Plasminogen Activator Therapy Research Articles

Continuous intrafemoral artery infusion of urokinase improves diabetic foot ulcers healing and decreases cardiovascular events in a long-term follow-up study

IntroductionDiabetic foot ulcer (DFU) is a disabling complication of diabetes mellitus. Here, we attempted to assess whether long-term intrafemoral artery infusion of low-dose urokinase therapy improved DFUs and decreased cardiovascular...

Minimally invasive puncture combined with a high frequency of urokinase therapy improves outcomes in patients with HICH

Minimally invasive puncture combined with urokinase is widely used in the treatment of hypertensive intracerebral hemorrhage (HICH). However, the appropriate frequency of urokinase following minimally invasive puncture in patients is still unclear. In total, 55 patients were enrolled in this study. According to the frequency of urokinase (10.0 ​× ​104 units) administration, 30 patients received urokinase at Q4h, while the other 25 patients received urokinase at Q8h. In the univariate analysis, preoperative GCS (p ​= ​0.0002), postoperative GCS (p ​= ​0.0007), the volume of residual hematoma (p ​= ​0.0179), and the frequency of urokinase (p ​= ​0.0110) were associated with unfavorable outcomes in patients with HICH in the basal ganglia. The multivariate analysis revealed that the frequency of urokinase was independently associated with unfavorable outcomes in patients with HICH in the basal ganglia (p ​= ​0.038, 1.109–35.380). The drainage time was significantly shorter in the Q4h group (14.17 ​± ​0.86 ​h) than in the Q8h group (27.36 ​± ​1.39 ​h) (p ​< ​0.0001). The GOS (4.37 ​± ​0.18), BI (75.52 ​± ​2.39), and mRS (1.67 ​± ​0.24) in the Q4h group were significantly ameliorated compared to those in the Q8h group (GOS 3.56 ​± ​0.18, BI 64.13 ​± ​2.22, and mRS 2.64 ​± ​0.28, respectively) (p ​= ​0.0004, p ​= ​0.0002, and p ​= ​0.0018) at 3 months of follow-up. Thus, minimally invasive puncture combined with urokinase is safe and efficient. Increasing the frequency of urokinase administration can produce faster and better postoperative recovery for patients with HICH in the basal ganglia.

Fiberoptic bronchoscopy combined with urokinase therapy for the treatment of fatal massive hemoptysis: A case report.

Fatal massive hemoptysis is a life-threatening emergency in the respiratory system. Currently, the treatment methods and techniques for massive hemoptysis are still limited, and there are often issues of delayed treatment or improper methods in clinical practice, leading to the difficulty of rescuing patients and high mortality rates. When fatal massive hemoptysis occurs, the key to successful treatment lies in whether intrapulmonary blood clots can be effectively cleared and airway patency can be ensured. Our practice of combining fiberoptic bronchoscopy with urokinase treatment to clear intrapulmonary blood clots after fatal massive hemoptysis demonstrates the effectiveness of this method. We report a 32-year-old female who experienced cough, accompanied by fatal massive hemoptysis with extensive blood clot obstruction in the airway. Considering the difficulty of clearing the airway using conventional methods, it was decided to perform fiberoptic bronchoscopy combined with urokinase therapy after reviewing relevant literature. After treatment, the intrapulmonary blood clots were successfully extracted, thereby relieving airway obstruction. Finally, the patient was successfully weaned off extracorporeal membrane oxygenation, extubated, and evacuated from the ventilator. Currently, the patient's condition is stable, and follow-up chest X-ray as well as computed tomography scans have shown improvement compared to previous assessments. Fatal massive hemoptysis is a intractable emergency in clinical practice. In this case, we confirmed that fiberoptic bronchoscopy combined with urokinase therapy may be effective and safe in the treatment of fatal massive hemoptysis.

Clinical Profile and Outcome of Children with Empyema Thoracis in Tertiary Hospital

Introduction: Empyema thoracis (ET) is an accumulation of pus in the pleural space. It is a common condition in childhood having significant morbidity and mortality. The clinical manifestations of empyema are high grade fever with chills and rigors, cough, breathlessness, chest pain. The present study analyses the epidemiological aspects of the disease, etiological agents, clinical features and associated lesions in diagnosis of empyema and the outcome of early Video-assisted thoracoscopic surgery (VATS) on morbidity of disease in children.&#x0D; Objectives: To study various demographic characteristic and to evaluate various management strategies and outcome in children with empyema thoracis.&#x0D; Methodology: This is a prospective hospital based observational study, conducted at Nobel Medical College Teaching Hospital Biratnagar, from December 2021 to November 2022. All children in the age group of 1month to 16 years diagnosed pyogenic empyema by lights criteria during the study are included in the study. Children below 1 month of age and pleural effusion not meeting the criteria for exudative pleural effusion by Light's criteria are excluded from the study.&#x0D; Results: Majority of the study population are in the age group of &gt;5 years. Males are more common than females. Most common clinical feature was fever followed by cough, chest pain and shortness of breath. Culture is positive in 68% out of which 32% is staphylococcus aureus, 20% is mycobacterium tuberculosis ,16% is streptococcus pneumonia. Duration of illness is &lt;1week in 48% of the children, 1-2weeks in 40% and &gt;3weeks in 12% of the children. In 80% of the children there is unilateral involvement in the x- ray chest. In the children who are uncomplicated all of them had intercoastal chest tube drain (ICD) usage,76.4% had urokinase therapy and 5.8% had undergone thoracotomy and none of them had need for surgery. In the children with complication 87.5% had ICD usage and urokinase therapy,25% of them had undergone thoracotomy and 12.5% had need for surgery.&#x0D; Conclusion: Empyema thoracis is more commonly seen in the males of the group&gt;5 years with duration of illness &lt;1 week maned mostly by ICD usage, where there was mostly unilateral involvement in x ray chest.

Intra-Arterial Urokinase for Acute Superior Mesenteric Artery Occlusion: A Retrospective 12-Year Report of 13 Cases

This retrospective study aimed to evaluate the outcomes of 13 patients with acute superior mesenteric artery (SMA) occlusion who underwent intra-arterial urokinase thrombolysis between 2008 and 2020. On angiography, seven presented with complete SMA occlusion versus six with incomplete occlusion. The median time from abdominal pain to attempting urokinase thrombolysis was 15.0 h (interquartile range, 6.0 h). After urokinase therapy, bowel perfusion was restored with bowel preservation in six patients; however, treatment failed in the other seven patients. The degree of SMA occlusion (complete vs. incomplete, p = 0.002), degree of recanalisation (p = 0.012), and length of stay (p = 0.032) differed significantly between groups. Of the seven patients with complete SMA occlusion, six underwent bowel resection, of whom three died, and the remaining patient died of shock due to delayed surgery. Among the six patients with incomplete SMA occlusion, no bowel resection was performed. In our experience, intra-arterial urokinase thrombolysis may serve as an adjunctive treatment modality, being a potential replacement for open thrombectomy that is able to preserve the bowel and obviate surgery in cases of incomplete SMA occlusion; however, its use is unsuitable in cases of complete SMA occlusion, for which surgery is warranted.

The relationship between serum bilirubin levels and early neurological improvement in patients with acute ischemic stroke treated with intravenous tissue plasminogen activator

Background &amp; Objective: Acute ischemic stroke is defined as the development of sudden neurological deficits resulting from a focal injury due to vascular occlusion in the central nervous system. Intravenous tissue plasminogen activator (t-PA) therapy in these patients is an internationally accepted, evidence- based effective treatment. Previous data suggest that increased serum bilirubin may reflect the intensity of oxidative stress associated with stroke severity. This study aimed to investigate the effect of bilirubin levels on early neurological improvement after intravenous t-PA treatment and whether bilirubin is a determinant in in-hospital mortality. Methods: The determinant role of admission bilirubin levels in the severity of stroke, in-hospital mortality and early neurological improvement after intravenous t-PA was investigated. An independent association of bilirubin with mortality and neurological improvement were identified by multivariate logistic regression analysis. Results: A total of 184 ischemic stroke patients who received intravenous t-PA were included in the study. Serum direct bilirubin, indirect bilirubin, and total bilirubin of patients in the group without early improvement were significantly higher than the group with improvement (p= 0.041, p= 0.030, p= 0.026, respectively). Also, in binary logistic regression analysis, total bilirubin was found to be an independent predictor for early neurological improvement (OR 6.257, 95%CI 1.482-26.413, p=0.013). Conclusions: There was a significant relationship between the severity of the stroke and in-hospital mortality and increased serum bilirubin levels in our study. Again, there was a significant relationship between the lack of early neurological improvement after intravenous t-PA and increased serum bilirubin levels, and serum direct bilirubin levels were independent predictor of neurological improvement.

Abstract TP7: Phase 2a Study Of Elezanumab In Patients With Acute Ischemic Stroke

Introduction: Treatment of acute ischemic stroke focuses on reperfusion but is limited by timing and other exclusions, and despite intervention, patients may sustain residual neurologic impairment. In addition to initial excitotoxic reactions following occlusion, upregulation of factors such as repulsive guidance molecule A (RGMa) inhibits cell survival and neuronal repair in infarcted regions. In vivo neutralization of RGMa is associated with decreased lesion size, reduced glial scarring, and enhanced functional recovery in animal models of cerebral artery occlusion; thus, RGMa suppression represents a novel therapeutic target due to its potential protective and restorative mechanisms. Elezanumab is an investigational monoclonal antibody that binds specifically to RGMa and is being evaluated for its function after ischemic stroke. Methods: Elezanumab in Acute Ischemic Stroke (EAISE) is a 52-week, phase 2a, randomized, double-blind, placebo-controlled study evaluating safety, efficacy, and pharmacokinetics of elezanumab in patients with acute ischemic stroke (NCT04309474). Patients will be randomized 1:1 within 23 hours since “last known normal” to receive elezanumab or placebo and every 4 weeks thereafter through week 48. Patients must be aged 30-90 years with a clinical diagnosis of acute ischemic stroke in anterior circulation and have a National Institutes of Health Stroke Scale (NIHSS) total score of 7 to 21. Patients who receive tissue plasminogen activator or endovascular therapy will be eligible if they continue to exhibit an NIHSS of 7 to 21 after treatment. Patients with evidence of seizure on stroke onset and history of repeated episodes of complex migraines will be excluded. Results: Projected enrollment is 120 patients across 45 sites in multiple countries. Primary endpoint is the NIHSS total score throughout the treatment period. Secondary endpoint is a favorable outcome based on the modified Rankin Scale, defined as a score of 0-2 at week 52. Exploratory outcomes include activities of daily living, cognition, mood, and fluid and imaging biomarkers. Conclusion: This phase 2 study will evaluate safety and efficacy of elezanumab, a novel therapeutic intervention to improve neurological recovery after acute ischemic stroke.

Aortic dissection diagnosed on stroke computed tomography protocol: a case report

BackgroundAortic dissection is one of the causes of stroke. Because cerebral infarction with aortic dissection is a contraindication to intravenous recombinant tissue plasminogen activator (rt-PA) therapy, exclusion of aortic dissection is necessary prior to its administration. However, imaging takes time to provide a diagnosis, possibly causing delays in surgical treatment.Case presentationA 65-year-old Japanese female patient was transported to the hospital for a suspected stroke, with back pain and left upper and lower extremity palsy which occurred while eating. Upon arrival at the hospital, the left lower limb paralysis had improved, but the left upper limb paralysis remained. Right back pain had also developed. A plain head computed tomography (CT) scan performed 110 minutes after onset showed no acute bleeding or infarction. Subsequent CT perfusion (CTP) showed acute perfusion disturbance in the right hemisphere without infarction, known as ischemic penumbra. The four-dimensional maximum-intensity projection image reconstructed from CTP showed a delayed enhancement at the right internal carotid and right middle cerebral arteries compared to the contralateral side, suggesting a proximal vascular lesion. Contrast helical CT from the neck to abdomen revealed an acute aortic dissection of Stanford type A with false lumen patency. The dissection extended to the proximal right common carotid artery. The patient underwent an emergency total arch replacement and open stent graft. After recovering well, the patient was ambulatory upon discharge from the hospital. The combination of plain head CT, CTP, and helical CT scan from the neck to abdomen enabled us to evaluate for stroke and aortic dissection within a short amount of time, allowing for early therapeutic intervention.ConclusionsWhen acute stroke is suspected due to neurological deficits, plain head CT is the first choice for imaging diagnosis. The addition of cervical CT angiography can reliably exclude stroke due to aortic dissection. CTP can identify ischemic penumbra, which cannot be diagnosed by plain head CT or diffusion-weighted magnetic resonance imaging. These combined stroke CT protocols helped us avoid missing an aortic dissection.

Acute Arterial Ischemic Stroke in a Treated Child with Hunter's Syndrome: A Case Report and Review of the Literature

AbstractEnzyme replacement therapy (ERT) has limited therapeutic effects on neurologic, skeletal, and cardiovascular pathophysiology. We report an acute right-sided flaccid hemiparesis in an 11-year-old boy with the severe neuronopathic phenotype of Hunter's syndrome who was receiving weekly idursulfase ERT. Due to his psychomotor regression and epilepsy, his presentation to the hospital was delayed. Computed tomography scan of brain showed no acute changes or hemorrhage. Stroke code was not called as patient was already outside of the time window for tissue plasminogen activator (tPA) therapy. Brain magnetic resonance imaging (MRI) showed diffuse cortical and deep atrophy consistent with his baseline neurological status and restricted diffusion in the territory of the left-middle cerebral artery (MCA) consistent with recent infarction. T1-weighted MRI revealed low signal intensity of the left insular cortex, as well as volume loss, consistent with previous undiagnosed stroke in the same vascular territory. In addition, MR angiogram (MRA) demonstrated left terminal M1 segment MCA occlusion. Echocardiogram showed aortic root dilation and moderate aortic valve insufficiency. Patient was also noted to have bacteremia related to port infection. ERT is limited by blood–brain barrier and the underlying glycosaminoglycans (GAGs) extracellular tissue accumulation which produces a proinflammatory state. GAG and bacterial lipopolysaccharide (LPS) are known to activate toll-like receptor 4 (TLR-4). GAGs released in the extracellular space of intracranial vessels induce inflammation by activating the TLR-4 pathway which is exacerbated by bacterial LPS contributing to focal arteritis. Our case suggests the importance of GAGs in the activation of the TLR-4 pathway as a cause of stroke in Hunter's syndrome.

Abstract P077: Hypertension And Ischemic Stroke; The Effect Of A Combined Anti-hypertension Medications And Thrombolytic Therapy

Background: The aim of this study is to identify clinical risk factors in acute ischemic stroke ( AIS) pretreated with anti-hypertensive (anti-HTN) medications with a subsequent thrombolytic therapy that are associated with potential worsening or improving neurological functions. Methods: We analyzed retrospectively collected data from consecutive AIS patients with a combined anti-HTN medications and recombinant tissue plasminogen activator (rtPA) therapy for AIS. We used logistic regression model to identify demographic and clinical risk factors that are associated with improving or worsening neurologic functions in AIS patients with a combined anti-HTN and thrombolytic therapy. The overall correct classification of the logistic regression models was determined using the Hosmer-Lemeshow test, while the area under the receiver operating characteristic curve was used to test the sensitivity of the model. The variance inflation factor was used to check for multicollinearity. Results: In the adjusted analysis, patients with increasing age (Odd ratio (OR)=1.035, 95% CI, 1.022-1.049, P &lt;0.001), female AIS patients (OR = 1.630, 95% CI, 1.182-2.248, P =0.002) with a history of substance abuse (OR = 2.315, 95% CI, 1.107-4.842, P = 0.026) were associated with worsening neurologic functions. However, Caucasians (OR = 0.535, 95% CI, 0.361-0.793, P = 0.002) with dyslipidemia (OR = 0.655, 95% CI, 0.479-0.897, P = 0.008), obesity (OR = 0.642, 95% CI, 0.472-0.873, P = 0.005), high-density lipoproteins (HDL; OR = 0.988, 95% CI, 0.976-1.000, P = 0.045), and with a direct admission (OR = 0.509, 95% CI, 0.341-0.761, P = 0.001) were associated with improving neurologic function in AIS patients with a combined anti-HTN medications and rtPA therapy. Conclusion: Our findings reveal specific demographic and clinical risk factors that are associated with worsening or improving neurological functions in AIS pretreated anti-HTN medications with a subsequent thrombolytic therapy. This finding suggests the development of management strategies to manage identified clinical risk factors in AIS patients pretreated with anti-HTN medications prior to thrombolytic therapy.

Clinical features and efficacy of reperfusion therapy in minor ischemic stroke patients with atrial fibrillation.

The efficacy of reperfusion therapy (RT) using intravenous infusion of recombinant tissue plasminogen activator and/or endovascular therapy for minor ischemic stroke (MIS) has not yet been established. The present study aimed to elucidate the clinical features of MIS patients with atrial fibrillation (AF) and examine whether they could be potential candidates for RT. Data of MIS patients, defined as those with a score ≤ 5 on the National Institute of Health Stroke Scale, were extracted from patients admitted to our hospital between 2006 and 2018, and clinical characteristics were compared between the AF and non-AF groups. Thereafter, the impact of RT on outcomes in the AF- group was evaluated using the modified Rankin scale (mRS) score 3months after onset and compared to that of standard medical therapy (SMT) using propensity score matching (PSM). Of 10,483 stroke patients, 3003 were shortlisted, and 457 AF patients and 2546 non-AF patients were finally selected. Patients in the AF group had more RT (13.3% vs. 5.7%, p < 0.001) than those in the non-AF group. Using PSM, 53 patients each were extracted from the AF-RT and AF-SMT groups. The frequencies of mRS = 0 or 1 for the AF-RT and AF-SMT groups were 69.8% and 64.2% (p = 0.536), respectively, with a significant difference in mRS = 0 (56.5% vs. 34.0%, p = 0.019). The present study found that MIS patients with AF underwent more RT than those without AF and that RT compared favorably with SMT for them; further study is warranted to examine whether these patients could be good candidates for RT.

Abstract WMP99: Alpha2-Antiplasmin Inactivation Reduces Hemorrhagic Transformation and Ischemic Brain Injury After Tissue Plasminogen Activator Therapy and Mechanical Reperfusion

Tissue plasminogen activator (r-tPA) therapy followed by thrombectomy-mediated, mechanical reperfusion profoundly reduces neurologic disability in appropriately selected patients. Nevertheless, a high proportion of these patients (20-37%) develop brain hemorrhage. We examined the contribution of α2-antiplasmin, a fast-acting plasmin inhibitor, to brain hemorrhage and ischemic injury following r-tPA treatment and mechanical reperfusion. Methods: Mice (C57Bl6) underwent 1 to 4 h of middle cerebral artery occlusion followed by treatment with r-tPA alone (10 mg/kg), r-tPA (10 mg/kg) plus an α2AP inhibitor (α2AP-I, 10 mg/kg) antibody or saline, followed by reperfusion. Mice were assessed by neurobehavioral measures (Bederson score and corner test) and histology 24 h post-ischemic stroke. Analyses were performed in a blinded fashion. Time course studies in r-tPA-treated mice showed that intracerebral hemorrhage (p&lt;0.05), brain infarct volume (p&lt;0.001) and brain swelling (p&lt;0.01) increased progressively with ischemic time, with a plateau at 3 h of ischemia, as compared to saline treated controls. Mice treated at 3 h with r r-tPA + α2AP-I showed significantly (p&lt;0.05) reduced brain hemorrhage, brain infarct volume (p&lt;0.01) and brain swelling (p&lt;0.05). Treatment with r-tPA + α2AP-I also significantly improved neurobehavioral deficits (p&lt;0.01) and sensory motor dysfunction (p&lt;0.01) at 24h of reperfusion. Conclusion: α2AP contributes to the increased brain hemorrhage and ischemic brain injury associated with r-tPA treatment followed by mechanical reperfusion. Targeting a2AP appears beneficial, because specific, monoclonal antibody-mediated inhibition of α2AP markedly reduced brain hemorrhage, infarction, swelling and neurobehavioral disability.

Abstract WP113: Impact of Apixaban on Clinical Outcome of the Patients With Large Vessel Occlusion or Stenosis (alvo) Study

Background: Efficacy and safety of direct oral factor Xa inhibitor in patients with acute large vessel occlusion (LVO) and nonvalvular atrial fibrillation (NVAF) were questionable because recombinant tissue plasminogen activator (rt-PA) and endovascular therapy (EVT) became the standard therapy. Methods: We conducted historical and prospective multicenter registry from July 2016 to Feb 2018 at 38 centers in Japan. The eligible criteria were 20-year old or elder and patients with NVAF and acute LVO who received apixaban within 14 days from the onset. The primary endpoint was a composite of all-cause death, International Society of Thrombosis and Hemostasismajor bleedings, and ischemic events. Ischemic events included ischemic stroke, acute coronary syndrome, acute myocardial infarction and systemic embolism. The secondary endpoints were each component of primary composite endpoint. Results: We registered 713 patients but 27 patients were excluded due to logical error or ineligibility. The mean age was 78 (SD 10) years and 52% were male among 686 enrolled patients. The median NIHSS and ASPECTS on admission were 14 (range 0-38) and 8 (range 0-10), respectively. The use of rt-PA and EVT were 39.1% and 52.3% of patients, respectively. The median time from onset to the start of apixaban was 2.5 days (range 0-14). The cumulative incidence of primary composite endpoint at 90 days and 365 days were 9.6% (95%CI 7.4-11.9) and 17.5% (95%CI 14.4-20.5), respectively. The cumulative incidence of primary composite endpoint were 15.6% and 12.2% in those with and without EVT at 365 days (p=0.20) The cumulative incidences of ISTH major bleedings and ischemic events at 365 days were 9.0% (95%CI 6.7-11.2) and 4.4% (95%CI 2.8-6.0), respectively. Conclusions: We estimated the cumulative incidences of bleeding and ischemic events as well as all-cause mortality in patients on apixaban for NVAF and acute LVO. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT02818868.)

Abstract TP159: Unilateral Spatial Neglect as an Independent Prognostic Factor for Poor Fim Efficiency in Patients With Mild to Moderate Ischemic Stroke

Background and Purpose: Unilateral spatial neglect (USN) is often observed in ischemic stroke patients suffered their right parietal lobe. USN is an obstacle to undergo rehabilitation smoothly, then might influence the recovery of activities of daily living (ADL) after stroke. We aimed to clarify the association between the presence of USN after ischemic stroke and the ADL improvement. Methods: Consecutive patients with first-ever ischemic stroke and left limb paralysis who admitted to within 7 days from onset during February 2011 and March 2019 were included. Patients met the following criteria were excluded: mRS ≥3 before onset, NIHSS &gt;15 on admission, without left limb paralysis, and missing NIHSS or functional independence measure (FIM) score on admission. Multiple regression analysis was performed to investigate the association between FIM efficiency score of acute phase and following factors: age, sex, acute reperfusion therapy (using an intravenous infusion of recombinant tissue plasminogen activator and/or endovascular therapy), FIM score on admission, and other clinical characteristics. All data were collected retrospectively using our electrical health record. Results: 721 ischemic stroke patients with left limb paralysis (320 women, median age 76) were included. Median FIM efficiency score was significantly lower in patients with USN than without USN (n=240, 481; 0.83 vs 1.63, respectively). Multiple regression analysis showed that USN, age, and acute reperfusion therapy were significant prognostic factors of FIM efficiency (coefficient and 95% confidence interval [CI]: -0.135 [-0.771 to -0.153], -0.106 [-0.022 to -0.002], and 0.224 [0.136 to 0.305], respectively). Conclusions: USN significantly influence the recovery of ADL after ischemic stroke. Clinicians should adequately evaluate USN after stroke and undergo USN-specific rehabilitation for them to optimize the effect of post-stroke rehabilitation. USN-specific rehabilitation might lead to better FIM efficiency.

Abstract TP298: Measuring Quality of Care for Acute Ischemic Stroke Treated With Acute Reperfusion Therapy in Japan: A Nationwide Quality Improvement Initiative of the J-aspect Study

Background and Purpose: There is no consensus about efficiently measuring quality indicators (QIs) of acute ischemic stroke (AIS) in Japan. To evaluate feasibility and reliability of measuring QIs for AIS patients who received intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular therapy (ET), by combining information from health insurance claims database and medical chart. Methods: AIS patients who received rt-PA or ET between 2013 and 2015 were identified from the J-ASPECT Diagnosis Procedure Combination (DPC) database. The 17 and 8 QI measures for primary and comprehensive stroke centers (PSCs and CSCs) were selected for AIS, respectively. More than 60% of data for calculating the QIs were obtained from the DPC database and preset in the tool. Responsible physicians were asked to review accuracy of preset data and add necessary information from medical chart. Adherence rates or performance measures for each QI were calculated for patient- and hospital-levels. Associations between adherence rates and hospital characteristics were analyzed using hierarchical logistic regression analysis. Result: In total, data of 8,506 patients (rt-PA 83.5%, ET 34.9%) from 173 hospitals were obtained. The median age was 76 (interquartile range 65–83) years, and 42.1% were women. Median National Institute of Health Stroke Scale (NIHSS) score at admission was 14 (7-21). All of the target QIs were successfully measured. Among PSC QIs, adherence rates were low (&lt;50%) (e.g. door-to-needle time &lt; 60 minutes 37.9%) and intermediate (50-75%) (e.g. stroke unit care 58.7%) in 4 each. For CSC QIs, median door-to-puncture time was 105 (76-147) minutes and TICI grade 2b and 3 recanalization were achieved in 73%. A higher number of stroke discharge was associated with greater adherence to stroke unit care, early rehabilitation and stroke education. Conclusion: Measuring QIs of AIS by this novel approach was feasible and reliable to provide a national benchmark.

Highly glycosylated CD147 promotes hemorrhagic transformation after rt-PA treatment in diabetes: a novel therapeutic target?

BackgroundDiabetes is known to be a main risk factor of post-stroke hemorrhagic transformation following recombinant tissue plasminogen activator (rt-PA) therapy. However, the mechanism through which diabetes exacerbates hemorrhagic transformation is insufficiently understood. We aimed to verify that CD147, the extracellular matrix metalloproteinase (MMP) inducer, played a vital role in the progress.MethodsWe performed middle cerebral artery occlusion on diabetic and non-diabetic rats, with or without rt-PA treatment, and then compared the glycosylation level of CD147, caveolin-1, MMPs activities, and blood-brain barrier (BBB) permeability. In vitro, tunicamycin treatment and genetic tools were used to produce non-glycosylated and lowly glycosylated CD147. An endogenous glucagon-like peptide-1 receptor (GLP-1R) agonist was used to downregulate the glycosylation of CD147 in vivo.ResultsCompared with non-diabetic rats, diabetic rats expressed higher levels of highly glycosylated CD147 in endothelium and astrocytes following rt-PA treatment accompanied by higher activity of MMPs and BBB permeability, in the middle cerebral artery occlusion model. Caveolin-1 was also overexpressed and co-localized with CD147 in astrocytes and endothelium in diabetic rats. In vitro, advanced glycation end products increased the expression of highly glycosylated CD147 in astrocytes and endothelial cells. Downregulating the glycosylation of CD147 lowered the activity of MMPs and promoted the expression of tight junction proteins. The expression of caveolin-1 in endothelial cells and astrocytes was not inhibited by tunicamycin, which revealed that caveolin-1 was an upstream of CD147. In vivo, GLP-1R agonist downregulated the glycosylation of CD147 and further reduced the activity of MMPs and protected the BBB in diabetic rats.ConclusionCD147 is essential for diabetes-associated rt-PA-induced hemorrhagic transformation, and downregulation of CD147 glycosylation is a promising therapy for neurovascular-unit repair after rt-PA treatment of patients with diabetes.

A severe case of Streptococcal pyogenes empyema following influenza A infection

BackgroundAny immunological mechanisms induced by influenza virus could cause severe secondary bacterial superinfection such as those by Streptococcus pyogenes [group A streptococcus (GAS)], Streptococcus pneumoniae or Staphylococcus aureus. Over recent years, the frequency of pleural empyema has increased in children with influenza infection.We present a severe case of acute empyema caused by S.pyogenes after influenza A infection.Case presentationA previously healthy 39-year old woman was diagnosed as influenza A and received oral Oseltamivir 75 mg twice daily for 5 days. She had no vaccination of influenza A. Although her influenza A infection improved, she complained of fever and cough to our institute. Chest radiography showed encapsulated pleural effusion of the left lung and pleural effusion which was consistent with acute empyema. Then, she was diagnosed as having acute empyema and was admitted to our institute. Streptococcus pyogenes was identified by pleural fluid culture on day 4. thus, MNZ was changed to clindamycin (CLDM) 600 mg three times a day. While thoracic drainage with intrapleural urokinase and combination antibiotic therapy of ceftriaxone and CLDM were performed, her general condition and chest radiographic findings were not improved. She received video-assisted thoracic debridement on day 10. After the operation, the antibiotic therapy was changed to ABPC 6 g daily iv. Due to good clinical course, the antibiotic therapy was switched to oral amoxicillin 500 mg three times daily on day 28. Then, she was discharged.ConclusionInfluenza A virus infection could lead to severe GAS infection, while the latter can occur in otherwise healthy individual as well. Physician must consider the possibility of severe GAS infection after influenza A infection.

Evaluation of the efficacy of recombinant tissue plasminogen activators in improving clinical status of acute ischemic stroke: A randomized clinical trial in Iran

Background: Acute ischemic stroke is caused by blockage of a cerebral artery and is also known as cerebrovascular accident (CVA). Recombinant tissue plasminogen activator (rt-PA) therapy is effective in reducing early and long-term neurologic disabilities if it is started quickly. Therefore, the aim of this study was to determine the efficacy of treatment with recombinant tissue plasminogen activators in improving the clinical status of acute ischemic stroke.&#x0D; Methods: The current study was performed as a clinical trial of two groups- treatment and control (n=20 per group). The treatment group consisted of patients who received rt-PA, while the control group consisted of patients who did not receive rt-PA. For each group, evaluation of neurological disabilities following ischemic stroke was based off the National Institutes of Health Stroke Scale (NIHSS), for early assessment of disability on the third day of treatment), and off the modified Rankin Scale (MRS) at 90 days after stroke. The drug effect criterion was used to reduce the neurological disability or the difference in NIHSS on day 3 after treatment. Also, the duration of onset of symptoms until the arrival of the patients to the emergency room (ER), as well as the risk factors, complications and number of deaths in both groups, were recorded. Data obtained were analyzed by SPSS software.&#x0D; Results: The results of the study showed that the mean of ER arrival time, NIHSS before treatment, and NIHSS on day 3 of treatment in the control group was higher than that of the treatment group; the difference was statistically significant (P&lt;0.05). The results also indicated that the probability of improvement of neurological disabilities in the experimental group was greater than that of the control group (relative risk (RR) =1.25). Additionally, the odds ratio (OR) for receiving rt-PA in the NIHSS positive treatment group compared to the control group was equal to 1/5 (OR=1.5). The results showed that 30% of the patients in the treatment group were treated with a complication. The mean of MRS was higher in the control group at 90 days after the stroke, compared with the treatment group.&#x0D; Conclusion: Treatment with rt-PA reduces the neurological disability in patients with ischemic stroke, since the mean of MRS is lower in the treatment group, compared with the control group, after 90 days of treatment.

Efficacy and Safety of Intravenous Urokinase and Sodium Ozagrel in Acute Ischemic Stroke

Urokinase and sodium ozagrel are widely used in patients with acute ischemic stroke (AIS) in China. But the effectiveness and safety of the two combinations are not yet clear. A total of 129 AIS patients who were treated with combined intravenous (IV) urokinase and sodium ozagrel within 6 hours of onset were included in this study. All the patients were assessed with the National Institute of Health Stroke Scale (NIHSS) score at baseline, 6 hours, at hospital discharge, and 1 month after AIS. All the patients were characterized into two groups based on early response (decrease in NIHSS score≥4 points at 6 hours) and good outcome (NIHSS score ≤ 1 at 1 month), and assessed treatment safety by evaluating intracranial hemorrhage and mortality. There were 54 patients in the good outcome group and 74 in the bad outcome group at the end. Multivariate analysis showed that shorter onset to treatment time, a lower baseline NIHSS score, and lack of large artery stenosis or occlusion werel associated with good outcome at 1 month. This study suggested that combined IV urokinase and sodium ozagrel therapy was effective and safe in treating patient with AIS within a 6-hour time window. With lower cost and a longer time window, it can be used as an alternative intravenous thrombolytic therapy in patients with AIS except rt-PA.

P3.12-002 Patients with Malignant Pleural Effusion who Succeeded Pleurodesis have a Longer Survival Rate - A 10-year Follow-Up

Pleurodesis is often used to prevent re-accumulation of malignant pleural effusions (MPE). Intrapleural urokinase (IPUK) therapy facilitates lung re-expansion for patients with loculated MPE or trapped lung and allows subsequent pleurodesis. The MPE management has been traditionally regarded as a symptomatic treatment with rare mention of its impact on survival. Our preliminary study involved 26 patients showed successful pleurodesis translates into a longer survival. (BMC Cancer 2016; 16:463) The successfully induced inflammatory response by sclerosing agent is supposed to prohibit tumor invasion and metastasis. Part I. Three hundred and eighty-nine consecutive patients with symptomatic MPE underwent minocycline pleurodesis with (n = 184) and without (n = 205) antecedent IPUK therapy between September 2005, and August 2015, were recruited for pleurodesis outcome and survival analysis. Part II. The pleural fluid pro-inflammatory (IL-6, TNF-α), or anti-inflammatory (IL-1β, IL-10, TGF-β) cytokines before and after pleurodesis in fifteen patients with MPE between September 2015 and April 2016 were measured using Bio-Plex® Multiplex assays and correlated with the pleurodesis outcome and patient survival. Part I. Patients numbering 109 (59.2%) responded to the IPUK therapy. The success rate of the subsequent pleurodesis was similar to that of the simple pleurodesis group (70.5% vs 69.0%; p = 0.804). In both groups, the patients who succeeded pleurodesis had a longer survival rate than those that failed (median, 259 vs 102 days; p <.001 and 414 vs 100 days; p <0.001 respectively). Multivariate analysis showed that successful pleurodesis was an independent prognosticator (hazard ratio, 0.374; p <0.001 and 0.271; p <0.001 respectively). The differences remained when lung and breast cancer patients were studied separately. Part II. After instillation of sclerosing agent, pleural fluid IL-1β and IL-10, with a lesser degree were elevated in the group of successful pleurodesis. There was no discrimination in the TGF-β1, and IL-6 level between those succeeded and failed pleurodesis. No consistent change of TNF-α was observed in either group. Successful pleurodesis translates into a better survival rate promotes performing pleurodesis on lung re-expansion. The selective elevation of anti-inflammatory cytokines following pleurodesis suggests an anti-tumor effect. The change of TGF-β1 correlated with its dual role in cancer. While chronic inflammation might promote tumor formation, therapy induced acute inflammation might well hamper the process, and is indeed used therapeutically to inhibit tumor. Further studies are warranted to clarify the mechanism and provide opportunities to develop novel therapeutic strategies.