Addition of neurological status to pediatric adjusted shock index to predict early mortality in trauma: A pediatric Trauma Quality Improvement Program analysis.

INTRODUCTION: Pediatric adjusted shock index (SIPA) has demonstrated the ability to prospectively identify children at the highest risk for early mortality. The addition of neurological status to shock index has shown promise as a reliable triage tool in adult trauma populations. This study sought to assess the utility of combining SIPA with Glasgow Coma Scale (GCS) for predicting early trauma-related outcomes. METHODS: Retrospective review of the 2017 Trauma Quality Improvement Program Database was performed for all severely injured patients younger than 18 years old. Pediatric adjusted shock index and reverse SIPA × GCS (rSIG) were calculated. Age-specific cutoff values were derived for reverse shock index multiplied by GCS (rSIG) and compared with their SIPA counterparts for early mortality assessment using area under the receiver operating characteristic curve analyses. RESULTS: A total of 10,389 pediatric patients with an average age of 11.4 years, 67% male, average Injury Severity Score of 24.1, and 4% sustaining a major penetrating injury were included in the analysis. The overall mortality was 9.3%. Furthermore, 32.1% of patients displayed an elevated SIPA score, while only 27.5% displayed a positive rSIG. On area under the receiver operating characteristic curve analysis, rSIG was found to be superior to SIPA as a predictor for in hospital mortality with values of 0.854 versus 0.628, respectively. CONCLUSION: Reverse shock index multiplied by GCS more readily predicted in hospital mortality for pediatric trauma patients when compared with SIPA. These findings suggest that neurological status should be an important factor during initial patient assessment. Further study to assess the applicability of rSIG for expanded trauma-related outcomes in pediatric trauma is necessary. LEVEL OF EVIDENCE: Prognostic study, level IV.

Celecoxib inhibits Ewing sarcoma cell migration via actin modulation.

BACKGROUND: Ewing sarcoma (ES) is an aggressive childhood solid tumor in which 30% of cases are metastatic at presentation, and subsequently carry a poor prognosis. We have previously shown that treatment with celecoxib significantly reduces invasion and metastasis of ES cells in a cyclooxygenase-2-independent fashion. Celecoxib is known to downregulate ß-catenin independently of cyclooxygenase-2. Additionally, the actin cytoskeleton is known to play an important role in tumor micrometastasis. We hypothesized that celecoxib's antimetastatic effect in ES acts via modulation of one of these two targets. METHODS: ES cells were treated with celecoxib, and the levels of ß-catenin and total actin were examined by Western blot and quantitative polymerase chain reaction. Cells were transfected with small interfering RNA targeting ß-catenin, and invasion assays were performed. Immunofluorescence staining for ß-catenin and F-actin was performed on treated and untreated cells. Additionally, cells were subjected to a wound healing assay to assess migration. RESULTS: Celecoxib had no effect on the messenger RNA or protein levels of ß-catenin but did significantly decrease the amount of total actin within ES cells. Reduction of ß-catenin by small interfering RNA had no effect on invasion, and celecoxib treatment of the ß-catenin depleted cells continued to inhibit invasion. Immunofluorescence staining demonstrated no change in ß-catenin with treatment but did show a significant reduction in the amount of F-actin, as well as morphologic changes of the cells. Wound healing assays demonstrated that celecoxib significantly inhibited migration. CONCLUSIONS: Celecoxib does not exert its antimetastatic effects in ES through alteration of ß-catenin but does significantly modulate the actin cytoskeleton.

Celecoxib inhibits invasion and metastasis via a cyclooxygenase 2-independent mechanism in an in vitro model of Ewing sarcoma.

BACKGROUND/INTRODUCTION: Previously, we reported that celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, prevented lung metastases but did not affect tumor growth in a model of Ewing sarcoma. Cyclooxygenase-2 inhibition has been proposed as an antimetastatic strategy. The mechanism of action remains unclear. METHODS: Ewing sarcoma cells were suspended in a soluble basement membrane extract (Cultrex; Trevigen, Inc, Gaithersburg, MD) and supplemented with celecoxib or with rofecoxib, a second COX-2 inhibitor, above a filter. Controls received solvent. After 48 hours, the cells that invaded through the basement membrane and filter were stained and counted. The assay was repeated with the addition of 500-nM prostaglandin E2 (PGE(2)). RESULTS: Invasion was significantly decreased in the celecoxib groups compared with the control. The addition of PGE(2) did not overcome celecoxib inhibition. Rofecoxib did not significantly affect invasion compared with control either with or without PGE(2). CONCLUSIONS: Celecoxib significantly inhibits invasion of Ewing sarcoma cells in vitro. Prostaglandin E2, a downstream product of COX-2, did not reverse in vitro inhibition, suggesting that celecoxib acts through a COX-2-independent mechanism. This is further supported by the failure of rofecoxib to inhibit invasion despite more selectively inhibiting COX-2.