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

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

Educating and Empowering Inner-City High School Students in Bleeding Control.

INTRODUCTION: Unintentional bleeding is the leading cause of death in people 1-44 years of age in the United States. The Stop the Bleed (STB) campaign is a nationwide course that teaches the public to ensure their own safety, call 911, find the bleeding injury, and achieve temporary hemorrhage control by several techniques. Although the national campaign for the training course was inspired by active shooter events, the training can be applied to motor vehicle accidents and small-scale penetrating and gunshot wounds. Extending the audience to inner-city high school students in a violence-prone neighborhood has the potential to save lives if they are first on the scene. OBJECTIVES: We hypothesized that students would have a greater degree of comfort, willingness, and preparedness to intervene in acute bleeding after taking the course. METHODS: This was a prospective, interventional pilot study in one inner-city high school in Brooklyn, New York. Students were given the option to participate in the STB course with pre- and post-surveys. We recruited 286 students from physical education or health education class to take a 50-minute bleeding control training course. Mean age was 15.7 years old. Students were divided into groups of 20-25 and taught by 2-3 emergency medicine, pediatric, or trauma surgery STB instructors. Each course included 2-3 skills stations for placing a tourniquet, wound packing, and pressure control. RESULTS: Prior to the course, only 43.8% of the students reported being somewhat likely or very likely to help an injured person who was bleeding. After the course, this increased to 80.8% of students even if no bleeding control kit was available. Additionally, there were significant improvements in self-rated comfort level from pre- to post-course 45.4% to 76.5%, and in self-rated preparedness from 25.1% to 83.8%. All three measures showed statistically significant improvement, P <.0001. CONCLUSION: Teaching the STB course to high school students from a community with high levels of violence resulted in increased comfort level, willingness, and preparedness to act to control bleeding. If these opinions translate into action, students' willingness to act could decrease pre-hospital blood loss and empower youth to perform life-saving interventions.

A narrative review of esophageal tissue engineering and replacement: where are we?

Long-gap esophageal defects, whether congenital or acquired, are very difficult to manage. Any significant surgical peri-esophageal dissection that is performed to allow for potential stretching of two ends of a defect interrupts the esophageal blood supply and leads to complications such as leak and stricture, even in the youngest, healthiest patients. The term "congenital" applied to these defects refers mainly to long-gap esophageal atresia (LGA). Causes of acquired long-segment esophageal disruption include recurrent leaks and fistulae after primary repair, refractory GERD, caustic ingestions, cancer, and strictures. 5,000-10,000 patients per year in the US require esophageal replacement. Gastric, colonic, and jejunal pull-up surgeries are fraught with high rates of both short and long term complications thus creating a space for a better option. Since the 1970's many groups around the world have been unsuccessfully attempting esophageal replacement with tissue-engineered grafts in various animal models. But, recent advances in these models are now combining novel technologic advances in materials bioscience, stem-cell therapies, and transplantation and are showing increasing promise to human translational application. Transplantation has been heretofore unsuccessful, but given modern improvements in transplant microsurgery and immunosuppressive medications, pioneering trials in animal models are being undertaken now. These rapidly evolving medical innovations will be reviewed here.

Sapovirus Gastroenteritis in Young Children Presenting as Distal Small Bowel Obstruction: A Report of 2 Cases and Literature Review.

Abdominal pain and distention in children are commonly encountered problems in the pediatric emergency room. The majority of complaints are found to be due to benign entities such as gastroenteritis and constipation. What confounds these diagnoses is that young children often deliver a challenging and unreliable exam. Thus, it often becomes exceedingly problematic to differentiate these benign conditions from surgical conditions requiring prompt attention including small or large bowel obstruction, volvulus, and appendicitis. The cases highlight Sapovirus as a cause of severe abdominal distention and vomiting in children and this report is the first to describe and demonstrate the impressive radiologic findings that may be associated with this infection. Surgeons should heed this information and hesitate to emergently operate on similar children.

Arterial shear stress reduces eph-b4 expression in adult human veins.

Vein graft adaptation to the arterial environment is characterized by loss of venous identity, with reduced Ephrin type-B receptor 4 (Eph-B4) expression but without increased Ephrin-B2 expression. We examined changes of vessel identity of human saphenous veins in a flow circuit in which shear stress could be precisely controlled. Medium circulated at arterial or venous magnitudes of laminar shear stress for 24 hours; histologic, protein, and RNA analyses of vein segments were performed. Vein endothelium remained viable and functional, with platelet endothelial cell adhesion molecule (PECAM)-expressing cells on the luminal surface. Venous Eph-B4 expression diminished (p = .002), Ephrin-B2 expression was not induced (p = .268), and expression of osteopontin (p = .002) was increased with exposure to arterial magnitudes of shear stress. Similar changes were not found in veins placed under venous flow or static conditions. These data show that human saphenous veins remain viable during ex vivo application of shear stress in a bioreactor, without loss of the venous endothelium. Arterial magnitudes of shear stress cause loss of venous identity without gain of arterial identity in human veins perfused ex vivo. Shear stress alone, without immunologic or hormonal influence, is capable of inducing changes in vessel identity and, specifically, loss of venous identity.

Vascular endothelial growth factor-A inhibits EphB4 and stimulates delta-like ligand 4 expression in adult endothelial cells.

BACKGROUND: During vein graft adaptation to the arterial circulation, vascular endothelial growth factor (VEGF) A expression transiently increases before becoming downregulated; however, the role of VEGF-A in venous remodeling is not clear. In addition, although VEGF-A stimulates angiogenesis and determines arterial identity in nascent arterial endothelial cells (EC), the role of VEGF-A in regulating identity in adult venous EC is also not clear. MATERIALS AND METHODS: EC, wild type (EphB4+/+) or heterozygous knockout (EphB4+/-), were stimulated with VEGF-A (0-100 ng/mL) and examined with quantitative polymerase chain reaction and western blotting. RESULTS: VEGF-A (100 ng/mL) inhibited expression of EphB4 and stimulated expression of delta-like ligand 4 (dll4) but did not stimulate either notch or EphrinB2 expression in adult venous EC. Pretreatment with VEGF receptor 2-neutralizing antibody abolished VEGF-stimulated downregulation of EphB4 but not the upregulation of dll4. Pretreatment with PD98059 or wortmannin showed that VEGF-A downregulation of EphB4 and upregulation of dll4 are mitogen-activated protein kinase kinase and extracellular signal-regulated kinase dependent but phosphatidylinositol 3 kinase-Akt independent. Compared with VEGF-induced EphB4 downregulation and dll4 upregulation in control EC, reduced EphB4 signaling in EphB4+/- EC showed even further downregulation of EphB4 and upregulation of dll4. CONCLUSIONS: Despite the genetic programming of arterial and venous EC fate, VEGF-A can repress venous identity in adult venous EC without induction of arterial identity. These changes in adult EC in vitro recapitulate the changes in identity described during vein graft adaptation to the arterial environment in vivo.

Cell-based interventions for therapeutic angiogenesis: review of potential cell sources.

Alternative therapies are currently being developed to treat patients with chronic limb ischemia who are unable to be revascularized in order to avoid amputation. Cell-based therapy using mononuclear cells is gaining attention as many clinical trials are currently underway. We review cell differentiation along with the different potential cell sources for use in therapeutic angiogenesis.

Age-related neointimal hyperplasia is associated with monocyte infiltration after balloon angioplasty.

Carotid angioplasty is associated with adverse events in elderly patients; it is unclear whether this is related to an altered inflammatory axis. The carotid arteries of young (6 months) or aged (22-24 months) Fischer 344 rats were balloon injured. Aged rats had reduced lumen area (0.18 ± 0.03 vs 0.24 ± 0.01 mm(2), p = .02) and increased neointimal thickening (0.15 ± 0.04 vs 0.08 ± 0.03 mm(2), p = .006). Aged rats had increased circulating monocytes (96 ± 21 vs. 54 ± 7; p = .002) as well as increased numbers of monocytes at the post-angioplasty site. Aged rats had sustained monocyte chemotactic protein-1 expression after angioplasty but young rats did not. Aged arteries also exhibited defective vasorelaxation and abnormal eNOS localization. Aged (≥80 years) human patients with high-grade carotid stenosis had increased number of monocytes (9.1% ± 0.4%) compared with younger (65-80 years) patients (8.1% ± 0.3%, p = .013). Aged rats develop neointimal hyperplasia after carotid angioplasty with increased numbers of monocytes, and elderly humans with carotid stenosis have increased numbers of circulating monocytes. These preliminary results may suggest a role for monocytes in the response to carotid angioplasty.

Age-related Notch-4 quiescence is associated with altered wall remodeling during vein graft adaptation.

BACKGROUND: The link of aging to specific mechanisms of vascular biology is not well understood. We have previously shown that aging is associated with increased vein graft wall thickness and that this process involves the VEGF-Delta/Notch-ephrin/Eph cascade. Therefore, we examined whether Dll-4 or Notch-4 are differentially expressed, according to age, during vein graft adaptation. MATERIALS AND METHODS: Vein grafts were performed in 6-mo and 24-mo Fischer 344 rats. Gene expression was analyzed by quantitative real-time PCR, and the distribution of Dll-4 and Notch-4 was observed by immunofluorescence. RESULTS: The expression of Dll-4 and Notch-4 was reduced in vein grafts performed in aged rats compared with the expression in young adult rats. Both Dll-4 and Notch-4 were distributed in vein graft endothelium as well as the outer adventitia, with reduced amounts in the outer adventitia of aged vein grafts. Aged veins had reduced eNOS membrane targeting and colocalization with caveolin-1 as well as reduced eNOS protein expression in comparison to young adult veins. In an exchange model between young and aged animals, heterogeneous vein grafts (Yo(Ag) and Ag(Yo)) showed significantly thicker neointima compared with young (Yo(Yo)) controls, and had Notch-4-positive cells, but not Dll-4-positive cells, diminished in the adventitia. Vein grafts that were air-denuded of endothelium did not show any adaptation to the arterial environment and also lacked both Dll-4 and Notch-4 expression at 3 wk. CONCLUSIONS: During vein graft adaptation to the arterial environment, both Dll-4 and Notch-4 expression are down-regulated in an aged, but not a young, background. Loss of Notch-4 is associated with loss of attenuation of neointima. The delta-Notch signaling pathway may be active during vein graft adaptation.

Current usage and future directions for the bovine pericardial patch.

Bovine pericardium (BP) is widely used in surgery and is commonly used as a patch after arteriotomy in cardiovascular surgery. BP patches have several advantages compared with prosthetic patches, including superior biocompatability, easy handling, less suture line bleeding, and possibly reduced rates of infection. These advantages of BP have led to its common use during carotid endarterectomy (CEA). However, long-term clinical results reported after CEA have suggested several issues that may be related to the patch, including restenosis, pseudoaneurysm formation, infection, fibrosis, calcification, and thrombosis. These complications may diminish the long-term efficacy of CEA and suggest potential areas for improvement of surgical patches. Understanding the mechanisms by which BP heals after patch angioplasty may lead to next generation tissue-engineered patches.

Mechanisms of vein graft adaptation to the arterial circulation: insights into the neointimal algorithm and management strategies.

For patients with coronary artery disease or limb ischemia, placement of a vein graft as a conduit for a bypass is an important and generally durable strategy among the options for arterial reconstructive surgery. Vein grafts adapt to the arterial environment, and the limited formation of intimal hyperplasia in the vein graft wall is thought to be an important component of successful vein graft adaptation. However, it is also known that abnormal, or uncontrolled, adaptation may lead to abnormal vessel wall remodeling with excessive neointimal hyperplasia, and ultimately vein graft failure and clinical complications. Therefore, understanding the venous-specific pathophysiological and molecular mechanisms of vein graft adaptation are important for clinical vein graft management. Of particular importance, it is currently unknown whether there exist several specific distinct molecular differences in the venous mechanisms of adaptation that are distinct from arterial post-injury responses; in particular, the participation of the venous determinant Eph-B4 and the vascular protective molecule Nogo-B may be involved in mechanisms of vessel remodeling specific to the vein. This review describes (1) venous biology from embryonic development to the mature quiescent state, (2) sequential pathologies of vein graft neointima formation, and (3) novel candidates for strategies of vein graft management. Scientific inquiry into venous-specific adaptation mechanisms will ultimately provide improvements in vein graft clinical outcomes.

Par6alpha signaling controls glial-guided neuronal migration.

Neuronal migrations along glial fibers provide a primary pathway for the formation of cortical laminae. To examine the mechanisms underlying glial-guided migration, we analyzed the dynamics of cytoskeletal and signaling components in living neurons. Migration involves the coordinated two-stroke movement of a perinuclear tubulin 'cage' and the centrosome, with the centrosome moving forward before nuclear translocation. Overexpression of mPar6alpha disrupts the perinuclear tubulin cage, retargets PKCzeta and gamma-tubulin away from the centrosome, and inhibits centrosomal motion and neuronal migration. Thus, we propose that during neuronal migration the centrosome acts to coordinate cytoskeletal dynamics in response to mPar6alpha-mediated signaling.