Evaluation of a collapsed-cone convolution algorithm for esophagus and surface mold 192Ir brachytherapy treatment planning

PurposeTG43 does not account for a lack of scatter and tissue and applicator heterogeneities. The advanced collapsed-cone engine (ACE) algorithm available for use in the Oncentra Brachy treatment planning system (Elekta AB, Stockholm, Sweden) can model these conditions more accurately and is evaluated for esophageal and surface mold brachytherapy treatments.Methods and MaterialsACE was commissioned for use then compared against TG43 for five esophageal and five surface mold treatment plans. Dosimetric differences between each algorithm were assessed using superimposed comparisons and dose-volume histogram statistics.ResultsEsophagus (6 Gy per fraction): Compared with TG43, ACE demonstrated up to a 0.63% and 0.05 Gy reduction in planning target volume (PTV) V100% and PTV D98, respectively. Lung D2cc and bone D2cc deviated by up to 0.09 Gy and 0.03 Gy, respectively. Lung D0.1 cc and bone D0.1 cc both deviated by up to 0.12 Gy.Surface mold (4.5 Gy per fraction): Compared with TG43, ACE demonstrated up to a 12.5% and 0.18 Gy reduction in PTV V80% and PTV D98, respectively. Bone D2cc and D0.1 cc both reduced by up to 0.2 Gy when modeled with ACE. Increasing mold size laterally increased the dosimetric differences between TG43 and ACE.ConclusionsTG43 generally overestimated dose delivered to the target volume and organs at risk for the sites investigated. Dosimetric differences observed for esophageal treatments were minimal; however, surface mold treatments would benefit from the increased dosimetric accuracy offered by ACE.Implementation should be considered for surface mold ¹⁹²Ir treatment planning, but increased calculation time, additional contouring, and mass density assignment requirements should be scrutinized with regard to their potentially negative impact on current clinical practice.     

Genetic and Environmental Factors in Parkinson's Disease Converge on Immune Function and Inflammation

Idiopathic Parkinson's disease (iPD) is a movement disorder characterized by the degeneration of dopaminergic neurons and aggregation of the protein α-synuclein. Patients with iPD vary in age of symptom onset, rate of progression, severity of motor and non-motor symptoms, and extent of central and peripheral inflammation. Genetic and environmental factors are believed to act synergistically in iPD pathogenesis. We propose that environmental factors (pesticides and infections) increase the risk for iPD via the immune system and that the role of PD risk genes in immune cells is worthy of investigation. This review highlights the major PD-relevant genes expressed in immune cells and key environmental factors that activate immune cells and, alone or in combination with other factors, may contribute to iPD pathogenesis. By reviewing these interactions, we seek to enable the future development of immunomodulatory approaches to prevent or delay onset of iPD. © 2020 International Parkinson and Movement Disorder Society     

Effective treatments for FGF12-related early-onset epileptic encephalopathies patients

BackgroundFGF12 (FHF1) gene encodes voltage-gated sodium channel (Nav)-binding protein fibroblast growth factor homologous factor 1, which could cause seizures by regulating voltage dependence of Nav fast inactivation and neuron excitability. The most common pathogenic variant FGF12 c.341G > A related early-onset epileptic encephalopathies (EOEE) was characterized by intractable seizures and developmental disabilities.ResultsUsing whole exome sequencing, a de novo hotspot variant c.341G > A (NM_021032.4) of FGF12 was identified in three unrelated EOEE probands. All probands were seizure free after a combination treatment of valproic acid (VPA) and topiramate (TPM). The motor and cognitive skills in two probands were improved due to the early and effective treatment. In order to compare the effectiveness of different treatment strategies for the disease, a review of treatments for FGF12-related epilepsy was made.ConclusionWe reported three FGF12 c.341G > A related EOEE patients responded well to a combination antiepileptic therapy of VPA and TPM. The current study is the first to describe the combination therapy of VPA and TPM in FGF12 c.341G > A related EOEE patients. This study may contribute to future medication consultation for intractable epilepsy with FGF12 hotspot variants.     

How is the COVID-19 pandemic affecting individuals with obsessive-compulsive disorder (OCD) symptoms?

The novel coronavirus disease (COVID-19) pandemic has caused substantial public health burden and widespread anxiety. The adverse mental health effects caused by COVID-19 may be particularly acute for individuals with obsessive-compulsive disorder (OCD). For the present study, we developed an online survey to investigate how COVID-19 has affected the OCD community. The survey included both quantitative and qualitative questions to assess multiple facets of how the pandemic has affected individuals with OCD symptoms. Responses were collected from adults with self-identified OCD recruited from OCD-specific forums and websites (n = 252). The majority (76.2 %) of respondents reported that their OCD symptoms had worsened since the outbreak, though there was substantial variability in individual responses. Negative effects of COVID-19 were more strongly linked to contamination and responsibility for harm symptoms than for other symptom dimensions. The self-identified OCD group also reported heightened concerns about COVID-19 compared to a community control sample recruited through Amazon’s Mechanical Turk (MTurk). Lastly, many participants reported that the pandemic had interfered with their OCD treatment, yet they remained mostly satisfied with how their treatment providers had handled the crisis. These results highlight the importance of considering how COVID-19 has affected the OCD community, with possible implications for treatment providers.     

A pilot study of intensive 7-day internet-based cognitive behavioral therapy for social anxiety disorder

Accessible, affordable cognitive behavioral therapy (CBT) options for Social Anxiety Disorder (SAD) that allow for rapid symptom improvement are needed. The present study investigated the first intensive, 7-day internet-based CBT for SAD. An open pilot trial was conducted to test the acceptability, feasibility and preliminary outcomes of the program in a sample of 16 participants (9 females, M age = 40.34, SD = 10.55) with a DSM-5 diagnosis of SAD. Participants were enrolled into the 6-lesson online program, and completed the Social Phobia Scale [SPS], Social Interaction Anxiety Scale [SIAS], Patient Health Questionnaire-9 (PHQ-9), and Work and Social Adjustment Scale (WSAS) at baseline, post and one month follow-up. We found support for the feasibility and acceptability of the program; 15 participants (93.8%) completed the program, and all participants reported the program was satisfactory. Large, significant reductions in social anxiety severity on both the SPS and SIAS (Hedges’ g_s = 1.26–1.9) and functional impairment (WSAS; g_s = 0.88–0.98) were found at post-treatment and follow-up. Medium, significant reductions in depressive symptom severity were also found (g_s = 0.88–0.98 at post and follow-up, respectively). A third of participants scored below the clinical cut-off on both the SPS and SIAS at post-treatment and follow-up. A randomized controlled trial with longer follow-up is needed to evaluate the efficacy of this intensive internet-based treatment for SAD. Implications and future research directions are discussed.     

Autoimmune encephalitis in a tertiary hospital in the Philippines

BackgroundAutoimmune encephalitis (AE) is an emerging disorder in adults and children. Due to its potentially reversible nature, prompt recognition and intervention are of utmost importance.ObjectiveTo describe the clinical and paraclinical features, as well as treatment outcomes of patients with AE admitted in a Philippine tertiary hospital.MethodsRetrospective case series of patients with definite AE.ResultsEighteen (18) patients were included (12 adults, 6 children), majority of whom had anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. The median age of onset was 32 (IQR: 10.8) years old and 13 (IQR: 4.8) years old in the adult and pediatric population, respectively. In both age groups, most presented with psychiatric symptoms and normal imaging findings. Cerebrospinal fluid (CSF) pleocytosis was detected in 8/12 (66.7%) adults and 2/6 (33.3%) children, while CSF protein elevation was only seen in 6/12 (50%) adults. Most patients presented with seizures, and the most frequent electroencephalography (EEG) abnormality detected was slow activity (70.5%). A high proportion of patients received high dose steroids, alone (35.3%) or in combination with intravenous immunoglobulin (IVIG, 52.9%). Overall, 66.7% had improved outcomes, mostly seen in the pediatric population.ConclusionThis study highlighted the broad clinical phenotype, as well as the similarities and differences of AE manifestations in adults and children. It demonstrated the limited but supportive role of laboratory investigations in the diagnosis of AE. It also underscored the importance of early intervention in AE and highlighted factors influencing treatment practices and discharge outcomes in the local setting.     

BOOSTING T CELL COSTIMULATION IN CANCER: THE POSSIBILITIES SEEM ENDLESS

Effective immune strategies for eradication of human malignancies will require a thorough understanding of the interactions of cancer with the immune system. It will be crucial to understand how to optimize and sustain a T cell immune response. Recently, our understanding of the molecular interaction that occurs between an APC and a T cell during cognate interaction has increased dramatically. In this review, various costimulatory and inhibitory molecules of the B7 and TNF families will be discussed. The emphasis will be on how these costimulatory molecules impact T cell activation and on how they can be potentially used for the treatment of cancer. costimulation cancer T cell activation     

三叉神经鞘瘤的临床分型及其手术疗效分析

目的探讨三叉神经鞘瘤的临床分型及其手术疗效。方法回顾性分析2017年1月至2019年11月首都医科大学附属北京天坛医院神经外科手术治疗的51例(包括少见部位和肿瘤最大径≥6 cm的患者)三叉神经鞘瘤患者的临床资料。根据Yoshida和Kawase的MPE分型分别采用颞下经岩前入路(30例)、经额颞断颧弓入路(12例)、经额眶颧人路(4例)、经枕下乙状窦后入路(2例)、经乙状窦前入路(2例)和经远外侧入路(1例)。术后随访MRI、新发症状及脑神经功能的恢复情况。结果51例患者中,肿瘤全切除46例(90.2%),近全切除4例,大部切除1例,无手术死亡病例。其中6例中线-鞍上扩展亚型的患者,肿瘤全切除2例,近全切除3例,大部切除1例。7例肿瘤直径≥6 cm的患者中,肿瘤全切除6例,肿瘤卒中1例;其中4例行游离脂肪填塞结合颅底硬膜缝合的颅底重建。51例患者的随访时间为(20.2±2.7)个月(3~38个月)。24例术前面部麻木的患者中,12例(50.0%)随访期间仍存在重度三叉神经麻搏表现。51例患者中,有13例(25.5%)术后新发三叉神经功能异常的患者中,7例随访期间遗留轻度三叉神经麻搏症状。其余脑神经症状较术前有所恢复,并且术后新发神经功能障碍者大多恢复正常。6例中线-鞍上扩展亚型的患者术后神经功能恢复较差。结论三叉神经鞘瘤在MPE分型的基础上可增加中线-鞍上扩展亚型,该亚型相对少见,但其临床表现具有特征性,手术全切除困难。手术对于改善三叉神经鞘瘤面部麻木作用有限,术前伴有面部麻木者三叉神经功能预后较差。     

不同类型基底动脉闭塞机械取栓的疗效观察

目的评价机械取栓治疗不同类型基底动脉(BA)闭塞的疗效。方法回顾性分析2013年9月至2019年9月海军军医大学附属长海医院脑血管病中心连续收治的95例行机械取栓治疗的BA闭塞患者的临床资料。根据BA闭塞是否为串联病变,分为非串联病变组(67例)和串联病变组(28例)。比较两组血管成功再通(改良脑梗死溶栓分级2b~3级)的比例、90 d预后良好(改良Rankin量表评分为0~3分)的比例、术中挽救措施及不良事件发生率等的差异。结果与非串联病变组相比,串联病变组的年龄偏低(P=0.002),而男性(P=0.009)、有吸烟史(P=0.014)、缺血性卒中TOAST分型为大动脉粥样硬化型(P=0.001)以及存在一侧椎动脉发育不良(P=0.036)的比例更高。两组患者在术前及术后24 h的美国国立卫生院卒中量表评分、股动脉穿刺至BA再灌注时间、血管成功再通比例及90 d预后良好比例方面的差异均无统计学意义(均P>0.05)。串联病变组的发病至就诊时间(P=0.049)、发病至BA再灌注时间(P=0.046)均较非串联病变组延长,且术中挽救措施(包括单纯球囊扩张、急诊支架置入、静脉应用替罗非班)的使用比例均更高(均P<0.05)。两组在手术相关的不良事件及病死率方面的差异均无统计学意义(均P>0.05)。结论对于不同类型的BA闭塞患者,应用机械取栓治疗的临床结局及不良事件的发生率无明显差异,但该结论仍需进一步扩大样本量或进行随机对照试验加以证实。     

显微血管减压术中单纯应用涤纶垫棉治疗基底动脉压迫所致三叉神经痛的临床疗效

目的初步探讨显微血管减压术中单纯应用涤纶垫棉治疗基底动脉压迫所致三叉神经痛的临床疗效。方法回顾性分析2012年1月至2019年12月陆军军医大学大坪医院神经外科收治的31例基底动脉压迫引发三叉神经痛患者的临床资料。31例患者在显微血管减压术中均单纯使用涤纶垫棉作为减压材料,且未使用其他减压方式。手术采用经乙状窦后入路,于脑干和责任动脉之间放置涤纶垫棉实现减压。采用巴罗神经学研究所(BNI)提出的疼痛分级评估手术效果。结果31例三叉神经痛患者中,27例(87.1%)术后疼痛即刻完全缓解(BNI分级Ⅰ级),3例在术后3个月内完全缓解(BNI分级Ⅰ级),1例疼痛部分缓解(BNI分级Ⅲ级)。5例(16.1%)患者术后出现面部感觉减退,其中3例自愈;1例患者出现渐进性听力下降。31例患者的随访时间为6~85个月(中位时间为40个月),随访期间有4例(12.9%)复发(BNI分级Ⅳ~Ⅴ级),其中2例再次接受手术治疗,另外2例采用立体定向放射治疗配合药物治疗可部分控制面部疼痛。结论显微血管减压术中单纯应用涤纶垫棉治疗基底动脉所致三叉神经痛的术后即刻效果显著,但其复发率及并发症的发生率较高。