RESUMO
BACKGROUND: Numerous states have introduced cardiopulmonary resuscitation (CPR) training mandates for high school students and staff to prevent sudden cardiac death (SCD). However, the content and implementation of these mandates vary substantially. Furthermore, a comprehensive and objective assessment of these mandates and their impact is lacking. OBJECTIVE: To conduct a thorough evaluation of CPR training mandates across the United States. METHODS: We developed a novel scoring system based on proposed CPR standards, training and certification requirements, and legislative action to assess current mandates. This was used to rate the CPR mandates across all 50 states and the District of Columbia. Mandate scores were then compared to available real-world registry data as a surrogate for efficacy from 2018 to 2021. RESULTS: State CPR mandate scores ranged from 0 to 47, with a higher score indicating more robust mandates. The median and mean scores were 24 [IQR 19.5-27] and 21.52±8.61, respectively, with 35 being the highest score. Intra-observer variability was 0.986 (95% CI 0.944-1.028; p<0.001). The year of implementation did not influence the strength of the score (R2=-0.173; 95% CI -0.447-0.131, p=0.262), Correlation between SCD rate (R2=-0.76; 95% CI -0.492-0.367, p=0.742), bystander-initiated CPR (R2= -0.006; 95% CI -0.437-0.427, p=0.978), automatic external defibrillator use (R2= -0.125; 95% CI -0.528-0.324, p=0.590), or cardiovascular death rate (R2=-0.13; 95% CI -0.379-0.21, p=0.355) failed to reach statistical significance. CONCLUSION: Modest scoring consistency highlights the need for robust, standardized CPR requirements to potentially mitigate SCD. This study lays the groundwork for evidence-informed policy development in this area.
RESUMO
Radiation therapy is a clinically proven, localized preventive measure for heterotopic ossification (HO). Despite its efficacy, there is a lack of standardization of radiation prescription dosing and fractionation, and the mechanism of the impact of radiation in HO prevention remains unknown. Here, using an established mouse model of traumatic HO induced by burn and tenotomy, we demonstrate that 7Gy in one fraction delivered to the injury site within 72 hours postoperatively significantly decreases HO formation and improves hindlimb range of motion. In-depth single-cell transcriptomic analyses, in combination with immunofluorescent staining, demonstrate decreased cellular numbers as well as aberrant endochondral differentiation and downregulation of associated upstream signaling pathways in irradiated mesenchymal progenitor cells. Our study provides the framework for future mechanistic and clinically relevant studies exploring radiation efficacy in preventing HO formation.
RESUMO
Heterotopic ossification (HO) is a challenging condition that occurs after musculoskeletal injury and is characterized by the formation of bone in non-skeletal tissues. While the effect of HO on blood vessels is well established, little is known about its impact on lymphatic vessels. Here, we use a mouse model of traumatic HO to investigate the relationship between HO and lymphatic vessels. We show that injury triggers lymphangiogenesis at the injury site, which is associated with elevated vascular endothelial growth factor C (VEGF-C) levels. Through single-cell transcriptomic analyses, we identify mesenchymal progenitor cells and tenocytes as sources of Vegfc. We demonstrate by lineage tracing that Vegfc-expressing cells undergo osteochondral differentiation and contribute to the formation of HO. Last, we show that Vegfc haploinsufficiency results in a nearly 50% reduction in lymphangiogenesis and HO formation. These findings shed light on the complex mechanisms underlying HO formation and its impact on lymphatic vessels.