RESUMEN
Hypertensive intracerebral hemorrhage (HICH) is a destructive disease with high mortality, incidence, and disability. Asiaticoside (AC) is a triterpenoid derivative that has demonstrated to exert a protective effect on neuron and blood vessel. To investigate the function and potential mechanism of AC on HICH. Human brain microvascular endothelial cells (hBMECs) were treated with 20 U/mL thrombin for 24 h to establish the HICH model in vitro, and AC with the concentration of 1, 2 and 4 µM were used to incubate hBMECs. The effect and potential mechanism of AC on HICH were investigated by using cell counting kit-8, flow cytometry, tube forming assays, vascular permeability experiments and western blot assays. In vivo, rats were injected with 20 µL hemoglobin with a concentration of 150 mg/mL, and then intragastrically administrated with 1.25, 2.5 and 5 mg/kg AC. Behavioral tests, brain water content measurement, hematoxylin-eosin (HE) staining, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling assays, and western blot were used to assess the effect and potential mechanism of AC on HICH. AC (at 2 and 4 µM) improved the proliferation, apoptosis, angiogenesis and vascular permeability in thrombin-induced hBMECs (p < 0.05). Besides, AC (2.5 and 5 mg/kg) ameliorated behavioral scores, brain water content, pathological lesion, apoptosis and the expression of vascular permeability-related proteins in rats with HICH (p < 0.05). In addition, AC elevated the expression of PI3K/AKT pathway after HICH both in cell and animal models (p < 0.05). Application of LY294002, an inhibitor of PI3K/AKT pathway, reversed the ameliorative effect of AC on the proliferation, apoptosis, angiogenesis and vascular permeability in thrombin-induced hBMECs (p < 0.05). AC reduced brain damage by increasing the expression of the PI3K/AKT pathway after HICH.
Asunto(s)
Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Transducción de Señal , Triterpenos , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Masculino , Humanos , Triterpenos/farmacología , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Hemorragia Intracraneal Hipertensiva/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Apoptosis/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Lesiones Encefálicas/prevención & control , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patología , Hemorragia Cerebral/complicacionesRESUMEN
BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating disease, its mortality and disability rate are high. In China, hypertensive intracerebral hemorrhage (HICH) is responsible for 75% of all the cases of primary ICH. A lot of randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) for treating HICH have been carried out. However, these RCTs have a lot of problems, such as heterogeneous outcomes, non-uniform point of measurement. These lead to systematic review/meta-analysis only can include a small number of studies. And outcome measures did not take the wishes of patients and other stakeholders into account. The aim of this study is to establish the core outcome set (COS) for future TCM clinical trials of HICH. METHODS AND ANALYSIS: First, we will develop a long list of general outcomes by making systematic literature review and semi-structured interviews. Then healthcare professionals and patients with HICH will be invited to participate in two rounds of the Delphi survey to determine the importance of the outcome. Finally, a face-to-face consensus meeting will be conducted to determine the final COS of HICH, including what outcomes should be measured and when and how to measure the outcomes. RESULTS: We aim to develop a COS that includes TCM core syndrome for HICH to determine what outcomes should be reported and when and how to measure them. CONCLUSION: By doing this, we can increase the reporting consistency and reduce the reporting bias in the outcome, which leads to the reuse of research data in meta-analysis and the making of informed healthcare decisions. ETHICS AND DISSEMINATION: The entire project has received approval from the Ethics Committee of Xiyuan Hospital, China Academy of Chinese Medical Sciences. The final COS will be published and reported at the national and international conferences. TRIAL REGISTRATION: This study is registered with the Core Outcome Measures in Effectiveness Trials database as study 1475 . Registered on December 2019.
Asunto(s)
Hemorragia Intracraneal Hipertensiva , Medicina Tradicional China , Técnica Delphi , Humanos , Hemorragia Intracraneal Hipertensiva/diagnóstico , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Medicina Tradicional China/efectos adversos , Medicina Tradicional China/métodos , Metaanálisis como Asunto , Evaluación de Resultado en la Atención de Salud/métodos , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del TratamientoRESUMEN
This paper mainly studies the clinical efficacy of sodium nitroprusside and urapidil in the treatment of acute hypertensive intracerebral hemorrhage and analyzes the brain CT image detection based on a deep learning algorithm. A total of 132 cases of acute hypertension admitted to XXX hospital from XX 2019 to XX 2020 were retrospectively analyzed. The diseases of all patients were clinically confirmed, and patients were divided into groups according to the differences in treatment methods. Urapidil was used for group 1; sodium nitroprusside was used for group 2; and urapidil combined with sodium nitroprusside was used for group 3. A convolutional neural network in deep learning is used to construct intelligent processing to classify brain CT images of patients. The network performance of AlexNet, GoogLeNet, and CNN3 is predicted. The results show that GoogLeNet has the highest prediction accuracy of 0.83, followed by AlexNet with 0.80 and CNN3 with 0.74. The results of the performance parameter curve show that the GoogLeNet has the highest performance parameter of 0.89, followed by AlexNet and CNN3 network. The performance parameter curve of machine learning is above 0.80. After five weeks of drug treatment, the hematoma volume was (3.8 ± 2.6) mL in group1, (7.6 ± 2.8) mL in group 2, and (2.8 ± 1.5) mL in group 3. After 5 days of treatment, the patients' heart rate changed compared with before treatment. Compared with group 2, there were significant differences between groups 1 and 3 (P < 0.01), indicating that the therapeutic effect of the combination group was significantly better than that of the other groups alone. In summary, the combination of sodium nitroprusside and urapidil has a significantly better effect than that of urapidil alone. A convolutional neural network based on deep learning improves the recognition accuracy of medical images.
Asunto(s)
Hemorragia Intracraneal Hipertensiva , Humanos , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Nitroprusiato/uso terapéutico , Piperazinas , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Anestésicos , Hemorragia Intracraneal Hipertensiva , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/cirugía , Craneotomía/efectos adversos , Hematoma/diagnóstico por imagen , Hematoma/cirugía , Humanos , Hemorragia Intracraneal Hipertensiva/diagnóstico por imagen , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Hemorragia Intracraneal Hipertensiva/cirugía , Sevoflurano , Resultado del TratamientoRESUMEN
OBJECTIVE: Accurate prediction of the rise of blood pressure is essential for the hypertensive intracerebral hemorrhage. This study uses the hybrid feature convolution neural network to establish the blood pressure model instead of the traditional method of pulse waves. METHODS: The pulse waves of 100 patients were collected, and the pulse wave was decomposed into three bell wave compound forms to obtain the accurate pulse wave propagation time. Then, the mixed feature convolution neural network model ABP-net was proposed, which combined the pulse wave propagation time characteristics with the pulse wave waveform characteristics automatically extracted by one-dimensional convolution to predict the arterial blood pressure. Finally, according to the prediction results, 20 patients were treated before the high blood pressure appeared (model group), and another 20 patients with a daily fixed treatment scheme were selected as the control group. RESULTS: In 80 training sets, compared with linear regression and the random forest method, the hybrid feature convolution neural network has higher accuracy in predicting blood pressure. In 20 test sets, the blood pressure error was eliminated within 5 mmHg. The total effective rate in the model group and the control group was 95.0% and 85.0%, respectively (P = 0.035). After treatment, the scores of self-care ability of daily life and limb motor function in the model group were higher than those in the control group (P < 0.05). There were 8 cases (13.6%) in the model group and 17 cases (28.3%) in the control group due to the recurrence of cerebrovascular accident (P = 0.043). CONCLUSION: Drug treatment guided by a blood pressure model based on a hybrid feature convolution neural network for patients with hypertensive cerebral hemorrhage can significantly and smoothly reduce blood pressure, promote the health recovery, and reduce the occurrence of cerebrovascular accidents.
Asunto(s)
Presión Sanguínea/fisiología , Hemorragia Intracraneal Hipertensiva/fisiopatología , Hemorragia Intracraneal Hipertensiva/rehabilitación , Modelos Cardiovasculares , Redes Neurales de la Computación , Adulto , Anciano , Algoritmos , Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Biología Computacional , Femenino , Humanos , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , RecurrenciaRESUMEN
The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.
Asunto(s)
Medicamentos Herbarios Chinos , Hemorragia Intracraneal Hipertensiva , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Medicina Tradicional China , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage, four Chinese databases, four English databases, clinical trials registration center(ClinicalTrials.gov) and Chinese clinical trial registry were retrieved. The retrieval time was from the establishment of each database to September 9, 2020. According to the set criteria, the randomized controlled trial(RCT) of Naoxueshu Oral Liquid combined with conventional Western medicine was selected. The "Cochrane bias risk assessment" tool was used to evaluate the quality of the included studies. RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators. Eleven studies were finally included, with a total sample size of 1 221 cases, 612 cases in the treatment group and 609 cases in the control group. Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS) after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10), but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI [-1.39,-0.94],P<0.000 01). Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05) and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],P<0.000 1), but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13). In terms of effective rate, studies using Guideline for clinical trials of new patent Chinese medicines, NHISS or Glasgow outcome scale(GOS) had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RR_(Guideline for clinical trials of new patent Chinese medicines)=1.27,95%CI[1.10,1.46],P=0.001;RR_(NHISS)=1.26,95%CI[1.13,1.40],P<0.000 1;RR_(GOS)=1.54,95%CI[1.22,1.93],P=0.000 2). In reduction of hematoma volume, Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD_(2 week)=-2.31,95%CI[-3.12,-1.49],P<0.000 01;MD_(4 week)=-2.04,95%CI[-2.41,-1.68],P<0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. In terms of adverse reactions, two of the included studies reported mild adverse reactions, and the rest of studies were not mentioned, so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid. This study showed that compared with conventional Western medicine, combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage. However, due to the high bias risk in the included studies, more large-sample and high-quality RCTs are still needed in the future.
Asunto(s)
Medicamentos Herbarios Chinos , Hemorragia Intracraneal Hipertensiva , Accidente Cerebrovascular , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Medicamentos sin PrescripciónRESUMEN
BACKGROUND: Intravitreal injections of anti-vascular endothelial growth factor are commonly used to treat macular diseases, including diabetic macular edema. Anti-vascular endothelial growth factor drugs can enter the systemic circulation after intravitreal injections and appear to suppress circulating vascular endothelial growth factor levels. However, whether this can cause any systemic adverse events remains unknown. CASE PRESENTATION: A 70-year-old Japanese man diagnosed with diabetic macular edema in both eyes was treated with anti-vascular endothelial growth factor intravitreal injections. One month after receiving two intravitreal injections of aflibercept 1 week apart for diabetic macular edema in both eyes, he complained of a severe acute headache. The patient was diagnosed with hypertensive cerebral hemorrhage of the occipital lobe based on an elevated blood pressure of 195/108 mmHg and the results of computed tomography and magnetic resonance imaging of his brain. The patient was treated with an intravenous injection of nicardipine hydrochloride to lower his systemic blood pressure. Two days after the stroke, the patient began oral treatment with 80 mg/day telmisartan, which was continued for 3 days, and the telmisartan dose was reduced to 40 mg/day thereafter. His blood pressure promptly dropped to 130/80 mmHg, and his severe headache disappeared. One year after the cerebrovascular stroke, the telmisartan was discontinued because his blood pressure stabilized at a normal level. His plasma vascular endothelial growth factor levels were measured via specific enzyme-linked immunosorbent assay before and after the intravitreal injections of aflibercept. Immediately before the injections, the vascular endothelial growth factor level was 28 pg/ml, but it rapidly fell below the detection limit within 1 week, where it remained for over 2 months. Two days before the cerebral hemorrhage, his plasma vascular endothelial growth factor level was below the detection limit, and 2 months later after the stroke, his plasma vascular endothelial growth factor level recovered to 41 pg/ml. CONCLUSION: This case suggests that hypertension and resultant cerebral hemorrhage can occur in patients with diabetic macular edema when plasma vascular endothelial growth factor levels are systemically decreased below the detection limit for a prolonged time after local injections of anti-vascular endothelial growth factor agents into the vitreous cavity. Therefore, severely reduced plasma vascular endothelial growth factor levels could be a higher risk factor to develop generally infrequent stroke. Ophthalmologists should be aware of possible severe reduction of plasma vascular endothelial growth factor levels and resultant increase in blood pressure after intravitreal injections of an anti-vascular endothelial growth factor drug. If the plasma vascular endothelial growth factor levels could be monitored more easily and quickly during the treatment, it would help to prevent adverse events.
Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Hemorragia Intracraneal Hipertensiva , Edema Macular , Preparaciones Farmacéuticas , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Retinopatía Diabética/tratamiento farmacológico , Humanos , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Inyecciones Intravítreas , Edema Macular/tratamiento farmacológico , Masculino , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Agudeza VisualRESUMEN
INTRODUCTION: Hypertensive intracerebral hemorrhage (HICH) is the most serious complication of hypertension. Clearing intracranial hematoma as soon as possible, reducing brain cell edema, and controlling intracranial pressure could effectively reduce neuron damage, lower patient mortality, and improve patient prognosis. At present, minimally invasive surgery (MIS) has been widely used and plays an important role in the treatment of HICH. However, it is still in controversies about the choice of surgical treatment and medication treatment for HICH. Therefore, we try to conduct a randomized, controlled, prospective trial to observe the efficacy of MIS treatment against HICH compared with medication treatment. METHODS: Patients will be randomly divided into treatment group and control group in a 1:1 ratio using the random number generator in Microsoft Excel. Stereotactic soft channel minimally invasive intracranial hematoma puncture and drainage treatment and medication treatment will be applied respectively. The outcomes of intracerebral hemorrhage volume, Glasgow coma scale, National Institutes of Health Stroke Scale will be recorded. CONCLUSIONS: The findings of the study will be helpful for the choice of MIS and conservative treatment when treating HICH patients. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/ME6Y5.
Asunto(s)
Craneotomía , Hemorragia Intracraneal Hipertensiva/cirugía , Humanos , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Procedimientos Quirúrgicos Mínimamente Invasivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage, four Chinese databases, four English databases, clinical trials registration center(ClinicalTrials.gov) and Chinese clinical trial registry were retrieved. The retrieval time was from the establishment of each database to September 9, 2020. According to the set criteria, the randomized controlled trial(RCT) of Naoxueshu Oral Liquid combined with conventional Western medicine was selected. The "Cochrane bias risk assessment" tool was used to evaluate the quality of the included studies. RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators. Eleven studies were finally included, with a total sample size of 1 221 cases, 612 cases in the treatment group and 609 cases in the control group. Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS) after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10), but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI [-1.39,-0.94],P<0.000 01). Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05) and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],P<0.000 1), but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13). In terms of effective rate, studies using Guideline for clinical trials of new patent Chinese medicines, NHISS or Glasgow outcome scale(GOS) had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RR_(Guideline for clinical trials of new patent Chinese medicines)=1.27,95%CI[1.10,1.46],P=0.001;RR_(NHISS)=1.26,95%CI[1.13,1.40],P<0.000 1;RR_(GOS)=1.54,95%CI[1.22,1.93],P=0.000 2). In reduction of hematoma volume, Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD_(2 week)=-2.31,95%CI[-3.12,-1.49],P<0.000 01;MD_(4 week)=-2.04,95%CI[-2.41,-1.68],P<0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. In terms of adverse reactions, two of the included studies reported mild adverse reactions, and the rest of studies were not mentioned, so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid. This study showed that compared with conventional Western medicine, combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage. However, due to the high bias risk in the included studies, more large-sample and high-quality RCTs are still needed in the future.
Asunto(s)
Humanos , Medicamentos Herbarios Chinos/efectos adversos , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Medicamentos sin Prescripción , Accidente CerebrovascularRESUMEN
The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.
Asunto(s)
Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Medicina Tradicional China , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND/OBJECTIVE: Intravenous nicardipine infusion is effective for rapid blood pressure control. However, its use requires hemodynamic monitoring in the intensive care unit (ICU) and is associated with high hospital cost. This study aimed to examine the effect of early versus late initiation of oral antihypertensives on ICU length of stay (LOS) and cost of hospitalization in patients with hypertensive intracerebral hemorrhage (ICH). METHODS: This is a single-center retrospective study of patients with hypertensive ICH treated with nicardipine infusion from January 1, 2013, to December 31, 2017. Patients were dichotomized into study and control groups, based on receiving oral antihypertensives within 24 h versus after 24 h of emergency department arrival. Baseline characteristics, duration of nicardipine infusion, LOS in the ICU and hospital, functional outcome at discharge, and hospital cost were compared between the two groups using univariate and multivariate analysis. RESULTS: A total of 90 patients in the study group and 76 in the control group were identified. There was no significant difference in demographics, past medical history, and initial SBP between the two groups. After adjusting for confounding factors with multivariate regression models, early initiation of oral antihypertensives was associated with significant reductions in duration of nicardipine infusion (55.5 ± 60.1 vs 121.6 ± 141.3 h, p <0.005), nicardipine cost ($14,207 vs $29,299, p < 0.01), ICU LOS (2 vs 5 days, p < 0.005), and cost of hospitalization ($24,564 vs $47,366, p < 0.01). There was no significant difference in adversary renal events, favorable outcomes, and mortality between the two groups. CONCLUSIONS: Early initiation of oral antihypertensives is safe and may have a significant financial impact on patients with hypertensive ICH.
Asunto(s)
Antihipertensivos/administración & dosificación , Costos de Hospital/estadística & datos numéricos , Hipertensión/tratamiento farmacológico , Unidades de Cuidados Intensivos , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Tiempo de Internación/estadística & datos numéricos , Nicardipino/uso terapéutico , Administración Oral , Anciano , Antihipertensivos/uso terapéutico , Intervención Médica Temprana , Femenino , Estado Funcional , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Nicardipino/economía , Resultado del TratamientoRESUMEN
OBJECTIVES: Acute intracerebral hemorrhage (ICH) is a very common cause of disability. Previous evidence suggests that fluoxetine and other selective serotonin reuptake inhibitors improve, the recovery of motor function in patients with cerebral infarct. The purpose of this study was to investigate whether fluoxetine also improves motor recovery in patients with ICH. PATIENTS AND METHODS: This is a double blind, placebo controlled, multicenter randomized trial, patients recruited from three centers were assigned to receive 20â¯mg/day of fluoxetine or matching placebo for three months from within ten days after onset of symptoms. Primary outcome was change in Fugl-Meyer Motor Scale from baseline to day 90. RESULTS: Thirty patients (50 % women) were recruited to the fluoxetine (nâ¯=â¯14) or placebo (nâ¯=â¯16) groups. Median age was 55 years, the cause of the ICH was hypertension in 93.3 %, median volume of the hematomas was 22mm3. Basal ganglia hematoma was present in 67 % and, lobar location in 20 % of the patients. Improvement in FMMS at day 90 was significatively higher in the treatment group (median score 23) than in the placebo group, (median score 48), pâ¯=â¯0.001. No serious adverse events occurred. CONCLUSION: In addition to standard treatment, early prescription of fluoxetine was safe and helped to increase motor recovery 90 days after ICH. This finding adds to the evidence regarding its beneficial effect upon stroke related disability. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01737541.
Asunto(s)
Fluoxetina/uso terapéutico , Accidente Cerebrovascular Hemorrágico/rehabilitación , Recuperación de la Función , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Anciano , Hemorragia de los Ganglios Basales/tratamiento farmacológico , Hemorragia de los Ganglios Basales/fisiopatología , Hemorragia de los Ganglios Basales/rehabilitación , Método Doble Ciego , Femenino , Accidente Cerebrovascular Hemorrágico/tratamiento farmacológico , Accidente Cerebrovascular Hemorrágico/fisiopatología , Humanos , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Hemorragia Intracraneal Hipertensiva/fisiopatología , Hemorragia Intracraneal Hipertensiva/rehabilitación , Masculino , Persona de Mediana Edad , Rehabilitación de Accidente Cerebrovascular , Resultado del TratamientoRESUMEN
Background and Purpose- It is unknown whether admission systolic blood pressure (SBP) differs among causes of intracerebral hemorrhage (ICH). We sought to elucidate an association between admission BP and ICH cause. Methods- We compared admission SBP across ICH causes among patients in the Cornell Acute Stroke Academic Registry, which includes all adults with ICH at our center from 2011 through 2017. Trained analysts prospectively collected demographics, comorbidities, and admission SBP, defined as the first recorded value in the emergency department or on transfer from another hospital. ICH cause was adjudicated by a panel of neurologists using the SMASH-U criteria. We used ANOVA to compare mean admission SBP among ICH causes. We used multiple linear regression to adjust for age, sex, race, Glasgow Coma Scale score, and hematoma size. In secondary analyses, we compared hourly SBP measurements during the first 72 hours after admission, using mixed-effects linear models adjusted for the covariates above plus antihypertensive agents. Results- Among 484 patients with ICH, admission SBP varied significantly across ICH causes, ranging from 138 (±24) mm Hg in those with structural vascular lesions to 167 (±35) mm Hg in those with hypertensive ICH (P<0.001). The mean admission SBP in hypertensive ICH was 17 (95% CI, 11-24) mm Hg higher than in ICH of all other causes combined. These differences remained significant after adjustment for age, sex, race, Glasgow Coma Scale score, and hematoma size (P<0.001), and this persisted throughout the first 72 hours of hospitalization (P<0.001). Conclusions- In a single-center ICH registry, SBP varied significantly among ICH causes, both on admission and during hospitalization. Our results suggest that BP in the acute post-ICH setting is at least partly associated with ICH cause rather than simply representing a physiological reaction to the ICH itself.
Asunto(s)
Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Hemorragia Cerebral/complicaciones , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Adulto , Anciano , Presión Sanguínea/fisiología , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/fisiopatología , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hemorragia Intracraneal Hipertensiva/fisiopatología , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Background and Purpose- It is unknown whether blood pressure (BP) reduction influences secondary brain injury in spontaneous intracerebral hemorrhage (ICH). We tested the hypothesis that intensive BP reduction is associated with decreased perihematomal edema expansion rate (PHER) in deep ICH. Methods- We performed an exploratory analysis of the ATACH-2 randomized trial (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2). Patients with deep, supratentorial ICH were included. PHER was calculated as the difference in perihematomal edema volume between baseline and 24-hour computed tomography scans divided by hours between scans. We used regression analyses to determine whether intensive BP reduction was associated with PHER and if PHER was associated with poor outcome (3-month modified Rankin Scale score 4-6). We then used interaction analyses to test whether specific deep location (basal ganglia versus thalamus) modified these associations. Results- Among 1000 patients enrolled in ATACH-2, 870 (87%) had supratentorial, deep ICH. Of these, 780 (90%) had neuroimaging data (336 thalamic and 444 basal ganglia hemorrhages). Baseline characteristics of the treatment groups remained balanced (P>0.2). Intensive BP reduction was associated with a decrease in PHER in univariable (ß= -0.15; 95% CI, -0.26 to -0.05; P=0.007) and multivariable (ß=-0.12; 95% CI, -0.21 to -0.02; P=0.03) analyses. PHER was not independently associated with outcome in all deep ICH (odds ratio, 1.14; 95% CI, 0.93-1.41; P=0.20), but this association was modified by the specific deep location involved (multivariable interaction P=0.02); in adjusted analyses, PHER was associated with poor outcome in basal ganglia (odds ratio, 1.42; 1.05-1.97; P=0.03) but not thalamic (odds ratio, 1.02; 95% CI, 0.74-1.40; P=0.89) ICH. Conclusions- Intensive BP reduction was associated with decreased 24-hour PHER in deep ICH. PHER was not independently associated with outcome in all deep ICH but was associated with poor outcome in basal ganglia ICH. PHER may be a clinically relevant end point for clinical trials in basal ganglia ICH.
Asunto(s)
Antihipertensivos/uso terapéutico , Edema Encefálico/patología , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Hemorragia Intracraneal Hipertensiva/patología , Nicardipino/uso terapéutico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios RetrospectivosRESUMEN
Background and Purpose- We investigated factors associated with early and delayed neurological deterioration (END and DND, respectively) after acute spontaneous intracerebral hemorrhage in the main INTERACT (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial)-2. Methods- INTERACT-2 was a randomized trial of early intensive versus guideline-recommended blood pressure lowering in hypertensive intracerebral hemorrhage (<6 hours from symptom onset) patients. END and DND were defined as a ≥4-point increase on the National Institutes of Health Stroke Scale or ≥2-point decrease on Glasgow Coma Scale, in periods baseline to 24 hours and 24 hours to 7 days, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and 90-day outcomes (death and dependency on the modified Rankin Scale). Results- Of 2598 participants, 450 (17.3%) had either END or DND. Non-China recruitment, higher systolic blood pressure, larger baseline hematoma volume, left hemisphere hematoma location, intraventricular hemorrhage, subarachnoid extension, heterogeneous hematoma density, and cerebral white matter lesions, were predictors of END (all P≤0.045). Higher systolic blood pressure, lower diastolic blood pressure, higher glucose, larger baseline hematoma volume, intraventricular hemorrhage, lobar location, brain atrophy, and heterogeneous hematoma density were predictors of DND (all P≤0.042). END and DND were both related to death, and death or major disability (modified Rankin Scale scores of 3-6), in adjusted analyses ( P<0.001). Conclusions- Common variables, most directly related to the intracerebral hemorrhage morphology and underlying cerebral features, determine END and DND and their influence on poor outcomes of death and major disability. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00716079.
Asunto(s)
Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Hematoma , Hemorragia Intracraneal Hipertensiva , Anciano , Femenino , Hematoma/complicaciones , Hematoma/tratamiento farmacológico , Hematoma/mortalidad , Hematoma/fisiopatología , Humanos , Hemorragia Intracraneal Hipertensiva/complicaciones , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Hemorragia Intracraneal Hipertensiva/mortalidad , Hemorragia Intracraneal Hipertensiva/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/mortalidad , Enfermedades del Sistema Nervioso/fisiopatologíaRESUMEN
Hypertensive intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease with no effective treatment. Lysyl hydroxylase 3 (LH3) is essential for collagen IV intermolecular crosslinking and stabilization. Deficiency in LH3 affects the assembly and secretion of collagen IV and basement membrane (BM) integrity of vessels. Here, we investigated whether LH3 has significant implications for disease progression and therapeutic intervention. Spontaneous hypertensive ICH of mice was induced by angiotensin II and L-NAME treatment. The adeno-associated virus was delivered into brain by stereotactic injection to knockdown or overexpress LH3. We found LH3 levels were reduced in human patients with ICH and gradually decreased in mice before ICH. LH3 knockdown increased the incidence of hypertensive ICH in mice. The incidence, number, and size of ICHs in mice were markedly reduced by LH3 overexpression. RNA-seq revealed that LH3 overexpression significantly reversed the profound alterations in gene transcriptional profiles of cerebral vessels. LH3 overexpression was sufficient to enhance BM integrity, inhibit matrix metalloproteinase activity, attenuate microglial activation and leukocyte infiltration, and reduce VSMC apoptosis before ICH. These results indicate that LH3 overexpression attenuates susceptibility to hypertensive ICH. We emphasize that LH3 modulation may serve as a viable approach for future investigations of ICH prevention.
Asunto(s)
Hemorragia Intracraneal Hipertensiva/prevención & control , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/metabolismo , Animales , Membrana Basal/irrigación sanguínea , Vasos Sanguíneos/efectos de los fármacos , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Incidencia , Hemorragia Intracraneal Hipertensiva/inducido químicamente , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Ratones , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/administración & dosificación , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/farmacologíaRESUMEN
BACKGROUND: Previous studies have revealed that hematoma growth mainly occurs during the first 6 h after the onset of spontaneous intracerebral hemorrhage (ICH). Early lowering of blood pressure (BP) may be beneficial for preventing hematoma growth. However, relationships between timing of BP lowering and hematoma growth in ICH remain unclear. We investigated associations between timing of BP lowering and hematoma growth for ICH. METHODS: The Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-ICH Study was a multicenter, prospective, observational study investigating the safety and feasibility of early (within 3 h from onset) reduction of systolic BP (SBP) to < 160 mm Hg with intravenous nicardipine for acute hypertension in cases of spontaneous ICH. The present study was a post hoc analysis of the SAMURAI-ICH study. We examined relationships between time from onset, imaging, and initiation of treatment to target SBP achievement and hematoma growth (absolute growth ≥6 mL) in ICH patients. Target SBP achievement was defined as the time at which SBP first became < 160 mm Hg. RESULTS: Among 211 patients, hematoma growth was seen in 31 patients (14.7%). The time from imaging to target SBP and time from treatment to target SBP were significantly shorter in patients without hematoma growth than in those with (p = 0.043 and p = 0.032 respectively), whereas no significant difference was seen in time from onset to SBP < 160 mm Hg between groups (p = 0.177). Patients in the lower quartiles of time from imaging to target SBP and time from treatment to target SBP showed lower incidences of hematoma growth (p trend = 0.023 and 0.037 respectively). The lowest quartile of time from imaging to target SBP (< 38 min) was negatively associated with hematoma growth on multivariable logistic regression (OR 0.182; 95% CI 0.038-0.867; p = 0.032). CONCLUSIONS: Early achievement of target SBP < 160 mm Hg is associated with a lower risk of hematoma growth in ICH.
Asunto(s)
Antihipertensivos/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Hematoma/prevención & control , Hipertensión/tratamiento farmacológico , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Nicardipino/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Antihipertensivos/efectos adversos , Estudios de Factibilidad , Femenino , Hematoma/diagnóstico por imagen , Hematoma/fisiopatología , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Hemorragia Intracraneal Hipertensiva/diagnóstico por imagen , Hemorragia Intracraneal Hipertensiva/fisiopatología , Japón , Masculino , Persona de Mediana Edad , Nicardipino/efectos adversos , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/fisiopatología , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective of the present study was to investigate the clinical efficacy of early application and ideal dosage of urokinase after minimally invasive surgery for hypertensive intracerebral hemorrhage (HICH). PATIENTS AND METHODS: We consecutively enrolled 132 patients with HICH who underwent CT-guided stereotactic intubation of the hematoma combined with dissolution using urokinase, where the urokinase was injected at 24 h after intubation. The 40 patients in the low-dosage group received 10-30 thousand units of urokinase; the 46 patients in the moderate-dosage group received 40-60 thousand units of urokinase; and the 46 patients in the high-dosage group received 70-100 thousand units of urokinase. After the drainage tubes were clamped for 4-6 h, clamps were removed for drainage for 24 h, and the intubated tubes were maintained for 3-5 d. Patients in all groups were followed up for 6 months, and the clinical outcomes were compared. RESULTS: The clearance of hematomas in the high-dosage group was significantly improved compared with the other two groups (p<0.05), and the occurrence rates of complications in the moderate- and high-dosage groups were significantly higher than in the low-dosage group (p<0.05). During follow-up, the Chinese stroke scale and Barthel index scores in the high-dosage group were higher than those in the other two groups (p<0.05). The serum levels of matrix metalloproteinase-9 (MMP-9) and neuron-specific enolase (NSE) in the high-dosage group were lower than those in the other two groups (p<0.05). CONCLUSIONS: CT-guided stereotactic intubation of the hematoma combined with dissolution using urokinase is effective for eliminating the hematoma for treatment of HICH with few complications. For recovery of neurological functions and improvement of regular life skills, it is considered to be associated with decreases in the serum levels of MMP-9 and NSE.
Asunto(s)
Hematoma/tratamiento farmacológico , Hemorragia Intracraneal Hipertensiva/cirugía , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Drenaje , Femenino , Humanos , Hemorragia Intracraneal Hipertensiva/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Arterial hypertension represents the most important risk factor for ischemic and haemorrhagic stroke, and an acute hypertensive response is often observed in patients with intracranial haemorrhage (ICH). Available data indicate that the vast majority (> 70%) of patient with acute ICH have a systolic BP above 140 mmHg at the time of presentation in the ED; about 20% have SBP values above 180 mmHg. Severe BP elevation in the presence of ICH represents a hypertensive emergency, and worsening of clinical conditions is not infrequent in the first hours after admission; an aggressive early management is therefore required for these patients. Despite this, appropriate management of BP in acute ICH is still controversial, due to the complex issues involved, and the heterogeneous results obtained in clinical trials. This article will review the available evidence supporting acute BP reduction in acute ICH.