A Decade of Firearm Injuries: Children Caught in the Crossfire.

INTRODUCTION: Firearm injuries (FIs) are the leading cause of preventable morbidity and mortality in pediatric patients. In this study, we aim to define evolving trends and avenues for prevention. METHODS: Following institutional review board approval, medical records of patients presenting to our two State-Designated Level 1 Pediatric Trauma Centers for treatment of FIs from 2010 to 2019 were retrospectively reviewed. Data was analyzed with Chi-Squared and Student's t-test; P-value <0.05 was significant. RESULTS: 1037 FI encounters from 1005 unique patients aged 0-21 y were included. 70.4% (n = 730) were determined to be assaults, 26.1% (n = 271) unintentional, and 1.7% (n = 18) self-inflicted injuries. Overall mortality was 4.5% (n = 45). FI victims were most commonly African American (n = 836, 80.6%), male (n = 869, 83.8%), aged 13-17 (n = 753, 72.6%), and from single-parent families (n = 647, 62.4%). The incidence of FIs increased significantly over the last 5 y of the study (2010-2014, 6.8 FIs/month), compared to 2015-2019 (averaging 10.6 FIs/month, P < 0.0001). Concurrently, FI related fatality increased from an average of 2.6 deaths/year (2010-2014) to 6.4 deaths/year (2015-2019, P = 0.064). Results were subanalyzed for pediatric patients aged 0-14 y. For the entire cohort, 12.1% (n = 116) recidivists were identified. Geographic patterns of injury were identified, with 75% of all FIs clustered in a single urban region. CONCLUSIONS: Incidence of pediatric FIs is increasing in recent years, with high mortality rates. Violence and recidivism are geographically concentrated, offering an opportunity for targeted interventions.

Operative Volumes and Postoperative Outcomes After Elective Resection of Congenital Lung Malformations in Infants.

OBJECTIVE: To determine whether hospital- and surgeon-level operative volumes are associated with differences in postoperative outcomes among infants undergoing elective lung surgery for a congenital lung malformation (CLM). SUMMARY BACKGROUND DATA: Infant lung surgery is a relatively uncommon procedure performed by pediatric surgeons nationwide. The relationship between surgical volume and postoperative outcomes remains unknown. METHODS: A retrospective cohort study of asymptomatic infants who underwent elective lung resection of a CLM was conducted using the Pediatric Health Information System database (2016-2020). Multivariable linear and poisson regressions were performed based on annual lung resection tertiles. RESULTS: There were 1420 infants managed by 48 hospitals and 309 primary surgeons. Institutions that performed seven or fewer CLM resections per year (56%) were associated with significantly higher postoperative complication rates compared to medium- and high-volume hospitals (low: 134 [34%], medium: 110 [21%], high: 144 [29%]; P<0.001). Surgeons who performed one or fewer CLM resections per year (82%) were associated with significantly higher complication rates compared to medium- and high-volume surgeons (low: 171 [31%], medium: 75 [26%], high: 119 [24%]; P=0.02). Multivariable analyses confirmed that low-volume hospitals were associated with higher complications (OR 1.81, CI 1.38-2.37; P<0.001), and low-volume surgeons had an increased risk of complications (overall: OR 1.37, CI 1.01-1.84; P=0.04). CONCLUSIONS: In this cohort study of infants undergoing elective lung resection for a CLM, lower volume providers were associated with higher postoperative patient morbidity. These findings represent an opportunity to inform quality improvement initiatives on pediatric lung resection and the debate on surgical subspecialization for this unique patient population.

Management of long-gap esophageal atresia.

A uniquely challenging subset of infants diagnosed with esophageal atresia (EA) are those born with long-gap EA (LGEA). The common unifying feature in infants with LGEA is that the proximal and distal segments of the esophagus are too far apart to enable primary anastomosis via a single operation in the newborn period. Although any type of EA can technically result in a long gap, the Gross type A variant occurs in 8% of all EA cases and is most commonly associated with LGEA. In this review, we provide an evidence-based approach to the current challenges and management strategies employed in LGEA. There are fortunately a range of available surgical techniques for LGEA repair, including delayed primary repair, staged repair based on longitudinal traction strategies to lengthen both ends (e.g., Foker procedure, internal traction), and esophageal replacement using other portions of the gastrointestinal tract. The literature on the management of LGEA has long been dominated by single-center retrospective reviews, but the field has recently witnessed increased multi-center collaboration that has helped to increase our understanding on how to best manage this challenging patient population. Delayed primary repair is strongly preferred as the initial approach in management of LGEA in the United States as well as several European countries and is supported by the American Pediatric Surgery Association recommendations. Should esophageal replacement be required in cases where salvaging the native thoracic esophagus is not possible, gastric conduits are the preferred approach, based on the relative simplicity of the operation, low postoperative morbidity, and long-term durability. Long-term followup for monitoring of swallowing function, nutritional status, aspiration/respiratory illnesses, gastroesophageal reflux, and associated comorbidities is essential in the comprehensive care of these complex patients.

Efficacy of Demineralized Bone Matrix for Revision Alveolar Bone Grafting in Patients Previously Treated with Bone Morphogenetic Protein 2 (BMP-2).

OBJECTIVE: This study investigates the effectiveness of demineralized bone matrix (DBX) to close alveolar clefts in patients previously treated with bone morphogenic protein-2 (BMP-2) who remained with bone nonunion. DESIGN: This is an IRB-approved retrospective, single-center study. SETTING: This study was conducted at a tertiary academic center. PATIENTS/PARTICIPANTS: We searched for all surgical encounters with the Current Procedural Terminology (CPT) code 42210 from the years 2013-2019. Included patients were diagnosed with cleft alveolus, previous BMP-2 exposure and required revision bone grafting during mixed dentition for persistent alveolar defects. INTERVENTIONS: 17 patients underwent revision alveolar bone grafting (ABG) with either DBX (n = 10) or autograft (n = 7) to repair persistent bony cleft. MAIN OUTCOME MEASURE(S): The primary study outcome measured was alveolar bone graft revision failure described as continued alveolar nonunion. RESULTS: The median age at revision ABG was 13.1 ± 3.3 years, with a mean follow-up time of 4.9 years (1.1-9.2 years). Patients were 53% male, 47% had a unilateral cleft lip and alveolus. 58.8% of patients were treated with DBX in the cleft, 41.2% treated with autograft from iliac crest. Overall, 11.8% (n = 2) of all revisions failed, requiring a second revision. The average time to reoperation was 2.06 years, and both were re-grafted with autograft. There was no statistically significant difference between the type of bone graft source used and the failure rate obtained (P = .1544). CONCLUSIONS: DBX and autologous iliac crest bone grafts achieve similar alveolar union rates during revision ABG in patients treated with previous BMP-2 to the alveolar cleft.

Seeing Cleft Lip from a New Angle: Crowdsourcing to Determine whether Scar Severity or Lip Angle Matters More to the General Public.

BACKGROUND: Modern cleft lip surgery aims to restore symmetry and create a level, normal-appearing Cupid's bow. However, families' concerns often center on the degree of scarring. The authors hypothesized that the lip angle would be less influential than scar severity in layperson ratings. METHODS: The authors received institutional review board approval for modifying patients' postoperative photographs to create systematic variations displaying different levels of scarring and lip angle. Each child's resulting composite images were presented in pairs to internet raters using Amazon Mechanical Turk. Users selected the simulated postoperative result they felt to be most normal. The Bradley-Terry model was used to determine raters' preferences between different levels of scarring and lip angle. RESULTS: Four children with primary unilateral cleft lip repair had their postoperative photographs modified (mean age, 1.4 years; mean follow-up, 1.0 years). Twelve-hundred crowdsourced pairwise ratings were collected for each patient (4800 combined ratings). For all four children, raters preferred images with more severe scarring than those with a greater lip angle, suggesting uneven lip angle has a more negative effect on perceived appearance. CONCLUSIONS: Online crowdsourcing postoperative lip angle had a significantly greater influence on ratings of normal appearance than does the severity of scarring. Although patients may ask about scars more often, clinically, this study suggests perceptions of a cleft lip repair result may be more likely influenced by the angle of the cleft lip repair.

Lipid absorption and overall intestinal lymphatic transport are impaired following partial small bowel resection in mice.

Short bowel syndrome (SBS) is associated with diminished levels of serum fats caused by unknown mechanisms. We have shown that mesenteric lymphatics remodel to a more primitive state one week after small bowel resection (SBR); therefore, this study focuses on the effect of chronic lymphatic remodeling and magnitude of resection on intestinal lipid uptake and transport. C57BL6 and Prox1 creER-Rosa26LSLTdTomato (lymphatic reporter) mice underwent 50% or 75% proximal SBR or sham operations. Functional transport of lipids and fecal fat content was measured and lymphatic vasculature was compared via imaging. There was a significant reduction in functional transport of cholesterol and triglyceride after SBR with increasing loss of bowel, mirrored by a progressive increase in fecal fat content. We also describe significant morphological changes in the lymphatic vasculature in both the lamina propria and mesentery. Intestinal lymphatic drainage assay in vivo demonstrated a marked reduction of systemic absorption after resection. Intestinal lymphatic vessels significantly remodel in the setting of chronic SBS. This remodeling may account at least in part for impaired intestinal uptake and transport of fat via the compromised lymphatic architecture. We believe that these changes may contribute to the development of intestinal failure associated liver disease (IFALD), a major morbidity in patients with SBS.

The Failed Bidirectional Glenn Shunt: Risk Factors for Poor Outcomes and the Role of Early Reoperation.

Background: Bidirectional Glenn shunt (BDG) failure carries high morbidity and mortality but the clinical factors associated with failure and the optimal management strategy are understudied. Methods: A total of 217 patients undergoing BDG at our institution between 1989 and 2020 were retrospectively reviewed and categorized as success or failure. Failure was defined as the need for reoperation (BDG takedown, reoperation for correction of cardiac defect, and/or transplantation) at any time postoperatively; operative mortality (death attributable to BDG malfunction occurring during the index hospitalization for BDG or within 30 days of discharge); or late mortality (death directly attributable to BDG malfunction occurring prior to Fontan or next-stage palliation). Univariate and binary logistic regression analyses were performed. Results: BDG failure occurred in 14 (6.5%) patients. Univariate predictors were: hypoplastic left heart syndrome (P = .037), right ventricular (RV) dominance (P = .010), greater pre-BDG pulmonary vascular resistance (PVR) (P = .012), concomitant atrioventricular valve repair (P = .020), prolonged pleural drainage (P = .001), intensive care unit (P<.001) and hospital (P = .002) stays, and extracorporeal membrane oxygenation (ECMO) requirement (P<.001). Multivariate predictors were: RV dominance (P = .002), greater PVR (P = .041), ICU (P<.001) and hospital (P = .020) stays, and need for ECMO (P<.001). As many as 10 of 14 (71%) patients with BDG failure died. Reoperation was performed for 10 patients with BDG failure. Five reoperation patients survived until discharge, with four patients alive at last follow-up (mean 7.9 years). Survivors underwent reoperation earlier than nonsurvivors (36 vs. 94 days). Conclusions: BDG failure carries high mortality, but preoperative predictors and postoperative indicators of failure exist. Early BDG takedown and insertion of aorta-pulmonary shunt may allow survival.

Liver injury after small bowel resection is prevented in obesity-resistant 129S1/SvImJ mice.

Intestinal failure-associated liver disease is a major morbidity associated with short bowel syndrome. We sought to determine if the obesity-resistant mouse strain (129S1/SvImJ) conferred protection from liver injury after small bowel resection (SBR). Using a parenteral nutrition-independent model of resection-associated liver injury, C57BL/6J and 129S1/SvImJ mice underwent a 50% proximal SBR or sham operation. At postoperative week 10, hepatic steatosis, fibrosis, and cholestasis were assessed. Hepatic and systemic inflammatory pathways were evaluated using oxidative markers and abundance of tissue macrophages. Potential mechanisms of endotoxin resistance were also explored. Serum lipid levels were elevated in all mouse lines. Hepatic triglyceride levels were no different between mouse strains, but there was an increased accumulation of free fatty acids in the C57BL/6J mice. Histological and serum markers of hepatic fibrosis, steatosis, and cholestasis were significantly elevated in resected C57BL/6J SBR mice as well as oxidative stress markers and macrophage recruitment in both the liver and visceral white fat in C57BL/6J mice compared with sham controls and the 129S1/SvImJ mouse line. Serum endotoxin levels were significantly elevated in C57BL/6J mice with significant elevation of hepatic TLR4 and reduction in PPARα expression levels. Despite high levels of serum lipids, 129S1/SvImJ mice did not develop liver inflammation, fibrosis, or cholestasis after SBR, unlike C57BL/6J mice. These data suggest that the accumulation of hepatic free fatty acids as well as increased endotoxin-driven inflammatory pathways through PPARα and TLR4 contribute to the liver injury seen in C57BL/6J mice with short bowel syndrome.NEW & NOTEWORTHY Unlike C57BL/6 mice, the 129S1/SvImJ strain is resistant to liver inflammation and injury after small bowel resection. These disparate outcomes are likely due to the accumulation of hepatic free fatty acids as well as increased endotoxin-driven inflammatory pathways through PPARα and TLR4 in C57BL/6 mice with short bowel syndrome.

Three-dimensional printing in medicine: a systematic review of pediatric applications.

BACKGROUND: Three-dimensional printing (3DP) addresses distinct clinical challenges in pediatric care including: congenital variants, compact anatomy, high procedural risk, and growth over time. We hypothesized that patient-specific applications of 3DP in pediatrics could be categorized into concise, discrete categories of use. METHODS: Terms related to "three-dimensional printing" and "pediatrics" were searched on PubMed, Scopus, Ovid MEDLINE, Cochrane CENTRAL, and Web of Science. Initial search yielded 2122 unique articles; 139 articles characterizing 508 patients met full inclusion criteria. RESULTS: Four categories of patient-specific 3DP applications were identified: Teaching of families and medical staff (9.3%); Developing intervention strategies (33.9%); Procedural applications, including subtypes: contour models, guides, splints, and implants (43.0%); and Material manufacturing of shaping devices or prosthetics (14.0%). Procedural comparative studies found 3DP devices to be equivalent or better than conventional methods, with less operating time and fewer complications. CONCLUSION: Patient-specific applications of Three-Dimensional Printing in Medicine can be elegantly classified into four major categories: Teaching, Developing, Procedures, and Materials, sharing the same TDPM acronym. Understanding this schema is important because it promotes further innovation and increased implementation of these devices to improve pediatric care. IMPACT: This article classifies the pediatric applications of patient-specific three-dimensional printing. This is a first comprehensive review of patient-specific three-dimensional printing in both pediatric medical and surgical disciplines, incorporating previously described classification schema to create one unifying paradigm. Understanding these applications is important since three-dimensional printing addresses challenges that are uniquely pediatric including compact anatomy, unique congenital variants, greater procedural risk, and growth over time. We identified four classifications of patient-specific use: teaching, developing, procedural, and material uses. By classifying these applications, this review promotes understanding and incorporation of this expanding technology to improve the pediatric care.

Small Bowel Resection Increases Paracellular Gut Barrier Permeability via Alterations of Tight Junction Complexes Mediated by Intestinal TLR4.

BACKGROUND: Short bowel syndrome resulting from small bowel resection (SBR) is associated with significant morbidity and mortality. Many adverse sequelae including steatohepatitis and bacterial overgrowth are thought to be related to increased bacterial translocation, suggesting alterations in gut permeability. We hypothesized that after intestinal resection, the intestinal barrier is altered via toll-like receptor 4 (TLR4) signaling at the intestinal level. METHODS: B6 and intestinal-specific TLR4 knockout (iTLR4 KO) mice underwent 50% SBR or sham operation. Transcellular permeability was evaluated by measuring goblet cell associated antigen passages via two-photon microscopy. Fluorimetry and electron microscopy evaluation of tight junctions (TJ) were used to assess paracellular permeability. In parallel experiments, single-cell RNA sequencing measured expression of intestinal integral TJ proteins. Western blot and immunohistochemistry confirmed the results of the single-cell RNA sequencing. RESULTS: There were similar number of goblet cell associated antigen passages after both SBR and sham operation (4.5 versus 5.0, P > 0.05). Fluorescein isothiocyanate-dextran uptake into the serum after massive SBR was significantly increased compared with sham mice (2.13 ± 0.39 ng/µL versus 1.62 ± 0.23 ng/µL, P < 0.001). SBR mice demonstrated obscured TJ complexes on electron microscopy. Single-cell RNA sequencing revealed a decrease in TJ protein occludin (21%) after SBR (P < 0.05), confirmed with immunostaining and western blot analysis. The KO of iTLR4 mitigated the alterations in permeability after SBR. CONCLUSIONS: Permeability after SBR is increased via changes at the paracellular level. However, these alterations were prevented in iTLR4 mice. These findings suggest potential protein targets for restoring the intestinal barrier and obviating the adverse sequelae of short bowel syndrome.

EGFR in enterocytes & endothelium and HIF1α in enterocytes are dispensable for massive small bowel resection induced angiogenesis.

BACKGROUND: Short bowel syndrome (SBS) results from significant loss of small intestinal length. In response to this loss, adaptation occurs, with Epidermal Growth Factor Receptor (EGFR) being a key driver. Besides enhanced enterocyte proliferation, we have revealed that adaptation is associated with angiogenesis. Further, we have found that small bowel resection (SBR) is associated with diminished oxygen delivery and elevated levels of hypoxia-inducible factor 1-alpha (HIF1α). METHODS: We ablated EGFR in the epithelium and endothelium as well as HIF1α in the epithelium, ostensibly the most hypoxic element. Using these mice, we determined the effects of these genetic manipulations on intestinal blood flow after SBR using photoacoustic microscopy (PAM), intestinal adaptation and angiogenic responses. Then, given that endothelial cells require a stromal support cell for efficient vascularization, we ablated EGFR expression in intestinal subepithelial myofibroblasts (ISEMFs) to determine its effects on angiogenesis in a microfluidic model of human small intestine. RESULTS: Despite immediate increased demand in oxygen extraction fraction measured by PAM in all mouse lines, were no differences in enterocyte and endothelial cell EGFR knockouts or enterocyte HIF1α knockouts by POD3. Submucosal capillary density was also unchanged by POD7 in all mouse lines. Additionally, EGFR silencing in ISEMFs did not impact vascular network development in a microfluidic device of human small intestine. CONCLUSIONS: Overall, despite the importance of EGFR in facilitating intestinal adaptation after SBR, it had no impact on angiogenesis in three cell types-enterocytes, endothelial cells, and ISEMFs. Epithelial ablation of HIF1α also had no impact on angiogenesis in the setting of SBS.

Transforming assessment of speech in children with cleft palate via online crowdsourcing.

OBJECTIVE: Speech intelligibility is fundamental to social interactions and a critical surgical outcome in patients with cleft palate. Online crowdsourcing is a burgeoning technology, with potential to mitigate the burden of limited accessibility to speech-language-pathologists (SLPs). This pilot study investigates the concordance of online crowdsourced evaluations of hypernasality with SLP ratings of children with cleft palate. METHODS: Six audio-phrases each from children with cleft palate were assessed by online crowdsourcing using Amazon Mechanical Turk (MTurk), and compared to SLP's gold-standard hypernasality score on the Pittsburgh Weighted Speech Score (PWSS). Phrases were presented to MTurk crowdsourced lay-raters to assess hypernasality on a Likert scale analogous to the PWSS. The survey included clickable reference audio samples for different levels of hypernasality. RESULTS: 1,088 unique online crowdsourced speech ratings were collected on 16 sentences of 3 children with cleft palate aged 4-8 years, with audio averaging 6.5 years follow-up after cleft palate surgery. Patient 1 crowd-mean was 2.62 (SLP rated 2-3); Patient 2 crowd-mean 2.66 (SLP rated 3); and Patient 3 crowd-mean 1.76 (SLP rated 2). Rounded for consistency with PWSS scale, all patients matched SLP ratings. Different sentences had different accuracies compared to the SLP gold standard scores. CONCLUSION: Online crowdsourced ratings of hypernasal speech in children with cleft palate were concordant with SLP ratings, predicting SLP scores in all 3 patients. This novel technology has potential for translation in clinical speech assessments, and may serve as a valuable screening tool for non-experts to identify children requiring further assessment and intervention by a qualified speech language pathology expert.

Systematic Review: Online Crowdsourcing to Assess Perceptual Speech Outcomes.

BACKGROUND: Speech is integral for human interaction and development. Speech assessments are critical in the growing child, especially in the surgical evaluation of patients undergoing cleft palate and speech surgeries. Online crowdsourcing enables layperson raters, allowing rapid and large-scale data collection. This systematic review analyzes the utility of online crowdsourcing to evaluate perceptual speech outcomes. METHODS: Terms related to "crowdsourcing" and "speech" were searched on PubMed, Scopus, CINAHL, Cochrane CENTRAL, and PsycINFO on August 16, 2017, returning 2812 unique articles. Inclusion and exclusion criteria concentrated on online crowdsourcing of perceptual speech outcomes: titles led to 140 abstracts that yielded 35 full-text articles, of which eight articles met criteria for analysis. RESULTS: All studies used Amazon Mechanical Turk for online crowd raters, and one used an additional crowdsourcing site (CrowdFlower). Disordered speech was provided by 376 speakers, for which 2203 crowd workers produced over 700,000 unique ratings. Five studies compared crowdsourced assessments to gold standards and found high concordances. Data collection time ranged from 59 min to 23 h, with worker payments ranging from $0.05 to $2.00 per task. Studies examined child pronunciation of the /r/ sound, dysarthria in Parkinson's speech, and articulation of English words produced by non-English speakers learning English. CONCLUSIONS: Online crowdsourcing for perceptual speech outcomes provides high-quality data consistent with previous speech-assessment standards in a rapid, cost-effective manner. This novel methodology incorporates lay perspective of speech intelligibility and has the potential to revolutionize surgical speech outcome assessments, including cleft palate and speech surgery.