Pub Date : 2026-02-03DOI: 10.1093/clinchem/hvaf129
Faisal A Hassan, Hind Malaeb, Ibrahim Choucair
{"title":"Metabolomic Signatures of Ultra-Processed Food Intake: Toward Objective Dietary Biomarkers.","authors":"Faisal A Hassan, Hind Malaeb, Ibrahim Choucair","doi":"10.1093/clinchem/hvaf129","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf129","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"72 2","pages":"323-324"},"PeriodicalIF":6.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112542","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}
Pub Date : 2026-02-03DOI: 10.1093/clinchem/hvaf173
Yasine Malki, Y M Dennis Lo
{"title":"Clinical Variables and Cell-Free DNA Fragmentomics: Biological and Clinical Insights.","authors":"Yasine Malki, Y M Dennis Lo","doi":"10.1093/clinchem/hvaf173","DOIUrl":"10.1093/clinchem/hvaf173","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"219-221"},"PeriodicalIF":6.3,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917200","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}
Pub Date : 2026-02-02DOI: 10.1093/clinchem/hvag001
Patrick L Day, Mikolaj A Wieczorek, Denise Rokke, Eric Lantz, Joshua A Bornhorst, Paul J Jannetto, Rickey E Carter
Background: Artificial intelligence (AI) augmented laboratory tests can improve quality, efficiency, cost-effectiveness, and staff satisfaction. However, the clinical success of these tests can introduce unforeseen challenges for model retraining. This study describes the discovery of an "AI label feedback loop" in a clinically implemented AI-augmented kidney stone composition test.
Methods: An AI-augmented kidney stone composition test (V1) has been previously deployed for clinical kidney stone characterization. After several years of clinical use, a retrained model (V2) was developed using 6 times more data. Model performance of both V1 and V2 were evaluated across 3 datasets: a recent production validation (hold-out) set (mostly AI-influenced labels), the original V1 validation set (pre-AI, entirely human-labeled), and a subset of recent cases with exclusively human-generated or human-corrected labels.
Results: V2 demonstrated a 10% lower concordance rate than V1 when evaluated on the recent production hold-out set, despite a much larger training dataset. Performance between V1 and V2 was similar when applied to the pre-AI validation set. Notably, V2 outperformed V1 on the recent subset of cases with human-only or human-corrected labels, particularly for less-common stone types. These findings revealed an AI label feedback loop, confounding retraining and evaluation.
Conclusions: The integration of AI into clinical practice can potentially influence reported test results, complicating the development and evaluation of future models. To mitigate AI label feedback loops, ongoing human annotation and careful validation set construction are essential. These strategies can ensure reliable performance assessment and support the safe evolution of clinical AI systems.
{"title":"Discovery of an Artificial Intelligence Label Feedback Loop: How the Success of a Clinically Implemented Artificial Intelligence Algorithm Has Created an Unforeseen Challenge to Algorithm Retraining.","authors":"Patrick L Day, Mikolaj A Wieczorek, Denise Rokke, Eric Lantz, Joshua A Bornhorst, Paul J Jannetto, Rickey E Carter","doi":"10.1093/clinchem/hvag001","DOIUrl":"https://doi.org/10.1093/clinchem/hvag001","url":null,"abstract":"<p><strong>Background: </strong>Artificial intelligence (AI) augmented laboratory tests can improve quality, efficiency, cost-effectiveness, and staff satisfaction. However, the clinical success of these tests can introduce unforeseen challenges for model retraining. This study describes the discovery of an \"AI label feedback loop\" in a clinically implemented AI-augmented kidney stone composition test.</p><p><strong>Methods: </strong>An AI-augmented kidney stone composition test (V1) has been previously deployed for clinical kidney stone characterization. After several years of clinical use, a retrained model (V2) was developed using 6 times more data. Model performance of both V1 and V2 were evaluated across 3 datasets: a recent production validation (hold-out) set (mostly AI-influenced labels), the original V1 validation set (pre-AI, entirely human-labeled), and a subset of recent cases with exclusively human-generated or human-corrected labels.</p><p><strong>Results: </strong>V2 demonstrated a 10% lower concordance rate than V1 when evaluated on the recent production hold-out set, despite a much larger training dataset. Performance between V1 and V2 was similar when applied to the pre-AI validation set. Notably, V2 outperformed V1 on the recent subset of cases with human-only or human-corrected labels, particularly for less-common stone types. These findings revealed an AI label feedback loop, confounding retraining and evaluation.</p><p><strong>Conclusions: </strong>The integration of AI into clinical practice can potentially influence reported test results, complicating the development and evaluation of future models. To mitigate AI label feedback loops, ongoing human annotation and careful validation set construction are essential. These strategies can ensure reliable performance assessment and support the safe evolution of clinical AI systems.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146104260","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}
Pub Date : 2026-01-29DOI: 10.1093/clinchem/hvaf190
Annelies Emmaneel,Jana Neirinck,Alba Torres-Valle,Sofie Van Gassen,Sarah Bonte,Malicorne Buysse,Jacques J M van Dongen,Alberto Orfao,Mirjam van der Burg,Tomas Kalina,Bart N Lambrecht,Ciel De Vriendt,Tessa Kerre,Filomeen Haerynck,Martin Pérez-Andrés,Mattias Hofmans,Carolien Bonroy,Yvan Saeys
BACKGROUNDPrimary immunodeficiencies (PIDs) are rare disorders caused by immune system defects that are commonly screened using multi-parameter flow cytometry (FCM). To counter the subjective and time-consuming manual data analysis of FCM data, we present PIDgeon, a fully automated computational pipeline based on artificial intelligence (AI) techniques. PIDgeon is designed to characterize PID immune profiles, suggest PID subtypes based on altered immune profiles, age, and immunoglobulin levels, and generate interpretable reports.METHODSThe PIDgeon pipeline, including FlowSOM and extreme gradient boosting models, was trained and tested on standardized FCM data generated according to EuroFlow procedures on 74 healthy controls and 399 patients (281 lymphoid-PID patients and 118 non-PID diseased controls) collected by the Ghent University Hospital. Subsequently, multi-centric validation was performed on internal (n = 211) and external (n = 338) independent data sets collected across 4 EuroFlow centers.RESULTSValidation demonstrated high accuracy in cell count enumeration, achieving correlation scores above 0.90 for the major lymphocyte subsets. Interestingly, PIDgeon showed high sensitivity (93% to 100%) in predicting PID with severe T-cell defects, such as severe combined immunodeficiency and late-onset combined immunodeficiency, and low false-negative rates (1.5% to 5.4%) for distinguishing other lymphoid-PID vs non-PID diseased controls across data sets. Additionally, PIDgeon gives a first hint toward prediction of subtypes of primary antibody deficiencies, such as common variable immunodeficiency.CONCLUSIONSIn summary, PIDgeon is an accessible and explainable AI-pipeline aligned with current clinical needs, aiding laboratory immunologists in early PID diagnostics and increasing data analysis efficiency.
{"title":"PIDgeon: An Explainable AI Model for Improved Flow Cytometry-Based Screening of Lymphoid Primary Immunodeficiencies.","authors":"Annelies Emmaneel,Jana Neirinck,Alba Torres-Valle,Sofie Van Gassen,Sarah Bonte,Malicorne Buysse,Jacques J M van Dongen,Alberto Orfao,Mirjam van der Burg,Tomas Kalina,Bart N Lambrecht,Ciel De Vriendt,Tessa Kerre,Filomeen Haerynck,Martin Pérez-Andrés,Mattias Hofmans,Carolien Bonroy,Yvan Saeys","doi":"10.1093/clinchem/hvaf190","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf190","url":null,"abstract":"BACKGROUNDPrimary immunodeficiencies (PIDs) are rare disorders caused by immune system defects that are commonly screened using multi-parameter flow cytometry (FCM). To counter the subjective and time-consuming manual data analysis of FCM data, we present PIDgeon, a fully automated computational pipeline based on artificial intelligence (AI) techniques. PIDgeon is designed to characterize PID immune profiles, suggest PID subtypes based on altered immune profiles, age, and immunoglobulin levels, and generate interpretable reports.METHODSThe PIDgeon pipeline, including FlowSOM and extreme gradient boosting models, was trained and tested on standardized FCM data generated according to EuroFlow procedures on 74 healthy controls and 399 patients (281 lymphoid-PID patients and 118 non-PID diseased controls) collected by the Ghent University Hospital. Subsequently, multi-centric validation was performed on internal (n = 211) and external (n = 338) independent data sets collected across 4 EuroFlow centers.RESULTSValidation demonstrated high accuracy in cell count enumeration, achieving correlation scores above 0.90 for the major lymphocyte subsets. Interestingly, PIDgeon showed high sensitivity (93% to 100%) in predicting PID with severe T-cell defects, such as severe combined immunodeficiency and late-onset combined immunodeficiency, and low false-negative rates (1.5% to 5.4%) for distinguishing other lymphoid-PID vs non-PID diseased controls across data sets. Additionally, PIDgeon gives a first hint toward prediction of subtypes of primary antibody deficiencies, such as common variable immunodeficiency.CONCLUSIONSIn summary, PIDgeon is an accessible and explainable AI-pipeline aligned with current clinical needs, aiding laboratory immunologists in early PID diagnostics and increasing data analysis efficiency.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"44 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069894","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}
Pub Date : 2026-01-28DOI: 10.1093/clinchem/hvaf187
Anna C H Hoge,Thomas E Grys,Erin H Graf
BACKGROUNDWhile most pulmonary infections with Coccidioides spp. are self-limited, a subset of patients is at higher risk for severe disease and extrapulmonary dissemination, including individuals with certain ethnic backgrounds. Disseminated disease can involve soft tissues, bones, and the central nervous system with high morbidity and mortality in the absence of antifungal treatment. Diagnosis of coccidioidomycosis can be challenged by the availability of specimens for culture or histopathology, confusion with, or lack of availability of various antibody tests and overall lack of consideration of Coccidioides spp. as the etiology of disease, especially in immunocompetent hosts.METHODSWe set out to characterize cases of disseminated coccidioidomycosis at our institution over a 7-year period, solely in immunocompetent hosts, to highlight diagnostic delays and determine which, if any, primary screening test might be the most useful.RESULTSA total of 40 cases met our inclusion criteria, and 100% of these cases had positive immunoglobulin G antibodies on a US FDA-cleared Coccidioides spp. enzyme immunoassay. Nearly all of the cases (87%) had a delay in diagnosis and associated worsening of disease (71%). Locations of initial presentations that led to delayed recognition included primary care settings (56%), emergency departments (33%), and urgent care centers (11%), all in the region of Coccidioides spp. endemicity.CONCLUSIONSThese findings highlight the need for interventions to increase awareness of the risk factors for, the symptoms of, and the appropriate testing options to diagnose disseminated coccidioidomycosis.
{"title":"Disseminated Coccidioidomycosis in Immunocompetent Hosts: Opportunities for Increased Recognition and Timely Diagnosis.","authors":"Anna C H Hoge,Thomas E Grys,Erin H Graf","doi":"10.1093/clinchem/hvaf187","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf187","url":null,"abstract":"BACKGROUNDWhile most pulmonary infections with Coccidioides spp. are self-limited, a subset of patients is at higher risk for severe disease and extrapulmonary dissemination, including individuals with certain ethnic backgrounds. Disseminated disease can involve soft tissues, bones, and the central nervous system with high morbidity and mortality in the absence of antifungal treatment. Diagnosis of coccidioidomycosis can be challenged by the availability of specimens for culture or histopathology, confusion with, or lack of availability of various antibody tests and overall lack of consideration of Coccidioides spp. as the etiology of disease, especially in immunocompetent hosts.METHODSWe set out to characterize cases of disseminated coccidioidomycosis at our institution over a 7-year period, solely in immunocompetent hosts, to highlight diagnostic delays and determine which, if any, primary screening test might be the most useful.RESULTSA total of 40 cases met our inclusion criteria, and 100% of these cases had positive immunoglobulin G antibodies on a US FDA-cleared Coccidioides spp. enzyme immunoassay. Nearly all of the cases (87%) had a delay in diagnosis and associated worsening of disease (71%). Locations of initial presentations that led to delayed recognition included primary care settings (56%), emergency departments (33%), and urgent care centers (11%), all in the region of Coccidioides spp. endemicity.CONCLUSIONSThese findings highlight the need for interventions to increase awareness of the risk factors for, the symptoms of, and the appropriate testing options to diagnose disseminated coccidioidomycosis.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"87 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056876","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}
Pub Date : 2026-01-28DOI: 10.1093/clinchem/hvaf168
Brandon R Allen,Jessica L Guidi,Gary Headden,Nicole Winden,Dileepa Alahapperuma,Robert H Christenson,W Franklin Peacock,Sean Collins,Elizabeth L Walters,James L Januzzi
BACKGROUNDDiagnosis and risk stratification of acute heart failure (HF) in the emergency department (ED) remains challenging. N-terminal pro-B type natriuretic peptide (NT-proBNP) measurement is useful in evaluating acute dyspnea. The objective of this study was to evaluate the diagnostic performance of a new Access NT-proBNP assay in a large cohort of ED patients presenting with suspected acute HF.METHODSThis prospective study enrolled 2701 ED patients across 17 US sites (Nov 2019 to May 2022). Diagnoses were adjudicated by a blinded Clinical Events Committee. The diagnostic performance of the new NT-proBNP assay was evaluated by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Secondary analyses included association of NT-proBNP levels with HF severity and 90-day major adverse cardiovascular events (MACE).RESULTSAmong 2384 patients, 45.5% had acute HF. The Access NT-proBNP assay demonstrated an area under the receiver operating characteristic curve (AUC) of 0.87 (P < 0.001). Sensitivity across age-based cutoffs was high: 96% (<300 ng/L), 90% (<450 ng/L under age 50), 85% (<900 ng/L ages 50 to 75), and 79% (<1800 ng/L over age 75). At a 300 ng/L threshold, NPV was 95% and PPV was 73%. Higher NT-proBNP levels correlated with greater HF severity and predicted shorter MACE-free survival. The Access assay showed similar performance (AUC 0.8536 vs 0.8562) as the Elecsys proBNP II assay.CONCLUSIONSThe new Access NT-proBNP assay provides strong diagnostic and prognostic performance in ED patients with suspected acute HF, with results comparable to a reference NT-proBNP assay.
{"title":"Evaluation of a New Antibody-Based NT-proBNP Assay for Acute Dyspnea in the Emergency Department.","authors":"Brandon R Allen,Jessica L Guidi,Gary Headden,Nicole Winden,Dileepa Alahapperuma,Robert H Christenson,W Franklin Peacock,Sean Collins,Elizabeth L Walters,James L Januzzi","doi":"10.1093/clinchem/hvaf168","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf168","url":null,"abstract":"BACKGROUNDDiagnosis and risk stratification of acute heart failure (HF) in the emergency department (ED) remains challenging. N-terminal pro-B type natriuretic peptide (NT-proBNP) measurement is useful in evaluating acute dyspnea. The objective of this study was to evaluate the diagnostic performance of a new Access NT-proBNP assay in a large cohort of ED patients presenting with suspected acute HF.METHODSThis prospective study enrolled 2701 ED patients across 17 US sites (Nov 2019 to May 2022). Diagnoses were adjudicated by a blinded Clinical Events Committee. The diagnostic performance of the new NT-proBNP assay was evaluated by sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Secondary analyses included association of NT-proBNP levels with HF severity and 90-day major adverse cardiovascular events (MACE).RESULTSAmong 2384 patients, 45.5% had acute HF. The Access NT-proBNP assay demonstrated an area under the receiver operating characteristic curve (AUC) of 0.87 (P < 0.001). Sensitivity across age-based cutoffs was high: 96% (<300 ng/L), 90% (<450 ng/L under age 50), 85% (<900 ng/L ages 50 to 75), and 79% (<1800 ng/L over age 75). At a 300 ng/L threshold, NPV was 95% and PPV was 73%. Higher NT-proBNP levels correlated with greater HF severity and predicted shorter MACE-free survival. The Access assay showed similar performance (AUC 0.8536 vs 0.8562) as the Elecsys proBNP II assay.CONCLUSIONSThe new Access NT-proBNP assay provides strong diagnostic and prognostic performance in ED patients with suspected acute HF, with results comparable to a reference NT-proBNP assay.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"74 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056877","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}
Pub Date : 2026-01-28DOI: 10.1093/clinchem/hvaf176
Stephen A Bustin,Carl T Wittwer
BACKGROUNDReal-time reverse transcription quantitative PCR (RT-qPCR) is utilized in many areas of the life sciences, diagnostics, and forensics, yet concerns about methodological quality and reporting transparency persist. Diagnostic testing during the recent pandemic brought those concerns into the public domain. The Minimum Information for Publication of Quantitative PCR Experiments (MIQE) guidelines, introduced in 2009 and updated in 2025, were intended to standardize assay design and reporting, but their impact has been modest.CONTENTWe assessed trends in RT-qPCR methodological reporting between 2007 and 2025 using PubMed Central searches and manual evaluation of 355 full-text articles from 2019 and 2024. Parameters analyzed included RNA integrity assessment, oligonucleotide sequence disclosure, reference gene validation, PCR efficiency reporting, and MIQE citation. In addition, targeted cohorts of 50 "reference gene" and 50 "PCR efficiency" publications from 2024/25 were evaluated. Results were compared across timepoints, geographic regions, and MIQE-citing vs non-citing studies.SUMMARYReporting of core parameters remained low or declined. Between 2019 and 2024, RNA integrity reporting fell (22% to 11%), reference gene validation was rare (13% to 5%), and PCR efficiency reporting collapsed (13% to 1%). MIQE-citing papers in 2024 showed better adherence (31% RNA integrity, 47% reference gene validation, and 40% PCR efficiency) but still omitted essential details. Asia now dominates RT-qPCR output by volume, while Europe contributes most MIQE-citing studies. Targeted cohorts reported more methodological information, yet many still failed to meet basic standards. These findings confirm that incomplete experimental design and reporting continue to undermine reproducibility and robustness of RT-qPCR assays.
{"title":"Real-Time Reverse Transcription Quantitative PCR (RT-qPCR) Methodological Standards and Reporting Practices.","authors":"Stephen A Bustin,Carl T Wittwer","doi":"10.1093/clinchem/hvaf176","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf176","url":null,"abstract":"BACKGROUNDReal-time reverse transcription quantitative PCR (RT-qPCR) is utilized in many areas of the life sciences, diagnostics, and forensics, yet concerns about methodological quality and reporting transparency persist. Diagnostic testing during the recent pandemic brought those concerns into the public domain. The Minimum Information for Publication of Quantitative PCR Experiments (MIQE) guidelines, introduced in 2009 and updated in 2025, were intended to standardize assay design and reporting, but their impact has been modest.CONTENTWe assessed trends in RT-qPCR methodological reporting between 2007 and 2025 using PubMed Central searches and manual evaluation of 355 full-text articles from 2019 and 2024. Parameters analyzed included RNA integrity assessment, oligonucleotide sequence disclosure, reference gene validation, PCR efficiency reporting, and MIQE citation. In addition, targeted cohorts of 50 \"reference gene\" and 50 \"PCR efficiency\" publications from 2024/25 were evaluated. Results were compared across timepoints, geographic regions, and MIQE-citing vs non-citing studies.SUMMARYReporting of core parameters remained low or declined. Between 2019 and 2024, RNA integrity reporting fell (22% to 11%), reference gene validation was rare (13% to 5%), and PCR efficiency reporting collapsed (13% to 1%). MIQE-citing papers in 2024 showed better adherence (31% RNA integrity, 47% reference gene validation, and 40% PCR efficiency) but still omitted essential details. Asia now dominates RT-qPCR output by volume, while Europe contributes most MIQE-citing studies. Targeted cohorts reported more methodological information, yet many still failed to meet basic standards. These findings confirm that incomplete experimental design and reporting continue to undermine reproducibility and robustness of RT-qPCR assays.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"42 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056878","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}
Pub Date : 2026-01-21DOI: 10.1093/clinchem/hvag011
Lori B Daniels,Christian Mueller,Evangelos Giannitsis,Steven J R Meex,David Buehlmann,Peter Dilba,Garnet Bendig,Mette Cole,Richard Body,Robert H Christenson,Christa Cobbaert,Christopher R deFilippi,Kai M Eggers,Kenji Inoue,Allan S Jaffe,Cian P McCarthy,James McCord,Johannes T Neumann,Torbjørn Omland,Cynthia Papendick,Yader Sandoval,Jack Wei Chieh Tan,Martin P Than,Raphael Twerenbold,W Frank Peacock,Nicholas L Mills
BACKGROUNDMeasurement of cardiac troponin (cTn) using high-sensitivity assays is recommended for the diagnosis of myocardial infarction. We determined sex-specific and uniform 99th percentile upper reference limits (URLs) using the new Elecsys® Troponin T high-sensitivity Gen 6 assay in a global, healthy reference range cohort.METHODSLithium-heparin (Li-Hep) plasma and serum samples were prospectively collected from apparently healthy individuals aged ≥20 years across 34 global sites in the United States, Europe, China, and Japan. cTnT was measured using the Troponin T high-sensitivity Gen 6 assay on the Cobas® e 801 analyzer. Exclusion criteria were defined according to the 2022 International Federation of Clinical Chemistry guidance. Uniform and sex-specific 99th percentile URLs and non-parametric 95% confidence intervals (CI) were determined in plasma and serum separately and combined.RESULTSThe final study population comprised 4147 participants (52.5% female) with a median (25-75th percentiles) age of 48.0 (33.0-59.0) years; 45.8%, 47.9%, 5.2% and 1.1% were White, Asian, Black, and other/unknown, respectively. For sample matrices combined (n=8294), 81.0% and 99.2% of cTnT values were above the limit of detection in females and males, respectively. Sex-specific 99th percentile URLs (95% CI) were 18 (16-23) ng/L for females and 32 (28-35) ng/L for males; the uniform 99th percentile URL was 27 (24-31) ng/L. URLs were comparable in plasma and serum samples.CONCLUSIONSThis study determined sex-specific and uniform 99th percentile URLs for the Troponin T high-sensitivity Gen 6 assay that were comparable irrespective of the matrix used, in a large, global, healthy reference population.
{"title":"Establishing Reference Values in Healthy Participants for the Cardiac Troponin T High-Sensitivity Gen 6 Assay: REF-TSIX Global Reference Study.","authors":"Lori B Daniels,Christian Mueller,Evangelos Giannitsis,Steven J R Meex,David Buehlmann,Peter Dilba,Garnet Bendig,Mette Cole,Richard Body,Robert H Christenson,Christa Cobbaert,Christopher R deFilippi,Kai M Eggers,Kenji Inoue,Allan S Jaffe,Cian P McCarthy,James McCord,Johannes T Neumann,Torbjørn Omland,Cynthia Papendick,Yader Sandoval,Jack Wei Chieh Tan,Martin P Than,Raphael Twerenbold,W Frank Peacock,Nicholas L Mills","doi":"10.1093/clinchem/hvag011","DOIUrl":"https://doi.org/10.1093/clinchem/hvag011","url":null,"abstract":"BACKGROUNDMeasurement of cardiac troponin (cTn) using high-sensitivity assays is recommended for the diagnosis of myocardial infarction. We determined sex-specific and uniform 99th percentile upper reference limits (URLs) using the new Elecsys® Troponin T high-sensitivity Gen 6 assay in a global, healthy reference range cohort.METHODSLithium-heparin (Li-Hep) plasma and serum samples were prospectively collected from apparently healthy individuals aged ≥20 years across 34 global sites in the United States, Europe, China, and Japan. cTnT was measured using the Troponin T high-sensitivity Gen 6 assay on the Cobas® e 801 analyzer. Exclusion criteria were defined according to the 2022 International Federation of Clinical Chemistry guidance. Uniform and sex-specific 99th percentile URLs and non-parametric 95% confidence intervals (CI) were determined in plasma and serum separately and combined.RESULTSThe final study population comprised 4147 participants (52.5% female) with a median (25-75th percentiles) age of 48.0 (33.0-59.0) years; 45.8%, 47.9%, 5.2% and 1.1% were White, Asian, Black, and other/unknown, respectively. For sample matrices combined (n=8294), 81.0% and 99.2% of cTnT values were above the limit of detection in females and males, respectively. Sex-specific 99th percentile URLs (95% CI) were 18 (16-23) ng/L for females and 32 (28-35) ng/L for males; the uniform 99th percentile URL was 27 (24-31) ng/L. URLs were comparable in plasma and serum samples.CONCLUSIONSThis study determined sex-specific and uniform 99th percentile URLs for the Troponin T high-sensitivity Gen 6 assay that were comparable irrespective of the matrix used, in a large, global, healthy reference population.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"1 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015130","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}
Pub Date : 2026-01-19DOI: 10.1093/clinchem/hvaf185
{"title":"Correction to: Impact of Clinical Variables on cfDNA Fragmentomic Signatures and Their Potential as Confounders in Cancer Detection.","authors":"","doi":"10.1093/clinchem/hvaf185","DOIUrl":"10.1093/clinchem/hvaf185","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002847","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}
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