Intra-tracheal administration of a naked plasmid expressing stromal derived factor-1 improves lung structure in rodents with experimental bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification and disordered angiogenesis. Stromal derived factor-1 (SDF-1) is a chemokine which modulates cell migration, proliferation, and angiogenesis. Here we tested the hypothesis that intra-tracheal (IT) administration of a naked plasmid DNA expressing SDF-1 would attenuate neonatal hyperoxia-induced lung injury in an experimental model of BPD, by promoting angiogenesis. DESIGN/METHODS: Newborn Sprague-Dawley rat pups (n = 18-20/group) exposed to room air (RA) or hyperoxia (85% O2) from postnatal day (P) 1 to 14 were randomly assigned to receive IT a naked plasmid expressing SDF-1, JVS-100 (Juventas Therapeutics, Cleveland, Ohio) or placebo (PL) on P3. Lung alveolarization, angiogenesis, inflammation, vascular remodeling and pulmonary hypertension (PH) were assessed on P14. PH was determined by measuring right ventricular systolic pressure (RVSP) and the weight ratio of the right to left ventricle + septum (RV/LV + S). Capillary tube formation in SDF-1 treated hyperoxia-exposed human pulmonary microvascular endothelial cells (HPMEC) was determined by matrigel assay. Data is expressed as mean ± SD and analyzed by two-way ANOVA. RESULTS: Exposure of neonatal pups to 14 days of hyperoxia decreased lung SDF-1 gene expression. Moreover, whilst hyperoxia exposure inhibited capillary tube formation in HPMEC, SDF-1 treatment increased tube length and branching in HPMEC. PL-treated hyperoxia-exposed pups had decreased alveolarization and lung vascular density. This was accompanied by an increase in RVSP, RV/LV + S, pulmonary vascular remodeling and inflammation. In contrast, IT JVS-100 improved lung structure, reduced inflammation, PH and vascular remodeling. CONCLUSIONS: Intratracheal administration of a naked plasmid expressing SDF-1 improves alveolar and vascular structure in an experimental model of BPD. These findings suggest that therapies which modulate lung SDF-1 expression may have beneficial effects in preterm infants with BPD.

National Trends of Acute Osteomyelitis and Peripherally Inserted Central Catheters in Children.

OBJECTIVES: Although a growing body of evidence suggests that early transition to oral antimicrobial therapy is equally efficacious to prolonged intravenous antibiotics for treatment of acute pediatric osteomyelitis, little is known about the pediatric trends in peripherally inserted central catheter (PICC) placements. Using a national database, we examined incidence rates of pediatric hospitalizations for acute osteomyelitis in the United States from 2007 through 2016, as well as the trends in PICC placement, length of stay (LOS), and cost associated with these hospitalizations. METHODS: This was a retrospective, serial cross-sectional study of the National Inpatient Sample database from 2007 through 2016. Patients ≤18 years of age with acute osteomyelitis were identified by using appropriate diagnostic codes. Outcomes measured included PICC placement rate, LOS, and inflation-adjusted hospitalization costs. Weighted analysis was reported, and a hierarchical regression model was used to analyze predictors. RESULTS: The annual incidence of acute osteomyelitis increased from 1.0 to 1.8 per 100 000 children from 2007 to 08 to 2015 to 16 (P < .0001), whereas PICC placement rates decreased from 58.8% to 5.9% (P < .0001). Overall, changes in LOS and inflation-adjusted hospital costs were not statistically significant. PICC placements and sepsis were important predictors of increased LOS and hospital costs. CONCLUSIONS: Although PICC placement rates for acute osteomyelitis significantly decreased in the face of increased incidence of acute osteomyelitis in children, LOS and hospital costs for all hospitalizations remained stable. However, patients receiving PICC placements had longer LOS. Further studies are needed to explore the long-term outcomes of reduced PICC use.