Pub Date : 2025-11-21DOI: 10.1016/j.clinbiochem.2025.111061
Jianjiao Mou , Qingfeng Tao , Lu Xu , Yifei Luo , Hui Zheng
This study aimed to systematically assess the diagnostic performance of multiple biomarkers for irritable bowel syndrome (IBS). Systematic electronic searches were conducted in PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science, with the search updated through May 18, 2025. Studies were evaluated in accordance with the Diagnostic Test Accuracy systematic review manual and the PRISMA-DTA reporting guidelines. Methodological quality of included studies was assessed using the QUADAS-2 and QUADAS-C tools. We synthesized summary sensitivity and specificity using a bivariate random-effects model within a hierarchical summary receiver operating characteristic framework. Of 9,078 initially identified studies, 24 eligible studies involving 9,343 participants were ultimately included in the meta-analysis. Pooled analysis revealed that urinary metabolic markers exhibited high diagnostic accuracy, with a pooled sensitivity of 0.988 (95% CI: 0.804–1.000) and a pooled specificity of 0.934 (95% CI: 0.629–0.993). In biomarker-type subgroup analyses, fecal peptidase activity yielded a sensitivity of 0.905 (0.438–0.990) and specificity of 0.883 (0.513–0.978), while RAID-IBS showed a sensitivity of 0.935 (0.548–0.994) and specificity of 0.919 (0.444–0.986). When stratified by comparator groups, urinary metabolites exhibited a sensitivity of 0.981 (0.800–0.999) and specificity of 0.803 (0.271–0.981) against healthy controls, compared to a sensitivity of 0.995 (0.926–1.000) and specificity of 0.996 (0.944–1.000) against inflammatory bowel disease. These results suggest that urinary metabolites, fecal peptidase activity, and RAID-IBS may achieve high sensitivity and specificity in the studies available.
本研究旨在系统评估多种生物标志物对肠易激综合征（IBS）的诊断性能。系统的电子检索在PubMed、Cochrane Central Register of Controlled Trials、Embase和Web of Science中进行，检索更新至2025年5月18日。根据诊断测试准确性系统评价手册和PRISMA-DTA报告指南对研究进行评估。采用QUADAS-2和QUADAS-C工具评估纳入研究的方法学质量。我们使用双变量随机效应模型在分级汇总接收者操作特征框架内综合汇总敏感性和特异性。在最初确定的9078项研究中，最终纳入了24项符合条件的研究，涉及9343名参与者。合并分析显示，尿代谢标志物具有较高的诊断准确性，合并敏感性为0.988 (95% CI: 0.804-1.000)，合并特异性为0.934 （95% CI: 0.629-0.993）。在生物标志物亚组分析中，粪便肽酶活性的敏感性为0.905(0.438 ~ 0.990)，特异性为0.883(0.513 ~ 0.978)，而RAID-IBS的敏感性为0.935(0.548 ~ 0.994)，特异性为0.919（0.444 ~ 0.986）。当按比较组分层时，尿代谢物对健康对照的敏感性为0.981(0.800-0.999)，特异性为0.803(0.271-0.981)，而对炎症性肠病的敏感性为0.995(0.926-1.000)，特异性为0.996（0.944-1.000）。这些结果表明，在现有的研究中，尿液代谢物、粪便肽酶活性和RAID-IBS可能具有很高的敏感性和特异性。
{"title":"Diagnostic accuracy of biomarkers for irritable bowel syndrome: a systematic review and meta-analysis","authors":"Jianjiao Mou , Qingfeng Tao , Lu Xu , Yifei Luo , Hui Zheng","doi":"10.1016/j.clinbiochem.2025.111061","DOIUrl":"10.1016/j.clinbiochem.2025.111061","url":null,"abstract":"<div><div>This study aimed to systematically assess the diagnostic performance of multiple biomarkers for irritable bowel syndrome (IBS). Systematic electronic searches were conducted in PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science, with the search updated through May 18, 2025. Studies were evaluated in accordance with the Diagnostic Test Accuracy systematic review manual and the PRISMA-DTA reporting guidelines. Methodological quality of included studies was assessed using the QUADAS-2 and QUADAS-C tools. We synthesized summary sensitivity and specificity using a bivariate random-effects model within a hierarchical summary receiver operating characteristic framework. Of 9,078 initially identified studies, 24 eligible studies involving 9,343 participants were ultimately included in the <em>meta</em>-analysis. Pooled analysis revealed that urinary metabolic markers exhibited high diagnostic accuracy, with a pooled sensitivity of 0.988 (95% CI: 0.804–1.000) and a pooled specificity of 0.934 (95% CI: 0.629–0.993). In biomarker-type subgroup analyses, fecal peptidase activity yielded a sensitivity of 0.905 (0.438–0.990) and specificity of 0.883 (0.513–0.978), while RAID-IBS showed a sensitivity of 0.935 (0.548–0.994) and specificity of 0.919 (0.444–0.986). When stratified by comparator groups, urinary metabolites exhibited a sensitivity of 0.981 (0.800–0.999) and specificity of 0.803 (0.271–0.981) against healthy controls, compared to a sensitivity of 0.995 (0.926–1.000) and specificity of 0.996 (0.944–1.000) against inflammatory bowel disease. These results suggest that urinary metabolites, fecal peptidase activity, and RAID-IBS may achieve high sensitivity and specificity in the studies available.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111061"},"PeriodicalIF":2.1,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-19DOI: 10.1016/j.clinbiochem.2025.111058
El Hadji Malick Ndour , Kuthala Mnika , El Hadj Ousmane Sene , Fatou Gueye Tall , Victoria Nembaware , Indou Deme Ly , Moussa Seck , Mara Sokhna , Rokhaya Dione , Coumba Kamby , Jean Pascal Demba Diop , Serigne Saliou Mbacke , Nene Oumou Kesso Barry , Moustapha Djité , Pape Matar Kandji , Rokhaya Ndiaye Diallo , Ibrahima Diagne , Saliou Diop , Papa Madieye Gueye , Philomene Lopez Sall , Ambroise Wonkam
Background
Sickle cell nephropathy (SCN) is a major chronic complication of sickle cell disease, and its progression may be influenced by genetic factors. This study aimed to investigate the association between variants in the MYH9 and BMPR1B genes and increased total proteinuria in patients with sickle cell anemia.
Materials and methods
This cross-sectional study included patients with homozygous (SS) sickle cell disease who were followed up in Dakar. Urinary albumin, total proteins, and creatinine levels, along with serum creatinine and urea concentrations, were measured. Genotyping of the single nucleotide variants MYH9-rs4821469, MYH9-rs3752462, MYH9-rs2032487, and BMPR1B-rs17022863 was performed using mass spectrometry (MassARRAY technology). Associations were evaluated using multivariate logistic regression analysis.
Results
The 150-patient cohort had a mean age of 20.44 ± 9.86 years, with a slight female majority (51 %). A high prevalence of increased total proteinuria (urine proteins-to-creatinine ratio ≥150 mg/g) was observed, affecting 50.67 % of this young population. Multivariate analysis identified relative systemic hypertension (blood pressure ≥130/80 mmHg) as a powerful and independent risk factor for increased total proteinuria. While an initial analysis suggested a protective association for the MYH9 − rs4821469 variant, this signal was unstable and lost statistical significance in more stringent models.
Conclusion
Increased total proteinuria is highly prevalent in this young cohort, indicating early onset of kidney damage. Relative systemic hypertension is a major modifiable risk factor, underscoring the need for rigorous blood pressure control. The instability of the initial genetic signal for MYH9-rs4821469, coupled with its strong linkage disequilibrium with APOL1, suggests that the observed association is likely confounded by ungenotyped APOL1 variants. This highlights the critical importance of including APOL1 analysis in future SCN genetic studies in African-ancestry populations.
{"title":"Association of hypertension and genetic variants in MYH9 and BMPR1B with increased proteinuria in sickle cell disease","authors":"El Hadji Malick Ndour , Kuthala Mnika , El Hadj Ousmane Sene , Fatou Gueye Tall , Victoria Nembaware , Indou Deme Ly , Moussa Seck , Mara Sokhna , Rokhaya Dione , Coumba Kamby , Jean Pascal Demba Diop , Serigne Saliou Mbacke , Nene Oumou Kesso Barry , Moustapha Djité , Pape Matar Kandji , Rokhaya Ndiaye Diallo , Ibrahima Diagne , Saliou Diop , Papa Madieye Gueye , Philomene Lopez Sall , Ambroise Wonkam","doi":"10.1016/j.clinbiochem.2025.111058","DOIUrl":"10.1016/j.clinbiochem.2025.111058","url":null,"abstract":"<div><h3>Background</h3><div>Sickle cell nephropathy (SCN) is a major chronic complication of sickle cell disease, and its progression may be influenced by genetic factors. This study aimed to investigate the association between variants in the <em>MYH9</em> and <em>BMPR1B</em> genes and increased total proteinuria in patients with sickle cell anemia.</div></div><div><h3>Materials and methods</h3><div>This cross-sectional study included patients with homozygous (SS) sickle cell disease who were followed up in Dakar. Urinary albumin, total proteins, and creatinine levels, along with serum creatinine and urea concentrations, were measured. Genotyping of the single nucleotide variants <em>MYH9</em>-rs4821469, <em>MYH9</em>-rs3752462, <em>MYH9</em>-rs2032487, and <em>BMPR1B</em>-rs17022863 was performed using mass spectrometry (MassARRAY technology). Associations were evaluated using multivariate logistic regression analysis.</div></div><div><h3>Results</h3><div>The 150-patient cohort had a mean age of 20.44 ± 9.86 years, with a slight female majority (51 %). A high prevalence of increased total proteinuria (urine proteins-to-creatinine ratio ≥150 mg/g) was observed, affecting 50.67 % of this young population. Multivariate analysis identified relative systemic hypertension (blood pressure ≥130/80 mmHg) as a powerful and independent risk factor for increased total proteinuria. While an initial analysis suggested a protective association for the <em>MYH9</em> − rs4821469 variant, this signal was unstable and lost statistical significance in more stringent models.</div></div><div><h3>Conclusion</h3><div>Increased total proteinuria is highly prevalent in this young cohort, indicating early onset of kidney damage. Relative systemic hypertension is a major modifiable risk factor, underscoring the need for rigorous blood pressure control. The instability of the initial genetic signal for <em>MYH9</em>-rs4821469, coupled with its strong linkage disequilibrium with <em>APOL1</em>, suggests that the observed association is likely confounded by ungenotyped <em>APOL1</em> variants. This highlights the critical importance of including <em>APOL1</em> analysis in future SCN genetic studies in African-ancestry populations.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111058"},"PeriodicalIF":2.1,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-16DOI: 10.1016/j.clinbiochem.2025.111057
Janet Zhou , Demitra Tsoukalas , Nethra Chittiprol , Peter Kavsak , Felix Leung , Jennifer Taher , Zahraa Ali-Mohammed , Saranya Arnoldo , Heather Tysick , Lei Fu , Sara A. Love , Rajeevan Selvaratnam
Background
Monitoring blood levels of lithium is important for maintaining therapeutic efficacy. Age-dependent therapeutic intervals have been recommended by the International Society for Bipolar Disorder (ISBD) task force, 0.4–0.8 mmol/L and 0.4–0.7 mmol/L for adults aged 60–79 and ≥80 years old, respectively. However, the suitability of common colorimetric methods for lithium measurements in the suggested therapeutic intervals has not been characterized, nor has the proposed therapeutic intervals been confirmed with real-world patient data.
Methods
Serum samples spiked with various concentrations of lithium ranging from 0 to 3.5 mmol/L were analyzed on six different methods for imprecision and relative comparability of lithium measurements. An indirect reference interval approach using refineR was employed to derive therapeutic limits using patient results spanning 5 years and compared with the therapeutic intervals recommended by the ISBD task force.
Results
Routinely employed colorimetric methods for lithium measurements have sufficient precision within the recommended therapeutic intervals, although select colorimetric methods are notably more imprecise at 0.4 mmol/L. The derived therapeutic intervals using patient data align with those proposed by the ISBD task force for older adults.
Conclusion
Routine colorimetric methods used for lithium measurements have adequate precision and detection capabilities in the therapeutic windows recommended by the ISBD task force. In addition, the proposed therapeutic intervals are verifiable by real-world patient data.
{"title":"Analytical Imprecision and Therapeutic Intervals for Lithium – Are There Implications for Old Age Patients with Bipolar Disorder?","authors":"Janet Zhou , Demitra Tsoukalas , Nethra Chittiprol , Peter Kavsak , Felix Leung , Jennifer Taher , Zahraa Ali-Mohammed , Saranya Arnoldo , Heather Tysick , Lei Fu , Sara A. Love , Rajeevan Selvaratnam","doi":"10.1016/j.clinbiochem.2025.111057","DOIUrl":"10.1016/j.clinbiochem.2025.111057","url":null,"abstract":"<div><h3>Background</h3><div>Monitoring blood levels of lithium is important for maintaining therapeutic efficacy. Age-dependent therapeutic intervals have been recommended by the International Society for Bipolar Disorder (ISBD) task force, 0.4–0.8 mmol/L and 0.4–0.7 mmol/L for adults aged 60–79 and ≥80 years old, respectively. However, the suitability of common colorimetric methods for lithium measurements in the suggested therapeutic intervals has not been characterized, nor has the proposed therapeutic intervals been confirmed with real-world patient data.</div></div><div><h3>Methods</h3><div>Serum samples spiked with various concentrations of lithium ranging from 0 to 3.5 mmol/L were analyzed on six different methods for imprecision and relative comparability of lithium measurements. An indirect reference interval approach using refineR was employed to derive therapeutic limits using patient results spanning 5 years and compared with the therapeutic intervals recommended by the ISBD task force.</div></div><div><h3>Results</h3><div>Routinely employed colorimetric methods for lithium measurements have sufficient precision within the recommended therapeutic intervals, although select colorimetric methods are notably more imprecise at 0.4 mmol/L. The derived therapeutic intervals using patient data align with those proposed by the ISBD task force for older adults.</div></div><div><h3>Conclusion</h3><div>Routine colorimetric methods used for lithium measurements have adequate precision and detection capabilities in the therapeutic windows recommended by the ISBD task force. In addition, the proposed therapeutic intervals are verifiable by real-world patient data.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111057"},"PeriodicalIF":2.1,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-14DOI: 10.1016/j.clinbiochem.2025.111041
Xiaopu Cui , Sixian Guo , Yu Zhang , Huixin Zhang , Hongxin Tian , Huafang Yang , Huacheng Zheng , Baoguang Li
Objective
This study aimed to analyze the clinical features, genetic basis, and management of late-onset carbamoyl phosphate synthetase 1 deficiency (CPS1D) through a pediatric case report and literature review, highlighting diagnostic challenges and therapeutic strategies.
Methods
We present a 19-year-old female with recurrent neurological symptoms since age 8. She underwent comprehensive metabolic screening, neuroimaging, and whole-exome sequencing of the CPS1 gene. Identified variants were assessed for pathogenicity using multiple orthogonal in silico prediction tools.
Results
The patient’s initial hyperammonemic crisis at age 8 was misdiagnosed as encephalitis. Workup at age 13 confirmed hyperammonemia (peak 168 µmol/L), hypocitrullinemia, and elevated glutamine. Genetic analysis identified compound heterozygous CPS1 variants: a novel c.1058 T > C (p.F353S) and known pathogenic c.1145C > T (p.P382L). A self-selected low-protein diet controlled acute crises but led to severe growth failure (height 145 cm, weight 30 kg).
Conclusion
Late-onset CPS1D’s nonspecific neurological symptoms often lead to misdiagnosis. Diagnosis requires a high index of suspicion, integrating metabolic profiling with genetic confirmation. This case expands the pathogenic genotypic spectrum of CPS1D. It crucially highlights that while dietary management is life-saving, it requires expert multidisciplinary oversight to prevent devastating consequences like growth failure, especially in resource-limited settings. Routine ammonia testing in unexplained encephalopathy is paramount.
目的：本研究旨在通过儿科病例报告和文献综述，分析迟发性磷酸氨甲酰合成酶1缺乏症（CPS1D）的临床特征、遗传基础和治疗，强调诊断挑战和治疗策略。方法：我们报告了一位19岁的女性，自8岁以来反复出现神经系统症状。她接受了全面的代谢筛查、神经成像和cps1基因全外显子组测序。鉴定出的变异采用多种正gonalin硅预测工具进行致病性评估。结果：患者8岁时首次出现高氨血症危象，误诊为脑炎。13岁时的检查证实了高氨血症（峰值168 µmol/L）、低氮血症和谷氨酰胺升高。遗传分析鉴定出复合杂合scps1变异：一种新的C .1058 T > C （p.F353S）和一种已知的致病性C . 1145c > T （p.P382L）。自我选择的低蛋白饮食控制了急性危机，但导致严重的生长衰竭（身高145 cm，体重30 kg）。结论：迟发性CPS1D的非特异性神经症状常导致误诊。诊断需要高度的怀疑指数，结合代谢谱和基因确认。本病例扩大了CPS1D的致病基因型谱。它至关重要地强调，虽然饮食管理可以挽救生命，但它需要多学科专家的监督，以防止生长衰竭等破坏性后果，特别是在资源有限的情况下。在不明原因的脑病中，常规氨检测是至关重要的。
{"title":"A case of late-onset carbamoyl phosphate synthetase 1 deficiency: diagnostic challenges and management in a low-resource setting","authors":"Xiaopu Cui , Sixian Guo , Yu Zhang , Huixin Zhang , Hongxin Tian , Huafang Yang , Huacheng Zheng , Baoguang Li","doi":"10.1016/j.clinbiochem.2025.111041","DOIUrl":"10.1016/j.clinbiochem.2025.111041","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to analyze the clinical features, genetic basis, and management of late-onset carbamoyl phosphate synthetase 1 deficiency (CPS1D) through a pediatric case report and literature review, highlighting diagnostic challenges and therapeutic strategies.</div></div><div><h3>Methods</h3><div>We present a 19-year-old female with recurrent neurological symptoms since age 8. She underwent comprehensive metabolic screening, neuroimaging, and whole-exome sequencing of the<!--> <em>CPS1</em> <!-->gene. Identified variants were assessed for pathogenicity using multiple orthogonal<!--> <em>in silico</em> <!-->prediction tools.</div></div><div><h3>Results</h3><div>The patient’s initial hyperammonemic crisis at age 8 was misdiagnosed as encephalitis. Workup at age 13 confirmed hyperammonemia (peak 168 µmol/L), hypocitrullinemia, and elevated glutamine. Genetic analysis identified compound heterozygous<!--> <em>CPS1</em> <!-->variants: a novel c.1058 T > C (p.F353S) and known pathogenic c.1145C > T (p.P382L). A self-selected low-protein diet controlled acute crises but led to severe growth failure (height 145 cm, weight 30 kg).</div></div><div><h3>Conclusion</h3><div>Late-onset CPS1D’s nonspecific neurological symptoms often lead to misdiagnosis. Diagnosis requires a high index of suspicion, integrating metabolic profiling with genetic confirmation. This case expands the pathogenic genotypic spectrum of CPS1D. It crucially highlights that while dietary management is life-saving, it requires expert multidisciplinary oversight to prevent devastating consequences like growth failure, especially in resource-limited settings. Routine ammonia testing in unexplained encephalopathy is paramount.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111041"},"PeriodicalIF":2.1,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/j.clinbiochem.2025.111055
Bertil Lindahl , Alexander JF Thurston , Yong Yong Tew , Michael McDermott , Takeshi Fujisawa , Stephen Lynch , Jamie G Cooper , Alasdair J Gray , Tomas Jernberg , Nicholas L. Mills , on behalf of the POC-ET investigators
Introduction
Persistently elevated cardiac troponin (cTn) values are observed in many patients with suspected acute coronary syndrome (ACS) in the absence of myocardial infarction and may reflect underlying cardiac disease. Chronic myocardial injury is defined where cTn values are elevated and vary by ≤ 20 % on sequential measurements. We aimed to evaluate whether these criteria are reliable over short intervals applied in accelerated diagnostic pathways.
Methods
In a secondary analysis of a prospective, multi-centre cohort study of patients with suspected ACS, cTnT was measured at presentation, 1, 2 and 6–36 h, and the final diagnosis adjudicated according to the Fourth Universal Definition of Myocardial Infarction. Two criteria for chronic myocardial injury were compared: a relative change in cTn of ≤ 20 % and an absolute change < 3 ng/L, and the findings externally validated.
Results
At presentation cTnT was elevated in 242 of 1,000 (24 %) patients (73 years, 42 % female), of whom 94/242 (39 %), 13/242 (5 %) and 137/242 (56 %) had myocardial infarction, acute or chronic myocardial injury, respectively. A relative change of ≤ 20 % misclassified 58 % (59/101) and 49 % (48/98) of patients with a final diagnosis of acute myocardial injury or infarction at 1 and 2 h, respectively, whereas an absolute change of < 3 ng/L misclassified 22 % (22/101) and 15 % (15/98). In the validation cohort (n = 621), the relative and absolute change criteria at one hour misclassified 43 % (13/30) and 17 % (5/30) of those with myocardial infarction.
Conclusions
Chronic myocardial injury cannot reliably be differentiated from acute myocardial injury or infarction by recommended criteria over short remeasurement intervals in the Emergency Department. Longer intervals between sampling and absolute rather than relative criteria may reduce the risk of misclassification.
{"title":"Change in cardiac troponin T to differentiate acute from chronic myocardial injury in the Emergency Department","authors":"Bertil Lindahl , Alexander JF Thurston , Yong Yong Tew , Michael McDermott , Takeshi Fujisawa , Stephen Lynch , Jamie G Cooper , Alasdair J Gray , Tomas Jernberg , Nicholas L. Mills , on behalf of the POC-ET investigators","doi":"10.1016/j.clinbiochem.2025.111055","DOIUrl":"10.1016/j.clinbiochem.2025.111055","url":null,"abstract":"<div><h3>Introduction</h3><div>Persistently elevated cardiac troponin (cTn) values are observed in many patients with suspected acute coronary syndrome (ACS) in the absence of myocardial infarction and may reflect underlying cardiac disease. Chronic myocardial injury is defined where cTn values are elevated and vary by ≤ 20 % on sequential measurements. We aimed to evaluate whether these criteria are reliable over short intervals applied in accelerated diagnostic pathways.</div></div><div><h3>Methods</h3><div>In a secondary analysis of a prospective, multi-centre cohort study of patients with suspected ACS, cTnT was measured at presentation, 1, 2 and 6–36 h, and the final diagnosis adjudicated according to the Fourth Universal Definition of Myocardial Infarction. Two criteria for chronic myocardial injury were compared: a relative change in cTn of ≤ 20 % and an absolute change < 3 ng/L, and the findings externally validated.</div></div><div><h3>Results</h3><div>At presentation cTnT was elevated in 242 of 1,000 (24 %) patients (73 years, 42 % female), of whom 94/242 (39 %), 13/242 (5 %) and 137/242 (56 %) had myocardial infarction, acute or chronic myocardial injury, respectively. A relative change of ≤ 20 % misclassified 58 % (59/101) and 49 % (48/98) of patients with a final diagnosis of acute myocardial injury or infarction at 1 and 2 h, respectively, whereas an absolute change of < 3 ng/L misclassified 22 % (22/101) and 15 % (15/98). In the validation cohort (n = 621), the relative and absolute change criteria at one hour misclassified 43 % (13/30) and 17 % (5/30) of those with myocardial infarction.</div></div><div><h3>Conclusions</h3><div>Chronic myocardial injury cannot reliably be differentiated from acute myocardial injury or infarction by recommended criteria over short remeasurement intervals in the Emergency Department. Longer intervals between sampling and absolute rather than relative criteria may reduce the risk of misclassification.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111055"},"PeriodicalIF":2.1,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-13DOI: 10.1016/j.clinbiochem.2025.111056
Kaitlyn Berchier , Chiara Nyffeler , Stephen Bruce , Clothilde Roux , Jean-Marc Nuoffer , Matthias Gautschi , Alexander Laemmle , Déborah Mathis
Background
Accurate quantification of small metabolites such as ketone bodies (KB: β-hydroxybutyrate (BHB), acetoacetate (AcAc)), pyruvate (Pyr), lactate (Lac) and tricarboxylic acid (TCA) cycle intermediates is essential for diagnostics, therapy monitoring and metabolic research. These metabolites serve as energy substrates and signaling molecules, with their interpretation often relying on physiologically meaningful ratios (Lac/Pyr, BHB/AcAc). However, their chemical instability and susceptibility to rapid post-collection metabolism pose significant pre-analytical challenges.
Method
We developed an LC-MS/MS method for the simultaneous quantification of KB, Pyr, Lac and TCA cycle intermediates, and systematically evaluated pre-analytical factors affecting their stability and accuracy. We compared lithium-heparin (LH), ethylenediaminetetraacetic acid (EDTA), sodium fluoride/EDTA (NaF/EDTA) and sodium citrate (NaCit) collection tubes and deproteinized whole blood (depWB) using perchloric acid. Stability was assessed in whole blood at RT over 24 h, as well as in LH and depWB at various temperatures (RT, 4 °C, –20 °C) over 7 days.
Results
Pyr, Lac, AcAc and fumarate were most labile, while BHB and citrate were stable across matrices. LH-plasma with prompt centrifugation showed minimal metabolic alterations, while NaF/EDTA effectively stabilized Lac but compromised Pyr and TCA cycle intermediates. DepWB improved Lac/Pyr ratio reliability but introduced higher variability and matrix effects. NaCit induced unexpected metabolic shifts, suggesting in-vitro TCA cycle activity.
Conclusions
Our findings highlight the critical impact of anticoagulants and processing conditions on metabolite stability. LH-plasma provides the best compromise for quantifying KB, Pyr and TCA cycle intermediates when processed rapidly, while depWB remains preferable for accurate Lac/Pyr ratio determination despite its higher variability.
{"title":"Pre-analytical considerations in the simultaneous quantification of ketone bodies, lactate, pyruvate and TCA cycle intermediates","authors":"Kaitlyn Berchier , Chiara Nyffeler , Stephen Bruce , Clothilde Roux , Jean-Marc Nuoffer , Matthias Gautschi , Alexander Laemmle , Déborah Mathis","doi":"10.1016/j.clinbiochem.2025.111056","DOIUrl":"10.1016/j.clinbiochem.2025.111056","url":null,"abstract":"<div><h3>Background</h3><div>Accurate quantification of small metabolites such as ketone bodies (KB: β-hydroxybutyrate (BHB), acetoacetate (AcAc)), pyruvate (Pyr), lactate (Lac) and tricarboxylic acid (TCA) cycle intermediates is essential for diagnostics, therapy monitoring and metabolic research. These metabolites serve as energy substrates and signaling molecules, with their interpretation often relying on physiologically meaningful ratios (Lac/Pyr, BHB/AcAc). However, their chemical instability and susceptibility to rapid post-collection metabolism pose significant pre-analytical challenges.</div></div><div><h3>Method</h3><div>We developed an LC-MS/MS method for the simultaneous quantification of KB, Pyr, Lac and TCA cycle intermediates, and systematically evaluated pre-analytical factors affecting their stability and accuracy. We compared lithium-heparin (LH), ethylenediaminetetraacetic acid (EDTA), sodium fluoride/EDTA (NaF/EDTA) and sodium citrate (NaCit) collection tubes and deproteinized whole blood (depWB) using perchloric acid. Stability was assessed in whole blood at RT over 24 h, as well as in LH and depWB at various temperatures (RT, 4 °C, –20 °C) over 7 days.</div></div><div><h3>Results</h3><div>Pyr, Lac, AcAc and fumarate were most labile, while BHB and citrate were stable across matrices. LH-plasma with prompt centrifugation showed minimal metabolic alterations, while NaF/EDTA effectively stabilized Lac but compromised Pyr and TCA cycle intermediates. DepWB improved Lac/Pyr ratio reliability but introduced higher variability and matrix effects. NaCit induced unexpected metabolic shifts, suggesting in-vitro TCA cycle activity.</div></div><div><h3>Conclusions</h3><div>Our findings highlight the critical impact of anticoagulants and processing conditions on metabolite stability. LH-plasma provides the best compromise for quantifying KB, Pyr and TCA cycle intermediates when processed rapidly, while depWB remains preferable for accurate Lac/Pyr ratio determination despite its higher variability.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111056"},"PeriodicalIF":2.1,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530612","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}
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.
In this report, we describe an exceptional case of extreme hypokalemia < 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.
{"title":"Extreme hypokalemia in an asymptomatic 40-year-old cachectic male","authors":"Stanislas Francois , Sreekanth Rajagopal , Anne Boutten , Alexandre Raynor , 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 < 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":"2025-11-12","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}
Pub Date : 2025-11-12DOI: 10.1016/j.clinbiochem.2025.111039
Amanda Cristina Meneguetti Berti , Bárbara Braga Vieira Marques , Victoria Simões Bernardo , Flaviene Felix Torres , Gabriela Alves Bernardino , Júlia Junqueira Ruiz Silva , Ingrid Souza Dias , Ana Clara Albertin Zucão , Danilo Grünig Humberto da Silva , Edis Belini-Júnior
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 (HBB:c.304G > C) and Hb S (HBB:c.20A > 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 HBB 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.
血红蛋白病是世界上最常见的遗传性疾病之一，由血红蛋白（Hb）基因的各种突变引起。这些突变可导致不同的临床结果，其中一些会引起严重症状，突出了它们在全球卫生和遗传研究中的重要性。在这种情况下，本病例报告详细介绍了已知的Hb Rush （HBB: C . 304g > C）和Hb S （HBB: C）的复合杂合性的第一个实例。20A > T)，强调罕见Hb变异带来的诊断挑战，特别是那些模拟Hb s。具体而言，一名14岁男性患者因轻度贫血、小细胞症和溶血而被转诊，怀疑患有镰状细胞病（SCD）。然而，血液学、生化、色谱和电泳分析与SCD不一致，促使进一步的分子研究。高效液相色谱鉴定出一种血红蛋白变体，其保留时间与Hbs重叠。此外，碱性电泳显示出不稳定Hb典型的杂交四聚体，如Hb Rush。这些实验室发现通过HBB基因的Sanger测序得到进一步证实，该基因显示Hb Rush和Hb S的杂合性，建立了一种以前未报道的罕见基因型。Hb Rush中涉及G3（101）谷氨酸-谷氨酰胺取代的热不稳定性和结构变化解释了在该患者中观察到的血液学表型。因此，在这种情况下，将各种实验室方法（如电泳和分子分析）与患者的临床信息结合起来是至关重要的。这种全面的方法能够对潜在的基因型进行关键的解释，确保准确的诊断，适当的临床随访和治疗。
{"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 , Bárbara Braga Vieira Marques , Victoria Simões Bernardo , Flaviene Felix Torres , Gabriela Alves Bernardino , Júlia Junqueira Ruiz Silva , Ingrid Souza Dias , Ana Clara Albertin Zucão , Danilo Grünig Humberto da Silva , 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 > C) and Hb S (<em>HBB</em>:c.20A > 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":"2025-11-12","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}
Pub Date : 2025-11-11DOI: 10.1016/j.clinbiochem.2025.111040
Lawrence de Koning , Shelina M. Jamal , Catherine Ross , Michael J. Esser , Erin Pols
Case Presentations
We describe two cases of children who were significantly impacted by incorrectly prepared, hyperosmolar formula delivered via enteral tubes. The first case is of a 5-month-old post-pancreatectomy patient with complex needs who received hyperosmolar formula while in a pediatric intensive care unit (PICU), whereas the second is of a 1-year-old with spinal muscular atrophy who received hyperosmolar formula at home – resulting in a PICU admission.
Discussion
Hypovolemic hypernatremia is an important but poorly understood complication that can occur if overly concentrated formula is fed to children. Risk is almost certainly greater in enteral-tube fed patients because of their medical fragility but also because tube-feeding delivers formula directly and potentially very rapidly to the gastrointestinal system.
Conclusions
Formula for medically fragile, enteral tube-fed children should be prepared with utmost care – particularly when family caregivers are responsible for home feeding. In these cases, additional education and feeding support should be considered – including provision of pre-mixed formula. The clinical biochemistry laboratory can verify formula osmolality for these high-risk patients.
{"title":"Incorrectly prepared formula contributing to severe hypovolemic hypernatremia in enteral tube-fed children: A report of two cases","authors":"Lawrence de Koning , Shelina M. Jamal , Catherine Ross , Michael J. Esser , Erin Pols","doi":"10.1016/j.clinbiochem.2025.111040","DOIUrl":"10.1016/j.clinbiochem.2025.111040","url":null,"abstract":"<div><h3>Case Presentations</h3><div>We describe two cases of children who were significantly impacted by incorrectly prepared, hyperosmolar formula delivered via enteral tubes. The first case is of a 5-month-old post-pancreatectomy patient with complex needs who received hyperosmolar formula while in a pediatric intensive care unit (PICU), whereas the second is of a 1-year-old with spinal muscular atrophy who received hyperosmolar formula at home – resulting in a PICU admission.</div></div><div><h3>Discussion</h3><div>Hypovolemic hypernatremia is an important but poorly understood complication that can occur if overly concentrated formula is fed to children. Risk is almost certainly greater in enteral-tube fed patients because of their medical fragility but also because tube-feeding delivers formula directly and potentially very rapidly to the gastrointestinal system.</div></div><div><h3>Conclusions</h3><div>Formula for medically fragile, enteral tube-fed children should be prepared with utmost care – particularly when family caregivers are responsible for home feeding. In these cases, additional education and feeding support should be considered – including provision of pre-mixed formula. The clinical biochemistry laboratory can verify formula osmolality for these high-risk patients.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111040"},"PeriodicalIF":2.1,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512135","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 : 2025-11-11DOI: 10.1016/j.clinbiochem.2025.111046
Sylvie Giroux , Seyedeh Saideh Daryabari , André Caron , François Rousseau
Background
Reference materials are essential for the validation, verification, and implementation of clinical assays. Seracare has developed the Seraseq line—commercial reference standards for non-invasive prenatal testing (NIPT)—which are designed to simulate maternal plasma containing cell-free DNA (cfDNA).
Objective
This study aims to evaluate the performance of Seraseq reference materials compared to natural maternal plasma, particularly assessing their quality and reliability as reference standards in NIPT workflows, both with and without size selection to enrich fetal fraction.
Methods
We analyzed six replicates from eight different Seraseq genotypes. cfDNA was extracted, prepared into sequencing libraries, and sequenced following the same protocols used for natural plasma samples. Size-selection was also applied to enrich shorter cfDNA fragments. The key performance metrics included cfDNA yield and integrity, library preparation efficiency, sequencing quality, fetal fraction estimation, and detection of aneuploidies and sex chromosome abnormalities.
Results
cfDNA quantity and quality from Seraseq materials were comparable to natural plasma. The materials yielded consistent library concentrations. Sequencing showed reliable detection of all targeted aneuploidies except the microdeletion del22q11, even with elevated fetal fraction. Size-selection increased fetal fraction and improved Z-scores for aneuploidy detection across all genotypes. Fragment size profiles exhibited slight but consistent deviations from natural plasma, notably after size selection.
Conclusions
Seraseq reference materials closely mimic the cfDNA characteristics of maternal plasma and perform reliably across multiple testing dimensions. While they may present slight differences in fragment size periodicity, these did not affect analytical performance. These materials are therefore suitable for validating and monitoring NIPT workflows.
{"title":"SeraSeq reference materials support non-invasive cfDNA screening methods","authors":"Sylvie Giroux , Seyedeh Saideh Daryabari , André Caron , François Rousseau","doi":"10.1016/j.clinbiochem.2025.111046","DOIUrl":"10.1016/j.clinbiochem.2025.111046","url":null,"abstract":"<div><h3>Background</h3><div>Reference materials are essential for the validation, verification, and implementation of clinical assays. Seracare has developed the Seraseq line—commercial reference standards for non-invasive prenatal testing (NIPT)—which are designed to simulate maternal plasma containing cell-free DNA (cfDNA).</div></div><div><h3>Objective</h3><div>This study aims to evaluate the performance of Seraseq reference materials compared to natural maternal plasma, particularly assessing their quality and reliability as reference standards in NIPT workflows, both with and without size selection to enrich fetal fraction.</div></div><div><h3>Methods</h3><div>We analyzed six replicates from eight different Seraseq genotypes. cfDNA was extracted, prepared into sequencing libraries, and sequenced following the same protocols used for natural plasma samples. Size-selection was also applied to enrich shorter cfDNA fragments. The key performance metrics included cfDNA yield and integrity, library preparation efficiency, sequencing quality, fetal fraction estimation, and detection of aneuploidies and sex chromosome abnormalities.</div></div><div><h3>Results</h3><div>cfDNA quantity and quality from Seraseq materials were comparable to natural plasma. The materials yielded consistent library concentrations. Sequencing showed reliable detection of all targeted aneuploidies except the microdeletion del22q11, even with elevated fetal fraction. Size-selection increased fetal fraction and improved Z-scores for aneuploidy detection across all genotypes. Fragment size profiles exhibited slight but consistent deviations from natural plasma, notably after size selection.</div></div><div><h3>Conclusions</h3><div>Seraseq reference materials closely mimic the cfDNA characteristics of maternal plasma and perform reliably across multiple testing dimensions. While they may present slight differences in fragment size periodicity, these did not affect analytical performance. These materials are therefore suitable for validating and monitoring NIPT workflows.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"141 ","pages":"Article 111046"},"PeriodicalIF":2.1,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512062","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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