Extubación ultra fast-track vs. convencional tras cirugía cardiaca en un centro de referencia cardiovascular en Colombia. Estudio longitudinal

Introduction

The fast track / ultra-fast-track protocols are techniques used to optimise the patient care process and a quick recovery after cardiac surgery. They are one of the mainstays of efficient practice. With their use, the length of hospital and intensive care unit (ICU) stays are reduced, with a direct impact on costs and the quality of the health service.

米索前列醇联合依沙吖啶在中晚期妊娠引产中的临床应用

目的 探讨米索前列醇联合依沙吖啶在中晚期妊娠引产中的应用效果。方法 选取西安交通大学附属3201医院2012年1月—2017年12月收治的138例中晚期妊娠引产患者，按引产方式分为对照组、观察组，各69例。对照组使用乳酸依沙吖啶注射液进行引产，观察组在对照组的基础上联合使用米索前列醇进行引产。比较两组引产效果、胎儿娩出时间、阴道出血量及不良反应的发生情况。结果 观察组引产有效率是100%，显著高于对照组的91.75%（P<0.05）。观察组胎儿娩出时间<35 h的人数占比显著高于对照组（P<0.05）。观察组患者阴道出血量显著低于对照组（P<0.05），两组不良反应的发生率间差异不显著。结论 米索前列醇联合依沙吖啶在中晚期妊娠引产中的效果较好，可显著提高引产有效率、缩短胎儿娩出时间，值得临床应用。     

Nanoparticle albumin bound-paclitaxel for treatment of advanced non-small cell lung cancer: an evaluation of the clinical evidence

Introduction: Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), a microtubule inhibitor, has demonstrated clinical efficacy in the treatment of advanced non-small cell lung cancer (NSCLC) either as monotherapy or in combination. Nab-paclitaxel was developed to reduce the toxicities associated with solvent-bound paclitaxel (sb-paclitaxel).

Areas covered: This review first focuses on the clinical trials evaluating the efficacy and tolerability of nab-paclitaxel in NSCLC at different settings. The approval of nab-paclitaxel in combination with carboplatin at the front-line setting for advanced NSCLC was based on the key phase III study, which showed that nab-paclitaxel/carboplatin was associated with superior overall response rate and favorable toxicity profile compared to sb-paclitaxel/carboplatin. The review also addresses the nab-paclitaxel pharmacology, other combinations (e.g. immunotherapy with PD-1/PD-L1 inhibitors), potential biomarkers (e.g. caveolin-1), and special subgroups (e.g. the elderly, squamous histology).

Expert opinion: Existing data has established the role of nab-paclitaxel in the management of advanced NSCLC. Emerging evidence, such as preliminary results from Keynote-407 and IMpower 131 studies, indicates that novel combinations of nab-paclitaxel/carboplatin and PD-1/PD-L1 inhibitors could further improve clinical benefits with manageable toxicity. Nevertheless, in order to better position nab-paclitaxel and to improve patient selection, future studies are warranted to further understand its mechanism of action, predictive biomarkers, and potential synergism with other agents.     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction

Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.     

壮医龙盘止咳方治疗小儿急性支气管炎风热犯肺证30例临床观察

目的:观察壮医龙盘止咳方治疗小儿急性支气管炎风热犯肺证的临床疗效。方法:选取60例急性支气管炎风热犯肺证的患儿,将其随机分为2组,每组各30例。治疗组采用壮医龙盘止咳方治疗,对照组予小儿宣肺止咳颗粒治疗,治疗5d后观察2组患儿的疗效、白介素-4(IL-4)和干扰素-γ(INF-γ)含量的变化情况,并进行中医证候评分。结果:总有效率治疗组为89.66%(26/29),对照组为76.67%(23/30),2组比较,差异有统计学意义(P<0.05);治疗组治疗后IL-4高于对照组,INF-γ及中医证候积分均低于对照组,各项指标组间比较,差异均有统计学意义(P<0.05)。结论:壮医龙盘止咳方治疗小儿急性支气管炎风热犯肺证疗效显著,值得推广应用。     

老年轻度认知障碍患者血清瘦素、甲状腺激素水平与局部脑血流量关系的研究

目的 通过检测老年轻度认知障碍（MCI）患者血清瘦素（LEP）、甲状腺激素水平，分析其与局部脑血流量（rCBF）的关系。方法 选择本院收治的128 例老年MCI 患者，另选健康者128 例作为对照组。检测血清LEP、甲状腺激素、大脑各区域rCBF 水平并分析其相关性。结果 老年MCI 组患者左右侧额叶、右侧颞叶、左侧顶叶、左右侧基底节区域脑血流量[（43.81±8.62）mL/（100 g·min）、（43.24±7.93）mL/（100 g·min）、（45.14±6.98）mL/（100 g·min）、（45.86±6.77）mL/（100 g·min）、（67.95±8.52）mL/（100 g·min）、（68.36±8.34）mL/（100 g·min）]低于对照组[（46.39±8.31）mL/（100 g·min）、（46.52±8.56）mL/（100 g·min）、（47.37±7.04）mL/（100 g·min）、（48.25±6.98）mL/（100 g·min）、（70.34±8.96）mL/（100 g·min）、（70.58±8.57）mL/（100 g·min）]（P＜0.05）。老年MCI 组患者血清LEP、T3、FT3 水平[（4.87±1.56）μg/L、（1.21±0.16）nmol/L、（3.04±0.36）pmol/L]低于对照组[（11.45±3.92）μg/L、（1.68±0.21）nmol/L、（4.82±1.21）pmol/L]（P＜0.05），TSH 水平为（2.78±0.75）IU/mL，高于对照组的（1.13±0.38）IU/mL（P＜0.05）。老年MCI 患者血清LEP 水平与左侧额叶、右侧颞叶、左侧顶叶rCBF 呈正相关（r=0.452、0.537、0.544，P 均＜0.05），T3 水平与左侧额叶、右侧颞叶rCBF 呈正相关（r=0.427、0.521，P 均＜0.05），FT3 水平与右侧颞叶rCBF 呈正相关（r=0.492，P＜0.05），TSH 水平与左侧额叶、右侧颞叶rCBF 呈负相关（r=-0.463、-0.489，P 均＜0.05）。结论 老年MCI 患者血清中LEP、T3、FT3 水平降低，TSH 水平升高，且与不同区域rCBF 有相关性，可通过调控脑血管功能影响rCBF 变化水平。     

宣白承气汤单独用药及联合用药治疗肺炎痰热壅肺证Meta分析

目的:系统评价宣白承气汤单用及联合用药治疗肺炎痰热壅肺证的临床疗效。方法:检索CNKI、万方、CBM、PubMed等数据库,筛选宣白承气汤治疗肺炎的随机对照试验(RCT),运用Cochrane协作网偏倚风险评价工具进行文献质量评价,使用Revman 5.3 软件进行Meta分析。结果:最终纳入16项研究,共1393例患者,纳入文献质量不高。Meta分析结果表明,与单纯西医治疗相比,使用宣白承气汤可明显提高肺炎痰热壅肺证的临床总有效率[RR=1.29,95%,CI(1.22,1.36),P<0.00001],且亚组分析显示单用或联用宣白承气汤的组间差异无统计学意义; 可明显改善APACHE II评分、CPIS评分,明显降低炎症因子水平,改善中医证候积分。结论:宣白承气汤可有效治疗肺炎痰热壅肺证,但鉴于纳入临床研究在质量上存在一定局限性,得出的阳性结果仅作为临床诊疗的提示与参考,急需开展更多的高质量大规模的RCT来进一步验证。