority, and inferiority studies in clinical laboratories, which can be used in evidence-based decision-making processes for laboratory professionals.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802765","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":"IgA-type macroprolactin among 130 patients with macroprolactinemia.","authors":"Masayuki Ishihara, Naoki Hattori, Norito Nishiyama, Kozo Aisaka, Takashi Adachi, Takanori Saito","doi":"10.1515/cclm-2025-0264","DOIUrl":"https://doi.org/10.1515/cclm-2025-0264","url":null,"abstract":"<p><strong>Objectives: </strong>Macroprolactin (macro-PRL) mostly comprises a complex of PRL with IgG. The aim of this study was to clarify whether IgA-type macro-PRL exists and, if so, to elucidate the prevalence of and differences in laboratory data from IgG-type.</p><p><strong>Methods: </strong>One hundred thirty patients with macroprolactinemia who were diagnosed through screening via the polyethylene glycol precipitation method followed by confirmation using gel filtration chromatography (GFC) were examined. IgA-type and IgG-type macro-PRLs were identified via Jacalin column/SDS‒PAGE and protein G columns, respectively.</p><p><strong>Results: </strong>SDS‒PAGE under nonreducing conditions followed by western blotting with an IgA antibody revealed that the fraction bound to the Jacalin column was actually IgA. The PRL band was detected at the same position as the IgA band, which was purified with a Jacalin column, suggesting that PRL was bound to IgA. The finding that the PRL band was observed not only at the same position as IgA but also at the same position as the 23 kDa PRL reference suggested that some PRL dissociated from IgA during SDS‒PAGE. The prevalence rates of macro-PRL of only IgA, IgA plus IgG, only IgG, and non-IgA/non-IgG types were 7.7, 3.1, 83.8, and 5.4 %, respectively. Neither the PEG precipitation ratios of PRL nor the macro-PRL ratios on GFC differed between IgA- and IgG-type macro-PRLs, whereas both ratios were significantly lower in non-IgA/non-IgG-type macro-PRL.</p><p><strong>Conclusions: </strong>IgA-type macro-PRL was demonstrated to exist. IgG-type macro-PRL was most prevalent, followed by IgA, non-IgA/non-IgG and IgA plus IgG-type macro-PRLs.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802766","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":"Liquid chromatography tandem mass spectrometry (LC-MS/MS) candidate reference measurement procedure for urine albumin.","authors":"Seiei Shiba, Zoi E Sychev, Michael D Evans, Jesse C Seegmiller","doi":"10.1515/cclm-2024-1374","DOIUrl":"https://doi.org/10.1515/cclm-2024-1374","url":null,"abstract":"<p><strong>Objectives: </strong>Urine albumin is a key biomarker utilized for diagnosis and monitoring progression of chronic kidney disease (CKD). These characteristics highlight the importance urine albumin serves in patient management. However, laboratory results are confounded by a lack of standardization where results may exceed 40 % difference between diagnostic platforms. This presents serious issues since current guideline clinical decision points are fixed values and misclassification may occur between laboratory methods. Therefore, standardization is needed for urine albumin measurements.</p><p><strong>Methods: </strong>A liquid chromatography tandem mass spectrometry (LC-MS/MS) reference measurement procedure (RMP) was developed. This RMP employed proteolysis using trypsin and examined six peptides specific to human serum albumin. The National Institute of Standards and Technology 2925 reference material was used to value assign calibrators. To improve imprecision and accuracy, all samples were run in quadruplicate. Urine from 98 patient specimens was analyzed.</p><p><strong>Results: </strong>RMP final results consisted of averaging four peptide transitions, yielding a 20-day coefficient of variation (CV) of <3.0 %. Factors considered in assigning RMP overall uncertainty included specimen and internal standard pipetting, calibration material, and LC-MS/MS imprecision. This RMP was compared to the Roche Cobas and Siemens Dimension Vista urine albumin assays and was found to have a -9.9 and 20.1 % bias, respectively. This RMP was found to have equivalent results to two other RMPs in a previous study.</p><p><strong>Conclusions: </strong>This RMP demonstrated excellent imprecision, achieving an overall CV of 2.8 % and meeting the CV ≤6.2 % performance specification required for standardizing urine albumin measurements in clinical laboratories.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802781","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":"Improving the efficiency of quality control in clinical laboratory with an integrated PBRTQC system based on patient risk.","authors":"Xincen Duan, Tony Badrick, Wenqi Shao, Andreas Bietenbeck, Xiao Tan, Jing Zhu, Wenhai Jiang, Ying Zhao, Chunyan Zhang, Baishen Pan, Beili Wang, Wei Guo","doi":"10.1515/cclm-2025-0163","DOIUrl":"https://doi.org/10.1515/cclm-2025-0163","url":null,"abstract":"<p><strong>Objectives: </strong>Recent advances in information technology have renewed interest in patient-based real-time quality control (PBRTQC) as an alternative to internal quality control (IQC). However, since regulations mandate IQC, PBRTQC can only be implemented as a separate system. The additional labor required for PBRTQC may hinder widespread adoption. Therefore, a more efficient system that integrates IQC with PBRTQC is needed for laboratories to implement the methods effectively.</p><p><strong>Methods: </strong>A QC system that integrates IQC with PBRTQC is proposed. The maximum average number of patients with unacceptable analytical errors (MaxANP_TE) was introduced as a critical metric to benchmark the efficiency of the integrated PBRTQC system against the IQC-only system using a modified Parvin patient risk model. With the historical data of serum sodium (Na), chloride (Cl), alanine aminotransferase (ALT), and creatinine (CREA) from Zhongshan Hospital, Fudan University, in 2019, the integrated system incorporating the simple PBRTQC model and the more advanced regression-adjusted real-time quality control (RARTQC) were compared with the IQC-only system.</p><p><strong>Results: </strong>In most cases, the integrated system incorporating RARTQC models outperformed the IQC-only system, particularly for ALT, where QC events were reduced by up to 45 %. Based on these findings, we proposed strategies for laboratories to design the integrated system.</p><p><strong>Conclusions: </strong>The study demonstrated the improvement of efficiency of the integrated PBRTQC system over the IQC-only system. These insights can help laboratories make informed decisions on adopting PBRTQC models and provide as evidence for revising regulation on IQC.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771423","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":"Consensus instability equations for routine coagulation tests.","authors":"Rubén Gómez Rioja, Andrea Caballero Garralda, Immaculada Comas Reixach, Carlos García Miralles, María Antonia Llopis Díaz, Débora Martínez Espartosa, Reyes Nicolás de Blas, Mariona Panadès Turró, Laura Puigví Fernández, Laura Rodelgo Jiménen, Berta Sufrate-Vergara, Emma Ventura Orriols","doi":"10.1515/cclm-2025-0117","DOIUrl":"https://doi.org/10.1515/cclm-2025-0117","url":null,"abstract":"<p><strong>Objectives: </strong>The stability of plasma samples for basic coagulation tests, prothrombin time (PT) and activated partial thromboplastin time (aPTT), has been widely studied. Recently, the Clinical and Laboratory Standards Institute (CLSI) updated its recommendations, extending the acceptable time frame for aPTT. These guidelines are based on experimental studies, which define limits according to different maximum permissible error (MPE) criteria. This study compiles raw data from 43 studies published over the last 30 years to develop a consensus instability equation that describes degradation independently of specific study parameters.</p><p><strong>Methods: </strong>A critical literature review was performed by collecting studies that included experimental stability data for PT, aPTT and the main procoagulant factors. The raw data of percentage deviation (PD%), time, and seven classification variables related to sample collection and handling were analysed. A regression model through the origin was applied to derive global instability equations and to assess influencing variables.</p><p><strong>Results: </strong>In frozen samples, PT and aPTT showed similar stability, with an average prolongation of 0.8 % per month. In non-frozen samples, tube handling affected stability more than storage temperature. The consensus equation for PT showed a linear average deterioration of 2.9 % per day, but model strength was limited. For aPTT, the consensus equation fitted better to a logarithmic decay model and predicted prolongations of 6.1 and 10 % at 6 and 24 h, respectively.</p><p><strong>Conclusions: </strong>The consensus instability equations obtained in this review provide a robust model for assessing coagulation tests stability, aligning with expert recommendations. These equations improve the understanding of sample degradation and systematic error quantification.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742481","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":"Novel Mindray high sensitivity cardiac troponin I assay for single sample and 0/2-hour rule out of myocardial infarction: MERITnI study.","authors":"Kevin G Buda, Yader Sandoval, Stephen W Smith, Barrett Wagner, Karen Schulz, Anne Sexter, Fred S Apple","doi":"10.1515/cclm-2024-1387","DOIUrl":"https://doi.org/10.1515/cclm-2024-1387","url":null,"abstract":"<p><strong>Objectives: </strong>We determined the efficacy of a high sensitivity cardiac troponin I (hs-cTnI) assay for newly derived 0 h and 0/2-h rule-out concentrations for myocardial infarction and determined the safety of incremental changes at low concentrations.</p><p><strong>Methods: </strong>Consecutive, emergency department patients undergoing serial hs-cTnI testing on clinical indication were studied in the 'Mindray hs-cTnI Assay Analytical and Clinical Evaluation for the Diagnosis and RIsk Assessment of Myocardial InfarctIon' (MERITnI) trial. Primary safety outcome was the composite of cardiac death and MI at 30 days.</p><p><strong>Results: </strong>In 1,556 patients (60.7 % male, 43.3 % White, 45.8 % Black. 34.8 % chest pain), 26.9 % patients had at least one hs-cTnI >99th percentile. 2.7 % had type 1 MI, 2.7 % type 2 MI, and 21.5 % non-MI myocardial injury. Single-sample MI rule-out using a normal ECG plus hs-cTnI of <2 ng/L (rounded) ruled out 13.8 % of patients, including early (<2 h) presenters. A 2-h delta of <2 ng/L ruled out an additional 39 % of patients. Based on European Society of Cardiology guidance, derived 0 h<15 ng/L and derived delta of <5 ng/L ruled out 42 % of patients. The Mindray assay showed incremental (non-rounded) analysis discriminated rule out from baseline of <0.1 ng/L at 1.2 % to 2.0 ng/L at 17.0 %. There were no missed adverse outcomes at 30-day assessment for composite of MI and cardiac death.</p><p><strong>Conclusions: </strong>The novel Mindray hs-cTnI assay enabled safe and early rule out of MI and cardiac death at very low concentrations in a diverse, cohort utilizing both single sample and 0/2-h rule out protocols, including early presenters.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691174","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":"<i>Lab Error Finder</i>: A call for collaboration.","authors":"Hikmet Can Çubukçu","doi":"10.1515/cclm-2025-0317","DOIUrl":"https://doi.org/10.1515/cclm-2025-0317","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691171","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":"Reply to \"Is this quantitative test fit-for-purpose?\"","authors":"Sarah J Lord, Andrea Rita Horvath, Phillip J Monaghan, Sverre Sandberg, Patrick M Bossuyt","doi":"10.1515/cclm-2025-0291","DOIUrl":"https://doi.org/10.1515/cclm-2025-0291","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673267","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":"Targeted proteomics of serum IGF-I, -II, IGFBP-2, -3, -4, -5, -6 and ALS.","authors":"Jakob Albrethsen, Lylia Drici, Lea Marie Slot Vilmann, Stine A Holmboe, Charlotte Ehlers Thomsen, Veronica Lykke Rogaczewska Groendahl, Maud Eline Ottenheijm, Annelaura Bach Nielsen, Christina Christoffersen, Lise Aksglaede, Casper P Hagen, Nicolai J Wewer Albrechtsen, Anders Juul","doi":"10.1515/cclm-2024-1428","DOIUrl":"https://doi.org/10.1515/cclm-2024-1428","url":null,"abstract":"<p><strong>Objectives: </strong>The insulin-like growth factors (IGFs) regulate growth in humans. IGF-I and IGF binding protein (IGFBP)-3 are biomarkers in children with growth disorders. We investigate a targeted proteomics method for absolute quantitation of eight IGF protein family members in human serum, including the peptide hormones IGF-I and -II, and the six binding proteins IGFBP-2, -3, -4, -5, -6 and acid labile subunit (ALS).</p><p><strong>Methods: </strong>Serum preparation was optimized for targeted proteomics of IGF related proteins on a clinical LC-MS/MS platform (UHPLC coupled with Triple-Q MS). We created quality controls, standards and internal standards and 289 serum samples from healthy children and adolescents were measured in ten batches over two months. The method was compared to WHO reference standards, clinical and research immunoassays, and relative proteomics profiling.</p><p><strong>Results: </strong>The sensitivity and reproducibility were sufficient for most but not all IGF protein family members. Targeted proteomics correlated well with clinical immunoassays for IGF-I (R²=0.88) and for IGFBP-3 (R²=0.46), (p<0.001). The correlation between targeted proteomics and non-clinical immunoassays for IGF-II, IGFBP-2, -4, -5, -6 and ALS varied between proteins.</p><p><strong>Conclusions: </strong>We present a method for parallel quantification of IGF-I, IGFBP-3, 5 and ALS for clinical verification studies, whereas targeted proteomics of the five remaining IGF related proteins (IGF-II, IGFBP-2, -4, and -6) require further examination. The sensitivity of our new IGF-I method suggests a possible diagnostic role for targeted proteomics of IGF-I in the management of children with extremely low levels of circulating IGF-I.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673268","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":"Antiphospholipid IgG Certified Reference Material ERM^®-DA477/IFCC: a tool for aPL harmonization?","authors":"Claudia Grossi, Liesbet Deprez, Caterina Bodio, Maria Orietta Borghi, Suresh Kumar, Nicola Pozzi, Paolo Macor, Silvia Piantoni, Angela Tincani, Massimo Radin, Savino Sciascia, Gustavo Martos, Evanthia Monogioudi, Ingrid Zegers, Joanna Sheldon, Rohan Willis, Pier Luigi Meroni","doi":"10.1515/cclm-2025-0032","DOIUrl":"https://doi.org/10.1515/cclm-2025-0032","url":null,"abstract":"<p><strong>Objectives: </strong>The Certified Reference Material (CRM) ERM^®-DA477/IFCC is a new polyclonal IgG anti-beta2-glycoprotein I (anti-β2GPI) material for the harmonization of the laboratory diagnosis of antiphospholipid syndrome (APS). We evaluated CRM's ability to represent the heterogeneity of APS patient anti-β2GPI antibodies and to calibrate IgG anti-β2GPI methods.</p><p><strong>Methods: </strong>We characterized CRM for its reactivity against domain-1, using the QUANTA Flash^® β2GPI-domain-1 assay, and against domains-4-5 of β2GPI, and single-domain-deleted β2GPI molecules using in-house ELISAs. We used QUANTA Lite^® ELISA, QUANTA Flash^® CLIA, and EliA™ FEIA methods to evaluate the CRM's anti-Cardiolipin (anti-CL) activity. Four anti-β2GPI IgG methods (in-house and QUANTA Lite^® ELISA, QUANTA Flash^® CLIA, and EliA™ FEIA) were also used to evaluate the CRM's calibration efficacy, alongside 133 clinical samples (CSs) and 99 controls.</p><p><strong>Results: </strong>The CRM showed high anti-domain-1 activity and no anti-domain-4-5 activity at the recommended assay dilution. The domain-dependent-β2GPI reactivity profiles were comparable with full-blown APS. There was acceptable dilution linearity for anti-CL assays with R² ranging from 0.957 to 0.997. For the four anti-β2GPI IgG assays, calibration with the CRM led to a good comparability of the average result of CSs for two of the assays. New cut-offs calculated from this work improved comparability in quantitative results between three of the assays: 85 % concordance with CRM compared to 66 % concordance with assay-specific-calibration.</p><p><strong>Conclusions: </strong>The CRM is representative of patient anti-β2GPI/CL heterogeneity and should improve anti-β2GPI IgG method harmonization. However, the level of achievable method harmonization is affected by differences in the selectivity among the assays.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662962","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}