Critical reviews in clinical laboratory sciences最新文献

{"title":"Pleural fluid biochemical analyses: a state-of-the-art review.","authors":"Wen-Qi Zheng, José M Porcel, Y C Gary Lee, Zhi-De Hu","doi":"10.1080/10408363.2025.2577984","DOIUrl":"10.1080/10408363.2025.2577984","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"287-304"},"PeriodicalIF":5.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488109","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 biomarkers for the diagnosis of chorioamnionitis following preterm premature rupture of membranes: a systematic review and meta-analysis of studies since 2020.","authors":"Antoine Puravet, Samy Kahouadji, Denis Gallot, Bruno Pereira, Damien Bouvier, Vincent Sapin","doi":"10.1080/10408363.2026.2665297","DOIUrl":"https://doi.org/10.1080/10408363.2026.2665297","url":null,"abstract":"<p><p>Human preterm premature rupture of membranes (PPROM) refers to the spontaneous rupture of fetal membranes before 37 weeks of gestation and prior to labor. Clinically, the decision to induce labor or continue expectant management must be balanced against the risk of infection, particularly chorioamnionitis. Early diagnosis is critical, as chorioamnionitis is associated with preterm birth and fetal (hypoxia and/or sepsis) and maternal (bacteremia, hemorrhage, and/or death) complications. Currently, no specific blood biomarker is routinely used, with only nonspecific parameters like C-reactive protein (CRP) and white blood cell (WBC) count available. This highlights the need to review and meta-analyze recent studies to summarize new maternal blood biomarkers and improve diagnostic performance. A meta-analysis was performed to assess the prognostic value of some current or new blood biomarkers in predicting histological or clinical chorioamnionitis in women after PPROM. A protocol was designed and registered with PROSPERO (CRD420251058686). Studies were chosen if they included women with PPROM who underwent blood biomarker measurements and histological evaluation of the fetal membranes or clinical assessment of chorioamnionitis. The quality of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria. Three databases (Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL)) were consulted. Of the 631 articles screened, 9 were finally selected for inclusion. The overall pooled sensitivity (Se) of CRP, WBC count, procalcitonin (PCT), and neutrophil-lymphocyte ratio (NLR) were respectively 71% (95% CIs of 60%-81%), 73% (95% CIs of 66%-79%), 83% (95% CIs of 68%-94%) and 75% (95% CIs of 68%-81%). The overall pooled specificity (Spe) of CRP, WBC, PCT, and NLR were respectively 75% (95% CIs of 73%-78%), 61% (95% CIs of 52%-63%), 41% (95% CIs of 10%-76%) and 82% (95% CIs of 61%-96). The area under the curve (AUC), obtained from receiver operating characteristic (ROC) curve analysis was 77%, 73%, 74%, and 77% for CRP, WBC count, PCT, and NLR, respectively. Evidently, no single biomarker currently appears capable of accurately predicting the occurrence of chorioamnionitis, as the diagnostic performance of tested biomarkers remains modest. Over the past five years, no new biomarker has been evaluated frequently enough to allow for a meta-analysis of its diagnostic accuracy. This emphasizes the importance of identifying new predictive biomarkers, particularly through large-scale proteomic approaches.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-17"},"PeriodicalIF":5.5,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148041032","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":"Diagnostic stewardship monitoring systems: institutional and system-level approaches.","authors":"Kuenyoul Park","doi":"10.1080/10408363.2026.2666326","DOIUrl":"10.1080/10408363.2026.2666326","url":null,"abstract":"<p><p>Diagnostic stewardship-performing the right test for the right patient at the right time-improves diagnostic accuracy and reduces healthcare resource waste. Various stewardship interventions have been introduced, yet their effects dissipate without systematic, sustained monitoring. One-time education and isolated system controls consistently show effect attenuation over time, and inappropriate ordering practices rapidly rebound once active oversight ceases. To date, the literature has focused on monitoring within single institutions; integration with population-level surveillance systems remains underexplored. This review proposes a framework linking institutional-level and system-level monitoring. At the institutional level, key performance indicators such as tests per patient-day and test-to-test ratios, combined with dashboard visualization, statistical process control charts, and cyclical audit-and-feedback structures, enable continuous surveillance of ordering patterns and drive behavioral change. Root cause analysis of monitoring data can identify specific drivers of over-ordering, and machine learning approaches show promise for predicting both overutilization and underutilization. These institutional tools, however, cannot track patients across facilities or assess population-level test appropriateness. At the system level, health insurance claims and administrative data enable macroscopic monitoring across entire populations. National experiences from Korea, Canada, and the United States demonstrate that ordering code pattern analysis can systematically identify inappropriate utilization-and that the structural design of reimbursement systems is more effective than voluntary recommendations in controlling low-value testing. The inherent limitation of claims data-the absence of test result values-can be partially overcome through linkage with other administrative databases. Bridging these two levels requires healthcare data standards and interoperability infrastructure, including Logical Observation Identifiers Names and Codes (LOINC), Nomenclature for Properties and Units (NPU), Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT), and Fast Healthcare Interoperability Resources (FHIR), yet practical barriers such as mapping quality variability, privacy constraints, and standardization costs persist. The scope of monitoring should extend beyond test ordering to encompass the entire total testing process, engaging diverse stakeholders across the testing continuum. With multidisciplinary workforce development, artificial intelligence-based clinical decision support, value-based reimbursement models, and rigorous multi-center studies, diagnostic stewardship monitoring can evolve into sustainable healthcare infrastructure that serves both individual patient safety and population health.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-17"},"PeriodicalIF":5.5,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873599","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":"Single cell mechanodeformation signatures as early biomarkers for hematological malignancies.","authors":"Ali Sani, Yang Yu, Muhammad Idrees Khan, Li Yuanrong, Yi Liu, Yaling Liu","doi":"10.1080/10408363.2026.2665294","DOIUrl":"10.1080/10408363.2026.2665294","url":null,"abstract":"<p><p>Single-cell mechanical profiling of deformations has become a promising method of identifying a functional biomarker in patients with blood cancers. By quantifying the physical and mechanical properties of individual cells, this method examines the biomechanical changes that occur after alterations in the structure of the cytoskeleton, as well as changes occurring within the nucleus or chromatin as it relates to being transformed by cancerous processes. Mechanodeformation signatures provide a unique, universally applicable, and label-free measure of cellular states; therefore, they provide a different methodological category compared with traditional approaches such as immunophenotyping and molecular assays. This article critically reviews the mechanobiological basis for deformation and describes and compares quantifiable measurement parameters of deformation (stiffness, deformation index, recoverability, and transition dynamics) as well as a comparison between traditional methods of deformability analysis with microfluidic technologies, including their respective analytical performance, throughput, and clinical readiness. Relevant data will be summarized for each of the three leukemias, multiple myelomas and lymphomas examined, with an emphasis on study design, sample size, and validation of mechanism based on established criteria of measurable outcomes. We will also discuss how clinical applications such as early diagnosis, risk stratification, treatment response analysis, and monitoring of people with minimal detectable percentile changes (MRD) can all be done in a clinical setting. A special emphasis will be placed on pre-and post-analytical variables, standardization, quality control, and reproducibility, all critical to successfully implementing laboratory assessments. Additionally, we will examine different levels of variation (e.g., biological heterogeneity, cross-platform comparison, bias due to artificial intelligence, and regulatory requirements). Current research supports biological plausibility and discrimination within studies; however, large-scale multi-site validation and harmonized reporting standards must still happen before establishing routine use. The development of mechanodeformation signatures will create the opportunity for it to be integrated into current functional imaging tests used as a standard metric with regular measurements being taken over time. This ongoing study will serve to expand the current utilization of single-cell biomechanical phenotyping to improve personalized/precision-based medicine within the field of hematology.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-27"},"PeriodicalIF":5.5,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927335","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":"Current practices in the diagnosis of Lyme disease.","authors":"Michael E Walsh, Lynn A Brunelle","doi":"10.1080/10408363.2026.2663780","DOIUrl":"https://doi.org/10.1080/10408363.2026.2663780","url":null,"abstract":"<p><p>Lyme disease (LD) is the most prevalent vector-borne disease in the Northern Hemisphere. The bacterial pathogen responsible for the disease is transmitted to humans and other mammals via the arthropod vector <i>Ixodes</i> spp. whose hematophagy lends itself to the acquisition and transmission of this pathogen. The spirochete pathogen responsible for LD belongs to the genus <i>Borrelia burgdorferi</i> sensu lato complex, who can be found in North America, South America, Eurasia, and Africa. The initial clinical presentation of LD typically manifests with an erythema migrans skin lesion (bull's-eye rash), and if left untreated, can develop into disseminated LD that can be accompanied by neuritis, meningitis, carditis, and/or arthritis. Diagnosis of LD is typically done via serological testing in the clinical laboratory. Advances in this area include the characterization and refinement of antigen targets utilized by immunoassays, more recent expansion of the testing algorithm to allow for the use of immunoassays over immunoblots, and the development of highly sensitive assays that readily allow for automation. Research into future directions for diagnostic testing in the clinical laboratory include the application of transcriptomics, proteomics, and metabolomics, many of which demonstrate promise for potential future application. Each of these areas will be discussed in detail to provide a broad understanding of the disease process, the diagnostic testing modalities currently available to the clinical laboratory, and where future research may lead one day.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-20"},"PeriodicalIF":5.5,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863807","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":"Pleural fluid biomarkers for the diagnosis and management of malignant pleural effusions: a clinical review.","authors":"Jose Diego Santotoribio","doi":"10.1080/10408363.2025.2559697","DOIUrl":"10.1080/10408363.2025.2559697","url":null,"abstract":"<p><p>Initial pleural fluid analysis is a fundamental step in the evaluation of suspected malignant pleural effusion (MPE). Most MPEs present as exudates, often hemorrhagic, with mononuclear cell predominance. Basic biochemical parameters-glucose, total protein, LDH, ADA, and pH-help distinguish MPE from other causes and offer prognostic information. Low glucose and pH, and elevated LDH, are associated with higher tumor burden and poorer outcomes. Flow cytometry can detect high-fluorescence cells suggestive of malignancy, while additional markers like CRP, cholesterol, amylase, and lipids provide complementary diagnostic value, especially when interpreted alongside tumor markers (TMs). Among TMs in pleural fluid, CEA is the most validated and widely used, showing high specificity for MPE. Others-such as CA 15.3, CYFRA 21-1, CA 125, CA 19.9, NSE, and HE4-offer variable sensitivity and specificity depending on tumor type and clinical context. False positives can occur in benign or inflammatory conditions, emphasizing the need for cautious interpretation. Other cancer biomarkers in pleural fluid-such as VEGF, Apolipoprotein E, calprotectin, endostatin, and homocysteine-may enhance diagnostic and prognostic capabilities. VEGF and endostatin reflect tumor angiogenesis and may also serve as therapeutic targets, while homocysteine shows promise in detecting MPEs not identified by conventional TMs. Multimarker strategies significantly improve diagnostic accuracy. Combinations of two pleural fluid TMs, such as CEA with CA 15.3, or diagnostic models like the MPER score (CEA + homocysteine), have shown excellent performance. Panels with three or more markers, including inflammatory or metabolic biomarkers (ADA, CRP, and %polymorphonuclear leukocytes) further enhance sensitivity and specificity. Molecular analysis in pleural fluid has emerged as a promising approach for the diagnosis of MPE, enabling the detection of mRNA, DNA methylation patterns, lncRNAs, miRNAs, or circulating tumor DNA. Although these biomarkers have demonstrated good diagnostic accuracy, they are not yet implemented in routine clinical practice, and most studies have primarily focused on MPE due to lung cancer. In malignant pleural mesothelioma, where cytology has limited sensitivity, the most extensively investigated markers in pleural fluid are mesothelin and fibulin-3. Among conventional tumor markers, the pleural fluid CYFRA 21-1/CEA ratio has shown high diagnostic accuracy, further enhanced when combined with mesothelin. Pleural fluid fibulin-3 has also been identified as an independent prognostic factor for survival.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"237-260"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111688","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":"Essential amino acids in celiac disease: key roles in immunogenicity, pathogenesis, and therapeutic approaches.","authors":"Sajjad Bakhtiari, Nastaran Asri, Andrea Masotti, Somayeh Jahani-Sherafat, Mostafa Rezaei Tavirani, Mohammad Rostami-Nejad","doi":"10.1080/10408363.2025.2551656","DOIUrl":"10.1080/10408363.2025.2551656","url":null,"abstract":"<p><p>Celiac disease (CD) is a chronic autoimmune disorder triggered by gluten ingestion, causing intestinal damage and systemic complications. Essential amino acids (EAAs) play crucial roles in immune function, intestinal integrity, and metabolic regulation; however, their malabsorption in CD contributes to disease progression. Tryptophan dysregulation may influence mood disorders in CD, while phenylalanine and lysine are linked to immune activation and gluten modification. Methionine impacts antioxidant defense and homocysteine metabolism, and disruptions in both pathways have been observed in CD patients. Branched-chain amino acids (BCAAs), crucial for muscle synthesis, remain deficient even in treated patients, suggesting long-term metabolic effects. Threonine, vital for gut barrier function, has been reported to show increased levels in CD, potentially reflecting altered metabolism and disease progression. Arginine metabolism shifts toward pro-inflammatory nitric oxide production, exacerbating intestinal damage. EAA imbalances may serve as biomarkers for disease activity, severity, and treatment response. Altered plasma and fecal amino acid profiles correlate with disease progression, offering diagnostic and monitoring potential. Addressing EAA deficiencies through targeted supplementation or dietary interventions could enhance intestinal healing, mitigate complications, and improve outcomes beyond a gluten-free diet (GFD). This review examines the interplay between EAAs and CD pathogenesis, highlighting their roles in immune modulation, gut barrier maintenance, systemic metabolic effects, and potential as disease biomarkers.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"204-219"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999856","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":"Data analytics for error detection in clinical laboratories.","authors":"Clarence W Chan","doi":"10.1080/10408363.2025.2555261","DOIUrl":"10.1080/10408363.2025.2555261","url":null,"abstract":"<p><p>Errors inevitably occur in the practice of laboratory medicine. A cornerstone of clinical laboratory quality management is the detection of erroneous results and the assessment of imprecision, bias, and other performance limitations of clinical test methods, particularly those affecting patient care. Errors can arise in each of what has been conventionally regarded as the three key phases of testing: pre-analytical, analytical, and post-analytical. In this review, both the standard concepts and methods of quantifying uncertainty and error are introduced in the context of clinical laboratory operations. Method validation and verification studies are presented as opportunities for preemptive and anticipatory error assessment-before tests are implemented for patient testing. Quality control monitoring is a key internal quality assurance strategy, whereas proficiency testing forms the basis of most external quality assurance initiatives. Data analytic approaches for error detection are reviewed, highlighting quantitative and statistical concepts on which they are based, and emerging machine learning and artificial intelligence algorithms are presented as contemporary tools currently under development for error detection in the clinical laboratory.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"220-236"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085200","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 MicroRNA network in sepsis: from biomarker discovery to novel targeted therapeutic strategies.","authors":"Jianyi Xie, Lingxuan Tang, Wangzheqi Zhang, Changli Wang","doi":"10.1080/10408363.2025.2561071","DOIUrl":"10.1080/10408363.2025.2561071","url":null,"abstract":"<p><p>Sepsis is a life-threatening multiple-organ dysfunction syndrome triggered by infection and mediated by host immune dysregulation. Its complex pathophysiological mechanisms and the lack of effective diagnostic and therapeutic approaches make it a major challenge for the global healthcare system. As key molecules in post-transcriptional gene regulation, microRNAs (miRNAs) play crucial roles in immune dyshomeostasis, inflammatory storms, and organ damage during sepsis, and have emerged as a research focus in this field in recent years. This review summarizes the research progress of miRNAs in sepsis, with a focus on their expression characteristics, regulatory mechanisms, and clinical translational value. miRNAs regulate inflammatory responses by targeting core signaling pathways such as the Toll-like receptor (TLR)/nuclear factor kappa B (NF-κB) pathway. The specific mechanisms include: blocking upstream pathway activation by targeting TLR ligands or adaptor proteins; directly regulating NF-κB subunits to inhibit the transcription of pro-inflammatory genes; modulating negative feedback loops; and interacting with other signaling cascades. Furthermore, certain miRNAs act as both key regulators of immune responses and potential diagnostic/prognostic biomarkers. In terms of organ damage, miRNAs display organ-specific characteristics by working as specific regulatory molecules in sepsis-associated cardiac, hepatic, and cerebral injuries. They affect organ function by targeting pathways such as phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase/signal transducer and activator of transcription (JAK/STAT). In terms of clinical translational value, miRNAs derived from human serum/plasma have shown significant potential in sepsis diagnosis, treatment guidance, and prognosis prediction. By dissecting the regulatory network of miRNAs in sepsis, this review not only provides a theoretical basis for understanding the complex pathophysiology of sepsis but also identifies key directions for developing miRNA-based precision diagnostic and therapeutic strategies (e.g. combined detection of multiple biomarkers and targeted delivery systems). It is anticipated to offer novel solutions for improving the prognosis of sepsis patients and reducing mortality.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"261-286"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205699","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":"Diagnostic performance and heterogeneity of validated flow cytometry scores: a systematic review.","authors":"Marc Sorigue","doi":"10.1080/10408363.2026.2651313","DOIUrl":"https://doi.org/10.1080/10408363.2026.2651313","url":null,"abstract":"<p><p>Most flow cytometry diagnostic scores are derived from single-center, retrospective studies, and the reproducibility of their reported performance in validation cohorts remains uncertain. We searched MEDLINE for FC diagnostic scores with at least one validation cohort published in the past 10 years, ultimately focusing on B lymphoid disorders (B-LPD) and myelodysplastic syndrome (MDS) scores, where most validation efforts have been undertaken. Forty-four publications were included: 29 on MDS (10 scores) and 15 on B-LPD (10 scores). Most scores were validated once or twice. For scores with both derivation and validation cohorts, sensitivity and specificity differences ranged from -0.25 to +0.29 (validation minus derivation). Among the three scores with more than five validated cohorts, I² values were consistently high for sensitivity and, in two cases, also for specificity, indicating high heterogeneity. To explain this variability, we systematically reviewed study methods and identified 31 potential sources of heterogeneity, spanning study design, pre-analytical, analytical, and post-analytical factors. In conclusion, few flow cytometry scores have been validated, most only in limited cohorts, and their reported diagnostic performance varies widely. While numerous potential sources of variability can be identified, the small number of available studies prevents reliable quantification of their impact. Published accuracy estimates should therefore not be accepted at face value, and proposed scores should be validated in-house before being adopted into diagnostic practice.</p>","PeriodicalId":10760,"journal":{"name":"Critical reviews in clinical laboratory sciences","volume":" ","pages":"1-15"},"PeriodicalIF":5.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653933","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}