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INTRODUCTION: This study aimed to quantify the contribution of various obstacles to timely reperfusion therapy in acute ST-elevation myocardial infarction (STEMI) and to improve performance in a mixed remote rural/urban region. METHODS: From November 1, 2020 to April 23, 2021, patients with acute STEMI were prospectively monitored with the critical time intervals, treatment modalities, and outcomes registered. Selected clinical decision-makers in 11 hospitals were appointed as improvement agents and systematically provided with weekly updated information about absolute and relative performance. Suggestions for improvements were invited and shared. RESULTS: Only 29% of the 146 patients received reperfusion therapy within recommended time limits [prehospital thrombolysis, 2/48; in-hospital thrombolysis, 0/20; primary percutaneous coronary intervention (pPCI), 37/68, with median intervals from the first medical contact of 44, 49, and 133 min, respectively]. Efficiency varied considerably between health trusts: median time from the first medical contact to prehospital thrombolysis ranged from 29 to 54 min (hazard ratio 4.89). The predominant, remediable causes for delays were erroneous tactical choices and protracted electrocardiographic diagnostication, decision-making, and administration of fibrinolytic medication. During the trial, the time to pPCI was non-significantly reduced. CONCLUSION: We found several targets for system improvements in order to mitigate reperfusion delays along the entire chain of care, regardless of reperfusion modality chosen. More patients should receive prehospital thrombolysis. The most important measures will be training to ensure a more efficient on-site workflow, improved protocols and infrastructure facilitating the communication between first responders and in-hospital clinicians, and education emphasizing prehospital transport times. CLINICAL TRIALS IDENTIFIER: NCT04614805.
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Several epidemiological studies have pointed at serum uric acid (SUA) as an independent risk factor for mortality, diabetes, hypertension, cardiovascular and kidney disease; however, no clear pathogenic pathway is established. Uric acid (UA) crystals show pro-inflammatory properties and can thus create or contribute to the state of chronic low-grade inflammation, a widely accepted pathogenic mechanism in several of the above-mentioned pathologies. On the other hand, soluble uric acid possesses antioxidant properties that might attenuate inflammatory responses. We aimed to explore the net effects of experimentally rising SUA in human whole blood cultures on several mediators of inflammation. Production of TNF-α, IL-1ß, IL-1RA, MCP-1 and IL-8 was assessed upon addition of 200 µM UA, 500 µM UA or monosodium urate (MSU) crystals in the presence or absence of 5 ng/ml lipopolysaccharide (LPS). RT-qPCR and multiplex bead based immunoassay were used to measure mRNA expression and cytokine release at 2 and 4 h of culture, respectively. 14C labeled UA was used to assess intracellular uptake of UA. We show that crystallized, but not soluble, UA induces production of pro-inflammatory mediators in human whole blood. Soluble UA is internalized in blood cells but does not potentiate or reduce LPS-induced release of cytokines.