Clinical chemistry最新文献

{"title":"Genomic Data and Privacy.","authors":"Candace T Myers, Runjun D Kumar, Lisa Pilgram, Luca Bonomi, Mara Thomas, Obi L Griffith, Stephanie M Fullerton, Richard A Gibbs","doi":"10.1093/clinchem/hvae184","DOIUrl":"https://doi.org/10.1093/clinchem/hvae184","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"71 1","pages":"10-17"},"PeriodicalIF":7.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921009","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":"Performance of Noninvasive Tests for Metabolic Dysfunction-Associated Steatohepatitis and Liver Fibrosis Resolution after Bariatric Surgery","authors":"Giulia Angelini, Simona Panunzi, Maurizio Pompili, Laura Riccardi, Matteo Garcovich, Ornella Verrastro, Sara Russo, Tracey Mare, James Luxton, Carel W le Roux, Marco Raffaelli, Geltrude Mingrone, Royce P Vincent","doi":"10.1093/clinchem/hvae208","DOIUrl":"https://doi.org/10.1093/clinchem/hvae208","url":null,"abstract":"Background Noninvasive tests (NITs) to monitor metabolic dysfunction-associated steatohepatitis (MASH) progression and response to interventions are needed because of the risks of liver biopsy. A monocytes-based diagnostic test using perilipin-2 (PLIN2) and Ras-related protein-14 (RAB14) predict the severity of MASH and fibrosis. Here we compared the performances of PLIN2 and RAB14 with cytokeratin-18 (CK18) assessed by Ella™ or M65 ELISA in predicting MASH and fibrosis resolution following bariatric surgery in a longitudinal and histologically characterized cohort of individuals with obesity. Methods Participants in the BRAVES randomized controlled trial underwent ultrasound-guided needle liver biopsy at baseline and 1 year after surgery. We evaluated NITs’ performance using area under the receiver operating characteristic and calculated accuracy, sensitivity, and specificity based on the Youden threshold. Univariable and multivariable logistic models were used to assess the role of recorded covariates in predicting MASH and fibrosis severity, as well as resolution or improvement. Results After surgery, patients who experienced MASH improvement or resolution showed a significant decrease in PLIN2 expression as compared to those who did not, while patients with fibrosis improvement displayed an increase in RAB14. No differences were found for CK18. The diagnostic accuracy of PLIN2 and RAB14 for the prediction of MASH resolution or fibrosis improvement was superior to CK18 assessed by either Ella or M65 ELISA. Conclusions PLIN2 and RAB14, but not CK18, are markers for monitoring improvements in MASH and fibrosis after interventions such as bariatric surgery. This may reduce or eliminate the need for frequent liver biopsies. ClinicalTrials.gov Registration Number: NCT03524365","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"4 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902272","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":"The Application of Digital PCR as a Reference Measurement Procedure to Support the Accuracy of Quality Assurance for Infectious Disease Molecular Diagnostic Testing.","authors":"Samreen Falak,Denise M O'Sullivan,Megan H Cleveland,Simon Cowen,Eloise J Busby,Alison S Devonshire,Esmeralda Valiente,Gerwyn M Jones,Martin Kammel,Mojca Milavec,Laura Vierbaum,Ingo Schellenberg,Heinz Zeichhardt,Andreas Kummrow,Peter M Vallone,Rainer Macdonald,Jim F Huggett","doi":"10.1093/clinchem/hvae187","DOIUrl":"https://doi.org/10.1093/clinchem/hvae187","url":null,"abstract":"BACKGROUNDNucleic acid amplification tests (NAATs) assist in the diagnosis of numerous infectious diseases. They are typically sensitive and specific and can be quickly developed and adapted. Far more challenging is the development of standards to ensure NAATs are performing within specification; reference materials take time to develop and suitable reference measurement procedures (RMPs) have not been available. This study investigated digital PCR (dPCR) RMP delivery of traceability for NAAT external quality assessment (EQA).METHODSThree National Metrology Institutes (NMIs) applied reverse transcription (RT)-dPCR as a candidate RMP to estimate the RNA quantity in 32 independent severe acute respiratory syndrome coronavirus 2 materials. The results were combined to value assign the respective materials: 21 materials were used in 6 rounds of EQA over 17 months for 61 laboratories for COVID-19 testing results compared with reference values.RESULTSThe agreement between the 3 NMIs showed <2-fold difference between laboratories. EQA laboratory reverse transcription quantitative PCR (RT-qPCR) values estimation of viral RNA quantity showed good median agreement with RT-dPCR reference value; however, RT-qPCR differences were generally between 10- and 50-fold between laboratories.CONCLUSIONThis work demonstrates how RT-dPCR can provide reference values for whole virus materials for NAAT quality assurance. RT-dPCR values guided EQA control material selection and provided EQA participants with traceability to RNA copy number delivered through the RMP. This approach can be used to support routine reference material use as well as to standardize quality assurance for NAATs where established reference materials are not available, such as in disease outbreaks.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"130 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887495","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":"Transitioning Alzheimer Disease Blood Biomarkers into Primary Care: Are We There Yet?","authors":"Katheryn A Q Cousins,Leslie M Shaw","doi":"10.1093/clinchem/hvae211","DOIUrl":"https://doi.org/10.1093/clinchem/hvae211","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"87 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887467","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":"Evolving Perspectives on Immune Repertoire Profiling: Challenges and Opportunities in the Era of Long-Read Sequencing.","authors":"Martin A Smith","doi":"10.1093/clinchem/hvae219","DOIUrl":"https://doi.org/10.1093/clinchem/hvae219","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"25 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887496","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":"Remnant Cholesterol: Quantification, Concentrations by Sex and Age, and Risk of Ischemic Heart Disease","authors":"Mie Balling, Shoaib Afzal, Anette Varbo, Børge G Nordestgaard, Anne Langsted","doi":"10.1093/clinchem/hvae217","DOIUrl":"https://doi.org/10.1093/clinchem/hvae217","url":null,"abstract":"Background Observational and genetic causal studies have shown an association between high concentrations of remnant cholesterol and increased risk of ischemic heart disease. However, findings from randomized intervention trials that reduced plasma triglycerides, a surrogate marker of remnant cholesterol, have been conflicting. The exact mechanisms by which remnant cholesterol contributes to atherosclerosis and, ultimately, ischemic heart disease remain incompletely understood. Additionally, insight on sex and age differences and the importance of measurement differences of remnant cholesterol in plasma concentrations and risk of ischemic heart disease are sparse. Content This review covers current knowledge regarding remnant cholesterol and its role in ischemic heart disease, with particular attention to measurement and sex- and age-specific differences. Summary Findings from observational, genetic, and mechanistic studies support the notion that higher remnant cholesterol may be an important cause of ischemic heart disease in both women and men. Concentrations of remnant cholesterol vary by age, with a sharp increase at early adulthood for men and around menopause for women. Remnant cholesterol can be calculated from a standard lipid profile and in addition measured directly using manual ultracentrifugation, automated assays, and nuclear magnetic resonance spectroscopy. Irrespective of the method used to assess plasma concentrations, high concentrations of remnant cholesterol are consistently associated with increased risk of myocardial infarction and ischemic heart disease in observational and genetic causal studies; cholesterol rather than triglycerides in remnants drive this risk. Importantly, results from ongoing randomized clinical trials aiming specifically at lowering remnant cholesterol and ischemic heart disease are eagerly awaited.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"14 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887498","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":"Optimal Cutoff Values and Utility of High-Sensitivity Troponin T and NT-proBNP for the Risk Stratification of Patients with Acute Pulmonary Embolism","authors":"Timothy M Matthews, Gregory A Peters, Grace Wang, Nora Horick, Kyle E Chang, Savanah Harshbarger, Christiana Prucnal, Drew A Birrenkott, Karsten Stannek, Eun Sang Lee, Isabel Dhar, Jesse O Wrenn, William B Stubblefield, Christopher Kabrhel","doi":"10.1093/clinchem/hvae212","DOIUrl":"https://doi.org/10.1093/clinchem/hvae212","url":null,"abstract":"Background Guidelines recommend using high-sensitivity troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) to risk stratify hemodynamically stable patients with acute pulmonary embolism (PE). However, there are no evidence-based cutoff values defined for this clinical application. Methods We performed a single-center, retrospective cohort study of patients with imaging-confirmed PE and hsTnT and/or NT-proBNP (ElecsysTM, Roche) measured 12 h before or 24 h after PE Response Team (PERT) activation. We excluded hypotensive patients. Our primary outcome was a composite of adverse outcomes or critical interventions within 7 days. We calculated the area under the receiver operating curve (AUC, ROC) for hsTnT and NT-proBNP and determined the optimal cutoffs using the distance from (0,1). We performed a subgroup analysis on patients with PE and right ventricular dysfunction on imaging. Results Two hundred thirty-four patients were included in the hsTnT analysis, and 727 in the NT-proBNP analysis. Mean age was 62 years (SD = 17) and 47% were female. The AUC for hsTnT was 0.64 (95% CI, 0.56–0.71) with an optimal cutoff of 46 ng/L, corresponding to a sensitivity of 59% (95% CI, 49–69) and a specificity of 61% (95% CI, 53–69). The AUC for NT-proBNP was 0.56 (95% CI, 0.51–0.61) with an optimal cutoff of 1092 pg/mL, corresponding to a sensitivity of 53% (95% CI, 45–61) and a specificity of 59% (95% CI, 55–63). Conclusion We identified an optimal cutoff of 46 ng/L for hsTnT and 1092 pg/mL for NT-proBNP, though the AUC for both markers suggests low to moderate performance for the risk stratification of initially hemodynamically stable PERT patients. Use of these biomarkers to risk stratify PE may require reconsideration.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"86 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858466","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":"Advances in Cardiac Troponin Composition Assays: A Step Closer to the Clinic?","authors":"Xander M R van Wijk, Sander A J Damen","doi":"10.1093/clinchem/hvae206","DOIUrl":"https://doi.org/10.1093/clinchem/hvae206","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853462","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":"Design and Analytical Evaluation of Novel Cardiac Troponin Assays Targeting Multiple Forms of the Cardiac Troponin I-Cardiac Troponin T-Troponin C Complex and Fragmentation Forms.","authors":"Ling Li, Yuqing Liu, Ivan A Katrukha, Litao Zhang, Xin Shu, Ao Xu, Juan Yang, Yu Wu, Yisha Jing, Hui Wang, Tongxin Ni, Karen Schulz, Anastasia V Bereznikova, Alexey G Katrukha, Fred S Apple, Yi Zhang, Zhenlu Zhang","doi":"10.1093/clinchem/hvae182","DOIUrl":"https://doi.org/10.1093/clinchem/hvae182","url":null,"abstract":"<p><strong>Background: </strong>Current studies suggest that cardiac troponin (cTn) forms in the circulation may vary in different clinical scenarios. Our aim was to design a combination of cTn assays specific to the main cTn forms and to evaluate their analytical performance.</p><p><strong>Methods: </strong>We developed immunoassays specific for measuring (1) long-cTnT cTnI-cTnT-TnC (ITC) ternary complex, with cTnT in long form without cleavage at the C-terminal amino acids residue 189-223, designated \"long-cTnT ITC complex assay;\" (2) both the long-cTnT ITC complex plus short-cTnT ITC complex, designated \"hs-total ITC complex assay;\" (3) the central part of cTnT of both the long-cTnT ITC complex and free cTnT, designated \"hs-cTnT assay.\" Sex-specific 99th percentile upper reference limits (URLs) were determined. High-sensitivity performance was assessed by examining the imprecision and detectable results above limit of detection (LoD) in the healthy population.</p><p><strong>Results: </strong>Both complex immunoassays exhibited excellent analytical sensitivity, precision, and specificity. The 99th percentile URLs were as follows: long-cTnT ITC complex: male 0.90 ng/L, female 0.87 ng/L; hs-total ITC complex: male 16.15 ng/L, female 10.08 ng/L; hs-cTnT: male 15.57 ng/L, female 14.28 ng/L. The total imprecision at or below the sex-specific 99th percentile URLs was <5% for all assays. The hs-total ITC complex and the hs-cTnT assays showed >50% of measurable concentrations above the LoD. However, <20% were measurable for the long-cTnT ITC complex assay.</p><p><strong>Conclusions: </strong>The cTn assays detected concentrations of major cTn forms in the circulation with high sensitivity, precision, and specificity, supporting their use for monitoring cTn complex and fragmentation forms during myocardial injuries.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853486","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":"Correction to: Prospective and External Validation of an Ensemble Learning Approach to Sensitively Detect Intravenous Fluid Contamination in Basic Metabolic Panels.","authors":"","doi":"10.1093/clinchem/hvae216","DOIUrl":"https://doi.org/10.1093/clinchem/hvae216","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845828","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}