Annals of Clinical Biochemistry最新文献

Combined or mixed hyperlipidaemia is characterised by hypercholesterolaemia together with high triglyceride concentrations. It is found in approximately 1 in 100 people in the United Kingdom. Most cases are secondary to an underlying condition such as the metabolic syndrome, diabetes mellitus (especially poorly controlled) or individuals with a high alcohol intake. Mixed hyperlipidaemia is also a feature of some primary hyperlipidaemia conditions such familial combined hyperlipidaemia (FCH) or type III hyperlipidaemia (dysbetalipoproteinaemia). One differential diagnosis for mixed hyperlipidaemia that can easily be overlooked is a patient with an underlying diagnosis of familial hypercholesterolaemia (FH) who also has a hypertriglyceridaemia due to any other cause. Those patients may have very high total and low-density lipoprotein cholesterol concentrations (LDL-C) with a moderately elevated triglyceride concentration. In this article, we report 4 cases of familial hypercholesterolaemia, confirmed by genetic testing, in patients initially presenting with hypertriglyceridaemia in addition to high total cholesterol and LDL-C. This article discusses the diagnostic challenges associated with this presentation and highlights the key role of directly measuring LDL-C to aid diagnosis in these specific situations.

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune condition that primarily affects the joints and periarticular soft tissues. In the past two decades, the discovery of new biomarkers has contributed to advances in the understanding of the pathogenesis and natural history of RA. These biomarkers, including genetic, clinical, serological and imaging biomarkers, play a key role in the different stages and aspects of RA, from the so called 'pre-clinical RA', which is characterized by subclinical pathological events, such as autoimmunity and inflammation, to diagnosis (including differential diagnosis), treatment decision making and disease monitoring.This review will provide an overview on the current role of traditional and newer biomarkers in the main aspects of RA management, from the identification of individuals 'at-risk' of RA who are likely to progress to clinically evident disease, to 'early' diagnosis of RA, prognosis, precision medicine, and prediction of response to treatment.

Background: The escalating prevalence of diabetes underscores the need for precise diagnostic tools to facilitate effective management. Hemoglobin A1c (HbA1c) is a crucial biomarker for long-term glycemic control in diabetic patients. Point-of-care testing (POCT) for HbA1c offers rapid, accessible alternatives to conventional laboratory methods, but uncertainties persist regarding the accuracy and reliability of POCT assays.

Methods: This study evaluates the analytical performance of two boronate-affinity based HbA1c POCT assays, the GreenCare A1c and Cera-Stat HbA1c. Various analytical parameters including precision, linearity, comparison, and accuracy are assessed following guidelines from Clinical and Laboratory Standards Institute (CLSI), with results applied to certification criteria from the National Glycohemoglobin Standardization Program (NGSP) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Furthermore, 52 and 13 frozen EDTA whole blood samples were respectively used for additional evaluation of accuracy and interference due to Hb variants for the GreenCare A1c assay.

Results: Both GreenCare and Cera-Stat demonstrated good precision (repeatability CV% 1.5-1.9 and total imprecision CV% 1.6-2.2), linearity (R² = 0.9996 & 0.9990), and correlation (r = 0.982 & 0.978) with an established HbA1c analyzer, the Bio-Rad D100. The GreenCare also exhibited good accuracy with frozen EDTA samples with known HbA1c values. Both assays met the certification criteria from NGSP and IFCC, classifying them as "standard" according to IFCC model for quality targets for HbA1c.

Conclusions: This evaluation affirms the reliability of GreenCare and Cera-Stat POCT assays for HbA1c measurements, which can potentially reduce unnecessary referrals and enhance the overall quality of diabetes diagnosis and treatment.

Background: ML predictive models have shown their capability to improve risk prediction and assist medical decision-making, nevertheless, there is a lack of accuracy systems to early identify future rapid CKD progressors in Colombia and even in South America.

Objective: The purpose of this study was to develop a series of interpretable machine learning models that predict GFR at 6-months, 9-months, and 12-months.

Study design and setting: Over 29,000 CKD patients stage 1 to 3b (estimated GFR, <60 mL/min/1.73 m²) with an average of 3-year follow-up data were included. We used the machine learning extreme gradient boosting (XGBoost) to build three models to predict the next eGFR. Models were internally and externally validated. In addition, we included SHapley Additive exPlanation (SHAP) values to offer interpretable global and local prediction models.

Results: All models showed a good performance in development and external validation. However, the 6-months XGBoost prediction model showed the best performance in internal (MAE average = 6.07; RSME = 78.87), and in external validation (MAE average = 6.45, RSME = 18.94). The top 3 most influential features that pushed the predicted eGFR value to lower values were the interpolated values for eGFR and creatinine, and eGFR at baseline.

Conclusion: In the current study we have developed and validated machine learning models to predict the next eGFR value at different intervals. Furthermore, we attempted to approach the need for prediction explanation by offering transparent predictions.

Background: Lysophosphatidylethanolamines (lyso-PEs) are the partial hydrolysis products of phosphatidylethanolamine. Although lyso-PEs are important biomarkers in various diseases, their determination is limited by the lack of simple and efficient quantification methods. This study aims to develop an improved quantitative method for the determination of lyso-PEs and its application to an epidemiological study.

Methods: Single reaction monitoring channels by collision-induced dissociation for seven lyso-PEs were established using liquid chromatography-tandem mass spectrometry. Plasma lyso-PEs were extracted with a single-phase method using an isotopically labelled internal standard for quantification. The proposed method was adopted to define lyso-PEs in plasma samples of children aged 9-12 years living in Sapporo, Japan.

Results: The limit of detection and limit of quantification for each lyso-PE ranged between 0.001-0.015 and 0.002-0.031 pmol/μL, respectively. Recoveries were found to be > 91% for all the species. The analysis results of children's plasma showed that the total lyso-PE concentrations in boys (n = 181) and girls (n = 161) were 11.53 and 11.00 pmol/μL (median), respectively. Participants were further classified by the percentage of overweight and subgrouped as underweight (n = 12), normal range (n = 292), or overweight (n = 38). Interestingly, the reduction of lyso-PE 16:0 and increased lyso-PE 22:6 were observed in overweight children compared with normal range (Fold change: 0.909 and 1.174, respectively).

Conclusions: This study successfully established a simple quantitative method to determine lyso-PE concentrations. Furthermore, our method revealed the possible relation between plasma lyso-PEs and overweight status.

Background: Robust preanalytical and analytical processes are critical for the detection of cryoproteins. There is significant variation in practice in the detection, analysis and reporting. Results: A survey in 2018 of 137 laboratories participating in the UK National External Quality Assessment Service (UK NEQAS) (6) quality control program showed significant variation in the laboratory processes which highlighted the need for standardisation of the detection, analysis and reporting of cryoglobulins.Conclusion: The first available EQA scheme aiming to harmonise practice for cryoprotein testing has been developed by UK NEQAS and laboratories should participate in an appropriate EQA scheme to fulfil requirements for ISO accreditation.

Background: Carnitine is essential for fatty acid metabolism. Free carnitine (FCA) is excreted in the urine in the glomerulus, but is partly reabsorbed by a carnitine transporter. The mechanism underlying the decrease in serum carnitine level during pregnancy is unclear.

Objective: To investigate whether low carnitine level is associated with increased renal excretion in pregnant women.

Methods: We recruited 43 healthy pregnant and 25 non-pregnant women. Total carnitine (TCA) and FCA levels were measured using the enzymatic cycling method, and the acylcarnitine (ACA) level was calculated. Fractional excretion (FE) was calculated as carnitine clearance divided by creatinine clearance.

Results: The mean TCA, FCA, and ACA levels were lower at 12 weeks of gestation in pregnant than non-pregnant women (P < .001); the levels decreased further at 36 weeks, reaching 39%, 36%, and 52% of those in non-pregnant women, respectively (P < .001). The FEs were 3-4-fold higher in pregnant women than non-pregnant women. Pregnant women had a lower serum FCA/TCA ratio than non-pregnant women (0.788 ± 0.098 vs 0.830 ± 0.074, respectively; P < .05), whereas the urine FCA/TCA ratio was similar between the groups.

Conclusion: Low carnitine level is associated with increased renal excretion during late pregnancy.

Background: Early diagnosis of thyroid cancer is hampered by the inability of fine-needle aspiration biopsy (FNAB) to accurately classify ∼30% of cases while preoperative cancer staging detects lymph nodal involvement in only half of cases. Liquid biopsy may present an accurate, non-invasive alternative for preoperative thyroid nodule assessment. Thyrotropin receptor (TSHR) mRNA, a surrogate marker for circulating cancer cells (CTC), may be an option for early detection of malignancy from peripheral blood, but requires methodological improvements. We aimed to investigate if TSHR mRNA can be detected in low sample volumes by employing an ultrasensitive method - droplet digital PCR (ddPCR).

Methods: Less than 5 mL of blood was collected from 47 patients with thyroid nodules (25 benign and 22 malignant). RNA was isolated from the fraction of mononuclear cells where CTCs segregate. Samples were analysed for the presence of TSHR mRNA by ddPCR.

Results: Thyrotropin receptor mRNA was detectable in 4 mL sample volumes, with the test having good specificity (80%) but modest diagnostic accuracy (68.1%). Combining TSHR mRNA with ultrasound features and FNAB diagnosis, the test reaches high rule-out performances (sensitivity = 90% and NPV = 88.2%). Strikingly, TSHR mRNA correctly classified all samples with thyroid capsule invasion, lymph node metastasis and extrathyroidal extension. If aggressiveness is defined using these parameters, TSHR mRNA test reaches 100% sensitivity and 100% NPV for detecting high-risk cases.

Conclusions: Employing ddPCR for TSHR mRNA improves its measurement by enabling detection in sample volumes common for laboratory testing. The test displays high prognostic performance, showing potential in preoperative risk assessment.

Purpose: The primary goal was to estimate reference values of parathyroid hormone (PTH) in very low birth weight infants without severe neonatal morbidity. A secondary objective was to assess the relationship between PTH serum levels and selected laboratory markers of bone metabolism.

Methods: Ninety two infants with birth weight less than 1500 g met the inclusion criteria of the study. Serum levels of PTH, 25-hydroxyvitamin-D [25(OH)D], C3-epi-25(OH)D, total calcium, phosphorus, and alkaline phosphatase, and urinary levels of calcium, phosphorus, and creatinine were examined on day 14 and subsequently every 2 weeks until discharge.

Results: Of the total 167 serum samples examined for PTH levels in infants without 25(OH)D deficiency the estimated range was 0.9-11.9 pmol/l (8.5-112.3 pg/mL). During the first month, no statistically significant correlation was observed between PTH level and that of 25(OH)D, C3-epimers of 25(OH)D, S-Ca, S-P, or ALP, nor with urinary excretion of calcium and phosphorus. From the second month of life, there was a moderately significant correlation between PTH and 25(OH)D (Rho = -0.40, P =< .001), between PTH and calcium/creatinine ratio (Rho = -0.56, P = < .001), and between PTH and phosphorus/creatinine ratio (Rho = 0.51, P = < .001).

Conclusions: The physiological range for PTH levels for preterm neonates without 25(OH)D deficiency was estimated as 0.9-11.9 pmol/l (8.5-112.3 pg/mL). It seems that elevation of serum PTH above this range can be considered as hyperparathyroidism in very low birth weight infants.