OBJECTIVE: To establish a machine learning model to predict the risk of early neurological deterioration (END) based on the clinical and laboratory data of patients with acute ischemic stroke (AIS) before intravenous thrombolysis. METHODS: The clinical data of AIS patients who received intravenous thrombolytic with recombinant tissue plasminogen activator (rt-PA) at the Stroke Center of the First Hospital of Qinhuangdao City from January 2019 to July 2022 were retrospectively analyzed. Patients were divided into END group and non-END group according to whether END appeared after intravenous thrombolytic. Clinical data of patients at admission were collected, including demographic characteristics, clinical evaluation, comorbidification, drug use history, laboratory tests, etc. Univariate and multivariate Logistic regression analysis were performed to screen out the independent predictors of the END of AIS patients after intravenous thrombolytic. The study subjects were randomly divided into a training set and a test set in a 7 : 3 ratio. Four machine learning prediction models, including Logistic regression (LR), K-nearest neighbor (KNN), support vector machine (SVM) and random forest (RF), were established based on independent predictors. The receiver operator characteristic curve (ROC curve) was used to evaluate the predictive ability of each model in END. RESULTS: A total of 704 patients were enrolled, of whom 99 were identified as END and 605 as non-END. Univariate and multivariate Logistic regression analysis was used to screen out the National Institutes of Health stroke scale [NIHSS, odds ratio (OR) = 1.049, 95% confidence interval (95%CI) was 1.015-1.082, P = 0.004], systolic blood pressure (OR = 1.013, 95%CI was 1.004-1.022, P = 0.004), lymphocyte percentage (LYM%, OR = 0.903, 95%CI was 0.853-0.953, P < 0.001), platelet to lymphocyte ratio (PLR, OR = 1.007, 95%CI was 1.002-1.014, P = 0.013) were the independent predictors of END in AIS patients after intravenous thrombolysis. The area under the curve (AUC) of LR, KNN, SVM, and RF machine learning models in the test dataset were 0.789 (95%CI was 0.675-0.902), 0.797 (95%CI was 0.685-0.910), 0.851 (95%CI was 0.751-0.952) and 0.809 (95%CI was 0.699-0.919), respectively. The RF model had the highest sensitivity (95.7%). The accuracy (0.736), specificity (72.0%) and AUC of SVM model were the highest, and its overall prediction ability was better than the other three models. CONCLUSIONS Machine learning models have a potential role in early predicting the risk of END after intravenous thrombolysis in AIS patients, and can provide help in clinical decision-making for intravenous thrombolysis.
Humans ; Tissue Plasminogen Activator/therapeutic use* ; Ischemic Stroke/drug therapy* ; Brain Ischemia ; Retrospective Studies ; Thrombolytic Therapy ; Stroke ; Fibrinolytic Agents/therapeutic use*

Objective To compare the clinical effects of three treatment methods including systemic thrombolysis(ST),catheter-directed thrombolysis(CDT),and AngioJet percutaneous mechanical thrombectomy(PMT)in acute lower extremity deep venous thrombosis(LEDVT). Methods The data of 82 patients diagnosed with LEDVT in the Department of Vascular and Gland Surgery of the First Affiliated Hospital of Hebei North University from January 2017 to December 2020 were collected.The patients were assigned into a ST group(n=50),a CDT group(n=16),and a PMT group(n=16)according to different treatment methods.The efficacy and safety were compared among the three groups. Results Compared with that before treatment,the circumferential diameter difference of both lower limbs on days 1,2,and 3 of treatment in the ST,CDT,and PMT groups reduced(all P<0.001).The PMT group showed smaller circumferential diameter difference of lower limbs on days 1,2,and 3 of treatment than the ST group(all P<0.001)and smaller circumferential diameter difference of the lower patellar margin on day 1 of treatment than the CDT group(P<0.001).The PMT group showed higher diminution rate for swelling of the affected limb at the upper and lower edges of the patella than the ST group(P<0.001)and higher diminution rate for swelling at the upper edge of the patella than the CDT group(P=0.026).The incidence of complications after treatment showed no significant differences among the three groups(all P>0.05).The median of hospital stay in the PMT group was shorter than that in the ST and CDT groups(P=0.002,P=0.001).The PMT group had higher thrombus clearance rate than the ST group(P=0.002)and no significant difference in the thrombus clearance rate from the CDT group(P=0.361).The vascular recanalization rates in the PMT(all P<0.001)and CDT(P<0.001,P=0.002,P=0.009)groups 3,6,and 12 months after treatment were higher than those in ST group,and there were no significant differences between PMT and CDT groups(P=0.341,P=0.210,P=0.341). Conclusions ST,CDT,and PMT demonstrated significant efficacy in the treatment of LEDVT,and PMT was superior to ST and CDT in terms of circumferential diameter difference of the lower limbs,diminution rate for swelling of the affected limb,thrombus clearance rate,length of hospital stay,and long-term vascular recanalization.There was no obvious difference in safety among the three therapies.
Humans ; Thrombolytic Therapy/methods* ; Fibrinolytic Agents/therapeutic use* ; Treatment Outcome ; Thrombectomy/methods* ; Venous Thrombosis/drug therapy* ; Lower Extremity/blood supply* ; Catheters ; Retrospective Studies

OBJECTIVE: To observe the effects of acupuncture on neurologic function and serum inflammatory factors in patients after thrombolysis in acute ischemic stroke (AIS). METHODS: A total of 102 AIS patients with onset to treatment time (OTT) ≤3 h were randomly divided into an observation group and a control group, 51 cases each group. In the control group, thrombolysis and conventional medical treatment were applied. On the basis of the treatment as the control group, acupuncture at Shuigou (GV 26), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), etc. was applied in the observation group, 30 min each time, once a day. Both groups were treated for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Rankin scale (mRS), modified Barthel index (MBI) and serum level of homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP) were compared, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the scores of NIHSS, mRS and serum level of Hcy, hs-CRP were decreased compared with those before treatment (P<0.05), while the MBI scores were increased (P<0.05) in the two groups. The scores of NIHSS, mRS and serum level of Hcy, hs-CRP in the observation group were lower than those in the control group (P<0.05, P<0.01), the MBI score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 88.2% (45/51) in the observation group, which was superior to 70.6% (36/51) in the control group (P<0.05). CONCLUSION Acupuncture could promote the recovery of neurologic function in patients after thrombolysis in AIS, improve the ability of daily living, which may be related to reducing the level of inflammatory factors, thus inhibiting inflammatory response and improving cerebral ischemia reperfusion injury.
United States ; Humans ; Ischemic Stroke ; C-Reactive Protein ; Acupuncture Therapy ; Inflammation ; Homocysteine ; Hypersensitivity ; Thrombolytic Therapy

OBJECTIVE: To observe the effects of the Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on hemorrhagic transformation and limb motor function after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in stroke patients. METHODS: A total of 130 stroke patients after rt-PA thrombolytic were divided into an acupuncture group (58 cases, 1 case dropped off) and a non-acupuncture group (72 cases, 7 cases dropped off) according to whether they received acupuncture treatment. Propensity score matching (PSM) was used to match each group, with 38 patients in each group. The patients in the non-acupuncture group received rt-PA thrombolytic therapy and western medical basic treatment. In addition to the basic treatment, the patients in the acupuncture group received Xingnao Kaiqiao acupuncture at Shuigou (GV 26), bilateral Neiguan (PC 6), and ipsilateral Sanyinjiao (SP 6), Chize (LU 5), once a day for 14 days. The incidence of hemorrhagic transformation within 30 days after onset was compared between the two groups. The Fugl-Meyer assessment (FMA) score and activities of daily living (ADL) score were observed at baseline and 30 days, 6 months, 1 year after onset in the two groups. The disability rate at 6 months and 1 year after onset was recorded, and safety was evaluated in both groups. RESULTS: The incidence of hemorrhagic transformation in the acupuncture group was 5.3% (2/38), which was lower than 21.1% (8/38) in the non-acupuncture group (P<0.05). At 30 days, 6 month, and 1 year after onset, the FMA and ADL scores of both groups were higher than those at baseline (P<0.01), and the scores in the acupuncture group were higher than those in the non-acupuncture group (P<0.01). The disability rate in the acupuncture group at 1 year after onset was 10.5% (4/38), which was lower than 28.9% (11/38) in the non-acupuncture group (P<0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). CONCLUSION The Xingnao Kaiqiao acupuncture method could reduce the incidence of hemorrhagic transformation in stroke patients after intravenous thrombolysis with rt-PA, improve their motor function and daily living ability, and reduce the long-term disability rate.
Humans ; Tissue Plasminogen Activator/adverse effects* ; Activities of Daily Living ; Prospective Studies ; Stroke ; Acupuncture Therapy ; Thrombolytic Therapy/adverse effects*

OBJECTIVE: To assess the effect of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on the efficacy and safety of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with cerebral infarction. METHODS: A total number of 142 patients of cerebral infarction undergoing rt-PA intravenous thrombolysis were randomized into an acupuncture-medication group (71 cases) and a western medication group (71 cases, 1 case dropped off). In the western medication group, rt-PA intravenous thrombolysis was given. In the acupuncture-medication group, besides the intervention as the control group, Xingnao Kaiqiao acupuncture was provided at Shuigou (GV 26), Neiguan (PC 6), Sanyinjiao (SP 6), Jiquan (HT 1), etc. once daily. One treatment session contained 6 treatments and 1 session was required. Before and after treatment, the score of the National Institute of Health stroke scale (NIHSS), the levels of the relevant indexes of symptomatic intracerebral hemorrhage (sICH) (platelet [PLT], D-dimer and fibrinogen), the incidences of sICH and adverse effect were compared between groups. The efficacy was assessed in two groups. RESULTS: After treatment, NIHSS scores and the levels of D-dimer were reduced compared with those before treatment in both groups (P<0.05), and those in the acupuncture-medication group were lower than the western medication group (P<0.05). The level of fibrinogen in the acupuncture-medication group was increased in comparison with that before treatment (P<0.05), and also higher than the western medication group (P<0.05). The incidence of sICH was 0% (0/71) in the acupuncture-medication group, lower than 8.6% (6/70) in the western medication group (P<0.05). The effective rate was 97.2% (69/71) in the acupuncture-medication group, higher than 87.1% (61/70) in the western medication group (P<0.05). The incidence of adverse effect was 2.8% (2/71) in the acupuncture-medication group, lower than 12.9% (9/70) in the western medication group (P<0.05). CONCLUSION Xingnao Kaiqiao acupuncture may improve the efficacy of rt-PA intravenous thrombolysis in the patients with cerebral infraction and decrease the incidences of sICH and adverse effect. The mechanism may be related to the regulation of fibrinogen and D-dimer levels.
Acupuncture Therapy/adverse effects* ; Cerebral Infarction/drug therapy* ; Fibrinogen ; Humans ; Stroke/drug therapy* ; Thrombolytic Therapy/adverse effects* ; Tissue Plasminogen Activator/adverse effects* ; Treatment Outcome

Cranial Sinuses ; Dilatation ; Fibrinolytic Agents/therapeutic use* ; Humans ; Sinus Thrombosis, Intracranial/therapy* ; Thrombolytic Therapy ; Treatment Outcome

BACKGROUND: Intravenous thrombolysis (IVT) is an effective way for treating acute ischemic stroke (AIS). However, its effects have not been established among AIS patients with unclear stroke symptoms or with stroke onset for >4.5 h. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and Google Scholar databases for randomized controlled trials that compared IVT (IVT group) and placebo or usual care (control group [CG]) in AIS patients with disease onset for >4.5 h. The outcomes of interest included the favorable functional outcome (defined as modified Rankin Scale [mRS] scores 0-1) at 90 days, the functional independence (defined as mRS scores 0-2) at 90 days, proportion of patients with symptomatic intracerebral hemorrhage (sICH) and death at 90 days. We assessed the risk of bias using the Cochrane tool. Pre-specified subgroup analyses were performed by age (≤70 years or >70 years), National Institute of Health Stroke Scale (NIHSS, ≤10 or >10) and time window (4.5-9.0 h or >9.0 h). RESULTS: Four trials involving 848 patients were eligible. The risk of bias of included trials was low. Patients in the IVT group were more likely to achieve favorable functional outcomes (45.8% vs. 36.7%; OR 1.48, 95% CI 1.12-1.96) and functional independence (63.8% vs. 55.7%; OR 1.43, 95% CI 1.08-1.90) at 90 days, but had higher risk of sICH (3.0% vs. 0.5%; OR 5.28, 95% CI 1.35-20.68) at 90 days than those in the CG. No significant difference in death at 90 days was found between the two groups (7.0% vs. 4.1%; OR 1.80; 95% CI 0.97-3.34). CONCLUSIONS Use of IVT in patients with extended time window may improve their functional outcomes at 90 days, although IVT may induce increased risk of sICH. Care of these patients should well balance the potential benefits and harms of IVT.
Administration, Intravenous ; Aged ; Brain Ischemia/drug therapy* ; Fibrinolytic Agents/therapeutic use* ; Humans ; Ischemic Stroke ; Stroke/drug therapy* ; Thrombolytic Therapy ; Treatment Outcome

Objective: To compare the efficacy and safety of pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction (STEMI). Methods: STEMI patients, who received intravenous thrombolytic therapy in Henan STEMI registry between September 2016 and August 2018, were eligible for this study. A total of 5479 patients from 66 hospitals were screened and patients were divided into pro-urokinase group (n=638) and reteplase group (n=702) according to thrombolytic drugs. Data including patient demographics, risk factors, medical histories, patient information at admission, in-hospital treatment, time delays, and clinical events were collected. The clinical recanalization rate, in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital main adverse cardiovascular and cerebrovascular events (MACCE, death or treatment withdrawal, congestive heart failure, reinfarction and ischemic stroke) and post-thrombolysis bleeding were compared between the two groups. Bleeding events were evaluated with Bleeding Academic Research Consortium (BARC) criteria. Results: The median age [61.8 (53.2, 69.0) vs. 62.6 (52.1, 69.8), P=0.833] or the proportion of women [23.0% (147/638) vs. 25.1% (176/702), P=0.385] were similar between the pro-urokinase and reteplase groups. Clinical recanalization rates were similar between the pro-urokinase and reteplase groups [82.1% (524/638) vs. 84.9% (596/702), P=0.172], and there was no difference in the median time from onset to thrombolysis [194.5 (135.0,290.0) min vs. 190 (126.0,292.0) min, P=0.431] and the median recanalization time [95 (67.5,120.0) min vs. 95 (71.0,119.0) min, P=0.561] between the two groups. There was no significant difference in in-hospital mortality [5.5% (35/638) vs. 5.1% (36/702), P =0.770], in-hospital all-cause mortality, treatment withdrawal [8.9% (57/638) vs.7.7% (54/702), P=0.410], and in-hospital MACCE [13.0% (83/638) vs. 10.4% (73/702), P=0.137] between pro-urokinase and reteplase groups. However, the incidence of post-thrombolysis bleeding was significantly higher in reteplase group than in pro-urokinase group [7.8% (55/702) vs. 3.8% (24/638), P=0.002]. Further analysis found that the incidence of oral bleeding and the BARC grades 1-2 bleeding were significantly higher in reteplase group than in pro-urokinase group, whereas the incidence of cerebral hemorrhage was similar between the two groups [0.6% (4/638) vs. 0.4% (3/702), P=0.715]. The comparison of efficacy and safety outcomes between the two groups after adjusting for baseline characteristics using general linear mixed models was consistent with those before the adjustment. There was no significant difference in in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital MACCE after adjusting for baseline characteristics and post-thrombolysis bleeding between the two groups. Conclusions: Pro-urokinase and reteplase have similar clinical efficacy in the treatment of STEMI. In terms of safety, the incidence of cerebral hemorrhage is similar, while the incidence of BARC grades 1-2 bleeding and oral bleeding is higher in reteplase group than in pro-urokinase group, which has no impact on in-hospital outcomes.
Female ; Fibrinolytic Agents/therapeutic use* ; Hospital Mortality ; Humans ; Myocardial Infarction/drug therapy* ; Recombinant Proteins ; ST Elevation Myocardial Infarction/drug therapy* ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; Treatment Outcome ; Urokinase-Type Plasminogen Activator

Objective: To determine the impact of inflammatory reaction levels and the culprit plaque characteristics on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The is a retrospective study. A total of 1 268 STEMI patients who underwent pre-intervention optical coherence tomography (OCT) examination of culprit lesion during emergency PCI were divided into 2 groups by preprocedural TIMI flow grade (TIMI 0-1 group (n =964, 76.0%) and TIMI 2-3 group (n =304, 24.0%)). Baseline clinical data of the 2 groups were collected; blood samples were collected for the detection of inflammatory markers such as high sensitivity C-reactive protein (hsCRP), myocardial injury marker, blood lipid, etc.; echocardiography was used to determine left ventricular ejection fraction; coronary angiography and OCT were performed to define the lesion length, diameter stenosis degree of the infarct-related arteries, presence or absence of complex lesions, culprit lesion type, area stenosis degree and vulnerability of culprit plaques. Multivariable logistic regression analysis was performed to identify independent correlation factors. The receiver operating characteristic (ROC) curve of continuous independent correlation factors was analyzed, and the best cut-off value of TIMI 0-1 was respectively determined according to the maximum value of Youden index. Results: The mean age of 1 268 STEMI patients were (57.6±11.4) years old and 923 cases were males (72.8%). Compared with TIMI 2-3 group, the patients in TIMI 0-1 group were older and had higher N-terminal-pro-B-type natriuretic peptide level, lower cardiac troponin I (cTnI) level, lower left ventricular ejection fraction, and higher hsCRP level (5.16(2.06, 11.78) mg/L vs. 3.73(1.51, 10.46) mg/L). Moreover, the hsCRP level of patients in TIMI 0-1 group was higher in the plaque rupture subgroup (all P<0.05). Coronary angiography results showed that compared with TIMI 2-3 group, the proportion of right coronary artery (RCA) as the infarct-related artery was higher, the angiographical lesion length was longer, minimal lumen diameter was smaller, and diameter stenosis was larger in TIMI 0-1 group (all P<0.05). The prevalence of plaque rupture was higher (75.8% vs. 61.2%) in TIMI 0-1 group. Plaque vulnerability was significantly higher in TIMI 0-1 group than that in TIMI 2-3 group with larger mean lipid arc (241.27°±46.78° vs. 228.30°±46.32°), more thin-cap fibroatheroma (TCFA, 72.4% vs. 57.9%), more frequent appearance of macrophage accumulation (84.4% vs. 70.7%) and cholesterol crystals (39.1% vs. 25.7%). Minimal flow area was smaller [1.3(1.1-1.7)mm² vs. 1.4(1.1-1.9)mm², all P<0.05] and flow area stenosis was higher (78.2%±10.6% vs. 76.3%±12.3%) in TIMI 0-1 group. Multivariable analysis showed that mean lipid arc>255.55°, cholesterol crystals, angiographical lesion length>16.14 mm, and hsCRP>3.29 mg/L were the independent correlation factors of reduced preprocedural TIMI flow grade in STEMI patients. Conclusions: Plaque vulnerability and inflammation are closely related to reduced preprocedural TIMI flow grade in STEMI patients.
Aged ; Coronary Angiography ; Humans ; Inflammation ; Male ; Middle Aged ; Myocardial Infarction/diagnostic imaging* ; Percutaneous Coronary Intervention ; Plaque, Atherosclerotic/diagnostic imaging* ; Retrospective Studies ; ST Elevation Myocardial Infarction/surgery* ; Stroke Volume ; Thrombolytic Therapy ; Ventricular Function, Left

Ischemic stroke is a major health crisis causing high mortality and morbidity. The key treatment relies on the rapid intervention to dissolve thrombus, to reduce bleeding side effect and re-canalize clotted blood vessels using clot lysis drugs. Tissue plasminogen activator (tPA) is the only FDA-approved drug for ischemic stroke, but it has many limitations in clinical use. In recent years, the development of thrombolytic drugs and treatment strategies based on tPA has been progressed rapidly. Here we review the recent progress in this field, including the contributions from us and others, to promote the future development of novel thrombolytic drugs.
Brain Ischemia/drug therapy* ; Fibrinolytic Agents/therapeutic use* ; Humans ; Research/trends* ; Stroke/drug therapy* ; Thrombolytic Therapy/trends* ; Tissue Plasminogen Activator/therapeutic use*