A definition of gentle ventilation in congenital diaphragmatic hernia: a survey of neonatologists and pediatric surgeons.

Ventilation practices have changed significantly since the initial reports in the mid 1980 of successful use of permissive hypercapnia and spontaneous ventilation [often called gentle ventilation (GV)] in infants with congenital diaphragmatic hernia (CDH). However, there has been little standardization of these practices or of the physiologic limits that define GV. We sought to ascertain among Diaphragmatic Hernia Research and Exploration; Advancing Molecular Science (DHREAMS) centers' GV practices in the neonatal management of CDH. Pediatric surgeons and neonatologists from DHREAMS centers completed an online survey on GV practices in infants with CDH. The survey gathered data on how individuals defined GV including ventilator settings, blood gas parameters and other factors of respiratory management. A total of 87 respondents, from 12 DHREAMS centers completed the survey for an individual response rate of 53% and a 92% center response rate. Approximately 99% of the respondents defined GV as accepting higher carbon dioxide (PCO2) and 60% of the respondents also defined GV as accepting a lower pH. There was less consensus about the use of sedation and neuromuscular blocking agents in GV, both within and across the centers. Acceptable pH and PCO2 levels are broader than the goal ranges. Despite a lack of formal standardization, the results suggest that GV practice is consistently defined as the use of permissive hypercapnia with mild respiratory acidosis and less consistently with the use of sedation and neuromuscular blocking agents. GV is the reported practice of surveyed neonatologists and pediatric surgeons in the respiratory management of infants with CDH.

Neonatal esophageal perforation: nonoperative management.

BACKGROUND: Esophageal perforation is a rare complication of enteric instrumentation in neonates. Enteric tube placement in micro-preemies poses a particular hazard to the narrow lumen and thin wall of the developing esophagus. The complication may be difficult to recognize or misdiagnosed as esophageal atresia, and is associated with considerable mortality. Historically, management of this life-threatening iatrogenic disease was operative, but trends have shifted toward nonoperative treatment. Here, we review neonatal esophageal perforation at our own institution for management techniques, risk factors, and outcomes. MATERIALS AND METHODS: Seven neonatal patients with esophageal perforation were identified and charts reviewed for demographics, comorbidities, etiology of perforation, diagnostic modalities, management decisions, complications, and outcomes. RESULTS: Mean gestational age was 27.2 ± 4.0 wk, and weight at diagnosis was 892 ± 674 g. All seven patients had esophageal perforation resulting from endotracheal or enterogastric intubation and were managed nonoperatively. Treatment included removal of the offending tube, nil per os, and antibiotics. Five patients required additional interventions: four tube thoracostomies for pneumothoraces and one peritoneal drain for pneumoperitoneum. Three patients died because of sequelae of prematurity (intraventricular hemorrhage, necrotizing enterocolitis, and sepsis). One patient was diagnosed as having esophageal atresia; esophagoscopy before surgical repair established the correct diagnosis. CONCLUSIONS: Neonates, particularly those under 1500 g, are at substantial risk for iatrogenic esophageal perforation during enterogastric intubation. Nonoperative management may be a safe initial strategy in the neonatal setting, but more aggressive interventions may ultimately be required. Despite recent improvement in early recognition of this injury, misdiagnosis still occurs.

Celecoxib inhibits Ewing sarcoma cell migration via actin modulation.

BACKGROUND: Ewing sarcoma (ES) is an aggressive childhood solid tumor in which 30% of cases are metastatic at presentation, and subsequently carry a poor prognosis. We have previously shown that treatment with celecoxib significantly reduces invasion and metastasis of ES cells in a cyclooxygenase-2-independent fashion. Celecoxib is known to downregulate ß-catenin independently of cyclooxygenase-2. Additionally, the actin cytoskeleton is known to play an important role in tumor micrometastasis. We hypothesized that celecoxib's antimetastatic effect in ES acts via modulation of one of these two targets. METHODS: ES cells were treated with celecoxib, and the levels of ß-catenin and total actin were examined by Western blot and quantitative polymerase chain reaction. Cells were transfected with small interfering RNA targeting ß-catenin, and invasion assays were performed. Immunofluorescence staining for ß-catenin and F-actin was performed on treated and untreated cells. Additionally, cells were subjected to a wound healing assay to assess migration. RESULTS: Celecoxib had no effect on the messenger RNA or protein levels of ß-catenin but did significantly decrease the amount of total actin within ES cells. Reduction of ß-catenin by small interfering RNA had no effect on invasion, and celecoxib treatment of the ß-catenin depleted cells continued to inhibit invasion. Immunofluorescence staining demonstrated no change in ß-catenin with treatment but did show a significant reduction in the amount of F-actin, as well as morphologic changes of the cells. Wound healing assays demonstrated that celecoxib significantly inhibited migration. CONCLUSIONS: Celecoxib does not exert its antimetastatic effects in ES through alteration of ß-catenin but does significantly modulate the actin cytoskeleton.

A Comprehensive Approach for the Prevention of Nausea and Vomiting Following Sleeve Gastrectomy: a Randomized Controlled Trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) following sleeve gastrectomy (SG) is a common occurrence. The effect of specific interventions in PONV prevention within enhanced recovery pathways remains unclear. The aim of this study was to evaluate the impact of a comprehensive approach for the prevention of PONV on patient outcomes and hospital resource utilization. METHODS: A prospective randomized trial was conducted for patients undergoing SG. The intervention group received aprepitant and transdermal scopolamine preoperatively followed by ondansetron and dexamethasone intraoperatively, with total intravenous anesthesia. The control group received inhalational anesthetic and two intraoperative antiemetics without preoperative prophylaxis. The primary endpoint was a PONV-related delay in hospital discharge. RESULTS: Eighty-three patients completed the study (41 in the intervention and 42 in the control group). Eighty-nine percent of patients were discharged home on the first postoperative day. Four patients in the control group and none in the intervention group experienced a PONV-related delay in discharge (9.5% vs 0, p = 0.119). Intervention patients reported significantly lower PONV scores at all in-hospital time points examined (p = 0.0392 for verbal scores and p < 0.0001 for Rhodes Index) and significantly higher self-rated quality of recovery at 24 h (Quality of Recovery-15 instrument, p < 0.05). CONCLUSIONS: A multilevel approach to PONV leads to significantly lower severity of PONV and improved self-reported quality of recovery, compared with control. PONV-related readmissions, ED visits, and discharge delays were uncommon within the overall enhanced recovery cohort.

Recent trends in the operative experience of junior pediatric surgical attendings: a study of APSA applicant case logs.

PURPOSE: Pediatric surgical education and workforce have changed significantly in the past decade. To document trends in the operative experiences of junior pediatric surgeons, we examined case logs submitted by applicants for membership to APSA. METHODS: Case logs for 164 APSA membership applicants from 2006 to 2013 were reviewed. Total case volume, categories, and specific operations were analyzed. Negative binomial regression assessed for significant associations between the number of cases and the application year, presence of a pediatric surgery training program, region of the country, and years since fellowship completion. RESULTS: Overall case numbers decreased initially after 2006/2007, but have remained stable since. Decreasing trends were seen in a number of specific cases/categories. The number of newborn cases did not change. Significant variations in operative experience were identified depending upon region, presence of a pediatric surgery training program, and years since fellowship completion. Median reported value for several important cases was ≤4 per year, and for some was zero. CONCLUSION: These data describing the experience of young pediatric surgeons supplement recent observations regarding pediatric surgery fellows and general surgery residents. The limited exposure of surgeons to particularly rare conditions appears to be an unresolved problem. This information will be useful in developing future workforce proposals.

The Macrophage Inhibitor CNI-1493 Blocks Metastasis in a Mouse Model of Ewing Sarcoma through Inhibition of Extravasation.

Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model of metastatic Ewing Sarcoma, CNI-1493 treatment dramatically reduces metastatic tumor burden. Furthermore, metastases in treated animals have a less invasive morphology. We show in vitro that CNI-1493 decreases M2-stimulated Ewing Sarcoma tumor cell invasion and extravasation, offering a functional mechanism through which CNI-1493 attenuates metastasis. These data indicate that CNI-1493 may be a safe and effective adjuvant agent for the prevention and treatment of metastatic Ewing Sarcoma.