Clinica Chimica Acta; International Journal Of Clinical Chemistry[JOURNAL]
Sun
200 papers
Serum sialic acid is independently associated with cerebrovascular atherosclerotic stenosis severity and total vascular burden: A retrospective cohort study.
Cai Q, Yang C, Luo L … +5 more , Huang Y, Xie Y, Liang X, Zhang R, Liu Y
Clin Chim Acta · 2026 Jul · PMID 42401419 · Publisher ↗
BACKGROUND: Atherosclerosis (AS) is still the major cause of cerebrovascular atherosclerotic stenosis (CAS). Sialic acid (SA) has garnered significant attention in atherosclerosis research. Some clinical studies demonstr...
BACKGROUND: Atherosclerosis (AS) is still the major cause of cerebrovascular atherosclerotic stenosis (CAS). Sialic acid (SA) has garnered significant attention in atherosclerosis research. Some clinical studies demonstrated the potential of SA as a predictive marker for cardiovascular diseases. However, no clinical studies have yet explored the relationship between SA and CAS. METHODS: From January 2017 to October 2023, 5806 patients aged over 18 years were retrospectively evaluated. Spearman correlation analysis examined the relationship between serum SA levels and clinical characteristics of CAS patients. Univariate and multivariate logistic regression analyses assessed the association between SA and stenosis. The Restricted Cubic Spline analysis method was used to reveal the influence of SA on CAS. The Receiver Operating Characteristic Curve was employed to describe the diagnostic efficacy of SA as a potential biomarker for predicting CAS. RESULTS: Our study identified a positive correlation between SA levels and CAS severity. Additionally, SA levels demonstrated a dose-response relationship with both the degree of stenosis and the number of stenotic vessels. Furthermore, a statistically significant difference in SA levels was observed between patients with symptomatic and asymptomatic CAS. The receiver operating characteristic (ROC) model showed an AUC of 0.713 (95% CI: 0.700-0.726) for SA in predicting CAS. CONCLUSION: Serum SA levels demonstrated a dose-response relationship with both the degree of stenosis and the number of stenotic vessels. These findings suggest that SA may serve as a potential biomarker for identifying CAS.
Measurement of low-density lipoprotein cholesterol and other circulating lipids in Brazil: a systematic literature review.
Conti DGA, Tosetti LS, Jablonka F … +5 more , Hix S, Wolska A, Amar M, Remaley AT, Fonseca FLA
Clin Chim Acta · 2026 Jul · PMID 42401080 · Publisher ↗
Accurate laboratory assessment of circulating lipids underpins cardiovascular risk stratification, yet clinical interpretation depends not only on the assays but on the formula chosen to estimate low-density lipoprotein...
Accurate laboratory assessment of circulating lipids underpins cardiovascular risk stratification, yet clinical interpretation depends not only on the assays but on the formula chosen to estimate low-density lipoprotein cholesterol (LDL-C). This review integrates the 2019-2025 evidence on laboratory methods for triglycerides (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDLC), and on the formulas estimating LDL-C, VLDL-C, and non-HDL cholesterol, to determine how these should be measured, reported, and harmonized in Brazil, where lipid thresholds are adapted from international consensus. A PRISMA 2020 systematic search (PROSPERO CRD420251241064) of PubMed/MEDLINE, Scopus, SciELO, LILACS, Web of Science, and Embase retrieved 57,915 records; after removing 38,210 duplicates, 19,705 titles/abstracts were screened, 312 full texts assessed, and 25 sources included. Enzymatic colorimetric assays remain standard for TG, TC, and HDLC. For LDL-C, Martin/Hopkins classifies more accurately than Friedewald (89.6% vs 83.2% correct categorization in 5,051,467 patients), particularly at high TG and low LDL-C, while Sampson/NIH and modified Sampson/NIH extend reliable estimation into hypertriglyceridemia and very low LDL-C; direct measurement is reserved for TG beyond the validated range. Although the review centers on the Friedewald, Martin/Hopkins, and Sampson/NIH families that dominate guideline practice, other published equations exist and are addressed in context. In Brazil, atherogenic-lipid thresholds are risk-based decision limits rather than reference intervals; national surveys describe lipid distributions but were not designed to establish them. Analytical standardization through traceability programs, multicenter validation of formulas, and-where the distribution-based construct applies (HDLC, pediatrics)-nationally derived reference intervals are priorities for equitable cardiovascular risk assessment in Brazil.
Reference intervals for venous blood gas measurement in a healthy Chinese population.
Jiang S, Zhao Q, Wang H … +3 more , Li M, Ou Y, Lin W
Clin Chim Acta · 2026 Jul · PMID 42392487 · Publisher ↗
OBJECTIVES: Venous blood gas (VBG) analysis has gained increasing popularity as an alternative to arterial blood gas (ABG) analysis, owing to its lower invasiveness and greater feasibility of sample collection. However,...
OBJECTIVES: Venous blood gas (VBG) analysis has gained increasing popularity as an alternative to arterial blood gas (ABG) analysis, owing to its lower invasiveness and greater feasibility of sample collection. However, currently available reference intervals may not be applicable to the Chinese population due to regional, ethnic, environmental, and lifestyle differences. Therefore, this study aimed to establish appropriate venous blood gas reference intervals (RI) for the Chinese population from plain areas. METHODS: A total of 1189 volunteers (595 males, 594 females, aged 10-97 years) and 149 validation volunteers (94 females, 55 males, aged 10-97 years) with conditions unlikely to influence blood gas and acid-base balance were enrolled. Venous blood samples were collected in syringes and analyzed using an ABL90 blood gas analyzer (Radiometer Pacific Pty. Ltd.). Non-parametric methods were applied to establish VBG reference intervals and parametric methods were applied to pCO reference intervals. RESULTS: After exclusions, VBG RI was derived from 1189 volunteers: pH 7.282-7.438, partial pressure of carbon dioxide(pCO2) Male 32.8-62.2 mmHg Female 33.2-58.7 mmHg, partial pressure of oxygen(pO2)16.0-74.0 mmHg, sodium 134-148 mmol/L, potassium 3.14-4.55 mmol/L, chloride 99-111 mmol/L, ionized calcium 1.07-1.26 mmol/L, total hemoglobin(THB) Male 10.69-17.5 g/dL Female 10.3-15.9 g/dL. After verification in 149 healthy individuals, all reference intervals showed qualified rates above 92%, supporting their clinical applicability.
Multiplex methylation marker analysis for ctDNA detection in liquid biopsies from anal cancer patients: an HPV-independent approach.
Kahns S, Canto LMD, Stokkebro LE … +10 more , Madsen JS, Steenbergen RDM, Lindebjerg J, Varnum C, Havelund BM, Jensen LH, Hansen TF, Jakobsen AKM, Spindler KG, Andersen RF
Clin Chim Acta · 2026 Jul · PMID 42392486 · Publisher ↗
BACKGROUND: Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal cancer linked to high-risk human papillomavirus (HPV) infection in approximately 90% of cases. Current circulating tumor DNA (ctDNA) approaches i...
BACKGROUND: Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal cancer linked to high-risk human papillomavirus (HPV) infection in approximately 90% of cases. Current circulating tumor DNA (ctDNA) approaches in ASCC primarily rely on pathogenic HPV-based biomarkers; however, these methods do not detect all HPV strains and are not applicable to HPV-negative tumors. To address this limitation, we developed a ddPCR assay targeting hypermethylated genomic CpG biomarkers, allowing ctDNA detection independent of tumor HPV status. METHODS: An anal cancer methylation-specific multiplex droplet digital PCR (AnMM-ddPCR) assay was developed to target five previously described CpG biomarkers hypermethylated in ASCC: ASCL1, LHX8, WDR17, ZIC1, and ZNF582, and the ALB reference gene. Patient samples and samples from non-cancer controls were analyzed using the BioRad QX600 ddPCR multiplexing platform. RESULTS: CpG-methylated biomarker levels were significantly higher in ASCC tissue compared with normal tissue and whole blood. The AnMM-ddPCR assay successfully detected all five ctDNA markers in plasma from ASCC patients, achieving an AUC of 0.72 (95% CI: 0.55-0.89; P = 0.018) in baseline plasma samples from ASCC patients with T1 or T2 tumors ≤4 cm, versus 0.90 (95% CI: 0.76-1.00; P = 0.0005) in plasma from patients with T2 tumors >4 cm or T3 tumors. At a specificity of 91.30%, sensitivity increased with stage from 52.94% (95% CI: 30.96-73.83) to 88.89% (95% CI: 56.50-99.43). CONCLUSION: The AnMM-ddPCR assay enables HPV-independent ctDNA detection in plasma samples from anal cancer patients and supports its evaluation in future liquid biopsy applications.
Development and validation of patient-based exponentially weighted moving average quality control models for three antipsychotic drugs and their metabolites by LC-MS/MS.
Guo Q, Pu Y, He J … +6 more , Ling S, Ruan C, Guo G, Zhou C, Liu C, Liu X
Clin Chim Acta · 2026 Jul · PMID 42392485 · Publisher ↗
BACKGROUND: Therapeutic drug monitoring of antipsychotics is essential for personalized dosing. Traditional internal quality control (IQC) lacks real-time capability, potentially delaying error detection. Patient-Based R...
BACKGROUND: Therapeutic drug monitoring of antipsychotics is essential for personalized dosing. Traditional internal quality control (IQC) lacks real-time capability, potentially delaying error detection. Patient-Based Real-Time Quality Control (PBRTQC) can overcome this by continuously analyzing patient data. However, its application to antipsychotic drug assays remains underexplored. OBJECTIVE: To develop and validate novel PBRTQC models based on the exponentially weighted moving average (EWMA) for the real-time monitoring of three first-line antipsychotics (aripiprazole, clozapine, quetiapine) and their major metabolites-addressing a critical gap in laboratory quality assurance for psychiatric pharmacotherapy. METHODS: Chronologically ordered concentration data were split into training and validation sets. Truncation limits were optimized via trimming and winsorization. Multiple EWMA models with different weighting factors (λ) were evaluated. Model selection was based on the false positive alarm rate (FAR) and the average number of patients before error detection (ANPed), validated using simulated constant and proportional errors. RESULTS: Optimal models for most analytes employed trimming at 1.5 standard deviation (SD) with λ = 0.03. The introduced PBRTQC system demonstrated high sensitivity: for a 15% analytical bias, the ANPed was <20 for quetiapine, <40 for desalkylquetiapine and aripiprazole, <50 for dehydroaripiprazole, and < 30 for clozapine/norclozapine. All ANPeds fell below 20 at a 30% bias, confirming effective error detection. CONCLUSION: EWMA-based PBRTQC models specifically tailored for antipsychotic drug monitoring were successfully established. The models provide a practical, real-time complement to traditional IQC, enabling the early detection of analytical shifts and enhancing the reliability of laboratory data for clinical decision-making in psychiatry.
Comparing conventional correction formulas and machine learning-based prediction of ionized calcium.
Kösem A, Öter A, Sağıroğlu Ş … +3 more , Sezer S, Topçuoğlu C, Yılmaz G
Clin Chim Acta · 2026 Jul · PMID 42385972 · Publisher ↗
BACKGROUND AND AIM: Accurate assessment of ionized calcium (Ca++) is critical in clinical settings but remains technically and logistically challenging in many healthcare facilities. This study aimed to evaluate the perf...
BACKGROUND AND AIM: Accurate assessment of ionized calcium (Ca++) is critical in clinical settings but remains technically and logistically challenging in many healthcare facilities. This study aimed to evaluate the performance of machine learning (ML) models in predicting Ca++ levels measured by blood gas analysis, using routinely available biochemical parameters-total calcium (TotCa), total protein, and albumin-and to compare them with values obtained through direct measurement and established correction formulas. MATERIALS AND METHODS: A retrospective analysis was conducted on 84,410 patients aged 20-70 years (43,863 men, 40,547 women). Whole-blood Ca++, serum TotCa, albumin, and total protein levels were retrieved from hospital records. Three ML algorithms-Support Vector Machine (SVM), Random Forest (RF), and Gradient Boosting (GB)-were trained and validated using 5-fold cross-validation. Their performance was benchmarked against three conventional correction formulas: Hanna, Zeisler, and Butler. RESULTS: Among the conventional formulas, the Hanna method showed the highest mean absolute error (MAE = 0.3626), while Zeisler (MAE = 0.0719) and Butler (MAE = 0.0988) performed more closely to measured Ca++. The ML models outperformed all formula-based methods, with GB (R = 0.6742), SVM (R = 0.6732), and RF (R = 0.6730) achieving the highest explained variance. In contrast, Butler and Zeisler yielded R values of 0.2684 and 0.4879, respectively. CONCLUSIONS: ML models demonstrate superior predictive accuracy for Ca++ compared with conventional correction formulas when using routine biochemical parameters. These findings support the potential integration of ML-based tools into clinical decision support systems. Future research should address model interpretability, pH incorporation, and prospective external validation.
Micro- and nanoplastics as emerging clinical analytes: analytical validation, interpretive uncertainty, and laboratory actionability in human specimens.
Alum EU, Uti DE
Clin Chim Acta · 2026 Jun · PMID 42379466 · Publisher ↗
Human exposure to micro- and nanoplastics (MNPs) is increasingly relevant to clinical toxicology, but the field is not yet ready for routine patient-level testing. This narrative review evaluates MNPs as emerging clinica...
Human exposure to micro- and nanoplastics (MNPs) is increasingly relevant to clinical toxicology, but the field is not yet ready for routine patient-level testing. This narrative review evaluates MNPs as emerging clinical analytes from the perspective of diagnostic laboratory medicine. The central question is how laboratories can measure, interpret and act on toxicological information in human specimens without overstating immature evidence. Current studies have reported MNP-related signals in blood, urine, placenta, breast milk, lung tissue, vascular plaques and other tissues, yet comparisons are constrained by inconsistent definitions, heterogeneous matrices, variable sample preparation, incomplete contamination control, method-dependent reporting units and limited outcome-linked data. Particle-based methods such as micro-Fourier-transform infrared and Raman spectroscopy preserve size and morphology information but have practical detection limits and throughput constraints. Mass-based approaches such as pyrolysis-gas chromatography/mass spectrometry quantify polymer mass but can lose particle-level information and may be vulnerable to matrix interferences. Clinical laboratories should therefore treat MNP measurement as a high-complexity analytical problem requiring matrix-matched validation, procedural and field blanks, uncertainty estimates, orthogonal confirmation for consequential claims, and conservative interpretive comments. At present, MNP testing is best suited to research biomonitoring, occupational and public-health surveillance, exposure-source investigations and translational cohorts linking particle measurements to validated effect biomarkers. The review proposes reporting tiers, readiness levels and a laboratory roadmap to convert uncertain exposure signals into reproducible, interpretable and clinically responsible toxicological information.
Performance of Free Light Chain reagents in the Dutch External Quality Assessment programme over the past 14 years.
Bioch MM, de Kat Angelino CM, Ten Haaken-Meijer AJ … +2 more , Thelen MHM, Jacobs JFM
Clin Chim Acta · 2026 Jun · PMID 42379465 · Publisher ↗
Serum free light chain measurements (sFLC) play a key role in the diagnosis and management of patients with monoclonal gammopathies. To obtain a realistic impression of between-method performance and agreement of sFLC an...
Serum free light chain measurements (sFLC) play a key role in the diagnosis and management of patients with monoclonal gammopathies. To obtain a realistic impression of between-method performance and agreement of sFLC analysis in The Netherlands, we studied results of 37 laboratories participating in 56 rounds of the Dutch External Quality Assessment (EQA) programme in the past fourteen years. Satisfactory overall method-specific between-laboratory precision was observed for both The Binding Site Freelite (mean CV κFLC 23.3% and λFLC 19.5%) and Siemens N Latex FLC (κFLC 10.8% and λFLC 15.2%). Within-laboratory precision as tested in seven EQA samples that were repeatedly sent to all participants was adequate for both Freelite (mean CV κFLC 16.4% and λFLC 15.6%) and N Latex FLC (κFLC 9.8% and λFLC 19.6%). Method comparison and Bland-Altman analyses demonstrated a systematic bias between both methods over the entire range of sFLC testing. In general, Freelite results were higher compared to N Latex FLC (relative median bias: κFLC +29.7% and λFLC +37.0%). Clinical concordance of the FLC ratio interpretation was high between both methods (88%). Especially at high FLC concentrations, strong method-specific differences were observed in individual EQA samples which also resulted in discordances in reported FLC ratio around clinically relevant cut-off points. Method-stratified sFLC reporting in EQA programmes creates awareness that current sFLC assays are not equivalent, hampering the application of universal diagnostic, prognostic, or response criteria. Such EQA may also provide opportunities for monitoring the success of future sFLC standardisation initiatives.
CRISPR-Cas12a-based liquid biopsy technology: challenges in large-scale clinical application.
Zhang Y, Lin X, Shi H … +4 more , Chen Z, Luo Q, Wu H, Zeng T
Clin Chim Acta · 2026 Jun · PMID 42379464 · Publisher ↗
Liquid biopsy technology, which enables the acquisition of tumor-related biomarkers in a minimally invasive and reproducible manner, has been widely applied in clinical scenarios such as early tumor detection, treatment...
Liquid biopsy technology, which enables the acquisition of tumor-related biomarkers in a minimally invasive and reproducible manner, has been widely applied in clinical scenarios such as early tumor detection, treatment response assessment, minimal residual disease (MRD) monitoring, and recurrence surveillance. However, its clinical utility is still limited by the extremely low abundance of clinically relevant targets, the inhibitory effects of complex matrices, and the high variability in pre-analytical stages. As a next-generation programmable nucleic acid diagnostic platform, CRISPR-Cas12a combines the unique mechanisms of sequence-specific recognition and trans-cleavage signal amplification, demonstrating significant technical advantages and translational potential in the detection of low-abundance targets in liquid biopsies. Nevertheless, a mere improvement in analytical sensitivity is insufficient to support its large-scale clinical application; the robustness of detection methods, the reproducibility of results, and clinical interpretability remain the key factors currently restricting its clinical translation. This review summarizes the mechanism of CRISPR-Cas12a. Focusing on seven representative clinical biofluids, including blood, urine, and cerebrospinal fluid, it analyzes the technical difficulties and adaptation strategies associated with different matrices, and summarizes the performance differences of detection methods alongside the most clinically rational application scenarios across various biofluids. Furthermore, it explores the primary bottlenecks this technology faces when transitioning from laboratory proof-of-concept to routine clinical application, and provides a preliminary discussion on its future development directions based on existing research. Ultimately, this review aims to provide a reference for promoting the clinical translation of CRISPR-Cas12a liquid biopsy technologies and the broader implementation of precision medicine.
Diagnostic biomarkers, prognostic signatures, and therapeutic resistance: shedding light on the dual role of autophagy in glioblastoma.
Aldiqs M, Aliev M, Gajjar TB … +5 more , Mangaraj S, Alhasso B, Urazbaeva D, Gulsara R, Tailor NK
Clin Chim Acta · 2026 Jun · PMID 42379463 · Publisher ↗
Glioblastoma (GBM) is an exceptionally aggressive brain malignancy with a dismal prognosis, characterized by a median survival of roughly 15 months despite standard radiotherapy and Temozolomide treatment. A primary driv...
Glioblastoma (GBM) is an exceptionally aggressive brain malignancy with a dismal prognosis, characterized by a median survival of roughly 15 months despite standard radiotherapy and Temozolomide treatment. A primary driver of this therapeutic resistance is autophagy. While initially tumor-suppressive, autophagy transitions into a cytoprotective mechanism in established GBM, acting as a molecular survival switch that enables cells to withstand metabolic stress, hypoxia, and therapy-induced DNA damage. Crucially, this complex intracellular degradation process has emerged as a powerful tool for GBM diagnosis and prognosis. Autophagy-related genes (ARGs) are now established as highly sensitive diagnostic and prognostic biomarkers. Utilizing advanced bioinformatics, researchers have constructed robust prognostic risk models, such as 4-gene, 7-gene, and 10-lncRNA-mRNA signatures, that can accurately stratify patient risk, forecast tumor progression, and estimate overall survival. These molecular signatures provide vital diagnostic utility by distinguishing aggressive GBM phenotypes from lower-grade gliomas. Furthermore, these prognostic models strongly correlate with tumor microenvironment dynamics and immune infiltration, providing deep insights into immunosuppressive macrophage polarization. By profiling these autophagy-driven markers, clinicians can reliably anticipate chemoresistance and tailor personalized immunotherapy regimens. This review explores the signaling pathways regulating autophagy, the mechanisms driving radioresistance and chemoresistance, and the profound diagnostic and prognostic value of ARG signatures, highlighting emerging translational strategies to therapeutically target autophagy, overcome resistance, and improve clinical outcomes.
Artificial intelligence in diagnostic software: validation, safety, and lifecycle challenges in Europe.
Bertok T, Pankuchova I, Jane E … +2 more , Batova Z, Tkac J
Clin Chim Acta · 2026 Jun · PMID 42379462 · Publisher ↗
Artificial intelligence, particularly machine learning and deep learning, is a rapidly evolving field that is increasingly permeating all areas of modern society, including public healthcare. In the present work, we prov...
Artificial intelligence, particularly machine learning and deep learning, is a rapidly evolving field that is increasingly permeating all areas of modern society, including public healthcare. In the present work, we provide a comprehensive introduction to the application of machine learning in routine clinical practice and biomedical research, including biomarker discovery. The most widely used machine learning models are introduced together with their key characteristics, strengths, and limitations. Furthermore, the fundamental principles governing the interpretation of model outputs and communication with regulatory authorities are discussed and illustrated using both real-world and synthetic datasets through modeling in the Python programming environment. Particular emphasis is placed on maintaining data quality and ensuring robust validation procedures in the context of dynamic, continuously updated AI systems intended for diagnostic software registered as medical devices (SaMDs). The importance of data governance, external validation, interpretability, and clinical oversight is highlighted as a prerequisite for safe and effective implementation of AI technologies in healthcare - throughout both the development and commercialization phases. Finally, current trends in medical artificial intelligence are reviewed, together with their potential benefits and associated risks for patients. The presented overview aims to facilitate a deeper understanding of the opportunities and challenges associated with the integration of AI-driven solutions into modern healthcare systems.
Strategies for effective occurrence Management in Resource-Limited Clinical Laboratories: Challenges and practical solutions.
Myke-Mbata BK, Basil B, Mba IN
Clin Chim Acta · 2026 Jun · PMID 42379461 · Publisher ↗
BACKGROUND: Clinical laboratory results guide the vast majority of medical management pathways and Occurrence Management ensures diagnostic safety across the total testing process (TTP). However, execution in resource-li...
BACKGROUND: Clinical laboratory results guide the vast majority of medical management pathways and Occurrence Management ensures diagnostic safety across the total testing process (TTP). However, execution in resource-limited settings (RLS) is severely hindered by infrastructural constraints like grid instability, workforce shortages, unreliable paper-based data systems, and punitive institutional cultures that suppress incident reporting and error capture. OBJECTIVES: This review evaluates unique system-level and organizational barriers to error management in low-resource laboratories and synthesizes a scalable, phased operational framework to optimize continuous quality improvement and patient safety. METHODS: A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and AJOL for publications from January 2010 to April 2026. Guided by the TTP framework integrated with the Plan-Do-Check-Act (PDCA) cycle, a PRISMA-informed screening isolated 67 eligible records for thematic synthesis and framework development. MAIN TEXT: Laboratory errors are highly asymmetric, with up to 68.2% concentrated in the pre-analytical phase. Primary failure points stem from human-system interface lapses, manual transcription workflows, and cold-chain failures during power outages. To bridge the gap with international quality standards (ISO 15189:2022), this paper establishes a phased, six-stage occurrence management roadmap scaled for varying tiers of healthcare delivery. Practical, low-cost interventions include implementing non-punitive "just culture" reporting policies, using cost-effective in-house pooled patient sera for quality control, deploying offline-capable open-source laboratory information systems, and forming interdisciplinary clinical-laboratory committees. To facilitate bench deployment, the framework is supported by open-access templates designed to guide standardized reporting, structured root cause analysis (Five Whys/Ishikawa checklists), corrective actions, ledger tracking, and automated Process Sigma performance indicator dashboard monitoring. CONCLUSION: Strengthening error tracking in RLS is fully viable through targeted operational changes without extensive capital investment. Shifting from an individual blame orientation to system-centric learning, paired with stepwise accreditation mentorship models (SLMTA/SLIPTA), significantly reduces diagnostic defects and ensures health system sustainability.
Kisspeptin-10/basal LH ratio improves differentiation of central precocious puberty and premature thelarche.
Banerjee AA, Bhanarkar SR, Kashikar S … +14 more , Keshwani R, Walia S, Kavya DR, Bombe S, Pande S, Modi DN, Pathak BR, Joshi B, Tandon D, Patil A, Begum S, Mahale SD, Rao S, Surve SV
Clin Chim Acta · 2026 Jun · PMID 42364891 · Publisher ↗
BACKGROUND: Distinguishing idiopathic central precocious puberty (ICPP) from premature thelarche (PT) remains a clinical challenge and often necessitates GnRH stimulation testing. Kisspeptin-10 (Kp-10), Neurokinin B (NKB...
BACKGROUND: Distinguishing idiopathic central precocious puberty (ICPP) from premature thelarche (PT) remains a clinical challenge and often necessitates GnRH stimulation testing. Kisspeptin-10 (Kp-10), Neurokinin B (NKB), and Neuropeptide Y (NPY) are key regulators of GnRH secretion and may serve as surrogate biomarkers. We evaluated whether these neuropeptides, alone or in combination with basal gonadotropins, could provide clinically useful discrimination of ICPP and PT. METHODS: In this prospective study, Indian girls aged 6-9 years were enrolled as controls (n = 40), ICPP (n = 33), and PT (n = 23). Anthropometry, basal LH, FSH, estradiol, pelvic ultrasonography, and plasma Kp-10, NKB, and NPY levels were assessed. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Logistic regression models assessed incremental predictive value: Model 1 included the Kp-10/basal LH ratio; Model 2 added bone age advancement (BA-CA); and Model 3 further included basal estradiol. Clinical utility was examined using decision curve analysis (DCA). RESULTS: Anthropometric parameters did not differ between ICPP and PT. Kp-10 and NKB levels were higher in both early-puberty groups than controls, but neither marker alone discriminated ICPP from PT. The composite Kp-10/basal LH ratio showed superior performance, with an ROC-derived cut-off <4.07 ng/mIU (sensitivity 72.7%, specificity 87.0%, accuracy 78%). All three models showed similar discrimination (AUC 0.78-0.79), with no meaningful improvement after adding BA-CA or estradiol. DCA demonstrated a higher net benefit for the Kp-10/basal LH ratio compared with treat-all or treat-none strategies across clinically relevant thresholds. CONCLUSION: The Kp-10/basal LH ratio provides robust discrimination and meaningful clinical utility in differentiating ICPP from PT and may reduce reliance on GnRH stimulation testing.
Presepsin outperforms conventional biomarkers for Sepsis diagnosis and 30-day mortality prediction: A multicenter prospective study in a north African ICU cohort.
Allam I, Derdoum A, Said A … +9 more , Boussaha H, Merah F, Belaid B, Ouchene N, Kassoul A, Yargui L, Sadat S, Hamidi RM, Djidjik R
Clin Chim Acta · 2026 Jun · PMID 42364890 · Publisher ↗
BACKGROUND: Sepsis remains a leading cause of intensive care unit (ICU) mortality, necessitating the identification of accurate biomarkers for diagnosis and prognosis. Presepsin (sCD14-ST), generated through monocyte/mac...
BACKGROUND: Sepsis remains a leading cause of intensive care unit (ICU) mortality, necessitating the identification of accurate biomarkers for diagnosis and prognosis. Presepsin (sCD14-ST), generated through monocyte/macrophage phagocytosis of bacterial components, offers infection-specific signals. This study compared the diagnostic and prognostic performance of with of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and interleukin-8 (IL-8) within the same patient cohort. PATIENTS AND METHODS: This prospective multicenter cohort study enrolled 184 participants across two Algerian tertiary ICUs: 60 healthy controls, 30 patients with pulmonary infection, 46 with sepsis, and 48 with septic shock (Sepsis-3 criteria). All biomarkers were measured using a single blood sample collected within six hours of admission. Diagnostic accuracy was assessed using ROC curve analysis and DeLong's test, and independent predictors of 30-day mortality were identified using binary logistic regression. RESULTS: All biomarkers differed significantly between the groups (p < 0.001). Presepsin achieved the highest diagnostic accuracy for septic shock versus healthy controls (AUC = 0.880) and was the best discriminator between sepsis and pulmonary infection (AUC = 0.941) and between septic shock and pulmonary infection (AUC = 0.959), significantly outperforming all the comparators by DeLong's test. The 30-day mortality rate was 51.1%. Non-survivors had markedly higher presepsin levels than survivors (8315.8 vs. 1453.5 pg/mL; p < 0.001). Presepsin yielded the best prognostic AUC for 30-day mortality (AUC = 0.821; cut-off: 2721.52 pg/mL), whereas PCT, CRP, IL-8, and WBC showed near-chance discrimination. In multivariable regression analysis, presepsin was the only independent predictor of mortality. CONCLUSION: Presepsin outperformed all evaluated biomarkers for sepsis diagnosis and 30-day mortality prediction, emerging as the sole independent prognostic marker after adjustment for confounding factors. These findings support its integration into ICU sepsis panels and provide the first validated presepsin mortality cut-off in a critically ill North African population.
Comparative stability analysis of RNA in dried blood spots for real-time PCR based molecular testing.
Natarajan K, Manoharan A, Uppugunduri CRS
Clin Chim Acta · 2026 Jun · PMID 42362137 · Publisher ↗
Dried blood spot (DBS) sampling represents a minimally invasive, cost-effective alternative to venous blood collection, and advantageous for resource-limited diagnostic settings. The reliability of RNA-based molecular as...
Dried blood spot (DBS) sampling represents a minimally invasive, cost-effective alternative to venous blood collection, and advantageous for resource-limited diagnostic settings. The reliability of RNA-based molecular assays using DBS depends on RNA stability under various storage conditions. This study evaluated RNA stability in DBS samples stored at varying temperatures and time points, with and without RNAlater pretreatment of Whatman 903™ protein saver cards to determine their suitability for quantitative PCR (qPCR)-based applications. Whole blood was applied onto standard and RNAlater-pretreated (10 μL; 10 spots/card) Whatman 903™ cards and stored at room temperature (RT), 4 °C, and - 20 °C for 1, 3, and 7 days. Total RNA was extracted, quantified, and assessed for purity prior to cDNA synthesis. ABL1 gene amplification was performed using SYBR green real-time PCR. Analytical agreement between matrices for RNA quantity was assessed using Bland-Altman plot, and cycle threshold (Ct) values were compared. RNA yield and purity varied across storage conditions. The highest RNA yield was observed in RNAlater-pretreated DBS cards stored at RT for 7 days (36.3 ± 0.665 ng/μL), with acceptable purity (A260/280 range: 1.7-2.0). On day 7, whole blood samples stored at 4 °C demonstrated reduced RNA yield compared to treated and untreated DBS cards irrespective of the storage temperature. Consistent ABL1 amplification confirmed preserved RNA integrity in both untreated and treated DBS samples (CV <1%), with improved stability in pretreated cards compared to whole blood (CV < 3%). RNAlater pretreatment enhances RNA stability in DBS, supporting its application for reliable qPCR-based molecular diagnostics in routine and field laboratory settings, especially when concordance is established between venous and capillary sampling.
Quality assessment, prognostic factors, and biomarkers for brain tumor analysis: a comprehensive systematic review.
Balaji P, Devasena D
Clin Chim Acta · 2026 Jun · PMID 42362136 · Publisher ↗
The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow...
The brain tumors possess different causative factors and properties, making their diagnosis and treatment difficult. Growth of these cancers usually leads to compression of the adjacent nerves and obstruction of the flow of cerebrospinal fluid, thus leading to increase in intracranial pressure. This affects the working of brain in many ways; thus, the difficulty involved in its treatment. With the improvements in technology in neuroimaging, including Diffusion Tensor Imaging (DTI), Positron Emission Tomography (PET), and multiparametric Magnetic Resonance Imaging (mpMRI), the diagnosis process has become easy. The effectiveness of any form of therapy in such patients depends primarily on their prognosis. While it is a common practice that physicians determine the prognosis of the disease by considering the age of the patient, histological grade of the tumor, and resection status, now this method has become more comprehensive by adding molecular signature and genetic analyses to the list of criteria. Next-generation sequencing (NGS) allows a reliable molecular classification. It increases the level of risk stratification, facilitating the application of therapies tailored to individual patients. Thus, molecular oncology has greatly changed our views on brain tumors' pathology and prognosis while neoadjuvant treatments aim at increasing the survival rate. On the other hand, radiogenomics is a field of study that combines non-invasive imaging phenotypes and genomic information in order to find unique molecular signatures of tumors without collecting samples from tumors. Molecular biomarkers are absolutely essential in the diagnosis of cancer, treatment monitoring, and recurrence of cancer. Advances in liquid biopsy technology, particularly the methods for circulating tumor DNA (ctDNA) and Extracellular Vesicle (EV) based analysis, have enabled the possibility of non-invasive monitoring of the progression of the tumors over time. This review highlights key studies and important scientific works about imaging technologies, biomarkers, and prognostic factors of malignant brain tumors.
Diagnostic and prognostic biomarkers in PCOS: Navigating insulin resistance, systemic inflammation, and endometrial receptivity.
El-Sehrawy AAMA, Aljumaili OI, Baig MR … +5 more , Nematov O, Sapaev IB, Badr IH, Smerat A, Basunduwah TS
Clin Chim Acta · 2026 Jun · PMID 42349674 · Publisher ↗
Polycystic ovary syndrome (PCOS) is a highly prevalent and phenotypically diverse endocrine disorder in which insulin resistance (IR) serves as a central molecular driver of major metabolic and reproductive complications...
Polycystic ovary syndrome (PCOS) is a highly prevalent and phenotypically diverse endocrine disorder in which insulin resistance (IR) serves as a central molecular driver of major metabolic and reproductive complications, including infertility, obesity, and increased long-term cardiovascular risk. This review examines the complex pathophysiology of PCOS, emphasizing how chronic systemic low-grade inflammation, gut microbiome dysbiosis, and oxidative stress interact to worsen hyperinsulinemia and hyperandrogenemia. It also highlights the clinical value of emerging diagnostic and prognostic biomarkers to improve risk stratification and patient management. Systemic biomarkers, such as pro-inflammatory cytokines, circulating endotoxemia arising from increased intestinal permeability, and epigenetic regulators including miR-146a, may provide prognostic insight into the trajectory of metabolic deterioration. In parallel, endometrial biomarkers, including the glucose transporter GLUT4, implantation-associated genes such as HOXA10, and inflammatory mediators like TNF-α, can support evaluation of impaired uterine receptivity, prediction of assisted reproductive technology (ART) outcomes, and stratification of miscarriage risk. By mapping key interactions within the gut-immune-metabolic axis and detailing localized endometrial dysfunction, this review proposes a framework for integrating targeted biomarker profiling into clinical practice to enable personalized, biomarker-informed interventions aimed at restoring fertility and metabolic health in patients with PCOS.
Biosensors for allergic diseases: Biomarker detection and monitoring.
Oriquat G, Fezea AA, Dhiaa AM … +4 more , Kubaev A, Ruziev O, Salih RM, Adil M
Clin Chim Acta · 2026 Jun · PMID 42342057 · Publisher ↗
Accurate diagnosis of allergic diseases demands sensitive measurement of biomarkers, particularly specific immunoglobulin E. Although standard laboratory tests can provide this information accurately, they have not been...
Accurate diagnosis of allergic diseases demands sensitive measurement of biomarkers, particularly specific immunoglobulin E. Although standard laboratory tests can provide this information accurately, they have not been able to keep up with the urgent need for speedy point-of-care alternatives. Biosensors, including immunosensors (antibody-antigen) and aptasensors (nucleic acid receptors), offer improved stability, reusability, and cost-effectiveness. Both types of biosensors have receptors that incorporate with transducers to produce measurable optical or electrochemical signals. This review consolidates known biomarkers for four major allergic conditions: asthma, atopic dermatitis (AD), allergic rhinitis, and food allergies. It then evaluates the analytical performance of optical and electrochemical immunosensors and aptasensors employed in diagnosing and monitoring these disorders. Furthermore, the development of point-of-care biosensor platforms for allergic disease detection is discussed, emphasizing their potential to enable rapid, decentralized testing and improve patient management through accessible, real-time diagnostic solutions. The primary focus remains on sensor-based platforms capable of detecting allergic disease biomarkers, providing meaningful insights into current technological capabilities and their clinical translation.
C-reactive protein as a universal prognosticator in hemorrhagic stroke: a meta-analysis of intracerebral and aneurysmal subarachnoid hemorrhage.
Juan CH, Lin C, Su Z … +8 more , Zhao J, Liu Y, Chang HC, Mo Y, Liao S, Zhang L, Lin R, Ding D
Clin Chim Acta · 2026 Jun · PMID 42342056 · Publisher ↗
BACKGROUND: Systemic inflammatory response plays a pivotal role in secondary brain injury following hemorrhagic stroke, including spontaneous intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (SAH). C...
BACKGROUND: Systemic inflammatory response plays a pivotal role in secondary brain injury following hemorrhagic stroke, including spontaneous intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (SAH). C-reactive protein (CRP) is a widely used biomarker of inflammation; however, a comprehensive meta-analysis directly comparing its prognostic utility across both major hemorrhagic stroke subtypes is lacking. This study aimed to quantitatively assess the common prognostic value of admission CRP levels for poor outcomes in patients with ICH and SAH. METHODS: Following PRISMA guidelines (PROSPERO: CRD42024510967), we systematically searched four databases up to January 1, 2026, for observational studies assessing CRP's association with outcomes in spontaneous ICH or SAH. Two investigators independently performed data extraction and quality assessment using the Newcastle-Ottawa Scale (NOS). Random-effects models were used to pool odds ratios (ORs) with 95% CIs. Prespecified subgroup analyses (hemorrhage type, geographic area, statistical model, etc.) and sensitivity analyses were conducted to explore heterogeneity and assess robustness. Publication bias was assessed using a funnel plot and Egger's test. RESULTS: Meta-analysis of 30 studies (n = 17,103) showed elevated CRP increased poor outcomes (OR = 1.22, 95% CI 1.12-1.32, P < 0.001). Associations were consistent across ICH/SAH, regions, and follow-up times, etc. CRP increased risks of functional disability, mortality, DCI, and CVS. The link with OS and DIND warrants caution (n = 2 studies). Effect sizes were higher in multivariate models (P for interaction = 0.0013). While significant in single-center studies, the association was non-significant in multicenter studies (OR = 1.46, 95% CI 0.87-2.47). Sensitivity analysis confirmed stability, with Egger's test suggesting small-study effects. CONCLUSION: Elevated admission CRP levels serve as a common and robust predictor of poor prognosis in both ICH and SAH patients. The consistency of this association across different hemorrhagic phenotypes underscores the universal impact of inflammation on secondary injury. Given its low cost and wide availability, CRP could serve as a valuable supplement to existing clinical scoring systems for early risk stratification, although causality remains to be established in future prospective studies.
Glycated albumin beyond HbA1c: an equity-ready laboratory pathway for emergency diabetes and cardiorenal risk screening.
Prasad A, Jayaswal RP
Clin Chim Acta · 2026 Jun · PMID 42336258 · Publisher ↗
Glycated albumin is gaining attention as a complementary biomarker for dysglycaemia, particularly when HbA1c interpretation is limited by altered erythrocyte survival, anaemia, haemoglobin variants, or chronic kidney dis...
Glycated albumin is gaining attention as a complementary biomarker for dysglycaemia, particularly when HbA1c interpretation is limited by altered erythrocyte survival, anaemia, haemoglobin variants, or chronic kidney disease. Building on the recent Clinica Chimica Acta study evaluating glycated albumin for emergency-department screening of undiagnosed prediabetes and diabetes, this correspondence argues for a broader equity-ready and cardiorenal-risk-aware implementation pathway. We propose a GA-PATH framework focused on population calibration, albumin-turnover safeguards, triage logic, harmonisation, and health-equity analytics. This approach may help transform glycated albumin from an alternative glycaemic marker into a context-aware laboratory tool for early detection, confirmatory referral, and global metabolic-risk prevention.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe