Pub Date : 2025-11-04DOI: 10.1016/j.clinbiochem.2025.111036
Kiara Theron , Jeannette Gauthier , Marijn Van Hulle , Murray Potter
{"title":"Corrigendum to “Optimization and validation of the Kairos Amino Acid Kit for plasma amino acid monitoring in inherited metabolic disorder patients” [Clin. Biochem. 138 (2025) 110960]","authors":"Kiara Theron , Jeannette Gauthier , Marijn Van Hulle , Murray Potter","doi":"10.1016/j.clinbiochem.2025.111036","DOIUrl":"10.1016/j.clinbiochem.2025.111036","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111036"},"PeriodicalIF":2.1,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451140","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 : 2025-11-01DOI: 10.1016/j.clinbiochem.2025.111037
Liubing Li , Ying Yuan , Siting Yi , Tangdan Ding , Hongji Zhu , Qiong Shi , Hongxia Tan , Runzhao Li , Yuheng Liu , Hongxu Xu , Min Liu , Dong Wang , Ruizhi Wang
Objective
To assess the diagnostic performance of soluble growth stimulation-expressed gene 2 (sST2) for cardiac involvement in patients with idiopathic inflammatory myopathies (IIMs).
Methods
From a cohort of 237 patients with IIMs, 86 were finally included and 18 exhibited cardiac involvement. The comparison of demographic, clinical, and laboratory parameters between IIM patients with and without cardiac involvement was conducted. Additionally, independent predictors for cardiac involvement and the diagnostic performance of sST2 were analyzed.
Results
The prevalence of cardiac involvement in IIMs was 20.9 %. The medians (interquartile range, IQR) of sST2 (65.6 [33.7–92.9] vs. 14.5 [7.8–25.4] μg/L) and N-terminal B-type pro-natriuretic peptide (NTproBNP, 120.2 [65.5–324.1] vs. 44.0 [16.8–104.6] ng/L) were significantly elevated in IIM patients with cardiac involvement compared with those without cardiac involvement. Multivariable logistic regression showed elevated levels of sST2 (OR = 3.936, 95 % CI 1.808–8.571, P = 0.001) and NTproBNP (OR = 2.308, 95 % CI 1.302–4.093, P = 0.004) were risk factors for cardiac involvement in IIM patients. The combined receiver operating characteristic (ROC) analysis of sST2 and NTproBNP indicated high diagnostic values in distinguishing IIM patients with cardiac involvement from those without cardiac involvement, with 94.4 % (95 % CI 72.2 %–99.7 %) sensitivity, 87.3 % (95 % CI 76.9 %–93.4 %) specificity, and 0.926 area under the ROC curve (95 % CI 0.840–1.000, P < 0.001).
Conclusion
sST2 serves as a valuable biomarker for detecting cardiac involvement in patients with IIMs.
{"title":"Assessment of serum sST2 for cardiac involvement in idiopathic inflammatory myopathies","authors":"Liubing Li , Ying Yuan , Siting Yi , Tangdan Ding , Hongji Zhu , Qiong Shi , Hongxia Tan , Runzhao Li , Yuheng Liu , Hongxu Xu , Min Liu , Dong Wang , Ruizhi Wang","doi":"10.1016/j.clinbiochem.2025.111037","DOIUrl":"10.1016/j.clinbiochem.2025.111037","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the diagnostic performance of soluble growth stimulation-expressed gene 2 (sST2) for cardiac involvement in patients with idiopathic inflammatory myopathies (IIMs).</div></div><div><h3>Methods</h3><div>From a cohort of 237 patients with IIMs, 86 were finally included and 18 exhibited cardiac involvement. The comparison of demographic, clinical, and laboratory parameters between IIM patients with and without cardiac involvement was conducted. Additionally, independent predictors for cardiac involvement and the diagnostic performance of sST2 were analyzed.</div></div><div><h3>Results</h3><div>The prevalence of cardiac involvement in IIMs was 20.9 %. The medians (interquartile range, IQR) of sST2 (65.6 [33.7–92.9] <em>vs.</em> 14.5 [7.8–25.4] μg/L) and N-terminal B-type pro-natriuretic peptide (NTproBNP, 120.2 [65.5–324.1] <em>vs.</em> 44.0 [16.8–104.6] ng/L) were significantly elevated in IIM patients with cardiac involvement compared with those without cardiac involvement. Multivariable logistic regression showed elevated levels of sST2 (OR = 3.936, 95 % CI 1.808–8.571, <em>P =</em> 0.001) and NTproBNP (OR = 2.308, 95 % CI 1.302–4.093, <em>P =</em> 0.004) were risk factors for cardiac involvement in IIM patients. The combined receiver operating characteristic (ROC) analysis of sST2 and NTproBNP indicated high diagnostic values in distinguishing IIM patients with cardiac involvement from those without cardiac involvement, with 94.4 % (95 % CI 72.2 %–99.7 %) sensitivity, 87.3 % (95 % CI 76.9 %–93.4 %) specificity, and 0.926 area under the ROC curve (95 % CI 0.840–1.000, <em>P</em> < 0.001).</div></div><div><h3>Conclusion</h3><div>sST2 serves as a valuable biomarker for detecting cardiac involvement in patients with IIMs.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111037"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430371","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 : 2025-11-01DOI: 10.1016/j.clinbiochem.2025.111033
Ricardo Rubio-Sánchez , Alberto Izquierdo-Martínez , Sara Martínez-Rodríguez , Lucia Mezquita Romero , José Ángel Noval-Padillo , Daniel Fatela-Cantillo , Juan M. Guerrero
Introduction
Blood hyperviscosity is a condition associated, in most cases, with Waldenström’s macroglobulinemia (WM) and other plasma cell dyscrasias, primarily due to the pentameric structure of immunoglobulin (Ig) M. Analytical interference in the determination of alanine aminotransferase with the Abbott Alinity c assay has recently been documented, related to increased blood viscosity as a result of a monoclonal component. The detection of this interference indicates a significant and isolated increase in the concentration of a single immunoglobulin, leading to the diagnosis of a previously unknown monoclonal gammopathy.
Case description
Thanks to the described interference and the expansion of analytical testing by the clinical laboratory, 15 patients with a previously unknown IgM monoclonal component were identified over 7 months. IgM levels ranged from 8.37 g/L, with a monoclonal component of 2.4 g/L, to 82.43 g/L, with a monoclonal component of 40.9 g/L. Ten patients were diagnosed with IgM monoclonal gammopathy of undetermined significance, one with asymptomatic biclonal gammopathy, and one with WM who presented with hyperviscosity syndrome, requiring plasmapheresis and treatment with rituximab-bendamustine.
Discussion
These cases highlight the importance of investigating laboratory test interferences, as they may be related to subclinical pathologies, such as monoclonal gammopathies. Detecting this interference and expanding laboratory testing can detect the pathology even before the appearance of related symptoms. This early identification allows for patient referral to the Hematology Department for appropriate follow-up, improving the prevention of complications and helping to make more timely therapeutic decisions.
{"title":"Diagnosis of patients with IgM monoclonal gammopathy due to analytical interference","authors":"Ricardo Rubio-Sánchez , Alberto Izquierdo-Martínez , Sara Martínez-Rodríguez , Lucia Mezquita Romero , José Ángel Noval-Padillo , Daniel Fatela-Cantillo , Juan M. Guerrero","doi":"10.1016/j.clinbiochem.2025.111033","DOIUrl":"10.1016/j.clinbiochem.2025.111033","url":null,"abstract":"<div><h3>Introduction</h3><div>Blood hyperviscosity is a condition associated, in most cases, with Waldenström’s macroglobulinemia (WM) and other plasma cell dyscrasias, primarily due to the pentameric structure of immunoglobulin (Ig) M. Analytical interference in the determination of alanine aminotransferase with the Abbott Alinity c assay has recently been documented, related to increased blood viscosity as a result of a monoclonal component. The detection of this interference indicates a significant and isolated increase in the concentration of a single immunoglobulin, leading to the diagnosis of a previously unknown monoclonal gammopathy.</div></div><div><h3>Case description</h3><div>Thanks to the described interference and the expansion of analytical testing by the clinical laboratory, 15 patients with a previously unknown IgM monoclonal component were identified over 7 months. IgM levels ranged from 8.37 g/L, with a monoclonal component of 2.4 g/L, to 82.43 g/L, with a monoclonal component of 40.9 g/L. Ten patients were diagnosed with IgM monoclonal gammopathy of undetermined significance, one with asymptomatic biclonal gammopathy, and one with WM who presented with hyperviscosity syndrome, requiring plasmapheresis and treatment with rituximab-bendamustine.</div></div><div><h3>Discussion</h3><div>These cases highlight the importance of investigating laboratory test interferences, as they may be related to subclinical pathologies, such as monoclonal gammopathies. Detecting this interference and expanding laboratory testing can detect the pathology even before the appearance of related symptoms. This early identification allows for patient referral to the Hematology Department for appropriate follow-up, improving the prevention of complications and helping to make more timely therapeutic decisions.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111033"},"PeriodicalIF":2.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145430376","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 : 2025-10-30DOI: 10.1016/j.clinbiochem.2025.111035
Helle Pilgaard Kristiansen , Jesper Petersen , Peter Schou , Peter H. Nissen , Anne Winther-Larsen
Background
Beta-thalassemia is a common monogenic disease, especially in malaria-endemic areas. It is mainly caused by point mutations in the beta-globin gene (HBB) while large deletions are more rarely described. Here, a novel, large deletion encompassing the entire HBB gene causing beta-thalassemia in an ethnically Danish male is described.
Case report
A 60-year-old male with no family history of anemia was admitted to the local Department of Medicine with microcytotic anemia. He had observed fatigue and slight dizziness, but despite this, he felt healthy. His blood tests showed no signs of iron deficiency and a hemoglobinopathy was suspected. Hemoglobin fractionation by ion-exchange high-performance liquid chromatography revealed an elevated HbF of 5.9 % and an increased HbA2 of 8.5 %. GAP-PCR of the alpha-thalassemia HBA1/HBA2 genes and Sanger sequencing of the HBB gene showed none of the common thalassemia-causing variations. Hence, multiplex ligation dependent probe amplification was performed and a deletion variant was identified that resulted in the complete loss of the HBB gene. The exact breakpoints were identified using Sanger sequencing, revealing a novel 17.9 kb deletion (NC000011.10:g.5211831_5229725del) not previously described in the literature or in databases. The deletion was consistent with beta-thalassemia trait in accordance with the patient’s symptoms.
Conclusion
We present a novel large deletion of the HBB gene causing beta-thalassemia trait detected in an ethnically Danish male. Thalassemia must be considered in patients with microcytosis of unknown cause despite a Northern European ethnicity.
{"title":"A novel 17.9 kb deletion of the beta-globin gene causing beta-thalassemia trait in a Danish male","authors":"Helle Pilgaard Kristiansen , Jesper Petersen , Peter Schou , Peter H. Nissen , Anne Winther-Larsen","doi":"10.1016/j.clinbiochem.2025.111035","DOIUrl":"10.1016/j.clinbiochem.2025.111035","url":null,"abstract":"<div><h3>Background</h3><div>Beta-thalassemia is a common monogenic disease, especially in malaria-endemic areas. It is mainly caused by point mutations in the beta-globin gene (<em>HBB</em>) while large deletions are more rarely described. Here, a novel, large deletion encompassing the entire <em>HBB</em> gene causing beta-thalassemia in an ethnically Danish male is described.</div></div><div><h3>Case report</h3><div>A 60-year-old male with no family history of anemia was admitted to the local Department of Medicine with microcytotic anemia. He had observed fatigue and slight dizziness, but despite this, he felt healthy. His blood tests showed no signs of iron deficiency and a hemoglobinopathy was suspected. Hemoglobin fractionation by ion-exchange high-performance liquid chromatography revealed an elevated HbF of 5.9 % and an increased HbA2 of 8.5 %. GAP-PCR of the alpha-thalassemia <em>HBA1</em>/<em>HBA2</em> genes and Sanger sequencing of the <em>HBB</em> gene showed none of the common thalassemia-causing variations. Hence, multiplex ligation dependent probe amplification was performed and a deletion variant was identified that resulted in the complete loss of the <em>HBB</em> gene. The exact breakpoints were identified using Sanger sequencing, revealing a novel 17.9 kb deletion (NC000011.10:g.5211831_5229725del) not previously described in the literature or in databases. The deletion was consistent with beta-thalassemia trait in accordance with the patient’s symptoms.</div></div><div><h3>Conclusion</h3><div>We present a novel large deletion of the <em>HBB</em> gene causing beta-thalassemia trait detected in an ethnically Danish male. Thalassemia must be considered in patients with microcytosis of unknown cause despite a Northern European ethnicity.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111035"},"PeriodicalIF":2.1,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412706","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 : 2025-10-28DOI: 10.1016/j.clinbiochem.2025.111034
Elisa Buzzatti , Fabiana Esposito , Maria Morello , Vanessa Rossi , Maria Christina Cox , Ombretta Annibali , Enrico Santinelli , Maria Antonietta Irno-Consalvo , Giovangiacinto Paterno , Lucia Cardillo , Massimiliano Postorino , Adriano Venditti , Maria Ilaria Del Principe
Introduction
A significant clinical challenge in the management of hematologic malignancies is the occurrence of central nervous system (CNS) involvement. In non-Hodgkin lymphoma (NHL), it occurs in varying percentages depending on the subtype and identifying patients is crucial but challenging. Furthermore, a definitive gold standard for diagnosing leptomeningeal involvement is still lacking. Conventional cytology (CC) of cerebrospinal fluid (CSF) has high specificity but low sensitivity. Multiparametric flow cytometry offers superior sensitivity but is limited by CSF cellularity and the need for specialized expertise, a resource not available at every institution. CSF cytokine analysis is emerging as a promising diagnostic approach, with IL-6 and IL-10 showing potential as biomarkers.
Objective
This prospective study investigated the utility of dosing the aforementioned cytokine in serum and CSF samples for diagnosing CNS involvement in non-primary CNS lymphoma patients.
Methods
CSF samples were analyzed using CC and IL-6/IL-10 assays. IL-6 and IL-10 levels were then compared between CC-positive (CC + ) and CC-negative (CC–) patients.
Results
The study cohort included 27 patients, with a median age of 71 years. Six patients (22.2 %) were CC + . In CSF, statistically significant differences were observed for both IL-6 (p = 0.02) and IL-10 (p = 0.04) levels between CC + and CC– patients, with higher levels in CC + patients. Elevated CSF IL-6 and IL-10 levels were also associated with elevated LDH, advanced disease stage, and elevated CSF protein.
Conclusions
This study suggests that CSF IL-6 and IL-10 are potential, widely available biomarkers for early detection of CNS involvement in NHL, offering a complement to traditional cytological analysis in clinical laboratories.
{"title":"The contribution of IL-10 and IL-6 as potential biomarkers for detecting central nervous system involvement in non-Hodgkin lymphomas","authors":"Elisa Buzzatti , Fabiana Esposito , Maria Morello , Vanessa Rossi , Maria Christina Cox , Ombretta Annibali , Enrico Santinelli , Maria Antonietta Irno-Consalvo , Giovangiacinto Paterno , Lucia Cardillo , Massimiliano Postorino , Adriano Venditti , Maria Ilaria Del Principe","doi":"10.1016/j.clinbiochem.2025.111034","DOIUrl":"10.1016/j.clinbiochem.2025.111034","url":null,"abstract":"<div><h3>Introduction</h3><div>A significant clinical challenge in the management of hematologic malignancies is the occurrence of central nervous system (CNS) involvement. In non-Hodgkin lymphoma (NHL), it occurs in varying percentages depending on the subtype and identifying patients is crucial but challenging. Furthermore, a definitive gold standard for diagnosing leptomeningeal involvement is still lacking. Conventional cytology (CC) of cerebrospinal fluid (CSF) has high specificity but low sensitivity. Multiparametric flow cytometry offers superior sensitivity but is limited by CSF cellularity and the need for specialized expertise, a resource not available at every institution. CSF cytokine analysis is emerging as a promising diagnostic approach, with IL-6 and IL-10 showing potential as biomarkers.</div></div><div><h3>Objective</h3><div>This prospective study investigated the utility of dosing the aforementioned cytokine in serum and CSF samples for diagnosing CNS involvement in non-primary CNS lymphoma patients.</div></div><div><h3>Methods</h3><div>CSF samples were analyzed using CC and IL-6/IL-10 assays. IL-6 and IL-10 levels were then compared between CC-positive (CC + ) and CC-negative (CC–) patients.</div></div><div><h3>Results</h3><div>The study cohort included 27 patients, with a median age of 71 years. Six patients (22.2 %) were CC + . In CSF, statistically significant differences were observed for both IL-6 (p = 0.02) and IL-10 (p = 0.04) levels between CC + and CC– patients, with higher levels in CC + patients. Elevated CSF IL-6 and IL-10 levels were also associated with elevated LDH, advanced disease stage, and elevated CSF protein.</div></div><div><h3>Conclusions</h3><div>This study suggests that CSF IL-6 and IL-10 are potential, widely available biomarkers for early detection of CNS involvement in NHL, offering a complement to traditional cytological analysis in clinical laboratories.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111034"},"PeriodicalIF":2.1,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408395","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 : 2025-10-25DOI: 10.1016/j.clinbiochem.2025.111032
Carl E. Wolf , Felix I Medrano , Justin L. Poklis , Paul J. Jannetto , Grace R. Williams
Background
The United States continues to face a persistent opioid epidemic, now in its fourth wave, characterized primarily by fentanyl analogs. Detecting fentanyl analogs and synthetic opioids is a critical concern to clinical and forensic laboratories.
Objectives
Evaluate the ability of each assay to detect the opioids at 1, 10, or 100 ng/mL. 216 opioids from the CDC’s TOM Kits® were evaluated using four commercially available fentanyl immunoassays: ARK™ Fentanyl II, Immunalysis Fentanyl Urine HEIA®, Immunalysis Fentanyl Urine SEFRIA® Drug Screening Kit, and the Lin-Zhi International Fentanyl II Enzyme Immunoassay.
Results
The difference in reactivity of the immunoassay’s reagents was evaluated in conjunction with the chemical structure of each opioid. All four immunoassays detected 106 of the 216 opioids at the concentrations tested. Twenty-eight opioids were not detected by any assay and 17 of these were the emerging synthetic opioids. At the lowest concentration tested (1 ng/mL), the ARK™ Fentanyl II assay detected 36 compounds, the Immunalysis SEFRIA® assay detected 74, LZI detected 5, and the Immunalysis HEIA® assay detected 18. The undetected opioids included the surgical anesthetic parent compounds remifentanil and alfentanil, and sufentanil’s metabolite, norsufentanil.
Conclusions
The detectability of fentanyl analogs and synthetic opioids varies by assay, and it may be possible to predict the detection or lack thereof for a particular assay based on a pattern elucidated by the analysis of the TOMs Opioid compound set. This data may be used to evaluate the potential false negative or false positive results of commercially available fentanyl and norfentanyl homogeneous immunoassays and to predict the likely target epitope of each assay.
{"title":"Determining the detection of 216 fentanyl analogs and synthetic opioids and predicting epitopes using four commercial immunoassays","authors":"Carl E. Wolf , Felix I Medrano , Justin L. Poklis , Paul J. Jannetto , Grace R. Williams","doi":"10.1016/j.clinbiochem.2025.111032","DOIUrl":"10.1016/j.clinbiochem.2025.111032","url":null,"abstract":"<div><h3>Background</h3><div>The United States continues to face a persistent opioid epidemic, now in its fourth wave, characterized primarily by fentanyl analogs. Detecting fentanyl analogs and synthetic opioids is a critical concern to clinical and forensic laboratories.</div></div><div><h3>Objectives</h3><div>Evaluate the ability of each assay to detect the opioids at 1, 10, or 100 ng/mL. 216 opioids from the CDC’s TOM Kits® were evaluated using four commercially available fentanyl immunoassays: ARK™ Fentanyl II, Immunalysis Fentanyl Urine HEIA®, Immunalysis Fentanyl Urine SEFRIA® Drug Screening Kit, and the Lin-Zhi International Fentanyl II Enzyme Immunoassay.</div></div><div><h3>Results</h3><div>The difference in reactivity of the immunoassay’s reagents was evaluated in conjunction with the chemical structure of each opioid. All four immunoassays detected 106 of the 216 opioids at the concentrations tested. Twenty-eight opioids were not detected by any assay and 17 of these were the emerging synthetic opioids. At the lowest concentration tested (1 ng/mL), the ARK™ Fentanyl II assay detected 36 compounds, the Immunalysis SEFRIA® assay detected 74, LZI detected 5, and the Immunalysis HEIA® assay detected 18. The undetected opioids included the surgical anesthetic parent compounds remifentanil and alfentanil, and sufentanil’s metabolite, norsufentanil.</div></div><div><h3>Conclusions</h3><div>The detectability of fentanyl analogs and synthetic opioids varies by assay, and it may be possible to predict the detection or lack thereof for a particular assay based on a pattern elucidated by the analysis of the TOMs Opioid compound set. This data may be used to evaluate the potential false negative or false positive results of commercially available fentanyl and norfentanyl homogeneous immunoassays and to predict the likely target epitope of each assay.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111032"},"PeriodicalIF":2.1,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516753","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 : 2025-10-22DOI: 10.1016/j.clinbiochem.2025.111030
Yubin Lei , Anik Forest , Caroline Daneault , Ying Liu , Kostas Pantopoulos , Adisak Tantiworawit , Arintaya Phrommintikul , Siriporn Chattipakorn , Nipon Chattipakorn , Christine Des Rosiers , Gary Sweeney
Objectives
Oxidative stress, driven by iron imbalance from recurrent blood transfusions, is a major contributor to cardiometabolic complications in transfusion-dependent thalassemia (TDT). N-acetylcysteine (NAC), a glutathione precursor, is a well-known antioxidant with cardioprotective effects achieved by mitigating the impact of oxidative stress on cell metabolism. Current study aimed to evaluate the effect of a six-month NAC intervention by focusing on previously reported changes in the plasma lipidome in TDT patients.
Design & Methods
A randomized cohort of 62 Thai TDT patients was divided into two groups: both received six months of cocktail therapy involving standardized blood transfusions and iron chelator therapy, with the intervention group additionally receiving 600 mg oral NAC daily and the control group receiving a placebo. Plasma lipidomic profiling was performed using mass spectrometry to assess 339 previously annotated lipid features significantly altered in TDT patients. Clinical parameters, including heart rate variability (HRV), were measured before and after the intervention.
Results
NAC treatment significantly altered 152 plasma lipid features (P < 0.03), 78 of which were also altered in the placebo group. Importantly, 29 lipid features (26 unique lipids) were restored toward healthy control levels following NAC treatment. Within this subset, circulating diacylglycerophosphocholines PC(14:0_20:4) and cholesteryl ester CE 18:3 positively correlated with HRV, a clinical marker markedly improved in NAC-treated patients.
Conclusions
Six-month oral NAC intervention modified the plasma lipidomic profile in TDT patients, partially restoring lipid species likely disrupted by chronic oxidative stress. The observed correlation between NAC-responsive lipids and improved HRV suggests a potential cardioprotective effect. These findings highlight the potential of NAC as an adjunctive therapy to mitigate cardiometabolic complications in TDT.
{"title":"Correlation of plasma lipidomic profiles with cardiometabolic disease in transfusion-dependent thalassemia patients with six-month N-acetylcysteine intervention: A prospective cohort study","authors":"Yubin Lei , Anik Forest , Caroline Daneault , Ying Liu , Kostas Pantopoulos , Adisak Tantiworawit , Arintaya Phrommintikul , Siriporn Chattipakorn , Nipon Chattipakorn , Christine Des Rosiers , Gary Sweeney","doi":"10.1016/j.clinbiochem.2025.111030","DOIUrl":"10.1016/j.clinbiochem.2025.111030","url":null,"abstract":"<div><h3>Objectives</h3><div>Oxidative stress, driven by iron imbalance from recurrent blood transfusions, is a major contributor to cardiometabolic complications in transfusion-dependent thalassemia (TDT). N-acetylcysteine (NAC), a glutathione precursor, is a well-known antioxidant with cardioprotective effects achieved by mitigating the impact of oxidative stress on cell metabolism. Current study aimed to evaluate the effect of a six-month NAC intervention by focusing on previously reported changes in the plasma lipidome in TDT patients.</div><div>Design & Methods</div><div>A randomized cohort of 62 Thai TDT patients was divided into two groups: both received six months of cocktail therapy involving standardized blood transfusions and iron chelator therapy, with the intervention group additionally receiving 600 mg oral NAC daily and the control group receiving a placebo. Plasma lipidomic profiling was performed using mass spectrometry to assess 339 previously annotated lipid features significantly altered in TDT patients. Clinical parameters, including heart rate variability (HRV), were measured before and after the intervention.</div></div><div><h3>Results</h3><div>NAC treatment significantly altered 152 plasma lipid features (P < 0.03), 78 of which were also altered in the placebo group. Importantly, 29 lipid features (26 unique lipids) were restored toward healthy control levels following NAC treatment. Within this subset, circulating diacylglycerophosphocholines PC(14:0_20:4) and cholesteryl ester CE 18:3 positively correlated with HRV, a clinical marker markedly improved in NAC-treated patients.</div></div><div><h3>Conclusions</h3><div>Six-month oral NAC intervention modified the plasma lipidomic profile in TDT patients, partially restoring lipid species likely disrupted by chronic oxidative stress. The observed correlation between NAC-responsive lipids and improved HRV suggests a potential cardioprotective effect. These findings highlight the potential of NAC as an adjunctive therapy to mitigate cardiometabolic complications in TDT.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111030"},"PeriodicalIF":2.1,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358079","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 : 2025-10-21DOI: 10.1016/j.clinbiochem.2025.111031
Raúl Rigo-Bonnin , Virgínia Mas-Bosch
<div><h3>Background</h3><div>Measurement uncertainty (MU) is essential for interpreting laboratory results. While MU is often reported for directly measured quantities, it is rarely considered for derived (calculated) ones, despite their widespread clinical use. This study assessed the impact of MU on interpretation of derived quantities by comparing directly measured and calculated results.</div><div><em>Design & Methods:</em> Following ISO/TS 20914:2019 and GUM guidelines, MU was estimated for directly measured and derived biological quantities. Ionized magnesium (iMg) was analyzed as a case, comparing direct measurement with regression-based estimates. The approach was extended to estimated glomerular filtration rate (eGFR), low-density lipoprotein cholesterol (cLDL, direct enzymatic vs. Friedewald), free testosterone (direct vs. Vermeulen calculation), and the anion gap (AG, incorporating calculated bicarbonate). Clinical interpretation was evaluated by comparing coverage intervals with biological reference intervals and clinical decision limits.</div></div><div><h3>Results</h3><div>Direct iMg measurement at 0.520 mmol/L yielded a relative expanded uncertainty (<em>U</em>, <em>k</em> = 2) of 4.1 %. Regression-derived values showed <em>U</em> up to 21.4 %. For eGFR, <em>U</em> ranged from 3.8 % to 5.5 %. At 63 mL/min/1.73 m<sup>2</sup>, coverage intervals overlapped the 60 mL/min/1.73 m<sup>2</sup> decision limit, altering chronic kidney disease staging. Direct cLDL measurement (2.54 mmol/L) had <em>U</em> = 4.8 %, while Friedewald calculation (2.60 mmol/L) showed <em>U</em> = 4.8 %; both overlapped therapeutic decision limits. Free testosterone measurement (0.221 nmol/L) had <em>U</em> = 13.9 %, whereas Vermeulen-derived values (0.210 nmol/L) reached 24.1 %. For AG, an abnormal value (28.2 mmol/L) remained pathological, but values of 20.3 or 14.0 mmol/L overlapped the 18 mmol/L limit, producing indeterminate classification.</div></div><div><h3>Conclusions</h3><div>MU significantly influences the interpretation of derived laboratory quantities, particularly near decision limits. Systematic reporting of MU, in line with international recommendations, would enable more reliable interpretation, improve patient safety, and reduce misclassification in clinical decision-making.</div><div>Abbreviations: MU, measurement uncertainty; eGFR, estimated glomerular filtration rate, cLDL, substance concentration of LDL-cholesterol in serum; fTes, substance concentration of free testosterone in serum; AG, anion gap; iMg, substance concentration of ionized magnesium in serum; tMg, substance concentration of (total) magnesium in serum; Alb, mass concentration of albumin in serum; IP, substance concentration of inorganic phosphate in serum; PaCO<sub>2</sub>, partial pressure of carbon dioxide in arterial blood; BRI, biological reference interval; <em>y</em>, derived quantity; <span><math><mrow><msub><mi>u</mi><mi>c</mi></msub><mrow><mo>(</mo><mi>y</mi><mo>)<
背景：测量不确定度（MU）对于解释实验室结果至关重要。虽然MU经常被报道为直接测量的数量，但很少考虑衍生（计算）的数量，尽管它们在临床广泛使用。本研究通过比较直接测量和计算结果，评估了MU对推导量解释的影响。设计和方法：根据ISO/TS 20914:2019和GUM指南，对直接测量和衍生的生物量进行了MU估计。以离子镁（iMg）为例，比较了直接测量和基于回归的估计。该方法扩展到估计肾小球滤过率（eGFR），低密度脂蛋白胆固醇（cLDL，直接酶法与弗里德瓦尔德法），游离睾酮（直接与Vermeulen法计算）和阴离子间隙（AG，结合计算的碳酸氢盐）。通过比较覆盖区间与生物学参考区间和临床决策界限来评估临床解释。结果：在0.520 mmol/L下直接测定iMg，相对扩展不确定度（U, k = 2）为4.1 %。回归值显示U高达21.4 %。对于eGFR， U范围从3.8 %到5.5 %。在63 mL/min/1.73 m2时，覆盖间隔重叠了60 mL/min/1.73 m2的决定界限，改变了慢性肾脏疾病的分期。直接cLDL测定（2.54 mmol/L） U = 4.8 %，Friedewald计算（2.60 mmol/L） U = 4.8 %；两者都有重叠的治疗决策限制。游离睾酮测量值（0.221 nmol/L） U = 13.9 %，而vermeulen衍生值（0.210 nmol/L）达到24.1 %。对于AG，异常值（28.2 mmol/L）仍然是病理的，但20.3或14.0 mmol/L的值与18 mmol/L的限值重叠，产生不确定的分类。结论：MU显著影响推导出的实验室数量的解释，特别是在决策极限附近。与国际建议一致的MU系统报告将实现更可靠的解释，提高患者安全，并减少临床决策中的错误分类。缩写词：MU，测量不确定度；eGFR，估计肾小球滤过率，cLDL，血清中ldl -胆固醇物质浓度；fTes：血清游离睾酮物质浓度；AG，阴离子间隙；iMg：血清中离子化镁的物质浓度；tMg：血清中（总）镁物质浓度；Alb：血清白蛋白质量浓度；IP：血清中无机磷酸盐物质浓度；PaCO2：动脉血中二氧化碳分压；BRI，生物参考区间；Y，导出量；Uc (y)，衍生量y的组合标准不确定度；Xi，测量量或经验常数i；Xj，测量量或经验常数j；[公式：见文]，量xi与xj的相关系数；∂y∂xi，测量常数或经验常数i的灵敏度系数；∂y∂xj，测量常数或经验常数j的灵敏度系数；Ucal，与最终用户校准器指定值相关的不确定度；uRw，与中间精度相关的不确定度；Ub，与偏差相关的任何校正因子相关的不确定性；IFU：使用说明；CI，置信区间；uciMg，与iMg相关的综合不确定性；与iMg相关的不确定性扩大。
{"title":"Measurement uncertainty in derived (calculated) biological quantities: Impact on clinical interpretation","authors":"Raúl Rigo-Bonnin , Virgínia Mas-Bosch","doi":"10.1016/j.clinbiochem.2025.111031","DOIUrl":"10.1016/j.clinbiochem.2025.111031","url":null,"abstract":"<div><h3>Background</h3><div>Measurement uncertainty (MU) is essential for interpreting laboratory results. While MU is often reported for directly measured quantities, it is rarely considered for derived (calculated) ones, despite their widespread clinical use. This study assessed the impact of MU on interpretation of derived quantities by comparing directly measured and calculated results.</div><div><em>Design & Methods:</em> Following ISO/TS 20914:2019 and GUM guidelines, MU was estimated for directly measured and derived biological quantities. Ionized magnesium (iMg) was analyzed as a case, comparing direct measurement with regression-based estimates. The approach was extended to estimated glomerular filtration rate (eGFR), low-density lipoprotein cholesterol (cLDL, direct enzymatic vs. Friedewald), free testosterone (direct vs. Vermeulen calculation), and the anion gap (AG, incorporating calculated bicarbonate). Clinical interpretation was evaluated by comparing coverage intervals with biological reference intervals and clinical decision limits.</div></div><div><h3>Results</h3><div>Direct iMg measurement at 0.520 mmol/L yielded a relative expanded uncertainty (<em>U</em>, <em>k</em> = 2) of 4.1 %. Regression-derived values showed <em>U</em> up to 21.4 %. For eGFR, <em>U</em> ranged from 3.8 % to 5.5 %. At 63 mL/min/1.73 m<sup>2</sup>, coverage intervals overlapped the 60 mL/min/1.73 m<sup>2</sup> decision limit, altering chronic kidney disease staging. Direct cLDL measurement (2.54 mmol/L) had <em>U</em> = 4.8 %, while Friedewald calculation (2.60 mmol/L) showed <em>U</em> = 4.8 %; both overlapped therapeutic decision limits. Free testosterone measurement (0.221 nmol/L) had <em>U</em> = 13.9 %, whereas Vermeulen-derived values (0.210 nmol/L) reached 24.1 %. For AG, an abnormal value (28.2 mmol/L) remained pathological, but values of 20.3 or 14.0 mmol/L overlapped the 18 mmol/L limit, producing indeterminate classification.</div></div><div><h3>Conclusions</h3><div>MU significantly influences the interpretation of derived laboratory quantities, particularly near decision limits. Systematic reporting of MU, in line with international recommendations, would enable more reliable interpretation, improve patient safety, and reduce misclassification in clinical decision-making.</div><div>Abbreviations: MU, measurement uncertainty; eGFR, estimated glomerular filtration rate, cLDL, substance concentration of LDL-cholesterol in serum; fTes, substance concentration of free testosterone in serum; AG, anion gap; iMg, substance concentration of ionized magnesium in serum; tMg, substance concentration of (total) magnesium in serum; Alb, mass concentration of albumin in serum; IP, substance concentration of inorganic phosphate in serum; PaCO<sub>2</sub>, partial pressure of carbon dioxide in arterial blood; BRI, biological reference interval; <em>y</em>, derived quantity; <span><math><mrow><msub><mi>u</mi><mi>c</mi></msub><mrow><mo>(</mo><mi>y</mi><mo>)<","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111031"},"PeriodicalIF":2.1,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354120","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 : 2025-10-15DOI: 10.1016/j.clinbiochem.2025.111023
Hongmei Yang, Jianxing Guo, Guowei Ye, Dongxia Wang, Yimin Yang
This case report describes a patient with HFE-related acute porphyria-like attack triggered by severe influenza A pneumonia. The patient was admitted with fever, dyspnea, and abdominal pain and was diagnosed with severe influenza A pneumonia, acute respiratory failure, and septic shock. On the third day of hospitalization, the patient developed profound shock requiring mechanical ventilation and tested positive for influenza A virus. During treatment, significant liver dysfunction was observed, along with clinical manifestations including abdominal pain, loss of consciousness, and bilateral strabismus, suggesting neurological involvement. The diagnosis of acute porphyria-like attack was confirmed by positive urine porphobilinogen testing and genetic detection of a HFEH63D mutation. This case highlights the importance of maintaining a high index of suspicion for porphyrin metabolism dysfunction in critically ill patients, particularly in the setting of infection or other precipitating factors. Timely diagnosis and management can significantly improve patient outcomes. These findings provide new insights into the clinical recognition of porphyria, especially in critically ill patients, and underscore the importance of multidisciplinary collaboration and meticulous diagnostic evaluation.
{"title":"HFE related acute porphyria-like attack induced by severe influenza A pneumonia","authors":"Hongmei Yang, Jianxing Guo, Guowei Ye, Dongxia Wang, Yimin Yang","doi":"10.1016/j.clinbiochem.2025.111023","DOIUrl":"10.1016/j.clinbiochem.2025.111023","url":null,"abstract":"<div><div>This case report describes a patient with <em>HFE</em>-related acute porphyria-like attack triggered by severe influenza A pneumonia. The patient was admitted with fever, dyspnea, and abdominal pain and was diagnosed with severe influenza A pneumonia, acute respiratory failure, and septic shock. On the third day of hospitalization, the patient developed profound shock requiring mechanical ventilation and tested positive for influenza A virus. During treatment, significant liver dysfunction was observed, along with clinical manifestations including abdominal pain, loss of consciousness, and bilateral strabismus, suggesting neurological involvement. The diagnosis of acute porphyria-like attack was confirmed by positive urine porphobilinogen testing and genetic detection of a <em>HFE<sup>H63D</sup></em> mutation. This case highlights the importance of maintaining a high index of suspicion for porphyrin metabolism dysfunction in critically ill patients, particularly in the setting of infection or other precipitating factors. Timely diagnosis and management can significantly improve patient outcomes. These findings provide new insights into the clinical recognition of porphyria, especially in critically ill patients, and underscore the importance of multidisciplinary collaboration and meticulous diagnostic evaluation.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111023"},"PeriodicalIF":2.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312149","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 : 2025-10-14DOI: 10.1016/j.clinbiochem.2025.111029
Manal O Elnenaei , Andrea Thoni , Andre Mattman
Healthcare contributes around 5–10% of global carbon emissions, alongside other pollutants, through utilization of over-stretched planetary resources. This creates a paradox in which efforts to protect health also generate risks to population health by contributing to the decline of planetary ecosystems- the foundation for health on which the healthcare system operates. This unsustainable cycle demands an urgent, unified front across all domains of clinical practice. Laboratory medicine, as a key entry point in the patient diagnostic pathway, is well-positioned to lead the required transformative change. While concepts such as sustainability and stewardship have been used interchangeably to rationalize resource use, the time has come to advance toward a model of ‘degrowth’ in the diagnostic laboratory. In healthcare, degrowth aims to minimize environmental harm by deliberately shrinking the consumption of unnecessary resources, particularly those from diagnostic and therapeutic interventions, without compromising patient outcomes. Diagnostic laboratories can support degrowth activities directly by adopting ‘green laboratory’ practices that include consuming less energy, minimizing waste (especially of reagents and non-recyclables) and optimizing test utilization by curbing low-value or unnecessary testing. They can also make an indirect impact by helping shift healthcare culture through shaping clinical guidelines using a degrowth lens, applying an environmental impact assessment whenever a new test is developed and advocating for sustainability declarations in publications that present new diagnostic approaches or technologies. When supported by effective stewardship programs, laboratories can serve as gatekeepers of diagnostic information and play a powerful role in aligning clinical decision-making with environmental responsibility. By embracing principles of degrowth in laboratory medicine, we have a chance, as well as a duty, to influence healthcare practices towards more ethical and environmentally responsible choices.
{"title":"Degrowth in the clinical laboratory: A key step towards integrating planetary health into the healthcare system","authors":"Manal O Elnenaei , Andrea Thoni , Andre Mattman","doi":"10.1016/j.clinbiochem.2025.111029","DOIUrl":"10.1016/j.clinbiochem.2025.111029","url":null,"abstract":"<div><div>Healthcare contributes around 5–10% of global carbon emissions, alongside other pollutants, through utilization of over-stretched planetary resources. This creates a paradox in which efforts to protect health also generate risks to population health by contributing to the decline of planetary ecosystems- the foundation for health on which the healthcare system operates. This unsustainable cycle demands an urgent, unified front across all domains of clinical practice. Laboratory medicine, as a key entry point in the patient diagnostic pathway, is well-positioned to lead the required transformative change. While concepts such as sustainability and stewardship have been used interchangeably to rationalize resource use, the time has come to advance toward a model of ‘degrowth’ in the diagnostic laboratory. In healthcare, degrowth aims to minimize environmental harm by deliberately shrinking the consumption of unnecessary resources, particularly those from diagnostic and therapeutic interventions, without compromising patient outcomes. Diagnostic laboratories can support degrowth activities directly by adopting ‘green laboratory’ practices that include consuming less energy, minimizing waste (especially of reagents and non-recyclables) and optimizing test utilization by curbing low-value or unnecessary testing. They can also make an indirect impact by helping shift healthcare culture through shaping clinical guidelines using a degrowth lens, applying an environmental impact assessment whenever a new test is developed and advocating for sustainability declarations in publications that present new diagnostic approaches or technologies. When supported by effective stewardship programs, laboratories can serve as gatekeepers of diagnostic information and play a powerful role in aligning clinical decision-making with environmental responsibility. By embracing principles of degrowth in laboratory medicine, we have a chance, as well as a duty, to influence healthcare practices towards more ethical and environmentally responsible choices.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111029"},"PeriodicalIF":2.1,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307057","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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