A multicenter evaluation of pediatric emergency department injury visits during the COVID-19 pandemic.

BACKGROUND: Injuries, the leading cause of death in children 1-17 years old, are often preventable. Injury patterns are impacted by changes in the child's environment, shifts in supervision, and caregiver stressors. The objective of this study was to evaluate the incidence and proportion of injuries, mechanisms, and severity seen in Pediatric Emergency Departments (PEDs) during the COVID-19 pandemic. METHODS: This multicenter, cross-sectional study from January 2019 through December 2020 examined visits to 40 PEDs for children < 18 years old. Injury was defined by at least one International Classification of Disease-10th revision (ICD-10) code for bodily injury (S00-T78). The main study outcomes were total and proportion of PED injury-related visits compared to all visits in March through December 2020 and to the same months in 2019. Weekly injury visits as a percentage of total PED visits were calculated for all weeks between January 2019 and December 2020. RESULTS: The study included 741,418 PED visits for injuries pre-COVID-19 pandemic (2019) and during the COVID-19 pandemic (2020). Overall PED visits from all causes decreased 27.4% in March to December 2020 compared to the same time frame in 2019; however, the proportion of injury-related PED visits in 2020 increased by 37.7%. In 2020, injured children were younger (median age 6.31 years vs 7.31 in 2019), more commonly White (54% vs 50%, p < 0.001), non-Hispanic (72% vs 69%, p < 0.001) and had private insurance (35% vs 32%, p < 0.001). Injury hospitalizations increased 2.2% (p < 0.001) and deaths increased 0.03% (p < 0.001) in 2020 compared to 2019. Mean injury severity score increased (2.2 to 2.4, p < 0.001) between 2019 and 2020. Injuries declined for struck by/against (- 4.9%) and overexertion (- 1.2%) mechanisms. Injuries proportionally increased for pedal cycles (2.8%), cut/pierce (1.5%), motor vehicle occupant (0.9%), other transportation (0.6%), fire/burn (0.5%) and firearms (0.3%) compared to all injuries in 2020 versus 2019. CONCLUSIONS: The proportion of PED injury-related visits in March through December 2020 increased compared to the same months in 2019. Racial and payor differences were noted. Mechanisms of injury seen in the PED during 2020 changed compared to 2019, and this can inform injury prevention initiatives.

A Fluorescent Reporter Mouse for In Vivo Assessment of Genome Editing with Diverse Cas Nucleases and Prime Editors.

CRISPR-based genome-editing technologies, including nuclease editing, base editing, and prime editing, have recently revolutionized the development of therapeutics targeting disease-causing mutations. To advance the assessment and development of genome editing tools, a robust mouse model is valuable, particularly for evaluating in vivo activity and delivery strategies. In this study, we successfully generated a knock-in mouse line carrying the Traffic Light Reporter design known as TLR-multi-Cas variant 1 (TLR-MCV1). We comprehensively validated the functionality of this mouse model for both in vitro and in vivo nuclease and prime editing. The TLR-MCV1 reporter mouse represents a versatile and powerful tool for expediting the development of editing technologies and their therapeutic applications.

Impact of institutional prophylaxis guidelines on rates of pediatric venous thromboembolism following trauma-A multicenter study from the pediatric trauma society research committee.

BACKGROUND: A paucity of data exists with regard to the incidence, management, and outcomes of venous thromboembolism (VTE) in injured children. We sought to determine the impact of institutional chemoprophylaxis guidelines on VTE rates in a pediatric trauma population. METHODS: A retrospective review of injured children (≤15 years) admitted between 2009 and 2018 at 10 pediatric trauma centers was performed. Data were gathered from institutional trauma registries and dedicated chart review. The institutions were surveyed as to whether they had chemoprophylaxis guidelines in place for high-risk pediatric trauma patients, and outcomes were compared based on the presence of guidelines using χ 2 analysis ( p < 0.05). RESULTS: There were 45,202 patients evaluated during the study period. Three institutions (28,359 patients, 63%) had established chemoprophylaxis policies during the study period ("Guidelines"); the other seven centers (16,843 patients, 37%) had no such guidelines ("Standard"). There were significantly lower rates of VTE in the Guidelines group, but these patients also had significantly fewer risk factors. Among critically injured children with similar clinical presentations, there was no difference in VTE rate. Specifically within the Guidelines group, 30 children developed VTE. The majority (17/30) were actually not indicated for chemoprophylaxis based on institutional guidelines. Still, despite protocols only one VTE patient in the guidelines group who was indicated for intervention ended up receiving chemoprophylaxis prior to diagnosis. No consistent ultrasound screening protocol was in place at any institution during the study. CONCLUSION: The presence of an institutional policy to guide chemoprophylaxis for injured children is associated with a decreased overall frequency of VTE, but this disappears when controlling for patient factors. However, the overall efficacy is impacted by a combination of deficits in guideline compliance and structure. Further prospective data are needed to help determine the ideal role for chemoprophylaxis and protocols in pediatric trauma. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Use of In-Situ Simulation Based Clinical Systems Test of Thoracic Robotic Surgery Emergencies.

INTRODUCTION: With the advancement of robotic surgery, some thoracic surgeons have been slow to adopt to this new operative approach, in part because they are un-scrubbed and away from the patient while operating. Aiming to allay surgeon concerns of intra-operative emergencies, an insitu simulation-based clinical system's test (SbCST) can be completed to test the current clinical system, and to practice low-frequency, high-stakes clinical scenarios with the entire operating room (OR) team. METHODS: Six different OR teams completed an insitu SbCST of an intra-operative pulmonary artery injury during a robot-assisted thoracic surgery at a single tertiary care center. The OR team consisted of an attending thoracic surgeon, surgery resident, anesthesia attending, anesthesia resident, circulating nurse, and a scrub technician. This test was conducted with an entire OR team along with study observers and simulation center staff. Outcomes included the identified latent safety threats (LSTs) and possible solutions for each LST, culminating in a complete failure mode and effects analysis (FMEA). A Risk Priority Number (RPN) was determined for each LST identified. Pre- and post-simulation surveys using Likert scales were also collected. RESULTS: The six FMEAs identified 28 potential LSTs in four categories. Of these 28 LSTs, nine were considered high priority based on their Risk Priority Number (RPN) with seven of the nine being repeated multiple times. Pre- and post-simulation survey responses were similar, with the majority of participants (94%) agreeing that high fidelity simulation of intra-operative emergencies is helpful and provides an opportunity to train for high-stakes, low-frequency events. After completing the SbCST, more participants felt confident that they knew their role during an intra-operative emergency than their pre-simulation survey responses. All participants agreed that simulation is an important part of continuing education and is helpful for learning skills that are infrequently used. Following the SbCST, more participants agreed that they knew how to safely undock the da Vinci robot during an emergency. CONCLUSIONS: SbCSTs provide an opportunity to test the current clinical system with a low-frequency, high-stakes event and allow medical personnels to practice their skills and teamwork. By completing multiple SbCSTs, we were able to identify multiple LSTs within different OR teams, allowing for a broader review of the current clinical systems in place. The use of these SbCSTs in conjunction with debriefing sessions and FMEA completion allows for the most significant potential improvement of the current system. This study shows that SbCST with FMEA completion can be used to test current systems and create better systems for patient safety.

Assessing screening, brief intervention, and referral to treatment (SBIRT) compliance and disparities for pediatric inpatients at a tertiary care facility.

BACKGROUND: Pediatric trauma centers are required to screen patients for alcohol or other drug use (AOD), Briefly Intervene, and Refer these patients to Treatment (SBIRT) to meet Level 1 and 2 trauma center requirements set by the American College of Surgeons. We evaluated if a mandatory electronic medical record tool increased SBIRT screening compliance for all trauma and non-trauma adolescent inpatients. METHODS: A SBIRT electronic medical record tool was implemented for pediatric inpatient AOD screening. A positive screen prompted brief intervention and referral for treatment in coordination with social work and psychiatric consultants. We compared pre and post- implementation screening rates among inpatients age 12-18 years and performed sub-group analyses. RESULTS: There were 873 patients before and 1,091 after implementation. Questionnaire screening increased from 0% to 34.4% (p < 0.001), without an increase in positivity rate, and lab screening decreased by 4.2% (p = 0.003). Females were more likely to receive a social work consultation than males (14.5 vs 7.5%, p < 0.001), despite a greater number of positive questionnaires among males (9.5 vs 17.9%, p = 0.013). White patients were more likely to receive a social work consultation (12.9%) compared to Asian (2%), Black (6.3%), and Other (6.9%) (p = 0.007), despite comparable rates of positive screenings. When comparing English to non-English speakers, English speakers were more likely to have a social work consult (12.0% vs 2.4%, p < 0.001) and psychiatry/psychology consult (13.6 vs 5.6%, p = 0.011). CONCLUSION: Multidisciplinary training along with an electronic medical record tool increased SBIRT protocol compliance. Demographic disparities in intervention rates may exist.

Caregiver-perceived neighborhood safety and pediatric asthma severity: 2017-2018 National Survey of Children's Health.

OBJECTIVE: To examine the association between caregiver-perceived neighborhood safety and pediatric asthma severity using a cross-sectional, nationally representative sample. STUDY DESIGN: Using data from the 2017-2018 National Survey of Children's Health, children aged 6-17 years with primary caregiver report of a current asthma diagnosis were included (unweighted N = 3209; weighted N = 3,909,178). Perceived neighborhood safety, asthma severity (mild vs. moderate/severe), demographic, household, and health/behavioral covariate data were collected from primary caregiver report. Poisson regression with robust error variance was used to estimate the association between perceived neighborhood safety and caregiver-reported pediatric asthma severity. RESULTS: Approximately one-third of children studied had moderate/severe asthma. A total of 42% of children with mild asthma and 52% of children with moderate/severe asthma identified as Hispanic or non-Hispanic Black. Nearly 20% of children with mild asthma and 40% of children with moderate/severe asthma were from families living below the federal poverty level (FPL). Children living in neighborhoods perceived by their caregiver to be unsafe had higher prevalence of moderate/severe asthma compared to those in the safest neighborhoods (adjusted prevalence ratio: 1.34; 95% confidence interval: 1.04-1.74). This association was found to be independent of race/ethnicity, household FPL, household smoking, and child's physical activity level after adjusting for covariates. CONCLUSIONS: Children living in neighborhoods perceived by their caregiver to be unsafe have higher prevalence of moderate or severe asthma. Further investigation of geographic context and neighborhood characteristics that influence childhood asthma severity may inform public health strategies to reduce asthma burden and improve disease outcomes.

An abbreviated Caprini model for VTE risk assessment in trauma.

The Caprini risk assessment model (RAM) is widely used to assess risk of venous thromboembolism (VTE). However, it is cumbersome with 31 variables and poses challenges with inter-rater reliability. This study aimed to determine if an abbreviated model could perform similarly in VTE risk assessment. We performed a retrospective review of trauma patients ≥ 18 years old and admitted for over 24 h at a Level I trauma center from January 1, 2018, to December 31, 2018. Demographic and clinical data were analyzed to generate Caprini scores. Using a p-value cutoff of < 0.05, the individual components of the original Caprini RAM most highly associated with VTE were identified and used to calculate an abbreviated Caprini score. Logistic regression assessed odds of inpatient VTE with the original or abbreviated Caprini RAMs. Receiver operating characteristic curves and c-statistics were generated to assess discriminatory ability. The study sample included 1279 patients. Ten risk factors were included in the abbreviated model (recent major surgery, length of surgery > 2 h, transfusion, restricted mobility > 72 h, central venous catheter, current major surgery, age, history of VTE, hip or leg fracture, and serious trauma). Compared to the original, the abbreviated model had a similar odds ratio (1.17 vs 1.07, both p-values < 0.001), c-statistic (0.747 vs 0.753), sensitivity (0.73 vs 0.76) and specificity (0.62 vs 0.61). An abbreviated Caprini RAM performs similarly to the original, may streamline workflow and allow for automation in electronic health records, potentially enhancing its use in resource limited settings.

Venous thromboembolism risk stratification in trauma using the Caprini risk assessment model.

INTRODUCTION: The Caprini risk assessment model is widely used for venous thromboembolism (VTE) but has limited data in trauma. The study objective was to determine if the Caprini risk assessment model could effectively risk stratify trauma patients. MATERIALS AND METHODS: We performed a retrospective review of trauma patients aged ≥18 years, admitted for greater than 24 h at a level one trauma center from January 1, 2018, to December 31, 2018. Demographic and clinical data were analyzed to generate Caprini scores. Multiple logistic regression assessed odds of inpatient VTE. RESULTS: A total of 1279 patients met study eligibility, with a total of 33 VTE (2.6%). When comparing those with VTE to those without, the mean age was lower (52.5 vs 59.5, p = 0.06, respectively), sex distribution was similar, but mean body mass index was higher (30.2 vs 27.4, p = 0.019, respectively). The mean Caprini score was 9.9, and 75.5% had a score >4, the traditional Caprini high-risk cutoff. The VTE group had a higher mean Injury Severity Score (17.8 vs 12.6, p = 0.011), and mean Caprini score (16.4 vs 9.8, p < 0.001). Multiple logistic regression found Caprini score, not Injury Severity Score, was associated with higher odds of VTE (adjusted odds ratio 1.06, 95% confidence interval 1.02-1.10), after adjusting for Injury Severity Score, any missed doses of VTE chemoprophylaxis, and VTE prophylaxis type. CONCLUSIONS: Higher Caprini scores are associated with elevated odds of inpatient VTE within hospitalized trauma patients. These data support using the Caprini risk assessment model in the trauma population, which may aid in risk stratification.

Venous thromboembolic risk stratification in pediatric trauma: A Pediatric Trauma Society Research Committee multicenter analysis.

BACKGROUND: Venous thromboembolism (VTE) in injured children is rare, but its consequences are significant. Several risk stratification algorithms for VTE in pediatric trauma exist with little consensus, and all are hindered in development by relying on registry data with known inaccuracies. We performed a multicenter review to evaluate trauma registry fidelity and confirm the effectiveness of one established algorithm across diverse centers. METHODS: Local trauma registries at 10 institutions were queried for all patients younger than 18 years admitted between 2009 and 2018. Additional chart review was performed on all "VTE" cases and random non-VTE controls to assess registry errors. Corrected data were then applied to our prediction algorithm using 10 real-time variables (Glasgow Coma Scale, age, sex, intensive care unit admission, transfusion, central line placement, lower extremity/pelvic fracture, major surgery) to calculate VTE risk scores. Contingency table classifiers and the area under a receiver operator characteristic curve were calculated. RESULTS: Registries identified 52,524 pediatric trauma patients with 99 episodes of VTE; however, chart review found that 13 cases were misclassified for a corrected total of 86 cases (0.16%). After correction, the algorithm still displayed strong performance in discriminating VTE-fated encounters (sensitivity, 69%; area under the receiver operating characteristic curve, 0.96). Furthermore, despite wide institutional variability in VTE rates (0.04-1.7%), the algorithm maintained a specificity of >91% and a negative predictive value of >99.7% across centers. Chart review also revealed that 54% (n = 45) of VTEs were directly associated with a central line, usually femoral (n = 34, p < 0.001 compared with upper extremity), and that prophylaxis rates were underreported in the registries by about 50%; still, only 19% of the VTE cases had been on prophylaxis before diagnosis. CONCLUSION: The VTE prediction algorithm performed well when applied retrospectively across 10 diverse pediatric centers using corrected registry data. These findings can advance initiatives for VTE screening/prophylaxis guidance following pediatric trauma and warrant prospective study. LEVEL OF EVIDENCE: Clinical decision rule evaluated in a single population, level III.

YAP1 Withdrawal in Hepatoblastoma Drives Therapeutic Differentiation of Tumor Cells to Functional Hepatocyte-Like Cells.

BACKGROUND AND AIMS: Despite surgical and chemotherapeutic advances, the 5-year survival rate for stage IV hepatoblastoma (HB), the predominant pediatric liver tumor, remains at 27%. Yes-associated protein 1 (YAP1) and ß-catenin co-activation occurs in 80% of children's HB; however, a lack of conditional genetic models precludes tumor maintenance exploration. Thus, the need for a targeted therapy remains unmet. Given the predominance of YAP1 and ß-catenin activation in HB, we sought to evaluate YAP1 as a therapeutic target in HB. APPROACH AND RESULTS: We engineered the conditional HB murine model using hydrodynamic injection to deliver transposon plasmids encoding inducible YAP1S127A , constitutive ß-cateninDelN90 , and a luciferase reporter to murine liver. Tumor regression was evaluated using bioluminescent imaging, tumor landscape characterized using RNA and ATAC sequencing, and DNA footprinting. Here we show that YAP1S127A withdrawal mediates more than 90% tumor regression with survival for 230+ days in mice. YAP1S127A withdrawal promotes apoptosis in a subset of tumor cells, and in remaining cells induces a cell fate switch that drives therapeutic differentiation of HB tumors into Ki-67-negative hepatocyte-like HB cells ("HbHeps") with hepatocyte-like morphology and mature hepatocyte gene expression. YAP1S127A withdrawal drives the formation of hbHeps by modulating liver differentiation transcription factor occupancy. Indeed, tumor-derived hbHeps, consistent with their reprogrammed transcriptional landscape, regain partial hepatocyte function and rescue liver damage in mice. CONCLUSIONS: YAP1S127A withdrawal, without silencing oncogenic ß-catenin, significantly regresses hepatoblastoma, providing in vivo data to support YAP1 as a therapeutic target for HB. YAP1S127A withdrawal alone sufficiently drives long-term regression in HB, as it promotes cell death in a subset of tumor cells and modulates transcription factor occupancy to reverse the fate of residual tumor cells to mimic functional hepatocytes.

A national analysis of pediatric falls from a building.

INTRODUCTION: Falls remain the leading cause of unintentional pediatric trauma in the United States. Identifying risk factors for pediatric building falls would influence public health policy. We hypothesized that building falls disproportionately affect low income communities. METHODS: We performed a cross-sectional analysis of the Kids' Inpatient Database for years 2006, 2009, and 2012. We identified cases (age <12 years) of falls from a building using external cause of injury codes. Patient characteristics and injuries were analyzed using ICD-9 codes. National estimates were obtained using case weighting. Multivariable logistic regression was performed to adjust for confounders. RESULTS: There were 2,294 hospitalizations nationally for pediatric falls from a building. The victims were predominately male, in early childhood, non-Hispanic White, in the lowest income quartile, resided in urban settings, and occurred during summer. The mean age was 3.76 years. Logistic regression revealed males were 33% more likely than females, and as compared to non-Hispanic White youth, Black (33%) and Asian or Pacific Islanders (65%) were more likely to experience a fall from a building. Toddlers and those in early childhood were at significantly increased odds than those younger than one year old. Children in the highest income quartile were 29% more likely to experience a building fall. CONCLUSIONS: Building falls are a common cause of injury in the U.S. for children under 12 years old. Injury prevention strategies focused on the parents of children aged 1-5 years has the potential to make a significant public health impact.

Pediatric snow sport injuries differ by age.

BACKGROUND: Unintentional injury is the leading cause of death among pediatric patients. There were 13,436 injuries related to snow sports in those younger than 15 in 2015, with 4.8% requiring admission. These sports are high-risk given the potential for injury even when using protective equipment. We hypothesized that snow sport injury patterns would differ based on patient age. METHODS: A cross-sectional analysis of the 2009 and 2012 Kids' Inpatient Database was performed. Cases of injuries were identified and analyzed using ICD-9 codes. National estimates were obtained using case weighting. Multivariable logistic regression was used to assess for confounders. RESULTS: Within 745 admissions, there was a statistically significant decrease in skull/facial fractures with increasing age and a statistically significant increase in abdominal injuries with increasing age. Children in early and middle childhood were at increased odds of being hospitalized with skull/facial fractures, while older children were more likely hospitalized with abdominal injuries. CONCLUSIONS: Within the pediatric snow sport population, younger children are more likely to experience head injuries, while older children are more likely to experience abdominal injuries. Further research is needed to determine the origin of this difference, and continued legislation on helmets is also necessary in reducing intracranial injuries. LEVEL OF EVIDENCE: III.

Intraventricular Hemorrhage and Patent Ductus Arteriosus Ligation Association with Infant Mortality.

BACKGROUND: Practice patterns for the management of patent ductus arteriosus (PDA) in premature infants are changing with advances in medical management. We sought to determine the increased mortality for premature infants who had a PDA ligation with a co-existing diagnosis of intraventricular hemorrhage (IVH). METHODS: Premature neonates (<1 y old with known gestational week ≤36 wk) with a diagnosis of IVH were identified within the Kids' Inpatient Database (KID) for the years 2006, 2009, and 2012. Diagnoses and procedures were analyzed by ICD-9 codes and stratified by a diagnosis of PDA and procedure of ligation. Case weighting was used to make national estimations. Multivariable logistic regression was performed to adjust for confounders. RESULTS: We identified 7567 hospitalizations for premature neonates undergoing PDA ligation. The population was predominately male (51.6%), non-Hispanic white (41.1%), were from the lowest income quartile (33.1%), had a gestational week of 25-26 wk (34.0%), and a birthweight between 500 and 749 g (37.3%). There was an increased mortality (10.7% versus 6.3%, P < 0.01) and an increased length of stay (88.2 d versus 74.4 d, P < 0.01) in those with any diagnosis of IVH compared with those without. Adjusted multivariable logistic regression demonstrated that high-grade IVH (III or IV) was associated with a significantly increased risk of mortality in those undergoing PDA ligation (aOR 2.59, P < 0.01). Specifically, grade III and IV were associated with an increased odds of in-hospital mortality (aOR 1.99 and 3.16, respectively, P < 0.01). CONCLUSIONS: Attitudes regarding the need for surgical intervention for PDA have shifted in recent years. This study highlights that premature neonates with grade III or IV IVH are at significantly increased risk of mortality if undergoing PDA ligation during the same hospitalization. LEVEL OF EVIDENCE: III.

Young lives cut short: The relationship between firearms and pediatric suicide.

BACKGROUND: To describe the demographic characteristics and burden of pediatric suicides by firearm in the United States using a large all-payer pediatric inpatient care database. METHODS: Children and young adults (<21 years old) were identified with an International Classification of Diseases, Ninth Revision diagnosis of suicide and self-inflicted injury with a firearm (SIF) in the Kids' Inpatient Database for the study years of 2006, 2009, and 2012. National estimates were obtained using case weighting. Multivariable logistic regression was performed to examine the association between SIF and risk factors while adjusting for various sociodemographic characteristics using separate models incorporating mental health diagnoses. RESULTS: There were a total of 613 hospitalizations for SIF during the years under study. Almost four hospitalizations per week occurred, and in-hospital mortality was 39.1%. The mean age of the study population was 17.3 years, and this population was predominantly male (87.5%), white (62.4%), resided in an urban area (43.8%), lived in the south (51.3%), and within the lowest income quartile (33.8%). Mental health (38.3%) and mood disorders (28.3%) were common. Males had a markedly increased likelihood of hospitalization for SIF (adjusted odds ratio [aOR], 7.56; 95% confidence interval [CI], 5.54-10.30). Children and adolescents from rural environments and those in the south were more likely to have a hospitalization for SIF than respective comparison groups. Using separate regression models, a diagnosis of any mental health disorder increased the likelihood of hospitalization for a SIF (aOR, 11.9: 95% CI, 9.51-14.9), mood disorders (aOR, 17.2; 95% CI, 13.3-22.3), and depression (aOR, 21.3; 95% CI, 16.1-28.3). CONCLUSION: Pediatric hospitalizations for SIF are a common occurrence with high associated mortality. The prevalence of mental health disorders and their impact on this population highlight the need for early identification and intervention for individuals at risk. LEVEL OF EVIDENCE: Epidemiological, level III.

Testicular Torsion: Current Evaluation and Management.

Testicular torsion is a urologic emergency, requiring prompt identification and management. Understanding the risk factors, presentation, and management is essential to decrease delays in diagnosis and intervention. This review discusses the prevalence, pathophysiology, management, and outcomes of testicular torsion.