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Abstract Background Acute ischemic stroke (AIS) is a major public health issue, and women have a disproportionate share of stroke-related disability and mortality, which is poorly understood. This study aimed to determine the effect of sex differences on AIS treated by thrombolysis using recombinant tissue plasminogen activator (rTPA). The study included 134 AIS patients eligible for rTPA. Risk factors, clinical presentation, thrombolysis response, complications, and outcomes were recorded. The outcomes were measured using the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) 3 months after stroke. The incidence of intracranial haemorrhage was also determined. Results Among 134 AIS patients treated with rTPA (59% male, 41% female), females had higher rates of hypertension (67.3% versus 49.4%, p = 0.040) and atrial fibrillation (AF) (12.7% versus 2.5%, p = 0.020), while smoking was more prevalent in males (31.6% versus 0%, p

Background: Acute ischemic stroke (AIS) is a major public health issue, and women have a disproportionate share of stroke-related disability and mortality, which is poorly understood. This study aimed to determine the effect of sex differences on AIS treated by thrombolysis using recombinant tissue plasminogen activator (rTPA). The study included 134 AIS patients eligible for rTPA. Risk factors, clinical presentation, thrombolysis response, complications, and outcomes were recorded. The outcomes were measured using the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) 3 months after stroke. The incidence of intracranial haemorrhage was also determined. Results: Among 134 AIS patients treated with rTPA (59% male, 41% female), females had higher rates of hypertension (67.3% versus 49.4%, p = 0.040) and atrial fibrillation (AF) (12.7% versus 2.5%, p = 0.020), while smoking was more prevalent in males (31.6% versus 0%, p < 0.0001). Cardioembolism was more frequent in females than in males (23.6% versus 6.3%, p = 0.004). Females also had shorter onset-to-door (110.7 ± 63 versus 131.1 ± 50.2 min, p = 0.035) and onset-to-needle times (151.6 ± 66.5 versus 173.7 ± 50.6 min, p = 0.046). Both sexes showed significant improvements in NIHSS (males: 11.58 ± 3.7 to 6.05 ± 5.6; females: 11.64 ± 4.7 to 6.9 ± 5.9; p < 0.0001) and mRS scores (males: 3.34 ± 1.05 to 2.03 ± 2; females: 3.53 ± 1 to 2.02 ± 2; p < 0.0001) over 3 months, with no significant differences between sexes. Predictors of poor outcome (mRS 3–6) differed: diabetes mellitus (DM) (OR 7.79, p = 0.002) and longer door-to-needle time (OR 1.04, p = 0.008) for males, and hemorrhage (OR 9.41, p = 0.048) for females. Hemorrhage predicted mortality in males (OR 27.08, p < 0.0001), while AF was associated with increased mortality in females (OR 8.06, p = 0.024). Conclusions: This study revealed sex-specific differences in AIS risk factors, aetiology, and rTPA treatment timelines, although post-treatment improvements were comparable between sexes. Notably, outcome predictors and mortality factors differed by sex. These findings emphasize the need for sex-specific considerations in AIS management and risk assessment. [ABSTRACT FROM AUTHOR]

DWI/FLAIR mismatch assessment for ischemic stroke patients shows promising results in determining if patients are eligible for recombinant tissue-type plasminogen activator (r-tPA) treatment. However, the mismatch criteria suffer from two major issues: binary classification of a non-binary problem and the subjectiveness of the assessor. In this article, we present a simple automatic method for segmenting stroke-related parenchymal hyperintensities on FLAIR, allowing for an automatic and continuous DWI/FLAIR mismatch assessment. We further show that our method's segmentations have comparable inter-rater agreement (DICE 0.820, SD 0.12) compared to that of two neuro-radiologists (DICE 0.856, SD 0.07), that our method appears robust to hyper-parameter choices (suggesting good generalizability), and lastly, that our methods continuous DWI/FLAIR mismatch assessment correlates to mismatch assessments made for a cohort of wake-up stroke patients at hospital submission. The proposed method shows promising results in automating the segmentation of parenchymal hyperintensity within ischemic stroke lesions and could help reduce inter-observer variability of DWI/FLAIR mismatch assessment performed in clinical environments as well as offer a continuous assessment instead of the current binary one. [ABSTRACT FROM AUTHOR]

Peri-pancreatic fluid collections are late complications of acute pancreatitis. Loculated peri-pancreatic fluid collections, even rare, remain the „black sheep" in terms of drainage, due to difficulty to puncture all compartments, thus prohibiting proper drainage of all compartments. Recombined tissue plasminogen activator (r-tPA) has been advocated as treatment of the loculated collections, due to its ability to dissolve the fibrinous strands and thus facilitate proper drainage. We report the case of a 58 years-old male presenting with a painful loculated peri-pancreatic fluid collection secondary to acute pancreatitis. We performed Alteplase injection, followed by successful endosonographic drainage with lumen apposing metal stent of the collection after 48 hours. Our observation suggests that r-tPA could be a new strategy for loculated collections management, ensuring better drainage and limiting the indication for surgical treatment. [ABSTRACT FROM AUTHOR]

Recombinant tissue plasminogen activator (r-tPA) is the first-line drug for the treatment of acute ischemic stroke, despite it may lead to a variety of complications in some cases. In patients with extensive stroke, infarction of the brain can cause suppression of the respiratory center in the brain leading to neurogenic pulmonary edema that potentially causes respiratory failure. Its etiology is either due to a neurogenic or non-neurogenic process. Nevertheless, the definite pathophysiology of these circumstances remains unclear. In this study, we reported four cases of post-thrombolytic ischemic stroke patients who suffer from pulmonary edema with different symptoms and onset times as well as we discuss the possible explanation behind these different outcomes.

Objective This study aimed to evaluate the effect of telestroke practices on patient prognosis and mortality by comparing the data of patients that presented before and during a period when tele-stroke application was in use. Method Stroke patients presenting from October, 2018 to October, 2019 for whom WhatsApp was used for telestroke purposes, were evaluated as the telestroke group. The previous year it was a pre-telestroke group. The two groups were compared in terms of factors affecting prognosis and mortality. All statistical analyses were performed using SPSS version 16.0 for Windows. Results A total of 727 patients clinically and radiologically confirmed to have ischemic stroke were included in the study. There were 252(34.6%) patients in the pre-telestroke group and 475(65,4%) patients in the telestroke group. Both rtPA and thrombectomy treatment were significantly higher in the telestroke group(p lt;0.001). In the first 24-hour evaluation, the rate of discharge increased and hospital admission and mortality decreased in the telestroke group(p lt;0.001). There was no statistically significant difference between the groups in terms of poor prognosis and 30-day mortality(p=0.470 and p=0.625, respectively). Conclusion Telestroke practices not only provide access to the relevant clinical branch for early consultation but also facilitate timely treatment thus leading to improvement in prognosis.

Fibrin deposition in the alveolar spaces during pulmonary involvement of COVID‐19 impairs the O2/CO2 exchange and leads to respiratory symptoms. In this report, Recombinant Tissue Plasminogen Activator (r‐tPA) has been nebulized to 3 critically ill COVID‐19 patients in order to resolve the deposited fibrin while avoiding the risk of bleeding. Based on these observations, nebulization of r‐tPA may be a potential therapeutic approach and new area of research for future studies. [ABSTRACT FROM AUTHOR]

BackgroundIntravenous 0.9 mg/kg recombinant tissue plasminogen activator (r-tPA) is one of the most effective treatments in acute ischemic stroke patients. Practically, the dose of r-tPA is still a topic that is constantly being discussed.MethodsFor this observational study, data were obtained from 537 patients who received r-tPA thrombolysis at Shanghai Sixth People's Hospital stroke center over 5 years (2014–2019). Patients were divided into two groups: a non-standard dose group (0.6 mg/kg ≤ dose < 0.9 mg/kg) and a standard dose group (0.9 mg/kg). Different outcomes were observed: efficacy: 3 months mRS 0-1 (3m-mRS0-1); safety: symptomatic intracranial hemorrhage within 24 h (24h-sICH) and 3 months mortality (3m-death). We also observed the effect of r-tPA dose coefficient on outcomes in different age groups and baseline National Institute of Health stroke scale (NIHSS) score subgroups.ResultsThere were 265 patients who gave the standard dose treatment and 272 gave the nonstandard dose. There was no significant difference between the non-standard dose group and the standard dose group in 3m-mRS0-1, 3m-death, and 24h-sICH (p = 0.567, 0.327, and 0.415, respectively). The dose coefficient presents a significant negative correlation (p = 0.034, B = −4.290) with 3m-death in NIHSS < 16 sub-group. Door-to-needle time (DNT) is the most important independent outcome-influential factor (MIOIF) in the NIHSS ≥16 sub-group. The diabetes history and baseline NIHSS score were the MIOIF in the age ≥80-year sub-group.ConclusionsThe non-standard dose group (0.6 mg/kg ≤ dose < 0.9 mg/kg) shows no difference in safety and effectiveness than the standard dose group (0.9 mg/kg) in our study. The standard dose should be considered first according to current evidence and Guidelines, but the non-standard dose (0.6 mg/kg ≤ dose < 0.9 mg/kg) might be an option in the actual diagnosis and treatment process considering the patient's clinical profile and financial condition.

Recombinant tissue plasminogen activator (r-tPA) is the first-line drug for the treatment of acute ischemic stroke, despite it may lead to a variety of complications in some cases. In patients with extensive stroke, infarction of the brain can cause suppression of the respiratory center in the brain leading to neurogenic pulmonary edema that potentially causes respiratory failure. Its etiology is either due to a neurogenic or non-neurogenic process. Nevertheless, the definite pathophysiology of these circumstances remains unclear. In this study, we reported four cases of post-thrombolytic ischemic stroke patients who suffer from pulmonary edema with different symptoms and onset times as well as we discuss the possible explanation behind these different outcomes. [ABSTRACT FROM AUTHOR]

Background: Thrombolysis with r-tPA is recommended for patients after acute ischemic stroke (AIS) within 4.5 h of symptom onset. However, only a few patients benefit from this therapeutic regimen. Thus, we aimed to develop an interpretable machine learning (ML)–based model to predict the thrombolysis effect of r-tPA at the super-early stage.Methods: A total of 353 patients with AIS were divided into training and test data sets. We then used six ML algorithms and a recursive feature elimination (RFE) method to explore the relationship among the clinical variables along with the NIH stroke scale score 1 h after thrombolysis treatment. Shapley additive explanations and local interpretable model–agnostic explanation algorithms were applied to interpret the ML models and determine the importance of the selected features.Results: Altogether, 353 patients with an average age of 63.0 (56.0–71.0) years were enrolled in the study. Of these patients, 156 showed a favorable thrombolysis effect and 197 showed an unfavorable effect. A total of 14 variables were enrolled in the modeling, and 6 ML algorithms were used to predict the thrombolysis effect. After RFE screening, seven variables under the gradient boosting decision tree (GBDT) model (area under the curve = 0.81, specificity = 0.61, sensitivity = 0.9, and F1 score = 0.79) demonstrated the best performance. Of the seven variables, activated partial thromboplastin clotting time (time), B-type natriuretic peptide, and fibrin degradation products were the three most important clinical characteristics that might influence r-tPA efficiency.Conclusion: This study demonstrated that the GBDT model with the seven variables could better predict the early thrombolysis effect of r-tPA.

Background: Thrombolysis with r-tPA is recommended for patients after acute ischemic stroke (AIS) within 4.5 h of symptom onset. However, only a few patients benefit from this therapeutic regimen. Thus, we aimed to develop an interpretable machine learning (ML)–based model to predict the thrombolysis effect of r-tPA at the super-early stage. Methods: A total of 353 patients with AIS were divided into training and test data sets. We then used six ML algorithms and a recursive feature elimination (RFE) method to explore the relationship among the clinical variables along with the NIH stroke scale score 1 h after thrombolysis treatment. Shapley additive explanations and local interpretable model–agnostic explanation algorithms were applied to interpret the ML models and determine the importance of the selected features. Results: Altogether, 353 patients with an average age of 63.0 (56.0–71.0) years were enrolled in the study. Of these patients, 156 showed a favorable thrombolysis effect and 197 showed an unfavorable effect. A total of 14 variables were enrolled in the modeling, and 6 ML algorithms were used to predict the thrombolysis effect. After RFE screening, seven variables under the gradient boosting decision tree (GBDT) model (area under the curve = 0.81, specificity = 0.61, sensitivity = 0.9, and F1 score = 0.79) demonstrated the best performance. Of the seven variables, activated partial thromboplastin clotting time (time), B-type natriuretic peptide, and fibrin degradation products were the three most important clinical characteristics that might influence r-tPA efficiency. Conclusion: This study demonstrated that the GBDT model with the seven variables could better predict the early thrombolysis effect of r-tPA. [ABSTRACT FROM AUTHOR]

Background: Fibrin degradation products (FDPs) are fragments released by the plasmin-mediated degradation of fibrinogen or fibrin. Whether plasma levels of these fragments can predict the thrombolytic effect of recombinant tissue plasminogen activator (r-tPA) remains unknown.Methods: We performed a hospital-based study of patients with acute ischemic stroke (AIS) to explore the relationship between FDP levels at admission and the NIH Stroke Scale (NIHSS) score 1 h after thrombolysis treatment. In this retrospective, single-center study, the data of all patients with AIS who received r-tPA treatment at Beijing Tiantan Hospital from January 2019 to October 2020 were collected and analyzed. Demographic and clinical data, including laboratory examinations, were also analyzed.Results: A total of 339 patients with AIS were included in this study. Of these, 151 showed favorable effects of r-tPA, and 188 showed unsatisfactory effects at 1 h after thrombolysis. Overall, we found an inverse relationship between the FDPs levels at admission and the NIHSS score. A significant difference was observed when using the interquartile range of the FDPs levels (1.31 μg/mL) as a cutoff value (P = 0.003, odds ratio [OR] = 1.95, 95% confidence interval [CI]: 1.26–3.01), even after adjusting for confounding factors (P = 0.003, OR = 2.23, 95% CI: 1.31–3.77). In addition, significant associations were observed in the tertile (T3) and quartile (Q3, Q4) FDP levels when compared with T1 or Q1. A nomogram was also employed to create a model to predict an unsatisfactory effect of r-tPA. We found that FDP levels, white blood cell count, age, D-dimer level, and body mass index could influence the thrombolytic effect of r-tPA.Conclusion: In conclusion, the present study demonstrated that the levels of FDPs at admission can be used as a prognostic factor to predict the curative effect of r-tPA.

Background: Fibrin degradation products (FDPs) are fragments released by the plasmin-mediated degradation of fibrinogen or fibrin. Whether plasma levels of these fragments can predict the thrombolytic effect of recombinant tissue plasminogen activator (r-tPA) remains unknown. Methods: We performed a hospital-based study of patients with acute ischemic stroke (AIS) to explore the relationship between FDP levels at admission and the NIH Stroke Scale (NIHSS) score 1 h after thrombolysis treatment. In this retrospective, single-center study, the data of all patients with AIS who received r-tPA treatment at Beijing Tiantan Hospital from January 2019 to October 2020 were collected and analyzed. Demographic and clinical data, including laboratory examinations, were also analyzed. Results: A total of 339 patients with AIS were included in this study. Of these, 151 showed favorable effects of r-tPA, and 188 showed unsatisfactory effects at 1 h after thrombolysis. Overall, we found an inverse relationship between the FDPs levels at admission and the NIHSS score. A significant difference was observed when using the interquartile range of the FDPs levels (1.31 μg/mL) as a cutoff value (P = 0.003, odds ratio [OR] = 1.95, 95% confidence interval [CI]: 1.26–3.01), even after adjusting for confounding factors (P = 0.003, OR = 2.23, 95% CI: 1.31–3.77). In addition, significant associations were observed in the tertile (T3) and quartile (Q3, Q4) FDP levels when compared with T1 or Q1. A nomogram was also employed to create a model to predict an unsatisfactory effect of r-tPA. We found that FDP levels, white blood cell count, age, D-dimer level, and body mass index could influence the thrombolytic effect of r-tPA. Conclusion: In conclusion, the present study demonstrated that the levels of FDPs at admission can be used as a prognostic factor to predict the curative effect of r-tPA. [ABSTRACT FROM AUTHOR]

Background: Stroke is the leading cause of death and disability. Nowadays, the standard treatment is Intravenous thrombolytic with alteplase (t-PA) within 4.5 hours after the stroke onset. However, some patients who arrived to the hospital within 4.5 hours after stroke onset haven't received the alteplase. Objective: To investigate the barriers to thrombolysis drug (alteplase) in acute ischemic stroke patients who arrived at the hospital within 4.5 hours after the stroke onset. Materials and Methods: A retrospective study of ischemic stroke patients who developed stroke symptoms and arrived at the hospital within 4.5 hours but did not receive the thrombolytic drug (non-treatment group). Data were collected at the North-East hospital of Thailand from the hospital stroke registry and the patient record from October 2014 to September 2015. The study focused on the reasons for which this group of patients was excluded from receiving the thrombolytic drug. Factors associated with the non-treatment group were investigated using multivariable logistic regression. Results: Of a total 229 patients who were diagnosed with acute ischemic stroke and arrived within 4.5 hours after stroke onset, 61 patients underwent thrombolytic therapy with alteplase. Of the 168 patients who did not receive the alteplase, the main reasons for this were mild or improving symptoms, contraindication to alteplase and uncertain onset time (including wake-up strokes). Factors associated with the non-treatment group were door time over three hours and patients who had an underlying history of hypertension or an old cerebrovascular accident (CVA). These patients were less likely to receive the thrombolytic drug. While patients with a National Institute of Health Stroke Scale (NIHSS) between 8 and 12, were more likely to receive the treatment. Conclusion: Barriers to use of the thrombolytic drug in acute ischemic stroke in Thai patients included mild or improved symptoms, relative contraindication to alteplase and uncertain onset time. In order to increase alteplase administration, the revision of relative contraindication in mild symptoms, seizure at onset of stroke and wake-up stroke or stroke with an uncertain time of onset should be considered. The application of neuroimaging can be useful to select the eligible cases. [ABSTRACT FROM AUTHOR]

Abstract Background Stroke induces immune alterations such as impaired oxidative burst and reduced release of neutrophil extracellular traps (NETs). We hypothesised that key enzymes of these defence mechanisms may be altered in ischaemic stroke. Therefore, we analysed the intra- and extracellular amounts of myeloperoxidase (MPO) and neutrophil elastase (NE) in patient sera and granulocytes and monocytes. Because the autonomous nervous system is thought to mediate stroke-induced immune alterations, we also studied the influence of stress hormones and acetylcholine on MPO and NE. Rapid recanalization by recombinant tissue plasminogen activator (r-tPA) is the only available treatment for ischaemic stroke besides thrombectomy, and its influence on antibacterial defence mechanisms of granulocytes and monocytes were addressed here. Methods Ex vivo: Intracellular and serum MPO and NE were measured on days 0, 1, 3 and 5 post-stroke by either flow cytometry or enzyme-linked immunosorbent assay (ELISA) and compared to controls. In vitro: Blood from healthy donors was incubated with catecholamines, dexamethasone and acetylcholine, and the percentage of NET-producing cells and the area covered by NETs were quantified immunohistochemically. Intra- and extracellular MPO and NE were quantified by flow cytometry or ELISA. Blood samples from healthy donors were incubated with r-tPA, and oxidative burst, phagocytosis, NETosis, cytokine release, MPO and NE were quantified by flow cytometry, ELISA and microscopy. Results MPO was reduced in granulocytes but increased in sera obtained from stroke patients compared to controls. NE was not altered intracellularly but was elevated in patient sera. The percentage of NET-producing neutrophils was decreased by stress hormones and increased by acetylcholine. Neither intracellular MPO nor NE was altered by hormone treatment; however, adrenaline and acetylcholine induced NE release. r-tPA led to reduced phagocytosis and oxidative burst in granulocytes and monocytes in vitro. NETosis, MPO release and cytokines were not altered, whereas NE release was enhanced by r-tPA. Conclusions Intracellular reduction of MPO might be responsible for reduced NETosis in stroke patients. The impact of enhanced MPO and NE serum levels in stroke patients should be addressed in future studies. r-tPA impaired antibacterial defence function in vitro. Therefore, patients who undergo unsuccessful recanalization therapy might be at higher risk for infection, which should be analysed in future investigations. Immune alterations due to r-tPA effects in stroke patients should also be investigated.

• Acute stroke care including thrombolysis in Low- and Middle-Income Countries (LMICs) remains suboptimal despite the significant burden of stroke in these setting. • CFIR is a practical meta-theoretical framework that integrates and combines a wide range of elements that impact how evidence-based interventions are implemented. • Delays in presentation due to lack of stroke symptom knowledge, cultural beliefs, and affordability of thrombolytics were identified as critical bottlenecks. Each year, stroke-related death and disability claim over 143 million years of healthy life globally. Despite accounting for much of the global stroke burden, acute stroke care in Low-and-Middle-Income Countries remains suboptimal. Thrombolysis, an effective treatment option for stroke, is only received by a minority of stroke patients in these settings. To determine the context-specific barriers and facilitators for the implementation of mainstream stroke thrombolysis in a Ghanaian hospital. We employed a mixed-methods approach involving key stakeholders (recipients, providers, and leaders) in the acute stroke care continuum. Surveys were administered to acute stroke patients, and in-depth key informant interviews were conducted with experts in stroke care, including a neurologist, medical director, neurology residents, a stroke nurse, emergency physicians, a radiologist, and a pharmacist. The data collected from these interviews were transcribed and analysed using content analysis with the CFIR (Consolidated Framework for Implementation Research) model as a guiding template. Two independent coders were involved in the analysis process to ensure reliability and accuracy. The stroke thrombolysis rate over a 6-month period was 0.83% (2 out of 242), with an average door-to-needle time among thrombolyzed patients being 2 hours, 37 minutes. Only 12.8% of patients (31 out of 242) presented within 4.5 hours of stroke symptom onset. The most significant obstacle to the implementation of acute stroke thrombolysis was related to the characteristics of the individuals involved, notably delays in presenting to the hospital among stroke patients due to a lack of knowledge about stroke symptoms and cultural beliefs. Additionally, a significant bottleneck that contributed to the discrepancy between the number of patients who presented within the 4.5-6 hour window and the number of patients who actually received thrombolysis was the inability to pay for the cost of thrombolytic agents. This was followed by challenges in the implementation processes. Addressing challenges related to stroke awareness, and financial constraints via multi-level stakeholder engagement, and enactment of stroke protocols are crucial steps in ensuring a successful implementation of a stroke thrombolysis program in a resource-limited setting. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of intravitreal gas (perfluoropropane, C3F8)–assisted displacement of submacular hemorrhage (SMH) secondary to recent or old blunt trauma. Methods: An interventional case series of three patients who presented with SMH after blunt trauma, ranging from 2 days to 2 weeks back. All three patients were treated with an intravitreal injection of 0.3 cc of 100% C3F8 with anterior chamber paracentesis. Strict prone position was advised for 2 weeks with a minimum of 6 to 8 hours per day. Documentation was done with serial recording of corrected distance visual acuity, fundus photographs, and spectral domain optical coherence tomography both before and after intervention. Results: The follow-up period ranged from 2 weeks to 3 months. All patients showed a significant displacement of SMH with recovery of the normal foveal contour; foveal thinning was noted in 2 cases. Best spectacle-corrected visual acuity improved from counting finger at 1 m to 20/30 in Case 1 and counting finger 3 m to 20/40 in Case 2. In Case 3, the visual acuity remained unchanged from the preoperative 20/60 which could be attributed to the presence of a choroidal rupture in the foveal area that became evident after the displacement of SMH. Conclusion: Pneumatic displacement is an effective technique in the management of SMH due to recent or old blunt trauma. [ABSTRACT FROM AUTHOR]

Administration of tissue plasminogen activator (tPA) during first 3-4.5 h after ischemic stroke is the main therapeutic strategy; however, its using after that, leads to reperfusion injury and neurotoxic effects. Additionally, inflammation has a critical role in secondary injury after late reperfusion therapy. Thus, this project was designed to explore the effects of JZL-184 (JZL), an agonist of type 1 cannabinoid receptor (CB1), on the side effects of recombinant tPA (r-tPA), which is administrated after 5 h of stroke onset in the mice middle cerebral artery occlusion (MCAO) model. After established the model of MCAO mouse, they were put to six groups, including intact, control, vehicle, JZL (4 mg/kg), r-tPA (9 mg/kg), and JZL plus r-tPA. Thereafter, brain levels of IL-10, TNF-α, and matrix metalloproteinase − 9 (MMP9), brain edema and infarction, and behavioral functions have been determined in the groups. JZL alone or in combination with r-tPA, but not r-tPA, reduced brain edema, infarct volume, brain levels of TNF-α, MMP9, and also improved behavioral tests. JZL and JZL plus r-tPA also increased brain levels of IL-10. According to the results, JZL can improve the effects of r-tPA to overcome stroke SSE, when used after 5 h of stroke onset. Based on the fact that there is limitation regarding using r-tPA after 3 h of stroke onset, using a combination of r-tPA/JZL can be considered for a future therapeutic strategy. [ABSTRACT FROM AUTHOR]

Objective To investigate the risk factors for hemorrhagic transformation (HT) after intravenous thrombolysis using a recombinant tissue plasminogen activator (r-tPA) in acute cerebral infarction. Methods Patients with acute cerebral infarction receiving r-tPA thrombolysis in Shanghai Eastern Hospital were retrospectively studied. Based on the cranial computed tomography or magnetic resonance imaging examination, after the intravenous thrombolysis, the patients were divided into 2 groups: an HT group and a non-HT group. The information was collected before or after thrombolysis. RESULTS: A total of 162 patients were included in the analysis. The age ranged from 25 to 86 years, with an average age of 65.6 ± 10.6 years. The average time from disease onset to thrombolysis was 188 ± 53.1 minutes. Cranial computed tomography or magnetic resonance imaging showed that 20 patients (12.3%) had HT after thrombolysis. Using univariate analysis, history of atrial fibrillation, positive expression of urinary protein, and high National Institutes of Health Stroke Scale (NIHSS) score before thrombolysis, we found that there was a significant difference between the HT and non-HT group ( P < 0.05) in the level of mean systolic pressure (MSP) 24 hours after thrombolysis. Multivariate logistic regression analysis indicated that age ≥80 years, MSP ≥140 mm Hg, NIHSS score, and fibrinogen concentration before thrombolysis were risk factors for HT after thrombolysis in patients with acute cerebral infarction. Conclusions Age, MSP, NIHSS score, and fibrinogen concentration before thrombolysis are risk factors for HT after thrombolysis in acute cerebral infarction. These 4 factors should be carefully taken into account before thrombolysis. [ABSTRACT FROM AUTHOR]

Introduction: Stroke is one of the leading causes of death and disability in the United States. Nationally, only 3-8% of patients with Acute Ischemic Stroke (AIS) who are eligible for thrombolysis currently receive recombinant tissue plasminogen factor (r-TPA). Lack of knowledge and familiarity with thrombolytics in stroke therapy are major impediments. We investigated the baseline stroke management concepts and knowledge of AIS therapy in Emergency Department (ED) healthcare providers and then assessed the impact of a brief educational intervention. Method: An anonymous 14-item (11 multiple choice and 3 open-ended) questionnaire was administered to a convenience sample of 58 healthcare providers in the ED of a Level-1, tertiary care, academic, urban hospital. The survey was collected and a 15-minute lecture was provided to the group. A post-test was administered immediately and six months after the intervention. Data collected were analyzed with chi-square, analysis of variance and Kruskal-Wallis analysis using SAS 9.1.3. Results: Of the 58 respondents 77% (45/58) identified r-TPA as the thrombolytic agent, but only 56% (33/58) knew the therapeutic window and 29% (17/58) knew the “Door-to-CT” time. Sixty-two percent (36/58) of the respondents reported unfamiliarity with the National Institute of Health’s Stroke Scale and the eligibility criteria of r-TPA. Median score pre-education was 5/14 which improved to 11/14 (CI 8-12, p

Given the constraints of resources, thrombolysis for acute ischemic stroke (AIS) is under evaluation in developing countries like India, especially in areas such as western Utter Pradesh, where it is overly crowded and there is poor affordability. Aim: This study was done to evaluate recombinant tissue plasminogen activator r-tpa in acute ischemic stroke in hyper acute phase, in selected patients of western Utter Pradesh, in terms of feasibility and effectivity. Design: Open, non randomized study. Materials and Methods: Thirty two patients were classified using Trial of ORG 10172 in Acute Stroke treatment (TOAST) criteria (large artery atherosclerotic = 8; cardio embolic = 6; small vessel occlusion = 14; other determined etiology = 2; undetermined etiology = 2). The mean time to reach the hospital was 2 h (1.15-3.0), the mean door to CT scan 20 min (10-40) and door to r-tpa injection was 30 min (24-68). The National Institute of Health Stroke Scale (NIHSS) scores ranged from 11-22 (mean 15.5 +2.7). The dose of r-tpa administered was 0.9 mg/kg. Results: Twenty one patients (65.6%) showed significant improvement on the NIHSS score, at 48 h (4 points). (Mean change = 10; range = 4-17). At one month, 25 (78%) recorded improvement on the Barthel index (mean change = 45%). One developed frontal lobe hemorrhage and another developed recurrent stroke; one died of aspiration; and four showed no improvement. Modified Rankin score (m RS) was administered at the end of three months to 28 patients (90%); however, the rest could not be directly observed. The average modified Rankin Score was 1.2 (0-2). Conclusions: Hyperacute thrombolysis was found feasible and effective in selected patients with AIS from western Utter Pradesh and who had poor affordability.

A 42-year-old female admitted with new-onset atrial fibrillation had a wakeup stroke on the high-dependency unit and the time last seen well (TLSW) was 6.5 h. She suffered left-sided body weakness and her National Institutes of Health Stroke Scale (NIHSS) score was 17. An emergency CT perfusion showed right M1 segment occlusion with more than 50% penumbra. She was given recombinant tissue plasminogen activator (r-tPA) at 9 h from TLSW. An immediate diagnostic angiogram with intention to treat, owing to the presence of large vessel occlusion, showed complete reperfusion after intravenous r-tPA. She was discharged with NIHSS of 2, and at 3-month follow up her Modified Rankin Scale was 0. We demonstrated a successful reperfusion and excellent clinical recovery with intravenous thrombolysis in a patient who presented with a wake-up stroke with underlying valvular atrial fibrillation despite evidence of large vessel occlusion. [ABSTRACT FROM AUTHOR]

The information about the thromboembolic events, the optimal treatment choice, the dose, and duration of antithrombotic therapy in children are limited. More clinical data are required. Recombinant tissue plasminogen activator (r-tPA) is increasingly used in pediatric thrombosis. We retrospectively analyzed the clinical course of 7 children (9.3 ± 2.1 years; 34 days to 16 years) with arterial thrombosis (n = 1) and intracardiac thrombosis (n = 6). The children were treated with r-tPA. The dose ranged between 0.2 and 0.4 mg/kg per h infused for 3 to 4 hours. This dose was repeated between 2 to 7 times till the thrombolysis was achieved. Treatment side effects were closely monitored. Complete clot lysis was achieved in all cases. None of them had severe bleeding except mild recurrent epistaxis occurring in 2 cases. In conclusion, r-tPA is an effective and safe therapy under close hemostatic control in children. [ABSTRACT FROM PUBLISHER]

Introduction: Stroke is one of the leading causes of death and disability in the United States. Nationally, only 3-8% of patients with Acute Ischemic Stroke (AIS) who are eligible for thrombolysis currently receive recombinant tissue plasminogen factor (r-TPA). Lack of knowledge and familiarity with thrombolytics in stroke therapy are major impediments. We investigated the baseline stroke management concepts and knowledge of AIS therapy in Emergency Department (ED) healthcare providers and then assessed the impact of a brief educational intervention. Method: An anonymous 14-item (11 multiple choice and 3 open-ended) questionnaire was administered to a convenience sample of 58 healthcare providers in the ED of a Level-1, tertiary care, academic, urban hospital. The survey was collected and a 15-minute lecture was provided to the group. A post-test was administered immediately and six months after the intervention. Data collected were analyzed with chi-square, analysis of variance and Kruskal-Wallis analysis using SAS 9.1.3. Results: Of the 58 respondents 77% (45/58) identified r-TPA as the thrombolytic agent, but only 56% (33/58) knew the therapeutic window and 29% (17/58) knew the "Door-to-CT" time. Sixty-two percent (36/58) of the respondents reported unfamiliarity with the National Institute of Health's Stroke Scale and the eligibility criteria of r-TPA. Median score pre-education was 5/14 which improved to 11/14 (CI 8-12, p<0.0001) and six months later was 8/14 (best score was 12, p<0.0001). Only 8% (5/58) of the respondents expressed a special interest in stroke. Conclusion: Few medical personnel express a special interest in stroke and many misunderstand basic management concepts as well as eligibility criteria for thrombolysis in AIS. A brief targeted intervention improves knowledge and familiarizes ED healthcare providers about the use of r-TPA in AIS. Improvement in knowledge was demonstrated on testing immediately and at six month follow-up. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical effect of r-tpa combined mannitol in treatment of cerebral infarction caused by vascular diseases. Methods: The patients with acute cerebral infarction (ACI) within 6 hours were randomly divided into treatment group and control group with 60 cases in each group. The patients in treatment group accepted r-tpa combined mannitol, and the patients in control group accepted ligustrazine injection. The clinical efficacy and recovery of neurological function were measured after 15 days treatment. Results: The clinical effect of treatment group was 93.33 %, which was obviously higher than 78.33 % of control group with statistically significance (P<0.05). The CSS scores of two groups after treatment were obviously lower than before, and the treatment group was much lower than control group (P<0.05). The ADL scores of two groups after treatment were obviously higher than before, and the treatment group was much higher than control group (P<0.05). Conclusions: Using r-tpa combined mannitol has good effect in treatment of cerebral infarction caused by vascular diseases, which is safe and good at symptom improvement of later stage. [ABSTRACT FROM AUTHOR]

Abstract: Background: Portal vein thrombosis is a frequent complication in liver cirrhosis. Encouraging reports of systemic thrombolysis in non-cirrhotic patients suffering from acute portal vein thrombosis led us to start a pilot study on the efficacy and safety of systemic low dose recombinant tissue plasminogen activator (Actilyse®, Boheringer Ingelheim, Florence, Italy). Patients: Nine cirrhotic patients (6 males and 3 females) with recent portal vein thrombosis were enrolled. Exclusion criteria were portal cavernomatosis, recent (30 days) surgery, active bleeding, hepatocellular carcinoma and cancer in other sites. Methods: All cases were treated for a maximum of 7 days by continuous i.v. infusion of 0.25mg/kg/die of r-tPA plus subcutaneous low molecular weight heparin. Efficacy was evaluated by colour doppler sonography monitoring and confirmed by contrast enhanced computerized tomography. Results: The combined r-tPA/LMWH treatment was well tolerated without clinically significant side effects. Complete resolution of thrombosis occurred in 4 cases, partial regression in 4 and none in 1. Retreatment of a complete recurrence in 1 patient was successful. Variceal pressure dropped from 30.7±4.5mmHg to 21.2±6.6mmHg (p =0.012). Conclusions: Our preliminary data demonstrate that thrombolytic treatment of recent portal vein thrombosis with i.v. r-tPA and LMWH in patients with cirrhosis appears to be safe and effective and can significantly reduce pressure in oesophageal varices. [Copyright &y& Elsevier]

Background and Purpose: Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition.Materials and Methods: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables.Results: A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group.Conclusions: Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition. [ABSTRACT FROM AUTHOR]

Summary: Background: Intrapleural recombinant tissue plasminogen activator (r-TPA) has been successfully evaluated in pediatric patients with complicated parapneumonic pleural effusion (CPE) and pleural empyema (PE). Yet, there is no data concerning r-TPA in adults with CPE/PE. The aim of our study was to investigate the efficacy and complications of r-TPA in adult patients with CPE/PE. Methods: Twenty consecutive patients (mean age 50±18.9 years) with pleural infection (14 CPE and 6 PE) were included. Chest tube was inserted under guidance of chest ultrasound and/or computed tomography. After failure of pleural fluid drainage, 25mg of r-TPA was administered intrapleurally in a single daily dose. The evaluation was made according to imaging and clinical status. Results: The mean volume of fluid increased significantly after r-TPA administration (p <0.0001). White blood cells count (WBC) and C-reactive protein (CRP) were significantly improved after r-TPA instillations (both p <0.0001). Significant clinical and imaging improvement was noted in all but one patient after r-TPA administration (overall p <0.0001). Complications observed were mild: pain in 4 (25%) and local bleeding in 3 (15%) patients. The median number of r-TPA instillations was 3 (range 2–5). Conclusion: Intrapleural instillation of r-TPA at a dose of 25mg is a well-tolerated and effective treatment in 95% of our adult patients with CPE/PE. [Copyright &y& Elsevier]

Myointimal hyperplasia is the condition usually responsible for recurrent stenosis (restenosis) after endarterectomy, bypass grafting and angioplasty. Its cause is still not known. The present study examined whether inhibition of thrombin by tissue plasminogen activator (r-TPA) or polyethylene glycol recombinant hirudin (PEG-hirudin) could reduce restenosis in an animal model. Restenosis was induced in 20 cholesterol-fed rabbits. The right carotid artery underwent a double-balloon injury while left carotid artery acted as a control. Recombinant tissue plasminogen activator (1 mg kg−1 s.c.) and PEG-hirudin (0.7 mg kg−1 s.c.) were given subcutaneously with normal saline acting as a control. Blood levels of PEG-hirudin were measured by both ELISA and an Ecarin (activity) assay. Vessel dimensions were measured in histological sections, obtained from perfusion-fixed tissue, using computerised planimetry. The model reproduced many of the histological changes found in human restenosis, such as intramural thrombus, rupture of the elastic lamina, macrophage infiltration and smooth muscle migration. Reinjury caused an almost three-fold reduction in the area of the lumen (median 0.25 mm2) compared with uninjured vessels (median 0.72 mm2). The mean plasma levels of PEG-hirudin and r-tPA achieved were 291 ng/ml (S.E.M. 28 ng/ml) and 34 IU/ml (S.E.M. 12 IU/ml), respectively. PEG-hirudin significantly inhibited the effect of balloon injury on luminal area compared with saline-treated controls (0.21 versus 0.44 mm2, respectively, P<0.05). Recombinant tPA also had a similar inhibitory affect, but this did not reach statistical significance (0.16 versus 0.44 mm2, respectively, P>0.05). The magnitude of luminal narrowing was significantly reduced by subcutaneous injection of PEG-hirudin. Further studies are required to determine whether this effect can be enhanced by other antithrombins or improved methods of delivery. [Copyright &y& Elsevier]

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Our objective was to identify the outcome of patients treated with tissue plasminogen activator (r-tPa) in Pakistan and compare these data to available regional and international data. The charts of all patients treated with r-tPa for acute stroke at two centers in Pakistan (Aga Khan University, Karachi and Liaquat National hospital, Karachi) were retrospectively reviewed. We identified 21 patients. The utilization of tPa at Aga Khan Hospital was 18/1,185 patients (1.5%) from 2005 to 2007 while at Liaquat National Hospital was 3/575 patients (0.52%) over 1 year (2007). Mean time interval between stroke onset and start of r-tPa infusion was 169 min. Three patients (14%) developed fatal hemorrhage and two (10%) developed non-fatal hemorrhage. Four patients (19%) died. We identified protocol violations in seven patients (33%). In conclusion, the utilization of thrombolytic therapy is low and complication rate is high. Interventions for training physicians are needed. [ABSTRACT FROM AUTHOR]

Introduction: Macular subretinal hematoma is a complication of age related macular degeneration (AMD) responsible for a severe change in vision. We evaluated anatomic and functional results of surgical treatment of hematoma by vitrectomy, subretinal injection of r-tPA (recombinant tissue plasminogen activator), intravitreal bevacizumab injection and air tamponade., Methods: Retrospective case series including 26 patients with submacular hemorrhage who underwent vitrectomy within 15 days after the onset of symptoms. Optical coherence tomography (OCT) was performed to measure the diameter of the hemorrhage and specify the location in relation to the retinal pigment epithelium. Anatomical success was defined as a total displacement of the hemorrhage out of the fovea at the first postoperative visit. Visual acuity improvement was measured at 1 and 6 months and at final postoperative visit., Results: The procedure resulted in hemorrhage displacement away from the fovea in 20 eyes (81%). Visual acuity significantly improved by 5.8 (±7.2) lines (P=0.0003) at 1 month postoperatively, 7.4 (±6.7) lines (P=0.0004) at 6 months and 7.4 (±7.4) lines (P=0.0002) at the final postoperative visit (16.5±19.8 months). There was an inverse correlation between hemorrhage diameter and final acuity improvement (Pearson correlation coefficient ρ=-0.60 (IC 95% [-0.81; -0.26]; P=0.002))., Conclusion: Vitrectomy with subretinal r-tPA injection was found to be effective for the displacement of AMD hemorrhage in 81% of the patients. Mean final visual acuity improved by more than 7 lines, confirming the efficacy and functional benefit of surgical displacement., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: To evaluate the anatomical and functional outcome of patients with traumatic submacular hemorrhage (SMH)., Methods: A retrospective, interventional case series of patients presenting between January 2016 and April 2018 was carried out at 4 tertiary eye care centers of India. Medical records of the patients with a history of blunt trauma and SMH were retrospectively reviewed. The intervention done was any one of the following: pneumatic displacement with 0.3 ml of intravitreal gas [100% perfluoropropane (C3F8) gas], pneumatic displacement with intravitreal 0.3 ml of 100% C3F8 gas combined with 100 μg/0.1 ml of recombinant tissue plasminogen activator (r-tpa), pars plana vitrectomy (PPV) with subretinal r-tpa and gas tamponade. The primary outcome measures included change in visual and anatomical status., Results: Twenty eyes of 20 patients with blunt trauma were analyzed. Thirteen patients had small size SMH, 5 patients had medium size SMH, and 2 patients had massive size SMH. Sixteen patients had a favorable functional outcome, and eighteen patients had favorable anatomical outcome. The size and duration of post-traumatic SMH did not significantly affect the anatomical ( P  = 0.123) or functional ( P  = 0.293) outcome in our study. The patients who presented with initial visual acuity of 6/60 or better showed better functional outcome, which was statistically significant ( P  = 0.007)., Conclusion: Minimally non-invasive procedure including intravitreal r-tpa and gas appear to be effective in the displacement of post-traumatic SMH., (© 2019 Iranian Society of Ophthalmology. Production and hosting by Elsevier B.V.)