{"title":"Commentary on An Unexpectedly High IgE Level during Allergic Exploration.","authors":"Rebecca S Treger","doi":"10.1093/clinchem/hvae176","DOIUrl":"https://doi.org/10.1093/clinchem/hvae176","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"71 2","pages":"246-247"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122365","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":"Rethinking Albuminuria in Low-Risk Patients and a Call for Urine Albumin Standardization.","authors":"Jesse C Seegmiller, Joachim H Ix","doi":"10.1093/clinchem/hvae157","DOIUrl":"10.1093/clinchem/hvae157","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"235-237"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521228","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":"Estimating Reference Change Values Using Routine Patient Data: A Novel Pathology Database Approach.","authors":"Eirik Åsen Røys, Kristin Viste, Ralf Kellmann, Nora Alicia Guldhaug, Bashir Alaour, Marit Sverresdotter Sylte, Janniche Torsvik, Heidi Strand, Michael Marber, Torbjørn Omland, Elvar Theodorsson, Graham Ross Dallas Jones, Kristin Moberg Aakre","doi":"10.1093/clinchem/hvae166","DOIUrl":"10.1093/clinchem/hvae166","url":null,"abstract":"<p><strong>Background: </strong>The reference change value (RCV) is calculated by combining the within-subject biological variation (CVI) and local analytical variation (CVA). These calculations do not account for the variation seen in preanalytical conditions in routine practice or CVI in patients presenting for treatment. As a result, the RCVs may not reflect routine practice or align with clinicians' experiences. We propose a novel RCV approach based on routine patient data that is potentially more clinically relevant.</p><p><strong>Methods: </strong>This study used the refineR algorithm to determine RCVs using serial patient data extracted from a local Laboratory Information System (LIS). The model was applied to biomarkers with a range of result ratio distributions varying from normal to log-normal. Results were compared against conventional formula-based RCVs using CVI estimates from a state-of-the-art biological variation study. Monte Carlo simulations were also used to validate the LIS data approach.</p><p><strong>Results: </strong>The RCVs estimated from LIS data were: 11-deoxycortisol (men): -70%/+196%, 17-hydroxyprogesterone (men): -49%/+100%, albumin: -10%/+11%, androstenedione (men): -47%/+96%, cortisol (men): -54%/+51%, cortisone (men): -32%/+51%, creatinine: -16%/+14%, phosphate (women): -23%/+29%, phosphate (men): -27%/+29%, testosterone (men): -38%/+60%. The formula-based RCV estimates showed similar but slightly lower results, and the Monte Carlo simulations confirmed the applicability of the new approach.</p><p><strong>Conclusions: </strong>RCVs may be estimated from patient results without prior assumptions about the shape of the ratios between serial results. Laboratories can determine RCVs based on local practice and population.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"307-318"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567858","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}
Maria B Nielsen, Marianne Benn, Børge G Nordestgaard, Lone Skov, Yunus Çolak
{"title":"Adiponectin and Risk of Psoriasis: Observational and Mendelian Randomization Studies in up to 900 000 Individuals.","authors":"Maria B Nielsen, Marianne Benn, Børge G Nordestgaard, Lone Skov, Yunus Çolak","doi":"10.1093/clinchem/hvae160","DOIUrl":"10.1093/clinchem/hvae160","url":null,"abstract":"<p><strong>Background: </strong>Psoriasis is a chronic inflammatory skin disorder often associated with obesity. Adiponectin, an anti-inflammatory protein-hormone secreted by adipose tissue, may be a link between obesity and psoriasis. We hypothesized that low plasma adiponectin is associated with an increased risk of psoriasis in observational and causal genetic studies.</p><p><strong>Methods: </strong>In observational analyses, we used information on plasma adiponectin and psoriasis in 30 045 individuals from the Copenhagen General Population Study (CGPS). In one-sample Mendelian randomization analyses, we used genetic information on adiponectin and psoriasis in 107 308 individuals from the CGPS. In two-sample Mendelian randomization analyses, we used genetic information on adiponectin from the ADIPOGen consortium and genetic information on psoriasis in 373 338 and 462 933 individuals from the FinnGen study and UK Biobank (UKB).</p><p><strong>Results: </strong>In observational analyses, a 1-unit log-transformed higher plasma adiponectin was associated with a hazard ratio (HR) for psoriasis of 0.67 (95% confidence interval: 0.48-0.94) in an age- and sex-adjusted model but not in a multivariable adjusted model including obesity measures with a HR of 0.95 (0.66-1.35). In genetic one-sample Mendelian randomization analysis, a 1-unit log-transformed higher plasma adiponectin was not associated with a causal risk ratio for psoriasis of 1.33 (0.77-2.32) in the CGPS. In two-sample Mendelian randomization analyses, a 1-unit log-transformed higher plasma adiponectin was not associated with causal risk ratios for psoriasis of 0.96 (0.81-1.14) in FinnGen and 1.00 (1.00-1.01) in UKB.</p><p><strong>Conclusions: </strong>Low plasma adiponectin is associated with increased risk of psoriasis in age- and sex-adjusted observational analyses; however, this was not the case after adjustment for obesity measures or in causal genetic analyses.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"286-295"},"PeriodicalIF":7.1,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544200","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}
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":"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}
{"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}
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}