Short-term beneficial effects of human dental pulp stem cells and their secretome in a rat model of mild ischemic stroke.

Although cell therapy has been applied in regenerative medicine for decades, recent years have seen greatly increased attention being given to the use of stem cell-based derivatives such as cell-free secretome. Dental pulp stem cells (DPSCs) are widely available, easily accessible, and have high neuroprotective and angiogenic properties. In addition, DPSC-derived secretome contains a rich mixture of trophic factors. The current investigation evaluated the short-term therapeutic effects of human DPSCs and their secretome in a rat model of mild ischemic stroke. Mild ischemic stroke was induced by 30 min middle cerebral artery occlusion, and hDPSCs or their secretome was administered intra-arterially and intranasally. Neurological function, infarct size, spatial working memory, and relative expression of seven target genes in two categories of neurotrophic and angiogenic factors were assessed three days after stroke. In the short-term, all treatments reduced the severity of neurological and histological deficits caused by ischemic stroke. Moreover, transient middle cerebral artery occlusion led to the striatal and cortical over-expression of BDNF, NT-3, and angiogenin, while NGF and VEGF expression was reduced. Almost all interventions were able to modulate the expression of target genes after stroke. The obtained data revealed that single intra-arterial administration of hDPSCs or their secretome, single intranasal transplantation of hDPSCs, or repeated intranasal administration of hDPSC-derived secretome was able to ameliorate the devastating effects of a mild stroke, at least in the short-term.

Early and mid-term outcomes of carotid angioplasty and stent placement in 579 patients.

BACKGROUND AND PURPOSE: Carotid angioplasty and stenting (CAS) could be considered for preventing stroke in patients with carotid artery stenosis. This study aimed to determine the incidence and the risk factors of the early and mid-term complications associated with CAS. METHODS: This is a retrospective cohort study conducted at Shiraz University of Medical Sciences from March 2011 to March 2019. Patients at high risk and standard risk for carotid endarterectomy were included. The primary composite outcome was defined as stroke, myocardial infarction (MI), and death in the first 30 days after CAS. All-cause mortality, vascular mortality, and stroke were investigated during mid-term follow-up. RESULTS: A total of 579 patients (618 CAS) were recruited (mean age: 71.52 years). Overall, 394 (68.40%), 211 (36.63%), 179 (31.07%), and 96 (16.72%) patients had hypertension, dyslipidemia, diabetes mellitus, or were cigarette smokers, respectively. Primary composite outcomes were observed in 2.59% of patients (1.55% stroke, 0.69% MI, and 1.72% death). Atrial fibrillation was a predictor of primary composite outcome in multivariate logistic regression (p = .048). The presence of total occlusion in the contralateral carotid artery was significantly associated with the risk of stroke in univariate logistic regression (p = .041). The patients were followed for a period ranging from 1 to 83 months. The overall survival rate for all-cause mortality was 93.48% at 1 year, 77.24% at 5 years, and 52.92% at 8 years. All-cause mortality was significantly higher among patients with symptomatic carotid stenosis (p = .014). CONCLUSION: CAS provides acceptable short-term and mid-term outcomes in a unique population of high- and standard-surgical-risk, symptomatic and asymptomatic, octogenarian, and nonoctogenarian patients.

The Hospitalization Rate of Cerebral Venous Sinus Thrombosis before and during COVID-19 Pandemic Era: A Single-Center Retrospective Cohort Study.

OBJECTIVES: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). MATERIALS AND METHODS: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. RESULTS: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients > 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P<0.001), malignancy (P = 0.041) and COVID-19 infection (P = 0.008) in COVID-19 period. CONCLUSION: Since there was a more dismal outcome in COVID-19 associated CVST, a high index of suspicion for CVST among COVID-19 positive is recommended.

Safety and efficacy of remote ischemic preconditioning in patients with severe carotid artery stenosis before carotid artery stenting: A proof-of-concept, randomized controlled trial.

Background: Remote ischemic preconditioning (RIPC) has been proposed as a possible potential treatment for ischemic stroke. This study aimed to investigate the frequency of micro-embolic brain infarcts after RIPC in patients with stroke who underwent elective carotid artery stenting (CAS) treatment. Methods: This study was managed at Shiraz University of Medical Sciences in southwest Iran. Patients undergoing CAS were randomly allocated into RIPC and control groups. Patients in the RIPC group received three intermittent cycles of 5-minute arm ischemia followed by reperfusion using manual blood cuff inflation/deflation less than 30 minutes before CAS treatment. Afterward, stenting surgery was conducted. Magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC), was acquired within the first 24 hours after CAS. Results: Seventy-four patients were recruited (79.7% men, age: 72.30 ± 8.57). Both groups of RIPC and control had no significant difference in baseline parameters (P > 0.05). Fifteen patients (40.5%) in the RIPC group and 19 (54.1%) patients in the control group developed restricted lesions in DWI MRI. In DWI+ patients, there were no significant differences according to the number of lesions, lesion surface area, largest lesion diameter, cortical infarcts percent, and ipsilateral and bilateral infarcts between the two groups. Conclusion: Although RIPC is a safe and non-invasive modality before CAS to decrease infarcts, this study did not show the advantage of RIPC in the prevention of infarcts following CAS. It may be because of the small sample size.

The Association Between Inflammatory Biomarkers and Vitamin D Level With the Evolution and Severity of Stroke.

Introduction: Vitamin D deficiency has been linked to the evolution of ischemic stroke, but the data regarding the association between stroke severity and vitamin D level is scarce. Methods: Patients with first-ever ischemic stroke in the middle cerebral artery territory, within seven days after the stroke, were recruited. The control group included age- and gender-matched individuals. We compared 25-OH vitamin D (vitamin D), high sensitive C-reactive protein (hsCRP), serum amyloid A (SAA), and osteopontin levels between stroke patients and the control group. The association between stroke severity according to the National Institutes of Health Stroke Scale (NIHSS) and the Alberta stroke program early CT score (ASPECTS) and levels of vitamin D and inflammatory biomarkers were also studied. Results: There was an association between hypertension (P=0.035), diabetes mellitus (P=0.043), smoking (P=0.016), history of ischemic heart disease (P=0.002), higher SAA (P<0.001), higher hsCRP (P<0.001), and lower vitamin D levels (P=0.002) and stroke evolution in a case-control study. Meanwhile, in stroke patients, its severity was associated with higher SAA (P=0.04) and hsCRP (P=0.001), and lower vitamin D levels (P=0.043) according to clinical scale (higher admission NIHSS). According to the ASPECT score, higher SAA (P=0.017) and hsCRP (P=0.007), but not lower vitamin D levels, were associated with more infarct areas (P=0.149). Conclusion: Vitamin D may play a role in both the evolution and severity of stroke.