ABSTRACT
BACKGROUND: Abusive head trauma (AHT) peaks during early infancy and decreases in toddler years. Infants and toddlers experience different injuries, possibly impacting the risk of mortality. We aimed to evaluate the association of age with mortality. METHODS: We conducted a retrospective study of AHT hospitalizations in 2000, 2003, 2006, 2009, and 2012 from the Kid's Inpatient Claims Database. An accidental head trauma cohort was included to hypothesize that the association between age and mortality is unique to abuse. A nested multivariable logistic regression was used to perform the analysis. RESULTS: Children aged 2 years to 4 years experienced higher mortality than those younger than 2 years (22% vs. 10%, p < 0.0001; adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1-2.2). The presence of subarachnoid hemorrhage (OR, 1.9; 95% CI, 1.3-2.9), cerebral edema (OR, 4.0; 95% CI, 2.9-5.4), and retinal hemorrhage (OR, 1.9; 95% CI, 1.5-2.5) were associated with an increase risk in mortality. Children younger than 2 years experienced more fractures and hemorrhage (subdural, subarachnoid, retinal) while children aged 2 years to 4 years encountered more internal injuries and cerebral edema.In children with accidental head trauma, those aged 2 years to 4 years have a lower mortality compared with those younger than 2 years (OR, 0.4; 95% CI, 0.3-0.6). Among children younger than 2 years, AHT and accidental trauma had comparable risk of mortality (OR, 0.9; 95% CI, 0.6-1.3). However, among those aged 22 years to 4 years, AHT had a higher risk of mortality than accidental trauma (OR, 3.3; 95% CI, 2.1-5.1). CONCLUSION: There is a considerable risk of mortality associated with age at diagnosis in children with AHT.Children younger than 2 years and those aged 2 years to 4 years present with different types of injuries. The high risk of mortality in the children aged 2 years to 4 years is unique to AHT. Efforts should be made to increase awareness about the risk of mortality and identify factors that can aide in a timely accurate diagnosis. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level III.
Subject(s)
Accidental Injuries/diagnosis , Brain Edema , Child Abuse/diagnosis , Craniocerebral Trauma , Subarachnoid Hemorrhage , Accidental Injuries/epidemiology , Age Factors , Brain Edema/diagnosis , Brain Edema/etiology , Child Abuse/statistics & numerical data , Child, Preschool , Craniocerebral Trauma/etiology , Craniocerebral Trauma/mortality , Craniocerebral Trauma/therapy , Diagnosis, Differential , Early Diagnosis , Female , Hospitalization/statistics & numerical data , Humans , Infant , Male , Mortality , Prognosis , Retrospective Studies , Risk Factors , Subarachnoid Hemorrhage/diagnosis , Subarachnoid Hemorrhage/etiologyABSTRACT
Mesenchymal stem cells (MSC) are known to facilitate healing of ischemic tissue related diseases through proangiogenic secretory proteins. Recent studies further show that MSC derived exosomes function as paracrine effectors of angiogenesis, however, the identity of which components of the exosome proteome responsible for this effect remains elusive. To address this we used high-resolution isoelectric focusing coupled liquid chromatography tandem mass spectrometry, an unbiased high throughput proteomics approach to comprehensively characterize the proteinaceous contents of MSCs and MSC derived exosomes. We probed the proteome of MSCs and MSC derived exosomes from cells cultured under expansion conditions and under ischemic tissue simulated conditions to elucidate key angiogenic paracrine effectors present and potentially differentially expressed in these conditions. In total, 6,342 proteins were identified in MSCs and 1,927 proteins in MSC derived exosomes, representing to our knowledge the first time these proteomes have been probed comprehensively. Multilayered analyses identified several putative paracrine effectors of angiogenesis present in MSC exosomes and increased in expression in MSCs exposed to ischemic tissue-simulated conditions; these include platelet derived growth factor, epidermal growth factor, fibroblast growth factor, and most notably nuclear factor-kappaB (NFkB) signaling pathway proteins. NFkB signaling was identified as a key mediator of MSC exosome induced angiogenesis in endothelial cells by functional in vitro validation using a specific inhibitor. Collectively, the results of our proteomic analysis show that MSC derived exosomes contain a robust profile of angiogenic paracrine effectors, which have potential for the treatment of ischemic tissue-related diseases.
