Annals of Clinical Biochemistry最新文献

IntroductionAnalytical quality is a crucial prerequisite for best practice in medical laboratory. Six-Sigma Methodology (SM) is a quality measurement tool used to evaluate laboratory performance. This study aims to assess the analytical phase baseline performance using SM and compare results using TEa of CLIA 1988 and CLIA 2024.Materials and methodsCoefficient of variation and bias were determined for 14 analytes. The sigma level for each parameter was calculated using total allowable error (TEa) for CLIA 1988 and CLIA 2024. The quality goal index ratio was calculated for analytes with Sigma less than 3. Normalized method decision Charts were plotted for level 1 and 2 Bio-Rad internal quality control for both CLIA 1988 and 2024.ResultsUsing CLIA TEa 1988, HDL-C, triglycerides & uric acid for level 1 and ALT, AST, HDL-C, calcium, triglycerides & uric acid for level 2 had six Sigma world class performance, meanwhile, only BUN for level 1 and 2 performed less than 3. Using CLIA TEa 2024, HDL-C, GGT, and triglycerides for level 1 and ALT, AST, calcium, GGT, and triglycerides for level 2 had world class quality performance. Meanwhile, creatinine, glucose, BUN for level 1 and BUN and creatinine for level 2 performed less than 3.ConclusionEvaluation of baseline analytical performance using SM revealed lower sigma values with stringent CLIA TEa 2024 versus tolerant CLIA TEa 1988. Improvement in the methodology of analytes with poor performance on some assay platforms with stringent quality control regimes is recommended.

BackgroundA critical pre-analytical phase of newborn screening (NBS) testing involves the drying of blood applied to the blood collection devices to form the dried blood spots (DBS). Guidance states that blood applied should be air-dried for a minimum of 3 h. A recent survey highlighted that a number of DBS specimens routinely received into laboratories have a 'crinkled' appearance and that DBS specimens collected in a hospital setting are transported to the laboratory in sealed plastic bags. To date no scientific studies have evaluated aspects of blood drying on DBS NBS analyte concentrations.MethodsWe undertook experiments to recreate 'crinkled' DBS specimens in the laboratory and assess the impact on analyte concentrations. We also assessed the impact of storing collection devices following blood application in hermetically sealed plastic bags to impede the drying process. Experiments were performed using whole blood enriched with thyroid stimulating hormone, immunoreactive trypsinogen, phenylalanine, tyrosine, leucine, methionine, octanoyl-carnitine, decanoyl-carnitine, isovaleryl-carnitine and glutaryl-carnitine to pathophysiological concentrations.Results'Crinkled' DBS specimens produced significantly lower results (mean -15.5%, range -25.1 to -4.7%) for all analytes measured versus air-dried DBS specimens (P < .05). Analyte concentrations obtained from DBS specimens following storage in plastic bags before drying were significantly lower (mean -41.6%, range -60.0 to -27.6%) for all analytes measured (P < .05) versus air-dried DBS specimens.ConclusionResults from this study demonstrate that all DBS specimens with a crinkled appearance and those received in plastic specimen bags should be rejected and a repeat specimen collected to prevent erroneous screening results.

BackgroundMeasurement of urine free metadrenalines offers potential diagnostic and practical advantages over urinary fractionated metadrenalines in detection of phaeochromocytoma and paraganglioma, including sample collection without acid preservative. Here, we evaluate stability with and without sample acidification as well as pH implications for analysis by solid-phase extraction (SPE) and liquid chromatography tandem mass spectrometry.MethodsSpot urine samples were adjusted to pH 3 or unacidified on day of collection and stored at room temperature, 4°C or -20°C, for up to 28 days to assess changes in free metadrenaline concentrations over time. Extraction of unacidified versus acidified urine was examined by comparing peak areas and measuring concentrations present in sample eluents according to two SPE methodologies.ResultsFree metadrenalines remained stable in urine with or without acidification for up to 28 days, with mean reduction in concentrations of <10% for all storage conditions. Measured concentrations progressively increased without acidification at room temperature at low concentrations but remained constant when spiked with pathological concentrations. Peak areas were up to 97-fold lower in acidified than unacidified samples when extracted using weak cation exchange (WCX). On average 64% of analyte eluted in the flowthrough in acidified samples relative to 1.5% without acidification. By contrast, over 99% was retained in the extract using polar extraction at either pH.ConclusionUrine free metadrenalines remain stable at room temperature for up to 28 days and are more efficiently extracted without use of acid preservative if using WCX methodology.

BackgroundThe Japanese Red Cross Society measures levels of glycated albumin (GA), an indicator of mean blood glucose levels, in blood obtained from all donors.MethodsChanges in mean GA levels and the percentage of cases of prediabetes from 2009 to 2018 were investigated in approximately 4.2 million, healthy, first-time blood donors aged 16-64 years, and the seasonal characteristics of GA and the association of the GA level with body mass index (BMI) were clarified.ResultsMean GA levels decreased over the decade, with a decrease of 0.42-0.77% in male and 0.39-0.49% in female donors in the groups categorised by age. The percentage of prediabetes cases also decreased over the decade, with the largest decrease in those in their 60s. GA levels were higher in the warm season than in the cold season. In 2018, the seasonal difference in the GA level was 0.48% (95% confidence interval [CI] 0.45-0.50%) for male and 0.45% (95% CI 0.41-0.48%) for female donors. GA had a linear negative correlation with BMI in the younger generation. A trend of increasing GA with BMI was noted in those in their 30s and older.ConclusionsMean GA levels and the percentage of prediabetic cases have decreased, possibly resulting from public health promotion efforts and early diagnosis of diabetes mellitus. The present data on GA seasonal variation, showing higher levels in the warm season, and the association between BMI and GA may be useful for clinical practice.

Background: Thalassemias are inherited disorders caused by reduced production of structurally normal haemoglobin chains. Haemoglobin A2 (HbA2) constitutes an important parameter in the diagnostic evaluation of thalassaemias. Insight into the factors that modulate HbA2 levels is critical for correct interpretation of laboratory results in cases where thalassaemia is suspected. Methods: A retrospective study was conducted on patients who underwent haemoglobin analysis by high-performance liquid chromatography (HPLC) at Amsterdam UMC. Patients with elevated haemoglobin A1c (HbA1c) levels due to chronic hyperglycaemia were compared with controls, an iron deficiency cohort, and α-thalassemia cohorts. Results: Patients with strongly elevated HbA1c levels (110-180 mmol/mol) showed significantly reduced HbA2 levels compared with controls (2.0% vs. 2.4%, P<0.0001). This reduction in HbA2 fraction was not observed when HbA2 was expressed relative to non-glycated HbA instead of all haemoglobin fractions. Red cell indices (MCH, MCV) and haemoglobin concentrations remained unaffected. The degree of HbA2 reduction in patients with high HbA1c was comparable to that observed in iron deficiency and α-thalassemia. Conclusions: Elevated HbA1c levels due to chronic hyperglycaemia lower measured HbA2 fractions, confounding the diagnostic evaluation of thalassaemias. Laboratories should consider HbA1c status when interpreting HbA2 results in patients with poorly controlled diabetes. Expressing HbA2 relative to non-glycated HbA may improve diagnostic accuracy in such cases.

Proprotein Convertase Subtilisin-Kexin type 9 (PCSK9) is a key regulator of lipid metabolism, binding to the low-density lipoprotein receptor (LDLR) on the cell surface and preventing its recycling, thereby reducing clearance of LDL cholesterol (LDLc) from the circulation. For this reason, it constitutes an alternative therapeutic target for the control of hypercholesterolaemia, with the development of monoclonal antibodies against PCSK9 occurring within 12 years of the protein's discovery. Recent research has also suggested an inflammatory role played by PCSK9, with elevated plasma levels identified in critical illnesses such as sepsis and Acute Respiratory Distress Syndrome, where PCSK9 is thought to reduce bacterial endotoxin clearance and may exacerbate inflammation. Further work is required in order to clarify the exact role played by PCSK9 in extra-hepatic tissues, and the potential benefits of its pharmacological inhibition.

IntroductionThe climate crisis presents a complex and growing challenge for healthcare systems around the world. Healthcare systems can contribute to substantial global emissions, with the UK's National Health Service (NHS) alone responsible for 4%-5% of the country's total carbon footprint. A wide range of clinical disciplines have already begun to assess and design interventions to tackle this issue. However, clinical and diagnostic laboratories remain underexplored.AimsWhat studies have been undertaken to assess and improve the environmental impact of clinical laboratories?MethodsThis scoping review undertook a multi-database search from date of inception to 5th February 2024. All primary studies that assessed the environmental outcomes of clinical laboratories were included. Studies were screened and data extracted by one reviewer with a 10% verification process at each stage. Studies were assessed based upon year of publication, geographical region, interconnectivity and area and type of clinical laboratory or test.FindingsThere has been some longstanding interest in understanding the environmental impact of clinical laboratories, and this field of investigation has gained popularity within the scholarly community in the last decade. Despite this recent increase in popularity there is a relatively limited number of intervention studies aimed at improving sustainability within clinical laboratories. Most research in this area originates from the United States, United Kingdom, and Australia, although the topic appears to be of global scholarly interest. There is limited interconnectivity of studies included in this review. Studies in this field have primarily been conducted at the clinical laboratory level, with a focus on quantifying waste in kilograms, measuring carbon dioxide equivalent (CO₂e) emissions, and categorizing laboratory waste by type. To a lesser degree these outcomes have been assessed for specific clinical tests. Across both clinical laboratory and specific test assessments there is notable heterogeneity in both methods used, and areas explored.DiscussionWhile this scoping review highlights a growing interest and awareness in this important field, the diversity of reported outcomes and the limited interconnectivity of studies indicate that it remains a developing area. The lack of consensus in methodologies and outcome measures suggests that establishing a baseline analysis remains a distant goal. Ideally, future efforts should prioritize improving the assessment of individual laboratory tests, fostering greater standardization, and enhancing repeatability to strengthen the reliability of environmental impact evaluations.

The aldosterone renin ratio (ARR) is used as a screening test for primary aldosteronism (PA), and this requires measurement of both aldosterone and renin. Aldosterone is usually measured using immunoassay or liquid chromatography-mass spectrometry techniques. Antihypertensive medications should be discontinued prior to screening as they can interfere with interpretation of results. Indapamide is a thiazide-like diuretic commonly used in the treatment of hypertension. NICE guidance (NG136 2019) recommends the use of indapamide over more conventional thiazide diuretics. Indapamide has been noted to cause interference in a liquid chromatography-mass spectrometry method by interfering in the measurement of aldosterone-d4 internal standard. This leads to falsely increased concentrations of aldosterone which can lead to unnecessary further investigations.

BackgroundMultiple myeloma patients may present with spuriously elevated serum phosphate levels resulting from the presence of paraproteins interfering in the phosphomolybdate UV assay. If this phenomenon is not recognized, patients possibly receive unnecessary treatments. This short report highlights the existence of paraprotein-related pseudohyperphosphatemia, and aims to provide accessible solutions to eliminate this interference.Material and MethodsIn a patient known with IgG multiple myeloma and unexplained hyperphosphatemia, the correlation between serum phosphate levels (phosphomolybdate UV assay) and IgG concentrations (immunoturbidimetry) was evaluated. To investigate the effect of the paraprotein on phosphate levels, phosphate was measured in one serum sample before and after protein removal by either dilution, protein precipitation with sulfosalicylic acid or zinc sulphate, or ultrafiltration.ResultsA patient with multiple myeloma presented with an unexplained hyperphosphatemia which correlated positively with serum IgG concentrations. As serum dilution normalized the phosphate level, it was hypothesized that precipitation of the paraprotein during the assay reaction interfered with the measurement and resulted in pseudohyperphosphatemia. Protein removal by precipitation with sulfosalicylic acid or zinc sulphate efficiently reduced the IgG level below the detection limit but did not result in a reliable phosphate measurement. Successful removal of proteins and a serum phosphate level that matched the patient's other biochemistry parameters and clinical condition were obtained by ultrafiltration.ConclusionParaproteins can interfere with the reaction components in the phosphomolybdate UV assay and result in pseudohyperphosphatemia. If the presence of this phenomenon is established, a reliable phosphate concentration can be obtained after ultrafiltration of the sample.