Clinical biochemistry最新文献_第3页

KNG1 mutations (c.618 T > G and c.1165C > T) cause disruption of the Cys206-Cys218 disulfide bond and truncation of the D5 domain leading to hereditary high molecular weight kininogen deficiency KNG1突变（c.618 T > G和c.1165C > T）导致Cys206-Cys218二硫键断裂和D5结构域截断，导致遗传性高分子量激肽原缺乏。

IF 2.5 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-01-10 DOI: 10.1016/j.clinbiochem.2025.110877

Xiaoying Lv , Pingping Li , Ying Gui , Caili Qin , Shan Huang , Yunwei Qi , Huaping Chen , Fuyong Zhang

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.

背景：由kininogen-1 （KNG1）基因编码的高分子量激肽原（High molecular weight kininogen， HMWK）是一种与血液凝固、肿瘤生长和其他病理过程密切相关的多功能糖蛋白。目的：我们对一例女性子宫平滑肌肉瘤患者的临床表型、基因突变和分子发病机制进行了研究，该患者表现为HMWK缺乏和分离的活化部分凝血活素时间（APTT）延长。方法：通过APTT混合研究、内在凝血因子活性定量评估、HMWK抗原水平和血栓弹性成像进行临床表型分析。遗传分析显示KNG1基因中有一个新的突变。随后的生物信息学分析侧重于KNG1基因618和1165密码子两侧区域的进化保守性，目的是预测突变的功能影响。结果：临床表型分析显示患者HMWK抗原水平严重不足，低于正常值的1.0 %。基因测序鉴定出KNG1基因的两个突变位点：外显子5的一个新的错义突变，c.618 T > G (p.Cys206Trp)，导致Cys206和Cys218之间的二硫键断裂；外显子10的一个已知的无义突变，c.1165C > T (p.g arg389x)，导致HMWK蛋白的D5结构域截断并减少其数量。这两种突变共同影响凝血系统中HMWK的激活。结论：复合杂合突变c.618 T > G （p.Cys206Trp）和c.1165C > T （p.Arg389X）导致HMWK功能丧失，导致激肽系统缺陷，从而导致APTT显著延长。这些发现促进了对凝血因子缺乏症的理解，并为HMWK缺乏症的诊断和治疗方法提供了信息，潜在地增强了临床管理策略。

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引用次数: 0

Clinical impact of PTEN rs701848 as a predictive marker for breast cancer PTEN rs701848作为乳腺癌预测标志物的临床影响

IF 2.5 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-01-08 DOI: 10.1016/j.clinbiochem.2025.110872

Basma EL-sayed Fotouh , Mai Abd El-Meguid , Ghada Maher Salum , Ghada Nabil El naggar , Ahmed F. El-Sayed , Reham Mohammed Dawood

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.

背景：乳腺癌（Breast cancer， BC）的发病率不断上升，已成为女性最常见的恶性肿瘤。磷酸酶和紧张素同源物（PTEN）在PI3K通路中阻断PIP3的磷酸化，是一种肿瘤抑制基因。方法：采用计算生物信息学工具确定PTEN rs701848T/C基因变异与乳腺癌进展之间的关系。50名健康的对照组和100名患有乳腺癌的埃及妇女参加了这项研究。采用qRT-PCR检测PTEN rs701848T/C多态性。ELISA法检测PTEN蛋白组学水平。结果：乳腺癌患者TC基因型频率明显高于对照组，p = 0.03。此外，TC携带者有更高的机会发展为晚期肿瘤，肿瘤大小较大，并转移到其他部位。PTEN蛋白组学水平显著下降与疾病进展显著相关。此外，ROC曲线分析显示PTEN蛋白在区分不同BC分期方面具有相当的诊断准确性。结论：目前的研究提供了PTEN在基因组和蛋白质组学水平上作为BC发生和进展的预测标志物的影响。

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引用次数: 0

CXCL5 as a biomarker for early diagnosis and prognosis of sepsis: A comprehensive clinical evaluation CXCL5作为脓毒症早期诊断和预后的生物标志物的综合临床评价

IF 2.5 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-01-07 DOI: 10.1016/j.clinbiochem.2025.110878

Rui Zhao , HangBo Li , Banglao Xu , Ju Cao

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.

目的：脓毒症是一种由宿主对感染反应失调引起的危重疾病，具有很高的发病率和死亡率。及时诊断和治疗对改善患者预后至关重要。本研究探讨CXCL5在脓毒症的诊断、严重程度评估和预后中的潜在作用。设计和方法：我们纳入147例败血症患者，50例全身性炎症反应综合征（SIRS）患者和120名健康对照。记录血清CXCL5水平、炎症评分（APACHE II、SOFA）及其他实验室指标。通过单因素和多因素logistic回归分析来评估CXCL5与脓毒症诊断、严重程度和预后的关系。构建预后nomogram，并使用受试者特征曲线、校准曲线和临床决策曲线进行评估。结果：脓毒症患者血清CXCL5水平明显高于SIRS患者和健康对照组。CXCL5被确定为脓毒症诊断的危险因素。脓毒性休克患者的CXCL5水平显著升高（P = 0.04），与幸存者相比，死亡患者的CXCL5水平显著升高（P ）。结论：血清CXCL5浓度是提高脓毒症诊断准确性和预后评估的有希望的生物标志物。所构建的多变量预测模型为脓毒症的预后提供了新的认识，但其能否直接应用于临床还有待进一步的验证。

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引用次数: 0

Association of phospholipid transfer protein (PLTP) and the effect of genetic variant rs5072 on hypertriglyceridemia and atherogenic dyslipidemia in children and adolescents from Southeastern Mexico 墨西哥东南部儿童和青少年中磷脂转移蛋白（PLTP）和遗传变异rs5072对高甘油三酯血症和动脉粥样硬化性血脂异常的影响

IF 2.5 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-01-05 DOI: 10.1016/j.clinbiochem.2024.110871

Luis E. Jiménez-Martínez , Anne Santerre , Héctor Ochoa-Díaz-López , Zendy Evelyn Olivo-Vidal , Itandehui Castro-Quezada , Cesar Antonio Irecta-Nájera

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.

简介：血脂异常的特征是血液中脂质和脂蛋白水平的变化，其中磷脂转移蛋白（PLTP）有助于调节和调节高密度脂蛋白（HDL）的大小，参与胆固醇的反向运输。ApoA-1是HDL的主要蛋白质成分，某些遗传变异如rs5072与儿童高甘油三酯血症有关。本研究旨在探讨PLTP浓度与遗传变异APOA1 rs5072对墨西哥东南部儿童高甘油三酯血症和动脉粥样硬化性血脂异常（AD）的影响之间的关系。材料和方法：采用病例对照设计对墨西哥恰帕斯州和塔巴斯科州364名2 - 17岁儿童进行横断面研究。采用ELISA试剂盒检测血清样本PLTP浓度，采用TaqMan®探针检测外周血样本DNA，采用q-PCR检测基因变异。在统计分析方面，媒介比较采用学生t检验，频率采用卡方检验，相关性采用Pearson分析。软件SNPStats用于继承模型。结果：高甘油三酯血症患儿PLTP水平（8.3±6.5 ng/ml）高于对照组（6.4±4.5 ng/ml）。同样，儿童AD患者PLTP水平较高，为8.0±6 ng/ml，主要发生在10 - 17岁的高甘油三酯儿童（9.7±8.0 ng/ml）。此外，在过显性遗传模型中，遗传变异rs5072对高甘油三酯血症具有保护作用（OR = 0.61, p = 0.024）。结论：在诊断为高甘油三酯血症和AD的10至17岁儿童患者中，PLTP水平升高。基因变异rs5072对高甘油三酯血症具有保护作用。

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引用次数: 0

Validation of glucose and lactate in cerebrospinal fluid (CSF) on a Radiometer blood gas analyzer ABL90 Flex plus 在Radiometer血气分析仪ABL90 Flex plus上验证脑脊液（CSF）中的葡萄糖和乳酸。

IF 2.5 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-01-05 DOI: 10.1016/j.clinbiochem.2025.110876

Vinita Thakur , Olatunji Anthony Akerele , Edward Randell

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 against Abbott Architect C16000. 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.

目的：急诊室和重症监护病房需要快速测定脑脊液（CSF）葡萄糖和乳酸。检测结果的周转时间过长对脑膜炎等神经系统感染的及时诊断和治疗产生不利影响。方法：在血气分析仪Radiometer ABL90 Flex Plus上测定脑脊液葡萄糖和乳酸含量。使用新鲜和加标的患者脑脊液样品测定线性、定量限（LOQ）和精密度。使用54份新鲜和49份冷冻脑脊液样本与stabbottarchitectc16000进行比较。在八家使用ABL90 Flex Plus的医院进行了实验室间比较。在室温和冷藏温度下测试了这两种测试的稳定性48小时。结果比较了离心和未离心的新鲜脑脊液样品，以确定未离心样品中的颗粒是否影响分析。结果：葡萄糖和乳酸测定分别在1-45 mmol/L和0-37 mmol/L的宽分析范围内呈线性，并与常规化学实验室方法具有良好的相关性。测定脑脊液葡萄糖的LOQ为0.4 mmol/L，变异系数为14.7%；测定脑脊液乳酸的LOQ为0.2 mmol/L，变异系数为0%。重复性和再现性表明这两种测定方法的不精确性很小。葡萄糖和乳酸在室温或冷藏温度下稳定超过48小时。样品颗粒对测量没有影响。实验室间比较在葡萄糖和乳酸的总允许误差范围内。结论：良好的性能特点、小样本量和快速TAT使ABL90 Flex Plus成为脑脊液葡萄糖和乳酸盐可接受的替代分析仪。

{"title":"Validation of glucose and lactate in cerebrospinal fluid (CSF) on a Radiometer blood gas analyzer ABL90 Flex plus","authors":"Vinita Thakur , Olatunji Anthony Akerele , Edward Randell","doi":"10.1016/j.clinbiochem.2025.110876","DOIUrl":"10.1016/j.clinbiochem.2025.110876","url":null,"abstract":"<div><h3>Purpose</h3><div>Rapid determination of cerebrospinal fluid</div><div>(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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>Acceptable performance characteristics, small sample volume, and rapid TAT make ABL90 Flex Plus an acceptable alternative analyzer for CSF glucose and lactate.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110876"},"PeriodicalIF":2.5,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142945705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Amikacin therapeutic drug monitoring: Evaluation of therapy performance and analytical techniques in a developing country setting 阿米卡星治疗药物监测：发展中国家环境中治疗效果和分析技术的评价。

IF 2.5 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-01-04 DOI: 10.1016/j.clinbiochem.2025.110874

Nadine Arnold Steffens , Rodrigo Redel Petreceli , Victor Coden Azevedo , Adriana Streher França , Roberta Zilles Hahn , Amanda Pacheco Bondan , Rafael Linden , Mariele Feiffer Charão , Alexandre de Vargas Schwarzbold , Natália Brucker

Introduction

Healthcare systems face several challenges, with microbial infections being one of the main concerns. Therapeutic drug monitoring (TDM) is a strategy that has been encouraged to optimize antimicrobial regimens, particularly those with significant toxicity and narrow therapeutic indices, such as amikacin (AMK). We aimed to evaluate AMK concentrations of patients in a non-routine TDM setting and compare the performance of immunoassay and chromatography methods for routine clinical use.

Material and Methods

In this prospective study, peak (C_max) and trough (C_min) plasma samples were collected from 39 adult patients and quantified by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS/MS). Relevant clinical information was collected from medical records. AMK concentrations and clinical data were analyzed to evaluate therapy performance and influencing factors. In addition, fluorescence polarized immunoassay (FPIA) and UPLC-MS/MS were compared with Passing-Bablok regression and Bland-Altman plot analysis.

Results

AMK concentrations varied widely, with a median C_max of 41.40 µg/mL (interquartile range [IQR] 27.60 – 56.75 µg/mL) and a median C_min of 1.87 µg/mL (IQR 0.7 – 6.19 µg/mL). A high proportion of patients (83.1 %) failed to achieve the C_max therapeutic target, while 31.7 % failed to achieve the C_min therapeutic target. Overall, elderly patients and those with reduced renal function had higher C_max target attainment, while the same groups had lower C_min target attainment. The method comparison showed a mean difference of 1.54 % (limits of agreement −42.46 % to 45.54 %) in measured concentrations, with good correlation and no constant or proportional differences.

Conclusion

Many patients failed to reach the C_max target and were at risk of treatment failure, although adequate C_min was achieved more often. TDM with dose adjustments could improve AMK therapy, but further research is needed.

卫生保健系统面临着几个挑战，微生物感染是主要问题之一。治疗性药物监测（TDM）是一种被鼓励用于优化抗菌方案的策略，特别是那些具有显著毒性和狭窄治疗指标的方案，如阿米卡星（AMK）。我们的目的是评估非常规性TDM患者的AMK浓度，并比较常规临床使用的免疫测定和色谱法的性能。材料和方法：本前瞻性研究采集39例成人患者的血浆峰（Cmax）和谷（Cmin）样品，采用超高效液相色谱-质谱联用（UPLC-MS/MS）进行定量分析。从病历中收集相关临床信息。分析AMK浓度及临床资料，评价治疗效果及影响因素。此外，荧光极化免疫分析法（FPIA）和UPLC-MS/MS与pass - bablok回归和Bland-Altman图分析进行比较。结果：AMK浓度变化很大，中位Cmax为41.40µg/mL（四分位数范围[IQR] 27.60 ~ 56.75µg/mL），中位Cmin为1.87µg/mL （IQR 0.7 ~ 6.19µg/mL）。高达83.1%的患者未能达到Cmax治疗目标，31.7%的患者未能达到Cmin治疗目标。总体而言，老年患者和肾功能下降患者的Cmax目标达到率较高，而同一组的Cmin目标达到率较低。方法比较表明，测定浓度的平均差异为1.54%（一致性限为42.46% ~ 45.54%），相关性良好，无恒定或比例差异。结论：许多患者未能达到Cmax目标，存在治疗失败的风险，尽管达到足够的Cmin的情况较多。调整剂量的TDM可以改善AMK治疗，但需要进一步的研究。

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引用次数: 0

Important quality parameters for macrocomplex investigation for cardiac troponin 心肌肌钙蛋白宏观复合物研究的重要质量参数。

IF 2.5 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-01-01 DOI: 10.1016/j.clinbiochem.2024.110866

Peter A. Kavsak , Won-Shik Choi , Paul Malinowski , Wael L. Demian , Vikas Tandon , Craig Ainsworth

引用次数: 0

Enhanced detection and Characterization of M-proteins in multiple myeloma patients using An Agilent AssayMAP Bravo liquid handling system coupled to an LC-QTOF 使用安捷伦AssayMAP Bravo液体处理系统耦合LC-QTOF增强多发性骨髓瘤患者m蛋白的检测和表征

IF 2.5 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-01-01 DOI: 10.1016/j.clinbiochem.2024.110870

Matthew Nichols , Chai W. Phua , Martha L. Louzada , Benjamin D. Hedley , Vipin Bhayana , Ian Chin-Yee , Angela C. Rutledge

Background

Mass spectrometry methods are emerging as tools to detect M−proteins in the serum of multiple myeloma patients with increased sensitivity and specificity compared to traditional electrophoretic methods.

Methods

A liquid handling system, the Agilent AssayMAP Bravo, with liquid chromatography high-resolution quadrupole-time-of-flight (LC-QTOF) mass spectrometry to analyze intact light chains was compared to immunofixation electrophoresis (IFE) for M−protein analysis. 210 patient serum samples were analyzed in a split sample comparison (LC-QTOF vs. IFE). LC-QTOF and IFE were interpreted by different individuals in a blinded fashion and results were grouped into four categories: IFE+/QTOF+, IFE+/QTOF-, IFE-/QTOF+, or IFE-/QTOF-.

Results

The LC-QTOF method is able to determine the isotype of M−proteins in a similar fashion to IFE. The estimated limit of detection was ∼ 35 mg/L for adalimumab. For split patient samples, 168 were QTOF+/IFE+, 25 were QTOF-/IFE-, 14 were QTOF+/IFE-, and three were QTOF-/IFE + . Excluding the QTOF+/IFE- results due to the improved sensitivity of the LC-QTOF method, the concordance of LC-QTOF with IFE was ∼ 98 %. The LC-QTOF method also offers improved specificity compared to electrophoretic methods due to inclusion of the accurate mass of the light chains.

Conclusions

The LC-QTOF method was deemed fit for clinical use as a qualitative test with increased sensitivity and specificity compared to IFE. The LC-QTOF can also better resolve therapeutic and multiple myeloma IgG-kappa M−proteins, which present a challenge for electrophoretic methods. Future work will determine suitability of this method as an assessment of minimal residual disease status.

背景：质谱法正在成为检测多发性骨髓瘤患者血清中m蛋白的工具，与传统的电泳方法相比，其灵敏度和特异性都有所提高。方法：采用液体处理系统Agilent AssayMAP Bravo，采用液相色谱高分辨率四极杆飞行时间（LC-QTOF）质谱法分析完整轻链，与免疫固定电泳（IFE）分析m蛋白进行比较。210例患者血清样本进行了拆分样本比较（LC-QTOF vs. IFE）。LC-QTOF和IFE由不同的个体以盲法解释，结果分为四类：IFE+/QTOF+、IFE+/QTOF-、IFE-/QTOF+或IFE-/QTOF-。结果：LC-QTOF方法能够以与IFE相似的方式确定m蛋白的同型。阿达木单抗的估计检出限为 ~ 35 mg/L。对于拆分的患者样本，168例QTOF+/IFE+， 25例QTOF-/IFE-， 14例QTOF+/IFE-， 3例QTOF-/IFE + 。排除由于LC-QTOF方法灵敏度提高而导致的QTOF+/IFE-结果，LC-QTOF与IFE的一致性为 ~ 98 %。由于LC-QTOF方法包含了轻链的精确质量，因此与电泳方法相比，LC-QTOF方法还提供了更好的特异性。结论：LC-QTOF作为一种定性检测方法，与IFE相比具有更高的灵敏度和特异性，适合临床应用。LC-QTOF还可以更好地分辨治疗性和多发性骨髓瘤IgG-kappa m蛋白，这对电泳方法提出了挑战。未来的工作将确定该方法作为最小残留疾病状态评估的适用性。

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引用次数: 0

YKL-40 levels in cerebrospinal fluid serve as a diagnostic biomarker for post-neurosurgical bacterial meningitis in patients with stroke 脑脊液中YKL-40水平可作为脑卒中患者术后细菌性脑膜炎的诊断生物标志物。

IF 2.5 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-01-01 DOI: 10.1016/j.clinbiochem.2024.110864

Jingtao Wang, Xiaofeng Wang, Hongwei Cheng, Lei Ye

Introduction

Previous studies have reported that YKL-40 can serve as a biomarker of infectious diseases and different stroke types. However, evidence supporting its role in diagnosing post-neurosurgical bacterial meningitis (PNBM) remains lacking.

Methods

A total of 110 patients with stroke who underwent neurosurgical treatment were recruited. Among these, 36 were diagnosed with PNBM based on the results of bacterial culture/Gram staining or cerebrospinal fluid (CSF) characteristics. CSF levels of YKL-40 and other biomarkers with potential diagnostic utility for PNBM were statistically analysed using univariate and logistic regression models. Receiver operating characteristic (ROC) analysis was performed to investigate diagnostic efficiency.

Results

According to univariate analysis, CSF levels of glucose, total protein, white blood cells, polymorphocytes, and YKL-40, as well as the CSF-to-blood glucose ratio, were significantly different between the PNBM and non-PNBM groups. Logistic regression analysis revealed that glucose (p = 0.026), total protein (p = 0.028), and YKL-40 (p = 0.006) levels in the CSF may have independent diagnostic utility for PNBM. Among the three biomarkers, CSF-to-blood glucose (area under the receiver operating characteristic curve [AUC] 0.9208) and YKL-40 (AUC 0.9587) demonstrated strong diagnostic utility.

Conclusion

CSF levels of YKL-40, glucose, and total protein played independent roles in the diagnosis of PNBM in patients with stroke.

导言：以前的研究表明，YKL-40 可作为感染性疾病和不同类型中风的生物标记物。方法：共招募了 110 名接受神经外科治疗的脑卒中患者。其中 36 例根据细菌培养/革兰氏染色结果或脑脊液（CSF）特征被诊断为 PNBM。采用单变量和逻辑回归模型对 YKL-40 和其他具有潜在诊断作用的 PNBM 生物标志物的 CSF 水平进行了统计分析。为研究诊断效率，还进行了接收者操作特征（ROC）分析：单变量分析显示，PNBM 组和非 PNBM 组之间的葡萄糖、总蛋白、白细胞、多形性细胞和 YKL-40 的 CSF 水平以及 CSF 与血糖比值存在显著差异。逻辑回归分析显示，脑脊液中的葡萄糖（p = 0.026）、总蛋白（p = 0.028）和 YKL-40 （p = 0.006）水平可能对 PNBM 有独立的诊断作用。在这三种生物标志物中，CSF-血糖（接收者操作特征曲线下面积 [AUC] 0.9208）和 YKL-40（AUC 0.9587）具有很强的诊断效用：结论：脑脊液中的 YKL-40、葡萄糖和总蛋白水平在脑卒中患者 PNBM 的诊断中发挥着独立作用。

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引用次数: 0

Exploratory study of extracellular matrix biomarkers for non-invasive liver fibrosis staging: A machine learning approach with XGBoost and explainable AI 用于无创肝纤维化分期的细胞外基质生物标志物的探索性研究：采用XGBoost和可解释人工智能的机器学习方法。

IF 2.5 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry

Pub Date : 2025-01-01 DOI: 10.1016/j.clinbiochem.2024.110861

Valeria Carnazzo , Stefano Pignalosa , Marzia Tagliaferro , Laura Gragnani , Anna Linda Zignego , Cosimo Racco , Luigi Di Biase , Valerio Basile , Gian Ludovico Rapaccini , Riccardo Di Santo , Benedetta Niccolini , Mariapaola Marino , Marco De Spirito , Guido Gigante , Gabriele Ciasca , Umberto Basile

Background

Novel circulating markers for the non-invasive staging of chronic liver disease (CLD) are in high demand. Although underutilized, extracellular matrix (ECM) components offer significant diagnostic potential. This study evaluates ECM-related markers in hepatitis C virus (HCV)-positive patients across varying fibrosis stages.

Methods

Sixty-eight patients with mild-to-moderate fibrosis (F1-F2), sixty-six with advanced fibrosis (F3-F4), and thirty healthy donors were recruited. Inclusion criteria were detectable HCV-RNA and no other liver diseases or co-infections. Levels of ECM markers—hyaluronic acid (HA), laminin (LN), collagen-III N-peptide (PIIIP N-P), collagen-IV (C-IV)—along with cholylglycine (CG) and Golgi protein-73 (GP73), were measured in serum using the MAGLUMI 800 CLIA platform.

Results

Levels of LN, HA, C-IV, PIIIP N-P (p < 0.001), and GP73 (p < 0.01) increased from controls to F1-F2 and F3-F4. CG levels were higher in pathological subjects compared to controls (p < 0.001), but no significant differences emerged between fibrosis stages. These trends persisted after adjusting for age and sex. A multivariate ordinal regression identified LN, PIIIP N-P, and C-IV as promising markers, with an accuracy of 0.77. An XGBoost model improved accuracy to 0.87 and enhanced other metrics. SHAP analysis confirmed these variables as key contributors to the model’s predictions.

Conclusion

This study underscores the potential of ECM biomarkers, particularly LN, PIIIP N-P, and C-IV, in non-invasively staging CLD. Furthermore, our preliminary data suggest that a machine learning approach, combined with explainable AI, could further enhance diagnostic accuracy, potentially reducing the need for invasive biopsies.

背景：用于慢性肝病（CLD）无创分期的新型循环标记物需求量很大。细胞外基质（ECM）成分虽然未得到充分利用，但却具有巨大的诊断潜力。本研究评估了丙型肝炎病毒（HCV）阳性患者不同纤维化阶段的 ECM 相关标记物：招募了 68 名轻度至中度纤维化患者（F1-F2）、66 名晚期纤维化患者（F3-F4）和 30 名健康供体。纳入标准为可检测到 HCV-RNA，且无其他肝病或合并感染。使用 MAGLUMI 800 CLIA 平台测量了血清中 ECM 标记物--透明质酸 (HA)、层粘连蛋白 (LN)、胶原蛋白-III N-肽 (PIIIP N-P)、胶原蛋白-IV (C-IV)--以及胆酰甘氨酸 (CG) 和高尔基体蛋白-73 (GP73) 的水平：结果：LN、HA、C-IV、PIIIP N-P（p）的水平均有所下降：本研究强调了 ECM 生物标志物，尤其是 LN、PIIIP N-P 和 C-IV 在对 CLD 进行无创分期方面的潜力。此外，我们的初步数据表明，机器学习方法与可解释的人工智能相结合，可进一步提高诊断准确性，从而减少有创活检的需要。

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