Clinical chemistry and laboratory medicine最新文献

{"title":"An untargeted metabolomics approach to evaluate enzymatically deconjugated steroids and intact steroid conjugates in urine as diagnostic biomarkers for adrenal tumors.","authors":"Nora Vogg, Eleanor North, Arne Gessner, Felix Fels, Markus R Heinrich, Matthias Kroiss, Max Kurlbaum, Martin Fassnacht, Martin F Fromm","doi":"10.1515/cclm-2024-1337","DOIUrl":"10.1515/cclm-2024-1337","url":null,"abstract":"<p><strong>Objectives: </strong>Urinary steroid profiling after hydrolysis of conjugates is an emerging tool to differentiate aggressive adrenocortical carcinomas (ACC) from benign adrenocortical adenomas (ACA). However, the shortcomings of deconjugation are the lack of standardized and fully validated hydrolysis protocols and the loss of information about the originally conjugated form of the steroids. This study aimed to evaluate the quality of the deconjugation process and investigate novel diagnostic biomarkers in urine without enzymatic hydrolysis.</p><p><strong>Methods: </strong>24 h urine samples from 40 patients with ACC and 40 patients with ACA were analyzed by untargeted metabolomics using liquid chromatography-high-resolution mass spectrometry both unmodified and after hydrolysis with arylsulfatase/glucuronidase from <i>Helix pomatia.</i> Both approaches were compared regarding the differentiation of ACC vs. ACA via ROC analyses and to evaluate the hydrolyzation efficiency of steroid conjugates.</p><p><strong>Results: </strong>Steroid glucuronides were fully deconjugated, while some disulfates and all monosulfates were still largely detectable after enzymatic hydrolysis, suggesting incomplete and variable deconjugation. In unhydrolyzed urine, steroid monosulfates showed the best differentiation between ACC and ACA (highest AUC=0.983 for C₂₁H₃₂O₆S, followed by its isomer and two isomers with the molecular formula C₂₁H₃₂O₇S). Moreover, several disulfates were highly abundant and increased in ACC compared to ACA.</p><p><strong>Conclusions: </strong>This work highlights the limitations of hydrolyzing steroid conjugates before analysis and shows a possible superiority of a direct analysis approach compared to a hydrolysis approach from a methodological point of view and regarding diagnostic accuracy. Several steroid conjugates were found as promising diagnostic biomarkers for differentiation between ACC and ACA.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":"1004-1015"},"PeriodicalIF":3.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930037","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":"Analytical characteristics and performance of a new hs-cTnI method: a multicenter-study.","authors":"Tommaso Fasano, Antonio Fortunato, Greta Giacomini, Alberto Aimo, Marco Moretti, Valentina Viola, Jacopo Sabbatinelli, Giorgia Farneti, Paolo Maltoni, Rino Biguzzi, Vittorio Sambri, Nadia Di Marco, Andrea Ripoli, Aldo Clerico","doi":"10.1515/cclm-2024-0905","DOIUrl":"10.1515/cclm-2024-0905","url":null,"abstract":"<p><strong>Objectives: </strong>The present multicenter study was designed to evaluate the analytical performance and the 99th percentile value of the reference healthy population i.e., 99th percentile upper reference limit of the MAGLUMI^® CLIA high-sensitivity cardiac troponin I (hs-cTnI) method.</p><p><strong>Methods: </strong>Analytical performances and the 99th percentile URL value of the chemi-luminescent-immuno-assay (CLIA) method were evaluated using validated and standardized experimental protocols. Two cohorts including healthy adult individuals were enrolled. The first one included 989 blood donor volunteers (489 women and 500 men) aged 18-70 years (mean age 43 years, interquartile range 31-54 years). The second population included 47 healthy individuals (31 women and 16 men, mean age 78 years, interquartile range 73-81 years) aged≥71 years.</p><p><strong>Results: </strong>The distributions of hs-cTnI levels in both sexes are highly right-skewed, and men show significantly (p=0.0028) higher biomarker values than women. Moreover, in both sexes the hs-cTnI levels progressively increase after the 55 years. In the multivariate analysis (n=958), hs-cTnI was found to be significantly associated to NT-proBNP (p<0.0001), sex (p<0.0001) and BMI (p=0.0424). The 99th percentile URL values, calculated using the bootstrap method in the total reference heathy population (age≥18 years), were: Females (n=521): 5.93 ng/L (CI 95 % 5.29-8.48), Males (n=516): 9.79 ng/L (CI 95 % 6.37-17.41 ng/L), Total Population (n=1,037): 7.18 ng/L (CI 6.08-12.20 ng/L).</p><p><strong>Conclusions: </strong>The MAGLUMI CLIA method met all the criteria for an hs-cTnI assay recommended by international guidelines. The hs-cTnI values measured with the CLIA method are higher in men compared to women at the same age, and also progressively increase after the age>55 years.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":"821-830"},"PeriodicalIF":3.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930047","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":"Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part II – EQA cycles","authors":"Christoph Buchta, Rachel Marrington, Barbara De la Salle, Stéphanie Albarède, Tony Badrick, Heidi Berghäll, David Bullock, Wim Coucke, Vincent Delatour, Wolf-Jochen Geilenkeuser, Andrea Griesmacher, Gitte M Henriksen, Jim F Huggett, Peter B Luppa, Jonna Pelanti, Paola Pezzati, Sverre Sandberg, Michael Spannagl, Marc Thelen, Veronica Restelli, Lucy A Perrone","doi":"10.1515/cclm-2024-1290","DOIUrl":"10.1515/cclm-2024-1290","url":null,"abstract":"<p><p>External quality assessment (EQA) cycles are the smallest complete units within EQA programs that laboratories can use to obtain external assessments of their performance. In each cycle, several samples are distributed to the laboratories registered for participation, and ideally, EQA programs not only cover the examination procedures but also the pre- and post-examination procedures. The properties and concentration range of measurands in individual samples are selected with regard to the intended challenge for the participants so that each sample fulfils its purpose. This aims to ensure the most significant possible information gain in every cycle using the lowest possible number of EQA samples and thus, under economically optimal conditions. Participants examine samples and the results are reported to the EQA provider, who compares them with the target values for individual measurands in every sample. The EQA provider assesses the laboratory performance, and finally communicates the assessment results to the participant. The participants evaluate the outcomes of the assessment of their examination results and can draw conclusions in the case of both failing and passing and, if necessary, define improvement measures. After completion, each cycle is evaluated by the provider so that limitations and weaknesses of the EQA program can be identified and appropriate measures taken, or to confirm its continued suitability and appropriateness.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":"859-867"},"PeriodicalIF":3.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926810","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":"Behind the scenes of EQA–characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part IV – Benefits for participant laboratories","authors":"Christoph Buchta, Barbara De la Salle, Rachel Marrington, Stéphanie Albarède, Tony Badrick, Wolfgang Bicker, Andreas Bietenbeck, David Bullock, Vincent Delatour, Elisabeth Dequeker, Mira Flasch, Wolf-Jochen Geilenkeuser, Jaap van Hellemond, Jim F Huggett, Viktoriia Ianovska, Patricia Kaiser, Martin Kammel, Anja Kessler, Nele Laudus, Peter B Luppa, Pierre-Alain Morandi, Gavin O'Connor, Mauro Panteghini, Paola Pezzati, Jennifer Rosendahl, Sverre Sandberg, Heinrich Scheiblauer, Milan Skitek, Michael Spannagl, Anne Stavelin, Marc Thelen, Ursula Unterberger, Heinz Zeichhardt, Veronica Restelli, Lucy A Perrone","doi":"10.1515/cclm-2024-1292","DOIUrl":"10.1515/cclm-2024-1292","url":null,"abstract":"<p><p>The main stakeholders in external quality assessment (EQA) programs are the participants, in whose interests these challenges are ultimately organised. EQA schemes in the medical field contribute to improving the quality of patient care by evaluating the analytical and diagnostic quality of laboratory and point-of-care tests (POCT) by independent third parties and, if necessary, pointing out erroneous measurement results and analytical or diagnostic improvement potential. Other benefits include the option of using EQA samples for other important laboratory procedures, such as the verification or validation of <i>in vitro</i> diagnostic medical devices (IVD-MDs), a contribution to the estimation of measurement uncertainty, a means of training and educating laboratory staff through educational EQA programmes or samples, or even for independent and documented monitoring of staff competence, such as on samples with unusual or even exceptional characteristics. Participation in an EQA scheme for beneficiaries like medical, microbiological and histo- and molecular pathology laboratories, users of POCT and self-testing systems as well as National Metrology Institutes, calibration laboratories and reference laboratories that are dedicated to specific tasks and have particular expectations of the EQA scheme are presented here.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":"879-897"},"PeriodicalIF":3.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926813","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":"Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part III – EQA samples","authors":"Christoph Buchta, Rachel Marrington, Barbara De la Salle, Stéphanie Albarède, Xavier Albe, Tony Badrick, Heidi Berghäll, David Bullock, Christa M Cobbaert, Wim Coucke, Vincent Delatour, Wolf-Jochen Geilenkeuser, Andrea Griesmacher, Gitte M Henriksen, Jim F Huggett, István Juhos, Martin Kammel, Peter B Luppa, Piet Meijer, Jonna Pelanti, Paola Pezzati, Sverre Sandberg, Michael Spannagl, Marc Thelen, Annette Thomas, Heinz Zeichhardt, Veronica Restelli, Lucy A Perrone","doi":"10.1515/cclm-2024-1291","DOIUrl":"10.1515/cclm-2024-1291","url":null,"abstract":"<p><p>Providers of external quality assessment (EQA) programs evaluate data or information obtained and reported by participant laboratories using their routine procedures to examine properties or measurands in samples provided for this purpose. EQA samples must offer participants an equal chance to obtain accurate results, while being designed to provide results in clinically relevant ranges. It is the responsibility of the EQA provider to meet the necessary requirements for homogeneity, stability and some other properties of the EQA items in order to offer participants a fair, reliable and technically interesting EQA experience. Thus, the samples are at the heart and in the centre of EQA and its success depends on their quality. This manuscript describes the requirements for EQA samples and the activities of EQA providers to achieve them.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":"868-878"},"PeriodicalIF":3.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926811","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":"Behind the scenes of EQA – characteristics, capabilities, benefits and assets of external quality assessment (EQA): Part I – EQA in general and EQA programs in particular","authors":"Christoph Buchta, Rachel Marrington, Barbara De la Salle, Stéphanie Albarède, Tony Badrick, Andreas Bietenbeck, David Bullock, Janne Cadamuro, Vincent Delatour, Enes Dusinovic, Wolf-Jochen Geilenkeuser, Gro Gidske, Andrea Griesmacher, Alexander Haliassos, Derek Holzhauser, Jim F Huggett, Serafeim Karathanos, Paola Pezzati, Sverre Sandberg, Aditi Sarkar, Anne Elisabeth Solsvik, Michael Spannagl, Marc Thelen, Veronica Restelli, Lucy A Perrone","doi":"10.1515/cclm-2024-1289","DOIUrl":"10.1515/cclm-2024-1289","url":null,"abstract":"<p><p>This is the first in a series of five papers that detail the role and substantial impact that external quality assessment (EQA) and their providers' services play in ensuring <i>in-vitro</i> diagnostic (IVD) performance quality. The aim is to give readers and users of EQA services an insight into the processes in EQA, explain to them what happens before EQA samples are delivered and after examination results are submitted to the provider, how they are assessed, what benefits participants can expect, but also who are stakeholders other than participants and what significance do EQA data and assessment results have for them. This first paper presents the history of EQA, insights into legal, financing and ethical matters, information technology used in EQA, structure and lifecycle of EQA programs, frequency and intensity of challenges, and unique requirements of extra-examination and educational EQA programs.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":"844-858"},"PeriodicalIF":3.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926809","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 indicators for urine sample contamination: can squamous epithelial cells and bacteria count be used to identify properly collected samples?","authors":"Gabriela Blauth Walber, José Antonio Tesser Poloni, Liane Nanci Rotta","doi":"10.1515/cclm-2024-1199","DOIUrl":"10.1515/cclm-2024-1199","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate urinalysis parameters useful for identifying mixed cultures in urine culture using an automated urinary particle analyzer to assess quality indicators (QIs) for urine sample contamination.</p><p><strong>Methods: </strong>A retrospective observational cross-sectional study was conducted with 2,527 urine samples from patients of a quaternary hospital in Brazil. Urine samples were processed simultaneously in Sysmex UF-5000 flow cytometry analyzer (urinalysis) and MALDI-TOF (culture).</p><p><strong>Results: </strong>For all samples, a cutoff of 123.8 bacteria/µL was established to discriminate culture-negative specimens. ROC curve indicated the following cutoffs for females and males, respectively: 193.65 and 23.55 bacteria/µL, and 21.35 and 5.05 squamous epithelial cells (SEC)/µL, with the latter two related to scenarios of sample contamination/colonization through mixed cultures. Performing univariate logistic regression, we found a 2.78 (CI95 %: 2.12-3.65) times higher chance of probable mixed culture when SEC values were above the cutoffs for each sex, and 6.91(CI95 %: 4.56-10.47) times for bacteria. For multivariate logistic regression, the OR values were 1.62 (CI95 %: 1.21-2.15) and 5.82 (CI95 %: 3.77-8.98), respectively.</p><p><strong>Conclusions: </strong>The fluorescent flow cytometry analyzers could efficiently identify urinary bacteria counts associated with contamination/colonization scenarios using the cutoffs of 21.35 SEC/µL for women and 5.05 SEC/µL for men. The cutoffs for bacteria/µL (193.65 for females and 23.55 for males) indicated that the presence of bacteria in male samples may be more associated with urinary tract infections (UTIs), while in female samples, it may be associated with either UTIs or contamination/colonization scenarios. This makes the analyzer a helpful tool as QI of sample contamination in urine cultures.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":"979-986"},"PeriodicalIF":3.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913817","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":"Comparative evaluation of peptide vs. protein-based calibration for quantification of cardiac troponin I using ID-LC-MS/MS.","authors":"Meltem Asicioglu, Claudia Swart, Evren Saban, Emrah Yurek, Nevin Gul Karaguler, Merve Oztug","doi":"10.1515/cclm-2024-0999","DOIUrl":"10.1515/cclm-2024-0999","url":null,"abstract":"<p><strong>Objectives: </strong>An analytical protocol based on isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS), which includes a peptide-based calibration strategy, was developed and validated for the determination of cardiac troponin I (cTnI) levels in clinical samples. Additionally, the developed method was compared with a protein-based calibration strategy, using cTnI serving as a model for low-abundant proteins. The aim is to evaluate new approaches for protein quantification in complex matrices, supporting the metrology community in implementing new methods and developing fit-for-purpose SI- traceable peptide or protein primary calibrators.</p><p><strong>Methods: </strong>To establish traceability to SI units, peptide impurity correction amino acid analysis (PICAA) was conducted to determine the absolute content of signature peptides in the primary standards. Immunoaffinity enrichment was used to capture cTnI from human serum, with a comparison between microbeads and nanobeads to improve enrichment efficiency. Parallel reaction monitoring was used to monitor two signature peptides specific to cTnI. Various digestion parameters were optimized to achieve complete digestion.</p><p><strong>Results: </strong>The analytical method demonstrated selectivity and specificity, allowing the quantification of cTnI within 0.9-22.0 μg/L. The intermediate precision RSD was below 28.9 %, and the repeatability RSD was below 5.8 % at all concentration levels, with recovery rates ranging from 87 % to 121 %. The comparison of calibration strategies showed similar LOQ values, but the peptide-based calibration exhibited significant quantitative bias in recovery rates. The data are available via ProteomeXchange (PXD055104).</p><p><strong>Conclusions: </strong>This isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method, based on peptide calibration, successfully quantified cTnI in human serum. Comparing this with protein-based calibration highlighted both the strengths and potential limitations of peptide-based strategies.</p>","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":"1016-1030"},"PeriodicalIF":3.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913676","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":"Refining within-subject biological variation estimation using routine laboratory data: practical applications of the refineR algorithm.","authors":"Eirik Åsen Røys, Kristin Viste, Christopher-John Farrell, Ralf Kellmann, Nora Alicia Guldhaug, Elvar Theodorsson, Graham Ross Dallas Jones, Kristin Moberg Aakre","doi":"10.1515/cclm-2024-1386","DOIUrl":"10.1515/cclm-2024-1386","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":"e146-e149"},"PeriodicalIF":3.8,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902776","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}

{"title":"An appeal for biological variation estimates in deep immunophenotyping.","authors":"Kai Guo, Xiaoran Feng, Shuxuan Ma","doi":"10.1515/cclm-2024-1318","DOIUrl":"10.1515/cclm-2024-1318","url":null,"abstract":"","PeriodicalId":10390,"journal":{"name":"Clinical chemistry and laboratory medicine","volume":" ","pages":"e130-e132"},"PeriodicalIF":3.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902775","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}