Background: During the COVID-19 pandemic, public health measures to encourage social distancing have been implemented, including cancellation of school and organized sports. A resulting change in pediatric fracture epidemiology is expected. This study examines the impact of the COVID-19 pandemic on fracture incidence and characteristics. Methods: This is a retrospective cohort study comparing acute fractures presenting to a single level I pediatric trauma hospital during the COVID-19 pandemic with fractures during a prepandemic period at the same institution. The “pandemic” cohort was gathered from March 15 to April 15, 2020 and compared with a “prepandemic” cohort from the same time window in 2018 and 2019. Results: In total, 1745 patients presenting with acute fractures were included. There was a significant decrease in the incidence of fractures presenting to our practice during the pandemic (22.5±9.1/d vs. 9.6±5.1/d, P<0.001). The presenting age for all fractures decreased during the pandemic (7.5±4.3 vs. 9.4±4.4 y, P<0.001) because of decreased fracture burden among adolescents. There were also a decrease in the number of fractures requiring surgery (2.2±1.8/d vs. 0.8±0.8/d, P<0.001). During the pandemic, there was an increase in the proportion of injuries occurring at home (57.8% vs. 32.5%, P<0.001) or on bicycles (18.3% vs. 8.2%, P<0.001), but a decrease in those related to sports (7.2% vs. 26.0%, P<0.001) or playgrounds (5.2% vs. 9.0%, P<0.001). There was no increase in time-to-presentation. Patients with distal radius torus fractures were more likely to receive a velcro splint during the pandemic (44.2% vs. 25.9%, P=0.010). Conclusions: Pediatric fracture volume has decreased 2.5-fold during the COVID-19 pandemic, partially because of cessation of organized sports and decreased playground use. In endemic regions, lower trauma volume may allow redeployment of orthopaedic surgeons and staff to other clinical arenas. Given the rising proportion of bicycling injuries, an emphasis on basic safety precautions could improve public health. An observed increase in the prescription of velcro splints for distal radius fractures highlights an opportunity for simplified patient care during the pandemic. Level of Evidence: Level III.

Objective NMDA induced pial artery dilation (PAD) is reversed to vasoconstriction after fluid percussion brain injury (FPI). Tissue type plasminogen activator (tPA) is upregulated and the tPA antagonist, EEIIMD, prevents impaired NMDA PAD after FPI. Mitogen activated protein kinase (MAPK), a family of at least 3 kinases, ERK, p38 and JNK, is also upregulated after TBI. We hypothesize that tPA impairs NMDA induced cerebrovasodilation after FPI in a MAPK isoform dependent mechanism. Methods Lateral FPI was induced in newborn pigs. The closed cranial window technique was used to measure pial artery diameter and to collect CSF. ERK, p38, and JNK MAPK concentrations in CSF were quantified by ELISA. Results CSF JNK MAPK was increased by FPI, increased further by tPA, but blocked by JNK antagonists SP600125 and D-JNKI1. FPI modestly increased p38 and ERK isoforms of MAPK. NMDA induced PAD was reversed to vasoconstriction after FPI, whereas dilator responses to papaverine were unchanged. tPA, in post FPI CSF concentration, potentiated NMDA induced vasoconstriction while papaverine dilation was unchanged. SP 600125 and D-JNKI1, blocked NMDA induced vasoconstriction and fully restored PAD. The ERK antagonist U 0126 partially restored NMDA-induced PAD, while the p38 inhibitor SB203580 aggravated NMDA-induced vasoconstriction observed in the presence of tPA after FPI. Discussion These data indicate that tPA contributes to impairment of NMDA mediated cerebrovasodilation after FPI through JNK, while p38 may be protective. These data suggest that inhibition of the endogenous plasminogen activator system and JNK may improve cerebral hemodynamic outcome post TBI.

Objective Traumatic brain injury (TBI) contributes to morbidity in children and boys are disproportionately represented. Cerebral autoregulation is impaired after TBI, contributing to poor outcome. Cerebral Perfusion Pressure (CPP) is often normalized by use of vasopressors to increase MAP. In prior studies, we observed that phenylephrine prevented in female but exacerbated impairment of autoregulation in male piglets after fluid percussion injury (FPI). In contrast, dopamine prevented impairment of autoregulation in both sexes after FPI, suggesting that pressor choice impacts outcome. The ERK isoform of mitogen activated protein kinase (MAPK) produces hemodynamic impairment after FPI, but the role of the cytokine IL-6 is unknown. We investigated whether norepinephrine (NE) sex dependently protects autoregulation and limits histopathology after FPI and the role of ERK and IL-6 in that outcome. Design Prospective, randomized animal study. Setting University laboratory. Subjects Newborn (1–5 day old) pigs. Interventions CPP, CBF, and pial artery diameter were determined before and after FPI in piglets equipped with a closed cranial window and post treated with NE. CSF ERK MAPK was determined by ELISA. Measurements and Main Results NE does not protect autoregulation or prevent reduction in CBF in male but fully protects autoregulation in female piglets after FPI. Papaverine induced dilation was unchanged by FPI and NE. NE increased ERK MAPK upregulation in male but blocked such upregulation in female piglets after FPI. NE aggravated IL-6 upregulation in males in an ERK MAPK dependent mechanism but blocked IL-6 upregulation in females after FPI. NE augments loss of neurons in CA1 and CA3 hippocampus of male piglets after FPI in an ERK MAPK and IL-6 dependent manner, but prevents loss of neurons in females after FPI. Conclusions NE protects autoregulation and limits hippocampal neuronal cell necrosis via modulation of ERK MAPK and IL-6 after FPI in a sex dependent manner.

Objective TBI contributes to morbidity in children and boys are disproportionately represented. Autoregulation is impaired more in male compared to female piglets after TBI through sex dependent upregulation of the spasmogen ET-1 and ERK mitogen activated protein kinase (MAPK, a family of 3 kinases, ERK, p38 and JNK). Elevation of mean arterial pressure (MAP) leading to increased cerebral perfusion pressure (CPP) via phenylephrine (Phe) improves impairment of autoregulation after TBI in female but not male piglets through modulation of ET-1 and ERK MAPK upregulation, blocked in females, but aggravated in males. We hypothesized that pressor choice to elevate CPP is important in improving cerebral hemodynamics after TBI and that dopamine (DA) will prevent impairment of autoregulation in both male and female piglets through blockade of ET-1 and ERK MAPK. Design Prospective, randomized animal study. Setting University laboratory. Subjects Newborn (1–5 day old) pigs. Interventions CPP and pial artery diameter were determined before and after lateral fluid percussion brain injury was produced in piglets equipped with a closed cranial window. DA (15 μg/Kg/min iv) was administered 30 min post FPI. CSF ERK MAPK was determined by ELISA. Measurements and Main Results DA increased CPP equivalently in both sexes and prevented sex dependent reductions in pial artery diameter after FPI. Loss of pial artery dilation during hypotension was greater in male compared to female piglets after FPI, but DA prevented such impairment equivalently in both sexes post injury. ET-1 and ERK MAPK release was greater in male compared to female piglets after FPI, but DA also blocked their upregulation equivalently in male and female piglets after FPI. Conclusions These data indicate that DA is protective of autoregulation after FPI in both sexes. These observations advocate for the consideration of development of sex based therapies for treatment of hemodynamic sequalae of pediatric TBI.