No abstract

Semi-automated detection of the LV endocardial surface from RT3DE data is suitable for clinical use because it allows rapid, accurate, and reproducible measurements of LV volumes, superior to conventional 2DE methods.

IMPORTANCEAcutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. OBJECTIVE To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm 3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m 2 .INTERVENTIONS Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. MAIN OUTCOMES AND MEASURESThe primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. RESULTSOn June 18, 2021, the trial data and safety monitoring board recommended early terminationbecauseoflowerthananticipatedeventrates;atthattime,657symptomaticoutpatients with COVID-19 had been randomized (median age, 54 years [IQR,[46][47][48][49][50][51][52][53][54][55][56][57][58][59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar.CONCLUSIONS AND RELEV...

Over the past several decades, there have been substantial advances in our knowledge of the pathophysiology of stroke. Understanding the benefits of timely reperfusion has led to the development of thrombolytic therapy as the cornerstone of current management of ischemic stroke, but there remains much to be learned about mechanisms of neuronal ischemic and reperfusion injury and associated inflammation. For ischemic stroke, novel therapeutic targets have continued to remain elusive. When considering modern molecular biologic techniques, advanced translational stroke models, and clinical studies, a consistent pattern emerges, implicating perturbation of the immune equilibrium by stroke in both central nervous system injury and repair responses. Stroke triggers activation of the neuroimmune axis, comprised of multiple cellular constituents of the immune system resident within the parenchyma of the brain, leptomeninges, and vascular beds, as well as through secretion of biological response modifiers and recruitment of immune effector cells. This neuroimmune activation can directly impact the initiation, propagation, and resolution phases of ischemic brain injury. In order to leverage a potential opportunity to modulate local and systemic immune responses to favorably affect the stroke disease curve, it is necessary to expand our mechanistic understanding of the neuroimmune axis in ischemic stroke. This review explores the frontiers of current knowledge of innate and adaptive immune responses in the brain and how these responses together shape the course of ischemic stroke.

Accurate intravascular volume assessment is critical in the treatment of patients who receive chronic hemodialysis (HD) therapy. Clinically assessed dry weight is a poor surrogate of intravascular volume; however, ultrasound assessment of the inferior vena cava (IVC) is an effective tool for volume management. This study sought to determine the feasibility of using operators with limited ultrasound experience to assess IVC dimensions using hand-carried ultrasounds (HCU) in the outpatient clinical setting. The IVC was assessed in 89 consecutive patients at two outpatient clinics before and after HD. Intradialytic IVC was recorded during episodes of hypotension, chest pain, or cramping. High-quality IVC images were obtained in 79 of 89 patients. Despite that 89% of patients presented at or above dry weight, 39% of these patients were hypovolemic by HCU. Of the 75% of patients who left HD at or below goal weight, 10% were still hypervolemic by HCU standards. Hypovolemic patients had more episodes of chest pain and cramping (33 versus 14%, P ‫؍‬ 0.06) and more episodes of hypotension (22 versus 3%, P ‫؍‬ 0.02). The clinic with a higher prevalence of predialysis hypovolemia had significantly more intradialytic adverse events (58 versus 27%; P ‫؍‬ 0.01). HCU measurement of the IVC is a feasible option for rapid assessment of intravascular volume status in an outpatient dialysis setting by operators with limited formal training in echocardiography. There is a poor relationship between dry weight goals and IVC collapsibility. Practice variation in the maintenance of volume status is correlated with significant differences in intradialysis adverse events.