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.     

基于网络药理学和实验验证探讨香菇多糖抑制三阴乳腺癌的作用机制

目的 基于网络药理学研究香菇多糖抑制三阴乳腺癌（TNBC）的作用机制并采用细胞和动物实验进行验证。方法 通过GeneCards数据库和DisGeNET数据库筛选与TNBC相关基因靶点，利用TCMID、PubChem、SwissTargetPrediction和GeneCards数据库查询香菇多糖相关基因靶点。使用Sangerbox软件进行基因本体论（GO）富集和京都基因与基因组百科全书（KEGG）通路富集分析。结合STRING数据库与Cytoscape 3.7.0软件将共同靶点进行可视化处理，筛选核心靶点，构建"化合物-靶点-通路"网络。利用Metascape软件进行转录因子及相关调控基因特异富集。体外培养小鼠TNBC细胞4T1和人TNBC细胞MDA-MB-231，磺酰罗丹明B染色法观察香菇多糖（31.25、62.5、125、250、500、1 000μg·mL^-1）对细胞存活率的影响；健康雌性BABLC小鼠sc接种1×10⁶个4T1-Luc细胞构建TNBC模型，通过小动物活体成像系统观察香菇多糖（100、200 mg·kg^-1）对肿瘤生长的影响，实时荧光定量PCR （qRT-PCR）技术检测肿瘤组织信号转导和转录活化因子3（STAT3）和血管内皮生长因子A （VEGFA） mRNA表达。结果 数据库及软件分析得到香菇多糖治疗TNBC关键靶点52个，靶点主要涉及PI3K-Akt、AGE-RAGE、HIF-1、MAPK信号通路和肿瘤蛋白多糖相关通路，PPI分析得到VEGFA、STAT3、MAPK1、IL2、TNF、RELA、AKT1、MAPK3、BCL2L1和HSP90AA1 10个hub基因。与对照组比较，香菇多糖对4T1和MDA-MB-231细胞存活率均有显著抑制作用（P<0.05、0.01），且作用呈浓度相关性；在给药14、21d后，与模型组比较，香菇多糖能够剂量相关性地抑制小鼠TNBC肿瘤的生长，高剂量组差异显著（P<0.05、0.01），21 d抑制率达到（91.9±4.7）%；与对照组比较，香菇多糖给药后能够剂量相关性抑制STAT3和VEGFA的mRNA表达，高剂量组差异显著（P<0.05、0.01）。结论 香菇多糖可通过多靶点、多途径协同作用抑制TNBC的生长。     

Changes in the National Endovascular Management of Femoropopliteal Arterial Disease: An Analysis of the 2011–2019 Medicare Data

PurposeTo describe national trends in the utilization of endovascular approaches (including balloon angioplasty, atherectomy, and stent placement) for the management of femoropopliteal peripheral arterial disease (PAD).Materials and MethodsThe Medicare Physician/Supplier Procedure Summary dataset containing 100% of Part B claims was interrogated for years 2011–2019. The Current Procedural Terminology codes specific for femoropopliteal angioplasty, stent placement, and atherectomy were used to create summary statistics for utilization by year, place of service (hospital inpatient, hospital outpatient, and office-based laboratory), and provider specialty (cardiology, radiology, and surgery).ResultsThe use of atherectomy increased from 34,732 (33%) procedures in 2011 to 75,435 (53%) procedures in 2019, and atherectomy became the dominant treatment strategy for femoropopliteal PAD. The relative utilization of stent placement (36,793 [35%] to 28,899 [20%]) and angioplasty only (34,398 [32%] to 38,228 [27%]) decreased concomitantly from 2011 to 2019. By 2019, the use of atherectomy was twofold higher in office-based laboratories than in the outpatient hospital setting (44,767 and 20,901, respectively). Treatment strategy varied by provider specialty in 2011 when cardiologists used atherectomy most frequently (17,925 [43%]), whereas radiologists used angioplasty alone (5,928 [6%]) and surgeons stented (18,009 [37%]) most frequently. By 2019, all specialties utilized atherectomy most frequently (29,564 [59%] for cardiology, 10,912 [58%] radiology, and 33,649 [47%] surgery).ConclusionsThe national approach to endovascular management of femoropopliteal PAD has changed since 2011 toward an implant-free strategy, including a multifold increase in the use of atherectomy. Discordant rates of atherectomy use between the ambulatory hospital and office-based settings highlight the need for comparative effectiveness studies to guide management.     

神经内科实习医师血管超声教学的问题及改进方法

血管超声知识是神经内科实习同学的重要学习内容之一,但传统本科教学中对血管超声部分内容局限,使进入神经内科实习的医师血管超声基础知识薄弱,且还存在实践操作的缺乏、教学方式单一等问题,不能在短期内较好的理解及掌握血管超声知识,使得实习效果欠佳。本研究通过对神经内科实习医师血管超声教学中存在的问题进行分析,提出改进方法,可以通过加强实习医师对血管超声的解剖和血流动力学的学习,打牢基础知识,同时将实习医师进行分组,互为模特进行操作实践,在操作实践中加深理论知识的理解和应用。同时还可采用微课等多媒体教学方式,提高实习医师的学习兴趣,显著提高实习效果。     

血清SCC-Ag、CYFRA21-1及VEGF水平与宫颈癌临床病理特征及预后的关系

目的:探讨血清鳞状细胞癌抗原（SCC-Ag）、细胞角蛋白19片段抗原(CYFRA21-1)及血管内皮生长因子（VEGF）水平与宫颈癌临床病理特征及预后的关系。方法:选取2010年1月至2012年12月海南西部中心医院收治的146例宫颈癌患者、50例宫颈上皮内瘤病变（CIN）患者(CIN组)和50例正常健康女性(对照组)，比较各组血清SCC-Ag、CYFRA21-1及VEGF水平。分析宫颈癌患者血清SCC-Ag、CYFRA21-1及VEGF水平与临床病理特征的关系，采用Kaplan-Meier法分析不同临床病理特征患者生存率差异，多因素COX比例风险回归模型分析宫颈癌患者预后的影响因素。结果:宫颈癌组血清SCC-Ag、CYFRA21-1及VEGF水平均明显高于CIN组和对照组［SCCA（ng/ml）:9.04±2.35 vs 1.91±0.62和0.65±0.14；CYFRA21-1（ng/ml）:5.48±1.62 vs 0.92±0.43和0.64±0.25；VEGF（pg/ml）:326.42±48.15 vs 125.48±23.60和108.62±18.73，均P＜0.01］。血清SCC-Ag、CYFRA21-1及VEGF水平与宫颈癌患者的临床分期、病理分级、淋巴结转移、浸润深度及脉管浸润相关（P＜0.05）。单因素及多因素COX回归分析显示，临床分期［HR（95%CI）:2.016（1.512～2.915）］、淋巴结转移［HR（95%CI）:4.013（2.937～6.016）］、SCC-Ag［HR（95%CI）:2.972（2.106～4.618）］、CYFRA21-1［HR（95%CI）:1.704（1.335～2.519）］及VEGF［HR（95%CI）:2.116（1.685～3.164）］阳性表达是宫颈癌患者预后不良的危险因素。结论:宫颈癌患者血清SCC-Ag、CYFRA21-1及VEGF水平明显升高，SCC-Ag、CYFRA21-1及VEGF阳性表达是影响宫颈癌患者预后不良的危险因素。     

脑血管畸形致脑出血患者手术治疗效果观察

目的分析脑血管畸形致脑出血患者应用手术治疗的临床疗效。方法纳入本院2018年1月—2020年1月收治的60例脑血管畸形致脑出血患者,随机分组(每组样本容量共计30例),参照组给予保守治疗,观察组给予手术治疗,对比两组临床疗效、治疗前、治疗1月后NIHSS评分、住院时间。结果临床总有效率观察组(93.33%)明显高于参照组(63.33%),观察组治疗1月后NIHSS评分明显低于参照组,观察组住院时间明显比参照组短,差异均具有统计学意义(P<0.05)。结论脑血管畸形致脑出血患者采纳手术治疗,可有效减轻患者神经功能受损情况,缩短治疗时间。     

Vascular endothelial growth factor and programmed death-1 pathway inhibitors in renal cell carcinoma

Advanced renal cell carcinoma has historically carried a poor prognosis with very limited treatment options. However, in recent years, the treatment landscape has changed drastically, with many new therapeutic options and improved survival for patients. Novel treatments consist of molecularly targeted agents against the vascular endothelial growth factor (VEGF) pathway as well as the immune checkpoint inhibitors, which stimulate an antitumor immune response. Recent strategy has focused on the development of combination therapy with the use of VEGF inhibitors and immune checkpoint inhibitors in the first-line setting. As more treatments are approved and the options for therapy expand further, there is a growing need for predictive biomarkers to personalize treatment choices for individual patients. Prospective clinical trials comparing the sequencing of treatments are needed to help determine the best therapeutic approach.