FXR deletion attenuates intestinal barrier dysfunction in murine acute intestinal inflammation.

Accumulating literature suggests that the farnesoid-X receptor (FXR), a nuclear bile acid receptor best known for its role in bile acid homeostasis, is also a potent context-dependent regulator of inflammation. FXR may thus be relevant to several intestinal disease states including inflammatory bowel disease, necrotizing enterocolitis, and sepsis. In this study, we tested the effects of FXR deletion on acute murine intestinal inflammation. We found that FXR knockout (KO) mice were protected from intestinal injury and barrier dysfunction induced by lipopolysaccharide (LPS) injection, dithizone (DI)/Klebsiella, and cecal ligation/puncture models. In the LPS model, RNA sequencing and qPCR analysis showed that this protection correlated with substantial reduction in LPS-induced proinflammatory gene expression, including lower tissue levels of Il1a, Il1b, and Tnf. Examining functional effects on the epithelium, we found that LPS-induced tight junctional disruption as assessed by internalization of ZO-1 and occludin was ameliorated in FXR KO animals. Taken together, these data suggest a role for FXR in the intestinal barrier during inflammatory injury.NEW & NOTEWORTHY Intestinal barrier failure is a hallmark in gut-origin sepsis. We demonstrate that the intestinal barriers of farnesoid-X receptor (FXR) knockout (KO) animals are protected from inflammatory insult using multiple models of acute intestinal inflammation. This protection is due to decreased inflammatory cytokine production and maintenance of tight junctional architecture seen within the KO animals. This is the first report of FXR deletion being protective to the intestinal barrier.

Clinical Characteristics of Avoidable Patient Transfers for Suspected Pediatric Appendicitis.

INTRODUCTION: Pediatric surgical care is becoming increasingly regionalized, often resulting in limited access. Interfacility transfers pose a significant financial and emotional burden to when they are potentially avoidable. Of transferred patients, we sought to identify clinical factors associated with avoidable transfers in pediatric patients with suspected appendicitis. METHODS: We performed a single-center retrospective study at an academic tertiary referral children's hospital in an urban setting. We included children who underwent interfacility transfer to our center with a transfer diagnosis of appendicitis from July 1, 2021 to June 30, 2023. Encounters were designated as either an appropriate transfer (underwent appendectomy) or an avoidable transfer (did not undergo appendectomy). Encounters treated nonoperatively for complicated appendicitis were excluded. Bivariate analysis was performed using Mann-Whitney test and chi-square tests. RESULTS: A total of 444 patients were included: 71.2% were classified as appropriate transfers and 28.8% as avoidable transfers. Patients with avoidable transfer were younger compared to those in the appropriate transfer cohort (median age 9 y, interquartile range: 7-13 versus 11 y, interquartile range: 8-14; P < 0.001). Avoidable transfers less frequently presented with the typical symptoms of fever, migratory abdominal pain, anorexia, and nausea/emesis (P = 0.005). Avoidable transfers also reported shorter symptom duration (P = 0.040) with lower median white blood cell count (P < 0.001), neutrophil percentage (P < 0.001), and C-reactive protein levels (P < 0.003). Avoidable transfers more frequently underwent repeat imaging upon arrival (42.9% versus 12.7%, P < 0.001). CONCLUSIONS: These findings highlight the importance of clinical history in children with suspected appendicitis. Younger patients without typical symptoms of appendicitis, those with a shorter duration of symptoms, and lower serum inflammatory markers may benefit from close observation without transfer.

Primary caregiver employment status is associated with traumatic brain injury in children in the USA.

BACKGROUND: Traumatic brain injury (TBI) is a common injury in children. Previous literature has demonstrated that TBI may be associated with supervision level. We hypothesised that primary caregiver employment would be associated with child TBI. METHODS: A retrospective cross-sectional study was performed for children aged 0-17 using the National Survey of Children's Health (NSCH) 2018-2019. The NSCH contains survey data on children's health completed by adult caregivers from randomly selected households across the USA. We compared current TBI prevalence between children from households of different employment statuses. Current TBI was defined by survey responses indicating a healthcare provider diagnosed TBI or concussion for the child and the condition was present at the time of survey completion. Household employment status was categorised as two caregivers employed, two caregivers unemployed, one of two caregivers unemployed, single caregiver employed and single caregiver unemployed. Multivariable logistic regression was performed, controlling for sociodemographic factors. RESULTS: Of 56 865 children, median age was 10 years (IQR: 5-14), and 0.6% (n=332) had a current TBI. Children with TBI were older than children without TBI (median 12 years vs 10 years, p<0.001). On multivariable regression, children with at least one caregiver unemployed had increased odds of current TBI compared with children with both caregivers employed. CONCLUSIONS: Children with at least one caregiver unemployed had increased TBI odds compared with children with both caregivers employed. These findings highlight a population of families that may benefit from injury prevention education and intervention.

Clinical outcomes of children with COVID-19 and appendicitis: a propensity score matched analysis.

OBJECTIVE: Early in the COVID-19 pandemic, many children with appendicitis and COVID-19 were initially treated non-operatively and later underwent interval appendectomy. Currently, children with both appendicitis and COVID-19 frequently undergo upfront appendectomy. The impact of this return to upfront surgical management on patient outcomes is unknown. This study compared outcomes of pediatric patients with and without COVID-19 infection undergoing appendectomy. STUDY DESIGN: A retrospective cohort study of children < 21y who underwent appendectomy from 3/19/2020 to 7/31/2022 at 50 Pediatric Health Information System children's hospitals was conducted. Children with documented COVID-19 were identified. Exclusions included preoperative ventilator or supplemental oxygen dependence, and missing data. To evaluate COVID-19 positive versus COVID-19 negative patients, we used a propensity score matched on sociodemographics, comorbidities, laparoscopy, perforation, and hospital. Chi-square and Mann-Whitney U tests identified differences between groups in length of stay, postoperative drain placement, 30-day re-admission, and mechanical ventilation requirements. RESULTS: Overall, 51,861 children of median age 11y (IQR: 8-14) underwent appendectomy, of whom 1,440 (2.3%) had COVID-19. Most were male (60.3%), White (72.1%) and non-Hispanic (61.4%). Public insurance was the most common (47.5%). We created a matched cohort of 1,360 COVID-19 positive and 1,360 COVID-19 negative children. Children with COVID-19 had shorter hospitalizations (1d, IQR: 1-4 vs. 2d, IQR: 1-5, p = 0.03), less postoperative peritoneal drain placement (2.4% vs. 4.1%, p = 0.01), and fewer 30-day readmissions (9.0% vs. 11.4%, p = 0.04). However, no difference in incidence or duration of mechanical ventilation (p > 0.05) was detected. CONCLUSIONS: Our findings suggest that upfront appendectomy for children with appendicitis and COVID-19 has similar outcomes compared to children without COVID-19. 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.

A Standardized Post-gastrostomy Feeding Protocol for Pediatric Patients Reduces Time to Postoperative Goal Feeding Volume.

BACKGROUND: Gastrostomy creation is a common pediatric surgical procedure, but the time to initiation of feeds and to goal feeding volumes postoperatively varies greatly. Delays in reaching goal feeding volumes promote malnutrition and may prolong hospital length of stay. We hypothesized that implementing an accelerated, standardized post-gastrostomy feeding protocol would allow patients to reach goal feeding volumes sooner, without increasing postoperative complications. METHODS: We conducted a retrospective cohort study of children who underwent gastrostomy tube placement between 1/1/2022 and 11/30/2023. The feeding protocol was implemented on 11/16/2022, with patients separated into pre- and post-protocol cohorts. Abstracted data included comorbidities, time to initiation of enteral feeds, time to goal feeding volume, and postoperative complications. RESULTS: 322 patients were included: 166 pre-protocol and 156 post-protocol. The post-protocol cohort had a greater proportion of patients with gastrointestinal and/or cardiac comorbidities (P < .001). Through the protocol, postoperative enteral feeds were initiated significantly faster (5.4 hrs [IQR 43-7.7] vs 7.0 hrs [IQR 5.6-14.3]; P < .001). The post-protocol cohort also achieved goal feeding volumes sooner (12.8 hrs [IQR 9.1-25.3] vs 26.3 hrs [IQR 21.6-38.9]; P < .001). Postoperative complication rates did not differ between cohorts. Sub-analysis of children with complex cardiac conditions also demonstrated faster time to goal nutrition without an associated increase in postoperative events. DISCUSSION: These findings demonstrate that our accelerated post-gastrostomy feeding protocol was effective in achieving goal enteral nutrition earlier without increasing postoperative adverse outcomes. This protocol may be used by other centers to safely expedite time to goal enteral feeds in children postoperatively.

Pediatric Trauma Mortality Differs by Neighborhood Opportunity Level.

OBJECTIVE: Traumatic injuries are a leading cause of death in children and a child's neighborhood characteristics can be a risk factor. Our objective was to describe the association between pediatric trauma mortality and Child Opportunity Index (COI). METHODS: A multicenter, retrospective cross-sectional study was conducted across 15 trauma centers from 2010 to 2021 within a large metropolitan county to evaluate trauma activation mortalities involving children <18 years-old. We examined clinical and demographic data from the county trauma registry and linked home zip code to COI, a measure of neighborhood level resources critical for children's development. Proportion of mortalities were compared to the proportion of children within each COI quintile and injury mechanism was evaluated across COI quintile. Analysis was performed using Kruskal-Wallis and chi-square tests (α = 0.05). RESULTS: Of 31,702 pediatric trauma activations, 513 (1.6%) mortalities occurred. Mortalities mostly resulted from assaults (37.0%), pedestrian injuries (26.7%), and motor-vehicle collisions (18.7%). Of all mortalities, 32.6% were firearm related, either from an assault or self-inflicted. A greater proportion of mortalities were children from very low (47.6%) and low (20.9%) COI neighborhoods with fewer from higher (8.8.% and 7.6%) COI-neighborhoods compared to the county's proportion of children within these quintiles (p < 0.001). The injury mechanisms were different, with mortalities of lower COI neighborhoods being associated with assaults (p = 0.005), while mortalities of higher COI neighborhoods were self-inflicted (p = 0.003). CONCLUSION: Lower opportunity neighborhoods had a higher incidence of pediatric trauma mortality. Mortality mechanism varied across neighborhoods with assault greater in lower opportunity neighborhoods and self-inflicted among higher opportunity neighborhoods. LEVEL OF EVIDENCE: Level III.

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.

Evaluation of Postoperative Outcomes After Enterostomy Closure in Low Body Weight Infants: A Multi-Center Retrospective Analysis.

BACKGROUND: The minimum weight for enterostomy closure (EC) in infants remains debated with the current acceptable cut-off of >2 kg. As enterostomy-related complications or high enterostomy output (>30cc/kg/d) may prohibit a premature infant from reaching 2 kg, additional data is needed to evaluate the safety of EC in infants <2 kg. The objective of this study was to evaluate postoperative outcomes in low body weight (<2 kg) infants undergoing EC compared to larger infants. METHODS: We performed a multi-center retrospective analysis from 1/1/2012-12/31/2022 of all infants (age <1 year) who were <4 kg at time of EC. Primary outcomes included postoperative complications and 30-day mortality. Non-parametric analysis was performed using the Kruskal-Wallis one-way analysis of variance and chi-square tests. Univariable logistic regression was performed to identify factors associated with postoperative complications. RESULTS: Of 92 infants, 15 infants (16.3%) underwent EC at <2 kg, 16 (17.4%) at 2-2.49 kg, 31 (33.7%) at 2.5-2.99 kg, and 30 (32.6%) at ≥3 kg. Infants <2 kg at time of EC exhibited higher rates of hyperbilirubinemia (P = .030), neurologic comorbidities (P = .030), and high enterostomy output (P = .041). There was no difference in postoperative complications (P = .460) or 30-day mortality (P = .460) between the <2 kg group and larger weight groups. Low body weight was not associated with an increased risk for developing a postoperative complication (OR: 1.001, 95% CI: 1.001-1.001; P = .032). CONCLUSION: Our findings suggest that EC in infants <2 kg may be safe with comparable postoperative outcomes to larger weight infants. Thus, the timing of EC should be based on the infant's physiologic status, in contrast to a predetermined minimum weight cut-off.

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.