Pub Date : 2025-02-18DOI: 10.1016/j.clinbiochem.2025.110898
Ming-Jun Jin , En-Min Li , Li-Yan Xu
Exhaled volatile organic compounds (VOCs) are being extensively studied for the purposes of noninvasive cancer diagnoses. This systematic review and meta-analysis aims to evaluate the diagnostic accuracy of breath tests based on VOCs for cancer detection, and to propose potential cancer biomarkers. This study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Relevant studies up to February 2024 were retrieved from public databases, including PubMed, EMBASE, and Web of Science. A total of 114 articles were included, covering 125 non-duplicate studies involving 8768 cancer patients. Meta-analysis showed that the VOC breath test demonstrated a sensitivity of 87% and a specificity of 81% in cancer diagnosis, with an area under the receiver operating characteristic curve (AUC) of 0.93. Subgroup analyses based on cancer types and breath detection techniques also showed high sensitivity and specificity in diagnosing cancer patients. These suggest that breath analysis for VOCs has excellent diagnostic accuracy for cancer. The breath test based on VOCs, as a non-invasive detection method, shows great potential for cancer diagnosis.
目前正在对呼出的挥发性有机化合物（VOCs）进行广泛研究，以用于非侵入性癌症诊断。本系统综述和荟萃分析旨在评估基于挥发性有机化合物的呼气测试对癌症检测的诊断准确性，并提出潜在的癌症生物标志物。本研究根据《系统综述和荟萃分析首选报告项目》（Preferred Reporting Items for Systematic Review and Meta-Analyses，PRISMA）指南进行。从公共数据库（包括 PubMed、EMBASE 和 Web of Science）中检索了截至 2024 年 2 月的相关研究。共纳入 114 篇文章，涵盖 125 项非重复研究，涉及 8768 名癌症患者。元分析表明，VOC 呼气试验在癌症诊断中的灵敏度为 87%，特异度为 81%，接收者操作特征曲线下面积 (AUC) 为 0.93。根据癌症类型和呼气检测技术进行的分组分析也显示，该方法在诊断癌症患者方面具有很高的灵敏度和特异性。这表明，挥发性有机化合物呼气分析对癌症的诊断准确性极高。基于挥发性有机化合物的呼气检测作为一种无创检测方法，在癌症诊断方面显示出巨大的潜力。
{"title":"Diagnostic accuracy of breath tests based on volatile organic compounds for cancer: A systematic review and meta-analysis","authors":"Ming-Jun Jin , En-Min Li , Li-Yan Xu","doi":"10.1016/j.clinbiochem.2025.110898","DOIUrl":"10.1016/j.clinbiochem.2025.110898","url":null,"abstract":"<div><div>Exhaled volatile organic compounds (VOCs) are being extensively studied for the purposes of noninvasive cancer diagnoses. This systematic review and <em>meta</em>-analysis aims to evaluate the diagnostic accuracy of breath tests based on VOCs for cancer detection, and to propose potential cancer biomarkers. This study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Relevant studies up to February 2024 were retrieved from public databases, including PubMed, EMBASE, and Web of Science. A total of 114 articles were included, covering 125 non-duplicate studies involving 8768 cancer patients. Meta-analysis showed that the VOC breath test demonstrated a sensitivity of 87% and a specificity of 81% in cancer diagnosis, with an area under the receiver operating characteristic curve (AUC) of 0.93. Subgroup analyses based on cancer types and breath detection techniques also showed high sensitivity and specificity in diagnosing cancer patients. These suggest that breath analysis for VOCs has excellent diagnostic accuracy for cancer. The breath test based on VOCs, as a non-invasive detection method, shows great potential for cancer diagnosis.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110898"},"PeriodicalIF":2.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463366","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}
Pub Date : 2025-02-14DOI: 10.1016/j.clinbiochem.2025.110897
Hiroyuki Azuma , Masafumi Tada , Hideyuki Matano , Naoki Yamada , Hiroyasu Uzui , Koji Maeno , Yoshimitsu Shimada , Hiroyuki Yoshida , Hajime Murahashi , Masaki Ando , Kenta Hachiya , Shun Tanaka , Tomonori Hattori , Akira Kuriyama , Takeshi Fujisawa , Andrew R. Chapman , Nicholas L. Mills , Hiroyuki Hayashi , Norio Watanabe , Toshi A Furukawa
Background
Few studies have comprehensively examined high-sensitivity cardiac troponin I (hs-cTnI) based diagnostic pathways for myocardial infarction (MI) in early presenters using a Siemens ADVIA Centaur hs-cTnI assay.
Methods
We conducted a prospective multicenter cohort study in Emergency Departments involving 414 patients suspected of MI within 6 h of symptom onset. We evaluated three hs-cTnI-based pathways (High-STEACS, ESC 0/1-h, 0/2-h); and four pathways incorporating medical history and physical findings (ADAPT, EDACS, HEART, GRACE). We evaluated negative predictive value (NPV) and sensitivity as safety measures, and percentage ruled out as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days.
Results
Median age was 72 years (interquartile range 58–82), and 30.4 % (126/414) of patients were over 80. Females comprised 44.2 % (183/414) of patients, 87.7 % (363/414) had chest pain, and the primary outcome occurred in 9.2 % (38/414). The High-STEACS pathway ruled out 62.0 % of patients without missing a case of an MI. The ESC 0/1-h and 0/2-h pathways showed high NPV and sensitivities; however, they ruled out fewer patients (35.9 % and 45.2 %, respectively). The ADAPT, EDACS, and HEART pathways demonstrated high NPV and sensitivities but ruled out fewer patients (15–27 %). The GRACE pathway missed 2 cases with primary clinical outcomes. Among patients over 80 without MI, initial hs-cTnI concentration was ≥ 3 ng/L in 99.1 % and ≥ 5 ng/L in 84.1 %.
Conclusions
The High-STEACS pathway was the most efficient among the hs-cTnI-based pathways while maintaining excellent safety performance in early presenters.
{"title":"Accelerated diagnostic pathways for myocardial infarction using a Siemens High-Sensitivity cardiac troponin I assay","authors":"Hiroyuki Azuma , Masafumi Tada , Hideyuki Matano , Naoki Yamada , Hiroyasu Uzui , Koji Maeno , Yoshimitsu Shimada , Hiroyuki Yoshida , Hajime Murahashi , Masaki Ando , Kenta Hachiya , Shun Tanaka , Tomonori Hattori , Akira Kuriyama , Takeshi Fujisawa , Andrew R. Chapman , Nicholas L. Mills , Hiroyuki Hayashi , Norio Watanabe , Toshi A Furukawa","doi":"10.1016/j.clinbiochem.2025.110897","DOIUrl":"10.1016/j.clinbiochem.2025.110897","url":null,"abstract":"<div><h3>Background</h3><div>Few studies have comprehensively examined high-sensitivity cardiac troponin I (hs-cTnI) based diagnostic pathways for myocardial infarction (MI) in early presenters using a Siemens ADVIA Centaur hs-cTnI assay.</div></div><div><h3>Methods</h3><div>We conducted a prospective multicenter cohort study in Emergency Departments involving 414 patients suspected of MI within 6 h of symptom onset. We evaluated three hs-cTnI-based pathways (High-STEACS, ESC 0/1-h, 0/2-h); and four pathways incorporating medical history and physical findings (ADAPT, EDACS, HEART, GRACE). We evaluated negative predictive value (NPV) and sensitivity as safety measures, and percentage ruled out as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days.</div></div><div><h3>Results</h3><div>Median age was 72 years (interquartile range 58–82), and 30.4 % (126/414) of patients were over 80. Females comprised 44.2 % (183/414) of patients, 87.7 % (363/414) had chest pain, and the primary outcome occurred in 9.2 % (38/414). The High-STEACS pathway ruled out 62.0 % of patients without missing a case of an MI. The ESC 0/1-h and 0/2-h pathways showed high NPV and sensitivities; however, they ruled out fewer patients (35.9 % and 45.2 %, respectively). The ADAPT, EDACS, and HEART pathways demonstrated high NPV and sensitivities but ruled out fewer patients (15–27 %). The GRACE pathway missed 2 cases with primary clinical outcomes. Among patients over 80 without MI, initial hs-cTnI concentration was ≥ 3 ng/L in 99.1 % and ≥ 5 ng/L in 84.1 %.</div></div><div><h3>Conclusions</h3><div>The High-STEACS pathway was the most efficient among the hs-cTnI-based pathways while maintaining excellent safety performance in early presenters.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110897"},"PeriodicalIF":2.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-10DOI: 10.1016/j.clinbiochem.2025.110895
Xiao Jiang , Jun Chen , Shujun Ding , Jun Yin , Jiying Gu , Xiangming Fang
Background
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The identification of new biomarkers is crucial for enhancing early detection and treatment outcomes. This study explores the role of Canopy FGF Signaling Regulator 2 (CNPY2) in NSCLC progression and its potential as a diagnostic and prognostic biomarker.
Methods
CNPY2 expression was analyzed in 228 NSCLC tumor samples and adjacent normal tissues using quantitative RT-PCR and ELISA. Serum CNPY2 levels were also measured in 160 healthy controls and NSCLC patients. The relationship between CNPY2 expression and clinicopathological features, including epithelial-mesenchymal transition (EMT) markers, was assessed. Receiver operator curve analysis was used to evaluate the diagnostic potential of serum CNPY2, while Kaplan-Meier survival analysis assessed its prognostic significance.
Results
CNPY2 levels were significantly elevated in NSCLC tissues compared to adjacent normal tissues. Higher CNPY2 expression was associated with larger tumor size, advanced T stage, and higher N stage. Furthermore, CNPY2 expression was positively correlated with Vimentin and N-cadherin, and negatively correlated with E-cadherin. Elevated serum CNPY2 levels in NSCLC patients demonstrated moderate diagnostic accuracy, with an area under the curve of 0.78. High CNPY2 expression was also linked to reduced overall survival (p = 0.001).
Conclusions
CNPY2 is markedly overexpressed in NSCLC and is associated with increased tumor aggressiveness and EMT. Serum CNPY2 shows promise as a non-invasive biomarker for NSCLC diagnosis, and elevated expression is correlated with a poorer prognosis. Thus, CNPY2 may serve as both a valuable biomarker and a potential therapeutic target in NSCLC.
{"title":"The expression of canopy FGF signaling regulator 2 serves as a diagnostic and prognostic indicator for NSCLC","authors":"Xiao Jiang , Jun Chen , Shujun Ding , Jun Yin , Jiying Gu , Xiangming Fang","doi":"10.1016/j.clinbiochem.2025.110895","DOIUrl":"10.1016/j.clinbiochem.2025.110895","url":null,"abstract":"<div><h3>Background</h3><div>Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The identification of new biomarkers is crucial for enhancing early detection and treatment outcomes. This study explores the role of Canopy FGF Signaling Regulator 2 (CNPY2) in NSCLC progression and its potential as a diagnostic and prognostic biomarker.</div></div><div><h3>Methods</h3><div>CNPY2 expression was analyzed in 228 NSCLC tumor samples and adjacent normal tissues using quantitative RT-PCR and ELISA. Serum CNPY2 levels were also measured in 160 healthy controls and NSCLC patients. The relationship between CNPY2 expression and clinicopathological features, including epithelial-mesenchymal transition (EMT) markers, was assessed. Receiver operator curve analysis was used to evaluate the diagnostic potential of serum CNPY2, while Kaplan-Meier survival analysis assessed its prognostic significance.</div></div><div><h3>Results</h3><div>CNPY2 levels were significantly elevated in NSCLC tissues compared to adjacent normal tissues. Higher CNPY2 expression was associated with larger tumor size, advanced T stage, and higher N stage. Furthermore, CNPY2 expression was positively correlated with Vimentin and N-cadherin, and negatively correlated with E-cadherin. Elevated serum CNPY2 levels in NSCLC patients demonstrated moderate diagnostic accuracy, with an area under the curve of 0.78. High CNPY2 expression was also linked to reduced overall survival (p = 0.001).</div></div><div><h3>Conclusions</h3><div>CNPY2 is markedly overexpressed in NSCLC and is associated with increased tumor aggressiveness and EMT. Serum CNPY2 shows promise as a non-invasive biomarker for NSCLC diagnosis, and elevated expression is correlated with a poorer prognosis. Thus, CNPY2 may serve as both a valuable biomarker and a potential therapeutic target in NSCLC.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110895"},"PeriodicalIF":2.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406051","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}
Pub Date : 2025-02-05DOI: 10.1016/j.clinbiochem.2025.110894
Wenyan Jian , Dewei Guo , Ruojin Yao , Mi Pei , Manhui Guo , Fang Yang
Objectives
To investigate changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the amniotic fluid of recipient twins with twin-twin transfusion syndrome (TTTS), analyze the correlation between NT-proBNP and cardiac linear measurements, and assess the feasibility of NT-proBNP as a biochemical marker for fetal cardiac function.
Design and methods
A total of 47 pregnancies with TTTS, 21 idiopathic polyhydramnios pregnancies, and 114 normal singleton pregnancies were included from Xiangya Hospital of Central South University between October 2020 and July 2023. Fetal cardiac linear parameters, amniotic fluid depth, and NT-proBNP levels in amniotic fluid were measured across the three groups. The correlation of NT-proBNP with amniotic fluid depth, cardiac linear parameters, and CHOP score in TTTS recipients was analyzed.
Results
There was no statistically significant difference in amniotic fluid NT-proBNP levels and cardiac linear parameters between idiopathic polyhydramnios and normal singletons. However, NT-proBNP levels and cardiac parameters in TTTS recipient twins were significantly higher than in the other two groups (p < 0.05). After adjusting for gestational variables, NT-proBNP levels in TTTS recipients showed significant correlations with atrial and ventricular diameters, ventricular wall thickness, cardiothoracic ratio, and CHOP score.
Conclusions
Amniotic fluid NT-proBNP is a sensitive and objective biochemical marker for assessing fetal cardiac function, independent of amniotic fluid volume. It serves as a valuable complement to echocardiographic assessment in evaluating the severity of fetal heart failure in TTTS recipients.
{"title":"Cardiac function impairment in recipient twins of twin-to-twin transfusion syndrome: Insights from NT-proBNP levels in amniotic fluid","authors":"Wenyan Jian , Dewei Guo , Ruojin Yao , Mi Pei , Manhui Guo , Fang Yang","doi":"10.1016/j.clinbiochem.2025.110894","DOIUrl":"10.1016/j.clinbiochem.2025.110894","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the amniotic fluid of recipient twins with twin-twin transfusion syndrome (TTTS), analyze the correlation between NT-proBNP and cardiac linear measurements, and assess the feasibility of NT-proBNP as a biochemical marker for fetal cardiac function.</div></div><div><h3>Design and methods</h3><div>A total of 47 pregnancies with TTTS, 21 idiopathic polyhydramnios pregnancies, and 114 normal singleton pregnancies were included from Xiangya Hospital of Central South University between October 2020 and July 2023. Fetal cardiac linear parameters, amniotic fluid depth, and NT-proBNP levels in amniotic fluid were measured across the three groups. The correlation of NT-proBNP with amniotic fluid depth, cardiac linear parameters, and CHOP score in TTTS recipients was analyzed.</div></div><div><h3>Results</h3><div>There was no statistically significant difference in amniotic fluid NT-proBNP levels and cardiac linear parameters between idiopathic polyhydramnios and normal singletons. However, NT-proBNP levels and cardiac parameters in TTTS recipient twins were significantly higher than in the other two groups (p < 0.05). After adjusting for gestational variables, NT-proBNP levels in TTTS recipients showed significant correlations with atrial and ventricular diameters, ventricular wall thickness, cardiothoracic ratio, and CHOP score.</div></div><div><h3>Conclusions</h3><div>Amniotic fluid NT-proBNP is a sensitive and objective biochemical marker for assessing fetal cardiac function, independent of amniotic fluid volume. It serves as a valuable complement to echocardiographic assessment in evaluating the severity of fetal heart failure in TTTS recipients.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110894"},"PeriodicalIF":2.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350435","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}
Pub Date : 2025-02-04DOI: 10.1016/j.clinbiochem.2025.110893
Timothy C.R. Prickett , Lynley K. Lewis , John F. Pearson , Eric A. Espiner
Background
Natriuretic peptides (NP) have important roles in regulating fat balance and metabolic health. Reduced concentrations of ANP and BNP in plasma are associated with increased insulin resistance in obesity. Whether this is due to increased clearance or reduced bioactivity of immunoreactive NP forms is unclear.
Design and Method
These questions were addressed in a community study of mildly obese subjects at middle age. The ratio of amino-terminal (NT) pro-NP to bioactive C-terminal NP was used as a putative index of the clearance of bioactive forms.
Results
Lower ratios of amino-terminal pro-NP to bioactive C-terminal NP were associated with increased insulin resistance. In linear regression models, NT-proANP and NT-proBNP outperformed ANP and BNP in predicting insulin resistance. Pro-NP glycosylation, which can impair NP and NT-proNP production in obesity, does not account for the diminished impact of ANP or BNP. Plasma concentrations of osteocrin, which competes for the NP clearance receptor (NPR-C) and potentially enhances NP bioactivity, was not associated with NPs, but did positively predict insulin resistance in females.
Conclusions
We find no evidence that increased clearance/degradation of NPs contributes to insulin resistance. Among the nine NP variants assessed, only NT-proANP and NT-proBNP independently predicted insulin resistance in both sexes. The impact of CNP on fat mass or insulin resistance was minor but significant in females. Lower concentrations of immunoreactive plasma ANP and BNP remains unexplained and requires closer study.
{"title":"Metabolism of Natriuretic peptides and impact on insulin resistance and fat mass in healthy subjects","authors":"Timothy C.R. Prickett , Lynley K. Lewis , John F. Pearson , Eric A. Espiner","doi":"10.1016/j.clinbiochem.2025.110893","DOIUrl":"10.1016/j.clinbiochem.2025.110893","url":null,"abstract":"<div><h3>Background</h3><div>Natriuretic peptides (NP) have important roles in regulating fat balance and metabolic health. Reduced concentrations of ANP and BNP in plasma are associated with increased insulin resistance in obesity. Whether this is due to increased clearance or reduced bioactivity of immunoreactive NP forms is unclear.</div></div><div><h3>Design and Method</h3><div>These questions were addressed in a community study of mildly obese subjects at middle age. The ratio of amino-terminal (NT) pro-NP to bioactive C-terminal NP was used as a putative index of the clearance of bioactive forms.</div></div><div><h3>Results</h3><div>Lower ratios of amino-terminal pro-NP to bioactive C-terminal NP were associated with increased insulin resistance. In linear regression models, NT-proANP and NT-proBNP outperformed ANP and BNP in predicting insulin resistance. Pro-NP glycosylation, which can impair NP and NT-proNP production in obesity, does not account for the diminished impact of ANP or BNP. Plasma concentrations of osteocrin, which competes for the NP clearance receptor (NPR-C) and potentially enhances NP bioactivity, was not associated with NPs, but did positively predict insulin resistance in females.</div></div><div><h3>Conclusions</h3><div>We find no evidence that increased clearance/degradation of NPs contributes to insulin resistance. Among the nine NP variants assessed, only NT-proANP and NT-proBNP independently predicted insulin resistance in both sexes. The impact of CNP on fat mass or insulin resistance was minor but significant in females. Lower concentrations of immunoreactive plasma ANP and BNP remains unexplained and requires closer study.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110893"},"PeriodicalIF":2.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349987","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}
Pub Date : 2025-02-01DOI: 10.1016/j.clinbiochem.2025.110892
Sara Cherkaoui, Slavka Penickova , Frederic Cotton
Objective of the study
To develop a machine learning algorithm aimed at predicting the presence of a monoclonal (M-) protein when the β-globulin fraction is elevated.
Materials and method
Patients were selected as part of the University Hospital Laboratory of Brussels routine diagnostic procedures from October 2021 to April 2022. Adult patients with serum protein electrophoresis showing elevated β1 and/or β2 fractions were included. The selection was done following strict exclusion criteria such as acute inflammation, iron deficiency anemia signs or supposed liver disease. To construct a predictive model for prediction of positive immunofixation (IFE) for monoclonality, the following factors were used: age, sex, β1 and β2 concentration (g/L), total proteins (g/L), IgA, IgM, IgG values (g/L) and hypogammaglobulinemia. The dataset underwent a random split, divided into a foundational training set (80%, 247 samples) and a foundational test set (20%, 62 samples). The training sets were subjected to five different algorithms: logistic regression, decision tree, random forest, gradient boosting, and support vector.
Results
309 patients were selected; 149 exhibited a negative IFE and 160 a positive IFE for monoclonality. The evaluation of the five tested models demonstrated very good performance, the chosen model was Random Forest for its high sensitivity (85%) and area under the receiver operating characteristic curve (91%).
Conclusion
An accurate algorithm was achieved for predicting the presence of M protein when the β-globulin fraction is elevated which enables early and improved diagnosis of monoclonal gammopathy.
{"title":"Quantitative abnormalities in the β-region of the electrophoretic profile of serum proteins as predictive markers of monoclonality: Machine learning for monoclonality prediction","authors":"Sara Cherkaoui, Slavka Penickova , Frederic Cotton","doi":"10.1016/j.clinbiochem.2025.110892","DOIUrl":"10.1016/j.clinbiochem.2025.110892","url":null,"abstract":"<div><h3>Objective of the study</h3><div>To develop a machine learning algorithm aimed at predicting the presence of a monoclonal (M-) protein when the β-globulin fraction is elevated.</div></div><div><h3>Materials and method</h3><div>Patients were selected as part of the University Hospital Laboratory of Brussels routine diagnostic procedures from October 2021 to April 2022. Adult patients with serum protein electrophoresis showing elevated β1 and/or β2 fractions were included. The selection was done following strict exclusion criteria such as acute inflammation, iron deficiency anemia signs or supposed liver disease. To construct a predictive model for prediction of positive immunofixation (IFE) for monoclonality, the following factors were used: age, sex, β1 and β2 concentration (g/L), total proteins (g/L), IgA, IgM, IgG values (g/L) and hypogammaglobulinemia. The dataset underwent a random split, divided into a foundational training set (80%, 247 samples) and a foundational test set (20%, 62 samples). The training sets were subjected to five different algorithms: logistic regression, decision tree, random forest, gradient boosting, and support vector.</div></div><div><h3>Results</h3><div>309 patients were selected; 149 exhibited a negative IFE and 160 a positive IFE for monoclonality. The evaluation of the five tested models demonstrated very good performance, the chosen model was Random Forest for its high sensitivity (85%) and area under the receiver operating characteristic curve (91%).</div></div><div><h3>Conclusion</h3><div>An accurate algorithm was achieved for predicting the presence of M protein when the β-globulin fraction is elevated which enables early and improved diagnosis of monoclonal gammopathy.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110892"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122467","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}
Pub Date : 2025-01-25DOI: 10.1016/j.clinbiochem.2025.110889
Josiane Aparecida de Miranda , Warlley Rosa Cunha , Júlio César Moraes Lovisi , Carla Márcia Moreira Lanna , Lucas Cézar Pinheiro , Riccardo Lacchini , José Eduardo Tanus-Santos , Vanessa de Almeida Belo
Objectives
This study explores the relationship between obesity, endothelial dysfunction, and the critical role of oxidative stress biomarkers in subclinical atherosclerosis.
Design & methods
The study included 114 adolescents aged 12–17 years from Juiz de Fora, Brazil, divided into 40 individuals with obesity and 74 controls. Physical and biochemical assessments were conducted, including measurements of Brachial Flow-Mediated Dilation (BFMD), Carotid Intima-Media Thickness (IMT), and oxidative biomarkers such as nitrite, nitrate, and 8-isoprostane. Multiple regression analyses were used to evaluate associations between obesity, oxidative biomarkers, and endothelial function.
Results
Adolescents with obesity exhibited significantly reduced BFMD at 60 s (5.44 ± 2.31 % vs. 7.82 ± 2.07 % in controls; p < 0.05) and 90 s (5.27 ± 2.64 % vs. 7.93 ± 2.12 % in controls; p < 0.05). IMT was significantly higher in the group with obesity for both the right carotid artery (0.054 ± 0.005 cm vs. 0.047 ± 0.004 cm in controls; p < 0.05) and the left carotid artery (0.053 ± 0.005 cm vs. 0.047 ± 0.004 cm in controls; p < 0.05). Additionally, 8-isoprostane levels were higher in adolescents with obesity (49.75 ± 22.62 pg/mL vs. 42.36 ± 17.35 pg/mL in controls; p < 0.05), indicating increased oxidative stress. Nitrite levels were significantly lower in adolescents with obesity (42.98 ± 10.62 nM vs. 49.94 ± 17.71 nM in controls; p < 0.05). Additionally, nitrate levels were inversely associated with IMT in both the right (p = 0.01) carotid arteries in the multiple linear regression analyses.
Conclusions
The study highlights the association between obesity and early vascular changes in adolescents, evidenced by reduced BFMD, increased IMT, and altered oxidative stress biomarkers.
{"title":"Oxidative stress and obesity are associated with endothelial dysfunction and subclinical atherosclerosis in adolescents","authors":"Josiane Aparecida de Miranda , Warlley Rosa Cunha , Júlio César Moraes Lovisi , Carla Márcia Moreira Lanna , Lucas Cézar Pinheiro , Riccardo Lacchini , José Eduardo Tanus-Santos , Vanessa de Almeida Belo","doi":"10.1016/j.clinbiochem.2025.110889","DOIUrl":"10.1016/j.clinbiochem.2025.110889","url":null,"abstract":"<div><h3>Objectives</h3><div>This study explores the relationship between obesity, endothelial dysfunction, and the critical role of oxidative stress biomarkers in subclinical atherosclerosis.</div></div><div><h3>Design & methods</h3><div>The study included 114 adolescents aged 12–17 years from Juiz de Fora, Brazil, divided into 40 individuals with obesity and 74 controls. Physical and biochemical assessments were conducted, including measurements of Brachial Flow-Mediated Dilation (BFMD), Carotid Intima-Media Thickness (IMT), and oxidative biomarkers such as nitrite, nitrate, and 8-isoprostane. Multiple regression analyses were used to evaluate associations between obesity, oxidative biomarkers, and endothelial function.</div></div><div><h3>Results</h3><div>Adolescents with obesity exhibited significantly reduced BFMD at 60 s (5.44 ± 2.31 % vs. 7.82 ± 2.07 % in controls; p < 0.05) and 90 s (5.27 ± 2.64 % vs. 7.93 ± 2.12 % in controls; p < 0.05). IMT was significantly higher in the group with obesity for both the right carotid artery (0.054 ± 0.005 cm vs. 0.047 ± 0.004 cm in controls; p < 0.05) and the left carotid artery (0.053 ± 0.005 cm vs. 0.047 ± 0.004 cm in controls; p < 0.05). Additionally, 8-isoprostane levels were higher in adolescents with obesity (49.75 ± 22.62 pg/mL vs. 42.36 ± 17.35 pg/mL in controls; p < 0.05), indicating increased oxidative stress. Nitrite levels were significantly lower in adolescents with obesity (42.98 ± 10.62 nM vs. 49.94 ± 17.71 nM in controls; p < 0.05). Additionally, nitrate levels were inversely associated with IMT in both the right (p = 0.01) carotid arteries in the multiple linear regression analyses.</div></div><div><h3>Conclusions</h3><div>The study highlights the association between obesity and early vascular changes in adolescents, evidenced by reduced BFMD, increased IMT, and altered oxidative stress biomarkers.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110889"},"PeriodicalIF":2.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051649","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}
Pub Date : 2025-01-25DOI: 10.1016/j.clinbiochem.2025.110890
Carley Karsten , Theodore Stier , Christina Wood-Wentz , Carin Smith , Yifei K. Yang , Melissa Snyder
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.
{"title":"Evaluation of an automated assay for eosinophil-derived neurotoxin in serum","authors":"Carley Karsten , Theodore Stier , Christina Wood-Wentz , Carin Smith , Yifei K. Yang , Melissa Snyder","doi":"10.1016/j.clinbiochem.2025.110890","DOIUrl":"10.1016/j.clinbiochem.2025.110890","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Materials and Methods</h3><div>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).</div></div><div><h3>Results</h3><div>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; <em>P</em> < 0.0001). However, individual patients may present with discordant presentation of eosinophil counts and EDN concentration.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110890"},"PeriodicalIF":2.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Assessing the predictive value of elevated triglycerides, triglyceride-glucose index (TyG), and TG/HDL ratios for cardiovascular disease and mortality during 20 years of follow-up: Tehran lipid and glucose study","authors":"Shayesteh Khalili , Atieh Amouzegar , Seyed Sattar Dorost , Fereidoun Azizi , Aryan Salahi-Niri","doi":"10.1016/j.clinbiochem.2025.110891","DOIUrl":"10.1016/j.clinbiochem.2025.110891","url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Design and methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110891"},"PeriodicalIF":2.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037397","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}
Pub Date : 2025-01-21DOI: 10.1016/j.clinbiochem.2025.110888
Elisa Nuez-Zaragoza , Indira Bhambi-Blanco , Mònica Vidal-Pla , Isabel Aparicio-Calvente , M. Rosa Escoda-Giralt , Joana Gallardo-Campos , Joan C. Ferreres , Luis Frisancho , Laia Mas-Maresma , Patricia Aguilera-Fernández , Sonia Marco-Continente , Marina Sierra-Boada , Pablo Andreu-Cobo , Miquel Gallego , Jaume Trapé , Vicente Aguadero
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.
{"title":"Utility of the combination of high fluorescence cells and tumor markers for the diagnosis of malignant pleural effusions","authors":"Elisa Nuez-Zaragoza , Indira Bhambi-Blanco , Mònica Vidal-Pla , Isabel Aparicio-Calvente , M. Rosa Escoda-Giralt , Joana Gallardo-Campos , Joan C. Ferreres , Luis Frisancho , Laia Mas-Maresma , Patricia Aguilera-Fernández , Sonia Marco-Continente , Marina Sierra-Boada , Pablo Andreu-Cobo , Miquel Gallego , Jaume Trapé , Vicente Aguadero","doi":"10.1016/j.clinbiochem.2025.110888","DOIUrl":"10.1016/j.clinbiochem.2025.110888","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>Per our findings, this model has high diagnostic performance and could serve as a swift, automated, dependable, non-invasive tool for MPE detection.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110888"},"PeriodicalIF":2.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028065","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}
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