Correlation between subretinal tissue plasminogen activator and air injection rates with pressure in a retina mimicking model.

By investigating the correlation between the injection rate and pressure of subretinal tissue plasminogen activator (tPA) and air using a standard Viscous Fluid Control (VFC) system with a 38-gauge cannula, we aimed to establish guidelines for stable injections. We fabricated a retina mimicking model (RMM) with 0.25% agarose solution and an aluminum plate, and substituted submacular hemorrhage (SMH) and tPA with blood-mimicking fluid (BMF) and balanced salt solution (BSS), respectively. The diameter of the pre-bleb mimicking SMH in RMM was 1.30 ± 0.16 cm, increasing to 1.98 ± 0.24 cm and 1.83 ± 0.22 cm after bleb propagation with BSS and air, respectively. BSS injection rates were 2.86 ± 0.04 µl/sec, 6.74 ± 0.48 µl/sec and 8.55 ± 0.16 µl/sec at 8, 12, and 16 psi, respectively. Air injection rates were 37.98 ± 3.11 µl/sec, 79.01 ± 5.13 µl/sec and 156.06 ± 13.72 µl/sec at 2, 3 and 4 psi, respectively. By experimenting with different pressures in the RMM, we found 12 psi to be the minimum for proper BSS injection and 2 psi for air. These findings provide crucial parameters for safer surgery to prevent irreversible damage.

Tenecteplase versus alteplase for acute stroke within 4·5 h of onset (ATTEST-2): a randomised, parallel group, open-label trial.

BACKGROUND: Tenecteplase has potential benefits over alteplase, the standard agent for intravenous thrombolysis in acute ischaemic stroke, because it is administered as a single bolus and might have superior efficacy. The ATTEST-2 trial investigated whether tenecteplase was non-inferior or superior to alteplase within 4·5 h of onset. METHODS: We undertook a prospective, randomised, parallel-group, open-label trial with masked endpoint evaluation in 39 UK stroke centres. Previously independent adults with acute ischaemic stroke, eligible for intravenous thrombolysis less than 4·5 h from last known well, were randomly assigned 1:1 to receive intravenous alteplase 0·9 mg/kg or tenecteplase 0·25 mg/kg, by use of a telephone-based interactive voice response system. The primary endpoint was the distribution of the day 90 modified Rankin Scale (mRS) score and was analysed using ordinal logistic regression in the modified intention-to-treat population. We tested the primary outcome for non-inferiority (odds ratio for tenecteplase vs alteplase non-inferiority limit of 0·75), and for superiority if non-inferiority was confirmed. Safety outcomes were mortality, symptomatic intracranial haemorrhage, radiological intracranial haemorrhage, and major extracranial bleeding. The trial was prospectively registered on ClinicalTrials.gov (NCT02814409). FINDINGS: Between Jan 25, 2017, and May 30, 2023, 1858 patients were randomly assigned to a treatment group, of whom 1777 received thrombolytic treatment and were included in the modified intention-to-treat population (n=885 allocated tenecteplase and n=892 allocated alteplase). The mean age of participants was 70·4 (SD 12·9) years and median National Institutes of Health Stroke Scale was 7 (IQR 5-13) at baseline. Tenecteplase was non-inferior to alteplase for mRS score distribution at 90 days, but was not superior (odds ratio 1·07; 95% CI 0·90-1·27; p value for non-inferiority<0·0001; p=0·43 for superiority). 68 (8%) patients in the tenecteplase group compared with 75 (8%) patients in the alteplase group died, symptomatic intracerebral haemorrhage (defined by SITS-MOST criteria) occurred in 20 (2%) versus 15 (2%) patients, parenchymal haematoma type 2 occurred in 37 (4%) versus 26 (3%) patients, post-treatment intracranial bleed occurred in 94 (11%) versus 78 (9%) patients, significant extracranial haemorrhage occurred in 13 (1%) versus six (1%) patients, respectively, and angioedema occurred in six (1%) participants in both groups. INTERPRETATION: Tenecteplase 0·25 mg/kg was non-inferior to 0·9 mg/kg alteplase within 4·5 h of symptom onset in acute ischaemic stroke. Easier administration of tenecteplase, especially in the context of interhospital transfers, indicates that tenecteplase should be preferred to alteplase for thrombolysis in acute ischaemic stroke. The ATTEST-2 population was large and representative of thrombolysis-eligible patients in the UK and, together with findings from other trials, provides robust evidence supporting the introduction of tenecteplase in preference to alteplase. FUNDING: The Stroke Association and British Heart Foundation.

Tenecteplase vs Alteplase in Acute Ischemic Stroke Within 4.5 Hours: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND AND OBJECTIVES: The current European Stroke Organisation expedited recommendation on tenecteplase (TNK) for acute ischemic stroke (AIS) advocates that TNK 0.25 mg/kg can be used alternatively to alteplase (tissue plasminogen activator [TPA]) for AIS of <4.5 hours duration, based on a meta-analytical approach establishing noninferiority. Since the publication of these guidelines, 4 additional randomized controlled clinical trials (RCTs) have provided further insight. METHODS: We conducted an updated systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of TNK 0.25 mg/kg compared with TPA for the treatment of AIS within 4.5 hours of onset. The primary outcome was defined as the excellent functional outcome at 3 months (modified Rankin Scale [mRS] score 0-1), whereas good functional outcome (mRS score 0-2), reduced disability at 3 months (≥1-point reduction across all mRS scores), symptomatic intracranial hemorrhage (sICH), and 3-month mortality were evaluated as secondary outcomes. Pooled estimates were calculated with random-effects model. A prespecified subgroup analysis was performed stratifying for TNK formulation, that is, original TNK vs biocopy: recombinant human TNK tissue-type plasminogen activator that is available in China and has a different production process. RESULTS: Eleven RCTs were included comprising a total of 3,788 patients treated with TNK vs 3,757 patients treated with TPA. TNK was associated with higher likelihood of excellent functional outcome (risk ratio [RR] 1.05, 95% CI 1.01-1.10; p = 0.012; I2 = 0%; risk difference 2.95%; 95% CI 0.76%-5.14%; p = 0.008; I2 = 0%) and reduced disability at 3 months (common odds ratio 1.10, 95% CI 1.01-1.19; p = 0.034; I2 = 0%) compared with TPA while good functional outcome (RR 1.03, 95% CI 0.99-1.07; p = 0.142; I2 = 28%) was similar between the groups. Regarding safety outcomes, similar rates of sICH (RR 1.12, 95% CI 0.83-1.53; p = 0.456; I2 = 0%) and 3-month mortality (RR 0.97, 95% CI 0.82-1.15; p = 0.727; I2 = 12%) were observed. When stratified for TNK regimen (original vs biocopy), statistical significance in achieving an excellent functional outcome at 3 months was retained for the original TNK (RR 1.05, 95% CI 1.00-1.10; p = 0.044; I2 = 0%). DISCUSSION: The updated meta-analysis confirms similar safety between TNK 0.25 mg/kg and TPA, while showing that TNK is superior to TPA regarding excellent functional outcome and reduced disability at 3 months. These findings support transitioning to TNK in clinical practice.

Efficacy and Safety of Intravenous Tenecteplase Versus Alteplase in Treating Acute Ischemic Stroke With Diabetes and Admission Hyperglycemia.

BACKGROUND: The aim of this study was to investigate the efficacy and safety of tenecteplase versus alteplase in patients with acute ischemic stroke, considering their diabetes history and admission hyperglycemia status. METHODS AND RESULTS: This was a post hoc analysis of the TRACE-2 (Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-2) randomized clinical trial that enrolled patients in China between June 2021 and May 2022. Eligible patients with acute ischemic stroke for standard intravenous thrombolysis, but ineligible for endovascular thrombectomy, were randomly assigned (1:1) to tenecteplase or alteplase within 4.5 hours of symptom onset. Admission hyperglycemia was defined as plasma glucose >7.8 mmol/L. The primary efficacy and safety outcome were excellent functional outcome at 90 days (modified Rankin Scale score of 0-1) and symptomatic intracranial hemorrhage within 36 hours, respectively. The Cochran-Mantel-Haenszel χ2 test was used for the outcomes. Of the 1382 patients included, 369 (26.7%) had a history of diabetes, and 482 (34.9%) experienced admission hyperglycemia. The primary efficacy outcome, comparing tenecteplase to alteplase, was achieved in 93 (56.7%) versus 97 (48.3%) among patients with a history of diabetes (P=0.11) and 335 (64.6%) versus 300 (62.2%) among those without diabetes (P=0.45), respectively. The primary efficacy outcome for tenecteplase versus alteplase was comparable among patients with and without admission hyperglycemia (57.5% versus 53.9%, P = 0.44; 65.4% versus 60.4%, P=0.12, respectively). No significant difference in the risk of symptomatic intracranial hemorrhage within 36 hours was observed between tenecteplase and alteplase, regardless of diabetes history or admission hyperglycemia. CONCLUSIONS: This study demonstrated that intravenous tenecteplase exhibits similar clinical outcomes compared with alteplase, irrespective of the patient's glucose metabolism status. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04797013.

Prognostic Value of Fibrosis-4 in Acute Ischemic Stroke Patients Undergoing Intravenous Thrombolysis.

Purpose: Although recombinant tissue plasminogen activator (rt-PA) treatment is efficient in patients with acute ischemic stroke (AIS), a significant percentage of patients who received rt-PA intravenous thrombolysis (IVT) do not achieve a good prognosis. Therefore, the factors that affect the poor prognosis of patients with IVT are needed. The Fibrosis-4 (FIB-4) index has been used as a liver fibrosis biomarker. We aimed to investigate the relationship between the FIB-4 index and functional outcomes in patients with AIS receiving IVT. Patients and Methods: This study prospectively included consecutive patients with AIS receiving IVT between April 2015 and May 2022. We collected clinical and laboratory data and calculated the FIB-4 index. Clinical outcome was poor functional outcome (mRS ≥3) at 3 months after IVT. Multivariate logistic regression analysis was used to analyze the association between FIB-4 and outcome. We explored the interactive effect of FIB-4 and dyslipidemia on poor outcomes, and subgroup analysis was performed. Furthermore, an individualized prediction model based on the FIB-4 for functional outcome was established in the dyslipidemia group. Results: A total of 1135 patients were included, and 41.50% had poor 3-month outcomes. After adjusted by other variants that P value <0.05 in univariable analysis, FIB-4 was independently associated with poor outcomes (OR=1.420; 95% CI: 1.113-1.812; P=0.004). There was a significant interaction between FIB-4 and dyslipidemia on poor outcome (P=0.036), and the independent association between FIB-4 and poor outcome was maintained in the dyslipidemia subgroup (OR=1.646; 95% CI: 1.228-2.206; P=0.001). Furthermore, in the dyslipidemia group, the FIB-4-based prediction model had good predictive value (the AUC of the training and validation sets were 0.767 and 0.708, respectively), good calibration (P-values for the Hosmer-Lemeshow test >0.05), and clinical usefulness. Conclusion: FIB-4 is an independent risk factor for poor outcomes in IVT patients with dyslipidemia, which can be used as a simple predictor of their prognosis.

Influence of Socioeconomic Status on Patients' Choice of Thrombolytic Agent and its Outcome in Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVE: Alteplase, a recombinant tissue-type plasminogen activator (rtPA) is the only FDA-approved thrombolytic drug in acute ischemic stroke (AIS). Tenecteplase is a modified rtPA, which is cheaper. We aimed to study influence of socioeconomic status (SES) in patients' preference of thrombolytic agent and its outcome. METHODS: This prospective observational study conducted in PGIMER, a tertiary care center in India, recruited AIS patients thrombolyzed between July 2017 and September 2018. We studied variables including SES, thrombolytic agent chosen, and outcomes like National Institutes of Health Stroke Scale (NIHSS) scores at 24-h and at discharge; and modified Rankin Scale (mRS) after 3 months. RESULTS: Thirty-nine patients received tenecteplase and 39 patients received alteplase. Seven patients belonged to upper class, all of whom (100%) chose alteplase. Thirty patients belonged to upper middle class, of whom 25 (83.3%) and five (16.7%) patients chose alteplase and tenecteplase, respectively. Twenty-five patients belonged to lower middle class in which seven (28%) and 15 (72%) chose alteplase and Tenecteplase, respectively. Twenty patients were in upper lower class, of whom 4 (20%) and 16 (80%) chose alteplase and Tenecteplase, respectively. The difference in distribution of SES in tenecteplase and alteplase groups was significant (P = 0.000). Median 3 month-mRS scores were 3 and 3.5 in alteplase and tenecteplase groups, respectively (P = 0.608). There were no significant differences in NIHSS score improvement at 24 h postthrombolysis (P = 0.537) or at discharge (P = 0.429) among different SES categories. No correlation between SES and 3 month-mRS score was found (Spearman's ρ = 0.101, P = 0.398). CONCLUSIONS: Majority of patients in upper and lower SES chose alteplase and Tenecteplase, respectively. However, there were no significant differences in outcomes among various SES categories.

Successfully intravenous thrombolytic therapy in systemic lupus erythematosus-related ischemic stroke: A case report.

RATIONALE: Stroke is a relatively frequent complication occurring in patients with systemic lupus erythematosus (SLE). The increasing number of patients with Ischemic Stroke secondary to SLE aroused the clinician's concern. SLE thrombosis markers, diagnostic high-resolution magnetic resonance image (HR-MRI), and therapeutic interventions for acute ischemic stroke were recently coming into focus perspectives from the field. PATIENT CONCERNS: A 42-year-old female with slurred speech and numbness in her left limb was admitted to our hospital. DIAGNOSES: Magnetic resonance imaging (MRI) revealed right thalamic infarction with diffusion-weighted lesions. Prior to admission, the patient had a National Institute of Health Stroke Scale (NIHSS) score of 3. INTERVENTIONS: In light of the clinical manifestation, the American Heart Association/American Stroke Association (AHA/ASA) Guidelines for Intravenous Thrombolysis in Acute Ischemic Stroke (2019) should be referred to. The patient was treated with thrombolytic alteplase (rt-PA). OUTCOMES: The patient was hospitalized for 2 weeks and discharged after his symptoms improved. LESSONS: After thrombolysis, the NIHSS score of the patient decreased to zero. The computed tomography scan was reexamined 24 hours later, and no acute changes or hemorrhage were identified in the infarcted area. Subsequent imaging and serological analyses indicated that HR-MRI of the responsible vessel was negative, but the infarction in this patient was still regarded as being caused by vasculitis of the right posterior cerebral artery in the region supplying the thalamus. This is the first case of successful intravenous thrombolytic therapy with rt-PA in a patient with SLE secondary to stroke with an NIHSS score of 3. This provides further evidence for expanding the reference of indications with rt-PA intravenous thrombolysis.

Outcome of intravenous thrombolysis in acute ischemic stroke patients with small vessel disease.

INTRODUCTION: Lacunar stroke (LS) subtype accounts for a quarter of ischemic strokes. Intravenous thrombolysis (IVT) is known to improve overall stroke outcomes. Very few studies have focused on the outcome of IVT in lacunar strokes. AIM: To detect the outcome of IVT in LS patients compared to non-thrombolysed LS patients. METHODS: Fifty patients presenting with LS received the standard protocol of IVT (Group I). They were compared to fifty matched LS patients who presented beyond the time window and were selected as the control group (Group II). Clinical outcome was measured using NIHSS within 24 h, NIHSS at discharge, and MRS after 3 months. Risk factors that could have affected clinical outcomes were compared in the thrombolysis group. RESULTS: The short-term clinical outcome of Group I showed statistically significant improvement of NIHSS after 24 hrs compared to Group II (mean NIHSS = 5.52±3.89 and 7.44±1.82 respectively), as well as on discharge (mean NIHSS = 3.88±3.50 and 5.78±2.97) respectively. For long-term outcomes, 94 % of GroupⅠ reached MRS 0, 1, and 2 (n = 47/50) versus 74 % (n = 36/50) in Group II. Longer door-to-needle time, severe WMCs (Fazekas score), and pneumonia were shown to be significant predictor factors for the worst outcome. CONCLUSION: IVT has improved short- and long-term outcomes in LS patients. Longer door-to-needle time, severe WMCs, and pneumonia were shown to be significant predictor factors for the worst outcome.

Validation of Prognostic Scales for Functional Outcome in Ischemic Stroke Patients Treated with Intravenous Thrombolysis in a Rural Setting.

INTRODUCTION: Early prediction of functional outcome after rtPA helps clinicians in prognostic conversations with stroke patients and their families. Three prognostic tools have been developed in this regard: DRAGON, MRI-DRAGON, and S-TPI scales. These tools, all performing with comparable accuracy, have been internally and externally validated in tertiary care centers. However, their performance in rural areas remains uncertain. This study addresses this gap in the literature by evaluating the effectiveness of those prognostic tools in stroke patients treated in a rural area of the Midwest. METHODS: We conducted a retrospective study of stroke patients treated with thrombolytics at Southern Illinois Healthcare Stroke Network from July 2017 to June 2024. Data on demographics, clinical presentations, laboratory values, neuroimaging, and stroke metrics were collected. Modified Rankin Scale (mRS) at 1 month, classified into good (mRS ≤2) and poor (mRS ≥5) outcomes were noted. DRAGON and MRI-DRAGON scores were calculated. S-TPI model was built. Area under the receiver operating characteristic curve (AUC) with its 95% confidence interval was calculated for each prognostic model. RESULTS: A total of 279 patients were included in this study. Of those, 43% (n = 119) were male. Median age (interquartile range [IQR]) was 69 (57-80) years. NIHSS at presentation (IQR) was 7 (4-13). 12% of the cohort (n = 34) had posterior circulation stroke. At 1 month, 66% of patients (n = 185) had mRS ≤2, whereas 14% of patients (n = 39) had mRS ≥5. MRI-DRAGON showed the highest accuracy in predicting both good (AUC = 0.86, 95% CI: 0.81-0.90) and poor outcomes (AUC = 0.84, 95% CI: 0.76-0.91). DRAGON also demonstrated high accuracy for good (AUC = 0.85, 95% CI: 0.80-0.89) and poor (AUC = 0.82, 95% CI: 0.75-0.90) outcomes. Conversely, in our population, the S-TPI model had the lowest accuracy for good (AUC = 0.56, 95% CI: 0.49-0.63) and poor (AUC = 0.68, 95% CI: 0.61-0.76) outcomes. CONCLUSION: Among the available grading scores, MRI-DRAGON score can be considered the more accurate short-term prognostic tool for stroke patients treated with rtPA in the rural setting.

Thrombolysis with Tenecteplase for Basilar Artery Occlusion in Neuro and Allied Clinic: Importance of Clinical Assessment and Drip and Ship Model in Nepal.

Tenecteplase, a new thrombolytic drug, is now widely recommended and used for treating acute ischemic stroke, and timely thrombolysis within 4.5 hours is crucial for better outcomes. However, due to limited stroke awareness, transportation difficulties, and inadequate access to experts and comprehensive stroke care centers, fewer than 15% of stroke patients in Nepal receive thrombolytic therapy. The "drip and ship" model, which involves starting thrombolysis at a noncomprehensive stroke care center and transferring the patient to another center for further care, can effectively overcome these obstacles, provided trained personnel are available at non-comprehensive stroke care centers. We report a case of acute ischemic stroke treated with thrombolysis within 4.5 hours of symptom onset at a non-comprehensive stroke care center, followed by transfer to another center for ongoing care, demonstrating the feasibility and potential benefits of the drip and ship model in resource-limited settings.

Advancing the management of acute intermediate-high-risk pulmonary embolism: The enduring legacy of Professor Guy Meyer.

Only few years after the first report on diagnosing acute pulmonary embolism (PE) with pulmonary angiography, studies began to investigate the effectiveness and safety of thrombolytic therapy for achieving early reperfusion. In 1992, Guy Meyer demonstrated the fast improvement of pulmonary haemodynamics after alteplase administration; this drug has remained the mainstay of thrombolysis for PE over almost 35 years. In the meantime, algorithms for PE risk stratification continued to evolve. The landmark Pulmonary Embolism International Thrombolysis (PEITHO) trial, led by Guy Meyer, demonstrated the clinical efficacy of thrombolysis for intermediate-risk PE, albeit at a relatively high risk of major, particularly intracranial bleeding. Today, systemic thrombolysis plays an only minor role in the real-world treatment of acute PE in the United States and Europe, but major trials are underway to test safer reperfusion regimens. Of those, the PEITHO-3 study, conceived by Guy Meyer and other European and North American experts, is an ongoing randomised, placebo-controlled, double-blind, multinational academic trial. The primary objective is to assess the efficacy of reduced-dose intravenous thrombolytic therapy against the background of heparin anticoagulation in patients with intermediate-high-risk PE. In parallel, trials with similar design are testing the efficacy and safety of catheter-directed local thrombolysis or mechanical thrombectomy. Increasingly, focus is being placed on long-term functional and patient-reported outcomes, including quality of life indicators, as well as on the utilization of health care resources. The pioneering work of Guy Meyer will thus continue to have a major impact on the management of PE for years to come.

Twenty-Four-Hour Post-Thrombolysis NIHSS Score As the Strongest Prognostic Predictor After Acute Ischemic Stroke: ENCHANTED Study.

BACKGROUND: This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). METHODS AND RESULTS: ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low-dose versus standard-dose intravenous alteplase and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90-day favorable functional recovery (modified Rankin Scale [mRS] score 0-2) and excellent functional recovery (mRS score 0-1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24-hour NIHSS score had the highest discriminative ability for predicting favorable 90-day functional recovery (mRS score 0-2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P<0.001) than baseline, absolute, and percentage change of NIHSS score, respectively. The optimal cutoff point of 24-hour NIHSS score for predicting favorable functional recovery was ≤4 (sensitivity 66.5%, specificity 87.1%, adjusted odds ratio, 9.44 [95% CI, 7.77-11.48]). The 24-hour NIHSS score (≤3) was the best predictor of 90-day excellent functional recovery (mRS score 0-1). Findings were consistent across subgroups, including sex, race, baseline NIHSS score, stroke subtype, and age. CONCLUSIONS: In thrombolysis-eligible patients with acute ischemic stroke, 24-hour NIHSS score (optimal cutpoint of 4) is the strongest predictor of 90-day functional recovery over baseline and early change of NIHSS score. REGISTRATION: URL: https://clinicaltrials.gov. Unique Identifier: NCT01422616.

Intravenous alteplase versus tenecteplase in patients with acute posterior circulation strokes: A secondary analysis from the AcT randomized controlled trial.

OBJECTIVES: There are limited data available demonstrating the safety and efficacy of intravenous tenecteplase versus alteplase in patients with acute ischemic stroke in the posterior circulation. MATERIALS AND METHODS: This is a post-hoc analysis of the Alteplase compared to Tenecteplase (AcT) pragmatic, phase 3, registry-linked randomized controlled trial. Patients with any posterior circulation vessel occlusion on baseline imaging were included. Study outcomes included 90-day modified Rankin Scale (mRS) 0-1, mRS 0-2, ordinal mRS, death within 90 days, 24 h symptomatic intracerebral haemorrhage (sICH) and successful reperfusion/recanalization. Mixed effects regression adjusting for age, sex and stroke severity was used to analyze differences in outcomes between patients administered tenecteplase vs. alteplase. Further, sensitivity analysis was conducted for basilar artery occlusion (BAO) alone. RESULTS: Of 1577 patients, 136 (8.6 %, 77:alteplase, 59:tenecteplase) had posterior circulation stroke. Baseline characteristics were similar[median age 71 (IQR 60-81) vs. 72 (IQR 65-82) years, 57.1 % vs. 67.8 % males, median baseline NIHSS 7 (IQR 4-12) vs. 7 (IQR 4-16) in alteplase vs. tenecteplase arms, respectively]. 28 patients (20.6 %, 16:alteplase, 12:tenecteplase arm) underwent EVT. The median 90-120 days mRS was 2 (IQR 1-4). There were no differences between alteplase and tenecteplase for 90-d mRS 0-1 (adjRR 0.93;95 %CI 0.63-1.36), 90-day mRS 0-2 (adjRR 0.95; 95 %CI 0.72-1.26), sICH (RR 0.65; 95 %CI 0.06-7.02) and mortality (RR 1.21; 95 %CI 0.61-2.38). Successful reperfusion eTICI 2b-3 and successful recanalization rAOL 2b-3 was achieved in 23/28 (82 %, 12:alteplase, 11:tenecteplase) and in 16/28 (57 %, 14:alteplase, 12:tenecteplase), respectively. Similar results were seen in 31 patients (22.8 %) with BAO. CONCLUSION: Intravenous tenecteplase has a similar effect on outcome as alteplase, without increased safety concerns in patients with acute posterior circulation strokes.

Poria cocos Extract Alleviates tPA-Induced Hemorrhagic Transformation after Ischemic Stroke through Regulation of Microglia M1/M2 Phenotypes Polarization.

Delayed thrombolytic therapy with tissue plasminogen activator (tPA), the only FDA-approved drug for ischemic stroke, can cause catastrophic hemorrhagic transformation (HT) after ischemic stroke. However, it remains largely unknown how microglial polarization dynamically changes in HT. Poria cocos is a widely used functional edible fungus in Asia and has been used for more than 2000 years as a food and medicine in China. Our preliminary study found that P. cocos extract (PCE) significantly reduced the volume of cerebral infarction. We performed the effects of PCE on tPA-induced HT in rat models of autologous thromboembolism middle cerebral artery occlusion in vivo and BV-2 cells injured by oxygen-glucose deprivation/reperfusion in vitro. Hemorrhage test and triphenyltetrazolium chloride staining were performed to examine the efficiency of PCE. The expression level of proteins associated with microglia polarization was detected using Western blotting and immunofluorescence staining. Small interfering RNA transfection reveals the regulatory mechanism of PCE on microglia polarization. PCE plus tPA reduced hemorrhage and infarct volumes after ischemic stroke. During tPA-induced HT, M1 microglia increased over time from 3 days onward and remained high for at least 7 days, reaching the peak at 7 days, M2 microglia gradually increased after 3 days and continued to increase for at least 14 days. Furthermore, PCE inhibited the secretion of pro-inflammatory cytokines in M1 microglia and improved the secretion of anti-inflammatory cytokines in M2 microglia, which related to the regulation of the IRF5-IRF4 axis. This current study indicates that PCE alleviates tPA-induced HT after ischemic stroke by modulating microglia M1/M2 phenotype polarization.

Warning of severe pulmonary embolism after cerebral angiography: A case report and literature review.

RATIONALE: Acute pulmonary embolism (PE), which can lead to cardiac and respiratory arrest, is a rare complication of cerebral angiography. However, neurologists do not pay attention to this. PATIENT CONCERNS: A 47-year-old male with a history of type 2 diabetes was admitted to our hospital for evaluation of surgical indications for unruptured ophthalmic aneurysms. After cerebral angiography, a fatal PE occurred. Through rapid identification and effective drug treatment, the patient recovered and was discharged. DIAGNOSES: A diagnosis of fatal PE was made based on the bedside ultrasonography and blood d-dimer level. INTERVENTIONS: Cardiopulmonary resuscitation and intravenous thrombolysis of "50 mg alteplase" for continuous intravenous drip for 2 hours. OUTCOMES: The patient was recovered and no special discomfort was reported. LESSONS: PE is a rare complication of cerebral angiography, but the fatality rate is very high. Neurologists must not only early identify and effectively treat this complication, but more importantly, pay attention to this complication, prevent it in advance, and reduce the occurrence of catastrophic events.

The changes of tPA/PAI-1 system are associated with the ratio of BDNF/proBDNF in major depressive disorder and SSRIs antidepressant treatment.

Increasing evidence demonstrates that brain-derived neurotrophic factor (BDNF) can be regarded as a biomarker for major depression. Our previous work found that the ratio of mature BDNF (mBDNF) to precursor-BDNF (proBDNF) was a pivotal factor in the pathogenesis of major depressive disorder (MDD). But the mechanism behind the ratio is still obscure. Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) both play essential roles in depression by regulating the ratio of BDNF/proBDNF. In present study, we analyzed BDNF, proBDNF, tPA and PAI-1 in the peripheral blood in 57 MDD patients pre- and post-treatment and in 57 healthy controls. We verified that BDNF and tPA levels were significantly decreased, whereas proBDNF and PAI-1 levels elevated obviously in MDD group pre-treatment. And after 4 weeks SSRIs treatment, the BDNF and tPA levels increased while the proBDNF and PAI-1 levels reduced. The MDD pre-treatment group had the lowest ratio of BDNF to proBDNF compared to MDD post-treatment group and control group. Though the ratio of tPA/PAI-1 in MDD pre-treatment had not reached the significance, it was still the lowest one among the three groups. The combination of tPA + PAI + BDNF showed the best diagnostic value for MDD. In summary, our data suggested that the interaction between tPA and PAI-1 implicated to the MDD and the antidepressant treatment which might through regulating the BDNF/proBDNF ratio. The combination of tPA, PAI-1 and BDNF might offer a helpful way for MDD diagnosis.

A retrospective study to evaluate the safety and efficacy of intrapleural alteplase in pediatric empyema.

INTRODUCTION: Medical treatment of pediatric empyema consists of appropriate antibiotics, chest tube insertion, and intrapleural fibrinolytic drugs to facilitate pleural drainage. There is a lack of consensus about the drug of choice for fibrinolytic therapy, so this study was designed to evaluate the safety and efficacy of intrapleural alteplase in pediatric empyema. MATERIAL AND METHODS: The medical records of all children with empyema treated with intrapleural alteplase at a university hospital between January 2016 and December 2020 were retrospectively reviewed. Efficacy outcomes were assessed by chest tube output before and after the first dose of alteplase, pleural fluid volume before and after therapy, a need for surgical intervention, and length of hospital stay. Safety was assessed by the frequency and severity of side effects. RESULTS: 40 children aged 2 months to 9 years hospitalized with empyema received intrapleural alteplase. Thirty patients (75%) experienced full recovery after three doses of intrapleural alteplase. The median length of hospital stay was 16 days. Chest tube output increased significantly after the first dose of alteplase. Pleural fluid volume decreased significantly after treatment. The most common side effect was pain (30%). Two patients experienced severe complications: 1 had a pulmonary hemorrhage and the other experienced a bronchopleural fistula. These patients recovered fully spontaneously. CONCLUSIONS: According to our results, the administration of intrapleural alteplase was safe and effective in facilitating pleural drainage in pediatric patients with empyema. However, further clinical trials will be needed to determine the optimal dose, frequency, and duration of intrapleural alteplase treatment.

Life-Threatening tPA-Associated Angioedema: A Rare Case Report and Critical Review.

BACKGROUND Angioedema is characterized by localized self-limiting edema of the deep dermis, subcutaneous, and submucosal tissues. Acute episodes often involve the skin of the face, lips, tongue, limbs, and genitals, as well as internal areas of the body and respiratory and gastrointestinal mucosa, which could be life-threatening. Histamine and bradykinin are the most recognized vasoactive mediators in the pathophysiology of angioedema. Tissue plasminogen activator (tPA) is a fibrinolytic that is commonly used for the treatment of cerebrovascular accidents. Angioedema is a rare adverse effect of tPA, with an estimated incidence of 0.02% in patients with myocardial infarction or pulmonary embolism and 0.2% to 5.1% in patients with stroke. We report a unique case of tPA-associated angioedema with 24-h management. CASE REPORT A 79-year-old male patient presented to the Emergency Department with acute onset right-sided weakness, right-sided facial droop, and speech difficulties. Following the initial evaluation, it was determined that he was a candidate for receiving tPA therapy. On arrival at the Intensive Care Unit, he was noted to have right upper and then lower lip swelling. The patient was asymptomatic and did not show any signs concerning airway compromise. Treatment included systemic corticosteroids and antihistamines. The progression of the angioedema was further described with sequential images. The angioedema was completely resolved with treatment. CONCLUSIONS Angioedema is a rare but potentially life-threatening adverse effect of tPA. Although it generally has a mild self-limiting course, it can cause life-threatening airway compromise.

Mortality Outcomes with Tenecteplase Versus Alteplase in the Treatment of Massive Pulmonary Embolism.

BACKGROUND: Pulmonary embolism (PE) leads to many emergency department visits annually. Thrombolytic agents, such as alteplase, are currently recommended for massive PE, but genetically modified tenecteplase (TNK) presents advantages. Limited comparative studies exist between TNK and alteplase in PE treatment. OBJECTIVE: The aim of this study was to assess the safety and mortality of TNK compared with alteplase in patients with PE using real-world evidence obtained from a large multicenter registry. Primary outcomes included mortality, intracranial hemorrhage, and blood transfusions. METHODS: This retrospective cohort study used the TriNetX Global Health Research Network. Patients aged 18 years or older with a PE diagnosis (International Classification of Diseases, 10th Revision, Clinical Modification code I26) were included. The following two cohorts were defined: TNK-treated (29 organizations, 266 cases) and alteplase-treated (22,864 cases). Propensity matching controlled for demographic characteristics, anticoagulant use, pre-existing conditions, and vital sign abnormalities associated with PE severity. Patients received TNK or alteplase within 7 days of diagnosis and outcomes were measured at 30 days post thrombolysis. RESULTS: Two hundred eighty-three patients in each cohort were comparable in demographic characteristics and pre-existing conditions. Mortality rates at 30 days post thrombolysis were similar between TNK and alteplase cohorts (19.4% vs 19.8%; risk ratio 0.982; 95% CI 0.704-1.371). Rates of intracerebral hemorrhages and transfusion were too infrequent to analyze. CONCLUSIONS: This study found TNK to exhibit a similar mortality rate to alteplase in the treatment of PE with hemodynamic instability. The results necessitate prospective evaluation. Given the cost-effectiveness and ease of administration of TNK, these findings contribute to the ongoing discussion about its adoption as a primary thrombolytic agent for stroke and PE.