Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

物理治疗翻转课堂教学应用效果的系统综述

目的 系统评价翻转课堂教学模式在物理治疗学教学中的应用效果。方法 计算机检索CENTRAL、MEDLINE、EMBASE、CINAHL Plus、Academic Search Premier、Teacher Reference Center、ERIC以及Education Research,纳入翻转课堂教学模式应用于物理治疗学教学的原始研究。检索时限为建库至2021年6月。由2名研究人员独立完成文献筛选、数据提取、质量评价,对翻转课堂教学模式对比传统教学模式在物理治疗学教学中的效果进行综述。结果与结论 共检索文献1 307篇,最终纳入7篇,包括至少770名学生。发表时间集中在2013年至2019年,研究对象为物理治疗学专业学生,主要结局指标为考试成绩。翻转课堂教学模式总体说来可提高学生的笔试成绩,增强高阶思维能力,得到了学生和教师的积极评价。     

Effectiveness and safety of extracorporeal shock wave treatment for low back pain：a systematic review and meta-analysis of RCTs

This meta-analysis was designed to assess the effectiveness and safety of extracorporeal shock wave therapy (ESWT) for patients with low back pain (LBP). Pubmed, Embase, Cochrane's library, PEDro (Physiotherapy Evidence Database), China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched until December 2019 to identify studies assessing the effectiveness and safety of EPSW for LBP. The prime outcome is pain intensity measured by Visual Analog Scale (VAS) or numeric rating scale (NRS). Other outcomes included functional status, quality of life, psychological outcomes measured by Oswestry Disability Index (ODI), as well as the adverse events. Mean differences (MD) were calculated for continuous outcomes, while odd ratios (OR) were calculated for binary outcomes. Revman 5.3 software was used for statistical analysis. Five randomized controlled trials (RCTs) were finally included in this meta-analysis. The pooled mean difference in post-treatment pain scores was −2.37 (P ＜0.0001), indicating that post-treatment pain scores was significantly higher by 2.37 in control group than in ESWT group. At a mean follow-up time of 4–6 weeks, the pooled mean difference in ODI scores was −14.10 (P ＜0.00001), indicating that the pooled mean difference of post-treatment ODI scores was 14.10 higher in control group than in ESWT group. The use of ESWT is effective in alleviating pain and improving the general functional state for patients with LBP. However, more evidence was needed to verify its safety.     

Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

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Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

Fungal mycobiome drives IL-33 secretion and type 2 immunity in pancreatic cancer

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右美托咪定联合综合体温保护对腔镜手术治疗老年恶性肿瘤患者苏醒期质量及免疫功能的影响

目的 探讨右美托咪定联合综合体温保护对腔镜手术治疗老年恶性肿瘤患者苏醒期质量及免疫功能的影响。方法 选择择期行腔镜手术治疗的老年恶性肿瘤患者90例，随机均分为3组：对照组（C组）、体温保护组（T组）和体温保护联合右美托咪定组（T-D组），每组30例。C组常规体温保护，T组和T-D组综合体温保护；T-D组麻醉诱导前10 min泵注右美托咪定0.5 μg/kg。记录3组患者麻醉诱导开始时（T₀）、手术开始30 min（T₁）、60 min（T₂）、90 min（T₃）、120 min（T₄）以及手术结束时（T₅）的鼻咽温度；于T₀、术后2 h（T₆）、24 h（T₇）和48 h（T₈）时抽取静脉血标本，测定T淋巴细胞亚群（CD3⁺、CD4⁺和CD8⁺）和自然杀伤细胞（NK cell）水平；记录患者术中麻醉药物用量及苏醒期质量指标。结果 与T₀比较，C组T₂～T₅时点鼻咽温度均明显降低（P < 0.05）；与C组比较，T组和T-D组T₂～T₅时点鼻咽温度明显升高（P < 0.05）。与T₀时点比较，C组、T组和T-D组T₆、T₇和T₈时点CD3⁺和NK cell活性均明显降低（P < 0.05）；C组在T₆、T₇和T₈时点，T组和T-D组在T₆和T₇时点，CD4⁺活性均明显降低（P < 0.05）。与C组比较，T组和T-D组T₆和T₇时点CD3⁺细胞活性均明显升高（P < 0.05）；T组在T₇时点，T-D组在T₆和T₇时点，CD4⁺细胞活性均明显升高（P < 0.05）；T组在T₇时点，T-D组在T₆、T₇和T₈时点，NK cell活性均明显升高（P < 0.05）。结论 采用体温保护措施联合右美托咪定能够维持老年恶性肿瘤患者的体温稳定，减少围手术期意外低体温（IPH）的发生，并有效提高患者苏醒期质量，减轻免疫抑制程度，加速患者早期恢复。