- Central Noradrenergic Agonists in the Treatment of Ischemic Stroke-an Overview. [Review]
- TSTransl Stroke Res 2019 Jul 20
- Ischemic stroke is the leading cause of morbidity and mortality with a significant health burden worldwide and few treatment options. Among the short- and long-term effects of ischemic stroke is the …
Ischemic stroke is the leading cause of morbidity and mortality with a significant health burden worldwide and few treatment options. Among the short- and long-term effects of ischemic stroke is the cardiovascular sympathetic autonomic dysfunction, presented in part as the by-product of the ischemic damage to the noradrenergic centers of the brain. Unlike high levels in the plasma, the brain may face suboptimal levels of norepinephrine (NE), with adverse effects on the clinical and functional outcomes of ischemic stroke. The intravenous administration of NE and other sympathomimetic agents, in an attempt to increase cerebral perfusion pressure, often aggravates the ischemia-induced rise in blood pressure (BP) with life-threatening consequences for stroke patients, the majority of whom present with hypertension at the time of admission. Unlike the systemic administration, the central administration of NE reduces BP while exerting anti-inflammatory and neuroprotective effects. These characteristics of centrally administered NE, combined with the short latency of response, make it an ideal candidate for use in the acute phase of stroke, followed by the use of centrally acting noradrenergic agonists, such as NE reuptake inhibitors and B2-adrenergic receptor agonists for stroke rehabilitation. In addition, a number of nonpharmacological strategies, such as transcutaneous vagus nerve stimulation (tVNS) and trigeminal nerve stimulation (TNS), have the potential to enhance the central noradrenergic functional activities and improve stroke clinical outcomes. Many factors could influence the efficacy of the noradrenergic treatment in stroke patients. These factors include the type of the noradrenergic agent; the dose, frequency, and duration of administration; the timing of administration in relation to the acute event; and the site and characteristics of the ischemic lesions. Having this knowledge, combined with the better understanding of the regulation of noradrenergic receptors in different parts of the brain, would pave the path for the successful use of the centrally acting noradrenergic agents in the management of ischemic stroke.
- Human intracerebroventricular (ICV) injection of autologous, non-engineered, adipose-derived stromal vascular fraction (ADSVF) for neurodegenerative disorders: results of a 3-year phase 1 study of 113 injections in 31 patients. [Journal Article]
- MBMol Biol Rep 2019 Jul 20
- We have chosen to test the safety of human intracerebroventricular (ICV) brain injections of autologous non-genetically-modified adipose-derived stromal vascular fraction (ADSVF). In this IRB-approve…
We have chosen to test the safety of human intracerebroventricular (ICV) brain injections of autologous non-genetically-modified adipose-derived stromal vascular fraction (ADSVF). In this IRB-approved trial, 24 patients received ICV ADSVF via an implanted reservoir between 5/22/14 and 5/22/17. Seven others were injected via their ventriculo-peritoneal shunts. Ten patients had Alzheimer's disease (AD), 6 had amyotrophic lateral sclerosis (ALS), 6 had progressive multiple sclerosis (MS-P), 6 had Parkinson's "Plus" (PD+), 1 had spinal cord injury, 1 had traumatic brain injury, and 1 had stroke. Median age was 74 (range 41-83). Injections were planned every 2-3 months. Thirty-one patients had 113 injections. Patients received SVF injection volumes of 3.5-20 cc (median:4 cc) containing 4.05 × 105 to 6.2 × 107 cells/cc, which contained an average of 8% hematopoietic and 7.5% adipose stem cells. Follow-up ranged from 0 to 36 months (median: 9.2 months). MRIs post injection(s) were unchanged, except for one AD patient whose hippocampal volume increased from < 5th percentile to 48th percentile (NeuroQuant® volumetric MRI). Of the 10 AD patients, 8 were stable or improved in tests of cognition. Two showed improvement in P-tau and β-amyloid levels. Of the 6 MS-P patients all are stable or improved. Four of 6 ALS patients died of disease progression. Twelve of 111 injections (11%) led to 1-4 days of transient meningismus, and mild temperature elevation, which resolved with acetaminophen and/or dexamethasone. Two (1.8% of injections) required hospitalization for these symptoms. One patient (0.9% of injections) had his reservoir removed and later replaced for presumed infection. In this Phase 1 safety trial, ADSVF was safely injected into the human brain ventricular system in patients with no other treatment options. Secondary endpoints of clinical improvement or stability were particularly promising in the AD and MS-P groups. These results will be submitted for a Phase 2 FDA-approved trial.
- Aspiration in the Fiberoptic Endoscopic Evaluation of Swallowing Associated with an Increased Risk of Mortality in a Cohort of Patients Suspected of Oropharyngeal Dysphagia. [Journal Article]
- DDysphagia 2019 Jul 20
- There is a general lack of published studies on the risk of mortality due to alterations in the safety of swallowing detected during the fiberoptic endoscopic evaluation of swallowing (FEES). We aime…
There is a general lack of published studies on the risk of mortality due to alterations in the safety of swallowing detected during the fiberoptic endoscopic evaluation of swallowing (FEES). We aimed at assessing the risk of mortality of the detection of aspiration, penetration, and pharyngeal residues by FEES. A cohort of consecutively evaluated patients suspected of experiencing oropharyngeal dysphagia undergoing FEES at a tertiary care university hospital were prospectively followed up on to assess mortality. The FEES findings, comorbidities, and potential confounders were studied as predictors of death using a Cox multivariate regression analysis. A total of 148 patients were included, 85 of whom were male (57.4%). The mean age (± standard deviation) was 52.7 years (± 22.1). The median of the follow-up time was 4.5 years. The most frequent conditions were stroke in 50 patients (33.8%), brain and spine traumas in 27 (18.2%), and neurodegenerative diseases in 19 (12.8%). Variables associated with mortality in bivariate analyses were age > 65 years (p < 0.001), pneumonia (p = 0.046), aspiration of any consistency (p < 0.001), and pharyngeal residues (p = 0.017). Variables independently associated with mortality in the Cox multivariate model were age (> 65 years) [adjusted hazard ratio (HR) 5.76; 95% CI 2.72 to 17.19; p = 0.001] and aspiration (adjusted HR: 3.96; 95% CI 1.82 to 14.64; p = 0.003). Aspiration detected by FEES and an age > 65 years are independent predictors of mortality in patients with oropharyngeal dysphagia.
- Genetic and lifestyle predictors of ischemic stroke severity and outcome. [Journal Article]
- NSNeurol Sci 2019 Jul 20
- CONCLUSIONS: APOA5 genotype (TC + CC), age, and obesity could be used as prognostic risk factors for a very severe stroke (NIHSS ≥ 21).
- The impact of aortic valve replacement on survival in patients with normal flow low gradient severe aortic stenosis: a propensity-matched comparison. [Journal Article]
- EHEur Heart J Cardiovasc Imaging 2019 Jul 21
- CONCLUSIONS: In patients with normal flow low gradient severe AS, AVR was associated with a significantly improved survival compared with those who received standard medical treatment.
- Evgeny Chazov: first thrombolysis for ischaemic stroke. [Journal Article]
- EHEur Heart J 2019 Jul 21; 40(28):2281-2283
- Valvular heart disease and calcification in CKD: more common than appreciated. [Journal Article]
- NDNephrol Dial Transplant 2019 Jul 21
- Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calc…
Ischaemic heart disease, sudden cardiac death and arrhythmias, heart failure, stroke and peripheral arterial disease make up >50% of the causes of death in advanced chronic kidney disease (CKD). Calcification of the vascular tree and heart valves is partially related to these complications and has received growing attention in the literature. However, the main focus of research has been on the pathophysiology and consequences of vascular calcification, with less attention being paid to valvular calcification (VC) and its impact on the survival of CKD patients. Although VC has long been seen as an age-related degenerative disorder with minimal functional impact, several studies proved that it carries an increased risk of death and clinical consequences different from those of vascular calcification. In dialysis patients, the annual incidence of aortic valve calcification is nearly 3.3% and the reported prevalence of aortic and mitral VC varies between 25% and 59%. Moreover, calcification of both valves occurs 10-20 years earlier in CKD patients compared with the general population. Therefore, the purpose of this review is to summarize the current knowledge on the pathophysiology and relevance of VC in CKD patients, and to highlight specific clinical consequences and potential therapeutic implications.
- Less invasive left ventricular assist device implantation may reduce right ventricular failure. [Journal Article]
- ICInteract Cardiovasc Thorac Surg 2019 Jul 21
- CONCLUSIONS: In this cohort, less invasive LVAD implantation appears to be associated with reduced postoperative RV failure, and equivalent or improved survival compared to conventional LVAD implantation.
- Changes in conventional cardiovascular risk factors and the estimated 10-year risk of acute myocardial infarction or cerebral stroke in Sami and non-Sami populations in two population-based cross-sectional surveys: the SAMINOR Study. [Journal Article]
- BOBMJ Open 2019 Jul 19; 9(7):e028939
- CONCLUSIONS: Independent of ethnicity, there was a decline in mean cholesterol, blood pressure, smoking, hypertension (women only) and 10-year risk of AMI or CS, but waist circumference increased. Relatively minor ethnic differences were found in changes of cardiovascular risk factors.
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- Rehabilitation for balance impairment in patients after stroke: a protocol of a systematic review and network meta-analysis. [Journal Article]
- BOBMJ Open 2019 Jul 19; 9(7):e026844
- Multiple rehabilitation therapies have been reported to be effective for poststroke balance impairment. However, the comparative effectiveness of these rehabilitation therapies is still unclear. Ther…
Multiple rehabilitation therapies have been reported to be effective for poststroke balance impairment. However, the comparative effectiveness of these rehabilitation therapies is still unclear. Therefore, the aim of this study is to summarise evidence and identify the most effective rehabilitation therapy for poststroke balance impairment.