Clinica Chimica Acta; International Journal Of Clinical Chemistry[JOURNAL]
Sun
200 papers
DNA aptamer based detection of thyroid stimulating hormone for point of care testing.
Rosandi R, Rudijanto A, Aulanni'am … +1 more , Sujuti H
Clin Chim Acta · 2026 May · PMID 42097194 · Publisher ↗
Thyroid stimulating hormone remains the central biomarker for the diagnosis and monitoring of hypothyroidism, yet its measurement continues to face challenges related to assay harmonization, matrix effects, and limited a...
Thyroid stimulating hormone remains the central biomarker for the diagnosis and monitoring of hypothyroidism, yet its measurement continues to face challenges related to assay harmonization, matrix effects, and limited accessibility outside centralized laboratories. These limitations have renewed interest in alternative biorecognition strategies that can support robust and decentralized testing. DNA aptamers have emerged as promising candidates due to their chemical stability, reproducible synthesis, and compatibility with diverse sensing platforms. This review summarizes recent advances in DNA aptamer selection and computational modeling approaches relevant to thyroid stimulating hormone detection, with particular emphasis on strategies that improve binding performance and translational potential. In addition, the implications of aptamer-based recognition for point of care testing are discussed from both clinical and bioengineering perspectives, including analytical performance requirements and integration into portable diagnostic systems. Together, these developments underscore the potential role of DNA aptamers in advancing accessible and reliable point of care diagnostics for hypothyroidism while underscoring the need for rigorous validation in clinically relevant settings.
Analytical approaches for the isolation and characterisation of circulating tumour cells in clinical practice.
Martín-Carbajo L, Hervás-Pérez JP, Moreno-Guzmán M … +1 more , Sánchez-Paniagua M
Clin Chim Acta · 2026 May · PMID 42097193 · Publisher ↗
Circulating tumour cells (CTC) are rare cells shed from primary and metastatic tumours into the bloodstream, representing a minimally invasive source of information on tumour biology, dissemination, and therapeutic resis...
Circulating tumour cells (CTC) are rare cells shed from primary and metastatic tumours into the bloodstream, representing a minimally invasive source of information on tumour biology, dissemination, and therapeutic resistance. Their detection, isolation, and characterisation have emerged as critical tools for precision oncology, serving as robust prognostic and predictive biomarkers that reflect metastatic potential, treatment response, and overall survival. CTC isolation and analysis are challenging due to their extremely low frequency-often one cell per million blood cells-and their phenotypic heterogeneity. Current strategies include enrichment-based methods, exploiting physical or molecular properties for selective capture, and non-enrichment approaches, which preserve cellular integrity for downstream molecular, functional, and imaging analyses. Key performance metrics for isolation platforms include capture efficiency, enrichment, purity, throughput, recovery, and cell viability. Validation often relies on spiked cell lines, though these models may overestimate performance compared with heterogeneous patient-derived CTCs. Integrative approaches combining multiple methodologies are essential to fully characterize CTC populations and overcome individual limitations. Technological advances, including microfluidics, single-cell sequencing, and artificial intelligence-driven analysis, have enhanced the sensitivity and specificity of CTC detection, enabling comprehensive molecular and functional profiling. The FDA-approved CellSearch® system remains the clinical gold standard, primarily in metastatic disease, but emerging platforms aim to enable early detection, real-time disease monitoring, and the identification of subpopulations with high metastatic potential. Future directions in CTC research focus on early cancer detection, longitudinal monitoring of therapeutic response, and personalized treatment adaptation. Integration with other circulating biomarkers, such as circulating tumour DNA and exosomes, promise enhanced prognostic and diagnostic accuracy. Standardization of protocols and validation in clinical samples will be critical for translating these technologies into routine oncology practice.
Harnessing exosomes for endometrial Cancer: From non-invasive diagnostics to precision therapies.
Saleh KA, Mutee AF, Kubaev A … +4 more , Choriyev M, Salih RM, Jaber MA, Hussen S
Clin Chim Acta · 2026 May · PMID 42092669 · Publisher ↗
Exosomes, a subset of extracellular vesicles (EVs), have emerged as pivotal players at the intersection of diagnostics and therapeutics in oncology. These nanoscale vesicles, which are secreted by virtually all cell type...
Exosomes, a subset of extracellular vesicles (EVs), have emerged as pivotal players at the intersection of diagnostics and therapeutics in oncology. These nanoscale vesicles, which are secreted by virtually all cell types, function as critical mediators of intercellular communication by transporting diverse cargoes of proteins, lipids, and nucleic acids between cells. In the context of endometrial cancer (EC), a heterogeneous malignancy with increasing global incidence, exosomes offer a unique opportunity for minimally invasive "liquid biopsy" approaches for diagnosis and prognosis while simultaneously serving as highly versatile platforms for targeted drug delivery. Owing to their natural biocompatibility, stability in circulation, and ability to cross biological barriers, these materials are ideal candidates for next-generation theranostic applications that combine both diagnostic and therapeutic functions. This review provides a comprehensive investigation into the dual role of exosomes in EC, integrating preclinical findings, emerging clinical data, and translational challenges. This study examines the utility of exosomal cargo as biomarkers across all EC subtypes and evaluates engineering strategies that enable its use as precision nanomedicines, ultimately charting a course for their future integration into clinical practice.
Analytical performance of cfDNA quantification methods in pediatric acute lymphoblastic leukemia plasma.
Rohilla G, Yadav A, Sharma A … +6 more , Kaushik R, Bazard G, Siwach K, Narwal S, Kaushik A, Vashist M
Clin Chim Acta · 2026 Jul · PMID 42092668 · Publisher ↗
OBJECTIVES: Cell-free DNA (cfDNA) is a highly regarded noninvasive biomarker in cancer diagnosis, but analytical variability may hinder its practical application. This study aims to assess the analytical performance of v...
OBJECTIVES: Cell-free DNA (cfDNA) is a highly regarded noninvasive biomarker in cancer diagnosis, but analytical variability may hinder its practical application. This study aims to assess the analytical performance of various cfDNA measurement techniques using plasma samples from children with acute lymphoblastic leukemia (ALL). METHODS: Plasma was obtained from 1500 pediatric patients with ALL between the ages of 4 and 13 years. Standardized methods for obtaining double-centrifuged plasma were used to reduce the possibility of contaminating genomic DNA. The extraction of cfDNA was done by a commercial kit using a silica membrane technique and optimized phenol-chloroform-isoamyl alcohol approach. Determination of concentration was done by fluorimetry, spectrophotometry, and enzyme-linked immunosorbent assay. Detection of cfDNA was done using PCR of PTEN gene. RESULTS: Concentrations of cfDNA were found to be significantly lower when determined using fluorometry compared to spectrophotometry with a higher level of consistency, implying that spectrophotometric detection was nonspecific. ELISA-based detection demonstrated relatively consistent signal generation across samples; however, it represents an indirect approach to cfDNA quantification. Manual extraction was associated with a higher concentration of cfDNA, while the kit method produced purified cfDNA samples suitable for PCR amplification. CONCLUSION: A high level of influence of analytical methodology is evident regarding the results of cfDNA quantitation in the blood plasma of patients with pediatric ALL.
Prediction of early mortality in acute pancreatitis using arterial base excess: an international multicenter cohort study.
Ren Y, Zhang Y, Xia L … +4 more , Zhu Y, Lu N, Wan J, He W
Clin Chim Acta · 2026 Jul · PMID 42081932 · Publisher ↗
BACKGROUND: Early mortality rates for severe acute pancreatitis (SAP) patients can reach 20-30%. This study aims to evaluate the predictive value of arterial base excess (BE) for early mortality in AP patients. METHODS:...
BACKGROUND: Early mortality rates for severe acute pancreatitis (SAP) patients can reach 20-30%. This study aims to evaluate the predictive value of arterial base excess (BE) for early mortality in AP patients. METHODS: This study included Nanchang cohort and MIMIC-IV database. Patients were categorized into four groups-based BE values. Multivariate logistic regression analysis was used to identify independent predictors of early mortality, and a nomogram model was developed for risk prediction. RESULTS: Patients in the lowest BE quartile (Q1) had significantly higher rates of SAP (48.2% vs. 15.3%), persistent multiple organ failure (21.1% vs. 2.5%), in-hospital mortality (13.3% vs. 1.3%), and 7-day mortality (5.4% vs. 0.3%) compared to those in the highest quartile (Q4) (all p < 0.001). Multivariate analysis showed that BE is an independent predictor of early mortality, with every 1-standard-deviation increase in BE was associated with a reduction in the risk of death within 7 days (OR = 0.59, 95% CI 0.49-0.71). The AUC of BE for predicting death within 7 days was 0.85 (95% CI: 0.80-0.90). A nomogram model integrating BE, age, LDH, mean arterial pressure, creatinine, and total bilirubin achieved an AUC of 0.918 in the training set and 0.885 in the test set. External validation in the MIMIC-IV cohort showed an AUC of 0.749. CONCLUSION: Arterial BE is a powerful independent predictor of early mortality in AP patients. The nomogram model developed in this study demonstrates good discrimination and clinical utility.
Strengthening laboratory quality through risk-based thinking: Implementation challenges and opportunities in Nigeria.
Basil B, Eze OE
Clin Chim Acta · 2026 Jul · PMID 42081931 · Publisher ↗
BACKGROUND: Medical laboratories in Nigeria are pivotal for national health security but operate under severe infrastructural deficits and a high disease burden. Traditional Quality Control (QC) methods are prevalent but...
BACKGROUND: Medical laboratories in Nigeria are pivotal for national health security but operate under severe infrastructural deficits and a high disease burden. Traditional Quality Control (QC) methods are prevalent but reactive and fail to address the high proportion of errors occurring in pre- and post-analytical phases. This necessitates a strategic shift toward Risk-Based Thinking (RBT) as mandated by the new ISO 15189:2022 standard to bridge the gap between international requirements and local environmental volatility. OBJECTIVES: This review assesses the current state of laboratory quality in Nigeria and evaluates the applicability of RBT frameworks (ISO 15189:2022 and CLSI EP23) in resource-limited settings. It aims to identify structural and cultural implementation barriers and propose actionable mitigation strategies. METHODS: This comprehensive narrative review utilized a systematic search strategy across PubMed, Scopus, and AJOL covering 2010-2025. Data from 85 identified sources, including 66 studies selected using a defined criticality matrix, were synthesized using the Plan-Do-Check-Act (PDCA) framework operationalized with specific quality indicators to contrast regulatory expectations with operational realities. MAIN TEXT: The sector is polarized, with elite private and donor-funded public laboratories driving accreditation (representing only 26 facilities or < 0.5% of the sector), while the majority struggle with a punitive blame culture, the "Japa" syndrome workforce crisis, and erratic power supply. RBT frameworks like Parvin's Risk Management Index offer tools to quantify these unique environmental risks and enable targeted resource allocation. Case studies from EL-LAB and HVL, alongside adaptive lessons from the COVID-19 pandemic, demonstrate that RBT facilitates resilience by scientifically validating investments in solar energy and staff competence to mitigate local hazards. CONCLUSION: Transitioning to RBT is critical for Nigerian laboratories to move from reactive compliance to proactive resilience. By managing risks like power instability and supply chain volatility, laboratories can effectively optimize scarce resources through data-driven mitigation to ensure patient safety.
Exploring the role of circulating glial fibrillary acidic protein and neurofilament light chain in myasthenia gravis.
Gambino CM, Agnello L, Scazzone C … +6 more , Tamburello M, Masucci A, Vassallo R, Di Stefano V, Brighina F, Ciaccio M
Clin Chim Acta · 2026 May · PMID 42081930 · Publisher ↗
BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction caused by antibodies against the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). Although these antibodies enable...
BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction caused by antibodies against the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). Although these antibodies enable diagnosis, they correlate poorly with disease activity and prognosis. Emerging data suggest that MG involves broader neuroimmune mechanisms beyond the peripheral synapse. Glial fibrillary acidic protein (GFAP), a marker of astroglial activation, and neurofilament light chain (NfL), a marker of neuroaxonal injury, have been proposed as circulating biomarkers in several neurological diseases. This study aimed to evaluate serum GFAP and NfL concentrations in MG patients and to assess its potential diagnostic utility. METHODS: In this retrospective case-control study, 137 patients with confirmed MG and 338 healthy controls were enrolled. Clinical classification followed MGFA criteria. Anti-AChR and anti-MuSK antibodies were measured by ELISA. Serum GFAP and NfL concentrations were quantified using a fully automated chemiluminescent immunoassay (Lumipulse G1200). Group comparisons were performed using non-parametric tests, correlations using Spearman analysis, and independent determinants assessed with multivariable linear regression. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic performance. RESULTS: Serum GFAP concentrations were higher in MG patients than controls (44.6 vs 29.6 pg/mL) and strongly correlated with age (r = 0.64, p < 0.0001), but not with antibody titers. In multivariable regression, age was the main independent determinant of GFAP (β = 0.00827, p < 0.0001), whereas MG status was not. GFAP showed moderate diagnostic performance (AUC = 0.704). In an age- and sex-matched analysis, NfL concentrations were modestly higher in MG patients compared with controls (30.2 vs 15.5 pg/mL; p = 0.047). A moderate positive correlation between GFAP and NfL was observed in both groups. CONCLUSIONS: Circulating GFAP levels are elevated in MG but are primarily driven by age and sex rather than disease-specific mechanisms, limiting their diagnostic utility. NfL shows a modest increase, suggesting subtle neuroaxonal involvement; however, its clinical relevance remains uncertain. Together, these findings indicate that GFAP and NfL reflect non-specific neurobiological processes rather than robust biomarkers of MG.
The role of coagulation waveform kinetic parameters in the early diagnosis and prognosis of coagulopathy in hepatitis and cirrhosis.
Lu Q, Zhou W, Pan M … +13 more , Hua S, Luo D, Yang L, Zhou X, Huang J, Wu R, Huang X, Liao S, Ni X, Mo D, Shao X, Dong J, Wang L
Clin Chim Acta · 2026 Apr · PMID 42069209 · Publisher ↗
BACKGROUND: To evaluate the clinical relevance of coagulation waveform analysis (CWA) kinetic parameters in the early detection, severity assessment, and prognosis of coagulopathy in patients with hepatitis and cirrhosis...
BACKGROUND: To evaluate the clinical relevance of coagulation waveform analysis (CWA) kinetic parameters in the early detection, severity assessment, and prognosis of coagulopathy in patients with hepatitis and cirrhosis. METHODS: Real-time CWA was performed alongside conventional coagulation tests (PT, APTT, TT, FIB). CWA kinetic parameters, including maximum velocity (Min1), acceleration (Min2), deceleration (Max2), and maximum clot density (Delta), were derived mathematically. RESULTS: CWA parameters detected early coagulopathy more sensitively than conventional assays. In hepatitis patients at the Child-Turcotte-Pugh (CTP)-A stage, PT-Min1 decreased significantly by 19.1% compared to controls, whereas conventional PT prolonged by only 4.5%. Furthermore, in the cirrhosis cohort, PT-Min1 correlated negatively with CTP class (r = -0.533, P < 0.001) and demonstrated a strong inverse correlation with conventional PT (r = -0.666, P < 0.001), served as a sensitive early warning indicator. CONCLUSION: PT-Min1 is a highly sensitive, early indicator of coagulopathy in hepatitis and cirrhosis. It detects significant hemostatic alterations during the CTP-A stage before substantial changes in conventional tests occur, facilitating earlier clinical intervention.
Pentraxin-3 as a diagnostic and prognostic biomarker in inflammatory lung diseases.
Singh Y, Gupta A, Gupta S … +7 more , Goud P, Pandey SN, Goyal K, Kumbhar PS, Singh SK, Dua K, Gupta G
Clin Chim Acta · 2026 Jul · PMID 42069208 · Publisher ↗
Inflammatory lung diseases, including community-acquired pneumonia, acute respiratory distress syndrome (ARDS), severe viral pneumonia (including COVID-19), ventilator-associated pneumonia, and exacerbations of chronic o...
Inflammatory lung diseases, including community-acquired pneumonia, acute respiratory distress syndrome (ARDS), severe viral pneumonia (including COVID-19), ventilator-associated pneumonia, and exacerbations of chronic obstructive pulmonary disease (COPD), necessitate prompt diagnostic and prognostic assessments accompanied by microbiological confirmation of the causative pathogen. Conventional biomarkers, including C-reactive protein and procalcitonin, are insufficient to distinguish between localized pulmonary and systemic inflammation. This narrative review summarizes the studies on Pentraxin-3 (PTX3), a locally synthesized, extrahepatic acute-phase protein secreted by endothelial cells, epithelial cells, and myeloid leukocytes at sites of inflammation, as a diagnostic and prognostic biomarker in the continuum of inflammatory lung diseases. Plasma PTX3 indicates systemic endothelial activation and disease severity, whereas bronchoalveolar lavage PTX3 concentrations provide compartment-specific diagnostic data, identify follow-up infections, and allow therapeutic escalation in relation to the disease phenotype. Nevertheless, clinical laboratory implementation involves matrix-specific reference levels, analytical validation containing limits of detection/quantification, precision, linearity, and interfering studies according to CLSI, commutable calibrators, and traceability hierarchies. The pre-analytical procedure is standardized, and platform-independent decision limits through harmonized assays, preparation of external quality assessment, and compatibility of acute-care turnaround times are required to implement multicenter PTX3 in routine clinical laboratory diagnostics.
Impact of angiotensin receptor-neprilysin inhibitor therapy on urinary C-peptide measurements: A potential pitfall in the β-cell function assessment.
Fujimura S, Usami Y, Sekido T … +5 more , Miyamoto Y, Yamamoto A, Suzuki H, Shimizu R, Ishimine N
Clin Chim Acta · 2026 Jul · PMID 42069207 · Publisher ↗
BACKGROUND: Angiotensin receptor-neprilysin inhibitor (ARNi) therapy, combining blockade of the renin-angiotensin-aldosterone system with the inhibition of neprilysin-mediated peptide degradation, is the standard therapy...
BACKGROUND: Angiotensin receptor-neprilysin inhibitor (ARNi) therapy, combining blockade of the renin-angiotensin-aldosterone system with the inhibition of neprilysin-mediated peptide degradation, is the standard therapy for heart failure with a reduced ejection fraction. Elevated urinary C-peptide (CPR) levels were recently reported in patients receiving ARNi, suggesting changes in the renal handling of CPR. However, a statistical comparison of ARNi users and non-users has not been performed. Therefore, this study aimed to statistically evaluate the impact of ARNi therapy on serum and urinary CPR levels by comparing ARNi users and non-users in a real-world clinical cohort. METHODS: We retrospectively analyzed 315 patients who underwent 24-h urinary C-peptide (U-CPR) testing at Shinshu University Hospital between January 2022 and March 2024. Demographic data, the diabetes status, and medication history, including ARNi use, were extracted from electronic medical records. Group comparisons were performed by the Mann-Whitney U test, correlations were analyzed by the Spearman's test, and multiple regression analyses identified independent predictors of serum and urinary CPR. RESULTS: Of 315 patients, 11 were ARNi users. U-CPR, serum CPR, the C-peptide index, and U-CPR/serum CPR ratio were significantly higher in ARNi users. Serum CPR moderately correlated with U-CPR in both groups; however, the regression slope was steeper in ARNi users, indicating a disproportionate rise in U-CPR. In multiple regression analyses, ARNi therapy was the strongest contributing factor for elevated U-CPR (β = 186.57 nmol/day) and serum CPR (β = 0.59 nmol /mL). CONCLUSIONS: ARNi therapy markedly increases U-CPR, likely through the neprilysin-induced inhibition of renal enzymatic degradation. Using U-CPR to assess β-cell function in patients receiving ARNi therapy is not recommended, while serum CPR remains a valid marker of insulin secretion.
Determination of cytomegalovirus IgG antibodies using stable element labeling and inductively coupled plasma mass spectrometry: Further evidence of the feasibility of antibody detection.
Jiang W, Li H, Sun G … +5 more , Ma R, Wu R, Sheng L, Shi Y, Zhang G
Clin Chim Acta · 2026 Jul · PMID 42069206 · Publisher ↗
Cytomegalovirus (CMV), a β-herpesvirus with broad infectivity, establishes lifelong latency and poses significant risks to immunocompromised individuals, pregnant women, and newborns. Current diagnostic assays detecting...
Cytomegalovirus (CMV), a β-herpesvirus with broad infectivity, establishes lifelong latency and poses significant risks to immunocompromised individuals, pregnant women, and newborns. Current diagnostic assays detecting serum immunoglobulin G (IgG) are mainly qualitative or semi-quantitative, limiting accurate quantification of high antibody levels. Inductively coupled plasma-mass spectrometry (ICP-MS), based on stable lanthanide rare-earth element labeling, offers high sensitivity, absence of signal interference, and a broad detection range, making it suitable for biomarker detection. This study proposes a technique that combines element-labeled immunoassay and ICP-MS, providing a novel integration for quantitatively detecting CMV IgG. The system was established based on the indirect method. Recombinant CMV antigens were immobilized on magnetic beads and interacted with target antibodies in serum. Following washing, Tb-labeled anti-human IgG antibodies were introduced to complete the immune complex. Quantitative analysis was performed by detecting the Tb signal through ICP-MS. Method validation and evaluation of diagnostic performance in clinical samples followed relevant regulatory and clinical laboratory standards. The test showed excellent linearity, with a maximum quantification limit of 900 U/mL. The coefficients of variation (CV) for low- and high-concentration samples were 4.1% and 5.5%. Interference and day-to-day variations were below 10%. Recoveries ranged from 90.62% to 102.74%. Receiver operating characteristic curve area versus Roche electrochemiluminescence immunoassay (ECLIA) was 0.908, indicating strong diagnostic performance. In summary, we have successfully established a quantitative detection system for CMV IgG antibodies based on stable element labeling and ICP-MS, which meets the requirements for clinical laboratory testing and represents a novel application of mass spectrometry in clinical practice.
Nanoparticle technologies in the diagnosis and therapy of gastrointestinal diseases: Progress, challenges, and future directions.
Arzikulovich YP, Khakimovna RN, Azizova N … +10 more , Umarjanovich SI, Shakhlo A, Tokhirjon S, Nilufar N, Agbarovich YA, Alimboevich MT, Khamraev F, Shukurova OP, Suvonova L, Fazliddin Z
Clin Chim Acta · 2026 Jul · PMID 42066971 · Publisher ↗
The application of nanotechnology in gastroenterology represents a significant shift toward more precise, effective, and less invasive management of gastrointestinal (GI) diseases. By engineering materials at the nanosca...
The application of nanotechnology in gastroenterology represents a significant shift toward more precise, effective, and less invasive management of gastrointestinal (GI) diseases. By engineering materials at the nanoscale, researchers have developed sophisticated systems capable of overcoming formidable biological barriers, enabling targeted drug delivery, and providing unprecedented insights into disease pathophysiology through advanced diagnostic imaging and sensing. This review provides a comprehensive analysis of nanoparticle-based approaches for the diagnosis and treatment of major GI conditions, including inflammatory bowel disease (IBD), Helicobacter pylori infection, colorectal cancer (CRC), and gastric ulcers. It synthesizes recent progress, critically evaluates persistent challenges related to manufacturing and safety, and explores the future directions essential for translating promising laboratory discoveries into routine clinical practice. The field is characterized by a dynamic interplay between rapid scientific innovation and the equally critical need to solve complex problems of scalability, standardization, and regulatory compliance.
Analytical performance of the VITA™ point-of-care CD4 enumeration assay.
Ong CM, Henriquez-Trujillo AR, Alamillo M … +5 more , Huang W, Goldberg E, Van den Bossche D, Gils T, Wu AHB
Clin Chim Acta · 2026 Jul · PMID 42066970 · Publisher ↗
CD4+ T-cell enumeration remains critical for management of people with HIV (PWH). In resource-limited settings, point-of-care CD4 testing can increase accessibility and decrease turnaround time compared to flow cytometry...
CD4+ T-cell enumeration remains critical for management of people with HIV (PWH). In resource-limited settings, point-of-care CD4 testing can increase accessibility and decrease turnaround time compared to flow cytometry. This study evaluated the performance of VITA™ point-of-care CD4 (Accesso Biotech; VITA™ CD4) compared to AQUIOS™ (Beckman Coulter; AQUIOS™) flow cytometry. Remnant venous blood samples from PWH with known CD4 counts on FDA-cleared AQUIOS™ flow cytometry were tested twice with VITA™ CD4. Statistical analyses included descriptive statistics, correlation analysis, Bland-Altman agreement analysis, and Passing-Bablok regression. The coefficient of variation was calculated on duplicate measurements. The University of San Francisco Institutional Review Board approved the study. VITA™ CD4 results showed strong correlation with AQUIOS flow cytometry (r = 0.973, p < 0.001). Bland-Altman analysis revealed a mean bias of -48.9 cells/μl (95% CI: -61.8 to -36.0), with limits of agreement from -231.1 to 133.3 cells/μl. For samples <500 CD4 cells/μL (n = 137), the mean bias was reduced to -8.6 cells/μl (95% CI: -17.8 to 0.6). Passing-Bablok regression suggested a small constant positive bias and proportional bias at counts above 500 cells/μl [y = 30.2 (95% CI: 19.3 to 44.2) + 0.83× (95% CI: 0.80-0.86)]. The coefficient of variation for duplicate VITA CD4 measurements was 11.86%. VITA™ CD4 results correlated strongly with flow cytometry at clinically relevant CD4 values. Its diagnostic performance and applicability at point-of-care make it a promising CD4 tool, also in settings with limited laboratory infrastructure. Further clinical validation and assessment of user acceptability is recommended.
Harmonizing sample collection quality indicator monitoring via an informatics platform in a regional medical laboratory network.
Chen D, Zhang Y, Liu L … +5 more , Jiang R, Ma Q, Wu H, Zhang X, Ou T
Clin Chim Acta · 2026 Apr · PMID 42061783 · Publisher ↗
OBJECTIVES: This study aimed to develop and implement an integrated informatics platform to harmonize sample collection quality indicators (QIs) monitoring across a regional medical laboratory center (RMLC), and to syste...
OBJECTIVES: This study aimed to develop and implement an integrated informatics platform to harmonize sample collection quality indicators (QIs) monitoring across a regional medical laboratory center (RMLC), and to systematically characterize the frequency and distribution of four key pre-analytical QIs using platform-generated data. METHODS: A standardized dictionary of rejection types and reasons was configured into the laboratory information system sample rejection menu. The web-based QIs management system (iLab system) was developed with key functions including automated data collection, QI calculation, visual analytics, and a corrective action implementation module. A 24-month retrospective analysis was performed on four sample rejection QIs. RESULTS: The iLab QIs management system was successfully implemented across the RMLC network. In total, 7,437,716 biological samples were received, with 4,208 (0.057%) rejected based on four QI criteria. Clotted samples (43.37% of total rejections) and incorrect sample volume (24.50%) were the leading causes, with "inadequate mixing" accounting for 62.25% of clotting incidents. Primary sample volume issues included insufficient volume in urine and empty tubes in stool. Nasopharyngeal swabs, urine, and secretion samples collectively represented over 50% of incorrect container incidents, while sputum incorrectly collected as stool or urine was a common sample type error. P-control charts were utilized for continuous rejection rate monitoring, and electronic forms for process automation supported collaborative non-conformity rectification. CONCLUSION: The iLab platform successfully harmonized pre-analytical QI monitoring, demonstrating that an integrated informatics framework enables standardized, automated data capture and precise, network-wide root cause attribution for sample rejection.
Multicenter comparison of three automated procalcitonin (PCT) assays and commutability evaluation of EQA/PT materials.
Zeng J, Teng C, Li H … +9 more , Li L, Xia J, Pang L, Zeng Z, Jin Y, Huang C, Zhou Y, Zhang T, Zhang C
Clin Chim Acta · 2026 Jul · PMID 42055310 · Publisher ↗
BACKGROUND: The aim of this study is to assess the comparability of three commercial procalcitonin (PCT) immunoassays, including Kryptor BRAHMS PCT sensitive, Beckman Coulter DXI 800 Access PCT and Roche BRAHMS PCT, and...
BACKGROUND: The aim of this study is to assess the comparability of three commercial procalcitonin (PCT) immunoassays, including Kryptor BRAHMS PCT sensitive, Beckman Coulter DXI 800 Access PCT and Roche BRAHMS PCT, and to evaluate the commutability of four types of External Quality Assessment/Proficiency Tests (EQA/PT) materials among the three assays. METHODS: The limits of quantitation or functional sensitivity (LoQ/FS) for the three PCT assays were validated according to the CLSI EP17 guidelines. Precision was verified at 0.5 μg/L and 2 μg/L according to CLSI EP15 document. A method comparison study was conducted using 506 clinical serum samples from individual patients. Seventeen EQA/PT materials, including frozen pooled human serum (FFS), lyophilized materials (Lyo), bovine serum albumin solution (BSA) with recombinant PCT, and human serum (HS) with recombinant PCT, were tested together with 50 clinical individual serum samples. The commutability of EQA/PT materials was evaluated using the difference in bias approach. RESULTS: The LoQ/FS and imprecision of all three assays met the claimed standards. Pairwise comparisons demonstrated high correlations ranging from 0.994 to 0.998 (all p < 0.0001), with relative biases between -13.9% and 23.3%. Clinical consistency at thresholds of 0.1 μg/L, 0.25 μg/L, 0.5 μg/L, 2.0 μg/L, and 10 μg/L exceeded 95% across all methods. The commutability of the four EQA/PT material types was generally poor. The proportions of commutable results were 6/18 for Lyo, 1/15 for BSA, 5/15 for HS, and 7/12 for FFS, with FFS showing the highest commutability among the materials tested. CONCLUSIONS: The assays meet clinical requirements for PCT testing. Among the four EQA/PT materials evaluated, the HS, Lyo, and BSA materials demonstrated limited commutability. Although FFS does not exhibit full commutability, it is considered the most suitable EQA/PT material among those tested. Some residual non-commutability still exists and warrants further investigation.
Bridging the gaps in Alzheimer's disease biomarker research: From multi-omics integration to point-of-care diagnostics, a comprehensive review.
Khasanov S, Tolibov M, Daminova N
Clin Chim Acta · 2026 Jul · PMID 42055309 · Publisher ↗
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, yet its early and definitive diagnosis remains a formidable clinical challenge. Over the past decade, substantial progress has been made in the i...
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, yet its early and definitive diagnosis remains a formidable clinical challenge. Over the past decade, substantial progress has been made in the identification and validation of AD biomarkers across cerebrospinal fluid (CSF), blood, and emerging non-invasive biofluids. The core CSF biomarkers-amyloid-β (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau)-have been integrated into revised diagnostic criteria, while blood-based biomarkers such as plasma p-tau217 and the Aβ42/Aβ40 ratio are approaching clinical readiness. Simultaneously, electrochemical biosensor technologies have demonstrated remarkable detection sensitivity at the femtomolar level, and multi-omics approaches combining metabolomics, lipidomics, proteomics, and epigenomics are revealing new molecular signatures of early AD. Despite these advances, several critical research questions remain unanswered, including how to optimally combine biomarkers across biofluids, how to translate biosensor technology from the laboratory to the clinic, how to integrate multi-omics data into practical diagnostic frameworks, how to validate non-invasive biofluid markers at clinical scale, and how to harmonize blood-based assays for global implementation. This review systematically examines the current state of AD biomarker science, identifies key unresolved challenges, evaluates the most promising existing approaches, and proposes specific methodological strategies to advance the field from discovery to clinical practice.
The diagnostic accuracy of synovial leukocyte esterase, glucose and calprotectin in diagnosing periprosthetic joint infection.
Alkadhem M, Ottink K, Wagenmakers L … +4 more , Ploegmakers J, Jutte P, Kobold AM, Wouthuyzen-Bakker M
Clin Chim Acta · 2026 Jul · PMID 42055308 · Publisher ↗
OBJECTIVES: Synovial leukocyte esterase, glucose and calprotectin have emerged as point-of-care biomarkers for diagnosing periprosthetic joint infections (PJI). Distinguishing chronic PJI from aseptic prosthetic failure...
OBJECTIVES: Synovial leukocyte esterase, glucose and calprotectin have emerged as point-of-care biomarkers for diagnosing periprosthetic joint infections (PJI). Distinguishing chronic PJI from aseptic prosthetic failure remains challenging, yet accurate preoperative diagnosis is essential for optimal management and clinical outcomes. This study evaluates the diagnostic value of synovial leukocyte esterase, glucose and calprotectin in diagnosing chronic PJI using the European Bone and Joint Infection Society (EBJIS) criteria as the reference standard. METHODS: Synovial fluid was prospectively collected from patients undergoing revision arthroplasty. Leukocyte esterase and glucose were assessed with a standard urine dipstick, and calprotectin with a lateral flow immunoassay. Patients were excluded if they had prior antibiotic use, insufficient culture sampling, or missing histology analysis or synovial leukocyte counts. RESULTS: Eighty-eight patients were included. 30 patients were diagnosed with PJI (34%). The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of synovial leukocyte esterase with a cut-off value of ++ was 37%, 93%, 73% and 74%, respectively. The sensitivity, specificity, PPV and NPV of glucose with a cut-off value of - was 77%, 41%, 40% and 77%, respectively. The sensitivity, specificity, PPV and NPV of synovial calprotectin with a cut-off value of 50 mg/L were 77%, 88%, 77% and 88%, respectively. CONCLUSIONS: Using the EBJIS definition of PJI, synovial calprotectin showed superior diagnostic accuracy compared to synovial leukocyte esterase and glucose, highlighting its potential as a screening biomarker for chronic PJI. Synovial leukocyte esterase may serve as a specific confirmatory test, although a negative result does not exclude an infection.
Exosome-mediated crosstalk in rheumatoid arthritis: Pathogenic mediators to next-generation therapeutics.
Roudsari ZO, Sadeghi F, Anarjan FS … +5 more , Rahdan F, Turaev B, Badr IH, Movahedpour A, Ehtiati S
Clin Chim Acta · 2026 Jul · PMID 42055307 · Publisher ↗
Rheumatoid arthritis (RA) is a debilitating chronic autoimmune disorder characterized by persistent synovial inflammation and progressive joint destruction. Despite advancements in pharmacology, many patients exhibit sub...
Rheumatoid arthritis (RA) is a debilitating chronic autoimmune disorder characterized by persistent synovial inflammation and progressive joint destruction. Despite advancements in pharmacology, many patients exhibit suboptimal responses to conventional therapies, necessitating the development of innovative therapeutic paradigms. Extracellular vesicles (EVs), specifically exosomes, have emerged as pivotal mediators in RA pathophysiology, acting as dual-purpose orchestrators of both disease progression and therapeutic modulation. These nanosized vesicles facilitate intricate intercellular communication by transporting bioactive cargo-including miRNAs and proteins-from diverse origins such as immune cells, mesenchymal stem cells (MSCs), and the microbiota. Pathologically, EVs derived from inflammatory niches can exacerbate systemic inflammation and accelerate joint degradation. Conversely, therapeutic EVs, particularly those harvested from MSCs or engineered immune cells, exert potent immunomodulatory effects by suppressing pro-inflammatory cytokines (e.g., TNF-α, IL-6), promoting M2 macrophage polarization, stabilizing the Th17/Treg balance, and inhibiting the activation of fibroblast-like synoviocytes (FLSs). Furthermore, bioengineering strategies now enable the utilization of EVs as precision drug delivery systems, enhancing the targeted transport of therapeutics like methotrexate. This review provides a comprehensive analysis of EV biogenesis and characterization, while consolidating evidence on their multifaceted roles in RA, highlighting their transformative potential as next-generation, cell-free diagnostic biomarkers and targeted therapeutic platforms.
When urinalysis speaks first: Unexpected atypical urothelial cells revealing upper tract urothelial carcinoma.
Pons-Belda OD, Prado-Majan C, López-Agulló P … +2 more , Calbet-Tur A, Moreno-Noguero E
Clin Chim Acta · 2026 Jul · PMID 42049109 · Publisher ↗
Urine analysis remains a fundamental tool for diagnosing renal and urothelial diseases. Although urinary sediment microscopy is primarily used to detect haematuria, leukocyturia, and other formed elements, it may occasio...
Urine analysis remains a fundamental tool for diagnosing renal and urothelial diseases. Although urinary sediment microscopy is primarily used to detect haematuria, leukocyturia, and other formed elements, it may occasionally reveal exfoliated malignant cells that prompt further diagnostic investigation. The detection of Upper Tract Urothelial Carcinoma (UTUC) through routine urinary sediment examination is uncommon, as voided urine samples typically show limited sensitivity for tumours arising in the upper urinary tract. We report the case of a 42-year-old woman who initially presented with persistent dysuria and abdominal discomfort and was treated empirically for a suspected urinary tract infection. Despite antibiotic therapy, symptoms persisted and urine culture remained negative. Subsequent urinalysis revealed proteinuria, haematuria, and leukocyturia. Microscopic examination of the urinary sediment demonstrated atypical cells characterized by nuclear membrane irregularity, coarse chromatin, prominent nucleolus, and an unusual cytoplasmic protrusion. These cytomorphological findings prompted further investigation with urine cytology, which was positive for malignant cells. Cystoscopy showed no abnormalities, leading to additional evaluation with computed tomography urography. Imaging revealed a large intraluminal mass occupying the left renal pelvis with associated hydronephrosis and para-aortic lymphadenopathy. Ureteroscopy with selective cytology and subsequent multidisciplinary assessment confirmed the diagnosis of high-grade UTUC. This case highlights the diagnostic value of meticulous urinary sediment examination. Although routine sediment analysis is not a substitute for cytology or imaging, careful morphological assessment may provide an early clue to underlying malignancy and trigger appropriate diagnostic pathways, particularly in patients with persistent urinary symptoms and negative urine cultures.
Longitudinal changes in fatty liver index, genetic susceptibility, and incident atrial fibrillation.
Liu S, He H, Chen H … +8 more , Duan H, Sun Y, Deng D, Gui Z, Liu L, Wang N, Shen J, Wan H
Clin Chim Acta · 2026 Jul · PMID 42049108 · Publisher ↗
BACKGROUND: Steatotic liver disease (SLD) may increase the risk of cardiovascular disease. However, few studies investigated such associations under dynamic changes in steatotic status. Thus, we aim to investigate the as...
BACKGROUND: Steatotic liver disease (SLD) may increase the risk of cardiovascular disease. However, few studies investigated such associations under dynamic changes in steatotic status. Thus, we aim to investigate the association between longitudinal changes in fatty liver index (FLI), a surrogate measure for assessing hepatic steatosis, and risk of incident atrial fibrillation (AF). MATERIALS AND METHODS: This study included 15,995 individuals from the UK Biobank whose hepatic steatosis status was assessed twice via the FLI in 2006-2010 and 2012-2013. We divided individuals into four groups: non-SLD (both FLI < 60), incident SLD (the first FLI < 60 and the second FLI ≥ 60), regressed SLD (the first FLI ≥ 60 and the second FLI < 60), and persistent SLD (both FLI ≥ 60). Multivariable Cox regressions, subgroup analyses by AF polygenic risk scores and mediation analysis to identify potential inflammatory mediators were performed. RESULTS: Over a median follow-up of 4.4 years, 931 (5.8%) AF cases were documented. Compared to persistent SLD, SLD regressed was associated with a 31% lower risk of incident AF (HR: 0.69, 95%CI: 0.52-0.92). In the interaction analyses, the above association was strengthened in those with high genetic risk of AF (P for interaction = 0.013): compared with persistent SLD, for those with high genetic risk, regressed SLD and non-SLD significantly decreased AF risk (0.48, 0.31-0.74; 0.73, 0.54-0.97, respectively), but this was not the case for those with middle genetic risk (1.03, 0.62-1.69; 1.27, 0.89-1.82, respectively) and low genetic risk (0.78, 0.43-1.40; 0.88, 0.56-1.38, respectively). Additionally, in the mediation analyses, changes in the C-reactive protein-albumin-lymphocyte (CALLY) index served as potential mediators (ACME = 0.04, P = 0.04, proportion mediated = 8.5%). CONCLUSION: In the middle-to-elderly aged population, FLI decrease may reduce AF risk, especially in individuals with high genetic risk. Moreover, this association was partially mediated by a change in the CALLY index.
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