Annals of Clinical Biochemistry最新文献

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.

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 "Metabolism of xenobiotics by cytochrome P450" 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.

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_A and CV_I.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_I 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_I estimate for Lp(a) that aligned consistently with recent studies adhering to the quality specifications outlined in the BIVAC checklist. The CV_I estimate was significantly lower than Lp(a) estimates reported in studies up to 2003. The CV_I 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.

Myocardial infarction remains a significant cause of mortality globally. High-sensitivity cardiac troponin is an essential criterion in the fourth universal definition of myocardial infarction. Our understanding of the structure and release mechanisms of troponin has been updated over the last decade, facilitated by ever more sensitive assays. This review initially outlines the structure and function of the troponin complex, then details the currently proposed mechanisms of release and elimination of troponin. It concludes by using this updated understanding to critique the current universal definition of myocardial infarction and injury.

BackgroundDiagnosing acute heart failure in patients presenting with acute dyspnea remains challenging. Current methods, including natriuretic peptide measurement and echocardiography, are time-consuming and not always immediately accessible. A novel biomarker, FILDARIA, may complement natriuretic peptides and enable faster diagnosis.MethodsIn this study (ClinicalTrials.gov: NCT01024049), samples were collected from 235 patients diagnosed via echocardiography: 89 with non-cardiac dyspnea (NCD), 55 with chronic heart failure (CHF), and 91 with acute heart failure (AHF). Levels of BNP and FILDARIA in each patient were measured using both ELISA and lateral flow assay tests.ResultsBNP levels were significantly elevated in AHF and CHF patients compared to NCD patients (905 vs 58 pg/mL, p < .0001; and 447 vs 58 pg/mL, p < .0001, respectively). Similarly, FILDARIA levels were markedly higher in AHF and CHF patients than in NCD patients (1493 vs 223 ng/mL, p < .0001; and 800 vs 223 ng/mL, p < .0001, respectively). The FILDARIA heart failure diagnostic rapid test device accurately identified all 91 AHF patients and correctly excluded 88 of 89 NCD patients, yielding one false positive. Overall diagnostic accuracy was 99.4% (95% CI: 96.9%-99.9%).ConclusionFILDARIA biomarker demonstrates strong potential as a rapid diagnostic tool for AHF in patients with acute dyspnea. Its high accuracy and compatibility with whole blood could make it an excellent solution for point-of-care testing. Further multicentre research could facilitate wider clinical use and clarify its utility in areas such as prognosis (ClinicalTrials.gov: NCT01024049).

Fourier-transformed infrared (FTIR) spectroscopy is a frequently requested test in patients with kidney stones. It is considered particularly useful when routine stone urine screens do not identify any significant abnormalities. This case report describes a patient with undiagnosed adenine phosphoribosyltransferase (APRT) deficiency, a disorder presenting with kidney stones, who had initial symptoms at 16 months of age but no diagnosis until they were 6 years old. Initial investigations including a urine stone screen did not show significant abnormalities; however, FTIR analysis suggested the stones had a significant component identified as lansoprazole, a drug the patient was not taking. After repeated stone formation, urinary tract infections and inpatient stays, the disorder was identified incidentally during validation of a method for purine and pyrimidines in urine. This case highlights that FTIR analysis, although useful, has pitfalls and that other investigations are of equal value in reaching a diagnosis.

BackgroundIn vitro haemolysis is a recurrent problem in emergency department samples. Potassium is one of the most critical tests and sensitive to increasing levels of in vitro haemolysis. Haemolysis results in a large number of invalidated potassium test results.MethodsWe set up an alert system to detect the risk of dyskalaemia based on potassium value and haemolysis index (HI). We retrospectively evaluated the effectiveness of the alert system for haemolysed blood samples from the emergency department.Results54 605 samples were included. Women more frequently had a sample with a high HI value, resulting in the invalidation of a potassium test result (3.22% vs 2.35%, P < 0.001). In the case of haemolysed samples, the frequency of alerts for hyperkalemia risk was similar in women and men. Hypokalaemia was significantly more frequent in women than in men (12.71% vs 9.38%, P < 0.001). Among the haemolyzed samples, no hypokalaemia risk alerts were observed and 42 patients had a hyperkalaemia risk alert. For these patients, the potassium value of a second sample was significantly higher in patients with an alert on the first sample (4.85 mmol/L vs 4.0 mmol/L, P < 0.001), with a higher rate of hyperkalaemia (57.14% vs 4.76%, P < 0.001) and critical hyperkalaemia (17.86% vs 0.3%, P < 0.001). Negative predictive value and positive predictive value to detect hyperkalaemia were 90.4% [89.6-91] and 41.3% [25.5%-59.1%].ConclusionsOur alert system was effective to detect the risk of hyperkalemia, and could help clinicians to better target patients requiring repeat sampling for potassium.

Sepsis accounts for approximately 20% of global deaths, and early diagnosis is a critical factor in intervention. In 2017, the FDA approved procalcitonin (PCT) to guide antibiotic use for patients with suspected sepsis, and there are recognized intervals for clinical interpretation. Therapeutic algorithms incorporating PCT measurement have implications for antibiotic stewardship in the age of antibiotic resistance. A 2021 review of external quality assurance programs for PCT, including the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) PCT program, highlighted variable performance between assays. We reviewed the RCPAQAP's PCT program results from 2019 to 2021 to analyse any variation in reported results. The RCPAQAP's PCT program is conducted annually and consists of a lyophilized human/bovine serum albumin base with added recombinant PCT sent to participating laboratories. Results received for the 2019, 2020 and 2021 PCT programs were analysed using two-way ANOVA with Tukey's multiple comparison test and a Student's t-test to investigate variation in assay performance. We found significant variation between the different assay manufacturers at all PCT concentrations analysed. Additionally, bimodal reporting was observed, where bioMerieux/Beckman Coulter/Siemens methods had significantly higher results when compared to Roche/Abbott methods. There was also a significant increase in the average coefficient of variation between 2019 and 2020/2021, coinciding with reported method changes. Finally, variable performance of the semi-quantitative PCT method at both low and high PCT concentrations was detected. These findings suggest that clinical decision cut-offs must be validated for each assay. However, the commutability of the program material has yet to be determined.