Clinical biochemistry最新文献

{"title":"Reframing liver test abnormalities after AAV gene therapy: a mechanistic diagnostic framework.","authors":"Brandon Michael Henry, Bernard Benichou, Melvin Y Rincon, Giuseppe Lippi, Lorenzo D'Antiga","doi":"10.1016/j.clinbiochem.2026.111217","DOIUrl":"https://doi.org/10.1016/j.clinbiochem.2026.111217","url":null,"abstract":"<p><p>Hepatotoxicity remains one of the most frequent and clinically important safety concerns in adeno-associated virus (AAV) gene therapy. Yet the laboratory patterns observed after vector administration are biologically complex and often difficult to interpret. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations are non-specific, as they may arise from AAV-induced innate and adaptive immune recognition of vector capsid, endoplasmic reticulum stress, mitochondrial strain, cholestasis, or background muscle turnover, especially in neuromuscular disorders where ALT and AST frequently exceed upper limits of normal at baseline. Traditional drug-induced liver injury frameworks, which rely on fixed multiples of population-derived reference ranges, are poorly suited to these settings and risk both overcalling benign changes and overlooking evolving toxicity. This clinical practice review outlines a mechanism-anchored strategy for interpreting hepatic biomarkers in AAV trials. We describe how vector tropism, intracellular capsid burden, and immune kinetics shape post-dose laboratory trajectories across systemic, liver-directed, and neuromuscular programs. The tissue specificity and kinetic behavior of hepatic biomarkers are examined to show why no single analyte is reliable in isolation. A personalized, baseline-anchored interpretive approach is proposed, with quantitative criteria for AAV-associated liver injury and phenotype-based classifications tailored to pediatric, neuromuscular, and liver disease populations. Finally, we translate these biological principles into a practical clinical framework emphasizing enzyme trajectory, corroboration with hepatic markers such as gamma glutamyl transferase (GGT), recognition of delayed adaptive immune responses, and early attention to bilirubin or international normalized ratio (INR) drift. Together, these concepts provide a structured and biologically grounded approach, proposed here, for interpreting liver tests after AAV gene therapy, strengthening safety monitoring while preserving transgene expression and trial integrity.</p>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"111217"},"PeriodicalIF":2.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of a large automated Analyzer system in clinical biochemistry laboratories: A practical framework.","authors":"Felix Leung","doi":"10.1016/j.clinbiochem.2026.111212","DOIUrl":"10.1016/j.clinbiochem.2026.111212","url":null,"abstract":"<p><p>Automation has become essential in clinical biochemistry laboratories to meet increasing demands for efficiency, standardization, and reliable turnaround times. Large automated analyzer (LAA) systems are now central to modern laboratory operations and are frequently integrated within total laboratory automation solutions encompassing pre-analytical, analytical, and post-analytical workflows. However, the implementation of LAA systems is complex and requires coordinated oversight across scientific, operational, informatics, and vendor stakeholders. This article presents a practical framework for the validation and implementation of LAA systems from the perspective of a clinical biochemist. Key aspects discussed include pre-implementation planning, management of unanticipated challenges, and implementation strategy with real world examples from our institutional experience. The overall goal of this article is to demonstrate that approaching LAA implementations with structured planning, effective collaboration, and risk-based decision-making can ensure implementation success in terms of analytical quality, operational continuity, and patient safety.</p>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"111212"},"PeriodicalIF":2.3,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating phosphatidylserine as a plasma biomarker for clinical staging and prognostic prediction in Parkinson's disease: A diagnostic validation study.","authors":"Haiqing Shen, Peili Sun, Beihai Ge, Jing Xiao, Xianyan Han","doi":"10.1016/j.clinbiochem.2026.111213","DOIUrl":"https://doi.org/10.1016/j.clinbiochem.2026.111213","url":null,"abstract":"<p><strong>Background: </strong>Circulating phosphatidylserine (cPS) may reflect neuronal injury in Parkinson's disease (PD), yet its diagnostic and prognostic utility remains unvalidated. This study aimed to evaluate cPS as a plasma biomarker for PD staging and outcome prediction.</p><p><strong>Methods: </strong>In this 24-month prospective cohort (STARD-compliant), 120 PD patients (40 early Hoehn and Yahr scale [H&Y] I-II, 40 moderate III, 40 advanced IV-V) and 40 matched controls were enrolled. cPS was quantified via ELISA. Disease severity was assessed by MDS-UPDRS-III and H&Y staging; outcomes included Barthel Index (BI≤40 defining poor prognosis) and cognitive decline (≥4-point Montreal Cognitive Assessment [MoCA] drop). Statistical analyses involved Spearman correlations, ROC curves, mixed-effects models, and multivariable regressions.</p><p><strong>Results: </strong>Baseline cPS increased with PD severity (control: 35.2 ± 8.45 vs. advanced: 89.45 ± 15.20 ng/mL, P < 0.001), correlating strongly with H&Y stage (ρ = 0.862, P < 0.001), MDS-UPDRS-III (ρ = 0.793, P < 0.001), and BI decline (ρ = -0.817, P < 0.001). ROC analysis showed cPS differentiated advanced vs. early PD with the highest AUC (0.95, 95% CI: 0.90-0.99, cutoff = 67.7 ng/mL, sensitivity = 97.0%, specificity = 82.0%). Longitudinal cPS increases were stage-dependent (early: +6.10 ± 2.45, moderate: +10.30 ± 3.15, advanced: +14.25 ± 4.50 ng/mL/year, P < 0.001). Multivariate Cox regression identified baseline cPS as an independent predictor of 24-month functional decline (BI ≤40: adjusted HR = 1.620, 95% CI: 1.382-1.898, P < 0.001). Logistic regression showed cPS predicted cognitive decline (MoCA ≥4-point drop: adjusted OR = 1.485, P < 0.001), independent of age and education.</p><p><strong>Conclusions: </strong>cPS levels correlate with PD severity, predict functional and cognitive decline, and exhibit stage-specific longitudinal changes, supporting cPS as a candidate biomarker for PD monitoring, though further validation is required.</p>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"111213"},"PeriodicalIF":2.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WITHDRAWN: Multiple myeloma revealed by a pulmonary embolism, with more anodal migration of λ IgG in the β₂ region on serum protein electrophoresis.","authors":"Chaymae Benmoussa, Ayoub Baroudi, Oumayma Abdesselami, Kaoutar Ghomari, Dounia El Moujtahide, El Houcine Sebbar, Mohammed Choukri","doi":"10.1016/j.clinbiochem.2026.111128","DOIUrl":"10.1016/j.clinbiochem.2026.111128","url":null,"abstract":"<p><strong>Introduction: </strong>Serum protein electrophoresis (SPE) is widely used to detect monoclonal gammopathies and other hematologic or inflammatory disorders. IgG monoclonal proteins typically migrate in the gamma region, while IgA frequently migrates in the beta region. However, IgG migration in the β₂ region is an exceptionally rare occurrence that can pose significant diagnostic challenges.</p><p><strong>Case presentation: </strong>We present the case of a 76-year-old woman who was initially diagnosed with acute bilateral pulmonary embolism and deep vein thrombosis as the first clinical manifestation of multiple myeloma. Laboratory findings revealed hypercalcemia, mild anemia, and a monoclonal IgG lambda peak in the β₂ region, which was confirmed by immunofixation. Echocardiography revealed left ventricular dilation with preserved right-sided heart structures. Ten days later, the patient developed cauda equina syndrome due to spinal involvement, requiring urgent surgical decompression.</p><p><strong>Discussion: </strong>This case highlights three exceptionally rare and clinically significant features: (1) IgG monoclonal protein migration in the β₂ region, (2) pulmonary embolism as the first manifestation of multiple myeloma, and (3) severe skeletal complications after minimal trauma. Clinicians should consider underlying monoclonal gammopathy in unexplained thromboembolic events and exercise caution when interpreting atypical SPE patterns, which may be crucial for early diagnosis. The unusual combination of these findings underscores the importance of a comprehensive approach to diagnosing plasma cell disorders.</p><p><strong>Conclusion: </strong>Recognition of more anodal IgG migration and awareness of thromboembolic presentation are crucial to ensure early diagnosis and appropriate management of multiple myeloma.</p>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":" ","pages":"111128"},"PeriodicalIF":2.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibody testing in neuromuscular medicine: assay technologies, interpretation, and clinical utility","authors":"Tony Zhang ,&nbsp;John R. Mills ,&nbsp;Divyanshu Dubey ,&nbsp;Christopher J. Klein","doi":"10.1016/j.clinbiochem.2026.111092","DOIUrl":"10.1016/j.clinbiochem.2026.111092","url":null,"abstract":"<div><div>Neuromuscular autoantibody testing is an essential component in the diagnosis and management of autoimmune neuromuscular disorders. These immune-mediated diseases target antigens found in nerves, muscles, and neuromuscular junctions, and may occasionally involve the central nervous system, resulting in complex clinical presentations. Developments in antibody identification and validation have provided clinically relevant biomarkers for diagnostic, therapeutic, and prognostic purposes. Among antibody-associated neuromuscular disorders, paraneoplastic onconeural autoantibodies are of particular significance, as their presence may direct search for specific underlying malignancies. Appropriate ordering and interpretation of these tests should be integrated with clinical and electrodiagnostic (CEDX) findings. Given that these disorders are often rare, estimating an optimal pre-test probability is important to improve test accuracy and reduce false positive outcomes. Online clinical calculators are available to help clinicians determine appropriate testing strategies for some disorders. This review summarizes principal neuromuscular antibodies, current testing approaches, and the influence of laboratory data on patient care.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"142 ","pages":"Article 111092"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence-based extension of reagent shelf-life beyond expiry using patient-based moving averages, westgard sigma rules, and CLSI EP25","authors":"Mohamed Mokhtar Khelil ,&nbsp;Tony Badrick","doi":"10.1016/j.clinbiochem.2026.111094","DOIUrl":"10.1016/j.clinbiochem.2026.111094","url":null,"abstract":"<div><h3>Background</h3><div>Reagent stability is a significant determinant of analytical reliability in clinical laboratories. Post-expiry reagent use is often discouraged due to the potential risk of systematic bias; however, empirical data supporting or refuting such restrictions are limited.</div></div><div><h3>Methods</h3><div>This study evaluated the post-expiry performance of free T3 (FT3) and free T4 (FT4) immunoassays on the Abbott Architect i1000SR analyzer using an integrated framework combining three complementary approaches: (i) a simulation-optimized moving average (MA) model based on real patient data (ii) Westgard Sigma rules quality control, and (iii) Clinical and Laboratory Standards Institute EP25-A drift analysis. The MA was optimised via Monte Carlo simulations using a step-shift bias model, which defined the optimal window size (N) for 90% detection power and 0% false rejection rate. Stability was then assessed across three reagent lots per analyte, spanning both pre- and post-expiration phases.</div></div><div><h3>Results</h3><div>Westgard rules provided the earliest analytical alerts, while EP25 confirmed sustained drift relative to allowable total error. The MA detected progressive instability, showing strong concordance with EP25 after lag correction (N × cadence). FT4 indicated extended stability of up to 19 months post-expiry, while FT3 showed limited stability (&lt;4 months). These differences reflected distinct assay robustness and kinetics.</div></div><div><h3>Conclusions</h3><div>The combination of Westgard sigma rules, EP25, and simulation-optimized MA provides a reproducible, data-driven framework for post-expiry reagent stability assessment. Optimizing MA with real patient data enhances detection performance, bridging theoretical quality-control design and routine laboratory application. This integrated approach enables laboratories to make scientifically justified, cost-effective decisions regarding reagent reuse beyond manufacturer expiry dates.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"142 ","pages":"Article 111094"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Improving the environmental impact paradox of clinical medical laboratories” [Clin. Biochem. 141 (2026) 111063]","authors":"Pernilla Sörme,&nbsp;Scott Weitze","doi":"10.1016/j.clinbiochem.2026.111091","DOIUrl":"10.1016/j.clinbiochem.2026.111091","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"142 ","pages":"Article 111091"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interference and failure: The challenge of high-concentration IgM monoclonal protein in capillary zone electrophoresis","authors":"Yanhua Zhao,&nbsp;Minjie Zhang,&nbsp;Wei Gan","doi":"10.1016/j.clinbiochem.2026.111099","DOIUrl":"10.1016/j.clinbiochem.2026.111099","url":null,"abstract":"<div><h3>Background</h3><div>Capillary zone electrophoresis (CZE) is a standard method for serum protein separation, but its performance can be compromised by IgM monoclonal proteins, leading to false-negative results.</div></div><div><h3>Methods</h3><div>We report a case of Waldenström macroglobulinemia (IgM 56.05 g/L) with repeated CZE failure. Immunofixation electrophoresis (IFE) confirmed an IgM kappa monoclonal protein. Four pretreatment protocols were evaluated: 1) 37°C incubation; 2) dilution with distilled water; 3) dilution with 0.9% saline; and 4) pretreatment with β‑mercaptoethanol (BME). Gel-based serum protein electrophoresis (SPE) and immunosubtraction CZE were also performed to investigate the interference mechanism.</div></div><div><h3>Results</h3><div>Initial CZE failed to yield an interpretable electrophoretogram. Incubation at 37°C showed no improvement. Dilution with distilled water induced visible precipitation and resulted in a false-negative electrophoretic pattern with a marked drop in measured total protein. Dilution with saline prevented precipitation but still failed to reveal a distinct monoclonal spike, despite biochemical measurements consistent with high globulin levels. In contrast, pretreatment with BME successfully restored a clear monoclonal spike in the β‑γ region on CZE, demonstrating restored solubility and proper migration. IFE corroborated the presence of the IgM kappa monoclonal protein. Gel-based SPE successfully showed a distinct M-protein band without interference, while immunosubtraction CZE failed under both temperature conditions, supporting cryoglobulin-related interference.</div></div><div><h3>Conclusions</h3><div>Very high IgM concentrations, particularly with cryoglobulin activity, can cause complete CZE failure not resolved by standard dilution or heating. The interference likely involves capillary obstruction from protein aggregation or temperature-dependent re-precipitation within the capillary. BME pretreatment is a critical intervention for unmasking IgM monoclonal proteins when CZE results are inconsistent with other laboratory findings, thereby preventing diagnostic errors.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"142 ","pages":"Article 111099"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing precision, bias, and sigma metrics of 22 measurands using Ricos and EFLM specifications and implementation of internal quality control procedure in clinical chemistry laboratory","authors":"Khouloud Hkimi ,&nbsp;Sonia Gara","doi":"10.1016/j.clinbiochem.2026.111108","DOIUrl":"10.1016/j.clinbiochem.2026.111108","url":null,"abstract":"<div><h3>Background</h3><div>The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) biological variation (BV) database is currently the reference source for BV-based specifications, providing evidence-based and more stringent limits than the historical Ricos database.</div></div><div><h3>Objective</h3><div>This study aimed to assess the impact of the transition from old to updated BV goals on sigma metrics in our laboratory.</div></div><div><h3>Methods</h3><div>The study was conducted at the National Institute of Salah Azaiz medical biology laboratory over an 8-month period. It included 22 biological parameters for which coefficients of variation and biases were calculated using internal and external quality control materials. Sigma metrics were determined using Ricos and the EFLM desirable specifications.</div></div><div><h3>Results</h3><div>Using Ricos desirable specifications, 27.3% of analytes (ALT, CK, iron, total bilirubin, triglycerides, and CA19-9) achieved sigma ≥ 6, 36.4% had sigma between 3 and 6 (AST, LDH, urea, uric acid, AFP, CEA, CA125, and CA15-3), and 36.4% had sigma &lt; 3 (calcium, creatinine, glucose, magnesium, potassium, sodium, total cholesterol, total protein). With the stricter EFLM targets, 6 sigma performers decreased to 19.1% (CK, iron, total bilirubin, triglycerides). 28.5% of analytes had sigma between 3 and 6 (ALT, AST, urea, uric acid, CEA, CA19-9), and 52.4% had sigma &lt; 3 (calcium, creatinine, glucose, LDH, magnesium, potassium, sodium, total cholesterol, total protein, AFP and CA125). The resulting internal quality control strategy hence differed. The quality goal index indicated that imprecision was the main limitation for most analytes.</div></div><div><h3>Conclusions</h3><div>Updating performance specifications from the historical Ricos database to the evidence-based EFLM resulted in more stringent BV goals that are challenging to achieve with current routine technologies. Intensified root-cause analysis, closer collaboration with manufacturers, and ongoing performance reassessment are necessary for poor performers.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"142 ","pages":"Article 111108"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel fibrinogen mutations in pediatric patients: implications for neonatal coagulation screening and family genetic counseling","authors":"Jie Jiang","doi":"10.1016/j.clinbiochem.2026.111102","DOIUrl":"10.1016/j.clinbiochem.2026.111102","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"142 ","pages":"Article 111102"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}