Implementing Screening, Brief Interventions, and Referral to Treatment at Pediatric Trauma Centers: A Step Wedge Cluster Randomized Trial.

BACKGROUND: Pediatric trauma centers have had challenges meeting the American College of Surgeons criteria for screening and intervening for alcohol with adolescent trauma patients. The study objective was to conduct an implementation trial to evaluate the effectiveness of the Science to Service Laboratory (SSL) implementation strategy in improving alcohol and other drugs (AOD) screening, brief intervention, and referral to treatment (SBIRT) delivery at pediatric trauma centers. METHODS: Using a stepped wedge cross-over cluster randomized design, 10 US pediatric trauma centers received the SSL implementation strategy to deliver SBIRT with admitted adolescent (12-17 years old) trauma patients. The strategy adapted three core SSL elements: didactic training, performance feedback, and facilitation. The main outcome measured was SBIRT reach. Data were collected from each center's electronic health record (EHR) during pre- and post-implementation wedges (2018-2022). RESULTS: EHR data from 8461 adolescent patients were extracted. Aggregated across all sites, the reach of screening with a validated AOD screening tool increased significantly from 25.2% (95% CI: 23.9, 26.5%) of adolescents during pre-implementation to 47.7% (95% CI: 46.3%, 49.2%) post-implementation. There was variability of change across centers. Brief interventions continued to be delivered at high levels to identified adolescents. Referral to primary care providers for further AOD discussion or referral to specialty service for adolescents with high risk use did not improve post-implementation and remained low. CONCLUSIONS: The SSL implementation strategy can be successfully utilized by pediatric trauma centers to improve AOD screening, but challenges exist in connecting adolescents for continuation of AOD discussions after discharge. LEVEL OF EVIDENCE: Level II, Therapeutic.

Examining the Influence of Historical Redlining on Firearm Injuries in Current Day Baltimore, Maryland.

Firearm injuries are a common and major public health problem in Baltimore, Maryland. The city is also one of the first U.S. cities in which the 1930s discriminatory practice of redlining first emerged. This study examines the association between current day firearm injuries and residence in these historically redlined areas at a neighborhood level using zip codes. Firearm injury outcomes in patients who presented to a hospital in Maryland from 2015 to 2020 were measured from the Health Services Cost Review Commission (HSCRC) in conjunction with both geospatial data from Richmond's Digital Scholarship Lab's Mapping Inequality project and population data from the U.S. Census. A redlining score was calculated to represent the extent of redlining in each zip code. Negative binomial regression models were utilized to measure the association between neighborhood zip codes and rate of firearm injuries. Our adjusted regression model shows that for every one-unit increase of the Home Owners' Loan Corporation (HOLC) redlining score, there is a 2.24-fold increase in the rate of firearm injuries (RR 2.24; 95% CI: 0.31, 1.31, p < 0.001). These findings suggest a strongassociation between historically redlined areas and population risk of firearm injury today. Further research is needed to investigate the underlying mechanisms that may contribute to this relationship, such as access to firearms or social and economic factors. Overall, our study highlights the potential impact of historical redlining policies on contemporary health outcomes in Baltimore.

Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies.

Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with a high risk of psychiatric and neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack of effective treatments underscore the urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as a crucial bidirectional pathway connecting the brain and the gastrointestinal (GI) system through an intricate network of neuronal, hormonal, and immunological pathways. Four main pathways are primarily implicated in this crosstalk, including the systemic immune system, autonomic and enteric nervous systems, neuroendocrine system, and microbiome. TBI induces profound changes in the gut, initiating an unrestrained vicious cycle that exacerbates brain injury through the brain-gut axis. Alterations in the gut include mucosal damage associated with the malabsorption of nutrients/electrolytes, disintegration of the intestinal barrier, increased infiltration of systemic immune cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction and disruption in the enteric nervous system (ENS) and autonomic nervous system (ANS). Collectively, these changes further contribute to brain neuroinflammation and neurodegeneration via the gut-brain axis. In this review article, we elucidate the roles of various anti-inflammatory pharmacotherapies capable of attenuating the dysregulated inflammatory response along the brain-gut axis in TBI. These agents include hormones such as serotonin, ghrelin, and progesterone, ANS regulators such as beta-blockers, lipid-lowering drugs like statins, and intestinal flora modulators such as probiotics and antibiotics. They attenuate neuroinflammation by targeting distinct inflammatory pathways in both the brain and the gut post-TBI. These therapeutic agents exhibit promising potential in mitigating inflammation along the brain-gut axis and enhancing neurocognitive outcomes for TBI patients.

Pediatric Trauma Recidivism: A Statewide Risk Factor Analysis of the Maryland Health Services Cost Review Commission (HSCRC).

BACKGROUND: National estimates suggest pediatric trauma recidivism is uncommon but are limited by short follow up and narrow ascertainment. We aimed to quantify the long-term frequency of trauma recidivism in a statewide pediatric population and identify risk factors for re-injury. METHODS: The Maryland Health Services Cost Review Commission Dataset was queried for 0-19-year-old patients with emergency department or inpatient encounters for traumatic injuries between 2013 and 2019. We measured trauma recidivism by identifying patients with any subsequent presentation for a new traumatic injury. Univariate and multivariable regressions were used to estimate associations of patient and injury characteristics with any recidivism and inpatient recidivism. RESULTS: Of 574,472 patients with at least one injury encounter, 29.6% experienced trauma recidivism. Age ≤2 years, public insurance, and self-inflicted injuries were associated with recidivism regardless of index treatment setting. Of those with index emergency department presentations 0.06% represented with an injury requiring inpatient admission; unique risk factors for ED-to-inpatient recidivism were age >10 years (aOR 1.61), cyclist (aOR 1.31) or burn (aOR 1.39) mechanisms, child abuse (aOR 1.27), and assault (aOR 1.43). Among patients with at least one inpatient encounter, 6.3% experienced another inpatient trauma admission, 3.4% of which were fatal. Unique risk factors for inpatient-to-inpatient recidivism were firearm (aOR 2.48) and motor vehicle/transportation (aOR 1.62) mechanisms of injury (all p < 0.05). CONCLUSIONS: Pediatric trauma recidivism is more common and morbid than previously estimated, and risk factors for repeat injury differ by treatment setting. Demographic and injury characteristics may help develop and target setting-specific interventions. LEVEL OF EVIDENCE: III (Retrospective Comparative Study).

Evaluation of cervical spine clearance scores in children younger than 3 years with blunt trauma.

OBJECTIVE: The PEDSPINE I and PEDSPINE II scores were developed to determine when patients require advanced imaging to rule out cervical spine injury (CSI) in children younger than 3 years of age with blunt trauma. This study aimed to evaluate these scores in an institutional cohort. METHODS: The authors identified patients younger than 3 years with blunt trauma who received cervical spine MRI from their institution's prospective database from 2012 to 2015. Patient demographics, injury characteristics, and imaging were compared between patients with and without CSI using chi-square and Wilcoxon rank-sum tests. RESULTS: Eighty-eight patients were identified, 8 (9%) of whom had CSI on MRI. The PEDSPINE I system had a higher sensitivity (50% vs 25%) and negative predictive value (93% vs 92%), whereas PEDSPINE II had a higher specificity (91% vs 65%) and positive predictive value (22% vs 13%). Patients with CSI missed by the scores had mild, radiologically significant ligamentous injuries detected on MRI. Both models would have recommended advanced imaging for the patient who required halo-vest fixation (risk profile: no CSI, 81.9%; ligamentous, 10.1%; osseous, 8.0%). PEDSPINE I would have prevented 52 (65%) of 80 uninjured patients from receiving advanced imaging, whereas PEDSPINE II would have prevented 73 (91%). Using PEDSPINE I, 10 uninjured patients (13%) could have avoided intubation for imaging. PEDSPINE II would not have spared any patients intubation. CONCLUSIONS: Current cervical spine clearance algorithms are not sensitive or specific enough to determine the need for advanced imaging in children. However, these scores can be used as a reference in conjunction with physicians' clinical impressions to reduce unnecessary imaging.

Documentation of Trauma-Informed Care Elements for Young People Hospitalized After Assault Trauma.

INTRODUCTION: Violent traumatic injury, including firearm violence, can adversely impact individual and community health. Trauma-informed care (TIC) can promote resilience and prevent future violence in patients who have experienced trauma. However, few protocols exist to facilitate implementation of TIC for patients who survive traumatic injury. The purpose of the study is to characterize documentation of TIC practices and identify opportunities for intervention in a single academic quaternary care center. METHODS: This study is a retrospective chart review analyzing the documentation of trauma-informed elements in the electronic medical record of a random sample of youth patients (ages 12-23) admitted for assault trauma to the pediatric (n = 50) and adult trauma (n = 200) services between 2016 and mid-2021. Descriptive statistics were used to summarize patient demographics, hospitalization characteristics, and documentation of trauma-informed elements. Chi-square analyses were performed to compare pediatric and adult trauma services. RESULTS: Among pediatric and adult assault trauma patients, 36.0% and 80.5% were hospitalized for firearm injury, respectively. More patients admitted to the pediatric trauma service (96%) had at least one trauma-informed element documented than patients admitted to the adult service (82.5%). Social workers were the most likely clinicians to document a trauma-informed element. Pain assessment and social support were most frequently documented. Safety assessments for suicidal ideation, retaliatory violence, and access to a firearm were rarely documented. CONCLUSIONS: Results highlight opportunities to develop trauma-informed interventions for youth admitted for assault trauma. Standardized TIC documentation could be used to assess risk of violent reinjury and mitigate sequelae of trauma.

Interposing Rectus and Gracilis Muscle Flaps For Pelvic Reconstruction in Bladder Exstrophy After Bladder Neck Closure.

BACKGROUND: The exstrophy-epispadias complex is a spectrum of ventral wall malformations including classic bladder exstrophy (CBE) and cloacal exstrophy (CE). Patients undergo multiple soft-tissues procedures to achieve urinary continence. If unsuccessful bladder neck closure (BNC) is performed, muscle flaps may be used to reinforce BNC or afterwards for fistula reconstruction. In this study, patients reconstructed using a rectus abdominis or gracilis muscle flap were reviewed. METHODS: A retrospective cohort study of exstrophy-epispadias complex patients who underwent BNC and had a muscle fap was performed. Indication for flap use, surgical technique, risks for BNC failure including mucosal violations (MVs) were reviewed. MVs were prior bladder mucosa manipulation for exstrophy closure, repeat closure(s) and bladder neck reconstruction. Success was defined as BNC without fistula development. RESULTS: Thirty-four patients underwent reconstruction. Indications included during BNC (n=13), fistula closure after BNC (n=17), following BNC during open cystolithotomy (n=1) or fistula closure after open cystolithotomy (n=3). A vesicourethral fistula developed most frequently in CBE (88.9%) and vesicoperineal fistula in CE (87.5%). Thirty-three rectus flaps and 3 gracilis flap were used with success achieved in 97.1% and 66.7%, respectively. All 34 patients achieved success and 2 CE patients required a second flap. CONCLUSION: The rectus flap is preferred as it covers the antero-inferior bladder and pelvic floor to prevent urethral, cutaneous, and perineal fistula formation. The gracilis flap only reaches the pelvic floor to prevent urethral and perineal fistula development. Increased MVs, increase the risk of fistula formation and may influence the need for prophylactic flaps.

Ccr2 Dependent Monocytes Exacerbate Intestinal Inflammation and Modulate Gut Serotonergic Signaling Following Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) leads to acute gastrointestinal dysfunction and mucosal damage, resulting in feeding intolerance. Ccr2+ monocytes are crucial immune cells that regulate the gut's inflammatory response via the brain-gut axis. Using CCR2KO mice, we investigated the intricate interplay between these cells to better elucidate the role of systemic inflammation after TBI. METHODS: A murine-controlled cortical impact model was utilized, and results were analyzed on post-injury days (PID) 1 and 3. The experimental groups included (1) Sham C57Bl/6 wild-type (WT), (2) TBI WT, (3) Sham CCR2KO and (4) TBI CCR2KO. Mice were euthanized on PID 1 and 3 to harvest the ileum and study intestinal dysfunction and serotonergic signaling using a combination of quantitative real-time PCR (qRT-PCR), immunohistochemistry, FITC-dextran motility assays, and flow cytometry. Student's t-test and one-way ANOVA were used for statistical analysis, with significance achieved when p < 0.05. RESULTS: TBI resulted in severe dysfunction and dysmotility of the small intestine in WT mice as established by significant upregulation of inflammatory cytokines iNOS, Lcn2, TNFα, and IL1ß and the innate immunity receptor toll-like receptor 4 (Tlr4). This was accompanied by disruption of genes related to serotonin synthesis and degradation. Notably, CCR2KO mice subjected to TBI showed substantial improvements in intestinal pathology. TBI CCR2KO groups demonstrated reduced expression of inflammatory mediators (iNOS, Lcn2, IL1ß, and Tlr4) and improvement in serotonin synthesis genes, including tryptophan hydroxylase 1 (Tph1) and dopa decarboxylase (Ddc). CONCLUSION: Our study reveals a critical role for Ccr2+ monocytes in modulating intestinal homeostasis after TBI. Ccr2+ monocytes aggravate intestinal inflammation and alter gut-derived serotonergic signaling. Therefore, targeting Ccr2+ monocyte-dependent responses could provide a better understanding of TBI-induced gut inflammation. Further studies are required to elucidate the impact of these changes on brain neuroinflammation and cognitive outcomes. STUDY TYPE: Original Article (Basic Science, level of evidence N/A).

Delphi Process for Validation of Fluid Treatment Algorithm for Critically Ill Pediatric Trauma Patients.

INTRODUCTION: While intravenous fluid therapy is essential to re-establishing volume status in children who have experienced trauma, aggressive resuscitation can lead to various complications. There remains a lack of consensus on whether pediatric trauma patients will benefit from a liberal or restrictive crystalloid resuscitation approach and how to optimally identify and transition between fluid phases. METHODS: A panel was comprised of physicians with expertise in pediatric trauma, critical care, and emergency medicine. A three-round Delphi process was conducted via an online survey, with each round being followed by a live video conference. Experts agreed or disagreed with each aspect of the proposed fluid management algorithm on a five-level Likert scale. The group opinion level defined an algorithm parameter's acceptance or rejection with greater than 75% agreement resulting in acceptance and greater than 50% disagreement resulting in rejection. The remaining were discussed and re-presented in the next round. RESULTS: Fourteen experts from five Level 1 pediatric trauma centers representing three subspecialties were included. Responses were received from 13/14 participants (93%). In round 1, 64% of the parameters were accepted, while the remaining 36% were discussed and re-presented. In round 2, 90% of the parameters were accepted. Following round 3, there was 100% acceptance by all the experts on the revised and final version of the algorithm. CONCLUSIONS: We present a validated algorithm for intavenous fluid management in pediatric trauma patients that focuses on the de-escalation of fluids. Focusing on this time point of fluid therapy will help minimize iatrogenic complications of crystalloid fluids within this patient population.

Counseling for opioids prescribed at discharge of hospitalized adolescent trauma patients.

BACKGROUND: Expert consensus recommends prescription opioid safety counseling be provided when prescribing an opioid. This may be especially important for youth with preexistent alcohol and other drug (AOD) use who are at higher risk of developing opioid use disorder. This study examined the frequency that adolescent trauma patients prescribed opioids at hospital discharge received counseling and if this differed by adolescents' AOD use. METHOD: This study was embedded within a larger prospective stepped-wedge type III hybrid implementation study of AOD screening across a national cohort of pediatric trauma centers. Data were collected during 2018-2021 from admitted adolescent trauma patients (12-17 yo) at seven centers. Patient data were extracted from the electronic health record (EHR) on any prescribed discharged opioids, documentation of counseling delivered on prescribed opioid, who delivered counseling, and patients' AOD screening results. Additionally, adolescents received an online survey within 30 days of hospital discharge that included asking about hospital discussions on safe use of prescription pain medication. RESULTS: Of the 247 adolescent trauma patients enrolled, 158 completed the 30-day survey. AOD screening results were documented in the EHR for 139 patients (88%), with 69 (44.1%) screening AOD-positive. Opioids at discharge were prescribed to 86 (54.4%) adolescent patients, with no significant difference between those screened AOD-positive and AOD-negative (42.4% vs. 46.3%, p = 0.89). Counseling was documented in the EHR for 30 (34.9%) of those prescribed an opioid and was not significantly different by sex, age, race, ethnicity or between adolescent patients with documentation of AOD use (29.3%) versus those who did not (33.3%, p = 0.71). According to the adolescent survey, among those prescribed an opioid, 61.2% reported someone had talked with them about safe use of newly prescribed pain medications with again no difference between AOD-positive and AOD-negative screening results (p = 0.34). CONCLUSIONS: Although adolescent trauma patients recalled discussions on safe use of prescribed pain medication more often than was documented in the EHR, these discussions were not universal and did not differ if adolescents had screened positive or negative for AOD use as documented in the EHR. TRIAL REGISTRY: clinicaltrials.gov NCT03297060.

Multi-staged vs Single-staged Pelvic Osteotomy in the Modern Treatment of Cloacal Exstrophy: Bridging the Gap.

PURPOSE: Staged pelvic osteotomy has been shown in the past to be an effective tool in the closure of the extreme pubic diastasis of cloacal exstrophy. The authors sought to compare orthopedic complications between non-staged pelvic osteotomies and staged pelvic osteotomies in cloacal exstrophy. METHODS: A prospectively maintained exstrophy-epispadias complex database of 1510 patients was reviewed for cloacal exstrophy bladder closure events performed with osteotomy at the authors' institution. Bladder closure failure was defined as any fascial dehiscence, bladder prolapse, or vesicocutaneous fistula within one year of closure. There was a total of 172 cloacal exstrophy and cloacal exstrophy variant patients within the database and only closures at the authors' institution were included. RESULTS: 64 closure events fitting the inclusion criteria were identified in 61 unique patients. Staged osteotomy was performed in 42 closure events and non-staged in 22 closures. Complications occurred in 46/64 closure events, with 16 grade III/IV complications. There were no associations between staged osteotomy and overall complication or grade III/IV complications (p = 0.6344 and p = 0.1286, respectively). Of the 46 total complications, 12 were orthopedic complications with 6 complications being grade III/IV. Staged osteotomy closure events experienced 10/42 orthopedic complications while non-staged osteotomy closures experienced 2/22 orthopedic complications, however this did not reach significance (p = 0.1519). Of the 64 closure events, 57 resulted in successful closure with 6 failures and one closure with planned cystectomy. CONCLUSION: This study confirms, in a larger series, superior outcomes when using staged pelvic osteotomy in cloacal exstrophy bladder closure. Staged osteotomy was shown to be a safe alternative to non-staged osteotomy that can decrease the risk of closure failure in this group. Staged pelvic osteotomy should be considered in all patients undergoing cloacal exstrophy bladder closure. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.

Mucosal Violations and Their Effect on Successful Bladder Neck Closure in Cloacal Exstrophy.

BACKGROUND: Cloacal exstrophy (CE) is rare and challenging to reconstruct. In the majority of CE patients voided continence cannot be achieved and so patients often undergo bladder neck closure (BNC). Prior mucosal violations (MVs), a surgical event when the bladder mucosa was opened or closed, significantly predicted failed BNC in classic bladder exstrophy with an increased likelihood of failure after 3 or more MVs. The aim of this study was to assess predictors for failed BNC in CE. METHODS: CE patients who underwent BNC were reviewed for risk factors for failure including osteotomy use, successful primary closure, and number of MVs. Chi-squared and Fisher's exact tests were used for comparing baseline characteristics and surgical details. RESULTS: Thirty-five patients underwent BNC. Eleven patients (31.4%) failed BNC including a vesicoperineal fistula in nine, vesicourethral and vesicocutaneous fistula in one each. The fistula rate in patients with 2 or more MVs was 47.4% (p = 0.0252). Two patients subsequently developed a vesicocutaneous fistula after undergoing repeated cystolithotomies. A rectus abdominis or gracilis muscle flap were used to close the fistula in 11 and 2 patients, respectively. CONCLUSIONS: MVs have a greater impact in CE with an increased risk of failed BNC after 2 MVs. CE patients are most likely to develop a vesicoperineal fistula while a vesicocutaneous fistula is more likely after repeat cystolithotomy. A prophylactic muscle flap should be considered at time of BNC in patients with 2 or more MVs. LEVELS OF EVIDENCE: Prognosis Study, Level III.

A Single-Institutional Experience With Prenatal Diagnosis of Cloacal Exstrophy: Room for Improvement.

INTRODUCTION: A single institutional study characterizes the rate of prenatal diagnosis of cloacal exstrophy (CE) and examines its role on successful primary closures. MATERIALS AND METHODS: An institutional database of 1485 exstrophy-epispadias patients was reviewed retrospectively for CE patients with confirmed presence/absence of prenatal diagnostics, primary exstrophy closure since 2000, institution of closure, and at least 1 year of follow up following closure. RESULTS: The cohort included 56 domestic patients and 9 international patients. Overall, 78.6% (n = 44) of domestic patients were prenatally diagnosed while 21.4% (n = 12) were diagnosed postnatally. A positive trend was observed in the rate of prenatal diagnosis across the study period, 56.3%, 84.2%, 88.9% respectively (p = 0.025). Confirmatory fMRI was obtained in 40.9% (n = 18) of prenatally diagnosed cases. Patients diagnosed prenatally were found to be more likely to undergo treatment at exstrophy centers of excellence (72.1% v 33.3%, p = 0.020). Prenatal diagnosis was not predictive of increased rate of successful primary closure (75.6% vs 75.0%; p = 1.00; OR: 1.03, 95% CI: 0.23-4.58). Primary closures undertaken at exstrophy centers of excellence were significantly more likely to be successful compared to outside hospitals (90.9% v 50.0%, p = 0.002). CONCLUSIONS: The rate of prenatal diagnosis of CE in patients referred for management to a high-volume exstrophy center is improving. Despite this improvement, patients continue to be missed in the prenatal period. While prenatal diagnosis offers the ideal opportunity to educate, counsel, and prepare expectant families, patients diagnosed at birth are not disadvantaged in their ability to receive a successful primary closure. Further research should investigate the benefit of patient referral to high-volume exstrophy centers of care to ensure optimal care and outcomes.

Epidemiology and clinical characteristics of drowning patients presenting to a pediatric emergency department from 2017 to 2020.

BACKGROUND: Drowning is a common mechanism of injury in the pediatric population that often requires hospitalization. The primary objective of this study was to describe the epidemiology and clinical characteristics of pediatric drowning patients evaluated in a pediatric emergency department (PED), including the clinical interventions and outcomes of this patient population. METHODS: A retrospective cohort study was conducted of pediatric patients evaluated in a mid-Atlantic urban pediatric emergency department from January 2017 to December 2020 after a drowning event. RESULTS: Eighty patients ages 0-18 were identified, representing 57 79 unintentional events and 1 intentional self-injury event. The majority of patients (50%) were 1-4 years of age. The majority (65%) of patients 4 years of age or younger were White, whereas racial/ethnic minority patients accounted for the majority (73%) of patients 5 years of age or older. Most drowning events (74%) occurred in a pool, on Friday through Saturday (66%) and during the summer (73%). Oxygen was used in 54% of admitted patients and only in 9% of discharged patients. Cardiopulmonary resuscitation (CPR) was performed in 74% of admitted patients and 33% of discharged patients. CONCLUSIONS: Drowning can be an intentional or unintentional source of injury in pediatric patients. Among the patients who presented to the emergency department for drowning, more than half received CPR and/or were admitted, suggesting high acuity and severity of these events. In this study population, outdoor pools, summer season and weekends are potential high yield targets for drowning prevention efforts.

Pharmacologic Toll-like receptor 4 inhibition skews toward a favorable A1/A2 astrocytic ratio improving neurocognitive outcomes following traumatic brain injury.

BACKGROUND: Astrocytes are critical neuroimmune cells that modulate the neuroinflammatory response following traumatic brain injury (TBI) because of their ability to acquire neurotoxic (A1) or neuroprotective (A2) phenotypes. Using C34, a novel pharmacologic Toll-like receptor (TLR) 4 inhibitor, we explored their respective polarization states after TBI. METHODS: A murine controlled cortical impact model was used, and the results were analyzed on postinjury days (PIDs) 1, 7, and 28. The experimental groups are as follows: (1) sham, (2) sham + C34, (3) TBI, and (4) TBI + C34. Quantitative real-time polymerase chain reaction was used to quantify gene expression associated with proinflammatory (A1) and anti-inflammatory (A2) phenotypes. Morris water maze was used to assess neurocognitive outcomes. Fixed frozen cortical samples were sectioned, stained for myelin basic protein and 4',6-diamidino-2-phenylindole, and then imaged. Student t test and one-way analysis of variance were used for statistical analysis with significance achieved when p < 0.05. RESULTS: On quantitative real-time polymerase chain reaction, C34-treated groups showed a significant decrease in the expression of A1 markers such as Gbp2 and a significant increase in the expression of A2 markers such as Emp1 when compared with untreated groups on PID 1. On PIDs 7 and 28, the expression of most A1 and A2 markers was also significantly decreased in the C34-treated groups. On immunohistochemistry, C34-treated groups demonstrated increased myelin basic protein staining into the lesion by PID 28. C34-treated groups showed more platform entries on Morris water maze when compared with untreated groups on PID 7 and PID 28. CONCLUSION: Following TBI, early TLR4 blockade modulates astrocytic function and shifts its polarization toward the anti-inflammatory A2-like phenotype. This is accompanied by an increase in myelin regeneration, providing better neuroprotection and improved neurocognitive outcomes. Targeting A1/A2 balance with TLR4 inhibition provides a potential therapeutic target to improve neurobehavioral outcomes in the setting of TBI.

Infiltrating anti-inflammatory monocytes modulate microglial activation through toll-like receptor 4/interferon-dependent pathways following traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of morbidity and mortality in the pediatric population. Microglia and infiltrating monocyte-derived macrophages are crucial immune cells that modulate the neuroinflammatory response following TBI. Using C34, a novel pharmacologic toll-like receptor 4 inhibitor, we investigated the intricate interactions between these cells in a murine TBI model. METHODS: A murine controlled cortical impact model was used, and the results were analyzed on postinjury days 1, 7, 28, and 35. The experimental groups are as follows: (1) sham C57BL/6 wild-type (WT), (2) TBI WT, (3) sham WT + C34, and (4) TBI WT + C34. Quantitative real-time polymerase chain reaction was used to quantify gene expression associated with microglial activation, apoptotic pathways, and type 1 interferon pathway. Flow cytometry was used to isolate microglia and infiltrating monocytes. Brain lesion volumes were assessed using magnetic resonance imaging. Last, neurocognitive outcomes were evaluated using the Morris Water Maze test. Student's t test and one-way analysis of variance were used for statistical analysis with significance achieved when p < 0.05. RESULTS: Toll-like receptor 4 inhibition leads to improved neurological sequela post-TBI, possibly because of an increase in infiltrating anti-inflammatory monocytes and a decrease in IFN regulatory factor 7 during acute inflammation, followed by a reduction in apoptosis and M2 microglial expression during chronic inflammation. CONCLUSION: Toll-like receptor 4 inhibition with C34 skews infiltrating monocytes toward an anti-inflammatory phenotype, leading to enhanced neurocognitive outcomes. Moreover, although M2 microglia have been consistently shown as inducers of neuroprotection, our results clearly demonstrate their detrimental role during the chronic phases of healing post-TBI.

Pelvic osteotomy in cloacal exstrophy: A changing perspective.

BACKGROUND: The type of osteotomy and pelvic fixation in the management of primary cloacal exstrophy (CE) closure is variable. The purpose of this study was to evaluate primary CE closure outcomes with osteotomy, immobilization, and multi-staging procedure trends over time. METHODS: An institutional database was retrospectively reviewed for patients who underwent primary CE closure from 1960 to 2020. Demographics, osteotomy, fixation, and outcomes were noted. Subanalyses by location of primary closure (AH=author's hospital; OH=outside hospital). RESULTS: Out of 122 patients, multi-stage became more common than single-stage procedures (p = 0.019), with multi-stage associated with higher success rates (77.4% v 45.7%; p = 0.001). The use of any osteotomy increased over time (p = 0.007), with a posterior approach falling out of favor and increasing prevalence of a combined osteotomy (p<0.001). The use of any osteotomy compared to no osteotomy was associated with successful closure (77.6% v 41.7%; p = 0.007). The combined, posterior, and anterior approaches were associated with 90%, 76.2%, and 60.9% successful primary closure rates, respectively (p<0.001). Fixation modalities changed over time as Buck's traction (p<0.001) and external fixation (p<0.001) became more prevalent. Spica casting has become less common (p = 0.0002). Immobilization type was associated with success rates with Buck's (92.1%; p<0.001) and external fixation (86.0%; p<0.001) performing best. CONCLUSIONS: The use of osteotomy and fixation in the CE spectrum has changed markedly. In this cohort, a staged approach with combination osteotomy was associated with better outcomes when using a multidisciplinary team approach. LEVEL OF EVIDENCE: This is a retrospective comparative study (Type of Study: Treatment; Evidence Level: III).

A traumatic pandemic: High acuity pediatric trauma in the COVID19 era.

OBJECTIVE: Gaps remain in our understanding on how COVID19 affects trends in pediatric trauma, the leading cause of mortality and morbidity during childhood and adolescence. METHODS: We compared high acuity trauma visits (requiring admission, surgery, or fatality) presenting between March through February 2021 to corresponding months in 2017-2019. We evaluated the differences in mechanisms of injury, age, and Area Deprivation Index (ADI), a measure of socioeconomic disadvantage, during this time period. Data were analyzed using longitudinal time series analyses and t-tests. RESULTS: Of 687 traumas presenting from March 2020 through February 2021, 322 were high acuity traumas. High acuity traumas declined significantly to a nadir of 16 in April 2020. High acuity traumas increased and surpassed previous years to a peak of 40 visits in August 2020 and from October through December 2020. There were more visits for high acuity assaults and confirmed or suspected physical child abuse but fewer for falls, drownings, and motor vehicle accidents from March to August 2020 and from October through December 2020 compared to prior years. High acuity assaults and physical child abuse cases on average were from the most disadvantaged areas, and physical child abuse patients were younger during the peak of the Pandemic compared to Pre-Pandemic months. CONCLUSION: This analysis provides insight into how the COVID19 pandemic has affected high acuity trauma in an inner-city pediatric population. Findings may be used to guide public health measures on safety and injury prevention as the pandemic continues.

Assessing the effect of COVID-19 stay-at -home orders on firearm injury in Maryland.

This study sought to characterize frequency and demographic characteristics of firearm injury and penetrating trauma in Maryland over the first year of the pandemic, by comparing these characteristics to those of the three years prior to stay-at-home order issuance. Patients were identified in the Maryland Health Services Cost Review Commission database using ICD-10 codes for firearm injury by all intents and assaults by penetrating trauma. Cases from July 1, 2017 to March 31, 2020 ("pre-stay-at-home") were compared to those from April 1, 2020 to March 31, 2021 ("post-stay-at-home") using descriptive statistics. There was no significant change overall in frequency or demographics of firearm injury or penetrating trauma in the year after stay-at-home orders were issued. Youth between ages 15 and 24, overwhelmingly male, comprise a disproportionately high percentage of firearm injuries and assaults, and most penetrating trauma occurs in urban environments where Black non-Hispanic youth and children of low socioeconomic status are at high risk. Our study also found unintentional firearm injury among adults was significantly increased during the pandemic. While increased unintentional firearm injury among adults was the major significant change found in our study, the persistence of firearm injury, particularly in youth, racial and ethnic minority groups, and those in urban environments, should be deeply concerning. Stay-at-home policies did not keep youth safer from firearm injury. With continued high rates of firearm injury and the national debate over how to prevent these incidents, increased education and comprehensive strategies for prevention are needed.

Developing and Implementing Electronic Consent Procedures in Response to Covid-19 Restrictions.

The Covid-19 pandemic resulted in unprecedented restrictions on many public, private, and workplace activities throughout the United States and elsewhere. When restrictions were imposed, we were conducting a type III hybrid effectiveness-implementation trial in 10 pediatric trauma centers. In response to several pandemic-based restrictions, we had to develop procedures for engaging with potential research participants while limiting nonclinical, in-person interactions. This manuscript describes the procedures and challenges of obtaining electronic informed consent and assent in a multisite trauma center-based research study. We developed, tested, and trained staff to implement three options for obtaining informed consent. Twenty-five participants were enrolled in the effectiveness-implementation multisite trial during the first six months of utilization of the consent options, with eleven of these individuals enrolled using hybrid or electronic consent procedures. The challenges we identified involving electronic consent procedures included confusion over who would complete the electronic consent process and difficulties reconnecting with families. Lessons learned can strengthen electronic consent and assent procedures for future studies. More research is needed to further strengthen this process and increase its utilization.