Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies

PurposeTo assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.Materials and MethodsThe VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7–21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging.ResultsEight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441–404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%–100%). There were no significant changes in perfusion imaging parameters after TACE.ConclusionsBTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.     

TRIM59 通过结合 BCLAF1 调控人皮肤黑色素瘤 SK-MEL-2 细胞的恶 性生物学行为

目的：探究三结构域蛋白59（TRIM59）调控人皮肤黑色素瘤细胞SK-MEL-2增殖、细胞周期、凋亡及迁移侵袭的作用机制，及其与Bcl2相关转录因子1（BCLAF1)之间的关系。方法：qPCR和WB法检测人表皮黑色素细胞HEMn-LP、人皮肤黑色素瘤细胞SK-MEL-2、UACC903、A375及36例邢台市人民医院2019年2月至2021年7月收集的皮肤黑色素瘤组织中TRIM59的mRNA和蛋白表达，使用脂质体将si-con、si-TRIM59转染至SK-MEL-2细胞中，WB法检测干扰TRIM59表达对细胞中周期蛋白D1（CCND1）、细胞周期素依赖性激酶2（CDK2）、肿瘤抑制蛋白基因（TP53）和 BCLAF1 蛋白表达的影响，CCK-8法、流式细胞术、划痕愈合实验、Transwell实验检测对细胞的活性、凋亡、迁移和侵袭的影响，免疫共沉淀（Co-IP）实验检测对细胞中TRIM59蛋白与BCLAF1结合能力的影响。结果：与HEMn-LP细胞相比，SK-MEL-2、UACC903、A375细胞中TRIM59 mRNA和TRIM59、BCLAF1蛋白均呈高表达（均P<0.05），SK-MEL-2细胞中TRIM59表达水平最高。相较于si-con组和Normal组，沉默TRIM59后，SK-MEL-2细胞的活性显著降低，细胞周期阻滞于G2期，CCND1、CDK2的蛋白表达显著降低，TP53蛋白和细胞凋亡率均显著升高，划痕抑制率明显升高，迁移侵袭细胞数明显降低（均P<0.05）。免疫共沉淀实验结果显示，TRIM59与BCLAF1之间存在蛋白结合关系。TRIM59与 BCLAF1 在肿瘤组织中的表达呈显著的正相关（r=0.878，P<0.001）。结论：干扰TRIM59表达能够抑制人皮肤黑色素瘤SK-MEL-2细胞的增殖、迁移和侵袭而促进凋亡，抑制SK-MEL-2细胞的恶性生物学行为，其机制可能与TRIM59结合BCLAF1有关。     

Start with reducing sedentary behavior: A stepwise approach to physical activity counseling in clinical practice

Recently, sedentary behavior recommendations have been included in the public health guidelines of multiple countries, pointing to new opportunities for prevention of chronic disease as well as a potential strategy for initiating long-term behavior change.ObjectiveTo propose an evidence-informed approach to physical activity counseling that starts with a focus on reducing sedentary time.MethodsWe put forward a case for addressing changes in sedentary behavior in clinical practice using a narrative review. We also propose a new approach for the assessment and counselling of patients with respect to movement behaviors.ResultsThere is evidence to support a stepwise approach to physical activity counseling that starts with targeting sedentary behavior, particularly in those who are highly sedentary, or those who have chronic disease, or physical impairments.ConclusionsOur approach encourages clinicians to consider sedentary behavior counseling as a critical first step to physical activity counseling. For many patients, this initial step of reducing sedentary behavior could build a pathway to an active lifestyle.Practical ImplicationsA shift from long periods of sedentary time to daily routines incorporating more light intensity physical activity could result in meaningful health improvements. Importantly, this approach may be more feasible for highly inactive patients.     

某三甲医院门诊预约精准性及其影响因素分析

目的了解某三甲综合医院患者门诊预约精准性及其影响因素,比较正确预约与错误预约患者在预约可及性因素上的差异,寻找提高门诊预约精准性的干预点。方法采用现场调查法,于2021年6月14—21日在四川省成都市某三甲综合医院对70例门诊患者进行面访调查。结果门诊预约精准性低,错误预约患者占36.75%。单因素分析显示,预约精准性正向影响因素包括医疗保险保障度(P=0.004)、线下信息可及度(P=0.049)以及医务人员推荐依从度(P<0.001),负向影响因素包括网络信息依从度(P=0.012)、传统媒体信息可及度(P=0.024)以及自媒体推荐依从度(P<0.001);二分类非条件logistic回归分析显示,预约精准性与听从医务人员推荐正相关(P=0.002),与听从自媒体推荐负相关(P=0.014)。结论医疗机构需要加强宣传力度、丰富宣传内容,提高患者就诊的可及性;建议加强网络及传统媒体虚假医疗信息整治力度能改变门诊患者预约精准性低的现况。