Yanchun Lin, Christopher W Farnsworth, Vahid Azimi, David B Liss, Michael E Mullins, Bridgit O Crews
{"title":"Xylazine Pharmacokinetics in Patients Testing Positive for Fentanyl and Xylazine.","authors":"Yanchun Lin, Christopher W Farnsworth, Vahid Azimi, David B Liss, Michael E Mullins, Bridgit O Crews","doi":"10.1093/clinchem/hvae163","DOIUrl":"10.1093/clinchem/hvae163","url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of xylazine in the illicit drug supply is a growing concern for major health consequences in individuals who use fentanyl mixed with xylazine, but limited data are available regarding the pharmacokinetics of xylazine in humans.</p><p><strong>Methods: </strong>Xylazine was quantified in serial remnant plasmas collected from 28 patients starting at the initial patient encounter and continuing for up to 52 h from presentation, using LC-MS/MS to calculate the terminal half-life for xylazine. Xylazine metabolites were identified by product ion scanning, and multiple reaction monitoring was used to estimate the relative abundance of xylazine metabolites in 74 collected plasma samples.</p><p><strong>Results: </strong>The median terminal half-life for xylazine was calculated to be 12.0 h (range: 5.9-20.8). Oxo-xylazine and sulfone-xylazine metabolites were detected in all plasma specimens that contained xylazine.</p><p><strong>Conclusions: </strong>The half-life of xylazine in humans is longer than previously observed in animal studies, which furthers the current understanding of the expected duration of effects in individuals who use fentanyl mixed with xylazine and the window of detection. Both oxo-xylazine and sulfone-xylazine appear to circulate in plasma for as long as xylazine.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"266-273"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675177","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":"Hiding in Plain Sight: Protein Electrophoresis Profile Inconsistent with Patient's Diagnosis.","authors":"Vrajesh Pandya, Julio C Delgado","doi":"10.1093/clinchem/hvae119","DOIUrl":"https://doi.org/10.1093/clinchem/hvae119","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"71 2","pages":"248-252"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122368","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}
Peter A Kavsak, Alexander Kumaritakis, Matthew Wong-Fung, Tony Badrick, Michael Knauer
{"title":"Validation of Analytical Performance Limits for Accuracy with High-Sensitivity Cardiac Troponin Assays.","authors":"Peter A Kavsak, Alexander Kumaritakis, Matthew Wong-Fung, Tony Badrick, Michael Knauer","doi":"10.1093/clinchem/hvae198","DOIUrl":"10.1093/clinchem/hvae198","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"332-334"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750282","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 American Society of Hematology Thrombophilia Guidelines Could Provoke Surge in Laboratory Testing.","authors":"Anna E Merrill, Steven R Lentz","doi":"10.1093/clinchem/hvae167","DOIUrl":"https://doi.org/10.1093/clinchem/hvae167","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"71 2","pages":"337-338"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122370","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":"Reflecting on 70 Years of Clinical Chemistry.","authors":"Jason Y Park","doi":"10.1093/clinchem/hvae209","DOIUrl":"10.1093/clinchem/hvae209","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"227-229"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022388","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}
Kang Yang, Yue Liu, Ji Zhang, Qian Yu, Feng Xu, Jiyuan Liu, Yuting Li, Xiaojie Zhang, Zhiqiang Wang, Ning Wang, Yuezhen Li, Yan Shi, Wan-Jin Chen
{"title":"dmTGS: Precise Targeted Enrichment Long-Read Sequencing Panel for Tandem Repeat Detection.","authors":"Kang Yang, Yue Liu, Ji Zhang, Qian Yu, Feng Xu, Jiyuan Liu, Yuting Li, Xiaojie Zhang, Zhiqiang Wang, Ning Wang, Yuezhen Li, Yan Shi, Wan-Jin Chen","doi":"10.1093/clinchem/hvae164","DOIUrl":"10.1093/clinchem/hvae164","url":null,"abstract":"<p><strong>Background: </strong>Tandem repeats (TRs) are abundant in the human genome and associated with repeat expansion disorders. Our study aimed to develop a tandem repeat panel utilizing targeted long-read sequencing to evaluate known TRs associated with these disorders and assess its clinical utility.</p><p><strong>Methods: </strong>We developed a targeted long-read sequencing panel for 70 TR loci, termed dynamic mutation third-generation sequencing (dmTGS), using the PacBio Sequel II platform. We tested 108 samples with suspected repeat expansion disorders and compared the results with conventional molecular methods.</p><p><strong>Results: </strong>For 108 samples, dmTGS achieved an average of 8000 high-fidelity reads per sample, with a mean read length of 4.7 kb and read quality of 99.9%. dmTGS outperformed repeat-primed-PCR and fluorescence amplicon length analysis-PCR in distinguishing expanded from normal alleles and accurately quantifying repeat counts. The method demonstrated high concordance with confirmatory methods (rlinear = 0.991, P < 0.01), and detected mosaicism with sensitivities of 1% for FMR1 CGG premutation and 5% for full mutations. dmTGS successfully identified interruptive motifs in genes that conventional methods had missed. For variable number TRs in the PLIN4 gene, dmTGS identified precise repeat counts and sequence motifs. Screening 57 patients with suspected genetic muscular diseases, dmTGS confirmed repeat expansions in genes such as GIPC1, NOTCH2NLC, NUTM2B-AS1/LOC642361, and DMPK. Additionally, dmTGS detected CCG interruptions in CTG repeats in 8 myotonic dystrophy type 1 patients with detailed characterization.</p><p><strong>Conclusions: </strong>dmTGS accurately detects repeat sizes and interruption motifs associated with repeat expansion disorders and demonstrates superior performance compared to conventional molecular methods.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"319-331"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567853","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":"Persistent Unexplained Polyclonal IgA Gammopathy in a Patient with Multiple Myeloma.","authors":"Paul E Young, Heba Badr, Anthony O Okorodudu","doi":"10.1093/clinchem/hvae136","DOIUrl":"https://doi.org/10.1093/clinchem/hvae136","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"71 2","pages":"335-336"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122371","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 Role of Laboratory Medicine in Improving Maternal Health Outcomes and Reducing Disparities.","authors":"Vahid Azimi,Ann M Gronowski","doi":"10.1093/clinchem/hvaf002","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf002","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"147 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056972","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":"How Can Digital PCR Support the Rapid Development of New Detection Tests in Future Pandemics?","authors":"Helene Péré,David Veyer,Valerie Taly","doi":"10.1093/clinchem/hvae225","DOIUrl":"https://doi.org/10.1093/clinchem/hvae225","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"27 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991731","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}