Allen GFG, Blampied S, Patel KA
… +3 more, McDonald TJ, Hattersley AT, Vaidya B
Ann Clin Biochem
· 2026 Feb · PMID 41663150
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BackgroundThe rise in serum thyroid stimulating hormone (TSH) in healthy older adults is well established. However, age-related reference intervals are not widely used. We aimed to establish all-adult and age-related ref...BackgroundThe rise in serum thyroid stimulating hormone (TSH) in healthy older adults is well established. However, age-related reference intervals are not widely used. We aimed to establish all-adult and age-related reference intervals for TSH, free thyroxine (FT4) and free triiodothyronine (FT3) and determine their impact on primary care thyroid testing results.MethodsWe measured TSH, FT4 and FT3 by Roche Cobas assays in a reference cohort of 1364 anti-thyroid peroxidase antibody negative adults with no self-reported medical conditions or medications. Reference intervals were generated for all-adult, 18-60 and over 60 years. Reference intervals were applied to 21,286 primary care tests with no known thyroid disease to assess effect on test interpretation.ResultsIn the reference cohort, 23.2% were over 60 years compared to 50.4% of those undergoing thyroid testing in primary care. With an all-adult reference interval, 8.2% of over 60s had an elevated TSH, 7.0% were classified as subclinical hypothyroid and 0.8% as overt hypothyroid. With age-related reference intervals, this fell to 4.4% with an elevated TSH, 3.7% subclinical hypothyroid and 0.4% overt hypothyroid. Minimal changes were seen in the 18-60 years group.ConclusionsAn all-adult reference interval derived from healthy and therefore younger individuals is less appropriate for the older subset of the population being tested. Application of an age-related reference interval for over 60s would reduce the proportion of patients with abnormal thyroid test results. In turn, this would decrease potentially unnecessary cascade and repeat testing as well as regular follow-up in primary care.
Xu M, Pu Y, Zhang T
… +12 more, Liu Z, Zhang Q, Zhou W, Deng Y, Zhang C, Zheng H, Zhao H, Zhang J, Zhang T, Wang J, Zeng J, Zhang C
Ann Clin Biochem
· 2026 Feb · PMID 41661942
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BackgroundSerum copper is an essential trace element, and accurate quantification is important for assessing copper status in pregnancy and supporting early clinical interventions. However, current serum copper assays fa...BackgroundSerum copper is an essential trace element, and accurate quantification is important for assessing copper status in pregnancy and supporting early clinical interventions. However, current serum copper assays face several challenges, including potential inaccuracy, poor comparability between methods, and difficulties in transferring reference intervals (RIs) between populations. This study aimed to establish a simple inductively coupled plasma mass spectrometry (ICP-MS)-based candidate reference method for serum copper to strengthen the reference measurement system, and to verify whether recently proposed multicenter RIs for serum copper can be transferred to a Chinese population.MethodsCobalt was used as the internal standard. After digestion with Optima-grade ultrapure nitric acid, samples were diluted 100-fold with ultrapure water. The Cu/Co ratio was measured in helium collision mode, with the gas flow rate set to 5 mL/min. Analytical performance was validated, and serum copper RIs in pregnant and non-pregnant women were subsequently verified.ResultsA candidate reference method was established. The method demonstrated excellent linearity, with a correlation coefficient (R) exceeding 0.99998 over the range 0-13.75 μg/g. The total precision ranged from 0.30% to 0.40%. The spike recovery was 100.06% (99.95-100.14%). Trueness was confirmed by measurements of NIST SRM 1598a, which fell within the certified value and its stated uncertainty. The RI for healthy non-pregnant women was transferable to healthy Chinese women, whereas the pregnancy-specific RI for serum copper was not fully transferable and requires further adjustment for Chinese women.ConclusionA highly sensitive and specific candidate reference method for serum copper was established, strengthening the reference measurement system and contributing to the standardization and harmonization of serum copper assays. Pregnancy-specific RIs for serum copper in Chinese women should be established.
BackgroundLaboratory test results are crucial for clinical decisions, but errors at any stage can compromise patient safety. Despite technological advances and quality systems, laboratory processes remain vulnerable, nec...BackgroundLaboratory test results are crucial for clinical decisions, but errors at any stage can compromise patient safety. Despite technological advances and quality systems, laboratory processes remain vulnerable, necessitating structured risk assessment. Limited research exists on integrating Failure Mode and Effects Analysis (FMEA) with Sigma metrics. This study addresses these gaps through a comprehensive risk assessment in a NABL-accredited tertiary care hospital laboratory.MethodsA retrospective observational study was conducted over 2.5 years. FMEA was used to identify errors across all phases of the total testing process. Quarterly error rates were calculated, converted to defects per million (DPM), and expressed as Sigma metrics. Risk Priority Numbers (RPN = severity × detectability × frequency) were scored quarterly to prioritize failures. The effect of corrective actions was evaluated by comparing pre- and post-intervention Sigma values.ResultsAcross 10 quarters (five pre- and five post-intervention), 23 error types were identified. The highest RPNs (>20) were observed for haemolyzed samples, clotted samples, and non-intimation of critical values. Haemolyzed samples declined from 0.97% to 0.49% (ARR 0.48%; RR 0.51; 95% CI 0.47-0.55; < .0001). Clotted samples reduced from 0.24% to 0.06% (ARR 0.18%; RR 0.24; 95% CI 0.20-0.29; < .0001). Non-intimation of critical values decreased from 2.63% to 2.18% (RR 0.83; 95% CI 0.70-0.99; = .065).ConclusionIntegrating FMEA with Sigma metrics provides a robust framework for identifying, prioritizing, and reducing laboratory errors. Continuous monitoring and corrective action are essential to sustain improvements in laboratory quality and patient safety.
van Driel MHE, Han A, Grünhagen DJ
… +1 more, Ramakers C
Ann Clin Biochem
· 2026 Feb · PMID 41628938
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ObjectivesTo evaluate the stability of commonly used biomarkers in whole blood under various storage conditions, in order to assess their suitability for home-based blood collection in remote care settings.MethodsWhole b...ObjectivesTo evaluate the stability of commonly used biomarkers in whole blood under various storage conditions, in order to assess their suitability for home-based blood collection in remote care settings.MethodsWhole blood samples were stored at 4-8°C, 20-25°C and 37°C for up to 72 h. Six pooled samples and two healthy volunteer samples were aliquoted and analysed at four time points (T0, T24, T48 and T72 h). A panel of 47 routine chemistry and immunochemistry biomarkers was measured in all samples. Recoveries relative to T0 were compared to within subject coefficients of variation of the individual biomarkers.ResultsMost biomarkers remained stable at refrigerated and room temperature conditions up to 72 h with a subset of biomarkers, mostly proteins and tumour markers also showing good to acceptable stability at 37°C. Several biomarkers, including potassium, inorganic phosphate and iron, consistently fell outside acceptable limits under multiple conditions. Others, such as sodium, calcium, ferritin, aspartate aminotransferase and cytokeratin fragment 21-1, were unstable only at 37°C. A few transient deviations were observed, but these were not consistent over time.ConclusionsHome-based blood sampling is feasible for a broad range of biomarkers, provided that heat exposure during transport is minimised. These findings are a first step in the further validation of selected analytes under real-world, capillary blood sampling conditions.
Koyano K, Arioka M, Noguchi Y
… +14 more, Shinabe Y, Kusaka T, Morita H, Nishioka K, Nakao Y, Inoue K, Morimoto A, Nakamura S, Kondo S, Konishi Y, Yasuda S, Okada H, Hirao K, Kusaka T
Ann Clin Biochem
· 2026 Feb · PMID 41628917
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BackgroundConventional transcutaneous bilirubinometers often underestimate total bilirubin (TB) levels at high concentrations, limiting their clinical utility in cases of neonatal hyperbilirubinemia. We aimed to address...BackgroundConventional transcutaneous bilirubinometers often underestimate total bilirubin (TB) levels at high concentrations, limiting their clinical utility in cases of neonatal hyperbilirubinemia. We aimed to address this shortcoming by developing and testing a novel type of advanced transcutaneous bilirubinometer that may enhance the early identification of severe hyperbilirubinemia, potentially reducing the need for invasive testing and exchange transfusions.MethodsWe developed a novel transcutaneous bilirubinometer with adjustable light intensity and detection distances. Transcutaneous bilirubin (TcB) measurements were obtained using both the novel device and a conventional JM-105 bilirubinometer in 66 instances in 62 neonates (≥36 weeks gestation). TB values measured in patient blood samples were used as reference values for calculating correlations and error metrics (i.e. mean squared error [MSE] and mean absolute error [MAE]).ResultsThe novel device showed strong correlation with TB values across all concentrations (R = 0.96), including those ≥15 mg/dL (R = 0.84), outperforming the JM-105 device (R = 0.60 for TBs ≥15 mg/dL). The novel device also yielded lower MSE (1.53 vs 2.95) and MAE values (1.00 vs 1.39) than the JM-105.ConclusionsOur novel transcutaneous bilirubinometer demonstrated improved accuracy at higher bilirubin concentrations compared with a conventional JM-105 device.
Ann Clin Biochem
· 2025 Dec · PMID 41399291
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BackgroundThe foetal anomaly screening (FAS) programme in England screens for trisomies 21, 18 and 13 using a combination of maternal age and biochemical and ultrasound markers in a multivariate Gaussian approach to calc...BackgroundThe foetal anomaly screening (FAS) programme in England screens for trisomies 21, 18 and 13 using a combination of maternal age and biochemical and ultrasound markers in a multivariate Gaussian approach to calculate the chance of a foetal trisomy. The screened population is divided into higher and lower chance categories using a 1 in 150 cut-off. A truncation of 1 in 5000 is used for the lowest chance results.A series of postal strikes resulted in delay to specimen delivery and necessitated rebleeding of hundreds of affected clients across England. The effect of delay in processing specimens was investigated based on the final chance reported, rather than the effect on the individual biomarkers used in the chance calculation.MethodsThe FAS chances from samples delayed in postal strikes were compared against those from repeat samples from the same patients to determine the absolute effect on the final chance reported rather than the individual biomarkers.ResultsA total of 119 of 120 chances reported remained in the same high/low chance category.ConclusionMarker concentrations are affected by delayed separation, but the effect on calculated chance is only significant in those close to the 1 in 150 cut-off. There is little benefit in rebleeding clients at very low chance or at very high chance as this leads to a delayed result and the possibility of missed screening for some affected pregnancies.
BackgroundThis study aimed to identify laboratory parameters that could optimize the PLASMIC score, thereby improving its diagnostic accuracy for thrombotic thrombocytopenic purpura (TTP).MethodsWe performed a retrospect...BackgroundThis study aimed to identify laboratory parameters that could optimize the PLASMIC score, thereby improving its diagnostic accuracy for thrombotic thrombocytopenic purpura (TTP).MethodsWe performed a retrospective analysis of 136 patients with suspected TTP who had available ADAMTS-13 activity measurements. Patients were stratified into two groups based on ADAMTS-13 activity: a TTP group (n = 49) and a non-TTP group (n = 87). Routine laboratory parameters-including hemoglobin (HGB), red blood cell distribution width-standard deviation (RDW-SD), mean corpuscular volume (MCV), platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBIL), indirect bilirubin (IBIL), lactate dehydrogenase (LDH), creatinine (CR), urea (UREA), international normalized ratio (INR), and D-dimer-were compared between groups. Statistically significant parameters were selected as candidate variables to refine the PLASMIC score. The diagnostic performance of the modified model was evaluated using receiver operating characteristic (ROC) curve analysis.ResultsSix parameters-HGB, PLT, ALT, RDW-SD, IBIL, and LDH-demonstrated significant differences between TTP and non-TTP patients. Multivariate logistic regression identified RDW-SD, PLT, and LDH as independent predictors of TTP. Based on these findings, we revised the PLASMIC score by substituting MCV with RDW-SD. The modified model exhibited a higher area under the curve (AUC) (0.907 vs 0.817) while maintaining sensitivity (95.9%) and improving specificity (70.1% vs 65.9%) compared to the original.ConclusionThe modified PLASMIC score model may improve diagnostic accuracy for TTP in similar patient populations, but requires external validation in diverse cohorts to confirm its broader utility.
ObjectivesAcidification of urine samples has long been used as a method of preservation to enhance analyte stability. However, there are inherent safety risks to staff and patients when acid preservatives are used. The A...ObjectivesAcidification of urine samples has long been used as a method of preservation to enhance analyte stability. However, there are inherent safety risks to staff and patients when acid preservatives are used. The Association of Laboratory Medicine National Audit Committee sought to assess urine acidification practices in NHS laboratories.MethodAn 11 question survey was sent to all Association of Laboratory Medicine members for completion between 24th January 2023 and 24th February 2023 and data analysis performed using Microsoft Excel. For a variety of analytes, laboratories were asked to detail the type of recommended and accepted collection containers, whether 24 h and/or spot urine samples were accepted, if preservative was added to samples on receipt if not collected with preservative and the storage conditions for unpreserved samples.Results69 laboratories responded. Safety information was provided to users by the majority of laboratories and 88% of laboratories would pH test samples prior to sending them to a referral laboratory if acidification was a prerequisite. Variation was noted in quoted time of sample stability when refrigerated. Laboratories provided answers about specific tests - sodium, potassium, osmolality, calcium, magnesium, phosphate, creatinine, Bence Jones protein, total protein, urate, citrate, oxalate, cysteine, catecholamines, metanephrines, 5-HIAA, VMA/HMMA, copper, amino acids, organics acids and glycosaminoglycans.ConclusionsThere is significant variation in the use of acid as a preservative for urine samples throughout NHS laboratories as well as historical requirements for urine acidification for certain analytes which evidence has indicated is no longer a requirement.
BackgroundPhosphatidylethanol (PEth) is formed in erythrocyte membranes after alcohol consumption. When abstaining, the PEth level falls with a rate proportional to its concentration, and a short apparent PEth half-life...BackgroundPhosphatidylethanol (PEth) is formed in erythrocyte membranes after alcohol consumption. When abstaining, the PEth level falls with a rate proportional to its concentration, and a short apparent PEth half-life supports abstinence. We here derive algorithms for calculating unbiased half-lives and confidence intervals (CIs).MethodsPEth was measured using Acquity UPC2-MS/MS systems in clinical blood samples from out-patients. We identified 6989 individuals having taken two or more PEth samples within 28 days. One measurement pair was randomly selected from everyone. We derived methods for and calculated PEth half-lives and corresponding 95% CIs for exact, rounded, and truncated data, on closed form, Monte Carlo methods and No-U-turn sampling.ResultsThe peak of the PEth half-life was at 8.62 days. Peak PEth half-life was 8.72 days for men and 8.47 days for women ( = 0.028) and on age: 8.55 days for age 18-39 years, 8.56 for age 40-59 years and 8.87 for 60+ years ( = 0.026). PEth concentration did not significantly affect half-life. CIs on a closed form performed excellently on exact data, with misclassification of abstinence for 16 out of 6989 observations (0.23%). When rounding or truncating data, misclassification occurred using Monte Carlo methods in 104 (1.5%) and 127 (1.8%) of the observations and using closed form algorithms in 855 (12.2%) and 777 (11.1%).ConclusionUnbiased PEth half-lives and CIs can be calculated and put into use in laboratory information systems. Rounding or truncating data used for PEth half-life calculation widened CIs with misinterpretations of alcohol abstinence.
Jacobi NF, Ciceri A, de Oliveira LE
… +8 more, Tioda I, Kaefer M, de Oliveira SA, Pasqualoto LB, Rossato BG, Moresco RN, Paniz C, de Carvalho JAM
Ann Clin Biochem
· 2025 Nov · PMID 41247850
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BackgroundCystatin C (CysC) is a biomarker used to assess kidney function. Produced by all nucleated cells, it is freely filtered by the glomeruli, and its serum levels increase rapidly following kidney injury. Establish...BackgroundCystatin C (CysC) is a biomarker used to assess kidney function. Produced by all nucleated cells, it is freely filtered by the glomeruli, and its serum levels increase rapidly following kidney injury. Establishing reference intervals (RIs) is fundamental for the clinical application of CysC, as these parameters vary with geographic region and ethnic origin. This study aimed to determine RIs for CysC in healthy children aged 5-11 years from public schools in Santa Maria, southern Brazil.MethodsWe enrolled 134 healthy children (aged 5-11 years, both sexes). Cystatin C levels were measured via immunoturbidimetry, and RIs were defined by the 2.5th and 97.5th percentiles.ResultsThe RI for serum CysC was 0.59 to 1.10 mg/L. Sex-specific analysis revealed CysC RIs of 0.53-1.10 mg/L for females and 0.61-1.10 mg/L for males.ConclusionsThese findings provide valuable insights for paediatric clinical decision-making in a previously unstudied population and underscore the need for further research to validate and refine the clinical applications of CysC in paediatrics.
Lundgren M, Ridefelt P, Svensson MK
… +3 more, Hagström E, Cars T, Larsson A
Ann Clin Biochem
· 2026 Jul · PMID 41247830
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BackgroundMeasurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF) are used in diagnosing heart failure (HF). The main aim was to explore the correlation between...BackgroundMeasurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF) are used in diagnosing heart failure (HF). The main aim was to explore the correlation between NT-proBNP and LVEF.MethodsPatient data for 14,962 patients were extracted from medical records and national registries and compiled in the Swedish DEMONSTRATE database. HF phenotype was categorized according to LVEF level: HF with reduced EF (≤40%, HFrEF); HF with mildly reduced EF (41-49%, HFmrEF); HF with preserved EF (≥50%, HFpEF). Spearman's rank was employed for correlation analysis and ROC curves for discrimination and classification.ResultsNT-proBNP correlated negatively with LVEF level (r = -0.40) and positively with age (r = 0.49), creatinine (r = 0.35), and cystatin C (r = 0.53). Individuals with an HF diagnosis were more likely to have higher NT-proBNP levels compared to those without. The association between NT-proBNP and LVEF remained statistically significant ( < .0001) also after adjusting for age and kidney function estimates (r = -0.20). NT-proBNP discriminated well between HFrEF (AUC = 0.80) and HFpEF (AUC = 0.78). In discriminating the presence of an HF diagnosis, NT-proBNP (AUC = 0.81) outperformed LVEF (AUC = 0.75). However, on an individual level the correlation between LVEF and NT-proBNP was modest.ConclusionsNT-proBNP levels increase when LVEF deteriorates but with large inter-individual differences. Further research is needed, but these findings show potential in optimizing the use of LVEF with the aid of sequential analysis of NT-proBNP as a complementary diagnostic and prognostic tool to enhance assessment of cardiac function.
BackgroundPoint of care (POC) tests may improve accessibility and reduce costs of blood tests including in prostate cancer. The Man Van project was a pilot designed to address health inequalities that affect prostate can...BackgroundPoint of care (POC) tests may improve accessibility and reduce costs of blood tests including in prostate cancer. The Man Van project was a pilot designed to address health inequalities that affect prostate cancer with novel community-based targeting of high-risk groups on a mobile clinical unit.MethodsThe i-CHROMA-II™ POC machine is a quantitative assay for the measurement of total prostate specific antigen (PSA) from capillary blood using fluorescence immunoassay technology. Laboratory based Serum PSA testing was compared with capillary blood POC testing using the i-CHROMA-II™ to determine its accuracy and impact on clinical decision making on the Man Van.Results28 men participated. The median age was 53 years (range 45-74). One POC test result was invalid. Nine POCT samples gave a result of <0.5 μg/L and were not included in the analysis. Of the remaining results (N = 18) the median PSA was 1.97 μg/L (range 0.54-31.22 μg/L). Using Lin's Concordance Correlation Coefficient of Absolute Agreement gave a value of 0.392 (N = 17). A Bland-Altman plot showed a mean difference of 0.377 μg/L.ConclusionsWe report the first testing of PSA using the i-Chroma-II™ machine, and the first real-world mobile testing using any POC PSA test. Our study did not show correlation between the laboratory and i-Chroma-II™, although it did replicate the positive bias seen in previous studies. Further testing and refinement of POC tests may help to achieve the goal to developing reliable POC PSA tests.
Shorten RJ, Sanders A, Farley M
… +5 more, Josse S, Shafiq S, Harris C, Clegg A, Hill J
Ann Clin Biochem
· 2026 May · PMID 41174983
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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 (N...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 (COe) 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.
Araki T, Nagai T, Miyata S
… +2 more, Tani Y, Satake M
Ann Clin Biochem
· 2026 May · PMID 41145238
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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...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.
Crossley E, Silversides JA, O'Kane CM
… +1 more, Hamilton PK
Ann Clin Biochem
· 2026 Jul · PMID 41145237
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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 clea...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.
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...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. 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. Patients with strongly elevated HbA1c levels (110-180 mmol/mol) showed significantly reduced HbA2 levels compared with controls (2.0% vs. 2.4%, <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. 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.
Ann Clin Biochem
· 2026 May · PMID 41038712
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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 chrom...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.