Clinica Chimica Acta; International Journal Of Clinical Chemistry[JOURNAL]
Sun
200 papers
Apolipoprotein B causes overestimation of serum albumin concentration measured by bromocresol green method in pediatric nephrotic syndrome patients.
Yang Q, Peng W, Wang W … +5 more , Feng Q, Wu L, Liang Z, Gao X, Liu F
Clin Chim Acta · 2026 May · PMID 42176932 · Publisher ↗
PURPOSE: Pediatric Nephrotic syndrome (PNS) is a prevalent major disorder in children. The precise detection of albumin is of crucial significance for the diagnosis, treatment decision-making, and prognosis improvement o...
PURPOSE: Pediatric Nephrotic syndrome (PNS) is a prevalent major disorder in children. The precise detection of albumin is of crucial significance for the diagnosis, treatment decision-making, and prognosis improvement of PNS. The bromocresol green (BCG) method is a commonly used method for clinical albumin detection. Typically, patients with PNS exhibit disordered lipid metabolism, with altered levels of apolipoprotein B (ApoB), haptoglobin (Hp), α2-macroglobulin (α2MG), and apolipoprotein A1 (ApoA1). The objective of this study was to determine whether these proteins interfere with the detection of serum albumin using the BCG method in PNS, and to evaluate the extent of interference and its clinical implications. METHODS: A total of 134 PNS patients were enrolled in the study. Serum albumin levels were measured simultaneously using both the BCG method (ALB-BCG) and the immunoturbidimetric assay (ALB-ITA). In addition, serum levels of Hp, α2MG, ApoB, and ApoA1 were measured and evaluated for their potential correlation with the discrepancy in albumin measurements between the two methods (ΔALB = ALB-BCG - ALB-ITA). Furthermore, to evaluate the interference of these proteins on albumin detection using the BCG or ITA method, an in vitro interference assay was performed by spiking purified proteins into standard albumin solutions at progressively increasing concentrations, thereby assessing their potential to interfere with albumin measurement. RESULTS: The children were stratified into three groups based on ALB-BCG levels, Group I, ALB-BCG ≥ 25 g/L (n = 43), Group II, 20 g/L ≤ ALB-BCG < 25 g/L (n = 35), Group III, ALB-BCG < 20 g/L (n = 56). Serum albumin concentrations measured by the BCG method were significantly higher than those obtained by the ITA method, with a difference (ΔALB) ranging from 0.2 to 6.9 g/L. ΔALB showed a significant negative correlation with serum albumin levels (P < 0.01). α2MG, ApoB, Hp and ApoA1 levels showed significant differences among the three groups (P < 0.05). ΔALB demonstrated moderate correlations with Hp, α2MG, and ApoB (P < 0.001), and a weak correlation with ApoA1 (P < 0.001). In vitro experiments demonstrated that ApoB caused a dose-dependent positive interference with the serum albumin detection using the BCG method (P < 0.001), but not with the ITA method. Although α2MG can bring about a slight decrease in ALB-BCG results (P = 0.024), it does not lead to a significant alteration in ΔALB. At physiological concentrations, Hp slightly raises ALB-BCG results, thus increasing ΔALB (P = 0.007), but the changes in ΔALB are only minimal. CONCLUSION: Elevated ApoB levels lead to a dose-dependent overestimation of albumin concentration when measured using BCG method. Thus, it is advisable to utilize the ITA method for the accurate determination of serum albumin levels in PNS patients. Meanwhile, when ITA is not readily available, the bromocresol purple (BCP) method can serve as a more practical alternative. This ensures a proper assessment of colloid osmotic pressure and nutritional status, thereby facilitating clinical diagnosis and therapeutic decision-making.
Clinical Spectrum and Management of Hypervitaminosis A: A Systematic Review of Case-Based Evidence.
Padmakar S
Clin Chim Acta · 2026 May · PMID 42176931 · Publisher ↗
BACKGROUND: Hypervitaminosis A, caused by excessive intake or pathological accumulation of vitamin A, can lead to severe and diverse adverse effects across multiple organ systems. With rising availability of over-the-cou...
BACKGROUND: Hypervitaminosis A, caused by excessive intake or pathological accumulation of vitamin A, can lead to severe and diverse adverse effects across multiple organ systems. With rising availability of over-the-counter supplements and expanding food fortification programmes, the evidence base remains fragmented and primarily reliant on sporadic case reports. This systematic review synthesizes available evidence on the adverse effects and management of hypervitaminosis A. METHODS: This systematic review was conducted according to the PRISMA 2020 guidelines. The literature was searched using various databases like PubMed, Scopus, Embase and Web of Science up to January 15, 2026 without any language restriction. The literature search, study selection, data extraction, and quality assessment of the included studies were performed by the author using a standardized extraction form with self-verification. JBI critical appraisal checklists were applied across all study designs: the 8-item tool for case reports, the 9-item tool for prevalence studies, and the 11-item tool for cohort studies. The inclusion criteria for this study included peer-reviewed literature like observational study, case reports, and case series among human subjects experiencing side effects or toxicity due to hypervitaminosis A. FINDINGS: From an initial pool of 326 literature, after screening and exclusion, a total of 31 studies were included in this review, comprising case reports (n = 26, 83.9%), case series (n = 3, 9.7%), one observational study (n = 1, 3.2%), and one retrospective study (n = 1, 3.2%). The literature was published primarily in the USA (n = 10, 32.3%). Various sources of vitamin A toxicity were reported, most commonly vitamin A capsules or tablets (n = 21, 67.7%). The most common adverse effect was hypercalcemia (n = 9, 29.0%), followed by gastrointestinal manifestations (n = 8, 25.8%), neurological manifestations (n = 7, 22.6%), hepatobiliary manifestations (n = 7, 22.6%), musculoskeletal manifestations (n = 6, 19.4%), and dermatological manifestations (n = 5, 16.1%). Acute toxicity commonly presented with neurological symptoms including headache, diplopia, and raised intracranial pressure, whereas chronic toxicity was more frequently associated with hepatobiliary complications, musculoskeletal manifestations, and hypercalcemia. The treatment includes discontinuation of vitamin A intake, bisphosphonates, prednisone, intravenous fluids, calcitonin, orthopaedic surgery, and liver transplantation. CONCLUSION: Hypervitaminosis A, particularly arising from non-prescription supplement misuse, mimics various disorders and presents commonly with hypercalcemia and neurological dysfunction. It is a preventable condition requiring early recognition, prompt discontinuation of vitamin A intake, and appropriate symptomatic management. A thorough dietary and supplementation history is essential for timely diagnosis.
Mitochondrial metabolism and succinylation-related gene signatures for predicting prognosis and drug resistance in colon adenocarcinoma.
Wei X, Qiu Z, Dong J … +3 more , Liu J, Hong T, Yang J
Clin Chim Acta · 2026 May · PMID 42176930 · Publisher ↗
BACKGROUND: Colon adenocarcinoma (COAD) has high incidence and mortality but lacks reliable molecular biomarkers for prognosis and individualized therapy. Mitochondrial metabolic reprogramming and succinylation are close...
BACKGROUND: Colon adenocarcinoma (COAD) has high incidence and mortality but lacks reliable molecular biomarkers for prognosis and individualized therapy. Mitochondrial metabolic reprogramming and succinylation are closely implicated in COAD progression, yet their synergistic mechanism remains unclear. This study aimed to analyze mitochondrial metabolism and succinylation-related gene (MMSRG) signatures, identify key biomarkers for COAD prognosis and drug resistance, and establish a robust prognostic model. METHODS: We retrieved 615 succinylation-related and 14,207 mitochondrial metabolism-related genes from GeneCards. Differentially-expressed MMSRGs were identified in the TCGA-COAD dataset (524 samples). A prognostic model was constructed using univariate/multivariate Cox and LASSO regression, and validated externally in GEO GSE38832. Functional enrichment, immune infiltration, drug sensitivity, single-cell sequencing (GSE231559), and qRT-PCR analyses were performed to explore hub gene functions and clinical value. RESULTS: A total of 144 differentially expressed MMSRGs were identified, and a two-hub-gene (MC1R, H2AC6) optimal prognostic index for survival-related variable (OPISV) model was established. Both genes were independent prognostic factors for COAD. The model achieved a 3-year time-dependent ROC AUC of 0.665 with good robustness in internal and external validation. MMSRGs were mainly enriched in protein heterodimerization and neutrophil extracellular trap formation. The low-risk group showed increased activated memory CD4 T-cell infiltration and higher chemotherapeutic and targeted drug sensitivity. Hub gene expression patterns were consistent across single-cell sequencing and qRT-PCR. CONCLUSION: MMSRG signatures are closely associated with COAD prognosis, immune infiltration, and drug resistance. The OPISV model represents a novel biomarker for COAD prognosis and individualized treatment, providing theoretical and experimental support for COAD precision medicine.
JAK2 V617F as a diagnostic and prognostic biomarker in myeloproliferative neoplasms.
Bhat AA, Fuloria S, Thapa R … +7 more , Narain K, Biswas A, Gnanam P, Dhandapani SV, Biswas S, Bhatia S, Fuloria NK
Clin Chim Acta · 2026 May · PMID 42176929 · Publisher ↗
Molecular analysis of BCR-ABL1-negative myeloproliferative neoplasms has shown a shared codon 617 substitution of JAK2 that leads to a constitutively active tyrosine kinase and a pathogenic lesion that unites all three p...
Molecular analysis of BCR-ABL1-negative myeloproliferative neoplasms has shown a shared codon 617 substitution of JAK2 that leads to a constitutively active tyrosine kinase and a pathogenic lesion that unites all three polycythemia vera, essential thrombocythemia, and primary myelofibrosis. This mutation interferes with the autoinhibitory regulation and results in persistent downstream JAK-STAT signaling, and thereafter, myeloid, megakaryocytic, and inappropriate erythroid proliferation. JAK2 V617F has emerged as a major molecular biomarker in the diagnostic workup and classification of myeloproliferative neoplasms in laboratory medicine when used together with blood counts, bone marrow morphology, serum erythropoietin, and other molecular markers, such as CALR and MPL. Outside its diagnostic application, variant allele burden has also been linked to thrombosis, disease phenotype, clonal growth, fibrotic development, and survival but not uniformly across disease subtypes and clinical contexts. JAK2 V617F detection in laboratories has moved beyond traditional approaches based on PCR to sensitive quantitative technologies, such as digital PCR and next-generation sequencing-based technologies, making the standardization of assays, assurance of quality and more clinically integrated interpretation more important. In general, JAK2 V617F is an effective prognostic and diagnostic biomarker in myeloproliferative neoplasms. It can be further enhanced in diagnostic laboratory hematology with further optimization of the strategies of molecular testing, reporting systems, and multi-marker diagnostic algorithms.
Cut-off values of urinary free cortisol and cortisone for diagnosing neoplastic hypercortisolism.
Koops K, Hillebrand JJ, Heijboer AC … +1 more , Bisschop PH
Clin Chim Acta · 2026 May · PMID 42173303 · Publisher ↗
BACKGROUND: Quantification of urinary free cortisol excretion is a recommended initial screening test for diagnosing hypercortisolism. This study aims to determine optimal cut-off values for urinary free cortisol (Cortis...
BACKGROUND: Quantification of urinary free cortisol excretion is a recommended initial screening test for diagnosing hypercortisolism. This study aims to determine optimal cut-off values for urinary free cortisol (Cortisol) and urinary free cortisone (Cortisone) for diagnosing neoplastic hypercortisolism and to determine whether either one has superior diagnostic accuracy. METHODS: We performed a retrospective study using clinical and laboratory data of subjects screened for neoplastic hypercortisolism at Amsterdam UMC between December 2015 and February 2022. Clinical follow-up data was used as the gold standard to define subjects with and without neoplastic hypercortisolism. Subjects collected urine for 24 h on two consecutive days. Cortisol and Cortisone concentrations were measured using LC-MS/MS. The average concentration of both urine collections was used for analysis. Diagnostic accuracy was evaluated by ROC-curve analysis. RESULTS: Cortisol was available from 27 subjects with, and 417 subjects without neoplastic hypercortisolism. In a subgroup of 17 subjects with, and 292 subjects without neoplastic hypercortisolism, Cortisone was also available. The optimal cut-off value for Cortisol was 120 nmol/24 h (sensitivity 89%, specificity 86%; ROC AUC: 0.937) and 300 nmol/24 h for Cortisone (sensitivity 94%, specificity 88%; ROC AUC: 0.941). The optimal cut-off value for the sum Cortisol + Cortisone was 460 nmol/24 h (sensitivity 94%, specificity 93%; ROC AUC: 0.947). CONCLUSIONS: We established cut-off values for Cortisol and Cortisone for the diagnosis of neoplastic hypercortisolism. Cortisol, Cortisone and their sum had comparable diagnostic accuracies. The proposed cut-off values can be used by other laboratories using LC-MS/MS methods following analytical method comparison and validation of the proposed cut-off values in a different cohort.
Targeted LC-MS/MS validation of unsaturated fatty acid dysregulation and PI3K-Akt-related metabolic signatures in immune thrombocytopenia.
Zhou X, Lu G, Tian X … +3 more , Zhang P, Shi Y, Shan N
Clin Chim Acta · 2026 May · PMID 42173302 · Publisher ↗
BACKGROUND: Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder characterized by immune dysregulation and thrombocytopenia. Metabolic reprogramming has been implicated in the pathogenesis of immune-...
BACKGROUND: Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder characterized by immune dysregulation and thrombocytopenia. Metabolic reprogramming has been implicated in the pathogenesis of immune-mediated diseases, while the PI3K-Akt signaling pathway acts as a critical link between immune response and metabolic regulation.Based on our previously published untargeted metabolomics findings, this study aimed to validate selected lipid metabolites in ITP and explore their potential association with PI3K-Akt-related metabolic signatures. METHODS: Twenty adults with newly diagnosed active ITP and 17 healthy controls were enrolled. Candidate metabolites were selected from our previously published untargeted metabolomics dataset and prioritized through metabolite annotation and KEGG pathway enrichment analysis. Serum oleic acid, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Statistical analyses were conducted to compare metabolite levels between the two groups, with P values adjusted for multiple comparisons using the Benjamini-Hochberg false discovery rate (FDR) method. Exploratory receiver operating characteristic (ROC) analyses were performed for individual metabolites, and a multivariable logistic regression model incorporating oleic acid, DHA, and EPA was constructed to evaluate their combined discriminative performance. RESULTS: Untargeted metabolomics showed clear metabolic separation between the ITP and control groups. KEGG analysis indicated enrichment in the PI3K-Akt signaling pathway and multiple lipid metabolism-related pathways. Targeted LC-MS/MS further confirmed that serum oleic acid, DHA, and EPA levels were all significantly higher in patients with ITP than in healthy controls (all FDR-adjusted P = 0.0008). Exploratory ROC analysis showed that oleic acid, EPA, and DHA individually yielded AUC values of 0.841, 0.829, and 0.826, respectively, while the combined logistic regression model incorporating all three metabolites achieved an AUC of 0.879. CONCLUSIONS: Patients with ITP exhibit measurable lipid metabolic abnormalities characterized by elevated oleic acid, DHA, and EPA levels. These findings provide targeted quantitative support for lipid metabolic dysregulation in ITP and suggest that these alterations may be associated with PI3K-Akt-related metabolic signatures inferred from pathway enrichment analysis.
Clinical utility of point-of-care biosensors for diagnosing chronic kidney disease.
Shukhrat V, Nigora F, Badritdinova M … +10 more , Aizhamal K, Dilfuza S, Usmanbekova G, Sardor Z, Dilfuza A, Murod E, Mirkurbanova T, Laylo K, Pulatova P, Jalilovna D
Clin Chim Acta · 2026 May · PMID 42167640 · Publisher ↗
Chronic kidney disease (CKD) is a significant global health concern characterized by a progressive decline in kidney function that often leads to severe complications and increased mortality. Early and accurate diagnosis...
Chronic kidney disease (CKD) is a significant global health concern characterized by a progressive decline in kidney function that often leads to severe complications and increased mortality. Early and accurate diagnosis is crucial for effective management and mitigation of CKD progression; however, traditional diagnostic methods are often invasive, time-consuming, and require centralized laboratory analysis, hindering timely intervention. Point-of-care (POC) biosensors offer a promising solution by enabling rapid, decentralized testing near the patient, thus facilitating early detection, continuous monitoring, and personalized treatment strategies. This narrative review explores the clinical utility of POC biosensors for CKD diagnosis, examining their design, application, and performance in detecting key CKD biomarkers. We discuss various biosensor technologies, including electrochemical, fluorescent, and colorimetric sensors, and innovative platforms such as lateral flow and microfluidic devices. This review highlights the potential of these technologies for real-time monitoring and early detection, ultimately aiming to improve patient outcomes and healthcare efficiency. Challenges and future perspectives in the clinical translation of POC biosensors for CKD will also be addressed.
Emerging nanoparticle approaches for early detection and therapeutic targeting of pancreatic cancer.
Abuhassan Q, Al-Ameer HJ, Younis SMD … +4 more , Rizaev J, Kibriyeva M, Salih RM, Jaber MA
Clin Chim Acta · 2026 May · PMID 42167639 · Publisher ↗
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies and is characterized by a poor overall survival rate largely because of its aggressive nature and frequent late-stage diagnosis. More th...
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies and is characterized by a poor overall survival rate largely because of its aggressive nature and frequent late-stage diagnosis. More than 80% of patients are diagnosed with unresectable disease at the time of presentation, underscoring the critical need for more effective detection and monitoring strategies. Conventional diagnostic methods, including imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI), often lack the sensitivity to identify small, early-stage tumors within the pancreas. Furthermore, the most widely used serum biomarker, carbohydrate antigen 19-9 (CA19-9), suffers from suboptimal sensitivity and specificity, limiting its utility for early risk assessment and screening. Recent studies have indicated that CA19-9 has a sensitivity of only 53% or 68% when predicting clinical presentation 12 or 24 months in advance, respectively, while maintaining 95% specificity. This diagnostic challenge has spurred significant research into nanotechnology, which offers novel solutions by enabling the detection of minuscule cancerous lesions and biomarkers at the molecular level. NPs can be engineered to overcome biological barriers, accumulate selectively in tumor tissue, and deliver potent contrast agents or therapeutic payloads, thereby increasing diagnostic accuracy and facilitating personalized treatment approaches. This review provides a comprehensive analysis of emerging nanoparticle-based strategies for PDAC detection and monitoring, covering advancements in imaging, theranostics, and liquid biopsies and their translation from preclinical models to clinical practice.
Dot-ELISA as a diagnostic tool: Detection of anti-Strongyloides antibodies in serum and saliva from donors at a regional blood Center in Northern Paraná.
Dos Santos Destro YM, Suzuki SM, Corral MA … +10 more , Nunes AP, Rossi IV, Lima DMC, Vasconcelos AM, Nunes CMDP, Roldán WH, Trigo FC, Gryschek RCB, de Paula FM, Costa IN
Clin Chim Acta · 2026 May · PMID 42167638 · Publisher ↗
BACKGROUND: Strongyloidiasis, caused by Strongyloides stercoralis, remains underdiagnosed due to limitations of conventional parasitological methods, including intermittent larval shedding and low sensitivity in chronic...
BACKGROUND: Strongyloidiasis, caused by Strongyloides stercoralis, remains underdiagnosed due to limitations of conventional parasitological methods, including intermittent larval shedding and low sensitivity in chronic and asymptomatic infections. This study aimed to evaluate the diagnostic performance of a Dot-ELISA assay for the detection of anti-S. stercoralis antibodies in serum and saliva samples from blood donors. METHODS: A total of 58 serum samples and 75 saliva samples from individuals previously classified by IgG ELISA and IgG Western blotting using heterologous Strongyloides venezuelensis antigen were analyzed. The diagnostic performance of Dot-ELISA was assessed using receiver operating characteristic (ROC) curves, sensitivity, and specificity, and results were compared with established serological methods. RESULTS: Dot-ELISA demonstrated high discriminatory ability between positive and negative serum samples and good performance in saliva samples, with results in agreement with ELISA and Western blotting. The assay successfully detected anti-S. stercoralis antibodies in both biological matrices, indicating reliable agreement with reference methods. The use of saliva as a biological sample represents a less invasive and more practical alternative for antibody detection. CONCLUSION: Dot-ELISA is a simple, low-cost method with reliable diagnostic performance for detecting S. stercoralis infection in both serum and saliva samples. Its application may improve access to diagnosis and support screening and surveillance strategies, particularly in endemic regions and settings with limited laboratory infrastructure.
Multi-omics biomarker in adrenocortical carcinoma: a clinical-chemistry perspective.
Gupta G, Patil DJ, Patel JR … +7 more , S RJ, Shefali, Karmakar R, Pant K, Bhopate K, Singh SK, Almalki WH
Clin Chim Acta · 2026 May · PMID 42167637 · Publisher ↗
Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor (incidence 0.7-2.0 per million per year) with a 5-year survival rate of less than 15% at the European Network for the Study of Adrenal Tumors stage...
Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor (incidence 0.7-2.0 per million per year) with a 5-year survival rate of less than 15% at the European Network for the Study of Adrenal Tumors stage IV. The standard diagnostic workup in clinical chemistry laboratories for the detection of functional tumors (serum cortisol, DHEAS, and 24 h urinary free cortisol) and the Weiss/Helsinki histological scoring system cannot detect non-functioning tumors, lacks a standardized approach for predicting prognosis, and does not have a validated minimal-residual-disease marker for postoperative monitoring. This narrative review evaluated 246 original research publications on four multi-omic layers in relation to clinical laboratories. Genomic and transcriptomic analyses, including TCGA-ACC pan-genomic profiling, revealed recurrent driver mutations and prognostic molecular subtypes that outperform the ENSAT staging. Tissue and circulating proteomic analyses identified HNRNPA1, KPNA2, SOAT1, and plasma AgRP as diagnostic and pharmacoproteomic targets. Urinary and serum steroid metabolomics (GC-MS and liquid chromatography-tandem mass spectrometry) validated in a 2017-patient prospective EURINE-ACT cohort provided clinically actionable diagnostic accuracy of over 85% and proved informative for post-surgical recurrence monitoring. Multi-omics classification consistently identifies two distinct biologically based subtypes with therapeutic implications. We also discuss the pre-analytical, analytical, and inter-laboratory standardization requirements that must be met before each biomarker layer can be translated to the clinical chemistry laboratory and advocate a multi-omic implementation strategy for ACC diagnosis, prognosis, and recurrence detection.
Systematic review of alpha-synuclein seed amplification assays for the detection of synucleinopathies.
López-Bellido A, Marti-Navia A, Cháfer-Pericás C
Clin Chim Acta · 2026 May · PMID 42167636 · Publisher ↗
Parkinson's disease and other synucleinopathies are neurodegenerative disorders defined by the pathological aggregation of alpha-synuclein (α-syn). The alpha-synuclein Seed Amplification Assay (α-syn SAA), also known as...
Parkinson's disease and other synucleinopathies are neurodegenerative disorders defined by the pathological aggregation of alpha-synuclein (α-syn). The alpha-synuclein Seed Amplification Assay (α-syn SAA), also known as real-time quaking-induced conversion (RT-QuIC), has gained recognition as a high-sensitivity, high-specificity diagnostic tool capable of detecting misfolded α-syn seeds in biological samples through cyclic amplification and thioflavin T-based fluorescence readout. Despite its diagnostic promise, the lack of standardized protocols across laboratories remains a critical obstacle to clinical implementation. This systematic review, conducted following PRISMA guidelines, analysed 78 studies published between 2019 and 2025 to comprehensively characterize the methodological parameters employed in α-syn SAA. Data extraction encompassed equipment settings (fluorescence reader model, incubation temperature, shaking speed and ratio, bead configuration), reaction mixture components (recombinant α-syn concentration and type, buffer composition, NaCl and SDS concentrations, thioflavin T concentration), sample types, investigated pathologies, and positivity criteria. Findings revealed relative consensus in certain parameters. First, 73% of studies used the same equipment, 0.1 mg/mL recombinant α-syn, and 10 μmol/L thioflavin T; while substantial heterogeneity persisted in incubation temperature, buffer composition, and diagnostic thresholds. Cerebrospinal fluid was the predominant sample type, and Parkinson's disease the most frequently studied condition. Positivity criteria varied widely, with no universally validated standard. These results underscore the urgent need for harmonized protocols to ensure reproducibility and facilitate the clinical translation of α-syn SAA as a reliable biomarker tool to detect synucleinopathies.
Exosomal miRNA in cerebrospinal fluid as biomarkers for neurodegenerative disease.
Alamri MA, Afzal M, Pandey SN … +3 more , Afzal O, Akela MA, Rekha A
Clin Chim Acta · 2026 May · PMID 42162905 · Publisher ↗
Cerebrospinal fluid protein biomarkers, such as the Aβ42/Aβ40 ratio, phosphorylated tau, and neurofilament light chain, have significantly advanced the diagnostic process for Alzheimer's disease. Nonetheless, these bioma...
Cerebrospinal fluid protein biomarkers, such as the Aβ42/Aβ40 ratio, phosphorylated tau, and neurofilament light chain, have significantly advanced the diagnostic process for Alzheimer's disease. Nonetheless, these biomarkers face challenges in effectively distinguishing Alzheimer's disease from frontotemporal dementia or Parkinson's disease from dementia with Lewy bodies. This limitation arises from overlapping protein profiles and the variability inherent in immunoassay techniques. A complementary class of analytes is exosomal microRNAs in cerebrospinal fluid, where these non-coding RNAs are secreted by neurons, astrocytes, and microglia, are resistant to RNase degradation, and have a disease-specific expression pattern. This review critically evaluates the existing evidence of cerebrospinal fluid exosomal miRNAs as diagnostic biomarkers in Alzheimer's disease, frontotemporal dementia, Parkinson's disease, dementia with Lewy bodies, and amyotrophic lateral sclerosis. Exosome isolation techniques and detection platform characteristics were compared using RT-qPCR, droplet digital PCR, and small RNA sequencing. Pre-analytical factors, such as collection protocols, hemolysis contamination, freeze-thaw cycling, and circadian sampling variation, were assessed. miRNA profiling data based on disease stratification, receiver operating characteristic performance of the combinatorial panel, and strategies combining exosomal miRNAs with core cerebrospinal fluid proteins were synthesized. This article brings together disease-specific miRNA signatures, pre-analytical standardization needs, and diagnostic accuracy analyses in a translational model to fill the literature gap and form the basis for developing exosomal miRNA panels for rigorously validated clinical laboratory practice.
Pre-analytical standardization and multi-biofluid harmonization for liquid biopsy biomarkers in lung cancer: From discovery to clinical laboratory implementation.
Sharapov S, Tolibov M, Khamidova F … +6 more , Akhmedova S, Khasanov S, Yusufova M, Azizov B, Dustova N, Yokubova M
Clin Chim Acta · 2026 May · PMID 42162904 · Publisher ↗
Lung cancer remains the leading cause of cancer-related mortality worldwide, with early detection being critical for improving survival outcomes. Liquid biopsy using circulating biomarkers from blood, urine, saliva, sput...
Lung cancer remains the leading cause of cancer-related mortality worldwide, with early detection being critical for improving survival outcomes. Liquid biopsy using circulating biomarkers from blood, urine, saliva, sputum, exhaled breath condensate (EBC), and sweat has emerged as a promising non-invasive approach for lung cancer diagnosis, prognosis, and treatment monitoring. However, despite an abundance of biomarker discovery studies, clinical translation has been critically hampered by the absence of standardized pre-analytical protocols, inter-platform analytical discordance, and a lack of systematic frameworks for integrating biomarkers across multiple biofluids. This review identifies and addresses a major unmet need in the field: the harmonization of pre-analytical, analytical, and post-analytical workflows across diverse non-invasive biofluids for lung cancer liquid biopsy. We systematically evaluate pre-analytical variables specific to each biofluid, including collection methods, processing timelines, storage conditions, and matrix-specific confounders such as hemolysis, salivary contamination, and volatile compound degradation. We compare analytical platforms, including qRT-PCR, next-generation sequencing, mass spectrometry, ELISA, and electrochemical biosensors, and assess their cross-platform reproducibility for key analyte classes: circulating tumor DNA, microRNAs, proteins, metabolites, volatile organic compounds, and extracellular vesicles. Furthermore, we propose a structured clinical implementation roadmap encompassing external quality assessment schemes, commutable reference materials, multi-center validation requirements, and regulatory considerations. We conclude that the integration of multi-biofluid biomarker panels with artificial intelligence-assisted interpretation, combined with rigorous pre-analytical standardization, holds the greatest promise for translating liquid biopsy from bench to bedside in lung cancer care.
Evaluation of key analytical performance metrics for reliable lymphocyte subset enumeration using full-spectrum flow cytometry.
Guo K, Feng X, Xu L … +5 more , Li X, Li C, Ma Y, Hu G, Peng M
Clin Chim Acta · 2026 May · PMID 42162903 · Publisher ↗
BACKGROUND AND AIMS: Full-spectrum flow cytometry (FS-FCM) is increasingly used in clinical laboratories, but practical analytical performance evaluation protocols tailored to FS-FCM-based lymphocyte subset enumeration r...
BACKGROUND AND AIMS: Full-spectrum flow cytometry (FS-FCM) is increasingly used in clinical laboratories, but practical analytical performance evaluation protocols tailored to FS-FCM-based lymphocyte subset enumeration remain insufficiently defined. To address this gap, this study aimed to evaluate a practical framework proposed for assessing the analytical performance of FS-FCM in TBNK lymphocyte subset enumeration, including both percentages and absolute counts. MATERIALS AND METHODS: Performance evaluation was conducted in accordance with relevant clinical guidelines and industry standards, including CLSI EP15 and EP06. Two protocols for precision and bias verification were evaluated: a "3 × 5" protocol with three replicates per day over five days and a "3 × 10" protocol with three replicates per day over ten days. The performance of the two protocols was compared using analytical performance specifications derived from biological variation (BV). Bias was estimated using two levels of reference materials with assigned values and associated expanded uncertainties provided by the National Center for Clinical Laboratories of China. Single-result agreement was assessed against predefined total error criteria. Linearity was evaluated using weighted regression with segmented assessment across the analytical range. Fluorescence detection threshold and fluorescence parameter linearity were assessed using an approach adapted to the optical characteristics of FS-FCM. RESULTS: FS-FCM showed acceptable precision. Most coefficients of variation (CVs) were < 5%, whereas CVs for low-abundance subsets were generally <7%. Biases were < 10% for most parameters, although some B-cell and NK-cell measurements in normal-level samples showed biases of 10%-15%. Bias estimates met the minimum BV-derived allowable bias criteria, and most met the desirable criteria, all within the verification intervals. The shorter "3 × 5" protocol yielded performance estimates similar to those obtained with the "3 × 10" protocol and satisfied the predefined BV-derived allowable criteria, indicating that it may serve as an acceptable streamlined alternative. Single-result agreement and segmented linearity assessed by weighted regression also met the predefined criteria. Using the modified approach, fluorescence detection thresholds were < 10 MESF, and the fluorescence parameters showed good linearity (r ≥ 0.9975), meeting the applicable evaluation requirements. CONCLUSIONS: Under the evaluated conditions, FS-FCM demonstrated acceptable analytical performance for the enumeration of the TBNK lymphocyte subset. The proposed evaluation protocols may provide a practical approach for routine local verification and may support future multicenter harmonization of FS-FCM assays.
Gene-based screening using GAP-PCR and MALDI-TOF MS versus haemogram-based screening for thalassaemia in early pregnancy in Vietnam.
Mai TH, Lam TT, Nguyen TD … +13 more , Dinh TL, Nguyen HN, Nguyen TTH, Nguyen TT, Trinh TD, Pham TV, Nghiem XH, Vu V, Phung TH, Nguy TV, Ta TKH, Tang HS, Nguyen CC
Clin Chim Acta · 2026 May · PMID 42142697 · Publisher ↗
BACKGROUND: Thalassaemia is a common inherited disorder in Southeast Asia, including Vietnam. Conventional haemogram-based screening is widely used in routine prenatal care but has limited specificity and may be confound...
BACKGROUND: Thalassaemia is a common inherited disorder in Southeast Asia, including Vietnam. Conventional haemogram-based screening is widely used in routine prenatal care but has limited specificity and may be confounded by other conditions. This study compared gene-based screening using gap polymerase chain reaction (GAP-PCR) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) with haematologic indices for thalassaemia carrier detection in early pregnancy. METHODS: A prospective diagnostic accuracy study was conducted amongst 572 first-trimester pregnant women at Hanoi Obstetrics and Gynecology Hospital. All participants underwent both haemogram-based screening (defined as positive when mean corpuscular volume (MCV) <80 fL or mean corpuscular haemoglobin (MCH) <28 pg) and gene-based screening for 24 common α- and β-thalassaemia mutations using GAP-PCR combined with MALDI-TOF MS. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared. RESULTS: Gene testing identified 101 carriers (17.7%): 64 α-thalassaemia (11.2%), 34 β-thalassaemia (5.9%), and 3 combined (0.5%). The predominant mutations were -SEA deletion (46.3% of α-thalassaemia) and HbE variant (48.6% of β-thalassaemia). Haematologic screening flagged 203 suspected cases (35.5%). Sensitivity was 100% for β-thalassaemia and 90.6% for α-thalassaemia, with a specificity of 77.1% for both. Six genetic carriers (all α-thalassaemia) had normal haematologic indices. PPVs were low (≤25.1%), while NPVs exceeded 98.9%. CONCLUSION: Gene-based screening enhances diagnostic accuracy and identifies silent carriers missed by haemogram-based methods. These findings suggest a potential role in antenatal screening in high-prevalence settings, although cost-effectiveness and feasibility require further evaluation.
Association between aldehyde dehydrogenase 4 family member A1 plasma concentrations and atherosclerotic disease in patients with ischemic stroke: Results from the prospective multicenter BIOSIGNAL study.
Dittrich TD, Zietz AV, Arnold M … +19 more , Gross F, Kriemler L, Inauen C, Westphal L, Pokorny T, Arnold M, Kahles T, Cereda CW, Kägi G, Bustamante A, Montaner J, Ntaios G, Foerch C, Spanaus K, Gawinecka J, von Eckardstein A, De Marchis GM, Katan M, BIOSIGNAL investigators
Clin Chim Acta · 2026 May · PMID 42142696 · Publisher ↗
BACKGROUND: The role of Aldehyde Dehydrogenase 4 Family Member A1 (ALDH4A1) in atherosclerotic disease is unclear. Experimental data suggests a possible involvement in atherogenesis. We investigated the association betwe...
BACKGROUND: The role of Aldehyde Dehydrogenase 4 Family Member A1 (ALDH4A1) in atherosclerotic disease is unclear. Experimental data suggests a possible involvement in atherogenesis. We investigated the association between circulating ALDH4A1 and atherosclerotic disease outcome measures in acute stroke patients. METHODS: Multicenter study using data from the prospective BIOSIGNAL cohort (2014-2017). ALDH4A1 plasma concentrations were measured in stored samples collected within 24 h after stroke onset. Primary outcome measure was large artery atherosclerotic stroke (LAAS) origin. Secondary outcome measures were atherosclerotic disease outcomes such as the maximum intima-media-thickness (IMT), the degree of stenosis on ultrasound, and a composite for atherosclerotic disease burden (large artery atherosclerotic index stroke, history of myocardial infarction, coronary or peripheral artery disease). Logistic regression analyses were performed to examine the association between ALDH4A1 plasma concentrations (absolute and log-transformed) and the primary and secondary outcome measures. RESULTS: Of 1759 stroke patients, 84.5% had available ALDH4A1 measurements. Circulating ALDH4A1 plasma concentrations were neither significantly associated with LAAS (logALDH4A1 aOR 0.97, 95%CI 0.79-1.21, p = 0.81) nor any secondary outcome measure including the maximum IMT, stenosis degree or the composite for atherosclerotic disease burden. Sensitivity analysis using inverse probability of treatment weighting were in line with the main findings. CONCLUSIONS: In acute stroke patients, we found no clear evidence of an association between ALDH4A1 plasma concentrations and clinically relevant atherosclerotic disease outcome measures, including maximum IMT. However, due to the lack of validated and standardized ALDH4A1 assays, and the resulting limited comparability with other cohorts, a potential association cannot be excluded. TRIAL REGISTRATION: NCT02274727 (ClinicalTrials.gov).
Laboratory testing for anti-synthetase antibodies: a novel algorithm to improve diagnostic accuracy.
Baucells A, Martínez-Martínez L, Fonolleda M … +5 more , Julià MR, Ochoa Grullón J, Juárez C, Gallardo E, Mariscal A
Clin Chim Acta · 2026 May · PMID 42142695 · Publisher ↗
BACKGROUND: Anti-synthetase syndrome (ASyS) is an autoimmune disorder that presents specific autoantibodies against aminoacyl-tRNA synthetases (ARS). Although numerous commercial assays are available to detect anti-ARS,...
BACKGROUND: Anti-synthetase syndrome (ASyS) is an autoimmune disorder that presents specific autoantibodies against aminoacyl-tRNA synthetases (ARS). Although numerous commercial assays are available to detect anti-ARS, their accuracy is highly variable. The aim of the present study is to evaluate the assays most commonly used in Spanish clinical laboratories. METHODS: We evaluated 99 serum samples from five Spanish laboratories. All samples tested positive for anti-ARS by line blot (LB) and were examined by indirect immunofluorescence (IIF) on HEp-2 cells. The samples were subsequently evaluated at a single central laboratory by dot blot (DB) and RNA immunoprecipitation (RNA-IP). If DB or RNA-IP confirmed the original finding, the test result was labeled as confirmed, and thus, a true positive. RESULTS: Of the 99 samples (2 double-positive excluded), 26 (27%) were confirmed. The confirmation rate for 1+ and 2+ LB intensity was only 5%. If the LB cut-off is raised to 3+ and the IIF pattern is considered, the confirmed rate reached 100%. RNA-IP was the most sensitive confirmatory technique for anti-PL-12, anti-EJ, and anti-OJ, whereas DB was more sensitive for the detection of anti-Jo-1 and anti-PL-7. CONCLUSIONS: Commercial LB methods demonstrate significant variability, as evidenced by the high unconfirmed rate (73%) in this study. We found that specificity can be significantly increased by using a LB signal intensity cut-off of 3+ together with the presence of a diagnosis-compatible IIF pattern. Based on these findings, we have developed a diagnostic algorithm to improve the reliability of anti-ARS detection in routine laboratory practice.
Holotranscobalamin-based algorithm for the identification of macro-vitamin B12 in analytical hypercobalaminemia.
Fernández-Tomás P, Ruiz L, Alegre E … +1 more , González Á
Clin Chim Acta · 2026 May · PMID 42142694 · Publisher ↗
BACKGROUND: Interference by vitamin B12 (B12) macrocomplexes is common but underappreciated in clinical practice. When unexpected hypercobalaminemia is detected, analytical interference must be considered. Holotranscobal...
BACKGROUND: Interference by vitamin B12 (B12) macrocomplexes is common but underappreciated in clinical practice. When unexpected hypercobalaminemia is detected, analytical interference must be considered. Holotranscobalamin (HoloTC) reflects the biologically active B12 fraction, but the impact of B12 macrocomplexes (M-B12) on HoloTC immunoassay performance remains unclear. METHODS: We collected 528 adult serum samples. Total B12 and HoloTC were measured by commercial immunoassays. M-B12 presence was defined as B12 recovery after polyethylene glycol precipitation (PEG) <50%. RESULTS: Samples were classified as HyperB12 (hypercobalaminemia) or NormoB12. M-B12 was detected in 16.0% (66/411) of HyperB12 samples but in none of NormoB12. In three M-B12 cases, B12 fell below the lower reference limit after PEG. B12 recovery was higher in NormoB12 than in NoM-HyperB12 (p < 0.001). HoloTC was measured in a subgroup of samples (NormoB12 n = 16; NoM-HyperB12 n = 41; M-HyperB12 n = 40). HoloTC was higher in M-HyperB12 (median 300 pmol/L) than in NoM-HyperB12 (median 120 pmol/L), while NormoB12 did not differ from NoM-HyperB12. After PEG precipitation, HoloTC recovery was lower than B12 recovery in HyperB12 samples (NoM-HyperB12: 29.8% vs 73.1%; M-HyperB12: 11.0% vs 27.5%), whereas the difference was not significant in NormoB12 (62.9% vs 83.5%). B12 and HoloTC concentrations showed correlation before (r = 0.45, p = 0.004) and after PEG (r = 0.52, p < 0.001) precipitation only in M-B12 group. HoloTC identified M-B12 presence (AUC 0.870) with 75.0% sensitivity and 95.1% specificity at 201 pmol/L. CONCLUSION: HoloTC concentrations are influenced by the presence of B12 macrocomplexes. The HoloTC assay may serve as a biomarker to screen for M-B12 in patients with analytical HyperB12.
Diagnostic accuracy of NGAL and HBP for the diagnosis of acute bacterial meningitis.
Jiang H, Wang D, Zhang Q … +7 more , Wu W, Li N, Wang Y, Xu Q, Dong L, Li S, Guan M
Clin Chim Acta · 2026 May · PMID 42142693 · Publisher ↗
BACKGROUND: Acute bacterial meningitis (BM) is a life-threatening neurological emergency requiring rapid differentiation from viral/fungal central nervous system (CNS) infections. This study develops a multivariate diagn...
BACKGROUND: Acute bacterial meningitis (BM) is a life-threatening neurological emergency requiring rapid differentiation from viral/fungal central nervous system (CNS) infections. This study develops a multivariate diagnostic model integrating cerebrospinal fluid (CSF) neutrophil gelatinase-associated lipocalin (NGAL), heparin-binding protein (HBP), and classical biomarkers for improved distinction. METHODS: In this single-center prospective study, 186 adults were enrolled and categorized into predefined groups, including 92 with BM, 63 with other CNS infections and inflammatory diseases (other CNS diseases), and 31 non-inflammatory controls. CSF and paired plasma samples were analyzed for neutrophil gelatinase-associated lipocalin (NGAL), heparin-binding protein (HBP), procalcitonin (PCT), interleukin-6 (IL-6), lactate, protein, and cell count. Diagnostic performance of biomarkers was assessed using AUROC, sensitivity, specificity, and multivariable logistic regression. RESULTS: CSF NGAL and HBP levels were significantly elevated in BM patients (median: 260.9 ng/mL and 106.6 ng/mL, respectively) compared to other CNS diseases group (9.9 ng/mL and 5.9 ng/mL) and control groups (1.8 ng/mL and 5.9 ng/mL; p < 0.001). CSF NGAL demonstrated an AUROC of 0.95 (95% CI, 0.92-0.98), while CSF white blood cell count, IL-6, and HBP showed AUROC values of 0.93 (95% CI, 0.90-0.97), 0.93 (95% CI, 0.89-0.97), and 0.90 (95% CI, 0.85-0.95), respectively. A combined model incorporating CSF NGAL, HBP, WBC, IL-6, and PCT yielded AUROC of 0.99 (95% CI, 0.97-1.00). Plasma levels showed no significant differences, indicating intrathecal production of NGAL. CONCLUSIONS: CSF NGAL and HBP provide incremental diagnostic value when combined with conventional CSF markers, enabling rapid (<2 h) and accurate differentiation of BM from other CNS diseases and supporting timely targeted antibiotic therapy.
Circulating microbial metabolites and the gut-prostate axis in prostate cancer: Implications for laboratory biomarkers and therapeutic response.
Tan MW, Clister D, Chandra QM … +11 more , Wangsa CE, Simone CN, Umaya C, Choi J, Park S, Rani A, Akter S, Kim B, Kim SH, de Azambuja Ribeiro RIM, Syahputra RA
Clin Chim Acta · 2026 May · PMID 42140378 · Publisher ↗
Prostate cancer progression and treatment response are influenced not only by tumor genomics and androgen receptor signaling but also by systemic host-microbiome interactions along the gut-prostate axis. Increasing evide...
Prostate cancer progression and treatment response are influenced not only by tumor genomics and androgen receptor signaling but also by systemic host-microbiome interactions along the gut-prostate axis. Increasing evidence indicates that gut microbial metabolism produces bioactive compounds that circulate in human body fluids and can influence immune regulation, hormone metabolism, and therapeutic outcomes. This review synthesizes current evidence on microbiome-derived metabolites that may serve as measurable biomarkers relevant to prostate cancer biology and clinical laboratory diagnostics. Microbial metabolism of dietary substrates generates circulating molecules-including short-chain fatty acids, secondary bile acids, indole derivatives, polyamines, and endotoxin-associated signals-that can modulate inflammation, epithelial barrier integrity, and systemic immune responses involved in tumor progression. In addition, intestinal microbes participate in steroid transformation and enterohepatic cycling of hormones, potentially influencing circulating androgen and estrogen levels that contribute to androgen-driven prostate cancer development and adaptation under androgen deprivation therapy. Importantly, many of these microbial metabolites are detectable in serum or plasma using validated analytical platforms such as liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry, supporting their potential integration into laboratory biomarker panels. Emerging multi-omics approaches combining metagenomics, metabolomics, host transcriptomics, and immune profiling are beginning to clarify mechanistic links between microbial activity and therapy response, including variability in outcomes with androgen-targeted agents, chemotherapy, radiotherapy, and immune checkpoint inhibitors. From a clinical chemistry perspective, characterization of circulating microbiome-derived metabolites may enhance the diagnostic and prognostic performance of established biomarkers such as prostate-specific antigen while providing new opportunities for non-invasive monitoring of disease progression and treatment response. Establishing reproducible microbial metabolic signatures across diverse patient populations will be essential to translate microbiome-informed biomarkers into next-generation diagnostic and prognostic tools in prostate cancer management.
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