Critical reviews in clinical laboratory sciences最新文献

{"title":"From fructose to the future: liver disease biomarkers and their prognostic value in acute liver failure.","authors":"Mitchell R McGill","doi":"10.1080/10408363.2025.2481081","DOIUrl":"10.1080/10408363.2025.2481081","url":null,"abstract":"<p><p>Acute liver failure (ALF) is an uncommon but severe condition with high morbidity and mortality. Advances in supportive care have improved patient outcomes, but liver transplantation remains the only life-saving intervention in many cases. Unfortunately, healthy donor livers are in short supply. In addition, transplant recipients face several potentially fatal risks including organ rejection, biliary and vascular complications, and infection. It is therefore critical to accurately identify patients who need a new liver while sparing those who do not. This also needs to be done quickly, within the first few days of hospital admission, due to the rapid progression of ALF. Prognostic tools, like the Clichy criteria, the King's College Criteria (KCC), the model for end-stage liver disease (MELD) score, the Acute Liver Failure Study Group Prognostic Index (ALFSGPI), and others have been available for this purpose since at least the 1980s and are commonly used today, but their performance is imperfect, leading to many efforts over the last several decades - and especially in recent years - to identify new noninvasive biomarkers. This review begins with a description of the earliest liver function (e.g. the levulose [fructose] test) and liver injury (e.g. alkaline phosphatase [ALP] and alanine aminotransferase [ALT]) tests and continues through the most recent proposed biomarkers, with critical evaluation of the prognostic utility of each using the KCC and MELD as benchmarks for comparison. Overall, there is as-yet no single biomarker that clearly and consistently performs better than the latter tools, though many may modestly improve the performance of the KCC or MELD when used in combination with them. The search for a better, single biomarker is therefore likely to continue.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"386-403"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729280","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":"A review of laboratory practices for CSF oligoclonal banding and associated tests.","authors":"Victoria Higgins, Yu Chen, Mark S Freedman, Karina Rodriguez-Capote, Daniel R Beriault","doi":"10.1080/10408363.2025.2490166","DOIUrl":"10.1080/10408363.2025.2490166","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic autoimmune disorder affecting the central nervous system, often emerging in early adulthood and representing a leading cause of neurological disability in young adults. Diagnosing MS involves a combination of clinical assessment, imaging and laboratory tests, with cerebrospinal fluid (CSF)-specific immunoglobulin G (IgG) oligoclonal bands (OCB) being an important marker for fulfilling the dissemination in time criteria. A recent survey of Canadian clinical laboratories highlighted considerable variation in OCB reporting practices nationwide, spanning quality control (QC) practices, acceptable time limits between paired CSF and serum sample collections, protocols for reporting band counts, interpretation and reporting of mirrored patterns, testing panels, and interpretive thresholds. These inconsistencies impact patient care and the comparability of laboratory results across different laboratories. The Harmonized CSF Analysis for MS Investigation (hCAMI) subcommittee of the Canadian Society of Clinical Chemists Reference Interval Harmonization Working Group was established to generate recommendations for laboratory processes and reporting of CSF OCB and associated tests supporting MS diagnosis. This review serves as a foundation for these efforts, summarizing the available evidence in areas where practice variations have been noted. This review begins by examining current practices and guidelines for standardized quality assurance, including optimal QC materials, frequency, documentation, and participation in external quality assurance programs. The disparity between paired CSF and serum sample acceptability time limits was further examined by reviewing current practices and recommendations as well as compiling evidence on IgG synthesis, turnover rate, biological variation, and stability in CSF and serum samples. Additionally, this review addresses the lack of consensus on reporting the number of CSF-specific and CSF-serum matched bands, focusing on interpreter variability and clinical utility. Contributing factors and clinical implications of mirror patterns, including discussion on monoclonal gammopathies and cases of matched bands of differing staining intensity, is provided. Testing panel components including adjunctive CSF tests, such as the IgG index, to support MS investigations despite their absence from clinical guidelines is also discussed. This review also provides a comprehensive analysis of current practices, guidelines, and the evidence surrounding different cutoffs for IgG index and CSF-specific bands.</p><p><p>Finally, the review considers emerging biomarkers, such as the kappa free light chain index and serum neurofilament light chain, which show promise for MS diagnosis and management. This comprehensive review of current practices, guidelines, and evolving evidence will guide the hCAMI subcommittee's efforts to harmonize CSF OCB analysis and improve MS diagnosis.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"363-385"},"PeriodicalIF":6.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978477","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":"Rigorous validation of machine learning in laboratory medicine: guidance toward quality improvement.","authors":"Hunter A Miller, Roland Valdes","doi":"10.1080/10408363.2025.2488842","DOIUrl":"10.1080/10408363.2025.2488842","url":null,"abstract":"<p><p>The application of artificial intelligence (AI) in laboratory medicine will revolutionize predictive modeling using clinical laboratory information. Machine learning (ML), a sub-discipline of AI, involves fitting algorithms to datasets and is broadly used for data-driven predictive modeling in various disciplines. The majority of ML studies reported in systematic reviews lack key aspects of quality assurance. In clinical laboratory medicine, it is important to consider how differences in analytical methodologies, assay calibration, harmonization, pre-analytical errors, interferences, and physiological factors affecting measured analyte concentrations may also affect the downstream robustness and reliability of ML models. In this article, we address the need for quality improvement and proper validation of ML classification models, with the goal of bringing attention to key concepts pertinent to researchers, manuscript reviewers, and journal editors within the field of pathology and laboratory medicine. Several existing predictive modeling guidelines and recommendations can be readily adapted to the development of ML models in laboratory medicine. We summarize a basic overview of ML and key points from current guidelines including advantages and pitfalls of applied ML. In addition, we draw a parallel between validation of clinical assays and ML models in the context of current regulatory frameworks. The importance of classification performance metrics, model explainability, and data quality along with recommendations for strengthening journal submission requirements are also discussed. Although the focus of this article is on the application of ML in laboratory medicine, many of these concepts extend into other areas of medicine and biomedical science as well.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"327-346"},"PeriodicalIF":5.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955362","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":"Blood glucose measurement inside and outside the laboratory: both preanalytical and analytical challenges.","authors":"Guillaume Grzych, Inès Defauwes, Pascal de Tullio, Jean David Pekar, Thierry Brousseau, Giuseppe Lippi, Etienne Cavalier","doi":"10.1080/10408363.2025.2533855","DOIUrl":"https://doi.org/10.1080/10408363.2025.2533855","url":null,"abstract":"<p><p>Glucose measurement is a critical investigation in metabolic disease management, especially in diabetes and inherited disorders. However, both laboratory-based and handheld point-of-care (HPOC) (glucometers) glucose testing face significant preanalytical and analytical challenges. In central laboratories, glycolysis in uncentrifuged samples leads to glucose consumption, which may compromise diagnostic accuracy. Although sodium fluoride (NaF) is commonly used as a glycolysis inhibitor, it has a delayed effect, requiring several hours to stabilize glucose concentrations. Recently, citrate-buffered NaF-EDTA (FCE) tubes have been introduced to inhibit glycolysis more effectively, yet they remain underused. Preanalytical variables, including sample collection, transport, and processing delays, further impact glucose stability and the diagnosis of diabetes, including gestational diabetes mellitus (GDM). HPOC devices provide an alternative by delivering rapid results and minimizing preanalytical errors, but glucose meters are prone to physiological and analytical interferences, such as hematocrit variations, environmental conditions, presence of redox-active drugs, and enzymatic specificity issues. These interferences may lead to inaccurate glucose readings, impairing clinical decision-making, especially in intensive care and emergency settings. Moreover, discrepancies between capillary and venous glucose concentrations can contribute to misdiagnosis and inappropriate glycemic management. This review provides a comprehensive analysis of glucose measurement methodologies, their limitations, and potential improvements, emphasizing the need for preanalytical harmonization in laboratory testing and a better understanding of interferences in HPOC testing. Standardization of blood sample handling and adoption of optimized collection tubes could enhance glucose measurement reliability, ultimately improving diabetes diagnosis and patient outcomes.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-18"},"PeriodicalIF":5.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945879","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 anion gap as a predictive tool for morbidity and mortality.","authors":"David N Alter, Li Zha","doi":"10.1080/10408363.2025.2526346","DOIUrl":"10.1080/10408363.2025.2526346","url":null,"abstract":"<p><p>Since the early 1970s, the anion gap has been a fundamental component of acid-base disorder diagnosis and workup. In the past decade, a vastly expanded and ever-increasing literature base has explored its utilization as a morbidity and mortality predictive parameter in various clinical conditions. This discussion will review its history/derivation and reference interval associated issues followed by a literature review of current studies focusing on its relatively recent use as a clinical predictive marker. An English language PUBMED search was performed to include all listings up through 12/31/2022 using the free text search term \"ANION GAP.\" In addition, clinical texts were identified and used as a metric of current standard of care utilization. All references were then sorted into predictive-related and non-predictive-related categories. The predictive references were thus classified by clinical cohort: critical patient, general population, glycemia, intoxication, lactic acidosis, myeloma, renal function, and seizure. A total of 2,068 references were identified and reviewed, of which 95 used the anion gap as a predictive marker and 15 significant for the reference interval discussion. Across all clinical cohorts, except lactic acidosis, an elevated anion gap was found to be significant in predicting morbidity and/or mortality. The published reference intervals of the anion gap were highly variable: the upper reference limit ranged from 10 mmol/L to 19 mmol/L, and the width of the reference intervals (upper minus lower reference limit) ranged from 2 mmol/L to 11 mmol/L. The flaws of the anion gap based on our review are outweighed by its benefits in terms of it being a significant predictive marker of morbidity and mortality. Significant variations in equations and reference limits in the literature raised the question of whether a \"normal range\" is necessary for utilizing this calculated construct for clinical management.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-17"},"PeriodicalIF":6.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658634","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":"Beyond newborn screening: the role of reverse cascade testing in familial disease detection.","authors":"Amy Gaviglio, Kostantinos Petritis, Veronica Tagi, Alessandra Vasco, Alessia Mauri, Gianvincenzo Zuccotti, Elvira Verduci, Cristina Cereda, Simona Ferraro","doi":"10.1080/10408363.2025.2527288","DOIUrl":"https://doi.org/10.1080/10408363.2025.2527288","url":null,"abstract":"<p><p>Over the past 60 years, preventative public health screening programs have evolved since their inception and now include newborn screening (NBS) aimed at identifying infants after birth for a number of rare, congenital, inherited diseases. Most of the conditions detected through NBS are autosomal recessive disorders or exhibit X-linked inheritance, meaning that family members of individuals with these conditions have a higher risk for being either affected or obligate heterozygotes. For example, the X-linked adrenoleukodystrophy (X-ALD) in the screening panel identifies affected newborns and asymptomatic relatives through subsequent testing. Thus, NBS becomes a gateway to family-wide prevention, through the application of reverse cascade testing (RCS). In this paper we examined the scenarios where RCS may be appropriate. Accordingly, we have identified a list of criteria assessing whether a NBS disease would benefit from RCS: (1) autosomal recessive or X-linked inheritance; (2) high carrier rates, (3) variable expressivity, (4) mild or late-onset forms; and (5) association with diagnostic delays and recent addition to the screening panel. More than one criterion usually needs to be met for a disease to benefit from RCS. We have identified a list of diseases and highlighted the potential benefits of RCS: X-ALD, Cystic Fibrosis, Sickle Cell Disease, Spinal Muscular Atrophy and Pompe disease. There are additional scenarios within NBS where disease maternal conditions (3-methylcrotonyl-CoA carboxylase deficiency and carnitine uptake deficiency) or nutritional maternal conditions (vitamin B12 deficiency) may cause a screen-positive NBS result. Whenever a maternal nutritional deficiency is a potential reason for a positive NBS, this is indicative of a non-inherited condition that may require treatment in the newborn owing to possible neurological damage and delay in normal growth in newborns with certain secondary deficiencies. For these cases RCS is recommended, as the mother's status may put her at risk for future adverse events (i.e. cardiovascular and musculoskeletal disorders, hepatic involvement, and neurodegeneration). The RCS-NBS strategy discussed in this paper offers a set of criteria against which diseases can be assessed for the potential need for RCS. Implementation of this strategy requires several considerations including educational needs, ethical issues, uptake of testing, logistics and costs for this expanded screening and counseling, and availability of appropriate specialists for ongoing management.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-11"},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648714","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":"Modern techniques used in the diagnosis of autoimmune rheumatic diseases.","authors":"Yana Kaliberda, Anna Wajda, Magdalena Węglarska, Agnieszka Paradowska-Gorycka","doi":"10.1080/10408363.2025.2528869","DOIUrl":"https://doi.org/10.1080/10408363.2025.2528869","url":null,"abstract":"<p><p>Laboratory diagnostics of diseases have improved significantly with modern laboratory techniques offering greater accuracy, earlier detection, and opportunities for personalized diagnosis. This review highlights the key techniques used in the diagnostics of autoimmune rheumatic diseases. Detection of autoantibodies is the basis for modern laboratory diagnostics of autoimmune rheumatic diseases. Immunofluorescent analysis, enzyme-linked immunosorbent assay, chemiluminescent immunoassay, and immunoblotting are nowadays common methods for differential diagnostics, screening, and monitoring the progression of autoimmune diseases. Polymerase chain reaction methods allow the identification of genetic markers associated with autoimmune disorders, which facilitates early diagnosis. Next Generation Sequencing allows for comprehensive analysis of genetic variants, identifying novel biomarkers, and furthering our understanding of disease mechanisms. Diagnostics and treatment are now approaching personalized medicine based mainly on modern molecular discoveries. Such an approach aims to determine disease risk, tailor treatment to individual patient needs, improve safety and efficacy, and reduce treatment costs. This review covers essential laboratory techniques for diagnosing autoimmune rheumatic diseases and aims to serve as a reliable resource for clinicians, including rheumatologists, and researchers.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-16"},"PeriodicalIF":6.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642026","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":"Strategies for energy conservation and sustainability in medical laboratories.","authors":"Snežana Jovičić, Neda Milinković","doi":"10.1080/10408363.2025.2527284","DOIUrl":"https://doi.org/10.1080/10408363.2025.2527284","url":null,"abstract":"<p><p>Medical laboratories require a great amount of energy, ranging from three to six times more than a standard office building. Also, they consume massive amounts of water and gases and produce diverse waste products, some of which are toxic. Their energy requirements are complex and when estimating the total carbon footprint of a medical laboratory, we need to keep in mind the different contributors present. First, laboratory instrumentation varies for various laboratory tests, requiring different amounts of electricity, gas, water, and consumables. Furthermore, according to some estimates, laboratory infrastructure of heating, ventilation, and air-conditioning (HVAC) system may account for 40-60% of energy consumption, depending on its complexity and different requirements for different buildings. A lighting/shading system may consume up to 15% of the total energy. Also, the computers and their supporting systems needed for laboratory data processing use electrical power and contribute to the carbon footprint of medical laboratories. The systematic approach to mitigate the environmental impact of the healthcare sector in general, and medical laboratories in particular, is the voluntary adoption of an Environmental Management System (EMS) according to the International Standards ISO 14001 or the European EMAS (Eco-Management and Audit Scheme). Focusing on managing energy efficiency, the ISO 50001 Energy Management Systems - Requirements with guidance for use, can help medical laboratories develop and implement an energy-saving strategy by establishing achievable energy usage goals, defining action plans to achieve them, and quantifying improvements. To prevent and manage the risks of uncontrolled energy consumption in medical laboratories, it is important to bear in mind the energy-intensive laboratory features, thus facilitating the implementation of strategies for energy conservation and sustainability. Additionally, laboratory buildings have a substantial embodied carbon that significantly affects their functional environmental impact. In recent years, many initiatives, tools, and methods that address the environmental sustainability of health research have been developed. Many of them are applicable and are used in clinical laboratory settings even though they are not developed specifically for it. Recently, the European Federation of Clinical Chemistry and Laboratory Medicine generated educational material that aims to both raise awareness of medical laboratories carbon footprint, and to guide them on how to decrease it. This review aims to give an overview of the current efforts to improve the sustainability of medical laboratories in the sense of energy conservation. We will present the extent of the environmental impact of healthcare structures and medical laboratories, identify the major contributors to their carbon footprint, focus on energy consumption, and finally, offer strategies that could mitigate it.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-19"},"PeriodicalIF":6.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607737","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":"Association of inflammatory biomarkers with morbidity and mortality risk in patients with peripheral artery disease: a systematic review and -meta-analysis.","authors":"Mariana Fragão-Marques, Maria Francisca-Marques, João Rocha Neves, Tomris Ozben","doi":"10.1080/10408363.2025.2512472","DOIUrl":"https://doi.org/10.1080/10408363.2025.2512472","url":null,"abstract":"<p><p>Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis, which might progress due to inflammation. This systematic review assessed the association of specific inflammatory biomarkers with morbidity and mortality in PAD patients. MEDLINE and EMBASE databases were systematically searched for studies assessing evidence between inflammatory biomarkers and morbidity and mortality risks in PAD patients. Results were reported as Hazard Ratios (HR), Odds Ratios (OR), or mean and standard deviation. Effect estimates for high-sensitivity C-reactive protein (hs-CRP) were pooled using a random-effects model and respectively displayed in forest plots. The study reviewed a total of 7024 records, out of which 26 studies were included for qualitative synthesis and nine for quantitative synthesis. A total of 4673 patients were analyzed in the meta-analysis. Elevated baseline IL-6 levels were consistently linked to poor outcomes, including loss of patency and composite endpoints, such as major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Tumor necrosis factor-α (TNF-α) and related biomarkers were associated with adverse outcomes like mortality and patency loss. Elevated IL-1 levels predicted worse cardiovascular outcomes and IL-1 receptor antagonist levels indicated recurrence or new lesions post-surgery. Hs-CRP was statistically significantly associated with all-cause mortality and MALE in the pooled analysis. The study highlights the ability of inflammatory biomarkers to predict clinical outcomes in PAD patients. The strength of these associations varies based on the specific biomarker and clinical context.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-20"},"PeriodicalIF":6.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293440","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":"Advances in multiple myeloma blood-based monitoring and its clinical applications.","authors":"Anastasia Tzasta, Charissa Wijnands, Kim Baalman, Alain J van Gool, Sonja Zweegman, Joannes F M Jacobs","doi":"10.1080/10408363.2025.2512466","DOIUrl":"https://doi.org/10.1080/10408363.2025.2512466","url":null,"abstract":"<p><p>Multiple myeloma (MM) is currently still considered incurable. The recent introduction of novel therapeutic options has significantly improved patient outcomes, with more patients achieving positive responses. While this is positive, these deep remissions pose a challenge in disease monitoring and early detection of relapse, causing uncertainty of disease status among patients and healthcare providers. Current blood-based M-protein diagnostics are not sensitive enough to detect minimal residual disease (MRD) and the gold standard method for MRD-evaluation relies on invasive bone marrow biopsies. Several blood-based methods are currently being investigated as potential minimally invasive alternatives. Of these, mass spectrometry-based methods targeting clonotypic peptides (MS-MRD) offers up to 1,000 times higher sensitivity than traditional electrophoresis and immuno-based techniques for M-protein quantification in blood. In addition, methods initially developed for detecting clonal plasma cells in bone marrow are now being explored in peripheral blood, where circulating myeloma cells and cell-free DNA provide independent prognostic value. Next to its value as biomarker of disease activity, the unique M-protein can also play a direct role in causing tissue damage through a variety of different mechanisms. Currently, no diagnostic tests are available that assess M-proteins pathogenicity. Mass spectrometry-based techniques are suited to characterize the structural properties, stability, and post-translational modifications of M-proteins. This may improve our understanding regarding the pathogenic potential of M-proteins and pave the way for novel diagnostics and early identification of those patients who are at risk. This review highlights the emerging landscape of blood-based diagnostics in MM and their potential for clinically relevant applications.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-19"},"PeriodicalIF":6.6,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293439","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}