Assessing the effects of Ang-(1-7) therapy following transient middle cerebral artery occlusion

The counter-regulatory axis, Angiotensin Converting Enzyme 2, Angiotensin-(1-7), Mas receptor (ACE2/Ang-1-7/MasR), of the renin angiotensin system (RAS) is a potential therapeutic target in stroke, with Ang-(1-7) reported to have neuroprotective effects in pre-clinical stroke models. Here, an extensive investigation of the functional and mechanistic effects of Ang-(1-7) was performed in a rodent model of stroke. Using longitudinal magnetic resonance imaging (MRI) it was observed that central administration of Ang-(1-7) following transient middle cerebral artery occlusion (MCAO) increased the amount of tissue salvage compared to reperfusion alone. This protective effect was not due to early changes in blood brain barrier (BBB) permeability, microglia activation or inflammatory gene expression. However, increases in NADPH oxidase 1 (Nox1) mRNA expression were observed in the treatment group compared to control. In order to determine whether Ang-(1-7) has direct cerebrovascular effects, laser speckle contrast imaging (LSCI) was performed to measure dynamic changes in cortical perfusion following reperfusion. Delivery of Ang-(1-7) did not have any effect on cortical perfusion following reperfusion however; it showed an indication to prevent the ‘steal phenomenon’ within the contralateral hemisphere. The comprehensive series of studies have demonstrated a moderate protective effect of Ang-(1-7) when given alongside reperfusion to increase tissue salvage

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke

MRI Radiomic Signature of White Matter Hyperintensities Is Associated With Clinical Phenotypes

Objective: Neuroimaging measurements of brain structural integrity are thought to be surrogates for brain health, but precise assessments require dedicated advanced image acquisitions. By means of quantitatively describing conventional images, radiomic analyses hold potential for evaluating brain health. We sought to: (1) evaluate radiomics to assess brain structural integrity by predicting white matter hyperintensities burdens (WMH) and (2) uncover associations between predictive radiomic features and clinical phenotypes. Methods: We analyzed a multi-site cohort of 4,163 acute ischemic strokes (AIS) patients with T2-FLAIR MR images with total brain and WMH segmentations. Radiomic features were extracted from normal-appearing brain tissue (brain mask–WMH mask). Radiomics-based prediction of personalized WMH burden was done using ElasticNet linear regression. We built a radiomic signature of WMH with stable selected features predictive of WMH burden and then related this signature to clinical variables using canonical correlation analysis (CCA). Results: Radiomic features were predictive of WMH burden (R2 = 0.855 ± 0.011). Seven pairs of canonical variates (CV) significantly correlated the radiomics signature of WMH and clinical traits with respective canonical correlations of 0.81, 0.65, 0.42, 0.24, 0.20, 0.15, and 0.15 (FDR-corrected p-valuesCV1–6 < 0.001, p-valueCV7 = 0.012). The clinical CV1 was mainly influenced by age, CV2 by sex, CV3 by history of smoking and diabetes, CV4 by hypertension, CV5 by atrial fibrillation (AF) and diabetes, CV6 by coronary artery disease (CAD), and CV7 by CAD and diabetes. Conclusion: Radiomics extracted from T2-FLAIR images of AIS patients capture microstructural damage of the cerebral parenchyma and correlate with clinical phenotypes, suggesting different radiographical textural abnormalities per cardiovascular risk profile. Further research could evaluate radiomics to predict the progression of WMH and for the follow-up of stroke patients’ brain health

Excessive White Matter Hyperintensity Increases Susceptibility to Poor Functional Outcomes After Acute Ischemic Stroke.

Objective: To personalize the prognostication of post-stroke outcome using MRI-detected cerebrovascular pathology, we sought to investigate the association between the excessive white matter hyperintensity (WMH) burden unaccounted for by the traditional stroke risk profile of individual patients and their long-term functional outcomes after a stroke. Methods: We included 890 patients who survived after an acute ischemic stroke from the MRI-Genetics Interface Exploration (MRI-GENIE) study, for whom data on vascular risk factors (VRFs), including age, sex, atrial fibrillation, diabetes mellitus, hypertension, coronary artery disease, smoking, prior stroke history, as well as acute stroke severity, 3- to−6-month modified Rankin Scale score (mRS), WMH, and brain volumes, were available. We defined the unaccounted WMH (uWMH) burden via modeling of expected WMH burden based on the VRF profile of each individual patient. The association of uWMH and mRS score was analyzed by linear regression analysis. The odds ratios of patients who achieved full functional independence (mRS < 2) in between trichotomized uWMH burden groups were calculated by pair-wise comparisons. Results: The expected WMH volume was estimated with respect to known VRFs. The uWMH burden was associated with a long-term functional outcome (β = 0.104, p < 0.01). Excessive uWMH burden significantly reduced the odds of achieving full functional independence after a stroke compared to the low and average uWMH burden [OR = 0.4, 95% CI: (0.25, 0.63), p < 0.01 and OR = 0.61, 95% CI: (0.42, 0.87), p < 0.01, respectively]. Conclusion: The excessive amount of uWMH burden unaccounted for by the traditional VRF profile was associated with worse post-stroke functional outcomes. Further studies are needed to evaluate a lifetime brain injury reflected in WMH unrelated to the VRF profile of a patient as an important factor for stroke recovery and a plausible indicator of brain health

Sex-specific lesion pattern of functional outcomes after stroke.

Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level

The Impact of COVID-19 Pandemic Lockdown on Emergency Department Visits in a Tertiary Hospital

Bisheng Shen,1 Baoxin Chen,2 Kuangyi Li,1 Weiyin Cheng,3 Mohammad Mofatteh,4 Robert W Regenhardt,5 Jack Wellington,6 Zhangrong Liang,1 Qi Tang,1 Jingli Chen,1 Yimin Chen7 1Department of Emergency Medicine, Foshan Hospital of Traditional Chinese Medicine, Foshan City, Guangdong Province, People’s Republic of China; 2Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, People’s Republic of China; 3Department of Clinical Nutrition, Foshan Hospital of Traditional Chinese Medicine, Foshan City, People’s Republic of China; 4School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK; 5Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 6School of Medicine, Cardiff University, Cardiff, Wales, UK; 7Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of ChinaCorrespondence: Baoxin Chen, Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, People’s Republic of China, Email [email protected] Kuangyi Li, Department of Emergency Medicine, Foshan Hospital of Traditional Chinese Medicine, Foshan City, Guangdong Province, People’s Republic of China, Email [email protected]: This study aimed to highlight the impact of the COVID-19 pandemic lockdown on emergency department (ED) visits of non-COVID-19 patients in a tertiary hospital and evaluate protocol development during this period.Patients and Methods: Clinical data of patients who visited the ED of Foshan Hospital of Traditional Chinese Medicine during the first-level response in Foshan, Guangdong province in 2020 (from January 23 to February 24) and the same period in 2019 and 2021 were collected. A retrospective cross-sectional analysis was performed to understand the characteristics of critically ill patients and compare the proportion of hospitalizations, deaths, and emergency ambulance calls (EACs).Results: The number of patients presenting to the ED was significantly decreased, with a 37.75% reduction in 2020 (6196) compared to the same period in 2019 (9954). A rise in patient ED presentations was observed in the same period in 2021 (10,503). This decline was mostly in the 15– 45 age group. In 2019, 2020, and 2021, critically ill patients treated by the ED totaled 568 (5.706%), 339 (5.495%), and 590 (5.617%), respectively. Compared to the same period in 2019 and 2021, the proportion of critically ill patients with respiratory system involvement, severe trauma, and poisoning decreased most significantly in 2020 (P< 0.05). In contrast, the rates of EACs, hospitalizations, and deaths increased significantly (P< 0.05).Conclusion: The number of ED visits to hospitals was decreased during the 2020 lockdown, while the rates of EACs, hospitalizations, and deaths increased significantly though there were no documented COVID-19 cases. Optimizing emergency medical resources and ensuring the safety of healthcare providers and patients were essential to provide efficient emergency diagnosis and treatment during the lockdown.Keywords: COVID-19 pandemic, emergency medicine, coping strategies, emergency visit, non-COVID-19 patient