Clinical chemistry最新文献

{"title":"Commentary on Alkaline Phosphatase Activity Inconsistent with Patient's Clinical Presentation: A Cautionary Tale.","authors":"Isabelle Piec","doi":"10.1093/clinchem/hvae134","DOIUrl":"https://doi.org/10.1093/clinchem/hvae134","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"70 12","pages":"1415"},"PeriodicalIF":7.1,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817275","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":"Virtual Gene Panels Have a Superior Diagnostic Yield for Inherited Rare Diseases Relative to Static Panels","authors":"Massomeh Sheikh Hassani, Ruchi Jain, Sathishkumar Ramaswamy, Shruti Sinha, Maha El Naofal, Nour Halabi, Sawsan Alyafei, Roudha Alfalasi, Shruti Shenbagam, Alan Taylor, Ahmad Abou Tayoun","doi":"10.1093/clinchem/hvae183","DOIUrl":"https://doi.org/10.1093/clinchem/hvae183","url":null,"abstract":"Background Exome- or genome-based panels—also known as slices or virtual panels—are now a popular approach that involves comprehensive genomic sequencing while restricting analysis to subsets of genes based on patients’ phenotypes. This flexible strategy enables frequent gene updates based on novel disease associations as well as reflexing to analyzing other genes up to the whole exome or genome. With recent improvements addressing limitations associated with virtual panels, the advantages of this approach, relative to static custom-based panels, remain to be systematically characterized. Methods Here we perform slice testing on 1014 patients (50.5% females; average age 17 years) referred from multiple pediatric clinics within a single center in the Middle East (83% Arab population). Results Initial analysis uncovered molecular diagnoses for 235 patients for a diagnostic yield of 23% (235/1014). “On the fly” focused analysis in most negative cases (N = 779) identified clinically significant variants correlating with patients’ presentations in genes outside the originally ordered panel for another 35 patients (3.5% or 35/1024) increasing the overall diagnostic yield to 27%. The pathogenic variants underlying the additional cases (13% of all positive cases) were excluded from the original “panel” gene list, mainly as result of issues related to panel selection, novel gene–disease associations, phenotype spectrum broadening, or gene lists variability. The additional findings led to changes in clinical management in most patients (94%). Conclusions Our findings support slice testing as an efficient and flexible platform that facilitates updates to gene lists to achieve high clinical sensitivity and utility.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"170 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678610","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":"Prospective and External Validation of an Ensemble Learning Approach to Sensitively Detect Intravenous Fluid Contamination in Basic Metabolic Panels","authors":"Nicholas C Spies, Leah Militello, Christopher W Farnsworth, Joe M El-Khoury, Thomas J S Durant, Mark A Zaydman","doi":"10.1093/clinchem/hvae168","DOIUrl":"https://doi.org/10.1093/clinchem/hvae168","url":null,"abstract":"Background Intravenous (IV) fluid contamination within clinical specimens causes an operational burden on the laboratory when detected, and potential patient harm when undetected. Even mild contamination is often sufficient to meaningfully alter results across multiple analytes. A recently reported unsupervised learning approach was more sensitive than routine workflows, but still lacked sensitivity to mild but significant contamination. Here, we leverage ensemble learning to more sensitively detect contaminated results using an approach which is explainable and generalizable across institutions. Methods An ensemble-based machine learning pipeline of general and fluid-specific models was trained on real-world and simulated contamination and internally and externally validated. Benchmarks for performance assessment were derived from in silico simulations, in vitro experiments, and expert review. Fluid-specific regression models estimated contamination severity. SHapley Additive exPlanation (SHAP) values were calculated to explain specimen-level predictions, and algorithmic fairness was evaluated by comparing flag rates across demographic and clinical subgroups. Results The sensitivities, specificities, and Matthews correlation coefficients were 0.858, 0.993, and 0.747 for the internal validation set, and 1.00, 0.980, and 0.387 for the external set. SHAP values provided plausible explanations for dextrose- and ketoacidosis-related hyperglycemia. Flag rates from the pipeline were higher than the current workflow, with improved detection of contamination events expected to exceed allowable limits for measurement error and reference change values. Conclusions An accurate, generalizable, and explainable ensemble-based machine learning pipeline was developed and validated for sensitively detecting IV fluid contamination. Implementing this pipeline would help identify errors that are poorly detected by current clinical workflows and a previously described unsupervised machine learning-based method.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"64 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637629","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":"Proteinuria, Blinded by Bright Light.","authors":"Mirthe Ubink, Judith Y M N Derijks-Engwegen, Miranda van Berkel, Harm Westdorp, Joannes F M Jacobs","doi":"10.1093/clinchem/hvae111","DOIUrl":"https://doi.org/10.1093/clinchem/hvae111","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"70 11","pages":"1393-1394"},"PeriodicalIF":7.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567937","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 Mosaic Copy Number Variation in a Patient with Cerebral and Pulmonary Arteriovenous Malformations and Recurrent Epistaxis.","authors":"Anne B S Giersch","doi":"10.1093/clinchem/hvae113","DOIUrl":"https://doi.org/10.1093/clinchem/hvae113","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"70 11","pages":"1320"},"PeriodicalIF":7.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567894","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":"Alzheimer Disease Blood-Based Biomarkers: Translation from Research into Clinical Use.","authors":"Lance A Ladic, Mari L DeMarco, Nicholas J Ashton, Andrew J Saykin, Louis B Jacques","doi":"10.1093/clinchem/hvae144","DOIUrl":"10.1093/clinchem/hvae144","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"1308-1314"},"PeriodicalIF":7.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371216","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":"Deconvolution of Human Urine across the Transcriptome and Metabolome.","authors":"Sevahn K Vorperian, Brian C DeFelice, Joseph A Buonomo, Hagop J Chinchinian, Ira J Gray, Jia Yan, Kathleen E Mach, Vinh La, Timothy J Lee, Joseph C Liao, Richard Lafayette, Gabriel B Loeb, Carolyn R Bertozzi, Stephen R Quake","doi":"10.1093/clinchem/hvae137","DOIUrl":"10.1093/clinchem/hvae137","url":null,"abstract":"<p><strong>Background: </strong>Early detection of the cell type changes underlying several genitourinary tract diseases largely remains an unmet clinical need, where existing assays, if available, lack the cellular resolution afforded by an invasive biopsy. While messenger RNA in urine could reflect the dynamic signal that facilitates early detection, current measurements primarily detect single genes and thus do not reflect the entire transcriptome and the underlying contributions of cell type-specific RNA.</p><p><strong>Methods: </strong>We isolated and sequenced the cell-free RNA (cfRNA) and sediment RNA from human urine samples (n = 6 healthy controls and n = 12 kidney stone patients) and measured the urine metabolome. We analyzed the resulting urine transcriptomes by deconvolving the noninvasively measurable cell type contributions and comparing to plasma cfRNA and the measured urine metabolome.</p><p><strong>Results: </strong>Urine transcriptome cell type deconvolution primarily yielded relative fractional contributions from genitourinary tract cell types in addition to cell types from high-turnover solid tissues beyond the genitourinary tract. Comparison to plasma cfRNA yielded enrichment of metabolic pathways and a distinct cell type spectrum. Integration of urine transcriptomic and metabolomic measurements yielded enrichment for metabolic pathways involved in amino acid metabolism and overlapped with metabolic subsystems associated with proximal tubule function.</p><p><strong>Conclusions: </strong>Noninvasive whole transcriptome measurements of human urine cfRNA and sediment RNA reflects signal from hard-to-biopsy tissues exhibiting low representation in blood plasma cfRNA liquid biopsy at cell type resolution and are enriched in signal from metabolic pathways measurable in the urine metabolome.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"1344-1354"},"PeriodicalIF":7.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388718","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":"Mosaic Copy Number Variation in a Patient with Cerebral and Pulmonary Arteriovenous Malformations and Recurrent Epistaxis.","authors":"Sharri S Cyrus, Michelle L Kluge, Cherisse A Marcou, Erik C Thorland, Vivek N Iyer, Linnea M Baudhuin","doi":"10.1093/clinchem/hvae101","DOIUrl":"https://doi.org/10.1093/clinchem/hvae101","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"70 11","pages":"1315-1319"},"PeriodicalIF":7.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567872","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":"Niacin and Risk of Cardiovascular Events: Deciphering the Paradox.","authors":"Ravinder Sodi","doi":"10.1093/clinchem/hvae064","DOIUrl":"10.1093/clinchem/hvae064","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"1305-1307"},"PeriodicalIF":7.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418255","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 Mosaic Copy Number Variation in a Patient with Cerebral and Pulmonary Arteriovenous Malformations and Recurrent Epistaxis.","authors":"Naif A M Almontashiri","doi":"10.1093/clinchem/hvae128","DOIUrl":"https://doi.org/10.1093/clinchem/hvae128","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"70 11","pages":"1319-1320"},"PeriodicalIF":7.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567899","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}