Clinical chemistry最新文献

{"title":"An AI Model (LORIS) to Predict Immune Checkpoint Blockade Response in Cancer: A Clinical Data Science Perspective.","authors":"Thomas E Tavolara, Wenchao Han, David S McClintock","doi":"10.1093/clinchem/hvae196","DOIUrl":"https://doi.org/10.1093/clinchem/hvae196","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834420","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":"Characterization of Cardiac Troponin Fragment Composition Reveals Potential for Differentiating Etiologies of Myocardial Injury.","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/hvae200","DOIUrl":"https://doi.org/10.1093/clinchem/hvae200","url":null,"abstract":"<p><strong>Background: </strong>Increased cardiac troponin (cTn) concentrations occur in acute myocardial injury and chronic diseases. Characterization of cTn composition in the circulation may assist in differentiating etiologies of myocardial injury. Our goal was to study cTn composition and kinetics in patients following type 1 myocardial infraction (T1MI), cardiac procedures, and chronic heart diseases to establish the relationship between cTn composition and clinical diagnosis.</p><p><strong>Methods: </strong>Plasma samples were collected from 201 patients with T1MI, 78 undergoing cardiac surgeries, and 218 with chronic cardiomyopathy or chronic heart failure. Major cTn forms in the circulation and their ratios were analyzed using cTn composition immunoassays, targeting (a) the long-cTnT cTnI-cTnT-TnC (ITC) ternary complex, short-cTnT ITC complex cleaved at amino acids residues 189-223 of cTnT, and the binary cTnI-TnC (IC) complex, and designated the \"high-sensitivity (hs)-cTnI assay;\" (b) the long-cTnT ITC complex, and designated the \"long-cTnT ITC complex assay;\" (c) the long-cTnT ITC complex and short-cTnT ITC complex, and designated the \"hs-total ITC complex assay;\" and (d) the central part of cTnT of both the long-cTnT ITC complex and free cTnT, and designated the \"hs-cTnT assay.\"</p><p><strong>Results: </strong>Early-stage T1MI patients showed a high ratio of long-cTnT ITC complex to cTnI (long-cTnT ITC complex/cTnI, R1). Similarly, patients after acute cardiac surgery exhibited increased cTn concentrations with high R1, which decreased rapidly. In chronic disease, cTn composition exhibited stable and low R1 and high ratios of cTnT to cTnI (cTnT/cTnI, R3).</p><p><strong>Conclusions: </strong>Kinetic differences in multiple cTn forms contribute to the differentiation between acute injury and chronic disease, with a high proportion of long-cTnT ITC complex implying occurrence of acute injury.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853485","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":"Measurement of Serum Free Vitamin D Concentrations: Importance, Challenges, and the Emerging Role of Mass Spectrometry","authors":"Anastasia Alexandridou, Caroline S Stokes, Dietrich A Volmer","doi":"10.1093/clinchem/hvae202","DOIUrl":"https://doi.org/10.1093/clinchem/hvae202","url":null,"abstract":"Background Serum total 25-hydroxyvitamin D [25(OH)D] concentration is the most widely used clinical biomarker for vitamin D status. Under certain physiological and pathological conditions, however, total 25(OH)D may not always be the best index for vitamin D status. Instead, the nonprotein-bound (free) fraction of total 25(OH)D has been suggested as a more appropriate marker in certain clinical situations. Content Free 25(OH)D levels can either be calculated or measured directly. Calculated free 25(OH)D depends on the concentrations of total serum 25(OH)D, vitamin D binding protein (VDBP), and albumin, as well as the affinity between analyte and binding proteins. Differences in VDBP concentrations are observed between populations as a result of health status, gene polymorphisms, and the assay used for determination. Direct measurement methods for free 25(OH)D are often complicated (dialysis, ultrafiltration) or susceptible to interferences, cross-reactivity, and type of antibody (immunoassays). Therefore, it is very important to develop tools that allow either accurate and precise measurement of VDBP or direct measurement of free 25(OH)D. For the latter, liquid chromatography combined with tandem mass spectrometry (LC–MS/MS) has recently shown promise for analysis of free vitamin D. In the current review, we present the importance and challenges regarding free 25(OH)D determination and the role of LC–MS-based methods in future studies. Summary More research is required to determine the role of free 25(OH)D in the assessment of vitamin D status in healthy subjects and in various clinical conditions. Recent advances in technology, including mass spectrometry, can provide the required assays for this purpose.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"27 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809731","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":"New Insights into Xylazine Pharmacokinetics in Humans.","authors":"Kara L Lynch","doi":"10.1093/clinchem/hvae201","DOIUrl":"https://doi.org/10.1093/clinchem/hvae201","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806001","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":"Proteomic Prediction Models.","authors":"Patrick M Bossuyt","doi":"10.1093/clinchem/hvae207","DOIUrl":"https://doi.org/10.1093/clinchem/hvae207","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806003","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":"In Reply to Beyond the Screen Positive Rate: Racial Equity Considerations for Serum Screening for Open Neural Tube Defects.","authors":"Geralyn Messerlian, Glenn E Palomaki","doi":"10.1093/clinchem/hvae154","DOIUrl":"10.1093/clinchem/hvae154","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"1496"},"PeriodicalIF":7.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371218","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":"Clonality Determination by Detecting Unmodified Monoclonal Serum Free Light Chains Using On-Probe Extraction Coupled with Liquid Chromatography-High-Resolution Mass Spectrometry.","authors":"Priscilla S W Yeung, Yajing Liu, Samuel Yang, Ashley Ruan, Christina R Kerr, Carolyn V Wong, Run-Zhang Shi, David J Iberri, Ruben Y Luo","doi":"10.1093/clinchem/hvae130","DOIUrl":"10.1093/clinchem/hvae130","url":null,"abstract":"<p><strong>Background: </strong>Serum free light chains (FLCs) are an essential clinical biomarker for the diagnosis and monitoring of patients with plasma cell neoplasms. The current widely used immunoassay methods quantify total serum FLCs, which include monoclonal FLCs as well as FLCs in the polyclonal background. Patients with chronic diseases, inflammatory disorders, or renal dysfunction can have elevated total FLCs that lead to ambiguous results. These patients may benefit from a direct measurement of monoclonal FLCs. The purpose of this study was to develop a method that couples on-probe extraction (OPEX) with liquid chromatography-high-resolution mass spectrometry (LC-HR-MS), abbreviated to OPEX-MS, to directly determine the clonality of FLCs.</p><p><strong>Methods: </strong>OPEX immunocapture was performed using microprobes loaded with anti-kappa or anti-lambda light chain antibodies. Captured proteins were separated by reversed-phase LC and analyzed by HR-MS.</p><p><strong>Results: </strong>Four cohorts of samples from unique patients were tested based on immunoassay FLC results. The LC-HR-MS analysis in the OPEX-MS method provides both a unique retention time along with deconvoluted masses of FLC monomers and dimers for each clone. The study found that 16 out of 49 (33%) kappa FLC elevated samples as well as 83 out of 100 (83%) dual kappa and lambda FLC elevated samples did not have monoclonal FLCs, which is consistent with the knowledge that there is often no clonal population in samples with mildly elevated FLC immunoassay results.</p><p><strong>Conclusions: </strong>The OPEX-MS method can serve as a complementary approach to directly determine clonality in patients with difficult-to-interpret FLC immunoassay results.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"1436-1442"},"PeriodicalIF":7.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388717","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":"Progressive Motor Regression in a 3-Year-Old: Dietary Trends Revive an Overlooked Diagnosis.","authors":"Ashley R Rackow, Claire E Knezevic","doi":"10.1093/clinchem/hvae125","DOIUrl":"https://doi.org/10.1093/clinchem/hvae125","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"70 12","pages":"1416-1419"},"PeriodicalIF":7.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817328","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":"Commentary on Progressive Motor Regression in a 3-Year-Old: Dietary Trends Revive an Overlooked Diagnosis.","authors":"Lawrence de Koning","doi":"10.1093/clinchem/hvae159","DOIUrl":"https://doi.org/10.1093/clinchem/hvae159","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"70 12","pages":"1421"},"PeriodicalIF":7.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817227","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":"Untargeted Metabolomics for Inborn Errors of Metabolism: Development and Evaluation of a Sustainable Reference Material for Correcting Inter-Batch Variability.","authors":"Rafael Garrett, Adam S Ptolemy, Sara Pickett, Mark D Kellogg, Roy W A Peake","doi":"10.1093/clinchem/hvae141","DOIUrl":"10.1093/clinchem/hvae141","url":null,"abstract":"<p><strong>Background: </strong>Untargeted metabolomics has shown promise in expanding screening and diagnostic capabilities for inborn errors of metabolism (IEMs). However, inter-batch variability remains a major barrier to its implementation in the clinical laboratory, despite attempts to address this through normalization techniques. We have developed a sustainable, matrix-matched reference material (RM) using the iterative batch averaging method (IBAT) to correct inter-batch variability in liquid chromatography-high-resolution mass spectrometry-based untargeted metabolomics for IEM screening.</p><p><strong>Methods: </strong>The RM was created using pooled batches of remnant plasma specimens. The batch size, number of batch iterations per RM, and stability compared to a conventional pool of specimens were determined. The effectiveness of the RM for correcting inter-batch variability in routine screening was evaluated using plasma collected from a cohort of phenylketonuria (PKU) patients.</p><p><strong>Results: </strong>The RM exhibited lower metabolite variability between iterations over time compared to metabolites from individual batches or individual specimens used for its creation. In addition, the mean variation across amino acid (n = 19) concentrations over 12 weeks was lower for the RM (CVtotal = 8.8%; range 4.7%-25.3%) compared to the specimen pool (CVtotal = 24.6%; range 9.0%-108.3%). When utilized in IEM screening, RM normalization minimized unwanted inter-batch variation and enabled the correct classification of 30 PKU patients analyzed 1 month apart from 146 non-PKU controls.</p><p><strong>Conclusions: </strong>Our RM minimizes inter-batch variability in untargeted metabolomics and demonstrated its potential for routine IEM screening in a cohort of PKU patients. It provides a practical and sustainable solution for data normalization in untargeted metabolomics for clinical laboratories.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"1452-1462"},"PeriodicalIF":7.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375271","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}