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stroke - Top 30 Publications

Spontaneous cervical artery dissection is accompanied by a hypercoagulable state and simultaneous inflammatory condition.

Spontaneous cervical artery dissections (sCAD) are often preceded by infections. However, existing data about inflammatory parameters remained inconsistent. Remarkably, concurrent information about the coagulation system, whose affection seems also reasonable to cause ischaemic events, are still lacking in sCAD patients. Thus, this study explores the association between the inflammatory and coagulation system in patients with sCAD.

Coated-Platelet Trends Predict Short-Term Clinical OutcomeAfter Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high socio-economic burden. Prothrombotic states of early brain injury (EBI) and delayed cerebral ischemia (DCI) after aSAH determine morbidity and mortality. To understand how activated platelets might contribute to such prothrombotic states, we studied trends in coated-platelets during EBI and DCI periods. Serial blood samples from a prospective cohort of aSAH patients were collected and assayed for coated-platelet levels. Patient's coated-platelet level during post-hospital discharge follow-up served as an estimate of baseline. Occurrence of DCI, Montreal cognitive assessment (MOCA) score of < 26, and modified Rankin scale (mRS) of 3-6 were considered poor clinical outcomes. Non-linear regression analysis detected a transition between periods of rising and declining coated-platelet levels at day 4. Additional regression analyses of coated-platelet trends before day 4 showed differences among patients with modified Fisher 3-4 [4.2% per day (95% CI 2.4, 6.1) vs. - 0.8% per day (95% CI - 3.4, 1.8); p = 0.0023] and those developing DCI [4.6% per day (95% CI 2.8, 6.5) vs. - 1.9% per day (95% CI - 4.5, 0.5); p < 0.001]. Differences between peak coated-platelet levels and baseline levels were larger, on average for those with DCI [18.1 ± 9.6 vs. 10.6 ± 8.0; p = 0.03], MOCA < 26 [17.0 ± 7.8 vs. 10.7 ± 7.4; p = 0.05] and mRS 3-6 [24.8 ± 10.5 vs. 11.9 ± 7.6; p = 0.01]. Coated-platelet trends after aSAH predict DCI and short-term clinical outcomes. The degree of rise in coated-platelets is also associated with adverse clinical outcomes.

Residual Risk of Atherosclerotic Cardiovascular Events in Relation to Reductions in Very-Low-Density Lipoproteins.

It is uncertain whether pharmacological reductions in very-low-density lipoproteins (VLDLs), and their component triglyceride and cholesterol could reduce residual risk of atherosclerotic cardiovascular disease (ASCVD) events among individuals in whom low-density lipoprotein cholesterol (LDL-C) has been adequately lowered. We examined whether individuals with greater on-statin reductions in VLDL-related measures-beyond reductions in LDL-C-were at further reduced risk of ASCVD.

Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With Hypercholesterolemia: A Meta-Analysis of 35 Randomized Controlled Trials.

We sought to examine the efficacy and safety of 2 PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors: alirocumab and evolocumab.

Papillary fibroelastoma: retrospective analysis. Clinical presentation and surgical results.

Papillary ibroelastomas are small benign intracardiac tumors known for their embolic potential. Since the introduction of echocardiography with improved resolution and transesophageal imaging techniques, they are being increasingly detected in clinical practice. In recent series, papillary fibroelastoma is considered the most frequent benign tumor of the heart. Our objective was to analyze characteristics and midterm surgical outcome of histologically-confirmed cases of papillary fibroelastoma. We conducted a retrospective study on patients with cardiac tumors submitted to surgical excision between June 1992 and February 2017. Out of 108 patients, 18 had papillary fibroelastomas. Their mean age was 58 years (22-77); 10 were men. The most frequent localizations were the aortic valve (7) and the mitral valve (5). None had significant valvular dysfunction. By transesophageal echocardiography, the tumor size (larger diameter) was 13.33 ± 5.55 mm (6.6-28.0). Two patients, both with tumor in the aortic valve, had suffered a stroke; other two had dyspnoea and atrial flutter, respectively. The remaining 14 patients were asymptomatic and their tumors were incidental findings. In 15 patients the valve was preserved. There was neither surgical mortality nor recurrence after 2.6 years of follow-up. In conclusion, most papillary fibroelastomas can be surgically removed with valve preservation and favorable clinical outcome. However, until the results of randomized trials support the decision, an aggressive surgical approach in asymptomatic patients needs to be defined in the context of surgical expertise.

Task-based and resting-state fMRI reveal compensatory network changes following damage to left inferior frontal gyrus.

Damage to left inferior prefrontal cortex in stroke aphasia is associated with semantic deficits reflecting poor control over conceptual retrieval, as opposed to loss of knowledge. However, little is known about how functional recruitment within the semantic network changes in patients with executive-semantic deficits. The current study acquired functional magnetic resonance imaging (fMRI) data from 14 patients with semantic aphasia, who had difficulty with flexible semantic retrieval following left prefrontal damage, and 16 healthy age-matched controls, allowing us to examine activation and connectivity in the semantic network. We examined neural activity while participants listened to spoken sentences that varied in their levels of lexical ambiguity and during rest. We found group differences in two regions thought to be good candidates for functional compensation: ventral anterior temporal lobe (vATL), which is strongly implicated in comprehension, and posterior middle temporal gyrus (pMTG), which is hypothesized to work together with left inferior prefrontal cortex to support controlled aspects of semantic retrieval. The patients recruited both of these sites more than controls in response to meaningful sentences. Subsequent analysis identified that, in control participants, the recruitment of pMTG to ambiguous sentences was inversely related to functional coupling between pMTG and anterior superior temporal gyrus (aSTG) at rest, while the patients showed the opposite pattern. Moreover, stronger connectivity between pMTG and aSTG in patients was associated with better performance on a test of verbal semantic association, suggesting that this temporal lobe connection supports comprehension in the face of damage to left inferior prefrontal cortex. These results characterize network changes in patients with executive-semantic deficits and converge with studies of healthy participants in providing evidence for a distributed system underpinning semantic control that includes pMTG in addition to left inferior prefrontal cortex.

Relationship between thrombus age in aspirated coronary material and mid-term major adverse cardiac and cerebrovascular events in patients with acute myocardial infarction.

Recent studies have shown that coronary thrombus histopathology is associated with impaired myocardial reperfusion and poor clinical outcome in patients with acute myocardial infarction (AMI). We sought to investigate the age of thrombi aspirated during percutaneous coronary intervention (PCI) in patients with AMI and evaluate the relationship between histopathologic findings and major adverse cardiac and cerebrovascular events (MACCEs) defined as all-cause death, stroke, or myocardial infarction within 6 months of PCI.

A new T2 lesion in a patient with the clinically isolated syndrome does not necessarily imply a conversion to multiple sclerosis.

In the follow-up of patients with the clinically isolated syndrome, both clinical and MRI findings should be carefully evaluated by clinicians to avoid misinterpretation and inappropriate diagnosis of multiple sclerosis. We describe a case of a patient with a previous diagnosis of clinically isolated syndrome who developed a new asymptomatic brain lesion at the MRI follow-up. The careful evaluation of clinical history and radiological findings allowed the correct diagnosis of cocaine-associated ischemic stroke. Our case highlights that, in patients with the clinically isolated syndrome, the appearance of a new lesion on MRI does not necessarily imply a conversion to multiple sclerosis. Among "better explanations", ischemic lesions are of relevance and, in patients without typical risk factors for stroke, rarer causes such as cocaine assumption should be considered.

Comparison of neuroplastic responses to cathodal transcranial direct current stimulation and continuous theta burst stimulation in subacute stroke.

To investigate the effects of cathodal transcranial direct current stimulation (tDCS) and continuous theta burst stimulation (cTBS) on neural network connectivity and motor recovery in individuals with subacute stroke.

Striking a chord with healthy aging: memory system cooperation is related to preserved configural response learning in older adults.

Evidence from tasks that primarily tap either hippocampal- or striatal-based memory systems suggests that although these systems often compete for control of behavior, aging is associated with greater cooperation between them. This may stem from altered prefrontal cortex function. Here, we use a configural response task designed to engage both memory systems to test how age affects their interaction with cortical regions including the prefrontal cortex. We found that although older and younger adults learned just as well, older adults showed greater initial activation in cortical networks associated with visuospatial-action mapping and resolving conflict for competing memory representations. Older adults also showed greater functional coupling of the striatum with the left inferior frontal gyrus, in parallel with similar hippocampal coupling to ventral visual regions as young adults. Overall, our results support the proposal that aging is associated with more cooperative memory systems, but we did not find that greater cooperation is associated with less interaction between the prefrontal cortex and core memory system structures during learning.

Comparative Risks of Ischemic Stroke in Atrial Flutter versus Atrial Fibrillation.

The aim of this study was to compare the risk of ischemic stroke in patients who have atrial fibrillation and patients who have atrial flutter.

The Relation between Blood Count Parameters and Stroke in Patients with Intermediate Carotid Artery Stenosis.

Long-term pulmonary and cardiovascular morbidities of neonatal hyperoxia exposure in mice.

Pulmonary hypertension (PH) frequently occurs in infants with bronchopulmonary dysplasia (BPD), causing increased mortality and right ventricular (RV) dysfunction that persists into adulthood. A first step in developing better therapeutic options is identifying and characterizing an appropriate animal model. Previously, we characterized the short-term morbidities of a model in which C57BL/6J wild-type (WT) mice were exposed to 70% O2 (hyperoxia) during the neonatal period. Here, we aimed to determine the long-term morbidities using lung morphometry, echocardiography (Echo), and cardiac magnetic resonance imaging (cMRI). The major highlight of this study is the use of the state-of-the art imaging technique, cMRI, in mice to characterize the long-term cardiac effects of neonatal hyperoxia exposure. To this end, WT mice were exposed to 21% O2 (normoxia) or hyperoxia for two weeks of life, followed by recovery in normoxia for six weeks. Alveolarization, pulmonary vascularization, pulmonary hypertension, and RV function were quantified at eight weeks. We found that hyperoxia exposure resulted in persistent alveolar and pulmonary vascular simplification. Furthermore, the Echo and cMRI studies demonstrated that hyperoxia-exposed mice had signs of PH and RV dysfunction as indicated by increased RV pressure, mass, and end-systolic and -diastolic volumes, and decreased RV stroke volume and ejection fractions. Taken together, our results demonstrate that neonatal hyperoxia exposure in mice cause cardiopulmonary morbidities that persists into adulthood and provides evidence for the use of this model to develop novel therapies for BPD infants with PH.

Edoxaban for the management of elderly Japanese patients with atrial fibrillation ineligible for standard oral anticoagulant therapies: Rationale and design of the ELDERCARE-AF study.

Edoxaban-a non-vitamin K antagonist oral anticoagulant (NOAC)- 60-mg and 30-mg once-daily dose regimens are noninferior versus well-managed warfarin for the prevention of stroke or systemic embolic events (SEE) with less major bleeding in patients with nonvalvular atrial fibrillation (NVAF). There are no published data from phase 3 clinical trials specifically evaluating the use of NOACs in elderly NVAF patients, especially those considered ineligible for available oral anticoagulants. The Edoxaban Low-Dose for EldeR CARE AF patients (ELDERCARE-AF) study is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study that will compare the safety and efficacy of once-daily edoxaban 15 mg versus placebo in Japanese patients with NVAF ≥80 years of age who are considered ineligible for standard oral anticoagulant therapy. A total of 800 patients (400 in each treatment group) are planned for randomization (1:1) to either edoxaban or placebo using a stratified randomization method with CHADS2 index score (2 points, ≥3 points) as a factor. The primary efficacy end point is the time to first onset of stroke or SEE. The net clinical outcome is the composite of stroke, SEE, major bleeding, and all-cause mortality. The primary safety end point is the incidence of major bleeding. The treatment period will continue until 65 patients with the primary efficacy events (ie, stroke or SEE) have been observed (2- to 2.5-year expected mean treatment period). The results of ELDERCARE-AF may provide clarity as to the efficacy and safety of edoxaban for the prevention of stroke or SEE in this high-risk population.

Outcomes of cardiac pacing in adult patients after a Fontan operation.

Cardiac pacing can be challenging after a Fontan operation, and limited data exist regarding pacing in adult Fontan patients. The objectives of our study were to determine risk factors for pacing and occurrence of device-related complications (DRCs) and pacemaker reinterventions.

Outcomes in elderly and young patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with bivalirudin versus heparin: Pooled analysis from the EUROMAX and HORIZONS-AMI trials.

Since older age is a strong predictor of not only bleeding but also of ischemic events, understanding the risk:benefit profile of bivalirudin in the elderly undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation (STEMI) is important. For this, we aim to compare elderly with young patients, who all underwent pPCI for STEMI and randomly received either bivalirudin or heparin.

Atrial fibrillation decision support tool: Population perspective.

Appropriate thromboprophylaxis for patients with atrial fibrillation or atrial flutter (AF) remains a national challenge. The recent availability of direct oral anticoagulants (DOACs) with comparable efficacy and improved safety compared with warfarin alters the balance between risk factors for stroke and benefit of anticoagulation. Our objective was to examine the impact of DOACs as an alternative to warfarin on the net benefit of oral anticoagulant therapy (OAT) in a real-world population of AF patients.

Contemporary rates and correlates of statin use and adherence in nondiabetic adults with cardiovascular risk factors: The KP CHAMP study.

Statin therapy is highly efficacious in the prevention of fatal and nonfatal atherosclerotic events in persons at increased cardiovascular risk. However, its long-term effectiveness in practice depends on a high level of medication adherence by patients.

International trends in clinical characteristics and oral anticoagulation treatment for patients with atrial fibrillation: Results from the GARFIELD-AF, ORBIT-AF I, and ORBIT-AF II registries.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world. We aimed to provide comprehensive data on international patterns of AF stroke prevention treatment.

Older Adults Undergoing Total Hip or Knee Arthroplasty: Chronicling Changes in Their Multimorbidity Profile in the Last Two Decades.

Despite the ubiquitous use of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in older adults, little is known about the multimorbidity (MM) profile of this patient population. This study evaluates the temporal trends of MM, hypothesizing that patients with MM have had an increasingly greater representation in THA and TKA patients over time.

Role of Carbon Monoxide in Neurovascular Repair Processing.

Carbon monoxide (CO) is a gaseous molecule produced from heme by heme oxygenase (HO). Endogenous CO production occurring at low concentrations is thought to have several useful biological roles. In mammals, especially humans, a proper neurovascular unit comprising endothelial cells, pericytes, astrocytes, microglia, and neurons is essential for the homeostasis and survival of the central nervous system (CNS). In addition, the regeneration of neurovascular systems from neural stem cells and endothelial precursor cells after CNS diseases is responsible for functional repair. This review focused on the possible role of CO/HO in the neurovascular unit in terms of neurogenesis, angiogenesis, and synaptic plasticity, ultimately leading to behavioral changes in CNS diseases. CO/HO may also enhance cellular networks among endothelial cells, pericytes, astrocytes, and neural stem cells. This review highlights the therapeutic effects of CO/HO on CNS diseases involved in neurogenesis, synaptic plasticity, and angiogenesis. Moreover, the cellular mechanisms and interactions by which CO/HO are exploited for disease prevention and their therapeutic applications in traumatic brain injury, Alzheimer's disease, and stroke are also discussed.

Bilateral early activity in the hip flexors associated with falls in stroke survivors: Preliminary evidence from laboratory-induced falls.

Falls are the most common and expensive medical complication following stroke. Hypermetric reflexes have been suggested to impact post-stroke balance but no study has evaluated reflex amplitudes under real conditions of falls in this population. Our objective was to quantify the early reflexive responses during falls induced in the laboratory.

Association between β-cell function estimated by HOMA-β and prognosis of nondiabetic patients with ischaemic stroke.

Studies showed β-cell dysfunction was associated with increased risk of cardiovascular disease and subclinical carotid atherosclerosis. This study aimed to investigate the association between β-cell function and prognosis of nondiabetic patients with ischaemic stroke.

Force coordination strategies in on-water single sculling: Are asymmetries related to better rowing performance?

Asymmetries of the rowing stroke cycle have been assessed with reference to kinematics and foot-force measures in laboratory testing environments. It remains unclear how asymmetries in propulsive kinetic measures are related to on-water rowing performance. A new approach for the evaluation of both global and local asymmetries across the entire movement was used to assess the continuous role of asymmetries and whether these change according to level of competitive representation. Twenty seven highly skilled female rowers (national and international competition level), rowing at 32 strokes per minute in a single scull boat were evaluated. A symmetry index (SI) and functional data analysis (FDA) techniques were applied to a continuous difference time-series, which described fluctuating asymmetry in propulsive pin forces for each rower. Univariate ANOVAs revealed that differences in asymmetries were present as a factor of competition level for the SI and results of FDA. International athletes were more likely to utilize an asymmetry strategy with increased stroke-side (port-side) force early in the drive phase, and increased bow-side (starboard) force through the second half of the drive. This was likely the result of international performers customizing their movement strategies relative to known boat mechanical offsets. The first half of the drive phase was also found to be an adaptive part of the rowing stroke cycle, suggesting asymmetries may have a functional role in successful execution of movements during the rowing stroke. This article is protected by copyright. All rights reserved.

Premorbid dietary intake of protein is associated with early outcomes but not with severity of ischemic stroke.

Dietary protein intake has been associated with reduced risk of stroke. This study aimed to examine the relationship between premorbid dietary intake of protein and both stroke severity and neurological outcomes in patients with acute ischemic stroke.

Free-breathing whole-heart 3D cine magnetic resonance imaging with prospective respiratory motion compensation.

To develop and validate a new prospective respiratory motion compensation algorithm for free-breathing whole-heart 3D cine steady-state free precession (SSFP) imaging.

Dominant role of microglial and macrophage innate immune responses in human ischemic infarcts.

Inflammatory mechanisms, involving granulocytes, T-cells, B-cells, macrophages and activated microglia, have been suggested to play a pathogenic role in experimental models of stroke and may be targets for therapeutic intervention. However, knowledge on the inflammatory response in human stroke lesions is limited. Here, we performed a quantitative study on the inflammatory reaction in human ischemic infarct lesions. We found increased numbers of T-lymphocytes, mainly CD8+ cells, but not of B-lymphocytes. Their number was very low in comparison to that seen in inflammatory diseases of the central nervous system and they did not show signs of activation. Polymorphonuclear leukocytes were present in meninges and less prominently in the perivascular space in early lesions, but their infiltration into the lesioned tissue was sparse with the exception of a single case. Microglia were lost in the necrotic core of fresh lesions, their number was increased in the surrounding penumbra, apparently due to proliferation. Using TMEM119 as a marker for the resident microglia pool, macrophages in lesions were in part derived from the original microglia pool, depending upon the lesion stage. Most microglia and macrophages revealed a pro-inflammatory activation pattern, expressing molecules involved in phagocytosis, oxidative injury, antigen presentation and iron metabolism and had partially lost the expression of P2RY12, an antigen expressed on homeostatic ("resting") microglia in rodents. At later lesion stages, the majority of macrophages showed intermediate activation patterns, expressing pro-inflammatory and anti-inflammatory markers. Microglia in the normal white matter of controls and stroke patients were already partly activated towards a pro-inflammatory phenotype. Our data suggest that the direct contribution of lymphocytes and granulocytes to active tissue injury in human ischemic infarct lesions is limited and that stroke therapy that targets pro-inflammatory microglia and macrophage activation may be effective. This article is protected by copyright. All rights reserved.

Middle Cerebral Artery Occlusion by an Intraluminal Suture Method.

Stroke represents the most common fatal neurological disease especially in highly developed countries. Even today, treatment options are very limited. The development of new therapeutic approaches replies, to a great extent, on experimental rodent models of focal cerebral ischemia. Since ~80% of ischemic strokes occur in the area of middle cerebral artery (MCA), a number of these stroke models are based on this artery. The intraluminal monofilament model of MCA occlusion involves the insertion of a surgical filament inside the external carotid artery and its extension into the internal carotid artery until the tip occludes the source of the MCA-thus arresting blood flow with resultant infarction in the MCA area. This technique can be utilized to model both permanent and transient occlusions. A major advantage of this technique is that it does not require craniectomy, which may affect intracranial pressure and temperature. Although the restored blood flow is unlike the pathophysiology of spontaneous human stroke, it more closely mimics the therapeutic state of mechanical thrombectomy which is increasingly being applied to patients with stroke.

CT based 3D printing is superior to transesophageal echocardiography for pre-procedure planning in left atrial appendage device closure.

Accurate assessment of the left atrial appendage (LAA) is important for pre-procedure planning when utilizing device closure for stroke reduction. Sizing is traditionally done with transesophageal echocardiography (TEE) but this is not always precise. Three-dimensional (3D) printing of the LAA may be more accurate. 24 patients underwent Watchman device (WD) implantation (71 ± 11 years, 42% female). All had complete 2-dimensional TEE. Fourteen also had cardiac computed tomography (CCT) with 3D printing to produce a latex model of the LAA for pre-procedure planning. Device implantation was unsuccessful in 2 cases (one with and one without a 3D model). The model correlated perfectly with implanted device size (R2 = 1; p < 0.001), while TEE-predicted size showed inferior correlation (R2 = 0.34; 95% CI 0.23-0.98, p = 0.03). Fisher's exact test showed the model better predicted final WD size than TEE (100 vs. 60%, p = 0.02). Use of the model was associated with reduced procedure time (70 ± 20 vs. 107 ± 53 min, p = 0.03), anesthesia time (134 ± 31 vs. 182 ± 61 min, p = 0.03), and fluoroscopy time (11 ± 4 vs. 20 ± 13 min, p = 0.02). Absence of peri-device leak was also more likely when the model was used (92 vs. 56%, p = 0.04). There were trends towards reduced trans-septal puncture to catheter removal time (50 ± 20 vs. 73 ± 36 min, p = 0.07), number of device deployments (1.3 ± 0.5 vs. 2.0 ± 1.2, p = 0.08), and number of devices used (1.3 ± 0.5 vs. 1.9 ± 0.9, p = 0.07). Patient specific models of the LAA improve precision in closure device sizing. Use of the printed model allowed rapid and intuitive location of the best landing zone for the device.

Meat intake and incidence of cardiovascular disease in Japanese patients with type 2 diabetes: analysis of the Japan Diabetes Complications Study (JDCS).

Excessive meat intake has been researched as a major cause of cardiovascular disease (CVD) among healthy adults, but data on this topic in Asian patients with diabetes are sparse. The quantity and variety of available meats vary widely between Asian and Western countries. As part of a nationwide cohort study we investigated the relationship between meat intake and incidence of CVD in Japanese patients with type 2 diabetes aged 40-70 years with HbA1c ≥ 6.5%.