Pressurized IntraPeritoneal Aerosol Chemotherapy with one minute of electrostatic precipitation (ePIPAC) is feasible,but the histological tumor response in peritoneal metastasis is insufficient

IntroductionElectrostatic precipitation Pressurized IntraPeritoneal Aerosol Chemotherapy (ePIPAC) has shown superior penetration depth and tissue uptake compared to standard PIPAC. We investigated the feasibility and objective tumor response to ePIPAC with 1 min of precipitation in patients with peritoneal metastasis (PM).Materials and methodsPatients with PM from various abdominal cancers were included in an amendment to the ongoing prospective PIPAC-OPC2 trial. Colorectal and appendiceal PM were treated with oxaliplatin, patients with PM from other primaries were treated with a combination of cisplatin and doxorubicin. Three ePIPAC procedures were planned in each patient including repeated peritoneal biopsies for response evaluation. After emission to the peritoneal cavity, the aerosolized chemotherapeutics were precipitated for 1 min followed by immediate exsufflation and abdominal closure. Histological regression from the first to the third ePIPAC was evaluated according to the Peritoneal Regression Grading Score (PRGS) and compared to data from the PIPAC-OPC1 trial. Complications and toxicities were recorded according to Dindo-Clavien and CTCAE.ResultsSixty-five ePIPAC procedures were performed in 33 patients (median 2, range 1–6). Ten patients were eligible for response evaluation based on biopsies from the first and third ePIPAC procedure. Four patients had disease progression, four patients had regressive disease, and two patients had stable disease according to PRGS. No life threatening adverse reactions and no mortality was observed following ePIPAC.ConclusionOne minute ePIPAC was feasible and safe, but the histological tumor response was insufficient compared to standard PIPAC directed therapy with 30 min passive diffusion time.     

盐酸氨溴索治疗小儿支气管肺炎的临床分析

目的分析研究盐酸氨溴索用于小儿支气管肺炎的临床效果。方法将本院2017年12月—2018年12月期间收治的小儿支气管肺炎患儿88例按照随机双盲法均分为对照组和治疗组,予以对照组44例患儿常规治疗,予以治疗组44例患儿常规治疗联合氧气驱动雾化吸入盐酸氨溴索治疗,对两组患儿的临床疗效和临床症状缓解时间进行对比。结果与对照组相比,治疗组患儿咳嗽、咳痰、胸片改善时间及肺部干湿啰音缓解时间均显著短于对照组,组间差异具有统计学意义(P<0.05),治疗组的临床总有效率为95.45%(42/44),明显高于对照组77.27%(34/44),组间差异具有统计学意义(P<0.05)。结论小儿支气管肺炎在临床常规治疗的基础上加用盐酸氨溴索治疗有助于患儿临床症状的缓解,效果明显。     

麻黄附子细辛汤联合常规疗法治疗感染后咳嗽的临床研究

目的探讨麻黄附子细辛汤治疗感染后咳嗽的临床效果。方法选取漯河市郾城区惠生堂门诊部和河南省漯河市第三人民医院呼吸内科于2017年5月—2018年10月诊治的感染后咳嗽患者240例,采用随机数字表法分为两组,对照组患者120例实施常规治疗(退热、吸氧、补液等),观察组患者120例联用麻黄附子细辛汤(紫苏子9 g,射干9 g,地龙9 g,炙麻黄6 g,细辛6 g)治疗,于治疗前后行生化指标(C反应蛋白、白细胞计数、白细胞介素-4)检测和症状(咳嗽、喘息、咳痰、哮鸣音)评分,比较两组患者的症状(咳嗽、喘息、咳痰、哮鸣音)改善时间、临床效果(显效、有效、无效、总有效)、不良反应情况(恶心呕吐、头晕头痛、胃肠道反应)。结果两组治疗后C反应蛋白、白细胞计数、白细胞介素-4、症状评分(咳嗽、喘息、咳痰、哮鸣音)较治疗前显著降低(P<0.05)。观察组治疗后C反应蛋白、白细胞计数、白细胞介素-4、症状评分(咳嗽、喘息、咳痰、哮鸣音)低于对照组(P<0.05)。观察组症状改善时间(咳嗽、喘息、咳痰、哮鸣音)早于对照组(P<0.05)。观察组总有效率(99.2%,119/120)高于对照组(90.0%,108/120)(P<0.05)。结论麻黄附子细辛汤治疗感染后咳嗽的效果显著,可缩短治疗时间并改善病症,值得临床推广使用。     

宽胸气雾剂改善冠心病合并活动后胸闷胸痛患者运动耐量临床研究

目的探索宽胸气雾剂对冠心病合并活动后胸闷胸痛患者的临床疗效。方法14例冠心病患者予宽胸气雾剂3次/天,每次1揿,共使用10天。测量治疗前后最大公斤摄氧量(VO2 max)、运动过程最大心输出量(COmax)、运动心肺数据及动态血流动力学,并观察胸闷胸痛症状是否缓解。结果最终12例患者纳入分析,其中9例(75.0%)自觉症状改善。与治疗前比较,治疗后COmax、呼吸熵、心率、无氧阈代谢当量、最大值左心做功指数及运动中心输出量均值升高(P<0.05,P<0.01)。结论宽胸气雾剂可有效提高心输出量,促进血氧结合,改善心脏冠脉缺血情况,增强患者的心脏功能及运动储备能力。     

复方鲜竹沥液联合噻托溴铵粉雾剂治疗慢性阻塞性肺疾病急性加重期的临床研究

目的研究复方鲜竹沥液联合噻托溴铵粉雾剂治疗慢性阻塞性肺疾病急性加重期的临床疗效。方法选取2018年9月—2019年9月在安阳市第六人民医院治疗的100例慢性阻塞性肺疾病急性加重期患者,将所有患者随机分为对照组和治疗组,每组各50例。对照组吸入噻托溴铵粉雾剂,1粒/次,1次/d。治疗组在对照组基础上口服复方鲜竹沥液,20 mL/次,3次/d。两组持续治疗3个月。观察两组的临床疗效,比较血气指标、肺功能指标、血清炎性因子水平。结果治疗后,治疗组总有效率94.00%显著高于对照组82.00%(P0.05)。治疗后,两组二氧化碳分压(pCO_2)显著降低,血氧分压(pO_2)显著升高(P0.05),且治疗组血气指标改善程度较大(P0.05)。治疗后,两组第一秒用力呼气容积(FEV1)占预计值百分比(FEV1%)、每分钟最大通气量(MVV)显著升高,残气量/肺总量(RV/TLC)明显降低(P0.05);且治疗组肺功能指标改善较多(P0.05)。治疗后,两组白细胞介素-17(IL-17)、IL-8、肿瘤坏死因子-α(TNF-α)水平显著降低(P0.05);并且治疗组血清炎性因子水平降低较多(P0.05)。结论复方鲜竹沥液联合噻托溴铵粉雾剂治疗慢性阻塞性肺疾病急性加重期具有较好的临床疗效,可改善血气指标和肺功能指标,降低血清炎性因子水平,值得在临床上推广应用。     

Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance

Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.     

百蕊颗粒结合氨溴索雾化吸入治疗慢性支气管炎急性发作临床研究

目的观察百蕊颗粒结合氨溴索雾化吸入治疗慢性支气管炎急性发作风热袭肺证的疗效。方法将本院2015年7月-2018年7月符合入选标准的150例慢性支气管炎急性发作患者,采用随机数字表法分为2组,每组75例。对照组在西医常规治疗基础上雾化吸入盐酸氨溴索,治疗组在对照组基础上冲服百蕊颗粒。2组均连续治疗2周。分别于治疗前后进行临床症状评分及风热袭肺证评分。采用肺功能仪检测FEV1占预计值百分比和FEV1/FVC;采用ELISA法分别检测血清及痰液中的TNF-α和IL-6水平,记录患者的咳嗽、喘息、咳痰、肺部啰音的消失时间,评价临床疗效。结果治疗组总有效率为98.6%(72/73)、对照组为88.9%(64/72),2组比较差异有统计学意义(χ^2=4.354,P=0.037)。治疗组咳嗽、喘息、咳痰、肺部啰音消失时间均早于对照组(t值分别为5.331、5.590、5.841、6.305,P<0.01)。治疗组治疗后咳嗽、喘息、咳痰、哮鸣音症状评分均低于对照组(t值分别为4.990、4.431、5.221、5.004,P值均<0.01);风热袭肺证咳喘、发热、口干咽痛、鼻塞、流涕评分均低于对照组(t值分别为5.652、5.190、5.311、5.793、5.643,P值均<0.01)。治疗后,治疗组FEV1占预计值百分比[(52.51±5.63)%比(47.30±5.21)%,t=8.931]、FEV1/FVC[(61.57±6.44)比(56.87±5.82),t=8.251]均高于对照组(P<0.01)。治疗组治疗后血清TNF-α、IL-6水平(t值分别5.331、4.908)及痰液中TNF-α、IL-6水平(t值分别6.001、4.803)均低于对照组(P<0.01)。结论百蕊颗粒结合雾化吸入氨溴索可有效降低慢性支气管炎急性发作患者的炎性细胞因子水平,改善临床症状,提高疗效。     

1,5-Iodonaphthyl azide-inactivated V3526 protects against aerosol challenge with virulent venezuelan equine encephalitis virus

Venezuelan equine encephalitis virus (VEEV) is a New World alphavirus. VEEV is highly infectious in aerosolized form and has been identified as a bio-terrorism agent. There is no licensed vaccine for prophylaxis against VEEV. The current IND vaccine is poorly immunogenic and does not protect against an aerosol challenge with virulent VEEV. We have previously shown that VEEV inactivated by 1,5-iodonaphthyl azide (INA) protects against footpad challenge with virulent VEEV. In this study, we inactivated an attenuated strain of VEEV, V3526, with INA and evaluated its protective efficacy against aerosol challenge with wild type VEEV. We demonstrated that among three routes of immunization, intramuscular immunization with INA-inactivate V3526 (INA-iV3526) provided complete protection against aerosol challenge with virulent VEEV. Our data suggests that INA-iV3526 can be explored further for development as an effective vaccine candidate against aerosol challenge of virulent VEEV.