Annals of Clinical Biochemistry最新文献

IntroductionShort Synacthen Test (SST), a standard diagnostic test to confirm Adrenal insufficiency (AI), involves substantial expenses.ObjectivesThis study aimed to assess the predictive value of baseline Cortisol levels for SST outcomes and establish baseline cut-off levels for confirming AI to minimize the necessity of SST.MethodsAll SST data from 2019 to 2024 at National Hospital Kandy, Sri Lanka, were obtained retrospectively. A peak Cortisol ≥500 nmol/L at 30 or 60-min post-SST was considered as a normal adrenal reserve, whereas failure indicated AI. Pearson's correlation and Logistic Regression analysis assessed baseline and post-SST Cortisol at 30 and 60-min. A 2 × 2 table assesses test agreement. Receiver operating characteristic (ROC) curve analysis evaluated the SST outcomes at 30 and 60-min separately assessing sensitivity, specificity, and area under the curve (AUC).ResultsA total of 307 patients were enrolled, and 63.19% exhibited a failed SST response. Baseline Cortisol positively correlated with post-SST Cortisol at 30-min (r = 0.74, P < .05) and 60-min (r = 0.68, P < .05) with a good AUC for both 30 min (AUC = 0.855) and 60 min (AUC = 0.829). Baseline Cortisol demonstrated the higher odds ratio per unit (OR = 1.015 per nmol/L), indicating greater sensitivity to small changes. ROC curves were utilized to derive cut-offs for baseline Cortisol levels predicting SST outcomes. At 30-min, baseline Cortisol <135 nmol/L suggests AI (100% sensitivity, 44% specificity), and >381.5 nmol/L indicates normal adrenal reserve (100% specificity, 21.8% sensitivity). Similarly at 60-min, baseline Cortisol <75.3 nmol/L suggests AI (100% sensitivity, 19.7% specificity), and >357 nmol/L indicates normal adrenal reserve (100% specificity, 16.8% sensitivity).ConclusionsApplying these cut-offs could avoid 41.69% (30 min) or 19% (60 min) of total SSTs, excluding AI and normal adrenal reserve. 30-min SST Cortisol correlates more strongly with baseline Cortisol, showing a higher r-value, higher OR and AUC. Hence, 30-min provides better cut-offs with higher sensitivity and specificity minimizing need for SST. Patients with baseline Cortisol between 135 and 381 nmol/L can undergo SST with only a 30-min Cortisol measurement.

BackgroundZinc deficiency is a global concern, particularly in low-income countries, but also among vulnerable groups in Western countries, such as children. Diagnosing mild or moderate zinc deficiency is however challenging because of nonspecific symptoms and due to circulating zinc showing only subtle changes, requiring high accuracy in measurement. Challenges to accurate measurement include variations from choice of analytical instrument, analysis performance, and preanalytical factors such as choice of sample matrices and delayed blood sample processing. This study aimed to examine the stability of zinc in plasma and serum, measured by the recommended inductively coupled plasma optical emission spectrometry (ICP-OES) method and a direct colourimetric assay on the fully automated Roche Cobas c702 analyzer.MethodsA total of 245 whole blood samples were stored at room temperature for 0-8 h after blood sampling, then centrifuged for 10 min at 2000 g (serum) or 5 min at 2650 g (plasma), frozen at -20°C, and analysed, respectively, on ICP-OES and Cobas, the latter with the colourimetric kit from Sentinel diagnostics.ResultsSerum zinc concentrations measured on Cobas and ICP-OES showed no statistically significant change up to 6 h and never exceeded acceptable limits. Plasma zinc concentrations increased steadily over time, exceeding acceptable limits after 6 h. There were statistically significant differences between zinc measurements on ICP-OES and Cobas in both serum and plasma.ConclusionsZinc is stable for at least 8 h in serum and up to 6 h in plasma when measured by either Sentinel diagnostic colourimetric method on Cobas or ICP-OES.

BackgroundThiopurine S-methyltransferase (TPMT) is crucial for metabolizing thiopurine drugs. This study aimed to establish the cutoff values for TPMT activity in a cohort of healthy individuals. We defined normal TPMT activity ranges and identified clinically applicable thresholds to distinguish individuals with normal TPMT function from those with reduced or deficient activity.MethodsA total of 457 participants, including 207 children and 250 healthy adults without prior thiopurine drug exposure, were enrolled. TPMT activity was measured and common defective genetic variants (TPMT*3A, TPMT*3B, and TPMT*3C) were detected. To determine TPMT activity cutoff values and maximize sensitivity and specificity, receiver operating characteristic curve analysis was employed.ResultsThe cutoff values for TPMT activity in children were ≥52.9 nmol 6-MMP/g Hb/h for persons of the wild type and <52.9 nmol 6-MMP/g Hb/h for individuals who were heterozygous. In adults, the cutoff values were ≥44.6, 31.58-44.5, and <31.58 nmol 6-MMP/g Hb/h for wild-type, heterozygous, and compound heterozygous individuals, respectively. The sensitivity and specificity were 79.29% and 100% in children, whereas, in adults, they were 61.86% and 78.57%, 38.46% and 64.73%, and 100% and 95.98% in the wild-type, heterozygous, and compound heterozygous, respectively.ConclusionsIdentifying TPMT activity cutoff values is crucial for managing patients receiving thiopurine therapy, especially in Thailand. This approach allows for personalized treatment plans and minimizes the risk of adverse drug reactions. Since TPMT activity cutoff values can differ by population and testing methods, it is important to establish specific cutoff values locally.

Background: 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.Methods: 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.Results: 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.Conclusion: 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.

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.

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 in vitro 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.

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.

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.

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.