Clinica Chimica Acta; International Journal Of Clinical Chemistry[JOURNAL]
Sun
200 papers
Matrix-assisted laser desorption/ionization mass spectrometry imaging for spatial clinical oncopathology: diagnosis, margins and therapy.
Hou Y, Li Z, Lian J
Clin Chim Acta · 2026 Jun · PMID 42285343 · Publisher ↗
Clinical oncology increasingly depends on molecular information, but many assays still detach analytes from the histological coordinates in which diagnostic decisions are made. Matrix-assisted laser desorption/ionization...
Clinical oncology increasingly depends on molecular information, but many assays still detach analytes from the histological coordinates in which diagnostic decisions are made. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is being investigated as a spatial molecular adjunct that can measure lipids, metabolites, peptides, proteins, glycans and drugs directly from tissue sections. This review evaluates applications in which spatial molecular evidence may refine, rather than replace, conventional oncopathology: molecularly resolved tumor histology, margin and adjacent-tissue assessment, tumor microenvironment interpretation and therapeutic-response prediction. We emphasize that clinical value requires alignment with hematoxylin and eosin (H&E) morphology, expert annotation, quality control, molecular-identification confidence and patient-level validation. The literature shows progress from visual ion-map comparison toward multimodal registration, machine-learning classification, spatial proteomics and spatial pharmacology. However, routine adoption remains constrained by pre-analytical variability, incomplete metabolite annotation, batch effects, validation leakage in pixel-level models and limited prospective evidence. The most realistic near-term role for MALDI-MSI is therefore a spatial molecular adjudicator for selected, decision-relevant problems such as difficult classification, uncertain margins, field effects, microenvironment-associated risk and heterogeneous drug exposure.
Xpert® bladder Cancer monitor urine test for non-muscle-invasive bladder cancer surveillance: a prospective clinical trial.
Trabelssi M, Lamy PJ, Daures JP … +2 more , Perriard F, Poinas G
Clin Chim Acta · 2026 Jun · PMID 42285342 · Publisher ↗
Cystoscopy and urinary cytology are the gold standard tools for monitoring non-muscle-invasive bladder cancer (NMIBC). A new biomarker-based test (Xpert® Bladder Cancer Monitor) has been developed to be used as a non-inv...
Cystoscopy and urinary cytology are the gold standard tools for monitoring non-muscle-invasive bladder cancer (NMIBC). A new biomarker-based test (Xpert® Bladder Cancer Monitor) has been developed to be used as a non-invasive aid to monitor bladder cancer recurrence in patients with NMIBC. To evaluate the diagnostic performance of the Xpert® Bladder Cancer Monitor test for monitoring patients with NMIBC. In this prospective, non-interventional, monocentric, blinded study, 304 follow-up visits were performed (corresponding to 193 patients) over a period of 18 months. Cystoscopy and cytology or Xpert® Bladder Cancer Monitor test were performed as part of the NMIBC surveillance. During the study period, histologically proven NMIBC recurrence was detected in 24 cases out of 221 tested, among whom 20 had a positive Xpert® Bladder Cancer Monitor test and 8 had positive urine cytology. The Xpert® Bladder Cancer Monitor test sensitivity was significantly higher than that of cytology (83.3% vs 33.3%; p = 0.0015 with continuity correction). The positive and negative predictive values of the Xpert® Bladder Cancer Monitor test were 27.78% [95% confidence interval (CI): 17.43%-38.12%] and 97.32% (95% CI: 94.72%-99.91%), respectively. The Xpert® Bladder Cancer Monitor test is a reliable and sensitive tool for monitoring patients with NMIBC. It performs better than urine cytology with higher sensitivity, and it appears to be more effective in detecting low- and high-grade NMIBC.
Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.
Nejatinejad M, Maleki-Aram A, Namavar Abibiglou A … +7 more , Vahedi C, Panahian A, Ebrahimi A, Yaghoubi R, Parsaei H, Vafaei S, Jafari D
Clin Chim Acta · 2026 Jun · PMID 42285341 · Publisher ↗
BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant...
BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.
Erythroferrone in β-thalassemia: Systematic review and meta-analysis.
Saboor M, Abass K
Clin Chim Acta · 2026 Jun · PMID 42285340 · Publisher ↗
Erythroferrone suppresses hepcidin and has emerged as a candidate biomarker of ineffective erythropoiesis in β-thalassemia. No prior meta-analysis has quantitatively synthesised circulating ERFE data. A PRISMA 2020-compl...
Erythroferrone suppresses hepcidin and has emerged as a candidate biomarker of ineffective erythropoiesis in β-thalassemia. No prior meta-analysis has quantitatively synthesised circulating ERFE data. A PRISMA 2020-compliant systematic review and meta-analysis (PROSPERO: CRD420261347288) searched PubMed/MEDLINE, Scopus, and Web of Science up to March 2026. Hedges' g was pooled using random-effects REML; correlation outcomes were Fisher z-transformed. Seven pre-specified sensitivity analyses evaluated robustness. Thirteen studies (975 patients; 350 controls; 2019-2026) were included. Six met primary meta-analysis criteria (k = 6; n = 541), yielding a large pooled effect (g = 2.700; 95%CI: 0.906-4.495; p = 0.003; I = 96.1%), with all seven sensitivity analyses remaining significant (g range: 1.882-3.028). The ERFE-hepcidin pool demonstrated a significant inverse association with zero heterogeneity (r = -0.342; 95%CI: -0.472, -0.197; p < 0.001; I = 0.0%). A significant positive ERFE-ferritin correlation was identified (r = +0.439; p = 0.0002); ERFE-hemoglobin was non-significant (r = -0.205; 95%CI: -0.515, +0.153; p = 0.260). Four studies reported formal ROC analyses yielding a weighted pooled AUC of 0.872 (range: 0.766-0.940). One study documented a 51% ERFE increase following luspatercept (p < 0.0001). ERFE is markedly elevated in β-thalassemia and inversely correlates with hepcidin in a homogeneous and reproducible manner. Assay standardisation and prospective validation are required before clinical implementation.
Clinical chemistry patient-based real-time quality control in a large academic hospital laboratory: 7 years of experience.
McShane AJ, Werts N, Légaré W
Clin Chim Acta · 2026 Jun · PMID 42285339 · Publisher ↗
INTRODUCTION: Patient-based real-time quality control (PBRTQC) is an attractive addition to a laboratory's quality assurance program. However, implementation for clinical chemistry analytes has been lacking. To assist wi...
INTRODUCTION: Patient-based real-time quality control (PBRTQC) is an attractive addition to a laboratory's quality assurance program. However, implementation for clinical chemistry analytes has been lacking. To assist with broader implementation, provided is PBRTQC protocols from a large hospital laboratory along with over 7 years of tabulated experience. MATERIALS AND METHODS: PBRTQC was initialized and monitored for 17 clinical chemistry analytes utilizing Data Innovations middleware. Gathered results include total alerts, true alerts, and true alert rates by year and analyte. RESULTS: Overall, there were 623 total alerts and 160 true alerts resulting in true alert rate of 25.7%. The true alert rates ranged from 0 to 100%, depending upon the analyte. CONCLUSIONS: PBRTQC provides a low/no cost tool providing real-time detection of systemic bias. Implementation assists the laboratory in providing high-quality results.
Corrigendum to "Multi-omics biomarker in adrenocortical carcinoma: a clinical-chemistry perspective" [Clin. Chim. Acta 590 (2026) 121103].
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 Jun · PMID 42276946 · Publisher ↗
Abstract loading — click title to view on PubMed.
Reference values for metal elements in the plasma of adults in rural southern Xinjiang, China.
Tian M, Zhao M, Gu S … +10 more , Wang L, Chen N, Tang G, Lu L, Tusunkali A, Guo H, Ma J, Niu Q, He M, He J
Clin Chim Acta · 2026 Jun · PMID 42269743 · Publisher ↗
BACKGROUND: Monitoring metal levels in humans is important for health assessment. However, reference values for interpreting such data vary by region and are currently lacking for Xinjiang, China. This study aimed to est...
BACKGROUND: Monitoring metal levels in humans is important for health assessment. However, reference values for interpreting such data vary by region and are currently lacking for Xinjiang, China. This study aimed to establish local reference ranges for 17 plasma metals in adults from rural Xinjiang, to support regional biomonitoring and health risk evaluation. METHODS: This cross-sectional study enrolled 1522 adults from rural southern Xinjiang. Data were collected via questionnaires and physical measurements. Plasma metals were measured using ICP-MS. Reference ranges were derived using nonparametric percentiles, with group comparisons via Wilcoxon tests and Kruskal-Wallis tests. RESULTS: Concentration distributions for multiple metals showed significant gender differences and age trends. Males exhibited higher median concentrations than females for zinc (843.27 μg/L vs. 814.00 μg/L), while lithium (4.00 μg/L) and strontium (108.95 μg/L) exhibited cumulative increases with age. Comparisons with domestic and international data reveal that the Xinjiang population exhibits higher copper (1117.78 μg/L) and manganese (2.56 μg/L) levels, while lead (0.67 μg/L) levels are relatively low, presenting a unique exposure profile. CONCLUSION: This study establishes the first localized reference ranges for 17 metallic elements in plasma among rural adults in Xinjiang, China. These ranges reveal the population's unique internal dose spectrum to metals, providing essential baseline data for precise clinical diagnosis, environmental toxicology research, and public health risk assessment in this region.
Optimization of blood sampling strategy to avoid spurious PTH elevation in patients with forearm parathyroid autotransplantation and arteriovenous fistula.
Fang W, Deng J, Hu R … +1 more , Ding X
Clin Chim Acta · 2026 Jun · PMID 42269742 · Publisher ↗
Accurate monitoring of parathyroid hormone (PTH) is critical for assessing surgical outcomes in patients with stage 5 chronic kidney disease (CKD), yet preanalytical factors such as sampling location are often neglected....
Accurate monitoring of parathyroid hormone (PTH) is critical for assessing surgical outcomes in patients with stage 5 chronic kidney disease (CKD), yet preanalytical factors such as sampling location are often neglected. We report a 52-year-old male with CKD5 who underwent total parathyroidectomy with autotransplantation (TPTX+AT) in the right forearm and arteriovenous fistula (AVF) creation in the left forearm. Routine PTH measurement showed an extremely elevated level (>530 pmol/L) that was inconsistent with his stable clinical condition. PTH was measured using a fully automated chemiluminescence analyzer (Roche Cobas e801,a third-generation assay). Multisite comparative sampling revealed that blood drawn within 5 cm of the graft site caused spuriously high PTH levels, whereas samples collected at least 10 cm away (including lower limb veins) returned expected values (10.6-12.9 pmol/L) consistent with systemic PTH concentrations. These results suggest that venipuncture near the autograft may induce artificial PTH elevation via direct tissue injury or local hormone diffusion. In CKD5 patients who have undergone TPTX+AT with concurrent AVF construction, we recommend blood sampling from the lower limbs or at least 10 cm away from the parathyroid autograft site on the ipsilateral arm to ensure reliable PTH measurement. This case underscores the importance of implementing standardized phlebotomy protocols, staff training, and integrated clinical-laboratory collaboration to minimize preanalytical errors in this vulnerable patient population.
Prognostic value of PIVKA-II and routine perioperative laboratory indices for recurrence prediction after curative resection of hepatocellular carcinoma.
Mo Y, Wu Y, Wu M … +1 more , Zhou Y
Clin Chim Acta · 2026 Jun · PMID 42269741 · Publisher ↗
BACKGROUND: Although α-fetoprotein (AFP) is widely used in hepatocellular carcinoma (HCC), its prognostic value is limited and approximately 30-40% of patients have non-elevated AFP at diagnosis. Protein induced by vitam...
BACKGROUND: Although α-fetoprotein (AFP) is widely used in hepatocellular carcinoma (HCC), its prognostic value is limited and approximately 30-40% of patients have non-elevated AFP at diagnosis. Protein induced by vitamin K absence-II (PIVKA-II) and routinely available perioperative laboratory parameters represent potentially underutilized prognostic resources, but their independent contribution to recurrence prediction following curative resection has not been systematically characterised within a unified hierarchical modelling framework with formal statistical comparison. METHODS: This single-centre retrospective cohort study included 517 consecutive patients undergoing curative hepatic resection for HCC between January 2018 and December 2020. Three hierarchically nested multivariable Cox proportional hazards models were constructed: M1 included clinical and pathological covariates; M2 added log-transformed AFP and PIVKA-II; M3 further incorporated ten preoperative hematological/biochemical indices. Model performance was evaluated via time-dependent area under the receiver operating characteristic curve (AUC) with bootstrap 95% confidence intervals, calibration, decision curve analysis, and SHapley Additive exPlanations (SHAP) interpretation, separately for progression-free survival (PFS) and distant metastasis-free survival (DMFS). Internal validation incorporating the entire model construction pipeline was performed using 200 bootstrap resamples. RESULTS: Among 517 patients, 302 PFS events and 62 distant metastasis events were observed during a maximum follow-up of 96 months. PIVKA-II emerged as the dominant prognostic predictor (M3 PFS: HR 1.295 [1.218, 1.376], Wald |z| = 8.20). The addition of AFP and PIVKA-II to clinical variables (M2 vs. M1) provided statistically significant discriminative gain for PFS (60-month AUC difference + 0.080 [0.051, 0.110], p < 0.001), whereas the further addition of ten hematologic indices (M3 vs. M2) produced only marginal and non-significant gain (60-month AUC difference + 0.006 [-0.004, 0.016], p = 0.232). For DMFS, M2 and M3 performed equivalently. Optimism-corrected C-index for M3 PFS, accounting for variable selection, was 0.766 [0.745, 0.788], with calibration slope 0.835 [0.562, 1.001] indicating mild overfitting. PIVKA-II demonstrated time-varying behaviour (pH p = 0.0001), with hazard ratio rising from 1.221 [1.132, 1.317] in the first 24 months to 1.573 [1.401, 1.766] thereafter; reported overall HR therefore represents a time-averaged estimate. CONCLUSIONS: PIVKA-II carries substantial independent prognostic information for postoperative HCC recurrence prediction, with effect magnitude exceeding all other examined predictors. The addition of broader hematological/biochemical panels yields small and statistically non-significant incremental gains over a clinically practical model using PIVKA-II alongside clinical variables. These findings, derived from a single-centre HBV-predominant cohort with internal validation only, are exploratory and hypothesis-generating; external validation in independent cohorts with diverse aetiologies is required before clinical implementation.
Expression characteristics of INPP4B, PTEN and SGK3 in papillary thyroid carcinoma and their correlations.
Bai Q, Wu C, Shen L … +3 more , Li N, Tan J, Li Q
Clin Chim Acta · 2026 Jun · PMID 42269740 · Publisher ↗
OBJECTIVE: To investigate the expression characteristics of type II inositol polyphosphate 4-phosphatase (INPP4B), phosphatase and tensin homolog (PTEN) and serum/glucocorticoid-regulated kinase 3 (SGK3) in papillary thy...
OBJECTIVE: To investigate the expression characteristics of type II inositol polyphosphate 4-phosphatase (INPP4B), phosphatase and tensin homolog (PTEN) and serum/glucocorticoid-regulated kinase 3 (SGK3) in papillary thyroid carcinoma (PTC) and to assess the correlations among their expressions. METHODS: Sixty tumor tissues from patients with PTC and corresponding adjacent normal thyroid tissues were obtained. Messenger RNA (mRNA) expression levels of INPP4B and protein expression levels of INPP4B, PTEN, and SGK3 were assessed using quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), respectively. Associations between protein expression levels and clinicopathological characteristics were analyzed. RESULTS: Protein expression levels of INPP4B and SGK3 were significantly elevated in PTC tissues compared with adjacent normal tissues (p < 0.05), whereas PTEN protein expression was significantly reduced (p < 0.05). Expression of INPP4B demonstrated a positive correlation with SGK3 (Spearman r = 0.4436, p < 0.05) and a weak negative correlation with PTEN (Spearman r = -0.2586, p < 0.05). Elevated SGK3 expression was significantly associated with lymph node metastasis in patients with PTC (p = 0.0425). Protein expression levels of INPP4B, PTEN, and SGK3 were not significantly associated with sex, age, nodule size, presence of calcification, or TNM stage (p > 0.05). CONCLUSION: INPP4B, PTEN, and SGK3 are abnormally expressed in PTC tissues, and there are significant correlations among their expressions. SGK3 expression may be associated with lymph node metastasis of PTC, which provides basic data for exploring the occurrence and development of PTC. Further studies are required to clarify their underlying molecular mechanisms.
Correlations between clot waveform analysis parameters and fibrinogen concentrations in cases with and without prolonged activated partial thromboplastin time or prothrombin time.
Wakui M, Fujimori Y, Oka S … +9 more , Nakagawa T, Nakamura S, Ozaki Y, Kurafuji Y, Yatabe Y, Ziparo M, Arai T, Haniu H, Matsushita H
Clin Chim Acta · 2026 Jun · PMID 42269739 · Publisher ↗
BACKGROUND: Clot waveform analysis (CWA) is performed to extend the interpretation of clotting reaction curves in activated partial thromboplastin time (APTT) or prothrombin time (PT) assays. The present study aims to in...
BACKGROUND: Clot waveform analysis (CWA) is performed to extend the interpretation of clotting reaction curves in activated partial thromboplastin time (APTT) or prothrombin time (PT) assays. The present study aims to investigate the relationship between CWA parameters and fibrinogen concentrations for elucidating how to use CWA for coagulation assessment. METHODS: Data regarding APTT-CWA, PT-CWA, and fibrinogen measurements were analyzed from 83 different individuals with prolonged APTT or PT and from 145 different individuals with APTT and PT within their reference ranges. CWA was adjusted to cancel out the influence of fibrinogen. RESULTS: The coefficient of variation (CV) was much lower in adjusted CWA parameters than in non-adjusted CWA parameters, concordant with canceling out the influence of fibrinogen concentrations. The CV in adjusted CWA parameters was higher in cases with prolonged APTT or PT compared to those with normal APTT and PT, likely due to the presence of various coagulopathies and anticoagulants. Regardless of APTT or PT data, non-adjusted CWA parameters and non-adjusted/adjusted CWA parameter ratios were positively correlated with fibrinogen concentrations. In APTT-CWA, the correlation coefficients of non-adjusted/adjusted CWA parameter ratios with fibrinogen concentrations were lower in cases of prolonged APTT or PT than in cases with normal APTT and PT, suggesting that other determinants than fibrinogen concentrations may alter turbidity changes and affect the CWA. CONCLUSION: The present study demonstrated correlations between CWA parameters and fibrinogen concentrations in clinical samples. The results are expected to help broaden the interpretation of clotting reaction curves in APTT and PT assays.
Biomarker-driven diagnostics and personalized treatment in polycystic ovary syndrome.
Gunasekaran K, Rajalakshmi M
Clin Chim Acta · 2026 Jun · PMID 42269738 · Publisher ↗
Polycystic Ovary Syndrome (PCOS) is a common and clinically heterogeneous endocrine disorder affecting approximately 4-20% of women worldwide. Its complex presentation frequently leads to delayed diagnosis, increasing th...
Polycystic Ovary Syndrome (PCOS) is a common and clinically heterogeneous endocrine disorder affecting approximately 4-20% of women worldwide. Its complex presentation frequently leads to delayed diagnosis, increasing the risk of long-term reproductive and metabolic complications. This review critically examines emerging biomarkers spanning hormonal, metabolic, inflammatory, and molecular pathways to support earlier diagnosis and enable personalized management strategies. The findings indicate that PCOS pathophysiology is multifactorial, underscoring the limitations of relying on individual biomarkers and highlighting the need for a comprehensive multi-marker diagnostic framework. Among hormonal indicators, Anti-Müllerian Hormone (AMH) remains the most reliable marker; however, diagnostic accuracy is enhanced when AMH is integrated with biomarkers of metabolic dysfunction (such as adiponectin and C-peptide), inflammatory status (hs-CRP), and molecular alterations, including microRNAs. Notably, artificial intelligence-assisted diagnostic models incorporating these parameters have demonstrated high predictive performance. Early identification of PCOS is essential for implementing individualized treatment approaches that emphasize lifestyle interventions alongside tailored pharmacological therapies, including combined oral contraceptives, metformin, and letrozole. Despite advances, challenges such as assay variability and the lack of standardized diagnostic criteria persist. Nevertheless, the future of PCOS management is moving toward point-of-care diagnostics and precision medicine approaches aimed at improving long-term health outcomes for affected women.
In-vitro diagnostics of adult immune thrombocytopenia - status quo and new developments.
Weber S, Luppa PB, Thaler MA … +2 more , Ruland J, Sachs UJ
Clin Chim Acta · 2026 Jun · PMID 42269737 · Publisher ↗
Adult immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet count, purpura signs, and hemorrhagic episodes. ITP without a known underlying disease is referred to as primary ITP. Secondary f...
Adult immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet count, purpura signs, and hemorrhagic episodes. ITP without a known underlying disease is referred to as primary ITP. Secondary forms are usually linked to identifiable causes, such as drugs or systemic autoimmune diseases. ITP is mediated by autoantibodies. These are directed against platelet membrane proteins, specifically glycoproteins (GPs). Antibody-coated platelets are cleared faster than usual by tissue macrophages, primarily in the spleen, shortening platelet half-life and resulting in thrombocytopenia. Additionally, T-cell-mediated cytotoxicity directed against bone marrow megakaryocytes leads to diminished platelet production. There are numerous specific diagnostic tests that assist in determining the underlying cause of thrombocytopenia and help to distinguish ITP from other disorders with similar clinical presentations. To confirm ITP, these tests rely on the identification of the underlying anti-platelet autoantibodies. The "monoclonal antibody immobilization of platelet antigens" (MAIPA) method, as the main exponent of these tests, is widely used in Europe. However, several additional assays are currently in use or under development and clinical validation. In general, assays for detecting anti-GP antibodies are characterized by high specificity but limited sensitivity. Their current role in the diagnostic evaluation of ITP, along with their advantages and limitations, are discussed in detail. This review gives an overview of the analytical techniques available and of the entire diagnostic evaluation of affected patients with primary or secondary ITP, including differential diagnostic considerations. In addition, it elucidates that personalized ITP treatment protocols require adequate laboratory diagnostic tests, which ensure treatment efficacy and safety.
Reference intervals for cholesterol and triglyceride in HDL subfractions in an adult Spanish population using a single-step precipitation method.
Ceacero-Marín D, Castro-Castro MJ, Riera-Mestre A … +1 more , Fernández-Cidón B
Clin Chim Acta · 2026 Jun · PMID 42263804 · Publisher ↗
INTRODUCTION: Quantification of cholesterol and triglyceride concentration within high-density lipoprotein (HDL) subfractions may provide a better prediction of cardiovascular disease risk than total HDL cholesterol seru...
INTRODUCTION: Quantification of cholesterol and triglyceride concentration within high-density lipoprotein (HDL) subfractions may provide a better prediction of cardiovascular disease risk than total HDL cholesterol serum concentration. However, its clinical application is limited by the lack of methodological standardization and absence of population-specific reference intervals (RIs), which restrict individualized advanced cardiovascular risk stratification. The objective was to establish RIs for HDL2 cholesterol (HDL2-C) and HDL3 cholesterol (HDL3-C) concentrations, and for HDL3 triglyceride (HDL3-TG) concentrations, in a Spanish adult population using a single-step precipitation method. METHODS: This study was conducted in two phases. In the first phase, a comprehensive analytical performance evaluation of the single-step precipitation method was performed. Secondly, RIs were derived based on 198 apparently healthy individuals aged 18-68 years from a Spanish population. Sex and age-partitioning was evaluated and RIs were calculated according to CLSI EP28-A3C Guidelines. RESULTS: The single-step precipitation method showed a satisfactory analytical performance. For males, RIs were: HDL2-C: 0.267-0.908 mmol/L; HDL3-C: 0.716-1.323 mmol/L and HDL3-TG: 0.215-0.385 mmol/L. For females, RIs were: HDL2-C: 0.298-1.022 mmol/L; HDL3-C: 0.739-1.538 mmol/L and HDL3-TG: 0.188-0.350 mmol/L (Table 2). Additional age partitioning using a 45-year cut-off was required for HDL2-C in females and for HDL3-TG in both males and females. CONCLUSIONS: Our study provides the first RIs for HDL2-C, HDL3-C and HDL3-TG in a Spanish adult population using a single-step precipitation method. The single-step precipitation method proved to be simple, reproducible, cost-effective and suitable for routine clinical laboratory practice in assessing cardiovascular risk.
Engineered CRISPR-Cas systems for transcriptional regulation and precision molecular diagnostics: advances, challenges, and emerging microfluidic integration.
Rambabu I, Baskar G, Suliman M … +4 more , Saeed M, Radhakrishnan M, Balu R, Palaniyandi T
Clin Chim Acta · 2026 Jun · PMID 42263803 · Publisher ↗
CRISPR-Cas technology has evolved rapidly from a bacterial adaptive immune system to transformative use in molecular diagnostic and genomic engineering. Beyond traditional genome-editing capabilities, newly engineered ve...
CRISPR-Cas technology has evolved rapidly from a bacterial adaptive immune system to transformative use in molecular diagnostic and genomic engineering. Beyond traditional genome-editing capabilities, newly engineered versions of CRISPR/Cas can be used for programmable transcriptional regulation, epigenetic modification, molecular imaging, and ultrasensitive nucleic acid detection. Specifically, catalytic-inactive Cas proteins like dCas9 and dCas12 retain their ability to bind specific sequences on DNA but do not cleave it. Therefore, these proteins can be reversibly regulated by either CRISPRi or CRISPRa to alter gene expression. Thus, they represent powerful tools for both functional genomic studies and synthetic biological applications. Advances in CRISPR engineering have recently greatly increased the diagnostic potential of Cas12 and Cas13 enzymes. For example, collateral cleavage activity allowed the creation of CRISPR-based diagnostic platforms (SHERLOCK, DETECTR and FELUDA), which can detect target DNA/RNA sequences at high sensitivity and specificity. Moreover, they were demonstrated to work in detecting several infectious pathogens (SARS-CoV-2, Zika virus, and M. tuberculosis) and thus have significant value in point-of-care testing, especially when there is limited availability of resources. CRISPR systems are also being combined with increasing frequency with epigenetic regulators, fluorescence microscopy methods, biosensors, and lab-on-a-chip platforms that incorporate microfluidics to provide improved molecular analysis and automated diagnosis. The purpose of this review is to describe how engineered CRISPR-Cas systems have been developed from primarily genome editing tools into multi-functional platforms for transcriptional regulation, epigenetic engineering, diagnostics, imaging, and emerging microfluidic integrations. Additionally, this review will address some of the current challenges that exist with using CRISPR-based technologies, including off-target effects, delivery efficiency, diagnostic standardization, scaling up production, and translating these technologies clinically.
Saliva as a diagnostic matrix for renal function.
Bommalaneni H, Velakaturi SC, Kasiralla B … +1 more , Buddolla V
Clin Chim Acta · 2026 Jun · PMID 42263802 · Publisher ↗
Assessment of renal function in clinical practice is largely dependent on serum-based biomarkers, particularly urea and creatinine, which remain central to the diagnosis and monitoring of kidney disease. Although analyti...
Assessment of renal function in clinical practice is largely dependent on serum-based biomarkers, particularly urea and creatinine, which remain central to the diagnosis and monitoring of kidney disease. Although analytically robust, blood-based testing requires venipuncture and laboratory infrastructure, limiting its practicality for frequent monitoring, large-scale screening, and use in vulnerable or resource-constrained populations. In this context, saliva has gained attention as a non-invasive biological matrix with potential diagnostic relevance. Salivary urea and creatinine are detectable in measurable concentrations and, in patients with renal impairment, often show positive associations with corresponding serum levels. These observations suggest that saliva may reflect systemic alterations in nitrogenous waste handling, particularly in moderate-to-advanced renal dysfunction. However, the clinical translation of salivary renal biomarkers is constrained by biological variability, low analyte concentrations, matrix-specific interferences, and the absence of standardized collection and analytical protocols. This review critically examines the biochemical basis for the appearance of urea and creatinine in saliva, evaluates current analytical methodologies and validation strategies, and summarizes evidence from comparative serum-saliva studies. The potential clinical applications of saliva-based testing, along with its limitations and future directions for integration into laboratory medicine, are discussed with an emphasis on translational feasibility rather than replacement of established serum assays.
Metabolomic machine learning predictor for the diagnosis of alcohol-associated liver disease.
Li Y, Zhao Y, Wang Y … +11 more , Liu L, Xu D, Yang X, Zhao C, Lin W, Guo T, Yue Z, Pei L, Jia M, Wang H, Cao LL
Clin Chim Acta · 2026 Jun · PMID 42259427 · Publisher ↗
BACKGROUND: It is urgent to find novel non-invasive biomarkers that can accurately diagnose alcohol-associated liver disease (ALD). The objective of this study was to explore dysregulated metabolites in the serum of ALD...
BACKGROUND: It is urgent to find novel non-invasive biomarkers that can accurately diagnose alcohol-associated liver disease (ALD). The objective of this study was to explore dysregulated metabolites in the serum of ALD patients by metabolomics, and establish a reliable diagnostic model by machine learning algorithms. METHODS: A total of 1800 participants, including ALD, metabolic dysfunction-associated steatotic liver disease (MASLD), chronic hepatitis B (CHB), alcohol use disorder (AUD) and normal control (NC) individuals were recruited from four medical centers. Steroid hormone and bile acid metabolism was identified to be dysregulated in ALD in the discovery cohort by untargeted metabolomic analysis, and further confirmed in the training cohort by absolute quantitative metabolomic analysis. A machine learning model named "Bashald" was built based on the training cohort, and further validated in three independent validation cohorts. RESULTS: Our Bashald model exhibited great diagnostic performance with an AUC of 0.942 (95% CI, 0.880-1.000) in an internal test subset. In the validation cohorts, Bashald maintained good predictive performances, with the AUCs of ≥0.821 for diagnosing ALD. In addition, Bashald demonstrated superior performance for the detection of early-stage ALD patients, with the AUCs of 0.870 and 0.792 for the training cohort and validation cohort 2, respectively, which had greatly surpassed traditional clinical indicators. CONCLUSIONS: Our research uncovered the specific metabolic profile of ALD and identified a distinct set of biomarkers that facilitate early detection, thereby promoting the application of precision diagnosis for ALD.
Analyte-containing dilution extends the functional range of clinical immunoassays for volume-limited specimens.
DiBianco LP, Lattin MT, Morgan SL … +6 more , Wei S, Viñas RF, Agama GP, Chen JSL, Forman EJ, Williams Z
Clin Chim Acta · 2026 Jun · PMID 42259426 · Publisher ↗
Accurate quantification of hormone concentrations using clinical immunoassays is often limited by minimum specimen volume requirements, particularly with microvolume collection devices such as microtainers and capillary...
Accurate quantification of hormone concentrations using clinical immunoassays is often limited by minimum specimen volume requirements, particularly with microvolume collection devices such as microtainers and capillary microsampling systems. When volume is insufficient to meet assay requirements, dilution is necessary; however, conventional dilution with analyte-free diluent proportionally reduces analyte concentration and may result in measurements falling below the assay's functional sensitivity, preventing reliable quantification. We evaluated an analyte-containing diluent strategy designed to preserve measurable signal and enable accurate hormone quantification from minimal serum volumes. Pooled human serum specimens were serially diluted and analyzed for estradiol (E2), luteinizing hormone (LH), and human chorionic gonadotropin (hCG) using the Beckman Coulter DxI 600 platform. Reverse-calculated concentrations from analyte-free and analyte-containing dilutions were compared with undiluted measurements using Passing-Bablok regression and recovery analysis. Analyte-containing dilution kept the measured concentration above the limit of quantitation at dilution factors up to 1:128, exceeding the dilution range over which conventional analyte-free dilution remained quantifiable. A hybrid correction model restored agreement with undiluted measurements, yielding recovery rates of 95.5% for hCG, 116.5% for E2, and 105.3% for LH across evaluable dilution ranges. This approach extends the functional analytical range of immunoassays and enables accurate hormone quantification from substantially reduced specimen volumes. Analyte-containing dilution provides a practical method compatible with existing clinical laboratory workflows and may enhance diagnostic testing reliability in microvolume and minimally invasive sampling applications.
Biomarker-driven biosensing strategies for early risk stratification in severe dengue.
Lim WY, Augustin Y, Krishna S … +2 more , Khor SM, Chung I
Clin Chim Acta · 2026 Jun · PMID 42251926 · Publisher ↗
Dengue is a major global public health burden, with increasing incidence of severe cases associated with high morbidity and mortality. While secondary infection is a major risk factor, severe dengue also occurs in clinic...
Dengue is a major global public health burden, with increasing incidence of severe cases associated with high morbidity and mortality. While secondary infection is a major risk factor, severe dengue also occurs in clinically classified primary infection, indicating mechanisms beyond antibody-dependent enhancement. In clinical practice, NS1 antigen and IgM ELISA remain the standard diagnostic tools to confirm dengue exposure. However, these approaches still fall short in achieving the sensitivity, specificity, and prognostic capability required for early identification of patients at risk of severe dengue. Consequently, disease severity is often recognized only after clinical deterioration. Severe dengue is driven by host immune dysregulation, characterized by dynamic changes in cytokines (e.g. IL-10, IL-6 and TNF-α), chemokines, and regulatory microRNAs (e.g., miR-21) that precede critical deterioration. However, their low abundance and temporal variability challenge conventional detection methods. Biosensors integrated with functional materials offer promising platforms for ultrasensitive and decentralized dengue diagnostics, yet most reported sensors remain focused on viral infection confirmation rather than severity prediction. This review presents a biomarker-driven framework that links host-response signatures to biosensor design for multiplexed detection and early risk stratification. We critically evaluate current biosensing platforms such as electrochemical, optical, plasmonic, lateral flow assay (LFA), quartz microbalance crystal (QCM)-based platform, together with biorecognition elements, and material innovations and discuss translational challenges and future directions toward clinically actionable biosensors for severe dengue.
Gasdermin proteins as pyroptosis-based biomarkers in ovarian cancer: Diagnostic and prognostic utility.
Alruwaili MM, Alenazi MS, Mostafa HM … +5 more , Rehman ZU, Alshammari MK, Alam A, Ali A, Khan A
Clin Chim Acta · 2026 Jun · PMID 42251925 · Publisher ↗
Current laboratory-based diagnostic approaches for ovarian cancer have important limitations, particularly in early stage detection and clinically meaningful prognostic stratification. Widely used biomarkers, such as CA1...
Current laboratory-based diagnostic approaches for ovarian cancer have important limitations, particularly in early stage detection and clinically meaningful prognostic stratification. Widely used biomarkers, such as CA125 and HE4, can support diagnosis and disease monitoring; however, their sensitivity and specificity remain inadequate across diverse clinical settings, including the evaluation of indeterminate adnexal masses and biologically heterogeneous tumors. Consequently, increasing attention has been directed towards mechanism-based biomarkers that more closely reflect tumor biology and clinically relevant disease states. Among these, gasdermin family proteins, particularly GSDMD, GSDME, and GSDMC, have emerged as promising candidates owing to their central role as executors of pyroptosis and their measurable alterations in tumor tissues and liquid biopsy specimens of patients with cancer. In ovarian tumor tissues, GSDMD and GSDMC are consistently upregulated, whereas GSDME is under expressed or activated in a context-specific manner. Additionally, circulating cleaved fragments were detectable in the serum and plasma, with AUC values supporting this observation. In this review, we discuss the potential of gasdermin-based biomarkers for improving the diagnosis and prognostic assessment of ovarian cancer. We evaluated tissue expression patterns, circulating cleavage-derived signals, epigenetic alterations, and transcriptomic signatures, highlighting their analytical relevance and potential clinical utility. We also examined the laboratory platforms used for their evaluation, including immunohistochemistry, ELISA, quantitative RT-PCR, and multiplex diagnostic approaches, and discussed how the integration of gasdermin-related markers with established biomarkers, such as CA125 and HE, c cand improve diagnostic precision and survival stratification. Finally, we addressed the major requirements for clinical translation, including multicenter analytical validation, commutable reference materials, external quality assessments, and decision-impact studies. The incorporation of gasdermin-based biomarkers into multiparameter diagnostic frameworks could support more accurate disease classification, improved prognostic evaluation, and more individualized management of ovarian cancer.
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