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
Burn depth determination is critical for patient care but is currently lacking accuracy. Recent animal studies showed that Short Wave Infrared (SWIR) imaging can distinguish between superficial and deep burns. This is a first human study correlating reflectance of multiple SWIR bands using a SWIR assessment tool (SWAT) with burn depth classifications by surgeons and histology. Burns and adjacent normal skin in 11 patients with thermal injuries were imaged with visual and narrow bands centred at 1200, 1650, 1940 and 2250 nm and biopsies were taken from select areas. Reflectance intensities for each band in 273 regions of interest (ROI) were divided by the normal skin reflectance and combined into three Reflectance Indices (RIs). In addition, burns in ROIs and biopsies were classified by five surgeons and three pathologists, respectively, as superficial partial, deep partial, or full thickness. Results show that for burn depth increase classified by the surgeons, reflectance increased at 1200 and 2250, decreased at 1940, and didn't change at 1650 nm. In contrast, all three RIs increase with burn depth and predict the deep and full depths ROIs representing operable regions (Area Under Curve >0.6507, p < 0.0001). Pathologists' classification matched surgeons' classification of burn category only in eight of 21 biopsies (38.1%), but reflectance at all bands and one RI for all deep partial and full thickness biopsies were larger than in non-biopsy normal and superficial partial thickness ROIs (p < 0.0118). In conclusion, multi-spectral imaging with a new SWAT is a promising approach for evaluation of burn wound depth.
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.
Assuntos
Linfangiogênese , Células-Tronco Mesenquimais , Ossificação Heterotópica , Fator C de Crescimento do Endotélio Vascular , Animais , Ossificação Heterotópica/metabolismo , Ossificação Heterotópica/patologia , Ossificação Heterotópica/genética , Fator C de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/genética , Camundongos , Células-Tronco Mesenquimais/metabolismo , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Diferenciação Celular , Tenócitos/metabolismo , Osteogênese , Haploinsuficiência , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , MasculinoRESUMO
BACKGROUND: The use of cardiopulmonary resuscitation (CPR) and automated external defibrillators (AEDs) significantly improve the chances of survival after out-of-hospital cardiac arrest. Subsequently, state laws mandate training in CPR and AED use for high school graduation. However, training and its impact vary and must be better understood. OBJECTIVE: We assessed the current CPR training mandates and their impact. METHODS: We performed a nationwide, cross-sectional, survey-based observational study of high schoolers in 9th to 12th grades in all 50 states from 2020 to 2022 (NCT04493970), assessing basic demographics, attitudes, knowledge and skills, and willingness to learn CPR and AED. RESULTS: We had an 8% response rate, resulting in 2395 high school students surveyed. The mean age of respondents was 16.8 ± 0.7 years, with 52.5% female students. Of these, 86% underwent some form of training, and 25.1% had CPR training in the last year. Only 58.7% knew how to use an AED. Notably, 26.9% had previously witnessed CPR, and almost all (94%) realized the importance of learning CPR. Most respondents also believed recurrent and longitudinal would be beneficial. CONCLUSION: Surprisingly, only a small cohort of students undergo CPR training even when it is mandatory. The quality of this training appears to be inadequate to impart appropriate confidence and knowledge levels. This suggests a need for a significant overhaul of CPR training mandates across the United States.
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: We aimed 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 with 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 (interquartile range, 19.5-27) and 21.52 ± 8.61, respectively, with 35 being the highest score. Intraobserver variability was 0.986 (95% CI, 0.944-1.028; P < .001). The year of implementation did not influence the strength of the score (R2 = -0.173; 95% CI, -0.447 to 0.131; P = .262). Correlation with SCD rate (R2 = -0.76; 95% CI, -0.492 to 0.367; P = .742), bystander-initiated CPR (R2 = -0.006; 95% CI, -0.437 to 0.427; P = .978), automated external defibrillator use (R2 = -0.125; 95% CI, -0.528 to 0.324; P = .590), and cardiovascular death rate (R2 = -0.13; 95% CI, -0.379 to 0.21; P = .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.