Clinica Chimica Acta最新文献_第10页

Can pharmacogenetics inform morphine dosing in the neonatal intensive care unit? A retrospective evaluation 药物遗传学可以告知新生儿重症监护病房吗啡的剂量吗？回顾性评价。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-30 DOI: 10.1016/j.cca.2025.120814

Anastasiya Mankouski , Luca Brunelli , Gwendolyn McMillin

Acutely ill infants in the neonatal intensive care unit (NICU) present with complex medical conditions necessitating individualized therapeutic strategies. These infants exhibit significant variability in gestational age, birth weight, organ maturity and drug metabolism, increasing the risk of adverse drug reactions. Morphine is commonly prescribed in the NICU and is associated with a wide range of dosing as well as a high risk of adverse events. The objective of this retrospective study was to explore the potential relevance of pharmacogenomics to morphine dosing for our local level III NICU. Infants admitted between March and December 2022 were enrolled. Residual EDTA blood collected during routine clinical care was retrieved, and DNA was extracted for 55 patients. Targeted genotyping was performed to detect the rs1799971G > A variant of OPRM1 and the rs4680 G > A variant of COMT. Morphine dosing details were retrieved from medical records, and they were compared to genotypes. Median morphine oral equivalents per day (mg/kg) trended with OPRM1 genotype: AA, 0.0916 (n = 40); AG, 0.1500 (n = 13); GG, 0.2284 (n = 2). Median morphine oral equivalents and the number of days of treatment trended with COMT genotype: GG, 0.1429 mg/kg, 4 days (n = 17); AG, 0.1231 mg/kg, 6 days (n = 22); AA, 0.0875 mg/kg, 8 days (n = 15). Extremely premature infants required the highest morphine doses for the longest duration. Although statistical significance of these findings was not achieved, our data suggest that further studies are warranted to determine whether pharmacogenomics may be beneficial to individualize morphine dose requirements and improve outcomes for acutely ill infants in the NICU.

新生儿重症监护病房（NICU）的急性患儿目前具有复杂的医疗条件，需要个性化的治疗策略。这些婴儿在胎龄、出生体重、器官成熟度和药物代谢方面表现出显著的差异，增加了药物不良反应的风险。在新生儿重症监护室，吗啡是常用的处方药物，其剂量范围广，不良事件风险高。本回顾性研究的目的是探讨药物基因组学与我们当地III级新生儿重症监护室吗啡剂量的潜在相关性。在2022年3月至12月期间入学的婴儿被录取。收集临床常规护理中采集的EDTA残留血，提取55例患者的DNA。进行靶向基因分型检测rs1799971G > A型OPRM1变异和rs4680 G > A型COMT变异。从医疗记录中检索吗啡的剂量细节，并将其与基因型进行比较。每日吗啡口服当量中位数（mg/kg）随OPRM1基因型变化趋势：AA， 0.0916 (n = 40)；AG, 0.1500 (n = 13)；GG = 0.2284 （n = 2）。COMT基因型吗啡口服当量中位数和治疗天数趋势为：GG， 0.1429 mg/kg， 4 天（n = 17）；AG 0.1231 mg/kg， 6 天（n = 22）；AA, 0.0875 mg/kg， 8 天（n = 15）。极度早产儿需要最大剂量的吗啡，持续时间最长。虽然这些发现没有统计学意义，但我们的数据表明，需要进一步的研究来确定药物基因组学是否有利于个性化吗啡剂量需求和改善新生儿重症监护病房急性患儿的预后。

{"title":"Can pharmacogenetics inform morphine dosing in the neonatal intensive care unit? A retrospective evaluation","authors":"Anastasiya Mankouski , Luca Brunelli , Gwendolyn McMillin","doi":"10.1016/j.cca.2025.120814","DOIUrl":"10.1016/j.cca.2025.120814","url":null,"abstract":"<div><div>Acutely ill infants in the neonatal intensive care unit (NICU) present with complex medical conditions necessitating individualized therapeutic strategies. These infants exhibit significant variability in gestational age, birth weight, organ maturity and drug metabolism, increasing the risk of adverse drug reactions. Morphine is commonly prescribed in the NICU and is associated with a wide range of dosing as well as a high risk of adverse events. The objective of this retrospective study was to explore the potential relevance of pharmacogenomics to morphine dosing for our local level III NICU. Infants admitted between March and December 2022 were enrolled. Residual EDTA blood collected during routine clinical care was retrieved, and DNA was extracted for 55 patients. Targeted genotyping was performed to detect the rs1799971G > A variant of <em>OPRM1</em> and the rs4680 G > A variant of <em>COMT</em>. Morphine dosing details were retrieved from medical records, and they were compared to genotypes. Median morphine oral equivalents per day (mg/kg) trended with <em>OPRM1</em> genotype: AA, 0.0916 (<em>n</em> = 40); AG, 0.1500 (<em>n</em> = 13); GG, 0.2284 (<em>n</em> = 2). Median morphine oral equivalents and the number of days of treatment trended with <em>COMT</em> genotype: GG, 0.1429 mg/kg, 4 days (<em>n</em> = 17); AG, 0.1231 mg/kg, 6 days (<em>n</em> = 22); AA, 0.0875 mg/kg, 8 days (<em>n</em> = 15). Extremely premature infants required the highest morphine doses for the longest duration. Although statistical significance of these findings was not achieved, our data suggest that further studies are warranted to determine whether pharmacogenomics may be beneficial to individualize morphine dose requirements and improve outcomes for acutely ill infants in the NICU.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120814"},"PeriodicalIF":2.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888544","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

Liposomal nano-formulations: advancement in lung cancer treatment 脂质体纳米制剂：肺癌治疗的进展。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-30 DOI: 10.1016/j.cca.2025.120813

Azzalfa Ashraf , Qurat ul Ain , Asmaa Qamar , Amina Nisar , Shumaila Arshad , Mulazim Hussain Asim , Hafiz Muhammad Irfan

According to the WHO statistical report of 2022, lung cancer has the highest cancer mortality rate with 1.8 million deaths annually. Conventional treatment options for lung cancer include chemotherapy, surgical treatment and radiotherapy. Chemotherapy is associated with various challenges of drug resistance and toxicity. Diagnosis of lung cancer is also difficult due to the non-specific symptoms that overlap with other respiratory disorders like chronic obstructive pulmonary disease (COPD). Nano-formulations and particularly liposomes, offer a modern approach to address these issues. These lipid-based nano-carriers can be equipped with imaging agents that help to establish accurate and timely diagnosis of lung cancers. Moreover, liposomes loaded with anti-cancer drugs and genetic materials for chemotherapy and gene therapy, respectively, have shown a high success rate in cell lines studies and clinical trials. Inhaled liposome formulations such as aerosols and nebulizers are another advanced approach that has been investigated over past few years. This review article will provide a comprehensive summary of liposomes as novel drug delivery system, their preparation, methods of drug-loading, and their key role for lung cancer treatment. Moreover, a comparative analysis of liposomes with other nanocarriers to treat lung cancer is provided. Lastly, we have communicated the diverse scope of liposomal aerosols in inhalation therapy and medical devices for application in lung cancer.

根据世界卫生组织2022年的统计报告，肺癌是癌症死亡率最高的疾病，每年有180万人死亡。肺癌的常规治疗方案包括化疗、手术治疗和放射治疗。化疗伴随着各种耐药性和毒性的挑战。肺癌的诊断也很困难，因为其非特异性症状与慢性阻塞性肺疾病（COPD）等其他呼吸系统疾病重叠。纳米制剂，特别是脂质体，提供了解决这些问题的现代方法。这些基于脂质的纳米载体可以配备显像剂，帮助建立准确和及时的肺癌诊断。此外，分别装载抗癌药物和用于化疗和基因治疗的遗传物质的脂质体在细胞系研究和临床试验中显示出很高的成功率。吸入脂质体制剂，如气雾剂和雾化器是过去几年研究的另一种先进方法。本文就脂质体作为新型给药系统的研究进展、制备方法、载药方法及其在肺癌治疗中的重要作用作一综述。此外，脂质体与其他纳米载体治疗肺癌的比较分析提供。最后，我们介绍了脂质体气雾剂在吸入治疗和肺癌医疗器械中的应用范围。

{"title":"Liposomal nano-formulations: advancement in lung cancer treatment","authors":"Azzalfa Ashraf , Qurat ul Ain , Asmaa Qamar , Amina Nisar , Shumaila Arshad , Mulazim Hussain Asim , Hafiz Muhammad Irfan","doi":"10.1016/j.cca.2025.120813","DOIUrl":"10.1016/j.cca.2025.120813","url":null,"abstract":"<div><div>According to the WHO statistical report of 2022, lung cancer has the highest cancer mortality rate with 1.8 million deaths annually. Conventional treatment options for lung cancer include chemotherapy, surgical treatment and radiotherapy. Chemotherapy is associated with various challenges of drug resistance and toxicity. Diagnosis of lung cancer is also difficult due to the non-specific symptoms that overlap with other respiratory disorders like chronic obstructive pulmonary disease (COPD). Nano-formulations and particularly liposomes, offer a modern approach to address these issues. These lipid-based nano-carriers can be equipped with imaging agents that help to establish accurate and timely diagnosis of lung cancers. Moreover, liposomes loaded with anti-cancer drugs and genetic materials for chemotherapy and gene therapy, respectively, have shown a high success rate in cell lines studies and clinical trials. Inhaled liposome formulations such as aerosols and nebulizers are another advanced approach that has been investigated over past few years. This review article will provide a comprehensive summary of liposomes as novel drug delivery system, their preparation, methods of drug-loading, and their key role for lung cancer treatment. Moreover, a comparative analysis of liposomes with other nanocarriers to treat lung cancer is provided. Lastly, we have communicated the diverse scope of liposomal aerosols in inhalation therapy and medical devices for application in lung cancer.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120813"},"PeriodicalIF":2.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145888590","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

Label-free gold nanostar-based SERS with machine learning: A platform for detecting endometrial cancer-associated polyamine metabolites 基于机器学习的无标记金纳米星SERS：检测子宫内膜癌相关多胺代谢物的平台。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-29 DOI: 10.1016/j.cca.2025.120811

Biqing Chen , Zengkun Wang , Jiayin Gao, Haizhu Sun, Yinghan Zhao, Yan Liu, Jianyu Liu, Xiaohong Qiu

The occurrence and progression of endometrial cancer are closely associated with metabolic reprogramming, in which polyamine metabolites play a critical role in tumor cell proliferation and invasion. In this study, we developed a label free surface enhanced Raman scattering (SERS) detection platform based on gold nanostars (AuNS), integrated with machine learning algorithms, to achieve highly sensitive detection and precise identification of polyamine metabolites related to endometrial cancer. In complex biological matrices such as serum, the platform yielded stable and reproducible spectral fingerprints, with a detection limit at the nanogram level. Furthermore, by constructing a polyamine metabolite spectral database and introducing machine learning models, both the classification accuracy and AUC values exceeded 95 %, enabling effective discrimination of different metabolic states and mixed systems. Taken together, the AuNS SERS strategy combined with machine learning provides a rapid, non-invasive, and intelligent detection tool for the early diagnosis and metabolic subtyping of endometrial cancer, with significant clinical application potential.

子宫内膜癌的发生和发展与代谢重编程密切相关，其中多胺代谢物在肿瘤细胞增殖和侵袭中起着关键作用。在本研究中，我们开发了一种基于金纳米星（AuNS）的无标记表面增强拉曼散射（SERS）检测平台，结合机器学习算法，实现了对子宫内膜癌相关多胺代谢物的高灵敏度检测和精确鉴定。在复杂的生物基质中，如血清，该平台产生稳定且可重复的光谱指纹，检测限在纳克水平。此外，通过构建多胺代谢物光谱数据库并引入机器学习模型，分类精度和AUC值均超过95 %，能够有效区分不同代谢状态和混合系统。综上所述，AuNS SERS策略结合机器学习为子宫内膜癌的早期诊断和代谢亚型分型提供了一种快速、无创、智能的检测工具，具有重要的临床应用潜力。

{"title":"Label-free gold nanostar-based SERS with machine learning: A platform for detecting endometrial cancer-associated polyamine metabolites","authors":"Biqing Chen , Zengkun Wang , Jiayin Gao, Haizhu Sun, Yinghan Zhao, Yan Liu, Jianyu Liu, Xiaohong Qiu","doi":"10.1016/j.cca.2025.120811","DOIUrl":"10.1016/j.cca.2025.120811","url":null,"abstract":"<div><div>The occurrence and progression of endometrial cancer are closely associated with metabolic reprogramming, in which polyamine metabolites play a critical role in tumor cell proliferation and invasion. In this study, we developed a label free surface enhanced Raman scattering (SERS) detection platform based on gold nanostars (AuNS), integrated with machine learning algorithms, to achieve highly sensitive detection and precise identification of polyamine metabolites related to endometrial cancer. In complex biological matrices such as serum, the platform yielded stable and reproducible spectral fingerprints, with a detection limit at the nanogram level. Furthermore, by constructing a polyamine metabolite spectral database and introducing machine learning models, both the classification accuracy and AUC values exceeded 95 %, enabling effective discrimination of different metabolic states and mixed systems. Taken together, the AuNS SERS strategy combined with machine learning provides a rapid, non-invasive, and intelligent detection tool for the early diagnosis and metabolic subtyping of endometrial cancer, with significant clinical application potential.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120811"},"PeriodicalIF":2.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877424","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

Next-generation nano-biosensors for hepatocellular carcinoma 用于肝细胞癌的下一代纳米生物传感器。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-27 DOI: 10.1016/j.cca.2025.120805

Qamar Abuhassan , Kamel Saleh , R. Roopashree , Jaya Bhanu Kanwar , T. Sudhakar , Vipasha Sharma , Ashish Singh Chauhan , Saida Khaitova

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis and the limited sensitivity of conventional biomarkers. The emergence of nanomaterial-based biosensors offers transformative potential for precision diagnostics by integrating advanced physicochemical properties with molecular recognition strategies. This narrative review current progress in next-generation nanomaterial biosensors, including carbon nanostructures, metal–organic frameworks, quantum dots, and plasmonic nanoparticles, highlighting their roles in enhancing the sensitivity, specificity, and multiplexed detection of HCC-associated biomarkers such as alpha-fetoprotein, glypican-3, and circulating nucleic acids. We discuss innovative design principles, translational challenges, and clinical validation pathways, emphasizing how nanomaterial-enabled platforms can bridge the gap between laboratory innovation and bedside application. By critically evaluating technological advances and unmet clinical needs, this review underscores the promise of nanomaterial biosensors in enabling earlier detection, personalized monitoring, and improved prognostic assessment of HCC, ultimately advancing precision oncology.

肝细胞癌（HCC）仍然是世界范围内癌症相关死亡的主要原因，主要是由于晚期诊断和传统生物标志物的敏感性有限。基于纳米材料的生物传感器的出现通过将先进的物理化学特性与分子识别策略相结合，为精确诊断提供了变革性的潜力。本文综述了下一代纳米材料生物传感器的最新进展，包括碳纳米结构、金属有机框架、量子点和等离子体纳米粒子，强调了它们在提高hcc相关生物标志物（如甲胎蛋白、甘聚糖-3和循环核酸）的灵敏度、特异性和多路检测方面的作用。我们讨论了创新的设计原则、转化挑战和临床验证途径，强调了纳米材料平台如何弥合实验室创新和床边应用之间的差距。通过批判性地评估技术进步和未满足的临床需求，本综述强调了纳米材料生物传感器在HCC早期检测、个性化监测和改善预后评估方面的前景，最终推动了精准肿瘤学的发展。

{"title":"Next-generation nano-biosensors for hepatocellular carcinoma","authors":"Qamar Abuhassan , Kamel Saleh , R. Roopashree , Jaya Bhanu Kanwar , T. Sudhakar , Vipasha Sharma , Ashish Singh Chauhan , Saida Khaitova","doi":"10.1016/j.cca.2025.120805","DOIUrl":"10.1016/j.cca.2025.120805","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis and the limited sensitivity of conventional biomarkers. The emergence of nanomaterial-based biosensors offers transformative potential for precision diagnostics by integrating advanced physicochemical properties with molecular recognition strategies. This narrative review current progress in next-generation nanomaterial biosensors, including carbon nanostructures, metal–organic frameworks, quantum dots, and plasmonic nanoparticles, highlighting their roles in enhancing the sensitivity, specificity, and multiplexed detection of HCC-associated biomarkers such as alpha-fetoprotein, glypican-3, and circulating nucleic acids. We discuss innovative design principles, translational challenges, and clinical validation pathways, emphasizing how nanomaterial-enabled platforms can bridge the gap between laboratory innovation and bedside application. By critically evaluating technological advances and unmet clinical needs, this review underscores the promise of nanomaterial biosensors in enabling earlier detection, personalized monitoring, and improved prognostic assessment of HCC, ultimately advancing precision oncology.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120805"},"PeriodicalIF":2.9,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145854671","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

Tamm-Horsfall protein biosensors for management of nephrolithiasis Tamm-Horsfall蛋白生物传感器用于肾结石的管理。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-26 DOI: 10.1016/j.cca.2025.120810

Waleed Hassan Almalki , Imran Kazmi , Alzarea Sami I , Omar Awad Alsaidan , A. Rekha , Nadeem Sayyed , Surya Nath Pandey , Sachin Kumar Singh , Gaurav Gupta , Salem Salman Almujri

Nephrolithiasis is a common urological condition characterized by kidney stone formation and complex metabolic imbalances. Uromodulin (Tamm-Horsfall protein, THP) is the principal urinary glycoprotein and a promising risk-stratifying biomarker and long-term follow-up marker for nephrolithiasis. This review examines the dual action of THP in stone disease. The normal glycosylated form of THP can inhibit the formation of calcium oxalate crystals, whereas structurally modified or hypoglycosylated THP can promote crystal adhesion and aggregation. We provide a critical comparison between conventional immunoassays and emerging THP biosensors with respect to analytical performance, selectivity, and preanalytical requirements for the measurement of urine with reasonable reliability. Electrochemical and optical biosensors, as well as nanomaterials, are increasingly being used in biosensors, with graphene, gold nanoparticles (AuNPs), and tantalum oxide. Non-Faradaic impedance (Ta₂O₅-passivated interdigitated electrodes) has been demonstrated to detect a 0.5 ng/mL LOD in artificial urine, and printed impedance sensors and AuNP-based lateral-flow formats have a typical LOD of 25 to 80 ng/mL and have been demonstrated using minimally processed urine (e.g., centrifugation and/or dilution), instead of crude samples. Since urinary THP is usually in the mg L⁻¹ range, sub-ng/mL sensitivity cannot be understood in standard terms of detectability, but in terms of special use-cases (e.g., highly diluted samples, low-THP phenotypes, or quantitative low-end monitoring), it can be detected. In conclusion, we examined several significant limitations to translation, including biological variability (such as hydration status, infection, and circadian variations), the influence of the matrix, the lack of calibration and traceability, and the imperative for prospective clinical validation. Although microfluidics and digital presentation facilitate point-of-care tracking, the integration of AI/ML is not yet prevalent.

肾结石是一种常见的泌尿系统疾病，其特征是肾结石形成和复杂的代谢失衡。尿调蛋白（Tamm-Horsfall protein， THP）是肾结石的主要糖蛋白，也是一种有前景的风险分层生物标志物和长期随访标志物。本文综述了THP在结石疾病中的双重作用。正常糖基化形式的THP可以抑制草酸钙晶体的形成，而结构修饰或低糖基化的THP可以促进晶体的粘附和聚集。我们对传统的免疫测定法和新兴的THP生物传感器在分析性能、选择性和分析前要求方面进行了比较，并提供了合理的可靠性。电化学和光学生物传感器以及纳米材料越来越多地应用于生物传感器中，如石墨烯、金纳米颗粒（AuNPs）和氧化钽。非法拉第阻抗（ta2o5钝化的指间电极）已被证明可以检测人工尿液中0.5 ng/mL的LOD，印刷阻抗传感器和基于aunp的横向流格式的典型LOD为25至80 ng/mL，并已被证明可以使用最低限度处理的尿液（例如，离心和/或稀释），而不是原始样品。由于尿THP通常在mg L-1范围内，低于ng/mL的灵敏度不能用标准的可检测性来理解，但在特殊用例（例如，高度稀释的样品，低THP表型或定量低端监测）中，可以检测到。总之，我们研究了翻译的几个重要限制，包括生物变异性（如水合状态、感染和昼夜变化）、基质的影响、缺乏校准和可追溯性，以及前瞻性临床验证的必要性。虽然微流体和数字演示促进了护理点跟踪，但人工智能/机器学习的集成尚未普及。

{"title":"Tamm-Horsfall protein biosensors for management of nephrolithiasis","authors":"Waleed Hassan Almalki , Imran Kazmi , Alzarea Sami I , Omar Awad Alsaidan , A. Rekha , Nadeem Sayyed , Surya Nath Pandey , Sachin Kumar Singh , Gaurav Gupta , Salem Salman Almujri","doi":"10.1016/j.cca.2025.120810","DOIUrl":"10.1016/j.cca.2025.120810","url":null,"abstract":"<div><div>Nephrolithiasis is a common urological condition characterized by kidney stone formation and complex metabolic imbalances. Uromodulin (Tamm-Horsfall protein, THP) is the principal urinary glycoprotein and a promising risk-stratifying biomarker and long-term follow-up marker for nephrolithiasis. This review examines the dual action of THP in stone disease. The normal glycosylated form of THP can inhibit the formation of calcium oxalate crystals, whereas structurally modified or hypoglycosylated THP can promote crystal adhesion and aggregation. We provide a critical comparison between conventional immunoassays and emerging THP biosensors with respect to analytical performance, selectivity, and preanalytical requirements for the measurement of urine with reasonable reliability. Electrochemical and optical biosensors, as well as nanomaterials, are increasingly being used in biosensors, with graphene, gold nanoparticles (AuNPs), and tantalum oxide. Non-Faradaic impedance (Ta<sub>2</sub>O<sub>5</sub>-passivated interdigitated electrodes) has been demonstrated to detect a 0.5 ng/mL LOD in artificial urine, and printed impedance sensors and AuNP-based lateral-flow formats have a typical LOD of 25 to 80 ng/mL and have been demonstrated using minimally processed urine (e.g., centrifugation and/or dilution), instead of crude samples. Since urinary THP is usually in the mg L<sup>−1</sup> range, sub-ng/mL sensitivity cannot be understood in standard terms of detectability, but in terms of special use-cases (e.g., highly diluted samples, low-THP phenotypes, or quantitative low-end monitoring), it can be detected. In conclusion, we examined several significant limitations to translation, including biological variability (such as hydration status, infection, and circadian variations), the influence of the matrix, the lack of calibration and traceability, and the imperative for prospective clinical validation. Although microfluidics and digital presentation facilitate point-of-care tracking, the integration of AI/ML is not yet prevalent.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120810"},"PeriodicalIF":2.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849115","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

Integrating molecular diagnostics and artificial intelligence in chronic microbial disease 整合分子诊断和人工智能在慢性微生物疾病中的应用。

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-26 DOI: 10.1016/j.cca.2025.120803

Bandita Dutta, Rina Ray Ray

Chronic microbial diseases, often driven by biofilm formation, pose a persistent global health burden due to their complex diagnosis, resistance mechanisms, and prolonged disease courses. Conventional diagnostic methods are time-consuming and often insufficient for early, precise detection and prognosis. Recent advances in molecular diagnostics, including PCR, hybridization, next-generation sequencing, and CRISPR-based assays, have enabled rapid, non-invasive, and highly sensitive detection of pathogens and resistance markers. Complementary “omics” technologies, like genomics, proteomics, and metabolomics, provide deeper insights into disease pathways, aiding in personalized treatment strategies. Furthermore, the integration of artificial intelligence (AI) and big data analytics enhances the interpretation of complex molecular datasets, enabling pattern recognition, risk prediction, and tailored therapeutic decisions. This manuscript reviews current tools and emerging technologies for the diagnosis and prognosis of chronic microbial diseases, highlighting the transformative potential of AI-driven precision medicine to improve patient outcomes through early detection, individualized treatment, and better disease management.

慢性微生物疾病通常由生物膜形成驱动，由于其复杂的诊断、耐药机制和延长的病程，造成了持续的全球健康负担。传统的诊断方法耗时长，而且往往不足以进行早期、精确的检测和预后。分子诊断的最新进展，包括PCR、杂交、下一代测序和基于crispr的检测，已经能够快速、无创和高度敏感地检测病原体和耐药性标记。互补的“组学”技术，如基因组学、蛋白质组学和代谢组学，提供了对疾病途径的更深入了解，有助于个性化治疗策略。此外，人工智能（AI）和大数据分析的集成增强了对复杂分子数据集的解释，实现了模式识别、风险预测和量身定制的治疗决策。本文回顾了目前用于慢性微生物疾病诊断和预后的工具和新兴技术，强调了人工智能驱动的精准医疗的变革潜力，通过早期发现、个性化治疗和更好的疾病管理来改善患者的预后。

{"title":"Integrating molecular diagnostics and artificial intelligence in chronic microbial disease","authors":"Bandita Dutta, Rina Ray Ray","doi":"10.1016/j.cca.2025.120803","DOIUrl":"10.1016/j.cca.2025.120803","url":null,"abstract":"<div><div>Chronic microbial diseases, often driven by biofilm formation, pose a persistent global health burden due to their complex diagnosis, resistance mechanisms, and prolonged disease courses. Conventional diagnostic methods are time-consuming and often insufficient for early, precise detection and prognosis. Recent advances in molecular diagnostics, including PCR, hybridization, next-generation sequencing, and CRISPR-based assays, have enabled rapid, non-invasive, and highly sensitive detection of pathogens and resistance markers. Complementary “omics” technologies, like genomics, proteomics, and metabolomics, provide deeper insights into disease pathways, aiding in personalized treatment strategies. Furthermore, the integration of artificial intelligence (AI) and big data analytics enhances the interpretation of complex molecular datasets, enabling pattern recognition, risk prediction, and tailored therapeutic decisions. This manuscript reviews current tools and emerging technologies for the diagnosis and prognosis of chronic microbial diseases, highlighting the transformative potential of AI-driven precision medicine to improve patient outcomes through early detection, individualized treatment, and better disease management.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120803"},"PeriodicalIF":2.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848962","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

Endothelial Glycocalyx biomarkers in acute lung injury 急性肺损伤中的内皮糖萼生物标志物

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-26 DOI: 10.1016/j.cca.2025.120804

M. Arockia Babu , A. Rekha , Kavita Goyal , Soumya V. Menon , Subhashree Ray , Prerna Uniyal , Chandana Maji , Abida Khan

Endothelial glycocalyx (eGC) degradation contributes to vascular and pulmonary dysfunction in acute lung injury (ALI). This study provides a comprehensive review of the structure of the endothelial glycocalyx (eGC) and the mechanisms underlying its injury. Additionally, it evaluates biomarkers indicative of glycocalyx disruption that have been investigated for clinical use, including syndecan-1, heparan sulfate, and hyaluronan. These biomarkers have been studied in both circulating and airway compartments, with some studies reporting signal size-dependent variations in their levels. Laboratory measurement methods, specifically immunoassays and mass spectrometry, are examined with an emphasis on preanalytical variables, analytical performance, interference, and existing deficiencies in standardization, calibration, and traceability. These deficiencies contribute to the challenges in achieving comparability across different studies. Subsequently, we assessed the evidence regarding the clinical utility of risk stratification and outcome prediction in the context of ALI/ARDS and sepsis heterogeneity, focusing on cohort characteristics, sampling intervals, and sample types. In conclusion, we propose the implementation of novel glycocalyx-stabilizing treatments and future advancements, such as multi-marker panels and their integration with microvascular imaging. Generally, the standardization of protocols and establishment of reporting systems are essential prerequisites for the incorporation of these biomarkers into routine clinical laboratory and intensive care unit workflows as reliable tools.

内皮糖萼（eGC）降解有助于急性肺损伤（ALI）的血管和肺功能障碍。本研究对内皮糖萼（eGC）的结构及其损伤机制进行了全面的综述。此外，它还评估了用于临床研究的糖萼破坏的生物标志物，包括syndecan-1、硫酸肝素和透明质酸。这些生物标志物已经在循环和气道室中进行了研究，一些研究报告了其水平的信号大小依赖性变化。实验室测量方法，特别是免疫测定法和质谱法，重点是分析前变量、分析性能、干扰和标准化、校准和可追溯性方面的现有缺陷。这些缺陷导致了在不同研究之间实现可比性的挑战。随后，我们评估了在ALI/ARDS和脓毒症异质性背景下风险分层和结果预测的临床应用证据，重点关注队列特征、采样间隔和样本类型。总之，我们建议实施新的糖萼稳定治疗和未来的进展，如多标记面板及其与微血管成像的集成。一般来说，将这些生物标志物作为可靠的工具纳入常规临床实验室和重症监护病房工作流程，方案的标准化和报告系统的建立是必不可少的先决条件。

{"title":"Endothelial Glycocalyx biomarkers in acute lung injury","authors":"M. Arockia Babu , A. Rekha , Kavita Goyal , Soumya V. Menon , Subhashree Ray , Prerna Uniyal , Chandana Maji , Abida Khan","doi":"10.1016/j.cca.2025.120804","DOIUrl":"10.1016/j.cca.2025.120804","url":null,"abstract":"<div><div>Endothelial glycocalyx (eGC) degradation contributes to vascular and pulmonary dysfunction in acute lung injury (ALI). This study provides a comprehensive review of the structure of the endothelial glycocalyx (eGC) and the mechanisms underlying its injury. Additionally, it evaluates biomarkers indicative of glycocalyx disruption that have been investigated for clinical use, including syndecan-1, heparan sulfate, and hyaluronan. These biomarkers have been studied in both circulating and airway compartments, with some studies reporting signal size-dependent variations in their levels. Laboratory measurement methods, specifically immunoassays and mass spectrometry, are examined with an emphasis on preanalytical variables, analytical performance, interference, and existing deficiencies in standardization, calibration, and traceability. These deficiencies contribute to the challenges in achieving comparability across different studies. Subsequently, we assessed the evidence regarding the clinical utility of risk stratification and outcome prediction in the context of ALI/ARDS and sepsis heterogeneity, focusing on cohort characteristics, sampling intervals, and sample types. In conclusion, we propose the implementation of novel glycocalyx-stabilizing treatments and future advancements, such as multi-marker panels and their integration with microvascular imaging. Generally, the standardization of protocols and establishment of reporting systems are essential prerequisites for the incorporation of these biomarkers into routine clinical laboratory and intensive care unit workflows as reliable tools.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120804"},"PeriodicalIF":2.9,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838151","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

Plasma and cerebrospinal fluid correlation for tryptophan and its metabolites and their expression in neurodegenerative, demyelinating, infectious diseases and CNS tumors 血浆和脑脊液中色氨酸及其代谢物的相关性及其在神经退行性、脱髓鞘、传染病和中枢神经系统肿瘤中的表达

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-25 DOI: 10.1016/j.cca.2025.120807

Yuhang Deng , Fenghao Xie , Yongjie Guan , Wenqing Wu , Sumei Han , Haoqin Jiang , Ming Guan

Background

To clarify the cerebrospinal fluid (CSF) and plasma correlation for tryptophan and its major metabolites in real clinical setting, and to explore their expression across common types of neurological disorders.

Methods

181 paired CSF and plasma samples from patients with neurological diseases and 67 plasma samples from healthy controls were collected. Tryptophan, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), melatonin, and kynurenic acid (KYNA) in those samples were measured using LC-MS/MS. Age- and sex-effects on plasma levels of those analytes were evaluated in healthy control. Pearson correlation analysis was used to assess CSF and plasma correlation. Patients were grouped into neurodegenerative, demyelinating, tumors, and infectious diseases for group comparisons.

Results

CSF and plasma correlation were weak but still statistically significant for most analytes (r = 0.15–0.3, p < 0.05); but no significant correlation was observed for 5-HIAA. In healthy controls plasma tryptophan and was higher in males than in females, but 5-HIAA was higher in females. The plasma concentrations of these analytes showed no significant differences among different diseases, nor between the disease groups and the control group. However, the level of 5-HIAA were significantly lower in all disease groups compared with the control group. By contrast, CSF tryptophan and KYNA levels in patients with CNS tumors were significantly higher than in patients with other diseases.

Conclusions

Plasma tryptophan and its metabolites do not reliably reflect their CSF levels. The selective elevation of CSF tryptophan and KYNA in tumor patients may reflect tumor-associated changes in metabolism, but their biological significance requires further investigation.

背景：明确脑脊液（CSF）和血浆中色氨酸及其主要代谢物在真实临床环境中的相关性，并探讨其在常见类型神经系统疾病中的表达。方法收集181例神经系统疾病患者配对脑脊液和血浆样本，67例健康对照者血浆样本。采用LC-MS/MS检测色氨酸、血清素、5-羟基吲哚乙酸（5-HIAA）、褪黑素和犬尿酸（KYNA）含量。在健康对照中评估了年龄和性别对这些分析物血浆水平的影响。Pearson相关性分析评价脑脊液与血浆的相关性。将患者分为神经退行性疾病、脱髓鞘疾病、肿瘤疾病和感染性疾病进行组间比较。结果scsf与血浆相关性较弱，但多数分析结果仍有统计学意义（r = 0.15 ~ 0.3, p < 0.05）；但5-HIAA无显著相关性。在健康对照中，男性血浆色氨酸含量高于女性，但5-HIAA在女性中较高。这些分析物的血浆浓度在不同疾病之间没有显着差异，在疾病组和对照组之间也没有显着差异。但与对照组相比，各疾病组5-HIAA水平均显著降低。相比之下，中枢神经系统肿瘤患者脑脊液色氨酸和KYNA水平明显高于其他疾病患者。结论血浆色氨酸及其代谢物不能可靠地反映脑脊液水平。肿瘤患者脑脊液色氨酸和KYNA的选择性升高可能反映了肿瘤相关的代谢变化，但其生物学意义有待进一步研究。

{"title":"Plasma and cerebrospinal fluid correlation for tryptophan and its metabolites and their expression in neurodegenerative, demyelinating, infectious diseases and CNS tumors","authors":"Yuhang Deng , Fenghao Xie , Yongjie Guan , Wenqing Wu , Sumei Han , Haoqin Jiang , Ming Guan","doi":"10.1016/j.cca.2025.120807","DOIUrl":"10.1016/j.cca.2025.120807","url":null,"abstract":"<div><h3>Background</h3><div>To clarify the cerebrospinal fluid (CSF) and plasma correlation for tryptophan and its major metabolites in real clinical setting, and to explore their expression across common types of neurological disorders.</div></div><div><h3>Methods</h3><div>181 paired CSF and plasma samples from patients with neurological diseases and 67 plasma samples from healthy controls were collected. Tryptophan, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), melatonin, and kynurenic acid (KYNA) in those samples were measured using LC-MS/MS. Age- and sex-effects on plasma levels of those analytes were evaluated in healthy control. Pearson correlation analysis was used to assess CSF and plasma correlation. Patients were grouped into neurodegenerative, demyelinating, tumors, and infectious diseases for group comparisons.</div></div><div><h3>Results</h3><div>CSF and plasma correlation were weak but still statistically significant for most analytes (<em>r</em> = 0.15–0.3, <em>p</em> < 0.05); but no significant correlation was observed for 5-HIAA. In healthy controls plasma tryptophan and was higher in males than in females, but 5-HIAA was higher in females. The plasma concentrations of these analytes showed no significant differences among different diseases, nor between the disease groups and the control group. However, the level of 5-HIAA were significantly lower in all disease groups compared with the control group. By contrast, CSF tryptophan and KYNA levels in patients with CNS tumors were significantly higher than in patients with other diseases.</div></div><div><h3>Conclusions</h3><div>Plasma tryptophan and its metabolites do not reliably reflect their CSF levels. The selective elevation of CSF tryptophan and KYNA in tumor patients may reflect tumor-associated changes in metabolism, but their biological significance requires further investigation.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120807"},"PeriodicalIF":2.9,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838150","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

Revolutionizing salivary biomarkers through machine learning and artificial intelligence 通过机器学习和人工智能彻底改变唾液生物标志物

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-25 DOI: 10.1016/j.cca.2025.120809

Jiahui Sun , Yuqing Jia , Xiaoxuan Wang , Zhengguo Cao , Guangxun Zhu

Chronic diseases remain major global health burdens, and early detection is essential for preventing progression and reducing complications. Saliva, a non-invasive, information-rich, and easily preserved biofluid, offers a viable alternative to invasive and costly traditional screening methods such as cytopathology and tissue biopsy. Recent advances in multi-omics technologies—including proteomics, transcriptomics, genomics, metabolomics, microbiomics, and exosome profiling—have uncovered diverse salivary biomarkers linked to oral and systemic diseases. However, the high dimensionality and complexity of these datasets require robust computational methods to extract clinically meaningful patterns. Machine learning (ML), as a key component of artificial intelligence (AI), provides such analytical capability by integrating heterogeneous data and improving biomarker-based classification performance. This review summarizes studies from 2010 to 2025 on AI-enabled saliva diagnostics, outlining major biomarker categories—including proteins, nucleic acids, metabolites, exosomes, and microbial signatures and commonly used algorithms. Key performance metrics such as accuracy (ACC), area under the receiver operating characteristic curve (AUC), sensitivity (SE), and specificity (SP) are discussed, together with methodological limitations. Current evidence supports the strong potential of ML-assisted salivary biomarker analysis to enhance early disease screening. These advances may help establish saliva as an accessible tool for large-scale prevention, particularly in resource-limited or high-risk settings.

慢性病仍然是全球主要的健康负担，早期发现对于预防进展和减少并发症至关重要。唾液是一种非侵入性的、信息丰富的、易于保存的生物液体，它为侵入性和昂贵的传统筛查方法（如细胞病理学和组织活检）提供了一种可行的替代方法。多组学技术的最新进展——包括蛋白质组学、转录组学、基因组学、代谢组学、微生物组学和外泌体谱分析——已经发现了与口腔和全身疾病相关的多种唾液生物标志物。然而，这些数据集的高维性和复杂性需要强大的计算方法来提取有临床意义的模式。机器学习（ML）作为人工智能（AI）的关键组成部分，通过整合异构数据和改进基于生物标志物的分类性能来提供这种分析能力。本文综述了2010年至2025年在人工智能唾液诊断方面的研究，概述了主要的生物标志物类别，包括蛋白质、核酸、代谢物、外泌体、微生物特征和常用算法。关键性能指标，如准确性（ACC），面积下的接收者工作特征曲线（AUC），灵敏度（SE）和特异性（SP）进行了讨论，以及方法学的局限性。目前的证据支持ml辅助唾液生物标志物分析在增强早期疾病筛查方面的强大潜力。这些进展可能有助于将唾液建立为大规模预防的可获得工具，特别是在资源有限或高风险环境中。

{"title":"Revolutionizing salivary biomarkers through machine learning and artificial intelligence","authors":"Jiahui Sun , Yuqing Jia , Xiaoxuan Wang , Zhengguo Cao , Guangxun Zhu","doi":"10.1016/j.cca.2025.120809","DOIUrl":"10.1016/j.cca.2025.120809","url":null,"abstract":"<div><div>Chronic diseases remain major global health burdens, and early detection is essential for preventing progression and reducing complications. Saliva, a non-invasive, information-rich, and easily preserved biofluid, offers a viable alternative to invasive and costly traditional screening methods such as cytopathology and tissue biopsy. Recent advances in multi-omics technologies—including proteomics, transcriptomics, genomics, metabolomics, microbiomics, and exosome profiling—have uncovered diverse salivary biomarkers linked to oral and systemic diseases. However, the high dimensionality and complexity of these datasets require robust computational methods to extract clinically meaningful patterns. Machine learning (ML), as a key component of artificial intelligence (AI), provides such analytical capability by integrating heterogeneous data and improving biomarker-based classification performance. This review summarizes studies from 2010 to 2025 on AI-enabled saliva diagnostics, outlining major biomarker categories—including proteins, nucleic acids, metabolites, exosomes, and microbial signatures and commonly used algorithms. Key performance metrics such as accuracy (ACC), area under the receiver operating characteristic curve (AUC), sensitivity (SE), and specificity (SP) are discussed, together with methodological limitations. Current evidence supports the strong potential of ML-assisted salivary biomarker analysis to enhance early disease screening. These advances may help establish saliva as an accessible tool for large-scale prevention, particularly in resource-limited or high-risk settings.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120809"},"PeriodicalIF":2.9,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838152","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

Rapid, robust LC–MS/MS quantification of cefazolin in whole blood microsamples, plasma, and plasma ultrafiltrate: Analytical method validation and preliminary clinical application in pediatric population 快速、稳健的LC-MS/MS定量全血微量样品、血浆和血浆超滤液中的头孢唑林：分析方法验证及在儿科人群中的初步临床应用

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta

Pub Date : 2025-12-25 DOI: 10.1016/j.cca.2025.120808

Arkadiusz Kocur , Agnieszka Czajkowska , Mateusz Moczulski , Anna Częczek , Małgorzata Mikaszewska-Sokolewicz

Optimal dosing of cephalosporins in pediatric ICU patients is difficult due to high inter-individual variability in β-lactam pharmacokinetics, limited blood volume, and the lack of validated microsampling-compatible clinical assays. We developed and validated a rapid and reliable liquid chromatography-tandem mass spectrometry method to measure cefazolin concentrations in lithium-heparin plasma, plasma ultrafiltrate (unbound fraction), and capillary whole blood collected with volumetric absorptive microsampling (VAMS). This method was applied in a pilot cohort of pediatric patients. Samples were protein precipitated with cryo-cooled organic solvents, separated by reversed-phase liquid chromatography (reversed-phase HPLC) using a polar C18 column, and detected by multiple reaction monitoring (MRM) on a hybrid triple quadrupole-linear ion trap (QTRAP) mass spectrometer. Cefotaxime-D₃ was used as the internal standard, and calibration curves (0.5–200 mg/L) were established for each matrix. The method was validated in accordance with ICH M10 bioanalytical guidelines for selectivity, linearity, accuracy, precision, carry-over, matrix effect, recovery, process efficiency, stability, and VAMS-specific factors (hematocrit and drying time). The total run time was 3 min, including the internal standard, with an LLOQ of 0.5 mg/L across all matrices. The coefficients of determination (R²) were > 0.995, IS-normalized matrix factors were close to 1.0, and accuracy and precision were within ±15 % at all quality control levels. Cefazolin remained stable under all preanalytical conditions studied. VAMS values were unaffected by changes in hematocrit within clinically relevant ranges. The feasibility of the multi-matrix analytical method in routine practice has been demonstrated. The multi-matrix, microsampling-compatible LC-MS/MS assay described is sensitive and specific for TDM and PK/PD studies, aimed at defining precise dosing regimens for cefazolin in neonatal and pediatric critical care settings.

由于β-内酰胺药代动力学的高度个体差异、有限的血容量以及缺乏有效的微采样兼容的临床分析，儿科ICU患者头孢菌素的最佳剂量是困难的。我们开发并验证了一种快速可靠的液相色谱-串联质谱法，用于测量锂-肝素血浆、血浆超滤液（未结合部分）和毛细管全血（VAMS）中头孢唑林的浓度。该方法应用于儿科患者的试点队列。样品采用低温有机溶剂沉淀蛋白质，极性C18柱反相液相色谱（reverse -phase HPLC）分离，混合三重四极线性离子阱（QTRAP）质谱仪多重反应监测（MRM）检测。以头孢噻肟- d3为内标，建立各基质0.5 ~ 200 mg/l的标定曲线。根据ICH M10生物分析指南对该方法进行了选择性、线性、准确度、精密度、结转、基质效应、回收率、工艺效率、稳定性和vams特异性因素（红细胞压积和干燥时间）的验证。包括内标在内，总运行时间为3 min，所有基质的定量限为0.5 mg/L。测定系数（R2）为 > 0.995，is归一化矩阵因子接近1.0，各质量控制水平准确度和精密度均在±15 %以内。头孢唑林在所有分析前条件下均保持稳定。在临床相关范围内，VAMS值不受血细胞比容变化的影响。多矩阵分析法在日常实践中的可行性得到了验证。所描述的多基质、微采样兼容的LC-MS/MS分析对TDM和PK/PD研究具有敏感性和特异性，旨在确定新生儿和儿科危重护理环境中头孢唑林的精确给药方案。

{"title":"Rapid, robust LC–MS/MS quantification of cefazolin in whole blood microsamples, plasma, and plasma ultrafiltrate: Analytical method validation and preliminary clinical application in pediatric population","authors":"Arkadiusz Kocur , Agnieszka Czajkowska , Mateusz Moczulski , Anna Częczek , Małgorzata Mikaszewska-Sokolewicz","doi":"10.1016/j.cca.2025.120808","DOIUrl":"10.1016/j.cca.2025.120808","url":null,"abstract":"<div><div>Optimal dosing of cephalosporins in pediatric ICU patients is difficult due to high inter-individual variability in β-lactam pharmacokinetics, limited blood volume, and the lack of validated microsampling-compatible clinical assays. We developed and validated a rapid and reliable liquid chromatography-tandem mass spectrometry method to measure cefazolin concentrations in lithium-heparin plasma, plasma ultrafiltrate (unbound fraction), and capillary whole blood collected with volumetric absorptive microsampling (VAMS). This method was applied in a pilot cohort of pediatric patients. Samples were protein precipitated with cryo-cooled organic solvents, separated by reversed-phase liquid chromatography (reversed-phase HPLC) using a polar C18 column, and detected by multiple reaction monitoring (MRM) on a hybrid triple quadrupole-linear ion trap (QTRAP) mass spectrometer. Cefotaxime-D<sub>3</sub> was used as the internal standard, and calibration curves (0.5–200 mg/L) were established for each matrix. The method was validated in accordance with ICH M10 bioanalytical guidelines for selectivity, linearity, accuracy, precision, carry-over, matrix effect, recovery, process efficiency, stability, and VAMS-specific factors (hematocrit and drying time). The total run time was 3 min, including the internal standard, with an LLOQ of 0.5 mg/L across all matrices. The coefficients of determination (R<sup>2</sup>) were > 0.995, IS-normalized matrix factors were close to 1.0, and accuracy and precision were within ±15 % at all quality control levels. Cefazolin remained stable under all preanalytical conditions studied. VAMS values were unaffected by changes in hematocrit within clinically relevant ranges. The feasibility of the multi-matrix analytical method in routine practice has been demonstrated. The multi-matrix, microsampling-compatible LC-MS/MS assay described is sensitive and specific for TDM and PK/PD studies, aimed at defining precise dosing regimens for cefazolin in neonatal and pediatric critical care settings.</div></div>","PeriodicalId":10205,"journal":{"name":"Clinica Chimica Acta","volume":"582 ","pages":"Article 120808"},"PeriodicalIF":2.9,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846279","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