Pub Date : 2025-12-06DOI: 10.1016/j.clinbiochem.2025.111062
Isaiah K. Mensah , Brittany Roemmich , Sydny Lawless , Alexis Wysocki , David Daghfal , Christian J. Hunter , Christopher W. Farnsworth
Background
N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement is recommended by guidelines for diagnosing and managing heart failure (HF). Accurate NT-proBNP measurement is critical for timely and effective treatment, but limited studies have compared NT-proBNP results from multiple platforms, and few studies have compared their concordance using commonly used clinical cutpoints.
Methods
The Alinity, PathFast, and Roche NT-proBNP assays were assessed in 276 patient samples, comprising 188 inpatients and 88 outpatients with normal renal function. Correlation and bias among the assays were assessed, and guideline-endorsed clinical cutpoints were used to evaluate concordance.
Results
Passing-Bablok regression revealed a slope of 1.00 (95% CI: 0.99–1.01) for Alinity vs. Roche, 1.14 (1.11–1.16) for PathFast vs. Roche, and 1.11 (1.01–1.13) for PathFast vs. Alinity. Bland-Altman analysis revealed minimal bias among the assays, with the closest agreement observed between PathFast and Alinity (−1.85%, −43.36 to 39.65). On inpatients, the concordance was 0.97 (0.94–0.99) for Alinity vs. Roche, 0.95 (0.92–0.99) for PathFast vs. Roche, and 0.94 (0.91–0.98) for PathFast vs. Alinity. For outpatients, the concordance was 0.92 (0.84–1.00) for Alinity vs. Roche, 0.90 (0.80–1.00) for PathFast vs. Roche, and 0.97 (0.92–1.00) for PathFast vs. Alinity.
Conclusion
Three NT-proBNP assay platforms demonstrated high correlation, minimal bias, and high clinical concordance. The results support the clinical interchangeability of these assays at commonly used and guideline-endorsed cutpoints.
{"title":"Evaluation of three NT-proBNP assays for heart failure","authors":"Isaiah K. Mensah , Brittany Roemmich , Sydny Lawless , Alexis Wysocki , David Daghfal , Christian J. Hunter , Christopher W. Farnsworth","doi":"10.1016/j.clinbiochem.2025.111062","DOIUrl":"10.1016/j.clinbiochem.2025.111062","url":null,"abstract":"<div><h3>Background</h3><div>N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement is recommended by guidelines for diagnosing and managing heart failure (HF). Accurate NT-proBNP measurement is critical for timely and effective treatment, but limited studies have compared NT-proBNP results from multiple platforms, and few studies have compared their concordance using commonly used clinical cutpoints.</div></div><div><h3>Methods</h3><div>The Alinity, PathFast, and Roche NT-proBNP assays were assessed in 276 patient samples, comprising 188 inpatients and 88 outpatients with normal renal function. Correlation and bias among the assays were assessed, and guideline-endorsed clinical cutpoints were used to evaluate concordance.</div></div><div><h3>Results</h3><div>Passing-Bablok regression revealed a slope of 1.00 (95% CI: 0.99–1.01) for Alinity vs. Roche, 1.14 (1.11–1.16) for PathFast vs. Roche, and 1.11 (1.01–1.13) for PathFast vs. Alinity. Bland-Altman analysis revealed minimal bias among the assays, with the closest agreement observed between PathFast and Alinity (−1.85%, −43.36 to 39.65). On inpatients, the concordance was 0.97 (0.94–0.99) for Alinity vs. Roche, 0.95 (0.92–0.99) for PathFast vs. Roche, and 0.94 (0.91–0.98) for PathFast vs. Alinity. For outpatients, the concordance was 0.92 (0.84–1.00) for Alinity vs. Roche, 0.90 (0.80–1.00) for PathFast vs. Roche, and 0.97 (0.92–1.00) for PathFast vs. Alinity.</div></div><div><h3>Conclusion</h3><div>Three NT-proBNP assay platforms demonstrated high correlation, minimal bias, and high clinical concordance. The results support the clinical interchangeability of these assays at commonly used and guideline-endorsed cutpoints.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111062"},"PeriodicalIF":2.1,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707534","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 : 2025-12-06DOI: 10.1016/j.clinbiochem.2025.111065
Mary Hainrichson , Nitzan Shamir , Naftalie Senderovich , May Levin , Husein Darawsha , Ayelet Raz , Salim Halabi , Oded Shaham , Roy Navon , Tanya M. Gottlieb , Barak Hershkovitz
Background
MeMed BV is a host-protein test for discriminating bacterial and viral infections. It was analytically and clinically validated in serum and venous whole blood samples. Here we investigated the comparability of venous versus capillary blood measurements of the MeMed BV score and of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) biomarkers.
Methods
Adult patients with suspected acute infection were enrolled prospectively at three medical centers. Eligibility criteria were based on MeMed BV instructions for use. Paired venous and capillary samples (50 µL) were collected and measured.
Three predetermined acceptance criteria for comparability for MeMed BV score were: (1) Slope 0.9–1.1 and intercept −5 to 5 in Passing-Bablok regression; (2) 95 % confidence intervals (CI) for bias at score bin cutoffs fall within −12.5 to 12.5; and (3) <5 % of paired scores fall in non-adjacent clinical interpretation bins.
Results
Among 58 patients (median age 58.5 years), TRAIL, IP-10, and CRP measurements in venous and capillary blood were highly correlated (r = 0.98–0.99). For the MeMed BV score, slope was 1.00 (95 % CI: 0.99, 1.01), intercept 0.00 (−1.04, 0.08), 95 % CI for bias at each cutoff was within limits and no paired scores fell in non-adjacent bins. All three criteria were met and findings were consistent in a single replicates analysis.
Conclusion
Venous and capillary blood yield comparable MeMed BV scores and biomarker values. The findings can serve as the basis for expanding MeMed BV’s use to include capillary blood specimens, potentially widening its clinical utility.
{"title":"Comparability of venous and capillary blood measurements for a host-protein test differentiating bacterial from viral infections","authors":"Mary Hainrichson , Nitzan Shamir , Naftalie Senderovich , May Levin , Husein Darawsha , Ayelet Raz , Salim Halabi , Oded Shaham , Roy Navon , Tanya M. Gottlieb , Barak Hershkovitz","doi":"10.1016/j.clinbiochem.2025.111065","DOIUrl":"10.1016/j.clinbiochem.2025.111065","url":null,"abstract":"<div><h3>Background</h3><div>MeMed BV is a host-protein test for discriminating bacterial and viral infections. It was analytically and clinically validated in serum and venous whole blood samples. Here we investigated the comparability of venous versus capillary blood measurements of the MeMed BV score and of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein-10 (IP-10), and C-reactive protein (CRP) biomarkers.</div></div><div><h3>Methods</h3><div>Adult patients with suspected acute infection were enrolled prospectively at three medical centers. Eligibility criteria were based on MeMed BV instructions for use. Paired venous and capillary samples (50 µL) were collected and measured.</div><div>Three predetermined acceptance criteria for comparability for MeMed BV score were: (1) Slope 0.9–1.1 and intercept −5 to 5 in Passing-Bablok regression; (2) 95 % confidence intervals (CI) for bias at score bin cutoffs fall within −12.5 to 12.5; and (3) <5 % of paired scores fall in non-adjacent clinical interpretation bins.</div></div><div><h3>Results</h3><div>Among 58 patients (median age 58.5 years), TRAIL, IP-10, and CRP measurements in venous and capillary blood were highly correlated (r = 0.98–0.99). For the MeMed BV score, slope was 1.00 (95 % CI: 0.99, 1.01), intercept 0.00 (−1.04, 0.08), 95 % CI for bias at each cutoff was within limits and no paired scores fell in non-adjacent bins. All three criteria were met and findings were consistent in a single replicates analysis.</div></div><div><h3>Conclusion</h3><div>Venous and capillary blood yield comparable MeMed BV scores and biomarker values. The findings can serve as the basis for expanding MeMed BV’s use to include capillary blood specimens, potentially widening its clinical utility.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111065"},"PeriodicalIF":2.1,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707483","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 : 2025-12-05DOI: 10.1016/j.clinbiochem.2025.111059
Parth Aphale, Shashank Dokania, Himanshu Shekhar
{"title":"Constructive critique on the development and validation of a multiplex LC-MS/MS DBS assay","authors":"Parth Aphale, Shashank Dokania, Himanshu Shekhar","doi":"10.1016/j.clinbiochem.2025.111059","DOIUrl":"10.1016/j.clinbiochem.2025.111059","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111059"},"PeriodicalIF":2.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699987","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 : 2025-12-02DOI: 10.1016/j.clinbiochem.2025.111064
Juan Huang , Duocai Wang , Ying Wang , Yongqiang Yang , Dong Peng , Meizhu Luo , Xiaoying Fu
Objectives
Congenital dysfibrinogenemia (CD) is a rare inherited disorder caused by qualitative abnormalities in fibrinogen, leading to discordance between functional and antigenic fibrinogen levels. Genetic testing plays a pivotal role in confirming diagnosis and elucidating phenotypic heterogeneity. This study aims to emphasize the diagnostic value of combining coagulation assays with genetic testing and underscore the clinical heterogeneity of CD through clinical cases of novel mutations.
Design & methods
Five pediatric patients with incidentally identified CD were diagnosed at Shenzhen Children’s Hospital. Peripheral blood samples were analyzed for coagulation parameters, including fibrinogen activity (FIB:C) by the Clauss method, fibrinogen derived from the prothrombin time (PT-dF), as well as activated partial thromboplastin time （aPTT）, PT, thrombin time (TT), and thromboelastography (TEG). Sanger sequencing was conducted to assess mutations in FGA, FGB, and FGG genes.
Results
Two unrelated patients harbored a known heterozygous mutation in FGG (c.902G > A; p.Arg301His). Two novel heterozygous mutations were identified: FGA (c.113G > A; p.Arg38Lys) and FGG (c.902G > T; p.Arg301Leu). A homozygous mutation in FGB (c.292G > A; p.Ala98Thr) was detected in another patient; this variant has been reported only twice before in the literature. All patients were asymptomatic. Coagulation testing revealed consistently decreased FIB:C with normal PT-dF, characteristic of CD. TEG analysis showed variable alterations in fibrinogen-related parameters, although no consistent genotype–phenotype correlation was observed.
Conclusion
This study expands the genetic and phenotypic spectrum of CD in children, reporting two novel mutations and documenting the first pediatric cases of these variants in a Chinese cohort. Given the potential long-term risks and diagnostic complexity in asymptomatic pediatric patients, individualized surveillance and management strategies are warranted. Further research is needed to evaluate the functional consequences of novel mutations and their implications for pediatric hemostasis.
{"title":"Novel and known fibrinogen gene mutations in Chinese pediatric patients with congenital dysfibrinogenemia: genetic and functional characterization","authors":"Juan Huang , Duocai Wang , Ying Wang , Yongqiang Yang , Dong Peng , Meizhu Luo , Xiaoying Fu","doi":"10.1016/j.clinbiochem.2025.111064","DOIUrl":"10.1016/j.clinbiochem.2025.111064","url":null,"abstract":"<div><h3>Objectives</h3><div>Congenital dysfibrinogenemia (CD) is a rare inherited disorder caused by qualitative abnormalities in fibrinogen, leading to discordance between functional and antigenic fibrinogen levels. Genetic testing plays a pivotal role in confirming diagnosis and elucidating phenotypic heterogeneity. This study aims to emphasize the diagnostic value of combining coagulation assays with genetic testing and underscore the clinical heterogeneity of CD through clinical cases of novel mutations.</div></div><div><h3>Design & methods</h3><div>Five pediatric patients with incidentally identified CD were diagnosed at Shenzhen Children’s Hospital. Peripheral blood samples were analyzed for coagulation parameters, including fibrinogen activity (FIB:C) by the Clauss method, fibrinogen derived from the prothrombin time (PT-dF), as well as activated partial thromboplastin time （aPTT）, PT, thrombin time (TT), and thromboelastography (TEG). Sanger sequencing was conducted to assess mutations in <em>FGA</em>, <em>FGB</em>, and <em>FGG</em> genes.</div></div><div><h3>Results</h3><div>Two unrelated patients harbored a known heterozygous mutation in <em>FGG</em> (c.902G > A; p.Arg301His). Two novel heterozygous mutations were identified: <em>FGA</em> (c.113G > A; p.Arg38Lys) and <em>FGG</em> (c.902G > T; p.Arg301Leu). A homozygous mutation in <em>FGB</em> (c.292G > A; p.Ala98Thr) was detected in another patient; this variant has been reported only twice before in the literature. All patients were asymptomatic. Coagulation testing revealed consistently decreased FIB:C with normal PT-dF, characteristic of CD. TEG analysis showed variable alterations in fibrinogen-related parameters, although no consistent genotype–phenotype correlation was observed.</div></div><div><h3>Conclusion</h3><div>This study expands the genetic and phenotypic spectrum of CD in children, reporting two novel mutations and documenting the first pediatric cases of these variants in a Chinese cohort. Given the potential long-term risks and diagnostic complexity in asymptomatic pediatric patients, individualized surveillance and management strategies are warranted. Further research is needed to evaluate the functional consequences of novel mutations and their implications for pediatric hemostasis.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111064"},"PeriodicalIF":2.1,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676361","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 : 2025-11-26DOI: 10.1016/j.clinbiochem.2025.111060
C. Hughes , M.A. Myers , M. Tickell-Painter , M. Aitchison , L. Roberts , R.J. Shorten
Introduction
The climate crisis is a health crisis, and healthcare contributes to this via consumption of resources, the release of greenhouse gases, and the generation of waste. Pathology testing underpins most healthcare, and the vast number of tests performed in clinical laboratories come with an environmental cost. There is a growing body of evidence demonstrating that many pathology tests are unnecessary, utilising finite resources, potentially causing patient harm, and generating a carbon footprint. Vitamin D testing is one such example.
Methods
A quasi-experimental study of three real-world diagnostic stewardship interventions to reduce inappropriate vitamin D testing. The number of vitamin D test requests were measured pre- and post- each intervention, and cardon dioxide equivalent (CO2e) savings were estimated for any reduction in testing that was realised.
Results
An intervention that passively provided information on best practice did not reduce testing volumes. Interventions that removed automated reflex testing in the emergency department, and the implementation of a best-practice clinical decision tool utilising national testing guidelines resulted in a statistically significant reduction of vitamin D requests. These reductions cumulatively saved almost 44,000 g CO2e across the three diagnostic stewardship interventions.
Discussion
This study showed that diagnostic stewardship interventions can reduce testing volumes and generate CO2e savings. While these savings are modest, it is possible to consider that if such interventions were used widely to prevent inappropriate testing across multiple test types, laboratories, and healthcare settings, the cumulative carbon and financial savings could be substantial. Such ‘soft stop’ interventions do not prevent a clinician who is determined to send such tests, and future work should combine these tools with behavioural change interventions to maximise their benefit.
{"title":"Reducing inappropriate vitamin D testing: an analysis of three sequential diagnostic stewardship interventions and the carbon footprint implications","authors":"C. Hughes , M.A. Myers , M. Tickell-Painter , M. Aitchison , L. Roberts , R.J. Shorten","doi":"10.1016/j.clinbiochem.2025.111060","DOIUrl":"10.1016/j.clinbiochem.2025.111060","url":null,"abstract":"<div><h3>Introduction</h3><div>The climate crisis is a health crisis, and healthcare contributes to this via consumption of resources, the release of greenhouse gases, and the generation of waste. Pathology testing underpins most healthcare, and the vast number of tests performed in clinical laboratories come with an environmental cost. There is a growing body of evidence demonstrating that many pathology tests are unnecessary, utilising finite resources, potentially causing patient harm, and generating a carbon footprint. Vitamin D testing is one such example.</div></div><div><h3>Methods</h3><div>A quasi-experimental study of three real-world diagnostic stewardship interventions to reduce inappropriate vitamin D testing. The number of vitamin D test requests were measured pre- and post- each intervention, and cardon dioxide equivalent (CO<sub>2</sub>e) savings were estimated for any reduction in testing that was realised.</div></div><div><h3>Results</h3><div>An intervention that passively provided information on best practice did not reduce testing volumes. Interventions that removed automated reflex testing in the emergency department, and the implementation of a best-practice clinical decision tool utilising national testing guidelines resulted in a statistically significant reduction of vitamin D requests. These reductions cumulatively saved almost 44,000 g CO<sub>2</sub>e across the three diagnostic stewardship interventions.</div></div><div><h3>Discussion</h3><div>This study showed that diagnostic stewardship interventions can reduce testing volumes and generate CO<sub>2</sub>e savings. While these savings are modest, it is possible to consider that if such interventions were used widely to prevent inappropriate testing across multiple test types, laboratories, and healthcare settings, the cumulative carbon and financial savings could be substantial. Such ‘soft stop’ interventions do not prevent a clinician who is determined to send such tests, and future work should combine these tools with behavioural change interventions to maximise their benefit.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111060"},"PeriodicalIF":2.1,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145615861","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 : 2025-11-21DOI: 10.1016/j.clinbiochem.2025.111061
Jianjiao Mou , Qingfeng Tao , Lu Xu , Yifei Luo , Hui Zheng
This study aimed to systematically assess the diagnostic performance of multiple biomarkers for irritable bowel syndrome (IBS). Systematic electronic searches were conducted in PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science, with the search updated through May 18, 2025. Studies were evaluated in accordance with the Diagnostic Test Accuracy systematic review manual and the PRISMA-DTA reporting guidelines. Methodological quality of included studies was assessed using the QUADAS-2 and QUADAS-C tools. We synthesized summary sensitivity and specificity using a bivariate random-effects model within a hierarchical summary receiver operating characteristic framework. Of 9,078 initially identified studies, 24 eligible studies involving 9,343 participants were ultimately included in the meta-analysis. Pooled analysis revealed that urinary metabolic markers exhibited high diagnostic accuracy, with a pooled sensitivity of 0.988 (95% CI: 0.804–1.000) and a pooled specificity of 0.934 (95% CI: 0.629–0.993). In biomarker-type subgroup analyses, fecal peptidase activity yielded a sensitivity of 0.905 (0.438–0.990) and specificity of 0.883 (0.513–0.978), while RAID-IBS showed a sensitivity of 0.935 (0.548–0.994) and specificity of 0.919 (0.444–0.986). When stratified by comparator groups, urinary metabolites exhibited a sensitivity of 0.981 (0.800–0.999) and specificity of 0.803 (0.271–0.981) against healthy controls, compared to a sensitivity of 0.995 (0.926–1.000) and specificity of 0.996 (0.944–1.000) against inflammatory bowel disease. These results suggest that urinary metabolites, fecal peptidase activity, and RAID-IBS may achieve high sensitivity and specificity in the studies available.
本研究旨在系统评估多种生物标志物对肠易激综合征（IBS）的诊断性能。系统的电子检索在PubMed、Cochrane Central Register of Controlled Trials、Embase和Web of Science中进行，检索更新至2025年5月18日。根据诊断测试准确性系统评价手册和PRISMA-DTA报告指南对研究进行评估。采用QUADAS-2和QUADAS-C工具评估纳入研究的方法学质量。我们使用双变量随机效应模型在分级汇总接收者操作特征框架内综合汇总敏感性和特异性。在最初确定的9078项研究中，最终纳入了24项符合条件的研究，涉及9343名参与者。合并分析显示，尿代谢标志物具有较高的诊断准确性，合并敏感性为0.988 (95% CI: 0.804-1.000)，合并特异性为0.934 （95% CI: 0.629-0.993）。在生物标志物亚组分析中，粪便肽酶活性的敏感性为0.905(0.438 ~ 0.990)，特异性为0.883(0.513 ~ 0.978)，而RAID-IBS的敏感性为0.935(0.548 ~ 0.994)，特异性为0.919（0.444 ~ 0.986）。当按比较组分层时，尿代谢物对健康对照的敏感性为0.981(0.800-0.999)，特异性为0.803(0.271-0.981)，而对炎症性肠病的敏感性为0.995(0.926-1.000)，特异性为0.996（0.944-1.000）。这些结果表明，在现有的研究中，尿液代谢物、粪便肽酶活性和RAID-IBS可能具有很高的敏感性和特异性。
{"title":"Diagnostic accuracy of biomarkers for irritable bowel syndrome: a systematic review and meta-analysis","authors":"Jianjiao Mou , Qingfeng Tao , Lu Xu , Yifei Luo , Hui Zheng","doi":"10.1016/j.clinbiochem.2025.111061","DOIUrl":"10.1016/j.clinbiochem.2025.111061","url":null,"abstract":"<div><div>This study aimed to systematically assess the diagnostic performance of multiple biomarkers for irritable bowel syndrome (IBS). Systematic electronic searches were conducted in PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science, with the search updated through May 18, 2025. Studies were evaluated in accordance with the Diagnostic Test Accuracy systematic review manual and the PRISMA-DTA reporting guidelines. Methodological quality of included studies was assessed using the QUADAS-2 and QUADAS-C tools. We synthesized summary sensitivity and specificity using a bivariate random-effects model within a hierarchical summary receiver operating characteristic framework. Of 9,078 initially identified studies, 24 eligible studies involving 9,343 participants were ultimately included in the <em>meta</em>-analysis. Pooled analysis revealed that urinary metabolic markers exhibited high diagnostic accuracy, with a pooled sensitivity of 0.988 (95% CI: 0.804–1.000) and a pooled specificity of 0.934 (95% CI: 0.629–0.993). In biomarker-type subgroup analyses, fecal peptidase activity yielded a sensitivity of 0.905 (0.438–0.990) and specificity of 0.883 (0.513–0.978), while RAID-IBS showed a sensitivity of 0.935 (0.548–0.994) and specificity of 0.919 (0.444–0.986). When stratified by comparator groups, urinary metabolites exhibited a sensitivity of 0.981 (0.800–0.999) and specificity of 0.803 (0.271–0.981) against healthy controls, compared to a sensitivity of 0.995 (0.926–1.000) and specificity of 0.996 (0.944–1.000) against inflammatory bowel disease. These results suggest that urinary metabolites, fecal peptidase activity, and RAID-IBS may achieve high sensitivity and specificity in the studies available.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111061"},"PeriodicalIF":2.1,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586099","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 : 2025-11-19DOI: 10.1016/j.clinbiochem.2025.111058
El Hadji Malick Ndour , Kuthala Mnika , El Hadj Ousmane Sene , Fatou Gueye Tall , Victoria Nembaware , Indou Deme Ly , Moussa Seck , Mara Sokhna , Rokhaya Dione , Coumba Kamby , Jean Pascal Demba Diop , Serigne Saliou Mbacke , Nene Oumou Kesso Barry , Moustapha Djité , Pape Matar Kandji , Rokhaya Ndiaye Diallo , Ibrahima Diagne , Saliou Diop , Papa Madieye Gueye , Philomene Lopez Sall , Ambroise Wonkam
Background
Sickle cell nephropathy (SCN) is a major chronic complication of sickle cell disease, and its progression may be influenced by genetic factors. This study aimed to investigate the association between variants in the MYH9 and BMPR1B genes and increased total proteinuria in patients with sickle cell anemia.
Materials and methods
This cross-sectional study included patients with homozygous (SS) sickle cell disease who were followed up in Dakar. Urinary albumin, total proteins, and creatinine levels, along with serum creatinine and urea concentrations, were measured. Genotyping of the single nucleotide variants MYH9-rs4821469, MYH9-rs3752462, MYH9-rs2032487, and BMPR1B-rs17022863 was performed using mass spectrometry (MassARRAY technology). Associations were evaluated using multivariate logistic regression analysis.
Results
The 150-patient cohort had a mean age of 20.44 ± 9.86 years, with a slight female majority (51 %). A high prevalence of increased total proteinuria (urine proteins-to-creatinine ratio ≥150 mg/g) was observed, affecting 50.67 % of this young population. Multivariate analysis identified relative systemic hypertension (blood pressure ≥130/80 mmHg) as a powerful and independent risk factor for increased total proteinuria. While an initial analysis suggested a protective association for the MYH9 − rs4821469 variant, this signal was unstable and lost statistical significance in more stringent models.
Conclusion
Increased total proteinuria is highly prevalent in this young cohort, indicating early onset of kidney damage. Relative systemic hypertension is a major modifiable risk factor, underscoring the need for rigorous blood pressure control. The instability of the initial genetic signal for MYH9-rs4821469, coupled with its strong linkage disequilibrium with APOL1, suggests that the observed association is likely confounded by ungenotyped APOL1 variants. This highlights the critical importance of including APOL1 analysis in future SCN genetic studies in African-ancestry populations.
{"title":"Association of hypertension and genetic variants in MYH9 and BMPR1B with increased proteinuria in sickle cell disease","authors":"El Hadji Malick Ndour , Kuthala Mnika , El Hadj Ousmane Sene , Fatou Gueye Tall , Victoria Nembaware , Indou Deme Ly , Moussa Seck , Mara Sokhna , Rokhaya Dione , Coumba Kamby , Jean Pascal Demba Diop , Serigne Saliou Mbacke , Nene Oumou Kesso Barry , Moustapha Djité , Pape Matar Kandji , Rokhaya Ndiaye Diallo , Ibrahima Diagne , Saliou Diop , Papa Madieye Gueye , Philomene Lopez Sall , Ambroise Wonkam","doi":"10.1016/j.clinbiochem.2025.111058","DOIUrl":"10.1016/j.clinbiochem.2025.111058","url":null,"abstract":"<div><h3>Background</h3><div>Sickle cell nephropathy (SCN) is a major chronic complication of sickle cell disease, and its progression may be influenced by genetic factors. This study aimed to investigate the association between variants in the <em>MYH9</em> and <em>BMPR1B</em> genes and increased total proteinuria in patients with sickle cell anemia.</div></div><div><h3>Materials and methods</h3><div>This cross-sectional study included patients with homozygous (SS) sickle cell disease who were followed up in Dakar. Urinary albumin, total proteins, and creatinine levels, along with serum creatinine and urea concentrations, were measured. Genotyping of the single nucleotide variants <em>MYH9</em>-rs4821469, <em>MYH9</em>-rs3752462, <em>MYH9</em>-rs2032487, and <em>BMPR1B</em>-rs17022863 was performed using mass spectrometry (MassARRAY technology). Associations were evaluated using multivariate logistic regression analysis.</div></div><div><h3>Results</h3><div>The 150-patient cohort had a mean age of 20.44 ± 9.86 years, with a slight female majority (51 %). A high prevalence of increased total proteinuria (urine proteins-to-creatinine ratio ≥150 mg/g) was observed, affecting 50.67 % of this young population. Multivariate analysis identified relative systemic hypertension (blood pressure ≥130/80 mmHg) as a powerful and independent risk factor for increased total proteinuria. While an initial analysis suggested a protective association for the <em>MYH9</em> − rs4821469 variant, this signal was unstable and lost statistical significance in more stringent models.</div></div><div><h3>Conclusion</h3><div>Increased total proteinuria is highly prevalent in this young cohort, indicating early onset of kidney damage. Relative systemic hypertension is a major modifiable risk factor, underscoring the need for rigorous blood pressure control. The instability of the initial genetic signal for <em>MYH9</em>-rs4821469, coupled with its strong linkage disequilibrium with <em>APOL1</em>, suggests that the observed association is likely confounded by ungenotyped <em>APOL1</em> variants. This highlights the critical importance of including <em>APOL1</em> analysis in future SCN genetic studies in African-ancestry populations.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111058"},"PeriodicalIF":2.1,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562783","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 : 2025-11-16DOI: 10.1016/j.clinbiochem.2025.111057
Janet Zhou , Demitra Tsoukalas , Nethra Chittiprol , Peter Kavsak , Felix Leung , Jennifer Taher , Zahraa Ali-Mohammed , Saranya Arnoldo , Heather Tysick , Lei Fu , Sara A. Love , Rajeevan Selvaratnam
Background
Monitoring blood levels of lithium is important for maintaining therapeutic efficacy. Age-dependent therapeutic intervals have been recommended by the International Society for Bipolar Disorder (ISBD) task force, 0.4–0.8 mmol/L and 0.4–0.7 mmol/L for adults aged 60–79 and ≥80 years old, respectively. However, the suitability of common colorimetric methods for lithium measurements in the suggested therapeutic intervals has not been characterized, nor has the proposed therapeutic intervals been confirmed with real-world patient data.
Methods
Serum samples spiked with various concentrations of lithium ranging from 0 to 3.5 mmol/L were analyzed on six different methods for imprecision and relative comparability of lithium measurements. An indirect reference interval approach using refineR was employed to derive therapeutic limits using patient results spanning 5 years and compared with the therapeutic intervals recommended by the ISBD task force.
Results
Routinely employed colorimetric methods for lithium measurements have sufficient precision within the recommended therapeutic intervals, although select colorimetric methods are notably more imprecise at 0.4 mmol/L. The derived therapeutic intervals using patient data align with those proposed by the ISBD task force for older adults.
Conclusion
Routine colorimetric methods used for lithium measurements have adequate precision and detection capabilities in the therapeutic windows recommended by the ISBD task force. In addition, the proposed therapeutic intervals are verifiable by real-world patient data.
{"title":"Analytical Imprecision and Therapeutic Intervals for Lithium – Are There Implications for Old Age Patients with Bipolar Disorder?","authors":"Janet Zhou , Demitra Tsoukalas , Nethra Chittiprol , Peter Kavsak , Felix Leung , Jennifer Taher , Zahraa Ali-Mohammed , Saranya Arnoldo , Heather Tysick , Lei Fu , Sara A. Love , Rajeevan Selvaratnam","doi":"10.1016/j.clinbiochem.2025.111057","DOIUrl":"10.1016/j.clinbiochem.2025.111057","url":null,"abstract":"<div><h3>Background</h3><div>Monitoring blood levels of lithium is important for maintaining therapeutic efficacy. Age-dependent therapeutic intervals have been recommended by the International Society for Bipolar Disorder (ISBD) task force, 0.4–0.8 mmol/L and 0.4–0.7 mmol/L for adults aged 60–79 and ≥80 years old, respectively. However, the suitability of common colorimetric methods for lithium measurements in the suggested therapeutic intervals has not been characterized, nor has the proposed therapeutic intervals been confirmed with real-world patient data.</div></div><div><h3>Methods</h3><div>Serum samples spiked with various concentrations of lithium ranging from 0 to 3.5 mmol/L were analyzed on six different methods for imprecision and relative comparability of lithium measurements. An indirect reference interval approach using refineR was employed to derive therapeutic limits using patient results spanning 5 years and compared with the therapeutic intervals recommended by the ISBD task force.</div></div><div><h3>Results</h3><div>Routinely employed colorimetric methods for lithium measurements have sufficient precision within the recommended therapeutic intervals, although select colorimetric methods are notably more imprecise at 0.4 mmol/L. The derived therapeutic intervals using patient data align with those proposed by the ISBD task force for older adults.</div></div><div><h3>Conclusion</h3><div>Routine colorimetric methods used for lithium measurements have adequate precision and detection capabilities in the therapeutic windows recommended by the ISBD task force. In addition, the proposed therapeutic intervals are verifiable by real-world patient data.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111057"},"PeriodicalIF":2.1,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548427","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 : 2025-11-14DOI: 10.1016/j.clinbiochem.2025.111041
Xiaopu Cui , Sixian Guo , Yu Zhang , Huixin Zhang , Hongxin Tian , Huafang Yang , Huacheng Zheng , Baoguang Li
Objective
This study aimed to analyze the clinical features, genetic basis, and management of late-onset carbamoyl phosphate synthetase 1 deficiency (CPS1D) through a pediatric case report and literature review, highlighting diagnostic challenges and therapeutic strategies.
Methods
We present a 19-year-old female with recurrent neurological symptoms since age 8. She underwent comprehensive metabolic screening, neuroimaging, and whole-exome sequencing of the CPS1 gene. Identified variants were assessed for pathogenicity using multiple orthogonal in silico prediction tools.
Results
The patient’s initial hyperammonemic crisis at age 8 was misdiagnosed as encephalitis. Workup at age 13 confirmed hyperammonemia (peak 168 µmol/L), hypocitrullinemia, and elevated glutamine. Genetic analysis identified compound heterozygous CPS1 variants: a novel c.1058 T > C (p.F353S) and known pathogenic c.1145C > T (p.P382L). A self-selected low-protein diet controlled acute crises but led to severe growth failure (height 145 cm, weight 30 kg).
Conclusion
Late-onset CPS1D’s nonspecific neurological symptoms often lead to misdiagnosis. Diagnosis requires a high index of suspicion, integrating metabolic profiling with genetic confirmation. This case expands the pathogenic genotypic spectrum of CPS1D. It crucially highlights that while dietary management is life-saving, it requires expert multidisciplinary oversight to prevent devastating consequences like growth failure, especially in resource-limited settings. Routine ammonia testing in unexplained encephalopathy is paramount.
目的：本研究旨在通过儿科病例报告和文献综述，分析迟发性磷酸氨甲酰合成酶1缺乏症（CPS1D）的临床特征、遗传基础和治疗，强调诊断挑战和治疗策略。方法：我们报告了一位19岁的女性，自8岁以来反复出现神经系统症状。她接受了全面的代谢筛查、神经成像和cps1基因全外显子组测序。鉴定出的变异采用多种正gonalin硅预测工具进行致病性评估。结果：患者8岁时首次出现高氨血症危象，误诊为脑炎。13岁时的检查证实了高氨血症（峰值168 µmol/L）、低氮血症和谷氨酰胺升高。遗传分析鉴定出复合杂合scps1变异：一种新的C .1058 T > C （p.F353S）和一种已知的致病性C . 1145c > T （p.P382L）。自我选择的低蛋白饮食控制了急性危机，但导致严重的生长衰竭（身高145 cm，体重30 kg）。结论：迟发性CPS1D的非特异性神经症状常导致误诊。诊断需要高度的怀疑指数，结合代谢谱和基因确认。本病例扩大了CPS1D的致病基因型谱。它至关重要地强调，虽然饮食管理可以挽救生命，但它需要多学科专家的监督，以防止生长衰竭等破坏性后果，特别是在资源有限的情况下。在不明原因的脑病中，常规氨检测是至关重要的。
{"title":"A case of late-onset carbamoyl phosphate synthetase 1 deficiency: diagnostic challenges and management in a low-resource setting","authors":"Xiaopu Cui , Sixian Guo , Yu Zhang , Huixin Zhang , Hongxin Tian , Huafang Yang , Huacheng Zheng , Baoguang Li","doi":"10.1016/j.clinbiochem.2025.111041","DOIUrl":"10.1016/j.clinbiochem.2025.111041","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to analyze the clinical features, genetic basis, and management of late-onset carbamoyl phosphate synthetase 1 deficiency (CPS1D) through a pediatric case report and literature review, highlighting diagnostic challenges and therapeutic strategies.</div></div><div><h3>Methods</h3><div>We present a 19-year-old female with recurrent neurological symptoms since age 8. She underwent comprehensive metabolic screening, neuroimaging, and whole-exome sequencing of the<!--> <em>CPS1</em> <!-->gene. Identified variants were assessed for pathogenicity using multiple orthogonal<!--> <em>in silico</em> <!-->prediction tools.</div></div><div><h3>Results</h3><div>The patient’s initial hyperammonemic crisis at age 8 was misdiagnosed as encephalitis. Workup at age 13 confirmed hyperammonemia (peak 168 µmol/L), hypocitrullinemia, and elevated glutamine. Genetic analysis identified compound heterozygous<!--> <em>CPS1</em> <!-->variants: a novel c.1058 T > C (p.F353S) and known pathogenic c.1145C > T (p.P382L). A self-selected low-protein diet controlled acute crises but led to severe growth failure (height 145 cm, weight 30 kg).</div></div><div><h3>Conclusion</h3><div>Late-onset CPS1D’s nonspecific neurological symptoms often lead to misdiagnosis. Diagnosis requires a high index of suspicion, integrating metabolic profiling with genetic confirmation. This case expands the pathogenic genotypic spectrum of CPS1D. It crucially highlights that while dietary management is life-saving, it requires expert multidisciplinary oversight to prevent devastating consequences like growth failure, especially in resource-limited settings. Routine ammonia testing in unexplained encephalopathy is paramount.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111041"},"PeriodicalIF":2.1,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534217","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 : 2025-11-13DOI: 10.1016/j.clinbiochem.2025.111055
Bertil Lindahl , Alexander JF Thurston , Yong Yong Tew , Michael McDermott , Takeshi Fujisawa , Stephen Lynch , Jamie G Cooper , Alasdair J Gray , Tomas Jernberg , Nicholas L. Mills , on behalf of the POC-ET investigators
Introduction
Persistently elevated cardiac troponin (cTn) values are observed in many patients with suspected acute coronary syndrome (ACS) in the absence of myocardial infarction and may reflect underlying cardiac disease. Chronic myocardial injury is defined where cTn values are elevated and vary by ≤ 20 % on sequential measurements. We aimed to evaluate whether these criteria are reliable over short intervals applied in accelerated diagnostic pathways.
Methods
In a secondary analysis of a prospective, multi-centre cohort study of patients with suspected ACS, cTnT was measured at presentation, 1, 2 and 6–36 h, and the final diagnosis adjudicated according to the Fourth Universal Definition of Myocardial Infarction. Two criteria for chronic myocardial injury were compared: a relative change in cTn of ≤ 20 % and an absolute change < 3 ng/L, and the findings externally validated.
Results
At presentation cTnT was elevated in 242 of 1,000 (24 %) patients (73 years, 42 % female), of whom 94/242 (39 %), 13/242 (5 %) and 137/242 (56 %) had myocardial infarction, acute or chronic myocardial injury, respectively. A relative change of ≤ 20 % misclassified 58 % (59/101) and 49 % (48/98) of patients with a final diagnosis of acute myocardial injury or infarction at 1 and 2 h, respectively, whereas an absolute change of < 3 ng/L misclassified 22 % (22/101) and 15 % (15/98). In the validation cohort (n = 621), the relative and absolute change criteria at one hour misclassified 43 % (13/30) and 17 % (5/30) of those with myocardial infarction.
Conclusions
Chronic myocardial injury cannot reliably be differentiated from acute myocardial injury or infarction by recommended criteria over short remeasurement intervals in the Emergency Department. Longer intervals between sampling and absolute rather than relative criteria may reduce the risk of misclassification.
{"title":"Change in cardiac troponin T to differentiate acute from chronic myocardial injury in the Emergency Department","authors":"Bertil Lindahl , Alexander JF Thurston , Yong Yong Tew , Michael McDermott , Takeshi Fujisawa , Stephen Lynch , Jamie G Cooper , Alasdair J Gray , Tomas Jernberg , Nicholas L. Mills , on behalf of the POC-ET investigators","doi":"10.1016/j.clinbiochem.2025.111055","DOIUrl":"10.1016/j.clinbiochem.2025.111055","url":null,"abstract":"<div><h3>Introduction</h3><div>Persistently elevated cardiac troponin (cTn) values are observed in many patients with suspected acute coronary syndrome (ACS) in the absence of myocardial infarction and may reflect underlying cardiac disease. Chronic myocardial injury is defined where cTn values are elevated and vary by ≤ 20 % on sequential measurements. We aimed to evaluate whether these criteria are reliable over short intervals applied in accelerated diagnostic pathways.</div></div><div><h3>Methods</h3><div>In a secondary analysis of a prospective, multi-centre cohort study of patients with suspected ACS, cTnT was measured at presentation, 1, 2 and 6–36 h, and the final diagnosis adjudicated according to the Fourth Universal Definition of Myocardial Infarction. Two criteria for chronic myocardial injury were compared: a relative change in cTn of ≤ 20 % and an absolute change < 3 ng/L, and the findings externally validated.</div></div><div><h3>Results</h3><div>At presentation cTnT was elevated in 242 of 1,000 (24 %) patients (73 years, 42 % female), of whom 94/242 (39 %), 13/242 (5 %) and 137/242 (56 %) had myocardial infarction, acute or chronic myocardial injury, respectively. A relative change of ≤ 20 % misclassified 58 % (59/101) and 49 % (48/98) of patients with a final diagnosis of acute myocardial injury or infarction at 1 and 2 h, respectively, whereas an absolute change of < 3 ng/L misclassified 22 % (22/101) and 15 % (15/98). In the validation cohort (n = 621), the relative and absolute change criteria at one hour misclassified 43 % (13/30) and 17 % (5/30) of those with myocardial infarction.</div></div><div><h3>Conclusions</h3><div>Chronic myocardial injury cannot reliably be differentiated from acute myocardial injury or infarction by recommended criteria over short remeasurement intervals in the Emergency Department. Longer intervals between sampling and absolute rather than relative criteria may reduce the risk of misclassification.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111055"},"PeriodicalIF":2.1,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518890","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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