{"title":"HOPEing That a PEACEful Resolution for the Clinical Utility of High-Sensitivity Cardiac Troponin in the Ambulatory Setting Will Improve Laboratory Testing.","authors":"Peter A Kavsak","doi":"10.1093/clinchem/hvaf034","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf034","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729239","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}
Simona Ferraro, Simona Da Molin, Cristina Cereda, Gianvincenzo Zuccotti, Santica Marcovina, Bruno Mario Cesana
{"title":"Vitamin B12 Deficiency and New Recommendations by the National Institute for Health and Care Excellence: A Challenging Clinical and Laboratory Topic.","authors":"Simona Ferraro, Simona Da Molin, Cristina Cereda, Gianvincenzo Zuccotti, Santica Marcovina, Bruno Mario Cesana","doi":"10.1093/clinchem/hvaf037","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf037","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729245","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}
Michelle Silasi, Marly Azzi, Sanela Potchileev, Luke Burns, Sarosh Rana
{"title":"Placental Biomarker Testing for Evaluation of Suspected Preeclampsia.","authors":"Michelle Silasi, Marly Azzi, Sanela Potchileev, Luke Burns, Sarosh Rana","doi":"10.1093/clinchem/hvaf024","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf024","url":null,"abstract":"<p><strong>Background: </strong>Worldwide, hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and neonatal morbidity and mortality (Semin Perinatol 2009;33:130-7). This is especially true in the United States where preeclampsia is a leading cause of premature births (Hypertens Pregnancy 2016;35:510-9 and Lancet 2008;371:164-75). Moreover, this disorder is costly due to the financial burden of the health services needed to care for mothers with preeclampsia and their very often preterm infants (Am J Obstet Gynecol 2017;217:235-6). Recently, placental biomarkers have been shown to aid in assessment of the risk of severe preeclampsia. In 2023, the FDA approved the use of soluble feline McDonough sarcoma (fms)-like tyrosine kinase-1 to placental growth factor ratio (sFlt-1/PlGF) as an additional tool for preeclampsia risk assessment between 23 and 35 weeks' gestation in high-risk patients in the United States. Use of these biomarkers will improve maternal and fetal/neonatal outcomes and may assist in decreasing the healthcare burden of these patients by adding to risk assessment and the current diagnosis and management of pregnancies with HDP.</p><p><strong>Content: </strong>The pathophysiology of preeclampsia stems from abnormal placentation that results in an imbalance of pro- and antiangiogenic factors leading to endothelial and vascular dysfunction and the clinical syndrome of preeclampsia (J Clin Invest 2003;111:649-58). The role of the sFlt-1/PlGF in the prediction of progression to preeclampsia has been demonstrated in multiple studies.</p><p><strong>Summary: </strong>The goal of this review is to demonstrate the role of placental biomarkers (sFlt-1 and PlGF) in the pathophysiology of preeclampsia, with an emphasis on clinical applications and cost-effectiveness in the United States, using real-world applications as examples.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699855","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 Economics of Cell-Free DNA Metagenomic Next-Generation Sequencing for Pathogen Detection.","authors":"Shangxin Yang","doi":"10.1093/clinchem/hvaf027","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf027","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699859","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":"Incidental Findings of Maternal Cancer in Noninvasive Prenatal Testing through Cell-Free DNA Sequencing.","authors":"Daniel J Smit, Klaus Pantel","doi":"10.1093/clinchem/hvaf014","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf014","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673535","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}
Megan Culler Freeman, Adam Sinder, Grace Conway, Sarah Chamseddine, Mariam Faiz Nassar, Bradley J Wheeler, Adam Anderson, Sarah E Wheeler
{"title":"Pediatric Vaccine-Induced Antibody Thresholds: Rethinking Pre-Immunosuppression Serologic Testing and Revaccination Implications","authors":"Megan Culler Freeman, Adam Sinder, Grace Conway, Sarah Chamseddine, Mariam Faiz Nassar, Bradley J Wheeler, Adam Anderson, Sarah E Wheeler","doi":"10.1093/clinchem/hvaf020","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf020","url":null,"abstract":"Background Immune response to vaccination is assessed when adequate vaccine protection is in question or immunosuppression is imminent through measurement of antibody levels, which wane as time from vaccination increases. The serologic cutoff value for adequate response is based on thresholds derived from studies in adults, and age-appropriate thresholds for children have not been established. We sought to investigate age-specific differences in antibody levels in healthy children to guide determination of vaccine immunity status when clinically indicated. Methods This cross-sectional study assessed clinical serology for measles, mumps, rubella (MMR), varicella, and hepatitis B (HepB) in an age-stratified cohort of 471 healthy children who were up to date for vaccination (1 to 18 years). Remnant specimens with sufficient volume were collected from July 23, 2019, to November 17, 2020, as convenience samples and chart reviewed for inclusion. Results While children of all ages had detectable titers to MMR, median titers for HepB and varicella waned by ages 11 to 12 and 9 to 10 years, respectively. Children had titers above adult thresholds for MMR at all measured timepoints, retrospectively resulting in 24.6% (95% CI, 21.6%–27.8%) of children having an inappropriate MMR classification when adult instead of pediatric thresholds were used. Current use of HepB and varicella serology may be inappropriate due to the rapid waning of titers. The adequacy of an individual’s response to one vaccine component did not infer adequate responses to other components. Conclusions Application of age-appropriate reference intervals for vaccine serologic tests will provide a foundation for improved treatment recommendations and standards of care.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"90 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653457","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}
Babak Yazdani, Graciela E Delgado, Anders H Berg, Christoph Wanner, Bernhard K Krämer, Winfried März, Marcus E Kleber, Christiane Drechsler
{"title":"Carbamylated Albumin, Heart Failure, and Mortality in Patients Undergoing Coronary Angiography.","authors":"Babak Yazdani, Graciela E Delgado, Anders H Berg, Christoph Wanner, Bernhard K Krämer, Winfried März, Marcus E Kleber, Christiane Drechsler","doi":"10.1093/clinchem/hvaf021","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf021","url":null,"abstract":"<p><strong>Background: </strong>Urea is elevated in chronic kidney disease (CKD) and end-stage renal disease (ESRD), and promotes the carbamylation of proteins, including human albumin, on multiple lysine side chains. Higher proportions of carbamylated albumin (C-Alb) have been associated with increased mortality risk in patients with ESRD. Whether C-Alb predicts mortality in patients with no or mild impairment of kidney function is unknown.</p><p><strong>Methods: </strong>We measured C-Alb in 3197 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study who had been referred to coronary angiography and followed-up for 10 years. Association of baseline C-Alb with all-cause and cause-specific mortality was investigated using Cox proportional hazards regression.</p><p><strong>Results: </strong>Higher quartiles of C-Alb were associated with a significantly increased risk of death from any cause, with hazard ratios (HRs, 95%CI) of 1.53 (1.26-1.85) and 2.52 (2.11-3.01) in the third and fourth quartiles, respectively. After adjustment for cardiovascular (CV) risk factors, including estimate glomerular filtration rate (eGFR), the association with mortality was attenuated with a HR of 1.25 (1.02-1.53) for the fourth quartile as compared to the first quartile. We observed the strongest association with death due to congestive heart failure (HF) with a HR of 7.19 (4.57-11.3) and 3.99 (2.40-6.63) per 1-unit increase of log-transformed C-Alb in unadjusted and multivariate adjusted analyses, respectively.</p><p><strong>Conclusions: </strong>We observed a strong association of C-Alb with CV risk in patients with no or mild CKD. This association was independent of traditional CV risk factors including eGFR and particularly strong regarding death due to congestive HF.</p>","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662930","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":"https://doi.org/10.1093/clinchem/hvaf017","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-03-12","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}
Eddie G Dominguez, Bradon R McDonald, Haikun Zhang, Michelle D Stephens, Elise C Dietmann, Megan Nedden, Nicole Byington, Sydney Thompson, Mary Junak, Caitlin S Pepperell, Mehreen T Kisat
{"title":"Enrichment of Microbial DNA in Plasma to Improve Pathogen Detection in Sepsis: A Pilot Study","authors":"Eddie G Dominguez, Bradon R McDonald, Haikun Zhang, Michelle D Stephens, Elise C Dietmann, Megan Nedden, Nicole Byington, Sydney Thompson, Mary Junak, Caitlin S Pepperell, Mehreen T Kisat","doi":"10.1093/clinchem/hvaf011","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf011","url":null,"abstract":"Background Diagnosis of sepsis and timely identification of pathogens in critically ill patients remains challenging. Plasma metagenomic sequencing to detect microbial cell-free DNA (mDNA) has shown promise, but low abundance of mDNA in plasma limits sensitivity and necessitates high sequencing depth. mDNA is shorter and more fragmented than human cell-free DNA. Here, we evaluated whether combining single-stranded DNA (ssDNA) sequencing library preparation and size selection can enrich mDNA and improve pathogen detection. Methods We prospectively enrolled 48 trauma patients and collected daily blood samples during the first 10 days of intensive care unit (ICU) admission. For patients with culture-proven infections, we extracted plasma DNA, prepared double-stranded DNA (dsDNA) and ssDNA sequencing libraries, and applied size selection to exclude fragments &gt;110 bp. Following sequencing, we performed taxonomic classification, and evaluated differences in mDNA fractions and in sensitivity for pathogen detection (compared to background noise). Results We analyzed 46 plasma samples from 5 patients who developed culture-proven infections, including 17 samples coincident with positive microbial cultures. Size-selected ssDNA libraries showed the total mDNA fraction 204-fold higher on average than conventional dsDNA libraries (P &lt; 0.0001). However, for pathogen-specific DNA (at the genus level), the highest sensitivity was observed in size-selected dsDNA (82%), compared to dsDNA (41%), ssDNA (71%), and size-selected ssDNA (35%) library preparations. Conclusions Our results demonstrate that combining ssDNA library preparation together with fragment size selection improves mDNA yield, potentially reducing sequencing requirements. However, at the genus level, this combination also increases background noise, which limits sensitivity for pathogen detection.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"213 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599830","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":"Comprehensive Annotation of Complete ABO Alleles and Resolution of ABO Variants by an Improved Full-Length ABO Haplotype Sequencing","authors":"Yanling Ying, Jingjing Zhang, Xiaozhen Hong, Wenjing Yuan, Kairong Ma, Xinyu Huang, Xianguo Xu, Faming Zhu","doi":"10.1093/clinchem/hvaf015","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf015","url":null,"abstract":"Background Full-length ABO haplotype sequencing is crucial for accurate genotyping, reference gene annotation, and molecular mechanism analysis of its variants. However, there is currently a deficiency of comprehensive annotation for full-length ABO haplotypes, spanning from the 5′ untranslated region (UTR) to the 3′ UTR. Methods Two sets of specimens (79 random blood donors and 47 ABO variants) were tested. The full-length ABO gene spanning the 5′ UTR to the 3′ UTR was amplified using an improved one-step ultra-long-range PCR with a pair of PCR suppression primers. A single-molecule real-time library was constructed, and ABO haplotype sequencing was performed. Data analysis including basecalling, aligning, variant calling, clustering, and variant annotation were performed. Results The amplicon measured 26.1 kb without splicing, representing the most complete ABO gene reported to date. The complete ABO haplotype sequence was obtained via long-read sequencing. The comprehensive ABO reference alleles were obtained and the ABO sequence patterns within each allele in a Chinese population were further classified. The full-length ABO gene haplotype analysis technique effectively resolved ABO variants with structural variations (SVs), including large fragment deletions, inversions, recombination, and chimeras. Conclusions Full-length ABO haplotype sequencing filled a gap that was missing with respect to the 3′ UTR sequences of ABO alleles and can advance blood group genomic analysis, aiding in ABO gene function analysis, evolutionary studies, and the resolution of ABO variants.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"18 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570438","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}