Clinical chemistry最新文献

{"title":"Commentary on An Ambiguous NUDT15 Signal in a Child with B-Cell Acute Lymphoblastic Leukemia.","authors":"Reynold C Ly","doi":"10.1093/clinchem/hvaf069","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf069","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"11 1","pages":"840-841"},"PeriodicalIF":9.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756126","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":"From Laptop to Laboratory: Development and Implementation of a Machine Learning Model for Detecting Iron-Deficiency Anemia.","authors":"Nicholas C Spies","doi":"10.1093/clinchem/hvaf083","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf083","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"14 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720024","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":"Assessment of Placental Chromosomal Mosaicism during Prenatal Cell-Free DNA Screening Refines Positive Predictive Values for Fetal Trisomy","authors":"Nicola J Flowers, Clare J Love, Katrina L Scarff, Olivia Giouzeppos, Alison D Archibald, Martin B Delatycki, Mark D Pertile","doi":"10.1093/clinchem/hvaf076","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf076","url":null,"abstract":"Background Confined placental mosaicism can cause false-positive prenatal cell-free DNA (cfDNA) screening results, thereby reducing the positive predictive value (PPV) of the test. We sought to investigate how PPVs for the common fetal trisomies can be refined based on the presence or absence of chromosomal mosaicism in cfDNA sequencing data. Methods The study cohort included singleton pregnancies tested between March 2019 and December 2021. Outcome data were requested for high-risk results. Mosaic ratio (MR) generated by VeriSeq NIPT Solution v2 was used to classify high-risk cfDNA results as mosaic trisomy (MR < 0.7) or non-mosaic trisomy (MR ≥ 0.7) and the PPVs calculated. Results The cohort consisted of 821 high-risk results from 76 329 tests (1.08%). Prior to applying MR, PPVs for T21, T18 and T13 were 93.3% [95% CI 90.2–95.5], 81% [95% CI 73.1–87.0], and 55.3% [95% CI 44.7–65.4], respectively. After applying MR, PPVs for non-mosaic trisomy results were significantly higher (P < 0.001) than the PPVs for mosaic trisomy results; T21: 99.3% and 50%, T18: 97.6% and 22.7%, T13: 93.9% and 0%, respectively. Conclusions Mosaic ratio can be used to calculate more specific PPVs for the common trisomies. There is currently limited guidance on the application of VeriSeq v2 MR. Our approach provides a framework for laboratories to consider using MRs to refine PPV estimates for the common trisomies. High-risk cfDNA screening results are distressing for tested individuals. A refined PPV incorporating the presence or absence of mosaicism provides patients with more accurate information on the likely outcome of the diagnostic testing result, helping guide genetic counseling, choice of prenatal procedure, and overall pregnancy management.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"710 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719394","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":"Continuous Glucose Monitors Have Acceptable Accuracy but High Discordance at High and Low Glucose Concentrations in Pediatric Hospitalized Patients.","authors":"Isaiah K Mensah,Vahid Azimi,Christopher W Farnsworth","doi":"10.1093/clinchem/hvaf080","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf080","url":null,"abstract":"BACKGROUNDContinuous glucose monitors (CGMs) assess interstitial glucose concentrations and improve diabetes management in outpatient settings. However, limited studies have assessed CGM performance in hospitalized pediatric patients, especially at high and low glucose thresholds near clinical decision limits.METHODSThis retrospective study included 72 hospitalized pediatric patients with dysglycemia who used CGMs during hospitalization. Paired CGM results within 10 min of laboratory (Lab) and point-of-care (POC) glucose results were retrieved. The mean absolute relative difference (MARD) and percentage of glucose values in acceptable Parkes error zones were assessed. Concordance of CGM and POC results and the frequency that CGM results <70 mg/dL and >180 mg/dL were confirmed (-15 min to +30 min) using POC was assessed.RESULTSThere were 2228 paired CGM and Lab or POC glucose results with a MARD of 14.8%, and 99.2% of results were in Parkes zones A and B. The MARD was 20.2% and 13.6% in the hypoglycemic and hyperglycemic ranges. The MARD for POC glucose meters was 15.6% and 8.2% for the hypoglycemic and hyperglycemic ranges. The Cohen kappa between CGM and POC was 0.66 (95% CI, 0.63-0.69). CGM results in the hypoglycemic and hyperglycemic ranges were repeated 80.2% and 16.5% of the time, respectively, with POC methods.CONCLUSIONThe MARD of CGM in hospitalized pediatric patients is clinically acceptable but there is high discordance between CGM and POC. This implies a clinical need to confirm high and low glucose concentrations with Lab or POC methods but confirmatory testing is commonly not performed.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"55 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144701037","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":"Diagnostic Value of Digital Estimates of Trophoblastic Mosaicism in Genome-Wide Cell-Free Fetal DNA Screening.","authors":"Geert A Martens,Dieter De Smet,Guy Froyen,Koen Swaerts,Annick Daniels,Elke Boone,Pieter-Jan Volders,Katrien De Mulder,Ellen Geerdens,Severine Berden,Jense Wils,Pauline Herroelen,Henk Louagie,Brigitte Maes","doi":"10.1093/clinchem/hvaf081","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf081","url":null,"abstract":"BACKGROUNDCell-free fetal DNA (cffDNA) screening exhibits higher sensitivity and lower false-positive rates (FPRs) compared to combined first-trimester screening for common trisomies. However, additional anomalies on other autosomes detected by genome-wide assays cause anxiety and trigger increased rates of amniocentesis. Here, we evaluated the diagnostic value of software-generated digital estimates of trophoblastic mosaicism to identify false-positive screenings and inform posttest counseling.METHODSA total of 32 175 pregnancies were screened using a commercial genome-wide cffDNA screening assay alongside an open-source bioinformatics pipeline for fetal fraction and aneuploidy analysis. Amniocentesis outcomes were utilized to calculate positive predictive values (PPV) for common trisomies, sex chromosomal aneuploidy (SCA), rare autosomal trisomies (RAT), and subchromosomal alterations (SA). Receiver operating characteristics and regression analysis were performed to identify read count metrics that minimize FPRs.RESULTSThe assay showed 100% sensitivity for detecting trisomies 21, 18, and 13, with PPV ranging from 17% (+13) to 75% (+21). For SCA, PPV varied from 50% (45, X) to 89% (47, XXY). PPV for SA was 37%. RAT were detected in 0.33% of cases with a PPV of 6.6%. A proprietary digital estimate of trophoblastic mosaicism (mosaic ratio) exhibited good diagnostic performance (area under the curve 0.83-0.95) for false positives: mosaic ratio below 0.50, observed in 64% of RATs, 24% of SAs, 17% of common trisomies, and 7% of 45,X cases, was never associated with fetal aneuploidy.CONCLUSIONSDigital estimates of trophoblastic mosaicism hold clinical significance for informing posttest counseling. Implementing these recommendations could reduce invasive testing for RAT from 0.33% to 0.11%.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"12 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669339","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":"Machine Learning for Detecting Iron Deficiency through Comprehensive Blood Analysis.","authors":"Yu-Hsin Chang,Chia-Yu Chen,Chiung-Tzu Hsiao,Yu-Chang Chang,Hsin-Yu Lai,Hsiu-Hsien Lin,Ya-Lun Wu,Chien-Chih Chen,Lin-Chen Hsu,Tzu-Ting Chen,Hong-Mo Shih,Po-Ren Hsueh,Der-Yang Cho","doi":"10.1093/clinchem/hvaf074","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf074","url":null,"abstract":"BACKGROUNDIron deficiency (ID) is a prevalent global health issue with a major impact on well-being. Early detection of ID is crucial but challenging due to its nonspecific symptoms and the limitations of traditional diagnostic tests, which are impractical for large-scale screening. This study proposes a machine learning (ML) approach using complete blood count (CBC) data and cell population data (CPD) for detecting ID in the general population.METHODSWe retrospectively collected patient data from 3 hospitals to develop and validate 5 ML models using CBC, CPD, and demographic information. After identifying the best-performing model, we evaluated the impact of various feature sets and also assessed model performance across different subgroups to ensure robustness in diverse populations. The model was also deployed and integrated into clinical workflows.RESULTSWe retrospectively enrolled 9608 adult patients across emergency, inpatient, and outpatient departments from 3 hospitals, and prevalence of ID ranged from 17.4% to 19.6%. The ML model achieved an area under the receiver operating characteristic curve (AUROC) exceeding 0.94 and a precision-recall curve values (AUPRC) exceeding 0.83 during validation. After integration into the clinical system, the model maintained stable real-world performance, with an AUROC of 0.948 and an AUPRC of 0.854. Subgroup analysis showed lower performance in male and nonanemic populations.CONCLUSIONSOur study highlights the effectiveness of a ML model integrating CPD with CBC parameters for screening ID in the general population. Leveraging routine blood data without requiring biochemical tests, the model enables efficient and consistent ID screening across cohorts.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"672 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Role of Cardiac Troponin-Specific Autoantibodies: Prolonged Cardiac Troponin Elimination, Reduced Clearance, and Variable Interference across 5 Commercial Assays.","authors":"Selma M Salonen,Jonas H Kristensen,Sara Simonen,Rasmus B Hasselbalch,Nina Strandkjær,Morten Østergaard,Hasse Møller-Sørensen,Morten Dahl,Mustafa Vakur Bor,Ruth Frikke-Schmidt,Niklas R Jørgensen,Line Rode,Lene Holmvang,Jesper Kjærgaard,Lia E Bang,Julie Forman,Kim P Dalhoff,Henning Bundgaard,Kasper K Iversen,Saara Wittfooth","doi":"10.1093/clinchem/hvaf077","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf077","url":null,"abstract":"BACKGROUNDHigh-sensitivity cardiac troponin (hs-cTn) assays are prone to negative and positive interferences caused by endogenous cardiac troponin-specific autoantibodies (cTnAAbs). Large macrotroponin complexes formed of cardiac troponin (cTn) and cTnAAbs may result in falsely elevated hs-cTn results. This is potentially due to reduced clearance of macrotroponin, but direct evidence is still lacking. In this study, we investigated the possible effects of cTnAAbs on the elimination of cTn.METHODSTwenty patients with ST-elevation myocardial infarction (MI) underwent plasmapheresis within 24 h after revascularization to harvest plasma with a high cTn concentration. After clinical recovery, patients returned to the hospital for autologous plasma re-transfusion. Following re-transfusion, blood samples were collected at fixed time points and analyzed with 5 commercial hs-cTn assays. The presence of cTnAAbs in the samples and the epitope specificity of cTnAAbs were investigated with in-house immunoassays.RESULTSAltogether, 2 out of 20 patients (10%) were cTnAAb-positive. With 4 commercial hs-cTn assays, cTnAAb-positive patients mainly showed longer elimination half-lives and slower cTn clearances than most cTnAAb-negative patients. One hs-cTn assay was prone to negative cTnAAb interference but correspondingly less prone to positive macrotroponin interference. The central part of cardiac troponin I (cTnI) was predominantly affected by cTnAAbs.CONCLUSIONSEndogenous cTnAAbs were for the first time shown to prolong the elimination half-life and reduce the clearance of cTn in the circulation. Additionally, the extent of analytical interference from cTnAAbs and their reactivity to macrotroponin varies among commercial hs-cTn assays, an important consideration for laboratories to ensure accurate diagnosis of MI.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"45 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Modified Sampson-NIH Equation with Improved Accuracy for Estimating Low Levels of Low-Density Lipoprotein-Cholesterol.","authors":"Maureen Sampson,Rafael Zubiran,Anna Wolska,Jeffrey W Meeusen,Leslie J Donato,Allan S Jaffe,Giorgio E M Melloni,Robert P Giugliano,Marc S Sabatine,Nicholas A Marston,Alan T Remaley","doi":"10.1093/clinchem/hvaf073","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf073","url":null,"abstract":"BACKGROUNDCardiovascular guidelines have long recommended low-density lipoprotein-cholesterol (LDL-C) as the primary target for lipid-lowering therapy. Recent guidelines have emphasized the importance of achieving low LDL-C levels; hence, the accurate measurement of low LDL-C is increasingly clinically relevant.METHODSUsing lipid panel test results from the Mayo Clinic (n = 24 590) and the FOURIER clinical trial of evolocumab (n = 9605), the following modified Sampson equation was developed by least-squares regression to match LDL-C (mg/dL) by the β-quantification reference method, by combining terms into non High Density Lipoprotein Cholesterol (nonHDLC = Total Cholesterol - High Density Lipoprotein Cholesterol) and forcing the coefficient to be one.RESULTSThe modified Sampson equation demonstrated significant improvement in its concordance to the reference method compared to other equations (the Lin Concordance Correlation Coefficient 0.992, P < 0.001). By overall kappa analysis, it showed the best agreement to the reference method at the 55 mg/dL cutpoint (1.4 mmol/L, 0.98 [P < 0.001], Sampson-NIH: 0.96, Martin-Hopkins: 0.96, Friedewald: 0.94) and the 70 mg/dL cutpoint (1.8 mmol/L, 0.97 [P < 0.001], Sampson-NIH: 0.94, Martin-Hopkins: 0.95, Friedewald: 0.92). The false classification rate of the modified Sampson equation was also significantly lower compared to the other equations at 55 mg/dL (15%, [P < 0.001], Sampson-NIH: 29%, Martin-Hopkins: 28%, Friedewald: 37%) and 70 mg/dL (18%, [P < 0.001]; Sampson-NIH: 30%, Martin-Hopkins: 28.%, Friedewald: 34%). The new equation increases the percentage of correctly classified patients with low LDL-C by approximately 10% to 20% over the other equations based on its net reclassification index.CONCLUSIONSThe modified Sampson equation shows improved accuracy compared to other equations for low LDL-C. It more accurately identifies high-risk patients, who are not at their LDL-C goals and could benefit from more intensive lipid-lowering therapy.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"265 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586676","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":"Diagnostic Accuracy of a Novel 0/1-H Algorithm Using Point-of-Care High-Sensitivity Troponin in the Emergency Department.","authors":"Viola I L Thulin,Gard M S Myrmel,Paul O Collinson,Fred S Apple,Kjell Vikenes,Rune O Bjørneklett,Torbjørn Omland,Kristin M Aakre","doi":"10.1093/clinchem/hvaf078","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf078","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"106 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578766","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":"Oropouche Virus: The Next (Re)Emerging Arboviral Threat?","authors":"Portia Mira, Elitza S Theel","doi":"10.1093/clinchem/hvaf017","DOIUrl":"10.1093/clinchem/hvaf017","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"731-733"},"PeriodicalIF":7.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604190","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}