Investigational therapies for the treatment of narcolepsy

Introduction: Narcolepsy is a chronic sleep disorder characterized by a pentad of excessive daytime sleepiness (EDS), cataplexy, sleep paralysis, hypnagogic/hypnopompic hallucinations, and disturbed nocturnal sleep. While non-pharmacological treatments are sometimes helpful, more than 90% of narcoleptic patients require a pharmacological treatment.

Areas covered: The present review is based on an extensive Internet and PubMed search from 1994 to 2017. It is focused on drugs currently in development for the treatment of narcolepsy.

Expert opinion: Currently there is no cure for narcolepsy, with treatment focusing on symptoms control. However, these symptomatic treatments are often unsatisfactory. The research is leading to a better understanding of narcolepsy and its symptoms. New classes of compounds with possible applications in the development of novel stimulant/anticataplectic medications are described. H3 receptor antagonists represent a new therapeutic option for EDS in narcolepsy. JZP-110, with its distinct mechanism of action, would be a new therapeutic option for the treatment of EDS in the coming years. In the future, hypocretin-based therapies and immune-based therapies, could modify the clinical course of the disease. However, more information would be necessary to completely understand the autoimmune process and also how this process can be altered for therapeutic benefits.     

Emerging oral VEGF inhibitors for the treatment of renal cell carcinoma

Introduction: The incidence of renal cell carcinoma (RCC) has increased in recent years and, unfortunately, many patients initially present with metastatic disease. When surgery is not an option, treatment involves administration of targeted therapies. The vascular endothelial growth factor (VEGF) pathway has been identified as an important mediator for the development of RCC. Numerous agents target VEGF-mediated signaling, yet resistance and progressive disease still persists. Novel small molecule VEGF inhibitors with high affinity for the VEGF receptor (VEGFR) have been discovered and are currently under investigation for the management of RCC.

Areas covered: The VEGFR pathway, its aberrant signaling, and the agents under development that inhibit VEGFR signaling are discussed. The mechanism(s), pharmacokinetics, pharmacodynamics, efficacy, and toxicity of these investigational agents are also reviewed.

Expert opinion: Management of metastatic RCC involves combination immunotherapy or administration of oral VEGFR inhibitors and largely depends on risk stratification. Emerging and investigational oral VEGFR inhibitors, given as monotherapy or in combination with immunotherapy, could augment current treatment approaches and may mitigate toxicities associated with VEGFR inhibition.     

小切口克氏针内固定和小切口钢板内固定治疗青年锁骨中段A型骨折的对比研究

目的：比较小切口克氏针内固定和小切口钢板内固定治疗青年锁骨中段A型骨折的临床疗效、安全性及卫生经济学指标。方法：回顾性分析接受手术治疗的52例青年锁骨中段A型骨折患者的病例资料,采用小切口克氏针内固定治疗者32例（A组）,采用小切口钢板内固定治疗者20例（B组）。比较2组患者的术中出血量、手术时间、骨折愈合时间、住院时间、住院费用、内固定取出费用、采用肩关节Neer评分评定的肩关节功能及并发症发生率。结果：①一般情况。52例患者均获随访,随访时间9-16个月,中位数11.5个月。2组患者的骨折愈合时间比较,差异无统计学意义[（10.70±2.20）周,（11.30±1.70）周t=0.942,P=0.351];A组患者术中出血量、手术时间、住院时间、住院费用及内固定取出费用均少于B组,差异有统计学意义[（20.32±17.51）mL,（40.73±15.11）mL,t=-5.860,P=0.000;（20.55±10.16）min,（50.12±17.26）min,t=-12.505,P=0.000;（6.63±1.27）d,（8.34±1.11）d,t=-4.182,P=0.000;（3 500.75±500.63）元,（7 500.74±300.85）元,t=-13.317,P=0.000;（1 100.23±350.93）元,（3 500.25±200.32）元,t=-16.708,P=0.000]。②肩关节功能。A组优18例、良12例、中2例,B组优10例、良9例、中1例。2组患者肩关节功能比较,差异无统计学意义（Z=-0.362,P=0.717）。③并发症发生率。A组术后2例患者出现针尾刺激症状,B组1例患者发生钢板远端螺钉拔出。2组患者并发症发生率比较,差异无统计学意义（χ2=0.000,P=1.000）。结论：小切口克氏针内固定和小切口钢板内固定都是治疗青年锁骨中段A型骨折的安全有效的治疗方法,但前者具有创伤小、费用低的优点。     

Transcatheter Pulmonary Valve Replacement With the Melody Valve in Small Diameter Expandable Right Ventricular Outflow Tract Conduits

Objectives

This study sought to evaluate the safety, feasibility, and outcomes of transcatheter pulmonary valve replacement (TPVR) in conduits ≤16 mm in diameter.

整脊推拿配合导引治疗神经根型颈椎病的临床研究

目的:观察整脊推拿配合导引治疗神经根型颈椎病的临床疗效。方法:将120例神经根型颈椎病患者随机分为2组,每组60例。其中男68例,女52例。年龄35～60岁,中位数47.5岁。病程2～49周,中位数14.5周。治疗组采用整脊推拿配合导引治疗,对照组单纯采用整脊推拿治疗。治疗结束后分别采用《中医病证诊断疗效标准》、神经根型颈椎病疗效评分方法及Bobor’s法比较2组患者的总体疗效、疗效评分及颈椎生理曲度。结果:①总体疗效。治疗组治愈47例,好转13例;对照组治愈31例,好转29例;治疗组患者总体疗效优于对照组(U=3.050,P=0.002)。②疗效评分。治疗前治疗组疗效评分(13.93±2.14)分,对照组疗效评分(14.07±2.19)分;治疗后治疗组疗效评分(28.44±1.52)分,对照组疗效评分(24.34±2.20)分;治疗前2组患者疗效评分比较,差异无统计学意义(t=0.354,P=0.723);治疗后2组患者的疗效评分均增加(t=42.819,P=0.000;t=25.627,P=0.000),治疗组增加更明显(t=15.898,P=0.000)。③颈椎生理曲度。治疗前治疗组颈椎生理曲度(2.72±1.60)mm,对照组颈椎生理曲度(2.64±1.34)mm;治疗后治疗组颈椎生理曲度(4.30±1.23)mm,对照组颈椎生理曲度(3.55±1.82)mm;治疗前2组患者颈椎生理曲度比较,差异无统计学意义(t=0.297,P=0.767);治疗后2组患者颈椎生理曲度均改善(t=6.064,P=0.000;t=3.119,P=0.002),治疗组改善更明显(t=15.041,P=0.000)。结论:整脊推拿配合导引能有效改善神经根型颈椎病患者的临床症状和颈椎生理曲度,是治疗该病的有效方法,值得临床推广应用。     

自体CD3AK细胞过继免疫治疗晚期恶性肿瘤的临床观察

目的观察抗CD3单克隆抗体（anti—CD3 mAb）激活的杀伤细胞（cD3AK）过继免疫治疗晚期恶性肿瘤的疗效。方法从51例恶性肿瘤患者自体外周血分离单个核细胞,加入anti—CD3mAb、重组人IL-2（rhIL-2）体外诱导后扩增培养,制备自体CD3AK细胞。待细胞培养至第10～12天时取样用于质控检测。收集质控检测合格的CD3AK细胞,调整至终浓度为（4．0～6．0）×10^9/L,静脉回输至患者体内,每例患者治疗3个疗程,每疗程回输5次（每2d回输1次）,每次回输细胞数不低于1×10^9,每疗程回输细胞总数大于5×10^＊。应用人T细胞亚群检测试剂盒和流式细胞仪测定治疗前后患者外周血CD3＋、CD4＋、CD8＋T细胞以及CD16＋56＋细胞（NK细胞）比例;观察治疗前后患者的相关化验指标、生活质量以及不良反应;评定疗效,计算有效率和临床受益率。结果分离制备的CD3AK细胞符合理想活性细胞质量要求,可用于进一步实验治疗。CD3AK细胞过继免疫治疗后,患者外周血CD3＋、CD4＋、CD8＋T细胞以及CD16＋56＋细胞（NK细胞）比例分别为（48．88±9．42）％、（35．09±4．11）％、（28．17±4．97）％、（20.31±6．98）％]均显著升高（均P〈0．05）。51例患者中,45例患者治疗后全身症状改善明显;所有患者治疗后相关化验指标均未出现异常变化,也未出现其他全身毒副反应;其中完全缓解6例、部分缓解14例、微效11例、稳定12例、进展8例,总有效率达60．8％,临床受益率达84．3％。结论CD3AK细胞过继免疫治疗恶性肿瘤疗效确切、安全且无副作用,能有效改善和提高患者的机体免疫功能。     

Advances in paclitaxel combinations for treating cervical cancer

ABSTRACT

Introduction

Cervical cancer is the fourth common cancer in women worldwide. While, in the past, locally advanced stage disease was treated by pelvic radiotherapy, nowadays the National Cancer Institute strongly recommends chemoradiation protocols. Weekly cisplatin was previously the standard of care in this setting; however, the low response rate and the short median progression-free survival (PFS) of patients have led researchers to investigate combinatory regimens.     

Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer

Introduction: Epidermal growth factor receptor (EGFR) mutations are well-described drivers of non-small cell lung cancer (NSCLC) and EGFR tyrosine kinase inhibitors (TKIs) have become key components of the NSCLC front-line treatment landscape. Tumors inevitably develop resistance to these agents, and development efforts continue to focus on identifying mechanisms of resistance and drugs to target these mechanisms.

Areas covered: With several EGFR TKIs approved for use in the first-line or in later-line settings, an understanding of the efficacy and safety of these inhibitors in various populations is warranted. Furthermore, given the frequent emergence of drug resistance in NSCLC, examination of tumor tissue throughout the disease course provides the opportunity to select treatments based on the tumor’s mutation profile. Here, we discuss: key efficacy and safety findings for approved and investigational EGFR TKIs; known mechanisms of resistance, particularly the T790M acquired EGFR mutation; and recent advances in EGFR mutational testing that may facilitate less invasive tissue testing and guide treatment selection.

Expert commentary: The expanding armamentarium of EGFR TKIs, improvements in the understanding of resistance mechanisms and technological developments in the molecular analysis of tumors may help render EGFR mutation-positive NSCLC a chronic disease in many patients by facilitating optimal sequential therapy.