Critical reviews in clinical laboratory sciences最新文献

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.

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.

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.

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.

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.

Non-coding RNAs (ncRNAs) are a class of functional transcripts that are not translated into proteins and primarily include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). In recent years, as therapeutic challenges such as tumor heterogeneity and drug resistance have become increasingly prominent, ncRNAs have emerged as pivotal targets in cancer mechanistic research and precision intervention strategies due to their central roles in tumor initiation, progression, metastasis, and therapeutic resistance. Given the limitations of conventional treatments, inadequate early detection methods, and significant inter-individual variability, elucidating the regulatory functions of ncRNA networks have become an urgent imperative for advancing cancer diagnosis and treatment. This review systematically integrates the regulatory mechanisms of miRNAs, lncRNAs, and circRNAs in key oncogenic processes from a pan-cancer perspective, including cell proliferation, cell cycle control, apoptosis evasion, metastatic activation, and resistance reprogramming, while highlighting their hub-like roles in multi-pathway crosstalk,the application of ncRNA in cancer diagnosis and its role in treatment and prognosis. Furthermore, future research must strive for breakthroughs in areas such as the optimization of nanodelivery systems, AI-driven target identification, and dynamic multi-omics integration, with the ultimate goal of achieving the systematic translation of ncRNAs into actionable strategies for personalized precision medicine-transforming "functional transcriptional regulation" into "targetable therapeutic intervention."

Blood-based biomarkers are an easily available and practical tool for Alzheimer's disease (AD) screening and diagnosis. Plasma phosphorylated Tau217 (p-tau217) is the front-runner candidate for AD diagnosis due to its strong correlation with core AD pathology determined either by cerebrospinal fluid biomarker (CSF) and positron emission tomography (PET) or postmortem examination. While plasma p-tau217 is firmly associated with AD pathology, it is crucial to evaluate its performance in distinguishing AD from mixed pathologies, as brain autopsies have shown the coexisting of AD pathology with other related types of dementia. Moreover, the measurement of AD biomarkers will be a crucial element in defining eligibility for disease-modifying treatment in clinical practice. Moreover, plasma p-tau217 is a highly efficacious biomarker in the early detection of Aβ pathology, making it a feasible test for AD screening in clinical practice. Several assays, including the ALZpath p-tau217 assay and the Fujirebio plasma p-tau217 assay, have been made commercially available for research use. A few studies analytically and clinically have validated these immunoassays as laboratory diagnostic tests for AD diagnosis and differentiating from non-AD neurodegenerative disorders in clinical practice.

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.

Implementing DP on a large scale is a complex, multi-dimensional process that requires strategic planning, technological adaptation, and change management. We provide a detailed account of the full-scale implementation of DP at the University Health Network (UHN), a multi-site tertiary clinical center in Canada, highlighting practical lessons learned, ongoing challenges, and mitigation strategies.

A phased implementation approach was adopted, involving pre-implementation planning, procurement, infrastructure development, and optimized validation protocols. Significant focus was placed on technical considerations, including system interoperability, storage capacity, and image quality. Procurement was structured to ensure vendor neutrality and long-term sustainability.A critical component of the implementation was "change management", addressing resistance to change through extensive training, real-time troubleshooting, utilizing "super users" as change champions. Attention was paid to pathologist office configuration.

A dual workflow model, with simultaneous access to both glass and digital slides, facilitated smoother transition. As of this writing all histopathology H&E cases and tissue hematopathology are being scanned. Efforts to implement digital liquid hematopathology and cytopathology are ongoing.

The financial implications of DP implementation were evaluated, including direct and indirect costs. While initial investments in scanners, storage, and software infrastructure were substantial, long-term savings are anticipated through increased efficiency, reduced physical slide storage, enhanced workload distribution and the integration of AI-based tools.

Continuous monitoring and feedback were established to assess system performance and address emerging challenges. Scalability and future applications of DP remain a priority. The adoption of AI-driven pathology tools, remote diagnostics, and cross-institutional data sharing are anticipated to further enhance the value of DP. UHN's experience underscores the importance of a structured, multidisciplinary approach to DP implementation.

Our experience offers a realistic and evolving roadmap for institutions considering DP adoption. We provide practical guidance, highlight persistent challenges and emphasize the importance of continuous evaluation and adaptation.