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1.
Artigo em Inglês | MEDLINE | ID: mdl-38273438

RESUMO

BACKGROUND: Timely identification of high-risk pediatric trauma patients and appropriate resource mobilization may lead to improved outcomes. We hypothesized that reverse shock index times the motor component of the Glasgow Coma Scale (rSIM) would perform equivalently to reverse shock index times the total Glasgow Coma Scale (rSIG) in the prediction of mortality and the need for intervention following pediatric trauma. METHODS: The 2017-2020 National Trauma Data Bank datasets were used. We included all patients <16 years of age that had a documented prehospital and trauma bay systolic blood pressure, heart rate, and total GCS. We excluded all patients who arrived at the trauma center without vital signs and interfacility transport patients. Receiver operating characteristic (ROC) curves were used to model the performance of each metric as a classifier with respect to our primary and secondary outcomes, and the area under the ROC curve (AUC) was used for comparison. Our primary outcome was mortality prior to hospital discharge. Secondary outcomes included blood product administration or hemorrhage control intervention (surgery or angiography) < 4 hours following hospital arrival and ICU admission. RESULTS: After application of exclusion criteria, 77,996 patients were included in our analysis. rSIM and rSIG performed equivalently as predictors of mortality in the 1-2 (p = 0.05) and 3-5 (p = 0.28) year categories, but rSIM was statistically outperformed by rSIG in the 6-12 (AUC: 0.96 vs. 0.95, p = 0.04) and 13-16 (AUC: 0.96 vs. 0.95, p < 0.01) year-old age categories. rSIM and rSIG also performed similarly with respect to prediction of secondary outcomes. CONCLUSION: rSIG and rSIM are both outstanding predictors of mortality following pediatric trauma. Statistically significant differences in favor of rSIG were noted in some age groups. Because of the simplicity of calculation, rSIM may be a useful tool for pediatric trauma triage. LEVEL OF EVIDENCE: III, Diagnostic Tests or Criteria.

2.
JBMR Plus ; 7(4): e10716, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37065628

RESUMO

Craniosynostosis is a congenital anomaly characterized by the premature fusion of cranial sutures. Sutures are a critical connective tissue that regulates bone growth; their aberrant fusion results in abnormal shapes of the head and face. The molecular and cellular mechanisms have been investigated for a long time, but knowledge gaps remain between genetic mutations and mechanisms of pathogenesis for craniosynostosis. We previously demonstrated that the augmentation of bone morphogenetic protein (BMP) signaling through constitutively active BMP type 1A receptor (caBmpr1a) in neural crest cells (NCCs) caused the development of premature fusion of the anterior frontal suture, leading to craniosynostosis in mice. In this study, we demonstrated that ectopic cartilage forms in sutures prior to premature fusion in caBmpr1a mice. The ectopic cartilage is subsequently replaced by bone nodules leading to premature fusion with similar but unique fusion patterns between two neural crest-specific transgenic Cre mouse lines, P0-Cre and Wnt1-Cre mice, which coincides with patterns of premature fusion in each line. Histologic and molecular analyses suggest that endochondral ossification in the affected sutures. Both in vitro and in vivo observations suggest a greater chondrogenic capacity and reduced osteogenic capability of neural crest progenitor cells in mutant lines. These results suggest that the augmentation of BMP signaling alters the cell fate of cranial NCCs toward a chondrogenic lineage to prompt endochondral ossification to prematurely fuse cranial sutures. By comparing P0-Cre;caBmpr1a and Wnt1-Cre;caBmpr1a mice at the stage of neural crest formation, we found more cell death of cranial NCCs in P0-Cre;caBmpr1a than Wnt1-Cre;caBmpr1a mice at the developing facial primordia. These findings may provide a platform for understanding why mutations of broadly expressed genes result in the premature fusion of limited sutures. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

3.
J Trauma Acute Care Surg ; 95(3): 334-340, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36899460

RESUMO

BACKGROUND: Motor vehicle collision (MVC) remains a leading cause of injury and death among children, but the proper use of child safety seats and restraints has lowered the risks associated with motor vehicle travel. Blunt cerebrovascular injury (BCVI) is rare but significant among children involved in MVC. This study reviewed the incidence of BCVI after MVC causing blunt injury to the head, face, or neck, comparing those that were properly restrained with those that were not. METHODS: A prospective, multi-institutional observational study of children younger than 15 years who sustained blunt trauma to the head, face, or neck (Abbreviated Injury Scale score >0) and presented at one of six level I pediatric trauma centers from 2017 to 2020 was conducted. Diagnosis of BCVI was made either by imaging or neurological symptoms at 2-week follow-up. Restraint status among those involved in MVC was compared for each age group. RESULTS: A total of 2,284 patients were enrolled at the 6 trauma centers. Of these, 521 (22.8%) were involved in an MVC. In this cohort, after excluding patients with missing data, 10 of 371 (2.7%) were diagnosed with a BCVI. For children younger than 12 years, none who were properly restrained suffered a BCVI (0 of 75 children), while 7 of 221 (3.2%) improperly restrained children suffered a BCVI. For children between 12 and 15 years of age, the incidence of BCVI was 2 of 36 (5.5%) for children in seat belts compared with 1 of 36 (2.8%) for unrestrained children. CONCLUSION: In this large multicenter prospectively screened pediatric cohort, the incidence of BCVI among properly restrained children under 12 years after MVC was infrequent, while the incidence was 3.2% among those without proper restraint. This effect was not seen among children older than 12 years. Restraint status in young children may be an important factor in BCVI screening. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.


Assuntos
Traumatismo Cerebrovascular , Ferimentos não Penetrantes , Humanos , Criança , Pré-Escolar , Incidência , Estudos Prospectivos , Estudos Retrospectivos , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/epidemiologia , Ferimentos não Penetrantes/complicações , Cintos de Segurança , Traumatismo Cerebrovascular/diagnóstico , Traumatismo Cerebrovascular/epidemiologia , Traumatismo Cerebrovascular/etiologia
4.
J Trauma Acute Care Surg ; 95(3): 327-333, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36693233

RESUMO

BACKGROUND: Blunt cerebrovascular injury (BCVI) is rare but significant among children. There are three sets of BCVI screening criteria validated for adults (Denver, Memphis, and Eastern Association for the Surgery of Trauma criteria) and two that have been validated for use in pediatrics (Utah score and McGovern score), all of which were developed using retrospective, single-center data sets. The purpose of this study was to determine the diagnostic accuracy of each set of screening criteria in children using a prospective, multicenter pediatric data set. METHODS: A prospective, multi-institutional observational study of children younger than 15 years who sustained blunt trauma to the head, face, or neck and presented at one of six level I pediatric trauma centers from 2017 to 2020 was conducted. All patients were screened for BCVI using the Memphis criteria, but criteria for all five were collected for analysis. Patients underwent computed tomography angiography of the head or neck if the Memphis criteria were met at presentation or neurological abnormalities were detected at 2-week follow-up. RESULTS: A total of 2,284 patients at the 6 trauma centers met the inclusion criteria. After excluding cases with incomplete data, 1,461 cases had computed tomography angiography and/or 2-week clinical follow-up and were analyzed, including 24 cases (1.6%) with BCVI. Sensitivity, specificity, positive predictive value, and negative predictive value for each set of criteria were respectively 75.0, 87.5, 9.1, and 99.5 for Denver; 91.7, 71.1, 5.0, and 99.8 for Memphis; 79.2, 82.7, 7.1, and 99.6 for Eastern Association for the Surgery of Trauma; 45.8, 95.8, 15.5, and 99.1 for Utah; and 75.0, 89.5, 10.7, and 99.5 for McGovern. CONCLUSION: In this large multicenter pediatric cohort, the Memphis criteria demonstrated the highest sensitivity at 91.7% and would have missed the fewest BCVI, while the Utah score had the highest specificity at 95.8% but would have missed more than half of the injuries. Development of a tool, which narrows the Memphis criteria while maintaining its sensitivity, is needed for application in pediatric patients. LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level II.


Assuntos
Traumatismo Cerebrovascular , Ferimentos não Penetrantes , Adulto , Humanos , Criança , Estudos Retrospectivos , Estudos Prospectivos , Ferimentos não Penetrantes/diagnóstico , Traumatismo Cerebrovascular/diagnóstico , Angiografia
5.
Development ; 149(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34878091

RESUMO

A major feature of Saethre-Chotzen syndrome is coronal craniosynostosis, the fusion of the frontal and parietal bones at the coronal suture. It is caused by heterozygous loss-of-function mutations in either of the bHLH transcription factors TWIST1 and TCF12. Although compound heterozygous Tcf12; Twist1 mice display severe coronal synostosis, the individual role of Tcf12 had remained unexplored. Here, we show that Tcf12 controls several key processes in calvarial development, including the rate of frontal and parietal bone growth, and the boundary between sutural and osteogenic cells. Genetic analysis supports an embryonic requirement for Tcf12 in suture formation, as combined deletion of Tcf12 in embryonic neural crest and mesoderm, but not in postnatal suture mesenchyme, disrupts the coronal suture. We also detected asymmetric distribution of mesenchymal cells on opposing sides of the wild-type frontal and parietal bones, which prefigures later bone overlap at the sutures. In Tcf12 mutants, reduced asymmetry is associated with bones meeting end-on-end, possibly contributing to synostosis. Our results support embryonic requirements of Tcf12 in proper formation of the overlapping coronal suture.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Craniossinostoses/metabolismo , Osteogênese , Crânio/embriologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Craniossinostoses/embriologia , Craniossinostoses/genética , Células-Tronco Mesenquimais/metabolismo , Mesoderma/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Crista Neural/metabolismo , Crânio/metabolismo
6.
Nat Commun ; 12(1): 4797, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376651

RESUMO

Sutures separate the flat bones of the skull and enable coordinated growth of the brain and overlying cranium. The coronal suture is most commonly fused in monogenic craniosynostosis, yet the unique aspects of its development remain incompletely understood. To uncover the cellular diversity within the murine embryonic coronal suture, we generated single-cell transcriptomes and performed extensive expression validation. We find distinct pre-osteoblast signatures between the bone fronts and periosteum, a ligament-like population above the suture that persists into adulthood, and a chondrogenic-like population in the dura mater underlying the suture. Lineage tracing reveals an embryonic Six2+ osteoprogenitor population that contributes to the postnatal suture mesenchyme, with these progenitors being preferentially affected in a Twist1+/-; Tcf12+/- mouse model of Saethre-Chotzen Syndrome. This single-cell atlas provides a resource for understanding the development of the coronal suture and the mechanisms for its loss in craniosynostosis.


Assuntos
Suturas Cranianas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Osteogênese/genética , Análise de Célula Única/métodos , Transcriptoma/genética , Acrocefalossindactilia/embriologia , Acrocefalossindactilia/genética , Acrocefalossindactilia/patologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Suturas Cranianas/citologia , Suturas Cranianas/embriologia , Dura-Máter/citologia , Dura-Máter/embriologia , Dura-Máter/metabolismo , Mesoderma/citologia , Mesoderma/embriologia , Mesoderma/metabolismo , Camundongos Knockout , Camundongos Transgênicos , Osteoblastos/citologia , Osteoblastos/metabolismo , RNA-Seq/métodos , Crânio/citologia , Crânio/embriologia , Crânio/metabolismo , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo
7.
Pediatr Emerg Care ; 37(6): e284-e291, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30106871

RESUMO

OBJECTIVE: Hypothermia is an independent risk factor for mortality in adult trauma patients. Two small studies have shown similar results in pediatric trauma patients. Temperature is not included in any pediatric trauma assessment scores. This study sought to compare mortality and various descriptive outcomes between pediatric hypothermic and normothermic trauma patients. METHODS: Data were obtained from the National Trauma Database from 2009 to 2012. Patients meeting inclusion criteria were stratified by presence of isolated head injury, head injury with multiple trauma, and absence of head injury. These groups were then subdivided into hypothermic (temperature ≤36°C) and normothermic groups. We used propensity score matching to 1:1 match hypothermic and normothermic patients. Mortality, neurosurgical interventions, endotracheal intubation, blood transfusion, length of stay, laparotomy, thoracotomy, conversion of cardiac rhythm, and time receiving mechanical ventilation were evaluated. RESULTS: Data from 3,011,482 patients were obtained. There were 414,562 patients who met the inclusion criteria. In all patients meeting inclusion criteria, hypothermia was a significant risk factor in all outcomes measured. Following stratification and 1:1 matching, in all groups, hypothermia was associated with increased mortality (P < 0.0001), increased rate of endotracheal intubation (P < 0.0002), increased need for blood transfusion (P < 0.0025), and conversion of cardiac rhythm (P < 0.0027). CONCLUSION: Hypothermia has been shown to be a significant prognostic indicator in the pediatric trauma patient with further potential application. Future studies are indicated to evaluate the incorporation of hypothermia into the Pediatric Trauma Score not only to help predict injury severity and mortality but also to improve appropriate and expeditious patient transfer to pediatric trauma centers and potentially facilitate earlier intervention.


Assuntos
Hipotermia , Adulto , Criança , Humanos , Hipotermia/terapia , Escala de Gravidade do Ferimento , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Centros de Traumatologia
8.
Elife ; 82019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31869306

RESUMO

The vertebrate skull varies widely in shape, accommodating diverse strategies of feeding and predation. The braincase is composed of several flat bones that meet at flexible joints called sutures. Nearly all vertebrates have a prominent 'coronal' suture that separates the front and back of the skull. This suture can develop entirely within mesoderm-derived tissue, neural crest-derived tissue, or at the boundary of the two. Recent paleontological findings and genetic insights in non-mammalian model organisms serve to revise fundamental knowledge on the development and evolution of this suture. Growing evidence supports a decoupling of the germ layer origins of the mesenchyme that forms the calvarial bones from inductive signaling that establishes discrete bone centers. Changes in these relationships facilitate skull evolution and may create susceptibility to disease. These concepts provide a general framework for approaching issues of homology in cases where germ layer origins have shifted during evolution.


Assuntos
Evolução Biológica , Mesoderma/crescimento & desenvolvimento , Crista Neural/crescimento & desenvolvimento , Crânio/crescimento & desenvolvimento , Animais , Suturas Cranianas/crescimento & desenvolvimento , Suturas Cranianas/patologia , Humanos , Crânio/patologia
9.
Stud Health Technol Inform ; 264: 403-407, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437954

RESUMO

In trauma care and trauma care research there exists an implementation gap regarding a consistent controlled vocabulary to describe organizational aspects of trauma centers and trauma systems. This paper describes the development and evaluation of a controlled vocabulary for trauma care organizations. We give a detailed description of the involvement of domain experts in the domain analysis workflow and the authoring of definitions and additional term descriptions. Finally, the paper details the evaluation methodology to assess the initial version of the controlled vocabulary. The results of the evaluation show that our development process yields terms most of which find approval from domain experts not involved in the development. In addition, our evaluation tools resulted in valuable domain expert input to optimize the controlled vocabulary.


Assuntos
Centros de Traumatologia , Vocabulário Controlado , Fluxo de Trabalho
10.
Elife ; 72018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30375332

RESUMO

Cranial sutures separate the skull bones and house stem cells for bone growth and repair. In Saethre-Chotzen syndrome, mutations in TCF12 or TWIST1 ablate a specific suture, the coronal. This suture forms at a neural-crest/mesoderm interface in mammals and a mesoderm/mesoderm interface in zebrafish. Despite this difference, we show that combinatorial loss of TCF12 and TWIST1 homologs in zebrafish also results in specific loss of the coronal suture. Sequential bone staining reveals an initial, directional acceleration of bone production in the mutant skull, with subsequent localized stalling of bone growth prefiguring coronal suture loss. Mouse genetics further reveal requirements for Twist1 and Tcf12 in both the frontal and parietal bones for suture patency, and to maintain putative progenitors in the coronal region. These findings reveal conservation of coronal suture formation despite evolutionary shifts in embryonic origins, and suggest that the coronal suture might be especially susceptible to imbalances in progenitor maintenance and osteoblast differentiation.


Assuntos
Acrocefalossindactilia/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Craniossinostoses/genética , Proteína 1 Relacionada a Twist/genética , Acrocefalossindactilia/patologia , Animais , Desenvolvimento Ósseo , Craniossinostoses/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Inativação de Genes , Humanos , Camundongos , Mutação , Crista Neural/crescimento & desenvolvimento , Crista Neural/patologia , Osteogênese/genética , Peixe-Zebra/genética
11.
J Vis Exp ; (140)2018 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-30371662

RESUMO

Neural crest cells (NCCs) are migrating multipotent stem cells that can differentiate into different cell types and give rise to multiple tissues and organs. The O9-1 cell line is derived from the endogenous mouse embryonic NCCs and maintains its multipotency. However, under specific culture conditions, O9-1 cells can differentiate into different cell types and be utilized in a wide range of research applications. Recently, with the combination of mouse studies and O9-1 cell studies, we have shown that the Hippo signaling pathway effectors Yap and Taz play important roles in neural crest-derived craniofacial development. Although the culturing process for O9-1 cells is more complicated than that used for other cell lines, the O9-1 cell line is a powerful model for investigating NCCs in vitro. Here, we present a protocol for culturing the O9-1 cell line to maintain its stemness, as well as protocols for differentiating O9-1 cells into different cell types, such as smooth muscle cells and osteoblasts. In addition, protocols are described for performing gene loss-of-function studies in O9-1 cells by using CRISPR-Cas9 deletion and small interfering RNA-mediated knockdown.


Assuntos
Técnicas de Cultura de Células , Células-Tronco Multipotentes/citologia , Crista Neural/citologia , Animais , Sistemas CRISPR-Cas , Diferenciação Celular , Linhagem Celular , Camundongos , Miócitos de Músculo Liso , Osteoblastos , RNA Interferente Pequeno/genética
13.
J Invest Dermatol ; 138(9): 2041-2050, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29577917

RESUMO

Cutaneous wounds in adult mammals typically heal by scarring. However, large full-thickness wounds undergo wound-induced hair follicle neogenesis (WIHN), a form of regeneration. Here, we show that WIHN requires transient expression of epidermal Msx2 in two phases: the wound margin early and the wound center late. Msx2 expression is present in the migrating epithelium during early wound healing and then presents in the epithelium and mesenchyme later in the wound center. WIHN is abrogated in germline and epithelial-specific Msx2 mutant mice. Unlike the full-length Msx2 promoter, a minimal Msx2 promoter fails activation in the wound center, suggesting complex regulation of Msx2 expression. The Msx2 promoter binding sites include Tcf/Lef, Jun/Creb, Pax3, and three SMAD sites. However, basal epithelial-induced BMP suppression by noggin overexpression did not affect WIHN. We propose that Msx2 signaling is required for the epidermis to acquire spatiotemporal competence during WIHN. Topologically, hair regeneration dominates in the wound center, coinciding with late Msx2 expression. Together, these results suggest that intrinsic Msx2 expression supports epithelial competency during hair follicle neogenesis. This work provides insight into endogenous mechanisms modulating competency of adult epidermal progenitors for mammalian ectodermal appendage neogenesis, and offers the target Msx2 for future regeneration-promoting therapies.


Assuntos
Regulação da Expressão Gênica , Folículo Piloso/patologia , Proteínas de Homeodomínio/genética , Regeneração/fisiologia , Pele/lesões , Cicatrização/genética , Ferimentos e Lesões/complicações , Animais , Modelos Animais de Doenças , Folículo Piloso/metabolismo , Proteínas de Homeodomínio/biossíntese , Camundongos Endogâmicos C57BL , Camundongos SCID , RNA/genética , Transdução de Sinais , Pele/metabolismo , Pele/patologia , Ferimentos e Lesões/genética , Ferimentos e Lesões/metabolismo
14.
J Trauma Acute Care Surg ; 84(5): 771-779, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29389839

RESUMO

BACKGROUND: In 2009, Arkansas implemented a statewide trauma system to address the high rates of mortality and morbidity due to trauma. The principal objective of the Arkansas Trauma System is to transport patients to the appropriate facility based on the injuries of the patients. This study evaluated four metrics that were crucial to system health. These measures included: treatment location, scene triage, admission to nondesignated facilities, and inpatient mortality. Furthermore, the authors sought to quantify how the system is selective toward the severely injured regarding triage and treatment location. The authors hypothesized that system implementation should increase the proportion of patients, particularly the severely injured, treated at Level I/II facilities. The system should increase the proportion of patients, especially the severely injured, admitted to Level I/II facilities directly from the scene. The system should result in fewer patients admitted to nondesignated facilities. Lastly, system implementation should result in fewer inpatient deaths. METHODS: A pre-post study design was used for this evaluation. Data from the Arkansas Hospital Discharge data set (2007 through 2012) identified patients who were admitted as a result of their injuries. The ICD-MAP software was used to categorize those with and without severe injuries based on an Injury Severity Score of 16 or greater or head Abbreviated Injury Scale score of 3 or greater. RESULTS: The results indicate that while there was an overall increase in odds of patients being admitted to Level I/II facilities, those with severe injuries were associated with an even greater odds of admission to Level I/II facilities (p < 0.0001). System implementation was also associated with more severely injured patients admitted to Level I/II facilities from the scene. There were also fewer patients admitted to nondesignated hospitals after system implementation (p < 0.0001). System implementation was associated with fewer inpatient deaths (p = 0.02). CONCLUSION: Two years after implementation, the trauma system showed significant progress. The measures evaluated in this study are believed to support the effectiveness of the trauma system. LEVEL OF EVIDENCE: Therapeutic study, level IV.


Assuntos
Pacientes Internados/estatística & dados numéricos , Transferência de Pacientes/organização & administração , Centros de Traumatologia/organização & administração , Triagem/organização & administração , Ferimentos e Lesões/mortalidade , Adolescente , Adulto , Arkansas/epidemiologia , Feminino , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transporte de Pacientes/organização & administração , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/terapia , Adulto Jovem
15.
J Am Coll Radiol ; 15(1 Pt A): 58-64, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28847467

RESUMO

BACKGROUND: Use of cranial CT scans in children has been increasing, in part due to increased awareness of sports-related concussions. CT is the largest contributor to medical radiation exposure, a risk factor for cancer. Long-term cancer risks of CT scans can be two to three times higher for children than for adults because children are more radiosensitive and have a longer lifetime in which to accumulate exposure from multiple scans. STUDY AIM: To compare the radiation exposure injured children receive when imaged at nonpediatric hospitals (NPHs) versus pediatric hospitals. METHODS: Injured children younger than 18 years who received a CT scan at a referring hospital during calendar years (CYs) 2010 and 2013 were included. Patient-level factors included demographics, mode of transportation, and Injury Severity Score, and hospital-level factors included region of state, radiology services, and hospital type and size. Our primary outcome of interest was the effective radiation dose. RESULTS: Four hundred eighty-seven children were transferred to the pediatric trauma center during CYs 2010 and 2013, with a median age of 7.2 years (interquartile range 5-13). The median effective radiation dose received at NPHs was twice that received at the pediatric trauma center (3.8 versus 1.6 mSv, P < .001). Results were confirmed in independent and paired analyses, after controlling for mode of transportation, emergency department disposition, level of injury severity, and at the NPH trauma center level, hospital type, size, region, and radiology services location. CONCLUSION: NPHs have the potential to substantially reduce the medical radiation received by injured children. Pediatric CT protocols should be considered.


Assuntos
Doses de Radiação , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Ferimentos e Lesões/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hospitais Pediátricos , Humanos , Escala de Gravidade do Ferimento , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Sistema de Registros , Centros de Traumatologia
16.
Sci Rep ; 7(1): 2497, 2017 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-28566723

RESUMO

Whereas Jagged1-Notch2 signaling is known to pattern the sensorineural components of the inner ear, its role in middle ear development has been less clear. We previously reported a role for Jagged-Notch signaling in shaping skeletal elements derived from the first two pharyngeal arches of zebrafish. Here we show a conserved requirement for Jagged1-Notch2 signaling in patterning the stapes and incus middle ear bones derived from the equivalent pharyngeal arches of mammals. Mice lacking Jagged1 or Notch2 in neural crest-derived cells (NCCs) of the pharyngeal arches display a malformed stapes. Heterozygous Jagged1 knockout mice, a model for Alagille Syndrome (AGS), also display stapes and incus defects. We find that Jagged1-Notch2 signaling functions early to pattern the stapes cartilage template, with stapes malformations correlating with hearing loss across all frequencies. We observe similar stapes defects and hearing loss in one patient with heterozygous JAGGED1 loss, and a diversity of conductive and sensorineural hearing loss in nearly half of AGS patients, many of which carry JAGGED1 mutations. Our findings reveal deep conservation of Jagged1-Notch2 signaling in patterning the pharyngeal arches from fish to mouse to man, despite the very different functions of their skeletal derivatives in jaw support and sound transduction.


Assuntos
Síndrome de Alagille/genética , Perda Auditiva Neurossensorial/genética , Proteína Jagged-1/genética , Receptor Notch2/genética , Síndrome de Alagille/fisiopatologia , Animais , Orelha Média/crescimento & desenvolvimento , Orelha Média/patologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Perda Auditiva Neurossensorial/patologia , Humanos , Camundongos , Camundongos Knockout , Crista Neural/crescimento & desenvolvimento , Crista Neural/patologia , Transdução de Sinais/genética
17.
Development ; 144(11): 2021-2031, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28455376

RESUMO

Jaw morphogenesis is a complex event mediated by inductive signals that establish and maintain the distinct developmental domains required for formation of hinged jaws, the defining feature of gnathostomes. The mandibular portion of pharyngeal arch 1 is patterned dorsally by Jagged-Notch signaling and ventrally by endothelin receptor A (EDNRA) signaling. Loss of EDNRA signaling disrupts normal ventral gene expression, the result of which is homeotic transformation of the mandible into a maxilla-like structure. However, loss of Jagged-Notch signaling does not result in significant changes in maxillary development. Here we show in mouse that the transcription factor SIX1 regulates dorsal arch development not only by inducing dorsal Jag1 expression but also by inhibiting endothelin 1 (Edn1) expression in the pharyngeal endoderm of the dorsal arch, thus preventing dorsal EDNRA signaling. In the absence of SIX1, but not JAG1, aberrant EDNRA signaling in the dorsal domain results in partial duplication of the mandible. Together, our results illustrate that SIX1 is the central mediator of dorsal mandibular arch identity, thus ensuring separation of bone development between the upper and lower jaws.


Assuntos
Endotelina-1/metabolismo , Proteínas de Homeodomínio/metabolismo , Maxila/embriologia , Maxila/metabolismo , Transdução de Sinais , Animais , Padronização Corporal/genética , Região Branquial/metabolismo , Anormalidades Craniofaciais/embriologia , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Embrião de Mamíferos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Integrases/metabolismo , Camundongos , Modelos Biológicos , Crista Neural/metabolismo , Receptor de Endotelina A/metabolismo , Receptores Notch/metabolismo , Proteínas Serrate-Jagged/metabolismo , Fator de Transcrição Sp7 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima/genética , Zigoma/embriologia , Zigoma/metabolismo
18.
Am J Surg ; 214(2): 336-340, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28277233

RESUMO

BACKGROUND: There is no required competency for pediatric vascular injury in surgical training. We sought to describe changes over time for surgical specialists operating on pediatric vascular trauma injuries at a pediatric trauma center. METHODS: Charts were retrospectively reviewed for vascular trauma injuries at a freestanding children's hospital between 1993 and 2015. Data were collected on mechanism, injured vessel(s), operation(s) performed, and specialists performing operation. Surgical specialists were compared over time. RESULTS: Ninety-four patients (median age = 12) underwent 101 pediatric vascular trauma operations. There were significant differences in frequency of types of operations (primary repairs, graft repairs, and ligations) performed by pediatric, vascular, and orthopedic surgeons (P < .001). The proportion of operations performed by vascular surgeons increased and those performed by pediatric surgeons decreased significantly over time. CONCLUSIONS: Various surgical specialists manage pediatric vascular trauma. With expansion of integrated residency programs, surgical specialists managing these patients in the future should be trained in both pediatric and vascular surgery.


Assuntos
Internato e Residência , Pediatria/educação , Especialidades Cirúrgicas/educação , Lesões do Sistema Vascular/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
19.
Am Surg ; 82(9): 825-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27670571

RESUMO

Major trunk trauma is common and costly, but comparisons of costs between trauma centers (TCs) are rare. Understanding cost is essential to improve quality, manage trauma service lines, and to facilitate institutional commitment for trauma. We have used results of a statewide trauma financial survey of Levels I to IV TC to develop a useful grouping method for costs and clinical characteristics of major trunk trauma. The trauma financial survey collected billing and clinical data on 75 per cent of the state trauma registry patients for fiscal year 2012. Cost was calculated by separately accounting for embedded costs of trauma response and verification, and then adjusting reasonable costs from the Medicare cost report for each TC. The cost-to-charge ratios were then recalculated and used to determine uniform cost estimates for each patient. From the 13,215 patients submitted for the survey, we selected 1,094 patients with major trunk trauma: lengths of stay ≥ 48 hours and a maximum injury of AIS ≥3 for either thorax or abdominal trauma. These patients were then divided into three Injury Severity Score (ISS) groups of 9 to 15, 16 to 24, or 25+ to stratify patients into similar injury groups for analysis of cost and cost drivers. For abdominal injury, average total cost for patients with ISS 9 to 15 was $17,429. Total cost and cost per day increased with severity of injury, with $51,585 being the total cost for those with ISS 25. Similar trends existed for thoracic injury. Use of the Medicare cost report and cost-to-charge ratios to compute uniform costs with an innovative grouping method applied to data collected across a statewide trauma system provides unique information regarding cost and outcomes, which affects quality improvement, trauma service line management, and decisions on TC participation.


Assuntos
Traumatismos Abdominais/economia , Custos Hospitalares/estatística & dados numéricos , Traumatismo Múltiplo/economia , Traumatismos Torácicos/economia , Centros de Traumatologia/economia , Traumatismos Abdominais/diagnóstico , Traumatismos Abdominais/terapia , Adulto , Idoso , Arkansas , Pesquisas sobre Atenção à Saúde , Preços Hospitalares/estatística & dados numéricos , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação/economia , Medicare/economia , Pessoa de Meia-Idade , Traumatismo Múltiplo/diagnóstico , Traumatismo Múltiplo/terapia , Traumatismos Torácicos/diagnóstico , Traumatismos Torácicos/terapia , Estados Unidos
20.
J Am Coll Radiol ; 13(11): 1397-1403, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27577592

RESUMO

PURPOSE: The long-term cancer risks for children exposed to radiologic images can be two to three times higher than for adults because children are more sensitive to radiation and have a longer lifetime in which to accumulate exposure from CT scans. Injured children often undergo repeat CT imaging if they are transferred from non-pediatric hospitals to a Level I pediatric trauma center (PTC). This study determined the impact of a statewide web-based image repository (WBIR) on repeat imaging among transferred injured children. METHODS: All injured children who underwent CT imaging and were transferred to the PTC in 2010 (pre-WBIR) and 2013 (post-WBIR) were included. Patient-level factors studied included demographics, body region of scan, Injury Severity Score, and Emergency Department (ED) disposition. Change from pre to post on rate of repeat imaging was assessed. RESULTS: Two hundred fifty-four and 233 children, with a median age of 7.3 years, were transferred to the Children's Hospital in 2010 and 2013, respectively. Repeat imaging levels at the PTC were lower post-WBIR than pre-WBIR (20% versus 33%, odds ratio [OR] 0.54, P = .005). Images of the head decreased most significantly (60% versus 33%, OR 0.33). Images performed at Level II and III trauma centers were repeated less often after WBIR. CONCLUSIONS: The WBIR significantly reduced repeat imaging among injured children transferred to a PTC, especially children transferred from Level II and Level III trauma centers, children with lower-acuity injuries, and children with initial scans of the head. Radiation savings are expected to be beneficial to children.


Assuntos
Internet , Doses de Radiação , Exposição à Radiação/efeitos adversos , Exposição à Radiação/estatística & dados numéricos , Sistema de Registros , Tomografia Computadorizada por Raios X , Ferimentos e Lesões/diagnóstico por imagem , Arkansas/epidemiologia , Carga Corporal (Radioterapia) , Criança , Pré-Escolar , Estudos Transversais , Demografia , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Neoplasias Induzidas por Radiação/epidemiologia , Transferência de Pacientes , Retratamento , Medição de Risco , Centros de Traumatologia , Ferimentos e Lesões/epidemiologia
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