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Application of Delta T1 maps for quantitative and objective assessment of extent of resection and survival prediction in glioblastoma. 应用 Delta T1 地图对胶质母细胞瘤的切除范围和生存预测进行定量客观评估。
Pub Date : 2024-03-01 Epub Date: 2024-01-17
Brandon R Laing, Melissa A Prah, Benjamin J Best, Max O Krucoff, Wade M Mueller, Kathleen M Schmainda

Background and objectives: Gross-total resection (GTR) and low residual tumor volume (RTV) have been associated with increased survival in glioblastoma. Largely due to the subjectivity involved, the determination of GTR and RTV remains difficult in the postoperative setting. In response, the objective of this study is to evaluate the clinical efficacy of an easy-to-use MRI metric, called delta T1 (dT1), to quantify extent of resection (EOR) and RTV, in comparison to radiologist impression, to predict overall survival (OS) in glioblastoma patients.

Methods: 59 patients who underwent resection of glioblastoma were retrospectively identified. Delta T1 (dT1) images, automatically created from the difference between calibrated post- and pre-contrast T1-weighted images, were used to quantify EOR and RTV. Kaplan-Meier survival estimates were determined for EOR categories, an RTV cutoff of 5cm3 and radiologist interpretation of EOR. Multivariate Cox proportional hazard regression analysis was used to evaluate RTV and EOR along with effects related to sex, KPS, MGMT, and age on OS.

Results: Kaplan-Meier analysis revealed a statistically significant difference in median OS for a dT1-determined RTV cutoff of 5 cm3 (P=.0024, HR=2.18 (1.232-3.856)), but not for radiological impression (P=0.666) or dT1-determined EOR (P=0.0803), which was limited to a comparison between partial and subtotal resections. Furthermore, when covariates were accounted for in multivariate Cox regression, significant differences in OS were retained for dT1-determined RTV. Additionally, a significantly strong yet short-term effect of MGMT methylation status on OS was revealed for each RTV and EOR model.

Conclusion: The utility of dT1 maps to quantify EOR and RTV in glioblastoma and predict survival, suggests an emerging role for dT1s with relevance for intraoperative MRI, neuro-navigation and postoperative disease surveillance.

背景和目的:全切(GTR)和低残留肿瘤体积(RTV)与胶质母细胞瘤生存率的提高有关。主要由于涉及主观因素,在术后环境中确定 GTR 和 RTV 仍然很困难。因此,本研究的目的是评估一种易于使用的磁共振成像指标--δT1(dT1)--的临床疗效,与放射科医生的印象相比,该指标可量化切除范围(EOR)和RTV,从而预测胶质母细胞瘤患者的总生存率(OS)。根据校准后和对比前 T1 加权图像之间的差异自动生成的 Delta T1(dT1)图像用于量化 EOR 和 RTV。根据 EOR 类别、5 立方厘米的 RTV 临界值和放射科医生对 EOR 的解释,确定了 Kaplan-Meier 生存估计值。多变量考克斯比例危险回归分析用于评估RTV和EOR以及性别、KPS、MGMT和年龄对OS的影响:Kaplan-Meier分析显示,dT1确定的RTV截断值为5 cm3时,中位OS有显著统计学差异(P=.0024,HR=2.18(1.232-3.856)),但放射学印象(P=0.666)或dT1确定的EOR(P=0.0803)则没有显著统计学差异,这仅限于部分切除和次全切除之间的比较。此外,在多变量考克斯回归中考虑协变量时,dT1确定的RTV在OS方面仍存在显著差异。此外,在每个RTV和EOR模型中,MGMT甲基化状态对OS都有明显的短期影响:dT1图谱在量化胶质母细胞瘤的EOR和RTV以及预测生存率方面的实用性表明,dT1在术中磁共振成像、神经导航和术后疾病监测方面发挥着新的作用。
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引用次数: 0
Phase 1, Dose Escalation, Nonrandomized, Open-Label, Clinical Trial Evaluating the Safety and Preliminary Efficacy of Allogenic Adipose-Derived Mesenchymal Stem Cells for Recurrent Glioblastoma: A Clinical Trial Protocol. 评估异基因脂肪来源间充质干细胞治疗复发性胶质母细胞瘤的安全性和初步疗效的 1 期、剂量递增、非随机、开放标签临床试验:临床试验方案》(Phase 1, Dose Escalation, Non-andomized, Open-Label, Clinical Trial Trial Evaluating the Safety and Preliminary Efficacy of Allogenic Adipose-Derived Mesenchymal Stem Cells for Recurrent Glioblastoma: A Clinical Trial Protocol.
Pub Date : 2023-12-01 Epub Date: 2023-10-13
Andres Ramos-Fresnedo, Rawan Al-Kharboosh, Erin L Twohy, Aleeshba N Basil, Ewa C Szymkiewicz, Abba C Zubair, Daniel M Trifiletti, Nisha Durand, Dennis W Dickson, Erik H Middlebrooks, David N Abarbanel, Stephany Y Tzeng, Joao Paulo Almeida, Kaisorn L Chaichana, Jordan J Green, Wendy J Sherman, Alfredo Quiñones-Hinojosa

Background and objectives: Despite standard of care with maximal safe resection and chemoradiation, glioblastoma is the most common and aggressive type of primary brain cancer. Surgical resection provides a window of opportunity to locally treat gliomas while the patient is recovering, and before initiating concomitant chemoradiation. To assess the safety and establish the maximum tolerated dose of adipose-derived mesenchymal stem cells (AMSCs) for the treatment of recurrent glioblastoma (GBM). Secondary objectives are to assess the toxicity profile and long-term survival outcomes of patients enrolled in the trial. Additionally, biospecimens will be collected to explore the local and systemic responses to this therapy.

Methods: We will conduct a phase 1, dose escalated, non-randomized, open label, clinical trial of GBM patients who are undergoing surgical resection for recurrence. Up to 18 patients will receive intra-cavitary application of AMSCs encapsulated in fibrin glue during surgical resection. All patients will be followed for up to 5 years for safety and survival data. Adverse events will be recorded using the CTCAE V5.0.

Expected outcomes: This study will explore the maximum tolerated dose (MTD) of AMSCs along with the toxicity profile of this therapy in patients with recurrent GBM. Additionally, preliminary long-term survival and progression-free survival outcome analysis will be used to power further randomized studies. Lastly, CSF and blood will be obtained throughout the treatment period to investigate circulating molecular and inflammatory tumoral/stem cell markers and explore the mechanism of action of the therapeutic intervention.

Discussion: This prospective translational study will determine the initial safety and toxicity profile of local delivery of AMSCs for recurrent GBM. It will also provide additional survival metrics for future randomized trials.

背景和目的:尽管采用了最大限度安全切除和化疗的标准治疗方法,但胶质母细胞瘤仍是最常见、最具侵袭性的原发性脑癌。手术切除为胶质瘤的局部治疗提供了机会之窗,在患者康复期间和开始化疗之前,可以对胶质瘤进行局部治疗。评估脂肪间充质干细胞(AMSCs)治疗复发性胶质母细胞瘤(GBM)的安全性并确定最大耐受剂量。次要目标是评估参加试验的患者的毒性概况和长期生存结果。此外,我们还将收集生物样本,以探索这种疗法的局部和全身反应:我们将对因复发而接受手术切除的 GBM 患者进行一期、剂量递增、非随机、开放标签的临床试验。多达 18 名患者将在手术切除过程中接受包裹在纤维蛋白胶中的 AMSCs 腔内应用。所有患者都将接受长达 5 年的随访,以获得安全性和存活率数据。将使用 CTCAE V5.0 记录不良事件:这项研究将探索 AMSCs 的最大耐受剂量(MTD)以及这种疗法在复发性 GBM 患者中的毒性概况。此外,初步的长期生存和无进展生存结果分析将用于进一步的随机研究。最后,将在整个治疗期间采集脑脊液和血液,以研究循环分子和炎症肿瘤/干细胞标志物,并探索治疗干预的作用机制:这项前瞻性转化研究将确定局部给药 AMSCs 治疗复发性 GBM 的初步安全性和毒性概况。它还将为未来的随机试验提供更多的生存指标。
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引用次数: 0
Brain Circuitry of Consciousness: A Review of Current Models and a Novel Synergistic Model With Clinical Application. 脑意识回路:当前模型综述和一种具有临床应用的新型协同模型。
Pub Date : 2023-06-01 DOI: 10.1227/neuprac.0000000000000031
Theresa C Gammel, Leor N Alkadaa, Jordan R Saadon, Sabir Saluja, John Servider, Nathaniel A Cleri, Michael Egnor, Raphael P Davis, Chuan Huang, Yuri B Saalmann, Sima Mofakham, Charles B Mikell

How consciousness arises in the brain has important implications for clinical decision-making. We summarize recent findings in consciousness studies to provide a toolkit for clinicians to assess deficits in consciousness and predict outcomes after brain injury. Commonly encountered disorders of consciousness are highlighted, followed by the clinical scales currently used to diagnose them. We review recent evidence describing the roles of the thalamocortical system and brainstem arousal nuclei in supporting awareness and arousal and discuss the utility of various neuroimaging studies in evaluating disorders of consciousness. We explore recent theoretical progress in mechanistic models of consciousness, focusing on 2 major models, the global neuronal workspace and integrated information theory, and review areas of controversy. Finally, we consider the potential implications of recent research for the day-to-day decision-making of clinical neurosurgeons and propose a simple "three-strikes" model to infer the integrity of the thalamocortical system, which can guide prognosticating return to consciousness.

意识如何在大脑中产生对临床决策具有重要意义。我们总结了意识研究的最新发现,为临床医生评估意识缺陷和预测脑损伤后的结果提供了一个工具包。强调了常见的意识障碍,其次是目前用于诊断它们的临床量表。我们回顾了最近描述丘脑皮质系统和脑干唤醒核在支持意识和唤醒中的作用的证据,并讨论了各种神经影像学研究在评估意识障碍中的应用。我们探讨了意识机制模型的最新理论进展,重点关注两大模型,即全局神经元工作空间和集成信息理论,并回顾了争议领域。最后,我们考虑了近期研究对临床神经外科医生日常决策的潜在影响,并提出了一个简单的“三振”模型来推断丘脑皮质系统的完整性,这可以指导预后恢复意识。
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引用次数: 1
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Neurosurgery practice
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