Critical reviews in clinical laboratory sciences最新文献

{"title":"Comparison of liquid biopsy-based technologies for cancer screening.","authors":"Andreas P Papanastasiou, Miyo K Chatanaka, Eleftherios P Diamandis","doi":"10.1080/10408363.2025.2606357","DOIUrl":"https://doi.org/10.1080/10408363.2025.2606357","url":null,"abstract":"<p><p>Circulating plasma DNA has found important applications in diverse medical fields, including prenatal testing, transplantation, and especially cancer. Many companies have developed products for detecting minimal residual disease, selecting or monitoring therapy, assessing prognosis, and confirming diagnosis. One major application is in screening asymptomatic individuals for the presence of cancer. Screening may facilitate better clinical outcomes through earlier interventions. Collectively, these technologies are widely known as \"liquid biopsies\". After the extraction of free DNA from the circulation, it is analyzed by various molecular techniques to explore differences between DNA originating from normal cells and cancer cells. Circulating plasma DNA originating from tumors (ctDNA) is expected to harbor the same molecular changes as tumor tissue itself. Thus, ctDNA is considered a surrogate of cancer tissue, but without the need to perform invasive biopsies to obtain it. Many new diagnostic companies have taken advantage of this new biomarker and developed technologies for screening for one or multiple cancers. We previously estimated the amount of ctDNA in circulation, which is admixed with DNA originating from normal cells. We concluded that since only a small fraction of the whole plasma (3 liters) is used for testing (3 to 4 mL), it is possible that the retrieved ctDNA may not be enough for cancer diagnosis in all patients. This problem is more acute with small tumors. Here, we mention some companies in the \"liquid biopsy\" arena and analyze their clinical data to establish if their tests are close to entering the clinic. We conclude from this analysis that current data do not support the use of these technologies for population screening due to many false negative and false positive results.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-12"},"PeriodicalIF":5.5,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846562","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":"Is screening for Alzheimer's disease ready for prime time? Ask Wilson and Jungner.","authors":"Miyo K Chatanaka, Maria Pascual Lorén, Eleftherios P Diamandis","doi":"10.1080/10408363.2025.2533860","DOIUrl":"10.1080/10408363.2025.2533860","url":null,"abstract":"<p><p>Population screening is an effective strategy for disease prevention, early diagnosis and treatment; however, the benefits and harms of disease screening need to be carefully evaluated before clinical implementation. Various national and international bodies, including the U.S. Preventive Services Task Force (USPSTF), periodically develop recommendations for screening after reviewing the available published evidence and, in some instances, expert opinions. In 1968, Wilson and Jungner formulated a set of 10 rules that must be considered and fulfilled before introducing screening for any disease into clinical practice. Alzheimer's disease (AD), a devastating chronic disease that affects millions of people worldwide and is the most common cause of dementia, has recently been reviewed in the context of population screening. Data and predictions show that the prevalence of AD is steadily increasing and will likely become one of the most common causes of death by 2060. Currently, there are no effective curative therapeutic options for this disease, but new developments have allowed earlier detection at asymptomatic and early symptomatic stages. New classes of disease-modifying therapeutics show promise of slowing the progression of the disease. These new developments prompted us to examine the near-future feasibility of screening for presymptomatic or early symptomatic AD by considering the general screening principles of Wilson and Jungner. In 2020, USPSTF published a guideline regarding screening for cognitive impairment, an AD symptom, and concluded that the current evidence is insufficient to assess the balance of benefits and harms and did not recommend screening for cognitive impairment in older adults. This was recapitulated in 2024 by the Canadian Task Force on Preventive Health Care (CTFPHC). After careful consideration, and despite the recent significant biological, diagnostic and therapeutic advances for AD, screening does not seem to be justified at present, due to numerous reasons, such as lack of trained professionals and specialized clinics to handle the anticipated highly increased workload, the huge cost, the ineffectiveness and side effects of current therapy, the lack of long-term therapy studies, and the disagreement among experts as to whom to test and treat and when (at either asymptomatic or early symptomatic stages).</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"631-645"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783682","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":"568-584"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","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":"Contribution of the medical laboratory in case of suspected insulin overdose.","authors":"Charline Bottinelli, Nathalie Cartiser, Fabien Bévalot, Laurent Fanton, Jérôme Guitton","doi":"10.1080/10408363.2025.2528877","DOIUrl":"10.1080/10408363.2025.2528877","url":null,"abstract":"<p><p>Insulins (human insulin and insulin analogues), widely used as hypoglycemic agents in the treatment of diabetes, can cause unexplained glycemic disorder. The medical laboratory then has a major role in determining and quantifying insulins. However, this is challenging, since pre-analytic and analytic aspects are specific, and appropriate interpretation is complex. This paper covers the various steps, and their pitfalls, for measuring insulins in blood samples. It provides a practical tool to apply in medical laboratories in case of suspected insulin overdose. Analytic strategy is presented, comparing immunoassays and chromatographic methods coupled to mass spectrometry. Tables summarize the appropriate standardized pre-analytic steps, from sampling to storage, to guarantee reliable measurement, a list of commercial immunoassays that measure insulins (with detailed cross-reactivity and sensitivity), and key parameters for interpretation of results in various unexplained glycemic events. Insulins degradation, adsorption, technical analytic limitations and variability in insulins kinetics are some of the pitfalls in insulins measurement. To avoid misinterpretation of results, a good mastery of the total testing process is required. The role of the medical laboratory is therefore central to provide the essential information to avoid the many pre-analytic and analytic pitfalls associated with the quantification of insulin and its analogues in blood. Finally, the article shows the importance of clinical-biological dialogue in interpreting results.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"604-612"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871848","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":"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":"585-603"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","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":"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":"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":"613-630"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","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":"Machine learning-based error detection in the clinical laboratory: a critical review.","authors":"Yanchun Lin, Isaiah K Mensah, Michelle Doering, Ryan C Shean, Nicholas C Spies","doi":"10.1080/10408363.2025.2512468","DOIUrl":"10.1080/10408363.2025.2512468","url":null,"abstract":"<p><p>Laboratory test results play a crucial role in the modern medical decision-making process. As such, errors in any phase of the testing process can have substantial clinical and operational impacts. While the development of increasingly robust quality assurance systems has enhanced the reliability of laboratory results, opportunities for improvement still exist. Machine learning approaches offer the potential to evaluate complex patterns and discriminate physiological variation from laboratory errors. In this work, we critically evaluate the current state of published machine learning solutions to laboratory errors, while highlighting unmet needs and potential barriers to widespread implementation.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"535-547"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265449","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":"Clinical utility of human epididymis protein 4.","authors":"Meihua Qiu, Shenchun Zou, Zhi Yu, Xueyuan Nian","doi":"10.1080/10408363.2025.2512467","DOIUrl":"10.1080/10408363.2025.2512467","url":null,"abstract":"<p><p>This review comprehensively elucidates the current clinical applications of human epididymis protein 4 (HE4) in various systemic diseases. Initially discovered in 1991 and linked to sperm maturation, HE4 has since been recognized for its significant expression in numerous malignant tumors. Currently, the main research areas concerning HE4 focus on its role in diagnosis, assessment of treatment efficacy, monitoring of recurrence, and evaluation of clinical prognosis in malignant tumors. Additionally, a notable area involves the application of HE4 in the diagnosis and prognostic assessment of fibrosis affecting multiple organs, such as the lung, liver, and kidney. Recent investigations have also explored the clinical utility of HE4 in biological fluids beyond serum, such as urine, bronchoalveolar lavage fluid, and ascitic fluid. Moreover, the combination of HE4 with other biomarkers and imaging techniques holds promise for enhancing its clinical applicability. However, the concentration of HE4 is subject to influence from various factors, which complicates its clinical implementation. Therefore, further research is warranted to improve the clinical utility of HE4.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"510-534"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233456","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":"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":"548-567"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","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":"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":"491-509"},"PeriodicalIF":5.5,"publicationDate":"2025-11-01","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}