Anticoagulation status and adherence in patients with atrial fibrillation hospitalized for ACS and the impact on 1-year prognosis: a multicenter cohort study / 中华心血管病杂志

Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.

Functionalized exosome-loaded ginsenoside Rg1 for the treatment of ischemic stroke / 生物工程学报

The aim of this study was to investigate the therapeutic effects and potential mechanism of c(RGDyK) peptide modified mesenchymal stem cell exosomes loaded with ginsenoside Rg1 (G-Rg1) on ischemic stroke. Thread-tying method was used to establish SD rats transient middle cerebral occlusion model (tMCAO). The model rats were randomly divided into tMCAO group, Exo group, free G-Rg1 group, Exo-Rg1 group and cRGD-Exo-Rg1 group, and sham group was used as control. The infarct volume was measured by 2, 3, 5-triphenyltetrachloride (TTC) staining, the changes of neuron and endothelium were observed by immunofluorescence, and the expression of related proteins was detected by Western blotting. The results showed that cRGD-Exo-Rg1 up-regulated the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factors (HIF-1α) by activating PI3K/AKT pathway, thus promoting angiogenesis and neurogenesis, effectively reducing the volume of cerebral infarction and improving neural function. In addition, the delivery of cRGD-Exo-Rg1 to ischemic brain tissue up-regulated the expression of occludin and claudin-5, and reduced the injury of blood-brain barrier. Taken together, cRGD-Exo-Rg1 was effective in the treatment of ischemic stroke by promoting angiogenesis and neurogenesis, which provided experimental evidence for the potential clinical benefits of other neuroprotective therapies.

Experiencia en el manejo del ataque cerebrovascular isquémico en dos centros de tercer nivel de la ciudad de Ibagué (Colombia) entre junio del 2019 y junio del 2020 / Ischemic stroke management - Experience in two third-level hospitals in Ibague (Colombia) from June 2019 to June 2020

RESUMEN INTRODUCCION: El ataque cerebrovascular (ACV) de etiología isquémica es una patología cuya incidencia y mortalidad aumentaron en la última década. Cuando se maneja oportunamente, mediante trombólisis como terapia inicial, mejora su desenlace y funcionalidad. En el departamento del Tolima (Colombia) no hay registros de esta patología y en el país la bibliografía al respecto es limitada. El objetivo de este estudio es evaluar los desenlaces clínicos del manejo agudo con r-tPA en los pacientes que presentaron ACV isquémico en dos instituciones de la ciudad de Ibagué, capital de dicho departamento, entre junio del 2019 y junio del 2020, e identificar los tiempos de atención hospitalaria y las principales variables asociadas con el grupo de pacientes que fallecieron. MATERIALES Y METODOS: Estudio descriptivo de corte transversal del manejo del ACV isquémico con r-tPA, en el que se describen las variables sociodemográficas, la escala NIHSS como evaluación neurológica inicial, los tiempos de atención (inicio-aguja, puerta-tac y puerta-aguja), los desenlaces postoperatorios y el Rankin modificado al egreso. RESULTADOS: Se incluyeron 38 pacientes con una media de 67,37 años, el 60,53 % fueron mujeres. La escala NIHSS al ingreso fue 13,47 puntos (DE 5,24). Los tiempos de atención fueron 183 minutos (DE 72,63) inicio-aguja, 41 minutos (RIQ 17-72) puerta-TAC y 101,50 minutos (RIQ 77 - 137,25) puerta-aguja. La mortalidad fue del 23,68 %. CONCLUSION: La mortalidad y el desenlace funcional del ACV en nuestra población fueron similares a los reportados en la literatura nacional e internacional, sin embargo, es preciso implementar protocolos de atención del infarto cerebral para incrementar el número de pacientes con desenlace favorable, acortando los tiempos de atención en toda la cadena del tratamiento adecuado del infarto cerebral.

ABSTRACT INTRODUCTION: Ischemic stroke is a growing disease in the last decade, increasing both its incidence and its mortality. However, timely thrombolysis management as initial therapy can improve both disease progression as well as an individual's functionality. In Tolima, there are no registries of this disease and in Colombia in general, the literature is limited. The objective of this study is to investigate the clinical outcomes of the acute management of ischemic stroke using r-tPA as well as identifying in-hospital treatment times, at two institutions in Ibague between 2019 and 2020. METHODS AND MATERIALS: Using a cross-sectional descriptive study, we describe the management of ischemic stroke using r-tPA, describing sociodemographic variables, NIHSS scale as the initial neurological evaluation, in-hospital treatment times (symptoms-to-needle, door-to-TAC, door-to-needle), the clinical outcomes, and lastly the modified Rankin score upon discharge. RESULTS: We included 38 patients with median age of 67,37 years, 60,53 % were females. The initial average NIHSS scale upon admission was 13,47 (DE 5,24). In-hospital attention time averages were: symptoms-to-needle 183 minutes (DE 72,63), door-to-CAT 41 minutes (RIQ 17-72), and door-to-needle 101,50 minutes (RIQ 77-137,25). Overall the rate of mortality was 23,68 %. CONCLUSIONS: Mortality and functionality outcomes of the stroke population observed was similar to previously reported, both nationally and internationally. However, protocols should be implemented for the timely ischemic stroke management to improve the number of patients with favorable outcomes, by reducing the in-hospital attention times in all areas of the management chain.

Protective effect and mechanism of Ershiwuwei Zhenzhu Pills on cerebral apoplexy rats / 中国中药杂志

To study the protective effect of Ershiwuwei Zhenzhu Pills on ischemic stroke rats. Ninety 4-weeks-old SPF male SD rats were randomly divided into 6 groups(n=15):sham operation group, model group, nimodipine group(12 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills high-dose group(400 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills medium-dose group(200 mg·kg~(-1)), Ershiwuwei Zhenzhu Pills low-dose group(100 mg·kg~(-1)).The permanent middle cerebral artery occlusion model(PMCAO) was established in the model group, nimodipine group, and Ershiwuwei Zhenzhu Pills groups by the improved thread plug method, while the sham operation group did not insert the thread plug.Nimodipine group and Ershiwuwei Zhenzhu Pills groups were given intragastric administration once a day for 24 days before the modeling operation, and once 1 hour before the modeling operation, while sham operation group and model group were given equal volumes of distilled water.The neuroethology of the surviving rats was measured; The volume of cerebral infarction in rats was measured by TTC method; The histopathology of rat brain was observed by HE method; The expression levels of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),malondialdehyde(MDA),superoxide dismutase(SOD) and catalase(CAT) in serum were detected by ELISA;The mRNA expressions of Notch 1,Jagged 1,Hes 1 and Bcl-2 in rat brain were detected by RT-PCR;Western blot was used to detect the expression levels of caspase-3 protein in rat brain; the expression levels of vascular endothelial growth factor(VEGF) and CD34 positive cells in rat brain were detected by immunofluorescence.The low, medium and high dose groups of Ershiwuwei Zhenzhu Pills and nimodipine group could significantly reduce the neurobehavioral score and cerebral infarction volume of rats with permanent middle cerebral artery occlusion, reduce the morphological changes of nerve cells, decrease the expression of TNF-α,IL-1β and IL-6 in rat serum, increase the activity of SOD and CAT,and reduce the level of MDA.Furthermore, the expression levels of Notch l, Jagged l, Hes l and Bcl-2 mRNA were significantly increased, and the expression level of caspase-3 protein was decreased.Meanwhile, the number of VEGF and CD34 positive cells increased in the treatment group.The differences were statistically significant. Ershiwuwei Zhenzhu Pills has a protective effect on ischemic stroke rats, and its mechanism may be related to anti-inflammation, anti-oxidation, promotion of nerve cell proliferation, inhibition nerve cell apoptosis and promotion of angiogenesis.

Chinese medicine Buyang Huanwu decoction promotes neurogenesis and angiogenesis in ischemic stroke rats by upregulating miR-199a-5p expression / 浙江大学学报·医学版

OBJECTIVE@#To investigate the mechanism of Chinese medicine Buyang Huanwu decoction (BYHWD) promoting neurogenesis and angiogenesis in ischemic stroke rats.@*METHODS@#Male SD rats were randomly divided into sham operation group, model group, BYHWD group, antagonist group and antagonist control group with 14 rats in each. Focal cerebral ischemia was induced by occlusion of the right middle cerebral artery for 90 min with intraluminal filament and reperfusion for 14 d in all groups except sham operation group. BYHWD (13 g/kg) was administrated by gastrogavage in BYHWD group, antagonist group and antagonist control group at 24 h after modeling respectively, and BrdU (50 mg/kg) was injected intraperitoneally in all groups once a day for 14 consecutive days. miR-199a-5p antagomir or NC (10 nmol) was injected into the lateral ventricle at d5 after ischemia in antagonist and antagonist control groups, respectively. The neurological deficits were evaluated by the modified neurological severity score (mNSS) and the corner test, and the infract volume was measured by toluidine blue staining. Neurogenesis and angiogenesis were detected by immunofluorescence double labeling method. The expression level of miR-199a-5p was tested by real-time RT-PCR, and the protein expressions of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were determined by Western blotting.@*RESULTS@#BYHWD treatment significantly promoted the recovery of neurological function (@*CONCLUSIONS@#Buyang Huanwu decoction promotes neurogenesis and angiogenesis in rats with cerebral ischemia, which may be related to increased protein expression of VEGF and BDNF through upregulating miR-199a-5p.