Annals of Clinical Biochemistry最新文献

BackgroundThe diagnosis of cystic fibrosis (CF) is challenging due to high quantity not sufficient (QNS) rates of sweat tests, leading to frequent retesting, increasing costs and adverse impacts on patient care. This study aimed to assess sweat test performance and implement a quality improvement project (QIP) to reduce QNS rates.MethodsA two-part retrospective audit was conducted. Part one spanned 2 years reviewing the two-tiered testing with sweat conductivity as a screening tool, followed by chloride testing. Part two evaluated the QNS rates over two 6-month periods, separated by a QIP, which involved technologist training, clinician education, patient preparation protocols and revised testing procedures.ResultsOver the 2-year period, 425 sweat tests were performed on 291 patients. Sweat conductivity testing demonstrated a lower QNS rate, 13% (31/238), compared to sweat chloride testing's 31% (33/105). High QNS rates were observed in younger infants and in malnourished or acutely ill patients. Post-QIP, the QNS rates for the total study population decreased by 5%, from an initial 30% to 25% in the sweat chloride cohort, while the acceptable QNS rate of 12% remained unchanged in the sweat conductivity cohort.ConclusionAchieving target QNS rates remains challenging, especially in younger infants, with improved QNS rates in older infants and children. Recommendations include limiting sweat testing to experienced technologists and ensuring patient readiness.

BackgroundCurrent coeliac disease (CD) NICE guidelines recommend testing IgA-endomysial antibodies (EMA) following a weak-positive IgA-tissue transglutaminase antibody (tTGA). Outside of patients with very high IgA-tTGA results, a positive IgA-EMA necessitates duodenal biopsy to confirm CD diagnosis, meaning a positive IgA-EMA does not alter the diagnostic pathway. Therefore, to be helpful, a negative IgA-EMA needs to reliably exclude CD.ObjectivesWe aimed to evaluate the negative predictive value (NPV) of IgA-EMA, following a weak-positive/positive IgA-tTGA, and to evaluate whether IgA-EMA result (positive or negative) affects duodenal biopsy rates.MethodsRetrospective patient cohort (n = 963) study of patients with IgA-EMA and IgA-tTGA testing, with or without evidence of duodenal biopsy. The NPV of IgA-EMA was assessed by comparison to duodenal biopsy. Duodenal biopsy rates were compared between patients with a positive/negative IgA-EMA (after positive/weak-positive IgA-tTGA).ResultsThe NPVs for CD of a negative IgA-EMA, in the context of a weak-positive or positive IgA-tTGA, were 41% and 0%, respectively (n = 45). There was a significant reduction in the proportion of patients who had a duodenal biopsy with a negative IgA-EMA (9.4%) compared to patients with a positive IgA-EMA (28.5%), following a positive/weak-positive IgA-tTGA (n = 963).ConclusionIgA-EMA does not reliably exclude CD following a positive/weak-positive IgA-tTGA result. Our data indicates that clinicians are utilizing a negative IgA-EMA, following a positive/weak-positive IgA-tTGA result, to inappropriately exclude CD. We recommend IgA-EMA be exclusively used in the context of a 'non-biopsy' approach to CD diagnosis, following a high positive IgA-tTGA, and that a negative IgA-EMA result should not be used to exclude CD in the context of a weak-positive/positive IgA-tTGA.

Background and objectivesSERPINA4 has been identified as a potential diagnostic biomarker for diabetic nephropathy (DN) in our previous research. This study aims to develop electrochemiluminescence immunoassay (ECLIA) methods for the detection of SERPINA4 and to establish a diagnostic model that incorporates additional indicators for DN.Materials and methodsAntibodies utilized in the ECLIA for the detection of SERPINA4 were labelled with ruthenium and biotin, respectively. The reliability of ECLIA was evaluated based on its linear range, precision, and hook effect. A total of 28 indicators were collected from 98 patients, including SERPINA4/UCr, diabetic retinopathy (DR), and duration of diabetes mellitus. A diagnostic model was developed employing Random Forest, Support Vector Machine (SVM), and Naive Bayes algorithms. The performance of the model was assessed using metrics such as area under the curve (AUC), precision, recall, and F1 score; ultimately selecting the best-performing model for final diagnosis.ResultThe ECLIA method established in this study for urinary SERPINA4 demonstrates a linearity range from 7.5 ng/mL to 16,000 ng/mL, with within-run precision (CV%) values of 0.25% and 3.78%. The diagnostic model developed using random forest exhibits optimal performance, achieving an AUC of 0.89, accuracy of 90%, sensitivity of 100%, and specificity of 70%. The top five variables ranked by importance are serum creatinine, microalbumin, SERPINA4/UCr ratio, systolic blood pressure, and total urine protein.ConclusionA method for the detection of urinary SERPINA4 using ECLIA has been successfully established. The combination of SERPINA4/UCr with other clinical indicators demonstrated strong performance in the diagnostic model developed through the random forest algorithm.

BackgroundThe six sigma model is widely used in laboratory quality management. For the first time, this study introduced total allowable error (TEa) from WS/T403-2024 and 'desirable' biological variation (BV) as dual quality goals to evaluate serum lipid analytes in six laboratories and develop individualized quality control (QC) strategies.MethodsWe collected internal quality control (IQC) and external quality assessment (EQA) data to calculate sigma values for each serum lipid analyte. Normalized sigma method decision charts were employed, and the Westgard sigma rule flow chart with batch size plus the quality goal index (QGI) guided individualized QC strategies and improvement plans.ResultsUnder the same quality goal, different QC concentrations produced varying sigma values. Sigma values also differed significantly between the two quality goals. When WS/T403-2024 was applied, all analytes except triglycerides (TGs) showed lower sigma values than under 'desirable' BV. Normalized sigma method decision charts effectively highlighted these differences. Based on the Westgard sigma rule flow chart with batch size and QGI, individualized QC strategies were created, and priority improvement measures were proposed for analytes with sigma values below six.ConclusionsThe six sigma model is a valuable tool for laboratory quality management, guiding laboratories to enhance the detection capabilities of serum lipid analytes through targeted QC strategies and improvement measures.

BackgroundModern analyzers employ the haemolysis index (HI) to identify interference in biochemical assays, yet manufacturer-defined HI thresholds may be inappropriate for true haemolysis effects, resulting in unnecessary sample rejections. This study aimed to validate these thresholds using non-simulated hemolyzed patient samples.MethodsPaired samples (hemolyzed primary and non-hemolyzed recollected) from 678 patients were analysed for haemolysis interference. Biochemical analytes and serum indices were measured using a Roche Cobas^® 8000 analyzer. Haemolysis effects on test results and lipaemia index (LI) were assessed. HI thresholds were derived from reference change value (RCV) limits and regression of HI versus percentage bias, then compared to the conventional 10% deviation criterion and Roche-defined cut-offs.ResultsSamples exhibited predominantly moderate haemolysis (72.3%, HI: 101-300). Strong HI correlations were observed for lactate dehydrogenase (51% change per 100-unit HI, R² = 0.6524, P < .0001), potassium (14% per 100-unit HI, R² = 0.5630, P < .0001), and sodium (-0.6% per 100-unit HI, R² = 0.5414, P < .0001). Elevated biases exceeded the RCV for these analytes, plus ammonia, aspartate aminotransferase, creatine kinase, γ-glutamyltransferase, and bilirubin-direct, whereas sodium showed a clinically significant reduction at heavy haemolysis (HI 560). RCV-derived thresholds exhibited comparable or higher than 10% change and Roche cut-offs. The elevated LI in hemolyzed samples with HI greater than 100 decreased significantly after recollection.ConclusionsPatient-based haemolysis data indicated that biases for most analytes remain within clinically acceptable limits, suggesting the manufacturer's HI thresholds may overestimate interference, supporting lab-validated, RCV-based cut-offs enhance clinical relevance and decrease unnecessary sample rejection.

BackgroundDyslipidemia is a lifestyle-related disease; therefore, cholesterol biosynthesis inhibitors in foods can be easily ingested on a daily basis and are effective in aiding treatment and prevention. To assess the impact of this diet on health, it is of the essential thing that food intake can be properly measured, and it is important to find biomarkers of food intake. Previously, we reported that ergosterol, which is present in mushrooms, inhibits cholesterol biosynthesis. In this study, we measured serum ergosterol levels in healthy participants who consumed maitake mushroom bread to confirm actual ingestion of maitake mushrooms.MethodsSerum samples from healthy participants who consumed maitake mushroom bread (n = 24) or normal bread without maitake mushroom (placebo, n = 26) were analysed for ergosterol levels using liquid chromatography-tandem mass spectrometry with diene derivatization.ResultsIn the placebo group, there was no significant difference in ergosterol concentrations between baseline (before consumption) and 18 weeks. In contrast, the ergosterol concentration was 5-fold higher at 18 weeks than at baseline in the maitake mushroom bread-intake group.ConclusionMaitake mushroom bread intake for 18 weeks significantly increased serum ergosterol levels in healthy participants, suggesting that ergosterol is useful as a biomarker of mushroom intake.

BackgroundTo assess utility of novel biomarkers in diagnosing children with clinical cobalamin deficiency. Current practice uses total vitamin B12 levels to confirm diagnosis, which lacks sensitivity when used in isolation.MethodsBetween November 2020 and September 2022, a prospective cross-sectional study was carried out in a tertiary teaching hospital. Children between 1 month and 18 years with clinical symptoms/at-risk of developing B12 deficiency were included. Relevant clinical and laboratory information (including total B12 and biomarker levels) was documented. Sensitivity and specificity of individual biomarkers were assessed using 4cB12, an indicator of functional B12 status. Version 4.2.1 of R language was used for statistical analysis.ResultsAnalysis was performed on 67 children. Anorexia, fatigue and behavioural abnormalities were among the leading clinical characteristics. 49% children had peripheral smear (PS) suggestive of cobalamin deficiency, and 43% had low total B12 levels. Among biomarkers, 85% children had low holotranscobalamin (HoloTC), and 73% and 55% had high methylmalonic acid (MMA) and elevated homocysteine (Hcy) levels, respectively. Sensitivity of total B12 was 51%, HoloTC 87%, MMA 83% and Hcy 64%. Combination of low HoloTC, macrocytosis and abnormal PS had 94% sensitivity while HoloTC with mean corpuscular volume (MCV) alone was 88% sensitive in detecting cobalamin deficiency.ConclusionLow total B12 levels lack sensitivity to diagnose cobalamin deficiency. Although combination of low HoloTC with abnormal smear and macrocytosis was found to have better sensitivity, reporting an abnormal smear is time consuming and requires skilled personnel. Combination of low HoloTC with macrocytosis has good sensitivity and can be considered a better screening tool for detecting B12 deficiency.

BackgroundThis study aimed to evaluate the early diagnostic value of C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), neutrophil ratio (NEUT%), and neutrophil-to-lymphocyte ratio (NLR) in patients with deep sternal wound infection (DSWI).MethodsA retrospective case-control study was conducted on 241 patients who underwent cardiac surgery (30 patients with DSWI and 211 patients without DSWI). The differences in inflammatory markers were compared between the two groups at 5 time points (days 1, 4, 7, 10, and 14 after cardiac surgery), and the optimal cut-off values of the inflammatory factors independently correlated with DSWI were determined.ResultsUnivariate and multivariate logistic regression analyses showed that CRP on days 10 and 14, and PCT on day 10, were independently correlated with the occurrence of DSWI. The ROC curve showed the optimal cut-off value of them (CRP on day 10: AUC = 0.786, optimal cut-off point = 170.205 mg/L, sensitivity = 50.0%, specificity = 95.7%; CRP on day 14: AUC = 0.800, optimal cut-off point = 64.36 mg/L, sensitivity = 83.3%, specificity = 70.1%; PCT on day 10: AUC = 0.728, optimal cut-off point = 2.359 ng/mL, sensitivity = 43.3%, specificity = 97.6%). There was no correlation between WBC, NEUT%, NLR, and the occurrence of DSWI.ConclusionsFor patients who underwent sternotomy, CRP levels from the 10th postoperative day were correlated with the occurrence of DSWI. Early diagnosis of DSWI using CRP may be effective and can be used as a focused indicator to detect the presence of DSWI in patients as early as possible.

BackgroundWe previously reported that salivary testosterone (Sal T) decreased following a morning meal but concluded that this decrease could be a postprandial effect or an inherent circadian rhythm or both. Since no studies describing diurnal variations in Sal T have considered the effect of meals, we investigated the temporal variation of Sal T independent of food consumption.MethodsSalivary samples were collected from 17 males at 09.00 h, 10.00 h, and 11.00 h and then at 22.00 h, 23.00 h, and 24.00 h following an 8 h fast for each collection period.ResultsMean (standard deviation) Sal T concentrations were 191.2 (56.68) pmol/L at 09.00 h, 174.2 (53.29) pmol/L at 10.00 h, 168.1 (52.61) pmol/L at 11.00, 120.2 (46.04) pmol/L at 22.00 h, 130.3 (35.72) pmol/L at 23.00 h and 125.1 (29.75) pmol/L at 24.00 h. Sal T at 09.00 h was higher (P < .05) than at all other time points. Sal T at 10.00 h was similar (P = .65) to that at 11.00 h and both were higher (P < .05) compared to all evening time points. Although some patients exhibited a nadir in Sal T at 22:00 followed by an increase, overall evening levels were not significantly different (P > .80).ConclusionWe report an inherent circadian rhythm in Sal T with higher levels in the morning than evening and report for the first time that it is independent of food consumption.