Clinical Biochemistry[JOURNAL]
Sun
200 papers
Analytical Imprecision and Therapeutic Intervals for Lithium - Are There Implications for Old Age Patients with Bipolar Disorder?
Zhou J, Tsoukalas D, Chittiprol N … +9 more , Kavsak P, Leung F, Taher J, Ali-Mohammed Z, Arnoldo S, Tysick H, Fu L, Love SA, Selvaratnam R
Clin Biochem · 2026 Jan · PMID 41253218 · Publisher ↗
BACKGROUND: Monitoring blood levels of lithium is important for maintaining therapeutic efficacy. Age-dependent therapeutic intervals have been recommended by the International Society for Bipolar Disorder (ISBD) task fo...
BACKGROUND: Monitoring blood levels of lithium is important for maintaining therapeutic efficacy. Age-dependent therapeutic intervals have been recommended by the International Society for Bipolar Disorder (ISBD) task force, 0.4-0.8 mmol/L and 0.4-0.7 mmol/L for adults aged 60-79 and ≥80 years old, respectively. However, the suitability of common colorimetric methods for lithium measurements in the suggested therapeutic intervals has not been characterized, nor has the proposed therapeutic intervals been confirmed with real-world patient data. METHODS: Serum samples spiked with various concentrations of lithium ranging from 0 to 3.5 mmol/L were analyzed on six different methods for imprecision and relative comparability of lithium measurements. An indirect reference interval approach using refineR was employed to derive therapeutic limits using patient results spanning 5 years and compared with the therapeutic intervals recommended by the ISBD task force. RESULTS: Routinely employed colorimetric methods for lithium measurements have sufficient precision within the recommended therapeutic intervals, although select colorimetric methods are notably more imprecise at 0.4 mmol/L. The derived therapeutic intervals using patient data align with those proposed by the ISBD task force for older adults. CONCLUSION: Routine colorimetric methods used for lithium measurements have adequate precision and detection capabilities in the therapeutic windows recommended by the ISBD task force. In addition, the proposed therapeutic intervals are verifiable by real-world patient data.
A case of late-onset carbamoyl phosphate synthetase 1 deficiency: diagnostic challenges and management in a low-resource setting.
Cui X, Guo S, Zhang Y … +5 more , Zhang H, Tian H, Yang H, Zheng H, Li B
Clin Biochem · 2026 Jan · PMID 41242372 · Publisher ↗
OBJECTIVE: This study aimed to analyze the clinical features, genetic basis, and management of late-onset carbamoyl phosphate synthetase 1 deficiency (CPS1D) through a pediatric case report and literature review, highlig...
OBJECTIVE: This study aimed to analyze the clinical features, genetic basis, and management of late-onset carbamoyl phosphate synthetase 1 deficiency (CPS1D) through a pediatric case report and literature review, highlighting diagnostic challenges and therapeutic strategies. METHODS: We present a 19-year-old female with recurrent neurological symptoms since age 8. She underwent comprehensive metabolic screening, neuroimaging, and whole-exome sequencing of theCPS1gene. Identified variants were assessed for pathogenicity using multiple orthogonalin silicoprediction tools. RESULTS: The patient's initial hyperammonemic crisis at age 8 was misdiagnosed as encephalitis. Workup at age 13 confirmed hyperammonemia (peak 168 µmol/L), hypocitrullinemia, and elevated glutamine. Genetic analysis identified compound heterozygousCPS1variants: a novel c.1058 T > C (p.F353S) and known pathogenic c.1145C > T (p.P382L). A self-selected low-protein diet controlled acute crises but led to severe growth failure (height 145 cm, weight 30 kg). CONCLUSION: Late-onset CPS1D's nonspecific neurological symptoms often lead to misdiagnosis. Diagnosis requires a high index of suspicion, integrating metabolic profiling with genetic confirmation. This case expands the pathogenic genotypic spectrum of CPS1D. It crucially highlights that while dietary management is life-saving, it requires expert multidisciplinary oversight to prevent devastating consequences like growth failure, especially in resource-limited settings. Routine ammonia testing in unexplained encephalopathy is paramount.
Pre-analytical considerations in the simultaneous quantification of ketone bodies, lactate, pyruvate and TCA cycle intermediates.
Berchier K, Nyffeler C, Bruce S … +5 more , Roux C, Nuoffer JM, Gautschi M, Laemmle A, Mathis D
Clin Biochem · 2026 Jan · PMID 41241322 · Publisher ↗
BACKGROUND: Accurate quantification of small metabolites such as ketone bodies (KB: β-hydroxybutyrate (BHB), acetoacetate (AcAc)), pyruvate (Pyr), lactate (Lac) and tricarboxylic acid (TCA) cycle intermediates is essenti...
BACKGROUND: Accurate quantification of small metabolites such as ketone bodies (KB: β-hydroxybutyrate (BHB), acetoacetate (AcAc)), pyruvate (Pyr), lactate (Lac) and tricarboxylic acid (TCA) cycle intermediates is essential for diagnostics, therapy monitoring and metabolic research. These metabolites serve as energy substrates and signaling molecules, with their interpretation often relying on physiologically meaningful ratios (Lac/Pyr, BHB/AcAc). However, their chemical instability and susceptibility to rapid post-collection metabolism pose significant pre-analytical challenges. METHOD: We developed an LC-MS/MS method for the simultaneous quantification of KB, Pyr, Lac and TCA cycle intermediates, and systematically evaluated pre-analytical factors affecting their stability and accuracy. We compared lithium-heparin (LH), ethylenediaminetetraacetic acid (EDTA), sodium fluoride/EDTA (NaF/EDTA) and sodium citrate (NaCit) collection tubes and deproteinized whole blood (depWB) using perchloric acid. Stability was assessed in whole blood at RT over 24 h, as well as in LH and depWB at various temperatures (RT, 4 °C, -20 °C) over 7 days. RESULTS: Pyr, Lac, AcAc and fumarate were most labile, while BHB and citrate were stable across matrices. LH-plasma with prompt centrifugation showed minimal metabolic alterations, while NaF/EDTA effectively stabilized Lac but compromised Pyr and TCA cycle intermediates. DepWB improved Lac/Pyr ratio reliability but introduced higher variability and matrix effects. NaCit induced unexpected metabolic shifts, suggesting in-vitro TCA cycle activity. CONCLUSIONS: Our findings highlight the critical impact of anticoagulants and processing conditions on metabolite stability. LH-plasma provides the best compromise for quantifying KB, Pyr and TCA cycle intermediates when processed rapidly, while depWB remains preferable for accurate Lac/Pyr ratio determination despite its higher variability.
Change in cardiac troponin T to differentiate acute from chronic myocardial injury in the Emergency Department.
Lindahl B, Thurston AJ, Tew YY … +8 more , McDermott M, Fujisawa T, Lynch S, Cooper JG, Gray AJ, Jernberg T, Mills NL, POC-ET investigators
Clin Biochem · 2026 Jan · PMID 41241321 · Publisher ↗
INTRODUCTION: Persistently elevated cardiac troponin (cTn) values are observed in many patients with suspected acute coronary syndrome (ACS) in the absence of myocardial infarction and may reflect underlying cardiac dise...
INTRODUCTION: Persistently elevated cardiac troponin (cTn) values are observed in many patients with suspected acute coronary syndrome (ACS) in the absence of myocardial infarction and may reflect underlying cardiac disease. Chronic myocardial injury is defined where cTn values are elevated and vary by ≤ 20 % on sequential measurements. We aimed to evaluate whether these criteria are reliable over short intervals applied in accelerated diagnostic pathways. METHODS: In a secondary analysis of a prospective, multi-centre cohort study of patients with suspected ACS, cTnT was measured at presentation, 1, 2 and 6-36 h, and the final diagnosis adjudicated according to the Fourth Universal Definition of Myocardial Infarction. Two criteria for chronic myocardial injury were compared: a relative change in cTn of ≤ 20 % and an absolute change < 3 ng/L, and the findings externally validated. RESULTS: At presentation cTnT was elevated in 242 of 1,000 (24 %) patients (73 years, 42 % female), of whom 94/242 (39 %), 13/242 (5 %) and 137/242 (56 %) had myocardial infarction, acute or chronic myocardial injury, respectively. A relative change of ≤ 20 % misclassified 58 % (59/101) and 49 % (48/98) of patients with a final diagnosis of acute myocardial injury or infarction at 1 and 2 h, respectively, whereas an absolute change of < 3 ng/L misclassified 22 % (22/101) and 15 % (15/98). In the validation cohort (n = 621), the relative and absolute change criteria at one hour misclassified 43 % (13/30) and 17 % (5/30) of those with myocardial infarction. CONCLUSIONS: Chronic myocardial injury cannot reliably be differentiated from acute myocardial injury or infarction by recommended criteria over short remeasurement intervals in the Emergency Department. Longer intervals between sampling and absolute rather than relative criteria may reduce the risk of misclassification.
Extreme hypokalemia in an asymptomatic 40-year-old cachectic male.
Francois S, Rajagopal S, Boutten A … +2 more , Raynor A, Peoc'h K
Clin Biochem · 2026 Jan · PMID 41237988 · Publisher ↗
Hypokalemia is a relatively common electrolyte disturbance that, despite its frequency, can pose a serious threat when it occurs in patients with end-stage chronic illnesses. In many individuals, mild to moderate reducti...
Hypokalemia is a relatively common electrolyte disturbance that, despite its frequency, can pose a serious threat when it occurs in patients with end-stage chronic illnesses. In many individuals, mild to moderate reductions in serum potassium may be surprisingly well tolerated over time; however, severe depletion remains a potentially life-threatening condition that demands rapid recognition and intervention. In this report, we describe an exceptional case of extreme hypokalemia < 2 mmol/L in a patient living with human immunodeficiency virus (HIV) infection, who also suffered from persistent chronic diarrhea and marked unintentional weight loss, yet exhibited few of the classical clinical signs usually associated with profound potassium deficiency. We outline the urgent procedures carried out by the laboratory under emergency conditions, examine the complex pathophysiological mechanisms, ranging from gastrointestinal potassium losses to altered renal handling, responsible for this critical imbalance, and detail the specific treatment regimen administered. By presenting these elements in concert, we aim to offer clinicians a clearer understanding of both the diagnostic approach and the therapeutic strategies necessary to manage similar high-risk patients effectively.
Incorrectly prepared formula contributing to severe hypovolemic hypernatremia in enteral tube-fed children: A report of two cases.
de Koning L, Jamal SM, Ross C … +2 more , Esser MJ, Pols E
Clin Biochem · 2026 Jan · PMID 41232589 · Publisher ↗
CASE PRESENTATIONS: We describe two cases of children who were significantly impacted by incorrectly prepared, hyperosmolar formula delivered via enteral tubes. The first case is of a 5-month-old post-pancreatectomy pati...
CASE PRESENTATIONS: We describe two cases of children who were significantly impacted by incorrectly prepared, hyperosmolar formula delivered via enteral tubes. The first case is of a 5-month-old post-pancreatectomy patient with complex needs who received hyperosmolar formula while in a pediatric intensive care unit (PICU), whereas the second is of a 1-year-old with spinal muscular atrophy who received hyperosmolar formula at home - resulting in a PICU admission. DISCUSSION: Hypovolemic hypernatremia is an important but poorly understood complication that can occur if overly concentrated formula is fed to children. Risk is almost certainly greater in enteral-tube fed patients because of their medical fragility but also because tube-feeding delivers formula directly and potentially very rapidly to the gastrointestinal system. CONCLUSIONS: Formula for medically fragile, enteral tube-fed children should be prepared with utmost care - particularly when family caregivers are responsible for home feeding. In these cases, additional education and feeding support should be considered - including provision of pre-mixed formula. The clinical biochemistry laboratory can verify formula osmolality for these high-risk patients.
A tale of two variants: The first reported case of hemoglobin Rush and hemoglobin S in a compound heterozygote.
Berti ACM, Marques BBV, Bernardo VS … +7 more , Torres FF, Bernardino GA, Silva JJR, Dias IS, Zucão ACA, da Silva DGH, Belini-Júnior E
Clin Biochem · 2026 Jan · PMID 41232588 · Publisher ↗
Hemoglobinopathies are among the most common inherited disorders worldwide, caused by various mutations in the hemoglobin (Hb) genes. These mutations can lead to different clinical outcomes, some of which cause significa...
Hemoglobinopathies are among the most common inherited disorders worldwide, caused by various mutations in the hemoglobin (Hb) genes. These mutations can lead to different clinical outcomes, some of which cause significant symptoms, highlighting their importance in global health and genetic research. In this context, this case report details the first known instance of compound heterozygosity for Hb Rush (HBB:c.304G > C) and Hb S (HBB:c.20A > T), emphasizing the diagnostic challenges posed by rare Hb variants, particularly those that mimic Hb S. Specifically, a 14-year-old male patient was referred due to mild anemia, microcytosis, and hemolysis, with a suspicion of sickle cell disease (SCD). However, hematological, biochemical, chromatographic, and electrophoretic analyses were inconsistent with SCD, prompting further molecular investigations. High-performance liquid chromatography identified a hemoglobin variant with a retention time overlapping Hb S. Additionally, alkaline electrophoresis revealed hybrid tetramers typical of unstable Hbs, such as Hb Rush. These laboratory findings were further confirmed through Sanger sequencing of the HBB gene, which demonstrated heterozygosity for both Hb Rush and Hb S, establishing a rare genotype that has not been previously reported. The thermal instability and structural changes involving the G3 (101) glutamate-to-glutamine substitution in Hb Rush account for the hematological phenotype observed in this patient. Therefore, in cases like this one, it is crucial to combine various laboratory methodologies-such as electrophoresis and molecular analysis-with the patient's clinical information. This comprehensive approach enables a critical interpretation of potential genotypes, ensuring accurate diagnosis, appropriate clinical follow-up, and treatment.
SeraSeq reference materials support non-invasive cfDNA screening methods.
Giroux S, Daryabari SS, Caron A … +1 more , Rousseau F
Clin Biochem · 2026 Jan · PMID 41232587 · Publisher ↗
BACKGROUND: Reference materials are essential for the validation, verification, and implementation of clinical assays. Seracare has developed the Seraseq line-commercial reference standards for non-invasive prenatal test...
BACKGROUND: Reference materials are essential for the validation, verification, and implementation of clinical assays. Seracare has developed the Seraseq line-commercial reference standards for non-invasive prenatal testing (NIPT)-which are designed to simulate maternal plasma containing cell-free DNA (cfDNA). OBJECTIVE: This study aims to evaluate the performance of Seraseq reference materials compared to natural maternal plasma, particularly assessing their quality and reliability as reference standards in NIPT workflows, both with and without size selection to enrich fetal fraction. METHODS: We analyzed six replicates from eight different Seraseq genotypes. cfDNA was extracted, prepared into sequencing libraries, and sequenced following the same protocols used for natural plasma samples. Size-selection was also applied to enrich shorter cfDNA fragments. The key performance metrics included cfDNA yield and integrity, library preparation efficiency, sequencing quality, fetal fraction estimation, and detection of aneuploidies and sex chromosome abnormalities. RESULTS: cfDNA quantity and quality from Seraseq materials were comparable to natural plasma. The materials yielded consistent library concentrations. Sequencing showed reliable detection of all targeted aneuploidies except the microdeletion del22q11, even with elevated fetal fraction. Size-selection increased fetal fraction and improved Z-scores for aneuploidy detection across all genotypes. Fragment size profiles exhibited slight but consistent deviations from natural plasma, notably after size selection. CONCLUSIONS: Seraseq reference materials closely mimic the cfDNA characteristics of maternal plasma and perform reliably across multiple testing dimensions. While they may present slight differences in fragment size periodicity, these did not affect analytical performance. These materials are therefore suitable for validating and monitoring NIPT workflows.
A large-scale survey on the knowledge, attitude, and practice of patient-based real-time quality control in China.
Leng D, Lyu M, Wei L … +7 more , Shang X, Lou X, Zhang M, Zhou Y, Badrick T, Zhou R, APFCB Working Group on Patient-based Real-Time Quality Control
Clin Biochem · 2026 Jan · PMID 41224190 · Publisher ↗
OBJECTIVES: Patient-based real-time quality control (PBRTQC) plays a promising role in monitoring the quality of medical laboratory testing processes worldwide. In contrast with traditional quality control, PBRTQC demons...
OBJECTIVES: Patient-based real-time quality control (PBRTQC) plays a promising role in monitoring the quality of medical laboratory testing processes worldwide. In contrast with traditional quality control, PBRTQC demonstrates numerous advantages, but the application status remains unclear. This study was conducted to assess the awareness and intention to apply PBRTQC in laboratories through a survey, providing a basis for subsequent research and promotion. DESIGN & METHODS: A questionnaire was constructed and extended on the basis of Badrick's fifteen core questions in 2023, which were distributed via the Star questionnaire platform to collect general information on relevant personnel, their cognition, attitude and practice of PBRTQC as well as their willingness to implement it. This survey was carried out in different kinds of clinical laboratories throughout the mainland area of China. RESULTS: A total of 1,844 valid questionnaires were collected. The survey showed that the average awareness rate of basic knowledge of PBRTQC among laboratory staff was above 50%, and their confidence in establishing and applying PBRTQC in their laboratories was relatively low. However, they recognized the role of PBRTQC in improving quality management. Among the existing PBRTQC related practices, reading literature was the most common. The main concerns for promoting PBRTQC included professional implementation guidelines and policy support, reliable commercial evaluations, software and hardware support, and usage training. CONCLUSIONS: The results of our study demonstrate that laboratory staff recognize the value of PBRTQC and have a generally positive attitude towards its application. In the future, efforts should be made to strengthen the formulation of standardized documents, improve evaluation methods, develop software and hardware, popularize knowledge, and provide technical training to promote the application of PBRTQC.
A novel Gasdermin D C-terminal neo-epitope as a biomarker for pyroptosis in sepsis.
Li J, Luo Y, Liu Y … +9 more , Cui S, Zhao L, Kang H, Huo L, Wang X, Jin E, Mao S, Cao Y, Wang J
Clin Biochem · 2026 Jan · PMID 41224189 · Publisher ↗
BACKGROUND: Gasdermin D (GSDMD)-mediated pyroptosis, a critical component of the innate immune response, is triggered by pathogenic microbial infections and plays a key role in host defense mechanisms. This process invol...
BACKGROUND: Gasdermin D (GSDMD)-mediated pyroptosis, a critical component of the innate immune response, is triggered by pathogenic microbial infections and plays a key role in host defense mechanisms. This process involves the cleavage of GSDMD by inflammatory caspases, releasing carboxy-terminal fragments (GSDMD-CT). Monitoring GSDMD-CT levels represents a promising approach for inflammatory diseases, including sepsis and systemic inflammatory response syndrome (SIRS). METHODS: We developed an immunoassay to measure plasma GSDMD-CT concentrations in 109 healthy individuals, 137 patients with SIRS, and 100 patients with sepsis. The diagnostic utility of GSDMD-CT in distinguishing sepsis from SIRS or healthy controls was assessed using receiver operating characteristic (ROC) analysis, alongside correlations with procalcitonin (PCT), and C-reactive protein (CRP). RESULTS: Plasma GSDMD-CT levels were significantly elevated in patients with sepsis compared to healthy control and SIRS groups. ROC analysis demonstrated an area under the curve of 0.870, with a sensitivity of 91.0% and specificity of 60.6% for differentiating sepsis from healthy controls. Comparable performance was observed in distinguishing SIRS from healthy controls. Diagnostic accuracy was further enhanced when GSDMD-CT was combined with CRP. Strikingly, GSDMD-CT mirrored the kinetic profile of PCT in antibiotic-treated patients with bacterial infections. CONCLUSION: The GSDMD-CT assay demonstrates high sensitivity as a biomarker, offering potential for early and differential diagnosis of sepsis across diverse pathogens.
The hemopexin-apolipoprotein B product: a novel biomarker integrating oxidative stress and lipid metabolism for coronary artery disease risk stratification.
Jin Y, Chen K, Fan Q
Clin Biochem · 2026 Jan · PMID 41218745 · Publisher ↗
OBJECTIVE: We hypothesized that the Hemopexin-Apolipoprotein B product (Hpx·apoB), a composite biomarker integrating lipid dysregulation and oxidative stress pathways, would improve coronary artery disease (CAD) diagnosi...
OBJECTIVE: We hypothesized that the Hemopexin-Apolipoprotein B product (Hpx·apoB), a composite biomarker integrating lipid dysregulation and oxidative stress pathways, would improve coronary artery disease (CAD) diagnosis and risk stratification. METHODS: This single-center cross-sectional study included 460 participants (350 CAD patients, 110 non-significant CAD controls). Plasma hemopexin (Hpx) was measured by liquid chromatography - tandem mass spectrometry, and the Hpx·apoB product was calculated. Multivariate logistic regression analyzed its CAD association, while area under the curve (AUC), net reclassification index (NRI), and integrated discrimination improvement (IDI) assessed its incremental predictive value over conventional risk factors and established models (Framingham, SCORE2). RESULTS: The Hpx·apoB product was significantly elevated in CAD patients compared to controls (median [IQR]: 2.35 [1.80-3.15] vs. 1.72 [1.30-2.25] mg/L, p < 0.001). After adjusting for traditional cardiovascular risk factors, Hpx·apoB remained an independent predictor of CAD (Odds Ratio [OR] = 2.61, 95 % Confidence Interval [CI]: 1.48-4.60, p = 0.001). Adding Hpx·apoB to a baseline model with conventional risk factors (hs-CRP + LDL-C) significantly improved the AUC from 0.75 (95 % CI: 0.70-0.80) to 0.83 (95 % CI: 0.79-0.87; p for ΔAUC < 0.001), with a continuous NRI of 0.352 (p < 0.001) and an IDI of 0.098 (p < 0.001). Furthermore, integrating Hpx·apoB into the Framingham and SCORE2 models also yielded significant improvements in risk reclassification (NRI = 29.5 % and 39.8 %, respectively; both p < 0.001). CONCLUSION: The Hpx·apoB biomarker, combining oxidative stress and lipid metabolism, independently predicts CAD presence and severity while improving existing risk models' accuracy, enhancing clinical risk stratification.
Decoding the interference: How therapeutic monoclonal antibodies challenge serum protein electrophoresis and immunofixation.
Milandri J, Jaillard M, Laffineur M … +2 more , Dechomet M, Kolopp-Sarda MN
Clin Biochem · 2025 Dec · PMID 41202911 · Publisher ↗
INTRODUCTION: Serum protein electrophoresis and immunofixation electrophoresis are routinely used to diagnose and monitor monoclonal gammopathies. However, several therapeutic monoclonal antibodies are detectable by thes...
INTRODUCTION: Serum protein electrophoresis and immunofixation electrophoresis are routinely used to diagnose and monitor monoclonal gammopathies. However, several therapeutic monoclonal antibodies are detectable by these techniques and may mimic a pathological monoclonal protein, leading to diagnostic confusion. This study aimed to evaluate potential interferences caused by these treatments and to characterize their electrophoretic migration profiles and detection thresholds. MATERIALS AND METHODS: Seven therapeutic monoclonal antibodies (daratumumab, isatuximab, rituximab, elranatamab, teclistamab, eculizumab, and ravulizumab) were assessed using an overloaded hypogammaglobulinemic serum model. Each antibody was tested at seven decreasing concentrations, from one point five grams per liter to zero point one gram per liter. All dilutions were analyzed by capillary electrophoresis and immunofixation electrophoresis. RESULTS: Validation was performed using daratumumab, for which interference is well documented. Rituximab and elranatamab consistently generated a discrete peak in the slow-gamma region on serum protein electrophoresis, associated with an IgG kappa band on immunofixation electrophoresis. Teclistamab migrated in the mid-gamma region and produced an IgG lambda band, detectable down to zero point fifteen gram per liter on serum protein electrophoresis and zero point zero two gram per liter on immunofixation electrophoresis. Ravulizumab, an IgG kappa antibody migrating in the beta-two region, remained detectable down to zero point five gram per liter and zero point one gram per liter, respectively. CONCLUSIONS: This work specifies the electrophoretic behavior of several monoclonal antibody therapies, helping distinguish therapy-related peaks from true monoclonal gammopathy. These findings support the systematic use of confirmatory strategies-particularly reflex immunofixation-to ensure accurate interpretation of electrophoresis results in patients receiving monoclonal antibody treatment.
Corrigendum to "Optimization and validation of the Kairos Amino Acid Kit for plasma amino acid monitoring in inherited metabolic disorder patients" [Clin. Biochem. 138 (2025) 110960].
Theron K, Gauthier J, Hulle MV … +1 more , Potter M
Clin Biochem · 2025 Dec · PMID 41193311 · Publisher ↗
Abstract loading — click title to view on PubMed.
Diagnosis of patients with IgM monoclonal gammopathy due to analytical interference.
Rubio-Sánchez R, Izquierdo-Martínez A, Martínez-Rodríguez S … +4 more , Romero LM, Noval-Padillo JÁ, Fatela-Cantillo D, Guerrero JM
Clin Biochem · 2025 Dec · PMID 41177329 · Publisher ↗
INTRODUCTION: Blood hyperviscosity is a condition associated, in most cases, with Waldenström's macroglobulinemia (WM) and other plasma cell dyscrasias, primarily due to the pentameric structure of immunoglobulin (Ig) M....
INTRODUCTION: Blood hyperviscosity is a condition associated, in most cases, with Waldenström's macroglobulinemia (WM) and other plasma cell dyscrasias, primarily due to the pentameric structure of immunoglobulin (Ig) M. Analytical interference in the determination of alanine aminotransferase with the Abbott Alinity c assay has recently been documented, related to increased blood viscosity as a result of a monoclonal component. The detection of this interference indicates a significant and isolated increase in the concentration of a single immunoglobulin, leading to the diagnosis of a previously unknown monoclonal gammopathy. CASE DESCRIPTION: Thanks to the described interference and the expansion of analytical testing by the clinical laboratory, 15 patients with a previously unknown IgM monoclonal component were identified over 7 months. IgM levels ranged from 8.37 g/L, with a monoclonal component of 2.4 g/L, to 82.43 g/L, with a monoclonal component of 40.9 g/L. Ten patients were diagnosed with IgM monoclonal gammopathy of undetermined significance, one with asymptomatic biclonal gammopathy, and one with WM who presented with hyperviscosity syndrome, requiring plasmapheresis and treatment with rituximab-bendamustine. DISCUSSION: These cases highlight the importance of investigating laboratory test interferences, as they may be related to subclinical pathologies, such as monoclonal gammopathies. Detecting this interference and expanding laboratory testing can detect the pathology even before the appearance of related symptoms. This early identification allows for patient referral to the Hematology Department for appropriate follow-up, improving the prevention of complications and helping to make more timely therapeutic decisions.
Assessment of serum sST2 for cardiac involvement in idiopathic inflammatory myopathies.
Li L, Yuan Y, Yi S … +10 more , Ding T, Zhu H, Shi Q, Tan H, Li R, Liu Y, Xu H, Liu M, Wang D, Wang R
Clin Biochem · 2025 Dec · PMID 41177328 · Publisher ↗
OBJECTIVE: To assess the diagnostic performance of soluble growth stimulation-expressed gene 2 (sST2) for cardiac involvement in patients with idiopathic inflammatory myopathies (IIMs). METHODS: From a cohort of 237 pati...
OBJECTIVE: To assess the diagnostic performance of soluble growth stimulation-expressed gene 2 (sST2) for cardiac involvement in patients with idiopathic inflammatory myopathies (IIMs). METHODS: From a cohort of 237 patients with IIMs, 86 were finally included and 18 exhibited cardiac involvement. The comparison of demographic, clinical, and laboratory parameters between IIM patients with and without cardiac involvement was conducted. Additionally, independent predictors for cardiac involvement and the diagnostic performance of sST2 were analyzed. RESULTS: The prevalence of cardiac involvement in IIMs was 20.9 %. The medians (interquartile range, IQR) of sST2 (65.6 [33.7-92.9] vs. 14.5 [7.8-25.4] μg/L) and N-terminal B-type pro-natriuretic peptide (NTproBNP, 120.2 [65.5-324.1] vs. 44.0 [16.8-104.6] ng/L) were significantly elevated in IIM patients with cardiac involvement compared with those without cardiac involvement. Multivariable logistic regression showed elevated levels of sST2 (OR = 3.936, 95 % CI 1.808-8.571, P = 0.001) and NTproBNP (OR = 2.308, 95 % CI 1.302-4.093, P = 0.004) were risk factors for cardiac involvement in IIM patients. The combined receiver operating characteristic (ROC) analysis of sST2 and NTproBNP indicated high diagnostic values in distinguishing IIM patients with cardiac involvement from those without cardiac involvement, with 94.4 % (95 % CI 72.2 %-99.7 %) sensitivity, 87.3 % (95 % CI 76.9 %-93.4 %) specificity, and 0.926 area under the ROC curve (95 % CI 0.840-1.000, P < 0.001). CONCLUSION: sST2 serves as a valuable biomarker for detecting cardiac involvement in patients with IIMs.
A novel 17.9 kb deletion of the beta-globin gene causing beta-thalassemia trait in a Danish male.
Kristiansen HP, Petersen J, Schou P … +2 more , Nissen PH, Winther-Larsen A
Clin Biochem · 2025 Dec · PMID 41173127 · Publisher ↗
BACKGROUND: Beta-thalassemia is a common monogenic disease, especially in malaria-endemic areas. It is mainly caused by point mutations in the beta-globin gene (HBB) while large deletions are more rarely described. Here,...
BACKGROUND: Beta-thalassemia is a common monogenic disease, especially in malaria-endemic areas. It is mainly caused by point mutations in the beta-globin gene (HBB) while large deletions are more rarely described. Here, a novel, large deletion encompassing the entire HBB gene causing beta-thalassemia in an ethnically Danish male is described. CASE REPORT: A 60-year-old male with no family history of anemia was admitted to the local Department of Medicine with microcytotic anemia. He had observed fatigue and slight dizziness, but despite this, he felt healthy. His blood tests showed no signs of iron deficiency and a hemoglobinopathy was suspected. Hemoglobin fractionation by ion-exchange high-performance liquid chromatography revealed an elevated HbF of 5.9 % and an increased HbA2 of 8.5 %. GAP-PCR of the alpha-thalassemia HBA1/HBA2 genes and Sanger sequencing of the HBB gene showed none of the common thalassemia-causing variations. Hence, multiplex ligation dependent probe amplification was performed and a deletion variant was identified that resulted in the complete loss of the HBB gene. The exact breakpoints were identified using Sanger sequencing, revealing a novel 17.9 kb deletion (NC000011.10:g.5211831_5229725del) not previously described in the literature or in databases. The deletion was consistent with beta-thalassemia trait in accordance with the patient's symptoms. CONCLUSION: We present a novel large deletion of the HBB gene causing beta-thalassemia trait detected in an ethnically Danish male. Thalassemia must be considered in patients with microcytosis of unknown cause despite a Northern European ethnicity.
The contribution of IL-10 and IL-6 as potential biomarkers for detecting central nervous system involvement in non-Hodgkin lymphomas.
Buzzatti E, Esposito F, Morello M … +10 more , Rossi V, Cox MC, Annibali O, Santinelli E, Irno-Consalvo MA, Paterno G, Cardillo L, Postorino M, Venditti A, Del Principe MI
Clin Biochem · 2025 Dec · PMID 41167499 · Publisher ↗
INTRODUCTION: A significant clinical challenge in the management of hematologic malignancies is the occurrence of central nervous system (CNS) involvement. In non-Hodgkin lymphoma (NHL), it occurs in varying percentages...
INTRODUCTION: A significant clinical challenge in the management of hematologic malignancies is the occurrence of central nervous system (CNS) involvement. In non-Hodgkin lymphoma (NHL), it occurs in varying percentages depending on the subtype and identifying patients is crucial but challenging. Furthermore, a definitive gold standard for diagnosing leptomeningeal involvement is still lacking. Conventional cytology (CC) of cerebrospinal fluid (CSF) has high specificity but low sensitivity. Multiparametric flow cytometry offers superior sensitivity but is limited by CSF cellularity and the need for specialized expertise, a resource not available at every institution. CSF cytokine analysis is emerging as a promising diagnostic approach, with IL-6 and IL-10 showing potential as biomarkers. OBJECTIVE: This prospective study investigated the utility of dosing the aforementioned cytokine in serum and CSF samples for diagnosing CNS involvement in non-primary CNS lymphoma patients. METHODS: CSF samples were analyzed using CC and IL-6/IL-10 assays. IL-6 and IL-10 levels were then compared between CC-positive (CC + ) and CC-negative (CC-) patients. RESULTS: The study cohort included 27 patients, with a median age of 71 years. Six patients (22.2 %) were CC + . In CSF, statistically significant differences were observed for both IL-6 (p = 0.02) and IL-10 (p = 0.04) levels between CC + and CC- patients, with higher levels in CC + patients. Elevated CSF IL-6 and IL-10 levels were also associated with elevated LDH, advanced disease stage, and elevated CSF protein. CONCLUSIONS: This study suggests that CSF IL-6 and IL-10 are potential, widely available biomarkers for early detection of CNS involvement in NHL, offering a complement to traditional cytological analysis in clinical laboratories.
Correlation of plasma lipidomic profiles with cardiometabolic disease in transfusion-dependent thalassemia patients with six-month N-acetylcysteine intervention: A prospective cohort study.
Lei Y, Forest A, Daneault C … +8 more , Liu Y, Pantopoulos K, Tantiworawit A, Phrommintikul A, Chattipakorn S, Chattipakorn N, Rosiers CD, Sweeney G
Clin Biochem · 2025 Dec · PMID 41135647 · Publisher ↗
OBJECTIVES: Oxidative stress, driven by iron imbalance from recurrent blood transfusions, is a major contributor to cardiometabolic complications in transfusion-dependent thalassemia (TDT). N-acetylcysteine (NAC), a glut...
OBJECTIVES: Oxidative stress, driven by iron imbalance from recurrent blood transfusions, is a major contributor to cardiometabolic complications in transfusion-dependent thalassemia (TDT). N-acetylcysteine (NAC), a glutathione precursor, is a well-known antioxidant with cardioprotective effects achieved by mitigating the impact of oxidative stress on cell metabolism. Current study aimed to evaluate the effect of a six-month NAC intervention by focusing on previously reported changes in the plasma lipidome in TDT patients. Design & Methods A randomized cohort of 62 Thai TDT patients was divided into two groups: both received six months of cocktail therapy involving standardized blood transfusions and iron chelator therapy, with the intervention group additionally receiving 600 mg oral NAC daily and the control group receiving a placebo. Plasma lipidomic profiling was performed using mass spectrometry to assess 339 previously annotated lipid features significantly altered in TDT patients. Clinical parameters, including heart rate variability (HRV), were measured before and after the intervention. RESULTS: NAC treatment significantly altered 152 plasma lipid features (P < 0.03), 78 of which were also altered in the placebo group. Importantly, 29 lipid features (26 unique lipids) were restored toward healthy control levels following NAC treatment. Within this subset, circulating diacylglycerophosphocholines PC(14:0_20:4) and cholesteryl ester CE 18:3 positively correlated with HRV, a clinical marker markedly improved in NAC-treated patients. CONCLUSIONS: Six-month oral NAC intervention modified the plasma lipidomic profile in TDT patients, partially restoring lipid species likely disrupted by chronic oxidative stress. The observed correlation between NAC-responsive lipids and improved HRV suggests a potential cardioprotective effect. These findings highlight the potential of NAC as an adjunctive therapy to mitigate cardiometabolic complications in TDT.
Measurement uncertainty in derived (calculated) biological quantities: Impact on clinical interpretation.
Rigo-Bonnin R, Mas-Bosch V
Clin Biochem · 2025 Dec · PMID 41130584 · Publisher ↗
BACKGROUND: Measurement uncertainty (MU) is essential for interpreting laboratory results. While MU is often reported for directly measured quantities, it is rarely considered for derived (calculated) ones, despite their...
BACKGROUND: Measurement uncertainty (MU) is essential for interpreting laboratory results. While MU is often reported for directly measured quantities, it is rarely considered for derived (calculated) ones, despite their widespread clinical use. This study assessed the impact of MU on interpretation of derived quantities by comparing directly measured and calculated results. DESIGN & METHODS: Following ISO/TS 20914:2019 and GUM guidelines, MU was estimated for directly measured and derived biological quantities. Ionized magnesium (iMg) was analyzed as a case, comparing direct measurement with regression-based estimates. The approach was extended to estimated glomerular filtration rate (eGFR), low-density lipoprotein cholesterol (cLDL, direct enzymatic vs. Friedewald), free testosterone (direct vs. Vermeulen calculation), and the anion gap (AG, incorporating calculated bicarbonate). Clinical interpretation was evaluated by comparing coverage intervals with biological reference intervals and clinical decision limits. RESULTS: Direct iMg measurement at 0.520 mmol/L yielded a relative expanded uncertainty (U, k = 2) of 4.1 %. Regression-derived values showed U up to 21.4 %. For eGFR, U ranged from 3.8 % to 5.5 %. At 63 mL/min/1.73 m, coverage intervals overlapped the 60 mL/min/1.73 m decision limit, altering chronic kidney disease staging. Direct cLDL measurement (2.54 mmol/L) had U = 4.8 %, while Friedewald calculation (2.60 mmol/L) showed U = 4.8 %; both overlapped therapeutic decision limits. Free testosterone measurement (0.221 nmol/L) had U = 13.9 %, whereas Vermeulen-derived values (0.210 nmol/L) reached 24.1 %. For AG, an abnormal value (28.2 mmol/L) remained pathological, but values of 20.3 or 14.0 mmol/L overlapped the 18 mmol/L limit, producing indeterminate classification. CONCLUSIONS: MU significantly influences the interpretation of derived laboratory quantities, particularly near decision limits. Systematic reporting of MU, in line with international recommendations, would enable more reliable interpretation, improve patient safety, and reduce misclassification in clinical decision-making. ABBREVIATIONS: MU, measurement uncertainty; eGFR, estimated glomerular filtration rate, cLDL, substance concentration of LDL-cholesterol in serum; fTes, substance concentration of free testosterone in serum; AG, anion gap; iMg, substance concentration of ionized magnesium in serum; tMg, substance concentration of (total) magnesium in serum; Alb, mass concentration of albumin in serum; IP, substance concentration of inorganic phosphate in serum; PaCO, partial pressure of carbon dioxide in arterial blood; BRI, biological reference interval; y, derived quantity; u(y), combined standard uncertainty for derived quantity y; x, measured quantity or empirical constant i; x, measured quantity or empirical constant j; [Formula: see text] , correlation coefficients between quantities x and x; ∂y∂x, sensitivity coefficient for the measured or empirical constant i; ∂y∂x, sensitivity coefficient for the measured or empirical constant j; u, uncertainty associated with the assigned value of the end-user calibrator; u, uncertainty related to the intermediate precision; u, uncertainty associated with any correction factors related to bias; IFU, Instructions for Use; CI, confidence interval; uiMg, Combined uncertainty related to the iMg; UiMg, Expanded uncertainty related to the iMg.
HFE related acute porphyria-like attack induced by severe influenza A pneumonia.
Yang H, Guo J, Ye G … +2 more , Wang D, Yang Y
Clin Biochem · 2025 Dec · PMID 41106535 · Publisher ↗
This case report describes a patient with HFE-related acute porphyria-like attack triggered by severe influenza A pneumonia. The patient was admitted with fever, dyspnea, and abdominal pain and was diagnosed with severe...
This case report describes a patient with HFE-related acute porphyria-like attack triggered by severe influenza A pneumonia. The patient was admitted with fever, dyspnea, and abdominal pain and was diagnosed with severe influenza A pneumonia, acute respiratory failure, and septic shock. On the third day of hospitalization, the patient developed profound shock requiring mechanical ventilation and tested positive for influenza A virus. During treatment, significant liver dysfunction was observed, along with clinical manifestations including abdominal pain, loss of consciousness, and bilateral strabismus, suggesting neurological involvement. The diagnosis of acute porphyria-like attack was confirmed by positive urine porphobilinogen testing and genetic detection of a HFE mutation. This case highlights the importance of maintaining a high index of suspicion for porphyrin metabolism dysfunction in critically ill patients, particularly in the setting of infection or other precipitating factors. Timely diagnosis and management can significantly improve patient outcomes. These findings provide new insights into the clinical recognition of porphyria, especially in critically ill patients, and underscore the importance of multidisciplinary collaboration and meticulous diagnostic evaluation.
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