阿替普酶和替奈普酶溶栓治疗对急性次大块肺栓塞的疗效及安全性的Meta分析

目的 评价溶栓治疗急性次大块肺栓塞(PE)的疗效和安全性.方法 计算机检索阿替普酶和替奈普酶用于次大块PE患者的随机对照试验,时间截止2014年3月.由2住研究者独立评价纳入研究的质量、提取数据,统计分析采用RevMan5.2.7软件进行.结果 共纳入8篇研究,总计676例次大块PE患者,其中溶栓组331例,对照组345例.分析显示:溶栓治疗并不能降低患者的早期病死率(RR=0.66;95％CI:0.31～1.40;P=0.28),可能不会降低溶栓后PE的再发生(RR=0.55;95％CI:0.21～1.40;P=0.21),也未增加主要出血事件发生率(RR=1.23;95％CI:0.57～2.68;P=0.60),但会增加次要出血事件发生风险(RR=3.88;95％CI:1.40～10.72;P=0.009).结论 溶栓治疗可能并不能改善次大块PE患者预后,而且会增加出血的风险,溶栓治疗对次大块PE患者预后影响仍需进一步证实.     

Intracoronary tenecteplase in STEMI with massive thrombus

Primary percutaneous coronary intervention is the current standard of care in ST elevation myocardial infarction (STEMI). However, large thrombus is an independent predictor for stent thrombosis and major adverse cardiac events in patients undergoing primary angioplasty for STEMI. Here we report a series of STEMI patients with large thrombus burden treated successfully with low dose intracoronary thrombolysis. There was prompt and early ST resolution. There was improvement in thrombolysis in myocardial infarction (TIMI) flow and myocardial blush grade postlysis in all patients. Majority had recanalised infarct related coronary artery thus obviating the need for stenting. There was no inhospital or 1 month mortality or bleeding events. Hence intracoronary thrombolysis is an option in patients with large thrombus burden.     

Efficacy and safety of different doses of tenecteplase for the treatment of acute ischemic stroke: A protocol for a systematic review and network meta-analysis

Background:Acute ischemic stroke (AIS) has become the major reason of causing death around the world. As a newer generation fibrinolytic agent, the potential of tenecteplase in treating AIS has been determined in clinical studies and meta-analysis. However, various doses have been prescribed for tenecteplase in clinical practice, and the optimal dose is not yet clear.Methods:We will perform a systematic search to capture all potential randomized controlled trials (RCTs) of persons with confirmed AIS who were instructed to administer tenecteplase that report at least one outcome in PubMed, Embase, and the Cochrane Library. Two reviewers will independently check the titles, abstracts, and full-texts, extracting data, assessing the risk of bias and evaluating the certainty of evidence. We will use a random-effect model based on the Bayesian framework to completely direct and network meta-analyses. We will also test the robustness of all pooled results through conducting subgroup analyses according to the following criteria:

• 1.low and high risk of bias;
• 2.impact factors (≥5, 3–5, and ≤3);
• 3.usage of endovascular thrombectomy or not.

Discussion:Our systematic review and network meta-analysis will generate several valuable findings and have several strengths including:

• 1.a systematic search string;
• 2.predesigned criteria for subgroup analysis;
• 3.determination of level of evidence with the GRADE system; and
• 4.graphic illustration of numerical results.

We therefore believe that findings from this network meta-analysis will benefit future study design and improve evidence-based treatment of AIS.Ethics and dissemination:We will disseminate the results from the present study through submitting it to conferences or peer-reviewed journal.Protocol registry:The protocol of our systematic review and network meta-analysis was registered in International Plateform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) platform with an approval number of INPLASY2020100086 (https://inplasy.com/inplasy-2020-10-0086/). Moreover, this protocol was funded through a protocol registry.     

Prolonged Chest Compressions during Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest due to Acute Pulmonary Embolism

Patients with hemodynamic collapse due to acute pulmonary embolism have a dismal prognosis if not treated rapidly. Therapeutic options include systemic thrombolytic therapy, rheolytic thrombectomy, and surgical embolectomy. However, the efficacy of thrombolytic therapy is diminished because the low-output state hinders effective delivery of the lytic agent to the thrombus. In the absence of any form of mechanical circulatory support, such as extracorporeal membrane oxygenation or cardiac surgery on site, we think that prolonged vigorous manual compressions might be the only way to support the circulation during the initial critical state, when thrombolytic therapy has been administered.We report the results of prolonged manual chest compressions (exceeding 30 minutes) on 6 patients who received tenecteplase in treatment of acute pulmonary embolism that induced in-hospital cardiopulmonary arrest. Four of 6 patients survived and were discharged from the hospital. In an era of increasing technologic complexity for patients with hemodynamic instability, we emphasize the importance of prolonged chest compressions, which can improve systemic perfusion, counteract the prothrombotic state associated with cardiopulmonary arrest, and give the lytic agent time to act.     

Investigation of the safety of tenecteplase to the outer retina

Purpose: To investigate the safety of the thrombolytic agent, tenecteplase to the outer retina in pig eyes. Methods: Tenecteplase (50 µg) was injected into the subretinal space in one eye while the fellow eye received balanced salt solution. At 24 h, 1 week and 9 weeks the eyes were examined by indirect ophthalmoscopy and photographed. Animals were killed at 9 weeks, eyes enucleated and processed for light and transmission electron microscopy. Three locations within the area of the injection bleb were analysed. Results: Retinal pigment epithelial defects, which appeared to be iatrogenic and confined to the injection site, were seen in most of the treated and control eyes. There was no significant difference in the degree of retinal damage between the two groups of eyes at the three sites examined (P > 0.05). Conclusion: Fifty micrograms of tenecteplase appears to be a safe dose with no evidence of toxicity to the outer retina and may have a potential role in the treatment of submacular haemorrhage.     

Issues in the assessment of the safety and efficacy of tenecteplase (TNK-tPA)

While thrombolytic agents have demonstrated improved mortality over the use of placebo, this has come at the expense of bleeding complications such as intracranial hemorrhage (ICH). Tenecteplase (TNK-tPA) is a novel thrombolytic agent engineered to improve upon the ease of use and safety of alteplase (t-PA). Given its longer half-life, TNK-tPA can be administered as a single bolus. The dosing of TNK-tPA has been weight optimized to enhance both safety and efficacy outcomes. Weight-optimized TNK-tPA dosing requires body weight estimation, which may introduce the potential for medication error. However, data from TNK-tPA clinical trials suggest that body weight estimates can err by up to 20 kg (44 lb) without an increased risk of ICH or death. Furthermore, the results of TNK-tPA clinical trials showed that even at the highest weight-optimized dosage of 50 mg, ICH rates were among the lowest reported in clinical trials of thrombolytics for acute myocardial infarction. In elderly female patients of low body weight, the use of weight-optimized TNK-tPA lowered the risk of ICH compared with the use of t-PA, expanding the potential use of thrombolytics to this high-risk patient population. Tenecteplase has demonstrated clinical equivalence to t-PA, but with a wider therapeutic margin of safety.     

Safety and efficacy of tenecteplase in acute myocardial infarction

The use of intravenous thrombolytic agents has revolutionised the treatment of acute myocardial infarction. However, the improved mortality achieved with these drugs is tempered by the risk of serious bleeding complications, especially intracranial haemorrhage (ICH). Tenecteplase (TNKase?, Genetech Inc.) is an engineered variant of alteplase (Activase^®, Genentech Inc.) designed to have increased fibrin specificity, greater efficacy and a longer half-life. The longer half-life of tenecteplase compared to alteplase allows for convenient single bolus administration of the drug. In addition, tenecteplase dosing is based on actual or estimated patient weight, which enhances both the safety and efficacy outcomes. Large clinical trials have demonstrated equivalence in mortality and ICH between tenecteplase and alteplase. Compared to alteplase, tenecteplase use leads to lower rates of bleeding complications and a decreased risk of ICH among low weight, elderly women.     

Advances in ischemic stroke treatment: neuroprotective and combination therapies

Thrombolysis with intravenous alteplase (recombinant tissue-type plasminogen activator) continues to be the sole recourse for acute ischemic stroke therapy, provided that patients seek treatment preferably within 3 h of stroke onset. The narrow window of efficacy, coupled with the significant risk of hemorrhage and the high mortality rate, preclude the use of alteplase beyond this time frame. Moreover, in part because of safety concerns, only a small percentage (6 – 15%) of eligible patients is treated with alteplase. Clearly, safer and more effective treatments that focus on improving the shortcomings of the present thrombolysis for stroke need to be identified. Therefore, newer thrombolytics are being developed with the goal of minimizing side effects, while also shortening the time of cerebral reperfusion and extending the therapeutic window of efficacy. Besides thrombolytics, new and potentially useful drugs and devices are also being studied either as monotherapeutic agents or for use in conjunction with alteplase. In animal models of stroke, neuroprotective agents that affect various components of the ischemic injury cascade that results in neurodegeneration have shown promise for the latter. Examples of such agents include spin traps that block oxidative stress, metalloprotease inhibitors that prevent vascular damage, anti-inflammatory drugs that suppress inflammation and transcranial infrared laser irradiation, which promotes recovery of function. Ideally, a successful combination of neuroprotectant (drug or device) and thrombolytic therapy for stroke would minimize the side effects of thrombolysis followed by supplementary neuroprotection thereafter.     

Fibrinolysis of Acute Peripheral Arterial Occlusion with Tenecteplase—A New Weight-Optimized Treatment Regimen

Peripheral arterial occlusions are associated with high morbidity. Thrombolysis has become established as effective treatment in clinical practice. Tenecteplase is a new thrombolytic agent that offers advantages over existing drugs with respect to mechanism of action and adverse effects.This case report describes successful thrombolysis of an acute thromboembolic brachial artery subtotal occlusion in a 76-year-old woman. In contrast to previously published data, tenecteplase was administered in a weight-adapted dose regimen over six hours, with application of one-fourth of the dose usually given in patients with myocardial infarction. Tenecteplase was immediately effective, and proved safe and well tolerated.