Necrotizing enterocolitis (NEC) is a serious intestinal disease that occurs in newborn infants. It is associated with major morbidity and affects 5% of all infants admitted to neonatal intensive care units. Probiotics have variable efficacy in preventing necrotizing enterocolitis. Tight junctions (TJ) are protein complexes that maintain epithelial barrier integrity. We hypothesized that the probiotics Lactobacillus rhamnosus and Lactobacillus plantarum strengthen intestinal barrier function, promote TJ integrity, and protect against experimental NEC. Both an in vitro and an in vivo experimental model of NEC were studied. Cultured human intestinal Caco-2 cells were pretreated with L. rhamnosus and L. plantarum probiotics. TJ were then disrupted by EGTA calcium switch or LPS to mimic NEC in vitro. Trans-epithelial resistance (TER) and flux of fluorescein isothiocynate dextran was measured. TJ structure was evaluated by ZO-1 immunofluorescence. In vivo effects of ingested probiotics on intestinal injury and ZO-1 expression were assessed in a rat model of NEC infected with Cronobacter sakazakii (CS). Caco-2 cells treated with individual probiotics demonstrated higher TER and lower permeability compared to untreated cells (p<0.0001). ZO-1 immunofluorescence confirmed TJ stability in treated cells. Rat pups fed probiotics alone had more intestinal injury compared with controls (p=0.0106). Probiotics were protective against injury when given in combination with CS, with no difference in intestinal injury compared to controls (p=0.21). Increased permeability was observed in the probiotic and CS groups (p=0.03, p=0.05), but not in the probiotic plus CS group (p=0.79). Lactobacillus sp. strengthened intestinal barrier function and preserved TJ integrity in an in vitro experimental model of NEC. In vivo, probiotic bacteria were not beneficial when given alone, but were protective in the presence of CS in a rat model of NEC.

Current methods for treatment of high-risk neuroblastoma patients include surgical intervention, in addition to systemic chemotherapy. However, only limited therapeutic tools are available to pediatric surgeons involved in neuroblastoma care, so the development of intraoperative treatment modalities is highly desirable. This study presents a silk film library generated for focal therapy of neuroblastoma; these films were loaded with either the chemotherapeutic agent doxorubicin or the targeted drug crizotinib. Drug release kinetics from the silk films were fine-tuned by changing the amount and physical crosslinking of silk; doxorubicin loaded films were further refined by applying a gold nanocoating. Doxorubicin-loaded, physically crosslinked silk films showed the best in vitro activity and superior in vivo activity in orthotopic neuroblastoma studies when compared to the doxorubicin-equivalent dose administered intravenously. Silk films were also suitable for delivery of the targeted drug crizotinib, as crizotinib-loaded silk films showed an extended release profile and an improved response both in vitro and in vivo when compared to freely diffusible crizotinib. These findings, when combined with prior in vivo data on silk, support a viable future for silk-based anticancer drug delivery systems.

We found that there is a high degree of variability in the antibiotic regimen for the treatment of NEC, even within a single NICU, with no regimen appearing superior over another. As data emerge that demonstrate the adverse effects of antibiotic overuse, our findings highlight the need for guidelines in the antibiotic treatment of NEC and suggest that an abbreviated course of post-operative antibiotics may be safe.

Peripherally inserted central catheters (PICCs) are widely used in the pediatric population, and their use continues to grow in popularity. These catheters provide a reliable source of venous access to neonatal patients but can also be the cause of life-threatening complications. There are several well-documented complications such as infections, catheter thrombosis, vascular extravasations, and fractured catheters. However, the complication of vascular erosion into the pleural space using both small and silicone-based catheters is rarely described. After obtaining institutional review board approval, we identified 4 cases to review of PICCs complicated by vascular erosions in the past 2 years. Herein, we also review the current literature of PICC complications. Getting the catheter tip as close to the atrial-caval junction as possible and confirmation of this placement are of the utmost importance. The thick wall of the vena cava near the atrium seems to be less likely to perforate; in addition, this position provides increased volume and turbulence to help dilute the hyperosmolar fluid, which seems to also be a factor in this complication. A daily screening chest x-ray in patients with upper extremity PICCs and ongoing parenteral nutrition (PN) are not necessary at this time given the overall low rate of vascular erosion and concerns regarding excessive radiation exposure in pediatric populations. However, a low threshold for chest x-ray imaging in patients with even mild respiratory symptoms in the setting of upper extremity PN is recommended.