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Revisiting Subject-Specific Analyses in Neuroimaging Data Using "Z-Score" Methods. 使用“Z-Score”方法重新审视神经影像学数据中特定受试者的分析。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-05 DOI: 10.1089/neu.2024.0434
Andrew R Mayer, Andrew B Dodd, Josef M Ling, Edward J Bedrick
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引用次数: 0
Authors' Response to "Revisiting Subject-Specific Analyses in Neuroimaging Data Using "Z-Score" Methods". 作者对“使用“Z-Score”方法重新审视神经影像学数据的特定主题分析”的回应。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-05 DOI: 10.1089/neu.2024.0546
Sarah I Gimbel, Lars Hungerford, Elizabeth W Twamley, Mark L Ettenhofer
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引用次数: 0
A Comprehensive Proteomic and Bioinformatic Analysis of Human Spinal Cord Injury Plasma Identifies Proteins Associated with the Complement Cascade and Liver Function as Potential Prognostic Indicators of Neurological Outcome. 一项对人脊髓损伤血浆的综合蛋白质组学和生物信息学分析确定了与补体级联和肝功能相关的蛋白质作为神经预后的潜在预后指标。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-05 DOI: 10.1089/neu.2023.0064
Gabriel Mateus Bernardo Harrington, Paul Cool, Charlotte Hulme, Jessica Fisher-Stokes, Mandy Peffers, Wagih El Masri, Aheed Osman, Joy Roy Chowdhury, Naveen Kumar, Srinivasa Budithi, Karina Wright
<p><p>Spinal cord injury (SCI) is a major cause of disability, with complications postinjury often leading to lifelong health issues with the need for extensive treatment. Neurological outcome post-SCI can be variable and difficult to predict, particularly in incompletely injured patients. The identification of specific SCI biomarkers in blood may be able to improve prognostics in the field. This study has utilized proteomic and bioinformatic methodologies to investigate differentially expressed proteins in plasma samples across human SCI cohorts with the aim of identifying candidate prognostic biomarkers and biological pathway alterations that relate to neurological outcome. Blood samples were taken, following informed consent, from American Spinal Injury Association impairment scale (AIS) grade C "improvers" (those who experienced an AIS grade improvement) and "nonimprovers" (no AIS change) and AIS grade A and D at <2 weeks ("acute") and ∼3 months ("subacute") postinjury. The total protein concentration from each sample was extracted, with pooled samples being labeled and nonpooled samples treated with ProteoMiner<sup>™</sup> beads. Samples were then analyzed using two 4-plex isobaric tag for relative and absolute quantification (iTRAQ) analyses and a label-free experiment for comparison before quantifying with mass spectrometry. Data are available via ProteomeXchange with identifiers PXD035025 and PXD035072 for the iTRAQ and label-free experiments, respectively. Proteomic datasets were analyzed using OpenMS (version 2.6.0). R (version 4.1.4) and, in particular, the R packages MSstats (version 4.0.1) and pathview (version 1.32.0) were used for downstream analysis. Proteins of interest identified from this analysis were further validated by enzyme-linked immunosorbent assay. The data demonstrated proteomic differences between the cohorts, with the results from the iTRAQ approach supporting those of the label-free analysis. A total of 79 and 87 differentially abundant proteins across AIS and longitudinal groups were identified from the iTRAQ and label-free analyses, respectively. Alpha-2-macroglobulin, retinol-binding protein 4 (RBP4), serum amyloid A1, peroxiredoxin 2 (PRX-2), apolipoprotein A1, and several immunoglobulins were identified as biologically relevant and differentially abundant, with potential as individual candidate prognostic biomarkers of neurological outcome. Bioinformatics analyses revealed that the majority of differentially abundant proteins were components of the complement cascade and most interacted directly with the liver. Many of the proteins of interest identified using proteomics were detected only in a single group and therefore have potential as binary (present or absent) biomarkers, RBP4 and PRX-2 in particular. Additional investigations into the chronology of these proteins and their levels in other tissues (cerebrospinal fluid in particular) are needed to better understand the underlying pathophysiology, including
脊髓损伤(SCI)是致残的主要原因,损伤后的并发症往往导致终身健康问题,需要广泛的治疗。脊髓损伤后的神经系统预后可能是可变的,难以预测,特别是在不完全损伤的患者中。在血液中识别特定的脊髓损伤生物标志物可能能够改善该领域的预后。本研究利用蛋白质组学和生物信息学方法研究人类脊髓损伤队列血浆样本中的差异表达蛋白,目的是确定与神经预后相关的候选预后生物标志物和生物通路改变。在知情同意的情况下,从美国脊髓损伤协会损伤量表(AIS) C级“改善者”(经历AIS级改善者)和“非改善者”(没有AIS变化)以及AIS A级和D级患者中采集血样。然后使用两个4-plex等压标签进行相对和绝对定量(iTRAQ)分析,并在质谱定量之前进行无标签实验进行比较。iTRAQ和无标签实验的数据可通过ProteomeXchange获得,标识符分别为PXD035025和PXD035072。使用OpenMS (version 2.6.0)分析蛋白质组学数据集。R(版本4.1.4),特别是R软件包MSstats(版本4.0.1)和pathview(版本1.32.0)用于下游分析。从该分析中鉴定的感兴趣的蛋白质通过酶联免疫吸附试验进一步验证。数据显示了两组之间的蛋白质组学差异,iTRAQ方法的结果支持无标签分析的结果。通过iTRAQ和无标签分析,在AIS和纵向组中分别鉴定出79和87个差异丰富的蛋白质。α -2巨球蛋白、视黄醇结合蛋白4 (RBP4)、血清淀粉样蛋白A1、过氧化物还蛋白2 (PRX-2)、载脂蛋白A1和几种免疫球蛋白被鉴定为生物学相关且差异丰富,具有作为神经预后的单个候选生物标志物的潜力。生物信息学分析显示,大多数差异丰富的蛋白质是补体级联的组成部分,并且大多数直接与肝脏相互作用。使用蛋白质组学鉴定的许多感兴趣的蛋白质仅在单一组中检测到,因此具有作为二元(存在或不存在)生物标志物的潜力,特别是RBP4和PRX-2。需要进一步研究这些蛋白质的年表及其在其他组织(特别是脑脊液)中的水平,以更好地了解潜在的病理生理学,包括任何潜在的可改变的靶标。通路分析强调了补体级联在不同功能恢复组中的重要性。
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引用次数: 0
The Functional Connectome and Long-Term Symptom Presentation Associated With Mild Traumatic Brain Injury and Blast Exposure in Combat Veterans. 战斗退伍军人轻度创伤性脑损伤和爆炸暴露相关的功能连接组和长期症状表现。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-20 DOI: 10.1089/neu.2023.0315
Jared A Rowland, Jennifer R Stapleton-Kotloski, Dwayne W Godwin, Craig A Hamilton, Sarah L Martindale

Mild traumatic brain injury (TBI) sustained in a deployment environment (deployment TBI) can be associated with increased severity of long-term symptom presentation, despite the general expectation of full recovery from a single mild TBI. The heterogeneity in the effects of deployment TBI on the brain can be difficult for a case-control design to capture. The functional connectome of the brain is an approach robust to heterogeneity that allows global measurement of effects using a common set of outcomes. The present study evaluates how differences in the functional connectome relate to remote symptom presentation following combat deployment and determines if deployment TBI, blast exposure, or post-traumatic stress disorder (PTSD) are associated with these neurological differences. Participants included 181 Iraq and Afghanistan combat-exposed Veterans, approximately 9.4 years since deployment. Structured clinical interviews provided diagnoses and characterizations of TBI, blast exposure, and PTSD. Self-report measures provided characterization of long-term symptoms (psychiatric, behavioral health, and quality of life). Resting-state magnetoencephalography was used to characterize the functional connectome of the brain individually for each participant. Linear regression identified factors contributing to symptom presentation including relevant covariates, connectome metrics, deployment TBI, blast exposure PTSD, and conditional relationships. Results identified unique contributions of aspects of the connectome to symptom presentation. Furthermore, several conditional relationships were identified, demonstrating that the connectome was related to outcomes in the presence of only deployment-related TBI (including blast-related TBI, primary blast TBI, and blast exposure). No conditional relationships were identified for PTSD; however, the main effect of PTSD on symptom presentation was significant for all models. These results demonstrate that the connectome captures aspects of brain function relevant to long-term symptom presentation, highlighting that deployment-related TBI influences symptom outcomes through a neurological pathway. These findings demonstrate that changes in the functional connectome associated with deployment-related TBI are relevant to symptom presentation over a decade past the injury event, providing a clear demonstration of a brain-based mechanism of influence.

在部署环境中遭受的轻度脑损伤(部署性脑损伤)可能与长期症状表现的严重程度增加有关,尽管人们普遍期望从单次轻度脑损伤中完全康复。病例对照设计很难捕捉到部署创伤性脑损伤对大脑影响的异质性。大脑功能连接组是一种可以克服异质性的方法,它允许使用一组共同的结果对影响进行全面测量。本研究评估了功能连接组的差异与作战部署后远程症状表现的关系,并确定部署创伤性脑损伤、爆炸暴露或创伤后应激障碍(PTSD)是否与这些神经差异有关。研究对象包括 181 名曾在伊拉克和阿富汗参加过战斗的退伍军人,他们在部署后约 9.4 年才出现症状。结构化临床访谈提供了创伤性脑损伤、爆炸暴露和创伤后应激障碍的诊断和特征。自我报告测量提供了长期症状(精神、行为健康和生活质量)的特征。静息态脑磁图(MEG)用于描述每位参与者的大脑功能连接组。线性回归确定了导致症状表现的因素,包括相关协变量、连接组指标、部署创伤性脑损伤、爆炸暴露创伤后应激障碍和条件关系。结果确定了连接组的各个方面对症状表现的独特贡献。此外,还发现了几种条件关系,表明只有在存在部署相关创伤性脑损伤(包括爆炸相关创伤性脑损伤、原发性爆炸创伤性脑损伤和爆炸暴露)的情况下,连接组才与结果相关。创伤后应激障碍没有发现条件关系;但是,创伤后应激障碍对症状表现的主效应在所有模型中都是显著的。这些结果表明,连接组捕捉到了与长期症状表现相关的大脑功能方面,突出表明与部署相关的创伤性脑损伤会通过神经途径影响症状结果。这些研究结果表明,与部署相关的创伤性脑损伤相关的功能连接组的变化与受伤事件发生后十多年的症状表现相关,清楚地证明了基于大脑的影响机制。
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引用次数: 0
SCAT Symptom Evolution in the Acute Concussion Phase: Findings from the NCAA-DoD CARE Consortium. SCAT 急性脑震荡阶段的症状演变:NCAA-DoD CARE 联合会的研究结果。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-20 DOI: 10.1089/neu.2024.0243
Reid A Syrydiuk, Adrian J Boltz, Landon B Lempke, Jaclyn B Caccese, Thomas W McAllister, Michael A McCrea, Paul F Pasquina, Steven P Broglio

The Sport Concussion Assessment Tool (SCAT) is the most widely used tool following sport-related concussion (SRC). Initial SCAT symptom burden is a strong predictor of recovery in collegiate athletes; however, it is unknown if symptom presentation varies within the acute (<48 h) post-SRC phase. The purpose of this cohort study was to examine acute SRC symptom presentation among the National Collegiate Athletic Association (NCAA) athletes. Concussed NCAA varsity athletes (n = 1,780) from 30 universities across the United States, which participated in the Concussion Assessment, Research, and Education (CARE) Consortium, were included. Time of injury occurrence and SCAT administration data were recorded, from which time-to-SCAT (hours, continuous) was calculated. The main outcome was SCAT total symptom severity [(TSS), 0-126]. Multivariable negative binomial regression was used to examine the association between time (hours) since injury and TSS. Covariates included sex, previous concussion, sport contact level, amnesia/loss of consciousness, immediate reporting of injury, and injury situation. A random effect (person level) accounted for multiple assessments. TSS score ratios (SR) with associated 95% confidence intervals (CI) were provided. The SCAT was administered an average of 14 (25th-75th percentile: 1.2-24) hours post-SRC, and average TSS was 27.35 ± 21.28 across all participants. Time-to-SCAT was associated with a 1% decrease in TSS after adjusting for covariate effects (SR: 0.99, 95% CI: 0.99-0.99, p < 0.001). Overall, we observed a small, but significant decrease in TSS with each hour post-SRC. Assessing a concussed athlete once in the acute phase will likely provide a sufficient sense of their symptomatic well-being, as measures did not fluctuate dramatically. Future research should aim to examine how acute symptom evolution influences recovery metrics.

运动脑震荡评估工具(SCAT)是运动相关脑震荡(SRC)后最广泛使用的工具。最初的 SCAT 症状负担是大学生运动员康复的有力预测指标;然而,在急性脑震荡(SRC)期间,症状表现是否会有所不同,目前还不得而知。
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引用次数: 0
Normative Neuroimaging Library: Designing a Comprehensive and Demographically Diverse Dataset of Healthy Controls to Support Traumatic Brain Injury Diagnostic and Therapeutic Development. 规范神经影像库:设计一个全面的、人口统计学上多样化的健康对照数据集,以支持创伤性脑损伤诊断和治疗的发展。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-05 DOI: 10.1089/neu.2024.0128
Allyson T Gage, James R Stone, Elisabeth A Wilde, Stephen R McCauley, Robert C Welsh, John P Mugler, Nick Tustison, Brian Avants, Christopher T Whitlow, Lee Lancashire, Seema D Bhatt, Magali Haas
<p><p>The past decade has seen impressive advances in neuroimaging, moving from qualitative to quantitative outputs. Available techniques now allow for the inference of microscopic changes occurring in white and gray matter, along with alterations in physiology and function. These existing and emerging techniques hold the potential of providing unprecedented capabilities in achieving a diagnosis and predicting outcomes for traumatic brain injury (TBI) and a variety of other neurological diseases. To see this promise move from the research lab into clinical care, an understanding is needed of what normal data look like for all age ranges, sex, and other demographic and socioeconomic categories. Clinicians can only use the results of imaging scans to support their decision-making if they know how the results for their patient compare with a normative standard. This potential for utilizing magnetic resonance imaging (MRI) in TBI diagnosis motivated the American College of Radiology and Cohen Veterans Bioscience to create a reference database of healthy individuals with neuroimaging, demographic data, and characterization of psychological functioning and neurocognitive data that will serve as a normative resource for clinicians and researchers for development of diagnostics and therapeutics for TBI and other brain disorders. The goal of this article is to introduce the large, well-curated Normative Neuroimaging Library (NNL) to the research community. NNL consists of data collected from ∼1900 healthy participants. The highlights of NNL are (1) data are collected across a diverse population, including civilians, veterans, and active-duty service members with an age range (18-64 years) not well represented in existing datasets; (2) comprehensive structural and functional neuroimaging acquisition with state-of-the-art sequences (including structural, diffusion, and functional MRI; raw scanner data are preserved, allowing higher quality data to be derived in the future; standardized imaging acquisition protocols across sites reflect sequences and parameters often recommended for use with various neurological and psychiatric conditions, including TBI, post-traumatic stress disorder, stroke, neurodegenerative disorders, and neoplastic disease); and (3) the collection of comprehensive demographic details, medical history, and a broad structured clinical assessment, including cognition and psychological scales, relevant to multiple neurological conditions with functional sequelae. Thus, NNL provides a demographically diverse population of healthy individuals who can serve as a comparison group for brain injury study and clinical samples, providing a strong foundation for precision medicine. Use cases include the creation of imaging-derived phenotypes (IDPs), derivation of reference ranges of imaging measures, and use of IDPs as training samples for artificial intelligence-based biomarker development and for normative modeling to help identify injury-induced
过去十年间,神经成像技术取得了令人瞩目的进步,从定性输出发展到定量输出。现有的技术现在可以推断白质和灰质中发生的微观变化,以及生理和功能的改变。这些现有的和新兴的技术有可能为创伤性脑损伤(TBI)和其他各种神经系统疾病的诊断和预后提供前所未有的能力。要将这一前景从研究实验室转化为临床治疗,就需要了解所有年龄段、性别以及其他人口和社会经济类别的正常数据是什么样的。临床医生只有知道病人的扫描结果与正常标准的比较情况,才能利用成像扫描结果支持他们的决策。在 TBI 诊断中利用磁共振成像 (MRI) 的这一潜力促使美国放射学会和 Cohen Veterans Bioscience 建立了一个包含神经成像、人口统计学数据、心理功能特征和神经认知数据的健康人参考数据库,作为临床医生和研究人员开发 TBI 和其他脑部疾病诊断和治疗方法的标准资源。本文旨在向研究界介绍经过精心整理的大型规范神经影像库(NNL)。NNL 由从 1900 名健康参与者收集的数据组成。NNL 的亮点在于:(1) 收集的数据来自不同的人群,包括平民、退伍军人和现役军人,其年龄范围(18-64 岁)在现有数据集中没有得到很好的体现;(2) 采用最先进的序列(包括结构、弥散和功能 MRI)采集全面的结构和功能神经影像;保留原始扫描仪数据,以便将来获得更高质量的数据;(3) 收集全面的人口统计学细节、病史和广泛的结构化临床评估,包括认知和心理量表,这些都与具有功能性后遗症的多种神经系统疾病相关。因此,NNL 提供了一个人口统计学上多样化的健康人群,可作为脑损伤研究和临床样本的对比组,为精准医疗奠定了坚实的基础。用例包括创建成像衍生表型(IDP)、推导成像测量的参考范围,以及将 IDP 用作基于人工智能的生物标记开发的训练样本和常模,以帮助识别损伤引起的异常变化,从而进行精准诊断和靶向治疗开发。NNL 发布后,将支持在临床医生决策支持工具中使用先进的成像技术,验证成像生物标记物,调查大脑行为异常,从而推动精准医疗领域的发展。
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引用次数: 0
Correction to: Impact of Low-Level Blast Exposure on Brain Function after a One-Day Tactile Training and the Ameliorating Effect of a Jugular Vein Compression Neck Collar Device; DOI: 10.1089/neu.2018.5737. Correction to:一天触觉训练后低水平爆炸暴露对大脑功能的影响以及颈静脉压迫颈圈装置的改善效果;DOI: 10.1089/neu.2018.5737。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-12 DOI: 10.1089/neu.2018.5737.correx
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引用次数: 0
Correction to: Neck Collar with Mild Jugular Vein Compression Ameliorates Brain Activation Changes During a Working Memory Task after a Season of High School Football; DOI: 10.1089/neu.2016.4834. 更正为轻度颈静脉压迫颈圈可改善高中橄榄球赛季后工作记忆任务中的大脑激活变化;DOI: 10.1089/neu.2016.4834。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-12 DOI: 10.1089/neu.2016.4834.correx
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引用次数: 0
Correction to: High School Sports-Related Concussion, and the Effect of a Jugular Vein Compression Collar: A Prospective Longitudinal Investigation of Neuroimaging and Neurofunctional Outcomes; DOI: 10.1089/neu.2021.0141. 更正为高中生运动相关脑震荡和颈静脉压迫颈圈的影响:神经影像学和神经功能结果的前瞻性纵向调查》;DOI: 10.1089/neu.2021.0141。
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-11-11 DOI: 10.1089/neu.2021.0141.correx
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引用次数: 0
Volumetric Assessment of Traumatic Intracranial Hematomas: Is ABC/2 Reliable? 外伤性颅内血肿的体积评估:ABC/2 是否可靠?
IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2024-12-01 Epub Date: 2024-09-04 DOI: 10.1089/neu.2024.0248
Alexander Fletcher-Sandersjöö, Anders Lewén, Anders Hånell, David W Nelson, Marc Maegele, Mikael Svensson, Bo-Michael Bellander, Per Enblad, Eric Peter Thelin, Teodor Svedung Wettervik

Accurate measurement of traumatic intracranial hematoma volume is important for assessing disease progression and prognosis, as well as for serving as an important end-point in clinical trials aimed at preventing hematoma expansion. While the ABC/2 formula has traditionally been used for volume estimation in spontaneous intracerebral hemorrhage, its adaptation to traumatic hematomas lacks validation. This study aimed to compare the accuracy of ABC/2 with computer-assisted volumetric analysis (CAVA) in estimating the volumes of traumatic intracranial hematomas. We performed a dual-center observational study that included adult patients with moderate-to-severe traumatic brain injury. Volumes of intracerebral, subdural (SDHs), and epidural hematomas from admission computed tomography scans were measured using ABC/2 and CAVA, and compared using the Wilcoxon signed-rank test, Spearman's rank correlation, Lin's concordance correlation coefficient (CCC), and Bland-Altman plots. Prognostic significance for outcomes was evaluated through logistic and linear regression models. In total, 1,179 patients with 1,543 hematomas were included. Despite a high correlation (Spearman coefficients between 0.95 and 0.98) and excellent concordance (Lin's CCC from 0.89 to 0.96) between ABC/2 and CAVA, ABC/2 overestimated hematoma volumes compared with CAVA, in some instances exceeding 50 ml. Bland-Altman analysis highlighted wide limits of agreement, especially in SDH. While both methods demonstrated comparable accuracy in predicting outcomes, CAVA was slightly better at predicting craniotomies and midline shift. We conclude that while ABC/2 provides a generally reliable volumetric assessment suitable for descriptive purposes and as baseline variables in studies, CAVA should be the gold standard in clinical situations and studies requiring more precise volume estimations, such as those using hematoma expansion as an outcome.

准确测量外伤性颅内血肿体积对于评估疾病进展和预后非常重要,同时也是旨在防止血肿扩大的临床试验的重要终点。传统上,ABC/2 公式一直用于自发性脑内出血的血肿体积估算,但其对创伤性血肿的适应性还缺乏验证。本研究旨在比较 ABC/2 公式与计算机辅助容积分析(CAVA)在估计外伤性颅内血肿体积方面的准确性。我们进行了一项双中心观察研究,研究对象包括中重度脑外伤成年患者。我们使用 ABC/2 和 CAVA 测量了入院 CT 扫描中的脑内血肿 (ICH)、硬膜下血肿 (SDH) 和硬膜外血肿 (EDH) 的体积,并使用 Wilcoxon 符号秩检验、Spearman 等级相关性、Lin 一致性相关系数 (CCC) 和 Bland-Altman 图进行了比较。通过逻辑和线性回归模型评估了预后的重要性。共纳入了 1,179 名患者,1,543 个血肿。尽管ABC/2和CAVA之间具有很高的相关性(Spearman系数介于0.95和0.98之间)和很好的一致性(Lin's CCC介于0.89和0.96之间),但与CAVA相比,ABC/2高估了血肿体积,在某些情况下超过了50毫升。Bland-Altman分析强调了两者之间的差异,尤其是在SDH方面。虽然两种方法预测结果的准确性相当,但 CAVA 在预测开颅手术和中线移位方面略胜一筹。我们的结论是,虽然 ABC/2 提供的容积评估基本可靠,适合用于描述性目的和作为研究中的基线变量,但在需要更精确容积估计的临床情况和研究中,如将血肿扩大作为结果的研究中,CAVA 应成为金标准。
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引用次数: 0
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Journal of neurotrauma
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