Annals of Clinical Biochemistry最新文献

BackgroundCalculated globulin, based on direct measurement of total protein and albumin, can be a useful addition to the routinely requested liver profile. However, a reference interval, established using CLSI EP28-A3c recommended direct methods, is lacking for the commonly used Roche method [albumin bromocresol green (BCG), total protein (biuret)].MethodsThis direct reference interval study was carried out between January and March 2024, based on Roche methods for total protein (biuret) and albumin (BCG). Reference individuals comprised 310 highly selected adults from primary care, ages ranging from 16 to 89 years. The CLSI guideline, EP28-A3c, was strictly followed. We also established a reference interval using an indirect approach for comparative purposes, using results from 8466 unselected primary care patients.ResultsThe reference interval for calculated globulin established using direct sampling techniques was 23 g/L (90% CI 22-24 g/L) - 35 g/L (90% CI 34-36 g/L). The reference interval established using indirect sampling techniques in a much larger unselected reference group was 22 g/L (90% CI 22-22 g/L) - 37 g/L (90% CI 37-37 g/L).ConclusionsWe have established a reference interval for calculated globulin, specific to the Roche total protein and BCG albumin methods. This will be a useful tool for other laboratories which use the Roche BCG albumin method, allowing adoption of this reference interval with a simple transference study. The range was a little broader but not materially altered (medians exactly the same) when strict exclusion criteria were removed and also when using a data mining approach, which resulted in a 27-fold larger reference group.

BackgroundTo clarify the fundamental characteristics of the Japan Society of Clinical Chemistry reference measurement procedure (JSCC RMP) for glycated albumin (GA), an additional performance study was performed and the correlation between the HPLC method and JSCC RMP was re-evaluated.MethodsRepeatability, detection limit, addition recovery, uncertainty of measurement, inter-laboratory comparison, correlation between JSCC RMP and HPLC method were evaluated.ResultsThe coefficient of variation (CV) of the total repeatability for the nine pretreated samples including isotope dilution and hydrolysis, defining that the averages of each of nine MS measurement samples are independent measurement vials, was 1.0%(n = 9). The limit of detection and Quantification of the GA values were 7.4 and 29.5 mmol/mol, respectively. Addition recovery rates were 99.6%-100.4%. The strong correlation (r = 0.999) of measured six serum samples between two laboratories was observed. Certified values and expanded uncertainties for JCCRM 611-2 (M, H, HH) using the JSCC RMP were as follows: JCCRM 611-2M: 232 and 9 mmol/mol, JCCRM611-2H: 359 and 14 mmol/mol, JCCRM611-2HH: 556 and 22 mmol/mol, respectively. The regression equation obtained using the Passing-Bablok method was GA (%)_HPLC = 0.0523 × GA (mmol/mol) _{JSCC RMP} + 1.315.ConclusionThe basic performance of the JSCC reference procedure for GA measurement was good, and similar results were obtained at other facilities, so it was considered to be robust and suitable as a reference method for GA measurement. Additionally, an equation was established to convert JSCC RMP (mmol/mol) values to the HPLC% values used in clinical practice.

ObjectivesChromosomal abnormalities and congenital anomalies have huge impact on infant mortality and morbidity. The combined incidence affects approximately 1 per 1000 pregnancies. Current diagnostic modalities include ultrasonography and biomarkers like Beta hCG, PAPP-A and Alpha fetoprotein which have limitations due to their varied sensitivity and specificity in aneuploidy and NTD detection. PCSK9, a proprotein converters appears to have an escalating role in neurogenesis, neuronal differentiation and neurological diseases apart from its role in lipid metabolism. This study estimates serum PCSK9 levels in pregnant women with normal gestation and those with high risk for Aneuploidy and NTDs.MethodsThis prospective case control study included 40 pregnant women with high risk of aneuploidy and NTDs (cases) diagnosed by prenatal screening with ultrasonography findings, Beta HCG, PAPP-A and 40 pregnant women with a healthy singleton pregnancy (controls). Statistical analyses were performed in SPSS software version 16. Fetal and maternal characteristics, serum Beta HCG, PAPP-A, PCSK-9 and aneuploidy risk scores were compared between two groups.ResultsThis study observed significant difference in Beta HCG, PAPP-A and PCSK9 levels between the groups (P < .05). The PCSK9 levels were lower in cases [82.95 (70.41-90.74)] than control group [123.84 (102.515-152.70)]. PCSK9 levels <96.8 ng/mL had an 85% sensitivity and specificity. Further PCSK9 correlated with Trisomy 21 risk score and Beta HCG (P < .05).ConclusionsMaternal serum PCSK9 is decreased in high-risk pregnancy during first trimester. With 85% sensitivity, the marker could be a reliable screening tool during prenatal screening which needs further validation.

BackgroundBilirubin photoisomers, generated during phototherapy or incidental light exposure, may interfere with direct bilirubin (DB) measurement using the bilirubin oxidase method. This interference is particularly relevant in neonates, who physiologically exhibit elevated levels of unconjugated bilirubin.MethodsResidual serum samples from 30 neonates were irradiated under controlled conditions to selectively produce bilirubin configurational isomers (BCIs) and structural isomers (BSIs). DB and total bilirubin (TB) were measured pre- and post- irradiation using the bilirubin oxidase method. BCI and BSI concentrations were quantified using high-performance liquid chromatography (HPLC), and their contributions to DB values were evaluated using linear and multiple regression analyses.ResultsPost-irradiation, DB levels increased significantly in correlation with BCI and BSI concentrations. Approximately 11% of BCI and 32% of BSI were quantified as DB using the bilirubin oxidase method. These findings were consistent across both individual and multiple regression models.ConclusionsBilirubin photoisomers significantly influence DB values measured by the bilirubin oxidase method, potentially leading to overestimation of conjugated bilirubin. In neonatal care, accurate interpretation of DB values requires attention to sample handling and awareness of photoisomer interference, particularly under light-expose conditions.

Over the past 50 years, External Quality Assessment (EQA) Schemes in the UK have changed from being overseen by the Department of Health and Social Security (DHSS) to a self-funding model post-1990, increasing competition among schemes. Despite reforms, there is no single source for assessing UK laboratories' performance. Laboratories often use a single manufacturer, which can restrict laboratories to having to use a poor method for some assays. Regulatory changes like the EU In Vitro Diagnostics Regulation (IVDR) impact manufacturers. The Medicines & Healthcare products Regulatory Agency (MHRA) oversees assay performance, focusing on patient harm. Participation in EQA is mandatory for ISO 15189 accreditation, but the holistic quality of EQA services vary. Four cases studies (calcium, testosterone, paracetamol and total bilirubin) are presented that illustrate how the current systems are being used in practice. These show different elements of quality assurance, but crucially in all cases patient management will have been impacted. Most performance issues are manufacturer-related. EQA helps monitor assay quality, but gaps in oversight remain. Diagnostic reform is progressing, but differences in assay results pose risks. Laboratories must collaborate with stakeholders to ensure high-quality services. Mechanisms are needed to rectify sub-optimal assays. The current system can lead to patient misdiagnosis or incorrect clinical pathways. A mechanism is required to ensure accurate results for the public, within acceptable error margins, and at a sustainable cost for the NHS.

BackgroundInternational guidelines give greatly varying definitions of 25-hydroxyvitamin D (25OHD) insufficiency and deficiency. Vitamin D testing is increasing despite 2016 UK guidance for adults advising routine vitamin D supplementation October-March and year-round for high risk groups. A service evaluation of vitamin D testing and biochemical osteomalacia in the North-East of Scotland (57-58°N) could inform definitions and testing guidance.MethodsWe identified adult 25OHD requests 8/7/2008-29/2/2020 and albumin-adjusted serum calcium (aCa), parathyroid hormone (PTH) and alkaline phosphatase (ALP) within 6 months of 25OHD testing. After excluding renal impairment and liver disease, we defined biochemical osteomalacia as ALP >130 IU/L and aCa <2.0 mmol/L and elevated PTH >9.2 or >6.8 pmol/L, depending on the assay. Possible biochemical osteomalacia was defined as 2 of these abnormalities in the absence of the third measurement. From these cases anonymised clinical data were then examined to confirm the diagnosis of osteomalacia.Results25,379 eligible patients had 25OHD measured: 25% were <25 nmol/L (6,258/25,379) and 18% <20 nmol/L (4,536/25,379). 0.5% (126/25,379) of eligible patients had biochemical or possible biochemical osteomalacia. After reviewing clinical records, only 0.1% (29/25,379) had clinically confirmed osteomalacia, equivalent to 2-3 cases/y for a population of 0.5 million, none of the untreated cases of clinically confirmed osteomalacia had 25OHD >25 nmol/L. For the entire tested population, when 25OHD was <25 nmol/L untreated osteomalacia confirmed by clinical records was rare (0.4%).ConclusionsOsteomalacia is rare in North-East Scotland. Our data call into question designating 25OHD 25-50 nmol/L 'insufficiency'. The risk of osteomalacia even when 25OHD is <25 nmol/L is very low.

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionised oncology care, by enhancing the body's T cell lymphocyte response against tumour cells. ICIs block the inhibitory signalling between tumour cells and the immune system, but consequently reduce immunological tolerance. Subsequently for some, this leads to immune-related adverse events (irAE), a spectrum term for autoimmune-like toxicities induced by ICIs that affects various tissues and organs. This limited narrative review will give a brief overview of immune checkpoint inhibitors and immune-related adverse events for laboratory professionals and review the current evidence for predictive biomarkers.MethodsA limited narrative review was conducted by accessing Pubmed and Google from June 2023 to January 2024 to identify references published from database inception to January 2024. Language was restricted to English.Results/findingsProfessional guidance does not recommend any biomarkers for irAE prediction. Some studies have found an association between the prediction of irAE and interleukin six (IL-6), C-reactive protein (CRP), thyroid stimulating hormone (TSH), albumin, ferritin, full blood count metrics, and lactate dehydrogenase (LDH). However, these have often been single-centre retrospective studies. While an abundance of societal guidance has been produced, it is unclear what blood tests should be included within a baseline profile.ConclusionsPresently, there is no singular biomarker routinely available in clinical laboratories that can predict the onset of irAE. A custom battery of tests may be more predictive, but evidence is currently lacking. In the meantime, due to the clinical significance of these complications, laboratory professionals should proactively support prospective studies.

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.

ObjectivesNeonatal respiratory distress syndrome (NRDS) is the most common respiratory disease in preterm infants (PIs). The implication of Angiopoietin-like 4 (ANGPTL4) was reported in lung diseases. We delved into the role of serum ANGPTL4 in NRDS diagnosis/prognosis.MethodsTotally 256 PIs were prospectively selected, including 128 NRDS infants and 128 non-NRDS PIs. NRDS infants were assigned into Survival and Death groups. ANGPTL4 level in PIs and its diagnostic and prognostic value for NRDS were separately assessed by ELISA and receiver operating characteristic curve. The independent risk factors (IRFs) for death in NRDS infants were analysed by multivariate logistic regression.ResultsNRDS infants exhibited reduced gestational age, birth weight, and 5 min Apgar score. ANGPTL4 level rose in NRDS infants, and increased with NRDS severity. Serum ANGPTL4 level was negatively correlated with 5 min Apgar score in NRDS infants. The area under the curve of serum ANGPTL4 for the diagnosis of NRDS was 0.902, with 88.28% sensitivity, 86.72% specificity, and 255.98 ng/mL cut-off value; the AUC for the diagnosis of severe NRDS was 0.741, with 66.67% sensitivity, 79.52% specificity, and 625.5 ng/mL cut-off value. Low gestational age, birth weight and 5 min Apgar score, severe NRDS, and elevated serum ANGPTL4 levels were IRFs for death in NRDS infants. NRDS infants with increased serum ANGPTL4 level displayed decreased survival rate and short survival time.ConclusionsANGPTL4 exhibited high diagnostic value and predictive value for death in NRDS, and it served as a biomarker for the diagnosis and prognosis of NRDS.