Clinical implications of microvascular obstruction and intramyocardial haemorrhage in acute myocardial infarction using cardiovascular magnetic resonance imaging

OBJECTIVES: To investigate the clinical implications of microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) in acute myocardial infarction (AMI). METHODS: Ninety patients with a first AMI undergoing primary percutaneous coronary intervention (PCI) were studied. T2-weighted, cine and late gadolinium-enhanced cardiovascular magnetic resonance imaging was performed at 5 ± 2 and 103 ± 11 days. Patients were categorised into three groups based on the presence or absence of MVO and IMH. RESULTS: MVO was observed in 54% and IMH in 43% of patients, and correlated significantly (r = 0.8, p < 0.001). Pre-PCI thrombolysis in myocardial infarction 3 flow was only observed in MVO(−)/IMH(−) patients. Infarct size and impairment of systolic function were largest in MVO(+)/IMH(+) patients (n = 39, 23 ± 9% and 47 ± 7%), smallest in MVO(−)/IMH(−) patients (n = 41, 8 ± 8% and 55 ± 8%) and intermediate in MVO(+)/IMH(−) patients (n = 10, 16 ± 7% and 51 ± 6%, p < 0.001). LVEF increased in all three subgroups at follow-up, but remained intermediate in MVO(+)/IMH(−) and was lowest in MVO(+)/IMH(+) patients. Using random intercept model analysis, only infarct size was an independent predictor for adverse LV remodelling. CONCLUSIONS: Intramyocardial haemorrhage and microvascular obstruction are strongly related. Pre-PCI TIMI 3 flow is less frequently observed in patients with MVO and IMH. Only infarct size was an independent predictor of LV remodelling

Maior mortalidade durante a pandemia de COVID-19 em áreas socialmente vulneráveis em Belo Horizonte: implicações para priorização da vacinação

Objective: To assess mortality during the COVID-19 pandemic according to social vulnerability by areas of Belo Horizonte (BH), aiming at strategies for vaccination. Methods: Ecological study with mortality analysis, according to census tracts classified by the Health Vulnerability Index, a composite indicator that includes socioeconomic and sanitation variables. Deaths due to natural causes and COVID-19 were obtained from the “Mortality Information System”, between the 10th and 43rd epidemiological weeks (EW) of 2020. Excess mortality was calculated by a time series model, considering observed deaths by EW, between 2015 and 2019, for census tracts. Mortality rates (MR) were calculated and age-standardized =using population estimates from 2010 census. Results: Excess mortality in BH was 16.1% (n =1524): 11.0%, 18.8% and 17.3% in the low, intermediate and high vulnerability areas, respectively. The differences between observed and expected age-standardized MR by natural causes were equal to 59/100,000 inhabitants in BH, increasing from 31 to 77 and 95/100,000 inhabitants, in the areas of low, intermediate and high vulnerability, respectively. There was an aging gradient in COVID-19 MR, ranging from 4 to 611/100,000 inhabitants among individuals of 20-39 years and 75+ years. The COVID-19 MR per 100,000 elderly (60+ years) was 292 in BH, increasing from 179 to 354 and 476, in the low, intermediate and high vulnerability areas, respectively. Conclusion: Inequalities in mortality, particularly among the elderly, combined with the limited supply of doses, demonstrate the importance of prioritizing socially vulnerable areas during vaccination against COVID-19.Objetivo: Avaliar a mortalidade por áreas de Belo Horizonte (BH) durante a pandemia de COVID-19 conforme vulnerabilidade social, visando estratégia de vacinação. Métodos: Estudo ecológico com análise de mortalidade, segundo setores censitários classificados pelo Índice de Vulnerabilidade da Saúde, composto por indicadores de saneamento e socioeconômicos. Óbitos por causas naturais e COVID-19 foram obtidos do Sistema de Informação sobre Mortalidade, entre a 10ª e 43ª semana epidemiológica (SE) de 2020. Calculou-se o excesso de mortalidade por modelo de série temporal, considerando as mortes observadas por SE, entre 2015 e 2019, por setor censitário. Taxas de mortalidade (TM) foram calculadas e padronizadas por idade a partir de estimativas populacionais do IBGE. Resultados: Houve 16,1% (n=1524) de excesso de mortalidade em BH: 11,0%, 18,8% e 17,3% nas áreas de baixa, média e elevada vulnerabilidade, respectivamente. As diferenças entre TM observadas e esperadas por causas naturais, padronizadas por idade, foi igual a 59/100.000 habitantes em BH, aumentando de 31 para 77 e 95/100.000, nas áreas de baixa, média e elevada vulnerabilidade, respectivamente. Houve gradiente de aumento com a idade nas TM por COVID-19, variando de 4 a 611/100.000 habitantes entre as idades de 20-39 anos e 75+ anos. A TM por COVID-19 por 100.000 idosos (60+ anos) foi igual a 292, aumentando de 179 para 354 e 476, nos setores de baixa, média e elevada vulnerabilidade, respectivamente. Conclusão: Desigualdades na mortalidade, mesmo entre idosos, aliadas à baixa oferta de doses, demonstram importância de priorizar áreas socialmente vulneráveis durante a vacinação contra COVID-19

Mesenchymal Stem Cells Induce T-Cell Tolerance and Protect the Preterm Brain after Global Hypoxia-Ischemia

Hypoxic-ischemic encephalopathy (HIE) in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of this study was to assess the neuroprotective and anti-inflammatory effects of intravenously delivered mesenchymal stem cells (MSC) in an ovine model of HIE. In this translational animal model, global hypoxia-ischemia (HI) was induced in instrumented preterm sheep by transient umbilical cord occlusion, which closely mimics the clinical insult. Intravenous administration of 2 x 106MSC/kg reduced microglial proliferation, diminished loss of oligodendrocytes and reduced demyelination, as determined by histology and Diffusion Tensor Imaging (DTI), in the preterm brain after global HI. These anti-inflammatory and neuroprotective effects of MSC were paralleled by reduced electrographic seizure activity in the ischemic preterm brain. Furthermore, we showed that MSC induced persistent peripheral T-cell tolerance in vivo and reduced invasion of T-cells into the preterm brain following global HI. These findings show in a preclinical animal model that intravenously administered MSC reduced cerebral inflammation, protected against white matter injury and established functional improvement in the preterm brain following global HI. Moreover, we provide evidence that induction of T-cell tolerance by MSC might play an important role in the neuroprotective effects of MSC in HIE. This is the first study to describe a marked neuroprotective effect of MSC in a translational animal model of HIE

Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists. METHODS: GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugar-sweetened beverages). FINDINGS: In 2016, the global number of individuals who lived with dementia was 43·8 million (95% uncertainty interval [UI] 37·8-51·0), increased from 20.2 million (17·4-23·5) in 1990. This increase of 117% (95% UI 114-121) contrasted with a minor increase in age-standardised prevalence of 1·7% (1·0-2·4), from 701 cases (95% UI 602-815) per 100 000 population in 1990 to 712 cases (614-828) per 100 000 population in 2016. More women than men had dementia in 2016 (27·0 million, 95% UI 23·3-31·4, vs 16.8 million, 14.4-19.6), and dementia was the fifth leading cause of death globally, accounting for 2·4 million (95% UI 2·1-2·8) deaths. Overall, 28·8 million (95% UI 24·5-34·0) DALYs were attributed to dementia; 6·4 million (95% UI 3·4-10·5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages. INTERPRETATION: The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide