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Age-Specific Control and Alzheimer Disease Reference Curves and z-Scores for Glial Fibrillary Acidic Protein in Blood. 血液中胶质纤维酸性蛋白的年龄特异性对照和阿尔茨海默病参考曲线和z-评分。
IF 6.3 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-02 DOI: 10.1093/clinchem/hvaf120
Steffen Halbgebauer, Badrieh Fazeli, Veronika Klose, Gabriele Nagel, Angela Rosenbohm, Dietrich Rothenbacher, Franziska Bachhuber, Sarah Jesse, Markus Otto, G Bernhard Landwehrmeyer, Ahmed Abdelhak, Axel Petzold, Albert C Ludolph, Hayrettin Tumani

Background: Serum glial fibrillary acidic protein (GFAP) is a biomarker for astrocytic injury and astrogliosis. Concentrations are elevated in numerous neurological disorders, including a pronounced increase in Alzheimer disease (AD). However, GFAP levels in the serum also increase with age. Consequently, the integration of GFAP levels into clinical routine and their interpretation demands age-adjusted reference values.

Methods: Serum from 1273 subjects (952 noninflammatory and nonneurodegenerative neurological controls and 321 subjects with AD) was analyzed for GFAP using the microfluidic Ella system. Age-dependent serum GFAP reference values were estimated by additive quantile regression analysis and visualized with percentiles and z-scores.

Results: AD exhibited elevated serum GFAP levels in comparison to control patients (P < 0.0001). This remained the case when the newly generated age-corrected z-scores were applied (P < 0.0001). In the control cohort, a nonlinear elevation of serum GFAP with increasing age was observed (Spearman correlation coefficient 0.62, 95% CI 0.58-0.66, P < 0.0001). In contrast, the AD cohort exhibited a more linear increase (0.16, 95% CI 0.05-0.26, P = 0.004). Age-dependent cut-offs for serum GFAP were determined for different AD age groups. The calculated areas under the curve (AUCs; 0.97) demonstrated excellent diagnostic test performance in the early-onset age group. This effect was less marked in the elderly subjects (AUC 0.72).

Conclusions: Our novel GFAP z-scores enable the integration and interpretation of serum GFAP levels in clinical practice, moving from the group to individual level. They support both intra- and interindividual interpretation of single GFAP levels in neurological diseases with astrocytic pathology, including an accurate discrimination of AD.

背景:血清胶质原纤维酸性蛋白(GFAP)是星形胶质细胞损伤和星形胶质增生的生物标志物。在许多神经系统疾病中浓度升高,包括阿尔茨海默病(AD)的显著增加。然而,血清中GFAP水平也随着年龄的增长而增加。因此,将GFAP水平纳入临床常规及其解释需要年龄调整的参考值。方法:采用微流控Ella系统分析1273例血清GFAP,其中952例为非炎症性和非神经退行性神经对照,321例为AD患者。年龄依赖性血清GFAP参考值通过加性分位数回归分析估计,并以百分位数和z分数可视化。结果:AD患者血清GFAP水平高于对照组(P < 0.0001)。当应用新生成的年龄校正z分数时,情况仍然如此(P < 0.0001)。在对照组中,血清GFAP随年龄增长呈非线性升高(Spearman相关系数0.62,95% CI 0.58-0.66, P < 0.0001)。相比之下,AD组表现出更线性的增加(0.16,95% CI 0.05-0.26, P = 0.004)。测定不同AD年龄组血清GFAP的年龄依赖性截止值。计算出的曲线下面积(auc; 0.97)在早发年龄组中表现出良好的诊断测试性能。这种效应在老年受试者中不太明显(AUC为0.72)。结论:我们的新GFAP z-评分能够在临床实践中整合和解释血清GFAP水平,从群体水平转移到个体水平。它们支持在星形细胞病理的神经系统疾病中单个GFAP水平的个体内和个体间解释,包括对AD的准确区分。
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引用次数: 0
Commentary on Aberrant Plasma Cells in the Absence of M-protein: Ancillary Testing beyond Protein Electrophoresis. 对缺乏m蛋白的异常浆细胞的评论:蛋白质电泳以外的辅助检测。
IF 6.3 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-02 DOI: 10.1093/clinchem/hvaf117
Louis Nevejan, Xavier Bossuyt
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引用次数: 0
Commentary on Aberrant Plasma Cells in the Absence of M-Protein: Ancillary Testing beyond Protein Electrophoresis. 对缺乏m蛋白的异常浆细胞的评论:蛋白质电泳以外的辅助检测。
IF 6.3 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-02 DOI: 10.1093/clinchem/hvaf130
Maria Alice Willrich, Linda B Baughn
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引用次数: 0
The Devil Is in the Details: Clinical Relevance of Serologic Antibody Titers to Predict the Diagnosis of Celiac Disease in Pediatric Type 1 Diabetes. 细节决定成败:血清学抗体滴度与儿童1型糖尿病乳糜泻诊断的临床相关性
IF 6.3 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-02 DOI: 10.1093/clinchem/hvaf102
Andrew M Ford, Alberto Rubio Tapia
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引用次数: 0
Aberrant Plasma Cells in the Absence of M-Protein: Ancillary Testing beyond Protein Electrophoresis. 缺乏m蛋白的异常浆细胞:蛋白电泳以外的辅助检测。
IF 6.3 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-02 DOI: 10.1093/clinchem/hvaf097
Lechuang Chen, Nourhan Garnal Elgela Ibrahim, Guilin Tang, Qing H Meng, Zhihong Hu
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引用次数: 0
Transdermal GFR Signals a New Horizon in Renal Diagnostics. 透皮GFR信号是肾脏诊断的新领域。
IF 6.3 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-12-02 DOI: 10.1093/clinchem/hvaf106
Vrajesh Pandya
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引用次数: 0
The Changing Face of Academic Laboratory Medicine-A Decade Later and Beyond. 学术检验医学的变化面貌——十年后及以后。
IF 9.3 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-11-19 DOI: 10.1093/clinchem/hvaf132
Khushbu Patel,Mitchell G Scott,Aasne K Aarsand,Ann M Gronowski,Shannon Haymond,Christina Lockwood,Nader Rifai,Mark D Zarella
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引用次数: 0
Diagnostic Value of Serum p-tau217 in Alzheimer Disease: Equal to Plasma in Levels and Clinical Utility? 血清p-tau217对阿尔茨海默病的诊断价值:与血浆水平相等及其临床应用?
IF 9.3 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-11-13 DOI: 10.1093/clinchem/hvaf162
Andrea L Benedet, Burak Arslan, Kubra Tan, Hanna Huber, Ilaria Pola, Guglielmo Di Molfetta, Hlin Kvartsberg, Anna Orduña Dolado, Shorena Janelidze, Kaj Blennow, Henrik Zetterberg, Oskar Hansson, Pedro Rosa-Neto, Nicholas J Ashton
Background Phosphorylated tau 217 (p-tau217) has emerged as a leading blood-based biomarker for Alzheimer disease (AD). While typically measured in plasma, serum is a widely used matrix in clinical laboratories, yet few p-tau217 assays have been validated for serum. Evaluating serum p-tau217 performance is essential for expanding its use in clinical and research settings, particularly for cohorts with only serum samples available. Methods We quantified p-tau217 in plasma and serum from individuals within the AD continuum (n = 100; mean age 72.5 ± 5.0 years; 54% female) using 6 assays across 4 platforms. Spearman correlation, Passing–Bablok regression, and receiver operating characteristics analysis were used to assess intermatrix agreement and diagnostic performance. Specific validation parameters (e.g., precision, parallelism, dilution linearity, stability) were evaluated in both matrices. Results High correlations between plasma and serum were observed for most assays (ρ &gt; 0.8), though plasma often yielded higher concentrations. Notably, the Lumipulse assay showed near-perfect correlation (ρ = 0.98) and minimal bias. Fold changes in p-tau217 levels across the AD continuum were comparable between matrices, though cutoffs for detecting AD pathology differed. Applying plasma-derived cutoffs to serum resulted in misclassification rates ranging from 16% to 47%, except for Lumipulse (10% in serum vs 5% in plasma). Not all assays performed equally in serum, as reflected in validation metrics. Conclusions Serum p-tau217, across multiple platforms, shows strong correlations with plasma p-tau217 and reflected comparable patterns across the AD continuum. However, absolute concentrations differed for most assays, thus requiring differing disease specific cutoffs. Most of the evaluated platforms demonstrated reliable quantification of p-tau217 in serum, yielding satisfactory validation performance. These findings support serum as a viable alternative to plasma for p-tau217 quantification in both research and clinical settings, provided matrix-specific validation is ensured.
磷酸化tau217 (p-tau217)已成为阿尔茨海默病(AD)的主要血液生物标志物。虽然通常在血浆中测量,但在临床实验室中,血清是一种广泛使用的基质,但很少有p-tau217测定法被用于血清。评估血清p-tau217的性能对于扩大其在临床和研究环境中的应用至关重要,特别是对于只有血清样本的队列。方法:通过4个平台的6项检测,对AD连续体个体(n = 100,平均年龄72.5±5.0岁,54%为女性)血浆和血清中的p-tau217进行定量分析。使用Spearman相关、passingbablok回归和受者操作特征分析来评估矩阵间一致性和诊断性能。在两种基质中评估特定的验证参数(例如,精密度、平行度、稀释线性度、稳定性)。结果血浆和血清之间的相关性很高(ρ > 0.8),尽管血浆中的浓度通常较高。值得注意的是,Lumipulse试验显示出接近完美的相关性(ρ = 0.98)和最小的偏差。p-tau217水平在AD连续体中的折叠变化在基质之间具有可比性,尽管检测AD病理的截止值不同。将血浆来源的截止值应用于血清导致误分类率从16%到47%不等,但Lumipulse除外(血清10% vs血浆5%)。正如验证指标所反映的那样,并非所有测定法在血清中的效果都是一样的。结论血清p-tau217在多个平台上与血浆p-tau217表现出很强的相关性,并反映了AD连续体的可比性模式。然而,大多数测定的绝对浓度不同,因此需要不同的疾病特异性截止值。大多数评估的平台显示可靠的血清中p-tau217的定量,产生令人满意的验证性能。这些发现支持在研究和临床环境中,血清作为p-tau217定量的可行替代血浆,前提是确保基质特异性验证。
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引用次数: 0
Per Se Driving Under the Influence of Cannabis Statutes and Blood Delta-9-Tetrahydrocannabinol Concentrations following Short-Term Cannabis Abstinence. 短期戒断大麻后,大麻法规和血液中δ -9-四氢大麻酚浓度影响下的自身驾驶。
IF 9.3 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-11-12 DOI: 10.1093/clinchem/hvaf121
Robert L Fitzgerald,Anya Umlauf,Raymond T Suhandynata,David J Grelotti,Marilyn A Huestis,Kyle F Mastropietro,Igor Grant,Thomas D Marcotte
BACKGROUNDSeveral US states have per se laws using 2 or 5 ng/mL of delta-9-tetrahydrocannabinol (THC) as cutpoints for driving under the influence of cannabis, while some have zero-tolerance statutes. These cutpoints are considered prima facia evidence of driving impairment.METHODSIn a cohort of people who regularly use cannabis (N = 190) we measured baseline concentrations of THC after instructing participants to abstain from cannabis for at least 48 hours. Baseline driving performance was evaluated using a driving simulator. We also measured blood THC concentrations serially following a smoking session (placebo or active cannabis).RESULTSForty-three percent of the participants exceeded zero-tolerance statutes (≥0.5 ng/mL) at baseline. Twenty-four percent had baseline blood THC concentrations that were ≥2 ng/mL and 5.3% were ≥5 ng/mL. The maximum observed baseline blood concentration was 16.2 ng/mL. Six hours after smoking active cannabis, the median (interquartile range) difference in THC concentrations compared with baseline was 0.5 (0-0.9) ng/mL; a 1-sample t-test comparing the mean change to 0 was significant (P < 0.001). There was no difference when comparing the mean change to 0 in the placebo group (P = 0.69). Simulated driving performance was not different between those who exceed zero tolerance and per se cutpoints vs those who are below these cutpoints (P > 0.05).CONCLUSIONSMany regular users of cannabis exceed zero tolerance and per se THC cutpoint concentrations days after their last use, risking legal consequences despite no evidence of impairment.
美国的几个州都有自己的法律,将2或5 ng/mL的δ -9-四氢大麻酚(THC)作为在大麻影响下驾驶的临界值,而一些州则有零容忍法规。这些交叉点被认为是驾驶障碍的初步证据。方法在一组经常使用大麻的人群中(N = 190),我们在指示参与者戒除大麻至少48小时后测量了四氢大麻酚的基线浓度。使用驾驶模拟器评估基线驾驶性能。我们还在吸烟(安慰剂或活性大麻)后连续测量了血液中四氢大麻酚的浓度。结果43%的参与者在基线时超过零容忍法规(≥0.5 ng/mL)。24%的患者基线血THC浓度≥2ng /mL, 5.3%的患者基线血THC浓度≥5ng /mL。观察到的最大基线血药浓度为16.2 ng/mL。吸食活性大麻6小时后,四氢大麻酚浓度与基线相比的中位数(四分位数范围)差异为0.5 (0-0.9)ng/mL;比较平均变化到0的单样本t检验是显著的(P < 0.001)。当将安慰剂组的平均变化与0进行比较时,没有差异(P = 0.69)。超过零容忍和本身临界值的人与低于这些临界值的人的模拟驾驶性能没有差异(P > 0.05)。结论:许多经常使用大麻的人在最后一次使用后几天内就超过了零容忍和本身的四氢大麻酚临界点浓度,尽管没有证据表明存在损害,但仍有可能承担法律后果。
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引用次数: 0
Emerging Threat of Xylazine. 新出现的噻嗪威胁。
IF 6.3 2区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pub Date : 2025-11-11 DOI: 10.1093/clinchem/hvaf147
Kyla M Jorgenson, Robert A Middleberg, Brandy L Young, Alex J Krotulski, Nicholas E Nacca, Tanzy M Love, Joshua Marvald, Rachel Becker, Marilyn A Huestis, Y Victoria Zhang

Background: The increasing reports of xylazine in clinical and postmortem toxicology necessitate a survey of its clinical impact. This review examines reports of xylazine across the peer-reviewed literature and grey literature (government and public health reports).

Content: Before 2005, reports of xylazine abuse primarily involved veterinary-associated accidental and intentional exposures. A notable shift occurred in 2006 with increasing xylazine exposure documented among persons with illicit drug use, including fatal and nonfatal overdoses. Xylazine prevalence continued to increase in clinical and postmortem cases. Cases of xylazine abuse began in the northeast United States and expanded nationwide, with persistent high prevalence in the East and Midwest. Xylazine has been most frequently identified with fentanyl in clinical, drug-impaired driving, and postmortem analyses.

Summary: Xylazine's rising prevalence, especially as a fentanyl adulterant, contributes to increased opioid-related morbidity and mortality. Its presence across clinical, forensic, and environmental samples underscores the urgent need for enhanced surveillance, clinician education, public awareness, and targeted policy responses.

背景:越来越多的临床和死后毒理学报告表明,有必要对其临床影响进行调查。本综述审查了同行评议文献和灰色文献(政府和公共卫生报告)中关于噻嗪的报告。内容:2005年以前,有关氯嗪滥用的报告主要涉及与兽医有关的意外和故意暴露。2006年发生了显著的变化,非法药物使用者(包括致命和非致命过量)中有记录的二嗪接触量增加。在临床和死后病例中,噻嗪的患病率继续上升。二甲肼的滥用始于美国东北部,并在全国范围内扩大,在东部和中西部地区持续高发。在临床、药物损伤驾驶和尸检分析中,Xylazine与芬太尼最常被识别。总结:氯拉嗪的流行率不断上升,特别是作为芬太尼掺杂剂,导致阿片类药物相关发病率和死亡率增加。它在临床、法医和环境样本中的存在强调了加强监测、临床医生教育、公众意识和有针对性的政策应对的迫切需要。
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引用次数: 0
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Clinical chemistry
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