Annals Of Clinical Biochemistry[JOURNAL]
Sun
200 papers
Performance of the Binding Site cerebrospinal fluid kappa free light chains assay.
Handley SA, Barnes S, Jenkins N … +1 more , Wanandy T
Ann Clin Biochem · 2025 Nov · PMID 40220016 · Publisher ↗
BackgroundMeasurement of cerebrospinal fluid (CSF) kappa free light chains (KFLCs) for the detection of intrathecal immunoglobulin synthesis has generated interest as an alternative to CSF oligoclonal bands due to its ra...
BackgroundMeasurement of cerebrospinal fluid (CSF) kappa free light chains (KFLCs) for the detection of intrathecal immunoglobulin synthesis has generated interest as an alternative to CSF oligoclonal bands due to its rapid turnaround time and ability to automate the assay. A turbidimetric immunoassay - Freelite Mx, is available from the Binding Site, but published data on performance is scant. Therefore, we undertook a multicentre sample comparison and investigated reagent lot-to-lot-variation (LTLV).MethodsIntra-/inter-assay accuracy and imprecision of the Freelite Mx assay on the Binding Site Optilite analyser was assessed. Twenty paired CSF/serum samples were sent to three laboratories within Australia for the measurement of CSF/serum KFLC/albumin and concentrations compared using the Kruskal-Wallis test, Spearman's rank (rs), and Passing-Bablok analysis. Lot-to-lot-variation between three reagent lots was undertaken by analysis of 20 CSF samples.ResultsIntra- and inter-assay imprecision was ≤4.4 and ≤4.1%, respectively. There was a good correlation (rs = ≥0.98) between sites for the measured CSF KFLC concentration, and no significant difference in the median concentration measured between sites (3.31, 2.78, and 3.48 mg/L, = .98). The median bias between reagent lots was <4%, the intercept of the regression between lots was between -0.02 and 0.06 mg/L, and the slope ranged from 0.96 to 1.07.ConclusionOverall, there was a good agreement in CSF KFLC concentrations among laboratories, and LTLV was deemed acceptable. Ascertaining biological variability of CSF KFLCs and the participation of laboratories in quality assurance schemes would assist with harmonisation.
Thyroid reference ranges in pregnancy utilizing an Abbott Alinity platform in a multi-ethnic population in the UK.
Scott RV, Abdel-Malek M, Zhu J … +16 more , Tan J, Thayabaran D, Valaiyapathi R, Padam P, Jackson E, Barnes SC, Fourie H, Al-Memar M, Kyriacou C, Nimura M, Bourne T, Martin NG, Agha-Jaffar R, Jones B, Khoo B, Tan TM
Ann Clin Biochem · 2025 Nov · PMID 40156169 · Publisher ↗
BackgroundMaternal thyroid function significantly affects fetal development. However, thyroid hormone concentrations change dynamically throughout pregnancy rendering non-pregnancy reference ranges inaccurate. We aimed t...
BackgroundMaternal thyroid function significantly affects fetal development. However, thyroid hormone concentrations change dynamically throughout pregnancy rendering non-pregnancy reference ranges inaccurate. We aimed to establish the trimester-, population-, and assay-specific reference ranges for thyroid hormones in pregnancy using the recently introduced Abbott Alinity thyroid function test, according to American Thyroid Association 2017 Guidelines for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum.MethodsThis study of 663, iodine-replete and thyroid peroxidase (TPO)-antibody negative female determined trimester-specific reference ranges for thyroid stimulating hormone (TSH), free thyroxine (fT4), and free tri-iodothyronine (fT3) using Abbott Alinity assays in accordance with ATA guidelines. Study participants were drawn from a multi-ethnic population with 49% non-white participants.ResultsFirst trimester reference ranges were TSH 0.06-2.73 mIU/l, fT4 9.9-15.3 pmol/l, and fT3 3.4-5.6 pmol/l. Second trimester reference ranges were TSH 0.02-2.47 mIU/l, fT4 8.5-14.4 pmol/l, and fT3 3.3-5.5 pmol/l. In the third trimester, TSH ranges were 0.41-2.80 mIU/l, fT4 7.6-12.3 pmol/l, and fT3 3.1-5.0 pmol/l. There were no significant differences in any trimester-specific analyte reference ranges when white and non-white populations were compared.ConclusionsThese reference ranges support the clinical care of female from diverse backgrounds with thyroid dysfunction in pregnancy using the thyroid function tests available on the Abbott Alinity platform.Study registrationISRCTN17018939.
Comparison of three blood collection tubes for 16 biochemical analytes and stability assessment of selected analytes: VACUETTE CAT serum Sep clot activator tube, VACUETTE LH lithium heparin Sep tube, and VACUETTE CAT serum fast separator tube.
Seo JD, Lee YJ, Ha C … +10 more , Choi JH, Shin SH, Han HY, Kim HJ, Kim SH, Kim BS, Kim H, Moon HW, Hur M, Yun YM
Ann Clin Biochem · 2025 Sep · PMID 40132209 · Publisher ↗
BackgroundAnalytical performance of VACUETTE® CAT Serum Fast Separator Tube (SFT; Greiner Bio-One, Austria), recently developed quick-clotting serum separator, was evaluated for correlation and stability, comparing with...
BackgroundAnalytical performance of VACUETTE® CAT Serum Fast Separator Tube (SFT; Greiner Bio-One, Austria), recently developed quick-clotting serum separator, was evaluated for correlation and stability, comparing with VACUETTE® CAT Serum Sep Clot Activator Tube (SST; Greiner Bio-One) and VACUETTE® LH Lithium Heparin Sep Tube (LiHep Tube; Greiner Bio-One).MethodFor 107 paired samples, 16 analytes (glucose, potassium, LDH, CRP, creatinine, AST, ALT, ALP, GGT, AFP, PSA, TSH, free T4, iPTH, CK-MB, and cardiac troponin I[cTnI]) were measured. Correlations were assessed using Passing-Bablok regression and paired t-tests. Differences were evaluated by comparing the mean percentage difference and estimated difference at medical decision limits (MDLs), to the acceptable desirable difference. For six analytes - glucose, potassium, LDH, AST, iPTH, and cTnI - known for different stabilities between sample types, stability was evaluated by comparing changes over time with desirable differences.ResultsAcross the evaluated range, SFT showed clinically comparable differences to SST, except for CK-MB which showed significant positive bias. Plasma exhibited unacceptable biases: negative for potassium and positive for LDH and CK-MB. Estimated differences at MDLs were acceptable in SFT except for potassium and CK-MB, while plasma showed unacceptable differences in potassium, LDH, creatinine, and CK-MB. LiHep Tube showed reduced stability than SST for all analytes except for iPTH, impairing retest reliability. SFT showed comparable stability except for LDH and iPTH, which showed slightly shortened stability.ConclusionsThe SFT demonstrated high correlation and comparable stability to SST, making it a suitable replacement for the LiHep Tube, as an alternative to SST for rapid testing.
Underreporting of synthetic cathinone poisoning with clinical immunoassays: An experimental and observational study.
Willeman T, Laudet M, Revol B … +4 more , Boudin C, Eysseric-Guerin H, Scolan V, Stanke-Labesque F
Ann Clin Biochem · 2025 Nov · PMID 40118811 · Publisher ↗
BackgroundThere is an increasing global concern about the use of synthetic cathinones (SCs). Detecting these drugs in human urine samples can be difficult, particularly in emergency settings. Cross-reactivity has been de...
BackgroundThere is an increasing global concern about the use of synthetic cathinones (SCs). Detecting these drugs in human urine samples can be difficult, particularly in emergency settings. Cross-reactivity has been described for several immunoassays. We evaluated the analytical interference caused by common SCs in MDMA and amphetamine assays that use the EMIT® Atellica CH (Siemens Healthineers) with both clinical and in vitro experimental data.MethodsDrug-free urine samples were spiked with various concentrations (5 to 100 µg/mL) of 2-methylmethcathinone (MMC), 3-MMC, 4-MMC, 3-chloromethcathinone (CMC), methylone and alpha-PHP and tested using EMIT® assays. The percentage of false-positive results was determined in urine samples from patients above 18 years of age admitted to the ICU or emergency department who underwent routine toxicology screening and urine immunoassays over a 4-year period. Confirmatory analyses of SC were performed by mass spectrometry techniques.ResultsFalse-positive results occurred for the MDMA assay with methylone (10 µg/mL) and 3-CMC (100 µg/mL) and for the amphetamine test with 2-MMC (50 µg/mL). We studied 2033 urine samples from 1812 patients (mean age 39 years, 61.8% male), of which 49 tested positive for amphetamine and 76 for MDMA. SCs were responsible for a false-positive rate of 16.3% for the amphetamine tests and 17.1% for the MDMA tests. Most of the false-positive tests occurred among young male patients (mean age 38 years, 92.8% male).ConclusionsThis study demonstrates that SC intoxication may be underreported in immunoassay toxicology testing. Due to a lack of specificity of screening immunoassay methods, positive results for amphetamine-type stimulants should be confirmed by specific MS methods.
A five-year retrospective analysis of a national external quality assessment program for urinary organic acid analysis in newborn screening for inherited metabolic disorders in China.
Du Y, Wang W, Yang Y … +1 more , Wang Z
Ann Clin Biochem · 2025 Nov · PMID 40118810 · Publisher ↗
ObjectivesUrinary organic acid analysis is crucial for diagnosing inherited metabolic disorders (IMDs). This study assesses the impact of an external quality assessment (EQA) scheme on standardizing urinary organic acid...
ObjectivesUrinary organic acid analysis is crucial for diagnosing inherited metabolic disorders (IMDs). This study assesses the impact of an external quality assessment (EQA) scheme on standardizing urinary organic acid detection in China from 2019 to 2023.MethodsThis retrospective longitudinal study analysed data from the NCCL-E-25 EQA scheme for urinary organic acid analysis using gas chromatography-mass spectrometry (GC-MS). Ten batches of EQA data over 5 years were included, focussing on eight key organic acid metabolites. Robust statistical methods were used to evaluate laboratory performance, including regional variations, sample preparation methods, and laboratory types.ResultsParticipating laboratories increased from 43 in 2019 to 76 in 2023, with high participation rates (median 94.74%). All eight target compounds showed significant reductions in robust coefficient of variation (CV) over time. Regional performance disparities narrowed, converging by 2022-2023. Extraction preparation methods generally outperformed non-extraction methods. Newborn Screening Centers (NBSCs) demonstrated lower robust CVs compared to non-NBSCs.ConclusionsThe EQA scheme effectively improved and standardized laboratory testing quality nationwide, particularly benefiting central and western regions. The study highlights the importance of standardized protocols and continuous improvement in enhancing IMD diagnostic accuracy. Future efforts should focus on encouraging wider participation, especially from underrepresented regions, and integrating quantitative and diagnostic capability assessments to comprehensively evaluate laboratory performance.
Importance of the preanalytical phase: Elevation of protein levels in cerebrospinal fluid samples due to inappropriate containers.
Izquierdo-Martínez A, Sánchez-Palacios C
Ann Clin Biochem · 2025 Nov · PMID 40085510 · Publisher ↗
Biomarkers in cerebrospinal fluid (CSF) are crucial for diagnosing, monitoring, and prognosing neurological disorders. This study evaluates the impact of preanalytical variables, particularly container choice, on CSF pro...
Biomarkers in cerebrospinal fluid (CSF) are crucial for diagnosing, monitoring, and prognosing neurological disorders. This study evaluates the impact of preanalytical variables, particularly container choice, on CSF protein measurements. Using 30 CSF samples, we compared sterile, additive-free tubes and lithium heparin tubes without separator gel. Protein levels were significantly elevated higher in heparin tubes (mean difference: 230.71 mg/dL, < .001). This overestimation underscores the necessity of adhering to preanalytical protocols to avoid erroneous clinical interpretations and ensure accurate diagnostic outcomes.
Sigma metrics for assessing the analytical performance of 14 biochemical analytes in Mansoura university children's hospital laboratories (MUCHLs) using CLIA LIMITS 1988 & 2024.
Karam N, El-Farahaty RM, El-Gilany AH … +1 more , Nosser NA
Ann Clin Biochem · 2025 Nov · PMID 40085496 · Publisher ↗
IntroductionAnalytical quality is a crucial prerequisite for best practice in medical laboratory. Six-Sigma Methodology (SM) is a quality measurement tool used to evaluate laboratory performance. This study aims to asses...
IntroductionAnalytical quality is a crucial prerequisite for best practice in medical laboratory. Six-Sigma Methodology (SM) is a quality measurement tool used to evaluate laboratory performance. This study aims to assess the analytical phase baseline performance using SM and compare results using TEa of CLIA 1988 and CLIA 2024.Materials and methodsCoefficient of variation and bias were determined for 14 analytes. The sigma level for each parameter was calculated using total allowable error (TEa) for CLIA 1988 and CLIA 2024. The quality goal index ratio was calculated for analytes with Sigma less than 3. Normalized method decision Charts were plotted for level 1 and 2 Bio-Rad internal quality control for both CLIA 1988 and 2024.ResultsUsing CLIA TEa 1988, HDL-C, triglycerides & uric acid for level 1 and ALT, AST, HDL-C, calcium, triglycerides & uric acid for level 2 had six Sigma world class performance, meanwhile, only BUN for level 1 and 2 performed less than 3. Using CLIA TEa 2024, HDL-C, GGT, and triglycerides for level 1 and ALT, AST, calcium, GGT, and triglycerides for level 2 had world class quality performance. Meanwhile, creatinine, glucose, BUN for level 1 and BUN and creatinine for level 2 performed less than 3.ConclusionEvaluation of baseline analytical performance using SM revealed lower sigma values with stringent CLIA TEa 2024 versus tolerant CLIA TEa 1988. Improvement in the methodology of analytes with poor performance on some assay platforms with stringent quality control regimes is recommended.
'Tired all the time': What general practitioners request and find in patients with tiredness/fatigue - an audit against NICE clinical knowledge summary of tiredness/fatigue in adults.
Handjiev S, Nobes J, Murphy MJ
Ann Clin Biochem · 2025 Sep · PMID 40085492 · Publisher ↗
BackgroundTiredness/fatigue is a common presenting complaint in primary care. Advice is available from the National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summary (CKS) on its investigation. T...
BackgroundTiredness/fatigue is a common presenting complaint in primary care. Advice is available from the National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summary (CKS) on its investigation. The application of this guidance has not been reported.AimTo audit the investigation of tiredness/fatigue in adults in primary care against NICE CKS recommendations.MethodsWe reviewed 16,889 primary care requests in 2019, where clinical details included: 'tired all the time' or 'TATT'; 'tired (ness)'; 'fatigue'. We report on how many first-line investigations recommended by the NICE CKS were requested, and, if they were, what the outcome was. We categorised outcomes as normal or abnormal, using relevant laboratory reference intervals.ResultsFirst-line investigations were requested, in decreasing order of frequency, as follows: full blood count (FBC) 89%, renal function (U&Es) 83%, liver function tests (LFTs) 80%, thyroid-stimulating hormone (TSH) 80%, bone profile 70%, C-reactive protein (CRP) 66%, plasma viscosity (PV) 46%, ferritin 9.4%, IgA tissue transglutaminase (TTG) 3.2%, and creatine kinase (CK) 1.4%. Likelihood of abnormal results was 37% for PV, 26% for ferritin, 25% for LFTs, 24% for bone profile, 23% for FBC, 15% for U&Es, 14% for CRP, 10% for TSH, 8% for CK, and 3% for TTG. (Requesting of diagnostic HbA1c (2.8%) was vetted in accordance with a local protocol; 59% of results were in the diabetic range).ConclusionThis is the first study to audit the application in primary care of NICE CKS advice on investigation of tiredness/fatigue in adults. Our findings provide an insight into 'real-world' primary care requesting behaviour, and outcomes of investigations.
A simpler and more sensitive modified catalytic (bleomycin detectable) iron assay.
Rajapurkar MM, Mukhopadhyay B, Lele SS … +1 more , Shah SV
Ann Clin Biochem · 2025 Nov · PMID 40085486 · Publisher ↗
BackgroundIron is ubiquitously distributed in biology, only a miniscule amount exists as free is capable of catalysing production of highly toxic reactive hydroxyl radicle. This free iron also called; labile iron, non-tr...
BackgroundIron is ubiquitously distributed in biology, only a miniscule amount exists as free is capable of catalysing production of highly toxic reactive hydroxyl radicle. This free iron also called; labile iron, non-transferrin bound iron or catalytic iron (CI). CI is measured by bleomycin detectable iron assay. The assay as described originally was difficult to perform accurately and reproducibly due to variations of pH in the assay mixture and due to the lack of properly diluted iron standards.MethodsIn our laboratory we modified the assay for serum/plasma so that the variations of pH in assay medium were constantly between 7.4 and 7.6 using acid diluted iron standards by multiple treatments of Chelex resin which is alkaline.ResultsIntra assay CV for low, medium, and high levels of catalytic iron was 0.05%, 0.61% and 0.68% whereas the interassay CV was 0.06%, 0.96% and 0.28% respectively. The modified assay is highly sensitive being able to detect levels as low as 0.1 μmoles/l. In patients on maintenance haemodialysis CI measured by the original assay failed to detect any catalytic iron in almost all of these samples whereas by modified method it was measurable in all patients with a mean of 0.66 ± 0.10 μmoles/l. Normal values for catalytic iron in subjects having no comorbidities measured by modified method is 0.11 ± 0.06 μmoles/l.ConclusionsThe modified assay is reproducible and more sensitive than original assay and has been validated in several clinical studies.
Decrease in the internal quality control intermediate reproducibility imprecision of Cystatin C results in China in the years from 2014 to 2023.
Zhang Z, Zeng J, Wang W … +5 more , Du Y, Yuan S, Dong N, Zhang C, Wang Z
Ann Clin Biochem · 2025 Sep · PMID 40085476 · Publisher ↗
ObjectivesWe evaluated the intermediate reproducibility imprecision of cystatin C results based on internal quality control (IQC) data.MethodsIQC data for cystatin C analyte were collected each year from 2014 to 2023. We...
ObjectivesWe evaluated the intermediate reproducibility imprecision of cystatin C results based on internal quality control (IQC) data.MethodsIQC data for cystatin C analyte were collected each year from 2014 to 2023. We used the coefficient of variation (CV) to evaluate the level of laboratory imprecision. Five performance specifications [1/3 total allowable error (TEa), 1/4TEa and three levels performance specifications based on biological variation] were used to calculate the proportion of laboratories with CVs less than or equal to the performance specifications, namely, the pass rate. Based on the reference interval of Chinese adult serum cystatin C (0.59-1.03 mg/L), the concentration of quality control materials was divided into two levels for CV analysis: Level 1 (≤1.03 mg/L) and Level 2 (>1.03 mg/L). Additionally, group analysis was conducted according to the reagent manufacturer. Peer groups were further divided based on instruments to study differences between instruments. Boxplots were drawn to analyze trends in CVs, and differences in CVs among different groups were assessed using the Kruskal-Wallis test and Mann-Whitney U test.ResultsThe number of participating laboratories increased significantly from 255 in 2014 to 1814 in 2023. The intermediate reproducibility imprecision of Cystatin C IQC results in China had decreased from 5.1% (CV%) in 2014 to 3.3% in 2023. The pass rates based on 1/3 TEa showed upward trends increasing from 67% in 2014 to 88% in 2023. The pass rates for the other four performance specifications were all below 80%. The CVs of two concentration levels showed significant differences in most years. Roche Diagnostics reagent manufacturer exhibited low intermediate reproducibility imprecision. The BSBE-Abbott Architect series platform achieved a 100% pass rate based on 1/3 TEa in 2023.ConclusionsThe intermediate reproducibility imprecision of cystatin C has been a continuous overall improvement in China. However, the performance specifications of Cystatin C based on BV are currently not applicable to some laboratories in China. In addition, attention should be paid to the differences in intermediate reproducibility imprecision between various analysis systems.
Elevated lactate dehydrogenase and reflexive myeloproliferative neoplasm molecular diagnostics.
Langabeer SE
Ann Clin Biochem · 2025 Sep · PMID 40069608 · Publisher ↗
Abstract loading — click title to view on PubMed.
Preβ1-high-density lipoprotein binds to TG-rich lipoproteins and its release is impaired in the postprandial state among patients with poorly controlled type 2 diabetes.
Horiuchi Y, Hirayama S, Hori A … +8 more , Ichikawa Y, Soda S, Seino U, Sekihara K, Ueno T, Fukushima Y, Kubono K, Miida T
Ann Clin Biochem · 2025 Sep · PMID 40038041 · Publisher ↗
BackgroundAlthough preβ1-high-density lipoprotein (preβ1-HDL) promotes cholesterol efflux, high fasting preβ1-high-density lipoprotein levels after breakfast are reduced in patients with poorly controlled type 2 diabetes...
BackgroundAlthough preβ1-high-density lipoprotein (preβ1-HDL) promotes cholesterol efflux, high fasting preβ1-high-density lipoprotein levels after breakfast are reduced in patients with poorly controlled type 2 diabetes.ObjectiveThis study investigated whether preβ1-high-density lipoprotein binds to triglyceride (TG)-rich lipoproteins (TGRLs) in the postprandial state and is released during lipolysis.MethodsWe measured preβ1-high-density lipoprotein concentrations, lecithin-cholesterol acyltransferase (LCAT) activity, and LCAT-dependent preβ1-high-density lipoprotein conversion before and after breakfast in patients with diabetes. We also performed studies using TGRLs. Preβ1-high-density lipoprotein was quantified by enzyme-linked immunosorbent assay and native two-dimensional gradient gel (N-2D-gel) electrophoresis.ResultsBefore breakfast, the diabetes group had higher preβ1-high-density lipoprotein concentrations than the healthy controls; after breakfast, levels in the two groups were similar. Neither LCAT mass nor the LCAT-dependent preβ1-high-density lipoprotein conversion rate changed after breakfast. Mixing of fasting plasma with chylomicrons or very-low-density lipoprotein (VLDL) reduced the preβ1-high-density lipoprotein level by 15% ± 4% and 45% ± 10%, respectively. N-2D-gel electrophoresis showed that preβ1-high-density lipoprotein was generated by bacteria-derived TG lipase only from postprandial VLDL of patients with type 2 diabetes.ConclusionPreβ1-high-density lipoprotein binds to TGRLs in the postprandial state and is released during lipolysis, implying that postprandial hyperlipidemia impairs reverse cholesterol transport in patients with poorly controlled type 2 diabetes.
Metamizole (dipyrone) as an interferent in biochemical assays.
Ceacero-Marín D, Martínez-Zamorano L, Gisbert-Alonso A … +3 more , Cachón-Suárez I, Mendoza-Javier KG, Castro-Castro MJ
Ann Clin Biochem · 2025 Sep · PMID 40037991 · Publisher ↗
BackgroundMetamizole (MMZ), commonly used as an analgesic/antipyretic in countries like Spain, faces restrictions elsewhere due to side effects. Despite this, its frequent use underscores the critical importance of study...
BackgroundMetamizole (MMZ), commonly used as an analgesic/antipyretic in countries like Spain, faces restrictions elsewhere due to side effects. Despite this, its frequent use underscores the critical importance of studying its impact on the accuracy of laboratory tests, particularly when blood samples are obtained shortly after intravenous administration.MethodsTo investigate the in vitro interfering effect of MMZ, 20 serum biochemical assays were selected. The concentrations of biochemical assays were measured in a serum pool spiked with increasing MMZ concentrations. For each assay, the percentage of interference was calculated and compared with our laboratory's quality requirements for bias.ResultsIn vitro interference was observed in some biochemical assays: cholesterol (CHOL), creatinine (CREA), high-density lipoprotein cholesterol (HDL), lactate (LAC), lactate dehydrogenase (LDH), triglycerides (TG) and uric acid (UA), leading to falsely reduced results. All of them, except for the LDH assay, exhibited clinically significant interference with CREA being the first to be affected at a metamizole concentration of 0.31 g/L. No interference was observed in the remaining assays.ConclusionsFalsely decreased and clinically significant CHOL, CREA, HDL, LAC, TG and UA results were observed in serum samples due to in vitro interference caused by MMZ contamination. Serum concentrations in patients receiving intravenous MMZ treatment may be falsely decreased due to interference by MMZ. Knowledge of such interferences in clinical laboratories is crucial for the correct diagnosis and treatment of patients.
Paired copy number variation analysis in siblings discordant for familial Parkinson's disease.
Atay S, Acarer A, Ak H … +2 more , Colakoglu Z, Aydin HH
Ann Clin Biochem · 2025 Sep · PMID 40037983 · Publisher ↗
ObjectivesNumerous studies on the genetic pathogenesis of familial Parkinson's Disease (PD) have explained the etiology of only a limited percentage of cases. In this study, we aimed to identify copy number variations (C...
ObjectivesNumerous studies on the genetic pathogenesis of familial Parkinson's Disease (PD) have explained the etiology of only a limited percentage of cases. In this study, we aimed to identify copy number variations (CNVs) in patients with familial PD compared to their healthy siblings.MethodsGenomic microarray analysis was performed using the CytoScan HD array platform, and paired copy number variation analysis was performed using Partek Genomics Suite.ResultsA total of 211 CNVs were detected in patients (genomic markers per CNV >10, markers per base pair >0.0005). Genes localized in CNV regions were enriched in the "" pathway. Subsequently, CNVs located in regions with segmental duplication, large genomic gap or "dosage sensitivity unlikely," with a frequency higher than 0.01%, and found to be "both amplified and deleted" in patients were excluded. Genes potentially affected by exonic copy number losses were HPGDS, TUBB8, ZMYND11, FLI-1, THADA, FAM47E, FAM47E-STBD1, AGMO, CYRIB, and MIR5194, while the detected copy number gains included the exons of the PCSK6, MIR4522, WSB1, C8orf44-SGK3, SGK3, and MCMDC2. No copy number variations were detected on chromosomes 13 and 18.ConclusionsHere, we report the results of the first paired CNV analysis in siblings discordant for Familial Parkinson's Disease. Validation and frequency determination of rare and novel CNVs identified in larger familial PD cohorts may reveal novel PD risk genes. The metabolism of xenobiotics by cytochrome P450 pathway deserves further functional and translational studies in familial Parkinson's disease.
A multicenter study comparing a point-of-care blood glucose metre with a blood gas analyser in infants by the Shikoku Neonatal Medical Research Group.
Kuboi T, Sugino M, Sadamura T … +13 more , Kawaguchi N, Tadatomo Y, Takada K, Okamoto N, Miyamoto K, Nakano A, Miura N, Nakata Y, Suga K, Ota M, Nakamura S, Koyano K, Kusaka T
Ann Clin Biochem · 2025 Sep · PMID 40022493 · Publisher ↗
BackgroundThere have been no reports on blood glucose metres for measurements in a wide variety of infant patients, from very preterm infants to mature infants and from the early neonatal period onwards. In this study, w...
BackgroundThere have been no reports on blood glucose metres for measurements in a wide variety of infant patients, from very preterm infants to mature infants and from the early neonatal period onwards. In this study, we evaluated the accuracy of the Glutest Mint II, a point-of-care blood glucose metre, by comparing blood glucose levels measured by this device with those measured by a blood gas analyser in infants of all gestational ages and birth weights at a number of time points after birth.MethodsInfants aged 22 weeks and 0 days of gestation or older who were born at any of six tertiary neonatal intensive care units between March 2022 and January 2023 and needed blood glucose monitoring were enrolled. Samples were collected into capillary tubes when the physician determined that a blood glucose test was necessary and could be taken at any time after birth and any number of times from the same individual. Blood glucose was measured using a Glutest Mint II and then using a blood gas analyser.ResultsIn total, 2943 blood glucose points were measured in 285 infants. Blood glucose levels measured using the Glutest Mint II were significantly correlated with those measured using a blood gas analyser. Neonatal-specific parameters such as hematocrit and total serum bilirubin levels may not have an effect.ConclusionsThe Glutest Mint II device can measure blood glucose levels with very high accuracy in the range used in the neonatal setting, comparable to the blood gas analyser.
Ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein tandem brain biomarker test in the prediction of CT evident brain injury: A prospective evaluation in the emergency department.
Curran JM, Onions K, Watts J … +4 more , Rana A, Hughes E, Allison J, Cooper JG
Ann Clin Biochem · 2025 Sep · PMID 40022482 · Publisher ↗
Patients with features of mild traumatic brain injury (mTBI) frequently present to the emergency department (ED) and often meet recognized criteria for CT head imaging. Observational studies suggest that use of a tandem...
Patients with features of mild traumatic brain injury (mTBI) frequently present to the emergency department (ED) and often meet recognized criteria for CT head imaging. Observational studies suggest that use of a tandem ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) brain biomarker test may significantly reduce need for CT scanning in this population, though data on patient flow are lacking. A prospective cohort evaluation of adult ED patients (≥18 years) with features of mTBI who met criteria for CT imaging within 12 hours of head injury had blood drawn for laboratory UCH-L1/GFAP testing. The diagnostic performance for CT-evident brain injury was expressed through the calculation of sensitivity and negative predictive value (NPV) with 95% confidence intervals (95% CI). Times from venepuncture to biomarker result availability, and from CT request to result availability were compared. A laboratory UCH-L1/GFAP test identified 21 of 89 (24%) patients as low-risk for CT-evident TBI with a sensitivity of 100% (95% CI 76%-100%) and NPV of 100% (95% CI 85%-100%). The median time to biomarker and CT results were 88 minutes and 89 minutes, respectively. However, 68 (76%) of patients with a positive biomarker test would then progress to CT imaging, significantly prolonging ED length of stay, and restricting usefulness in adoption into clinical pathways. Evaluation of a laboratory UCH-L1/GFAP test in a UK population with mTBI demonstrates excellent performance for the exclusion of CT-evident brain injury. However, adoption into clinical patient pathways is likely to be limited until the test is available in whole blood at the point-of-care, and evidence of safe rationalization of CT imaging confirmed in randomized studies.
Falsely elevated type IV collagen caused in part by heterophilic antibodies: A case report.
Lv XM, Xiao L, Yu HL … +1 more , Yan LW
Ann Clin Biochem · 2025 Sep · PMID 39976395 · Publisher ↗
Immunoassays, which are used ubiquitously in clinical practice, are inherently vulnerable to distortions arising from endogenous immunoglobulins, particularly heterophilic antibodies. While many studies have explored int...
Immunoassays, which are used ubiquitously in clinical practice, are inherently vulnerable to distortions arising from endogenous immunoglobulins, particularly heterophilic antibodies. While many studies have explored interference in substances measured using chemiluminescence or electrochemiluminescence methods based on the double-antibody sandwich principle, there are limited data on interference in immunoturbidimetric assays, particularly for type IV collagen. This article presents the first report of a noteworthy increase in serum type IV collagen levels stemming from heterophilic antibody interference detected through an immunoturbidimetric assay. The present study investigated the mechanisms of this interference and the differences introduced by heterophilic antibodies between the two methodologies. Additionally, it outlines strategies for identifying and mitigating such interference, and discusses the principles, limitations, and considerations of each corrective approach. The objective is to raise awareness among clinical laboratory professionals concerning the potential interference of heterophilic antibodies in immunoturbidimetric assays. Increased awareness will aid in the prompt detection and correction of this issue, ensuring the provision of accurate and reliable laboratory data for informed clinical decision-making and the prevention of adverse medical outcomes.
Determination of the biological variation and reference change value of lipoprotein (a).
Antwi K, Downie P, Mbagaya W
Ann Clin Biochem · 2025 Sep · PMID 39947649 · Publisher ↗
BackgroundUnderstanding lipoprotein (a) [Lp(a)] measurement variability is essential in establishing its coronary heart disease (CHD) association, and optimizing assessment and management of atherosclerotic cardiovascula...
BackgroundUnderstanding lipoprotein (a) [Lp(a)] measurement variability is essential in establishing its coronary heart disease (CHD) association, and optimizing assessment and management of atherosclerotic cardiovascular disease (ASCVD) risk. We established the components of biological variation (BV) and reference change value (RCV) of Lp(a) in a UK cohort.Method22 healthy individuals were recruited to the study. Blood samples were collected for six consecutive weeks and analysed in duplicate using the Lp(a) assay by Sentinel Diagnostics on the Beckman Coulter AU5800. Outlier, heterogeneity, normality, and trend analysis were performed, followed by CV-ANOVA to determine estimates of BV, adhering to the 14 BIVAC quality items. RCV was calculated based on estimated CV and CV.ResultsFour participants were excluded from the analysis as their mean Lp(a) levels fell below the functional sensitivity of the assay. Mean Lp(a) concentration ranged from 14 to 241 nmol/L. The overall estimate of CV for all participants was 10.9% (95% CI of 9.1 - 13.0%). The RCV for Lp(a) was +31.6%/-24.0%.ConclusionOur study obtained a CV estimate for Lp(a) that aligned consistently with recent studies adhering to the quality specifications outlined in the BIVAC checklist. The CV estimate was significantly lower than Lp(a) estimates reported in studies up to 2003. The CV estimate highlights the limitations of relying solely on a single Lp(a) measurement for prognosticating ASCVD risk and identifying candidates for novel Lp(a) therapies, particularly when the measured value is near clinical decision thresholds.
Metronidazole is a chromatographic interference on a routine HPLC-UV assay for thiopurine metabolites.
Wood AA, Mason SR, Robson AF
Ann Clin Biochem · 2025 Sep · PMID 39875128 · Publisher ↗
BackgroundThiopurine metabolites, 6-thioguanine (6TG) and 6-methylmercaptopurine (6MMP), are monitored to aid therapeutic management of thiopurine drugs. At Manchester University NHS Foundation Trust (MFT), thiopurine me...
BackgroundThiopurine metabolites, 6-thioguanine (6TG) and 6-methylmercaptopurine (6MMP), are monitored to aid therapeutic management of thiopurine drugs. At Manchester University NHS Foundation Trust (MFT), thiopurine metabolites are measured by high performance liquid chromatography with ultraviolet detection (HPLC-UV). Whole blood samples are lysed and subjected to hydrolysis with derivatisation of 6MMP before HPLC-UV detection at 304 nm for the 6MMP-derivative and 342 nm for 6TG. For some samples, 6MMP cannot be reported due to a chromatographic interference at 304 nm co-eluting with the 6MMP peak. An investigation was performed to identify the interfering compound.MethodsPatient medication histories were examined to identify candidate compounds for the interference. Candidate compounds were spiked into blood at supraphysiological concentrations and tested on the assay.ResultsMetronidazole was identified as being prescribed to all patients whose samples demonstrated the interference. Metronidazole and its metabolite, hydroxymetronidazole, were spiked into blood. HPLC-UV analysis of spiked blood demonstrated similar UV absorbance patterns to those seen in patient samples with the interference. Hydroxymetronidazole co-eluted with 6MMP causing interference in the measurement.ConclusionMetronidazole and its major metabolite can interfere with 6MMP measurement by HPLC-UV analysis at 304 nm.
A United Kingdom-wide audit of the laboratory investigation of primary aldosteronism.
Davies SL, Cuthbertson DJ, Ward LJ … +3 more , Wassif WS, Gurnell M, Davison AS
Ann Clin Biochem · 2025 Jul · PMID 39875127 · Publisher ↗
ObjectivesPrimary aldosteronism (PA) is a common but under-recognised cause of secondary hypertension. Early diagnosis with targeted medical and/or surgical intervention is important to prevent irreversible end-organ dam...
ObjectivesPrimary aldosteronism (PA) is a common but under-recognised cause of secondary hypertension. Early diagnosis with targeted medical and/or surgical intervention is important to prevent irreversible end-organ damage. An Endocrine Society Clinical Practice Guideline was used to define audit standards against which to assess current United Kingdom (UK) laboratory practice.MethodsA survey comprising 22 questions, which captured information on screening, confirmatory testing and adrenal vein sampling (AVS), was distributed to all UK Clinical Biochemistry laboratories by the Association for Laboratory Medicine. Consultation with clinical colleagues was encouraged.Results50 of 147 laboratories (34.0%) responded, 17 of which provided an analytical service for plasma aldosterone concentration (PAC) and renin, measured as plasma renin activity (PRA) or direct renin concentration (DRC). PRA/DRC, PAC and aldosterone:renin ratios were used to screen for PA. Saline infusion testing was the most common confirmatory test. AVS was used to aid lateralisation. Chemiluminescence immunoassay and liquid chromatography tandem mass spectrometry were the preferred analytical methods for PAC and PRA/DRC. However, there was considerable variation across centres in respect of reference intervals and cutoffs, which were not fully accounted for by differences in analytical platforms. Although diagnostic algorithms, with pre- and post-analytical support, were in evidence in some centres, these were not universal or always embedded in a multidisciplinary team setting.ConclusionsWe observed significant heterogeneity in the laboratory investigation of PA across the United Kingdom. Therefore, this work serves as a stimulus for greater collaboration to permit national harmonisation/standardisation of analytical and clinical aspects of UK PA practice.
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