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.     

应用Fast-fix 360全内缝合技术修复半月板Ramp区损伤的临床研究

目的探讨应用Fast-fix 360全关节内缝合技术修补半月板Ramp区损伤的方法和疗效。方法2016年10月至2018年4月,中部战区总医院骨科足踝与运动医学中心使用Fast-fix 360缝合技术修补经镜下确诊为内侧半月板Ramp区损伤病人15例,其中男14例,女1例,平均年龄为23.6岁,病人均合并前交叉韧带(anterior cruciate ligament,ACL)断裂,均予以一期行ACL自体腘绳肌单束重建,6例合并外侧半月板损伤亦同期处理。术后行膝关节标准化功能康复。收集病例手术时间、术中出血量、术后并发症情况;术前、术后半年、术后1年的Lysholm膝关节评分、国际膝关节评分委员会(International Knee Documentation Committee,IKDC)评分;术后半年、1年分别复查患膝关节MRI,评估Ramp区损伤修复情况。结果病人随访13~26个月(平均17.8个月)。手术时间为(90.8±21.4)min,术中出血量为(50.5±10.6)ml。术后2例病人移植肌腱供区伤口浅表感染,经延长换药后均愈合;无伤口深部感染及膝关节感染;未出现腘窝血管神经损伤情况。术后半年及1年的Lysholm膝关节评分、IKDC评分均显著高于术前,差异均有统计学意义(P均<0.05)。术后半年MRI评估Ramp区的愈合率为73.3%,术后1年其愈合率提高至86.7%。结论使用Fast-fix 360全关节内缝合技术修补半月板Ramp区损伤,同时一期重建ACL,可获得较满意的临床疗效,方法简单、手术时间短,可作为半月板Ramp区损伤的一种常规修复方法。     

Nurse Practitioner Student Clinical Placements: A Rural Community Immersion

This article describes a collaboration between a university and a medically underserved area in California’s central valley. Students participate in a community-based clinical immersion to provide care to a medically underserved population. Faculty collaborate with community-based partners to develop and implement clinical experiences. Students are provided opportunities to meet clinical course objectives while developing skills necessary to care for a medically underserved population as part of an interdisciplinary team.     

抗血小板聚集治疗在大面积脑梗塞中的应用分析

目的探讨抗血小板聚集对大面积脑梗塞进行治疗的临床效果。方法选取100例大面积脑梗塞患者作为研究对象,并将其随机列入观察组和对照组,各50例。观察组应用抗血小板聚集进行治疗,对照组行常规治疗。对比分析两组的疗效。结果观察组的总有效率、神经功能的缺损积分以及日常生活能力的恢复情况均显著优于对照组(P0.05)。结论应用抗血小板聚集对大面积脑梗塞患者进行治疗,疗效确切,安全性强。     

Clinical Implications of Poststent Optical Coherence Tomographic Findings: Severe Malapposition and Cardiac Events

ObjectivesThis study sought to evaluate the impact of poststent optical coherence tomography (OCT) findings, including severe malapposition, on long-term clinical outcomes.BackgroundSuboptimal OCT findings following percutaneous coronary intervention (PCI) are highly prevalent; however, their clinical implications remain controversial.MethodsOf the patients registered in the Yonsei OCT registry, a total of 1,290 patients with 1,348 lesions, who underwent OCT immediately poststenting, were consecutively enrolled for this study. All patients underwent implantation of drug-eluting stents. Poststent OCT findings were assessed to identify predictors of device-oriented clinical endpoints (DoCE), including cardiac death, target vessel-related myocardial infarction (MI) or stent thrombosis, and target lesion revascularization (TLR). Significant malapposition criteria associated with major safety events (MSE) were also investigated, such as cardiac death, target vessel-related MI, or stent thrombosis.ResultsThe median follow-up period was 43.0 months (interquartile range [IQR] 21.4 to 56.0 months). The incidence rates of stent edge dissection, tissue prolapse, thrombus, and malapposition after intervention were not associated with occurrence of DoCE. However, patients with significant malapposition (total malapposition volume [TMV] ≥7.0 mm³] exhibited more frequent MSE. A smaller minimal stent area (MSA) was identified as an independent predictor for DoCE (hazard ratio [HR]: 1.20 [95% confidence interval [CI]: 1.00 to 1.43]; p = 0.045). Malapposition with TMV ≥7.0 mm³ was found to be an independent predictor of MSE (HR: 6.12 [95% CI: 1.88 to 19.95]; p = 0.003). Follow-up OCT at 3, 6, or 9 months after PCI showed that poststent TMV ≥7.0 mm³ was related to a greater occurrence of late malapposition and uncovered struts.ConclusionsAlthough most suboptimal OCT findings were not associated with clinical outcomes, a smaller MSA was associated with DoCE, driven mainly by TLR, and significant malapposition with TMV ≥7.0 mm³ was associated with more MSE after PCI. (Yonsei OCT [Optical Coherence Tomography] Registry for Evaluation of Efficacy and Safety of Coronary Stenting; Yonsei OCT registry; NCT02099162)     

Arterial endofibrosis in endurance athletes: Prospective comparison of the diagnostic accuracy of intra-arterial digital subtraction angiography and computed tomography angiography

PurposeTo prospectively compare the diagnostic capabilities of computed tomography angiography (CTA) to those of digital subtraction angiography (DSA) in endurance athletes with suspicion of arterial endofibrosis.Materials and methodsForty-five athletes (39 men, 6 women; median age: 30 years, interquartile range: 23–42 years) prospectively underwent DSA and CTA without (n = 5) or with (n = 40) electrocardiogram gating. DSA was interpreted by a single expert (experience of 15 years). CTA was independently interpreted by three other readers (experience of 5–8 years). Readers assessed the presence and degree of stenoses on iliac and femoral arteries and the overall diagnosis (negative, uncertain, positive) of endofibrosis at the limb level. Sensitivities and specificities of DSA and CTA were estimated at the limb level using histological findings and long-term follow-up as reference, and compared using the McNemar test.ResultsFor diagnosing and quantifying stenoses, concordance between DSA and CTA was moderate-to-good for common and external iliac arteries, moderate for lateral circumflex arteries and poor-to-moderate for the other branches of the deep femoral artery. It was good for all readers for the overall diagnosis of endofibrosis. After long-term follow-up (median, 95 months; interquartile range: 7–109 months), DSA sensitivity and specificity were respectively 88.6% (39/44; 95% confidence interval [CI]: 76–95%) and 75% (24/32; 95% CI: 57.9–86.7%); CTA sensitivity and specificity were respectively 88.6% (39/44; 95% CI: 76–95%; P > 0.99) and 84.4% (27/32; 95% CI: 68.2–93.1%; P = 0.51), 86.3% (38/44; 95% CI: 73.3–93.6%; P > 0.99) and 75% (24/32; 95% CI: 57.9–86.7%; P > 0.99), and 84.1% (37/44; 95% CI: 70.6–92.1%; P = 0.68) and 75% (24/32; 95% CI: 57.9–86.7%; P > 0.99) for the three readers.ConclusionCTA shows performances similar to those of DSA in predicting the long-term diagnosis of endofibrosis in endurance athletes with suggestive symptoms.