Clinica Chimica Acta最新文献

Objective: This study aims to assess the predictive value of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) in colorectal liver metastasis (CRLM) patients.

Methods: A total of 507 participants were recruited for this study, comprising 162 healthy controls (HCs), 186 non-CRLM patients, and 159 CRLM patients. Serum Lp-PLA2 levels were measured across these three groups, and a CRLM prediction model was developed using machine learning (ML) algorithms in conjunction with traditional serological markers. The performance of each model was assessed using the area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, and other relevant metrics.

Results: The serum Lp-PLA2 levels in CRLM patients were significantly elevated compared to those in HCs group and the non-CRLM group (P < 0.0001). The CRLM prediction model developed using the Random forest algorithm demonstrated superior performance, incorporating six features: Lp-PLA2, ALB, GLB, ALT, LDH, and TC. This model achieved an AUC of 0.918, with a sensitivity of 0.823, specificity of 0.889, positive predictive value (PPV) of 0.861, and negative predictive value (NPV) of 0.857.

Conclusion: The Random forest model, incorporating serum Lp-PLA2 level and conventional laboratory parameters, demonstrates robust predictive capability for CRLM and holds promise for enhancing early detection in CRLM patients.

Background: It is necessary and challenging to establish reasonable and feasible total error specifications for coagulation factor assays for quality control and assessment. The aim of this study is to establish new total error specifications for coagulation factor assays by combining External Quality Assessment data with reliable biological variation data.

Methods: Data from China National External Quality Assessment Scheme (28,408 results from 1,381 laboratories) were analyzed, stratifying External Quality Assessment data by reference intervals to establish concentration-dependent total error specifications. A "state-of-the-art" total error was defined at 80% best results of the participants. Then these specifications were compared with biological variation-derived total error to determine recommended total error specifications for different concentration levels.

Results: None of the measurands could meet biological variation-derived optimum total error. Eight parameters (FII, FVIII, FX at both high and low levels; FVII and FIX at high level) reached the desirable criteria. Only FXI at low level can't met the minimum criteria.

Conclusions: The establishment of total error specifications for coagulation factor assays should be set separately according to different concentration levels and attainability of current testing technologies. Setting total error specifications should also consider clinical requirements and regulatory standards across different regions. Analyte concentration significantly influences laboratory performance, particularly for low-concentration coagulation factors. Total error specifications need updated periodically in the further.

Abbreviations: Tea, allowable total error; BV, biological variation; SOTA, state of the art; EQAS, External quality assessment schemes; ME, measurement error; RIs, reference intervals; BIVAC, Biological Variation Data Critical Appraisal Checklist; QIs, quality items; EFLM, European Federation of Clinical Chemistry and Laboratory Medicine; APS, analytical quality specifications; ISO, International Organization for Standardization; EQA, External quality assessment; PT, proficiency testing; RCPA, Royal College of Pathologists of Australasia; RfB, Reference Institute for Bioanalytics; ECAT, External Quality Control for Assays and Tests.

24-h urinary free cortisol (UFC) measurements are fundamental in the diagnosis and follow-up of Cushinǵs syndrome (CS) and immunoassays (IA) are the most widely used tests for its quantification in clinical laboratory practice. However, their suitability has been questioned mainly due to their limitations concerning analytical specificity. The aim of this research project was to evaluate a novel algorithm for CS diagnosis and follow-up in the clinical laboratory, based on the combination of IA tests with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for UFC quantification. A quantitative LC-MS/MS approach based on liquid-liquid extraction for sample preparation was developed and fully characterized. A population-based reference range was established and the level of agreement for UFC values when compared to IA approach was assessed in patients under CS follow-up or clinical suspicion for hypercortisolism. Significantly higher UFC values were observed for IA when compared to LC-MS/MS approach, therefore population-based reference range was established for the latter (i.e. 4 - 41 µg/day). The clinical application of the herein presented LC-MS/MS approach to be used as a confirmation procedure for CS management was assessed and a high level of agreement with IA UFC values, except in the case of IA undetectable results, was observed. However, IA potential false negative (FN) and false positive (FP) findings were also noted. Higher clinical sensitivity for CS diagnosis / follow-up was observed for LC-MS/MS when compared to IA, supporting the advantage and necessity of implementing LC-MS/MS as a confirmation procedure in the clinical laboratory.

Background: Citrin deficiency (CD) is an autosomal recessive metabolic disorder affecting the urea cycle and energy production. Diagnosis involves measuring ammonia and amino acid levels (eg: citrulline), with confirmation through solute carrier family 25 member 13 (SLC25A13) gene mutation analysis. Herein, we present a case report of a variant in the SLC25A13 gene that has not been previously reported in the literature.

Case report and results: The subject was a full-term Hispanic girl infant who was provisionally diagnosed with amino aciduria/urea cycle disorder with citrullinemia of unidentified type based on the second newborn screen performed at the 10th day of life. Sequence analysis and deletion/duplication testing using a panel consisting of 5 genes pertaining to citrullinemia revealed the patient carried a frameshift variant in the SLC25A13 gene (c.429_430del; pArg144fs) consistent with elevated citrulline results. The variant is not found in population databases (gnomAD). While ClinVar has only one entry for this variant (Variation ID: 1076508) and classifies it as pathogenic/likely pathogenic, no case report association exists between this variant and citrullinemia/CD or any SLC25A13-related conditions.

Conclusion: This case study expands the CD variant spectrum and describes a frameshift variant in the SLC25A13 gene in a patient linked to pathology. The finding emphasizes the importance of integrating clinical features with biochemical and genetic analysis to better understand genotype-phenotype correlations in CD and improve management strategies.

Preeclampsia (PE) is a gestational complication affecting 5% to 10% of all pregnancies. PE is characterized by hypertension and endothelial dysfunction, whose etiology involves, among other factors, alterations in the extracellular matrix (ECM) that can compromise vascular remodeling and trophoblast invasion, ie, processes essential for placental development. Endothelial dysfunction is caused by release of antiangiogenic factors, mainly a soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes two endothelial angiogenic factors, the vascular endothelial growth factor (VEGF) and placental growth factor (PLGF). This angiogenic imbalance contributes to clinical symptoms including hypertension and multisystem dysfunction. This review aims to summarize recent advances in understanding PE, particularly with altered ECM components such as heparan sulfate proteoglycans, the glycosidase heparanase, fibronectin, collagen XVIII (endostatin), and metalloproteases. This comprehensive narrative review was conducted on PubMed from 1994 to 2024, focusing on articles on the pathophysiology of PE, particularly endothelial dysfunction caused by ECM modifications. The data shows a reduced expression of matrix metalloproteinases, increased collagen fragment XVIII, and significant changes in fibronectin associated with PE. Furthermore, endothelial dysfunction was associated with increased degradation of heparan sulfate chains from proteoglycans and increased sFlt-1. Understanding these ECM modifications is crucial for developing potential new therapeutic interventions that improve maternal and fetal outcome in PE.

Atrial fibrillation (AF), the most common type of heart arrhythmia, is recognized as an independent risk factor for stroke. Fortunately, catheter ablation (CA) offers an effective treatment option for AF patients. However, numerous studies have reported suboptimal outcomes, as AF recurrence rates often remain elevated even after CA. Consequently, there exists a need for early identification of patients prone to recurrence, necessitating anti-inflammatory and/or antiarrhythmic treatment post-CA. The discovery and application of markers associated with AF recurrence could significantly aid in this early identification process. In this review, we present an overview of AF recurrence markers from three distinct perspectives (biochemical, imaging, and electrocardiographic markers).

Extracellular vesicles (EVs) are nanoscale, membrane-enclosed structures released by cells into the extracellular milieu. These vesicles encapsulate a diverse array of molecular constituents, including nucleic acids, proteins, and lipids, which provide insights into the physiological or pathological conditions of their parent cells. Despite their potential, the study of EV-derived DNA (EV-DNA) has gathered relatively limited attention. This review aims to present a thorough examination of the emerging knowledge surrounding the utility of EV-DNA as a non-invasive biomarker across a spectrum of diseases. The review delves into various mechanisms underlying DNA packaging within EVs and the prevalent methodologies employed for extraction of EV-DNA. The relevance of EV-DNA is assessed across numerous health conditions, notably cancer, cardiovascular diseases, neurodegenerative disorders, infectious diseases, and pregnancy-related complications. The use of EV-DNA for cancer mutation detection has demonstrated remarkable sensitivity and specificity, thereby enhancing both diagnostic accuracy and therapeutic monitoring. In the context of cardiovascular diseases, EV-DNA serves as a predictive marker for events such as myocardial infarctions and shows a correlation with the severity of the disease. With respect to neurodegenerative conditions, including Parkinson's and Alzheimer's, EV-DNA contributes to the understanding of disease mechanisms and progression. Additionally, it plays an essential role in modulating immune tolerance and facilitating communication between maternal and fetal systems. Although there is a pressing need for standardized protocols for EV isolation and DNA analysis to facilitate clinical implementation, the prospect of EV-DNA as a non-invasive biomarker for diagnostic and prognostic purposes across diverse pathological conditions is considerable.

Background: HbA1c levels are affected by both glycemia and erythrocyte lifespan. Erythrocyte creatine (EC) indicates mean erythrocyte age. Although EC levels differ between adolescent males and females, with higher levels in females, the mechanism remains unclear. We examined the EC and HbA1c levels in non-diabetic children.

Methods: This study included 85 children aged 3-18 years (male/female: 44/41) without diabetes or anemia. Data on EC, age, HbA1c, glycated albumin (GA), casual plasma glucose (PG), and complete blood count were measured. We examined correlation among EC, age, and HbA1c levels separately in males and females. Additionally, we compared women with and without menstruation.

Results: Age, EC, HbA1c, GA, and PG levels were comparable between the sexes. HbA1c levels were not correlated with age in either group (males: R = 0.063, p = 0.684; females: R = 0.112, p = 0.486). In males, EC levels were not correlated with age (R = 0.089, p = 0.567), but showed a negative trend with HbA1c (R = 0.281, p = 0.065). In females, EC levels were positively correlated with age (R = 0.557, p < 0.001), but not with HbA1c (R = 0.140, p = 0.383). Females with menstruation had higher EC levels (1.64 ± 0.43 µmol/g Hb) than those without menstruation (1.23 ± 0.23 µmol/g Hb, p = 0.004): however, HbA1c differences were not significant (5.44 ± 0.28 % vs, 5.41 ± 0.22 %, p = 0.771).

Conclusions: No significant correlation was observed between EC and HbA1c levels in non-diabetic and non-anemic children. However, the discrepancy between HbA1c and EC levels in relation to age in females was observed. These findings indicate that in females, but not in males, EC may be falsely elevated irrespective of erythrocyte lifespan after puberty.

Background: The complement membrane attack complex involves C5b-mediated assembly of C6-C9 polymers to form pores in cell membranes during complement activation. Inactive complexes can become soluble C5b-9 (sC5b-9) when they bind to Protein S. Elevated sC5b-9 levels are associated with increased risk of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA), a serious condition which can be improved with eculizumab therapy. Early detection of TA-TMA is essential for improving patient outcomes and optimizing the use of this costly treatment. We assessed the Quidel Microvue sC5b-9 Plus Enzyme Immunoassay on the Dynex-DS2 platform to screen for patients at risk of TA-TMA.

Methods: EDTA plasma samples were collected from bone marrow transplant (BMT) patients and others not at risk for TA-TMA. Assay validation included correlation with another laboratory, precision, linearity, and hemolysis interference. Additionally, clinical accuracy was assessed through retrospective patient data analyses.

Results: The assay showed acceptable intra- and interday precision, with less than 13 % variation. Linearity ranged from 80 to 1600 ng/mL, and there was no hemolysis interference up to 800 mg/dL. Clinical data revealed that monitoring sC5b-9 levels could detect significant increases indicative of TA-TMA, facilitating timely eculizumab intervention. Analytically, changes in sC5b-9 by 2- to 3-fold were significant for patient monitoring of TA-TMA. Lastly, a retrospective analysis on utility of the assay demonstrated effective utilization at our institution.

Conclusion: The Quidel Microvue sC5b-9 Plus Enzyme Immunoassay demonstrated good analytical and clinical performance in screening patients with increased risk of TA-TMA.