Rebleeding and bleeding in the year following intracranial aneurysm coiling: analysis of a large prospective multicenter cohort of 1140 patients-Analysis of Recanalization after Endovascular Treatment of Intracranial Aneurysm (ARETA) Study.
颅内动脉瘤弹簧圈栓塞术后一年的再出血和出血: 1140 例患者的大型前瞻性多中心队列分析-颅内动脉瘤血管内治疗后再通分析 (ARETA) 研究。
- 作者列表："Pierot L","Barbe C","Herbreteau D","Gauvrit JY","Januel AC","Bala F","Ricolfi F","Desal H","Velasco S","Aggour M","Chabert E","Sedat J","Trystram D","Marnat G","Gallas S","Rodesch G","Clarençon F","Papagiannaki C","White P","Spelle L
BACKGROUND:Endovascular treatment is the first line therapy for the management of ruptured and unruptured intracranial aneurysms, but delayed aneurysm rupture leading to bleeding/rebleeding can occur subsequently. ARETA (Analysis of Recanalization after Endovascular Treatment of intracranial Aneurysm) is a prospective, multicenter study conducted to analyze aneurysm recanalization. We analyzed delayed bleeding and rebleeding in this large cohort. METHODS:16 neurointerventional departments prospectively enrolled patients treated for ruptured and unruptured aneurysms between December 2013 and May 2015 (ClinicalTrials.gov: NCT01942512). Participant demographics, aneurysm characteristics and endovascular techniques were recorded. Data were analyzed from participants with ruptured or unruptured aneurysms treated by coiling or balloon-assisted coiling. Rates of bleeding and rebleeding were analyzed and associated factors were studied using univariable and multivariable analyses. RESULTS:The bleeding rate was 0.0% in patients with unruptured aneurysms and 1.0% (95% CI 0.3% to 1.7%) in patients with ruptured aneurysms. In multivariate analysis, two factors were associated with rebleeding occurrence: incomplete aneurysm occlusion after initial treatment (2.0% in incomplete aneurysm occlusion vs 0.2% in complete aneurysm occlusion, OR 10.2, 95% CI 1.2 to 83.3; p=0.03) and dome-to-neck ratio (1.5±0.5 with rebleeding vs 2.2±0.9 without rebleeding, OR 0.2, 95% CI 0.04 to 0.8; p=0.03). Modalities of management of aneurysm rebleeding as well as clinical outcomes are described. CONCLUSIONS:Aneurysm coiling affords good protection against bleeding (for unruptured aneurysms) and rebleeding (for ruptured aneurysms) at 1 year with rates of 0.0% and 1.0%, respectively. Aneurysm occlusion and dome-to-neck ratio are the two factors that appear to play a role in the occurrence of rebleeding.
背景: 血管内治疗是治疗破裂和未破裂颅内动脉瘤的一线治疗方法，但随后可发生迟发性动脉瘤破裂导致出血/再出血。ARETA (颅内动脉瘤血管内治疗后再通分析) 是一项前瞻性、多中心研究，旨在分析动脉瘤再通情况。我们分析了这个大型队列中的迟发性出血和再出血。 方法: 16 个神经介入部门前瞻性入选 2013 年 12 月至 2015 年 5 月期间接受破裂和未破裂动脉瘤治疗的患者 (ClinicalTrials.gov: NCT01942512)。记录参与者人口统计学、动脉瘤特征和血管内技术。对经弹簧圈栓塞或球囊辅助弹簧圈栓塞治疗的破裂或未破裂动脉瘤参与者的数据进行分析。分析出血率和再出血率，并采用单变量和多变量分析研究相关因素。 结果: 未破裂动脉瘤患者的出血率为 0.0%，破裂动脉瘤患者的出血率为 1.0% (95% ci 0.3% ~ 1.7%)。在多变量分析中，两个因素与再出血发生相关: 初始治疗后动脉瘤不完全闭塞 (动脉瘤不完全闭塞 2.0% vs 动脉瘤完全闭塞 0.2%，OR 10.2，95% CI 1.2 ~ 83.3; p = 0.03) 和圆顶-颈比 (1.5 ± 0.5 伴再出血 vs 2.2 ± 0.9 不伴再出血，或 0.2,95% CI 0.04 ~ 0.8; p = 0.03)。描述了动脉瘤再出血的处理方式以及临床结果。 结论: 动脉瘤弹簧圈栓塞在 1 年时对出血 (对于未破裂动脉瘤) 和再出血 (对于破裂动脉瘤) 提供了良好的保护，发生率分别为 0.0% 和 1.0%。动脉瘤闭塞和瘤颈比是似乎在再出血发生中起作用的两个因素。
METHODS:PURPOSE:To generate a preclinical model of isocitrate dehydrogenase (IDH) mutant gliomas from glioma patients and design a MRS method to test the compatibility of 2-hydroxyglutarate (2HG) production between the preclinical model and patients. METHODS:Five patient-derived xenograft (PDX) mice were generated from two glioma patients with IDH1 R132H mutation. A PRESS sequence was tailored at 9.4 T, with computer simulation and phantom analyses, for improving 2HG detection in mice. 2HG and other metabolites in the PDX mice were measured using the optimized MRS at 9.4 T and compared with 3 T MRS measurements of the metabolites in the parental-tumor patients. Spectral fitting was performed with LCModel using in-house basis spectra. Metabolite levels were quantified with reference to water. RESULTS:The PRESS TE was optimized to be 96 ms, at which the 2HG 2.25 ppm signal was narrow and inverted, thereby leading to unequivocal separation of the 2HG resonance from adjacent signals from other metabolites. The optimized MRS provided precise detection of 2HG in mice compared to short-TE MRS at 9.4 T. The 2HG estimates in PDX mice were in excellent agreement with the 2HG measurements in the patients. CONCLUSION:The similarity of 2HG production between PDX models and parental-tumor patients indicates that PDX tumors retain the parental IDH metabolic fingerprint and can serve as a preclinical model for improving our understanding of the IDH-mutation associated metabolic reprogramming.
METHODS:BACKGROUND:Gliomas consist of a heterogeneous group of tumors. This study aimed to report the incidences of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p19q co-deletion, isocitrate dehydrogenase (IDH) gene mutations, and inactivating mutations of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) in high-grade gliomas in an ethnically diverse population. METHODS:Records of patients who underwent surgery for high-grade gliomas from January 2013 to March 2017 at our institution were obtained. The patients' age, gender, ethnicity, Karnofsky Performance Scale (KPS) score, ability to perform activities of daily living (ADLs), tumor location and biomarkers status were recorded. Data were analyzed using chi-square and Mann-Whitney U tests, Kaplan-Meier estimates and log-rank test. RESULTS:181 patients were selected (56 with grade III gliomas, 125 with grade IV gliomas). In the grade III group, 55% had MGMT promoter methylation, 41% had 1p19q co-deletion, 35% had IDH1 mutation and none had ATRX loss. In the grade IV group, 30% had MGMT promoter methylation, 2% had 1p19q co-deletion, 15% had IDH1 mutation and 8% had ATRX loss. After adjusting for effects of age, surgery and pre-operative ADL statuses, only MGMT promoter methylation was found to be significantly associated with longer overall survival time in grade III (p = 0.024) and IV patients (p = 0.006). CONCLUSIONS:The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.
METHODS:BACKGROUND:Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. Tumor recurrence occurs in virtually all cases, therefore, despite any treatment, the median survival is very low (14.6 months), which makes the approach to these patients a challenging clinical issue. MAIN BODY:The escalating costs and times required for new medications to reach the bedside make repurposing or repositioning of old drugs, when scientific bases allow their use in other pathologies, an appealing strategy. Here, we analyze a number of literature data concerning the antipsychotic chlorpromazine, the founder of the phenothiazines class of drugs, a medication widely used in the clinics for approximately 60 years. The drug exerts its effects on psychiatric patients by interfering with the dopamine receptor D2, although more recent pharmacodynamics studies ascribe chlorpromazine a series of biological effects on cancer cells, all converging in hindering also glioblastoma survival capabilities. SHORT CONCLUSIONS:On these bases, and assisted by the information on the well-established chlorpromazine toxicity and dosage in humans, we designed a Phase II clinical trial involving the combination of chlorpromazine with the standard treatment, temozolomide, in the adjuvant phase of the therapeutic protocol. Patients displaying hypo-methylation of the MGMT gene, and thus intrinsically resistant to temozolomide, will be enrolled. The endpoints of this study are the analysis of toxicity and clinical activity, as evaluated in terms of Progression-Free Survival, of the association of chlorpromazine with the first-line treatment for this very serious form of cancer.