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Immune complexome analysis reveals an autoimmune signature predictive of COVID-19 severity 免疫复合物分析揭示了可预测COVID-19严重程度的自身免疫特征。
IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.clinbiochem.2024.110865
Marino Moriishi , Takahiro Takazono , Junya Hashizume , Nozomi Aibara , Yuki Jimbayashi Kutsuna , Masaki Okamoto , Toyomitsu Sawai , Teppei Hoshino , Yusuke Mori , Yuichi Fukuda , Yukikazu Awaya , Hirotomo Yamanashi , Yuichiro Furusato , Toyoshi Yanagihara , Hirotaka Miyamoto , Kayoko Sato , Yukinobu Kodama , Shusaku Mizukami , Noriho Sakamoto , Kazuko Yamamoto , Kaname Ohyama

Background

The factors contributing to the development of severe coronavirus disease 2019 (COVID-19) following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. Although the presence of immune complexes (ICs), formed between antibodies and their antigens, has been linked to COVID-19 severity, their role requires further investigation, and the antigens within these ICs are yet to be characterized.

Method

Here, a C1q enzyme-liked immunosorbent assay and immune complexome analysis were used to determine IC concentrations and characterize IC antigens, respectively, in the sera of 64 unvaccinated COVID-19 patients with PCR-confirmed SARS-CoV-2 infection, enrolled at seven participating centers in 2020. For the analysis, the patients were split into the severe (n = 35) and non-severe (n = 28) groups on the basis of their COVID-19 symptoms.

Results

We found that neither serum IC concentration nor IC antigen number was associated with COVID-19 severity. However, we identified six IC antigens, which were significantly enriched in the severe versus non-severe group. These IC antigens were all derived from human proteins, namely haptoglobin, the serum amyloid A-2 protein, the serum amyloid A-1 protein, clusterin, and lipopolysaccharide-binding protein, and complement-factor-H-related protein 3. Meanwhile, we found no association between COVID-19 severity and IC antigens derived from SARS-CoV-2 proteins. Collectively, the six IC antigens predicted COVID-19 severity with a moderate degree of accuracy (area under the receiver operating characteristic curve = 0.90, sensitivity = 94 %, specificity = 79 %).

Conclusions

The IC antigen signature identified in this study may have important implications for the diagnosis and treatment of severe COVID-19.
背景:严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)感染后发生严重冠状病毒病2019 (COVID-19)的因素尚不清楚。虽然在抗体和抗原之间形成的免疫复合物(ic)的存在与COVID-19的严重程度有关,但它们的作用需要进一步研究,而且这些ic内的抗原尚未被表征。方法:本研究采用C1q酶样免疫吸附试验和免疫络合体分析分别测定了64例未接种疫苗的SARS-CoV-2感染患者血清中的IC浓度和IC抗原特征,这些患者于2020年在7个参与中心登记。为了进行分析,根据患者的COVID-19症状将患者分为重症组(n = 35)和非重症组(n = 28)。结果:我们发现血清IC浓度和IC抗原数量与COVID-19严重程度无关。然而,我们发现了6种IC抗原,在严重组和非严重组中显著富集。这些IC抗原均来源于人蛋白,即:触珠蛋白、血清淀粉样蛋白A-2、血清淀粉样蛋白A-1、聚簇蛋白和脂多糖结合蛋白、补体因子- h相关蛋白3。同时,我们发现COVID-19严重程度与SARS-CoV-2蛋白衍生的IC抗原之间没有关联。总的来说,6种IC抗原预测COVID-19严重程度的准确度中等(受试者工作特征曲线下面积 = 0.90,灵敏度 = 94 %,特异性 = 79 %)。结论:本研究确定的IC抗原特征可能对重症COVID-19的诊断和治疗具有重要意义。
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引用次数: 0
Evaluation of a new soluble transferrin receptor assay and comparison to three measurement procedures 一种新的可溶性转铁蛋白受体测定方法的评价和三种测量方法的比较。
IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.clinbiochem.2024.110862
Mary Kathryn Bohn , Marvin Berman , Salman Ali , Pow Lee Cheng , Xiao Yan Wang , Randal J. Schneider , Vathany Kulasingam

Background

Soluble transferrin receptor (sTfR) is a useful marker in the differentiation of anemia. Clinical utility is limited by lack of standardization between measurement procedures and interpretative recommendations. Our objective was to evaluate the analytical performance of a research sTfR immunoturbidimetric assay (Alinity c, Abbott Diagnostics) and compare it to three established measurement procedures.

Methods

Assay imprecision was assessed with 7 panels across the analytical measuring interval. 159 patient samples were measured across four instrument systems (Alinity c [Abbott Diagnostics], Tina-quant c502 [Roche Diagnostics], Quantex Biokit [Werfen], and ACCESS [Beckman Coulter]). Ferritin was also measured to calculate an sTfR/Log Ferritin ratio. Sera from 100 reference individuals were assayed for sTfR and ferritin (Alinity) for reference interval (RI) verification (sTfR) or establishment (sTfR index).

Results

Assay imprecision met defined goals. Method comparison between Alinity c and ACCESS sTfR assays showed good agreement (slope: 1.06, intercept: −0.12, r: 0.989). Comparisons across other assays demonstrated significant proportional bias with slopes ranging from 0.44 (Tina-quant c502, mean bias: −2.52 mg/L) to 1.24 (Quantex Biokit, mean bias: 0.60 mg/L). A proportional bias was observed between other instruments. While the sTfR RI was verified on the Alinity assay, agreement in interpretation (within vs outside RI) between Alinity and other platforms ranged from 74.2 to 80.5 %.

Conclusion

We report the first characterization of the performance of a research sTfR immunoturbidimetric assay (Alinity c, Abbott Diagnostics). Our findings emphasize the lack of harmonization between measurement procedures and result interpretation for sTfR and sTfR index, necessitating standardization efforts and clinical studies.
背景:可溶性转铁蛋白受体(sTfR)是鉴别贫血的有用标志物。临床应用受到测量程序和解释性建议之间缺乏标准化的限制。我们的目的是评估研究sTfR免疫比浊法(Alinity c, Abbott Diagnostics)的分析性能,并将其与三种已建立的测量程序进行比较。方法:在整个分析测量区间内用7个面板评估分析不精密度。159例患者样本通过四种仪器系统(Alinity c [Abbott Diagnostics]、Tina-quant c502 [Roche Diagnostics]、Quantex Biokit [Werfen]和ACCESS [Beckman Coulter])进行测量。测定铁蛋白以计算sTfR/Log铁蛋白比率。测定100例参考个体血清的sTfR和铁蛋白(aliniity),用于验证参考区间(RI) (sTfR)或建立参考区间(sTfR指数)。结果:测定不精密度达到规定目标。Alinity c和ACCESS sTfR检测结果一致(斜率:1.06,截距:-0.12,r: 0.989)。其他试验的比较显示出显著的比例偏差,斜率范围从0.44 (Tina-quant c502,平均偏差:-2.52 mg/L)到1.24 (Quantex Biokit,平均偏差:0.60 mg/L)。在其他仪器之间观察到比例偏差。虽然在Alinity检测中验证了sTfR RI,但Alinity与其他平台之间的解释一致性(在RI内与外部)范围为74.2-80.5 %。结论:我们报告了研究sTfR免疫比浊测定性能的第一个特征(Alinity c, Abbott Diagnostics)。我们的研究结果强调了sTfR和sTfR指数的测量程序和结果解释之间缺乏一致性,需要标准化工作和临床研究。
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引用次数: 0
Constructing a predictive model for high intraoperative excessive bleeding in patients undergoing posterior lumbar decompression and fusion internal fixation surgery during outpatient visits. 建立腰椎后路减压融合内固定手术患者门诊时术中大量大出血的预测模型。
IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-01-01 Epub Date: 2024-12-01 DOI: 10.1016/j.clinbiochem.2024.110856
Zhenmin Sun, Nan Yang, Lei Wang, Jiansuo Zhou, Hua Zhang, Jun Wang

Objective: 1. Construct a risk prediction model to predict the factors of high intraoperative bleeding in patients undergoing posterior lumbar decompression and fusion internal fixation surgery during outpatient visits. 2. Implement pre-hospital blood management for surgery patients, to improve clinical outcomes.

Design & methods: We collected patients who underwent two-segment and three-segment posterior lumbar decompression and fusion internal fixation surgery in our hospital from 2016 to 2021. A total of 24 preoperative indicators were analyzed, covering medical history, demographic characteristics, segment, operator and laboratory test results. We used a logistic regression model to optimize the model's feature selection. The predictive model was constructed using the multivariable logistic regression method with all included methods, and a nomogram was created to display the model. Activated partial thromboplastin time, surgeon volume, American Society of Anesthesiologists classification, body mass index, and the number of fusion and fixation lumbar segments were used to construct the predictive model. The predictive model's discrimination, calibration, clinical applicability, and rationality were evaluated.

Results: The predictive model's area under the receiver operating characteristic curve is 0.723, with a 95% confidence interval of (0.685-0.760). The training set's decision curve analysis demonstrates that applying this diagnostic curve will increase the net benefit when the threshold probability is between 5% and 40%.

Conclusion: This study developed a novel nomogram with relatively good accuracy to assist clinical doctors in assessing the high intraoperative bleeding risk in patients undergoing posterior lumbar decompression and fusion internal fixation surgery during outpatient visits. By evaluating individual risk, surgeons can develop an individualized treatment plan to reduce the risk of intraoperative bleeding for each patient.

目的:1。建立风险预测模型,预测门诊腰椎后路减压融合内固定手术患者术中高出血因素。2. 对手术患者实施院前血液管理,提高临床疗效。设计与方法:我们收集2016年至2021年在我院行二节段和三节段后路腰椎减压融合内固定手术的患者。共分析24项术前指标,包括病史、人口统计学特征、手术部位、手术操作者和实验室检查结果。我们使用逻辑回归模型来优化模型的特征选择。采用多变量logistic回归方法建立了预测模型,并建立了模型的模态图。激活部分凝血活素时间、外科医生体积、美国麻醉医师学会分类、体重指数、融合固定腰椎节段数量被用于构建预测模型。对预测模型的鉴别、校正、临床适用性和合理性进行评价。结果:预测模型的受试者工作特征曲线下面积为0.723,95%置信区间为(0.685 ~ 0.760)。训练集的决策曲线分析表明,当阈值概率在5% ~ 40%之间时,应用该诊断曲线可以提高净效益。结论:本研究开发了一种准确度相对较高的新型nomogram方法,可帮助临床医生在门诊期间评估后路腰椎减压融合内固定手术患者的高术中出血风险。通过评估个体风险,外科医生可以制定个性化的治疗计划,以减少每个患者术中出血的风险。
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引用次数: 0
DNA methylation levels may contribute to severe hypertriglyceridemia in multifactorial chylomicronemia syndrome DNA甲基化水平可能导致多因子乳糜微粒血症综合征中的严重高甘油三酯血症。
IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.clinbiochem.2025.110873
Simon-Pierre Guay , Martine Paquette , Amélie Taschereau , Véronique Desgagné , Luigi Bouchard , Sophie Bernard , Alexis Baass

Background and aims

Familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS) are the two main causes of severe hypertriglyceridemia (sHTG). FCS is a rare autosomal recessive form of sHTG, whereas MCS is mainly polygenic in nature with both common and rare variants accumulating and leading to sHTG. However, 30 to 50% of MCS patients have no identified genetic cause of sHTG. DNA methylation (DNAm) is a non-traditional heritable factor known to be associated with triglyceride (TG) levels. The aim of this study is to determine if DNAm level at three candidate genes for hypertriglyceridemia (ABCG1, CPT1A and SREBF1) could contribute to sHTG in MCS patients.

Methods

A total of 114 MCS and 20 FCS patients were included in this retrospective study. DNAm levels were measured at ABCG1 (cg06500161), CPT1A (cg00574958), and SREBF1 (cg11024682) gene loci using pyrosequencing of bisulfite-treated DNA.

Results

DNAm levels at ABCG1, CPT1A and SREBF1 were significantly associated with TG levels or minimal TG levels in MCS patients. Prevalence of patients with at least 2 loci with DNAm levels into the top tertile of DNAm associated with hypertriglyceridemia was significantly higher in MCS patients with genetically undefined sHTG compared to MCS patients with polygenic sHTG and FCS patients (57 % vs. 24 % vs. 0 %, respectively; p < 0.0001).

Conclusion

This study suggests for the first time that DNAm could contribute to sHTG in MCS patients. It suggests that further studies of epivariations may contribute to better understand the clinical heterogeneity seen in MCS patients.
背景和目的:家族性乳糜微粒血症综合征(FCS)和多因素乳糜微粒血症综合征(MCS)是导致严重高甘油三酯血症(sHTG)的两个主要原因。FCS 是一种罕见的常染色体隐性高甘油三酯血症(sHTG),而 MCS 主要是多基因遗传,常见变异和罕见变异都会累积并导致高甘油三酯血症(sHTG)。然而,30%至 50%的 MCS 患者并没有发现导致 sHTG 的遗传原因。DNA甲基化(DNAm)是一种非传统遗传因素,已知与甘油三酯(TG)水平有关。本研究旨在确定高甘油三酯血症的三个候选基因(ABCG1、CPT1A 和 SREBF1)的 DNAm 水平是否会导致 MCS 患者的高甘油三酯血症:这项回顾性研究共纳入了 114 名 MCS 和 20 名 FCS 患者。结果:ABCG1、CPT1A和SREBF1基因位点的DNAm水平可能是导致MCS患者SHTG的原因之一:ABCG1、CPT1A和SREBF1基因位点的DNAm水平与MCS患者的TG水平或最低TG水平显著相关。与多基因 sHTG 的 MCS 患者和 FCS 患者相比(分别为 57% vs. 24% vs. 0%;P 结论:该研究首次表明,在 MCS 患者中,DNAm 水平与高甘油三酯血症相关的至少 2 个位点达到最高三分位点的患者比例明显较高:本研究首次表明,DNAm 可能是导致 MCS 患者 sHTG 的原因之一。这表明,进一步研究外显子可能有助于更好地理解 MCS 患者的临床异质性。
{"title":"DNA methylation levels may contribute to severe hypertriglyceridemia in multifactorial chylomicronemia syndrome","authors":"Simon-Pierre Guay ,&nbsp;Martine Paquette ,&nbsp;Amélie Taschereau ,&nbsp;Véronique Desgagné ,&nbsp;Luigi Bouchard ,&nbsp;Sophie Bernard ,&nbsp;Alexis Baass","doi":"10.1016/j.clinbiochem.2025.110873","DOIUrl":"10.1016/j.clinbiochem.2025.110873","url":null,"abstract":"<div><h3>Background and aims</h3><div>Familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS) are the two main causes of severe hypertriglyceridemia (sHTG). FCS is a rare autosomal recessive form of sHTG, whereas MCS is mainly polygenic in nature with both common and rare variants accumulating and leading to sHTG. However, 30 to 50% of MCS patients have no identified genetic cause of sHTG. DNA methylation (DNAm) is a non-traditional heritable factor known to be associated with triglyceride (TG) levels. The aim of this study is to determine if DNAm level at three candidate genes for hypertriglyceridemia (<em>ABCG1</em>, <em>CPT1A</em> and <em>SREBF1</em>) could contribute to sHTG in MCS patients.</div></div><div><h3>Methods</h3><div>A total of 114 MCS and 20 FCS patients were included in this retrospective study. DNAm levels were measured at <em>ABCG1</em> (cg06500161), <em>CPT1A</em> (cg00574958), and <em>SREBF1</em> (cg11024682) gene loci using pyrosequencing of bisulfite-treated DNA.</div></div><div><h3>Results</h3><div>DNAm levels at <em>ABCG1</em>, <em>CPT1A</em> and <em>SREBF1</em> were significantly associated with TG levels or minimal TG levels in MCS patients. Prevalence of patients with at least 2 loci with DNAm levels into the top tertile of DNAm associated with hypertriglyceridemia was significantly higher in MCS patients with genetically undefined sHTG compared to MCS patients with polygenic sHTG and FCS patients (57 % vs. 24 % vs. 0 %, respectively; <em>p</em> &lt; 0.0001).</div></div><div><h3>Conclusion</h3><div>This study suggests for the first time that DNAm could contribute to sHTG in MCS patients. It suggests that further studies of epivariations may contribute to better understand the clinical heterogeneity seen in MCS patients.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110873"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930660","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}
引用次数: 0
Serial secretoneurin measurement and risk of ventricular arrhythmias and death in patients with left ventricular systolic dysfunction 左心室收缩功能不全患者的连续分泌神经素测定与室性心律失常和死亡的风险。
IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-01-01 DOI: 10.1016/j.clinbiochem.2024.110868
Torbjørn Omland , Helge Røsjø , Torbjørn Wisløff , Michael L. Bernard , A.Elise Hiltbold , Sammy Khatib , Glenn M. Polin , Paul A. Rogers , Daniel P. Morin

Background

Secretoneurin, a member of the granin protein family, is associated with the risk of mortality in patients with acute and chronic heart failure. Secretoneurin may play an important role in cardiomyocyte calcium handling, suggesting that it may influence cardiac arrhythmia risk. We hypothesized that baseline and serial measurements of circulating secretoneurin are associated with the risk of incident ventricular tachyarrhythmias (VA) and death, and that serial measurement would provide prognostic information beyond baseline values.

Methods

We measured circulating secretoneurin concentrations in blood samples obtained at 3-month intervals for one year in a prospectively enrolled cohort of ambulatory patients with left ventricular ejection fraction (LVEF) ≤ 35 % and a primary-prevention implanted cardioverter defibrillator (ICD). Associations between secretoneurin modeled as a time-dependent variable and the incidences of VA and death were assessed.

Results

154 patients (66 ± 14 years, LVEF 23 ± 8 %) were included in the analysis. During one-year follow-up, 26 (17 %) patients experienced VA, and 16 (10 %) died. Adjusting for age, sex, eGFR, and LVEF, baseline secretoneurin concentration was associated with the risk of death (hazard ratio (HR) per 10 pmol/L increase: 1.14 (95 % CI: 1.02–1.27), p = 0.020) but not VA (HR: 0.98 (0.81–1.19), p = 0.856). Using serial measurements at 3-month intervals, time-varying secretoneurin was associated with a similarly higher risk of death (HR: 1.14 (1.02–1.27), p = 0.017) but not of VA (HR: 0.97 (0.81–1.17), p = 0.776).

Conclusion

In stable ambulatory patients with reduced LV systolic function and a primary prevention indication for ICD, secretoneurin concentration was associated with the risk of death but not ventricular tachyarrhythmia.
背景:分泌神经蛋白是颗粒蛋白家族的一员,与急性和慢性心力衰竭患者的死亡风险相关。分泌神经素可能在心肌细胞钙处理中起重要作用,提示它可能影响心律失常的风险。我们假设循环分泌神经素的基线和连续测量与室性心动过速(VA)和死亡的风险相关,并且连续测量将提供超出基线值的预后信息。方法:我们对一组左室射血分数(LVEF) ≤ 35 %并使用一级预防植入式心律转复除颤器(ICD)的非住院患者进行前瞻性研究,每隔3个月采集血液样本,测量血液中循环分泌神经蛋白的浓度。作为时间相关变量的分泌神经素模型与VA和死亡发生率之间的关系进行了评估。结果:154例患者(66 ± 14 岁,LVEF 23 ± 8 %)纳入分析。在一年的随访中,26例(17 %)患者发生了VA, 16例(10 %)死亡。调整年龄、性别、eGFR和LVEF后,基线分泌神经素浓度与死亡风险相关(每增加10 pmol/L风险比(HR): 1.14(95 % CI: 1.02-1.27), p = 0.020),但与VA无关(HR: 0.98 (0.81-1.19), p = 0.856)。通过间隔3个月的连续测量,时间变化的分泌神经素与同样较高的死亡风险相关(HR: 1.14 (1.02-1.27), p = 0.017),但与VA无关(HR: 0.97 (0.81-1.17), p = 0.776)。结论:在稳定的左室收缩功能降低且有ICD一级预防指征的门诊患者中,分泌神经蛋白浓度与死亡风险相关,但与室性心动过速无关。
{"title":"Serial secretoneurin measurement and risk of ventricular arrhythmias and death in patients with left ventricular systolic dysfunction","authors":"Torbjørn Omland ,&nbsp;Helge Røsjø ,&nbsp;Torbjørn Wisløff ,&nbsp;Michael L. Bernard ,&nbsp;A.Elise Hiltbold ,&nbsp;Sammy Khatib ,&nbsp;Glenn M. Polin ,&nbsp;Paul A. Rogers ,&nbsp;Daniel P. Morin","doi":"10.1016/j.clinbiochem.2024.110868","DOIUrl":"10.1016/j.clinbiochem.2024.110868","url":null,"abstract":"<div><h3>Background</h3><div>Secretoneurin, a member of the granin protein family, is associated with the risk of mortality in patients with acute and chronic heart failure. Secretoneurin may play an important role in cardiomyocyte calcium handling, suggesting that it may influence cardiac arrhythmia risk. We hypothesized that baseline and serial measurements of circulating secretoneurin are associated with the risk of incident ventricular tachyarrhythmias (VA) and death, and that serial measurement would provide prognostic information beyond baseline values.</div></div><div><h3>Methods</h3><div>We measured circulating secretoneurin concentrations in blood samples obtained at 3-month intervals for one year in a prospectively enrolled cohort of ambulatory patients with left ventricular ejection fraction (LVEF) ≤ 35 % and a primary-prevention implanted cardioverter defibrillator (ICD). Associations between secretoneurin modeled as a time-dependent variable and the incidences of VA and death were assessed.</div></div><div><h3>Results</h3><div>154 patients (66 ± 14 years, LVEF 23 ± 8 %) were included in the analysis. During one-year follow-up, 26 (17 %) patients experienced VA, and 16 (10 %) died. Adjusting for age, sex, eGFR, and LVEF, baseline secretoneurin concentration was associated with the risk of death (hazard ratio (HR) per 10 pmol/L increase: 1.14 (95 % CI: 1.02–1.27), p = 0.020) but not VA (HR: 0.98 (0.81–1.19), p = 0.856). Using serial measurements at 3-month intervals, time-varying secretoneurin was associated with a similarly higher risk of death (HR: 1.14 (1.02–1.27), p = 0.017) but not of VA (HR: 0.97 (0.81–1.17), p = 0.776).</div></div><div><h3>Conclusion</h3><div>In stable ambulatory patients with reduced LV systolic function and a primary prevention indication for ICD, secretoneurin concentration was associated with the risk of death but not ventricular tachyarrhythmia.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110868"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of three different cystatin C measurement procedures in a pediatric chronic kidney disease cohort: Calibration for longitudinal measurements and implications for clinical estimation of GFR. 儿童慢性肾病队列中三种不同胱抑素C测量方法的比较:纵向测量的校准及其对GFR临床估计的影响
IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-12-24 DOI: 10.1016/j.clinbiochem.2024.110869
Derek K Ng, George J Schwartz, Bradley A Warady, Susan L Furth, Jesse C Seegmiller

Introduction: Serum cystatin C (CysC) is used to estimate glomerular filtration rate (eGFR), including in the Chronic Kidney Disease in Children (CKiD) Under 25 years (U25eGFR) equations. Several CysC measurement procedures available from diagnostic vendors include reference material for calibration, but the extent of heterogeneity across manufacturers is unclear. Since heterogeneity may have clinical and research implications for eGFR, we evaluated three CysC procedures in samples from the CKiD study representing a wide spectrum of kidney function.

Materials and methods: The three CysC measurement procedures evaluated were: Siemens BN II N Latex CystatinC Assay; Gentian CystatinC Immunoassay; and Roche Tina-quant CystatinC Gen.2. Bland-Altman quantified agreement with Siemens as reference because that method was used for longitudinal CKiD samples from 2003 to 2023. We present derivation of the interquartile range (IQR) of U25eGFR as a measure of precision and describe differences outside this range.

Results: From 53 samples from 44 participants, Gentian measurements were 7 % higher than Siemens (95 %CI: +5.6 %,+8.5 %), while Roche measurements were 4.8 % lower on average (95 %CI: -6.2 %,-3.3 %). Both had very high correlation: 0.9926 and 0.9906, respectively. There was strong agreement across procedures, but a simple correction factor of 7 % reduction applied to Gentian yielded unbiased estimates (+0.03 %, 95 %CI: -1.3 %,+1.4 %) and strong performance in Deming regression. For precision, 98 % of U25eGFR values based on Gentian and Roche CysC were each within the IQR of the Siemens-based estimates.

Conclusions: Despite reference material calibration, heterogeneity across CysC measurement procedures was observed. Procedure variability was within the limits of U25eGFR estimates indicating that practically, all procedures are appropriate for clinical use. Clinicians may consider calculating IQR of U25eGFR estimates for pediatric chronic kidney disease management.

血清胱抑素C (CysC)用于估计肾小球滤过率(eGFR),包括在25岁以下儿童慢性肾病(CKiD) 年(U25eGFR)方程中。诊断供应商提供的几种CysC测量程序包括用于校准的参考材料,但各制造商之间的异质性程度尚不清楚。由于异质性可能对eGFR具有临床和研究意义,我们评估了CKiD研究样本中的三种CysC程序,代表了广泛的肾功能。材料和方法:评估的三种CysC测量方法为:Siemens BN II N Latex CystatinC Assay;龙胆CystatinC免疫测定;和罗氏Tina-quant CystatinC Gen.2。Bland-Altman量化了Siemens的一致性作为参考,因为该方法用于2003年至2023年的纵向CKiD样本。我们提出了U25eGFR的四分位数范围(IQR)的推导,作为精度的度量,并描述了该范围之外的差异。结果:在44名参与者的53份样本中,龙胆草的测量值比西门子高7 %(95 %CI: +5.6 %,+8.5 %),而罗氏的测量值平均低4.8 %(95 %CI: -6.2 %,-3.3 %)。两者的相关性都非常高,分别为0.9926和0.9906。在整个过程中有很强的一致性,但对龙胆草进行简单的校正因子7 %的减少产生了无偏估计(+0.03 %,95 %CI: -1.3 %,+1.4 %),并且在Deming回归中表现良好。为了精确起见,98 %基于龙胆草和罗氏CysC的U25eGFR值都在基于西门子的估计的IQR内。结论:尽管进行了标准物质校准,但在CysC测量过程中观察到异质性。手术的可变性在U25eGFR估计的范围内,这表明实际上,所有手术都适合临床使用。临床医生可以考虑计算IQR的U25eGFR估计儿童慢性肾脏疾病的管理。
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引用次数: 0
Re-evaluating the utility of iron indices in hereditary hemochromatosis genotyping: A retrospective study 重新评价铁指标在遗传性血色素沉着病基因分型中的应用:一项回顾性研究
IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-11-29 DOI: 10.1016/j.clinbiochem.2024.110860
Amy Lou , Manal O. Elnenaei , Julie Zhu , Kevork Peltekian , Eric Liu , Jennifer A. Jamieson , Hammam Said , Bassam A. Nassar

Introduction

Hereditary hemochromatosis (HH), associated with C282Y or H63D mutations in the HFE gene, is the commonest genetic disorder in Canada. The majority of HH cases are attributable to C282Y homozygosity which can precipitate iron overload and organ damage, but with low penetrance. Elevated transferrin saturation (TSat) and ferritin levels are key biochemical indicators of iron overload in C282Y homozygotes. This retrospective study examined TSat and ferritin levels as predictors of C282Y homozygosity in genotyped patients.

Methods

This study included 23,432 individuals from Maritime provinces who underwent HFE genotyping from 2009 to 2022. Those with available biomarkers (TSat, ferritin, ALT) were included in the study sample. C282Y and H63D variants were identified based on HFE genotying. Median values for each biomarker were compared across genotypes and their diagnostic performance in predicting C282Y homozygosity evaluated using ROC analysis.

Results

1241 individuals (5.3 %) showed C282Y homozygosity, marking the largest North American study cohort. C282Y homozygotes showed significantly higher median TSat and ferritin levels than wildtypes. TSat showed the best diagnostic performance in detecting C282Y homozygosity (AUC = 0.82, 95 % CI: 0.78–0.85), outperforming ferritin (AUC = 0.54, 95 % CI: 0.50–0.58) and ALT (AUC = 0.59, 95 % CI: 0.56–0.63). TSat thresholds of 32 % (females) and 35 % (males) had a 90 % sensitivity for C282Y homozygosity. Using thresholds of TSat ≤46 % and ferritin ≤370 µg/L (females), and TSat ≤49 % and ferritin ≤703 µg/L (males) reduced the need for genotyping by up to 50 % without missing significant biochemical iron overload cases. Implementing this strategy across 23,432 tests could save $1,701,163 and potentially reduce unnecessary downstream management.

Conclusion

Our study suggests significant efficiency savings by implementing an algorithm to reduce unnecessary HFE genotyping and alleviate unwarranted genetic testing anxiety.
遗传性血色素沉着症(HH)与HFE基因的C282Y或H63D突变相关,是加拿大最常见的遗传性疾病。大多数HH病例可归因于C282Y纯合性,可导致铁超载和器官损伤,但外显率低。转铁蛋白饱和度(TSat)和铁蛋白水平升高是C282Y纯合子铁超载的关键生化指标。本回顾性研究检验了TSat和铁蛋白水平作为基因型患者C282Y纯合性的预测因子。方法本研究纳入2009 - 2022年来自沿海省份的23,432例HFE基因分型患者。具有可用生物标志物(TSat、铁蛋白、ALT)者纳入研究样本。通过HFE基因测序鉴定C282Y和H63D变异。比较各基因型生物标志物的中位数,并使用ROC分析评估其预测C282Y纯合性的诊断性能。结果1241例(5.3%)个体显示C282Y纯合性,是北美最大的研究队列。C282Y纯合子的TSat和铁蛋白水平中位数明显高于野生型。TSat对C282Y纯合性的诊断效果最好(AUC = 0.82, 95% CI: 0.78 ~ 0.85),优于铁蛋白(AUC = 0.54, 95% CI: 0.50 ~ 0.58)和ALT (AUC = 0.59, 95% CI: 0.56 ~ 0.63)。TSat阈值为32%(女性)和35%(男性),对C282Y纯合性的敏感性为90%。使用TSat≤46%和铁蛋白≤370µg/L(女性)以及TSat≤49%和铁蛋白≤703µg/L(男性)的阈值,在不遗漏显著生化铁超载病例的情况下,减少了高达50%的基因分型需求。在23,432个测试中实施该策略可以节省1,701,163美元,并可能减少不必要的下游管理。结论本研究表明,通过实施一种算法来减少不必要的HFE基因分型和减轻不必要的基因检测焦虑,可以显著节省效率。
{"title":"Re-evaluating the utility of iron indices in hereditary hemochromatosis genotyping: A retrospective study","authors":"Amy Lou ,&nbsp;Manal O. Elnenaei ,&nbsp;Julie Zhu ,&nbsp;Kevork Peltekian ,&nbsp;Eric Liu ,&nbsp;Jennifer A. Jamieson ,&nbsp;Hammam Said ,&nbsp;Bassam A. Nassar","doi":"10.1016/j.clinbiochem.2024.110860","DOIUrl":"10.1016/j.clinbiochem.2024.110860","url":null,"abstract":"<div><h3>Introduction</h3><div>Hereditary hemochromatosis (HH), associated with C282Y or H63D mutations in the HFE gene, is the commonest genetic disorder in Canada. The majority of HH cases are attributable to C282Y homozygosity which can precipitate iron overload and organ damage, but with low penetrance. Elevated transferrin saturation (TSat) and ferritin levels are key biochemical indicators of iron overload in C282Y homozygotes. This retrospective study examined TSat and ferritin levels as predictors of C282Y homozygosity in genotyped patients.</div></div><div><h3>Methods</h3><div>This study included 23,432 individuals from Maritime provinces who underwent HFE genotyping from 2009 to 2022. Those with available biomarkers (TSat, ferritin, ALT) were included in the study sample. C282Y and H63D variants were identified based on HFE genotying. Median values for each biomarker were compared across genotypes and their diagnostic performance in predicting C282Y homozygosity evaluated using ROC analysis.</div></div><div><h3>Results</h3><div>1241 individuals (5.3 %) showed C282Y homozygosity, marking the largest North American study cohort. C282Y homozygotes showed significantly higher median TSat and ferritin levels than wildtypes. TSat showed the best diagnostic performance in detecting C282Y homozygosity (AUC = 0.82, 95 % CI: 0.78–0.85), outperforming ferritin (AUC = 0.54, 95 % CI: 0.50–0.58) and ALT (AUC = 0.59, 95 % CI: 0.56–0.63). TSat thresholds of 32 % (females) and 35 % (males) had a 90 % sensitivity for C282Y homozygosity. Using thresholds of TSat ≤46 % and ferritin ≤370 µg/L (females), and TSat ≤49 % and ferritin ≤703 µg/L (males) reduced the need for genotyping by up to 50 % without missing significant biochemical iron overload cases. Implementing this strategy across 23,432 tests could save $1,701,163 and potentially reduce unnecessary downstream management.</div></div><div><h3>Conclusion</h3><div>Our study suggests significant efficiency savings by implementing an algorithm to reduce unnecessary HFE genotyping and alleviate unwarranted genetic testing anxiety.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110860"},"PeriodicalIF":2.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Longitudinal changes in plasma Cystatin C and all-cause mortality risk among the middle-aged and elderly Chinese population 中国中老年人群血浆胱抑素 C 与全因死亡风险的纵向变化
IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-11-23 DOI: 10.1016/j.clinbiochem.2024.110858
Ying Zhang , Ling Zhang , Jie Xing , Yujie Weng , Wangquan Xu , Liping Zhi , Min Yuan

Objective

Elevated plasma Cystatin C levels are associated with an increased mortality risk among middle-aged and elderly Chinese individuals. This study explores whether tracking the longitudinal changes in Cystatin C can improve the prediction of mortality risk and allow better risk stratification, jointly with baseline measurements.

Design & Methods

This analysis includes 3,195 participants from the China Health and Retirement Longitudinal Study who completed plasma Cystatin C measurements in two waves (2011 and 2015) and were followed through 2020. To evaluate the association between Cystatin C levels/changes and mortality risk, multivariate Cox proportional hazard models were employed, adjusting for potential confounders. Survival probabilities were compared using Kaplan-Meier curves and log-rank tests, while restricted cubic splines were utilized to illustrate any nonlinear relationships between Cystatin C levels and hazard ratios.

Results

Participants in the highest quartile of baseline Cystatin C show an increased risk of mortality compared to those in the lowest quartile (hazard ratio (HR): 1.51, 95 % CI: 1.02–2.24, p = 0.04). Including longitudinal changes in Cystatin C further strengthens this association (HR: 1.81, 95 % CI: 1.20–2.74, p < 0.001). Kaplan-Meier plots show that baseline levels effectively stratify both the entire cohort and gender-specific subgroups (p < 0.001). Moreover, integrating baseline levels with the longitudinal changes in Cystatin C levels provides additional stratification benefits. The predictive performance significantly improves by including longitudinal changes in Cystatin C in baseline-only models, with the concordance index increasing from 0.745 to 0.839 and the area under the receiver operator characteristic curve rising from 0.751 to 0.845. Additionally, significant nonlinear relationships between changes in Cystatin C and HR are observed in the entire population, the males and the females (p = 0.003, 0.018, 0.025).

Conclusions

Dynamic monitoring of changes in Cystatin C could enhance the prediction of mortality risk among middle-aged and elderly individuals.
目的血浆胱抑素 C 水平升高与中国中老年人死亡风险增加有关。本研究探讨了追踪胱抑素 C 的纵向变化是否能改善对死亡风险的预测,并结合基线测量结果更好地进行风险分层。为了评估胱抑素 C 水平/变化与死亡风险之间的关系,我们采用了多变量 Cox 比例危险模型,并对潜在的混杂因素进行了调整。使用卡普兰-梅耶曲线和对数秩检验比较生存概率,同时使用限制性三次样条来说明胱抑素 C 水平与危险比之间的非线性关系。结果与基线胱抑素 C 最高四分位数的参与者相比,基线胱抑素 C 最低四分位数的参与者的死亡风险更高(危险比 (HR):1.51,95 % CI:1.02-2.24,p = 0.04)。胱抑素 C 的纵向变化进一步加强了这种关联(HR:1.81,95 % CI:1.20-2.74,p = 0.001)。Kaplan-Meier 图显示,基线水平有效地对整个队列和特定性别的亚组进行了分层(p < 0.001)。此外,将基线水平与胱抑素 C 水平的纵向变化结合起来还能带来额外的分层优势。将胱抑素 C 的纵向变化纳入纯基线模型后,预测性能明显提高,一致性指数从 0.745 提高到 0.839,接收者运算特征曲线下面积从 0.751 提高到 0.845。结论 动态监测胱抑素 C 的变化可提高对中老年人死亡风险的预测能力。
{"title":"Longitudinal changes in plasma Cystatin C and all-cause mortality risk among the middle-aged and elderly Chinese population","authors":"Ying Zhang ,&nbsp;Ling Zhang ,&nbsp;Jie Xing ,&nbsp;Yujie Weng ,&nbsp;Wangquan Xu ,&nbsp;Liping Zhi ,&nbsp;Min Yuan","doi":"10.1016/j.clinbiochem.2024.110858","DOIUrl":"10.1016/j.clinbiochem.2024.110858","url":null,"abstract":"<div><h3>Objective</h3><div>Elevated plasma Cystatin C levels are associated with an increased mortality risk among middle-aged and elderly Chinese individuals. This study explores whether tracking the longitudinal changes in Cystatin C can improve the prediction of mortality risk and allow better risk stratification, jointly with baseline measurements.</div></div><div><h3>Design &amp; Methods</h3><div>This analysis includes 3,195 participants from the China Health and Retirement Longitudinal Study who completed plasma Cystatin C measurements in two waves (2011 and 2015) and were followed through 2020. To evaluate the association between Cystatin C levels/changes and mortality risk, multivariate Cox proportional hazard models were employed, adjusting for potential confounders. Survival probabilities were compared using Kaplan-Meier curves and log-rank tests, while restricted cubic splines were utilized to illustrate any nonlinear relationships between Cystatin C levels and hazard ratios.</div></div><div><h3>Results</h3><div>Participants in the highest quartile of baseline Cystatin C show an increased risk of mortality compared to those in the lowest quartile (hazard ratio (HR): 1.51, 95 % CI: 1.02–2.24, p = 0.04). Including longitudinal changes in Cystatin C further strengthens this association (HR: 1.81, 95 % CI: 1.20–2.74, p &lt; 0.001). Kaplan-Meier plots show that baseline levels effectively stratify both the entire cohort and gender-specific subgroups (p &lt; 0.001). Moreover, integrating baseline levels with the longitudinal changes in Cystatin C levels provides additional stratification benefits. The predictive performance significantly improves by including longitudinal changes in Cystatin C in baseline-only models, with the concordance index increasing from 0.745 to 0.839 and the area under the receiver operator characteristic curve rising from 0.751 to 0.845. Additionally, significant nonlinear relationships between changes in Cystatin C and HR are observed in the entire population, the males and the females (p = 0.003, 0.018, 0.025).</div></div><div><h3>Conclusions</h3><div>Dynamic monitoring of changes in Cystatin C could enhance the prediction of mortality risk among middle-aged and elderly individuals.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110858"},"PeriodicalIF":2.5,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698579","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}
引用次数: 0
Cardiac biomarkers and CT coronary angiography for the assessment of coronary heart disease 用于评估冠心病的心脏生物标记物和 CT 冠状动脉造影。
IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-11-23 DOI: 10.1016/j.clinbiochem.2024.110857
Gard Mikael Sæle Myrmel , Ryan Wereski , Iman Karaji , Nasir Saeed , Kristin Moberg Aakre , Nicholas L. Mills , Eva Ringdal Pedersen
Over the last 30 years, the widespread use of cardiac biomarkers has transformed the diagnostic evaluation of patients with coronary heart disease. Cardiac troponin is integral to the definition of acute myocardial infarction. High-sensitivity cardiac troponin (hs-cTn) assays can improve risk stratification to facilitate both the rapid rule out of myocardial infarction and prediction of future cardiovascular events. Numerous circulating biomarkers representing different pathological pathways improve prediction of atherosclerotic cardiovascular disease (ACVD) and coronary artery disease (CAD). In parallel, coronary computed tomography angiography (CCTA) has become the most widely used imaging modality for the evaluation of patients with possible angina. CCTA now allows for the quantification of coronary calcification, atherosclerotic plaque volume and different plaque characteristics, enabling the identification high-risk features and inflammation. In the future, the use of CCTA is likely to extend to risk stratification for the prevention of ACVD. As such, how to integrate these diagnostic and prognostic circulating and imaging biomarkers is a topic of considerable interest. This review aims to describe current status and future possibilities for the integration of CCTA and cardiac biomarker testing to improve the identification and treatment of individuals with coronary heart disease and heightened cardiovascular risk.
在过去的 30 年中,心脏生物标记物的广泛应用改变了对冠心病患者的诊断评估。心肌肌钙蛋白是定义急性心肌梗死不可或缺的指标。高灵敏度心肌肌钙蛋白(hs-cTn)测定可改善风险分层,有助于快速排除心肌梗死并预测未来的心血管事件。代表不同病理途径的大量循环生物标记物可改善对动脉粥样硬化性心血管疾病(ACVD)和冠状动脉疾病(CAD)的预测。与此同时,冠状动脉计算机断层扫描血管造影术(CCTA)已成为评估可能患有心绞痛的患者最广泛使用的成像方式。目前,冠状动脉计算机断层扫描可量化冠状动脉钙化、动脉粥样硬化斑块的体积和不同斑块的特征,从而识别高危特征和炎症。未来,CCTA 的应用可能会扩展到预防心血管疾病的风险分层。因此,如何整合这些诊断和预后的循环和成像生物标志物是一个颇受关注的话题。本综述旨在描述整合 CCTA 和心脏生物标志物检测的现状和未来可能性,以改进对冠心病和心血管风险增高患者的识别和治疗。
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引用次数: 0
Biochemical exploration of cholestasis: interpretation, traps and interferences 胆汁淤积症的生化探索:解读、陷阱和干扰。
IF 2.5 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2024-11-22 DOI: 10.1016/j.clinbiochem.2024.110852
Nicolas Stojkoski , Maylis Bertrand , Khaled Messaoudi , Claude Bendavid , Redwan Al-Shami , Caroline Moreau
We described the case of a 33-year-old patient who presented to the emergency department with non-febrile jaundice associated with epigastric pain. He suffered from acute non-severe alcoholic hepatitis and cholestasis. Biochemical investigations highlighted a huge elevation of the alpha-1-globulins fraction with an unexpected peak in the alpha-1-globulins area in serum protein electrophoresis, a severe hypercholesterolemia without xanthelasmas nor cholesterolomas. Investigations revealed an abnormal lipoprotein, Lipoprotein X (LpX) that can be responsible for the hypercholesterolemia, but also interferes with biochemical tests like direct low-density lipoprotein cholesterol, albumin, and serum electrolytes assays. LpX is an abnormal lipoprotein, which can be present in patients with liver dysfunction, notably in cholestasis-related conditions where the metabolism of plasma lipoproteins is altered. Cholestasis prevents the normal formation of bile acids, leading to the formation of LpX, which is rich in phospholipids and unesterified cholesterol, but poor in esterified cholesterol, triglycerides and proteins. The accumulation of LpX can lead to severe hypercholesterolemia, but this remains uncommon and data regarding the pathophysiology and incidence of this disease is scarce. The laboratory investigation of patients with suspected Lpx can be challenging, due to the lack of available methods for measurement of LpX. In conclusion, LpX-induced hyperlipidemia must be identified to prevent interference in results for a number of biochemical tests, and additionally to improve patient care.
我们描述了一例 33 岁患者的病例,他因非发热性黄疸伴上腹疼痛到急诊科就诊。他患有急性非重度酒精性肝炎和胆汁淤积症。生化检查结果显示,α-1-球蛋白部分显著升高,血清蛋白电泳中α-1-球蛋白区域出现意外峰值,严重高胆固醇血症,但无黄疽或胆固醇瘤。检查发现了一种异常脂蛋白--脂蛋白 X(LpX),它可能是导致高胆固醇血症的原因,但也会干扰生化检测,如直接低密度脂蛋白胆固醇、白蛋白和血清电解质检测。LpX 是一种异常脂蛋白,可出现在肝功能异常的患者中,尤其是在胆汁淤积相关疾病中,因为在这些疾病中,血浆脂蛋白的代谢会发生改变。胆汁淤积会阻碍胆汁酸的正常形成,从而形成 LpX,它富含磷脂和未酯化胆固醇,但酯化胆固醇、甘油三酯和蛋白质含量较低。LpX 的积累可导致严重的高胆固醇血症,但这种情况并不常见,有关这种疾病的病理生理学和发病率的数据也很少。由于缺乏测量 LpX 的可用方法,对疑似 Lpx 患者进行实验室检查具有挑战性。总之,必须识别由 LpX 引起的高脂血症,以防止一些生化检验结果受到干扰,并改善对患者的护理。
{"title":"Biochemical exploration of cholestasis: interpretation, traps and interferences","authors":"Nicolas Stojkoski ,&nbsp;Maylis Bertrand ,&nbsp;Khaled Messaoudi ,&nbsp;Claude Bendavid ,&nbsp;Redwan Al-Shami ,&nbsp;Caroline Moreau","doi":"10.1016/j.clinbiochem.2024.110852","DOIUrl":"10.1016/j.clinbiochem.2024.110852","url":null,"abstract":"<div><div>We described the case of a 33-year-old patient who presented to the emergency department with non-febrile jaundice associated with epigastric pain. He suffered from acute non-severe alcoholic hepatitis and cholestasis. Biochemical investigations highlighted a huge elevation of the alpha-1-globulins fraction with an unexpected peak in the alpha-1-globulins area in serum protein electrophoresis, a severe hypercholesterolemia without xanthelasmas nor cholesterolomas. Investigations revealed an abnormal lipoprotein, Lipoprotein X (LpX) that can be responsible for the hypercholesterolemia, but also interferes with biochemical tests like direct low-density lipoprotein cholesterol, albumin, and serum electrolytes assays. LpX is an abnormal lipoprotein, which can be present in patients with liver dysfunction, notably in cholestasis-related conditions where the metabolism of plasma lipoproteins is altered. Cholestasis prevents the normal formation of bile acids, leading to the formation of LpX, which is rich in phospholipids and unesterified cholesterol, but poor in esterified cholesterol, triglycerides and proteins. The accumulation of LpX can lead to severe hypercholesterolemia, but this remains uncommon and data regarding the pathophysiology and incidence of this disease is scarce. The laboratory investigation of patients with suspected Lpx can be challenging, due to the lack of available methods for measurement of LpX. In conclusion, LpX-induced hyperlipidemia must be identified to prevent interference in results for a number of biochemical tests, and additionally to improve patient care.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"135 ","pages":"Article 110852"},"PeriodicalIF":2.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Clinical biochemistry
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