Clinical chemistry and laboratory medicine最新文献

{"title":"The neglected issue of pyridoxal- 5' phosphate.","authors":"Mario Plebani, Joris Delanghe","doi":"10.1515/cclm-2025-0258","DOIUrl":"https://doi.org/10.1515/cclm-2025-0258","url":null,"abstract":"","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":"143662963","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":"Use of the BIOGROUP^® French laboratories database to conduct CKD observational studies: a pilot EPI-CKD1 study.","authors":"Claire Visseaux, Guillaume Pénaranda, Cécile Conte, Fanny Raguideau, Julien L'hirondel, Claire Vignault, Philippe Zaoui, Isabelle Sebaoun-Rivière","doi":"10.1515/cclm-2024-1399","DOIUrl":"https://doi.org/10.1515/cclm-2024-1399","url":null,"abstract":"<p><strong>Objectives: </strong>Medical biology is essential for diagnosing and monitoring cardio-reno-metabolic diseases. The EPI-CKD1 study utilizes data from Biogroup^® French laboratories to examine the burden of chronic kidney disease (CKD) and the effect of heart failure, and diabetes in an outpatient setting in order to address gaps in national databases that lack biological data.</p><p><strong>Methods: </strong>All adults (≥18 years) with at least one blood creatinine test between January 1st of 2021, and June 30th of 2022 were included. Key biomarkers measured included serum creatinine, estimated glomerular filtration rate (eGFR), hemoglobin A_1c, B-type natriuretic peptide (BNP), NT-Pro BNP, and urinary albumin/creatinine ratio (uACR).</p><p><strong>Results: </strong>Among a total of 4,061,208 adults with at least one blood creatinine test, 465,225 (11.5 %) had altered kidney function. Their mean age was 57.9 years (SD 18.8), with 56.7 % women. Diabetes was present in 8.3 %, and heart failure in 1.4 %. Altered kidney function standardized prevalence was estimated to 8.06 %, with an incidence of 5.10 %. Patients with end-stage CKD had an average of 7.9 eGFR measurements, compared to 2 for those with eGFR >60 mL/min/1.73 m². Older age, diabetes, and heart failure were associated with an increased risk of eGFR <60 mL/min/1.73 m².</p><p><strong>Conclusions: </strong>The EPI-CKD1 study demonstrates the utility of Biogroup^® data for large-scale observational studies, offering precise, medically relevant insights on patients at cardio-renal risk. Future studies should focus on data enrichment and long-term follow-up to deepen understanding.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656276","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":"Reliable detection of sex chromosome abnormalities by quantitative fluorescence polymerase chain reaction.","authors":"Camilla Mains Balle, Dorte L Lildballe, Ivonne Bedei, Ruth Luschka, Anne Skakkebæk, Simon Chang, Zeynep Agirman, Jan Keller, Axel Weber, Ramón E Schäfer, Johannes Becker-Follmann, Claus H Gravholt","doi":"10.1515/cclm-2024-1400","DOIUrl":"https://doi.org/10.1515/cclm-2024-1400","url":null,"abstract":"<p><strong>Objectives: </strong>Many patients with sex chromosome abnormalities (SCAs) are diagnosed late in life or remain undiagnosed, leading to delayed or inadequate medical intervention and care. This study aimed to develop a reliable, rapid and cost-effective test for identifying SCAs using a blood sample - an essential step toward establishing a neonatal screening program.</p><p><strong>Methods: </strong>A total of 360 blood samples (180 SCA patients, and 180 controls) were obtained from four cross-sectional studies of adult patients with SCAs and age-matched controls. Informed consent was collected, and all procedures followed the Declaration of Helsinki. Multiplex quantitative fluorescence polymerase chain reaction (QF-PCR) utilizing short tandem repeat (STR) and X-linked segmental duplication (SD) markers was performed. Results were analyzed using an automated algorithm. Deviant results were manually reviewed to differentiate errors in the PCR process from those in automated data analysis.</p><p><strong>Results: </strong>Following automated data analysis of QF-PCR results, the method accurately identified 174 SCA patients (sensitivity: 96.7 %) and 171 controls (specificity: 95.0 %). Mosaic karyotypes were particularly challenging to diagnose. Manual reanalysis of the QF-PCR results corrected all false positives, achieving 100 % specificity.</p><p><strong>Conclusions: </strong>This method is promising for reliable SCA detection in blood samples, offering cost-effectiveness and scalability. The specificity following automated data analysis was not satisfactory. The underlying PCR technique, however, demonstrated 100 % specificity, indicating that refining the automated analysis algorithm would significantly reduce false positive results. With further refinements, we believe this test would be highly suitable for further evaluation in a newborn screening setting.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656274","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 protocol for metabolomics data normalization and biomarker discovery in human tears.","authors":"Joan Serrano-Marín, Silvia Marin, Alberto Iglesias, Jaume Lillo, Claudia Garrigós, Toni Capó, Irene Reyes-Resina, Hanan Awad Alkozi, Marta Cascante, Juan Sánchez-Navés, Rafael Franco, David Bernal-Casas","doi":"10.1515/cclm-2024-1360","DOIUrl":"https://doi.org/10.1515/cclm-2024-1360","url":null,"abstract":"<p><strong>Objectives: </strong>Human tear analysis holds promise for biomarker discovery, but its clinical utility is hindered by the lack of standardized reference values, limiting interindividual comparisons. This study aimed at developing a protocol for normalizing metabolomic data from human tears, enhancing its potential for biomarker identification.</p><p><strong>Methods: </strong>Tear metabolomic profiling was conducted on 103 donors (64 females, 39 males, aged 18-82 years) without ocular pathology, using the AbsoluteIDQ™ p180 Kit for targeted metabolomics. A predictive normalization model incorporating age, sex, and fasting time was developed to correct for interindividual variability. Key metabolites from six compound families (amino acids, biogenic amines, acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, and sphingomyelins) were identified as normalization references. The approach was validated using Linear Discriminant Analysis (LDA) to test its ability to classify donor sex based on metabolite concentrations.</p><p><strong>Results: </strong>Metabolite concentrations exhibited significant interindividual variability. The normalization model, which predicted metabolite concentrations based on a reference \"concomitant\" metabolite from each compound family, successfully reduced this variability. Using the ratio of observed-to-predicted concentrations, the model enabled robust comparisons across individuals. LDA classification of donor sex using acylcarnitine C4 achieved 78 % accuracy, correctly identifying 92 % of female donors. This approach outperformed traditional statistical and machine learning methods (Lasso logistic regression and Random Forest classification) in sex discrimination based on tear metabolomics.</p><p><strong>Conclusions: </strong>This novel normalization protocol significantly improves the reliability of tear metabolomics by enabling standardized interindividual comparisons. The approach facilitates biomarker discovery by mitigating variability in metabolite concentrations and may be extended to other biological fluids, enhancing its applicability in precision medicine.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647527","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":"Is this quantitative test fit-for-purpose?","authors":"Arne Åsberg, Bjørn Johan Bolann","doi":"10.1515/cclm-2025-0194","DOIUrl":"https://doi.org/10.1515/cclm-2025-0194","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647514","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 biopsy in oncology: navigating technical hurdles and future transition for precision medicine.","authors":"Mengxiao Xie, Shiyang Pan, Mario Plebani","doi":"10.1515/cclm-2025-0271","DOIUrl":"https://doi.org/10.1515/cclm-2025-0271","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647516","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":"Artificial base mismatches-mediated PCR (ABM-PCR) for detecting clinically relevant single-base mutations.","authors":"Cia-Hin Lau, Kejiang Guo, Gang Chen, Minghai Zou, Zhongqi Zhou, Tao Wang, Zhihao Huang, Jiaqi Li, Wenjiao Dong, Yumei Huang, Pik Kwan Lo, Hongman Xue, Xiaojun Huang, Meijing Xu, Chung Tin, Haibao Zhu","doi":"10.1515/cclm-2024-0962","DOIUrl":"https://doi.org/10.1515/cclm-2024-0962","url":null,"abstract":"<p><strong>Objectives: </strong>Detecting point mutations with high sensitivity and specificity can be technically very challenging, but it is crucial for early diagnosis and effective drug treatment of cancers. To enable ultrasensitive and ultraspecific detection of single-base mutations in simple and economical ways, we have developed an artificial base mismatches-mediated PCR (ABM-PCR) detection approach.</p><p><strong>Methods: </strong>ABM-PCR was applied to quantitative PCR (qPCR) and droplet digital PCR (ddPCR) detection platforms. The impact of mismatches on the thermodynamic stability of the primer-template duplex and the ability of Taq polymerase to catalyze the extension was examined. Effects of the sequence, position, and the number of mismatches on genotyping performance were characterized.</p><p><strong>Results: </strong>As proof of principle, we demonstrated the feasibility of ABM-PCR in detecting epidermal growth factor receptor (EGFR) and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations that are clinically relevant to diagnosis and prognosis of lung and thyroid cancers. Our ABM-PCR enabled the detection of 0.1 % mutation without amplification of the wild-type DNA strand, even in the presence of a 300 ng human genomic DNA background. It enables ultrasensitive (≥95 %) and ultraspecific (≥95 %) diagnosis of clinical samples for thyroid papilloma and lung cancers. Based on these findings, we have established a set of rules and developed a user-friendly web primer design tool for designing effective ABM-PCR primers.</p><p><strong>Conclusions: </strong>This study highlights the impact of primer-template mismatches on PCR amplification and provides insights into rational design of effective ABM-PCR primers for detecting single-base mutations with high specificity and sensitivity. It is highly valuable for clinical diagnosis and prognosis use.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633681","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":"Impact of delayed centrifugation on the stability of 32 biochemical analytes in blood samples collected in serum gel tubes and stored at room temperature.","authors":"María Sanz-Felisi, Paula Tauler-Quetglas, Teresa Escartín-Díez, Ariadna Arbiol-Roca, Dolors Dot-Bach","doi":"10.1515/cclm-2025-0109","DOIUrl":"https://doi.org/10.1515/cclm-2025-0109","url":null,"abstract":"<p><strong>Objectives: </strong>Evaluate the stability of 32 biochemical analytes in venous blood samples stored at 18-25 °C under different time delays prior to centrifugation.</p><p><strong>Methods: </strong>A prospective study was conducted involving 33 healthy volunteers. Four venous blood samples were collected from each participant. One sample was designated as baseline and processed immediately according to the tube manufacturer's guidelines for centrifugation and analysis. The remaining three samples were stored under predefined conditions and centrifuged at different time intervals before undergoing analysis.</p><p><strong>Results: </strong>Acceptable stability over the maximum storage time of 8 h was observed for 25 of the analytes tested in this study. However, direct bilirubin became unstable at 6 h and triglycerides at 8 h of storage prior to centrifugation. Calcium, gamma-glutamyl transferase, glucose, inorganic phosphate and potassium were found to be unstable in serum after 4 h of delayed centrifugation.</p><p><strong>Conclusions: </strong>A delay in centrifugation of samples affected the stability of several analytes evaluated in the study, resulting in changes in their concentration or integrity. The analytical results for these analytes cannot be considered reliable as they do not meet the standards required for clinical validation. This underscores the importance of following stringent pre-analytical protocols to maintain the accuracy and reliability of laboratory diagnostic results.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623451","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":"Concordance between the updated Elecsys cerebrospinal fluid immunoassays and amyloid positron emission tomography for Alzheimer's disease assessment: findings from the Apollo study.","authors":"Henrik Schinke, Magnus Förnvik Jonsson, Mayme Gummesson, Rikard Nilsson, Stefanie Gaupp, Ekaterina Manuilova, Silja McIlwrick, Jan-Philipp Weinberger, Sandra Rutz, Margherita Carboni, Erik Stomrud","doi":"10.1515/cclm-2024-1476","DOIUrl":"https://doi.org/10.1515/cclm-2024-1476","url":null,"abstract":"<p><strong>Objectives: </strong>The Apollo study was designed to support the clinical performance verification of the adjusted cutoffs of the Elecsys^® β-Amyloid(1-42) (Aβ₄₂) cerebrospinal fluid (CSF) II, β-Amyloid(1-40) (Aβ₄₀) CSF, Phospho-Tau (181P) (pTau) CSF and Total-Tau (tTau) CSF immunoassays (Roche Diagnostics International Ltd) for measuring fresh CSF samples, and assess the concordance of the Elecsys CSF pTau/Aβ₄₂, tTau/Aβ₄₂ and Aβ₄₂/Aβ₄₀ ratios, as well as Aβ₄₂ alone, with amyloid positron emission tomography (PET) visual read status.</p><p><strong>Methods: </strong>The primary study endpoint was to assess the concordance of the Elecsys CSF ratios and Aβ₄₂ alone with amyloid PET visual read status using fresh CSF samples collected from individuals with subjective cognitive decline or mild cognitive impairment, handled with a new routine-use pre-analytical procedure and measured with the Elecsys CSF immunoassays. The sample stability after 1- to 13-week storage at -20 °C was also investigated in an exploratory analysis.</p><p><strong>Results: </strong>Of 108 screened individuals, 91 met the eligibility criteria, of whom 44.0 % were amyloid PET-positive and 56.0 % amyloid PET-negative. Positive percent agreement (PPA) and negative percent agreement, respectively, were 0.800 and 0.882 for pTau/Aβ₄₂, 0.775 and 0.902 for tTau/Aβ₄₂, and 0.950 and 0.824 for Aβ₄₂/Aβ₄₀. For Aβ₄₂, PPA was 0.975 and negative likelihood ratio was 0.039. Overall, 33 samples (36.3 %) were frozen at -20 °C for 1-13 weeks. All concentration recoveries were within 100 ± 10 % when stored at -20 °C for ≤8 weeks.</p><p><strong>Conclusions: </strong>Elecsys CSF ratios and Aβ₄₂ alone may be reliable alternatives to amyloid PET for identifying amyloid positivity in clinical practice.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604207","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":"Flow-cytometric MRD detection in pediatric T-ALL: a multicenter AIEOP-BFM consensus-based guided standardized approach.","authors":"Michaela Reiterová, Saskia Kohlscheen, Oscar Maglia, Simona Sala, Angela Schumich, Margarita Maurer-Granofszky, Giovanni Faggin, Pamela Scarparo, Elena Varotto, Zuzana Šestáková, Peter Švec, Tamar Feuerstein, Helly Vernitsky, Daniela Kužílková, Ondřej Hrušák, Barbara Buldini, Michael Dworzak, Monika Brüggemann, Giuseppe Gaipa, Tomáš Kalina","doi":"10.1515/cclm-2024-1503","DOIUrl":"https://doi.org/10.1515/cclm-2024-1503","url":null,"abstract":"<p><strong>Objectives: </strong>Risk-based stratification approaches using measurable residual disease (MRD) successfully help to identify T-acute lymphoblastic leukemia (T-ALL) patients at risk of relapse, whose treatment outcomes are very poor. Because of T-ALL heterogeneity and rarity, a reliable and standardized approach for flow cytometry (FC)-based MRD measurement and analysis is often missing.</p><p><strong>Methods: </strong>Within the international AIEOP-BFM-ALL-FLOW study group we made a consensus on markers and a standard operating procedure for common 8- and 12-color T-ALL MRD panels. Custom manufactured tubes with dried backbone antibodies were tested in parallel to local FC standards.</p><p><strong>Results: </strong>Altogether, 66 diagnostic and 67 day 15 samples were analyzed. We designed two guided MRD gating strategies to identify blast cells in parallel to expert-based evaluation. We proved that the optimized tubes allowed the correct identification of blast cells in all diagnostic samples. Both, expert and guided analysis of day 15 samples correlated to local standard (Spearman R=0.98 and R=0.94, respectively). Only in 2 (3 %) and 4 (6 %) patients expert gating and guided analysis results were substantially discordant from local standard, respectively. The cases that require an individualized approach may be partially identified at diagnosis through a rare immunophenotype or mixed phenotype acute leukemia status.</p><p><strong>Conclusions: </strong>Our work shows that standardized operating procedures together with guided analysis are applicable in a great majority of T-ALL cases. Further improvement of MRD detection is needed, as in some cases an individualized analytical approach is still required due to the challenging nature of the T-ALL phenotype.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604211","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}