Recanalization of Embolized Endovascular Intracranial Aneurysms and Changes in the Blood Viscosity: A Pilot Study.
- 作者列表："Morga R","Moskała M","Popiela T","Rajzer M","Wilk A","Kłosiński M","Muszyński T","Trystuła M
:BACKGROUND The purpose of our research was to evaluate the relationships between blood viscosity and recanalization of coiled intracranial aneurysms. MATERIAL AND METHODS The study included consecutives patients treated endovascularly by a team of experienced neurosurgeons and neuroradiologists due to brain aneurysm. A total of 50 patients (the average age was 57.48 years, SD=13.71) were assigned to 2 groups: group A with recanalization (4 male and 8 female patients) and group B without recanalization (10 male and 28 female patients) were examined. All patients underwent a 6-month follow-up of the whole-blood viscosity test with a Brookfield DV III+pro cone-plate viscometer using the Rheocalc program. Differences between groups were assessed using the Statistica 12 computer program (StatSoft Inc., Tulsa, OK, USA). RESULTS Studies have shown no significant difference in the age range between group A and B (P=0.31). In group A, higher viscosity values were found for whole blood [median: 4.14 dyn×sec/cm² (mPa×sec) quartile range 0.42], compared to group B [median: 3.92 dyn×sec/cm² (mPa×sec); quartile range 0.40; (P=0.04)]. This difference was significant (P=0.04). Additionally, the level of hematocrit was positively related with recanalization, the higher the hematocrit, the more frequent recanalization. A very strong and statistically significant relationship occurred between the frequency of recanalization and smoking (P<0.001). CONCLUSIONS The occurrence of higher values of whole blood viscosity which increase turbulent flow through the vessels may be a risk for recanalization of the coiled intracranial aneurysm.
背景: 我们研究的目的是评估血液粘度与卷曲颅内动脉瘤血管再通之间的关系。材料和方法该研究包括由一组经验丰富的神经外科医生和神经放射科医生因脑动脉瘤进行血管内治疗的连续患者。共 50 例患者 (平均年龄 57.48 岁，SD = 13.71) 被分配到 2 组: A 组再通 (4 例男性和 8 例女性患者) 未再通的 B 组 (男性 10 例，女性 28 例)。所有患者使用 Rheocalc 程序，用 Brookfield DV III + pro 锥板粘度计进行了 6 个月的全血粘度试验随访。使用 Statistica 12 计算机程序 (StatSoft inc.，Tulsa，OK，USA) 评估组间差异。结果研究显示 A 组和 B 组的年龄范围无显著差异 (P = 0.31)。在 A 组中，发现全血粘度值较高 [中位数: 4.14 dyn × sec/cm ² (mpa × sec) 四分位数范围 0.42]，而 B 组 [中位数: 3.92 dyn × sec/cm ² (mpa × sec); 四分位数范围 0.40; (P = 0.04)]。这种差异是显著的 (P = 0.04)。红细胞压积与血管再通呈正相关，红细胞压积越高，血管再通越频繁。复通频率与吸烟之间存在非常强且具有统计学意义的关系 (P<0.001)。结论较高的全血粘度值增加血管湍流的发生可能是盘绕颅内动脉瘤血管再通的危险因素。
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.