Emergency department utilization and disposition outcomes by pediatric patients with cancer in Maryland and New York from 2013 to 2017.

BACKGROUND: Pediatric patients with cancer commonly seek emergency department (ED) care, yet there is limited evidence on ED utilization patterns and disposition outcomes among these patients. METHODS: Retrospective analysis of the Healthcare Cost and Utilization Project State Emergency Department Databases and State Inpatient Databases for Maryland and New York from 2013 to 2017. We compared ED visits and disposition outcomes for 5.8 million pediatric patients (<18 years old) with and without cancer, and used multivariable regressions to estimate associations between the number of ED visits, hospital (inpatient) admissions through the ED, and ED or inpatient mortality and sociodemographic and clinical factors within the cancer cohort. RESULTS: Pediatric patients with cancer had more ED visits per year on average (2.4 vs. 1.5, p < .001), higher shares of admissions (56.8% vs. 6.6%, p < .001) and mortality (1.2% vs. 0.1%, p < .001) compared to those without cancer. Among patients with cancer, uninsured pediatric patients had fewer ED visits and lower risk of admission to a hospital through the ED compared to those with Medicaid coverage (total visits: incidence rate ratio [IRR]: 0.82, 95% confidence intervals [CI]: 0.75-0.90; admission: IRR: 0.75, 95% CI: 0.65-0.86). Mortality risks were higher for pediatric patients with cancer residing in areas with the lowest median household income, and with no health insurance coverage (IRR: 2.81, 95% CI: 1.21-6.51) compared to Medicaid. CONCLUSIONS: Our findings emphasize the importance of enhancing health insurance coverage policies and social services for pediatric patients with cancer and their families to address clinical and nonclinical needs.

Generation of a 3D Liver Model Comprising Human Extracellular Matrix in an Alginate/Gelatin-Based Bioink by Extrusion Bioprinting for Infection and Transduction Studies.

Bioprinting is a novel technology that may help to overcome limitations associated with two-dimensional (2D) cell cultures and animal experiments, as it allows the production of three-dimensional (3D) tissue models composed of human cells. The present study describes the optimization of a bioink composed of alginate, gelatin and human extracellular matrix (hECM) to print human HepaRG liver cells with a pneumatic extrusion printer. The resulting tissue model was tested for its suitability for the study of transduction by an adeno-associated virus (AAV) vector and infection with human adenovirus 5 (hAdV5). We found supplementation of the basic alginate/gelatin bioink with 0.5 and 1 mg/mL hECM provides desirable properties for the printing process, the stability of the printed constructs, and the viability and metabolic functions of the printed HepaRG cells. The tissue models were efficiently transduced by AAV vectors of serotype 6, which successfully silenced an endogenous target (cyclophilin B) by means of RNA interference. Furthermore, the printed 3D model supported efficient adenoviral replication making it suitable to study virus biology and develop new antiviral compounds. We consider the approach described here paradigmatic for the development of 3D tissue models for studies including viral vectors and infectious viruses.

Regulation of ß1 integrin-Klf2-mediated angiogenesis by CCM proteins.

Mechanotransduction pathways are activated in response to biophysical stimuli during the development or homeostasis of organs and tissues. In zebrafish, the blood-flow-sensitive transcription factor Klf2a promotes VEGF-dependent angiogenesis. However, the means by which the Klf2a mechanotransduction pathway is regulated to prevent continuous angiogenesis remain unknown. Here we report that the upregulation of klf2 mRNA causes enhanced egfl7 expression and angiogenesis signaling, which underlies cardiovascular defects associated with the loss of cerebral cavernous malformation (CCM) proteins in the zebrafish embryo. Using CCM-protein-depleted human umbilical vein endothelial cells, we show that the misexpression of KLF2 mRNA requires the extracellular matrix-binding receptor ß1 integrin and occurs in the absence of blood flow. Downregulation of ß1 integrin rescues ccm mutant cardiovascular malformations in zebrafish. Our work reveals a ß1 integrin-Klf2-Egfl7-signaling pathway that is tightly regulated by CCM proteins. This regulation prevents angiogenic overgrowth and ensures the quiescence of endothelial cells.

Blood flow and Bmp signaling control endocardial chamber morphogenesis.

During heart development, the onset of heartbeat and blood flow coincides with a ballooning of the cardiac chambers. Here, we have used the zebrafish as a vertebrate model to characterize chamber ballooning morphogenesis of the endocardium, a specialized population of endothelial cells that line the interior of the heart. By combining functional manipulations, fate mapping studies, and high-resolution imaging, we show that endocardial growth occurs without an influx of external cells. Instead, endocardial cell proliferation is regulated, both by blood flow and by Bmp signaling, in a manner independent of vascular endothelial growth factor (VEGF) signaling. Similar to myocardial cells, endocardial cells obtain distinct chamber-specific and inner- versus outer-curvature-specific surface area sizes. We find that the hemodynamic-sensitive transcription factor Klf2a is involved in regulating endocardial cell morphology. These findings establish the endocardium as the flow-sensitive tissue in the heart with a key role in adapting chamber growth in response to the mechanical stimulus of blood flow.

Children's mental health emergencies-part 1: challenges in care: definition of the problem, barriers to care, screening, advocacy, and resources.

OBJECTIVE: At a time when there has been a reduction in mental health resources nationwide, the incidence of mental health disorders in children has seen a dramatic increase for many reasons. METHODS: A review of the literature was done to identify the epidemiology, barriers to care, useful emergency department (ED) screening methods, and resources regarding pediatric mental health disorders in the ED. RESULTS: Although there are many challenges to the provision of care for children with mental health emergencies, some resources are available. Furthermore, ED screening and intervention may be effective in improving patient outcomes. CONCLUSIONS: Collaborative efforts with multidisciplinary services can create a continuum of care, promote better identification of children and adolescents with mental health disorders, and promote early recognition and intervention, which are key to effective referral and treatment.