Brian P. Blackwood

Focal therapy of neuroblastoma using silk films to deliver kinase and chemotherapeutic agents in vivo

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.

Probiotic Lactobacillus Species Strengthen Intestinal Barrier Function and Tight Junction Integrity in Experimental Necrotizing Enterocolitis

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.

Observation for isolated traumatic skull fractures in the pediatric population: unnecessary and costly

BACKGROUND Blunt head trauma accounts for a majority of pediatric trauma admissions. There is a growing subset of these patients with isolated skull fractures, but little evidence guiding their management. We hypothesized that inpatient neurological observation for pediatric patients with isolated skull fractures and normal neurological examinations is unnecessary and costly. METHODS We performed a single center 10year retrospective review of all head traumas with isolated traumatic skull fractures and normal neurological examination. Exclusion criteria included: penetrating head trauma, depressed fractures, intracranial hemorrhage, skull base fracture, pneumocephalus, and poly-trauma. In each patient, we analyzed: age, fracture location, loss of consciousness, injury mechanism, Emergency Department (ED) disposition, need for repeat imaging, hospital costs, intracranial hemorrhage, and surgical intervention. RESULTS Seventy-one patients presented to our ED with acute isolated skull fractures, 56% were male and 44% were female. Their ages ranged from 1week to 12.4years old. The minority (22.5%) of patients were discharged from the ED following evaluation, whereas 77.5% were admitted for neurological observation. None of the patients required neurosurgical intervention. Age was not associated with repeat imaging or inpatient observation (p=0.7474, p=0.9670). No patients underwent repeat head imaging during their index admission. Repeat imaging was obtained in three previously admitted patients who returned to the ED. Cost analysis revealed a significant difference in total hospital costs between the groups, with an average increase in charges of

Peripherally Inserted Central Catheters Complicated by Vascular Erosion in Neonates

4,291.50 for admitted patients (p<0.0001). CONCLUSION Pediatric isolated skull fractures are low risk conditions with a low likelihood of complications. Further studies are necessary to change clinical practice, but our research indicates that these patients can be discharged safely from the ED without inpatient observation. This change in practice, additionally, would allow for huge health care dollar savings.

Overweight and Obese Pediatric Patients Have an Increased Risk of Developing a Surgical Site Infection.

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.

Pediatric Intussusception: Decreased Surgical Risk with Timely Transfer to a Childrenâs Hospital

BACKGROUND Obesity is a known risk factor in adult surgical site infections (SSIs), but its significance in pediatrics is unclear. We hypothesized that overweight and obese children have increased risk for SSI. PATIENTS AND METHODS A National Surgical Quality Improvement Program-Pediatric (NSQIP-P) file and single-center reviews identified surgical patients (2-18 years) who developed SSIs. Patients were classified as underweight, normal, overweight, or obese based on body mass index (BMI). Comorbidities associated with SSI were analyzed. Sub-specialties and operations were recorded. RESULTS National Surgical Quality Improvement Program-Pediatric review identified 66,671 patients and 1,380 SSIs. Seven hundred sixty-seven (767) were male and 613 female. Multivariable analysis revealed overweight and obese BMI to be risk factors for SSIs (odds ratio [OR] 1.23, 95% confidence interval [CI] 1.06-1.43; OR 1.43, 95% CI 1.25-1.63). Most commonly, overweight and obese cohorts had superficial incisional SSIs. Pediatric general surgery (3.6%) and cardiothoracic surgery (2.5%) had the highest rates of SSIs. Single-center review identified 115 SSIs. Of these, 29.6% were overweight or obese with few other identifiable SSI risk factors. Sub-specialties with the most SSIs were pediatric surgery and pediatric orthopedics. Appendectomy was the most common procedure associated with SSIs. CONCLUSION Herein we show elevated BMI to be a significant risk factor for SSIs. This information should be used in assessing and counseling pre-operative pediatric patients and families.

10-year analysis of benign ovarian teratomas: Outcomes and follow-up

Introduction Intussusception is a potentially life-threatening condition, and a frequent cause of bowel obstruction during the first two years of life. We hypothesized that patients who were transferred from outside community hospitals, or OSH, without tertiary care capabilities for pediatric services to a large academic children’s hospital with intussusception were more likely to require operative management for their intussusception than those who were directly admitted. Methods The electronic medical record was queried for patients presenting to Ann and Robert H. Lurie Children’s Hospital of Chicago with a diagnosis of intussusception (July 1st, 2009–July 1st, 2014). Age, sex, symptom duration, radiologic management, and surgical care were recorded. OSH and transfer reports were analyzed for those patients that presented as a transfer. Statistical analysis was performed. Results We identified 270 patients with intussusception. 232 (80%) were successfully treated non-surgically. 58 (20%) required surgical management. Of the patients requiring surgery, there were 38 reductions (24 laparoscopic, 14 open) and 20 bowel resections (1 laparoscopic, 19 open). Of those patients requiring surgery, 37 (63.8%) had presented as a transfer from an OSH. We found that transferred patients, requiring surgery, spent a mean 7.77 hours at the OSH compared to 4.03 hours for the transferred patients that did not require surgery (p=0.0188). There was no significant difference in transport time (p=0.44). Conclusion In conclusion, we identified the amount of time patients spend at hospitals without pediatric surgical capabilities as an independent risk factor necessitating surgical management of intussusception. These data suggest that patients with intussusception who present to hospitals without pediatric radiology or pediatric surgery, should be transferred in an expedited fashion. In the event of a failed enema reduction at an OSH, the transport of the patient should not be delayed as this may result in a higher likelihood of surgical management.