Clinical biochemistry最新文献

{"title":"Impact of the implementation of the Sampson-NIH equation for the calculation of LDL-C in a large community cohort of adult and pediatric patients in Ontario","authors":"Nicole White-Al Habeeb ,&nbsp;Terence Agbor ,&nbsp;Difei Sun ,&nbsp;Adam Wan ,&nbsp;Michelle Seaton ,&nbsp;Peter Catomeris ,&nbsp;Danijela Konforte","doi":"10.1016/j.clinbiochem.2025.111071","DOIUrl":"10.1016/j.clinbiochem.2025.111071","url":null,"abstract":"<div><h3>Introduction</h3><div>Low-density lipoprotein cholesterol (LDL-C), a known risk factor for cardiovascular disease, is commonly estimated using the Friedewald equation. Although the Sampson-NIH equation has been recommended by the Canadian Society of Clinical Chemists for its improved accuracy, particularly in cases of high triglyceride and low LDL-C concentration, its adoption across Canada has been limited.</div></div><div><h3>Objective</h3><div>Assess the impact of implementation of the Sampson-NIH equation for the calculation of LDL-C in a large community population in Ontario, including reporting frequency, reclassification and agreement with non-HDL-C.</div></div><div><h3>Methods</h3><div>Results for total cholesterol, HDL-C, non-HDL cholesterol and triglycerides were obtained from Dynacare and LifeLabs community samples (n = 474,911). LDL-C was calculated using Friedewald and Sampson-NIH equations, followed by regression and clinical impact analysis.</div></div><div><h3>Results</h3><div>Samples with triglycerides ≤ 4.52 mmol/L, showed excellent comparison between Friedewald and Sampson-NIH calculated results (R² = 0.995, y = 1.00x + 0.08, both cohorts). Samples with triglycerides 4.53–9.04 mmol/L, showed worsening agreement between the two equations (R² = 0.994, y = 0.81x + 0.79, both cohorts). The comparison results were similar when analyzed across ages (pediatric and adults) and fasting status. Implementation of the Sampson-NIH equation allowed reporting of an additional 1.49% patients (n = 7055). Minor reclassification was observed based on pediatric and adult LDL-C decision thresholds. The Sampson-NIH calculated LDL-C showed better agreement with non-HDL-C than Friedewald calculated LDL-C (86.0 % vs 84.2 %).</div></div><div><h3>Conclusion</h3><div>There is excellent agreement between Sampson-NIH equation and Friedewald equations, resulting in reclassification of only a small proportion of patients. This study demonstrated the impact of the Sampson-NIH equation for LDL-C in a large pediatric and adult Canadian community population.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111071"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833248","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}

{"title":"Extreme hypokalemia in an asymptomatic 40-year-old cachectic male","authors":"Stanislas Francois ,&nbsp;Sreekanth Rajagopal ,&nbsp;Anne Boutten ,&nbsp;Alexandre Raynor ,&nbsp;Katell Peoc’h","doi":"10.1016/j.clinbiochem.2025.111042","DOIUrl":"10.1016/j.clinbiochem.2025.111042","url":null,"abstract":"<div><div>Hypokalemia is a relatively common electrolyte disturbance that, despite its frequency, can pose a serious threat when it occurs in patients with end-stage chronic illnesses. In many individuals, mild to moderate reductions in serum potassium may be surprisingly well tolerated over time; however, severe depletion remains a potentially life-threatening condition that demands rapid recognition and intervention.</div><div>In this report, we describe an exceptional case of extreme hypokalemia &lt; 2 mmol/L in a patient living with human immunodeficiency virus (HIV) infection, who also suffered from persistent chronic diarrhea and marked unintentional weight loss, yet exhibited few of the classical clinical signs usually associated with profound potassium deficiency. We outline the urgent procedures carried out by the laboratory under emergency conditions, examine the complex pathophysiological mechanisms, ranging from gastrointestinal potassium losses to altered renal handling, responsible for this critical imbalance, and detail the specific treatment regimen administered. By presenting these elements in concert, we aim to offer clinicians a clearer understanding of both the diagnostic approach and the therapeutic strategies necessary to manage similar high-risk patients effectively.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111042"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145523079","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}

{"title":"A tale of two variants: The first reported case of hemoglobin Rush and hemoglobin S in a compound heterozygote","authors":"Amanda Cristina Meneguetti Berti ,&nbsp;Bárbara Braga Vieira Marques ,&nbsp;Victoria Simões Bernardo ,&nbsp;Flaviene Felix Torres ,&nbsp;Gabriela Alves Bernardino ,&nbsp;Júlia Junqueira Ruiz Silva ,&nbsp;Ingrid Souza Dias ,&nbsp;Ana Clara Albertin Zucão ,&nbsp;Danilo Grünig Humberto da Silva ,&nbsp;Edis Belini-Júnior","doi":"10.1016/j.clinbiochem.2025.111039","DOIUrl":"10.1016/j.clinbiochem.2025.111039","url":null,"abstract":"<div><div>Hemoglobinopathies are among the most common inherited disorders worldwide, caused by various mutations in the hemoglobin (Hb) genes. These mutations can lead to different clinical outcomes, some of which cause significant symptoms, highlighting their importance in global health and genetic research. In this context, this case report details the first known instance of compound heterozygosity for Hb Rush (<em>HBB</em>:c.304G &gt; C) and Hb S (<em>HBB</em>:c.20A &gt; T), emphasizing the diagnostic challenges posed by rare Hb variants, particularly those that mimic Hb S. Specifically, a 14-year-old male patient was referred due to mild anemia, microcytosis, and hemolysis, with a suspicion of sickle cell disease (SCD). However, hematological, biochemical, chromatographic, and electrophoretic analyses were inconsistent with SCD, prompting further molecular investigations. High-performance liquid chromatography identified a hemoglobin variant with a retention time overlapping Hb S. Additionally, alkaline electrophoresis revealed hybrid tetramers typical of unstable Hbs, such as Hb Rush. These laboratory findings were further confirmed through Sanger sequencing of the <em>HBB</em> gene, which demonstrated heterozygosity for both Hb Rush and Hb S, establishing a rare genotype that has not been previously reported. The thermal instability and structural changes involving the G3 (101) glutamate-to-glutamine substitution in Hb Rush account for the hematological phenotype observed in this patient. Therefore, in cases like this one, it is crucial to combine various laboratory methodologies—such as electrophoresis and molecular analysis—with the patient’s clinical information. This comprehensive approach enables a critical interpretation of potential genotypes, ensuring accurate diagnosis, appropriate clinical follow-up, and treatment.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111039"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512109","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}

{"title":"Association of hypertension and genetic variants in MYH9 and BMPR1B with increased proteinuria in sickle cell disease","authors":"El Hadji Malick Ndour ,&nbsp;Kuthala Mnika ,&nbsp;El Hadj Ousmane Sene ,&nbsp;Fatou Gueye Tall ,&nbsp;Victoria Nembaware ,&nbsp;Indou Deme Ly ,&nbsp;Moussa Seck ,&nbsp;Mara Sokhna ,&nbsp;Rokhaya Dione ,&nbsp;Coumba Kamby ,&nbsp;Jean Pascal Demba Diop ,&nbsp;Serigne Saliou Mbacke ,&nbsp;Nene Oumou Kesso Barry ,&nbsp;Moustapha Djité ,&nbsp;Pape Matar Kandji ,&nbsp;Rokhaya Ndiaye Diallo ,&nbsp;Ibrahima Diagne ,&nbsp;Saliou Diop ,&nbsp;Papa Madieye Gueye ,&nbsp;Philomene Lopez Sall ,&nbsp;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":"2026-01-01","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}

{"title":"Diagnostic accuracy of biomarkers for irritable bowel syndrome: a systematic review and meta-analysis","authors":"Jianjiao Mou ,&nbsp;Qingfeng Tao ,&nbsp;Lu Xu ,&nbsp;Yifei Luo ,&nbsp;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":"2026-01-01","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}

{"title":"A large-scale survey on the knowledge, attitude, and practice of patient-based real-time quality control in China","authors":"Dong Leng ,&nbsp;Mengxue Lyu ,&nbsp;Li Wei ,&nbsp;Xueling Shang ,&nbsp;Xia Lou ,&nbsp;Minglong Zhang ,&nbsp;Yali Zhou ,&nbsp;Tony Badrick ,&nbsp;Rui Zhou ,&nbsp;On behalf of the APFCB Working Group on Patient-based Real-Time Quality Control","doi":"10.1016/j.clinbiochem.2025.111044","DOIUrl":"10.1016/j.clinbiochem.2025.111044","url":null,"abstract":"<div><h3>Objectives</h3><div>Patient-based real-time quality control (PBRTQC) plays a promising role in monitoring the quality of medical laboratory testing processes worldwide. In contrast with traditional quality control, PBRTQC demonstrates numerous advantages, but the application status remains unclear. This study was conducted to assess the awareness and intention to apply PBRTQC in laboratories through a survey, providing a basis for subsequent research and promotion.</div></div><div><h3>Design &amp; Methods</h3><div>A questionnaire was constructed and extended on the basis of Badrick’s fifteen core questions in 2023, which were distributed via the Star questionnaire platform to collect general information on relevant personnel, their cognition, attitude and practice of PBRTQC as well as their willingness to implement it. This survey was carried out in different kinds of clinical laboratories throughout the mainland area of China.</div></div><div><h3>Results</h3><div>A total of 1,844 valid questionnaires were collected. The survey showed that the average awareness rate of basic knowledge of PBRTQC among laboratory staff was above 50%, and their confidence in establishing and applying PBRTQC in their laboratories was relatively low. However, they recognized the role of PBRTQC in improving quality management. Among the existing PBRTQC related practices, reading literature was the most common. The main concerns for promoting PBRTQC included professional implementation guidelines and policy support, reliable commercial evaluations, software and hardware support, and usage training.</div></div><div><h3>Conclusions</h3><div>The results of our study demonstrate that laboratory staff recognize the value of PBRTQC and have a generally positive attitude towards its application. In the future, efforts should be made to strengthen the formulation of standardized documents, improve evaluation methods, develop software and hardware, popularize knowledge, and provide technical training to promote the application of PBRTQC.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111044"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502407","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}

{"title":"A case of late-onset carbamoyl phosphate synthetase 1 deficiency: diagnostic challenges and management in a low-resource setting","authors":"Xiaopu Cui ,&nbsp;Sixian Guo ,&nbsp;Yu Zhang ,&nbsp;Huixin Zhang ,&nbsp;Hongxin Tian ,&nbsp;Huafang Yang ,&nbsp;Huacheng Zheng ,&nbsp;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 &gt; C (p.F353S) and known pathogenic c.1145C &gt; 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":"2026-01-01","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}

{"title":"Reducing inappropriate vitamin D testing: an analysis of three sequential diagnostic stewardship interventions and the carbon footprint implications","authors":"C. Hughes ,&nbsp;M.A. Myers ,&nbsp;M. Tickell-Painter ,&nbsp;M. Aitchison ,&nbsp;L. Roberts ,&nbsp;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 (CO₂e) 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 CO₂e 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 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.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111060"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","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}

{"title":"A novel Gasdermin D C-terminal neo-epitope as a biomarker for pyroptosis in sepsis","authors":"Jun Li ,&nbsp;Yunyun Luo ,&nbsp;Ying Liu ,&nbsp;Shujing Cui ,&nbsp;Lixin Zhao ,&nbsp;Haoxiang Kang ,&nbsp;Lijing Huo ,&nbsp;Xu Wang ,&nbsp;Erling Jin ,&nbsp;Sufang Mao ,&nbsp;Yu Cao ,&nbsp;Jianxia Wang","doi":"10.1016/j.clinbiochem.2025.111045","DOIUrl":"10.1016/j.clinbiochem.2025.111045","url":null,"abstract":"<div><h3>Background</h3><div>Gasdermin D (GSDMD)-mediated pyroptosis, a critical component of the innate immune response, is triggered by pathogenic microbial infections and plays a key role in host defense mechanisms. This process involves the cleavage of GSDMD by inflammatory caspases, releasing carboxy-terminal fragments (GSDMD-CT). Monitoring GSDMD-CT levels represents a promising approach for inflammatory diseases, including sepsis and systemic inflammatory response syndrome (SIRS).</div></div><div><h3>Methods</h3><div>We developed an immunoassay to measure plasma GSDMD-CT concentrations in 109 healthy individuals, 137 patients with SIRS, and 100 patients with sepsis. The diagnostic utility of GSDMD-CT in distinguishing sepsis from SIRS or healthy controls was assessed using receiver operating characteristic (ROC) analysis, alongside correlations with procalcitonin (PCT), and C-reactive protein (CRP).</div></div><div><h3>Results</h3><div>Plasma GSDMD-CT levels were significantly elevated in patients with sepsis compared to healthy control and SIRS groups. ROC analysis demonstrated an area under the curve of 0.870, with a sensitivity of 91.0% and specificity of 60.6% for differentiating sepsis from healthy controls. Comparable performance was observed in distinguishing SIRS from healthy controls. Diagnostic accuracy was further enhanced when GSDMD-CT was combined with CRP. Strikingly, GSDMD-CT mirrored the kinetic profile of PCT in antibiotic-treated patients with bacterial infections.</div></div><div><h3>Conclusion</h3><div>The GSDMD-CT assay demonstrates high sensitivity as a biomarker, offering potential for early and differential diagnosis of sepsis across diverse pathogens.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111045"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145486055","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}

{"title":"Change in cardiac troponin T to differentiate acute from chronic myocardial injury in the Emergency Department","authors":"Bertil Lindahl ,&nbsp;Alexander JF Thurston ,&nbsp;Yong Yong Tew ,&nbsp;Michael McDermott ,&nbsp;Takeshi Fujisawa ,&nbsp;Stephen Lynch ,&nbsp;Jamie G Cooper ,&nbsp;Alasdair J Gray ,&nbsp;Tomas Jernberg ,&nbsp;Nicholas L. Mills ,&nbsp;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 &lt; 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 &lt; 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":"2026-01-01","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}