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AIMS: The risk of adverse events in atrial fibrillation (AF) patients was commonly stratified by risk factors or clinical risk scores. Risk factors often do not occur in isolation and are often found in multimorbidity 'clusters' which may have prognostic implications. We aimed to perform cluster analysis in a cohort of AF patients and to assess the outcomes and prognostic implications of the identified comorbidity cluster phenotypes. METHODS AND RESULTS: The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Hierarchical cluster analysis was performed on 4304 patients (mean age: 73.6 years, female; 40.3%, mean CHA2DS2-VASc score 3.37 ± 1.69), using 42 baseline clinical characteristics. On hierarchical cluster analysis, AF patients could be categorized into six statistically driven comorbidity clusters: (i) younger ages (mean age: 48.3 years) with low prevalence of risk factors and comorbidities (n = 209); (ii) elderly (mean age: 74.0 years) with low prevalence of risk factors and comorbidities (n = 1301); (iii) those with high prevalence of atherosclerotic risk factors, but without atherosclerotic disease (n = 1411); (iv) those with atherosclerotic comorbidities (n = 440); (v) those with history of any-cause stroke (n = 681); and (vi) the very elderly (mean age: 83.4 years) (n = 262). Rates of all-cause mortality and major adverse cardiovascular or neurological events can be stratified by these six identified clusters (log-rank test; P < 0.001 and P < 0.001, respectively). CONCLUSIONS: We identified six clinically relevant phenotypes of AF patients on cluster analysis. These phenotypes can be associated with various types of comorbidities and associated with the incidence of clinical outcomes. CLINICAL TRIAL REGISTRATION INFORMATION: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834.
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Fibrilación Atrial , Accidente Cerebrovascular , Anciano , Anciano de 80 o más Años , Anticoagulantes , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND: While water intake is frequently recommended to prevent cerebral infarction (CI), only few studies have been published on this topic. OBJECTIVES: This study retrospectively estimated the daily non-alcohol drink (NAD) intake in CI patients before CI onset and compared it with NAD in healthy subjects. METHODS: We performed a cross-sectional study on CI patients in 3 hospitals and healthy subjects in the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) study. Data from 1,287 subjects (274 CI patients and 1,013 healthy subjects) were used for the analyses. By dividing the CI patients into "increased", "unchanged", and "decreased" groups according to their current NAD intake, we compared the NAD intake between these 3 groups and healthy subjects by analyses of covariance and the post hoc test, adjusting for sex, age, surveyed month, body mass index, alcohol drinking history, and smoking history. Under the assumption that the NAD intake in the "unchanged" group was equal to the NAD intake before CI onset, the OR of less NAD intake for CI adjusting for the relevant variables in the "unchanged" group and the healthy subjects was calculated; the cut-off point was chosen using Youden's index. RESULTS: The mean age (mean ± SD) of the participants was 62.8 ± 9.3 years. One hundred and fifty-one patients (36 women) were included in the "increased" group; 105 (30 women), in the "unchanged" group; 18 (2 women), in the "decreased" group; and 1,013 (706 women), in the "healthy" group. The mean NAD intake was 1,702.5 ± 670.2 mL in the "increased" group, 1,494.2 ± 611.2 mL in the "unchanged" group, 1,268.0 ± 596.1 mL in the "decreased" group, and 1,720.6 ± 686.0 mL in the "healthy" group. After adjusting for the relevant variables, a significant difference in NAD intake between the groups was observed (F = 6.1, p < 0.001), and a post hoc test demonstrated significant differences (p < 0.05) in NAD intake between the "healthy" and "unchanged" groups, and between the "increased" and "unchanged" groups. The OR of less NAD intake (<1,570 mL/day, chosen using Youden's index) for CI was 2.48 (95% CI 1.52-4.07). CONCLUSION: This study showed that daily NAD intake before CI onset in CI patients was less than that in healthy persons, indicating that sufficient intake of NAD may be protective for CI.
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Infarto Cerebral/epidemiología , Ingestión de Líquidos , Hábitos , Anciano , Infarto Cerebral/diagnóstico , Infarto Cerebral/prevención & control , Estudios Transversales , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Factores Protectores , Ingesta Diaria Recomendada , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: We report a case of symptomatic, progressive stenosis of a persistent primitive hypoglossal artery (PPHA), which was successfully treated with percutaneous transluminal angioplasty (PTA) of the origin of the PPHA. The PPHA is a type of carotid-basilar anastomosis with an incidence of 0.02% to 0.10%. It originates from the internal carotid artery (ICA), passes through the hypoglossal canal, and merges with the basilar artery. In many cases, the ipsilateral vertebral artery is hypoplastic; therefore, PPHA stenosis causes cerebral infarction in the posterior circulation territory, as in this case. OBSERVATIONS: The patient's right PPHA had severe and progressive stenosis; therefore, he experienced cerebral infarction despite medical treatment. Therefore, PTA for the stenosis was performed, which ceased the recurrence of cerebral infarction and dizziness by improving blood flow in the posterior circulation. LESSONS: Several reports have described ICA stenosis accompanied by PPHA or PPHA stenosis in patients receiving endovascular treatments. Almost all cases were nonprogressive, and the treatment procedure was stenting. However, in our case, the PPHA stenosis was progressive, and we performed PTA because the patient experienced resistance to antiplatelet drugs and had poor collateral flow.
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BACKGROUND: The authors report a case of symptomatic cavernous sinus (CS) dural arteriovenous fistula (dAVF) that was successfully treated using direct puncture of the superior ophthalmic vein (SOV) with craniotomy. CS dAVF is commonly treated using transvenous embolization (TVE), with the most common access route via the inferior petrosal sinus (IPS). However, this route is sometimes unavailable because of an occluded, hypoplastic, aplastic, or tortuous IPS. The SOV is an alternative, albeit tortuous and long, route to the CS; therefore, direct SOV puncture is occasionally performed. Direct SOV puncture is mostly percutaneous; however, in this case, it was difficult because of subcutaneous SOV narrowing. OBSERVATIONS: As the patient experienced increased intraocular pressure, decreased vision, and eye movement disorders, CS embolization was performed via direct puncture with a craniotomy because of other access difficulties. LESSONS: Several reports have described CS dAVF in patients receiving endovascular treatment via direct SOV puncture using a transorbital approach. However, to the best of the authors' knowledge, this is the first reported case of a CS dAVF treated using TVE with craniotomy. This approach is useful when the SOV cannot be reached intravenously and its distance from the epidermis is long.
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Malignant pleural mesothelioma (MPM) remains suffering poor prognosis in spite of recent diagnostic and therapeutic progress. Although there is currently no established evidence, early diagnosis and early intervention may play a key role to improve prognosis of MPM, similarly to other malignancies. As pleural effusion is usually the first clinical sign of MPM, pleural effusion cytology is often the first diagnostic examination to be carried out. Since the sensitivity of pleural effusion cytology is approximately 60%, however, false-negative diagnosis is given to almost half of true MPM patients at this clinical step. One practical way to reduce the number of misdiagnosed MPM is to encourage performing thoracoscopic pleural biopsy unless definitive diagnosis other than MPM is established. There still remain a considerable number of patients with radiological/thoracoscopic T0 MPM who are misdiagnosed with nonspecific pleuritis after a complete investigation including thoracoscopic biopsies. Such patients will turn out to be malignant during follow-up period, although they have the best opportunity for long-term survival if only early therapeutic intervention is given. Currently, we are performing diagnostic total parietal pleurectomy in highly selected patients, who are characterized with strong clinical suspicion, positive pleural effusion cytology but uncertain pathological diagnosis, excellent cardiopulmonary reserve, and with written informed consent for highly invasive diagnostic surgery for pathologically unproven disease.
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Detección Precoz del Cáncer , Mesotelioma/diagnóstico , Pleura/cirugía , Neoplasias Pleurales/diagnóstico , Humanos , Mesotelioma/patología , Mesotelioma/cirugía , Estadificación de Neoplasias , Derrame Pleural Maligno/patología , Neoplasias Pleurales/patología , Neoplasias Pleurales/cirugía , PronósticoRESUMEN
Background: Atrial fibrillation (AF) increases the risk of heart failure (HF); however, little focus is placed on the risk stratification for, and prevention of, incident HF in patients with AF. Objectives: This study aimed to construct and validate a machine learning (ML) prediction model for HF hospitalization in patients with AF. Methods: The Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto, Japan. We divided the data set of the registry into derivation (n = 2,383) and validation (n = 2,011) cohorts. An ML model was built to predict the incidence of HF hospitalization using the derivation cohort, and predictive ability was examined using the validation cohort. Results: HF hospitalization occurred in 606 patients (14%) during a median follow-up period of 4.4 years in the entire registry. Data of transthoracic echocardiography and biomarkers were frequently nominated as important predictive variables across all 6 ML models. The ML model based on a random forest algorithm using 7 variables (age, history of HF, creatinine clearance, cardiothoracic ratio on x-ray, left ventricular [LV] ejection fraction, LV end-systolic diameter, and LV asynergy) had high prediction performance (area under the receiver operating characteristics curve [AUC]: 0.75) and was significantly superior to the Framingham HF risk model (AUC: 0.67; P < 0.001). Based on Kaplan-Meier curves, the ML model could stratify the risk of HF hospitalization during the follow-up period (log-rank; P < 0.001). Conclusions: The ML model revealed important predictors and helped us to stratify the risk of HF, providing opportunities for the prevention of HF in patients with AF.
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The CHADS2 and CHA2DS2-VASc scores are widely used to assess ischemic risk in the patients with atrial fibrillation (AF). However, the discrimination performance of these scores is limited. Using the data from a community-based prospective cohort study, we sought to construct a machine learning-based prediction model for cerebral infarction in patients with AF, and to compare its performance with the existing scores. All consecutive patients with AF treated at 81 study institutions from March 2011 to May 2017 were enrolled (n = 4396). The whole dataset was divided into a derivation cohort (n = 1005) and validation cohort (n = 752) after excluding the patients with valvular AF and anticoagulation therapy. Using the derivation cohort dataset, a machine learning model based on gradient boosting tree algorithm (ML) was built to predict cerebral infarction. In the validation cohort, the receiver operating characteristic area under the curve of the ML model was higher than those of the existing models according to the Hanley and McNeil method: ML, 0.72 (95%CI, 0.66-0.79); CHADS2, 0.61 (95%CI, 0.53-0.69); CHA2DS2-VASc, 0.62 (95%CI, 0.54-0.70). As a conclusion, machine learning algorithm have the potential to perform better than the CHADS2 and CHA2DS2-VASc scores for predicting cerebral infarction in patients with non-valvular AF.
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Fibrilación Atrial , Accidente Cerebrovascular , Fibrilación Atrial/complicaciones , Infarto Cerebral/epidemiología , Infarto Cerebral/etiología , Humanos , Aprendizaje Automático , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de RiesgoRESUMEN
BACKGROUND: It is difficult to predict the development of carotid stenosis by means of the known risk factors. Using a computational fluid dynamics analysis, we examined the hemodynamic risks for carotid stenosis, focusing on wall shear stress (WSS) disturbances. METHODS: In 59 patients with unilateral carotid stenosis, the plaque was removed from the original three-dimensional computed tomography angiographic images, and the vessel shape before stenosis was artificially reproduced. A multivariate regression analysis was performed to determine the associations between the degree of area stenosis and hemodynamic and morphologic factors after adjustment for 6 known risk factors. RESULTS: Metrics for WSS disturbances were higher at and distal to a bifurcation in the carotid arteries after plaque removal compared with the normal carotid arteries, and metrics for WSS magnitudes were lower. In the plaque-removed arteries, the degree of stenosis was significantly negatively correlated with the ratio of stenotic to distal values of metrics for WSS disturbances and the diameter ratio of the external to common carotid artery, and positively correlated with the ratio of proximal to stenotic values of metrics for WSS magnitudes. CONCLUSIONS: Rapid increases in WSS from the common carotid artery toward the bifurcation, rapid decreases in WSS disturbance from the bifurcation toward the internal carotid artery, and lower diameter ratio of the external to common carotid artery are more likely than other risk factors to cause future severe stenosis. In patients with these hemodynamic risks, underlying diseases should be controlled more strictly, with imaging examinations at shorter intervals.
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Estenosis Carotídea , Arterias Carótidas , Arteria Carótida Interna/diagnóstico por imagen , Arteria Carótida Interna/cirugía , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/cirugía , Hemodinámica , Humanos , Factores de Riesgo , Estrés MecánicoRESUMEN
BACKGROUND: Criteria to decide whether carotid endarterectomy (CEA) or carotid artery stenting (CAS) is the best mode of therapy in a specific case of cervical carotid stenosis have not been established. Overall, recent randomized clinical trials have reported that the effect on the prevention of stroke is not significantly different between CEA and CAS. CEA is more appropriate than CAS for soft atherosclerotic plaques, since such soft plaques are associated with a high incidence of ischemic complications during CAS. Therefore identification of the plaque type with noninvasive preoperative examinations plays an important role for selecting the suitable surgical method, CEA or CAS. OBJECTIVE: The objective of this study was to evaluate the association among findings of carotid ultrasonography (carotid US), black blood magnetic resonance imaging (BB-MRI), and the histopathological findings of plaque specimens removed during CEA, and secondly to consider whether these diagnostic tools are useful to predict the characteristics of carotid plaques. METHOD: We investigated a total of 25 consecutive patients who underwent CEA from November 2008 to June 2010 at Kyoto Medical Center. We examined carotid plaque in 17 patients employing both carotid US and BB-MRI, 7 patients by carotid US, and 1 patient by BB-MRI. The plaque echogenicity was qualitatively assessed as low, intermediate, or high, and the MR signal intensity of the carotid plaque was classified as low or high compared with the intensity of the ipsilateral sternocleidomastoid muscle. The plaque specimens were macroscopically and pathophysiologically classified as soft or hard plaque. RESULTS: All low-echogenic plaques on carotid US were histologically soft plaques. The high-intensity plaques on T1-weighted imaging (T1WI) showed a tendency toward soft plaque. Thirteen of 14 plaques with high signal intensity on T1WI were morphologically soft. Eleven of 14 plaques with an intermediate echogenicity on carotid US were also morphologically soft. CONCLUSION: The findings of carotid ultrasonography and BB-MRI are closely associated with the CEA specimen's morphology. Ultrasonography alone is insufficient to diagnose the plaque type accurately in some patients. Employing both carotid US and BB-MRI is useful for evaluating the characteristics of carotid plaque.
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Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/patología , Placa Aterosclerótica/patología , Estenosis Carotídea/cirugía , Endarterectomía Carotidea/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Stents , UltrasonografíaRESUMEN
The indication for carotid endarterectomy (CEA) or carotid artery stenting (CAS) has not been established, although the beneficial effects of these surgical treatments for severe cervical carotid stenosis have been confirmed by clinical trial studies. We report our clinical results of CAS and CEA and suggest an appropriate treatment strategy, especially for high-risk patients. From January 2001 to December 2009, we treated 171 carotid lesions by CEA and 251 lesions by CAS. Stenosis was symptomatic in 68%, and the average stenotic rate was 83% in the CEA group. In the CAS group, stenosis was symptomatic in 62%, and the average stenotic rate was 65%. Stenosis was relieved in all cases after CEA or CAS. Surgical mortality with CEA and CAS was 0.6% (1/171) and 0.4% (1/251), respectively. Surgical morbidity by ischemic stroke with CEA and CAS was 2.9% (5/171) and 1.2% (3/251), respectively. Surgical morbidity was not increased in patients with medical risk factors. The long-term outcome after CAS was not inferior to that after CEA. In conclusion, carotid stenosis can be treated with comparably low morbidity and mortality rates using CEA or CAS even in high-risk patients when the method is appropriately selected considering the characteristics of the carotid stenosis.
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Angioplastia de Balón/métodos , Estenosis Carotídea/cirugía , Endarterectomía Carotidea/métodos , Anciano , Estenosis Carotídea/mortalidad , Angiografía Cerebral/métodos , Femenino , Humanos , Estudios Longitudinales , Masculino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Leukocytes (neutrophils, monocytes) in the active circulation exhibit multiple phenotypic indicators for a low level of cellular activity, like lack of pseudopods and minimal amounts of activated, cell-adhesive integrins on their surfaces. In contrast, before these cells enter the circulation in the bone marrow or when they recross the endothelium into extravascular tissues of peripheral organs they are fully activated. We review here a multifaceted mechanism mediated by fluid shear stress that can serve to deactivate leukocytes in the circulation. The fluid shear stress controls pseudopod formation via the FPR receptor, the same receptor responsible for pseudopod projection by localized actin polymerization. The bioactivity of macromolecular factors in the blood plasma that interfere with receptor stimulation by fluid flow, such as proteolytic cleavage in the extracellular domain of the receptor or the membrane actions of cholesterol, leads to a defective ability to respond to fluid shear stress by actin depolymerization. The cell reaction to fluid shear involves CD18 integrins, nitric oxide, cGMP and Rho GTPases, is attenuated in the presence of inflammatory mediators and modified by glucocorticoids. The mechanism is abolished in disease models (genetic hypertension and hypercholesterolemia) leading to an increased number of activated leukocytes in the circulation with enhanced microvascular resistance and cell entrapment. In addition to their role in binding to biochemical agonists/antagonists, membrane receptors appear to play a second role: to monitor local fluid shear stress levels. The fluid shear stress control of many circulating cell types such as lymphocytes, stem cells, tumor cells remains to be elucidated.
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Leucocitos , Mecanotransducción Celular , Neutrófilos , Seudópodos , Resistencia al Corte , Estrés MecánicoRESUMEN
Purpose: Endovascular therapy for emergent large vessel occlusion has been established as the standard approach for acute ischaemic stroke. However, the effectiveness and safety of endovascular therapy in the very elderly population has not been proved. Objective: To determine the safety and effectiveness of endovascular therapy in octogenarians and nonagenarians. Methods: We retrospectively reviewed all patients who underwent endovascular therapy at two stroke centres between April 2012 and July 2018. Functional outcome was assessed using the modified Rankin scale at 90 days after stroke or at discharge. A favourable outcome was defined as a modified Rankin scale score of 0-2 or not worsening of the modified Rankin scale score before stroke. Outcome was compared between younger patients (aged 46-79 years, n = 40) and octogenarians and nonagenarians (aged 80-97 years, n = 19). Results: Octogenarian and nonagenarian patients had pre-stroke functional deficit (modified Rankin scale score >1) more frequently than younger patients (57.9% vs. 20.0%, respectively, P = 0.0059). No difference was observed between very elderly and younger patients in the rate of successful reperfusion (89.5% vs. 67.5%, respectively, P = 0.11), favourable functional outcome (47.4% vs. 45.0%, respectively, P = 1.00) and mortality (21.1% vs. 27.5%, respectively, P = 1.00). On multiple regression analysis, successful reperfusion, concomitant use of intravenous thrombolysis, and out-of-hospital onset were independent predictors of favourable outcome (P = 0.0003, 0.015 and 0.028, respectively). Conclusions: Successful reperfusion, concomitant use of intravenous thrombolysis, and out-of-hospital onset were clinical predictors of favourable outcome. However, we did not observe an age-dependent effect of clinical outcome after endovascular therapy.
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Isquemia Encefálica/terapia , Procedimientos Endovasculares/métodos , Accidente Cerebrovascular/terapia , Distribución por Edad , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Fibrinolíticos/administración & dosificación , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Imagen Multimodal , Estudios Prospectivos , Reperfusión/métodos , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
PURPOSE: Carotid artery stenting (CAS) is a valuable alternative to carotid endarterectomy, especially in high-risk patients. However, the reported incidences of perioperative stroke and death remain higher than for carotid endarterectomy, even when using embolic protection devices (EPDs) during CAS. Our purpose was to evaluate 30-day major adverse events after CAS when selecting the most appropriate EPD. METHODS: We reviewed the clinical outcomes of 61 patients with 64 lesions who underwent CAS with EPDs. Patients who underwent CAS associated with thrombectomy and who had a preoperative modified Rankin scale score >3 were excluded from the analysis. The EPD was selected based on symptoms, carotid wall magnetic resonance imaging and lesion length, and we analyzed combined 30-day complication rates (transient ischemic attack, minor stroke, major stroke or death). RESULTS: Forty-nine patients were men and 12 were women. The median age was 72 years (range: 59-89 years) and 44 lesions were asymptomatic. A filter-type EPD was selected in 23 procedures, distal-balloon protection in 14 procedures and proximal-occlusive protection in 27 procedures. Two patients (3.1%) experienced a transient ischemic attack and one patient (1.6%) had a minor stroke within 30 days of the procedure. No patients experienced procedure-related morbidities (modified Rankin score >2) or death. CONCLUSIONS: The perioperative stoke rate was low when we selected a proximal-occlusive-type EPD in high-risk patients with vulnerable carotid artery disease. Our algorithm for EPD selection was an effective tool in the perioperative management of carotid artery stenosis.
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Arteria Carótida Interna/cirugía , Estenosis Carotídea/cirugía , Dispositivos de Protección Embólica , Stents , Anciano , Anciano de 80 o más Años , Algoritmos , Femenino , Humanos , Ataque Isquémico Transitorio/etiología , Masculino , Persona de Mediana Edad , Seguridad del Paciente , Selección de Paciente , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Accidente Cerebrovascular/etiologíaRESUMEN
OBJECTIVE: There are no effective therapeutic drugs for cerebral aneurysms, partly because the pathogenesis remains unresolved. Chronic inflammation of the cerebral arterial wall plays an important role in aneurysm formation, but it is not clear what triggers the inflammation. The authors have observed that vascular endothelial P2X4 purinoceptor is involved in flow-sensitive mechanisms that regulate vascular remodeling. They have thus hypothesized that shear stress-associated hemodynamic stress on the endothelium causes the inflammatory process in the cerebral aneurysm development. METHODS: To test their hypothesis, the authors examined the role of P2X4 in cerebral aneurysm development by using P2X4-/- mice and rats that were treated with a P2X4 inhibitor, paroxetine, and subjected to aneurysm-inducing surgery. Cerebral aneurysms were induced by unilateral carotid artery ligation and renovascular hypertension. RESULTS: The frequency of aneurysm induction evaluated by light microscopy was significantly lower in the P2X4-/- mice (p = 0.0488) and in the paroxetine-treated male (p = 0.0253) and female (p = 0.0204) rats compared to control mice and rats, respectively. In addition, application of paroxetine from 2 weeks after surgery led to a significant reduction in aneurysm size in the rats euthanized 3 weeks after aneurysm-inducing surgery (p = 0.0145), indicating that paroxetine suppressed enlargement of formed aneurysms. The mRNA and protein expression levels of known inflammatory contributors to aneurysm formation (monocyte chemoattractant protein-1 [MCP-1], interleukin-1ß [IL-1ß], tumor necrosis factor-α [TNFα], inducible nitric oxide synthase [iNOS], and cyclooxygenase-2 [COX-2]) were all significantly elevated in the rats that underwent the aneurysm-inducing surgery compared to the nonsurgical group, and the values in the surgical group were all significantly decreased by paroxetine administration according to quantitative polymerase chain reaction techniques and Western blotting. Although immunolabeling densities for COX-2, iNOS, and MCP-1 were not readily observed in the nonsurgical mouse groups, such densities were clearly seen in the arterial wall of P2X4+/+ mice after aneurysm-inducing surgery. In contrast, in the P2X4-/- mice after the surgery, immunolabeling of COX-2 and iNOS was not observed in the arterial wall, whereas that of MCP-1 was readily observed in the adventitia, but not the intima. CONCLUSIONS: These data suggest that P2X4 is required for the inflammation that contributes to both cerebral aneurysm formation and growth. Enhanced shear stress-associated hemodynamic stress on the vascular endothelium may trigger cerebral aneurysm development. Paroxetine may have potential for the clinical treatment of cerebral aneurysms, given that this agent exhibits efficacy as a clinical antidepressant.
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Primary intracranial leiomyosarcoma (LMS) is an extremely rare tumor of the central nervous system. Only sporadic case reports have been published, and therefore data regarding long-term prognosis remain scarce. A 76-year-old woman presented with a right parietal mass, which had grown rapidly in the month prior to admission. Neuroimaging showed a resemblance to intraosseous meningioma. Gross total resection of the tumor was achieved, and histological diagnosis confirmed LMS. Because positron emission tomography (PET) with fluorodeoxyglucose (FDG) just after the resection showed no abnormal uptake, we diagnosed the tumor as primary intracranial LMS. Follow-up PET at 16 months after treatment showed two foci of FDG uptake in the bilateral lungs. Histological diagnosis by surgical resection identified the lesions as lung metastases of LMS. In addition, follow-up head magnetic resonance imaging (MRI) at 31 months showed local recurrence, and we conducted salvage therapy using CyberKnife system (Accuray incorporated) and pazopanib. To date, for 15 months after local recurrence, she is alive with intracranial recurrent disease remained inactive.
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BACKGROUND: Large-scale clinical trials have analyzed risk factors for any ischemic stroke in patients with atrial fibrillation (AF). However, the risk factors for cardioembolic stroke (CES), specifically, have not been reported. To clarify the risk factors for CES and clinically significant cardioembolic infarction, we examined the incidence of CES and larger infarct volume (IV) (> 30 mL) CES, employing the Fushimi AF Registry, a community-based prospective cohort of AF patients in the Fushimi ward, Kyoto, Japan. METHODS: A total of 4,182 Fushimi AF patients were enrolled from March 2011 to December 2014. The risk factors for CES were evaluated using multivariate analysis. RESULTS: Of 4,182 patients enrolled, 3,749 patients were observed for ≥1 year. During the follow-up period (mean duration, 979 ± 7.7 days), 91/3,749 patients experienced a CES (2.43%). Significant risk factors associated with CES were older age (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.01-1.72; p = 0.046), low body weight (OR, 1.30; 95% CI, 1.03-1.65; p = 0.033), sustained AF (OR, 1.67; 95% CI, 1.05-2.71; p = 0.034), and previous stroke or transient ischemic attack (TIA) (OR, 1.94; 95% CI, 1.22-3.06; p = 0.004). Predictors of a large IV were chronic kidney disease (CKD) (OR, 2.08; 95% CI, 1.09-4.05; p = 0.027) and previous stroke/TIA (OR, 2.27; 95% CI, 1.19-4.24; p = 0.011). CONCLUSIONS: In this population-based cohort of Japanese patients with AF, in addition to previous stroke/TIA and older age, sustained AF and low body weight emerged as risk factors for CES, as opposed to any stroke, which may have a different risk profile. Patients with CKD or previous stroke/TIA who developed cardioembolic infarction exhibited more advanced severity. There is a need for direct oral anticoagulants that can be used safely in patients with comorbid AF and CKD.
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Fibrilación Atrial/epidemiología , Embolia Intracraneal/epidemiología , Accidente Cerebrovascular/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/diagnóstico , Peso Corporal , Distribución de Chi-Cuadrado , Comorbilidad , Femenino , Humanos , Incidencia , Embolia Intracraneal/diagnóstico por imagen , Japón/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Pronóstico , Estudios Prospectivos , Recurrencia , Sistema de Registros , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Factores de TiempoRESUMEN
We review recent evidence which suggests that leukocytes in the circulation and in the tissue may readily respond to physiological levels of fluid shear stress in the range between about 1 and 10 dyn/cm 2, a range that is below the level to achieve a significant passive, viscoelastic response. The response of activated neutrophilic leukocytes to fluid shear consists of a rapid retraction of lamellipodia with membrane detachment from integrin binding sites. In contrast, a subgroup of non-activated neutrophils may project pseudopods after exposure to fluid shear stress. The evidence suggests that G-protein coupled receptor downregulation by fluid shear with concomitant downregulation of Rac-related small GTPases and depolymerization of F-actin serves to retract the lamellipodia in conjunction with proteolytic cleavage of beta 2 integrin to facilitate membrane detachment. Furthermore, there exists a mechanism to up- and down-regulate the fluid shear-response, which involves nitric oxide and the second messenger cyclic guanosine monophosphate (cGMP). Many physiological activities of circulating leukocytes are under the influence of fluid shear stress, including transendothelial migration of lymphocytes. We describe a disease model with chronic hypertension that suffers from an attenuated fluid shear-response with far reaching implications for microvascular blood flow.
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Leucocitos/fisiología , Mecanotransducción Celular/fisiología , Animales , Adhesión Celular/fisiología , Membrana Celular/fisiología , Quimiotaxis de Leucocito/fisiología , Citoplasma/fisiología , Hemorreología , Humanos , Activación Neutrófila/fisiologíaRESUMEN
There is compelling evidence that circulatory hemodynamics prevent neutrophil activation, including adhesion to microvessels, in the microcirculation. However, the underlying mechanism or mechanisms by which that mechanoregulation occurs remain unresolved. Here, we report evidence that exposure to fluid shear stress (FSS) promotes neutrophils to release cathepsin B (ctsB) and that this autocrine regulatory event is antiadhesive for neutrophils on endothelial surfaces through Mac1-selective regulation. We used a combined cell-engineering and immunocytochemistry approach to find that ctsB was capable of cleaving Mac1 integrins on neutrophils and demonstrated that this proteolysis alters their adhesive functions. Under no-flow conditions, ctsB enhanced neutrophil migration though a putative effect on pseudopod retraction rates. We also established a flow-based cell detachment assay to verify the role of ctsB in the control of neutrophil adhesion by fluid flow stimulation. Fluid flow promoted neutrophil detachment from platelet and endothelial layers that required ctsB, consistent with its fluid shear stress-induced release. Notably, compared with leukocytes from wild-type mice, those from ctsB-deficient (ctsB -/- ) mice exhibited an impaired CD18 cleavage response to FSS, significantly elevated baseline levels of CD18 surface expression, and an enhanced adhesive capacity to mildly inflamed postcapillary venules. Taken together, the results of the present study support a role for ctsB in a hemodynamic control mechanism that is antiadhesive for leukocytes on endothelium. These results have implications in the pathogenesis of chronic inflammation, microvascular dysfunction, and cardiovascular diseases involving sustained neutrophil activation in the blood and microcirculation.
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Catepsina B/inmunología , Antígeno de Macrófago-1/inmunología , Activación Neutrófila , Neutrófilos/inmunología , Resistencia al Corte , Animales , Catepsina B/genética , Adhesión Celular/genética , Adhesión Celular/inmunología , Movimiento Celular/genética , Movimiento Celular/inmunología , Femenino , Células HL-60 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Antígeno de Macrófago-1/genética , Masculino , Ratones , Ratones NoqueadosRESUMEN
Objectives The aim of this study was to examine the feasibility, technique, and clinical and angiographic outcomes of endovascular coiling to treat a cerebral aneurysm with a branch incorporated into the aneurysmal wall. Methods From 2012 to 2016, 25 patients with 26 cerebral aneurysms having a branch incorporated into the aneurysm (9 unruptured, 17 ruptured) were treated to prevent rupture or re-bleeding from the sac while preserving the incorporated branch by using single-catheter ( n = 18), balloon-remodeling ( n = 4), stent-assisted coiling ( n = 3), or double-catheter ( n = 1) techniques. Results Endovascular coiling was conducted in 26 procedures without angiographic occlusion of the incorporated branch. Post-embolization angiography revealed near-complete occlusion ( n = 8; 30.7%), neck remnant ( n = 13; 50%), and incomplete occlusion ( n = 5; 19.3%) aneurysms. Thromboembolisms were observed in four (15.4%) patients during or after the procedure. A procedure-related neurological deficit was observed in one (3.8%) patient. When patients with a preictal modified Rankin Scale (mRS) score of 3 presenting with grade 5 subarachnoid hemorrhage were excluded, all patients had favorable outcomes (mRS 0-2). Six (23.1%) recurrent aneurysms were observed during follow-up, five of which were treated endovascularly at 5-22 months without complication. The location of an aneurysm at the ICA-posterior communicating artery associated with the dominant-type posterior communicating artery was significantly associated with recurrence ( p = 0.041). Conclusions Cerebral aneurysms with an incorporated branch were safely treated using conventional endovascular coiling. However, treatment durability was unsatisfactory, especially for dominant-type ICA-posterior communicating artery aneurysms.
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Embolización Terapéutica/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/terapia , Adulto , Anciano , Anciano de 80 o más Años , Angiografía Cerebral , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
The mechanisms for elevation of peripheral vascular resistance in spontaneously hypertensive rats (SHR), a glucocorticoid-dependent form of hypertension, are unresolved. An increase in hemodynamic resistance caused by circulating blood may be a factor. Physiological fluid shear stress induces a variety of responses in circulating leukocytes, including pseudopod retraction. Due to high rigidity, leukocytes with pseudopods have greater difficulty to pass through capillaries. Because SHR have more circulating leukocytes with pseudopods, we hypothesize that inhibition of the leukocyte shear response by glucocorticoids in SHR impairs normal leukocyte passage through capillaries and causes enhanced resistance in capillary channels. Fluid shear leads to retraction of pseudopods in normal leukocytes, whereas shear induces pseudopod projection in SHR and dexamethasone-treated Wistar rats. The high incidence of circulating leukocytes with pseudopods results in slower cell passage through capillaries under normal blood flow and during reduced flow enhanced capillary plugging both in vivo and in vitro. SHR blood requires higher pressure (90.0+/-8.2 mm Hg) than Wistar Kyoto rat (WKY, 69.6+/-6.5 mm Hg; P<0.0001) or adrenalectomized SHR (73.5+/-2.1 mm Hg; P=0.0009) at the same flow rate in the resting hemodynamically isolated skeletal muscle microcirculation. Intravenous injection of blood from SHR, but not WKY, causes blood pressure increase in normal rats, which depends on pseudopod formation. We conclude that in addition to enhanced vascular tone, pseudopod formation with lack of normal fluid shear response may serve as mechanisms for an elevated hemodynamic resistance in SHR.