Five-Year Outcomes of Gastric Bypass in Adolescents as Compared with Adults.

BACKGROUND: Bariatric surgery results in weight loss and health improvements in adults and adolescents. However, whether outcomes differ according to the age of the patient at the time of surgery is unclear. METHODS: We evaluated the health effects of Roux-en-Y gastric bypass in a cohort of adolescents (161 patients enrolled from 2006 through 2012) and a cohort of adults (396 patients enrolled from 2006 through 2009). The two cohorts were participants in two related but independent studies. Linear mixed and Poisson mixed models were used to compare outcomes with regard to weight and coexisting conditions between the cohorts 5 years after surgery. The rates of death and subsequent abdominal operations and selected micronutrient levels (up to 2 years after surgery) were also compared between the cohorts. RESULTS: There was no significant difference in percent weight change between adolescents (-26%; 95% confidence interval [CI], -29 to -23) and adults (-29%; 95% CI, -31 to -27) 5 years after surgery (P = 0.08). After surgery, adolescents were significantly more likely than adults to have remission of type 2 diabetes (86% vs. 53%; risk ratio, 1.27; 95% CI, 1.03 to 1.57) and of hypertension (68% vs. 41%; risk ratio, 1.51; 95% CI, 1.21 to 1.88). Three adolescents (1.9%) and seven adults (1.8%) died in the 5 years after surgery. The rate of abdominal reoperations was significantly higher among adolescents than among adults (19 vs. 10 reoperations per 500 person-years, P = 0.003). More adolescents than adults had low ferritin levels (72 of 132 patients [48%] vs. 54 of 179 patients [29%], P = 0.004). CONCLUSIONS: Adolescents and adults who underwent gastric bypass had marked weight loss that was similar in magnitude 5 years after surgery. Adolescents had remission of diabetes and hypertension more often than adults. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number, NCT00474318.).

Initial Laparotomy Versus Peritoneal Drainage in Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis or Isolated Intestinal Perforation: A Multicenter Randomized Clinical Trial.

OBJECTIVE: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches. RESULTS: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage [adjusted relative risk (aRR) 1.0; 95% confidence interval (CI): 0.87-1.14]. A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (P = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR 0.81; 95% CI: 0.64-1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference <0) for a preoperative diagnosis of NEC was 97%. For preoperative diagnosis of IP, death or NDI occurred in 69% after laparotomy versus 63% with drainage (aRR, 1.11; 95% CI: 0.95-1.31); Bayesian probability of benefit with laparotomy = 18%. CONCLUSIONS: There was no overall difference in death or NDI rates at 18 to 22 months corrected age between initial laparotomy versus drainage. However, the preoperative diagnosis of NEC or IP modified the impact of initial treatment.

Nutritional Risks in Adolescents After Bariatric Surgery.

BACKGROUND & AIMS: Little is known about prevalence and risk factors for nutritional deficiencies in adolescents after metabolic bariatric surgery. We performed a 5-year prospective cohort study of these. METHODS: Adolescents who had Roux-en-Y gastric bypass (RYGB, n = 161) or vertical sleeve gastrectomy (VSG, n = 67) were enrolled at 5 tertiary-care centers from March 2007 through February 2012. The final analysis cohort included 226 participants (161 who had RYGB and 65 who had VSG). We measured serum levels of ferritin; red blood cell folate; vitamins A, D, B1, B12; and parathyroid hormone at baseline and annually for 5 years. General linear mixed models were used to examine changes over time and identify factors associated with nutritional deficiencies. RESULTS: The participants were 75% female and 72% white, with a mean age of 16.5 ± 1.6 years and mean body mass index of 52.7 ± 9.4 kg/m2 at surgery. Mean body mass index decreased 23% at 5 years, and did not differ significantly between procedures. After RYGB, but not VSG, serum concentrations of vitamin B12 significantly decreased whereas serum levels of transferrin and parathyroid hormone increased. Ferritin levels decreased significantly after both procedures. Hypo-ferritinemia was observed in 2.5% of patients before RYGB and 71% at 5 y after RYGB (P < .0001), and 11% of patients before VSG and 45% 5 y after VSG (P = .002). No significant changes in serum levels of folate or vitamins A, B1, or D were found between baseline and 5 y after either procedure. By 5 y, 59% of RYGB and 27% of VSG recipients had 2 or more nutritional deficiencies. Risk factors associated with specific deficiencies included surgery type, female sex, black race, supplementation intake, weight regain, and for females, pregnancy. CONCLUSIONS: In a prospective study of adolescents who underwent RYGB or VSG, we observed nutritional deficiencies by 5 y after the procedures-particularly in iron and B12 after RYGB. Ongoing nutrient monitoring and supplementation are recommended for all patients, but surgery type, supplementation intake, sex, and race might affect risk. (Clinical trial registration: Adolescent Bariatrics: Assessing Health Benefits and Risk [also known as Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS)], NCT00474318.).

Weight Loss and Health Status 3 Years after Bariatric Surgery in Adolescents.

BACKGROUND: Bariatric surgery is increasingly considered for the treatment of adolescents with severe obesity, but few prospective adolescent-specific studies examining the efficacy and safety of weight-loss surgery are available to support clinical decision making. METHODS: We prospectively enrolled 242 adolescents undergoing weight-loss surgery at five U.S. centers. Patients undergoing Roux-en-Y gastric bypass (161 participants) or sleeve gastrectomy (67) were included in the analysis. Changes in body weight, coexisting conditions, cardiometabolic risk factors, and weight-related quality of life and postoperative complications were evaluated through 3 years after the procedure. RESULTS: The mean (±SD) baseline age of the participants was 17±1.6 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 53; 75% of the participants were female, and 72% were white. At 3 years after the procedure, the mean weight had decreased by 27% (95% confidence interval [CI], 25 to 29) in the total cohort, by 28% (95% CI, 25 to 30) among participants who underwent gastric bypass, and by 26% (95% CI, 22 to 30) among those who underwent sleeve gastrectomy. By 3 years after the procedure, remission of type 2 diabetes occurred in 95% (95% CI, 85 to 100) of participants who had had the condition at baseline, remission of abnormal kidney function occurred in 86% (95% CI, 72 to 100), remission of prediabetes in 76% (95% CI, 56 to 97), remission of elevated blood pressure in 74% (95% CI, 64 to 84), and remission of dyslipidemia in 66% (95% CI, 57 to 74). Weight-related quality of life also improved significantly. However, at 3 years after the bariatric procedure, hypoferritinemia was found in 57% (95% CI, 50 to 65) of the participants, and 13% (95% CI, 9 to 18) of the participants had undergone one or more additional intraabdominal procedures. CONCLUSIONS: In this multicenter, prospective study of bariatric surgery in adolescents, we found significant improvements in weight, cardiometabolic health, and weight-related quality of life at 3 years after the procedure. Risks associated with surgery included specific micronutrient deficiencies and the need for additional abdominal procedures. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; Teen-LABS ClinicalTrials.gov number, NCT00474318.).

Minimally invasive surgical exposure among US and Canadian pediatric surgery trainees, 2004-2016.

BACKGROUND: Minimally invasive pediatric surgery has increased in breadth and complexity over the past several decades, with little data on minimally invasive surgery (MIS) training in US and Canadian pediatric surgery fellowship programs. METHODS: We performed a time series analysis of Accreditation Council for Graduate Medical Education pediatric surgery fellow case logs from 2003 to 2016. Proportions of cases performed in an MIS fashion as well as per-fellow MIS case averages were recorded over time. RESULTS: There was a 30.9% increase in average number of MIS cases per fellow over the study time period. Twenty-three recorded procedures included MIS and open options (17 abdominal, three thoracic, and three genitourinary). The proportion of cases performed using a minimally invasive approach increased by an average of 29.0%, 14.6%, and 47.0% for each of these categories, respectively. Significant variability was observed in specific cases such as laparoscopic and open inguinal hernias, ranging from 0 to 85 and nine to 152 per trainee, respectively, in the final year of data collection. When examining pyloromyotomy, a high-volume procedure with a known increase in the MIS approach, the proportion of cases performed MIS increased by 83.3%. The minimum and maximum number of cases per fellow recorded ranged from 0 to 114 during the eight years in which MIS pyloromyotomy was recorded. CONCLUSIONS: MIS case exposure among graduating US and Canadian pediatric survey fellows increased substantially during the study period. More granular data, however, are needed to better define the current operative experience and criteria for determination of competency in advanced MIS.

Molecular signatures of human melanocortin receptors for ligand binding and signaling.

Human melanocortin receptors (hMCRs) belong to the seven-transmembrane (TM) domain proteins. There are five hMCR subtypes and each of these receptor subtypes has different patterns of tissue expression and physiological function. The endogenous agonists for hMCRs are α-, ß-, and γ-MSH and ACTH and endogenous antagonists are Agouti and AGRP which are the only known naturally occurring antagonists for the receptors. These peptides have their own profiles regarding the relative potency for specific hMCR subtype. Extensive studies have been performed to examine the molecular basis of the hMCRs for different ligand binding affinity and potency. Studies indicate that natural ligand α-MSH utilizes conserved amino acid residues for MCR specific binding (orthosteric binding) while synthetic ligands utilize non-conserved amino acid residues for receptor subtype specific binding (allosteric binding). ACTH is the only endogenous agonist for hMC2R and more amino acid residues at hMC2R are required for ACTH binding and signaling. HMCR computer modeling provides the detailed information of ligand and MCR interaction. This review provides the latest understanding of the molecular basis of the hMCRs for ligand binding and signaling. This article is part of a Special Issue entitled: Melanocortin Receptors - edited by Ya-Xiong Tao.

Biliary Dyskinesia in Children: A Systematic Review.

Cholecystectomy rates for biliary dyskinesia in children are rising in the United States, but not in other countries. Biliary dyskinesia is a validated functional gallbladder disorder in adults, requiring biliary colic in the diagnosis. In contrast, most studies in children require upper abdominal pain, absent gallstones on ultrasound, and an abnormal gallbladder ejection fraction (GBEF) on cholecystokinin-stimulated cholescintigraphy for diagnosis. We aimed to systematically review existing literature in biliary dyskinesia in children, determine the validity and reliability of diagnostic criteria, GBEF, and to assess outcomes following cholecystectomy. We performed a systematic review following the PRISMA checklist and searched 7 databases including PubMed, Scopus, Embase, Ovid, MEDLINE, ProQuest, Web of Science, and the Cochrane library. Bibliographies of articles were screened for additional studies. Our search terms yielded 916 articles of which 28 were included. Three articles were manually added from searched references. We reviewed 31 peer-reviewed publications, all retrospective chart reviews. There was heterogeneity in diagnostic criteria and GBEF values. Outcomes after laparoscopic cholecystectomy varied from 34% to 100% success, and there was no consensus concerning factors influencing outcomes. The observational, retrospective study designs that comprised our review limited interpretation of safety and efficacy of the investigations and treatment in biliary dyskinesia in children. Symptoms of biliary dyskinesia overlapped with functional dyspepsia. There is a need for consensus on symptoms defining biliary dyskinesia, validation of testing required for diagnosis of biliary dyskinesia, and randomized controlled trials comparing medical versus surgical management in children with upper abdominal pain.

Novel use of porcine extracellular matrix in recurrent stricture following repair of tracheoesophageal fistula.

Anastomotic stricture is a common complication following repair of esophageal atresia (EA). Many factors are thought to contribute to stricture formation and a variety of management techniques have been developed. In this case report, we describe the treatment of a recurrent anastomotic stricture following repair of long-gap esophageal atresia. Porcine bladder extracellular matrix (ECM) was mounted on a stent and delivered endoscopically to the site of recurrent stricture. An appropriate positioning was confirmed using direct endoscopic visualization and intra-operative fluoroscopy. The patient recovered well with persistent radiographic and functional improvements in previous stricture.

Third transmembrane domain of the adrenocorticotropic receptor is critical for ligand selectivity and potency.

The ACTH receptor, known as the melanocortin-2 receptor (MC2R), plays an important role in regulating and maintaining adrenocortical function. MC2R is a subtype of the melanocortin receptor (MCR) family and has unique characteristics among MCRs. Endogenous ACTH is the only endogenous agonist for MC2R, whereas the melanocortin peptides α-, ß-, and γ-melanocyte-stimulating hormone and ACTH are full agonists for all other MCRs. In this study, we examined the molecular basis of MC2R responsible for ligand selectivity using ACTH analogs and MC2R mutagenesis. Our results indicate that substitution of Phe(7) with D-Phe or D-naphthylalanine (D-Nal(2')) in ACTH(1-24) caused a significant decrease in ligand binding affinity and potency. Substitution of Phe(7) with D-Nal(2') in ACTH(1-24) did not switch the ligand from agonist to antagonist at MC2R, which was observed in MC3R and MC4R. Substitution of Phe(7) with D-Phe(7) in ACTH(1-17) resulted in the loss of ligand binding and activity. Molecular analysis of MC2R indicated that only mutation of the third transmembrane domain of MC2R resulted in a decrease in D-Phe ACTH binding affinity and potency. Our results suggest that Phe(7) in ACTH plays an important role in ligand selectivity and that the third transmembrane domain of MC2R is crucial for ACTH selectivity and potency.

High Prevalence of Nonalcoholic Fatty Liver Disease in Adolescents Undergoing Bariatric Surgery.

BACKGROUND & AIMS: Little is known about the prevalence of nonalcoholic fatty liver disease (NAFLD) among severely obese adolescents or factors that determine its development. We investigated the prevalence of NAFLD in a multicenter cohort of adolescents undergoing bariatric surgery and the factors associated with it. METHODS: We enrolled 242 adolescents undergoing bariatric surgery between March 2007 and February 2012 at 5 tertiary care centers into a multicenter, prospective observational cohort study. Intraoperative core liver biopsies were collected from 165 subjects; 17 were excluded because of insufficient liver tissue or use of hepatotoxic medications, so 148 remained in the study (mean age, 16.8 ± 1.6 years; median body mass index = 52 kg/m(2)). Liver tissues were analyzed by histology using validated criteria. Hepatic gene expression was analyzed in 67 samples. RESULTS: NAFLD was present in 59% of this predominantly female (72%), white (68%), non-Hispanic (91%) cohort. Of subjects with NAFLD, 24% had borderline and 10% had definite nonalcoholic steatohepatitis (NASH). Mild fibrosis (stage 2 or lower) was observed in 18% of liver biopsies and stage 3 was observed in 0.7%, but cirrhosis was not detected. Dyslipidemia was present in 78% of subjects, hypertension in 44%, and diabetes in 14%. More severe NAFLD was associated with increasing levels of alanine aminotransferase, fasting glucose level, hypertension (each P < .01), and white blood cell count (P = .04). Only diabetes was associated with detection of fibrosis (odds ratio = 3.56; 95% confidence interval: 1.93-6.56). Microarray analysis associated presence of NASH with altered expression of genes that regulate macrophage chemotaxis, cholesterol absorption, and fatty acid binding. CONCLUSIONS: More than half of adolescents undergoing bariatric surgery in this cohort had NAFLD, yet the prevalence of severe or fibrotic NASH was low. Increasing severity of NAFLD was associated with level of alanine aminotransferase and cardiometabolic risk factors, but not body mass index. Based on gene expression analysis, borderline and definite NASH were associated with abnormal immune function, intestinal cholesterol absorption, and lipid metabolism.

Repair of esophageal atresia with proximal fistula using endoscopic magnetic compression anastomosis (magnamosis) after staged lengthening.

We describe the treatment of a patient with long-gap esophageal atresia with an upper pouch fistula, mircogastria and minimal distal esophageal remnant. After 4.5 months of feeding via gastrostomy, a proximal fistula was identified by bronchoscopy and a thoracoscopic modified Foker procedure was performed reducing the gap from approximately 7-5 cm over 2 weeks of traction. A second stage to ligate the fistula and suture approximate the proximal and distal esophagus resulted in a gap of 1.5 cm. IRB and FDA approval was then obtained for endoscopic placement of 10-French catheter mounted magnets in the proximal and distal pouches promoting a magnetic compression anastomosis (magnamosis). Magnetic coupling occurred at 4 days and after magnet removal at 13 days an esophagram demonstrated a 10 French channel without leak. Serial endoscopic balloon dilation has allowed drainage of swallowed secretions as the baby learns bottling behavior at home.

Severe obesity and comorbid condition impact on the weight-related quality of life of the adolescent patient.

OBJECTIVES: To assess links between comorbid health status, severe excess weight, and weight-related quality of life (WRQOL) in adolescents with severe obesity and undergoing weight-loss surgery (WLS) to inform clinical care. STUDY DESIGN: Baseline (preoperative) data from Teen Longitudinal Assessment of Bariatric Surgery, a prospective multicenter observational study of 242 adolescents with severe obesity (MedianBMI = 50.5 kg/m(2); Meanage = 17.1; 75.6% female; 71.9% white) undergoing WLS, were used to examine the impact of demographics, body mass index (BMI), presence/absence of 16 comorbid conditions, and a cumulative comorbidity load (CLoad) index on WRQOL scores (Impact of Weight on Quality of Life-Kids). RESULTS: WRQOL was significantly lower than reference samples of healthy weight, overweight, and obese samples. Of 16 comorbid conditions, the most prevalent were dyslipidemia (74.4%), chronic pain (58.3%), and obstructive sleep apnea (56.6%). Male subjects had a greater CLoad (P = .01) and BMI (P = .01), yet less impairment in total WRQOL (P < .01) than females. CLoad was a significant predictor of male WRQOL. For females, psychosocial (vs physical) comorbidities, BMI, and white race were significant predictors of WRQOL impairment. Less prevalent conditions (eg, stress urinary incontinence) also emerged as contributors to lower WRQOL. CONCLUSIONS: WRQOL impairment is substantial for adolescents with severe obesity undergoing WLS, with predictors varying by sex. These patient-data highlight targets for education, support, and adjunctive care referrals before WLS. Furthermore, they provide a comprehensive empirical base for understanding heterogeneity in adolescent WRQOL outcomes after WLS, as weight and comorbidity profiles change over time.

Single-incision pediatric endosurgery (SIPES) splenectomy: what dictates the need for additional ports?

BACKGROUND: As proficiency with single-incision pediatric endosurgery (SIPES) increases, more challenging operations are being performed. While the ultimate goal is safe surgery, it may be beneficial to know what anatomical and technical factors contribute to the need for additional ports. This aspect of SIPES splenectomy has yet to be evaluated. The study objective was to identify these factors, potentially allowing surgeons to gauge appropriateness for single incision and to tailor techniques for optimal results. METHODS: This was an institutional review board-approved retrospective analysis of prospectively collected data (FWA00005960). SIPES splenectomies performed at a tertiary children's hospital since March of 2009 were included. Demographic and technical factors pertaining to each operation were available in our SIPES database. Fischer's exact and Wilcoxon rank sum tests were used to analyze categorical and continuous variables, respectively. RESULTS: Thirty-seven patients 18 years of age and younger underwent attempted SIPES splenectomy. Two operations were converted directly to open and were excluded from analysis. Of the remaining 35 operations, 15 (42.9 %) were completed with additional ports. Gender, age, body mass index, splenic weight, indication for operation and the presence of accessory spleens did not contribute to the need for added ports. The only factor to reach statistical significance was the number of channels present in the SIPES access device (p = 0.002). CONCLUSIONS: Completion of SIPES splenectomy was associated with the decision to utilize an access device with four channels. Anatomic variables did not appear to affect the ability to complete SIPES splenectomy.

Diabetes Status and Race are Associated with Cardiovascular Risk Markers in Obese Adolescents.

OBJECTIVE: The objective of this study was to evaluate differences in cardiovascular disease (CVD) risk markers in obese adolescents based on diabetes status and race in order to improve risk-reduction intervention strategies. METHODS: This was a retrospective, cross-sectional study of obese adolescents, age 10 to 21 years, who were evaluated at Children's of Alabama between 2000 and 2012. Subjects were classified by glycated hemoglobin (HbA1c) as having normoglycemia, prediabetes, or type 2 diabetes mellitus (T2DM). RESULTS: There were a total of 491 African American (AA) or Caucasian American (CA) subjects. Body mass index was not different between HbA1c and racial groups. Compared to subjects with normoglycemia or prediabetes, subjects with T2DM had higher levels of total cholesterol (TC) (178.6 ± 43.8 mg/dL vs. 161.5 ± 32.5 mg/dL vs. 162.4 ± 30.6 mg/dL; P<.0001) and low-density-lipoprotein cholesterol (107.4 ± 39.2 mg/dL vs. 97.0 ± 31.0 mg/dL vs. 97.5 ± 26.9 mg/dL; P = .0073). Compared with AA subjects, CA subjects had lower high-density-lipoprotein cholesterol (HDL-C) levels (40.4 ± 10.4 mg/dL vs. 44.3 ± 11.9 mg/dL; P = .0005) and higher non-HDL-C levels (129.6 ± 36.2 mg/dL vs. 122.5 ± 37.5 mg/dL; P = .0490). Of the characteristics studied, HbA1c had the most significant positive association with dyslipidemia and was strongly correlated with both TC (ß, 4.21; P<.0001) and non-HDL-C (ß, 4.3; P<.0001). CONCLUSION: Obese adolescents with T2DM have more abnormal lipoprotein profiles than those with normoglycemia or prediabetes. Obese CA adolescents have more abnormal lipids than obese AA adolescents. HbA1c was the characteristic most highly associated with abnormal lipoprotein profiles in our subjects. Our results show that CVD risk markers in obese adolescents vary by race and HbA1c concentration.

DIABETES AND PREDIABETES ARE SIGNIFICANTLY HIGHER IN MORBIDLY OBESE CHILDREN COMPARED WITH OBESE CHILDREN.

OBJECTIVE: The objective of this study was to examine the prevalence and characteristics of comorbidities in obese and morbidly obese children with a comparison between the 2 sets of children. METHODS: This was a retrospective electronic chart review of obese and morbidly obese children and adolescents as defined by body mass index. We evaluated medical history of comorbid conditions, medication use, and cardiovascular risk markers, including blood pressure, lipid profile, and glycosylated hemoglobin. RESULTS: There were 1,111 subjects (African American = 635; non-Hispanic white = 364; Hispanic = 36; others = 86), of which 274 were obese and 837 were morbidly obese children with a mean age of 12.7 ± 3.37 years. Morbidly obese children had a higher prevalence of prediabetes (19.5% of obese versus 27.3% of morbidly obese; P<.0001) and type 2 diabetes (39.8% of obese versus 52.4% of morbidly obese; P<.0001). Use of medications for treatment of asthma was significantly higher in the morbidly obese group compared with the obese group (21% versus 14%; P = .01). CONCLUSION: Morbidly obese children have a higher prevalence of diabetes, prediabetes, and use of asthma medications compared with obese children.

Structural insight into the MC4R conformational changes via different agonist-mediated receptor signaling.

The melanocortin-4 receptor (MC4R) plays a key role in the regulation of food intake and body weight. Previous studies indicate that α-melanocyte stimulating hormone (α-MSH) binds to MC4R and activates three signal pathways (cAMP, calcium, and mitogen-activated protein kinase pathways), whereas MC4R synthetic agonist THIQ can activate only the cAMP pathway. The molecular basis of the MC4R responsible for different ligand-mediated signaling is unknown. We hypothesize that different MC4R agonists can stabilize different MC4R conformations and result in ligand-mediated signal transduction. In this study, we examined the effect of the MC4R conformational change in cAMP signaling pathways mediated by different agonists by cross-linking two transmembrane helices (TM3 and TM6). We generated and tested 11 single and 8 double mutations that are located at the end of TM3 and beginning of TM6 in MC4R. Our results indicate that (1) single or double mutations of the MC4R did not significantly alter cAMP production induced by NDP-MSH compared to that of wild-type MC4R except single mutation 243H (the mutation 243H significantly decreased cAMP production mediated by NDP-MSH or THIQ due to a low level of receptor expression at the cell surface), (2) the mutation 247H significantly decreased THIQ-mediated cAMP production but not NDP-MSH, and (3) the receptor cAMP signaling pathway activation by THIQ is blocked in the presence of Zn(2+) with the double mutation I150/242H but activation by NDP-MSH is not, suggesting that the activated conformation of MC4R mediated by NDP-MSH and THIQ is different. This study provides insight into the molecular basis of MC4R responsible for receptor signaling mediated by different agonists.

Utility of immature granulocyte percentage in pediatric appendicitis.

BACKGROUND: Acute appendicitis is the most common cause of abdominal surgery in children. Adjuncts are used to help clinicians predict acute or perforated appendicitis, which may affect treatment decisions. Automated hematologic analyzers can perform more accurate automated differentials including immature granulocyte percentages (IG%). Elevated IG% has demonstrated improved accuracy for predicting sepsis in the neonatal population than traditional immature-to-total neutrophil count ratios. We intended to assess the additional discriminatory ability of IG% to traditionally assessed parameters in the differentiation between acute and perforated appendicitis. MATERIALS AND METHODS: We identified all patients with appendicitis from July 2012-June 2013 by International Classification of Diseases-9 code. Charts were reviewed for relevant demographic, clinical, and outcome data, which were compared between acute and perforated appendicitis groups using Fisher exact and t-tests for categorical and continuous variables, respectively. We used an adjusted logistic regression model using clinical laboratory values to predict the odds of perforated appendicitis. RESULTS: A total of 251 patients were included in the analysis. Those with perforated appendicitis had a higher white blood cell count (P=0.0063), C-reactive protein (CRP) (P<0.0001), and IG% (P=0.0299). In the adjusted model, only elevated CRP (odds ratio 3.46, 95% confidence interval 1.40-8.54) and presence of left shift (odds ratio 2.66, 95% confidence interval 1.09-6.46) were significant predictors of perforated appendicitis. The c-statistic of the final model was 0.70, suggesting fair discriminatory ability in predicting perforated appendicitis. CONCLUSIONS: IG% did not provide any additional benefit to elevated CRP and presence of left shift in the differentiation between acute and perforated appendicitis.

The value of Pa(CO2) in relation to outcome in congenital diaphragmatic hernia.

BACKGROUND: Postnatal assessment of disease severity is critical for analysis of mortality rates and development of future interventions in congenital diaphragmatic hernia (CDH). OBJECTIVE: The objective of this study was to stratify the risk of mortality based on arterial Paco 2. METHODS: Retrospective analysis of infants (n = 133) with CDH admitted to a regional extracorporeal membrane oxygenation (ECMO) center in two different periods: period I (1987-1996; n = 46) and period II (2002-2010; n = 87). RESULTS: The mortality rate (37%) was similar in both periods (p = 0.98). Paco 2 < 60 mm Hg in the first arterial blood gas (ABG) was an independent predictor of survival in both periods (p = 0.03). The predicted survival rate was 84% if initial Paco 2 was < 55 mm Hg. For infants with initial Paco 2 > 55 mm Hg treated with ECMO (n = 83), the predicted survival rate was 11% if the Paco 2 was > 88 mm Hg before the initiation of ECMO. CONCLUSION: Paco 2, a surrogate of lung hypoplasia, may be useful for risk stratification in CDH. Paco 2 < 60 mm Hg in the first ABG may indicate milder pulmonary hypoplasia. A Paco 2 > 80 mm Hg in the first ABG and/or before ECMO may indicate severe pulmonary hypoplasia.

Tales from previous times: important eponyms in pediatric surgery.

The use of eponyms in medicine has a long and captivating tradition, which applies to pediatric surgery as well. Unfortunately, even though these eponyms are widely used, oftentimes the fascinating personalities and lives behind these names remain unrecognized or underappreciated, especially among residents, fellows and younger-generation pediatric surgeons. Therefore, in this article, we review 15 names that are frequently used as eponyms in modern pediatric surgery and hereby enlighten the personalities behind them. Given their particular frequency, we choose the following eponyms: Ramstedt pylorotomy, Nissen fundoplication, Murphy's sign and sequence, McBurney's sign and incision, Meckel's diverticulum, Kasai portoenterostomy, Ladd's procedure, Morgagni and Bochdalek hernia, Ravitch operation, Nuss procedure, Hirschsprung disease, Swenson pullthrough, Peña procedure and Wilms tumor. A detailed description of the historical importance of these personalities and their contribution to our field is given. Without the appropriate historical background, it is difficult for the current younger and next generation pediatric surgeons to grasp the full spectrum of the ongoing progress in our field. Therefore, our article conveys not only important insight into the past, but also provides young surgeons with an important historical perspective essential to understand the current and future developments in modern pediatric surgery.