The impact of the updated EORTC/MSG criteria on the classification of hematological patients with suspected invasive pulmonary aspergillosis

ObjectivesOur aim was to evaluate the effect of the updated European Organization for Research and Treatment of Cancer (EORTC) and Mycoses Study Group 2019 definitions for invasive pulmonary aspergillosis (IPA) on patient classification and the related all-cause 12-week mortality.MethodsIn this retrospective cohort study from our tertiary care centre, we reclassified patients with haematological malignancy who underwent bronchoalveolar lavage between 2014 and 2019 for suspected IPA using the novel EORTC 2019 criteria. We performed receiver operating characteristic curve analysis to define the optimal cut-off for positive PCR and galactomannan and present survival analyses and their possible association with these diagnostic criteria through post hoc comparisons with log rank and Cox regression.ResultsFrom 323 episodes of suspected IPA in 282 patients, 73 were reclassified: 31 (42.5%) from possible to probable IPA, 5 (6.8%) from EORTC criteria not met to probable IPA, and 37 (50.7%) from EORTC criteria not met to possible IPA. Probable IPA increased therefore 11.1% (64/323, 19.8% to 100/323, 30.9%), mostly due to positive PCR (31/36, 86.1%). There was no difference in mortality between newly defined possible and probable IPA (log rank p = 0.950). Mortality was higher in probable cases with lower cycle thresholds (Ct values) versus higher Ct values (p = 0.004). Receiver operating characteristic curve analysis showed an optimal Ct value cut-off of 36.8 with a sensitivity of 75% (95% CI 64.9%–85.1%) and a specificity of 61.7% (95% CI 53.5–69.9) for 12-week mortality.DiscussionThe new EORTC criteria led to 11.1% more probable IPA diagnoses, mostly due to Aspergillus PCR. Restricting positive PCR to below a certain threshold might improve the discrimination of the new EORTC IPA categories for mortality.     

补肾纳气法治疗小儿支气管哮喘的临床分析

目的：探讨分析补肾纳气法治疗小儿支气管哮喘的临床效果。方法方便选取该院儿科于2013年3月—2014年11月收治的小儿支气管哮喘患者67例，根据随机数字法分为对照组33例和观察组34例，对照组患者予以氨茶碱片治疗，观察组患者实施补肾纳气法治疗，观察两组患者的治疗效果，进行临床对照性分析。结果对照组患者不良反应发生率24.2%，观察组患者不良反应发生率5.8%，观察组不良反应发生率明显低于对照组(P﹤0.05)；对照组患者总有效率60.6%，观察组患者总有效率85.3%。观察组患者治疗后总有效率明显高于对照组(P﹤0.05)。结论补肾纳气法治疗小儿支气管哮喘的临床效果好，应用价值高，值得在临床实践中推广应用。     

关节滑液检测在关节假体周围感染诊断中的研究进展

关节假体周围感染(periprosthetic joint infection,PJI)是人工关节置换术后可能发生的一种严重并发症,其导致的严重后果,无论对于医生还是患者来说,都很难接受。目前,由于多种不确定因素的存在,PJI诊断的准确性较低。传统的血清学检查、影像学检查有一定的价值,但是易受全身情况的影响,导致特异性不高。为了正确诊断关节假体周围感染,不同学科的研究人员采用各种不同的方法进行了大量的诊断研究,并取得了丰富的成果。近年来,关节滑液炎性标志物检测、分子生物学方法等被研究证实具有较高的敏感性和特异性。因此,关节滑液CRP、-防御素、白细胞酯酶、PCR技术等被广泛研究,期望能从中找到诊断关节假体周围感染的特异性指标,提高临床诊断的准确性。     

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.     

脑脊液降钙素原及乳酸测定在早期诊断颅脑术后颅内感染的意义

目的研究降钙素原(PCT)及乳酸水平在早期诊断颅脑术后颅内感染的意义。方法颅脑术后颅内感染患者(n=20)和非颅内感染患者(n=20)的脑脊液和血液样本,检测脑脊液和血清PCT,脑脊液和血液乳酸水平等指标并进行统计分析。结果感染组脑脊液和血清PCT、乳酸水平较非感染组显著升高,差异有统计学意义(P0.05)。脑脊液PCT和乳酸水平诊断敏感性及特异性均较血清PCT和乳酸水平高。结论脑脊液PCT、乳酸在颅脑手术术后颅内感染的诊断中均有意义,其中脑脊液PCT较乳酸敏感性更高,临床应用价值更大。     

支气管哮喘患儿中性粒细胞胞外诱捕网水平与患者免疫功能及临床预后的关系

目的探讨支气管哮喘患儿中性粒细胞胞外诱捕网水平与患者免疫功能及临床预后的关系。方法选取本院2017年9月-2018年9月支气管哮喘患者80例作为观察组,并以同期健康体检的30例儿童作为对照组,采用pico Green dsDNA荧光染色定量检测支气管哮喘患者NETs水平,采用T淋巴细胞亚群评价患者免疫功能,对比不同NETs水平患者免疫功能及临床特点,采用Logistic回归分析探讨小儿支气管哮喘急性发作的风险因素。结果观察组白细胞、中性粒细胞、单核细胞、Cf-DNA/NETs水平均高于对照组(P <0. 05),而淋巴细胞水平低于对照组,差异均有统计学意义(P <0. 05)。Logistic回归分析显示,哮喘家族史、呼吸道感染、Cf-DNA/NETs水平上升、有害气体接触、被动吸烟均是支气管哮喘急性发作的独立危险因素(P <0. 05)。结论中性粒细胞胞外诱捕网水平与支气管哮喘患者免疫功能及预后密切相关,值得临床重点关注。     

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.