Clinical Biochemistry[JOURNAL]
Sun
200 papers
Persistent red fluorescence interference in anti-PLA2R indirect immunofluorescence assays associated with liposomal doxorubicin.
Lopes-Paciencia S, Caron NJ, Salesse C … +3 more , Claveau JS, Laurin LP, Benkirane K
Clin Biochem · 2026 May · PMID 42097480 · Publisher ↗
BACKGROUND: Analytical interference can occasionally affect indirect immunofluorescence (IIF) assays and lead to unexpected fluorescence signals. CASE: We report this type of interference during anti-phospholipase A2 rec...
BACKGROUND: Analytical interference can occasionally affect indirect immunofluorescence (IIF) assays and lead to unexpected fluorescence signals. CASE: We report this type of interference during anti-phospholipase A2 receptor (anti-PLA2R) testing in a patient investigated for primary membranous nephropathy (pMN). Cells incubated with the patient's sample exhibited an unexpected intense red fluorescence signal, deviating from the typical green fluorescence indicative of a positive result or the absence of fluorescence in negative cases. DISCUSSION: This unexpected signal appeared to depend on the type of fixative used for the cells and raised concerns regarding result interpretation. Subsequent analyses, including ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS), identified the source of interference as doxorubicin, a chemotherapeutic agent known for its intrinsic red fluorescence. Notably, this interference persisted for up to three weeks after the last chemotherapy administration, likely due to the prolonged circulation of its PEGylated liposomal formulation. CONCLUSIONS: This case highlights the need for heightened awareness of potential fluorescence interferences in IIF assays, particularly in patients receiving liposomal formulations of intrinsically fluorescent drugs such as doxorubicin. Clinicians and laboratory personnel should consider recent exposure to such medications when interpreting unexpected fluorescence signals in IIF assays to avoid potential misinterpretation. In these situations, alternative analytical methods such as ELISA or delayed testing may help ensure accurate assessment.
Multiple myeloma revealed by a pulmonary embolism, with more anodal migration of λ IgG in the β region on serum protein electrophoresis.
Benmoussa C, Baroudi A, Abdesselami O … +4 more , Ghomari K, Moujtahide DE, Sebbar EH, Choukri M
Clin Biochem · 2026 Apr · PMID 42067177 · Publisher ↗
INTRODUCTION: 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...
INTRODUCTION: 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 β region is an exceptionally rare occurrence that can pose significant diagnostic challenges. CASE PRESENTATION: 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 β 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. DISCUSSION: This case highlights three exceptionally rare and clinically significant features: (1) IgG monoclonal protein migration in the β 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. CONCLUSION: Recognition of more anodal IgG migration and awareness of thromboembolic presentation are crucial to ensure early diagnosis and appropriate management of multiple myeloma.
Verification of pleural fluid pH on radiometer ABL 90 flex plus blood gas analyzer.
Thakur V, Akerele OA, Randell E
Clin Biochem · 2026 Apr · PMID 42067176 · Publisher ↗
BACKGROUND: Pleural fluid pH analysis was verified on three new ABL90 Flex Plus blood gas analyzers (M/S Radiometer, Canada) placed at the primary site of St. Clare's Mercy Hospital. METHOD: To verify precision of the as...
BACKGROUND: Pleural fluid pH analysis was verified on three new ABL90 Flex Plus blood gas analyzers (M/S Radiometer, Canada) placed at the primary site of St. Clare's Mercy Hospital. METHOD: To verify precision of the assay, buffered pleural fluid samples of pH 6.8, 7.0 and 7.8 were measured in triplicate for 5 days. Linearity and method comparison between ABL 90 and Orion Pro Star PH211 pH meter (Thermo Fisher) were evaluated using buffered samples at each pH level ranging from 6.8 to 7.8. Method comparison was also done using unmodified patient fluid samples (n = 31) analyzed on three blood gas analyzers and Cole-Parmer PHR-146 Micro-Combination pH Electrode meter. The stability of the assay was verified for 120 min and 7 days at room temperature and at -80℃, respectively, using buffered samples. Impacts of fluid matrix on Orion and ABL90 were studied using aqueous buffered samples and buffered patient fluid samples. RESULTS: Precision shows a small variation in assay results. The assay was linear over pH 6.8 to 7.8. Stability studies indicated very small change at both ambient temperature and at -80℃. Good correlation was found between ABL90 blood gas analyzers and laboratory pH meters with unmodified patient samples and buffered pleural fluid samples of different pHs including medical decision limit of pH 7.3. The substantial bias observed between ABL90, and Orion pH measurements is attributed to sample matrix effect on measurement systems. CONCLUSIONS: The ABL90 analyzer is an acceptable device for measuring pleural fluid pH with short turnaround time. Multiple approaches are required to assure reliability of test results when a reference method is not available, and the analyte level is unstable under normal laboratory conditions.
Utilization of HLA-B27 genotyping in a mixed primary-hospital care (2023-2025): Test yield by requesting service, demographic predictors, and prevention of unnecessary duplicate genetic testing.
Obelleiro Campos AX, Malagón C, Ribera M … +2 more , Fernández R, Pedrique M
Clin Biochem · 2026 Apr · PMID 42044736 · Publisher ↗
BACKGROUND: HLA-B27 is a constitutional genetic marker strongly associated with spondyloarthritis and HLA-B27-associated acute anterior uveitis; its diagnostic value depends on clinical context and pre-test probability....
BACKGROUND: HLA-B27 is a constitutional genetic marker strongly associated with spondyloarthritis and HLA-B27-associated acute anterior uveitis; its diagnostic value depends on clinical context and pre-test probability. For "once-in-a-lifetime" constitutional genetic tests, repeat testing rarely adds clinical value and is a target for laboratory stewardship. METHODS: Retrospective observational study of all HLA-B27 genotyping requests recorded from 3 Jan 2023 to 31 Dec 2025 in a mixed primary-hospital care network. We described positivity overall and by requesting service/demographics. Multivariable logistic regression assessed predictors of positivity (sex, age, year, service). Requests without a reported result were classified as laboratory cancellations due to unnecessary duplicate testing when a prior historical HLA-B27 result was identified in the laboratory information system (LIS). RESULTS: Among 1,340 requests, 1,273 (95.0%) had a reported result: 151 positive (11.9%) and 1,122 negative (88.1%). Positivity varied by service (Family Medicine 10.0%, Rheumatology 16.7%, Rehabilitation 9.4%, Ophthalmology 25.0%). Adjusted odds of positivity were higher for Ophthalmology (OR 2.98, 95%CI 1.33-6.66) and Rheumatology (OR 1.74, 95%CI 1.15-2.62). Sixty-seven requests (5.0%) were cancelled as duplicates. CONCLUSIONS: HLA-B27 yield is strongly service-dependent, supporting targeted clinician education and feedback as a stewardship tool. Prior-result verification through a manual laboratory workflow prevented duplicate constitutional genetic testing in 5.0% of requests; automated LIS duplicate-checking represents a scalable next step.
Corrigendum to "Biological variability of lipoprotein-associated phospholipase A activity in healthy individuals" [Clin. Biochem. 50 (2017) 347-349].
Donato LJ, Meeusen JW, Jenkins SM … +5 more , Hartman SJ, Saenger AK, Baumann NA, Block DR, Jaffe AS
Clin Biochem · 2026 Jun · PMID 42034471 · Publisher ↗
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Troponin I interference in an 18-year-old patient with bradycardia: a case study.
Qian H, Jin H, Li S
Clin Biochem · 2026 Jun · PMID 42031157 · Publisher ↗
OBJECTIVE: To investigate the cause of markedly elevated cardiac troponin I (cTnI) levels that were inconsistent with the clinical presentation in an 18-year-old male patient with bradycardia. METHODS: Serial dilution an...
OBJECTIVE: To investigate the cause of markedly elevated cardiac troponin I (cTnI) levels that were inconsistent with the clinical presentation in an 18-year-old male patient with bradycardia. METHODS: Serial dilution analysis, heterophile antibody blocking test (HBT), polyethylene glycol 6000 (PEG6000) precipitation, and recovery rate calculation were performed on the patient samples, and the experiments were repeated three times. Additionally, continuous monitoring of cTnI, cardiac troponin T, myoglobin, creatine kinase (CK) and CK-MB was conducted on the patient. The recovery rate in the control group was derived from 20 troponin-positive patients. RESULTS: The serial dilution test showed good linearity. After HBT treatment, the cTnI concentration was 3744 ng/L, while the control tube was 4024 ng/L, showing no significant change. In contrast, cTnI decreased markedly to 142 ng/L after PEG6000 precipitation. The recovery rate was only 5.61%, which was significantly lower than the mean recovery rate of 53.33% observed in the control group. CONCLUSION: The patient was ultimately diagnosed with falsely elevated cTnI caused by macrotroponin interference. This case suggests that when laboratory results are inconsistent with clinical findings, the possibility of analytical interference should be carefully considered, and effective communication between the laboratory and clinicians is essential to avoid misleading diagnostic and therapeutic decisions.
Pre-analytic error and possible misinterpretation for macrotroponin.
Kavsak PA, Okwuegbuna O, Naz N
Clin Biochem · 2026 Jun · PMID 41967561 · Publisher ↗
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Investigation of alkaline phosphatase discrepancies on the Roche cobas® pro: causes, solutions, and workflow optimization.
Seiden-Long I, Niemann K, Moses K … +4 more , Butorin Y, Venner AA, Tsui AKY, Raizman JE
Clin Biochem · 2026 Jun · PMID 41935601 · Publisher ↗
BACKGROUND: A high frequency of delta check flags for alkaline phosphatase (ALP) on the Roche cobas® pro revealed non-reproducible and spurious ALP discrepancies. Multi-site studies were performed to characterize discrep...
BACKGROUND: A high frequency of delta check flags for alkaline phosphatase (ALP) on the Roche cobas® pro revealed non-reproducible and spurious ALP discrepancies. Multi-site studies were performed to characterize discrepancy frequency, identify root causes, and develop mitigation strategies. METHOD: ALP in lithium heparin plasma separator tubes (PST) were measured in duplicate on the Roche cobas® pro c503 at 9 sites and cobas® 8000 c702 at one site. Duplicate results exceeding the total allowable error (TEa: ≤150 U/L ± 15 U/L or > 150 U/L ± 10%) were defined as discrepancies. Three protocols were evaluated over 4-36 weeks: 1) repeat centrifugation and measurement, 2) use of an alternative tube type with cleaner plasma (BD Barricor) and 3) on-board 1:5 dilutions. RESULTS: A total of 563 ALP discrepancies were identified across c503 sites, whereas none were observed on the c702. Discrepancy frequency varied by sites (0.04-1.51% of total ALP volumes). Repeat centrifugation improved duplicate agreement and reduced discrepancies by 99.5%. Barricor tubes reduced discrepancies by 81.4%, but did not eliminate them, while dilution reduced discrepancies by 95.4%. An automated protocol combining dilution with respinning completely eliminated discrepancies. CONCLUSION: ALP discrepancies occurred across multiple c503 analyzers but were absent on the c702. The improvements observed with respinning, dilution, and Barricor tubes indicate a preanalytical source of error and suggest that the c503 may be more susceptible to plasma contaminants than the c702. Implementing an automated workflow integrating on-board dilution and additional centrifugation provided a cost-effective, reliable, and streamlined solution to fully mitigate ALP discrepancies.
Resolving method-dependent M-protein detection: a case of oligoclonality revealed through complementary immunotyping techniques.
Wang B, Cui Y, Man Q … +1 more , Song Y
Clin Biochem · 2026 Jun · PMID 41935600 · Publisher ↗
OBJECTIVES: This report exemplifies a critical diagnostic pitfall where differing results from two immunotyping methods-immunofixation electrophoresis (IFE) and capillary electrophoresis immunotyping (CE-IT) were the key...
OBJECTIVES: This report exemplifies a critical diagnostic pitfall where differing results from two immunotyping methods-immunofixation electrophoresis (IFE) and capillary electrophoresis immunotyping (CE-IT) were the key to identifying an infection-related oligoclonal process, thereby preventing misdiagnosis of a monoclonal gammopathy. DESIGN AND METHODS: We detail the case of a 54 years old febrile woman with active cytomegalovirus infection. Initial diagnostic workup included serum protein electrophoresis (SPE), IFE, and CE-IT. Results were integrated with clinical context, viral serology, serum free light chain analysis, and reviewed multidisciplinary. Confirmatory follow-up studies were performed one month after antiviral therapy. RESULTS: A key finding emerged from comparing the two methods: IFE revealed a faint but discrete, well-defined IgMλ band and a separate, more diffuse λ-band that was not associated with a detectable heavy chain, while CE-IT identified an IgGλ type component. These method-dependent results pointed to an underlying oligoclonal process. The diagnosis of a reactive oligoclonal response was supported by the confirmed viral infection, a normal free light chain ratio, and the absence of other clinical evidence of malignancy. Follow-up confirmed the hypothesis, demonstrating resolution of the initial electrophoretic abnormality and marked attenuation of the IFE band in parallel with clinical and virological improvement. CONCLUSIONS: This case establishes that method-dependent IFE and CE-IT findings should prompt consideration of a reactive oligoclonal etiology. It validates a diagnostic algorithm where such complementary findings, when interpreted within the full clinical context and followed by targeted treatment and short-term monitoring, can definitively resolve the dilemma between benign and malignant paraproteins.
Stability study of 17 clinical immunoassays analytes in serum and plasma samples within an automated storage and retrieval module: Assessment of add-on testing policies.
Mohammed B, Cyril L, Hélène K … +2 more , Emmanuelle PG, Clément C
Clin Biochem · 2026 Jun · PMID 41912004 · Publisher ↗
BACKGROUND: Additional tests are often requested on previously collected and stored samples. Automated storage and retrieval modules (SRMs) which are integrated into total laboratory automation (TLA) systems provide seal...
BACKGROUND: Additional tests are often requested on previously collected and stored samples. Automated storage and retrieval modules (SRMs) which are integrated into total laboratory automation (TLA) systems provide sealed, temperature-controlled storage and could potentially extend the scope of add-on testing. However, there is a lack of data regarding the stability of immunoassays when using an automated SRM. METHODS: We evaluated the short-term stability of 17 immunoassay analytes. Fresh serum and plasma samples were analysed using the Atellica IM (Siemens Healthineers) system at baseline and after storage in the SRM at 2-8 °C for 24, 48, and 72 h. Stability was assessed as the mean percentage change compared to the total limit of change (TLC), derived from analytical and biological variability. RESULTS: Most analytes remained stable for up to 72 h in both matrices. No significant differences were observed between serum and plasma, except for free T4, which exceeded its TLC in plasma after 72 h (+9.2%). CONCLUSIONS: This study demonstrates that most clinical immunoassays assessed on the Atellica IM module remained stable for up to 72 h in serum and plasma when stored in an automated SRM environment, except for free T4, which remained stable for up to 48 h in plasma. These findings support the feasibility and safety of performing delayed add-on tests in laboratories using TLA.
A novel missense variant in the SMC1A gene causing Cornelia de Lange syndrome in a Chinese neonate.
Yang Y, Wen Z
Clin Biochem · 2026 Jun · PMID 41905567 · Publisher ↗
BACKGROUND: Exome sequencing (ES) can improve the diagnostic yield of neonates with multisystem anomalies, but interpreting its results in the clinical setting remains challenging. CASE REPORT: A neonate showing multiple...
BACKGROUND: Exome sequencing (ES) can improve the diagnostic yield of neonates with multisystem anomalies, but interpreting its results in the clinical setting remains challenging. CASE REPORT: A neonate showing multiple abnormalities and his parents underwent trio-based ES. Sanger sequencing was applied to validate the variant. A novel hemizygous missense variant c.103G > A (p.Gly35Ser) was identified in exon 1 of the SMC1A gene in the neonate, but was not detected in his parents. The neonate was diagnosed with Cornelia de Lange syndrome. CONCLUSION: This study identified the novel hemizygous missense variant c.103G > A (p.Gly35Ser) in SMC1A as the likely molecular etiology of the neonate's multisystem abnormalities. We broadened the variant spectrum of the SMC1A gene and expanded the understanding of genotype-phenotype relationship of this gene.
Detecting Siemens macrotroponin by a point of care high sensitivity troponin I assay: A first look.
Karin A
Clin Biochem · 2026 Jun · PMID 41895503 · Publisher ↗
INTRODUCTION: Macrotroponins are increasingly recognized as the most common interference that confound interpretation of high sensitivity troponin I (hs-cTnI) results. Techniques for detection of macrotroponin presence t...
INTRODUCTION: Macrotroponins are increasingly recognized as the most common interference that confound interpretation of high sensitivity troponin I (hs-cTnI) results. Techniques for detection of macrotroponin presence tend to be slow and resource intensive. We evaluated the possibility of using a novel point of care hs-cTnI assay to rapidly distinguish samples with macrotroponin when original testing is performed on the Siemens Atellica hs-cTnI. MATERIALS AND METHODS: 64 residual plasma specimens from 56 patients with low likelihood of macrotroponin (reference group) were retested on iSTAT hs-cTnI. A second group of 29 samples with previously confirmed macrotroponin I using selective IgG depletion were also re-tested on both assays (macrotroponin group). RESULTS: In the reference group samples, all except 4 showed close agreement between methods (median bias = -1.4% [90% CI -7.2%, +2.4%]) whereas macrotroponin-positive samples generally showed larger biases (median bias = -57% [90% CI -68%, -52%]). All 4 clearly discordant samples in the reference group showed low recovery after IgG depletion consistent with presence of macrotroponin. Despite the bias, 93% of macrotroponin-positive samples also produced iSTAT hs-TnI results above its sex-specific 99th percentiles. CONCLUSIONS: These preliminary data suggest analysing plasma on iSTAT hs-cTnI is a promising tool for rapid and specific macrotoponin detection in the central laboratory for investigation of clinically discordant troponin results produced by the Siemens Atellica platform.
Validation and optimization of reference intervals for serum free light chains in Chinese patients with chronic kidney disease.
Xu W, Shen Y, Huang J … +6 more , Xiong Y, Pan B, Wang B, Guo W, Zhu J, Shao W
Clin Biochem · 2026 Jun · PMID 41881099 · Publisher ↗
OBJECTIVE: To explore the applicability of the laboratory-specific sFLC reference intervals in patients with CKD and to define new sFLC reference intervals on N-Latex platform in Chinese CKD patients. METHODS: We retrosp...
OBJECTIVE: To explore the applicability of the laboratory-specific sFLC reference intervals in patients with CKD and to define new sFLC reference intervals on N-Latex platform in Chinese CKD patients. METHODS: We retrospectively analyzed clinical data from 1,700 patients at all stages of CKD who attended Zhongshan Hospital, Fudan University, between 1 January 2023 and 31 December 2025; the cohort comprised 1,066 males and 538 females with 60 (IQR49-69) years. sFLC concentrations and κ/λ ratio were characterized, and stage-specific 95% reference intervals were derived from 1,135 randomly selected CKD patients and validated in other 565 patients. The clinical utility of these intervals was further validated with 36 patients initially diagnosed with LC-monoclonal gammopathy and eGFR < 60 mL/min/1.73 m. RESULTS: The laboratory-specific reference intervals (κFLC 9.6-23.2 mg/L, λFLC 11.6-37.5 mg/L, κ/λ ratio 0.540-1.150) showed limitations in CKD patients, with 96.2%, 85.0% and 12.2% of individuals falling outside these intervals, respectively. We derived CKD-stage-specific 95% reference intervals stratified by eGFR: eGFR 30-59 mL/min/1.73 m: κFLC 17.9-103.0 mg/L, λFLC 20.7-112.3 mg/L, κ/λ ratio 0.489-1.401; eGFR < 30 mL/min/1.73 m: κFLC 42.5-297.8 mg/L, λFLC 49.7-338.8 mg/L, κ/λ ratio 0.518-1.245. The novel CKD-specific reference intervals led a reduction of 11.3% and 3.9% in abnormal κ/λ ratio rates among patients with eGFR 30-59 mL/min/1.73 m and eGFR < 30 mL/min/1.73 m, respectively. All 36 LC-monoclonal gammopathy patients with eGFR < 60 mL/min/1.73 m exhibited an abnormal κ/λ ratio ;none fell within the novel κ/λ ratio reference interval. CONCLUSION: The CKD-specific sFLC reference intervals on N-Latex platform significantly reduce the proportion of abnormal sFLC results and enhance the application value of sFLC in CKD patients.
Corrigendum to "Genomic sequencing enhances metabolic newborn screening in Thailand" [Clin. Biochem. 142 (2026) 111107].
Kuptanon C, Innark P, Punnapum K … +7 more , Nammoonnoy S, Pankanjanato R, Numnuan M, Sripichai O, Wattanapokayakit S, Kunhapan P, Kunphol E
Clin Biochem · 2026 Jun · PMID 41820069 · Publisher ↗
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Clinical evaluation of CTS-1 specific coccidioidal immunodiffusion reagents for improved sensitivity and enhanced agreement with complement fixation testing.
Kaleta E, Grill FJ, Ronz B … +2 more , Grys T, Lake DF
Clin Biochem · 2026 Jun · PMID 41812697 · Publisher ↗
INTRODUCTION: Coccidioidomycosis is a fungal infection endemic to the southwestern United States and northern Mexico. Laboratory evaluation often includes serological methods including enzyme immunoassays (EIA), immunodi...
INTRODUCTION: Coccidioidomycosis is a fungal infection endemic to the southwestern United States and northern Mexico. Laboratory evaluation often includes serological methods including enzyme immunoassays (EIA), immunodiffusion (ID), and complement fixation (CF). This study evaluated a newly available chitinase-1 (CTS-1) specific ID assay for serodiagnosis of Coccidioides infections. MATERIALS AND METHODS: Sera from 1544 specimens were tested by traditional EIA, ID, CF assays, and simultaneously assayed using Cactus Bio CTS-1 ID reagents to compare the ability to identify seropositive patients. Positivity rates before and after implementing this CTS-1 specific ID, as well as agreement with CF results were measured. RESULTS: Initial evaluation demonstrated 97.8% positive agreement and 86.9% negative agreement between new and reference ID assays. Reviewing cases of disagreement revealed that many positive ID results by this new method, but negative by reference ID, were on patients with history of coccidioidomycosis, suggesting increased sensitivity of the new ID test. Thus, results were reconsidered using ID, CF and recent history of positive results as the reference result. This improved positive and negative agreement to 98.6 and 95.7%, respectively. Furthermore, the high negative predictive value of this CTS-1 specific ID assay allowed for reflexive ordering patterns, reducing unnecessary testing of CF on negative patients. CONCLUSION: This study demonstrates the effective use of Cactus Bio anti-CTS-1 ID for serodiagnosis of Coccidioides infections, which has been implemented as part of routine clinical care in our institution. Sensitivity and agreement with CF results are improved with this new testing strategy.
Normal serum cholinesterase does not exclude donepezil or galantamine toxicity: an interpretive pitfall of BuChE-based testing.
Mayahara T, Katayama T, Matsuura K … +2 more , Arai H, Maruo E
Clin Biochem · 2026 Jun · PMID 41806946 · Publisher ↗
Routine "serum cholinesterase" testing primarily reflects butyrylcholinesterase (BuChE) activity and may not exclude toxicity from relatively acetylcholinesterase (AChE)-selective agents such as donepezil and galantamine...
Routine "serum cholinesterase" testing primarily reflects butyrylcholinesterase (BuChE) activity and may not exclude toxicity from relatively acetylcholinesterase (AChE)-selective agents such as donepezil and galantamine. We conducted a targeted PubMed/MEDLINE search through December 2025 and identified published reports with documented cholinesterase measurements in clinically significant toxicity. Across these cases, serum BuChE and/or erythrocyte AChE activity was reported within the stated reference range despite symptomatic overdose. Potential explanations include limited BuChE inhibition by these agents and assay-related underestimation of reversible AChE inhibition under dilutional conditions. Normal serum cholinesterase should therefore not be used to rule out donepezil or galantamine toxicity; clearer test labeling as BuChE activity may reduce misinterpretation.
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.
Hkimi K, Gara S
Clin Biochem · 2026 Mar · PMID 41771415 · Publisher ↗
BACKGROUND: 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...
BACKGROUND: 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. OBJECTIVE: This study aimed to assess the impact of the transition from old to updated BV goals on sigma metrics in our laboratory. METHODS: 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. RESULTS: 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 < 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 < 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. CONCLUSIONS: 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.
Genomic sequencing enhances metabolic newborn screening in Thailand.
Kuptanon C, Innark P, Punnapum K … +7 more , Nammoonnoy S, Pankanjanato R, Numnuan M, Sripichai O, Wattanapokayakit S, Kunhapan P, Kunphol E
Clin Biochem · 2026 Mar · PMID 41724458 · Publisher ↗
OBJECTIVES: Thailand expanded metabolic newborn screening (NBS) program to include inherited metabolic diseases (IMDs) using tandem mass spectrometry since 2022. Molecular testing has increasingly been used as a second-t...
OBJECTIVES: Thailand expanded metabolic newborn screening (NBS) program to include inherited metabolic diseases (IMDs) using tandem mass spectrometry since 2022. Molecular testing has increasingly been used as a second-tier tool to clarify ambiguous results or confirm diagnosis for abnormal metabolic NBS screening. This study aimed to assess the performance of whole genome sequencing (WGS) as a second-tier test for abnormal IMD screening results in Thai neonates. DESIGN AND METHODS: From August 2023 to December 2024, neonates with abnormal IMD screens were recruited for WGS, in addition to the routine biochemical confirmation. RESULTS: Seventy-four newborns and 27 mothers were included in the study. Biochemical testing confirmed 40 IMDs, 12 borderline, and 21 normal cases, while WGS identified 3 additional IMDs and 8 carriers. Among 73 newborns, WGS identified 41 IMD cases and 32 normal (22 carriers), achieving 95% sensitivity, 100% specificity, 100% positive predictive value, and 97% negative predictive value. WGS refined disease subtypes, resolved borderline amino acid abnormalities, and guided individualized management. Limitations included missed large structural variants and lower sensitivity for detecting single heterozygous variants, emphasizing that molecular testing complements rather than replaces biochemical confirmation. CONCLUSIONS: WGS as a second-tier test enhances diagnostic precision, clarifies ambiguous NBS results, supports early, targeted intervention, and precision care in Thai newborns.
Evaluating prognostic performance for acute delta changes of high-sensitivity cardiac troponin T in emergency department patients.
Wu F, Love T, Cai X … +3 more , Mathias A, Lewandrowski KB, Liu L
Clin Biochem · 2026 Mar · PMID 41722718 · Publisher ↗
OBJECTIVES: To evaluate the prognostic value of 0/1h and 0/3h high-sensitivity cardiac troponin T (hs-cTnT) delta values for 30-day and 1-year all-cause mortality among emergency department (ED) patients. METHODS: This r...
OBJECTIVES: To evaluate the prognostic value of 0/1h and 0/3h high-sensitivity cardiac troponin T (hs-cTnT) delta values for 30-day and 1-year all-cause mortality among emergency department (ED) patients. METHODS: This retrospective study included two study cohorts from two academic medical centers. Cohort 1 included 18,022 ED patients with hs-cTnT measured using 0/3h algorithm, and Cohort 2 included 5,003 ED patients with hs-cTnT tested using 0/1h algorithm. hs-cTnT deltas were stratified into four categories: <4, 4-7, 8-11, and ≥12 ng/L for 0/3h testing, and <3, 3-5, 6-8, and ≥9 ng/L for 0/1h testing. Kaplan-Meier analysis, multivariable Cox proportional hazard models, and multivariable logistic regression models were performed to assess the prognostic values of 1 h and 3 h delta hs-cTnT for mortality. RESULTS: 0/1h and 0/3h hs-cTnT deltas were significantly higher in patients who died within 30 days or 1 year compared with survivors. After adjustment for baseline hs-cTnT, age, sex, and eGFR, a 3 h delta ≥4 ng/L was associated with approximately 2-fold higher 30-day mortality and 1.6-fold higher 1-year mortality; ≥12 ng/L was associated with approximately 4-fold and 2-fold increases in mortality risk, respectively. The 1 h delta showed similar predictive performance. In continuous log2-transformed models, each doubling of delta hs-cTnT increased the 30-day and 1-year mortality by 22% and 11% in the 0/3h algorithm and by 14% and 10% in the 0/1h algorithm. Incorporating delta hs-cTnT into multivariable logistic models improves model performance, with higher AUCs and lower AICs than models with baseline hs-cTnT alone. CONCLUSIONS: Acute hs-cTnT delta changes provide strong and independent prognostic information for all-cause mortality in ED patients. Incorporating delta hs-cTnT into ED risk stratification may support early identification of high-risk patients.
Outlook on ACADSB variants shaping metabolomic patterns and clinical outcomes - experience from a Central European country.
Bandura A, Chandoga J, Vengríni J … +9 more , Juhosová M, Vavrová A, Gregová E, Lysinová M, Mydlová Z, Brennerová K, Šaligová J, Maceková D, Böhmer D
Clin Biochem · 2026 Mar · PMID 41722717 · Publisher ↗
BACKGROUND: Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) is an autosomal recessive defect of L-isoleucine catabolism caused by pathogenic variants in the ACADSB gene. While early reports described neur...
BACKGROUND: Short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) is an autosomal recessive defect of L-isoleucine catabolism caused by pathogenic variants in the ACADSB gene. While early reports described neurological symptoms, expanded newborn screening cohorts have revealed predominantly asymptomatic individuals, raising questions regarding the clinical significance and optimal management. METHODS: We performed an evaluation of three probands with a biochemical profile consistent with SBCADD identified in a Central European country. Acylcarnitines were measured by liquid chromatography with tandem mass spectrometry, urinary organic acids by gas chromatography with mass spectrometry, and ACADSB was sequenced. Clinical data were collected from regional paediatric follow-up. RESULTS: Three individuals with a biochemical profile consistent with SBCADD were identified in Slovakia. Two were detected through newborn screening, whereas one was diagnosed at 5 years of age. All three showed elevated C5-acylcarnitine; the C5/C8 ratio was increased in two patients, while in the third it remained within the reference range despite persistently elevated C5. Urinary 2-methylbutyrylglycine and 2-ethyl-3-hydroxypropionate were elevated in all cases and showed intra-individual variability; in one sample, 2-methylbutyrylglycine remained increased while 2-ethyl-3-hydroxypropionate had normalised. Two patients carried pathogenic ACADSB variants (one homozygous splice-site variant c.303 + 1G > A, one compound heterozygous for p.Thr148Ile and p.Glu387Lys), whereas genetic testing was not performed in the third case. Over the available follow-up period, no episodes of metabolic decompensation were observed; two patients remained clinically well, and one patient had autism spectrum disorder. Free carnitine concentrations were within the reference range in all probands. CONCLUSIONS: Our findings support SBCADD as a primarily biochemical phenotype with a largely benign course, while illustrating variability of urinary biomarkers and C5/C8 ratios. Accurate differentiation from isovaleric acidemia and careful integration of biochemical, genetic and clinical data remain essential.
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