Erythro-myeloid progenitors can differentiate from endothelial cells and modulate embryonic vascular remodeling

Erythro-myeloid progenitors (EMPs) were recently described to arise from the yolk sac endothelium, just prior to vascular remodeling, and are the source of adult/post-natal tissue resident macrophages. Questions remain, however, concerning whether EMPs differentiate directly from the endothelium or merely pass through. We provide the first evidence in vivo that EMPs can emerge directly from endothelial cells (ECs) and demonstrate a role for these cells in vascular development. We find that EMPs express most EC markers but late EMPs and EMP-derived cells do not take up acetylated low-density lipoprotein (AcLDL), as ECs do. When the endothelium is labelled with AcLDL before EMPs differentiate, EMPs and EMP-derived cells arise that are AcLDL+. If AcLDL is injected after the onset of EMP differentiation, however, the majority of EMP-derived cells are not double labelled. We find that cell division precedes entry of EMPs into circulation, and that blood flow facilitates the transition of EMPs from the endothelium into circulation in a nitric oxide-dependent manner. In gain-of-function studies, we inject the CSF1-Fc ligand in embryos and found that this increases the number of CSF1R+ cells, which localize to the venous plexus and significantly disrupt venous remodeling. This is the first study to definitively establish that EMPs arise from the endothelium in vivo and show a role for early myeloid cells in vascular development

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Registro Nacional do Controle da Hipertensão Arterial Avaliado pela Medida de Consultório e Residencial no Brasil: Registro LHAR

Resumo Fundamento Sabe-se que em torno de 30% dos pacientes apresentam valores de pressão arterial (PA) mais elevados quando examinados no consultório do que em suas residências. No mundo, admite-se que apenas 35% dos hipertensos já tratados tenham alcançado meta pressórica. Objetivo Fornecer dados epidemiológicos sobre o controle da PA nos consultórios, em uma amostra de cardiologistas brasileiros, avaliado pela medida de consultório e monitorização residencial da pressão arterial (MRPA). Métodos Análise transversal. Observou-se pacientes com diagnóstico de hipertensão arterial, em tratamento anti-hipertensivo, podendo ou não estar com a PA controlada. A PA foi verificada no consultório por profissional médico, e no domicílio através da MRPA. A associação entre variáveis categóricas se deu por meio do teste do qui-quadrado (p < 0,05). Resultados Foram incluídos 2.540 pacientes, com idade média 59,7 ± 15,2 anos. A maioria dos pacientes eram mulheres (62%; n = 1.575). O estudo mostrou uma prevalência de 15% (n = 382) de hipertensão do avental branco não controlada, e 10% (n = 253) de hipertensão mascarada não controlada. A taxa de controle da PA no consultório foi 56,3%, e no domicílio, de 61%; 46,4% dos pacientes tiveram PA controlada no consultório e fora dele. Observou-se maior controle no sexo feminino e na faixa etária 49-61 anos. Observando o controle domiciliar com o novo ponto de corte das Diretrizes Brasileiras de Hipertensão Arterial de 2020, a taxa de controle foi de 42,4%. Conclusão O controle pressórico nos consultórios em uma amostra de cardiologistas brasileiros foi de 56,3%; 61% quando a PA foi obtida no domicílio, e 46,4% quando o controle foi observado tanto no consultório como no domicílio

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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