PECARN prediction rule for cervical spine imaging of children presenting to the emergency department with blunt trauma: a multicentre prospective observational study.

BACKGROUND: Cervical spine injuries in children are uncommon but potentially devastating; however, indiscriminate neck imaging after trauma unnecessarily exposes children to ionising radiation. The aim of this study was to derive and validate a paediatric clinical prediction rule that can be incorporated into an algorithm to guide radiographic screening for cervical spine injury among children in the emergency department. METHODS: In this prospective observational cohort study, we screened children aged 0-17 years presenting with known or suspected blunt trauma at 18 specialised children's emergency departments in hospitals in the USA affiliated with the Pediatric Emergency Care Applied Research Network (PECARN). Injured children were eligible for enrolment into derivation or validation cohorts by fulfilling one of the following criteria: transported from the scene of injury to the emergency department by emergency medical services; evaluated by a trauma team; and undergone neck imaging for concern for cervical spine injury either at or before arriving at the PECARN-affiliated emergency department. Children presenting with solely penetrating trauma were excluded. Before viewing an enrolled child's neck imaging results, the attending emergency department clinician completed a clinical examination and prospectively documented cervical spine injury risk factors in an electronic questionnaire. Cervical spine injuries were determined by imaging reports and telephone follow-up with guardians within 21-28 days of the emergency room encounter, and cervical spine injury was confirmed by a paediatric neurosurgeon. Factors associated with a high risk of cervical spine injury (>10%) were identified by bivariable Poisson regression with robust error estimates, and factors associated with non-negligible risk were identified by classification and regression tree (CART) analysis. Variables were combined in the cervical spine injury prediction rule. The primary outcome of interest was cervical spine injury within 28 days of initial trauma warranting inpatient observation or surgical intervention. Rule performance measures were calculated for both derivation and validation cohorts. A clinical care algorithm for determining which risk factors warrant radiographic screening for cervical spine injury after blunt trauma was applied to the study population to estimate the potential effect on reducing CT and x-ray use in the paediatric emergency department. This study is registered with ClinicalTrials.gov, NCT05049330. FINDINGS: Nine emergency departments participated in the derivation cohort, and nine participated in the validation cohort. In total, 22 430 children presenting with known or suspected blunt trauma were enrolled (11 857 children in the derivation cohort; 10 573 in the validation cohort). 433 (1·9%) of the total population had confirmed cervical spine injuries. The following factors were associated with a high risk of cervical spine injury: altered mental status (Glasgow Coma Scale [GCS] score of 3-8 or unresponsive on the Alert, Verbal, Pain, Unresponsive scale [AVPU] of consciousness); abnormal airway, breathing, or circulation findings; and focal neurological deficits including paresthesia, numbness, or weakness. Of 928 in the derivation cohort presenting with at least one of these risk factors, 118 (12·7%) had cervical spine injury (risk ratio 8·9 [95% CI 7·1-11·2]). The following factors were associated with non-negligible risk of cervical spine injury by CART analysis: neck pain; altered mental status (GCS score of 9-14; verbal or pain on the AVPU; or other signs of altered mental status); substantial head injury; substantial torso injury; and midline neck tenderness. The high-risk and CART-derived factors combined and applied to the validation cohort performed with 94·3% (95% CI 90·7-97·9) sensitivity, 60·4% (59·4-61·3) specificity, and 99·9% (99·8-100·0) negative predictive value. Had the algorithm been applied to all participants to guide the use of imaging, we estimated the number of children having CT might have decreased from 3856 (17·2%) to 1549 (6·9%) of 22 430 children without increasing the number of children getting plain x-rays. INTERPRETATION: Incorporated into a clinical algorithm, the cervical spine injury prediction rule showed strong potential for aiding clinicians in determining which children arriving in the emergency department after blunt trauma should undergo radiographic neck imaging for potential cervical spine injury. Implementation of the clinical algorithm could decrease use of unnecessary radiographic testing in the emergency department and eliminate high-risk radiation exposure. Future work should validate the prediction rule and care algorithm in more general settings such as community emergency departments. FUNDING: The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration of the US Department of Health and Human Services in the Maternal and Child Health Bureau under the Emergency Medical Services for Children programme.

Implications of chronic moderate protein-deficiency malnutrition on doxorubicin pharmacokinetics and cardiotoxicity in early post-weaning stage.

BACKGROUND: Malnutrition is a common problem in developing countries, and the impact of severe malnutrition on optimal treatment outcomes of chemotherapy in pediatric cancer patients is well documented. However, despite being a more prevalent and distinct entity, moderate malnutrition is until now unexplored for its effects on treatment outcomes. AIMS: In this study we aimed to investigate the molecular basis of altered pharmacokinetics and cardiotoxicity of doxorubicin observed in early-life chronic moderate protein deficiency malnutrition. MATERIALS AND METHODS: We developed an animal model of early-life moderate protein-deficiency malnutrition and validated it using clinical samples. This model was used to study pharmacokinetic and toxicity changes and was further utilized to study the molecular changes in liver and heart to get mechanistic insights. KEY FINDINGS: Here we show that moderate protein-deficiency malnutrition in weanling rats causes changes in drug disposition in the liver by modification of hepatic ABCC3 and MRP2 transporters through the TNFα signalling axis. Furthermore, malnourished rats in repeat-dose doxorubicin toxicity study showed higher toxicity and mortality. A higher accumulation of doxorubicin in the heart was observed which was associated with alterations in cardiac metabolic pathways and increased cardiotoxicity. SIGNIFICANCE: Our findings indicate that moderate malnutrition causes increased susceptibility towards toxic side effects of chemotherapy. These results may necessitate further investigations and new guidelines on the dosing of chemotherapy in moderately malnourished pediatric cancer patients.

Childhood opportunity and appropriate use of child safety restraints in motor vehicle collisions.

Objectives: Safety restraints reduce injuries from motor vehicle collisions (MVCs) but are often improperly applied or not used. The Childhood Opportunity Index (COI) reflects social determinants of health and its study in pediatric trauma is limited. We hypothesized that MVC patients from low-opportunity neighborhoods are less likely to be appropriately restrained. Methods: A retrospective cross-sectional study was performed on children/adolescents ≤18 years old in MVCs between January 1, 2011 and December 31, 2021. Patients were identified from the Children's Hospital Los Angeles trauma registry. The outcome was safety restraint use (appropriately restrained, not appropriately restrained). COI levels by home zip codes were stratified as very low, low, moderate, high, and very high. Multivariable regression controlling for age identified factors associated with safety restraint use. Results: Of 337 patients, 73.9% were appropriately restrained and 26.1% were not appropriately restrained. Compared with appropriately restrained patients, more not appropriately restrained patients were from low-COI (26.1% vs 20.9%), high-COI (14.8% vs 10.8%) and very high-COI (10.2% vs 3.6%) neighborhoods. Multivariable analysis demonstrated no significant associations in appropriate restraint use and COI. There was a non-significant trend that children/adolescents from moderate-COI neighborhoods were more likely than those from very low-COI neighborhoods to be appropriately restrained (OR=1.82, 95% CI 0.78, 4.28). Conclusion: Injury prevention initiatives focused on safety restraints should target families of children from all neighborhood types. Level of evidence: III.

PECARN prediction rules for CT imaging of children presenting to the emergency department with blunt abdominal or minor head trauma: a multicentre prospective validation study.

BACKGROUND: The intra-abdominal injury and traumatic brain injury prediction rules derived by the Pediatric Emergency Care Applied Research Network (PECARN) were designed to reduce inappropriate use of CT in children with abdominal and head trauma, respectively. We aimed to validate these prediction rules for children presenting to emergency departments with blunt abdominal or minor head trauma. METHODS: For this prospective validation study, we enrolled children and adolescents younger than 18 years presenting to six emergency departments in Sacramento (CA), Dallas (TX), Houston (TX), San Diego (CA), Los Angeles (CA), and Oakland (CA), USA between Dec 27, 2016, and Sept 1, 2021. We excluded patients who were pregnant or had pre-existing neurological disorders preventing examination, penetrating trauma, injuries more than 24 h before arrival, CT or MRI before transfer, or high suspicion of non-accidental trauma. Children presenting with blunt abdominal trauma were enrolled into an abdominal trauma cohort, and children with minor head trauma were enrolled into one of two age-segregated minor head trauma cohorts (younger than 2 years vs aged 2 years and older). Enrolled children were clinically examined in the emergency department, and CT scans were obtained at the attending clinician's discretion. All enrolled children were evaluated against the variables of the pertinent PECARN prediction rule before CT results were seen. The primary outcome of interest in the abdominal trauma cohort was intra-abdominal injury undergoing acute intervention (therapeutic laparotomy, angiographic embolisation, blood transfusion, intravenous fluid for ≥2 days for pancreatic or gastrointestinal injuries, or death from intra-abdominal injury). In the age-segregated minor head trauma cohorts, the primary outcome of interest was clinically important traumatic brain injury (neurosurgery, intubation for >24 h for traumatic brain injury, or hospital admission ≥2 nights for ongoing symptoms and CT-confirmed traumatic brain injury; or death from traumatic brain injury). FINDINGS: 7542 children with blunt abdominal trauma and 19 999 children with minor head trauma were enrolled. The intra-abdominal injury rule had a sensitivity of 100·0% (95% CI 98·0-100·0; correct test for 145 of 145 patients with intra-abdominal injury undergoing acute intervention) and a negative predictive value (NPV) of 100·0% (95% CI 99·9-100·0; correct test for 3488 of 3488 patients without intra-abdominal injuries undergoing acute intervention). The traumatic brain injury rule for children younger than 2 years had a sensitivity of 100·0% (93·1-100·0; 42 of 42) for clinically important traumatic brain injuries and an NPV of 100·0%; 99·9-100·0; 2940 of 2940), whereas the traumatic brain injury rule for children aged 2 years and older had a sensitivity of 98·8% (95·8-99·9; 168 of 170) and an NPV of 100·0% (99·9-100·0; 6015 of 6017). The two children who were misclassified by the traumatic brain injury rule were admitted to hospital for observation but did not need neurosurgery. INTERPRETATION: The PECARN intra-abdominal injury and traumatic brain injury rules were validated with a high degree of accuracy. Their implementation in paediatric emergency departments can therefore be considered a safe strategy to minimise inappropriate CT use in children needing high-quality care for abdominal or head trauma. FUNDING: The Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Centiles for the shock index among injured children in the prehospital setting.

OBJECTIVE: The shock index (SI), the ratio of heart rate to systolic blood pressure, is a clinical tool for assessing injury severity. Age-adjusted SI models may improve predictive value for injured children in the out-of-hospital setting. We sought to characterize the proportion of children in the prehospital setting with an abnormal SI using established criteria, describe the age-based distribution of SI among injured children, and determine prehospital interventions by SI. METHODS: We performed a multi-agency retrospective cross-sectional study of children (<18 years) in the prehospital setting with a scene encounter for suspected trauma and transported to the hospital between 2018 and 2022 using the National Emergency Medical Services (EMS) Information System datasets. Our exposure of interest was the first calculated SI. We identified the proportion of children with an abnormal SI when using the SI, pediatric age-adjusted (SIPA); and the pediatric SI (PSI) criteria. We developed and internally validated an age-based distributional model for the SI using generalized additive models for location, scale, and shape to describe the age-based distribution of the SI as a centile or Z-score. We evaluated EMS interventions (basic airway interventions, advanced airway interventions, cardiac interventions, vascular access, intravenous fluids, and vasopressor use) in relation to both the SIPA, PSI, and distributional SI values. RESULTS: We analyzed 1,007,863 pediatric EMS trauma encounters (55.0% male, median age 13 years [IQR, 8-16 years]). The most common dispatch complaint was for traffic/transport related injury (32.9%). When using the PSI and SIPA, 13.1% and 16.3% were classified as having an abnormal SI, respectively. There were broad differences in the percentage of encounters classified as having an abnormal SI across the age range, varying from 5.1 to 22.8% for SIPA and 3.7-20.1% for PSI. The SIPA values ranged from the 75th to 95th centiles, while the PSI corresponded to an SI greater than the 90th centile, except in older children. The centile distribution for SI declined during early childhood and stabilized during adolescence and demonstrated a difference of <0.1% at cutoff values. An abnormal PSI, SIPA and higher SI centiles (>90th centile and >95th centiles) were associated with interventions related to basic and advanced airway management, cardiac procedures, vascular access, and provision of intravenous fluids occurred with greater frequency at higher SI centiles. Some procedures, including airway management and vascular access, had a smaller peak at lower (<10th) centiles. DISCUSSION: We describe the empiric distribution of the pediatric SI across the age range, which may overcome limitations of extant criteria in identifying patients with shock in the prehospital setting. Both high and low SI values were associated with important, potentially lifesaving EMS interventions. Future work may allow for more precise identification of children with significant injury using cutpoint analysis paired to outcome-based criteria. These may additionally be combined with other physiologic and mechanistic criteria to assist in triage decisions.

Comparison of Vital Sign Cutoffs to Identify Children With Major Trauma.

Importance: Vital signs are essential components in the triage of injured children. The Advanced Trauma Life Support (ATLS) and Pediatric Advanced Life Support (PALS) physiologic criteria are frequently used for trauma assessments. Objective: To evaluate the performance of ATLS and PALS criteria vs empirically derived criteria for identifying major trauma in children. Design, Setting, and Participants: This retrospective cohort study used 2021 American College of Surgeons Trauma Quality Improvement Program (TQIP) data contributed by US trauma centers. Included encounters involved pediatric patients (aged <18 years) with severe injury, excluding those who experienced out-of-hospital cardiac arrest, were receiving mechanical ventilation, or were transferred from another facility. Data were analyzed between April 9 and December 21, 2023. Exposure: Initial hospital vital signs, including heart rate, respiratory rate, and systolic blood pressure (SBP). Main Outcome and Measures: Major trauma, determined by the Standard Triage Assessment Tool, a composite measure of injury severity and interventions performed. Multivariable models developed from PALS and ATLS vital sign criteria were compared with models developed from the empirically derived criteria using the area under the receiver operating characteristic curve. Validation of the findings was performed using the 2019 TQIP dataset. Results: A total of 70 748 patients (median [IQR] age, 11 [5-15] years; 63.4% male) were included, of whom 3223 (4.6%) had major trauma. The PALS criteria classified 31.0% of heart rates, 25.7% of respiratory rates, and 57.4% of SBPs as abnormal. The ATLS criteria classified 25.3% of heart rates, 4.3% of respiratory rates, and 1.1% of SBPs as abnormal. Among children with all 3 vital signs documented (64 326 [90.9%]), PALS had a sensitivity of 88.4% (95% CI, 87.1%-89.3%) and specificity of 25.1% (95% CI, 24.7%-25.4%) for identifying major trauma, and ATLS had a sensitivity of 54.5% (95% CI, 52.7%-56.2%) and specificity of 72.9% (95% CI, 72.6%-73.3%). The empirically derived cutoff vital sign z scores had a sensitivity of 80.0% (95% CI, 78.5%-81.3%) and specificity of 48.7% (95% CI, 48.3%-49.1%) and area under the receiver operating characteristic curve of 70.9% (95% CI, 69.9%-71.8%), which was similar to PALS criteria (69.6%; 95% CI, 68.6%-70.6%) and greater than ATLS criteria (65.4%; 95% CI, 64.4%-66.3%). Validation using the 2019 TQIP database showed similar performance to the derivation sample. Conclusions and Relevance: These findings suggest that empirically derived vital sign criteria strike a balance between the sensitivity of PALS criteria and the specificity of ATLS criteria in identifying major trauma in children. These criteria may help to identify children at greatest risk of trauma-related morbidity and mortality.

Acute care utilization for ambulatory care-sensitive conditions among publicly insured children.

BACKGROUND: Although characteristics of preventable hospitalizations for ambulatory care-sensitive conditions (ACSCs) have been described, less is known about patterns of emergency and other acute care utilization for ACSCs among children who are not hospitalized. We sought to describe patterns of utilization for ACSCs according to the initial site of care and to determine characteristics associated with seeking initial care in an acute care setting rather than in an office. A better understanding of the sequence of health care utilization for ACSCs may inform efforts to shift care for these common conditions to the medical home. METHODS: We performed a retrospective analysis of pediatric encounters for ACSCs between 2017 and 2019 using data from the IBM Watson MarketScan Medicaid database. The database includes insurance claims for Medicaid-insured children in 10 anonymized states. We assessed the initial sites of care for ACSC encounters, which were defined as either acute care settings (emergency or urgent care) or office-based settings. We used generalized estimating equations clustered on patient to identify associations between encounter characteristics and the initial site of care. RESULTS: Among 7,128,515 encounters for ACSCs, acute care settings were the initial site of care in 27.9%. Diagnoses with the greatest proportion of episodes presenting to acute care settings were urinary tract infection (52.0% of episodes) and pneumonia (44.6%). Encounters on the weekend (adjusted odds ratio [aOR] 6.30, 95% confidence interval [CI] 6.27-6.34 compared with weekday) and among children with capitated insurance (aOR 1.55, 95% CI 1.54-1.56 compared with fee for service) were associated with increased odds of seeking care first in an acute care setting. CONCLUSIONS: Acute care settings are the initial sites of care for more than one in four encounters for ACSCs among publicly insured children. Expanded access to primary care on weekends may shift care for ACSCs to the medical home.

Trends and Variation in Cervical Spine Imaging Utilization Across Children's Hospitals for Pediatric Trauma.

BACKGROUND: Cervical spine evaluation is a critical component in trauma evaluation, and though several pediatric cervical spine evaluation algorithms have been developed, none has been widely implemented. Here, we assess rates of cervical spine imaging use across children's hospitals, specifically temporal trends in imaging use, variation across hospitals in imaging used, and timing of magnetic resonance imaging in admitted patients. METHODS: Data from the Children's Hospital Associations Pediatric Health Information System was abstracted from 2015 to 2020. Patients less than 18 years of age seen in the emergency department with an International Classification of Diseases (ICD)-10 code indicative of trauma and cervical spine plain radiograph or computed tomography in the emergency department were included. Data visualization and descriptive statistics were used to assess rates of imaging use by age, year, hospital, injury severity, and day of service. Changes in rates of imaging use over time were evaluated via Chi-square test. RESULTS: Across 25,238 patient encounters at 35 children's hospitals, there was an increase in use of cervical spine computed tomography from 2015 to 2020 (28.5 to 36.5%). There was substantial inter-institutional variation in rates of use of plain radiographs versus computed tomography for initial evaluation of the cervical spine across all age groups and regardless of rates of severe injury across institutions. Magnetic resonance imaging was obtained more than three days after admission in 31.5% of intensive care patients who received this imaging. CONCLUSIONS: Increasing use of computed tomography, substantial inter-institutional variation in rates of use of plain radiographs versus computed tomography, and heterogenous timing of magnetic resonance imaging for evaluation of the pediatric cervical spine demonstrate the growing need for development and implementation of an age-specific cervical spine evaluation algorithm to guide judicious use of diagnostic resources. LEVEL OF EVIDENCE: Level III, Epidemiologic.

Association Between Hospital Arrival Time and Avoidable Transfer in Pediatric Trauma.

BACKGROUND: Avoidable transfers (AT) in pediatric trauma can increase strain on healthcare resources and families. We sought to identify characteristics of patients and their injuries that are associated with AT. METHODS: A multicenter retrospective cross-sectional study of the regional Trauma Registry was conducted from 1/1/10-12/31/21 of children <18 years-old who experienced an interfacility transfer. AT was defined as receiving hospital length of stay (LOS) < 48 hrs without procedure or intervention performed. Patient demographics, mechanism of injury, and arrival time were analyzed with descriptive statistics. A multivariable logistic regression was performed to analyze demographic and clinical factors associated with AT. RESULTS: We included 5438 trauma transfers, of which 2187 (40.2%) were AT. Patients experiencing AT had a median [IQR] age of 5 years [1-12] and most were male (67%) and Hispanic/Latino (46.3%). The odds of experiencing AT decreased as age increased and were less likely in females and Non-Hispanic Black children. Injuries from falls (ground level (OR = 2.48; 95%CI = 1.89-3.28) and >10 ft (OR = 3.20; 95%CI = 2.35-4.39)), sports/recreational activities (OR = 2.36; 95%CI = 1.78-3.16), MVCs (OR = 1.44; 95%CI = 1.05-1.98), and firearms (OR = 1.74; 95%CI = 1.15-2.62) were associated with an increased odds of AT. Time of arrival at the receiving facility in early hours (00:00-07:59) (OR = 1.48; 95%CI = 1.24-1.76) and evening hours (17:00-23:59) (OR = 1.75; 95%CI = 1.47-2.07) were associated with an increased odds of AT. CONCLUSION: Younger patients, injuries from falls, sports/recreational activities, MVCs, and firearms as well as arrival time outside of standard work hours are more likely to result in AT. Knowing these results, we can begin working with our referral centers to improve communication and strengthen institutional transfer criteria for pediatric trauma patients. Further investigation will then be needed to determine if the changes implemented have influenced care and lowered rates of avoidable transfer. LEVEL OF EVIDENCE: Level III.

Seasonality and temporal variation of pediatric trauma in Southern California.

INTRODUCTION: Seasonality of pediatric trauma has been previously described, although the association of season with hour of presentation is less understood. Both factors have potential implications for resource allocation and team preparedness. METHODS: A multicenter retrospective study was conducted to analyze the records of injured children <18 years-old who presented to one of the 15 trauma centers within Los Angeles County. Data from the County Trauma and Emergency Medicine Information System Registry was abstracted from 1/1/10 to 12/31/21. Patient demographics, mechanism of injury (MOI) and time of presentation by season were analyzed using Kruskal Wallis tests and chi-square tests. RESULTS: A total of 30,444 pediatric trauma presentations were included. Both the time of presentation and the MOI differed significantly by season with p < 0.001. Autumn had a higher incidence of pedestrian injuries during hours of 08:00 and 15:0020:00, and sports injuries from 16:00 to 21:00. In the Summer there were more burns between 17:00 and 23:00 and falls from greater than 10 ft after 13:00. The mode of transport used was also different across seasons (p = 0.03), with the use of both air and ground EMS greatest during summer and least during winter. The hours of greatest utilization remained relatively constant for all seasons for air transport (18:00-19:00 h) and ground transport (19:00-20:00 h). CONCLUSION: These data demonstrate the significant seasonal and temporal variation within pediatric trauma. These findings could be used to inform improvements in emergency response, and resource allocation in particular.

Pediatric Firearm Injury Emergency Department Visits From 2017 to 2022: A Multicenter Study.

BACKGROUND AND OBJECTIVE: Pediatric firearm injuries increased during the coronavirus disease 2019 pandemic, but recent trends in firearm injury emergency department (ED) visits are not well described. We aimed to assess how pediatric firearm injury ED visits during the pandemic differed from expected prepandemic trends. METHODS: We retrospectively studied firearm injury ED visits by children <18 years old at 9 US hospitals participating in the Pediatric Emergency Care Applied Research Network Registry before (January 2017 to February 2020) and during (March 2020 to November 2022) the pandemic. Multivariable Poisson regression models estimated expected visit rates from prepandemic data. We calculated rate ratios (RRs) of observed to expected visits per 30 days, overall, and by sociodemographic characteristics. RESULTS: We identified 1904 firearm injury ED visits (52.3% 15-17 years old, 80.0% male, 63.5% non-Hispanic Black), with 694 prepandemic visits and 1210 visits during the pandemic. Death in the ED/hospital increased from 3.1% prepandemic to 6.1% during the pandemic (P = .007). Firearm injury visits per 30 days increased from 18.0 prepandemic to 36.1 during the pandemic (RR 2.09, 95% CI 1.63-2.91). Increases beyond expected rates were seen for 10- to 14-year-olds (RR 2.61, 95% CI 1.69-5.71), females (RR 2.46, 95% CI 1.55-6.00), males (RR 2.00, 95% CI 1.53-2.86), Hispanic children (RR 2.30, 95% CI 1.30-9.91), and Black non-Hispanic children (RR 1.88, 95% CI 1.34-3.10). CONCLUSIONS: Firearm injury ED visits for children increased beyond expected prepandemic trends, with greater increases among certain population subgroups. These findings may inform firearm injury prevention efforts.

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 109/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 109/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

Critical Emergency Department Interventions and Clinical Deterioration in Children With Nonsevere Traumatic Intracranial Hemorrhage.

OBJECTIVE: Substantial practice variation exists in the management of children with nonsevere traumatic intracranial hemorrhage (tICH). A comprehensive understanding of rates and timing of clinically important tICH, including critical interventions and deterioration, along with associated clinical and neuroradiographic characteristics, will inform accurate risk stratification. METHODS: We conducted a single-center retrospective cohort study of children aged younger than 18 years evaluated in the emergency department (ED) from May 1, 2014 to February 28, 2020 with tICH and initial Glasgow Coma Scale (GCS) score of higher than 8. We determined rates of clinically important tICH after injury and within 96 hours of ED arrival, defined as immediate ED interventions (intubation, hyperosmotic agents, or neurosurgery within 4 hours of arrival) or clinically important deterioration (signs/symptoms with change in management). Associations between outcome and clinical and neuroradiographic characteristics were calculated using individual logistic regression models. RESULTS: Our sample included 135 children. Clinically important tICH was observed in 13.3% (n = 18); 9 (6.7%) underwent immediate ED interventions and 9 (6.7%) developed deterioration. Most (93.3%, n = 127) presented with an initial GCS ≥ 14, including all children who later deteriorated. Initial GCS (P = 0.001) and nonaccidental trauma (P = 0.024) mechanism were associated with the outcome. None of the 71 (52.6%) children with initial GCS ≥ 14, isolated, nonepidural hemorrhage after accidental injury developed clinically important tICH. CONCLUSIONS: Clinically important tICH occurred in 13% of children with nonsevere tICH, and 7% of children who did not undergo immediate ED interventions later deteriorated, all of whom had an initial GCS ≥ 14. However, a subgroup of children was identified as low risk based on clinical and neuroradiographic characteristics.

Firearm Injuries in Lower Opportunity Neighborhoods During the COVID Pandemic.

OBJECTIVES: We aimed to describe changes in pediatric firearm injury rates, severity, and outcomes after the coronavirus disease 2019 stay-at-home order in Los Angeles (LA) County. METHODS: A multicenter, retrospective, cross-sectional study was conducted on firearm injuries involving children aged <18-years in LA County before and after the pandemic. Trauma activation data of 15 trauma centers in LA County from the Trauma and Emergency Medicine Information System Registry were abstracted from January 1, 2018, to December 31, 2021. The beginning of the pandemic was set as March 19, 2020, the date the county stay-at-home order was issued, separating the prepandemic and during-pandemic periods. Rates of firearm injuries, severity, discharge capacity, and Child Opportunity Index (COI) were compared between the groups. Analysis was performed with χ2 tests and segmented regression. RESULTS: Of the 7693 trauma activations, 530 (6.9%) were from firearm injuries, including 260 (49.1%) in the prepandemic group and 270 (50.9%) in the during-pandemic group. No increase was observed in overall rate of firearm injuries after the stay-at-home order was issued (P = .13). However, firearm injury rates increased in very low COI neighborhoods (P = .01). Mechanism of injury, mortality rates, discharge capacity, and injury severity score did not differ between prepandemic and during-pandemic periods (all P values ≥.05). CONCLUSIONS: Although there was no overall increase in pediatric firearm injuries during the pandemic, there was a disproportionate increase in areas of very low neighborhood COI. Further examination of community disparity should be a focus for education, intervention, and development.

Secretory phospholipase (sPLA2-IIA) regulates breast cancer stem cells differentiation and metastatic potential.

Breast cancer is the second most cancer worldwide in females. The primary factor responsible for tumor recurrence is the presence of breast cancer stem cells (BCSCs), which escape the chemo-radiotherapy. In this study, we have investigated the role of Secretory phospholipase-A2 Group 2A (sPLA2-IIA) that is overexpressed in BCSCs of MCF7 and MDA-MB-231 breast cancer cell lines. Further, overexpression of sPLA2-IIA revealed an increased EGFR/JNK/c-JUN/c-FOS signaling in BCSCs, while sPLA2-IIA knockdown significantly reduced the percentage of BCSCs and decreased signaling in both the cell lines. Importantly, sPLA2-IIA knockdown showed differentiation of BCSCs. Strikingly, PET imaging showed a decreased metastatic potential of BCSCs. Our study revealed a novel role of sPLA2-IIA in regulating BCSCs, which play a crucial role in regulating the differentiation and metastatic potential of BCSCs.

Multicenter evaluation of a method to identify delayed diagnosis of diabetic ketoacidosis and sepsis in administrative data.

OBJECTIVES: To derive a method of automated identification of delayed diagnosis of two serious pediatric conditions seen in the emergency department (ED): new-onset diabetic ketoacidosis (DKA) and sepsis. METHODS: Patients under 21 years old from five pediatric EDs were included if they had two encounters within 7 days, the second resulting in a diagnosis of DKA or sepsis. The main outcome was delayed diagnosis based on detailed health record review using a validated rubric. Using logistic regression, we derived a decision rule evaluating the likelihood of delayed diagnosis using only characteristics available in administrative data. Test characteristics at a maximal accuracy threshold were determined. RESULTS: Delayed diagnosis was present in 41/46 (89 %) of DKA patients seen twice within 7 days. Because of the high rate of delayed diagnosis, no characteristic we tested added predictive power beyond the presence of a revisit. For sepsis, 109/646 (17 %) of patients were deemed to have a delay in diagnosis. Fewer days between ED encounters was the most important characteristic associated with delayed diagnosis. In sepsis, our final model had a sensitivity for delayed diagnosis of 83.5 % (95 % confidence interval 75.2-89.9) and specificity of 61.3 % (95 % confidence interval 56.0-65.4). CONCLUSIONS: Children with delayed diagnosis of DKA can be identified by having a revisit within 7 days. Many children with delayed diagnosis of sepsis may be identified using this approach with low specificity, indicating the need for manual case review.

OUTCOMES OF MISSED DIAGNOSIS OF PEDIATRIC APPENDICITIS, NEW-ONSET DIABETIC KETOACIDOSIS, AND SEPSIS IN FIVE PEDIATRIC HOSPITALS.

BACKGROUND: Missed diagnosis can predispose to worse condition-specific outcomes. OBJECTIVE: To determine 90-day complication rates and hospital utilization after a missed diagnosis of pediatric appendicitis, new-onset diabetic ketoacidosis (DKA), and sepsis. METHODS: We evaluated patients under 21 years of age visiting five pediatric emergency departments (EDs) with a study condition. Case patients had a preceding ED visit within 7 days of diagnosis and underwent case review to confirm a missed diagnosis. Control patients had no preceding ED visit. We compared complication rates and utilization between case and control patients after adjusting for age, sex, and insurance. RESULTS: We analyzed 29,398 children with appendicitis, 5366 with DKA, and 3622 with sepsis, of whom 429, 33, and 46, respectively, had a missed diagnosis. Patients with missed diagnosis of appendicitis or DKA had more hospital days and readmissions; there were no significant differences for those with sepsis. Those with missed appendicitis were more likely to have abdominal abscess drainage (adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 2.4-3.6) or perforated appendicitis (aOR 3.1, 95% CI 2.5-3.8). Those with missed DKA were more likely to have cerebral edema (aOR 4.6, 95% CI 1.5-11.3), mechanical ventilation (aOR 13.4, 95% CI 3.8-37.1), or death (aOR 28.4, 95% CI 1.4-207.5). Those with missed sepsis were less likely to have mechanical ventilation (aOR 0.5, 95% CI 0.2-0.9). Other illness complications were not significantly different by missed diagnosis. CONCLUSIONS: Children with delayed diagnosis of appendicitis or new-onset DKA had a higher risk of 90-day complications and hospital utilization than those with a timely diagnosis.

Pivotal role of AKR1B1 in pathogenesis of colitis associated colorectal carcinogenesis.

Identifying the target linking inflammation and oxidative stress to aggravate the disease progression will help to prevent colitis associated carcinogenesis. Since AKR1B1 overexpression is observed in inflammatory diseases and various cancers, we have investigated the role of AKR1B1 in colitis-associated colon carcinogenesis with the aid of epalrestat and its potent analogue NARI-29 (investigational molecule) as pharmacological probes. A TNF-α inducible NF-κB reporter cell line (GloResponse™ NF-κB-RE-luc2P HEK293) and dextran sodium sulfate (DSS) and 1,2 dimethyl hydrazine (DMH))-induced mouse model was used to investigate our hypothesis in vitro and in vivo. Clinically, an increased expression of AKR1B1 was observed in patients with ulcerative colitis. Our in vitro and in vivo findings suggest that the AKR1B1 modulated inflammation and ROS generation for the progression of colitis to colon cancer. AKR1B1 overexpression was observed in DSS + DMH-treated mice colons. Moreover, we could observe histopathological changes like immune cell infiltration, aberrant crypt foci, and tumour formation in DC groups. Mechanistically, we have witnessed modulation of the IKK/IκB/NF-κB and Akt/FOXO-3a/DR axis, increased inflammatory cytokines, increased expression of proliferative markers, Ki-67 and PCNA, and accumulation of ß-catenin in the colon epithelium. However, pharmacological inhibition of AKR1B1 using NARI-29 or EPS has reversed the clinical, histopathological, and molecular alterations induced by DSS + DMH, confirming the obvious role of AKR1B1 in the promotion of colitis-associated carcinogenesis. In conclusion, our findings suggest that AKR1B1 targeted therapy could be a promising strategy for preventing CA-CRC and NARI-29 could be developed as a potent AKR1B1 inhibitor.