Critical reviews in clinical laboratory sciences最新文献

Antiphospholipid antibodies (aPL) may interfere with prothrombin time (PT) and international normalized ratio (INR) assays. Patients with antiphospholipid syndrome (APS) are often treated with vitamin K antagonists and require therapeutic monitoring with the INR. However, it remains unclear to what extent these assays are influenced by aPL and the consequent clinical relevance. This scoping review aimed to map the available evidence on the impact of APS and aPL on PT/INR assays, describe the methods used in research in this area, and identify gaps to guide future investigations. Two databases (MEDLINE and Embase) were searched, in the date range of 1 January 1984 to 10 June 2025, for reports describing clinical or in vitro research involving human subjects with APS or aPL that were analyzed with INR/PT assays. Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-Scr) guideline. 3,824 records were retrieved and after deduplication, title/abstract screening, and full-text screening, 39 studies were included in the review. Based on study design, we identified 23 observational clinical studies, 11 case reports/series, and 5 studies reporting in vitro aPL investigations with one report also including a case-control study. Observational studies showed that INR assays utilizing thromboplastin with recombinant human tissue factor (TF), including point-of-care tests (POCT), are more influenced by aPL than assays based on tissue-derived thromboplastins, although not consistently. Case reports described patients, mostly with the presence of multiple aPL, with clinically significant misinterpretation of their anticoagulation status. In vitro studies demonstrated reagent- and antibody-dependent effects, with anti-β2-glycoprotein I and antiprothrombin immunoglobulin G antibodies variably prolonging or shortening the PT. Evidence from both clinical and in vitro studies indicates that INR results in APS patients may be unreliable, particularly with specific recombinant human TF-based and POCT reagents, although not systematically. Interference is antibody profile-, antibody level-, and reagent-dependent. However, studies remain heterogeneous, often small in scale, and methodologically inconsistent with variable evaluation criteria. Well-defined future research should aim to identify in which APS patient subgroups an INR would not be reliable with specific assays.

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).

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.

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.

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.

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.

Biomarkers are critical tools in the diagnosis and monitoring of neurodegenerative diseases. Reliable quantification depends on assay validity, especially the demonstration of parallelism between diluted biological samples and the assay's standard curve. Inadequate parallelism can lead to biased concentration estimates, jeopardizing both clinical and research applications. Here, we systematically review the evidence of analytical parallelism in body fluid (serum, plasma, cerebrospinal fluid) biomarker assays for neurodegeneration and evaluate the extent, reproducibility, and reporting quality of partial parallelism. This systematic review was registered on PROSPERO (CRD42024568766) and conducted in accordance with PRISMA guidelines. We included studies published between December 2010 to July 2024 without language restrictions. Eligible studies included original research assessing biomarker concentrations in body fluids with data suitable for evaluating serial dilution and standard curve parallelism. The data extraction for interrogating parallelism included dilution steps, measured concentrations, and sample types. For each study, we generated parallelism plots in a uniform and comparable way. These graphs were used to come to a balanced decision on whether parallelism or partial parallelism was present. The risk of bias was assessed based on sample preparation, buffer consistency, and methodological transparency. Of 44 eligible studies, 19 provided sufficient data for generating 49 partial parallelism plots. Only 7 plots (14%) demonstrated clear partial parallelism. Partial parallelism was typically achieved over a narrow dilution range of about three doubling steps. Most assays deviated from parallelism, risking over- or underestimation of biomarker levels if determined at different dilution steps. A high risk of bias was identified in 9 studies using spiked or artificial samples, inconsistent dilution buffers, or incomplete reporting. Several studies assessed sample-to-sample parallelism rather than sample-to-standard, contrary to guidelines by regulatory authorities. In conclusion, partial parallelism was infrequently observed and inconsistently reported in most biomarker assays for neurodegeneration. Narrow dilution ranges and variable methodologies limit generalizability. Transparent reporting of dilution protocols and adherence to established analytical validation guidelines are needed. This systematic review has practical implications for clinical trial design, regulatory approval processes, and the reliability of biomarker-based diagnostics.

Pleural fluid biochemical analyses are of great value in verifying the etiology of undiagnosed pleural effusions. The preanalytical phase of pleural fluid biochemical analyses refers to the potential errors associated with specimen collection procedures, transportation, and sample stability. The analytical phase refers to the matrix effects and interference. The post-analytical phase refers to the clinical interpretation of the biochemical analyses. This review summarizes the preanalytical, analytical, and postanalytical phases of pleural fluid biochemical analyses. Evidence regarding potential preanalytical errors (e.g. stability, interference, and effects of anticoagulants on biomarker results) was summarized. In addition, we compiled evidence on the clinical interpretation of pleural fluid biomarkers, particularly from systematic reviews and meta-analyses. Finally, we discuss the future directions of biochemical analyses of pleural fluid.

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.

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.