改良电场贴片操作方法对胶质母细胞瘤肿瘤电场治疗患者头皮不良反应的影响

目的 探讨改良电场贴片操作方法对胶质母细胞瘤(GBM)肿瘤电场治疗(TTFields)头皮不良反应的影响。方法 选取于空军军医大学唐都医院2019年5月—2022年7月接受TTFields的73例GBM患者为研究对象,其中2021年4月前的36例采用常规电场贴片操作方法的患者为对照组,2021年5月后的37例在电场贴片粘贴、移除、高温环境维护等环节进行改进的患者为改良组。比较两组患者TTFields头皮不良反应的发生率、佩戴电场治疗的依从性等指标。结果 改良组患者发生头皮瘙痒(P=0.024 6)、接触性皮炎(P=0.025 3)、皮肤溃疡(P=0.029 9)的发生率显著低于对照组,佩戴电场治疗依从性≥90%的几率较对照组显著提高(分别为81.1%和52.8%,P=0.010 1)。针对两组患者头皮不良反应的研究发现,夏季患者头皮不良反应的发生率最高(56.16%),冬季则最低(8.22%),采用改良电场贴片操作方法后,可以显著降低在夏季(P=0.000 2)、秋季(P=0.041 1)和春季(P=0.034 2)的头皮不良反应的发生。结论 胶质母细胞瘤TTFields患者采用改良电...     

肿瘤电场治疗脑胶质瘤的临床研究进展

胶质母细胞瘤(GBM)是颅内最常见的原发性恶性脑肿瘤,具有高复发率和高死亡率。目前GBM的标准治疗方案为外科手术,然后放疗同步替莫唑胺(TMZ)化疗和进一步TMZ化疗。肿瘤电场治疗(TTFields)是一种新兴的肿瘤治疗方法,当与标准治疗方案联合时,GBM患者的无进展生存期和总生存期可以得到显著改善。基于多项临床研究结果,TTFields已经在国内外获批上市,且得到了相关指南和共识的推荐。本文将重点述评TTFields的发展及其在GBM治疗中的一系列临床研究,并展望其未来的研究方向。     

肿瘤治疗电场联合替莫唑胺化疗与单独使用替莫唑胺化疗对胶质母细胞瘤临床疗效比较的Meta分析

目的 探讨单独使用替莫唑胺（TMZ）与替莫唑胺联合肿瘤治疗电场（TTF）治疗胶质母细胞瘤安全性和疗效的比较。方法 检索Pubmed、Cochrance、Embase、Ovid、Scopus、Web of Science、中国知网、万方数据知识服务平台、维普中文期刊数据库、中国生物医学文献服务系统数据库、谷歌学术自建库至2020年4月5日的文献,筛选TMZ和TTF+TMZ进行疗效比较的随机对照研究,按照纳入和排除标准,把总体生存率（OS）和无进展生存期（PFS）作为结局指标,最后使用Review Manager进行统计分析。结果 最终纳入4篇研究,共1091例患者,其中单纯TMZ组381例,TTF+TMZ组710例。TTF+TMZ组的平均OS （26.9个月）和平均PFS （14.7个月）,优于单纯TMZ组的平均OS （12.63个月）和平均PFS （5个月）（P<0.01）。结论 TTF+TMZ治疗GBM的有效性优于单纯使用TMZ的患者。     

肿瘤治疗电场在胶质母细胞瘤中的临床应用研究进展

肿瘤治疗电场(TTFields)是利用特定低强度、中频率的交变电场干扰肿瘤细胞的有丝分裂,从而抑制肿瘤细胞增殖的新型治疗手段。研究表明,TTFields具有抗肿瘤的疗效,且不良反应轻微,能提高脑胶质瘤患者的生命质量、延长患者的总生存期。TTFields现已被国家卫生健康委员会纳入《脑胶质瘤诊疗规范》,是一项在胶质母细胞瘤治疗中具有潜力的新兴技术。本文拟结合国内外最新研究,对TTFields在临床应用方面的研究进展进行综述。     

植入式肿瘤电场治疗胶质母细胞瘤的建模与仿真研究

目的 研究植入式肿瘤电场治疗胶质母细胞瘤的可行性。方法 通过COMSOL有限元仿真,探索相位差、触点设置、电极数量和电压等参数对电场的分布的影响,逐步优化参数,探索电场覆盖范围的影响因素。结果 合理地设置相位差在相同电压下可以扩大电场覆盖的范围,并提出了一种双层环绕递增相差设置方法。以5根电极5 V电压为例,对比了不同数量的触点激活的电场分布范围,阐明了双层触点激活的优势及触点选择的方式。仿真了使1 V/cm的有效治疗电场覆盖不同大小残腔切除边缘所需的最少电极数量和最小整数电压,3根电极6 V的电压即可覆盖直径2 cm残腔的切除边缘,而直径5 cm的残腔需要5根电极和10 V的电压。针对直径3.5 cm的残腔探究了电极数量与电压的相互替代关系。结论 脑肿瘤切除术后通过植入式电极可以将中频交变电场聚焦在切除边缘附近,优化参数可以覆盖残腔表面,场强超过1 V/cm,表明植入式肿瘤电场治疗是一种潜在可行的治疗方案。该治疗方案的安全性、器械小型化和供能则仍需进一步的研究。     

贝伐单抗治疗复发胶质母细胞瘤的研究进展

<正>手术切除、术后放疗以及同步替莫唑胺化疗是治疗初发胶质母细胞瘤的标准治疗方案。对于经过标准化治疗后肿瘤进展的病人,可以采用继续手术、化疗、放疗等方法,但现在仍没有统一的治疗方案[1]。胶质母细胞瘤是一种高度血管化的肿瘤,高度表达血管表皮生长因子(vascular endothelial growthfactor,VEGF)。贝伐单抗可以高度选择性的作用于VEGF,从而达到阻断肿瘤生长的作用。最新美国国立综合癌症网络指南,已经将贝伐单抗作为临床一线药物治疗复发胶质母细胞瘤。     

造血干细胞支持下复发脑胶质母细胞瘤化疗的初步研究

目的 观察自身外周造血干细胞支持下大剂量化疗治疗脑胶质瘤的疗效、毒性及可行性。方法 将20例复发胶质母细胞瘤病人随机分组，分别采用常规剂量化疗和大剂量化疗 自身外周造血干细胞移植，化疗方案主要是尼莫司汀(ACNU) 威猛，大剂量组为常规剂量的2倍。结果 常规剂量化疗组13例中，有效1例，微效7例，无变化4例，恶化1例；均有较为严重的骨髓抑制反应。大剂量化疗7例中，有效4例，微效3例，骨髓抑制反应较轻，且能迅速恢复。结论 自身外周血造血干细胞支持下大剂量化疗治疗复发性胶质母细胞瘤疗效好，引起的骨髓抑制在短期内可恢复。     

靶向调节胶质母细胞瘤血管生成的治疗进展

<正>胶质母细胞瘤(glioblastoma,GB)作为中枢神经系统最常见的恶性肿瘤,其恶性程度最高,也是最富血管的恶性肿瘤之一,可表达多种特异性肿瘤血管调节因子,这些因子在肿瘤分级、预后或疗效监测等方面起着重要作用,也是基因靶向治疗的靶标与临床研究的对象[1]。血管生成是由促血管生成因子与其相应受体结合,从而启动一个步进式的血管发生、形成的过程。而血管生成抑制因子则可通过干扰促血管生成因子与其受体的结合,从源头     

多形性脑胶质母细胞瘤化疗对预后的评价

多形性胶质母细胞瘤（glioblastoma multiforme,GBM）,按Kernohan分类属于星形细胞瘤Ⅲ～Ⅳ级,WHO2007年中枢神经系统肿瘤分类标准将其归类为星形细胞瘤Ⅳ级,占中枢神经系统恶性肿瘤的25％。该病男性发病率高于女性,具有家族聚集倾向。以往研究认为该病平均发病年龄为60岁,但近些年患者呈现出年轻化的趋势。     

BTPCs在胶质母细胞瘤治疗中的研究进展

胶质母细胞瘤(glioblastoma,GBM)是成人神经上皮性肿瘤中恶性程度最高、最具侵袭性、预后最差的肿瘤[1],中位生存期仅12~18.5个月[2]。脑胶质瘤的细胞来源仍众说纷纭,星形胶质细胞、神经干细胞和少突胶质前体细胞等均有可能是胶质瘤的起源细胞[3]。研究表明,高级别胶质瘤更有可能起源于神经干细胞(neural stem cell,NSCs)[4]。     

A prospective PET study of patients with glioblastoma multiforme

OBJECTIVE: To study the post-surgical metabolic and structural cerebral changes in patients with glioblastoma multiforme (GBM). MATERIALS AND METHODS: We examined ten patients prospectively with newly diagnosed GBM. All patients were primarily treated with surgery, followed by chemotherapy (carmustine, cisplatine and etoposide) and radiotherapy. Positron emission tomography (PET) was used to measure tumor- and cerebral metabolism. CT or MRI was used to estimate tumor volume by measurements of tumor area. RESULTS: Tumor metabolism was not increased during chemotherapy (P = 0.71), but increased during radiotherapy (P = 0.01). CT/MRI showed similar results with no increase in tumor area during chemotherapy (P = 0.33) but increase during radiotherapy (P = 0.002). During the entire study, tumor metabolism and area increased evenly (P = 0.01). CONCLUSIONS: Our study did not show a gain of PET compared with structural imaging in the prospective evaluation of GBM. We found a difference in metabolic increase and tumor growth between the two treatment regimens, although this finding has limited relevance due to the design of the study.     

Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective,multicenter, randomized,placebo-controlled,single-blinded clinical trial

Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promising candidate for the treatment of intractable spinal cord injury(SCI).Clinical studies on patients with early chronic SCI(from 2 months to 1 year post-injury),which is clinically common,are rare;therefore,we will conduct a prospective,multicenter,randomized,placebo-controlled,single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University,West China Hospital of Sichuan University,and Shanghai East Hospital,Tongji University School of Medicine,China.The trial plans to recruit 66 early chronic SCI patients.Eligible patients will undergo randomization at a 2:1 ratio to two arms:the observation group and the control group.Subjects in the observation group will receive four intrathecal transplantations of stem cells,with a dosage of 1×106/kg,at one calendar month intervals.Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations.Clinical safety will be assessed by the analysis of adverse events and laboratory tests.The American Spinal Injury Association(ASIA)total score will be the primary efficacy endpoint,and the secondary efficacy outcomes will be the following:ASIA impairment scale,International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale,muscle tension,electromyogram,cortical motor and cortical sensory evoked potentials,residual urine volume,magnetic resonance imaging–diffusion tensor imaging,T cell subtypes in serum,neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid.All evaluations will be performed at 1,3,6,and 12 months following the final intrathecal administration.During the entire study procedure,all adverse events will be reported as soon as they are noted.This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI.Moreover,it will establish whether cytotherapy can ameliorate local hostile microenvironments,promote tracking fiber regeneration,and strengthen spinal conduction ability,thus improving overall motor,sensory,and micturition/defecation function in patients with early chronic SCI.This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2018]-02)on March 30,2018,and was registered with ClinicalTrials.gov(registration No.NCT03521323)on April 12,2018.The revised trial protocol(protocol version 4.0)was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2019]-10)on February 25,2019,and released on ClinicalTrials.gov on April 29,2019.     

An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: a pilot study

Recent preclinical studies implicate N-acetylcysteine (NAC), a cysteine prodrug, as a potential medication for preventing relapse to cocaine use; however, little is known about the safety and tolerability of NAC in cocaine-dependent subjects in an outpatient setting. This pilot study examines the safety and tolerability of 3 doses of NAC for the treatment of cocaine dependence. Twenty three treatment-seeking cocaine-dependent patients participated in a 4-week medication trial and received NAC at doses of 1200 mg/day, 2400 mg/day or 3600 mg/day. Results suggested that the three doses were well tolerated. Overall, the retention rates appeared to favor higher doses of NAC (2400 mg/day and 3600 mg/day). The majority of subjects who completed the study (n=16) either terminated use of cocaine completely or significantly reduced their use of cocaine during treatment. Overall the findings suggest that it is feasible to treat cocaine-dependent treatment seekers with N-acetylcysteine on an outpatient basis.     

Tiagabine for the treatment of generalized anxiety disorder: a randomized, open-label, clinical trial with paroxetine as a positive control

BACKGROUND: Gamma-aminobutyric acid (GABA) plays a central role in the pathophysiology of anxiety. Tiagabine, a selective GABA reuptake inhibitor, enhances normal GABA tone. This 10-week, randomized, open-label trial evaluated tiagabine in patients with generalized anxiety disorder (GAD), with paroxetine serving as a positive control. METHOD: Adult patients with DSM-IV GAD were randomly assigned to receive either tiagabine or paroxetine. Tiagabine was initiated at 4 mg/day (2 mg morning and evening) during week 1. Between weeks 2 and 6, the dose was individually titrated in 2-mg increments (maximum increase of 4 mg/week) for optimal response to a maximum dose of 16 mg/day (8 mg morning and evening). During weeks 7 through 10, patients received the dosage determined during the titration period. Paroxetine was initiated at 20 mg nightly for the first week and similarly titrated in 10-mg increments to a maximum dose of 60 mg/day. Assessments included the Hamilton Rating Scale for Anxiety (HAM-A), Hospital Anxiety and Depression Scale (HADS), Hamilton Rating Scale for Depression (HAM-D), Pittsburgh Sleep Quality Index (PSQI), and Sheehan Disability Scale (SDS). RESULTS: Forty patients were enrolled (tiagabine, N = 20; paroxetine, N = 20). Mean final doses were tiagabine 10 mg/day (range, 4-16 mg/day) or paroxetine 27 mg/day (range, 20-40 mg/day). Tiagabine and paroxetine significantly reduced anxiety (HAM-A and HADS total and anxiety subscales). Although patients were not diagnosed with a mood disorder, both tiagabine and paroxetine reduced comorbid depressive symptoms (HAM-D total and HADS total and depressive subscale). Tiagabine and paroxetine significantly improved sleep quality (PSQI) and functioning (SDS). Both tiagabine and paroxetine were well tolerated. CONCLUSION: The selective GABA reuptake inhibitor tiagabine and the positive control paroxetine significantly reduced anxiety and comorbid depressive symptoms, improved sleep quality and functioning, and were well tolerated in patients with GAD. Tiagabine may be a therapeutic option for the treatment of anxiety disorders.     

Low-dose fluvoxamine treatment of children and adolescents with pervasive developmental disorders: a prospective,open-label study

The objective of this study was to assess the efficacy and tolerability of low-dose fluvoxamine (1.5 mg/kg/day) in youngsters with pervasive developmental disorders (PDDs). This was a prospective, open-label trial that included 18 subjects with a mean age of 11.3 ± 3.6 years. Fourteen children (78%) completed the 10-week study. Premature discontinuation due to behavioral activation occurred in three participants. Although there was no response for the group as a whole, eight subjects (including all four females) were considered at least partial responders in intent-to-treat analyses. Neither pubertal status nor serotonin levels predicted clinical response. Fluvoxamine can be beneficial in the treatment of select children and adolescents with PDDs. Gender differences in selective serotonin reuptake inhibitor (SSRI) response warrant further investigation.     

Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: a prospective, open-label extension study

PurposeThis prospective, open-label extension (SP702; NCT00594165) of a 6-month double-blind, randomized study investigated the long-term safety and tolerability of rotigotine transdermal system in early Parkinson’s disease (PD).MethodsPatients with early-stage idiopathic PD received transdermal rotigotine for up to 6 years at optimal dose (up to 16 mg/24 h). Adjunctive levodopa was allowed. Primary outcomes included adverse events (AEs) and extent of rotigotine exposure. Other outcomes included time to levodopa, incidence of dyskinesias, and efficacy using the Unified Parkinson’s Disease Rating Scale (UPDRS) II + III total score.ResultsOf 217 patients entering the open-label study, 47% were still in the study upon closure; 24% withdrew because of AEs and 6% because of lack of efficacy. The median exposure to rotigotine was 1910 days (～5 years, 3 months; range 1–2188 days). Most common AEs were somnolence (23% per patient-year), falls (17%), peripheral edema (14%), nausea (12%), and application site reactions (ASRs; 12%). 3% withdrew because of ASRs. 26% patients did not initiate levodopa; of those who did, fewer than half started levodopa in the first year. Dyskinesias were reported by 25% patients; the majority (83%) reported their first episode after initiating levodopa. Mean UPDRS II + III total scores remained below double-blind baseline for up to 2 years of open-label treatment.ConclusionThis is the longest interventional study of rotigotine conducted to date. Transdermal rotigotine was generally well tolerated for up to 6 years; AEs reported were similar to those observed in shorter studies and led to discontinuation in only 24% patients.     

Olanzapine treatment for tardive dyskinesia in schizophrenia patients: a prospective clinical trial with patients randomized to blinded dose reduction periods

BACKGROUND: Tardive dyskinesia (TD) is a potentially persistent and disabling abnormal involuntary movement disorder. The aim of this 8-month study was to determine if olanzapine treatment could lead to a significant and persistent reduction in preexisting TD. METHODS: Eligible schizophrenia patients met restricted Research Diagnosis criteria of TD requiring, in part, a rating of at least moderate severity (score > or = 3) in one or more of seven body regions on the Abnormal Involuntary Movement Scale (AIMS). Patients received olanzapine, 5-20 mg/day, for 8 months. During this period, they underwent one to two dose reduction periods under blinded conditions. Concurrent changes in TD, psychopathology, parkinsonism and akathisia were assessed with the AIMS, the Positive and Negative Syndrome Scale (PANSS), and the Simpson-Angus and Barnes Akathisia Scales, respectively. RESULTS: A significant reduction in mean AIMS total score was demonstrated at endpoint (n = 92; p < 0.001) as well as at each visit (p < 0.001) and as early as Week 1 on olanzapine. Approximately 70% of patients no longer met the restricted Research Diagnostic criteria for persistent TD (RD-TD) after 8 months of treatment. No statistically significant rebound worsening of TD was found during either blinded drug reduction period. Significant improvement in psychopathology (p = 0.001) and parkinsonism (p < 0.001) was observed. CONCLUSIONS: Improvement in the severity of preexisting TD was achieved with olanzapine and persisted throughout the 8-month study and during each dose reduction period. Overall improvement in clinical status suggests that olanzapine may be effective for the long-term management of schizophrenia patients with preexisting TD.