Clinical biochemistry最新文献

Introduction: Eosinophil-derived neurotoxin (EDN) is a promising biomarker for eosinophil activation during inflammatory responses. Here we evaluate the analytical performance of an automated fluorescence enzyme immunoassay for EDN in serum and explore its relationship with eosinophil counts in both healthy participants and those with eosinophilic conditions.

Materials and methods: Paired serum samples were collected from individuals for whom a complete blood count with differential was ordered. EDN was measured using the ImmunoCAP EDN Assay Kit (research use only, Phadia AB / provided by Thermo Fisher Scientific) and 40 samples were also measured using an ELISA kit (research use only, ALPCO).

Results: The analytical measurement range of the ImmunoCAP assay was 2.6-200 µg/L. The imprecision across different EDN concentrations was ≤ 7.0 %. Stability and preanalytical requirements were determined. To minimize ex vivo degranulation and false elevation of EDN levels, serum should be removed from the cell pellet immediately after centrifugation. There was strong correlation for EDN measurements between ImmunoCAP and the comparative ELISA (r = 0.974), although a significant bias was observed. A 95th percentile reference range in 180 presumed healthy adults was calculated at 101 µg/L. Overall EDN was significantly higher in serum from patients with elevated circulating eosinophil counts (median = 120.0; P < 0.0001). However, individual patients may present with discordant presentation of eosinophil counts and EDN concentration.

Conclusions: Together these results demonstrate that the ImmunoCAP EDN Assay Kit can reliably measure EDN in serum and may be useful for the evaluation of patients with conditions associated with hypereosinophilia.

Objectives: Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality globally, influenced by a complex interplay of risk factors including lipid disorders and insulin resistance (IR). The triglyceride-glucose (TyG) index and the triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio have emerged as potential indicators for assessing cardiovascular risk. This study aimed to evaluate the predictive value of hypertriglyceridemia, the TyG index, and the TG/HDL ratio for mortality and CVD occurrence within an Iranian population.

Design and methods: Conducted within the Tehran Lipid and Glucose Study over 20 years, this research analyzed 7,117 participants to assess the association between these lipid biomarkers and CVD risk and mortality. Participants were stratified by their TyG and TG/HDL indices, with Cox proportional hazards models determining risk ratios across three adjusted models considering various demographic and clinical variables.

Results: The study found significant associations between elevated triglycerides, TyG, and TG/HDL levels with increased risks of mortality and CVD during the 20-year follow-up. Specifically, the hazard ratios for CVD events were notably significant in the second triglyceride group (150-250 mg/dL), with a hazard ratio of 1.36 (1.19-1.55) in both Model 1 and Model 2, and in the third group (250-400 mg/dL), with ratios of 1.88 (1.63-2.17) in Model 1, 1.90 (1.65-2.19) in Model 2, and 1.44 (1.24-1.67) in Model 3.

Conclusion: Hypertriglyceridemia, the TyG index, and the TG/HDL ratio are easily calculable and clinically relevant markers for cardiovascular risk assessment. Their integration into routine health evaluations could facilitate early detection and management of at-risk individuals, potentially reducing the incidence and impact of CVD within the community.

Background: New diagnostic tools have emerged to assist the traditional diagnosis of malignant pleural effusion (MPE), such as high fluorescence cells (HFc) and tumor markers (TMs), determined by clinical laboratory automated pleural fluid workup. This study aimed to evaluate the diagnostic ability of the combination of HFc and TMs for diagnosing MPE.

Methods: We recruited hospitalized patients with pleural effusion at Parc Taulí University Hospital. We collected and analyzed pleural fluid and serum samples in the clinical laboratory, and we sent a sample of pleural fluid to the Pathology Department for cytology workup. We determined the pleural fluid cell count by Sysmex XN-10 and assessed TMs (CEA, CA19.9, and CA15.3) using the ECLIA Cobas e801 Roche in both pleural fluid and serum samples. We established the final MPE diagnosis based on positive cytology and/or positive pleural biopsy. We classified patients based on these final diagnoses and conducted a comparison between variables, along with multivariate logistic regression.

Results: The study included 316 pleural effusions from 221 patients recruited. Multivariate logistic regression indicated the most significant predictor variables for MPE were CA15.3 in serum, CEA ratio, and HFc. We calculated two different models: one excluding HFc and one including it, with the latter displaying superior diagnostic ability (area under the curve 0.91). This model could identify 100 % of MPE cases with 30 % specificity at low cut-offs, and higher values could help identify 60 % of MPE cases with 100 % specificity.

Conclusions: Per our findings, this model has high diagnostic performance and could serve as a swift, automated, dependable, non-invasive tool for MPE detection.

Objective: To investigate the clinical significance of fecal Syndecan-2 (SDC2) gene methylation combined with blood tumor abnormal protein (TAP) detection for the diagnosis of colorectal cancer (CRC) and its precancerous lesions.

Methods: A retrospective study was conducted to collect patients diagnosed with CRC or colorectal adenoma (Ade) from March 2020 to March 2023, and healthy people (Nor) without any gastrointestinal diseases during the same period as the control group. All participants underwent the fecal SDC2 gene methylation test, blood TAP test and fecal occult blood test (FOBT). The differences in the positivity rates of each index were compared, receiver operator characteristic curves were plotted and the area under the curve (AUC) was calculated to evaluate the diagnostic effects of different testing methods on CRC and its precancerous lesions.

Results: A total of 146 individuals were included in the study, including 69 CRC patients, 47 patients with Ade and 30 healthy individuals. The results showed that, SDC2, TAP and the combined assay had high comprehensive diagnostic efficacy for the diagnosis of CRC, but there was no significant difference between the three methods in terms of AUC, sensitivity, and specificity. However, for Ade, the combined detection was statistically significant, with a high AUC (0.905), high sensitivity (95.7%), and high specificity (86.7%).

Conclusion: Fecal SDC2 gene methylation combined with blood TAP detection is an effective noninvasive screening and diagnostic method to enhance the early detection and treatment of CRC precancerous lesions, such as Ade, thereby reducing the incidence and mortality of CRC.

Background: Acarbose is an α-glucosidase inhibitor widely used clinically for its significant hypoglycemic effect, albeit with inter-individual variations in response. The sucrase-isomaltase (SI) enzyme is the primary target of acarbose. This study aims to investigate the impact of genetic polymorphisms in the SI gene on the pharmacodynamics of acarbose.

Methods: The Illumina sequencing platform and variation-related databases were employed to analyze probable gene polymorphism sites of SI. Based on the SI polymorphism sites, Chinese subjects (n = 66) were categorized into the wild-type homozygous group (Group A) and the heterozygous variant group (Group B, SI 43 G > T). The validated hexokinase method was utilized to determine glucose concentrations in participants' serum samples. The differences in blood glucose concentration reduction and pharmacodynamic parameters peak concentration (C_max) and area under the curve (AUC_0-2h) after administering the same dose of acarbose were analyzed between the two groups of subjects.

Results: Our results showed that the mean changes in glucose C_max, AUC_0-2h, maximum increase, and maximum decrease in Group B were each lower by 67.66 %, 63.05 %, 53.17 %, and 50 % compared to Group A (all p < 0.05).

Conclusions: These data suggested that genetic polymorphism of the SI gene can significantly influence the hypoglycemic efficacy of acarbose, and the polymorphism of SI is associated with individual differences in clinical treatment outcomes.

Background: High molecular weight kininogen (HMWK), encoded by the kininogen-1 (KNG1) gene, is a multifunctional glycoprotein closely associated with the initiation of blood coagulation, tumor growth, and other pathological processes.

Objective: We conducted a study on the clinical phenotype, genetic mutations, and molecular pathogenesis of a female patient with uterine leiomyosarcoma, who presented with HMWK deficiency and an isolated prolonged activated partial thromboplastin time (APTT).

Methods: Clinical phenotyping was conducted through APTT mixing studies, quantitative assessments of intrinsic coagulation factor activities, antigen levels of HMWK, and thromboelastography. Genetic analysis revealed a novel mutation within the KNG1 gene. Subsequent bioinformatics analysis focused on the evolutionary conservation of regions flanking codons 618 and 1165 of the KNG1 gene, with an aim of predicting the mutation's functional impact.

Results: Clinical phenotypic analysis indicated a severe deficiency of HMWK antigen levels in the patient, with levels below 1.0 % of normal. Genetic sequencing identified two mutation sites in the KNG1 gene: a novel missense mutation in exon 5, c.618 T > G (p.Cys206Trp), which leads to disruption of the disulfide bond between Cys206 and Cys218, and a known nonsense mutation in exon 10, c.1165C > T (p.Arg389X), resulting in truncation of the D5 domain in the HMWK protein and reducing its quantity. These two mutations collectively impact the activation of HMWK within the coagulation system.

Conclusion: The compound heterozygous mutations, c.618 T > G (p.Cys206Trp) and c.1165C > T (p.Arg389X), result in a loss of HMWK function, leading to a deficiency in the kinin system and consequently a significant prolongation of the APTT. These findings advance understanding of coagulation factor deficiencies and inform diagnostic and therapeutic approaches for HMWK deficiency, potentially enhancing clinical management strategies.

Background: The incidence of Breast cancer (BC) is currently augmented and it has become the most common malignant cancer in females. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene as a result of blocking the phosphorylation of PIP3 in PI3K pathway.

Methods: The computational bioinformatics tools were performed to determine the link between PTEN rs701848T/C genetic variants and breast cancer progression. 50 healthy matched controls and 100 Egyptian women with breast cancer were enrolled in the study. The PTEN rs701848T/C polymorphism was assessed using qRT-PCR. Then the proteomic level of PTEN was measured by ELISA technique.

Results: Breast cancer patients had considerably higher (TC) genotype frequency than controls, p = 0.03. Moreover, TC carriers had a higher chance of developing tumors with advanced stage, big tumor size, and metastasis at further sites. Regarding proteomic level of PTEN, a remarkable decline was correlated significantly with disease progression. Moreover, the ROC curve analysis showed that the PTEN protein showed comparable diagnostic accuracy in distinguishing between different BC stages.

Conclusion: The current research provides insight into the impact of PTEN as a predictive marker for BC development and progression at genomic and proteomic levels.

Objectives: Sepsis, a critical condition caused by a dysregulated host response to infection, has high morbidity and mortality rates. Timely diagnosis and treatment are vital for improving patient outcomes. This study explores the potential role of CXCL5 in the diagnosis, severity assessment, and prognosis of sepsis.

Design and methods: We included 147 sepsis patients, 50 patients with systemic inflammatory response syndrome (SIRS) and 120 healthy controls. Serum CXCL5 levels, inflammation scores (APACHE II, SOFA), and other laboratory indicators were recorded. Univariate and multivariate logistic regression analyses were conducted to assess the relationship between CXCL5 and sepsis diagnosis, severity, and prognosis. A prognostic nomogram was constructed and evaluated using receiver operator characteristic curves, calibration curves, and clinical decision curves.

Results: Serum CXCL5 levels in sepsis patients were significantly higher than those in patients with SIRS and healthy controls. CXCL5 was identified as a risk factor for sepsis diagnosis. CXCL5 levels were significantly elevated in patients with septic shock (P = 0.04) and in deceased patients compared to survivors (P < 0.001). The prognostic model, incorporating CXCL5, lactate, APACHE II scores, C-reactive protein levels, and respiratory rate, demonstrated high predictive accuracy with an area under the curve of 0.873. Calibration and decision curve analyses demonstrated the model's good predictive performance and potential clinical value.

Conclusions: Serum CXCL5 concentration is a promising biomarker for enhancing the diagnostic accuracy and prognostic evaluation of sepsis. The constructed multivariate prediction model offers new insights into sepsis prognosis, but its direct application in clinical practice requires further validation.

Introduction: Dyslipidemia is characterized by changes in lipid and lipoprotein levels in the blood where phospholipid transfer protein (PLTP) helps to regulate and modulate the size of high-density lipoproteins (HDL), working on the reverse transport of cholesterol. ApoA-1 is the primary protein component of HDL, and certain genetic variants like rs5072, have been associated with hypertriglyceridemia in children. This study aimed to explore the association between PLTP concentrations and the effect of the genetic variant APOA1 rs5072 on hypertriglyceridemia and atherogenic dyslipidemia (AD) in the pediatric population of Southeastern Mexico.

Materials and methods: A cross-sectional study was carried out with a case-control design for 364 pediatric patients between 2 and 17 years old in Chiapas and Tabasco, Mexico. Serum samples were used to evaluate PLTP concentrations using ELISA kits, and DNA from peripheral blood samples was used to study genetic variation using q-PCR with TaqMan® probes. For statistical analysis, Student t-test for media comparison, Chi-square for frequency and Pearson analysis for correlation was performed. The software SNPStats was used for inheritance models.

Results: Children with hypertriglyceridemia had higher levels of PLTP (8.3 ± 6.5 ng/ml) than the control group (6.4 ± 4.5 ng/ml). Similarly, the pediatric patients with AD had higher PLTP levels of 8.0 ± 6 ng/ml, mainly in children with high triglycerides who were between 10 and 17 years old (9.7 ± 8.0 ng/ml). Also, it was found that the genetic variant rs5072 had a protective effect against hypertriglyceridemia (OR = 0.61, p = 0.024) in the over-dominant inheritance model.

Conclusion: PLTP levels increase in pediatric patients aged 10 to 17 years with a diagnosis of hypertriglyceridemia and AD. The genetic variant rs5072 has a protective effect in hypertriglyceridemia.

Purpose: Rapid determination of cerebrospinal fluid (CSF) glucose and lactate is required by emergency rooms and intensive care units. Long turnaround time (TAT) on test results negatively impacts timely diagnosis and treatment of neurological infections like meningitis.

Methods: The CSF glucose and lactate assays were evaluated on a blood gas analyzer, Radiometer ABL90 Flex Plus. Linearity, limit of quantitation (LOQ), and precision were determined using fresh and spiked patient CSF samples. Fifty-four fresh and 49 frozen CSF samples were used to compare the method againstAbbottArchitectC16000. An inter-laboratory comparison was done across eight hospital sites having ABL90 Flex Plus. The stability of both tests was tested for 48 h at ambient and refrigerated temperatures. Results were compared between centrifuged and uncentrifuged fresh CSF samples to determine if particulate in uncentrifuged samples impacted analysis.

Results: Glucose and lactate assays were linear over a broad analytical range of 1-45 mmol/L and 0-37 mmol/L, respectively, and demonstrated a good correlation with the routine chemistry laboratory method. LOQ was determined as 0.4 mmol/L for CSF glucose with a coefficient of variation (CV) of 14.7 % and 0.2 mmol/L with 0 % CV for CSF lactate respectively. Repeatability and reproducibility show small imprecision for both these assays. Glucose and lactate were stable for over 48 h at room or refrigeration temperatures. Sample particulates had no impact on the measurement. The inter-laboratory comparison was within total allowable error for glucose and lactate.

Conclusions: Acceptable performance characteristics, small sample volume, and rapid TAT make ABL90 Flex Plus an acceptable alternative analyzer for CSF glucose and lactate.