Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy can be caused by deficiency of either vitamin B12 or folate. Hyperhomocysteinemia (HHcy) can be responsible of different systemic and neurological disease. Actually, HHcy has been considered as a risk factor for systemic atherosclerosis and cardiovascular disease (CVD) and HHcy has been reported in many neurologic disorders including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. HHcy is typically defined as levels >15 micromol/L. Treatment of hyperhomocysteinemia with folic acid and B vitamins seems to be effective in the prevention of the development of atherosclerosis, CVD, and strokes. However, data from literature show controversial results regarding the significance of homocysteine as a risk factor for CVD and stroke and whether patients should be routinely screened for homocysteine. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum (ER) stress have been considered to play an important role in the pathogenesis of several diseases including atherosclerosis and stroke. The aim of our research is to review the possible role of HHcy in neurodegenerative disease and stroke and to understand its pathogenesis.

Background:The COVID-19 pandemics required several changes in stroke management and it may have influenced some clinical or functional characteristics. We aimed to evaluate the effects of the COVID-19 pandemics on stroke management during the first month of Italy lockdown. In addition, we described the emergency structured pathway adopted by an Italian University Hub Stroke Unit in the cross-border Italy-Slovenia area. Methods: We analyzed admitted patients' clinical features and outcomes between 9th March 2020 and 9th April 2020 (first month of lockdown), and compared them with patients admitted during the same period in 2019. Results: Total admissions experienced a reduction of 45% during the lockdown compared to the same period in 2019 (16 vs 29, respectively), as well as a higher prevalence of severe stroke (NIHSS > 10) at admission (n = 8, 50% vs n = 8, 28%). A dramatic prevalence of stroke of unknown symptom onset was observed in 2020 (n = 8, 50% vs n = 3, 10%). During lockdown, worse functional and independence outcomes were found, despite the similar proportion of reperfused patients. Similar 'symptoms alert-to-admission' and 'door-to-treatment' times were observed. During lockdown hospitalization was shorter and fewer patients completed the stroke work-up. Conclusion:In conclusion, the adopted strategies for stroke management during the COVID-19 emergency have suggested being effective, while suffering a reduced and delayed reporting of symptoms. Therefore, we recommend raising awareness among the population against possible stroke symptoms onset. Thus, think F.A.S.T. and do not stay-at-home at all costs.

Background A meta-analysis is presented of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) versus placebo on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods We did an electronic search up to June 30, 2021, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). We included data from 8 CVOTs and 60,080 patients (72.4% with established cardiovascular disease). Results GLP-1RA reduced major cardiovascular events (MACE) by 14% (HR = 0.86, 95% CI 0.79–0.94, P = 0.006) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (P = 0.127). GLP-1RA also reduced the risk of cardiovascular death by 13% (P = 0.016), nonfatal stroke by 16% (P = 0.007), hospitalization for heart failure by 10% (P = 0.023), all-cause mortality by 12% (P = 0.012), and the broad composite kidney outcome by 17% (P = 0.012), which was driven by a reduction in macroalbuminuria only (HR = 0.74, 0.67–0.82, P < 0.001). Conclusions GLP-1RA have moderate benefits on MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also have robust benefits on reducing the incidence of macroalbuminuria.

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Background Small vessels have the pivotal role for the brain’s autoregulation. The arteriosclerosis-dependent alteration of the brain perfusion is one of the major determinants in small vessel disease. Endothelium distress can potentiate the flow dysregulation and lead to subcortical vascular dementia (sVAD). sVAD increases morbidity and disability. Epidemiological studies have shown that sVAD shares with cerebrovascular disease most of the common risk factors. The molecular basis of this pathology remains controversial. Purpose To detect the possible mechanisms between small vessel disease and sVAD, giving a broad vision on the topic, including pathological aspects, clinical and laboratory findings, metabolic process and cholinergic dysfunction. Methods We searched MEDLINE using different search terms (“vascular dementia”, “subcortical vascular dementia”, “small vessel disease”, “cholinergic afferents”, etc). Publications were selected from the past 20 years. Searches were extended to Embase, Cochrane Library, and LILIACS databases. All searches were done from January 1, 1998 up to January 31, 2018. Results A total of 560 studies showed up, and appropriate studies were included. Associations between traditional vascular risk factors have been isolated. We remarked that SVD and white matter abnormalities are seen frequently with aging and also that vascular and endothelium changes are related with age; the changes can be accelerated by different vascular risk factors. Vascular function changes can be heavily influenced by genetic and epigenetic factors. Conclusion Small vessel disease and the related dementia are two pathologies that deserve attention for their relevance and impact in clinical practice. Hypertension might be a historical problem for SVD and SVAD, but low pressure might be even more dangerous; CBF regional selective decrease seems to be a critical factor for small vessel disease-related dementia. In those patients, endothelium damage is a super-imposed condition. Several issues are still debatable, and more research is needed.