Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

解析PD-1/PD-L1抑制剂分子结构差异与不良反应的相关性

针对程序性死亡受体1(programmed cell death protein 1,PD-1)及程序性死亡配体1(programmed cell death ligand 1,PD-L1)的免疫治疗作为一种新兴的方法在恶性肿瘤的治疗中起到越来越大的作用,相较于传统的化学治疗体现出更好的疗效。然而在应用针对PD-1/PD-L1的免疫检查点抑制剂的过程中也出现了许多不良反应,并且这些不良反应在不同药物中的发生率也不完全相同。由于区分不同药物的一个重要指标是它们的分子结构,故本文将从不同PD-1/PD-L1免疫检查点抑制剂的结构出发,通过综述不良反应的meta分析以及回顾性研究的结果解析分子结构与不良反应发生情况之间的相关性。

Initial Experience in GeminiOne^(TM)Transcatheter Mitral Valve Edge-to-edge Repair Device

Transcatheter edge-to-edge repair(TEER)of the mitral valve has emerged as a standard treatment for patients with severe degenerative mitral regurgitation at high or prohibitive surgical risk.The devices approved by the Food and Drug Administration including MitraClip(Abbott Vascular,California,USA)and PASCAL(Edwards Lifesciences,California,USA)cost over$33,000 in western countries.[1]This pricing presents a significant economic burden especially in developing countries,where TEER devices are typically not covered by health insurance.

Remarkable-cycle-performanceβ-bismuthene/graphene heterostructure anode for Li-ion battery

Remarkable Li-ion battery(LIB)anode materials need to have long cycle life and fast charge/discharge rate,however they are difficult to be realized in the monolayer anode materials.The monolayerβ-Bi has the stiffness of only 33.0 N/m,thus the Bi/G heterostructure is proposed to improve the electronic and mechanical properties and to produce better LIB anode performance in this paper.The calculated results show that Bi/G heterostructure has excellent thermodynamic,dynamical and mechanical stability.The band gap is only 0.04 eV,which ensures remarkable electrical conductivity.In addition,the Bi/G heterostructure has higher stiffness(369.2 N/m)than that of monolayerβ-Bi and graphene.The diffusion barrier(E_(barrier)) of 0.32 e V and volume expansion ratio(VER)of only 4%can ensure the rapid transport of Li^(+) ions in the charge/discharge cycling process and long life of the LIB.These calculated theoretical results for describing the detail properties of Li storage and diffusion in the Bi/G heterostructure can supply adequate conclusive evidence for the prediction of remarkable properties of Bi/G heterostructure as an anode material for LIBs.

新型完全生物可吸收封堵器经导管封堵膜周部室间隔缺损:一项多中心前瞻性随机对照研究

生物可吸收封堵器的应用有望降低传统金属封堵器并发症的风险.之前研制的生物可吸收封堵器存在不完全降解的局限性并导致新的并发症,因此目前尚未有相关产品获批上市.本研究使用了一种新型完全可吸收封堵器,旨在探索完全可吸收封堵器治疗室间隔缺损的疗效和安全性.从2019年4月到2020年1月,本研究在七个医学中心入组125名膜周部室间隔缺损患者,经筛查后108名患者被纳入研究并随机分为植入生物可吸收封堵器实验组和金属封堵器组.所有受试者均成功植入封堵器并完成24个月的随访.生物可吸收封堵器组患者经胸超声心动图显示高亮回声在24个月内逐渐消失,说明可吸收封堵器在体内实现完全降解.对比金属封堵器,实验组器械相关心律失常发生率(5.56%vs.14.81%,P=0.112)和持续传导阻滞发生率(0/54 vs.6/54,P=0.036)显著降低.本研究提示新型完全可吸收封堵器可以在单纯超声引导下实现成功植入,同时降低术后永久性心律失常的发生率.

Transcatheter mitral edge-to-edge repair:past,present,and the future

Mitral valve regurgitation(MR)is a common heart valve disease that affects>10%of the elderly population.Epidemiological data estimate that the number of MR patients has reached more than2.5 million in the USA,with an extremely low surgical intervention rate(<5%)[1].

A fully biodegradable polydioxanone occluder for ventricle septal defect closure

Ventricular septal defect(VSD)is one of the commonest congenital heart diseases(CHDs).Current occluders for VSD treatment are mainly made of nitinol,which has the risk of nickel allergy,persistent myocardial abrasion and fatal arrythmia.Herein,a fully biodegradable polydioxanone(PDO)occluder equipped with a shape line and poly-L-lactic acid PLLA membranes is developed for VSD closure without the addition of metal marker.PDO occluder showed great mechanical strength,fatigue resistance,geometry fitness,biocompatibility and degradability.In a rat subcutaneous implantation model,PDO filaments significantly alleviated inflammation response,mitigated fibrosis and promoted endothelialization compared with nitinol.The safety and efficacy of PDO occluder were confirmed in a canine VSD model with 3-year follow-up,demonstrating the biodegradable PDO occluder could not only effectively repair VSD,induce cardiac remodeling but also address the complications associated with metal occluders.Furthermore,a pilot clinical trial with five VSD patients indicated that all the occluders were successfully implanted under the guidance of echocardiography and no adverse events occurred during the 3-month follow-up.Collectively,the fully bioresorbable PDO occluder is safe and effective for clinical VSD closure and holds great promise for the treatment of structural CHDs.