Utility of admission serum lactate in pediatric trauma.

BACKGROUND/PURPOSE: Serum lactate measurement has a predictive value in adult trauma. To date, there has been no prospective analysis of the predictive value of admission serum lactate in pediatric trauma. METHODS: Admission serum lactate was prospectively measured over a two year period on all children under age 15 years who met trauma alert criteria at an urban Level 1 trauma center. Elevated serum lactate (>2.0 mmol/L) was correlated with Injury Severity Scores (ISS), injury types, and hospital outcomes. RESULTS: A total of 277 injured children with admission lactate measurements were evaluated. Patients with elevated lactate had higher mean ISS than those with normal lactate (12.8 vs. 5.1, p<0.01), and increased need for intubation, major procedures and ICU admission. Elevated lactate was associated with low specificity (54.4%), moderate sensitivity (86.7%) and high negative predictive value (94.5%) for detecting injury (ISS>15). Lactate measurements over 4.7 mmol/L were highly specific (95.8%) for injury. CONCLUSIONS: Elevated admission venous lactate level is associated with injury and outcomes, but lacks adequate sensitivity and specificity. Lactate over 4.7 mmol/L is strongly suggestive of severe injury, while lactate below 2.0 mmol/L is reassuring for not having injury. Lactates between 2.0 and 4.7 mmol/L remain indeterminate in predictive potential for injury or outcomes.

Rapamycin increases neuroblastoma xenograft and host stromal derived osteoprotegerin inhibiting osteolytic bone disease in a bone metastasis model.

PURPOSE: Osteoprotegerin (OPG) is a decoy receptor for the Receptor of NF-κB (RANK) ligand that can inhibit osteoclastogenesis. Previous studies have suggested that Mammalian Target of Rapamycin (mTOR) inhibition upregulates OPG production. We tested the hypothesis that the mTOR inhibitor rapamycin could inhibit neuroblastoma bone metastases through its action on OPG. EXPERIMENTAL DESIGN: An orthotopic model of bone metastasis was established. Mice with established disease were subsequently treated with rapamycin (5mg/kg IP daily) or vehicle control (DMSO 1:1000). X-rays were obtained twice a week to detect pathologic fractures. Serum OPG levels were measured by ELISA after two weeks of treatment. RESULTS: Mice with bone disease receiving rapamycin had increased serum levels of OPG in the CHLA-20 mice compared to controls (36.89 pg/mL ± 3.90 vs 18.4 pg/mL ± 1.67, p=0.004) and NB1691 tumor-bearing groups (46.03 ± 2.67 pg/mL vs 17.96 ± 1.84pg/mL, p=0.001), and a significantly longer median time to pathologic fractures with CHLA-20 (103 days vs 74.5 days, p=0.014) and NB1691 xenografts. CONCLUSION: In a xenograft model, increased OPG expression correlated with a delay to pathologic fracture suggesting a potential role for mTOR inhibitors in the treatment of neuroblastoma bone metastases.

The effects of irrigation on outcomes in cases of perforated appendicitis in children.

INTRODUCTION: Appendicitis is the most common indication for urgent abdominal operation in children. Approximately 20%-30% of patients will have a perforation at operation. Intra-abdominal abscess after appendectomy is reported in 3%-20% of patients and adds significantly to hospital stay with increased morbidity and overall cost. Surgical dogma has long advocated for irrigation in the setting of gross pus to prevent abscess formation. METHODS: Following IRB approval, data were retrospectively collected for children who had undergone appendectomy for perforated appendicitis at one of two children's hospitals over the course of 5 y. Perforation was determined by review of operative notes. All patients had free fluid in their peritoneal cavity evacuated by suction, whereas some of the patients also had their peritoneal cavity irrigated with normal saline. Postoperative intra-abdominal abscess rates were determined based on clinical symptoms and confirmatory radiologic studies. RESULTS: There were 99 patients in the suction-only group and 139 in the irrigation group. Standard demographics were relatively similar between the two groups. There were significantly lower rates of intra-abdominal abscess formation (4.0% versus 17.2%, P = 0.002) and wound infection (1.0% versus 8.6%, P = 0.003) in the suction-only group compared with the irrigation group. We further analyzed abscess rates by surgical treatment, either laparoscopic or open appendectomy. There were 85 patients in the laparoscopic group and 152 patients in the open appendectomy group. In this subgroup analysis, there were also significantly lower rates of abscess formation in patients treated with suction only compared with irrigation in the laparoscopic (3.5% versus 18.8%, P = 0.012) and open appendectomy groups (4.2% versus 16.3%, P = 0.036). CONCLUSIONS: Results of this retrospective review indicate that a suction-only approach significantly decreased rates of abscess formation and wound infections compared to irrigation in cases of perforated appendicitis in children.

Bevacizumab-induced tumor vessel remodeling in rhabdomyosarcoma xenografts increases the effectiveness of adjuvant ionizing radiation.

PURPOSE: Inhibition of vascular endothelial growth factor (VEGF) may effect transient "normalization" of tumor vasculature by pruning immature vessels, resulting in improved tumor perfusion and oxygenation. This may improve the efficacy of adjuvant ionizing radiation (IR). We tested this hypothesis using bevacizumab, an anti-VEGF antibody, in rhabdomyosarcoma (RMS) xenografts. METHODS: Mice bearing orthotopic alveolar RMS xenografts were treated with a single dose of bevacizumab, IR, or a combination of the two on different schedules. Tumors were then evaluated for changes in microvessel density, vessel maturity, vessel permeability, intratumoral oxygenation, as well as altered growth. RESULTS: After bevacizumab treatment, a significant decrease in tumor microvessel density and a significant increase in tumor vessel maturity, defined as the ratio of pericytes to endothelial cells, were observed, suggesting pruning of immature vessels lacking pericytes. Tumor vessel permeability was also significantly decreased and intratumoral oxygen tension increased 2 and 5 days after bevacizumab owing to a transient improvement in tumor perfusion. Treatment with IR 2 or 5 days after bevacizumab resulted in the greatest antitumor activity. CONCLUSION: Our findings support the hypothesis that VEGF inhibition with bevacizumab transiently normalizes the dysfunctional vasculature of RMS xenografts, improving tumor oxygenation and increasing tumor sensitivity to adjuvant IR.

Artificial rearing of mouse pups: development of a mouse pup in a cup model.

Artificial rearing of rat pups has been used in the investigation of the neonatal gut. We propose to adapt the model of artificially rearing rat pups for use in mouse pups, thereby allowing the use of transgenic animals for our research. We hypothesized that gastrostomy catheters may be placed successfully into neonatal mouse pups and that the pups may be artificially reared without significant alterations in their growth or intestinal development. Gastrostomy tubes are placed into 5-d-old mouse pups [artificially reared (AR); n = 32], and the mice are fed rodent milk substitute. Littermate pups [maternally reared (MR); n = 22] are used as controls. After 5 d, pups are killed and their organs are harvested. Intestinal villus measurements, protein content, and DNA content are determined. Data are reported as mean +/- SEM, compared with appropriate statistical methods, and significance is determined at P < 0.05. Initial weights and lengths are not different between the two groups, but after 5 d, MR pups weigh more than their AR counterparts (5.0 +/- 0.13 versus 4.1 +/- 0.14 g, MR versus AR; P < 0.01). However, the pups' length and the intestinal villus height-to-width ratios, protein, and DNA content are not different between the MR and AR pups. To our knowledge, this is the first report of artificially rearing mouse pups. Development of this technique will permit nutritional manipulation in neonatal mice, a mammalian model wherein the genome is sequenced and transgenic mutants are available.