Clinica Chimica Acta; International Journal Of Clinical Chemistry[JOURNAL]
Sun
200 papers
Advances in monitoring and therapy from minimal residual disease to CAR-T cells in multiple myeloma and precursor disorders.
El-Sehrawy AAMA, Oriquat G, Saidov S … +5 more , Ruzikulov U, Shakhmurova G, Jbl BJ, Singhal D, Shefali
Clin Chim Acta · 2026 May · PMID 42140377 · Publisher ↗
Monoclonal gammopathies encompass a continuous spectrum of clonal plasma-cell disorders ranging from indolent precursor states, such as MGUS and SMM, to overt multiple myeloma (MM), each distinguished by its biological c...
Monoclonal gammopathies encompass a continuous spectrum of clonal plasma-cell disorders ranging from indolent precursor states, such as MGUS and SMM, to overt multiple myeloma (MM), each distinguished by its biological complexity, clinical course, and therapeutic implications. Recent advances in molecular diagnostics and immune-based therapies have transformed disease management from empirical observation to precision-guided care. Highly sensitive techniques, such as mass spectrometry for M-protein detection, next-generation flow cytometry and sequencing for minimal residual disease (MRD), PET-CT imaging, and circulating tumor cell assays, have enabled earlier and more accurate detection of subclinical disease and treatment response. MRD negativity has emerged as a powerful prognostic and predictive marker, correlating strongly with prolonged progression-free and overall survival. Parallel insights into clonal evolution, epigenetic remodeling, and microenvironmental influences, including hypoxia, cytokine networks, and stromal adhesion, have deepened understanding of resistance and relapse mechanisms. Therapeutically, the development of T-cell-redirecting immunotherapies, especially BCMA-directed CAR-T cells, bispecific antibodies, and emerging dual-antigen or "off-the-shelf" platforms, has achieved unprecedented response depth. Nonetheless, major challenges remain, including standardization of MRD methodologies, the validation of MRD as a regulatory endpoint, management of CAR-T-related toxicities, and overcoming economic, logistical, and geographic barriers that limit equitable access to advanced therapies. Addressing these challenges will be essential to translating molecular precision and cellular innovation into durable remission and, ultimately, a functional cure for multiple myeloma.
Combined effect of elevated lipoprotein (a) and high-sensitivity C-reactive protein on the risk of coronary heart disease.
Yang L, Sun J, Zhuang Q … +7 more , Zhao X, Chen Y, Wei P, Xie H, Liu J, Yang S, Shen C
Clin Chim Acta · 2026 May · PMID 42140376 · Publisher ↗
BACKGROUND: Elevated lipoprotein (a) [Lp(a)] is linked to increased coronary heart disease (CHD) risk in Europeans with systemic inflammation, whereas evidence in other populations is limited. This study examined the com...
BACKGROUND: Elevated lipoprotein (a) [Lp(a)] is linked to increased coronary heart disease (CHD) risk in Europeans with systemic inflammation, whereas evidence in other populations is limited. This study examined the combined effects of elevated Lp(a) and high-sensitivity C-reactive protein (hsCRP) on CHD risk in Chinese populations. METHODS: The prospective cohort included 4128 participants followed for a median of 14.16 years. Lp(a) and hsCRP were stratified into age- and sex-specific tertiles based on Generalized Additive Models for Location, Scale and Shape (GAMLSS) analysis. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CHD risk and their interactions. Sensitivity analyses used clinical cut-offs, median splits, continuous modelling, and competing risk models. Population attributable fraction (PAF) quantified risk. RESULTS: Lp(a) was not independently associated with CHD in the overall population. In the highest hsCRP tertile, medium and high Lp(a) tertiles showed increased CHD risk, with adjusted HRs (95% CIs) of 1.837 (1.052-3.206) and 2.021 (1.174-3.481), respectively (P = 0.014), explaining 37.986% of the CHD burden in that stratum. Joint analysis revealed significant associations only when using maximally selected rank statistics to identify optimal cut-points, with the dual-high group exhibiting the highest risk (HR = 1.626, P = 0.003). Additive and multiplicative interactions were significant for the tertile, optimal, and median cut-points (all P < 0.050). Sensitivity analyses confirmed the robustness. CONCLUSION: The impact of high Lp(a) levels on CHD risk is contingent upon elevated hsCRP, suggesting that hyperinflammation drives the pathogenic effect of Lp(a) in CHD development.
Measurement uncertainty in urine drug analysis: A comparison of ISO/TS 20914 and GUM/Eurachem approaches.
Şeneş M, Alpdemir M, Yurt EF
Clin Chim Acta · 2026 May · PMID 42134677 · Publisher ↗
BACKGROUND: Urine drug screening and confirmation tests play a critical role in forensic and clinical toxicology applications. This study evaluates and methodologically compares ISO/TS 20914 and GUM/EURACHEM approaches f...
BACKGROUND: Urine drug screening and confirmation tests play a critical role in forensic and clinical toxicology applications. This study evaluates and methodologically compares ISO/TS 20914 and GUM/EURACHEM approaches for estimating measurement uncertainty of multiple drugs of abuse analyzed by LC-MS/MS. METHODS: Seventeen target analytes, including drugs of abuse and their metabolites, were analyzed by LC-MS/MS, and measurement uncertainty was estimated using calibration data, one-year internal quality control results, and external quality assessment data according to both GUM/EURACHEM and ISO/TS 20914 approaches (95% confidence, k = 2). RESULTS: The GUM/EURACHEM approach yielded higher uncertainty estimates than ISO/TS 20914 for all analytes, primarily due to calibration and preparation components. The highest expanded uncertainty was observed for buprenorphine and heroin (17.7%) and the lowest for MDEA (5.9%). Relative differences (%ΔU) consistently favored the ISO/TS 20914 approach, with the calibration curve being the main contributor in the GUM/EURACHEM model. CONCLUSIONS: The ISO/TS 20914 approach provides a practical and sustainable framework for routine high-throughput toxicology laboratories, whereas the GUM/EURACHEM approach is more suitable for detailed uncertainty assessment during method development and validation. Measurement uncertainty should be considered in result interpretation, particularly for samples near decision thresholds, where it may influence classification and impact forensic and clinical decision-making.
Multi-omics precision diagnosis of brucellosis: Advances in biomarker discovery and clinical application.
Cai Y, Yang J, Hou M … +4 more , Su W, Liang F, Zhu M, Wu T
Clin Chim Acta · 2026 May · PMID 42128325 · Publisher ↗
Brucellosis, a neglected zoonosis caused by intracellular Brucella bacteria, remains a formidable global public health challenge, especially in developing regions. The notorious ability of Brucella to evade host immunity...
Brucellosis, a neglected zoonosis caused by intracellular Brucella bacteria, remains a formidable global public health challenge, especially in developing regions. The notorious ability of Brucella to evade host immunity and establish chronic focal infections limits the utility of traditional diagnostic methods like bacterial culture and serology for early detection, therapeutic monitoring, and disease staging. This review comprehensively synthesizes the ongoing paradigm shift from pathogen-centric detection toward multi-omics precision diagnosis. We critically evaluate advances in nucleic acid amplification technologies (NAATs), charting the progression from quantitative PCR to absolute quantification via droplet digital PCR (ddPCR) and examining the transformative potential of CRISPR-Cas biosensing for ultrasensitive, instrument-free detection. The discussion also encompasses the renaissance of serology through immunoproteomics, which has identified novel serodominant antigens and multi-epitope fusion proteins to address the persistent specificity problems arising from cross-reacting bacteria. Furthermore, we analyze the emerging landscape of host-response biomarkers, integrating transcriptomic, metabolomic, and single-cell RNA sequencing data to delineate distinct immune signatures of acute and chronic infection. Finally, we consider how artificial intelligence (AI) can integrate these multi-dimensional datasets to build predictive diagnostic models. This consolidated multi-omics framework charts a course for precision medicine in brucellosis, aiming to bridge the gap between biomarker discovery and point-of-care clinical application. SUMMARY: Multi-omics technologies (genomics, proteomics, metabolomics, transcriptomics) are advancing brucellosis diagnosis via sensitive detection and accurate biomarkers, and improving treatment through novel strategies like nano-delivery, vaccines, and AI integration.
Biochemical diagnosis of pheochromocytoma and paraganglioma: analytical challenges and perspectives for optimization.
Fraissinet F, Charpentier T, Girot H … +3 more , Brunel V, Prévost G, Lopez AG
Clin Chim Acta · 2026 May · PMID 42128324 · Publisher ↗
Pheochromocytomas and paragangliomas (PPGL) are rare but potentially life-threatening neuroendocrine tumors whose diagnosis relies primarily on the biochemical detection of excessive catecholamine production or metabolis...
Pheochromocytomas and paragangliomas (PPGL) are rare but potentially life-threatening neuroendocrine tumors whose diagnosis relies primarily on the biochemical detection of excessive catecholamine production or metabolism. Plasma free metanephrines and urinary fractionated metanephrines remain the cornerstone biomarkers recommended for initial screening. However, their performance is influenced by substantial pre-analytical and analytical variability, requiring strict standardization in sampling conditions and assay methodology. The emergence of liquid chromatography-tandem mass spectrometry (LC-MS/MS) has improved specificity, but inter-laboratory variability and lack of harmonized cut-offs still challenge reproducibility. Chromogranin A (CgA), while broadly used in neuroendocrine tumor monitoring, shows poor diagnostic accuracy for PPGL. Recent advances in molecular profiling, metabolomics, and artificial intelligence (AI) suggest future opportunities for more integrated diagnostic pathways, although these approaches remain investigational in PPGL. This review critically examines the current biochemical tools used in PPGL diagnosis, discusses pitfalls and limitations, and focuses on unresolved analytical vulnerabilities, inter-laboratory variability, and the translational implications of these issues for routine laboratory practice, while also proposing perspectives for optimization, including emerging biomarkers, integrative diagnostics, and harmonization strategies.
Extracellular vesicle-derived protein biomarkers for breast Cancer diagnosis: a systematic review, meta-analysis, and umbrella review.
Parron-Carreño T, Nievas-Soriano BJ, Lozano-Paniagua D … +2 more , Murillo-Cancho AF, Cristobal-Cañadas D
Clin Chim Acta · 2026 May · PMID 42128323 · Publisher ↗
Extracellular vesicle (EV)-derived proteins are increasingly investigated as liquid biopsy biomarkers because they can reflect tumour-associated molecular processes in clinically accessible biofluids. However, their diag...
Extracellular vesicle (EV)-derived proteins are increasingly investigated as liquid biopsy biomarkers because they can reflect tumour-associated molecular processes in clinically accessible biofluids. However, their diagnostic performance and methodological robustness in breast cancer remain incompletely defined. This study evaluated EV-derived protein biomarkers for breast cancer diagnosis through a systematic review and meta-analysis of primary studies, complemented by an umbrella review of published systematic reviews and meta-analyses. A structured search was conducted in PubMed/MEDLINE, Web of Science, and Scopus from database inception to February 2026 and subsequently updated during revision. Primary studies assessing EV-derived proteins or proteomic signatures in clinically relevant biofluids and reporting diagnostic performance metrics were eligible for quantitative synthesis. Methodological quality was assessed using QUADAS-2, and the quality of secondary reviews was evaluated with AMSTAR 2. Six independent studies were included in the meta-analysis. The pooled area under the receiver operating characteristic curve was 0.90 (95% CI 0.86-0.94), indicating high discriminatory capacity. However, the estimate should be interpreted cautiously because of the limited number of studies and substantial heterogeneity (I = 84.6%). The umbrella review identified four main functional domains: diagnostic applications, therapeutic resistance, tumour progression and metastasis, and global proteomic characterisation. EV-derived protein biomarkers show potential for breast cancer diagnosis, but current evidence is limited by methodological heterogeneity, incomplete analytical standardisation, and the lack of clinically actionable thresholds. Future progress will depend on harmonised pre-analytical and analytical protocols, multicentre validation, and diagnostic frameworks supporting their potential implementation in clinical laboratory practice.
Detection and characterization of SMN1 deletions in type IV spinal muscular atrophy using long-read whole-genome sequencing.
Zhong Z, Mai J, Chen D … +9 more , Lamu Y, Zhou W, Mao R, Zeng X, Zhang Z, Deng J, Wu X, Chen J, Li L
Clin Chim Acta · 2026 May · PMID 42128322 · Publisher ↗
Spinal muscular atrophy (SMA) is a neuromuscular disorder primarily caused by homozygous deletion of the SMN1 gene, with disease severity influenced by SMN2 copy number. Detecting SMN1 deletions is complicated by high se...
Spinal muscular atrophy (SMA) is a neuromuscular disorder primarily caused by homozygous deletion of the SMN1 gene, with disease severity influenced by SMN2 copy number. Detecting SMN1 deletions is complicated by high sequence homology with SMN2 and complex genomic architecture. Here we applied long-read whole-genome sequencing (LR-WGS), multiplex ligation-dependent probe amplification (MLPA), and targeted PCR to two adult patients with type IV SMA. We identified and precisely mapped two novel large deletions encompassing the entire SMN1 locus and observed significantly reduced full-length SMN mRNA levels. Our findings demonstrate LR-WGS's capability to resolve complex structural variants in highly homologous regions. Integrating LR-WGS with orthogonal validation enhances diagnostic precision, informing genetic counseling and advancing molecular diagnostics for SMA.
Bridging innovation and implementation in laboratory medicine: insights from a global survey on unmet needs and emerging technologies.
Gruson D, Gouget B, Karathanos S … +4 more , Greaves R, Liu Y, Ebert S, Shah S
Clin Chim Acta · 2026 May · PMID 42119761 · Publisher ↗
Technological innovation in laboratory medicine is advancing rapidly, driven by artificial intelligence, next-generation sequencing, high-resolution mass spectrometry, novel biomarkers, and decentralized point-of-care te...
Technological innovation in laboratory medicine is advancing rapidly, driven by artificial intelligence, next-generation sequencing, high-resolution mass spectrometry, novel biomarkers, and decentralized point-of-care testing. However, the translation of these advances into routine clinical practice remains uneven worldwide. To explore current barriers and priorities, the IFCC Emerging Technologies Division conducted a multi-regional survey among laboratory leaders and functional unit representatives. The survey identified a persistent gap between innovation and implementation. Major challenges included unequal access to advanced diagnostics, financial constraints, regulatory complexity, and workforce preparedness. Respondents highlighted disparities in infrastructure and expertise, particularly in low- and middle-income settings, raising concerns about widening global health inequities. Economic sustainability emerged as a central barrier, with high capital costs, uncertain reimbursement pathways, and the need for robust evidence of clinical utility and cost-effectiveness. Regulatory requirements, including evolving frameworks such as IVDR, were perceived as increasing compliance burdens and potentially limiting availability of specialized tests. A significant proportion of respondents also emphasized the need for structured implementation support, including training programs (64.7%), improved access to resources (64.7%), and strengthened networking and partnerships (66.7%). A significant skills gap related to artificial intelligence, data science, and bioinformatics was also reported, emphasizing the need for competency-based education and interdisciplinary collaboration. Six strategic priority domains were identified: AI integration, genomics capacity, global harmonization, decentralized diagnostics, biomarker validation, and implementation science. Bridging innovation and implementation will require coordinated global leadership, structured support from scientific organizations, and sustained investment to ensure equitable, clinically impactful adoption of emerging technologies.
Inflammation and cardiovascular risk in autoimmune diseases: Mechanisms, biomarkers, and clinical implications.
Daoud E, Abduvoyitov B, Kurbonov T … +5 more , Alhady NA, Suleman AD, Singhal D, Panigrahi R, Tailor NK
Clin Chim Acta · 2026 May · PMID 42119760 · Publisher ↗
The intersection of autoimmune diseases and cardiovascular disease (CVD) represents a critical frontier in modern medicine. Patients with chronic inflammatory and autoimmune conditions exhibit a significantly elevated ri...
The intersection of autoimmune diseases and cardiovascular disease (CVD) represents a critical frontier in modern medicine. Patients with chronic inflammatory and autoimmune conditions exhibit a significantly elevated risk of premature and accelerated cardiovascular events, a phenomenon rooted not only in shared risk factors but also in a deeply intertwined pathophysiology. The persistent inflammatory state characteristic of these disorders creates a proatherogenic environment, leading to systemic effects that manifest as subclinical cardiac involvement long before overt clinical events occur. Recognizing this profound link, professional bodies have issued guidelines advocating for proactive cardiovascular risk management in patients with autoimmune rheumatic diseases, including rheumatoid arthritis (RA), vasculitis, and systemic sclerosis (SSc). This review provides a comprehensive analysis of the full spectrum of cardiovascular biomarkers utilized in this context. This study examines their roles in elucidating disease mechanisms, diagnosing active cardiovascular involvement, monitoring disease activity, predicting future risk, and ultimately guiding personalized therapeutic strategies. The analysis spans from well-established clinical markers to cutting-edge discoveries in proteomics and immunology, offering a holistic view of how molecular indicators are transforming the understanding and management of CVD in autoimmune populations.
Both of coagulopathy and neutrophil extracellular trap markers are associated with poor prognosis of dabie bandavirus infection.
Bai F, Lei Z, Bai H … +2 more , Li D, Tang N
Clin Chim Acta · 2026 May · PMID 42114670 · Publisher ↗
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), caused by Dabie bandavirus (DBV), has a high mortality. Coagulopathy and neutrophil extracellular traps (NETs) formation are implicated in disease progressi...
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), caused by Dabie bandavirus (DBV), has a high mortality. Coagulopathy and neutrophil extracellular traps (NETs) formation are implicated in disease progression, and their combined prognostic value remains unclear. OBJECTIVES: To investigate the relationship between the levels and changes of coagulation and NETs markers in early admission of SFTS patients and their prognosis, as well as the differences between SFTS and Hemorrhagic fever with renal syndrome (HFRS) patients. METHODS: A prospective cohort of 124 SFTS patients was analyzed. Coagulation parameters, NETs biomarker (Citrullinated histone H3, CitH3) and other routine laboratory parameters were measured on admission and day 3. During the same period, the coagulation and NETs indicators were measured in 13 HFRS patients on admission. RESULTS: Multivariate analysis identified activated partial thromboplastin time (APTT) (OR: 1.051, p = 0.010), D-dimer (OR: 1.174, p = 0.044), and CitH3 (OR: 1.002, p = 0.020) as independent mortality predictors in SFTS patients. Optimal cut-offs stratified patients into risk groups, with triple-positive markers (APTT >60.8 s, D-dimer >4.96 μg/mL, CitH3 > 942 pg/mL) showing the highest mortality (p < 0.05). Survivors exhibited significant reductions in APTT and D-dimer by day 3. The SFTS patients had higher CitH3 level and 28-day mortality compared to the HFRS patients (p < 0.05). CONCLUSION: Both coagulopathy and NETs markers are predictive of mortality in SFTS patients, dynamic monitoring of coagulation parameters in the early stage of admission has the potential to be used for prognostic evaluation and guiding treatment.
Extracellular vesicle crosstalk in urinary tract infections: Integrating host exosomes and pathogen-derived membrane vesicles for antimicrobial resistance monitoring and diagnostic innovation.
Tolibov M, Khasanov S, Mirzabekova O … +2 more , Ismatova M, Proshad R
Clin Chim Acta · 2026 May · PMID 42114669 · Publisher ↗
Urinary tract infections (UTIs) remain a major global health burden, with rising antimicrobial resistance (AMR) posing severe challenges to diagnosis and treatment. While host-derived urinary exosomes have been recognize...
Urinary tract infections (UTIs) remain a major global health burden, with rising antimicrobial resistance (AMR) posing severe challenges to diagnosis and treatment. While host-derived urinary exosomes have been recognized as promising noninvasive biomarkers for UTI, the role of pathogen-derived outer membrane vesicles (OMVs) in UTI pathogenesis and AMR has been comparatively underexplored. No comprehensive framework currently integrates both host extracellular vesicles (EVs) and pathogen-derived EVs in the context of UTI diagnosis and antimicrobial resistance monitoring. This review addresses this gap by synthesizing current evidence on the bidirectional EV crosstalk between uropathogens and host cells during UTI. We examine how host exosomes carry antimicrobial effectors and inflammatory signals, while pathogen OMVs serve as vehicles for horizontal gene transfer of antibiotic resistance genes, enzymatic degradation of antibiotics, and immune evasion. We evaluate the diagnostic potential of dual EV profiling, integrating host exosomal markers such as Akt, CD9, and miR-18a-5p with pathogen OMV markers including beta-lactamases and antibiotic resistance genes, to enable simultaneous UTI diagnosis and AMR prediction. We further discuss emerging microfluidic technologies for rapid EV isolation and characterization, the Target Product Profile and Target Specimen Profile frameworks essential for clinical translation, the role of fit-for-purpose specimen panels from professional biobanks in analytical and clinical validation, and the challenges in translating these findings into clinical practice. By bridging the host-pathogen EV divide, this review proposes a paradigm shift toward integrated extracellular vesicle-based diagnostics that could transform UTI management in the era of antimicrobial resistance.
Emerging biomarkers in IgA nephropathy, membranous nephropathy, and lupus nephritis.
Kobayashi H, Murata Y, Akiya Y … +6 more , Matsuoka T, Otsuka H, Tsunemi A, Nakamura Y, Azuma M, Abe M
Clin Chim Acta · 2026 May · PMID 42107815 · Publisher ↗
INTRODUCTION: Diabetic kidney disease (DKD) studies have identified circulating proteins linked to progression to kidney function decline. Whether these markers generalize to autoimmune nephritides is unclear. We evaluat...
INTRODUCTION: Diabetic kidney disease (DKD) studies have identified circulating proteins linked to progression to kidney function decline. Whether these markers generalize to autoimmune nephritides is unclear. We evaluated DKD-derived biomarkers in IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN) for associations with renal pathology and longitudinal kidney function decline. METHODS: In a single-center cohort of biopsy-proven IgAN (n = 82), MN (n = 22), and LN (n = 22) with healthy controls (n = 88), serum was obtained immediately before renal biopsy. Seven proteins (KIM1, WFDC2, EPHA2, EFNA4, DLL1, LAYN, PVRL4) were quantified by Olink® proximity-extension assay; MMP7 by ELISA. We compared biomarker levels between diseases and controls, examined associations with clinical measures and disease-specific histopathology, and tested prognostic value for kidney function decline-incident CKD stage 3 or ≥ 30% eGFR loss using Cox proportional hazards models. RESULTS: Across groups, KIM1, WFDC2, EPHA2, DLL1, LAYN, and PVRL4 exceeded controls; EFNA4 was elevated in IgAN; MMP7 was greatest in IgAN. Proteins generally correlated with eGFR (inverse), proteinuria, and urinary NAG; β2-microglobulin correlated in MN/LN only. In IgAN, WFDC2 independently predicted the composite outcome (adjusted HR 3.63; P < 0.001), whereas others did not. No protein predicted outcomes in MN or LN. In IgAN, WFDC2 associated with tubular atrophy/interstitial fibrosis (T) but not with M, E, or S. CONCLUSIONS: DKD-derived proteins are broadly increased in autoimmune nephritides, but only WFDC2 was independently associated with kidney outcome in IgAN and with tubulointerstitial fibrosis. These findings suggest that disease-specific biomarker panels may be needed and warrant multicenter validation.
Circulating suPAR in autoimmune liver diseases: advancing global noninvasive fibrosis and immune profiling.
Jayaswal RP
Clin Chim Acta · 2026 May · PMID 42105944 · Publisher ↗
The soluble urokinase-type plasminogen activator receptor (suPAR) is a biologic marker of systemic immune activation and fibrotic burden in chronic inflammatory disorders. Recent studies have shown that suPAR has shown p...
The soluble urokinase-type plasminogen activator receptor (suPAR) is a biologic marker of systemic immune activation and fibrotic burden in chronic inflammatory disorders. Recent studies have shown that suPAR has shown potential to distinguish autoimmune liver diseases (AILD) from other liver disorders, and is associated with non-invasive fibrosis indices and immunologic activity. This commentary outlines the evidence for analytical, clinical, and translational potential of suPAR in patients with AILDs. The assay variability and differentiation between liver and systemic inflammation are discussed. Recommendations are made for the establishment of standardized cutoffs for suPAR in diverse populations. Gaps that exist in the current literature regarding suPAR include a lack of histological verification, no long-term data, and no stratification of AILD subtypes. A four-phase innovation model is presented that emphasizes analytic standardization, composite biomarker models, trajectory-based tracking, and equitable global application of suPAR testing. Collectively, these considerations support suPAR as a potential adjunct biomarker with translational relevance in hepatology and immunology, warranting further validation before broader clinical adoption.
Chemical and biochemical derivates of trans-3-methylglutaconyl CoA: A molecular labyrinth.
Jennings EA, Jones DE, Ryan RO
Clin Chim Acta · 2026 May · PMID 42105943 · Publisher ↗
trans-3-Methylglutaconyl (3MGC) CoA is a seemingly innocuous metabolic intermediate that, in human intermediary metabolism, appears only in the leucine catabolism pathway. However, in multiple pathophysiological conditio...
trans-3-Methylglutaconyl (3MGC) CoA is a seemingly innocuous metabolic intermediate that, in human intermediary metabolism, appears only in the leucine catabolism pathway. However, in multiple pathophysiological conditions, it is now recognized that trans-3MGC CoA can be generated via an alternate biosynthetic route. In such cases, as well as rare inborn errors of metabolism in genes encoding leucine catabolism pathway enzymes, increased levels of trans-3MGC CoA trigger the formation of a series of chemical derivates that represent potential disease biomarkers. Trans-3MGC CoA is a relatively unstable chemical entity that is prone to isomerize to cis-3MGC CoA, which spontaneously undergoes an intramolecular cyclization reaction, forming 3MGC anhydride and free CoA. The anhydride is susceptible to hydrolysis, forming the organic acid, 3MGC acid, which is excreted in urine as a mixture of cis- and trans-diastereomers. Alternatively, the anhydride can react with lysine side chain amino groups, resulting in protein 3MGCylation. Another derivate of trans-3MGC CoA, 3-methylglutaryl (3MG) CoA, is apparently formed by enzyme-mediated reduction of the double bond in trans-3MGC CoA. Once formed, 3MG CoA has three potential fates, including cyclization to form the corresponding anhydride which can either be hydrolyzed to 3MG acid or react with lysine residues to 3MGylate protein substrates. Alternatively, 3MG CoA can react with l-carnitine, via carnitine acyltransferase, generating 3MG carnitine and free CoA as products. This acylcarnitine derivate of trans-3MGC CoA has gained attention recently as a readily detectable biomarker of mitochondrial dysfunction in a growing number of disease processes.
Biological variation of serum Anti-Müllerian Hormone in healthy adult men.
Kılınçer RB, Caniklioğlu A, Ercan M
Clin Chim Acta · 2026 May · PMID 42105942 · Publisher ↗
OBJECTIVES: Anti-Müllerian hormone (AMH) is a dimeric glycoprotein essential for male sex differentiation during embryogenesis and a widely used biomarker of testicular function in adult men. This study aimed to determin...
OBJECTIVES: Anti-Müllerian hormone (AMH) is a dimeric glycoprotein essential for male sex differentiation during embryogenesis and a widely used biomarker of testicular function in adult men. This study aimed to determine within-subject (CV) and between-subject (CV) biological variation data for serum AMH in healthy adult men. METHODS: Between November 2024 and March 2025, this Turkey-based study enrolled 20 healthy adult male volunteers selected using predefined inclusion and exclusion criteria. Blood samples were collected over four consecutive weeks, resulting in four specimens per participant. The serum AMH concentration was analyzed on a Roche Cobas e601 analyzer. Statistical analyses included outlier detection; assessment of data distribution, steady-state conditions, and homogeneity; analysis of variance with a 95% confidence interval (CI); estimation of analytical performance specifications (APSs); and calculation of the individuality index (II) and reference change value (RCV). RESULTS: CV was 3.5% (95% CI: 2.93-4.3), while CV was 34.72% (95% CI: 26.38-50.75) in this study. The II value was 0.1, and the asymmetrical RCV was +9% for increases and - 8.2% for decreases. Desirable APSs were imprecision <1.75%, bias <8.72%, and total allowable error < 11.61%. CONCLUSIONS: The low CV for AMH in men indicates stringent homeostatic regulation. The low II signifies high individuality, suggesting that RCV utilization is more appropriate than population-based reference intervals for clinical monitoring. To the best of our knowledge, this is the first comprehensive study reporting biological variation data for AMH in men.
Thrombosis at the crossroads of inflammation, coagulation, and vascular biology: Recent advances and emerging therapeutic strategies.
Ramarajan MG, Reda A, Ghozy S … +2 more , Ranatunga W, Kadirvel R
Clin Chim Acta · 2026 May · PMID 42105941 · Publisher ↗
Thrombosis is a multifaceted pathological process involving intravascular clot formation that drives a range of cardiovascular and cerebrovascular diseases, including myocardial infarction, ischemic stroke, venous thromb...
Thrombosis is a multifaceted pathological process involving intravascular clot formation that drives a range of cardiovascular and cerebrovascular diseases, including myocardial infarction, ischemic stroke, venous thromboembolism, and cancer-associated thrombosis. Despite major advances in anticoagulation and thrombolytic therapies, clinical outcomes remain limited by bleeding risk, incomplete clot dissolution, and variable patient response. Emerging evidence increasingly portrays thrombosis as a dynamic immunoinflammatory disorder, integrating coagulation, inflammation, and immune signaling into what is collectively termed thrombo-inflammation. Mechanistic insights have uncovered crucial roles for neutrophil extracellular traps (NETs), platelet-leukocyte interactions, complement activation, and metabolites derived from gut microbiota in facilitating the formation and persistence of thrombi. Translational research has mirrored this trend, with the development of innovative therapeutics such as Factor XI/XII inhibitors, RNA-based agents, and nanocarrier-guided delivery systems. These are crafted to precisely modulate antithrombotic efficacy while ensuring the preservation of hemostatic balance. At the same time, advancements in thrombolytic techniques, such as clot-sensitive fibrinolytics and interventions using ultrasound assistance and catheter guidance, provide treatment options focused on precision. Advances in diagnostic platforms, including artificial intelligence (AI) -enhanced imaging, microfluidic assays, and multi-omics biomarker profiling, are further transforming early detection and individualized risk stratification. This review brings together current molecular and translational insights to map out the evolving paradigm of thrombosis as a systemic, multifactorial process. It emphasizes the emerging connections among bioengineering, omics-based profiling, and artificial intelligence, showcasing their combined potential to revolutionize prevention, diagnosis, and treatment strategies. By integrating these multidimensional perspectives, this review aims to chart the path toward precision thrombosis medicine and mechanism-targeted therapeutic innovation.
Multi-omics identification of aging-related diagnostic genes and therapeutic targets in renal fibrosis.
Yin S, Gong J, Huang D … +3 more , Wen D, Quan Z, Shu C
Clin Chim Acta · 2026 May · PMID 42102994 · Publisher ↗
BACKGROUND: Renal fibrosis is a pathological hallmark of progressive chronic kidney disease, partly driven by aging-related molecular alterations. However, clinically relevant diagnostic biomarkers and therapeutic target...
BACKGROUND: Renal fibrosis is a pathological hallmark of progressive chronic kidney disease, partly driven by aging-related molecular alterations. However, clinically relevant diagnostic biomarkers and therapeutic targets remain limited. METHODS: We integrated four GEO datasets (GSE76882, GSE65326, GSE22459, GSE7392) to identify aging-related differentially expressed genes (DE-ARGs) in renal fibrosis. Functional enrichment, GSEA, and GSVA were performed to explore biological pathways. A total of 108 machine learning models were constructed to identify optimal diagnostic signatures. Immune infiltration (CIBERSORT), single-cell RNA sequencing (GSE269062), drug-target enrichment, molecular docking, and Mendelian randomization (MR) were used to evaluate key genes. Experimental validation was conducted using RT-PCR and immunohistochemistry in the UUO-induced renal fibrosis mouse model. RESULTS: We identified 84 DE-ARGs enriched in inflammatory, senescence-related, and transcriptional pathways. A 7-gene diagnostic model (MMP7, AGR2, RASSF5, AHR, HIF1A, AXL, PTTG1), constructed using Random Forest and Elastic Net, showed strong predictive performance (AUC = 0.790-0.917). These genes were significantly associated with T cells and macrophages. Single-cell analysis revealed cell-type specificity, such as MMP7 in collecting duct cells and AHR in macrophages. Drug-target analysis identified 1-(5-deoxypentofuranosyl)-5-fluoropyrimidine-2,(1H,3H)-dione as a potential multitarget agent. Molecular docking confirmed stable binding. RT-PCR and IHC confirmed significant upregulation of model genes, especially LCN2. MR further supported LCN2 as a causal plasma protein for renal fibrosis. CONCLUSIONS: We identified and validated a robust aging-related diagnostic gene signature for renal fibrosis using integrated bioinformatics and experimental approaches, offering novel insights and actionable targets for future intervention.
Serial monitoring of cytokine profile, liver function, and hematological biomarkers in severe CRS and CLS following CAR-T cell therapy for relapsed hepatocellular carcinoma: a case report.
Wu M, Guo W, Wang B … +2 more , Gu M, Wang C
Clin Chim Acta · 2026 May · PMID 42097197 · Publisher ↗
BACKGROUND: Liver cancer is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated great potenti...
BACKGROUND: Liver cancer is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. In recent years, chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated great potential and promising prospects in cancer treatment. However, CAR-T cell infusion is associated with various severe side effects. There is a paucity of reports describing serial monitoring of laboratory biomarkers in complications. CASE PRESENTATION: Here we report a patient with relapsed hepatocellular carcinoma who developed grade-3 cytokine-release syndrome and moderate capillary-leak syndrome after infusion of CAR-T cells. Following CAR-T infusion, the serum cytokine profile and liver enzyme levels were significantly elevated, accompanied by pancytopenia and coagulopathy. CONCLUSION: After CAR-T-cell administration, laboratory parameters should be closely monitored and complications such as CRS and CLS managed promptly and effectively, which will improve the safety of CAR-T therapy.
Closing the evidence gap: Capillary high-sensitivity troponin I verification in an African population using point of care.
Ann MA, Doreen J, Siyabonga K … +1 more , Chemedzai C
Clin Chim Acta · 2026 May · PMID 42097196 · Publisher ↗
BACKGROUND: High sensitivity cardiac troponin I (hs-cTnI) assays are central to the early diagnosis and rule-out of acute myocardial infarction (AMI). In resource-limited settings, point-of-care (POC) platforms using cap...
BACKGROUND: High sensitivity cardiac troponin I (hs-cTnI) assays are central to the early diagnosis and rule-out of acute myocardial infarction (AMI). In resource-limited settings, point-of-care (POC) platforms using capillary blood may reduce turnaround time and improve access to timely decision-making. This study evaluated the performance of capillary hs-cTnI POC sampling in an African population. METHODS: This cross-sectional method comparison study evaluated paired capillary hs-cTnI measurements obtained on POC against corresponding venous serum and plasma samples analysed on a central laboratory assay. Samples were collected from adults presenting with suspected AMI to Charlotte Maxeke Johannesburg Academic Hospital Emergency Department. Analytical verification was performed in accordance with Clinical and Laboratory Standards Institute protocols. Agreement was assessed using Bland Altman analysis. Diagnostic concordance at sex-specific 99th percentile decision thresholds and misclassification rates were determined. RESULTS: In this study, 110 patients were recruited, of whom 91 were deemed eligible for analysis. Capillary hs-cTnI showed moderate correlation with both plasma (r = 0.788; 95% CI 0.694-0.855) and serum (r = 0.791; 95% CI 0.699-0.857). Mean bias of capillary versus plasma was -15.9% (-173% to +143%) and - 12.9% (-171% to +145%) compared with serum. Serum comparison met the predefined allowable minimum bias of 13.6%. Overall agreement at the 99th percentile was 92.1% (83/91), with substantial inter-method agreement (κ >0.75). No significant asymmetry in discordant classifications was observed (p = 0.7266; 95% CI -8.27 to 3.88). CONCLUSION: Capillary whole-blood hs-cTnI testing demonstrated acceptable analytical agreement and high clinical concordance with central laboratory measurement, supporting its implementation to enhance rapid AMI assessment in resource-limited emergency settings.
Free light chain EQA: Analytical variability with clinical consequences - Data from 25 Italian EQA exercises (2021-2025).
Pasotti F, Da Molin S, Bosoni T … +5 more , Azzarà G, Liga G, Moriello G, Zaccaria B, Buoro S
Clin Chim Acta · 2026 May · PMID 42097195 · Publisher ↗
Serum free light chains (FLC) κ and λ, and the κ/λ ratio, are key biomarkers for the diagnosis, risk stratification and monitoring of monoclonal gammopathies. However, substantial between-method variability still limits...
Serum free light chains (FLC) κ and λ, and the κ/λ ratio, are key biomarkers for the diagnosis, risk stratification and monitoring of monoclonal gammopathies. However, substantial between-method variability still limits harmonised interpretation. We analysed five years of external quality assessment (EQA) data from an Italian FLC scheme. Twenty-five EQA rounds (2021-2025) yielded 2218 results: 746 for κ FLC, 746 for λ FLC and 726 for the κ/λ ratio. Data were processed according to ISO 13528 using robust statistics and method-specific peer groups. Inter-laboratory precision within homogeneous peer groups was generally acceptable, with typical coefficients of variation around 10-20% for κ and λ FLC. By contrast, marked between-method differences were observed. Compared with Siemens N Latex, Binding Site Freelite assays yielded approximately two-fold higher mean κ FLC concentrations (relative mean bias ≈ +94%) and lower mean λ FLC concentrations (relative mean bias ≈ -82%), leading to substantial discrepancies in κ/λ ratio interpretation. Stratified analysis across low, intermediate and high concentration bands showed that the positive κ bias of Freelite persisted throughout the analytical range, whereas the global negative λ bias was largely driven by a subset of high-concentration samples with very high N Latex values. Bland-Altman analysis confirmed wide limits of agreement for both analytes. These findings indicate that current FLC assays are not interchangeable and that κ/λ ratios should not be interpreted using universal reference intervals. Method-specific cut-offs, method-consistent follow-up and method-stratified EQA schemes are required pending international standardization of FLC measurement.
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