Lower dosage of recombinant tissue-type plasminogen activator (rt-PA) in the treatment of acute pulmonary embolism: A systematic review and meta-analysis

Background and Objective

According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100 mg infusion is recommended for eligible patients with acute pulmonary embolism (PE). However,there exists evidence implying that a lower dosage of rt-PA can be equally effective but potentially safer compared with rt-PA 100 mg regimen. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of low dose rt-PA in the treatment of acute PE.

Material and Method

We searched Pubmed, EMBASE, the Cochrane library and CBM Literature Database for randomized controlled trials (RCT) focusing on low dose rt-PA for acute PE. Outcomes were described in terms of changes of image tests and echocardiography, major bleeding events, all-cause death, and recurrence of PE.

Results

Five studies (440 patients) were included, three of which compared low dose rt-PA (0.6 mg/kg, maximum 50 mg or 50 mg infusion 2 h) with standard dose (100 mg infusion 2 h). There were more major bleeding events in standard dose rt-PA group than in low dose group (OR 0.33, 95%CI 0.12-0.91;P = 0.94,I² = 0%), while there were no statistical differences in recurrent PE or all cause mortality between these two groups. Two studies compared low dose (0.6 mg/kg, maximum 50 mg/2 min bolus or 10 mg bolus, ≤ 40 mg/2 h) with heparin. There was no significant difference in major bleeding events (OR 0.73, 95% CI 0.14-3.98;P = 0.72), recurrent PE or all cause mortality. No dose-related heterogeneity was found for all the included studies.

Conclusions

The results of this meta-analysis were hypothesis-generating. Based on the limited data, our systematic review suggested that low dose rt-PA had similar efficacy but was safer than standard dose of rt-PA. In addition, compared with heparin, low dose rt-PA didn’t increase the risk of major bleeding for eligible PE patients.     

慢性血栓栓塞性肺动脉高压患者肺血管平滑肌细胞膜电位的改变

目的探讨分离培养的慢性血栓栓塞性肺动脉高压患者肺血管平滑肌细胞的方法,观察其电生理学特性。方法分离慢性血栓栓塞性肺动脉高压(chronic thromboembolic pulmonary hypertension,CTEPH)患者内膜剥脱术后的肺组织标本(CTEPH患者组)和肺癌或肺大泡患者正常肺组织标本(正常对照组)的肺血管平滑肌细胞,并进行体外培养,用特异性抗体(smoothmuscle-α-actin,SM-α-actin)进行免疫荧光鉴定。膜片钳记录两组肺血管平滑肌细胞的静息膜电位和动作电位,分析比较两者的异同。结果①酶解法成功分离肺血管平滑肌细胞,经鉴定SM-α-actin阳性细胞达90%以上;②CTEPH患者组肺血管平滑肌细胞静息膜电位(-21.05 mV±2.20 mV,n=11)明显低于正常对照组(-38.12 mV±2.28 mV,n=10),细胞膜电位降低了约45%,处于明显去极化状态(P<0.001);③CTEPH患者组肺血管平滑肌细胞动作电位时程(action potential duration,APD):APD50(0.185 s±0.035 s),APD75(0.277 s±0.053 s),APD90(0.333 s±0.064 s)与正常对照组APD50(0.100 s±0.016 s),APD75(0.150 s±0.024 s),APD90(0.180 s±0.028 s)相比,均明显延长(P<0.05)。结论 CTEPH患者肺血管平滑肌细胞静息膜电位明显减小,动作电位时程延长,提示CTEPH患者肺血管平滑肌细胞存在明显的电生理学特性改变,该变化可能是细胞膜上电压依赖性钙离子通道激活、钙离子浓度增加、肺血管重构发生的重要因素。     

老年肺血栓栓塞症的特点和临床诊治思路

老年人群是肺血栓栓塞症（PTE）的高危人群,有研究显示随着年龄增长,PTE的发病率呈现升高趋势,且老年PTE的病死率、复发率和出血发生率较年轻人明显升高。 因此,老年PTE作为一个重要的国际性医疗保健问题已引起各国普遍关注。在过去的20年间,老年PTE的诊断和治疗取得了很大进步,如新的诊断策略的建立（包括Wells评分和改良的Geneva评分）、年龄调整的D?二聚体界限值对于PTE的排除诊断价值、新型抗凝药物在老年患者中的应用等。本文我们主要针对老年PTE诊断治疗方面的最新进展进行了总结,以期对临床肺血管病医师有所帮助。     

Altered Th1/Th2 commitment contributes to lung senescence in CXCR3-deficient mice

Aging is an inevitable process associated with immune imbalance, which is characterized by a progressive functional decline in major organs, including lung. However, effects of altered Th1/Th2 commitment on lung senescence are largely unknown. To examine effects of altered Th1/Th2 balance on lung aging, we measured proportions of Th1 and Th2 cells and expression of cytokines, chemokines, collagen deposition and other relevant physiological and pathological parameters in 2- and 20-months-old (mo) CXCR3-deficient (CXCR3^−/−) C57BL/6J mice compared with wild-type (WT) mice. There was a significant weight-loss observed in 20-mo CXCR3^−/− mice compared with the same aged WT group. Although lung function and structure changed with age in both groups, central airway resistance (Rn), tissue elastance (H) and damping (G) were significantly lower in 20-mo CXCR3^−/− mice than those of WT mice. In contrast, the whole lung volume (V_L), the mean linear intercept length of alveolar (L_m), and the total lung collagen content were significantly elevated in 20-mo CXCR3^−/− mice. With aging, the lungs of WT mice had typical Th1-type status (increased population of Th1 cells and concentrations of cytokine IFN-γ and CXCR3 ligands) while CXCR3^−/− mice showed Th2-type polarization (decreased proportion of Th1 cells and concentrations of CXCR3 ligands but increased level of IL-4). Our data suggest that Immunosenescence is associated with lung aging, and that altered Th1/Th2 imbalance favors Th2 predominance in CXCR3^−/− mice, which contributes to the process of accelerated lung aging in this model.     

无创正压通气治疗Ⅱ型呼吸衰竭失败预测因素分析

目的探讨无创正压通气(NPPV)治疗Ⅱ型呼吸衰竭失败的预测因素。方法前瞻性收集首都医科大学附属北京朝阳医院呼吸重症监护病房2004年1月至2009年12月应用NPPV治疗Ⅱ型呼吸衰竭患者的临床资料,根据NPPV成功与否将患者分为成功组与失败组,比较两组患者的基础资料,在NPPV前、NPPV2 h后及NPPV24 h后的主要生命体征和血气分析等的变化以及不良反应的发生情况,分析失败原因并寻找失败的危险因素。结果共89例患者入选,其中16例患者NPPV失败。失败组NPPV前白细胞计数和中性粒细胞比例(N)显著高于成功组(P<0.05),血红蛋白(Hb)、白蛋白(ALB)、前白蛋白显著低于成功组(P<0.05)。与NPPV前比较,成功组pH、动脉血二氧化碳分压(PaCO2)及心率(HR)在NPPV2 h后和NPPV24 h后均有显著改善(P<0.05);失败组pH和HR无明显变化(P>0.05),PaCO2在NPPV24 h后有显著改善(P<0.05)。但与成功组比,改善幅度缩小。排痰障碍致呼衰加重是NPPV失败的主要原因,失败组中有11例患者均因此给予气管插管。多因素分析发现,NPPV前N≥0.90、NPPV前ALB<28 g/L以及出现不良反应为排痰障碍为NPPV失败的高危因素。结论 NPPV可作为无绝对禁忌证的Ⅱ型呼吸衰竭患者的首选呼吸支持方式。对于肺部感染较重、出现排痰障碍或营养状况较差患者,NPPV失败的危险性较高;对于在短时间应用NPPV后pH、PaCO2、血流动力学状况无明显改善或改善幅度较小患者,或Hb水平较低患者,NPPV失败的可能性也较大。     

Contact lens management of pellucid marginal corneal degeneration in a Saudi Arabia teaching hospital

The distinguishing features of pellucid marginal cornea degeneration and keratoconus are outlined in the ophthalmic literature, but the former is often misdiagnosed as keratoconus or even myopia with low irregular astigmatism. This makes its diagnosis and treatment clinically challenging to the optometrist and the ophthalmologist. Improper diagnosis will always lead to treatment modalities that will not give desired relief to patients. This case report discusses the contact lens management of pellucid corneal degeneration in a patient who was initially misdiagnosed as having high myopia and treated with photorefractive keratectomy.