Annals of Clinical Biochemistry最新文献

Atherosclerotic cardiovascular disease remains a major cause of premature death in the United Kingdom. Lipid testing is a key tool used to assess cardiovascular risk and guide clinical management decisions. There are currently no national guidelines to provide evidence-based recommendations on lipid testing and reporting for UK laboratories and clinicians. Here we present consensus guidance, following a review of published evidence by a multidisciplinary group of UK experts across a range of laboratory and clinical services. Recommendations include the composition of a standard lipid profile; indications for, and composition of, an enhanced lipid profile including apolipoprotein B and lipoprotein (a); use of the Sampson-NIH calculation for LDL-c estimation and guidance on when to flag abnormal results. This consensus guidance on lipid testing and reporting in the United Kingdom has been endorsed by HEART UK and The Association for Laboratory Medicine.

BackgroundGrossly lipaemic samples are a significant cause of analytical errors, potentially impacting patient care. The causes of lipaemia are varied and often unavoidable, while methods to reduce lipaemia through gold-standard ultracentrifugation are limited by availability, transportation and cost. Benchtop centrifugation has been proposed as an alternative method to reduce lipaemia.MethodsFifty-three grossly lipaemic serum samples (lipaemia >201.8 mg/dL) that were unsuitable for analysis were selected and centrifugated at 18840 g for different time-periods with lipaemia measured prior to and after centrifugation. Core analytes were measured on serum samples free of lipaemia before and after 30 min of centrifugation at 18840 g to assess the effect of the centrifugation process.ResultsAfter centrifugation for 5 min, 90% of grossly lipaemic samples were either ideal (lipaemia <50 mg/dL) or adequate (lipaemia 50.1-201.7 mg/dL) for analyte testing. All samples were either adequate or ideal for testing following centrifugation for 30 min. Although some analytes showed a statistically significant change in the measured concentration post high-speed centrifugation, none had clinically significant changes according to analyte specific reference change value (RCV) analysis. Aspartate aminotransferase (AST) and creatine kinase (CK) demonstrated the most notable reductions in activity, but these did not exceed their RCV.ConclusionsBenchtop centrifugation shows potential laboratory utility in reducing lipaemia whilst maintaining clinically reliable results, however small sample sizes preclude firm conclusions. Further research is warranted to increase the sample size with finer time-point tuning, sub-group analysis and temperature analysis, due to the potential for sample heat injury, to balance practicality and accuracy.

We describe the utility of 'folic and folinic acid load tests' in the investigation of a 26-year-old woman with persistently low serum folate and moderate hyperhomocysteinaemia unresponsive to folic acid supplements. Serum folate, plasma 5-methyltetrahydrofolate (5-MTHF), red cell 5-MTHF and plasma total homocysteine at baseline, 2-h, 4-h and 2- or 4-days (if applicable) post administration of a large dose of oral folic acid, or oral or parenteral folinic acid were measured. The tests confirmed non-compliance but also suggested an unsuspected possible defect in the folate pathway based on differential response to folic versus folinic acid supplements. The folic and folinic acid load tests identify non-compliance and can help identify possible defects related to the absorption, transportation, or metabolism of folate.

AimThird-generation whole PTH (1-84) parathyroid hormone (PTH) assays do not recognize the PTH 7-84 fragment whereas second-generation (intact) assays detect both 1-84 and 7-84 PTH fragments. This study aimed to compare the second-generation Roche intact PTH method with the third-generation Roche whole PTH (1-84) method, examining differences based on estimated glomerular filtration rate (eGFR).MethodsThe intact PTH method and whole PTH (1-84) method were compared using 100 serum samples selected across eGFR quintiles for chronic kidney disease (CKD) stages 1-5 in accordance with Kidney Disease: Improving Global Outcomes (KDIGO).ResultsMethod comparison based on eGFR showed that differences between both PTH methods were not significant at eGFR >60 mL/min/1.73 m². There was a statistically significant difference at eGFR <60 mL/min/1.73 m². The whole PTH (1-84) method produced lower results as eGFR decreased: CKD Stage 3 (mean difference: -21%; 95% confidence interval: -16 to -26%) to CKD Stage 5 (mean difference: -46%; 95% confidence interval: -40 to -52%).ConclusionsDifferences observed between the two assays may be due to second-generation PTH assays overestimating PTH concentration by measuring both 1-84 PTH and C-terminal fragments, notably PTH (7-84) in patients with significant renal impairment. The whole PTH (1-84) assay may be used to monitor metabolic bone disease risk. Initial dual reporting of PTH by both methods is recommended for eGFR <60 mL/min to educate users due to the difference in results.

BackgroundThe Sampson-NIH and Martin-Hopkins low-density lipoprotein cholesterol (LDL-C) equations are advocated as being superior to the Friedewald calculation. However, their mathematical complexity means they may have different biological and analytical variation when tracking LDL-C in the same patient. This study has established the biological variation (BV) of calculated and directly measured LDL-C (dLDL-C) in patients taking equivalent doses of a long (atorvastatin) and short (simvastatin) half-life statin. It also modelled how analytical imprecision might add to these BVs.MethodsIn a crossover study of lipid BV involving 26 patients with type 2 diabetes (T2DM) initially taking either simvastatin 40 mg or atorvastatin 10 mg, fasting lipids were measured 10 times over 5 weeks after a 3 month run-in. The same procedure was then followed for the alternate statin. Outlier removal and CV-ANOVA established the BV of dLDL and each formula. Analytical measurement uncertainty was estimated from 6 months of real-world data.ResultsThe intra-individual BV of dLDL-C measurement was considerably lower with atorvastatin than simvastatin (CV 1.3%(95% CI 1.1-1.5%) vs. 11.1%(10.2-12.2%), respectively). No equation could distinguish this difference (Friedewald 11.0%(95% CI 10.0-12.1%) vs. 12.9%(11.8-14.2%), Sampson-NIH 10.4%(9.5-11.5%) vs. 11.7% (10.7-12.8%) and Martin-Hopkins 9.3%(8.5-10.3%) vs. 11.3%(10.3-12.4%)). Real-world analytical CVs were 2.6% (Sampson-NIH), 2.6% (Martin-Hopkins) 2.8% (Friedewald) and 2.0% (dLDL-C).ConclusionsInherent biological LDL-C variability using these formulae is substantially greater than direct measurement in T2DM patients taking atorvastatin. Typical analytical imprecision was also greater. Together, this may fundamentally limit these equations' ability to track true LDL-C changes in patients taking popular statin treatments.

A case involving the incidental diagnosis of multiple myeloma (MM) due to interference in the 25-hydroxy-vitamin D (25(OH) vitamin D) immunoassay is presented. The patient, under the care of rheumatology and receiving treatment with alendronic acid and vitamin D supplements, was referred to endocrinology for investigation of acromegaly. Acromegaly was subsequently ruled out; however, during the investigations, consistently elevated levels of 25(OH) vitamin D were noted, raising suspicion of vitamin D resistance syndrome. The laboratory and endocrinology teams engaged in discussions, and following the cessation of medication, repeated analyses for 25(OH) vitamin D and a single analysis of 1,25-dihydroxy-vitamin D levels were requested, yielding high and normal results, respectively. The laboratory conducted a three-step interference investigation, ultimately identifying a high molecular weight molecule responsible for the initially elevated 25(OH) vitamin D levels. Due to the clinical presentation of back pain, a proteinogram was requested, revealing a monoclonal band of 36 g/L. Subsequent free light chain analysis indicated an elevated ratio. With three risk factors identified, this was classified as an established MM and urgently referred to haematology for correct management. Laboratory assay interferences have the potential to disrupt the accurate diagnostic workup of patients. Collaborative discussions between laboratory and clinical teams regarding such cases aid in directing the diagnostic pathway appropriately, facilitating prompt and proper diagnosis and management.

IntroductionThe aim of our study was to determine reference intervals for serum pentraxin 3 and calprotectin, as well as for urine calprotectin according to the CLSI EP28-A3C guidelines for defining, establishing, and verifying reference intervals in the clinical laboratory.Materials and methodsA total of 120 serum and urine samples from either healthy volunteers or outpatients were used for reference interval establishment. The participants had CRP levels, leucocyte counts, serum urea levels, creatinine levels, and estimated glomerular filtration rates (CKD-EPI eGFRs) within the reference range and no medical history of acute/chronic inflammatory diseases/conditions or cancer. Calprotectin was measured via a commercially available turbidimetric method - the Bühhlmann fCAL® Turbo Reagent Kit - while pentraxin 3 was measured using the Human Pentraxin 3 ELISA Kit from the BioVendor Group.ResultsThe serum calprotectin reference range was ≤3.6 mg/L, the 90% CI for the upper reference range was 3.1-4.1 mg/L, while the serum pentraxin 3 reference concentration was ≤3.0 µg/L, and the 90% CI for the upper reference range being 2.7-3.2 µg/L. Additionally, the urinary calprotectin concentration was ≤1.4 mg/L, with a 90% CI for the upper reference range of 1.0-1.7 mg/L.ConclusionThis study reports sample and method-specific reference intervals for the detection of various inflammatory conditions.

BackgroundAs cortisol and metanephrine are involved in the stress response, it is often recommended that individuals are relaxed at the time of venepuncture, however, evidence behind these recommendations is lacking. We investigated the effects of acute psychological stress on serum cortisol and plasma metanephrine concentrations in healthy individuals exposed to varying levels of psychological stress and compared these results to self-reported measures of stress.MethodsTen medical students completed two medical in-person simulations (one low-complexity, one high-complexity) in a random order. At four times, participants completed the State-Trait Anxiety Inventory (STAI) and serum cortisol and plasma metanephrine/normetanephrine were tested.ResultsMedian (interquartile range) STAI prior to the low-complexity simulation was 44 (18) versus 33 (13) afterwards (P = 0.050). STAI prior to the high-complexity simulation was 33 (10) versus 48 (17) afterwards (P = 0.007). Cortisol prior to the low-complexity simulation was 272 nmol/L (115) versus 247 (115) afterwards (P = 0.333). Prior to the high-complexity simulation, cortisol was 246 (70) versus 261 (137) afterwards (P = 0.859). Metanephrine prior to the low-complexity simulation was 242 pmol/L (79) versus 247 (93) afterwards (P = 0.515). Metanephrine prior to the high-complexity simulation was 220 (81) versus 251 pmol/L (120) afterwards (P = 0.074). Normetanephrine prior to the low-complexity simulation was 593 pmol/L (247) versus 682 (281) afterwards (P = 0.047 for the difference). Normetanephrine prior to the high-complexity simulation was 696 (123) versus 705 pmol/L (224) afterwards (P = 0.169).ConclusionsThe trend in cortisol levels largely reflected changes in STAI. We outline some implications of these findings for current practice and future research.

ObjectiveThis study aimed to examine the levels of solute carrier family seven number 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the serum of patients with acute ischaemic stroke (AIS) and their relationship with disease severity.MethodsA total of 148 patients with AIS together with 148 healthy controls (HCs) were enrolled. The expression levels of SLC7A11 and GPX4 in serum were detected immediately as early as possible. Radiographic severity was detected by Alberta Stroke Program Early CT Score (ASPECTS). Disease severity was evaluated using modified Rankin Scale (mRS). High-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9) expression levels were also measured. A correlation analysis was conducted to determine the relationship between the expression levels of SLC7A11 and GPX4 with the clinical severity of the disease and the levels of hs-CRP and MMP-9. Furthermore, receiver operating characteristic (ROC) curve analysis was utilized to assess the potential of SLC7A11 and GPX4 as diagnostic markers.ResultsCompared to the HC group, the serum expression levels of SLC7A11 and GPX4 were significantly lower in the AIS group. Serum SLC7A11 levels were positively associated with serum GPX4 levels. The AIS group included 50 patients with mild neurological impairment, 52 with moderate neurological impairment, and 46 with severe neurological impairment. AIS patients with mild neurological impairment had drastically higher serum SLC7A11 and GPX4 levels compared with those with moderate neurological impairment. AIS patients with moderate neurological impairment showed significantly higher serum SLC7A11 and GPX4 concentrations compared with those with severe neurological impairment. ROC curve analysis demonstrated that both serum SLC7A11 and GPX4 may both act as potential indicators for evaluating of AIS disease severity. In addition, both serum SLC7A11 and GPX4 levels were positively correlated with ASPECTS. Both serum SLC7A11 and GPX4 levels were negatively associated with hs-CRP as well as MMP-9 levels. Serum SLC7A11 and GPX4 levels were significantly increased following comprehensive therapy.ConclusionsDecreased SLC7A11 and GPX4 levels may reflect disease severity of AIS.