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}
Pub Date : 2025-10-10DOI: 10.1016/j.clinbiochem.2025.111024
Gonzalo Verdú , Antonio Jesús Blanco-Carrasco , Raquel Ruiz-García , Albert Saiz , Manuel Morales-Ruiz , Gregori Casals
Introduction
Anti-GAD65 is an established diagnostic biomarker for autoimmune diabetes and neurological syndromes associated with GAD antibody-spectrum disorders. Automated chemiluminescence-based immunoassays such as Maglumi are increasingly used, but their behavior at high antibody concentrations remains poorly characterized. We report the analytical concordance between Maglumi and radioimmunoassay (RIA), the cut-off titer that differentiates neurological from diabetic patients, and the hook effect of the immunoassay.
Materials and methods
Anti-GAD65 levels were analyzed in samples from 90 patients with suspected autoimmune diabetes or neurological syndromes, using Maglumi 2000® and RIA (Medipan®). Analytical concordance was assessed by Passing–Bablok regression, Bland–Altman plots, and Cohen’s kappa. ROC curve analysis identified diagnostic thresholds, and dilution studies were performed in samples with unexpectedly low values to assess a potential hook effect.
Results
Maglumi results were approximately five times higher than RIA results (slope = 5.364; R2 = 0.908); agreement was higher in endocrine (R2 = 0.998) than in neurological patients (R2 = 0.891). A cutoff of 6778 IU/mL discriminated neurological patients from diabetic patients (AUC = 0.96). Sixteen samples showed a hook effect, with direct (undiluted) values ≤273 IU/mL, while the corrected titers after dilution exceeded 20,000 IU/mL. A linear regression confirmed an inverse relationship between direct and true titers (r = –0.79, p < 0.05).
Discussion
Maglumi anti-GAD65 immunoassay provides reliable discrimination between endocrine and neurological patients but requires method-specific cutoffs to avoid misclassification. Hook effect was frequent in high-titer neurological samples, potentially leading to misdiagnosis, underscoring the need for routine dilution protocols to improve diagnostic reliability.
Conclusions
Standardized dilution protocols and appropriate cutoffs are essential to ensure reliable anti-GAD65 testing with Maglumi chemiluminescent immunoassay, particularly in neurological indications.
{"title":"Clinical relevance of the Maglumi immunoassay for anti-GAD65 in diabetes and neurological disorders: Analytical challenges and diagnostic insights","authors":"Gonzalo Verdú , Antonio Jesús Blanco-Carrasco , Raquel Ruiz-García , Albert Saiz , Manuel Morales-Ruiz , Gregori Casals","doi":"10.1016/j.clinbiochem.2025.111024","DOIUrl":"10.1016/j.clinbiochem.2025.111024","url":null,"abstract":"<div><h3>Introduction</h3><div>Anti-GAD65 is an established diagnostic biomarker for autoimmune diabetes and neurological syndromes associated with GAD antibody-spectrum disorders. Automated chemiluminescence-based immunoassays such as Maglumi are increasingly used, but their behavior at high antibody concentrations remains poorly characterized. We report the analytical concordance between Maglumi and radioimmunoassay (RIA), the cut-off titer that differentiates neurological from diabetic patients, and the hook effect of the immunoassay.</div></div><div><h3>Materials and methods</h3><div>Anti-GAD65 levels were analyzed in samples from 90 patients with suspected autoimmune diabetes or neurological syndromes, using Maglumi 2000® and RIA (Medipan®). Analytical concordance was assessed by Passing–Bablok regression, Bland–Altman plots, and Cohen’s kappa. ROC curve analysis identified diagnostic thresholds, and dilution studies were performed in samples with unexpectedly low values to assess a potential hook effect.</div></div><div><h3>Results</h3><div>Maglumi results were approximately five times higher than RIA results (slope = 5.364; R<sup>2</sup> = 0.908); agreement was higher in endocrine (R<sup>2</sup> = 0.998) than in neurological patients (R<sup>2</sup> = 0.891). A cutoff of 6778 IU/mL discriminated neurological patients from diabetic patients (AUC = 0.96). Sixteen samples showed a hook effect, with direct (undiluted) values ≤273 IU/mL, while the corrected titers after dilution exceeded 20,000 IU/mL. A linear regression confirmed an inverse relationship between direct and true titers (r = –0.79, p < 0.05).</div></div><div><h3>Discussion</h3><div>Maglumi anti-GAD65 immunoassay provides reliable discrimination between endocrine and neurological patients but requires method-specific cutoffs to avoid misclassification. Hook effect was frequent in high-titer neurological samples, potentially leading to misdiagnosis, underscoring the need for routine dilution protocols to improve diagnostic reliability.</div></div><div><h3>Conclusions</h3><div>Standardized dilution protocols and appropriate cutoffs are essential to ensure reliable anti-GAD65 testing with Maglumi chemiluminescent immunoassay, particularly in neurological indications.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111024"},"PeriodicalIF":2.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145262378","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 : 2025-10-10DOI: 10.1016/j.clinbiochem.2025.111026
Meifang Wang , Deliang Cao
{"title":"A rebuttal to: A letter to editor entitled: “A panel (CA19-9, CEA and PIVKA-II) of serum markers for pancreatic cancer diagnosis”","authors":"Meifang Wang , Deliang Cao","doi":"10.1016/j.clinbiochem.2025.111026","DOIUrl":"10.1016/j.clinbiochem.2025.111026","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111026"},"PeriodicalIF":2.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273959","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 : 2025-10-10DOI: 10.1016/j.clinbiochem.2025.111028
Tiziana Zangardi , Sara Altinier , Monica Maria Mion , Michele Cennamo , Ada Aita , Silvia Bressan , Daniela Basso
Introduction
A 4-year-old girl accidentally ingested an unknown quantity of bisoprolol (2.5 mg)-hydrochlorothiazide (6.25 mg) pills. Initialy asymptomatic, laboratory testing revealed elevated concentrations of cardiac and skeletal muscle injury markers. This case provided insight into potential myocardial toxicity and bone remodeling effects of these antihypertensive medications following acute overdose ingestion.
Materials and methods
Upon admission, the patient underwent clinical and laboratory evaluations, which included electrocardiogram (ECG), echocardiography, blood gas analysis, and assessment of biochemical markers for cardiac injury (high sensitivity troponin [hs-TnI], N-terminal pro brain natriuretic peptide [NT-proBNP]) and bone turnover (parathyroid hormone [PTH], vitamin D, bone alkaline phosphatase [bALP], beta cross-laps [CTX]). Bisoprolol was measured in plasma and urine. Creatine kinase (CK) isoenzymes were performed on agarose gel electrophoresis. Activated charcoal was administered; fluids and electrolytes were closely monitored. Clinical and laboratory follow-up continued for two months.
Results
The child’s vital signs were stable, but a reduced heart rate (75 bpm) developed within 24 h. Elevated hs-TnI and NT-proBNP levels indicated myocardial stress, despite normal ECG and echocardiography findings. The CK-BB isoenzyme increased to 8 % of total CK by day 3. An increase of CTX along with decreased PTH and bALP, suggested thiazide-induced osteoclastic activation. Bisoprolol concentrations quickly decreased over 12 h. The patient was discharged in good condition after 36 h. All biomarkers normalized progressively during follow-up.
Conclusions
This case highlights subclinical myocardial toxicity and an unexpected bone remodeling after a pediatric overdose of bisoprolol-hydrochlorothiazide. CK-BB elevation, likely due to osteoclast activity, underscores the importance of monitoring skeletal biomarkers in thiazide exposures. Clinical recovery can occur before biochemical normalization, emphasizing the need for extended follow-up even in asymptomatic cases.
{"title":"Myocardial damage in a 4-year old who ingested bisoprolol and hydrochlorothiazide – Incidental CK-BB highlighted other tissue toxicity","authors":"Tiziana Zangardi , Sara Altinier , Monica Maria Mion , Michele Cennamo , Ada Aita , Silvia Bressan , Daniela Basso","doi":"10.1016/j.clinbiochem.2025.111028","DOIUrl":"10.1016/j.clinbiochem.2025.111028","url":null,"abstract":"<div><h3>Introduction</h3><div>A 4-year-old girl accidentally ingested an unknown quantity of bisoprolol (2.5 mg)-hydrochlorothiazide (6.25 mg) pills. Initialy asymptomatic, laboratory testing revealed elevated concentrations of cardiac and skeletal muscle injury markers. This case provided insight into potential myocardial toxicity and bone remodeling effects of these antihypertensive medications following acute overdose ingestion.</div></div><div><h3>Materials and methods</h3><div>Upon admission, the patient underwent clinical and laboratory evaluations, which included electrocardiogram (ECG), echocardiography, blood gas analysis, and assessment of biochemical markers for cardiac injury (high sensitivity troponin [hs-TnI], N-terminal pro brain natriuretic peptide [NT-proBNP]) and bone turnover (parathyroid hormone [PTH], vitamin D, bone alkaline phosphatase [bALP], beta cross-laps [CTX]). Bisoprolol was measured in plasma and urine. Creatine kinase (CK) isoenzymes were performed on agarose gel electrophoresis. Activated charcoal was administered; fluids and electrolytes were closely monitored. Clinical and laboratory follow-up continued for two months.</div></div><div><h3>Results</h3><div>The child’s vital signs were stable, but a reduced heart rate (75 bpm) developed within 24 h. Elevated hs-TnI and NT-proBNP levels indicated myocardial stress, despite normal ECG and echocardiography findings. The CK-BB isoenzyme increased to 8 % of total CK by day 3. An increase of CTX along with decreased PTH and bALP, suggested thiazide-induced osteoclastic activation. Bisoprolol concentrations quickly decreased over 12 h. The patient was discharged in good condition after 36 h. All biomarkers normalized progressively during follow-up.</div></div><div><h3>Conclusions</h3><div>This case highlights subclinical myocardial toxicity and an unexpected bone remodeling after a pediatric overdose of bisoprolol-hydrochlorothiazide. CK-BB elevation, likely due to osteoclast activity, underscores the importance of monitoring skeletal biomarkers in thiazide exposures. Clinical recovery can occur before biochemical normalization, emphasizing the need for extended follow-up even in asymptomatic cases.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111028"},"PeriodicalIF":2.1,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145273981","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 : 2025-10-08DOI: 10.1016/j.clinbiochem.2025.111027
Natalia Volodko , Mathew P. Estey , Dustin Proctor , Lily Olayinka , Michelle L. Parker , Ashley Newbigging , Victoria Higgins
Introduction
Helicobacter pylori (H. pylori) colonization increases the risk of upper gastrointestinal disorders and can be detected by various tests, including the stool antigen test (HpSAT). DiaSorin recommends an HpSAT equivocal/indeterminate zone of 0.90-<1.10, but high variability observed in our laboratory prompted clinical implementation of a broader zone (0.60-<1.80). This study aimed to define an optimal HpSAT indeterminate zone using molecular as reference and urea breath test (UBT) for confirmation.
Materials and Methods
HpSAT and stool molecular results were available from 379 patients, of which 52 had follow-up UBTs. HpSAT was analyzed by the LIAISON HpSAT assay (DiaSorin), UBT by isotope ratio mass spectrometry, and molecular testing by qPCR targeting H. pylori DNA. Logistic regression modeled HpSAT index values against PCR positivity to define an optimal indeterminate zone, supported by clinical performance and flagging rates analyses.
Results
Logistic regression determined an HpSAT index of 0.79 (95 % CI: 0.34–1.14) had 90 % probability of a negative PCR result, and 4.99 (4.09–6.63) had 90 % probability of a positive result, rounded to an indeterminate zone of 0.80-<5.00. Lower thresholds assessed all had ≤ 2 % false negatives, while upper thresholds exhibited decreased false positive rates (22 % to 6 %) as thresholds increased (1.10 to 5.00), with minimal improvement beyond 3.00 (9 %). A modified zone of 0.80–<3.00 offered high accuracy with 12.9 % indeterminate results (DiaSorin’s threshold: 2.8 %; laboratory’s current threshold: 13.1 %).
Conclusions
Our findings show that DiaSorin’s HpSAT indeterminate zone is too narrow to reliably distinguish true positive and negative results in clinical practice. A modified broader zone (0.80–<3.00), derived via logistic regression using PCR as reference, improves diagnostic accuracy while minimizing indeterminate results.
{"title":"Optimizing the indeterminate zone for the DiaSorin LIAISON H. Pylori stool antigen test","authors":"Natalia Volodko , Mathew P. Estey , Dustin Proctor , Lily Olayinka , Michelle L. Parker , Ashley Newbigging , Victoria Higgins","doi":"10.1016/j.clinbiochem.2025.111027","DOIUrl":"10.1016/j.clinbiochem.2025.111027","url":null,"abstract":"<div><h3>Introduction</h3><div><em>Helicobacter pylori</em> (<em>H. pylori</em>) colonization increases the risk of upper gastrointestinal disorders and can be detected by various tests, including the stool antigen test (HpSAT). DiaSorin recommends an HpSAT equivocal/indeterminate zone of 0.90-<1.10, but high variability observed in our laboratory prompted clinical implementation of a broader zone (0.60-<1.80). This study aimed to define an optimal HpSAT indeterminate zone using molecular as reference and urea breath test (UBT) for confirmation.</div></div><div><h3>Materials and Methods</h3><div>HpSAT and stool molecular results were available from 379 patients, of which 52 had follow-up UBTs. HpSAT was analyzed by the LIAISON HpSAT assay (DiaSorin), UBT by isotope ratio mass spectrometry, and molecular testing by qPCR targeting <em>H. pylori</em> DNA. Logistic regression modeled HpSAT index values against PCR positivity to define an optimal indeterminate zone, supported by clinical performance and flagging rates analyses.</div></div><div><h3>Results</h3><div>Logistic regression determined an HpSAT index of 0.79 (95 % CI: 0.34–1.14) had 90 % probability of a negative PCR result, and 4.99 (4.09–6.63) had 90 % probability of a positive result, rounded to an indeterminate zone of 0.80-<5.00. Lower thresholds assessed all had ≤ 2 % false negatives, while upper thresholds exhibited decreased false positive rates (22 % to 6 %) as thresholds increased (1.10 to 5.00), with minimal improvement beyond 3.00 (9 %). A modified zone of 0.80–<3.00 offered high accuracy with 12.9 % indeterminate results (DiaSorin’s threshold: 2.8 %; laboratory’s current threshold: 13.1 %).</div></div><div><h3>Conclusions</h3><div>Our findings show that DiaSorin’s HpSAT indeterminate zone is too narrow to reliably distinguish true positive and negative results in clinical practice. A modified broader zone (0.80–<3.00), derived via logistic regression using PCR as reference, improves diagnostic accuracy while minimizing indeterminate results.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111027"},"PeriodicalIF":2.1,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257500","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 : 2025-10-07DOI: 10.1016/j.clinbiochem.2025.111025
Guo-Ming Zhang
{"title":"A panel (CA19-9, CEA and PIVKA-II) of serum markers for pancreatic cancer diagnosis","authors":"Guo-Ming Zhang","doi":"10.1016/j.clinbiochem.2025.111025","DOIUrl":"10.1016/j.clinbiochem.2025.111025","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111025"},"PeriodicalIF":2.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249966","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 : 2025-10-07DOI: 10.1016/j.clinbiochem.2025.111014
Pankaj Kumar, Ali Mousavi, Hans Frykman
{"title":"Corrigendum to “The biological diagnosis of Alzheimer’s disease using blood-based biomarkers: A Canadian prospective” [Clin. Biochem. 139 (2025); pages 1–17 /110980]","authors":"Pankaj Kumar, Ali Mousavi, Hans Frykman","doi":"10.1016/j.clinbiochem.2025.111014","DOIUrl":"10.1016/j.clinbiochem.2025.111014","url":null,"abstract":"","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"140 ","pages":"Article 111014"},"PeriodicalIF":2.1,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516769","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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