Prevalence of Imaging Targets in Patients With Minor Stroke Selected for IV tPA Treatment Using MRI: The Treatment of Minor Stroke With MRI Evaluation Study (TIMES).

OBJECTIVE: To determine the IV tissue plasminogen activator (tPA) treatment rate of patients with minor acute ischemic stroke (mAIS) at our centers and compare the frequency of MRI targets by treatment stratification and clinical severity, we evaluated clinical characteristics and baseline MRIs for tPA-treated and untreated patients. METHODS: Patients with ischemic stroke from 2015 to 2017 with admit NIH Stroke Scale (NIHSS) <6 were considered. The treated cohort received standard IV tPA and was screened with baseline MRI. The untreated cohort received no acute intervention and baseline MRI was <4 hours from onset. Patients were stratified into "clearly" and "not clearly" disabling deficits by NIHSS elements. Baseline MRI was evaluated by independent raters for AIS targets, with frequencies compared between groups. RESULTS: Of 255 patients with mAIS ≤4.5 hours from onset, 140 (55%) received IV tPA, accounting for 46% of all IV tPA patients (n = 305). Eighty-five percent (n = 119) were screened with baseline MRI and had significantly more frequent imaging targets compared to those untreated (n = 90). Of this treated cohort, 75% (n = 89) were not clearly disabling. Except for perfusion-diffusion mismatch (81% clearly disabling vs 56% not clearly disabling [p = 0.036]), there were no significant differences in the frequency of imaging targets across the treated cohort stratified by clinical severity. CONCLUSIONS: In MRI-screened mAIS, imaging targets were more frequently seen in patients treated with IV tPA, with similar frequencies even in those without clearly disabling deficits. MRI targets could be used to guide thrombolytic therapy in patients with mAIS; however, a randomized trial is needed to demonstrate efficacy.

Mechanical cardiopulmonary resuscitation for venoarterial ECMO implantation in pulmonary embolism complicated by type B aortic dissection and retroperitoneal hemorrhage.

A patient with acute pulmonary embolism suffered cardiac arrest, received manual and mechanical cardiopulmonary resuscitation and tissue plasminogen activator before extracorporeal cardiopulmonary resuscitation was initiated. She suffered a type B aortic dissection and retroperitoneal hemorrhage secondary to resuscitation measures. This case report describes high-risk anticoagulation management for contradicting treatment goals in preparation for pulmonary embolectomy on cardiopulmonary bypass.

Corneal and scleral permeability of Desmoteplase in different species.

OBJECTIVE: Intraocular fibrin clots caused by severe uveitis can be a sight-threatening condition that needs to be resolved quickly and reliably. Intracameral injection of tissue-plasminogen activator (tPA) is commonly used to resolve intraocular fibrin. However, the drug does not reach fibrinolytic concentrations after topical application. Desmoteplase (DSPA) is a structurally similar but smaller fibrinolytic agent with a higher fibrin selectivity, a longer half-life, and better biocompatibility compared with tPA. This study was designed to evaluate the corneal and scleral permeability of DSPA in rabbits, pigs, dogs, horses, and humans ex vivo. PROCEDURES: Corneal and scleral tissues (n = 5 per group) were inserted into Franz-type diffusion chambers and exposed to 1.4 mg/mL DSPA for 30 minutes. Drug concentrations on the receiver side were determined by liquid chromatography-tandem mass spectrometry. RESULTS: Concentrations of DSPA after corneal and scleral permeation through fresh tissues ranged from 0.0 to 16.3 µg/mL and 0.0 to 11.4 µg/mL (rabbits), 0.3 to 5.6 µg/mL and 3.1 to 9.2 µg/mL (dogs), 2.1 to 14.9 µg/mL and 4 to 8.7 µg/mL (horses), and 0.6 to 3 µg/mL and 2.9 to 18.1 µg/mL (pigs), respectively. A concentration of 0.07-12.9 µg/mL DSPA was detectable after diffusion through tissue culture preserved human donor bank corneas (Table 1). CONCLUSIONS: Desmoteplase has the ability to permeate both cornea and sclera ex vivo in all species tested. Implications of the ex vivo permeability of DSPA suggest that in vivo permeability may be possible, and if so, it could lead to a novel topical application for lysing fibrin.

Engineered microparticles and nanoparticles for fibrinolysis.

Fibrinolytic agents including plasmin and plasminogen activators improve outcomes in acute ischemic stroke and thrombosis by recanalizing occluded vessels. In the decades since their introduction into clinical practice, several limitations of have been identified in terms of both efficacy and bleeding risk associated with these agents. Engineered nanoparticles and microparticles address some of these limitations by improving circulation time, reducing inhibition and degradation in circulation, accelerating recanalization, improving targeting to thrombotic occlusions, and reducing off-target effects; however, many particle-based approaches have only been used in preclinical studies to date. This review covers four advances in coupling fibrinolytic agents with engineered particles: (a) modifications of plasminogen activators with macromolecules, (b) encapsulation of plasminogen activators and plasmin in polymer and liposomal particles, (c) triggered release of encapsulated fibrinolytic agents and mechanical disruption of clots with ultrasound, and (d) enhancing targeting with magnetic particles and magnetic fields. Technical challenges for the translation of these approaches to the clinic are discussed.

Is Direct Endovascular Treatment as an Alternative of Bridging Therapy in Acute Stroke Patients with Large Vessel Occlusion?

BACKGROUND: Although endovascular treatment (EVT) is very effective for acute ischemia stroke (AIS) patients with proximal large vessels occlusion (LVO), whether bridging rPA before EVT in stroke patients of LVO is of any benefit and is currently one of the most urgent unanswered questions. We aim to comprehensively determine the efficacy and safety of direct EVT (DEVT) in AIS patients with LVO versus bridging therapy (BT). METHODS: Clinical researches published in the Embase, PubMed, and Cochrane Library electronic databases up to May 2017 were identified for analysis. Two reviewers extracted data and conducted quality assessment independently. Statistical tests were performed to check for heterogeneity and publication bias. Subgroup and sensitivity analysis were also conducted to evaluate the robustness of the conclusions. RESULTS: Overall, 13 studies involving 3302 patients met the inclusion criteria. The AIS patients with DEVT had a similar likelihood to achieve good functional outcome at 3 months (risk ratio [RR] = .93, 95% confidence interval [CI] = .85-1.01, P = .094), mortality at 3 months (RR = 1.10, 95% CI = .91-1.33, P = .33), and symptomatic intracranial hemorrhage (RR = 1.06, 95% CI = .74-1.51, P = .75) versus BT; furthermore, the risk of intracranial hemorrhage was lower in DEVT group (RR = .76, 95% CI = .60-.95, P = .02). No significant difference in recanalization rate existed between the 2 groups (RR = .97, 95% CI = .92-1.02, P = .22); however, in the subgroup analysis, it had a rise trend after DEVT than BT in IVT-eligible group (RR = 1.45, 95% CI = .95-2.22, P = .09). CONCLUSIONS: DEVT appears to have equally effectiveness to BT with a low risk of intracranial hemorrhage in AIS patients with LVO, especially for anterior circulation, which offered a practical information to select appropriate therapeutic strategies for patients with LVO, though the level of evidence seems to be quite shaky.

Fibrinolytic Capacity of Desmoteplase Compared to Tissue Plasminogen Activator in Rabbit Eyes.

PURPOSE: Desmoteplase (DSPA) was evaluated and compared with tissue plasminogen activator (t-PA) for its intraocular fibrinolytic effect and short-term toxicity in an in vivo study using rabbit eyes. METHODS: Fibrin clots were induced in the anterior chamber of 44 rabbit eyes, and drug efficacy was measured by clot size reduction over 24 h. Topical DSPA eye drops (1.4 and 2 mg/mL) were compared with vehicle solution in a multiple-drop regimen in 8 animals per group. Intracameral injections of 0.6 µg DSPA (n = 14) and 25 µg t-PA (n = 14) were evaluated for their fibrinolytic efficacy. Animals were euthanized 24 h after drug application. RESULTS: No significant differences were seen between topically treated DSPA and vehicle-treated animals. Intracameral t-PA had a higher fibrinolytic efficacy than DSPA at early time points, but no significant difference was seen between both groups at 24-h postapplication. Animals with t-PA treatment demonstrated significantly more side effects compared with DSPA-treated animals. DSPA showed no-to-mild side effects after topical and intracameral treatment. Histologically, no toxic effects were observed in any globe. CONCLUSIONS: DSPA is a promising drug with fewer side effects and similar fibrinolytic efficacy compared with t-PA 24 h after intracameral application in rabbit eyes at the tested concentration. Drug efficacy might be improved by increasing intracameral DSPA doses.

Plasminogen activator system homeostasis and its dysregulation by ethanol in astrocyte cultures and the developing brain.

In utero alcohol exposure can cause fetal alcohol spectrum disorders (FASD), characterized by structural brain abnormalities and long-lasting behavioral and cognitive dysfunction. Neuronal plasticity is affected by in utero alcohol exposure and can be modulated by extracellular proteolysis. Plasmin is a major extracellular serine-protease whose activation is tightly regulated by the plasminogen activator (PA) system. In the present study we explored the effect of ethanol on the expression of the main components of the brain PA system in sex-specific cortical astrocyte primary cultures in vitro and in the cortex and hippocampus of post-natal day (PD) 9 male and female rats. We find that ethanol alters the PA system in astrocytes and in the developing brain. In particular, the expression of tissue-type PA (tPA), encoded by the gene Plat, is consistently upregulated by ethanol in astrocytes in vitro and in the cortex and hippocampus in vivo. Astrocytes exhibit endogenous plasmin activity that is increased by ethanol and recombinant tPA and inhibited by tPA silencing. We also find that tPA is expressed by astrocytes of the developing cortex and hippocampus in vivo. All components of the PA system investigated, with the exception of Neuroserpin/Serpini1, are expressed at higher levels in astrocyte cultures than in the developing brain, suggesting that astrocytes are major producers of these proteins in the brain. In conclusion, astrocyte PA system may play a major role in the modulation of neuronal plasticity; ethanol-induced upregulation of tPA levels and plasmin activity may be responsible for altered neuronal plasticity in FASD.

Transfemoral thrombectomy in the cavernous sinus and superior ophthalmic vein.

Cavernous sinus thrombosis (CST) is a rare condition that can cause death, neurologic disability, and visual loss. A pre-teen with septic CST leading to ocular hypertension and acute visual loss was treated at our institution with thrombectomy and thrombolysis of the cavernous sinuses and superior ophthalmic veins. Successful recanalization of the bilateral cavernous sinuses and superior ophthalmic veins was achieved in two separate procedures without complication. The patient showed immediate symptomatic relief. He was neurologically intact without visual deficits at the 2 month follow-up. This is the first report in the literature showing the feasibility of cavernous sinus thrombectomy using current devices and techniques. Early endovascular therapy may help preserve vision in patients with acute CST.

Effectiveness and Cost of Weekly Recombinant Tissue Plasminogen Activator Hemodialysis Catheter Locking Solution.

BACKGROUND AND OBJECTIVES: Evidence to guide hemodialysis catheter locking solutions is limited. We aimed to assess effectiveness and cost of recombinant tissue plasminogen activator (rt-PA) once per week as a locking solution, compared with thrice weekly citrate or heparin, in patients at high risk of complications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used a prospective design and pre-post comparison in three sites across Canada. Pre-post comparisons were conducted using multilevel mixed effects regression models accounting for cluster with site and potential enrollment of patients more than once. In the pre period, catheter malfunction was managed as per site-specific standard of care. The intervention in the post period was once weekly rt-PA as a locking solution (with citrate or heparin used for other sessions). The primary outcome was rate of rt-PA use for treatment of catheter malfunction. Secondary outcomes included rates of bacteremia, management of catheter malfunction, and cost. RESULTS: There were 374 patients (mean age 68 years; 52% men) corresponding to 506 enrollments. Mean length of enrollment was 200 days (SD 119) in the pre period and 187 days (SD 101) in the post period. There was a significant decline in rate of rt-PA use for treatment of catheter malfunction in the post compared with pre period (adjusted incidence rate ratio, 0.39; 95% confidence interval, 0.30 to 0.52); however, there was no difference in the rate of bacteremia, or catheter stripping or removal/replacement. The increase in mean total health care cost in the post period was CAD$962 per enrollment, largely related to costs of rt-PA as a locking solution. CONCLUSIONS: Once weekly rt-PA as a catheter locking solution was associated with a reduction in rt-PA use for treatment of catheter malfunction. Our results showing a reduction in rescue rt-PA use are consistent with a prior randomized trial, although we did not observe a reduction in bacteremia or catheter stripping/removal and did observe an increased incremental cost of this strategy primarily accounted for by the cost of the rt-PA.

Efficacy and safety of desmoteplase in acute ischemic stroke patients: A systematic review and meta-analysis.

BACKGROUND: Pending results from double-blind, multicenter, parallel-group, randomized trials, the benefit and safety of the novel plasminogen activator, desmoteplase remain undetermined. The aim of this meta-analysis was to help evaluate desmoteplase's efficacy and safety. METHODS: A thorough search was performed of the Cochrane Library, PubMed, and Embase from the inception of electronic data to March 2017, and double-blind, multicenter, parallel-group, randomized trials were chosen. We conducted a meta-analysis of studies investigating intravenous desmoteplase treatment of acute ischemic stroke patients 3 to 9 hours after symptom onset. Asymptomatic intracerebral hemorrhage, good clinical outcome at 90 days, and reperfusion 4 to 8 hours posttreatment were variables assessing efficacy; symptomatic intracerebral hemorrhage and death rates were measures of safety. RESULTS: Six trials involving 1071 patients thrombolyzed >3 hours postonset were included (600 received intravenous desmoteplase, 471 placebo). Desmoteplase was associated with increased reperfusion (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.10-2.24; P = .01 vs control) and showed a tendency to increase asymptomatic intracerebral hemorrhage (OR 1.25; 95% CI, 0.97-1.62; P = .09 vs control), whereas there was no increase in symptomatic intracerebral hemorrhage and death rate with desmoteplase. However, there was no difference in the clinical response at 90 days (OR 1.14; 95% CI, 0.88-1.49; P = .31 vs control). Subgroup analysis showed that desmoteplase 90 µg/kg (OR 1.53; 95% CI, 1.07-2.21; P = .02 vs control) and 125 µg/kg (OR 4.07; 95% CI, 1.16-14.24; P = .03 vs control) were associated with an increase in reperfusion. Also, we found desmoteplase 90 µg/kg showed a tendency to increase asymptomatic intracerebral hemorrhage (OR 1.25; 95% CI, 0.95-1.63; P = .11 vs control). CONCLUSION: Intravenous desmoteplase is associated with a favorable reperfusion efficacy and acceptable safety in ischemic stroke treatment >3 hours after symptom onset. Well-designed randomized controlled trials with larger patient cohorts and a moderate dose of drugs are needed to further evaluate the true efficacy of desmoteplase in stroke patients. TRIAL REGISTRATION: URL: http://www.crd.york.ac.uk/PROSPERO; PROSPERO registration number: CRD42016037667).

The evolution of recombinant thrombolytics: Current status and future directions.

Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration.

Desmoteplase 3 to 9 Hours After Major Artery Occlusion Stroke: The DIAS-4 Trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke).

BACKGROUND AND PURPOSE: The DIAS-3 trial (Efficacy and Safety Study of Desmoteplase to Treat Acute Ischemic Stroke [phase 3]) did not demonstrate a significant clinical benefit of desmoteplase administered 3 to 9 hours after stroke in patients with major artery occlusion. We present the results of the prematurely terminated DIAS-4 trial together with a post hoc pooled analysis of the concomitant DIAS-3, DIAS-4, and DIAS-J (Japan) trials to better understand the potential risks and benefits of intravenous desmoteplase for the treatment of ischemic stroke in an extended time window. METHODS: Ischemic stroke patients with occlusion/high-grade stenosis in major cerebral arteries were randomly assigned to intravenous treatment with desmoteplase (90 µg/kg) or placebo. The primary outcome was modified Rankin Scale (mRS) score of 0 to 2 at day 90. Safety assessments included mortality, symptomatic intracranial hemorrhage, and other serious adverse events. RESULTS: In DIAS-4, 52 of 124 (41.9%) desmoteplase-treated and 46 of 128 (35.9%) placebo-treated patients achieved an mRS score of 0 to 2 (odds ratio, 1.45; 95% confidence interval, 0.79; 2.64; P=0.23) with equal mortality, frequency of symptomatic intracranial hemorrhage, and other serious adverse events in both the treatment arms. In the pooled analysis, mRS score of 0 to 2 was achieved by 184 of 376 (48.9%) desmoteplase-treated versus 171 of 381 (44.9%) placebo-treated patients (odds ratio, 1.33; 95% confidence interval, 0.95; 1.85; P=0.096). Treatment with desmoteplase was safe and increased the recanalization rate (107/217 [49.3%] versus 85/222 [38.3%]; odds ratio, 1.59; 95% confidence interval, 1.08-2.35; P=0.019). Recanalization was associated with favorable outcomes (mRS 0-2) at day 90 in both the treatment arms. CONCLUSIONS: Late treatment with intravenous 90 µg/kg desmoteplase is safe, increases arterial recanalization, but does not significantly improve functional outcome at 3 months. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856661.

Cerebral infarction due to cardiac myxoma developed with the loss of consciousness immediately after defecation-a case report.

A 74-year-old man lost consciousness immediately after defecation. The loss of consciousness lasted for several minutes, and he experienced difficulty in walking when he regained consciousness. He was transferred to our hospital via an ambulance. Upon neurological examination, nystagmus and ataxia in the left arm and leg were noted. An MRI of the brain revealed multiple acute infarcts mainly in the bilateral cerebellum. Intravenous thrombolytic therapy with alteplase was initiated 3 h and 20 min after the onset of symptoms, and an improvement in neurological symptoms was observed. Echocardiography displayed a mobile mass in the left atrium, suggesting myxoma. After 14 days from the onset of symptoms, the tumor was surgically resected, and a pathological diagnosis of myxoma was established. Because of the unique event surrounding the onset in this case, we considered that there was a potential detachment of myxoma and/or thrombi fragments triggered by an increase in intrathoracic pressure induced by the action of defecation. This present case suggests that clinicians should consider cardiac myxoma in patients with cerebral infarction if the stroke is preceded by a Valsalva maneuver-like action and accompanied by the loss of consciousness.

Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin.

Thrombus formation leading to vaso-occlusive events is a major cause of death, and involves complex interactions between coagulation, fibrinolytic and innate immune systems. Leukocyte recruitment is a key step, mediated partly by chemotactic complement activation factors C3a and C5a. However, mechanisms mediating C3a/C5a generation during thrombosis have not been studied. In a murine venous thrombosis model, levels of thrombin-antithrombin complexes poorly correlated with C3a and C5a, excluding a central role for thrombin in C3a/C5a production. However, clot weight strongly correlated with C5a, suggesting processes triggered during thrombosis promote C5a generation. Since thrombosis elicits fibrinolysis, we hypothesized that plasmin activates C5 during thrombosis. In vitro, the catalytic efficiency of plasmin-mediated C5a generation greatly exceeded that of thrombin or factor Xa, but was similar to the recognized complement C5 convertases. Plasmin-activated C5 yielded a functional membrane attack complex (MAC). In an arterial thrombosis model, plasminogen activator administration increased C5a levels. Overall, these findings suggest plasmin bridges thrombosis and the immune response by liberating C5a and inducing MAC assembly. These new insights may lead to the development of strategies to limit thrombus formation and/or enhance resolution.

Safety and Tolerability of Desmoteplase Within 3 to 9 Hours After Symptoms Onset in Japanese Patients With Ischemic Stroke.

BACKGROUND AND PURPOSE: This study investigated the safety and tolerability of desmoteplase administered within 3 to 9 hours after stroke symptoms onset in Japanese patients with acute ischemic stroke. METHODS: Patients were randomized to treatment with either desmoteplase or placebo in a 2:1 ratio in 2 consecutive cohorts (70 µg/kg and then 90 µg/kg). Included patients had a baseline National Institutes of Health Stroke Scale score of 4 to 24 and occlusion or high-grade stenosis in the middle cerebral artery segment M1 or M2 on magnetic resonance angiography. The incidence of symptomatic intracranial hemorrhage (≤72 hours) was defined as the primary end point. The occurrence of asymptomatic ICH, symptomatic cerebral edemas, and adverse events were other safety outcomes of special interest. RESULTS: Symptomatic intracranial hemorrhage was observed within 72 hours in 2 patients treated with placebo and in 1 patient treated with 70 µg/kg desmoteplase. Any ICH (symptomatic or asymptomatic ICH) within 72 hours were observed in 7 (43.8%) patients treated with placebo, in 8 (50%) patients treated with 70 µg/kg desmoteplase, and in 9 (56.3%) patients treated with 90 µg/kg desmoteplase. Desmoteplase treatment with 70 or 90 µg/kg was not associated with an increased risk of symptomatic cerebral edema compared with placebo. There were no other serious safety concerns associated with desmoteplase. CONCLUSIONS: Desmoteplase in both 70 and 90 µg/kg doses had a favorable safety profile and was well tolerated in Japanese patients with acute ischemic stroke when administered 3 to 9 hours after stroke symptoms onset. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01104467.

Safety and efficacy of desmoteplase given 3-9 h after ischaemic stroke in patients with occlusion or high-grade stenosis in major cerebral arteries (DIAS-3): a double-blind, randomised, placebo-controlled phase 3 trial.

BACKGROUND: Current treatment of ischaemic stroke with thrombolytic therapy is restricted to 3-4·5 h after symptom onset. We aimed to assess the safety and efficacy of desmoteplase, a fibrin-dependent plasminogen activator, given between 3 h and 9 h after symptom onset in patients with occlusion or high-grade stenosis in major cerebral arteries. METHODS: In a prospective, double-blind, multicentre, parallel-group, randomised trial, we enrolled patients from 77 hospitals in 17 countries who had ischaemic stroke and occlusion or high-grade stenosis in major cerebral arteries. We randomly assigned patients in a 1:1 ratio, using computer-generated randomisation lists with stratification for baseline National Institutes of Health Stroke Scale and age, to treatment with desmoteplase (90 µg/kg) given 3-9 h after symptom onset or to placebo. Patients, investigators, staff, and the funder were masked to treatment assignment. The primary outcome was a favourable modified Rankin Scale score (0-2) at day 90 in all treated patients who had at least one postbaseline measurement of the modified Rankin Scale. Safety was assessed in all randomly assigned patients who received study drugs. This trial is registered with ClinicalTrials.gov, number NCT00790920. FINDINGS: Between Feb 6, 2009, and Nov 27, 2013, we enrolled 492 patients and randomly assigned 247 to desmoteplase and 245 to placebo (236 in the desmoteplase group and 237 in the placebo group were included in the analysis of the primary endpoint). Median time from stroke onset to treatment was 6·9 h (IQR 5·7-8·0) for placebo and 7·0 h (6·0-7·9) for desmoteplase. Modified Rankin Scale score (0-2) at day 90 occurred in 121 (51%) patients given desmoteplase and 118 (50%) patients given placebo (adjusted odds ratio 1·20, 95% CI 0·79-1·81, p=0·40). 24 (10%) of 240 patients given desmoteplase died compared with 23 (10%) of 238 patients given placebo. Serious adverse events occurred in 64 (27%) of 240 patients receiving desmoteplase compared with 69 (29%) of 238 patients receiving placebo; frequency of symptomatic intracranial haemorrhage (six [3%] patients in the desmoteplase group vs five [2%] in the placebo group), symptomatic cerebral oedema (five [2%] vs four [2%]), and major haemorrhage (ten [4%] vs 15 [6%]) was much the same between treatment groups. INTERPRETATION: Treatment with desmoteplase did not cause safety concerns and did not improve functional outcome when given to patients who had ischaemic stroke and major cerebral artery occlusion beyond 3 h of symptom onset. FUNDING: H Lundbeck A/S.

A case of neonatal myocardial infarction: left coronary artery thrombus resolution and normalisation of ventricular function by intracoronary low-dose tissue plasminogen activator.

Neonatal myocardial infarction is a rare clinical entity that is associated with high mortality. Reported treatment strategies include supportive care, extracorporeal membrane oxygenation, thrombolytics, and surgical thrombectomy. Herein we report a neonate who developed an acute myocardial infarction owing to a thrombus in the proximal left coronary artery. At 24 hours of life, he was treated with local (intracoronary) thrombolytic therapy at a lower dose than previously reported, as well as with systemic anticoagulation. There was subsequent angiographic resolution of the thrombus and normalisation of left ventricular function.

Safety and Effectiveness of Intravenous Thrombolysis with Recombinant Tissue Plasminogen Activator in 80 Years and Older Acute Ischemic Stroke Patients.

This study aims to explore the safety and efficacy of intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) in elderly (≥80 years old) acute ischemic stroke (AIS) patients. The clinical data of patients who were treated in Tianjin Huanhu Hospital from June 2012 to November 2013 were retrospectively analyzed; among them, 404 patients had received IVT with rt-PA and 200 patients had not received IVT. Among ≥80-year-old patients, 204 had received IVT and 200 had not. And the 404 patients who had received IVT were divided into two subgroups: elderly (≥80 years of age; n = 204) and controls (<80 years old; n = 200). The incidence of intracranial hemorrhage (ICH) and symptomatic intracranial hemorrhage, case fatality rate, and other prognostic indicators were compared. Among all ≥80-year-old patients, the IVT subgroup had significantly superior good outcome rates than the non-IVT subgroup at 24-h and 3-month along with significantly lower case fatality rate. But for the patients those who had received IVT, the incidence of ICH and the 7-day case fatality rate were not significantly increased in both the elderly and control subgroups. The 24-h and 3-month good outcome rates were not significantly different between these two subgroups as well. IVT with rt-PA is a safe and effective treatment for ≥80-year-old AIS patients.