Clinica Chimica Acta; International Journal Of Clinical Chemistry[JOURNAL]
Sun
200 papers
Corrigendum to "Blood clot and fibrin recognition method for serum images based on deep learning" [Clin. Chim. Acta 553 (2024) 117732].
Hou J, Ren W, Zhao W … +6 more , Li H, Liu M, Wang H, Duan Y, Wang C, Liu C
Clin Chim Acta · 2026 Jul · PMID 42000290 · Publisher ↗
Abstract loading — click title to view on PubMed.
Cerebrospinal fluid biomarkers in Alzheimer's disease: enhancing diagnostic precision and guiding therapeutic strategies.
Azadovich AP, Oralov B, Sherzod K … +10 more , Kudeshova G, Feruza A, Umida B, Kambarova O, Farkhod R, Baxtiyor S, Jurabek Y, Narzikulova K, Nazirova S, Egamberdieva S
Clin Chim Acta · 2026 Jul · PMID 41999930 · Publisher ↗
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a growing global impact. Early and accurate diagnosis is crucial for effective management and therapeutic development. Cerebrospinal fluid (CSF) b...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a growing global impact. Early and accurate diagnosis is crucial for effective management and therapeutic development. Cerebrospinal fluid (CSF) biomarkers have revolutionized AD diagnostics, reflecting core pathological hallmarks such as amyloid plaques and neurofibrillary tangles. Core CSF biomarkers, including amyloid-beta 42 (Aβ42), total tau (T-tau), and phosphorylated tau (p-tau), demonstrate high diagnostic accuracy, identifying AD even in early stages and predicting the conversion from mild cognitive impairment (MCI) to dementia. These biomarkers are invaluable not only for diagnosis but also for monitoring therapeutic responses in clinical trials and assessing the biochemical effects of disease-modifying treatments. This narrative review synthesizes the evolving role of CSF biomarkers in AD, focusing on their strategic application in enhancing diagnostic precision, enabling therapeutic monitoring, and facilitating clinical implementation. We explore the established utility of core CSF biomarkers, the development of novel markers, and the ongoing efforts to standardize assays and integrate these tools into routine clinical practice, ultimately aiming to improve patient outcomes and accelerate the development of effective AD interventions.
Cortisol as a stress biomarker: analytical perspectives and challenges.
Suryawanshi R, Sharma S
Clin Chim Acta · 2026 Jul · PMID 41999929 · Publisher ↗
Point-of-care testing (POCT) has emerged as a transformative approach in modern healthcare for the rapid detection of physiological abnormalities through minimally or non-invasively collected samples. Biological matrices...
Point-of-care testing (POCT) has emerged as a transformative approach in modern healthcare for the rapid detection of physiological abnormalities through minimally or non-invasively collected samples. Biological matrices such as saliva, urine, hair, blood, and interstitial fluid contain clinically significant biomarkers that may serve as indicators of physiological disorders. Among these, cortisol is the key stress biomarker and exerts substantial effects on body metabolism, acting on both peripheral tissues and the CNS. This review comprehensively outlines the evolution of cortisol detection strategies, progressing from conventional laboratory-based immunoassays to advanced analytical platforms, including electrochemical biosensors, wearable devices, and microfluidic systems. Accurate and reliable detection of elevated cortisol levels is crucial for improving diagnostic, therapeutic, and preventive strategies for stress-related disorders. By tracing the analytical window, the work describes the detection of cortisol from traditional immunoassays to innovative biosensing platforms. Moreover, recent advances in nanomaterials, sensor design, and data integration have enabled continuous, on-site monitoring of cortisol levels, thereby enhancing their applicability across diverse clinical and non-clinical settings. This integration of physiological insight with technological advancement provides a comprehensive overview of developments in cortisol assessment, connecting fundamental endocrine science with practical diagnostic applications. The review underscores the potential of next-generation POCT systems to improve early diagnosis, therapeutic monitoring, and personalized healthcare through real-time biomarker analysis.
New insights into the TB-IGRA: Impact of endotoxin in blood collection tubes on test results.
Huang B, Xia W, Wang J … +3 more , Liu C, Xu Y, Song W
Clin Chim Acta · 2026 Jul · PMID 41990987 · Publisher ↗
OBJECTIVE: To investigate the impact of the collection tube as an external factor contributing to high background signals in the tuberculosis-interferon gamma release assay (TB-IGRA), with a specific focus on the influen...
OBJECTIVE: To investigate the impact of the collection tube as an external factor contributing to high background signals in the tuberculosis-interferon gamma release assay (TB-IGRA), with a specific focus on the influence of endotoxin contamination in blood collection tubes. METHODS: We conducted a retrospective analysis of TB-IGRA test results and clinical data from 334 patients. Patients were stratified into high and low background value groups based on median IFN-γ levels in the negative control wells of the TB-IGRA test. Additionally, blood samples from 25 healthy subjects were collected using two brands of blood collection tubes- Brand 1 and Brand 2-to assess differences in background signal intensity. Endotoxin levels in both tube types were measured, and graded concentrations of exogenous endotoxin were added in vitro to blood samples to evaluate the impact on IFN-γ background levels in the TB-IGRA test. RESULTS: Among clinical samples, 31.44% (105/334) exhibited elevated background values (IFN-γ levels≥0.438 IU/mL). Patients in the high background signal group had higher levels of white blood cell, neutrophils, lymphocytes, monocytes, and C-reactive protein (P < 0.05). Notably, the use of Brand 1 tubes was associated with high background values (P < 0.001). In healthy subjects, the mean IFN-γ value obtained with Brand 1 tubes was significantly higher than that with Brand 2 tubes (0.407 vs. 0.180 IU/mL, P = 0.038). In vitro experiments demonstrated a dose-dependent increase in IFN-γ background levels following endotoxin exposure. CONCLUSION: Endotoxin contamination in blood collection tubes is a significant factor contributing to elevated background signals in TB-IGRA tests. Clinical laboratories should carefully consider the endotoxin control standards of blood collection tubes for use.
Convergence of multiplexed immunosensors, nanotechnology, and AI for early pancreatic cancer diagnosis.
Abuhassan Q, Mutee AF, Shareef A … +10 more , Pate PN, Jyothi SR, Singh G, Maharana L, Arora V, Polatova D, Sameer HN, Yaseen A, Athab ZH, Adil M
Clin Chim Acta · 2026 Jul · PMID 41985833 · Publisher ↗
Pancreatic cancer (PC) remains one of the deadliest malignancies, largely because of its asymptomatic onset, rapid progression, and absence of sensitive, specific tools for early detection at the population level. Conven...
Pancreatic cancer (PC) remains one of the deadliest malignancies, largely because of its asymptomatic onset, rapid progression, and absence of sensitive, specific tools for early detection at the population level. Conventional biomarkers such as carbohydrate antigen 19-9 (CA19-9) and standard imaging modalities offer limited performance in identifying pre-malignant or early-stage disease, underscoring the urgent need for next-generation diagnostic strategies. This narrative review examines the emerging convergence of multiplexed immunosensors, nanotechnology-enabled signal amplification, and artificial intelligence (AI)-driven data integration as a transformative framework for early PC diagnosis. We first summarize the evolving biomarker landscape, including circulating proteins, autoantibodies, exosomes, circulating tumor DNA, noncoding RNAs, and tumor-educated platelets, with an emphasis on multianalyte panels that capture tumor heterogeneity and tumor-host interactions. We then discuss the principles and design of multiplexed immunosensors across electrochemical, optical, and microfluidic formats and describe how nanomaterials such as nanoparticles, nanowires, quantum dots, and two-dimensional materials enhance analytical performance through increased surface area, improved biorecognition density, and engineered transduction mechanisms. Building on this foundation, we highlight integrated nanoimmunosensor platforms that combine microfluidics, lab-on-a-chip architectures and point-of-care configurations to enable low-volume, rapid, and potentially noninvasive testing from blood, saliva, or other biofluids. Finally, we explore how machine learning and deep learning models can fuse high-dimensional biosensor outputs with clinical, radiological, and genomic data to achieve robust feature selection, risk stratification, and individualized probability estimates for early PC.
Pentraxin-3, a complementary biomarker in hepatocellular carcinoma: Systematic review and Meta-analysis.
Amdetsion GY, Murali AR, Pan CW … +6 more , Miranda C, Sueldo A, Tebeje HG, Guifarro D, Kwei-Nsoro R, Kotwal V
Clin Chim Acta · 2026 Jun · PMID 41985832 · Publisher ↗
BACKGROUND: Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) diagnosis; however, its sensitivity is limited, especially for early-stage disease and in AFP-negative HCC cases. P...
BACKGROUND: Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) diagnosis; however, its sensitivity is limited, especially for early-stage disease and in AFP-negative HCC cases. Pentraxin-3 (PTX3), a marker of local inflammation and angiogenesis, may outperform AFP in detection by reflecting distinct biological pathways involved in hepatocarcinogenesis. METHODS: PubMed, Embase, Web of Science, Cochrane, and ClinicalTrials.gov were searched through December 2025 following PRISMA guidelines. Eligible studies included adults with chronic liver disease evaluated for suspected or established HCC. Pooled sensitivity and specificity were calculated using the bivariate Reitsma model, and the overall diagnostic performance was assessed using. sensitivity, specificity, and diagnostic odds ratio, along with determining the area under the curve (AUC). RESULTS: Five retrospective studies involving 1179 participants, including 362 patients with HCC, met the inclusion criteria. Using the bivariate Reitsma model, the pooled sensitivity and specificity of PTX3 were 0.79 (95% CI 0.74-0.84) and 0.83 (95% CI 0.76-0.88), respectively, with an AUC of 0.876. AFP alone showed a sensitivity of 0.76 (95% CI 0.70-0.80) and specificity of 0.81 (95% CI 0.74-0.86), with an AUC of 0.849. The combined PTX3 + AFP approach had sensitivity of 0.92 (95% CI 0.89-0.94), specificity of 0.85 (95% CI 0.77-0.90), with a DOR of 65.8 and an AUC of 0.942. CONCLUSIONS: PTX3 demonstrated diagnostic performance comparable to AFP; however, the combination of PTX3 and AFP was associated with higher pooled sensitivity.
Linc00261: A potential liquid biopsy biomarker for colorectal cancer early detection and prognosis.
Fathi D, Zaki MB, Abulsoud AI … +3 more , Al-Noshokaty TM, Fawzy A, Rizk NI
Clin Chim Acta · 2026 Jun · PMID 41974403 · Publisher ↗
BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death worldwide; thus, early diagnosis is crucial. Linc00261, a long noncoding RNA (lncRNA) linked to cancers, including CRC, requires clarification of its...
BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death worldwide; thus, early diagnosis is crucial. Linc00261, a long noncoding RNA (lncRNA) linked to cancers, including CRC, requires clarification of its clinical utility. This study explored plasma Linc00261 level in CRC patients and its association with progression. METHODS: Linc00261 expression was measured via qRT-PCR in vitro (CRC cell lines HCT116, Caco-2, SW620; normal colon line CCD 112 CoN) and in plasma from CRC patients (n = 90) and controls (n = 30). Conventional biomarkers CEA and CA 19.9 were measured via chemiluminescence. RESULTS: Linc00261 was significantly decreased in all CRC patients versus controls. Levels were significantly lower in both early-stage (I-II) and late-stage (III-IV) patients versus controls, in late-stage versus early-stage patients, and in stage IV versus stage III patients. Linc00261 was significantly negatively correlated with tumor stage, tumor size, CEA, and CA 19.9. Linc00261 also demonstrated superior diagnostic utility over CEA and CA 19.9 for CRC diagnosis. CONCLUSION: Linc00261 is a potential diagnostic/prognostic biomarker for CRC and may be an important molecular mediator in CRC pathogenesis.
MassARRAY-based targeted detection of SLC22A5 mutations: A feasibility study for secondary screening of primary carnitine deficiency in newborns.
Gong L, Zhao J, Li L … +7 more , Liu W, Wan Z, Tang Y, Wang S, Cai B, Zhao Y, Kong Y
Clin Chim Acta · 2026 Jun · PMID 41974402 · Publisher ↗
This study aimed to evaluate the feasibility of using MassARRAY molecular mass spectrometry to detect SLC22A5 gene mutations in second-tier screening for primary carnitine deficiency (PCD) among newborns. The goal is to...
This study aimed to evaluate the feasibility of using MassARRAY molecular mass spectrometry to detect SLC22A5 gene mutations in second-tier screening for primary carnitine deficiency (PCD) among newborns. The goal is to provide technical evidence to support improvements in PCD screening and to reduce diagnostic delays. We first reviewed literature and databases to identify commonly reported pathogenic variants in the SLC22A5 gene among the Chinese population and established a hotspot mutation panel. MassARRAY analysis was conducted on dried blood spot samples using multiplex PCR, single-base extension, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The constructed panel included 29 mutations with an estimated allele coverage of 87.3%, and the assay achieved a detection success rate of 99.75%. A total of 1200 neonates suspected of having PCD, identified via tandem mass spectrometry (MS/MS) between January 2023 and December 2024 in Beijing, were consecutively enrolled in this study. Out of the 1200 newborns, 125 (10.42%) carried at least one mutation: five cases (0.42%) had two variants and 120 cases (10%) had a single variant. A total of 991 samples (82.58%) were mutation-negative, though one case was a confirmed false negative. Incomplete mutation data were observed in 84 samples (7%). Among the 29 targeted sites, 19 mutations were detected (65.52%), with the most frequent being c.1400C > G (p.S467C), followed by c.51C > G (p.F17L), c.92C > T (p.P31L), and c.428C > T (p.P143L). Eight PCD cases were clinically confirmed; five were identified as having two mutations via MassARRAY, two had single mutations, and one showed no detectable mutation. MassARRAY-based detection of SLC22A5 mutations offers a viable method for second-tier PCD screening. It can reduce recall rates and false positives in initial MS/MS screening and shorten the diagnostic process. Further validation in larger cohorts and continued expansion of the mutation panel are recommended to enhance the accuracy of this method.
Electrochemical biosensing of circulating MicroRNAs in endometrial Cancer.
Patel N, Afzal M, Mishra R … +7 more , Upadhya S, Phalak P, Pandey SN, Thakur P, Shahwan M, Kalra A, Mishra R
Clin Chim Acta · 2026 Jun · PMID 41956145 · Publisher ↗
The global incidence of endometrial cancer (EC) is increasing; however, current diagnostic and surveillance methodologies, which rely on invasive sampling and imaging, are insufficient for detecting early molecular alter...
The global incidence of endometrial cancer (EC) is increasing; however, current diagnostic and surveillance methodologies, which rely on invasive sampling and imaging, are insufficient for detecting early molecular alterations and accurately predicting treatment resistance and recurrence. Circulating microRNAs (c-miRNAs) are promising minimally invasive biomarkers that reflect tumor biology and disease dynamics. Nevertheless, their application in laboratory medicine is limited due to their low concentrations in circulation, the high degree of sequence homology among miRNA family members, interference from isomiRs, and preanalytical variability, all of which compromise reproducibility and inter-laboratory comparability. Electrochemical biosensing is an emerging analysis platform in clinical chemistry because of its ability to directly transduce signal changes as a result of hybridization, high turnaround, capability to operate using low sample volumes, and compatibility with automated and decentralized workflows. The nanostructuring of electrodes, engineering of probes, and integration of microfluidic systems have significantly enhanced the sensitivity of analytical processes and improved multiplexing capabilities. However, some of the critical barriers to translation, such as the absence of standardized calibration and normalization protocols, inadequate validation in clinically relevant matrices (plasma/serum) and a complete comparison of methods with established reference procedures, such as quantitative PCR and digital PCR, are still present. This review critically evaluates c-miRNA signatures and electrochemical biosensing platforms in laboratory medicine, examining validation, quality assurance, and regulatory processes for clinically actionable assays supporting early detection, risk stratification, therapy monitoring, and recurrence assessment. The future use of clinical methods will hinge on their reproducibility in actual matrices, their traceability to reference methods, and their accreditation.
Methylated Septin9 as an auxiliary biomarker for the diagnostic, recurrence monitoring and prognosis of colorectal cancer.
Wang J, Li Y, Liu X … +2 more , Gao Q, Yi L
Clin Chim Acta · 2026 Jun · PMID 41941932 · Publisher ↗
OBJECTIVE: The liquid biopsy biomarker "methylated Septin9 (mSEPT9)" has emerged as a prominent tool in colorectal cancer (CRC) screening. This study aims to explore the clinical significance of mSEPT9 in the diagnosis,...
OBJECTIVE: The liquid biopsy biomarker "methylated Septin9 (mSEPT9)" has emerged as a prominent tool in colorectal cancer (CRC) screening. This study aims to explore the clinical significance of mSEPT9 in the diagnosis, evaluation of surgical efficacy, monitoring of recurrence, and prognostic assessment of colorectal cancer, while also comparing its performance with that of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). MATERIAL AND METHODS: We conducted a retrospective cohort study using clinical data from Xiangya Hospital of Central South University (March 2017-November 2024). Three independent patient groups were identified: (1) Diagnosis group: 461 treatment-naïve patients with newly diagnosed colorectal cancer (CRC); (2) Post-treatment group: 72 patients with CRC who underwent curative-intent resection and had paired plasma mSEPT9 measurements preoperatively and at postoperative day 7; (3) Recurrence-monitoring group: 138 patients with AJCC stage I-III CRC who underwent curative resection, for whom recurrence-free survival (RFS) was the primary endpoint and for whom preoperative and postoperative month 1 (POM1) plasma mSEPT9 levels were available-associations between mSEPT9 and RFS were evaluated using Kaplan-Meier analysis (log-rank test) and Cox proportional hazards regression. RESULTS: Plasma mSEPT9 detected CRC with 67.9% sensitivity (313/461) and 94.0% specificity in distinguishing patients from healthy controls (NED), yielding an AUC of 0.809, which was higher than that of CEA (0.692) and CA19-9 (0.584).The combination of mSEPT9, CEA, and CA19-9 achieved an AUC of 0.849 (P < 0.001 vs. mSEPT9 alone). Sensitivity increased with tumor stage: 22.2% (stage I), 65.2% (II), 66.2% (III), and 81.5% (IV). In the 72-patient post-treatment group, mSEPT9 positivity decreased from 61.1% preoperatively to 38.9% at 7 days postoperatively (P < 0.001). Among the 138 patients in the recurrence-monitoring group, 49 (35.5%) developed recurrence. Independent predictors of shorter RFS were POM1 mSEPT9 positivity (HR = 6.25, 95% CI: 3.29-11.88; P < 0.001), advanced N stage (HR = 3.43, 95% CI: 1.66-7.08; P = 0.001), perineural invasion (HR = 2.04, 95% CI: 1.08-3.85; P = 0.028), and preoperative CEA > 5 ng/mL (HR = 2.21, 95% CI: 1.06-4.61; P = 0.035). Patients positive for both POM1 mSEPT9 and preoperative CEA > 5 ng/mL had the shortest RFS (P < 0.001).For recurrence prediction, POM1 mSEPT9 achieved an AUC of 0.721 (sensitivity 51.0%, specificity 93.3%), POM1 CEA yielded an AUC of 0.616 (sensitivity 26.5%, specificity 96.6%), and their combination resulted in an AUC of 0.725. CONCLUSION: The mSEPT9 can be used as a sensitive and efficient indicator for CRC diagnosis and surgical efficacy evaluation, outperforming both CEA and CA19-9. A combined panel of mSEPT9, CEA, and CA19-9 was shown to achieve superior diagnostic performance compared to mSEPT9 alone. More significantly, our findings highlight the significant value of mSEPT9 in monitoring postoperative recurrence and metastasis in CRC patients. Specifically, mSEPT9 detection at one month after surgery could be an independent predictor, capable of predicting the recurrence or metastasis of CRC.
Evaluation of a fluorescent-based point-of-care AMH assay: A bicentric assessment of analytical performance, method agreement, and usability.
Khatib A, Gruson D, Azariouh I … +3 more , Draoui S, Zreikat W, K Nasrallah G
Clin Chim Acta · 2026 Jun · PMID 41933681 · Publisher ↗
BACKGROUND: Anti-Müllerian hormone (AMH) measurement is central to ovarian reserve assessment but remains affected by inter-method variability among immunoassays. Point-of-care testing (POCT) enables rapid and decentrali...
BACKGROUND: Anti-Müllerian hormone (AMH) measurement is central to ovarian reserve assessment but remains affected by inter-method variability among immunoassays. Point-of-care testing (POCT) enables rapid and decentralized AMH testing; however, independent evaluation of analytical performance and agreement with routine laboratory methods is required prior to clinical implementation. OBJECTIVE: To evaluate the analytical performance, method agreement, and usability of a fluorescent-based point-of-care AMH assay using a bicentric study design. METHODS: Analytical precision and trueness were assessed at two independent sites using three levels of quality control material. Method comparison was performed on 304 anonymized residual serum samples from routine laboratory requests, including infertility assessment, polycystic ovary syndrome (PCOS) investigation, in vitro fertilization (IVF) monitoring, and cancer surveillance, covering a clinically relevant AMH range (0.1-13 ng/mL). Statistical analyses included Passing-Bablok regression, Spearman correlation, and Bland-Altman analysis. System usability was assessed using a structured questionnaire. RESULTS: A strong correlation was observed between the POCT AMH assay and the routine laboratory method (Spearman r = 0.967, p < 0.0001). Passing-Bablok regression showed a slope of 0.925 and an intercept of 0.213, indicating a proportional bias. Quality control imprecision ranged from 4.1% to 13.6% (CV), with positive biases between 2.9% and 17.8%. A concentration-dependent pattern was observed, with overestimation at low concentrations, increased deviation in the mid-range, and near-equivalence at higher values. Bland-Altman analysis confirmed greater dispersion at low-to-mid AMH levels. Usability evaluation indicated high ease of use and limited training requirements. CONCLUSIONS: The fluorescent-based AMH POCT assay demonstrated acceptable analytical performance, strong correlation with a routine laboratory method, and favourable usability. However, until harmonisation across methods is achieved, cautious interpretation and confirmatory laboratory testing remain essential when results are close to clinical decision thresholds.
Small extracellular vesicles as biomarkers and therapeutic targets in breast Cancer.
Saleh KA, Mutee AF, Kubaev A … +4 more , Ochilova D, Salih RM, Jaber MA, Hussen S
Clin Chim Acta · 2026 Jun · PMID 41933680 · Publisher ↗
Small extracellular vesicles (sEVs) represent a novel frontier in oncology, functioning as critical mediators of intercellular communication that profoundly influence the biology of breast cancer. These nano-sized partic...
Small extracellular vesicles (sEVs) represent a novel frontier in oncology, functioning as critical mediators of intercellular communication that profoundly influence the biology of breast cancer. These nano-sized particles, typically ranging from 30 to 200 nm in diameter, are released by virtually all cell types into the extracellular space and circulate in biofluids like blood, urine, and saliva. Encased within a lipid bilayer, sEVs carry a complex molecular payload including proteins, lipids, various nucleic acids like microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and metabolites that reflects the physiological or pathological state of their parent cell. In the context of breast cancer, these vesicles are not merely cellular debris but are active participants in orchestrating tumor progression, shaping the tumor microenvironment (TME), facilitating metastasis, and mediating resistance to therapies. This dual nature positions sEVs at the heart of precision medicine, offering immense potential as minimally invasive "liquid biopsies" for real-time diagnosis, prognosis, and treatment monitoring, while simultaneously presenting themselves as powerful tools for targeted therapeutic intervention. This review provides a comprehensive investigation into the multifaceted roles of sEVs in breast cancer, examining their applications as biomarkers and therapeutic targets across all major subtypes, integrating insights on underlying biological mechanisms, and critically evaluating their path toward clinical translation.
LC-MS/MS methods for synthetic opioids in urine: analytical and clinical evaluation.
Al S, Kul A, Sagirli O
Clin Chim Acta · 2026 Jun · PMID 41933679 · Publisher ↗
Opioids are potent analgesic compounds that exert their effects on the central nervous system and are widely used in clinical practice; however, their increasing misuse and associated health risks necessitate reliable an...
Opioids are potent analgesic compounds that exert their effects on the central nervous system and are widely used in clinical practice; however, their increasing misuse and associated health risks necessitate reliable and sensitive analytical monitoring. Urine remains the primary biological matrix for assessing compliance and detecting illicit opioid use. This review critically evaluates liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for the determination of buprenorphine, methadone, tramadol, fentanyl, and pethidine in urine. Across the reviewed studies, diverse sample preparation strategies were employed, with calibration ranges typically reported at the ng/mL level. Limits of detection ranged from 0.005 to 10 ng/mL, while limits of quantification varied between 0.025 and 208 ng/mL. Analysis times ranged between approximately 2.5 and 24 min, reflecting differences in analytical throughput and chromatographic resolution. Sample preparation strategies, including solid-phase extraction, liquid-liquid extraction, and microextraction techniques, were critically compared in terms of recovery, matrix effects, and efficiency. Chromatographic separation predominantly relied on C18 columns with mobile phases containing formic acid, ammonium formate, or ammonium bicarbonate, and all methods applied positive electrospray ionization. Importantly, analytical trade-offs between opioid-specific assays and broader multi-analyte LC-MS/MS workflows were identified, particularly regarding sensitivity, metabolite coverage, and robustness against matrix effects. Overall, LC-MS/MS remains the most reliable confirmatory approach for urinary opioid analysis; however, challenges persist in the harmonization of analytical protocols, differentiation of structurally similar analogs, and standardization of matrix-effect evaluation. Future developments should focus on harmonization and integration of advanced analytical strategies to enhance clinical and forensic applicability.
Circulating biomarkers in bladder cancer: emerging evidence and future directions for personalized therapy.
AlRamadneh TN, Mutee AF, Kubaev A … +4 more , Qayumova S, Salih RM, Jaber MA, Hussen S
Clin Chim Acta · 2026 Jun · PMID 41933678 · Publisher ↗
Bladder cancer diagnosis and surveillance remain anchored in cystoscopy and urine cytology, despite their invasiveness, operator dependence, and limited sensitivity for low-grade or flat lesions. These constraints have a...
Bladder cancer diagnosis and surveillance remain anchored in cystoscopy and urine cytology, despite their invasiveness, operator dependence, and limited sensitivity for low-grade or flat lesions. These constraints have accelerated interest in liquid biopsy approaches that provide noninvasive, real-time molecular insights into tumor biology. This narrative review examines emerging evidence on three key classes of circulating biomarkers, namely, circulating tumor DNA (ctDNA), exosomes, and circulating tumor cells (CTCs), and their expanding roles in diagnosis, prognosis, and treatment guidance. ctDNA reflects tumor-specific genomic alterations and shows particular strength in detecting minimal residual disease, identifying early molecular relapse, and monitoring therapeutic response, although its diagnostic sensitivity remains moderate. Urinary exosomes demonstrate some of the highest diagnostic accuracies among liquid biopsy platforms, with multimarker RNA panels achieving sensitivities and specificities above 90%, while their diverse cargo of miRNAs, mRNAs, and lncRNAs provides robust prognostic information linked to recurrence and survival. CTCs, although technically challenging to isolate owing to their phenotypic heterogeneity, offer valuable insights into tumor aggressiveness, metastatic potential, and treatment responsiveness, especially in muscle-invasive disease. Advances in ultrasensitive sequencing, microfluidic CTC capture, and multi-omics integration are accelerating clinical translation. Collectively, circulating biomarkers are poised to complement and, in selected contexts, transform bladder cancer management by enabling earlier detection, individualized risk stratification, and more precise therapeutic decision-making.
Development of a novel high-affinity anti-NGAL monoclonal antibody pair for sensitive detection of acute kidney injury.
Liao N, Duan C, Liu J … +8 more , Peng S, Zhang S, Wan T, Deng X, Zhang X, Qiu Y, Hou D, Liu R
Clin Chim Acta · 2026 Jun · PMID 41932421 · Publisher ↗
Neutrophil Gelatinase-Associated Lipocalin (NGAL) is an early marker for Acute Kidney Injury (AKI) recommended by the International Society of Nephrology (ISN). This study obtained recombinant NGAL protein via a prokaryo...
Neutrophil Gelatinase-Associated Lipocalin (NGAL) is an early marker for Acute Kidney Injury (AKI) recommended by the International Society of Nephrology (ISN). This study obtained recombinant NGAL protein via a prokaryotic expression system. After immunizing BALB/c mice, four NGAL-specific monoclonal antibodies were screened using hybridoma technology. Through paired screening, mAb-14/mAb-21 was identified as the optimal antibody pair. Based on this, two immunological detection methods were preliminarily established: magnetic particle chemiluminescence assay (MPs-CLIA) and colloidal gold immunochromatography assay (GICA). According to the performance evaluation, MPs-CLIA exhibited a detection limit of 0.53 ng/mL across a range of 15.625-500 ng/mL, with a superb fit (R = 0.9996). It demonstrated a significant association with the commercial kit (R = 0.9489, r = 0.9499, P < 0.0001). The recovery rate for spiked samples ranged from 92.08% to 92.33% (CV < 10%). In clinical serum samples, GICA obtained 97.5% accuracy and detected analytes down to 12.5 ng/mL. The established detection system addresses diverse application needs, ranging from highly sensitive quantification to rapid screening, and provides a reliable technical solution for the early diagnosis of AKI.
Corrigendum to "Engineered Bacteria as living detectors of tumor DNA: A new diagnostic frontier" [Clin. Chim. Acta 586 (2026) 120914].
Ghasemian A, Al-Marzoqi AH, Al-Taee ZM … +5 more , Norouzi F, Abdollahi A, Montaseri Z, Memariani M, Zarenezhad E
Clin Chim Acta · 2026 Mar · PMID 41925390 · Publisher ↗
Abstract loading — click title to view on PubMed.
Novel biomarkers for early diagnosis and treatment strategies of diabetic retinopathy: A comprehensive review.
Saravanan K, Elavarasi S, Revathi G … +3 more , Karuppannan P, Ashokkumar M, Kumar KJS
Clin Chim Acta · 2026 Jun · PMID 41921728 · Publisher ↗
Diabetic retinopathy (DR) is one of the most frequent microvascular complications of diabetes mellitus, and one of the most frequent causes of avoidable blindness in working-age adults. Although it is common, early detec...
Diabetic retinopathy (DR) is one of the most frequent microvascular complications of diabetes mellitus, and one of the most frequent causes of avoidable blindness in working-age adults. Although it is common, early detection of DR in asymptomatic patients is a difficult task because it does not have any dependable biomarkers. Nowadays, DR is normally diagnosed at very late stages when characteristic morphological lesions can be observed through the fundoscope. The chronic hyperglycemia results in specific changes in the retinal vessel calibre, blood flow, oxygen saturation, and capillary network structure, which precede the development of apparent DR lesions. The available evidence indicates that neurodegenerative alterations in the retina start at an early stage of diabetes, and the disintegration of the retinal neurovascular unit precedes the onset of microvascular damage. This review explains the major biomarkers used in the early diagnosis of DR, their possible role in the detection of persons at high risk of development. The validation of these biomarkers would probably contribute significantly to early diagnosis and enable the creation of personal treatment plans, which would positively affect clinical outcomes and prevent the loss of vision.
Integrating multi-omics data and artificial intelligence for personalized medicine in glioblastoma.
Abuhassan Q, Al-Ameer HJ, Patel PN … +5 more , Jyothi SR, Singh G, Maharana L, Arora V, Khalikova N
Clin Chim Acta · 2026 Jun · PMID 41921727 · Publisher ↗
Glioblastoma (GBM) is one of the most lethal primary brain tumors and is characterized by profound molecular heterogeneity, rapid progression, and limited therapeutic responsiveness. Traditional diagnostic and treatment...
Glioblastoma (GBM) is one of the most lethal primary brain tumors and is characterized by profound molecular heterogeneity, rapid progression, and limited therapeutic responsiveness. Traditional diagnostic and treatment paradigms have struggled to capture the complex, multilayered biology that drives GBM evolution. Recent advances in multi-omics technologies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and single-cell profiling, have offered unprecedented resolution into the tumor ecosystem, revealing actionable biomarkers and mechanistic pathways. In parallel, artificial intelligence (AI) and machine learning (ML) have emerged as transformative tools capable of integrating high-dimensional omics data with clinical, radiological, and pathological information to generate predictive models for diagnosis, prognosis, and treatment response. This narrative review synthesizes current progress in multi-omics-AI integration for GBM, highlighting methodological innovations, emerging biomarker signatures and applications in precision oncology. We discuss challenges related to data harmonization, interpretability, model generalizability, and clinical translation and outline future directions for building robust, ethically grounded, and clinically deployable AI-driven personalized medicine frameworks. Together, multi-omics and AI have the potential to redefine GBM management by enabling individualized therapeutic strategies and accelerating the discovery of novel targets.
Inflammatory-nutritional biomarker scores and risk of malignant effusion in a pan-cancer cohort of 68,916 patients: Nonlinear associations and machine learning validation.
Haoyu Liu RN, Yunhui Chen RN, Shouyan Wang RN
Clin Chim Acta · 2026 Jun · PMID 41921726 · Publisher ↗
PURPOSE: Inflammatory-nutritional biomarker scores derived from routine blood tests have established prognostic value in cancer, yet their association with the occurrence of malignant effusions remains unexplored. This s...
PURPOSE: Inflammatory-nutritional biomarker scores derived from routine blood tests have established prognostic value in cancer, yet their association with the occurrence of malignant effusions remains unexplored. This study systematically evaluated six composite scores: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), and albumin-to-globulin ratio (AGR), for their nonlinear associations with cancer-related malignant effusion, and constructed an interpretable machine learning (ML) model to independently validate the role of the nutritional-immune axis. METHODS: This cross-sectional study included 68,916 cancer inpatients (2333 effusion events; 3.39%). Track 1 employed DAG-guided multivariable logistic regression and restricted cubic splines for nonlinear modeling; Track 2 built an XGBoost identification model via nested cross-validation with SHAP interpretability analysis. RESULTS: All six scores were independently associated with malignant effusion (all P < 0.0001). PNI exhibited the strongest protective association (adjusted OR 0.492 per SD increase) and the highest discrimination (AUC 0.697). Restricted cubic splines revealed significant nonlinear relationships with clinically actionable inflection points. The XGBoost model achieved AUROC 0.867; SHAP identified albumin and lymphocyte percentage, the core components of PNI and LMR, respectively, as top modifiable features, converging with Track 1 findings. CONCLUSION: Six blood-derived inflammatory-nutritional scores show independent, nonlinear associations with malignant effusion risk. Convergent statistical and ML evidence supports integrating these accessible biomarkers into early risk stratification, warranting prospective validation.
Emerging LncRNA HOTAIR and NME1 polymorphisms in ovarian cancer risk: A pilot case-control study in South Indian women.
Sistla HC, Seshachalam A, Rathnam KK … +3 more , Rajagopal T, Talluri S, Dunna NR
Clin Chim Acta · 2026 Jun · PMID 41921725 · Publisher ↗
BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly recognized as clinically relevant regulators of cancer susceptibility, progression, and therapeutic response. However, the contribution of low-penetrance geneti...
BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly recognized as clinically relevant regulators of cancer susceptibility, progression, and therapeutic response. However, the contribution of low-penetrance genetic variants affecting lncRNAs and metastasis suppressor genes to ovarian cancer (OC) risk remains incompletely defined. In this population-based case-control study, we evaluated the genetic and clinical relevance of polymorphisms in HOTAIR (rs1899663, rs920778) and NME1 (rs2302254, rs16949649) in South Indian women for the first time. MATERIALS & METHODS: A total of 494 subjects (240 OC patients and 254 age-matched controls) were enrolled. Genomic DNA was isolated from peripheral whole blood, and genotyping was performed using the PCR-RFLP method. Logistic regression models were applied to estimate OC risk, while linkage disequilibrium (LD), haplotype, and clinicopathological correlation analyses were conducted to assess combined genetic effects on the disease susceptibility. RESULTS: Both HOTAIR variants showed significant associations with increased OC susceptibility. Carriers of the rs1899663 G/T and T/T genotypes exhibited 2.88- and 2.23-fold elevated risk, respectively (p < 0.001), while the rs920778 C/C genotype conferred a 2.24-fold increased risk (p = 0.006). NME1 rs2302254 was also strongly associated with OC risk, particularly the T/T genotype (OR = 3.79; p < 0.0001), whereas rs16949649 showed no significant effect. Clinically, rs920778 correlated with tumor stage and age at onset, and rs2302254 was associated with advanced disease stage. Gene-specific haplotype analysis revealed significant associations for HOTAIR (T-C and T-T) and NME1 (T-T and C-T) haplotypes with OC risk (global p < 0.001), although LD between variants within each locus was weak, suggesting largely independent allelic contributions. CONCLUSION: Overall, these findings suggest that HOTAIR and NME1 polymorphisms may contribute to genetic susceptibility in OC and warrant further investigation and functional validation in larger, well-characterized cohorts for their potential utility as biomarkers for risk stratification.
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