Annals of Clinical Biochemistry最新文献

BackgroundPoint of care (POC) tests may improve accessibility and reduce costs of blood tests including in prostate cancer. The Man Van project was a pilot designed to address health inequalities that affect prostate cancer with novel community-based targeting of high-risk groups on a mobile clinical unit.MethodsThe i-CHROMA-II™ POC machine is a quantitative assay for the measurement of total prostate specific antigen (PSA) from capillary blood using fluorescence immunoassay technology. Laboratory based Serum PSA testing was compared with capillary blood POC testing using the i-CHROMA-II™ to determine its accuracy and impact on clinical decision making on the Man Van.Results28 men participated. The median age was 53 years (range 45-74). One POC test result was invalid. Nine POCT samples gave a result of <0.5 μg/L and were not included in the analysis. Of the remaining results (N = 18) the median PSA was 1.97 μg/L (range 0.54-31.22 μg/L). Using Lin's Concordance Correlation Coefficient of Absolute Agreement gave a value of 0.392 (N = 17). A Bland-Altman plot showed a mean difference of 0.377 μg/L.ConclusionsWe report the first testing of PSA using the i-Chroma-II™ machine, and the first real-world mobile testing using any POC PSA test. Our study did not show correlation between the laboratory and i-Chroma-II™, although it did replicate the positive bias seen in previous studies. Further testing and refinement of POC tests may help to achieve the goal to developing reliable POC PSA tests.

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.

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.

BackgroundInorganic phosphate (Pi) is a crucial electrolyte for maintaining homeostasis. Most methods measure Pi using ammonium phosphomolybdate under highly acidic conditions. Phospholipid-rich substances, such as liposomal amphotericin B, have been previously reported to artificially elevate Pi levels due to phospholipid hydrolysis in the acidic medium. This study aimed to investigate whether endogenous lipoproteins interfere with Pi measurement in cases of hyperlipidemia.MethodsWe conducted a retrospective study comparing mean Pi levels in 194,636 patients divided in groups with varying degrees of lipemia. Additionally, we performed a prospective study involving 85 patients presenting a range of lipemia to evaluate changes in Pi levels before and after plasma high-speed centrifugation-filtration, which retains all endogenous lipoproteins.ResultsThe retrospective study revealed a significant increase in Pi levels in relation with the degree of lipemia (P < .0001). The prospective study demonstrated a significant decrease in phosphatemia (P < .0001), with mean Pi levels of 1.36 mmol/L (4.22 mg/dL) before filtration and 1.27 mmol/L (3.94 mg/dL) after filtration, representing a mean decrease of 6.8%. Furthermore, the bias, defined as 100*(([Pi]_before - [Pi]_after)/[Pi]_before), was correlated with the lipemia level (r = 0.34, P = .001).ConclusionsThis study confirms that hyperlipidemia induces an analytically significant pseudohyperphosphatemia in a lipemia-dependent manner.

BackgroundSerum free testosterone is commonly used as a parameter to evaluate testosterone exposure and is mostly calculated using mathematical approximations. As the principal testosterone-binding protein, SHBG concentration is always included in such calculations. However, variability in SHBG measurements may affect reported SHBG levels and consequently free testosterone calculations. In this study, we re-evaluate the effects of SHBG assay choice and interlaboratory variability on calculated free testosterone (cFT).MethodsSerum samples from 113 men and 106 women were collected. SHBG levels were measured using three different SHBG immunoassays (Roche, Abbott and Siemens). Testosterone levels were measured using LC-MS/MS. Afterwards, cFT was calculated using the Vermeulen formula and measured directly. SHBG concentrations, and derived cFT concentrations, from different assays were compared. To simulate interlaboratory SHBG variability, measured levels were modified by 15% after which cFT was recalculated using the Vermeulen, Ly, Sartorius and Södergard formulae. The proportions of diagnoses of hypogonadism or hyperandrogenism were compared.ResultsAssessed SHBG assays showed very good conformity. The largest difference was 7%, between the Abbott and Siemens assay. The difference in cFT levels was at most 3% between the Abbott and Siemens assay. Interlaboratory variability affected the proportion of diagnoses depending on the used formula.ConclusionsOur results do not show large differences between SHBG assays and only minor effects on cFT levels. Therefore, SHBG assay choice is not expected to greatly influence clinical decision making. In contrast, interlaboratory variation in SHBG measurements and choice of formula might considerably affect cFT results and their interpretation.

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, P = .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.

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.

Background: Biomarkers in cerebrospinal fluid (CSF) are crucial for diagnosing, monitoring, and prognosing neurological disorders.Purpose: This study evaluates the impact of preanalytical variables, particularly container choice, on CSF protein measurements.Analysis: Using 30 CSF samples, we compared sterile, additive-free tubes and lithium heparin tubes without separator gel.Results: Protein levels were significantly elevated higher in heparin tubes (mean difference: 230.71 mg/dL, P < .001).Conclusions: This overestimation underscores the necessity of adhering to preanalytical protocols to avoid erroneous clinical interpretations and ensure accurate diagnostic outcomes.

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.

BackgroundIt is well established that high bilirubin concentrations can lead to erroneous creatinine results when measured by a Jaffe-based method. However, the effects of bilirubin on enzymatic methods appear less well-defined. The Roche Cobas 8000 enzymatic creatinine (CREP2) has an unconjugated bilirubin icterus limit of 20 mg/dL, equivalent to a bilirubin concentration of 342 µmol/L. Many hepatology patients have bilirubin levels much higher than this limit, and laboratories are unable to release creatinine results on these complex patients. This is particularly challenging for patient management, as creatinine is a key test and is a prerequisite for many procedures, imaging studies and treatments.MethodsTwo spiking studies were carried out, the first to define the interference effect of bilirubin on enzymatic creatinine measurement, and the second to see if this interference could be mitigated via dilution. Serum samples (n = 50) were spiked with a concentrated bilirubin solution. Indices, bilirubin and creatinine were measured using the Roche Cobas 8000 c702 automated analyser according to manufacturer instructions.ResultsThe spiking study found a negative linear relationship and as bilirubin concentrations increased, the measured creatinine concentration decreased (R² = 0.7828, y = -0.0597x + 15.603). Samples with a bilirubin concentration over 246 µmol/L demonstrated an average 1.48% drop in creatinine concentration per 25 µmol/L increase in bilirubin.ConclusionsA service improvement was applied where creatinine results can be released on samples with a bilirubin concentration up to 550 µmol/L, with an appropriate comment, upon request by the clinician.