Journal of Mass Spectrometry and Advances in the Clinical Lab最新文献

{"title":"Impact of VALID Act implementation on mass spectrometry-based clinical proteomic laboratory developed tests","authors":"Yanchun Lin ,&nbsp;Stefani N. Thomas","doi":"10.1016/j.jmsacl.2023.02.001","DOIUrl":"10.1016/j.jmsacl.2023.02.001","url":null,"abstract":"<div><p>Mass spectrometry (MS)-based clinical proteomic Laboratory Developed Tests (LDTs) for the measurement of protein biomarkers related to endocrinology, cardiovascular disease, cancer, and Alzheimer’s disease are gaining traction in clinical laboratories due to their value in supporting diagnostic and treatment decisions for patients. Under the current regulatory landscape, MS-based clinical proteomic LDTs are regulated by Clinical Laboratory Improvement Amendments (CLIA) under the auspices of the Centers for Medicaid and Medicare Services (CMS). However, should the Verifying Accurate Leading-Edge In Vitro Clinical Test Development (VALID) Act pass, it will grant the FDA greater authority to oversee diagnostic tests, including LDTs. This could impede clinical laboratories' ability to develop new MS-based proteomic LDTs to support existing and emerging patient care needs. Therefore, this review discusses the currently available MS-based proteomic LDTs and their current regulatory landscape in the context of the potential impacts imposed by the passage of the VALID Act.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 30-34"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/85/8a/main.PMC9971545.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9078218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UTI detection by PCR: Improving patient outcomes","authors":"Brian N. Kelly","doi":"10.1016/j.jmsacl.2023.02.006","DOIUrl":"10.1016/j.jmsacl.2023.02.006","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 60-62"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e8/32/main.PMC9988651.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9088010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case series evaluation of comprehensive drug testing in the pediatric acute care setting","authors":"Kara L. Lynch","doi":"10.1016/j.jmsacl.2023.02.011","DOIUrl":"10.1016/j.jmsacl.2023.02.011","url":null,"abstract":"<div><h3>Introduction</h3><p>Drug testing typically follows a one-size-fits-all approach that is inadequate in some clinical scenarios, such as child maltreatment, neglect, and unintentional drug exposure. Results from immunoassay-based testing, which are non-specific, insensitive, and far from comprehensive, can lead to unintended consequences for children and their families.</p></div><div><h3>Objectives</h3><p>The objective of this retrospective case series study is to evaluate the utility of real-time (0–1 day) comprehensive drug testing as an alternative to immunoassay-based testing in the pediatric acute care setting.</p></div><div><h3>Methods</h3><p>Comprehensive drug testing results obtained by mass spectrometry testing and associated medical data for all pediatric cases (0–12 years) at one institution from 2019 to 2022 were included in the analysis. The final case series (n = 7) included all cases from patients &lt;3 years with comprehensive drug testing results that were inconsistent with medication history and/or toxicology results by immunoassay.</p></div><div><h3>Results</h3><p>Comprehensive drug testing by mass spectrometry was ordered for 174 urine and blood samples representing 97 patients (0–12 years) from 2019 to 2022. Of these, 76 cases were from patients &lt;3 years old; results were consistent with medication history and confirmatory for immunoassay results (n = 34), consistent with medication history (n = 14), confirmatory for immunoassay results (n = 10), negative (n = 9), or medical history was incomplete (n = 2). The remaining 7 cases were included in the final case series.</p></div><div><h3>Conclusions</h3><p>The cases highlight the value of real-time comprehensive drug testing in acute pediatric cases. Testing results can rule out toxic exposure from the diagnostic differential when negative, and lead to appropriate medical and social interventions when positive.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 75-79"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/ad/main.PMC9995460.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9108719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a biomarker for β-Thalassemia by HPLC-MS and improvement from Proton Transfer Reaction – Parallel Ion Parking","authors":"Yuan Lin ,&nbsp;Archana M. Agarwal ,&nbsp;Lissa C. Anderson ,&nbsp;Alan G. Marshall","doi":"10.1016/j.jmsacl.2023.01.004","DOIUrl":"10.1016/j.jmsacl.2023.01.004","url":null,"abstract":"<div><p>β-thalassemia is a quantitative hemoglobin (Hb) disorder resulting in reduced production of Hb A and increased levels of Hb A₂. Diagnosis of β-thalassemia can be problematic when combined with other structural Hb variants, so that the separation approaches in routine clinical centers are not sufficiently decisive to obtain accurate results. Here, we separate the intact Hb subunits by high-performance liquid chromatography, followed by top-down tandem mass spectrometry of intact subunits to distinguish Hb variants. Proton transfer reaction-parallel ion parking (PTR-PIP), in which a radical anion removes protons from multiply charged precursor ions and produces charge-reduced ions spanning a limited <em>m</em>/<em>z</em> range, was used to increase the signal-to-noise ratio of the subunits of interest. We demonstrate that the δ/β ratio can act as a biomarker to identify β-thalassemia in normal electrospray ionization MS1 and PTR-PIP MS1. The application of PTR-PIP significantly increases the sensitivity and specificity of the HPLC-MS method to identify δ/β ratio as a thalassemia biomarker.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 20-26"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/93/66/main.PMC9939715.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurement of kynurenine pathway metabolites by tandem mass spectrometry","authors":"Sedat Abusoglu ,&nbsp;Duygu Eryavuz Onmaz ,&nbsp;Gulsum Abusoglu ,&nbsp;Fatma Humeyra Yerlikaya ,&nbsp;Ali Unlu","doi":"10.1016/j.jmsacl.2023.04.003","DOIUrl":"10.1016/j.jmsacl.2023.04.003","url":null,"abstract":"<div><h3>Objectives</h3><p>Recent studies have shown that derangements in kynurenine pathway metabolite levels are associated with various pathologies such as neurodegenerative diseases, schizophrenia, depression, bipolar disorder, rheumatoid arthritis, and cancer. Therefore, reliable, accurate, fast, and multiplex measurement methods for kynurenines have become increasingly important. This study aimed to validate a new mass spectrometric method for analyzing tryptophan metabolites.</p></div><div><h3>Methods</h3><p>A tandem mass spectrometric method, including protein precipitation and evaporation steps, was developed to measure serum levels of tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid. Samples were separated using a Phenomenex Luna C18 reversed-phase column. The kynurenine pathway metabolites were detected by tandem mass spectrometry. The developed method was validated according to Clinical &amp; Laboratory Standards Institute (CLSI) guidelines and applied to hemodialysis samples.</p></div><div><h3>Results</h3><p>The developed method was linear at the concentrations of 48.8 – 25,000, 0.98 – 500, 1.2–5000, 1.2–5000, and 0.98–250 ng/mL for tryptophan, kynurenic acid, kynurenine, 3-hydroxyanthranilic acid, and 3-hydroxykynurenine, respectively. The imprecisions were less than 12 %. The median serum concentrations of tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid were 10530, 1100, 218, 17.6, and 25.4 ng/mL in pre-dialysis blood samples, respectively. They were 4560, 664, 135, 7.4, and 12.8 ng/mL in post-dialysis blood samples, respectively.</p></div><div><h3>Conclusions</h3><p>A fast, simple, cost-effective, accurate, robust, and validated tandem mass spectrometric method was developed, and the method was successfully used for the quantitation of kynurenine pathway metabolite concentrations in hemodialysis patients.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 114-121"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10127116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9718449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the loss of laboratory developed mass spectrometry testing at a major academic medical center","authors":"K. Aaron Geno ,&nbsp;Mark A. Cervinski","doi":"10.1016/j.jmsacl.2023.02.005","DOIUrl":"10.1016/j.jmsacl.2023.02.005","url":null,"abstract":"<div><h3>Background</h3><p>Our laboratory historically performed immunosuppressant and definitive opioid testing in-house as laboratory developed (LDT) mass spectrometry-based tests. However, staffing constraints and supply chain challenges associated with the COVID-19 pandemic forced us to refer this testing to a national reference laboratory. The VALID Act could impose onerous requirements for laboratories to develop LDTs. To explore the potential effect of these additional regulatory hurdles, we used the loss of our own LDT tests to assess the impact on patient care and hospital budgets.</p></div><div><h3>Methods</h3><p>Laboratory information systems data and historical data associated with test costs were used to calculate turnaround times and financial impact.</p></div><div><h3>Results</h3><p>Referral testing has extended the reporting of immunosuppressant results by an average of approximately one day and up to two days at the 95th percentile. We estimate that discontinuing in-house opioid testing has cost our health system over half a million dollars in the year since testing was discontinued.</p></div><div><h3>Conclusions</h3><p>Barriers that discourage laboratories from developing in-house testing, particularly in the absence of FDA-cleared alternatives, can be expected to have a detrimental effect on patient care and hospital finances.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 63-66"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d3/0b/main.PMC9938756.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10831260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-analytical sample handling standardization for reliable measurement of metabolites and lipids in LC-MS-based clinical research","authors":"A. Sens ,&nbsp;S. Rischke ,&nbsp;L. Hahnefeld ,&nbsp;E. Dorochow ,&nbsp;S.M.G. Schäfer ,&nbsp;D. Thomas ,&nbsp;M. Köhm ,&nbsp;G. Geisslinger ,&nbsp;F. Behrens ,&nbsp;R. Gurke","doi":"10.1016/j.jmsacl.2023.02.002","DOIUrl":"10.1016/j.jmsacl.2023.02.002","url":null,"abstract":"<div><p>The emerging disciplines of lipidomics and metabolomics show great potential for the discovery of diagnostic biomarkers, but appropriate pre-analytical sample-handling procedures are critical because several analytes are prone to <em>ex vivo</em> distortions during sample collection. To test how the intermediate storage temperature and storage period of plasma samples from K3EDTA whole-blood collection tubes affect analyte concentrations, we assessed samples from non-fasting healthy volunteers (n = 9) for a broad spectrum of metabolites, including lipids and lipid mediators, using a well-established LC-MS-based platform. We used a fold change-based approach as a relative measure of analyte stability to evaluate 489 analytes, employing a combination of targeted LC-MS/MS and LC-HRMS screening. The concentrations of many analytes were found to be reliable, often justifying less strict sample handling; however, certain analytes were unstable, supporting the need for meticulous processing. We make four data-driven recommendations for sample-handling protocols with varying degrees of stringency, based on the maximum number of analytes and the feasibility of routine clinical implementation. These protocols also enable the simple evaluation of biomarker candidates based on their analyte-specific vulnerability to <em>ex vivo</em> distortions. In summary, pre-analytical sample handling has a major effect on the suitability of certain metabolites as biomarkers, including several lipids and lipid mediators. Our sample-handling recommendations will increase the reliability and quality of samples when such metabolites are necessary for routine clinical diagnosis.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 35-46"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8c/c4/main.PMC9975683.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10847454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulatory landscape of laboratory developed tests: Past, present, and a perspective on the future","authors":"Melissa M. Budelier ,&nbsp;Jacqueline A. Hubbard","doi":"10.1016/j.jmsacl.2023.02.008","DOIUrl":"10.1016/j.jmsacl.2023.02.008","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 67-69"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/f0/main.PMC9985058.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10861157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A customized mass array panel for BCR::ABL1 tyrosine kinase domain mutation screening in chronic myeloid leukemia","authors":"Nittaya Limsuwanachot ,&nbsp;Budsaba Rerkamnuaychoke ,&nbsp;Pimjai Niparuck ,&nbsp;Roongrudee Singdong ,&nbsp;Adcharee Kongruang ,&nbsp;Piyapha Hirunpatrawong ,&nbsp;Thanaporn Siriyakorn ,&nbsp;Pa-thai Yenchitsomanus ,&nbsp;Teerapong Siriboonpiputtana","doi":"10.1016/j.jmsacl.2023.04.002","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2023.04.002","url":null,"abstract":"<div><h3>Introduction</h3><p>The therapeutic strategy and management of chronic myeloid leukemia (CML) have rapidly improved with the discovery of effective tyrosine kinase inhibitors (TKIs) to target BCR::ABL1 oncoprotein. However, nearly 30% of patients develop TKI resistance due to acquired mutations on the tyrosine kinase domain (TKD) of <em>BCR</em>::<em>ABL1</em>.</p></div><div><h3>Methods</h3><p>We customized a mass array panel initially intended to detect and monitor the mutational burden of hotspot <em>BCR</em>::<em>ABL1</em> TKD mutations accumulated in our database, including key mutations recently recommended by European LeukemiaNet. Additionally, we extended the feasibility of using the assay panel for the molecular classification of myeloproliferative neoplasms (MPNs) by incorporating primer sets specific for analyzing <em>JAK2</em> V617F, <em>MPL</em> 515 K/L, and <em>CALR</em> types 1 and 2.</p></div><div><h3>Results</h3><p>We found that the developed mass array panel was superior for detecting and monitoring clinically significant <em>BCR</em>::<em>ABL1</em> TKD mutations, especially in cases with low mutational burden and harboring compound/polyclonal mutations, compared with direct sequencing. Moreover, our customized mass array panel detected common genetic alterations in MPNs, and the findings were consistent with those of other comparable assays available in our laboratory.</p></div><div><h3>Conclusions</h3><p>Our customized mass array panel was practicably used as a routine robust assay for screening and monitoring <em>BCR</em>::<em>ABL1</em> TKD mutations in patients with CML undergoing TKI treatment and feasible for analyzing common genetic mutations in MPNs.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 122-132"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49741227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small molecule biomarker discovery: Proposed workflow for LC-MS-based clinical research projects","authors":"S. Rischke ,&nbsp;L. Hahnefeld ,&nbsp;B. Burla ,&nbsp;F. Behrens ,&nbsp;R. Gurke ,&nbsp;T.J. Garrett","doi":"10.1016/j.jmsacl.2023.02.003","DOIUrl":"10.1016/j.jmsacl.2023.02.003","url":null,"abstract":"<div><p>Mass spectrometry focusing on small endogenous molecules has become an integral part of biomarker discovery in the pursuit of an in-depth understanding of the pathophysiology of various diseases, ultimately enabling the application of personalized medicine. While LC-MS methods allow researchers to gather vast amounts of data from hundreds or thousands of samples, the successful execution of a study as part of clinical research also requires knowledge transfer with clinicians, involvement of data scientists, and interactions with various stakeholders.</p><p>The initial planning phase of a clinical research project involves specifying the scope and design, and engaging relevant experts from different fields. Enrolling subjects and designing trials rely largely on the overall objective of the study and epidemiological considerations, while proper pre-analytical sample handling has immediate implications on the quality of analytical data. Subsequent LC-MS measurements may be conducted in a targeted, semi-targeted, or non-targeted manner, resulting in datasets of varying size and accuracy. Data processing further enhances the quality of data and is a prerequisite for in-silico analysis. Nowadays, the evaluation of such complex datasets relies on a mix of classical statistics and machine learning applications, in combination with other tools, such as pathway analysis and gene set enrichment. Finally, results must be validated before biomarkers can be used as prognostic or diagnostic decision-making tools. Throughout the study, quality control measures should be employed to enhance the reliability of data and increase confidence in the results.</p><p>The aim of this graphical review is to provide an overview of the steps to be taken when conducting an LC-MS-based clinical research project to search for small molecule biomarkers.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"28 ","pages":"Pages 47-55"},"PeriodicalIF":2.2,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10836640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}