Clinical Biochemistry[JOURNAL]
Sun
200 papers
HER2 gene mutations and matrix biomarkers in breast cancer.
Karimova L, Azizova G, Shahverdiyeva I
Clin Biochem · 2025 Dec · PMID 40912526 · Publisher ↗
OBJECTIVE: Breast cancer (BC) remains a leading cause of morbidity and mortality among women globally. This study aims to investigate HER2 mutations in HER2-negative BC and evaluate the diagnostic potential of matrix met...
OBJECTIVE: Breast cancer (BC) remains a leading cause of morbidity and mortality among women globally. This study aims to investigate HER2 mutations in HER2-negative BC and evaluate the diagnostic potential of matrix metalloproteinases (MMP-7, MMP-9) and CYR61 as serum biomarkers. MATERIAL AND METHODS: The study involved 74 women diagnosed with BC (HER2-positive: n = 33; HER2-negative: n = 33; triple negative: n = 8) and 25 healthy controls. HER2 gene mutations were analyzed using the "AmoyDx HER2 Mutation Detection" kit. Serum MMP-7, MMP-9, and CYR61 levels were quantified using Bio-Techne kits (R&D Systems) using the Quantikine ELISA method. RESULTS: The study found no mutations (A775_G776insYVMA, M774_A775insAYVM, G776 > VC, G776R, G776C, P780_Y781insGSP, V777L, L755P) in exons 18 and 20 of the HER2 gene in HER2 negative BC patients. MMP-9 serum levels were significantly reduced in BC patients compared to the control group (p < 0.001). However, MMP-7 levels showed no significant variation when compared to healthy women (p = 0.464). CYR61 exhibited high diagnostic accuracy (AUC = 0.95), supporting its potential as a reliable biomarker. CONCLUSION: The reduction in serum MMP-9 levels correlates with ongoing tissue processes, primarily due to increased consumption in the extracellular matrix. CYR61 overexpression is observed across all breast cancer subtypes, independent of HER2 activity, suggesting its significant potential for use in BC diagnosis and treatment.
Method choice for investigation of macrotroponin interference with the Siemens Atellica high sensitivity troponin I assay.
Karin A, Cheng C
Clin Biochem · 2025 Dec · PMID 40907679 · Publisher ↗
OBJECTIVES: Macrotroponin refers to circulating immunoglobulin-bound cardiac troponin species that may elevate troponin results in patients with or without myocardial injury, causing diagnostic confusion. Clinical labora...
OBJECTIVES: Macrotroponin refers to circulating immunoglobulin-bound cardiac troponin species that may elevate troponin results in patients with or without myocardial injury, causing diagnostic confusion. Clinical laboratories have been recommended to provide a service for troponin interference investigation. We evaluated the applicability of a Protein A/G IgG-depletion procedure as well as polyethylene glycol (PEG) precipitation for detecting macrotroponin interference with the Siemens Atellica troponin I (TnIH) assay. METHODS: Troponin I, IgG, and albumin (internal standard) were measured (Atellica) on the neat and treated plasma to calculate recovery. Reference samples with TnIH ranging from < 1x to > 1000x times the 99th percentile were selected to verify expected recovery. To minimize likelihood of macrotroponin in the reference group, samples with elevated results were only included if recent acute changes in TnIH was documented. 40 samples were used for the IgG-depletion method and 20 for PEG precipitation. 25 samples from patients with unexplained elevation in TnIH were assessed by IgG-depletion. RESULTS: 38 of 40 reference group recoveries exceeded 70 % (median 91 %, IQR 15 %, max 129 %) in the IgG-depletion group consistent with literature on other assays. Specimens from patients with incongruent clinical picture had IgG-depletion recovery median of 11 % (IQR 14 %, max 37 %). PEG-precipitation showed large variation (median 103 %, IQR 89 %, max 227 %). CONCLUSIONS: IgG depletion using Protein A/G can reliably establish IgG-mediated interference with Atellica TnIH. PEG precipitation results are difficult to interpret likely due to matrix effects, especially at values closer to the 99th percentile.
Circulating free PSA in breast cancer patients: is it a reliable biomarker?
Susini V, Franzini M, Ursino S … +6 more , Ghilardi M, Morganti R, Scatena C, Bianco I, Mazzoni A, Ghilli M
Clin Biochem · 2025 Dec · PMID 40902839 · Publisher ↗
INTRODUCTION: Prostate-specific antigen (PSA), a serine protease primarily expressed in the prostate, has also been detected in hormonally regulated female tissues, including the breast. Some studies suggest a correlatio...
INTRODUCTION: Prostate-specific antigen (PSA), a serine protease primarily expressed in the prostate, has also been detected in hormonally regulated female tissues, including the breast. Some studies suggest a correlation between increased levels of circulating free PSA (fPSA) and breast cancer, but its role remains debated. This study aimed to evaluate this association while minimizing hormonal confounding factors. METHODS: A total of 82 breast cancer patients (aged 35-86 years) and 31 healthy premenopausal women (aged 18-58 years) were enrolled. Patients had a primary breast cancer diagnosis with no other malignancies and had not undergone preoperative chemotherapy or radiotherapy. Participants with hormonal conditions affecting PSA expression were excluded. fPSA levels were measured using an improved VIDAS® fPSA immunoassay with enhanced analytical sensitivity. RESULTS: Despite the increased sensitivity of the modified assay, fPSA was undetectable in all plasma samples. This may be due to the exclusion of participants with hormonal imbalances who might exhibit higher PSA expression. CONCLUSIONS: The absence of androgen receptor (AR)-positive triple-negative breast cancer (TNBC) patients in this cohort further supports the role of androgens in PSA regulation. These findings suggest that fPSA may not be a reliable circulating biomarker for breast cancer. However, a key limitation is the lack of fPSA assessment within breast cancer tissue. Future studies should investigate its expression in tumors, particularly in AR-positive TNBC, and evaluate circulating fPSA and testosterone levels as potential biomarkers of tumor androgenic activity.
How effective is serum FGL1 measurement in assessing disease activity: A cross-sectional study in rheumatoid arthritis.
Ates M, Ates M, Gurler M … +2 more , Tasci M, Yis OM
Clin Biochem · 2025 Dec · PMID 40897229 · Publisher ↗
INTRODUCTION: In rheumatoid arthritis, which is an autoimmune inflammatory disease with multisystemic involvement, especially the joints, tracking disease activity is quite valuable in order to improve the quality of lif...
INTRODUCTION: In rheumatoid arthritis, which is an autoimmune inflammatory disease with multisystemic involvement, especially the joints, tracking disease activity is quite valuable in order to improve the quality of life of patients and to develop individualized treatment strategies. In this study, we evaluated the role of Fibrinogen-Like Protein 1 (FGL1), which has recently been shown to be associated with various rheumatological and autoimmune diseases, in disease diagnosis and activity in rheumatoid arthritis (RA). MATERIAL AND METHODS: In this prospective study consisting of 108 RA patients divided into two groups as low disease activity-remission group (LDA) and moderate-high disease activity group (MHA) according to the Disease Activity Score 28-C-reactive protein score and 56 controls, serum FGL1 level was measured by Enzyme Linked ImmunoSorbent Assay (ELISA). RESULTS: Serum FGL1 level was found to be statistically significantly higher in RA patients compared to the control group, and in the MHA group compared to the LDA group. The mean FGL1 level was determined as 805.37 ng/ml in the LDA group, 1055.5 ng/ml in the MHA group and 652.31 ng/ml in the control group (p < 0.001). There was a positive correlation between FGL1 level and CRP, Erythrocyte Sedimentation Rate (ESR), CRP/Albumin levels. CONCLUSIONS: Increased serum FGL1 levels were found to increase the likelihood of identifying patients with moderate-to-high disease activity RA. FGL1 is also effective in evaluating disease activity when used together with other inflammation markers, especially CRP/Albumin.
Minimizing high sensitivity troponin T delta variation at low concentration using BD Barricor blood collection tube.
Tsui AKY, Qiu J, Seiden-Long I … +1 more , Cembrowski G
Clin Biochem · 2025 Dec · PMID 40886787 · Publisher ↗
OBJECTIVE: Reproducible low troponin concentrations from high-sensitivity troponin (hs-cTn) assays are paramount to accurate risk determination in the accelerated diagnostic pathway. Total variation consists of pre-analy...
OBJECTIVE: Reproducible low troponin concentrations from high-sensitivity troponin (hs-cTn) assays are paramount to accurate risk determination in the accelerated diagnostic pathway. Total variation consists of pre-analytical, analytical and biological components. While analytical and biological variations cannot be readily modifiable, minimizing pre-analytical variation is desirable and potentially attainable. The BD Barricor collection tube has previously been demonstrated to reduce pre-analytical variation in test results. The goal of the study is to determine whether BD Barricor tubes provide more reproducible hs-cTnT results compared to plasma separator tubes (PST) at concentrations ≤ 20 ng/L. METHODS: Paired intra-patient hs-cTnT results collected less than 1 h apart in the emergency department were retrospectively analyzed from nine urban hospitals which primarily use either PST (n = 336 pairs) or Barricor (n = 327 pairs) collection tubes for troponin. Total variation of the replicated measurements was calculated for hs-cTnT ≤ 20 ng/L. The numbers of paired intra-patient samples were grouped based on decisive absolute delta thresholds as indicated by the European Society of Cardiology 0/1 h algorithm; delta < 3 ng/L, 3-4 ng/L, ≥5 ng/L. RESULTS: The total testing variation for hs-cTnT collected in PST is 14.8 % while Barricor is 8.6 % for hs-cTnT ≤ 20 ng/L. The proportion of delta values < 3 ng/L between the intra-patient replicates is 80.4 % (95 % CI: 75.7-84.5 %) in PST compared to 95.4 % (95 % CI: 92.5-97.4 %) in Barricor (p < 0.001). Median time for serial sampling in PST is 41 min (IQR:18-53) and Barricor is 45 min (IQR 23-54). CONCLUSION: The use of Barricor tubes demonstrated reproducible and less variable hs-cTnT replicates at concentration ≤ 20 ng/L when compared to a hospital that does not use Barricor tubes.
Comparison of capillary dried blood spot and capillary microtubes with venous immunoglobulin G levels for routine diagnostics.
Boland SL, Doeleman MJH, Hofstee LGE … +6 more , Soels L, Visser TSQ, de Roock S, Hamann D, van Montfrans JM, Tiel Groenestege WM
Clin Biochem · 2025 Dec · PMID 40865669 · Publisher ↗
BACKGROUND AND AIMS: Patients with primary antibody deficiencies receiving immunoglobulin replacement therapy require frequent monitoring of immunoglobulin G (IgG) levels. Capillary IgG measurements from dried blood spot...
BACKGROUND AND AIMS: Patients with primary antibody deficiencies receiving immunoglobulin replacement therapy require frequent monitoring of immunoglobulin G (IgG) levels. Capillary IgG measurements from dried blood spots (DBS) or microtubes offer several advantages over samples obtained by venipuncture, including facilitating remote self-sampling. However, the validity of this alternative method is still unknown. We evaluated the comparability of IgG levels measured in venous samples with capillary blood samples collected on DBS cards and in microtubes. METHODS: Paired venous and capillary finger-stick DBS and microtube samples were collected from 100 patients. IgG was extracted from DBS with phosphate buffered saline and measured with a Siemens Atellica CH. For method comparison we performed Deming regression analysis. Absolute mean bias and limits of agreement were calculated with Bland-Altman analysis. The method comparison followed the Clinical Laboratory Improvement Amendments' (CLIA) recommended approach, but stricter limits proposed by the EFLM were applied. Relative mean differences were compared to a 10.9 % total allowable error (TEa). RESULTS: Method comparison of venous versus capillary DBS samples resulted in an R of 0.77. Mean bias was 0.23 g/L with limits of agreement of -4.06 g/L to 4.53 g/L. Method comparison of venous versus capillary microtube samples resulted in an R of 1.00. Mean bias was -0.11 g/L with -0.67 g/L to 0.46 g/L limits of agreement. Relative mean differences were 2.2 % for DBS sampling and -0.6 % for capillary sampling, both fall within 10.9 % TEa and CLIA criteria. CONCLUSION: IgG measurements from DBS demonstrated insufficient correlation and excessively broad limits of agreement, making it unsuitable for accurately determining IgG levels. This result hampers implementation of DBS in routine diagnostics. Conversely, capillary microtube samples demonstrated a strong correlation and narrow limits of agreement, which makes them a viable alternative to venipuncture.
An improved and economical LLE-LC/MS method for quantifying phosphatidylethanol: Identification and separation of isotopic cross-talk in clinical alcohol testing.
Yerra NV, Pini C, Cordon-Cardo C … +1 more , Mendu DR
Clin Biochem · 2025 Oct · PMID 40850364 · Publisher ↗
OBJECTIVE: Phosphatidylethanol (PEth) is a group of phospholipids formed in the presence of ethanol on the red blood cell membrane. Due to their stability in blood for 3-4 weeks, they have become reliable direct biomarke...
OBJECTIVE: Phosphatidylethanol (PEth) is a group of phospholipids formed in the presence of ethanol on the red blood cell membrane. Due to their stability in blood for 3-4 weeks, they have become reliable direct biomarkers for long-term monitoring of alcohol use. This study aimed to develop and validate a robust, high-throughput liquid chromatography and tandem mass spectrometry (LC-MS/MS) method for the routine clinical quantification of the two most common PEth homologues, PEth 16:0/18:1 (POPEth) and PEth 16:0/18:2 (PLPEth), while addressing common analytical challenges. METHODS: An established quantification method employing liquid-liquid extraction was used with optimized LC-MS/MS parameters. The method was validated for correlation studies, precision, analytical measurement range, analytical sensitivity, analytical specificity, carryover, dilution linearity, stability, matrix effect and extraction recovery, with specific attention to eliminating isotopic cross-talk and chromatographic interferences. A method comparison was performed using specimens analyzed by an external reference laboratory. RESULTS: The method demonstrated excellent linearity for both POPEth and PLPEth across the analytical measurement range (10-2000 ng/mL), with correlation coefficients (r) of 0.99. Intra- and inter-assay precision values were within ± 10 % coefficient of variation. Recovery yields ranged from 78-85 %. The optimized method resolved isotopic cross-talk and exhibited no carryover. Comparison with an external laboratory showed strong correlation for both homologues (slopes of 0.979 and 1.049; r = 0.99). CONCLUSION: We developed and validated a sensitive and specific LC-MS/MS method for the quantification of POPEth and PLPEth. The assay provides improved recovery, eliminates isotopic cross-talk, shows no carryover, and is suitable for high-throughput clinical laboratories. This method enables reliable and cost-effective monitoring of alcohol use in routine clinical practice.
Defining a clinically relevant thyroglobulin antibody interference threshold for high-sensitivity thyroglobulin immunoassays: a single institution case study.
Patel S, Peck Palmer OM, Lay CB … +3 more , Mulvey K, Shurin MR, Wheeler SE
Clin Biochem · 2025 Oct · PMID 40848842 · Publisher ↗
BACKGROUND: The interpretation of serum thyroglobulin (Tg) levels in differentiated thyroid cancer is complicated by interference from thyroglobulin antibodies (TgAb) and there is no standardized threshold to determine i...
BACKGROUND: The interpretation of serum thyroglobulin (Tg) levels in differentiated thyroid cancer is complicated by interference from thyroglobulin antibodies (TgAb) and there is no standardized threshold to determine interference. Following implementation of a new instrument, we observed increased TgAb-positive samples which reflex to alternate send-out Tg methods with reduced analytic sensitivity but which are more robust to TgAb interference. This resulted in fewer patients having detectable Tg for monitoring, longer turnaround times, and higher costs. We hypothesized that the TgAb assay limit of detection (LOD) was lower than the clinically meaningful interference threshold. METHODS: We analyzed 119 serum specimens with an electrochemiluminescent TgAb immunoassay (ECLIA-TgAb) ≥ 10 IU/mL, comparing TgAb measurements by radioimmunoassay (RIA-TgAb) and Tg levels measured via immunometric assay (IMA-Tg) and RIA (RIA-Tg; reference method), and clinical adjudication of discrepant samples. RESULTS: Of ECLIA-TgAb specimens above the LOD (10 IU/mL), 30 % were positive by RIA-TgAb. Increasing the ECLIA-TgAb threshold to 20 IU/mL improved concordance to 90 %. A 20 IU/mL threshold optimized qualitative agreement between IMA-Tg and RIA-Tg (95 %). Retrospective chart review of patient diagnosis and treatment indicated that there would be no change in patient management with the revised threshold. CONCLUSIONS: We found that an ECLIA-TgAb threshold of 20 IU/mL allowed more patients to be followed by the high sensitivity IMA-Tg method with no change to clinical decision-making, reducing send-out testing by 66 %. This approach offers an accessible and practical strategy for individual laboratories to define clinically appropriate TgAb thresholds to maximize the samples eligible for highly sensitive Tg measurement.
Analytical performance and clinical evaluation of CL AIA-PACK® hs-E2, a high-sensitivity estradiol sandwich immunoassay using an anti-immunocomplex antibody.
Fujimura S, Usami Y, Yamamoto A … +1 more , Ishimine N
Clin Biochem · 2025 Oct · PMID 40835216 · Publisher ↗
INTRODUCTION: The CL AIA-PACK® hs-E2 (hs-E2) is a high-sensitivity estradiol (E2) sandwich immunoassay employing an anti-immunocomplex antibody. This study aimed to evaluate its analytical performance and clinical utilit...
INTRODUCTION: The CL AIA-PACK® hs-E2 (hs-E2) is a high-sensitivity estradiol (E2) sandwich immunoassay employing an anti-immunocomplex antibody. This study aimed to evaluate its analytical performance and clinical utility at low concentration ranges relevant to aromatase inhibitor therapy and pediatric endocrinology, where accurate E2 measurement is clinically important. METHODS: The hs-E2 assay was evaluated for its precision, linearity, sensitivity, and interference. Its performance was compared with a conventional competitive immunoassay (Elecsys® E2) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Estradiol levels were measured in patients with estrogen receptor-positive breast cancer receiving selective estrogen receptor modulator or aromatase inhibitor therapy to assess clinical applicability. RESULTS: The assay showed excellent precision (CVs < 6.4 %) and linearity across a broad concentration range. The limit of detection and limit of quantification were 4.84 and 7.11 pmol/L (10 % CV), respectively. Conjugated bilirubin induced a mild concentration-dependent decrease in measured E2 values. The hs-E2 assay showed a strong correlation with LC-MS/MS, even at low concentration ranges (r = 0.998), while Elecsys showed a weaker correlation below 147 pmol/L. In breast cancer patients, hs-E2 revealed significant differences in E2 levels across treatment groups, which were not detectable by the Elecsys assay. CONCLUSIONS: The hs-E2 immunoassay using an anti-immunocomplex antibody exhibited superior analytical sensitivity and precision at low concentration ranges to conventional methods. Its strong agreement with LC-MS/MS and enhanced clinical discrimination support its utility in monitoring E2 levels in hormone-treated breast cancer patients and other low-E2 clinical conditions.
Gaps in guideline adherence: evaluating HLA-B*57:01 screening for abacavir sensitivity and the implementation of evidence-based HIV care.
Kalman LV, Xia Y, Huang YA … +3 more , Buchacz K, Astles R, O'Shea J
Clin Biochem · 2025 Oct · PMID 40829703 · Full text
OBJECTIVE: Approximately 5-8 % of the population carries the HLA-B*57:01 allele, which increases the risk of severe hypersensitivity reactions to abacavir. Current guidelines and an FDA black box warning recommend HLA-B*...
OBJECTIVE: Approximately 5-8 % of the population carries the HLA-B*57:01 allele, which increases the risk of severe hypersensitivity reactions to abacavir. Current guidelines and an FDA black box warning recommend HLA-B*57:01 screening for all patients before starting abacavir. We assessed the proportion of patients who undergo screening before initiating abacavir to evaluate adherence to guidelines. DESIGN: A retrospective cohort study using national IQVIA® PharMetrics Plus reimbursement data. METHODS: Data from the 2014-2022 IQVIA® PharMetrics Plus March 2023 dataset were analyzed. We identified patients aged ≥ 18 years who were newly prescribed abacavir, with ≥ 12 months of continuous enrollment before their first abacavir prescription. We examined the proportion of individuals who received HLA-B*57:01 screening any time before their initial abacavir prescription and conducted a multivariable logistic regression analysis on the receipt of HLA-B*57:01 screening adjusting for sex, age, year, and region. RESULTS: We identified 7,391 patients newly prescribed abacavir between 2014 and 2022. Approximately 46 % received an HLA-B*57:01 screen before initiation of abacavir. Annual screening rates ranged from 44 % to 50 % between 2015 and 2018 and dropped to 17 % by 2022. Screening was less likely to occur after 2018, compared to earlier in the study period, and more likely for younger as well as male patients. CONCLUSIONS: These findings highlight broader challenges in HIV guideline adherence, emphasizing the need for ongoing evaluation and systematic interventions to improve implementation and patient safety.
Ionized magnesium-the forgotten strong ion in pediatric critical care.
Filler G
Clin Biochem · 2025 Oct · PMID 40819827 · Publisher ↗
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Capillary electrophoresis mis-anchoring in a case of Hb Hope with HbE.
Higgins V, Volodko N, Parker ML … +6 more , Estey MP, Proctor D, Olayinka L, Newbigging A, Bordeleau P, Powell M
Clin Biochem · 2025 Oct · PMID 40818619 · Publisher ↗
BACKGROUND: Capillary electrophoresis is a widely used method for hemoglobin (Hb) fraction separation and relative quantitation, where pre-defined Hb peaks (typically HbA and HbA2) act as reference points to "anchor" the...
BACKGROUND: Capillary electrophoresis is a widely used method for hemoglobin (Hb) fraction separation and relative quantitation, where pre-defined Hb peaks (typically HbA and HbA2) act as reference points to "anchor" the electropherogram and define migration zones. In cases lacking HbA or involving variants with migration patterns similar to HbA or HbA2, mis-anchoring can occur-leading to incorrect zoning of Hb variants. This presents a diagnostic challenge, where follow-up investigations, often including molecular testing, are required to establish an accurate diagnosis. CASE REPORT: We report a case of a 43-year-old Thai female who underwent hemoglobinopathy investigation for microcytic anemia. Capillary electrophoresis showed peaks in the HbA (70.8%), HbA2 (24.4%), and HbC (2.9%) zones, as well as two small peaks in the Z11 (0.9%) and HbD (1.0%) zones. Gel electrophoresis at acid pH showed a band in the HbA position and one slightly anodal to the HbF position and at alkaline pH showed a band in the HbC/E position and another slightly anodal to the HbA position. HBB sequencing identified heterozygosity for the pathogenic HbE and clinically benign Hb Hope variants. HBA PCR detected a single alpha globin gene deletion (αα/α-3.7), consistent with alpha thalassemia silent carrier. Reinterpretation of the electropherogram showed that Hb Hope and HbE mis-anchored as HbA and HbA2, respectively, due to their similar migration deltas. CONCLUSION: This is the first documented case of compound heterozygosity for Hb Hope and HbE characterized by capillary electrophoresis. It highlights how beta chain variants with similar migration spacing to HbA and HbA2 can mis-anchor, emphasizing the need for molecular testing when results are unclear. Definitive testing helps avoid diagnostic misclassification and ensure accurate interpretation in complex hemoglobinopathy cases.
Critical role of laboratory and multidisciplinary strategies in the early diagnosis of acquired haemophilia a for life-saving management.
Belardi R, Emili M, Viola FG … +8 more , Velocci S, Baldetti M, Minieri M, Pieri M, Picchi E, Morosetti D, Bernardini S, Terrinoni A
Clin Biochem · 2025 Oct · PMID 40818618 · Publisher ↗
BACKGROUND: Acquired haemophilia A (AHA) is a rare but potentially life-threatening autoimmune disorder characterized by the development of autoantibodies against coagulation factor VIII (FVIII). It manifests with sponta...
BACKGROUND: Acquired haemophilia A (AHA) is a rare but potentially life-threatening autoimmune disorder characterized by the development of autoantibodies against coagulation factor VIII (FVIII). It manifests with spontaneous, severe bleeding in patients without a personal or family history of bleeding disorders. Early recognition and rapid treatment are crucial to reduce morbidity and mortality. CASE PRESENTATION: Here we describe two cases of AHA in elderly female patients with no prior history of coagulopathy. The first case involved an 81-year-old woman presenting with extensive spontaneous haematomas and severe anaemia. Laboratory findings revealed an isolated prolonged activated partial thromboplastin time (aPTT), undetectable FVIII activity, and the presence of a low-titre FVIII inhibitor (2.24 BU/mL). Treatment with recombinant activated factor VII (rFVIIa) and corticosteroids led to clinical improvement and inhibitor reduction. The second case concerned an 85-year-old woman who developed severe haemorrhagic manifestations following ureteric stenting. Coagulation studies showed markedly prolonged aPTT and a high-titre FVIII inhibitor (165 BU/mL). Despite initiation of immunosuppressive therapy the patient experienced fatal complications due to uncontrolled bleeding and multi-organ failure. CONCLUSIONS: These cases underscore the importance of considering a possible AHA in patients with isolated aPTT prolongation and unexplained bleeding. Punctual laboratory diagnosis, including mixing studies and FVIII inhibitor assays, is essential for early life-saving interventions. Multi-disciplinary management and rapid initiation of haemostatic and immunosuppressive therapies are key to improving outcomes in this challenging condition.
Diagnostic value of serum TSI levels in Graves' disease and direct comparison of diagnostic performance with TRAb: A systematic review and meta-analysis.
Jiang Z, Li S, Yang L … +6 more , Song X, Zhang X, Guo L, Guo J, Zhang H, Chen D
Clin Biochem · 2025 Oct · PMID 40789418 · Publisher ↗
This study aimed to systematically assess the diagnostic value of thyroid-stimulating immunoglobulin on the Siemens Immulite platform (the TSI assay) and to conduct a direct comparison with thyrotropin receptor antibodie...
This study aimed to systematically assess the diagnostic value of thyroid-stimulating immunoglobulin on the Siemens Immulite platform (the TSI assay) and to conduct a direct comparison with thyrotropin receptor antibodies on the Roche cobas platform (the TRAb assay) for the diagnosis of Graves' disease (GD). We performed systematic literature searches across multiple databases. Following strict screening, we identified 20 eligible clinical studies that evaluated the diagnostic value of the TSI assay, either alone or in comparison with the TRAb assay. Using random-effects models, we calculated pooled estimates of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Diagnostic accuracy was further evaluated through summary receiver operating characteristic curve analysis. The findings revealed that the TSI assay demonstrated excellent diagnostic accuracy, with pooled SEN of 0.933 (95 % CI: 0.924 - 0.941), SPE of 0.961 (95 % CI: 0.956 - 0.964), PLR of 24.078 (95 % CI: 16.727 - 34.659), NLR of 0.036 (95 % CI: 0.020 - 0.066), and DOR of 778.29 (95 % CI: 343.45 - 1763.67), supported by an area under the curve (AUC) of 0.9919. In direct comparison to the TRAb assay, the TSI assay showed slightly better SEN (0.967 vs. 0.889), DOR (1310.03 vs. 692.73), and NLR (0.023 vs. 0.046), comparable SPE (0.964 vs. 0.959) and PLR (29.954 vs. 30.066), and higher AUC (0.9963 vs. 0.9899). These results conclusively demonstrate that the TSI assay shows high sensitivity and specificity in the diagnosis of GD, exceeding or at least comparable to TRAb, making it a valuable tool for clinical diagnosis.
Rethinking research funding through a sustainability Lens.
Tu KJ, Greever-Wilson C
Clin Biochem · 2025 Oct · PMID 40780586 · Publisher ↗
Research funders can play a transformative role in reducing the environmental footprint of science without compromising its quality or productivity. Scientific research is among the most energy- and resource-intensive se...
Research funders can play a transformative role in reducing the environmental footprint of science without compromising its quality or productivity. Scientific research is among the most energy- and resource-intensive sectors globally, with its carbon footprint estimated to rival that of the aviation industry-contributing approximately 2 % of global greenhouse gas emissions. Yet the organizations that fund scientific research, particularly in the United States, structurally disincentivize sustainability, often rewarding waste rather than resource efficiency. We highlight how this is beginning to change across Europe, where major funding agencies are leading a growing movement to embed sustainability into research operations-from including environmental impact assessments in grant proposals to supporting green lab certification programs. These policies are on track to accelerate operational efficiency, reduce costs, and align research practices with climate action goals. Finally, we outline specific policy reforms and practical steps that researchers, institutions, and funders everywhere can adopt to build a more sustainable future for science-one where environmental stewardship is a core expectation of research.
Best practice guidelines on reference interval harmonization in Canada: Evidence-based recommendations from the CSCC working group on reference interval harmonization (CSCC WG-hRI).
Bohn MK, Nyholt D, Balion C … +13 more , Cembrowski G, Collier C, Guire V, Higgins V, Jung B, Landon O, Mohammed-Ali Z, Seccombe D, Taher J, Tsui AKY, Venner AA, Al-Habeeb NW, Adeli K
Clin Biochem · 2025 Oct · PMID 40763882 · Publisher ↗
Unnecessary variation in reference intervals across clinical laboratories increases the risk of inconsistent or misinformed clinical decision-making. Development of harmonized or common reference intervals for assays tha...
Unnecessary variation in reference intervals across clinical laboratories increases the risk of inconsistent or misinformed clinical decision-making. Development of harmonized or common reference intervals for assays that demonstrate minimal bias across measurement procedures and laboratories is an important step towards standardized quality healthcare. The aim of this document is to recommend evidence-based harmonized reference intervals for routine clinical laboratory tests that can be implemented in hospital and community settings across Canada. The approach that was taken for these recommendations included several important steps. Candidate analytes for harmonization were selected based on documented traceability and external quality assessment performance. Two years of patient test result data for 16 routine clinical chemistry analytes were extracted from four provincial community laboratories across Canada. A robust indirect statistical algorithm was applied to assess the feasibility of harmonization and harmonized reference intervals were established for appropriate analytes. Derived harmonized reference intervals were compared to existing data from healthy individuals from Canadian and international studies. All recommended harmonized reference intervals were verified across nine Canadian laboratories that included all main manufacturers using serum and plasma samples collected from 60 healthy volunteers. Based on our findings, evidence-based harmonized reference intervals are recommended for 13 analytes, including: albumin (bromocresol green method only), alanine aminotransferase (ALT) with and without pyridoxal 5'-phosphate, alkaline phosphatase (ALP), calcium, carbon dioxide (total), chloride, creatinine, lactate dehydrogenase (LDH), phosphate, potassium (serum only), magnesium, total protein, and thyroid stimulating hormone (TSH). These recommendations will support national harmonization of laboratory reference intervals with the goal of improving and standardizing clinical decision-making and patient care across Canada.
The biological diagnosis of Alzheimer's disease using blood-based biomarkers: A Canadian prospective.
Kumar P, Mousavi A, Frykman H
Clin Biochem · 2025 Oct · PMID 40752564 · Publisher ↗
Dementia is the most common type of neurodegenerative diseases, with Alzheimer's Disease (AD) constituting about two-thirds of these cases. In Canada, an estimated 674,000 individuals may have AD by 2031, nearly doubling...
Dementia is the most common type of neurodegenerative diseases, with Alzheimer's Disease (AD) constituting about two-thirds of these cases. In Canada, an estimated 674,000 individuals may have AD by 2031, nearly doubling from 2011. The total annual economic burden of dementia in Canada was about $40 billion in 2020, with an approximate average of $67,200 per person with dementia and if current trends continue, its annual burden could grow by 275 % over 30 years. AD is a double proteinopathy with its fundamental neuropathologic features defined by amyloid-beta (Aβ) plaques and neurofibrillary tangles with aggregated tau proteins. This supports the potential mechanism-based proteomic biomarkers to be detected in biofluids. Pathophysiologic and topographical biomarkers have significantly improved the diagnosis of typical and atypical phenotypes of AD, helping clinicians recognize and differentiate AD phenotypes from other types of dementia and neurodegenerative diseases. The CSF Aβ42/Aβ40 ratio measurement is a robust biomarker in detecting cerebral Aβ pathology and AD diagnosis. A number of very sensitive assays for measuring AD blood biomarkers including p-tau217, front-runner candidate for AD diagnosis, have been developed during last years. In this review we discus the biological configuration and normal function of involved proteomic in AD including amyloid β and tau protein, particularly tau phosphorylation and biochemistry of tau isoforms and their detection feasibility in plasma using novel technologies. Then, we critically review Blood-Based biomarkers' analytical and clinical validations, focusing more on plasma p-tau217 and their availability and prospects in Canada.
Waste management and environmental health impact: sustainable laboratory medicine as mitigating response.
Nwobi NL, Anetor GO, Nwobi JC … +4 more , Igharo GO, Adeyemi AV, Badrick T, Anetor JI
Clin Biochem · 2025 Oct · PMID 40752563 · Publisher ↗
Unregulated and unsustainable human, industrial, and scientific activities generate various forms of waste which contribute immensely to the current rising global, multifaceted environmental health challenges. Laboratory...
Unregulated and unsustainable human, industrial, and scientific activities generate various forms of waste which contribute immensely to the current rising global, multifaceted environmental health challenges. Laboratory medicine practices continue to be a key contributor to this menace with continuous generation of waste ranging from hazardous chemicals and toxic heavy metals to pathogenic biological waste, all of which pose significant risks to environmental and public health. While the wider scientific community has made significant attempts to adopt sustainable practices aligned with the United Nations Sustainable Development Goals, the laboratory medicine sector has lagged behind in implementing effective waste management strategies, particularly in developing countries, highlighting the need for targeted sustainable laboratory medicine practices. This review analysed relevant existing literature on the impact of laboratory waste on environmental health and explored sustainable laboratory medicine as a potential mitigating approach. The findings revealed that inefficient waste management significantly contributes to environmental degradation. Implementing sustainable laboratory (also known as green laboratory) practices such as use of eco-friendly materials, energy-efficient protocols, resource conservation, innovative waste minimisation, and treatment technologies appears to be a crucial framework that will mitigate the threat posed by laboratory-derived waste on environmental health. The review emphasised the need for a paradigm shift towards sustainable laboratory practices, advocating for comprehensive training, institutional commitment, and regulatory support to mitigate the environmental health impacts of laboratory-generated waste. This will ensure that laboratory medicine continues to advance without compromising public health or the planet.
Monitoring free plasma hemoglobin in ECMO patients: a two-center comparative study of second-derivative spectrophotometry and hemolysis indexes.
Sharaiha T, Pellecuier N, Dabernat S … +7 more , Mestari F, Colombiès B, Richard E, Alkouri R, Bonnefont-Rousselot D, Rucheton B, Bats ML
Clin Biochem · 2025 Oct · PMID 40730295 · Publisher ↗
BACKGROUND AND AIMS: Extracorporeal membrane oxygenation (ECMO) can induce massive intravascular hemolysis, commonly quantified by plasma free hemoglobin (fHb) measurement. While manual spectrophotometry using second der...
BACKGROUND AND AIMS: Extracorporeal membrane oxygenation (ECMO) can induce massive intravascular hemolysis, commonly quantified by plasma free hemoglobin (fHb) measurement. While manual spectrophotometry using second derivative spectrophotometry (sDS) is the reference method, a recent assessment tool based on the hemolysis index (HI) was developed for fHb determination on different automated systems. This study compares the performance of two HI methods-on Roche Cobas c502 and Abbott Architect c16000-versus sDS in 83 ECMO patients. MATERIALS AND METHODS: Method validation was performed on both automated HI systems, including determination of linearity, precision, and analytical interference from lipemia and icterus. Plasma fHb measurements in 83 ECMO patients from two hospital centers were compared between the two HI-derived methods and two manual sDS methods (at 415 nm and 578 nm). RESULTS: Both HI-automated methods showed excellent linearity (0.04-20 g/L) and reproducibility (CVs between 2.3 % and 6.3 %). However, they exhibited sensitivity to interference by high lipemic index, leading to underestimation of fHb for Abbott Architect and overestimation for Roche Cobas. In non-lipemic ECMO samples with fHb levels >0.10 g/L, a very good correlation was found between HI and sDS, especially at 578 nm. However, discrepancies were observed in lipemic samples, leading to clinically relevant biases for fHb values >0.50 g/L. CONCLUSION: The Roche Cobas and Abbott Architect HI methods are reliable tools for monitoring fHb in ECMO patients, with good reproducibility and linearity. However, in the presence of significant lipemia, confirmation by sDS is recommended to ensure accurate assessment of hemolysis. This approach facilitates an efficient and automated monitoring of fHb, essential for daily managing ECMO-related complications and improving patient outcomes.
Low vacuum (3 mL) rapid serum tubes offer better protection from hemolysis than plasma separator tubes collected in the emergency department.
Shang E, Takasugi T, Prellwitz P … +6 more , Figueroa Villalba C, Sangal RB, Venkatesh AK, Maciejak L, Oberle E, El-Khoury JM
Clin Biochem · 2025 Oct · PMID 40721040 · Publisher ↗
INTRODUCTION: Hemolysis is a major source of interference with laboratory testing, especially for the emergency department (ED), leading to longer turnaround times for test results, repeated blood draws, delay in care de...
INTRODUCTION: Hemolysis is a major source of interference with laboratory testing, especially for the emergency department (ED), leading to longer turnaround times for test results, repeated blood draws, delay in care delivery, and increased hospital costs. Rapid serum tubes (RST) can reduce transport-induced hemolysis, especially for samples sent via the pneumatic tube system, as compared with plasma separator tubes (PST). Previously, studies testing the efficacy of RST used larger volume 5 mL tubes to compare to 4.5 mL PST tubes. In this study, a lower vacuum RST (3 mL) is compared to PST (3.5 mL) for hemolysis reduction. METHODS: Paired PST and RST blood samples from 47 ED patients were included in this study. RST and PST samples were sent via the pneumatic tube system and inspected for degree of clotting prior to centrifugation. All samples were tested within the hour for high-sensitivity troponin (hs-cTnT), hemolysis, lactate dehydrogenase, and potassium. RESULTS: Degree of hemolysis was significantly lower in fully clotted RSTs compared to PSTs (p = 0.0005). In RSTs that only partially clotted and PSTs, differences in hemolysis rates were non-significant (p = 0.273). The hs-cTnT levels in RST and PST are concordant with a slope of 0.96, an intercept of 1.01 ng/L and an R-squared value of 0.9318. CONCLUSION: Fully clotted low-vacuum RSTs provide improved protection from transport-induced hemolysis compared to low-vacuum PSTs or partially clotted RSTs. Low-vacuum RSTs also provided more hemolysis protection than larger volume RSTs previously studied. Clot formation prior to transport is key to the protective mechanism of RST. Blood device manufacturers are encouraged to develop low vacuum RST for use by the ED and other areas with high hemolysis rates.
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