Administration Of Tissue Plasminogen Activator Research Articles

What can the common fruit fly teach us about stroke?: lessons learned from the hypoxic tolerant Drosophila melanogaster.

Stroke, resulting in hypoxia and glucose deprivation, is a leading cause of death and disability worldwide. Presently, there are no treatments that reduce neuronal damage and preserve function aside from tissue plasminogen activator administration and rehabilitation therapy. Interestingly, Drosophila melanogaster, the common fruit fly, demonstrates robust hypoxic tolerance, characterized by minimal effects on survival and motor function following systemic hypoxia. Due to its organized brain, conserved neurotransmitter systems, and genetic similarity to humans and other mammals, uncovering the mechanisms of Drosophila's tolerance could be a promising approach for the development of new therapeutics. Interestingly, a key facet of hypoxic tolerance in Drosophila is organism-wide metabolic suppression, a response involving multiple genes and pathways. Specifically, studies have demonstrated that pathways associated with oxidative stress, insulin, hypoxia-inducible factors, NFκB, Wnt, Hippo, and Notch, all potentially contribute to Drosophila hypoxic tolerance. While manipulating the oxidative stress response and insulin signaling pathway has similar outcomes in Drosophila hypoxia and the mammalian middle cerebral artery occlusion (MCAO) model of ischemia, effects of Notch pathway manipulation differ between Drosophila and mammals. Additional research is warranted to further explore how other pathways implicated in hypoxic tolerance in Drosophila, such as NFκB, and Hippo, may be utilized to benefit mammalian response to ischemia. Together, these studies demonstrate that exploration of the hypoxic response in Drosophila may lead to new avenues of research for stroke treatment in humans.

Evaluating the effects of simulation training on stroke thrombolysis: a systematic review and meta-analysis

BackgroundIschaemic strokes are medical emergencies, and reperfusion treatment, most commonly intravenous thrombolysis, is time-critical. Thrombolysis administration relies on well-organised pathways of care with highly skilled and efficient clinicians. Simulation training is a widespread teaching modality, but results from studies on the impact of this intervention have yet to be synthesised. This systematic review and meta-analysis aimed to synthesise the evidence and provide a recommendation regarding the effects of simulation training for healthcare professionals on door-to-needle time in the emergency thrombolysis of patients with ischaemic stroke.MethodsSeven electronic databases were systematically searched (last updated 12th July 2023) for eligible full-text articles and conference abstracts. Results were screened for relevance by two independent reviewers. The primary outcome was door-to-needle time for recombinant tissue plasminogen activator administration in emergency patients with ischaemic stroke. The secondary outcomes were learner-centred, improvements in knowledge and communication, self-perceived usefulness of training, and feeling ‘safe’ in thrombolysis-related decision-making. Data were extracted, risk of study bias assessed, and analysis was performed using RevMan™ software (Web version 5.6.0, The Cochrane Collaboration). The quality of the evidence was assessed using the Medical Education Research Study Quality Instrument.ResultsEleven studies were included in the meta-analysis and nineteen in the qualitative synthesis (n = 20,189 total patients). There were statistically significant effects of simulation training in reducing door-to-needle time; mean difference of 15 min [95% confidence intervals (CI) 8 to 21 min]; in improving healthcare professionals’ acute stroke care knowledge; risk ratio (RR) 0.42 (95% CI 0.30 to 0.60); and in feeling ‘safe’ in thrombolysis-related decision-making; RR 0.46 (95% CI 0.36 to 0.59). Furthermore, simulation training improved healthcare professionals' communication and was self-perceived as useful training.ConclusionThis meta-analysis showed that simulation training improves door-to-needle times for the delivery of thrombolysis in ischaemic stroke. However, results should be interpreted with caution due to the heterogeneity of the included studies.

Priming and Combined Strategies for the Application of Mesenchymal Stem Cells in Ischemic Stroke: A Promising Approach.

Ischemic stroke (IS) is a leading cause of death and disability worldwide. Tissue plasminogen activator (tPA) administration and mechanical thrombectomy are the main treatments but have a narrow time window. Mesenchymal stem cells (MSCs), which are easily scalable in vitro and lack ethical concerns, possess the potential to differentiate into various types of cells and secrete a great number of growth factors for neuroprotection and regeneration. Moreover, MSCs have low immunogenicity and tumorigenic properties, showing safety and preliminary efficacy both in preclinical studies and clinical trials of IS. However, it is unlikely that MSC treatment alone will be sufficient to maximize recovery due to the low survival rate of transplanted cells and various mechanisms of ischemic brain damage in the different stages of IS. Preconditioning was used to facilitate the homing, survival, and secretion ability of the grafted MSCs in the ischemic region, while combination therapies are alternatives that can maximize the treatment effects, focusing on multiple therapeutic targets to promote stroke recovery. In this case, the combination therapy can yield a synergistic effect. In this review, we summarize the type of MSCs, preconditioning methods, and combined strategies as well as their therapeutic mechanism in the treatment of IS to accelerate the transformation from basic research to clinical application.

Factors affecting improvement after intravenous administration of recombinant tissue plasminogen activator (rtPA) among patients with acute ischemic stroke: A historical cohort study.

One of the most effective treatments for patients with acute ischemic stroke (AIS) is intravenous recombinant tissue plasminogen activator (rtPA) which can minimize mortality and morbidities. In this historical cohort study, we investigate the factors affecting clinical outcomes after IV thrombolysis for AIS. We included 87 patients with acute ischemic stroke who were treated with rtPA between 2015 and 2019. Demographic and clinical data were recorded. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the clinical outcomes. 36 patients showed lack of improvement at discharge. In unadjusted model, hypercholesterolemia was the only predictor of lack of improvement (P= 0.043; OR=0.304; CI= 0.096-0.963). After adjusting, hypertension (P= 0.018; OR= 0.18; CI= 0.043-0.749) and hypercholesterolemia (P= 0.008; OR= 8.68; CI= 1.773-42.54) were independent determinants of lack of clinical response. To evaluate risk factors in association with the duration of hospitalization, we found variables which lengthened hospitalization span including; age over 60 years (HR= 0.42 P= 0.002), hypercholesterolemia (HR= 2.19 P= 0.031), Angiotensin-converting enzyme (ACE) Inhibitors consumption (HR= 1.87 P= 0.022), and type of infarction (non-lacunar) (HR= 0.51 P= 0.026). Results indicated no considerable relationship between dose of rtPA and the appropriate response to treatment (OR=8.686 P= 0.324). The closer dose of rtPA goes up to standard range, the more chance of improvement will gain without increasing the risk of symptomatic intra-cerebral hemorrhage (SICH). Determining factors involved in intravenous reperfusion outcomes help physicians to identify the patients who benefit the most from rtPA.

Impact of Successful Recanalization and Clinical Outcomes of Patients With Acute Ischemic Stroke with 5 or More Thrombectomy Passes

Background As the number of thrombectomy passes increases during endovascular therapy (EVT) for acute stroke, neurointerventionalists must weigh the risks of potential complications against the risk of failing to recanalize the affected vessel. Thus, we investigated the effectiveness and safety of EVT for patients with acute stroke in which ≥5 EVT passes were performed. Methods This retrospective cohort study from January 2013 to December 2022 included 31 thrombectomy‐capable centers. Patients in whom ≥5 EVT passes were made were included in the analysis. The patients with successful recanalization defined as modified Thrombolysis in Cerebral Infarction ≥2b at 5, 6, 7, or more passes were compared with unsuccessful recanalization. We also compared procedure time, separated by 30 minutes. Primary outcome was a favorable 90‐day outcome (modified Rankin scale score of 0–2). Secondary outcomes were intracranial hemorrhage and death. Results A total of 407 patients met the inclusion criteria, of which 175 were women (43.1%); the mean age was 67.3 years. In 265 (65.1%) patients, successful recanalization was achieved: 134 patients with 5 passes, 67 patients with 6 passes, and 64 with ≥7 passes. Intravenous recombinant tissue plasminogen activator administration was more common in the unsuccessful recanalization group (successful recanalization with 5, 6, and ≥7 EVT passes and unsuccessful recanalization: 35.3%, 30.3%, 18.8%, and 45.4%, respectively). Successful recanalization with 5, 6, and ≥7 EVT passes was associated with favorable outcome compared with unsuccessful recanalization group (adjusted odds ratio successful recanalization with 5, 6, and ≥7 EVT passes to unsuccessful recanalization [95% CIs]: 8.29 [2.13–32.3]; 14.0 [3.27–60.3]; and 5.26 [1.12–24.8], respectively). However, symptomatic intracranial hemorrhage was not significantly different between the groups. Regarding procedure time, favorable outcome was not significantly different in each group, while symptomatic intracranial hemorrhage occurred more frequently in the 60 to 89 minutes group compared with the <30 minutes group (adjusted odds ratio, 60–89 minutes group to <30 minutes group [95% CI]: 5.86 [1.09–31.6]). Conclusion These findings suggest that a benefit in outcome persists for recanalization, without significant increase in complications. In addition, there was no significant difference in favorable outcomes among procedure time.

A Successful Treatment Approach in 2 Patients With Type 1 Plasminogen Deficiency: Intratracheal Application of Fresh Frozen Plasma and Tissue Plasminogen Activator.

Respiratory system involvement is common in congenital plasminogen deficiency. Although many treatment approaches have been tried, there is still no definitive treatment for respiratory system involvement. We report 2 congenital plasminogen deficiency cases, who presented with severe respiratory symptoms, for whom a novel treatment modality was tried. After intravenous administration of FFP (fresh frozen plasma), tissue plasminogen activator and FFP were administered intratracheally, and respiratory system findings improved. Intratracheal administration of tissue plasminogen activator and FFP is an available treatment modality for patients with lung involvement. Fibrin plaques should be carefully removed and new lesion formation should be prevented.

Способ малоинвазивной транслокации организовавшегося субфовеального кровоизлияния

Purpose. To present a method of minimally invasive surgery, including two-port 27G surgery with controlled administration of a solution of recombinant prourokinase in a patient with organized submacular hemorrhage (SMH). Material and methods. A patient with SMH lasting for 30 days underwent a procedure developed on the basis of the N.I. Pirogov National Medical Surgical Center. It's a minimally invasive technique that includes a two-port 27G access without vitrectomy with controlled administration of a solution of recombinant prourokinase 500 ME through a 38G cannula subretinally, followed by tamponade of the vitreal cavity with a 20 % gasair mixture of hexafluoroethane C2F6. A standard ophthalmological examination was performed before the start of treatment, on the 1st day, 2 weeks later, 6 months after vitreoretinal intervention. Results. Visual acuity was 0.1 at the initial examination and 0.05 upon admission to the surgical hospital. Follow-up showed an increase in visual function to 0.3 at 1 month and to 0.5 at 6 months with antivasoproliferative therapy. According to optical coherence tomography at the initial examination, the central retinal thickness (CRT) was 642 µm, followed by a depression of up to 451 µm by the time of hospitalization. On the 14th day, the decrease in CRT reached 267 µm with complete translocation of the hemorrhage and 243 µm after 6 months. The height of detachment of the retinal pigment epithelium at the initial examination showed a value of 167 µm, and at subsequent observation it was 45 µm, 38 µm and 12 µm on the 1st, 14th day and after 6 months, respectively. Against the background of anatomical results, there was a decrease in the zone of absolute scotoma from 25 loci at the time of admission to 3 loci after 6 months, and an increase in total photosensitivity from 4.5 dB to 15.6 dB, respectively. Conclusion. The use of a minimally invasive method for the treatment of SMH, including subretinal administration of tissue plasminogen activator without vitrectomy with gas-air tamponade, improves morphological and functional prognosis. However, further study of the proposed technique on long-term hemorrhages is required. Keywords: submacular hemorrhage, tissue plasminogen activator, pneumodislocation

P.058 Reasons for withholding tissue Plasminogen Activator (tPA) administration during the COVID-19 pandemic at a tertiary stroke centre

Background: Stroke is a leading cause of death and disability worldwide, including Canada. Treatments for stroke are time dependent and IV tPA for acute ischemic stroke decreases the chance of disability at 90 days if given within 4.5 hours of symptom onset. The onset of the Covid-19 pandemic was initially associated with a decrease in acute stroke treatment with thrombolysis across North America. These decreases seemed transient, with a rebound in numbers seen in other provinces across Canada as widespread lockdown orders were lifted. However, a rebound in thrombolysis was not seen at Royal University Hospital (RUH) in Saskatoon, Saskatchewan during the same period. We will analyze documented reasons why thrombolysis was withheld. Methods: We conducted a retrospective chart review of adult patients with ischemic strokes presenting within 4.5 hours of symptom onset to the RUH from March 2019 –January 2021. We received a waiver of consent from the Research Ethics Board. Results: 128 patients met the inclusion criteria. Statistical analysis is currently ongoing. Conclusions: Initial results suggest that there are similar reasons for withholding tPA before and after the Covid-19 pandemic. The main reasons include rapidly resolving/resolved symptoms and a documented tPA exclusion criterion.

Central Line Patency: Management With Normal Saline Flushes for Adult Patients With Cancer.

Central venous catheter (CVC) maintenance is critical in administering chemotherapy, transfusions, and high-frequency laboratory draws. Although normal saline (NS) flushes have been associated with similar incidences of irreversible port occlusions as heparin among adult patients with cancer and ports, additional research is needed regarding NS efficacy in other central line maintenance within large populations with cancer. The aim of this study was to analyze changes in reported CVC line patency via tissue plasminogen activator (tPA) administration rates in ports and other central lines because of an institutional switch from heparin to NS as preferred flushes in adult ambulatory patients with cancer. Retrospective data were collected from patients with ports (3,706 prepolicy, 3,402 postpolicy) and nonport CVCs (816 prepolicy, 694 postpolicy). Patients with nonport CVCs experienced similar tPA usage pre- versus postpolicy, versus an increased rate of tPA usage for ports. This policy resulted in institutional savings of $28,695.92. NS flushes are as effective as heparin for maintaining patency in ports and other CVCs for adult outpatients with cancer and address safety concerns with heparin-associated complications.

Reduced-Dose Systemic Fibrinolysis in Massive Pulmonary Embolism: A Pilot Study.

Severe pulmonary embolism (PE) has a high mortality rate, which can be lowered by thrombolytic therapy (TT). However, full-dose TT is associated with major complications, including life-threatening bleeding. The aim of this study was to explore the efficacy and safety of extended, low-dose administration of tissue plasminogen activator (tPA) on in-hospital mortality and outcomes in massive PE. This was a single-center, prospective cohort trial at a tertiary university hospital. A total of 37 consecutive patients with massive PE were included. A peripheral intravenous infusion was used to administer 25 mg of tPA over 6 hours. The primary endpoints were in-hospital mortality, major complications, pulmonary hypertension, and right ventricular dysfunction. The secondary endpoints were 6-month mortality and pulmonary hypertension and right ventricular dysfunction 6 months after the PE. The mean age of the patients was 68.76±14.54 years. The mean pulmonary artery systolic pressure (PASP; 56.51±7.34 mmHg vs. 34.16±2.81 mmHg, P<0.001) and right/left ventricle diameter (1.37±0.12 vs. 0.99±0.12, P<0.001) decreased significantly after TT. Tricuspid annular plane systolic excursion (1.43±0.33 cm vs. 2.07±0.27 cm, P<0.001), myocardial performance index (0.47±0.08 vs. 0.55±0.07, P<0.001), and systolic wave prime (9.6±2.8 vs. 15.3±2.6) increased significantly after TT. No major bleeding or stroke was observed. There was one in-hospital death and two additional deaths within 6 months. No cases of pulmonary hypertension were identified during follow-up. The results of this pilot study suggest that an extended infusion of low-dose tPA is a safe and effective therapy in patients with massive PE. This protocol was also effective in decreasing PASP and restoring right ventricular function.

Малоинвазивное хирургическое лечение организовавшегося субмакулярного кровоизлияния

Purpose. To present a method of minimally invasive surgery, including two-port 27G surgery with controlled administration of a solution of recombinant prourokinase in a patient with organized submacular hemorrhage (SMH). Material and methods. A patient with SMC lasting 30 days underwent a procedure developed on the basis of the Center for Ophthalmology «N.M. N.I. Pirogov» is a minimally invasive technique that includes a two-port 27G access without vitreectomy with controlled administration of a solution of recombinant prourokinase 500 ME through a 38G cannula subretinally, followed by tamponade of the vitreal cavity with a 20% gas-air mixture of hexafluoroethane C2F6. A standard ophthalmological examination was performed before the start of treatment, on the 1st day, 2 weeks later, 6 months after vitreoretinal intervention. Results. Visual acuity was 0.1 at the initial examination and 0.05 upon admission to the surgical hospital. Follow-up showed an increase in visual function to 0.3 at 1 month and to 0.5 at 6 months with antivasoproliferative therapy. According to optical coherence tomography at the initial examination, the central retinal thickness (CRT) was 642 µm, followed by a depression of up to 451 µm by the time of hospitalization. On the 14th day, the decrease in CRT reached 267 µm with complete translocation of the hemorrhage and 243 µm after 6 months. The height of detachment of the retinal pigment epithelium at the initial examination showed a value of 167 µm, and at subsequent observation it was 45 µm, 38 µm and 12 µm on the 1st, 14th day and after 6 months, respectively. Against the background of anatomical results, there was a decrease in the zone of absolute scotoma from 25 loci at the time of admission to 3 loci after 6 months, and an increase in total photosensitivity from 4.5 dB to 15.6 dB, respectively. Conclusion. The use of a minimally invasive method for the treatment of SMH, including subretinal administration of tissue plasminogen activator without vitreectomy with gas-air tamponade, improves morphological and functional prognosis. However, further study of the proposed technique on long-term hemorrhages is required. Key words: submacular hemorrhage, tissue plasminogen activator, pneumodislocation

The gut-brain connection: Inflammatory bowel disease increases risk of acute ischemic stroke.

Chronic inflammation of the gastrointestinal tract is a hallmark of inflammatory bowel disease (IBD). This increased inflammation is thought to induce a hypercoagulable state that increases the risk for stroke. However, few studies have examined the association between IBD and acute ischemic stroke (AIS). Thus, this study aims to investigate the incidence, treatments, complications, and outcomes of AIS in patients with IBD. ICD-9-CM and ICD-10-CM codes were used to query the National Inpatient Sample for AIS and IBD diagnosis. Baseline demographics, clinical characteristics, complications, treatments, and outcomes were assessed through descriptive statistics, multivariate regression, and propensity score matching (PSM) analysis. Acute stroke severity was assessed using the National Institute of Heath's Stroke Severity Score (SSS) as a template. 1,609,817 patients were diagnosed with AIS between 2010 through 2019. 7468 (0.46%) had concomitant diagnoses of IBD. AIS patients with IBS were younger, more likely to be white and female, but less likely to be obese. Although IBD patients had comparable stroke severities (p = 0.64) to their non-IBS counterparts, they received stroke intervention at statistically different rates than their non-IBD counterparts. Additionally, IBD patients had higher rates of in-hospital complications (p < 0.01) and longer lengths of stay (LOS) (p < 0.01). IBD patients develop AIS at a younger age with similar rates of stroke severity to their non-IBD counterparts, but receive higher rates of tissue plasminogen activator administration and decreased rates of mechanical thrombectomy. Our research shows that patients with IBD are at risk for AIS at an earlier age and are more likely to have complications. This underlies a connection between IBD and a hypercoagulable state that could predispose patients to AIS.

Intrapleural tissue plasminogen activator and deoxyribonuclease administered concurrently and once daily for complex parapneumonic pleural effusion and empyema.

Pleural infection is life-threatening and increasingly prevalent. In addition to usual care, twice-daily, separate administration of tissue plasminogen activator and deoxyribonuclease (tPA-DNase) reduces radiological pleural opacity with lower surgical referral rates. This retrospective cohort study examines the use of once-daily, concurrent administration of tPA-DNase for complex parapneumonic pleural effusion and empyema. Patients with pleural infection who received intrapleural tPA-DNase between October 2014 and July 2020 at Logan Hospital, where it is given concurrently and once-daily as salvage therapy, were retrospectively identified. Radiographic opacification, inflammatory markers, clinical response and complications were examined. Thirty-one patients were identified. Mean age was 48.8 years (standard deviation [SD], 17.2). Median tPA-DNase administration was 3 (interquartile range [IQR], 2-3). Chest x-ray pleural opacity decreased significantly (P = 0.047) from a median of 39.6% (IQR, 28.8-65.7%) to 9.7% (IQR, 2.5-23.2%), a median relative reduction of 75.5% (IQR, 47.7-93.9%). White cell count and C-reactive protein improved significantly (P = 0.002 and P = 0.032, respectively) from a median of 16.3 × 109 /L (IQR, 11.8-20.6 × 109 /L) to 9.9 × 109 /L (IQR, 8.0-12.3 × 109 /L) and 311.0 mg/L (IQR, 218.8-374.0 mg/L) to 69.0 mg/L (IQR, 36.0-118.0 mg/L), respectively. No patients experienced significant bleeding or died. Five patients (16.1%) were referred for surgery. This is pilot evidence that a practical regimen of concurrent, once-daily intrapleural tPA-DNase improved pleural opacification and inflammatory markers without bleeding or mortality. The surgical referral rate was higher than in studies assessing twice-daily administration, though the validity of this outcome as a measure of treatment success is limited, and further studies are needed to assess the optimal dose and frequency of intrapleural therapy and indications for surgical referral.

Intravenous tPA administration in patients with negative diffusion-weighted imaging (DWI) study on the MRI brain (P1-4.006)

<h3>Objective:</h3> To identify and analyze the clinical characteristics of the patients that had stroke-like symptoms (stroke mimics) on presentation and received IV tPA but subsequently were found not to have an ischemic stroke. <h3>Background:</h3> Intravenous tissue plasminogen activator (tPA) administration within 4.5 hours of last known normal to the patients presenting with symptoms of stroke is the standard of care. Stroke mimics are a diverse group that is difficult to identify. They present with acute-onset focal neurological deficits, however further work up including MRI (magnetic resonance imaging) of the brain show no evidence of stroke or TIA. The aim of our study is to identify such patients and understand their clinical characteristics. <h3>Design/Methods:</h3> We retrospectively reviewed the medical records and analyzed all the patients in a span of one year that presented with stroke like symptoms and received IV tPA. <h3>Results:</h3> We identified a total of 107 pts that received tPA in a span of year at our institute. Among them there were 11 patients that showed no changes in the DWI sequence of MRI imaging and did not have stroke as their discharge diagnosis. Overall, we found that stroke mimics compromise 10.2 % of the pts that got administered tPA. The age of this group ranged from 38–73. There were seven women and four men. The NIHSS at the time of presentation ranged from 3–19. We identified three patients with hypertensive crisis, two with cervical radiculopathy, two with suspicion of conversion disorder: one each with normal pressure hydrocephalus, sepsis with neurosyphilis, pulmonary embolism with aortic regurgitation and methamphetamine abuse. Majority of them presented with unilateral weakness along with facial weakness and speech difficulties. <h3>Conclusions:</h3> We conclude that in our patient population, only few patients were found to be stroke mimics. <b>Disclosure:</b> Dr. Badugu has nothing to disclose. Dr. PANDEY has nothing to disclose. Dr. Chappidi has nothing to disclose. Dr. Kelley has nothing to disclose.

Nanotechnology in Stroke: New Trails with Smaller Scales.

Stroke is a leading cause of death, long-term disability, and socioeconomic costs, highlighting the urgent need for effective treatment. During acute phase, intravenous administration of recombinant tissue plasminogen activator (tPA), a thrombolytic agent, and endovascular thrombectomy (EVT), a mechanical intervention to retrieve clots, are the only FDA-approved treatments to re-establish cerebral blood flow. Due to a short therapeutic time window and high potential risk of cerebral hemorrhage, a limited number of acute stroke patients benefit from tPA treatment. EVT can be performed within an extended time window, but such intervention is performed only in patients with occlusion in a larger, anatomically more proximal vasculature and is carried out at specialty centers. Regardless of the method, in case of successful recanalization, ischemia-reperfusion injury represents an additional challenge. Further, tPA disrupts the blood-brain barrier integrity and is neurotoxic, aggravating reperfusion injury. Nanoparticle-based approaches have the potential to circumvent some of the above issues and develop a thrombolytic agent that can be administered safely beyond the time window for tPA treatment. Different attributes of nanoparticles are also being explored to develop a multifunctional thrombolytic agent that, in addition to a thrombolytic agent, can contain therapeutics such as an anti-inflammatory, antioxidant, neuro/vasoprotective, or imaging agent, i.e., a theragnostic agent. The focus of this review is to highlight these advances as they relate to cerebrovascular conditions to improve clinical outcomes in stroke patients.

Recanalization Rate and Clinical Outcomes of Intravenous Tissue Plasminogen Activator Administration for Large Vessel Occlusion Stroke Patients.

Stroke caused from large vessel occlusion (LVO) has emerged as the most common stroke subtype worldwide. Intravenous tissue plasminogen activator administration (IV-tPA) and additional intraarterial thrombectomy (IA-Tx) is regarded as standard treatment. In this study, the authors try to find the early recanalization rate of IV-tPA in LVO stroke patients. Total 300 patients undertook IA-Tx with confirmed anterior circulation LVO, were analyzed retrospectively. Brain computed tomography angiography (CTA) was the initial imaging study and acute stroke magnetic resonance angiography (MRA) followed after finished IV-tPA. Early recanalization rate was evaluated by acute stroke MRA within 2 hours after the IV-tPA. In 167 patients undertook IV-tPA only and 133 non-recanalized patients by IV-tPA, additional IA-Tx tried (IV-tPA + IA-Tx group). And 131 patients, non-recanalized by IV-tPA (IV-tPA group) additional IA-Tx recommend and tried according to the patient condition and compliance. Early recanalization rate of LVO after IV-tPA was 12.0% (36/300). In recanalized patients, favorable outcome (modified Rankin Scale, 0-2) was 69.4% (25/36) while it was 32.1% (42/131, p<0.001) in non-recanalized patients. Among 133 patients, nonrecanalized after intravenous recombinant tissue plasminogen activator and undertook additional IA-Tx, the clinical outcome was better than not undertaken additional IA-Tx (favorable outcome was 42.9% vs. 32.1%, p=0.046). Analysis according to the perfusion/diffusion (P/D)-mismatching or not, in patient with IV-tPA with IA-Tx (133 patients), favorable outcome was higher in P/ D-mismatching patient (52/104; 50.0%) than P/D-matching patients (5/29; 17.2%; p=0.001). Which treatment tired, P/D-mismatching was favored in clinical outcome (iv-tPA only, p=0.008 and IV-tPA with IA-Tx, p=0.001). The P/D-mismatching influences on the recanalization and clinical outcomes of IV-tPA and IA-Tx. The authors would like to propose that we had better prepare IA-Tx when LVO is diagnosed on initial diagnostic imaging. Furthermore, if the patient shows P/D-mismatching on MRA after IV-tPA, additional IA-Tx improves treatment results and lessen the futile recanalization.

Efficacy Evaluation of Tissue Plasminogen Activator with Anti-Vascular Endothelial Growth Factor Drugs for Submacular Hemorrhage Treatment: A Meta-Analysis.

Submacular hemorrhage (SMH) is the accumulation of blood in the macular area that can severely damage the macular structure and visual function. Recently, the intraocular administration of tissue plasminogen activator (TPA) with anti-vascular endothelial growth factor (anti-VEGF) drugs was reported to have a positive effect on SMH. This meta-analysis aimed to explore the efficacy and safety of the drug combination. We systematically searched the Web of Science, MEDLINE, EMBASE, and Cochrane Library databases and screened relevant full-length literature reports. The quality of the reports was assessed by two independent reviewers. The best-corrected visual acuity (BCVA) and foveal thickness (FT) were considered the main indicators of efficacy. RevMan 5.4 software was used for this meta-analysis. Twelve studies were analyzed, and the results showed that BCVA at 1 month (p < 0.001), 3 months (p < 0.001), 6 months (p < 0.001), and the last follow-up (p < 0.001) was improved relative to the preoperative value. The postoperative FT was lower than the preoperative FT (p < 0.001). No significant difference in efficacy was observed between subretinal and intravitreal TPA injections (p = 0.37). TPA with anti-VEGF drugs is safe for SMH treatment and can significantly improve BCVA and reduce FT.

Reverse Translation to Develop Post-stroke Therapeutic Interventions during Mechanical Thrombectomy: Lessons from the BACTRAC Trial.

The majority of strokes, approximately 87%, are ischemic in etiology with the remaining hemorrhagic in origin. Emergent large vessel occlusions (ELVOs) are a subtype of ischemic stroke accounting for approximately 30-40% of acute large vessel blockages. Treatment for ELVOs focuses on recanalization of the occluded vessel by time-sensitive administration of tissue plasminogen activator (tPA) or thrombus removal using mechanical thrombectomy. Although a great deal of time and resources have focused on translational stroke research, little progress has been made in the area of identifying additional new treatments for stroke. Translational limitations include difficulty simulating human comorbid conditions in animal models, as well as the temporal nature of stroke pathology. The Blood And Clot Thrombectomy Registry And Collaboration represents an ongoing tissue registry for thrombectomy patients and includes collection of intracranial arterial blood, systemic arterial blood, thrombi, as well as a series of clinical and radiographic data points for analysis. This chapter will explore the methodologies employed and results obtained from studying BACTRAC-derived human biological specimens and how they can inform translational experimental design in animal studies.

Alteplase associated Orolingual angioedema: A case report and literature review

Orolingual angioedema (OA) is a rare but life-threatening complication of intravenous thrombolysis using alteplase. Angioedema can be caused by almost any medication. Administration of recombinant tissue plasminogen activator causes atypical angioedema. This study aimed to investigate factors related to and treatment of OA after thrombolysis with alteplase. We describe the case of a 53-year-old man with a history of hypertension managed with enalapril, who presented with ischemic cerebrovascular stroke. Intravenous alteplase was administered, and within 54 minutes, the patient developed severe orolingual edema requiring emergent intubation. Subsequent imaging revealed an acute-to-subacute infarct in the left occipital lobe of the posterior cerebral artery. The most common factor for increased risk of OA after recombinant tissue plasminogen activator was concomitant use of angiotensin-converting enzyme inhibitors (ACEI). Before intravenous thrombolytic therapy, patients should be asked if they have a history of allergies, are currently using ACEI, and try to avoid using ACEI antihypertensive drugs before and after thrombolytic therapy.

Neutrophilic noncoding RNAs predict outcomes of acute ischemic stroke patients treated with recombinant tissue plasminogen activator.

There’s no evidence demonstrating the association between noncoding RNAs levels before IV recombinant tissue plasminogen activator (rtPA) administration and the outcomes of acute ischemic stroke (AIS). 145 AIS patients received rtPA treatment were recruited at the stroke center from 2018 to 2019, and 103 patients were included in this study. A panel of noncoding RNAs (miRNA-23a, miRNA-193a, miRNA-128, miRNA-99a, miRNA-let-7a, miRNA-494, miRNA-424, and lncRNA H19) were measured in the circulating neutrophils of AIS patients before rtPA treatment. Endpoints included excellent outcome (modified Rankin Scale score [mRS] 0–1) or poor outcome (mRS > 1) at 3 months and symptomatic intracerebral hemorrhage (sICH) after rtPA treatment. Among the eight noncoding RNAs detected in circulating neutrophils of the 103 participants, miRNA-23a levels were associated with the stroke severity on admission and symptom progression at 24 h after rtPA treatment. A noncoding RNA score composed of miRNA-23a, miRNA-99a, and lncRNA H19 was screened to predict the functional outcome at 3 months and the incidence of sICH after rtPA treatment. In the logistic regression analysis, the noncoding RNA score ≥ −0.336 (OR = 2.862 [1.029–7.958], p = 0.044) was an independent predictor of the poor outcome at 3 months after adjustment of clinical variables, the addition of the noncoding RNA score to the clinical model improved the discrimination (IDI% = 4.68 [0.65–8.71], p = 0.020), as well as the net reclassification (NRI% = 33.04 [0.54–71.49], p = 0.016). The noncoding RNA score ≥ −0.336 (OR = 5.250 [1.096–25.135], p = 0.038) was also independently predicted the sICH, the addition of the noncoding RNA score to the clinical variables improved discrimination and reclassification as well. The noncoding RNA score was also associated with the infarct volume and symptom improvement at 7 days after rtPA treatment. In conclusion, a higher neutrophilic noncoding RNA score provides predictive value to identify AIS patients with worse outcomes after rtPA treatment. miRNA-23a, miRNA-99a, and lncRNA H19 are worth further investigation for their effects in thrombolysis after AIS.