Effects of Bone Marrow Mesenchymal Stem Cells on Neurological Function, Transforming Growth Factor Beta 1 and Nogo-A Expression in Stroke Rats

To investigate BMSCs’ effect on neurological function, TGF-β1 and Nogo-A expression in stroke rats. Rats were assigned into sham operation group, ischemia group (MACO rat model) and BMSCs group (BMSCs transplantation) followed by analysis of neurological function, brain pathological changes, cerebral infarction volume, TGF-β1 and Nogo-A level by Western blot. Compared with sham operation group, the score of rats was significantly elevated in ischemic group and decreased in BMSCs group (P <0.05). Compared with sham-operated group, ischemic group showed significantly increased cerebral infarction area (P <0.05) and BMSCs group had a significant decreased water level and brain infarct volume (P < 0.05). Compared with sham-operated group, ischemic group had more edema in the nerve cells with serious vacuole, uneven cytoplasm staining and reduced number of neurons, which were all significantly improved in BMSCs group. Compared to sham group, ischemic group showed significantly reduced TGF-β1 and increased Nogo-A level (P <0.05), which were all reversed in BMSCs group (P <0.05). BMSCs transplantation can significantly improve the nerve function of stroke rats, promote TGF-β1 secretion and inhibit Nogo-A expression.

Diagnostic Efficacy of CCTA And CT-FFR Based On Risk Factors For Myocardial Ischemia

Background: Coronary artery CCTA can observe the degree of coronary artery stenosis and FFR can evaluate the physiological function of coronary artery. However, noninvasive imaging examination that can both observe the above two methods at the same time has not yet been elucidated.Objective: To investigate the diagnostic efficacy of coronary computed tomography angiography (CCTA) and computed tomography-derived fractional flow reserve (CT-FFR) based on different risk factors for myocardial ischemia.Methods: Patients undergoing CCTA in our hospital from August 18, 2020 to April 28, 2021 were randomly selected, and the data were subjected to CT-FFR analysis. Vascular characteristics were measured, including total plaque volume, calcified plaque volume, non-calcified plaque volume, plaque length, and lumen stenosis, and the patients were categorized into a non-ischemia group (FFR>0.8) and an ischemia group (FFR≤0.8). Plaque characteristics were compared between the two groups, and logistic regression analysis was employed to explore the correlations between plaque characteristics and ischemic lesions.Results: From a total of 122 patients enrolled in the study, there were 218 vascular branches with FFR>0.8 and 174 vascular branches with FFR≤0.8. There were significant group differences in total plaque volume, calcified plaque volume, plaque length, and lumen stenosis >50% (n). The obtained data were as follows: non-ischemic group 10.57 (4.80, 259.65), ischemic group 14.87 (3.39, 424.45), Z=9.772, p=0.002, non-ischemic group 10.57 (0, 168.77), ischemic group 14.87 (0, 191.00), Z=2.503，p≤0.001), non-ischemic group 8.17 (37.05, 40.53), ischemic group 8.38 (56.66, 86.47), Z=5.923, p=0.016, and lumen stenosis >50%, non-ischemic group 46, ischemic group 90, x2=14.77，p≤0.001. The regression analysis results indicated that total plaque volume, calcified plaque volume, plaque length and lumen stenosis >50% were risk factors for myocardial ischemia, with ORs and p values of (2.311, p=0.002), (1.021, p=0.004), (2.159, p<0.001), and (0.181, p<0.001), respectively.Conclusion: Total plaque volume, calcified plaque volume, plaque length and lumen stenosis >50% are predictors for myocardial ischemia. Coronary artery CCTA combined with CT-FFR could simultaneously observe the anatomical stenosis and evaluate myocardial blood supply at the functional level. Thus, myocardial ischemia could be better diagnosed.

Continuous-Flow Left Ventricular Assist Device Support in Patients with Ischemic Versus Nonischemic Cardiomyopathy

To determine whether the cause of cardiomyopathy affects outcomes in patients who undergo continuous-flow left ventricular assist device support, we compared postimplant adverse events and survival between patients with ischemic and nonischemic cardiomyopathy. The inclusion criteria for the ischemic group were a history of myocardial infarction or revascularization (coronary artery bypass grafting or percutaneous coronary intervention), ≥75% stenosis of the left main or proximal left anterior descending coronary artery, or ≥75% stenosis of ≥2 epicardial vessels. From November 2003 through March 2016, 526 patients underwent device support: 256 (48.7%) in the ischemic group and 270 (51.3%) in the nonischemic group. The ischemic group was older (60.0 vs 50.0 yr), included more men than women (84.0% vs 72.6%), and had more comorbidities. More patients in the nonischemic group were able to have their devices explanted after left ventricular recovery (5.9% vs 2.0%; P=0.02). More patients in the ischemic group had gastrointestinal bleeding (31.2% vs 22.6%; P=0.03), particularly from arteriovenous malformations (20.7% vs 11.9%; P=0.006) and ulcers (16.4% vs 9.3%; P=0.01). Kaplan-Meier analysis revealed no difference in overall survival between groups (P=0.24). Older age, previous sternotomy, higher total bilirubin level, and concomitant procedures during device implantation independently predicted death (P ≤0.03), whereas cause of heart failure did not (P=0.08). Despite the similarity in overall survival between groups, ischemic cardiomyopathy was associated with more frequent gastrointestinal bleeding. This information may help guide the care of patients with ischemic cardiomyopathy who receive continuous-flow left ventricular assist device support.

Cerebrovascular Manifestations of Adult-Onset Varicella Zoster Virus Infection in the Central Nervous System: A Literature Review

Background Cerebrovascular complications after adult-onset varicella-zoster virus (VZV) infection have been increasingly recognized. The aim of this study was to analyze clinical and neuroimaging findings, treatment and outcome of these patients. Methods Systematic literature review from January 2000 to December 2019. Results We analyzed 31 articles with a total of adult-onset 34 cases, including 25 (73.53%) cases of ischemic stroke (median age 52 years), 6 of intracerebral hemorrhage (median age 70.5 years) and 3 with venous sinus thrombosis. The incidence in men was higher than in women in ischemia (72% and 28%) or venous sinus thrombosis groups (100% for men). There was median time with 42.8 days from herpes zoster infection to hospital in patients with ischemic stroke. Cognitive impairment was the most common symptoms either in the ischemic group (56%) or hemorrhagic group (83.33%). The lesions after VZV-associated cerebral infarction or hemorrhage were mutifocal and was most common in the parietal lobe. Venous sinus thrombosis was common in the transverse sinus (100%). Lesions in large vessels (48%) were common, followed by small vessels (36%) in ischemic group and multiple beaded stenosis (16.67%) were showed in hemorrhagic group by digital subtraction angiography or magnetic resonance angiography. 60.87% of the patients with antiviral treatment in the ischemic group had favorable prognosis. All patients with anticoagulant therapy in venous sinus thrombosis group improved well (100%), however, 60% of the patients with intracerebral hemorrhage had a poor prognosis or died. Conclusion We found ischemic stroke related with VZV encephalitis is common and mainly affects the middle-aged. In general, the young patients with venous sinus thrombosis improve completely, however, the old patients with intracerebral hemorrhage have poor prognosis. When the patient represents with some neurological symptoms within 2 months after VZV infection, and multiple lesions probably induced by vasculitis showed in neuroimaging, cerebral complications related with VZV infection should be considered even though the existence of some vascular risk factors for atherosclerosis.

Heart Failure Etiology in Patients Undergoing Cardiac Resynchronization Therapy: Is It Relevant?

Background: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure with reduced ejection fraction (HfrEF). Etiology may influence the outcome of patients undergoing CRT. Objective: to evaluate whether etiology (ischemic vs non-ischemic) influences the response to CRT and overall outcome. Methods: Our study included HFrEF patients undergoing CRT between January 2017-November 2019. We assessed right ventricle (RV) and left ventricle (LV) function using transthoracic echocardiography at baseline and one year after CRT. The response to CRT was defined by a decrease of more than 15% of left ventricle systolic volume. Patients were divided in two groups: ischemic and non-ischemic based on personal history. Adverse events (HF related hospitalizations and deaths) were tracked for 33± 12.8 months. Results: 52 patients undergoing CRT were included (64±13.5 years, 55.7% male, 70% non-ischemic etiology) The two groups were similar considering LV systolic baseline parameters and volumes. Ischemic etiology was associated with non-LBBB morphology on ECG (p=0.03), a more severe LV diastolic dysfunction using E/e ratio (p<0.05), and a more severe RV dysfunction using TAPSE (p=0.008) and RV fractional area change (FAC) (p<0.05). There was no significant difference in CRT response between ischemic and non-ischemic etiology. 14 (26.9%) patients had events (10 hospitalizations and 4 deaths) with a higher prevalence in the ischemic group (58.33% vs 25%, p=0.01). Univariate Cox regression analysis reported a higher risk of cardiovascular events for ischemic etiology (HR 2.4, 95% CI [0.8-8.1], p <0.05). In our cohort there was no significant difference in use of an implantable cardioverter-defibrillator in addition to CRT between ischemic and non-ischemic group (64.2% respectively 63.3%, p =0.3). Conclusion: Our study shows that ischemic and nonischemic HF patients had similar response to CRT. However, ischemic etiology was associated with a higher risk ofadverse cardiovascular events and a worse RV systolic dysfunction at baseline.

Sudden cardiac death risk stratification in patients with a preserved or mildly reduced ejection fraction: role of cardiac magnetic resonance and electrophysiological study

Funding Acknowledgements Type of funding sources: None. BACKGROUND Patients presenting with syncope of suspected arrhythmogenic origin or symptomatic documented non sustained ventricular tachycardia (NSVT) may represent a population with higher risk for sudden cardiac death (SCD). However today there are still no defined criteria to stratify the risk of SCD in this population. PURPOSE To assess the prognostic value of magnetic resonance (MRI) and electrophysiological study (EPS) in the risk stratification for SCD of patients with a preserved or mildly-reduced ejection fraction (EF) that may benefit from implantable cardiac defibrillator (ICD) therapy. METHODS We selected ischemic and non-ischemic patients with a preserved or mildly-reduced ejection fraction who came to our attention either after a probably arrhythmogenic syncopal event or a documented NSVT between 12/2018 and 09/2020. Patients with other ICD indications following current guideline-criteria were excluded (id est Brugada syndrome, Long QT and hypertrophic cardiomyopathy). All patients underwent an echocardiography, a coronary angiography, and an MRI with gadolinium, those among them with a positive LGE also underwent an induction EPS. Non inducible patients were followed-up clinically or with an implantable event-recorder, while inducible patients received an ICD. RESULTS In our observational study seventeen patients with preserved or only mildly-reduced EF were enrolled (13 males and 5 females; mean age 68 years). Among these patients, nine were identified with an underlying myocardial scar with positive Late-Gadolinium-Enhancement (LGE) in MRI. Based on the clinical orientation and the MRI LGE pattern patients were divided in ischemic group (5 patients) and non-ischemic group (4 patients). All 9 patients underwent an induction EPS. Three of them, 2 with non-ischemic and 1 with an ischemic pattern, demonstrated a reproducible inducibility of a sustained ventricular tachycardia or ventricular fibrillation and were implanted with an ICD. During our follow-up two of the three patients had an adequate shock within a year from the ICD implantation. Among the 6 patients with negative induction EPS there were no clinical events in the follow up, except one death for unknown causes. CONCLUSION Our preliminary results demonstrated that in patients with ischemic or non ischemic cardiopathy with preserved or mildly reduced EF, a positive MRI LGE pattern and the inducibility of ventricular arrhythmias during induction EPS identify a population at higher risk for clinical recurrence of ventricular arryhthmic events. Further investigation is needed to validate this combined diagnostic strategy as new SCD prevention tool.

Impact of summer heat waves on key parameters of oxidative stress in patients with coronary artery disease

Aim. To assess the impact of summer heat waves on key parameters of oxidative stress in patients with coronary heart disease. Materials and methods. We included 30 male patients aged 5213 years with stable angina pectoris of IIIII functional class with at least one coronary artery stenosis proved by angiography (ischemic group) in comparison with 10 male patients aged 487 years with no angiographic sings of significant coronary stenosis and without angina manifestation (non-ischemic group). The following parameters were studied: activity of superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), the level of malondialdehyde (MDA) and MDA-modified low-density lipoproteins (MDA-LDL). The analysis of indicators was performed at normal average daily temperature (daytime temperature not higher than 20С) and after a heat wave (daytime temperature above 27C for more than 2 consecutive days). Results. Our study revealed the decrease of CAT and GSH-Px activities with increased activity of Cu,Zn-SOD in both groups after the heat wave. At the same time we observed accumulation of MDA and increased MDA-LDL level in both groups. Initially ischemic patients showed significantly increased level of CAT and GSH-Px activity compared to the non-ischemic group, while it was no difference in activity of Cu,Zn-SOD and MDA and MDA-LDL level. We observed significant reduce of Cu,Zn-SOD activity in ischemic patients compared to non-ischemic group with no significant differences in all other studied parameters of oxidative stress after heat wave. Conclusion. Changes in the key parameters of oxidative stress in patients with ischemic heart disease during summer heat waves are comparable to those in patients without ischemia, however significantly greater inhibition of GSH-Px activity and significantly lower increase in Cu,Zn-SOD activity was noted. These results may indicate misregulation of free radical processes in patients with ischemic heart decease

Effectiveness of neutrophil/lymphocyte, lymphocyte/MPV and platelet/MPV ratios in the classification and mortality prediction of acute stroke

Objective: The aim of this study is to investigate whether Neutrophil / lymphocyte (NLR), Lymphocyte / MPV (mean platelet volume) (LMR) and thrombocyte / MPV (PMR) ratios obtained from the complete blood count, can be used as an effective marker in acute stroke for determining the prognosis and subtype of stroke. Material and methods: Patients admitted to the emergency department with acute stroke symptoms between January 1, 2020 and December 31, 2020 were evaluated retrospectively. The patients were divided into two groups as hemorrhagic or ischemic cerebrovascular disease (CVD) according to the radiological findings. NLR, LMR and PMR ratios were calculated. The last diagnosis and hospitalization information were recorded and their 28-day mortality status was evaluated. Results: A total of 764 patients were included in the study. The median age of the patients included in the study was 68 (IQR 25-75: 59-78) and 404 (52.9%) of the patients were male. In the analysis performed; it was observed that the LMR, NLR and PMR levels were significantly different in those who developed mortality on the 28th day (p = 0.009), (p = 0.002), (p = 0.026). In addition, only the NLR level was found to be significantly different in the ischemic group (p <0.001). Conclusion: We think that in cases with stroke, NLR, LMR and PMR levels can be used in predicting the prognosis of this disease. Also, NLR is significantly higher in ischemic stroke, and also significant in terms of showing that CVD type is hemorrhagic or ischemic.

Post-stroke dysphagia: frequency, risk factors, and topographic representation: hospital-based study

Background The frequency of dysphagia varies considerably across literature. Post-stroke dysphagia is a common cause of increased morbidity and length of hospitalization. This study aimed to estimate the frequency, risk factors of dysphagia following first-ever ischemic or hemorrhagic stroke and its neuroradiological correlation. Methods Two hundred fifty patients (180 ischemic and 70 hemorrhagic strokes) with first-ever stroke were recruited within 72 h of onset. Detailed history, neurological examination, and computed tomography and/or magnetic resonance were done for each patient. Severity of stroke was evaluated by the National Institutes of Health Stroke Scale (NIHSS). Swallowing function was assessed by water swallowing test (WST) and dysphagia outcome severity scale (DOSS). Results Ninety-eight (39.2%) of all stroke patients had dysphagia, 57 (31.7%) of ischemic group, 41 (58.6%) of hemorrhagic group. The mean age of ischemic group with dysphagia was older than ages of non-dysphagic and older than hemorrhagic stroke with dysphagia group. The mean total NIHSS was higher in dysphagic group than non-dysphagic group in both ischemic and hemorrhagic stroke. Dysphagia in ischemic group was highly associated with diabetes mellitus (DM), hypertension (HTN), and atrial fibrillation (AF). Dysphagia was commonly associated with middle cerebral artery (MCA), brainstem, and capsular infarctions as well as with intracerebral hemorrhage (ICH) with ventricular extension. Stroke severity and lesion size were the main determinant of dysphagia severity. Conclusions The frequency of post-stroke dysphagia is consistent with other studies. Advanced age, DM, HTN, and AF were the main risk factors. MCA, brain stem, capsular infarctions, and ICH with ventricular extension were frequently associated with dysphagia. Stroke severity and lesion size were independent predictors of dysphagia severity.

Study of Neuroprotection by a Combination of the Biological Antioxidant (Eucalyptus Extract) and the Antihypertensive Drug Candesartan against Chronic Cerebral Ischemia in Rats

Chronic cerebral ischemia with a notable long-term cessation of blood supply to the brain tissues leads to sensorimotor defects and short- and long-term memory problems. Neuroprotective agents are used in an attempt to save ischemic neurons from necrosis and apoptosis, such as the antioxidant agent Eucalyptus. Numerous studies have demonstrated the involvement of the renin-angiotensin system in the initiation and progression of cardiovascular and neurodegenerative diseases. Candesartan is a drug that acts as an angiotensin II receptor 1 blocker. We established a rat model exhibiting sensorimotor and cognitive impairments due to chronic cerebral ischemia induced by the ligation of the right common carotid artery. Wistar male rats were randomly divided into five groups: Sham group, Untreated Ligated group, Ischemic group treated with Eucalyptus (500 mg/kg), Ischemic group treated with Candesartan (0.5 mg/kg), and Ischemic group treated with a combination of Eucalyptus and Candesartan. To evaluate the sensorimotor disorders, we performed the beam balance test, the beam walking test, and the modified sticky test. Moreover, the object recognition test and the Morris water maze test were performed to assess the memory disorders of the rats. The infarct rat brain regions were subsequently stained using the triphenyltetrazolium chloride staining technique. The rats in the Sham group had normal sensorimotor and cognitive functions without the appearance of microscopic ischemic brain lesions. In parallel, the untreated Ischemic group showed severe impaired neurological functions with the presence of considerable brain infarctions. The treatment of the Ischemic group with a combination of both Eucalyptus and Candesartan was more efficient in improving the sensorimotor and cognitive deficits (p < 0.001) than the treatment with Eucalyptus or Candesartan alone (p < 0.05), by the comparison to the non-treated Ischemic group. Our study shows that the combination of Eucalyptus and Candesartan could decrease ischemic brain injury and improve neurological outcomes.