Clinical chemistry最新文献

Full-Length Immune Repertoire Reconstruction and Profiling at the Transcriptome Level Using Long-Read Sequencing 利用长读数测序在转录组水平重建和分析全长免疫谱系

IF 9.3 2区医学

Clinical chemistry Pub Date : 2024-09-17 DOI: 10.1093/clinchem/hvae138

Xuanmei Luo, Lili Zhang, Yifei Li, Chang Li, Gaoyuan Sun, Chunli Zhang, Yu Fu, Haozhen Lv, Ming Liu, Hongyuan Cui, Dali Cai, Lihui Zou, Jie Ma, Fei Xiao

{"title":"Full-Length Immune Repertoire Reconstruction and Profiling at the Transcriptome Level Using Long-Read Sequencing","authors":"Xuanmei Luo, Lili Zhang, Yifei Li, Chang Li, Gaoyuan Sun, Chunli Zhang, Yu Fu, Haozhen Lv, Ming Liu, Hongyuan Cui, Dali Cai, Lihui Zou, Jie Ma, Fei Xiao","doi":"10.1093/clinchem/hvae138","DOIUrl":"https://doi.org/10.1093/clinchem/hvae138","url":null,"abstract":"Background Due to the diversity of the immune repertoire (IR), reconstructing full-length IR using traditional short-read sequencing has proven challenging. Methods A full-length IR sequencing (FLIRseq) work flow was developed with linear rolling circle amplification and nanopore sequencing. Its accuracy and quantification ability were verified by plasmid mixtures and commercial B-cell receptor/T-cell receptor sequencing (BCR/TCR-seq) based on short reads. IRs in tissues and the peripheral blood from 8 patients with acute lymphoblastic leukemia, 3 patients with allergic diseases, 4 patients with psoriasis, and 5 patients with prostate cancer were analyzed using FLIRseq. Results FLIRseq reads had lower mismatch rates and gap rates, and higher identify rates than nanopore reads (all P &lt; 2.2 × −16). The relative quantification of components by FLIRseq was consistent with the actual quantification (P &gt; 0.05). FLIRseq had superiority over BCR/TCR-seq, providing the long complementarity-determining region 3, B-cell isotype, and the rarely used V gene sequence. FLIRseq observed an increase in clonotype diversity (P &lt; 0.05) and a decrease in the percentage of abnormal BCRs/TCRs in patients with leukemia in remission. For patients with allergic diseases or psoriasis, FLIRseq provided direct insights into V(D)J recombination and specific immunoglobulin classes. Compared with that in prostate cancer tissues, the full-length V segment of the biased T-cell receptor β chain from lymphocytes in psoriatic tissues showed a more consistent AlphaFold2-predicted protein structure (P &lt; 0.05). Conclusions FLIRseq enables unbiased and comprehensive analyses of direct V(D)J recombination and immunoglobulin classes, thereby contributing to characterizing pathogenic mechanisms, monitoring minimal residual disease, and customizing adoptive cell therapy.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236867","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}

引用次数: 0

Clinical Decision-Making Suffers from Inequivalent Measurement Results and Inadequate Reference Intervals 临床决策受制于不等效的测量结果和不适当的参考区间

IF 9.3 2区医学

Clinical chemistry Pub Date : 2024-09-17 DOI: 10.1093/clinchem/hvae129

Marith van Schrojenstein Lantman, Miranda van Berkel, Philip Kuijper, Marloes Langelaan, Nannette Brouwer, Marc Thelen

{"title":"Clinical Decision-Making Suffers from Inequivalent Measurement Results and Inadequate Reference Intervals","authors":"Marith van Schrojenstein Lantman, Miranda van Berkel, Philip Kuijper, Marloes Langelaan, Nannette Brouwer, Marc Thelen","doi":"10.1093/clinchem/hvae129","DOIUrl":"https://doi.org/10.1093/clinchem/hvae129","url":null,"abstract":"Background Appropriate clinical decision-making relies on the interpretation of equivalent measurement results in the context of valid clinical decision limits. Besides guideline-based decision limits, reference intervals (RIs) are commonly used to discriminate between abnormal results and results from “healthy” individuals. This study evaluated the suitability of RIs in light of the analytical bias for laboratories in the Netherlands using one standardized, one harmonized, and one unharmonized measurand (creatinine, hemoglobin, and ferritin, respectively). Methods Three types of data were collected: (a) external quality assessment (EQA) performance data from the Dutch Foundation for Quality Assurance in Laboratory Medicine (SKML); (b) the RIs reported by laboratories for a 55-year-old female; and (c) harmonized RIs established by using unique routine patient results using RefineR. Routinely used RIs (b) were compared to the harmonized RIs (c) and evaluated in combination with the analytical bias at the lower and upper reference limits. Results Laboratories reported a variety of routinely used RIs that were inconsistent with the analytical bias, with differences between measurement procedures. The use of assays that perform within allowable bias limits does not automatically guarantee that the appropriate RI is used, allowing potential for structural misinterpretation of important diagnoses in patients. Conclusions The use of RIs that are inconsistent with the analytical bias causes unnecessary between-laboratory differences in clinical decision-making. Adopting harmonized RIs facilitates similar interpretation of results across facilities. Harmonized RIs can be adopted immediately if the observed bias is acceptable or eliminated, or after standardization/harmonization of measurands without complete metrological traceability.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236641","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}

引用次数: 0

Validating, Implementing, and Monitoring Machine Learning Solutions in the Clinical Laboratory Safely and Effectively. 在临床实验室安全有效地验证、实施和监控机器学习解决方案。

IF 9.3 2区医学

Clinical chemistry Pub Date : 2024-09-10 DOI: 10.1093/clinchem/hvae126

Nicholas C Spies,Christopher W Farnsworth,Sarah Wheeler,Christopher R McCudden

{"title":"Validating, Implementing, and Monitoring Machine Learning Solutions in the Clinical Laboratory Safely and Effectively.","authors":"Nicholas C Spies,Christopher W Farnsworth,Sarah Wheeler,Christopher R McCudden","doi":"10.1093/clinchem/hvae126","DOIUrl":"https://doi.org/10.1093/clinchem/hvae126","url":null,"abstract":"BACKGROUNDMachine learning solutions offer tremendous promise for improving clinical and laboratory operations in pathology. Proof-of-concept descriptions of these approaches have become commonplace in laboratory medicine literature, but only a scant few of these have been implemented within clinical laboratories, owing to the often substantial barriers in validating, implementing, and monitoring these applications in practice. This mini-review aims to highlight the key considerations in each of these steps.CONTENTEffective and responsible applications of machine learning in clinical laboratories require robust validation prior to implementation. A comprehensive validation study involves a critical evaluation of study design, data engineering and interoperability, target label definition, metric selection, generalizability and applicability assessment, algorithmic fairness, and explainability. While the main text highlights these concepts in broad strokes, a supplementary code walk-through is also provided to facilitate a more practical understanding of these topics using a real-world classification task example, the detection of saline-contaminated chemistry panels.Following validation, the laboratorian's role is far from over. Implementing machine learning solutions requires an interdisciplinary effort across several roles in an organization. We highlight the key roles, responsibilities, and terminologies for successfully deploying a validated solution into a live production environment. Finally, the implemented solution must be routinely monitored for signs of performance degradation and updated if necessary.SUMMARYThis mini-review aims to bridge the gap between theory and practice by highlighting key concepts in validation, implementation, and monitoring machine learning solutions effectively and responsibly in the clinical laboratory.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":null,"pages":null},"PeriodicalIF":9.3,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170558","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}

引用次数: 0

Critical Results in Laboratory Medicine. 实验室医学的关键成果

IF 7.1 2区医学

Clinical chemistry Pub Date : 2024-09-09 DOI: 10.1093/clinchem/hvae120

Kobe Truijens, Glynis Frans, Pieter Vermeersch

{"title":"Critical Results in Laboratory Medicine.","authors":"Kobe Truijens, Glynis Frans, Pieter Vermeersch","doi":"10.1093/clinchem/hvae120","DOIUrl":"https://doi.org/10.1093/clinchem/hvae120","url":null,"abstract":"Background: Timely and accurate notification of critical results is crucial in laboratory medicine and mandated by accreditation standards like ISO15189. Alert lists do, however, vary widely and clinical laboratories typically rely on a combination of in-house agreed and/or literature-based critical values. Communication by phone is still the preferred method of notification, but digital communication could help improve communication of critical results.Content: We review the available evidence concerning critical result thresholds and critical result notification practices. The evidence is ranked using an adaptation of the Stockholm Hierarchy. In addition, we propose an evidence-based list of critical result thresholds for hospitalized patients that laboratories can use as a starter list and further customize based on the clinical needs of their patient population.Summary: A clear distinction between critical results and significantly abnormal results is essential for effective and timely healthcare interventions. Implementation of a policy using differentiated thresholds taking into account individual patient characteristics and how fast medical attention is needed, and the use alternative communication methods could enhance communication efficiency and reduce notification fatigue.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153347","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}

引用次数: 0

Congenital Syphilis: An Emerging, Preventable Public Health Crisis. 先天性梅毒：新出现的、可预防的公共卫生危机。

IF 7.1 2区医学

Clinical chemistry Pub Date : 2024-09-03 DOI: 10.1093/clinchem/hvae042

Fnu Sapna, Kayode Balogun

引用次数: 0

Hypertension and Hypokalemia in a Patient Treated for Invasive Aspergillosis. 一名接受侵袭性曲霉菌病治疗的患者出现高血压和低钾血症。

IF 7.1 2区医学

Clinical chemistry Pub Date : 2024-09-03 DOI: 10.1093/clinchem/hvae083

Damien Denimal

引用次数: 0

Vitamin D: Analytical Advances, Clinical Impact, and Ongoing Debates on Health Perspectives. 维生素 D：分析进展、临床影响以及对健康前景的持续争论。

IF 7.1 2区医学

Clinical chemistry Pub Date : 2024-09-03 DOI: 10.1093/clinchem/hvae056

Etienne Cavalier, Konstantinos Makris, Annemieke C Heijboer, Markus Herrmann, Jean-Claude Souberbielle

{"title":"Vitamin D: Analytical Advances, Clinical Impact, and Ongoing Debates on Health Perspectives.","authors":"Etienne Cavalier, Konstantinos Makris, Annemieke C Heijboer, Markus Herrmann, Jean-Claude Souberbielle","doi":"10.1093/clinchem/hvae056","DOIUrl":"10.1093/clinchem/hvae056","url":null,"abstract":"Background: Vitamin D, acknowledged since the 1930s for its role in preventing rickets, gained additional prominence in relation to fragility fracture prevention in the late 1980s. From the early 2000s, connections between vitamin D deficiency and extra-skeletal pathologies emerged, alongside increased awareness of widespread deficits. This prompted crucial debates on optimal serum concentrations, expected to conclude when the outcomes of high-dose supplementation randomized controlled trials were available. Skepticism arose with inconclusive results from these trials.Content: This review begins with an exploration of vitamin D metabolism, followed by a detailed description of the measurement of vitamin D metabolites and the crucial role of standardization. Subsequent sections focus on the association of vitamin D with bone health and explore the extra-skeletal effects. The review concludes with a comprehensive discussion on the definition of vitamin D status and its implications for supplementation.Summary: Despite standardization efforts, assay variations and challenges still exist, especially in specific patient groups. Vitamin D supplementation has a significant impact on bone metabolism and optimal vitamin D status improves the efficacy of antiresorptive drugs such as bisphosphonates. The extra-skeletal effects of vitamin D remain debated, but may include potential benefits in conditions such as respiratory infections and cancer mortality, particularly in deficient individuals. The definition of vitamin D sufficiency is nuanced, especially when variations in population groups and analytical methods are taken into account. Despite ongoing debates and recent mega-trials tempering enthusiasm, vitamin D remains a complex and essential element in human health. Further research is needed to clarify its role in various health outcomes and guide supplementation strategies.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854973","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}

引用次数: 0

The Era of Early Detection and Treatment of Brain Amyloid Deposition in Asymptomatic Individuals? 无症状个体脑淀粉样蛋白沉积的早期检测和治疗时代到来了吗？

IF 7.1 2区医学

Clinical chemistry Pub Date : 2024-09-03 DOI: 10.1093/clinchem/hvae094

Danni Li, William G Mantyh

引用次数: 0

Proteomic Identification of Plasma Proteins Associated with Future Dementia Development. 与未来痴呆症发展相关的血浆蛋白质的蛋白质组鉴定

IF 7.1 2区医学

Clinical chemistry Pub Date : 2024-09-03 DOI: 10.1093/clinchem/hvae004

Joshua A Bornhorst, Alicia Algeciras-Schimnich

引用次数: 0

Clinical Utility of LC-MS/MS for Blood Myo-Inositol in Patients with Acute Kidney Injury and Chronic Kidney Disease. LC-MS/MS 检测急性肾损伤和慢性肾病患者血液肌醇的临床实用性

IF 7.1 2区医学

Clinical chemistry Pub Date : 2024-09-03 DOI: 10.1093/clinchem/hvae097

Catherine L Omosule, Connor J Blair, Elizabeth Herries, Mark A Zaydman, Christopher Farnsworth, Jack Ladenson, Dennis J Dietzen, Joseph P Gaut

{"title":"Clinical Utility of LC-MS/MS for Blood Myo-Inositol in Patients with Acute Kidney Injury and Chronic Kidney Disease.","authors":"Catherine L Omosule, Connor J Blair, Elizabeth Herries, Mark A Zaydman, Christopher Farnsworth, Jack Ladenson, Dennis J Dietzen, Joseph P Gaut","doi":"10.1093/clinchem/hvae097","DOIUrl":"10.1093/clinchem/hvae097","url":null,"abstract":"Background: Diagnosing acute kidney injury (AKI) and chronic kidney disease (CKD) relies on creatinine, which lacks optimal diagnostic sensitivity. The kidney-specific proximal tubular enzyme myo-inositol oxygenase (MIOX) catalyzes the conversion of myo-inositol (MI) to D-glucuronic acid. We hypothesized that proximal tubular damage, which occurs in AKI and CKD, will decrease MIOX activity, causing MI accumulation. To explore this, we developed an LC-MS/MS assay to quantify plasma MI and assessed its potential in identifying AKI and CKD patients.Methods: MI was quantified in plasma from 3 patient cohorts [normal kidney function (n = 105), CKD (n = 94), and AKI (n = 54)]. The correlations between MI and creatinine were determined using Deming regression and Pearson correlation and the impact of age, sex, and ethnicity on MI concentrations was assessed. Receiver operating characteristic curve analysis was employed to evaluate MI diagnostic performance.Results: In volunteers with normal kidney function, the central 95th percentile range of plasma MI concentrations was 16.6 to 44.2 µM. Age, ethnicity, and sex showed minimal influence on MI. Patients with AKI and CKD exhibited higher median MI concentrations [71.1 (25th percentile: 38.2, 75th percentile: 115.4) and 102.4 (77, 139.5) µM], respectively. MI exhibited excellent sensitivity (98.9%) and specificity (100%) for diagnosing CKD. In patients with AKI, MI increased 32.9 (SD 16.8) h before creatinine.Conclusions: This study unveils MI as a potential renal biomarker, notably elevated in plasma during AKI and CKD. Plasma MI rises 33 h prior to serum creatinine, enabling early AKI detection. Further validation and exploration of MI quantitation in kidney disease diagnosis is warranted.","PeriodicalId":10690,"journal":{"name":"Clinical chemistry","volume":null,"pages":null},"PeriodicalIF":7.1,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874424","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}

引用次数: 0