ABSTRACT
Cardiac left ventricular outflow tract (LVOT) defects represent a common but heterogeneous subset of congenital heart disease for which gene identification has been difficult. We describe a 46,XY,t(1;5)(p36.11;q31.2)dn translocation carrier with pervasive developmental delay who also exhibited LVOT defects, including bicuspid aortic valve (BAV), coarctation of the aorta (CoA) and patent ductus arteriosus (PDA). The 1p breakpoint disrupts the 5' UTR of AHDC1, which encodes AT-hook DNA-binding motif containing-1 protein, and AHDC1-truncating mutations have recently been described in a syndrome that includes developmental delay, but not congenital heart disease [Xia, F., Bainbridge, M.N., Tan, T.Y., Wangler, M.F., Scheuerle, A.E., Zackai, E.H., Harr, M.H., Sutton, V.R., Nalam, R.L., Zhu, W. et al. (2014) De Novo truncating mutations in AHDC1 in individuals with syndromic expressive language delay, hypotonia, and sleep apnea. Am. J. Hum. Genet., 94, 784-789]. On the other hand, the 5q translocation breakpoint disrupts the 3' UTR of MATR3, which encodes the nuclear matrix protein Matrin 3, and mouse Matr3 is strongly expressed in neural crest, developing heart and great vessels, whereas Ahdc1 is not. To further establish MATR3 3' UTR disruption as the cause of the proband's LVOT defects, we prepared a mouse Matr3(Gt-ex13) gene trap allele that disrupted the 3' portion of the gene. Matr3(Gt-ex13) homozygotes are early embryo lethal, but Matr3(Gt-ex13) heterozygotes exhibit incompletely penetrant BAV, CoA and PDA phenotypes similar to those in the human proband, as well as ventricular septal defect (VSD) and double-outlet right ventricle (DORV). Both the human MATR3 translocation breakpoint and the mouse Matr3(Gt-ex13) gene trap insertion disturb the polyadenylation of MATR3 transcripts and alter Matrin 3 protein expression, quantitatively or qualitatively. Thus, subtle perturbations in Matrin 3 expression appear to cause similar LVOT defects in human and mouse.
Subject(s)
Aortic Coarctation/genetics , Aortic Valve/abnormalities , Ductus Arteriosus, Patent/genetics , Heart Valve Diseases/genetics , Nuclear Matrix-Associated Proteins/genetics , RNA-Binding Proteins/genetics , Adolescent , Animals , Aortic Coarctation/metabolism , Aortic Valve/metabolism , Bicuspid Aortic Valve Disease , Child, Preschool , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Ductus Arteriosus, Patent/metabolism , Female , Gene Silencing , Heart Valve Diseases/metabolism , Heart Ventricles/abnormalities , Heart Ventricles/metabolism , Humans , Infant, Newborn , Male , Mice , Mutagenesis, Insertional , Nuclear Matrix-Associated Proteins/metabolism , RNA-Binding Proteins/metabolism , Translocation, GeneticABSTRACT
The care of severely burned patients comes with unique requirements for specialized burn centers. The American Burn Association sets guidelines for burn centers and provides a voluntary program to verify their quality of care. However, not all burn centers are verified, and it is unclear which nonverified centers have met requirements set by their state health departments. To compile a complete database of all U.S. emergency departments in facilities with confirmed burn centers, we investigated state requirements to supplement data from the American Burn Association verification process. In 2020, only 13 states set requirements for burn centers; 3 states explicitly required American Burn Association verification, 4 used modified American Burn Association criteria, and 6 used alternate criteria. Only two states had separate requirements for pediatric burn centers. Based on adherence to state and American Burn Association criteria, we identified 90 confirmed burn centers in 2020, 85 of which had emergency departments. Of these 85, 45 (53%) were only verified, 17 (20%) were only state-confirmed, and 23 (27%) were both. Emergency departments in a confirmed burn center were more likely-than those without-to have higher adult and pediatric visit volumes, be academic, be a stroke or trauma (adult or pediatric) center, have a dedicated pediatric area, and have a pediatric emergency care coordinator. We compiled the first unified burn center database that incorporates state and American Burn Association lists. This database can be utilized in future health services research and is available to the public through a smartphone application.
Subject(s)
Burns , Emergency Medical Services , Adult , Burn Units , Burns/epidemiology , Burns/therapy , Child , Databases, Factual , Emergency Service, Hospital , Humans , United StatesABSTRACT
INTRODUCTION: Millions of people visit US national parks annually to engage in recreational wilderness activities, which can occasionally result in traumatic injuries that require timely, high-level care. However, no study to date has specifically examined timely access to trauma centers from national parks. This study aimed to examine the accessibility of trauma care from national parks by calculating the travel time by ground and air from each park to its nearest trauma center. Using these calculations, the percentage of parks by census region with timely access to a trauma center was determined. METHODS: This was a cross-sectional study analyzing travel times by ground and air transport between national parks and their closest adult advanced trauma center (ATC) in 2018. A list of parks was compiled from the National Parks Service (NPS) website, and the location of trauma centers from the 2018 National Emergency Department Inventory (NEDI)-USA database. Ground and air transport times were calculated using Google Maps and ArcGIS, with medians and interquartile ranges reported by US census region. Percentage of parks by region with timely trauma center access-defined as access within 60 minutes of travel time-were determined based on these calculated travel times. RESULTS: In 2018, 83% of national parks had access to an adult ATC within 60 minutes of air travel, while only 26% had timely access by ground. Trauma center access varied by region, with median travel times highest in the West for both air and ground transport. At a national level, national parks were unequally distributed, with the West housing the most parks of all regions. CONCLUSION: While most national parks had timely access to a trauma center by air travel, significant gaps in access remain for ground, the extent of which varies greatly by region. To improve the accessibility of trauma center expertise from national parks, the study highlights the potential that increased implementation of trauma telehealth in emergency departments (EDs) may have in bridging these gaps.