The Changes of Vasoactive Substances Originated Endotheiium in Patients with Unstable Angina Pectoris Treated by Improved Thrombolytic Therapy

Objectives To analyze the changes of vasoactive substances originated from endo- theiium in patients with unstable angina pectoris treated by modified thrombolytic therapy and explore the mech- anisms of the drug to treat unstable angina pectoris. Methods 120 patients with unstable angina pectoris who were not well responsed to common medication were studied. Their ECG stress tests were abnormal and there were ischemic changes in Holter. Urokinase 300,000 U was added in 100 ml normal saline and in- jected within 30 min once a day for 3 days. 300 mg as- pirin was administrated a day before and during uroki- nase applications. Before and after urokinase treat- ments , endothelin-1 , plasma tissue plasminogen activa- tor and its inhibitor-lwere determined. Results Compared with pretreatments, after treatments, the ac- tivities of tissue plasminogen activator increased, endo- thelin-1 and the inhibitor-1 decreased. The changes were significant. Conclusions Modified thrombolytic therapy can regulate the vasoactive substances origina- ted endotheiium in patients with unstable angina pecto- ris . The major substances include endothelin-1, plasma tissue plasminogen activator and inhibitor-1. This mechanism may suggest that urokinase can treat coro- nary heart disease effectively.

Predictors of long-term clinical outcome of patients with acute massive pulmonary embolism after thrombolytic therapy

To assess the in-hospital clinical course and the long-term evolution of acute massive pulmonary embolism after thrombolytic therapy and to identify predictors of adverse clinical outcome Methods A total of 260 patients hospitalized from January 1989 to October 1998 were retrospectively reviewed and followed up for 3 9 to 8 4 years Baseline characteristics and variables pre- and post-thrombolysis were identified Particular attention was paid to the clinical events, including death, recurrent thromboembolism, chronic thromboembolic pulmonary hypertension, and major bleeding attributable to the use of anticoagulants Kaplan-Meier event-free survival curves were generated Univariate analysis by means of the log-rank test was used to test each candidate variable for association with clinical outcome Multivariate analysis with the Cox proportional hazard model was used to determine independent predictors of the long-term outcome Results The in-hospital mortality rate was 8 5%, with 68 2% due to pulmonary embolism itself, and the follow-up mortality rate was 31 7%, with 29 2% due to recurrent embolism Factors associated with an adverse outcome in univariate analysis were: (1) prior thromboembolic diseases; (2) duration of anticoagulant therapy <6 months; (3) inferior vena caval filter placement; (4) acute right ventricular dysfunction/dilation detected echocardiographically after thrombolysis; (5) Doppler recording of pulmonary artery systolic pressure >50 mmHg after thrombolysis; and (6) greater than 30% obstruction of pulmonary vasculature identified by pulmonary ventilation/perfusion scintigraphy before hospital discharge Multivariate analysis identified three independent predictors of poor long-term outcome for patients with acute massive pulmonary embolism after thrombolysis; which were: (1) Doppler recording of pulmonary artery systolic pressure >50 mm Hg, with relative risk of 3 78 and a 95% confidence interval of 2 70 to 4 86; (2) echocardiographic evidence of right ventricular dysfunction/dilatation (relative risk: 2 18; 95% confidence interval: 1 48 to 2 88); and (3) greater than 30% obstruction of pulmonary vasculature documented by lung scan (relative risk: 1 99; 95% confidence interval: 1 25 to 2 70) Conclusion The study showed that Doppler echocardiographic assessments after thrombolytic therapy and ventilation/perfusion scintigraphy prior to hospital discharge are valuable to establishment of new baseline characteristics, which is informative for risk stratification and prognostication of the long-term outcome for patients with acute massive pulmonary embolism

Thrombolytic therapy for femoral artery thrombosis after left cardiac catheterization in children

Background Femoral artery thrombosis is one of the most common complications of catheterizations in infants and young children. This study was conducted to investigate the feasibility and effectiveness of thrombolytic therapy for femoral artery thrombosis after left cardiac catheterization in children. Methods Thrombolytic therapy with urokinase was carried out in children with femoral artery thrombosis after left cardiac catheterization. Each patient was given a bolus injection of heparin （100 U/kg）. A bolus of urokinase （30 000 - 100 000 U） was injected intravenously, and then a continuous infusion of 10 000-50 000 U/h was administered. Transcatheter thrombolysis was performed once previous procedures failed. Results Eight patients （aged （3.1±2.3） years （8 months to 7 years）, body weight （13.1±4.2） kg （7 to 20 kg）） presented lower limbs ischemia after left cardiac catheterizations was performed. Seven patients accepted thrombolytic therapy with urokinase. In 5 patients, peripheral intravenous thrombolysis was successful with restoration of a normal pulse. In the other 3 cases, peripheral intravenous thrombolysis failed, followed by successful transcatheter thrombolysis. The average duration of therapy was （7.25±5.31） hours （1-17 hours）. The average doses of heparin and urokinase were （1600±723） U （800-3000 U） and （268 571±177 240） U （50 000-500 000 U）, respectively. There were no statistically significant differences in partial thromboplastin time before and during urokinase therapy （（40.6±22.3） to （49.9±39.2） seconds）. However, the prothrombin time was significantly longer （（12.7±2.58） to （48.1±18.6） seconds, P〈0.05）. Patency of the target vessel was evaluated in all the patients for 2 weeks and no occlusion recurred. Conclusion Thrombolytic therapy with urokinase is a safe and useful modality in children with femoral artery thrombosis after left cardiac catheterization.

THROMBOLYTIC THERAPY FOR ACUTE CEREBRAL VASCULAR OCCLUSION

Superselective intra-arterial thrombolytic therapy with urokinase infusion was effective in 10 patients with acute cerebral vascular occlusion. PATIENTS AND METHODS In the 10 patients, 8 were men and 2 women. Their age ranged from 34 to 70 years.

Effect of fibrinolytic therapy on ST-elevation myocardial infarction clinical outcomes during the COVID-19 pandemic:A systematic review and meta-analysis

BACKGROUND ST-elevation myocardial infarction(STEMI)is the result of transmural ischemia of the myocardium and is associated with a high mortality rate.Primary percutaneous coronary intervention(PPCI)is the recommended first-line treatment strategy for patients with STEMI.The timely delivery of PPCI became extremely challenging for STEMI patients during the coronavirus disease 2019(COVID-19)pandemic,leading to a projected steep rise in mortality.These delays were overcome by the shift from first-line therapy and the development of modern fibrinolytic-based reperfusion.It is unclear whether fibrinolytic-based reperfusion therapy is effective in improving STEMI endpoints.AIM To determine the incidence of fibrinolytic therapy during the COVID-19 pandemic and its effects on STEMI clinical outcomes.METHODS PubMed,Google Scholar,Scopus,Web of Science,and Cochrane Central Register of Controlled Trials were queried from January 2020 up to February 2022 to identify studies investigating the effect of fibrinolytic therapy on the prognostic outcome of STEMI patients during the pandemic.Primary outcomes were the incidence of fibrinolysis and the risk of all-cause mortality.Data were meta-analyzed using the random effects model to derive odds ratios(OR)and 95%confidence intervals.Quality assessment was carried out using the Newcastle-Ottawa scale.RESULTS Fourteen studies including 50136 STEMI patients(n=15142 in the pandemic arm;n=34994 in the pre-pandemic arm)were included.The mean age was 61 years;79%were male,27%had type 2 diabetes,and 47%were smokers.Compared with the pre-pandemic period,there was a significantly increased overall incidence of fibrinolysis during the pandemic period[OR:1.80(1.18 to 2.75);I2=78%;P=0.00;GRADE:Very low].The incidence of fibrinolysis was not associated with the risk of all-cause mortality in any setting.The countries with a low-and middle-income status reported a higher incidence of fibrinolysis[OR:5.16(2.18 to 12.22);I2=81%;P=0.00;GRADE:Very low]and an increased risk of all-cause mortality in STEMI patients[OR:1.16(1.03 to 1.30);I2=0%;P=0.01;GRADE:Very low].Meta-regression analysis showed a positive correlation of hyperlipidemia(P=0.001)and hypertension(P<0.001)with all-cause mortality.CONCLUSION There is an increased incidence of fibrinolysis during the pandemic period,but it has no effect on the risk of all-cause mortality.The low-and middle-income status has a significant impact on the all-cause mortality rate and the incidence of fibrinolysis.

Serum calcium,albumin,globulin and matrix metalloproteinase-9 levels in acute cerebral infarction patients

BACKGROUND Hemorrhagic transformation(HT)is a common complication in patients with cerebral infarction.However,its pathogenesis is poorly understood.The knowledge of factors that may increase risk for HT may help in improving the safety of thrombolytic therapy.AIM To investigate the predictive value of serum calcium,albumin,globulin and matrix metalloproteinase-9(MMP-9)levels for HT after intravenous thrombolysis(IVT)in patients with acute cerebral infarction.METHODS Five hundred patients with acute cerebral infarction who received IVT with alteplase within 4.5 h after the onset of disease between January 2018 and January 2021 at our hospital were selected as the study subjects.They were divided into groups based on computed tomography scan results of the brain made within 36 h after thrombolysis.Forty patients with HT were enrolled in an observation group and 460 patients without HT were enrolled in a control group.Serum calcium,albumin,globulin and MMP-9 levels were compared between the two groups.Regression analysis was used to discuss the relationship between these indices and HT.RESULTS The previous history of hypertension,diabetes,atrial fibrillation,cerebrovascular diseases,smoking and alcohol intake were not associated with HT after IVT in patients with acute cerebral infarction(all P>0.05).The National Institutes of Health stroke scale(NHISS)score was associated with HT after IVT in patients with acute cerebral infarction(P<0.05).The serum calcium and albumin levels were lower in the observation group than in the control group(all P<0.05).The levels of globulin and MMP-9 were significantly higher in the observation group than in the control group(all P<0.05).Logistic regression analysis showed that NHISS score,serum calcium,albumin,globulins and MMP-9 were independent factors influencing the occurrence of HT following IVT in patients with cerebral infarction(P<0.05).CONCLUSION Serum calcium,albumin,globulin and MMP-9 levels are risk factors for HT after IVT in patients with acute cerebral infarction.Moreover,NHISS score can be used as a predictor of post-thrombolytic HT.

Nano-Medicine for Thrombosis:A Precise Diagnosis and Treatment Strategy

Thrombosis is a global health issue and one of the leading factors of death.However,its diagnosis has been limited to the late stages,and its therapeutic window is too narrow to provide reasonable and effective treatment.In addition,clinical thrombolytics suffer from a short half-life,allergic reactions,inactivation,and unwanted tissue hemorrhage.Nano-medicines have gained extensive attention in diagnosis,drug delivery,and photo/sound/magnetic-theranostics due to their convertible properties.Furthermore,diagnosis and treatment of thrombosis using nano-medicines have also been widely studied.This review summarizes the recent advances in this area,which revealed six types of nanoparticle approaches:(1)in vitro diagnostic kits using“synthetic biomarkers”;(2)in vivo imaging using nano-contrast agents;(3)targeted drug delivery systems using artificial nanoparticles;(4)microenvironment responsive drug delivery systems;(5)drug delivery systems using biological nanostructures;and(6)treatments with external irradiation.The investigations of nano-medicines are believed to be of great significance,and some of the advanced drug delivery systems show potential applications in clinical theranotics.

Starting thrombolytic therapy for patients with acute myocardial infarction in Accident and Emergency Department:from implementation to evaluation

Objective To evaluate the effectiveness of initiating thrombolysis for patients with acute myocardial infarction (AMI) in the Accident and Emergency Department. Methods From January 1993 to December 1995, all AMI patients who were admitted to the United Christian Hospital and given thrombolytic therapy were studied. The patients' demographic data, time and mode of presentation, site of myocardial infarction, treatment modality and timing, and complications related to AMI or treatment were recorded prospectively in our AMI database. The frequency of thrombolysis administered in Accident and Emergency Department and Coronary Care Unit, as well as the median door-to-needle time (time interval between hospital arrival to initiation of thrombolytic therapy) were compared. Cases of inappropriate thrombolysis and complication were also analyzed.Results Over these 3 years, 257 patients received thrombolysis in the United Christian Hospital. The percentage of patients receiving thrombolysis in Accident and Emergency Department increased from 3.2% in 1993 to 12.3% in 1994, and to 39.4% in 1995. The median time interval between arrival to hospital and thrombolysis (door-to-needle time) was 25 minutes, compared with 81 minutes in the Coronary Care Unit. The door-to-needle time also improved over these 3 years: from 95 minutes in 1993 to 75 minutes in 1995 in Coronary Care Unit group, and from 35 minutes in 1993 to 20 minutes in 1995 in the Accident and Emergency Department group. Over these 3 years, 2 cases of inappropriate thrombolysis were reported but these did not result in any mortality. Four complications from thrombolytic therapy were reported, and these were managed appropriately by the staff in Accident and Emergency Department and did not result in mortality. Conclusions Starting thrombolytic therapy in Accident and Emergency Department is safe and effectively decreases the door-to-needle time.

Operative or Interventional Treatment in Infrainguinal Bypass Occlusion:Are There Predictive Factors Affecting Outcome?

Purpose: To evaluate outcome of interventional and surcigal treatment in infrainguinal bypass occlusion and to identify predictive factors affecting therapeutic success. Material and Methods: Over a period of three years 96 patients with infrainguinal bypass occlusion were included in this retrospective study. 52 patients were treated by catheter-directed thrombolysis and 44 patients by reconstructive vascular surgery. Results: 41 grafts could be reopened in thrombolytic group (78.8%), thrombolysis failed in 11 cases (21.2%). 34 grafts were treated successfully by reconstructive vascular surgery (77.3%), 10 grafts couldn’t be reopened or reoccluded within 30 days after surcical therapy. After a median observation time of 14.7 months 30 of 48 (62.5%) bypass grafts treated with intraarterial thrombolysis and 19 of 27 (70.4%) grafts treated with thrombectomy were overall patent. Limb salvage was 81.3% in thrombolytic group and 88.8% in surgery group. No predictive factors affecting outcome could be identified in both groups except the localization of the occluded graft (above/below knee). Conclusion: Infrainguinal bypass occlusion is a serious and challenging complication in vascular surgery. Our study showed similar results for both therapeutic strategies. Despite our data was retrospective with a small number of patients the localization of the occluded graft as predictive pretherapeutic factor was significant in thrombolytic and surgery group. Based on these scientific findings we established a guideline for choice of therapeutic treatment in our institution after searching current literature.

Tenecteplase versus alteplase in treatment of acute ST-segment elevation myocardial infarction:A randomized non-inferiority trial

Background:A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator(rhTNK-tPA)has previously shown its preliminary efficacy in ST elevation myocardial infarction(STEMI)patients.This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase(rt-PA)in Chinese patients with STEMI.Methods:In this multicenter,randomized,open-label,non-inferiority trial,patients with acute STEMI were randomly assigned(1:1)to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min.The primary endpoint was recanalization defined by thrombolysis in myocardial infarction(TIMI)flow grade 2 or 3.The secondary endpoint was clinically justified recanalization.Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events(MACCEs)and safety endpoints.Results:From July 2016 to September 2019,767 eligible patients were randomly assigned to receive rhTNK-tPA(n=384)or rt-PA(n=383).Among them,369 patients had coronary angiography data on TIMI flow,and 711 patients had data on clinically justified recanalization.Both used a–15%difference as the non-inferiority efficacy margin.In comparison to rt-PA,both the proportion of patients with TIMI grade 2 or 3 flow(78.3%[148/189]vs.81.7%[147/180];differences:–3.4%;95%confidence interval[CI]:–11.5%,4.8%)and clinically justified recanalization(85.4%[305/357]vs.85.9%[304/354];difference:–0.5%;95%CI:–5.6%,4.7%)in the rhTNK-tPA group were non-inferior.The occurrence of 30-day MACCEs(10.2%[39/384]vs.11.0%[42/383];hazard ratio:0.96;95%CI:0.61,1.50)did not differ significantly between groups.No safety outcomes significantly differed between groups.Conclusion:rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery,a validated surrogate of clinical outcomes,among Chinese patients with acute STEMI.Trial registration:www.ClinicalTrials.gov(No.NCT02835534).

Stereotactic aspiration and thrombolysis of spontaneous intracerebellar hemorrhage

Background Spontaneous intracerebellar hemorrhage （SCH） accounts for 10% of intracerebral hemorrhages. Up to now stereotactic aspiration and thrombolysis of SCH was less reported. The aim of this study was to assess the effect and feasibility of the method, and to refine the clinical protocol. Methods Eighteen patients with SCH were treated by stereotactic aspiration and thrombolysis and reviewed in this report. The 3-ram axial stereotactic computed tomoaraDhv slices throughout the hematoma were obtained.

Optional therapeutic strategies based on clinically different types of acute pulmonary embolism

OBJECTIVE: To establish a clinical classification of pulmonary embolism (PE), and to evaluate the optional treatment strategies for different types of PE. METHODS: From December 1995 to July 2001, 45 patients with acute PE were hospitalized, of which 33 received intravenous thrombolytic therapy or interventional treatment. RESULTS: Misdiagnostic rate in the 45 patients with acute PE during first visit was 62.2% and mortality rate was 28.9%. Misdiagnostic rate in acute PE patients who had undergone surgery was 82% and mortality rate was 73%. The effective rate of thrombolytic therapy was 77.7%. Clinical symptoms rapidly disappeared in massive PE patients treated with interventional therapies. CONCLUSIONS: Intravenous thrombolytic therapy is one of the most effective methods for treating acute PE. Application of interventional therapy for severe acute PE is also promising.

Thrombolysis lead to better long-term outcome in Chinese stroke patients

Aim:The rate of thrombolysis in Chinese acute ischemic stroke(AIS)was low and little was known about the long-term outcome.We aimed to compare the prognosis between thrombolysis and ordinary anti-platelet strategies in AIS.Methods:Patients,who were consecutively registered in our hospital from January 2005 to June 2012,were retrospectively studied.Inclusion criteria:(1)primary diagnoses of cerebral infarction coded with implantable cardioverter defibrillator-10 I63 to I69;(2)symptoms onset to treatment time(OTT)within 6 h;(3)thrombolysis with alteplase(TROM)or ordinary anti-platelet therapy(ANTP).Exclusion criteria:(1)symptoms and signs diminished rapidly without apparent neurological deficits;(2)no visible lesions on diffusion weighted image in magnetic resonance imaging;(3)cerebral infarction caused by serious metabolic in-balance or infections.The endpoints were defined as favorable(modified Rankin Scale 0-2)or being survival.Proportions of favorable outcome or survival were estimated by Kaplan-Meier curve and Cox regression.Results:One hundred and sixty eight cases were analyzed.Ninety one were in TROM and 77 in ANTP.Male accounted for 82(48.8%)and female 86(51.2%).The median of age was 74[interquartile range(IQR)67-79],national institute of health stroke scale(NIHSS 9)(IQR 5-17)and OTT 3.9 h(IQR 3.0-4.8)respectively.The median length of follow-up was 112(IQR 63.4-163.8)weeks.By the end of December 31,2012,87 patients(51.8%)reached favorable outcome while 81(48.2%)unfavorable.Forty five(26.8%)cases deceased.Kaplan-Meier curve estimation showed a longer favorable period of time in TROM than those in ANTP(212 weeks 95%confidence interval(CI)169.5-254.5 vs.126.9 weeks 95%CI 105.2-148.6;Log-Rank test x^(2)=19.632,P=0.000),while no significance was seen in survival time(258.0 weeks 95%CI 231.5-284.5 vs.160.8 weeks 95%CI 153.0-168.5;Log-Rank test x^(2)=2.427,P=0.119).In Cox regression,thrombolysis showed an independent protective effect for longer period of favorable outcome[202 vs.151 weeks,P=0.026,heart rate(HR)1.96,95%CI 1.958-3.540]and longer survival time instead(333 vs.170 weeks,P=0.000,HR 4.322,95%CI 1.942-9.618).The estimated proportion of favorable outcome in Chinese urban AIS was about 91%for 1 year and 50%for about 3.4 years,while the estimated proportion of survival was about 98.5%for 1 year and 50%for about 5.3 years,respectively.Conclusion:Chinese urban AIS patients who underwent thrombolysis with alteplase might have a better long-term outcome than those receiving ordinary anti-platelet therapy.