Development and Validation of A Predictive Model For Childhood Mortality After A Traumatic Brain Injury: Analysis of the National Trauma Data Bank

Introduction: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in children. While most TBI-related admissions are mild, identifying early predictors of poor outcome may assist clinicians with timely medical decisions and effective triage utilization. Objective: We sought to develop and validate a clinical tool for predicting in-hospital death in children after a traumatic brain injury. Methods: Data was collected for children (≤18 years) from the National Trauma Data Bank between the years of 2007 to 2015. We included children who sustained any TBI, defined as: (i) open and closed skull fractures, (ii) cerebellar, cortical, or brain stem contusions, and (iii) subarachnoid, subdural, or epidural hemorrhages. We excluded studies that did not report patient age or individuals who were dead on arrival or died in the emergency room (ER). Our interest was in clinical variables that can be readily measured upon admission to the ER. As such, the predictors included patient demographics, mechanism and intent of injury, vital signs in the ER, mode of transportation, respiratory status, time from injury to ER arrival, Glasgow Coma Score (GCS), and Injury Severity Score (ISS). Multivariable logistic regression, with forward selection, was used to investigate associations between predictive variable and mortality. We randomly split the samples into a training set (70%) and a test set (30%). Model performance was measured via the C-statistic and accuracy [(true positive + true negative) / patient population]. Results: A total of 124,078 children were included in the study (69% male; median [IQR] age, 13.0 [6.0, 16.0.] years; 69% White). The rate of death was 5.5% (n=6,862). Children more likely to die were older (16 vs. 12 years, p Conclusion: Herein, we provide an accurate early prediction model for mortality in children after a TBI. Translation of our findings has led to the development of a web application that can be used by emergency healthcare providers in trauma centers

Global Prevalence of Bronchopulmonary Dysplasia in Very Low Birth Weight Neonates: A Systematic Review and Meta-Analysis

Importance: Large-scale estimates of bronchopulmonary dysplasia (BPD) are warranted for adequate prevention and treatment. However, systematic approaches to ascertain global rates of BPD are lacking. Objective: To conduct a systematic review and meta-analysis to assess the prevalence of BPD in very low birth weight (≤1,500 grams) or very low gestational age (\u3c32 \u3eweeks) neonates. Data sources: A search of MEDLINE from January 1990 until September 2019 using search terms related to BPD and prevalence was performed. Study selection: Randomized controlled trials and observational studies evaluating rates of BPD in very low birth weight or very low gestational age were eligible. Included studies defined BPD as positive pressure ventilation or oxygen requirement at 28 days (BPD28) or at 36 weeks postmenstrual age (BPD36). Data extraction and synthesis: Two reviewers independently conducted all stages of the review. Random-effects meta-analysis was used to calculate the pooled prevalence. Subgroup analyses included gestational age group, birth weight group, setting, study period, continent, and gross domestic product. Meta-regression was performed to identify the impact of significant variables on study effect. Main outcomes and measures: Prevalence of BPD defined as BPD28, BPD36, AnyBPD (BPD 28 or BPD 36), and by subgroups. Results: A total of 82 articles and 696,881 patients were included in this review. The pooled prevalence was 23% (95% CI, 17%-30%) for BPD28 (n=29 studies, 101,848 neonates), 21% (95% CI, 17%-24%) for BPD36 (n=56 studies, 584,448 neonates), and 19% (95% CI, 16%-22%) for any BPD (n=70 studies, 607,653 neonates). In subgroup meta-analyses, birth weight was the strongest driver of the pooled prevalence of BPD. Conclusions and relevance: This study provides a global estimation of BPD prevalence in very low birth weight/low gestation neonates

Intranasal Delivery of Human Umbilical Cord Stromal Cell Conditioned Media Improves Alveolar Growth and Vascular Remodeling In Experimental Bronchopulmonary Dysplasia

Introduction: Bronchopulmonary dysplasia (BPD) is a lung disease with high morbidity and mortality in premature neonates exposed to mechanical ventilation and oxygen support. Preclinical studies demonstrate mesenchymal stromal cell (MSC) conditioned media (CdM) improves histologic changes in BPD via the release of paracrine factors. Current modes of administration include intratracheal or intraperitoneal routes with CdM cultured in ambient air. Objectives: The objective of this study was twofold: (i) assess the efficacy of intranasal delivery of CdM, and (ii) determine whether hypoxic preconditioning stimulates the therapeutic potential of CdM. Methods: Newborn rat pups were randomly assigned to four groups: (1) room air treated with αMEM vehicle (RA+Veh), (2) four days of hyperoxia (BPD+Veh), (3) BPD treated with CdM from normoxic MSCs (BPD+CdM), and (4) BPD treated with CdM from hypoxic preconditioned (1% O2) MSCs (BPD+hypoCdM). Twenty μL of human mesenchymal stromal cell CdM or hypoxic CdM (hypoCdM) was administered intranasally to rat pups on days 4, 10, and 20. Mean linear intercept, medial wall thickness, and vascular density were used to assess alveolarization, pulmonary remodeling, and vascular growth, respectively. Gene expression of cytokines and growth factors in animal lungs and CdM were measured. Results and Discussion: Intranasal CdM, but not hypoxic CdM, improved lung alveolarization. Both CdM and hypoCdM improved pulmonary vascular remodeling; however, only hypoCdM restored vascular density. CdM upregulated the expression of genes involved in wound healing and inflammation. Conclusion: Intranasal delivery of CdM/hypoCdM restored lung development in a BPD rat model. Mechanisms by which umbilical cord-derived stem cell CdM provides pulmonary benefit points toward wound repair and immunomodulation. Future directions include: (i) optimizing the timing, volume, frequency, and concentration of the CdM and (ii) improving the preconditioning approach for MSCs to enhance the therapeutic efficacy. Acknowledgements: Data were generated in the Flow Cytometry Shared Resource Facility, which is supported by UTHSCSA, NIH-NCI P30 CA054174-20 (Cancer Therapy and Research Center at UTHSCSA) and UL1 TR001129 (Clinical and Translational Science Award). Our gratitude extends to the Pathology Core at UTHSCSA