Clinical chemistry最新文献

{"title":"Automated and Decentralized Genomic Profiling of Plasma Cell-Free DNA for Identification of Targetable and Resistance Alterations in Advanced Solid Tumors","authors":"Hiu Ting Chan, Masumi Otaki, Naomi Hayashi, Ippei Fukada, Yoon Ming Chin, Naoki Fukuda, Mari Hosonaga, Xiaofei Wang, Mayu Yunokawa, Eiji Shinozaki, Kensei Yamaguchi, Takeru Wakatsuki, Akiyoshi Kasuga, Yusuke Nakamura, Shunji Takahashi, Siew-Kee Low","doi":"10.1093/clinchem/hvaf045","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf045","url":null,"abstract":"Background Existing circulating cell-free DNA (cfDNA) assays are primarily centralized, requiring specialized sample handling and transportation. Implementing a flexible, decentralized sequencing system at point of care, with minimal technical oversight, can enhance turnaround times and patient access to genomic profiling. In this study, we aimed to evaluate the clinical feasibility of an automated and decentralized cfDNA next-generation sequencing (NGS) assay for identifying actionable alterations in advanced solid tumors. Methods Genomic profiling of plasma cfDNA from 298 patients with advanced solid tumors was conducted using an automated NGS assay. We assessed concordance of tumor mutations detected in plasma cfDNA and patient-matched tumor tissues analyzed by an FDA-approved assay, investigating clinical factors influencing circulating tumor DNA (ctDNA) aberration (mut-ctDNA) detection sensitivity. Results Sequencing success rates for cfDNA genomic profiling was significantly higher than archived tumor tissue (99% vs 96%). Mut-ctDNA detection rates ranged from 20% to 67% across different solid tumors. Targetable or resistance alterations were found in 18% of the patients. About 72% of the patients showed concordant alterations from tissue and plasma. The level of concordance was associated with the cancer type, tumor burden, and metastatic location. Notably, 63 plasma-only alterations were identified in 18% of patients and were more frequently observed in those with prior targeted treatments (24%) compared to chemotherapy (10%). Conclusions This study underscores the clinical feasibility of an automated, decentralized cfDNA genomic profiling approach. It emphasizes the importance of considering confounding clinical factors when selecting plasma- or tissue-based profiling assay. Such an approach holds promise for enhancing patient access to timely genomic profiling and targeted therapy selection.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"69 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910145","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 Slow Progress in Developing Better Long-Term Cardiovascular Risk Assessment in Women Continues.","authors":"Leslie J Donato, Kyla M Lara-Breitinger, Allan S Jaffe","doi":"10.1093/clinchem/hvaf003","DOIUrl":"10.1093/clinchem/hvaf003","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"535-537"},"PeriodicalIF":7.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381822","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 Secondary Amenorrhea and Clinical Hyperandrogenism in a 34-Year-Old Female: Polycystic Ovary Syndrome or Not?","authors":"Jeffrey R Vercollone","doi":"10.1093/clinchem/hvaf006","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf006","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"64 1","pages":"547"},"PeriodicalIF":9.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903029","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":"Secondary Amenorrhea and Clinical Hyperandrogenism in a 34-Year-Old Female: Polycystic Ovary Syndrome or Not?","authors":"Sameen Hassan,Beth M Lalande,Robert D Nerenz","doi":"10.1093/clinchem/hvae214","DOIUrl":"https://doi.org/10.1093/clinchem/hvae214","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"10 1","pages":"542-545"},"PeriodicalIF":9.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903030","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 Secondary Amenorrhea and Clinical Hyperandrogenism in a 34-Year-Old Female: Polycystic Ovary Syndrome or Not?","authors":"Graham Robert Lee","doi":"10.1093/clinchem/hvae224","DOIUrl":"https://doi.org/10.1093/clinchem/hvae224","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"8 1","pages":"546"},"PeriodicalIF":9.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902902","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":"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":"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":"548-558"},"PeriodicalIF":7.1,"publicationDate":"2025-05-02","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":"Quality Control Measurements Yield Similar Variation Below and Above Limit of Quantification for High-Sensitivity Cardiac Troponin I Assays.","authors":"Peter A Kavsak,Won-Shik Choi,Wael L Demian,Curtis Oleschuk","doi":"10.1093/clinchem/hvaf057","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf057","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"18 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903031","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":"10.1093/clinchem/hvaf027","url":null,"abstract":"","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":" ","pages":"532-534"},"PeriodicalIF":7.1,"publicationDate":"2025-05-02","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":"Biological Variation of Erythrocyte Total, Metal-Free, and Zinc Protoporphyrin IX in Patients with Erythropoietic Protoporphyria and Healthy Subjects: Implications for Clinical Interpretation and Monitoring","authors":"Paul Kjetel Soldal Lillemoen, Pernille Kjeilen Fauskanger, Sverre Sandberg, Aasne Karine Aarsand","doi":"10.1093/clinchem/hvaf055","DOIUrl":"https://doi.org/10.1093/clinchem/hvaf055","url":null,"abstract":"Background There is a lack of robust biological variation (BV) data for porphyria-related biomarkers. Our study aimed to estimate BV of erythrocyte total, metal-free, and zinc protoporphyrin IX in patients with erythropoietic protoporphyria (EPP) and healthy subjects and to explore the clinical implications of these data. Methods Fourteen patients with EPP and 15 healthy subjects were sampled quarterly for 2 years, and erythrocyte protoporphyrin analyses were performed in duplicate in all samples. A Bayesian method was used to estimate the within-subject (CVI) and personal (CVP(i)) BV. Results Based on clinical and laboratory assessments, EPP patients were stable during the study, with only 2 data points excluded. CVI in the EPP cohort was estimated as 9.8% (95% credible interval 8.5%–11.5%) for erythrocyte total protoporphyrin, 10.5% (9.0%–12.3%) for metal-free protoporphyrin, and 5.9% (4.3%–8.0%) for zinc protoporphyrin. Baseline metal-free protoporphyrin ranged from 6.9 to 139.8 µmol/L, but the CVP(i)s derived for each patient were similar (20th and 80th percentile of predicted distribution 9.5%–11.5%), and data were homogeneously distributed. Metal-free protoporphyrin was not measurable in the healthy cohort. Data for zinc protoporphyrin were heterogeneously distributed in both study cohorts. Conclusions The EPP patients had different set points for metal-free protoporphyrin, but the CVP(i) was similar, supporting the use of the same treatment goals when monitoring. This study is the first to use Bayesian analysis to demonstrate that personal BV is similar in patients with stable, chronic disease and different set points.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":"20 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901787","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":"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":"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":"587-598"},"PeriodicalIF":7.1,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046634/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}