Early transition to oral antibiotics for treatment of perforated appendicitis in pediatric patients: Confirmation of the safety and efficacy of a growing national trend.

PURPOSE: We performed a quality improvement initiative to monitor the change in protocol from purely intravenous therapy for perforated appendicitis to oral antibiotics at discharge once patients could tolerate eating. METHODS: Standardized prospective data were gathered on all children with perforated appendicitis treated under the new oral protocol from January 1 to December 31, 2014. Retrospective data through chart review were gathered on all children treated for perforated appendicitis during 2013. We compared demographics, clinical parameters, and hospital charges. RESULTS: Comparing 115 patients in 2013 and 144 in 2014, demographics and clinical characteristics were similar. In 2014, 95% of patients were discharged on oral therapy. Compared to the intravenous group, the enteric group had statistically lower rates of repeat ultrasound imaging (49.6% vs 35.1%) and PICC placement (98.3% vs 9.1%) and similar rates of intraabdominal abscess (20.9% vs 16.0%) and antibiotic change (26.1% vs 22.2%). In 2014, 55% of patients were discharged by postoperative day 5, compared to 33% in 2013. Total antibiotic days and readmission rate were similar, while hospital charges decreased by half. CONCLUSION: Our results reaffirm that transition to oral antibiotics is safe, effective, and cost-efficient in treatment of perforated appendicitis in the child.

The receptor for advanced glycation end products promotes pancreatic carcinogenesis and accumulation of myeloid-derived suppressor cells.

Pancreatic ductal adenocarcinoma (PDA) has an aggressive natural history and is resistant to therapy. The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor for many damage-associated molecular pattern molecules. RAGE is overexpressed in both human and murine models of PDA as well as most advanced epithelial neoplasms. The immunosuppressive nature of the PDA microenvironment is facilitated, in part, by the accumulation of regulatory immune cell infiltrates such as myeloid-derived suppressor cells (MDSCs). To study the role of RAGE expression in the setting of mutant Ras-promoted pancreatic carcinogenesis (KC), a triple-transgenic model of spontaneous murine PDA in a RAGE-null background (KCR) was generated. KCR mice had markedly delayed pancreatic carcinogenesis and a significant diminution of MDSCs compared with KC mice at comparable time points postweaning. Although RAGE was not required for the development or suppressor activity of MDSCs, its absence was associated with temporally limited pancreatic neoplasia and altered phenotype and function of the myeloid cells. In lieu of MDSCs, KCR animals at comparable time points exhibited mature CD11b(+)Gr1(-)F4/80(+) cells that were not immunosuppressive in vitro. KCR mice also maintained a significantly less suppressive milieu evidenced by marked decreases in CCL22 in relation to CXCL10 and diminished serum levels of IL-6.

Weight-specific health-related quality of life in adolescents with extreme obesity.

The objectives of this multisite study were to: (i) examine differences by gender and race on generic and weight- specific health-related quality of life (HRQOL) in adolescents with extreme obesity (BMI > or = 40 kg/m(2)) and (ii) explore HRQOL differences based on treatment pursued (behavioral vs. bariatric surgery). Study participants included 145 obese adolescents (mean age = 15.3 years; 68% female; 46% black; mean BMI = 50.6) referred to pediatric weight management programs. Participants completed generic (PedsQL) and weight-specific (Impact of Weight on Quality of Life-Kids (IWQOL-Kids)) HRQOL measures. Generic and weight-specific measures indicated global (e.g., all domains) HRQOL impairment and significant differences by race. Physical, emotional, and social scores of the PedsQL (Ps < 0.01) and the physical comfort and body esteem scores of the IWQOL-Kids (Ps < 0.001) were significantly higher for black compared to white adolescents with extreme obesity. Extremely obese adolescents pursuing bariatric surgery reported similar HRQOL to adolescents pursuing behavioral treatment (n = 30 matched pairs). HRQOL did not differ for extremely obese adolescents based on type of treatment sought, but race/ethnicity should be considered when characterizing these youth. Although racial differences in adolescent body image/esteem have been reported, it is unknown why black adolescents with extreme obesity would report less impact of weight on their physical functioning. Overall, these data suggest that HRQOL is not homogenous in adolescents with extreme obesity.

Health-related quality of life before and after bariatric surgery in adolescents.

BACKGROUND: Recent data reaffirm decreased health-related quality of life (HRQL) in obese adults and children. Health-related quality of life is markedly improved after bariatric surgery in adults. Little HRQL data are available in adolescents undergoing bariatric surgery. METHODS: Sixteen patients (14-20 years old) underwent gastric bypass. Thirteen patients completed a general HRQL measure (Short Form 36 [SF-36]) before surgery. Of these, 9 completed the SF-36 again at various follow-up times, as well as a measure of weight-related quality of life (Impact of Weight on Quality of Life-Lite). Three patients completed postsurgical forms only. Data were analyzed using t test and analysis of variance. Results are reported as mean +/- SD. RESULTS: Mean age and body mass index at operation were 18.5 +/- 1.7 years and 54 +/- 7.6 kg/m(2). Postoperatively, patients lost an average of 66% +/- 29% excess weight over a mean follow-up of 17 +/- 12 (range, 1-39) months. Mean preoperative SF-36 physical component score was 34.7 +/- 10 and mental component score was 40.6 +/- 13.5 (adult population mean = 50.0 +/- 10 for each). At last follow-up, mean physical component score had increased to 55.5 +/- 5, and mental component score, to 55.2 +/- 8.6 (P < .0001). Adolescent Impact of Weight on Quality of Life-Lite scores after surgery did not differ from means for normal weight adults (93% +/- 7% vs 96% +/- 7%, P = .15). CONCLUSIONS: Health-related quality of life in adolescents and young adults undergoing bariatric surgery improves dramatically in early follow-up. Long-term data are needed to definitively study this surgical therapy for obesity in adolescents.

Regulation of FAT/CD36 mRNA gene expression by long chain fatty acids in the differentiated 3T3-L1 cells.

Defects in fatty acid translocase (FAT/CD36) have been identified as a major factor in insulin resistance and defective fatty acid and glucose metabolism. Therefore, understanding of the regulation of FAT/CD36 expression and function is important for a potential therapeutic target for type II diabetes. We differentiated 3T3-L1 preadipocytes into matured adipocytes and examined the roles of insulin and long chain fatty acids on FAT/CD36 expression and function. Our results indicate that FAT/CD36 mRNA expression was not detected at preadipocyte but was significantly increased at matured adipocyte. In fully differentiated 3T3-L1 adipocytes, insulin significantly increased FAT/CD36 mRNA and protein expression in a dose dependent manner. The free fatty acid stearic acid reduced FAT/CD36 mRNA expression while the non-metabolizable free fatty acid alpha-bromopalmitate (2-BP) significantly increased FAT/CD36 mRNA and protein expression. Isoproterenol, in contrast, dose-dependently reduced FAT/CD36 mRNA expression and increased free fatty acid release. Mechanism analysis indicated that the effect of insulin and 2-BP on the FAT/CD36 mRNA gene expression may be mediated through activation of PPAR-gamma, suggesting that FAT/CD36 may have important implications in the pathophysiology of defective fatty acid metabolism.

Revision Nissen fundoplication can be completed laparoscopically with a low rate of complications: a single-institution experience with 72 children.

PURPOSE: Recurrent gastroesophageal reflux is a common complication after fundoplication and is often treated with revision fundoplication. We report our experience with laparoscopic redo fundoplication. METHODS: The medical records of all patients in whom laparoscopic revision fundoplication was attempted over a 7 1/2-year period were reviewed. RESULTS: Redo laparoscopic fundoplication was attempted in 72 pediatric patients. Ten patients had undergone initial open fundoplication, and 9 additional patients had prior abdominal surgery. Fifty-one percent of patients were neurologically impaired. Laparoscopic fundoplication was completed in 89% of first-time redo operations and 68% of second revisions with average operative times of 2.2 +/- 1.0 and 2.6 +/- 0.9 hours, respectively. Herniation of the fundoplication through the hiatus was common (75%) and the fundoplication was intact in 49%. Conversions to laparotomy were because of difficulties with dissection or visualization. No patients required intraoperative transfusion. No patients required reoperation in the perioperative period. There were no perioperative deaths. Twenty-six percent of the 72 patients went on to a third operation for gastroesophageal reflux, and 4 of these had a fourth. CONCLUSION: Revision laparoscopic fundoplication is a technically challenging operation but can usually be completed and is characterized by a low rate of complications.

The role of hyperglycemia in FAT/CD36 expression and function.

FAT/CD36 is a long-chain fatty acid transporter and scavenger receptor for oxidized LDL. Defects in FAT/CD36 have been linked to the hypertriglyceridemia and insulin resistance. Expression of FAT/CD36 was reported increase in type 1 diabetes; however, it remains unclear whether serum glucose or insulin plays an important role in this regulation. To elucidate the individual contribution of plasma glucose and insulin in the regulation of FAT/CD36 mRNA expression, we induced type 1 diabetes in male Sprague-Dawley rats using streptozotocin (STZ) and compared traditional insulin treatment with administration of the orally absorbed chemical agent vanadate, which reduces blood glucose levels via mechanisms that bypass insulin receptor action. STZ-exposed animals showed significant decreases in body weight (285.5 +/- 2.8 vs. 233.1 +/- 3.5 g, P < 0.001) and serum insulin levels (9.7 +/- 0.7 vs. 2.8 +/- 0.6 microU/ml, P < 0.05), accompanied by significant increases in blood glucose (71 +/- 3 vs. 433 +/- 11 mg/dl, P < 0.001), water intake (38.9 +/- 0.9 vs. 205.9 +/- 3.3 ml/day, P < 0.001) and food intake (22.0 +/- 0.4 vs. 36.9 +/- 1.0 g/day, P < 0.001). Diabetic animals demonstrated significant increases in FAT/CD36 mRNA levels in duodenum (2.2-fold), jejunum (1.8-fold), ileum (1.5-fold), adipose tissue (1.7-fold), and heart (2.5-fold) (P < 0.05). Insulin treatment reversed body weight loss and corrected hyperglycemia at diabetic rats as expected. Insulin treatment also corrected increased FAT/CD36 mRNA expression at diabetic rats. Vanadate significantly reduced serum glucose levels without increasing serum insulin or affecting body weight but reversed increased FAT/CD36 mRNA expression in diabetic rats. These data suggest that plasma glucose levels play more important role in the regulation of FAT/CD36 expression than concurrent changes in plasma insulin.

Molecular mechanism of the intracellular segments of the melanocortin-4 receptor for NDP-MSH signaling.

Mutations of the human melanocortin-4 receptor (hMC4R) have been previously identified to be the most common cause of monogenic human obesity. Specifically, mutations of the intracellular C terminus and the third intracellular loop of hMC4R have been reported to play an important role in human obesity. However, the molecular basis of these hMC4R intracellular segments in receptor function remains unclear. In this study, we utilized deletions and mutations of specific portions of the hMC4R to determine the molecular mechanism of both the C terminus and the third intracellular loop in receptor signaling. Our results indicate that deletions of the distal 25 (the entire C terminus), 22, 18, 17, 16, and 15 amino acids of the C terminus result in the complete loss of both [Nle(4)-d-Phe(7)]-alpha-melanocyte stimulating hormone (NDP-MSH) binding and NDP-MSH-mediated cAMP production. Deletion of the distal 14 amino acids of the C terminus significantly decreases both NDP-MSH binding affinity and potency, but deletion of the distal 13 amino acids of the C terminus does not affect NDP-MSH activity. Further analysis revealed that the proximal 12 amino acids of the C terminus are not only important for receptor signaling but also important for ligand binding. Our results also indicate that the third intracellular loop of the hMC4R is important for receptor signaling but not ligand binding. In summary, our findings suggest that the proximal region of the melanocortin-4 receptor (MC4R) C terminus is crucial not only for receptor signaling but also for ligand binding, while the third intracellular loop is important mainly for receptor signaling.