Mike K. Chen

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.).

Reversal of Type 2 Diabetes Mellitus and Improvements in Cardiovascular Risk Factors After Surgical Weight Loss in Adolescents

OBJECTIVES. Type 2 diabetes mellitus is associated with obesity, dyslipidemia, and hypertension, all well-known risk factors for cardiovascular disease. Surgical weight loss has resulted in a marked reduction of these risk factors in adults. We hypothesized that gastric bypass would improve parameters of metabolic dysfunction and cardiovascular risk in adolescents with type 2 diabetes mellitus. PATIENTS AND METHODS. Eleven adolescents who underwent Roux-en-Y gastric bypass at 5 centers were included. Anthropometric, hemodynamic, and biochemical measures and surgical complications were analyzed. Similar measures from 67 adolescents with type 2 diabetes mellitus who were treated medically for 1 year were also analyzed. RESULTS. Adolescents who underwent Roux-en-Y gastric bypass were extremely obese (mean BMI of 50 ± 5.9 kg/m2) with numerous cardiovascular risk factors. After surgery there was evidence of remission of type 2 diabetes mellitus in all but 1 patient. Significant improvements in BMI (−34%), fasting blood glucose (−41%), fasting insulin concentrations (−81%), hemoglobin A1c levels (7.3%–5.6%), and insulin sensitivity were also seen. There were significant improvements in serum lipid levels and blood pressure. In comparison, adolescents with type 2 diabetes mellitus who were followed during 1 year of medical treatment demonstrated stable body weight (baseline BMI: 35 ± 7.3 kg/m2; 1-year BMI: 34.9 ± 7.2 kg/m2) and no significant change in blood pressure or in diabetic medication use. Medically managed patients had significantly improved hemoglobin A1c levels over 1 year (baseline: 7.85% ± 2.3%; 1 year: 7.1% ± 2%). CONCLUSIONS. Extremely obese diabetic adolescents experience significant weight loss and remission of type 2 diabetes mellitus after Roux-en-Y gastric bypass. Improvements in insulin resistance, β-cell function, and cardiovascular risk factors support Roux-en-Y gastric bypass as an intervention that improves the health of these adolescents. Although the long-term efficacy of Roux-en-Y gastric bypass is not known, these findings suggest that Roux-en-Y gastric bypass is an effective option for the treatment of extremely obese adolescents with type 2 diabetes mellitus.

The effects of endotoxin on the splanchnic metabolism of glutamine and related substrates

The effects of endotoxemia on glutamine metabolism by the splanchnic bed was studied in vivo in adult rats 12 hours following administration of E. coli LPS. Glutamine uptake by the portal-drained viscera fell in the endotoxin-treated animals while glucose uptake doubled. Simultaneously, hepatic glutamine uptake increased ten-fold owing to both an increase in hepatic blood flow and glutamine extraction from the bloodstream. Hepatic alanine uptake, oxygen consumption, and glucose release were also accelerated in endotoxemic rats. The increase in liver glutamine utilization was associated with increases in parenchymal DNA and glutathione levels and an increase in glutathione and urea release into the systemic circulation. This marked increase in metabolic activity occurred in animals with chemical evidence of hepatocellular injury and histologic evidence of hepatocyte necrosis. During endotoxemia the liver becomes the major organ of glutamine consumption. This accelerated utilization provides carbons for energy and gluconeogenesis, nitrogen for ureagenesis, and substrate for nucleotide and glutathione biosynthesis in order to support cell repair and detoxification reactions.

Outcomes of treatment of childhood achalasia

PURPOSE The optimal management of achalasia in children and adolescents remains unclear. The aim of this study was to review a single institutions experience with endoscopic and surgical interventions in children with achalasia. METHODS A retrospective review was conducted of the medical records of children treated for achalasia from 1978 to 2008. Patient demographics and interventions were reviewed. Outcomes after procedural intervention were evaluated. RESULTS Thirty-five patients with achalasia were identified, and data were available for 34 (age, 13 +/- 6 years; male, 62%). Eighteen patients underwent esophageal dilation (ED), and 16 patients underwent Heller myotomy (HM). Follow-up was available for 30 patients (ED, 15; HM, 15). There was symptom recurrence in 15 of 15 ED cases and 8 (53%) of 15 HM cases (P < .01). Additional interventions were performed in 14 (93%) of 15 ED cases and 6 (40%) of 15 HM cases (P < .01). CONCLUSIONS Heller myotomy may provide more durable long-term outcomes, as defined by symptom recurrence and need for subsequent intervention, and may be considered the procedure of choice.

Early coagulopathy is an independent predictor of mortality in children after severe trauma.

ABSTRACT To determine whether early coagulopathy affects the mortality associated with severe civilian pediatric trauma, trauma patients younger than 18 years admitted to a pediatric intensive care unit from 2001 to 2010 were evaluated. Patients with burns, primary asphyxiation, preexisting bleeding diathesis, lack of coagulation studies, or transferred from other hospitals more than 24 h after injury were excluded. Age, sex, race, mechanism of injury, initial systolic blood pressure, Glasgow Coma Scale score, Injury Severity Score, prothrombin time, partial thromboplastin time, platelet count, and international normalized ratio were recorded. An arterial or venous blood gas was performed, if clinically indicated. Coagulopathy was defined as an international normalized ratio greater than 1.2. The primary outcome was in-hospital mortality. Secondary outcomes were lengths of intensive care unit and hospital stay. Eight hundred three patients were included in the study. Overall mortality was 13.4%. The incidence of age-adjusted hypotension was 5.4%. Early coagulopathy was observed in 37.9% of patients. High Injury Severity Score and/or hypotension were associated with early coagulopathy and higher mortality. Early coagulopathy was associated with a modest increase in mortality in pediatric trauma patients without traumatic brain injury (TBI). In contrast, the combination of TBI and early coagulopathy was associated with a fourfold increase in mortality in this patient population. Early coagulopathy is an independent predictor of mortality in civilian pediatric patients with severe trauma. The increase in mortality was particularly significant in patients with TBI either isolated or combined with other injuries, suggesting that a rapid correction of this coagulopathy could substantially decrease the mortality after TBI in pediatric trauma patients.

Adaptive Regulation in Skeletal Muscle Glutamine Metabolism in Endotoxin-Treated Rats

The effects of a single dose of endotoxin (7.5 mg/kg BW) on skeletal muscle glutamine metabolism were studied in vivo in rats to gain further understanding of the altered glutamine metabolism that characterizes sepsis and other catabolic diseases. In endotoxin-treated animals the arterial glutamine concentration fell early initially and then increased compared with control values. Twelve hours after treatment, the arteriovenous concentration difference for glutamine across the hindquarter doubled, resulting in a significant increase in net muscle glutamine release in endotoxin-treated rats. As a consequence, the muscle glutamine concentration fell in the endotoxin-treated animals by 25%-40%, an event that was apparent as early as two hours after endotoxin treatment. Skeletal muscle glutaminase activity, the major enzyme of glutamine breakdown, was unchanged by endotoxemia, but expression of glutamine synthetase mRNA and glutamine synthetase specific activity increased in a time-dependent fashion. The glutamine depletion that develops in skeletal muscle during endotoxemia is caused by accelerated muscle glutamine release rather than an increase in intracellular degradation or a fall in intracellular biosynthesis. The adaptive increase in glutamine synthetase expression that occurs requires de novo RNA and protein synthesis and may be designed to prevent complete depletion of the intracellular glutamine pool.

Traumatic aortic injuries in the pediatric population

BACKGROUND/PURPOSE Blunt trauma is the leading cause of pediatric injury, but pediatric aortic injuries are rare. We undertook this study to investigate the demographics, treatment, and outcomes of children with blunt aortic injuries and report our experience over a 10-year period. METHODS After Institutional Review Board approval, a 10-year retrospective review of all pediatric patients admitted with blunt aortic injury was performed. Patient demographics, injury details and severity score (Injury Severity Score), treatment, and outcomes were recorded. RESULTS There were 11 children, with ages ranging from 7 to 19 years. The most common mechanism of injury was motor vehicle crashes (8). Initial computed tomography demonstrated all 11 injuries: 7 thoracic aortic (TA) and 4 abdominal aortic (AA) injuries. Associated injuries were common. The TA injuries included 4 transections, 2 intimal flaps, and 1 pseudoaneurysm. Three of these were managed nonoperatively. The AA injuries included 3 intimal flaps and 1 dissection. Three of these were also managed nonoperatively. There were no complications in the 4 children with AA or in the 3 children with TA managed nonoperatively. Complications in the 4 children undergoing operative repair of the TA included paraplegia, renal failure, recurrent laryngeal nerve injury, and pulmonary embolus. The mean hospital stay was 8 days. All children survived, with all but one discharged directly to home. CONCLUSIONS Blunt aortic injury in children is uncommon and is primarily associated with motor vehicle crashes. Injuries to the abdominal aorta were seen with restrained children vs those to the thoracic aorta that were seen in children who were unrestrained.

Position paper on laparoscopic antireflux operations in infants and children for gastroesophageal reflux disease

The use of the laparoscopic approach to perform antireflux procedures has increased dramatically since its introduction in 1991. To date, no prospective randomized studies comparing open surgery to the minimal invasive approach in children have been reported. Many retrospective reviews and case series have demonstrated that laparoscopic antireflux procedures are safe and effective once the learning curve is achieved. This position paper is coauthored by the New Technology Committee of the American Pediatric Surgery Association. The goal is to discuss the ongoing controversies and summarize the available evidence to identify the risks and benefits of laparoscopic antireflux procedures.

Cytokine regulation of intestinal glutamine utilization

The effects of cytokines on intestinal glutamine metabolism were studied to gain further insight into the regulation of altered glutamine metabolism that occurs during severe infection. One hundred thirteen adult rats were given a single dose of interleukin-1 (IL-1, 50 micrograms/kg), tumor necrosis factor (TNF, 50 micrograms/kg or 150 micrograms/kg), or saline (controls), and flux studies were performed 4 or 12 hours later. Intestinal blood flow was not different between control and cytokine-treated animals at either time point. At the 4-hour time point, arterial glutamine fell by 16% to 21% in the cytokine-treated animals (p less than 0.05); at the 12-hour time point, the arterial glutamine concentration had returned to normal. Intestinal glutamine extraction decreased in the animals treated with IL-1 at both time points (4 hours: 13% +/- 1.3% in IL-1 versus 20% +/- 1.6% in controls, p less than 0.05; and 12 hours: 9% +/- 2% in IL-1 versus 17% +/- 2% in controls, p less than 0.05). Consequently, net intestinal glutamine uptake fell in the animals treated with IL-1 at both time points (p less than 0.05). Similarly, the activity of mucosal glutaminase, the principal enzyme of glutamine hydrolysis in the gut, fell by 50% in the 4-hour study (6.1 +/- 0.6 mumol/h/mg protein in IL-1 versus 9.6 +/- 0.8 mumol/h/mg protein in controls, p less than 0.01) and by 40% in the 12-hour study (5.4 +/- 0.5 mumol/h/mg protein in IL-1 versus 8.8 +/- 0.4 mumol/h/mg protein in controls, p less than 0.05). Concomitant with the aforementioned decrease in gut glutamine metabolism was a 25% incidence of positive blood cultures for gram-negative organisms in IL-1 treated rats studied at the 12-hour time point (p = 0.05 versus controls). In the doses administered and at the time points studied, TNF had no effects on the parameters of gut glutamine metabolism examined. The results indicate that IL-1 is a potential mediator of the alterations in gut glutamine metabolism observed in sepsis and endotoxemia.

Equestrian injuries in children

PURPOSE Equestrian activities are regarded by some as high-risk sports, and our recent experience suggested this to be true. We undertook this study to review our experience with pediatric equestrian injuries. METHODS After institutional review board approval, we reviewed emergency department and hospital admissions for children 0 to 18 years, with equestrian trauma, over an 11-year period. RESULTS There were 164 encounters with 135 girls and 29 boys. Most injuries (82%) occurred after falling or being thrown from the animal, and only 12% occurred during jumping or rodeo competitions. The remaining injuries were secondary to being trampled, kicked, or trapped under the animal. Eighty-seven children required hospital admission. Lacerations and contusions (58%) or orthopedic injuries (31%) were most common in the emergency department cohort. In the admission cohort, injury sites included orthopedic (34%), head (23%), abdomen (21%), and chest (11%). Multiple injuries occurred in 13%. A significant number of children required surgical interventions, including 19 orthopedic procedures, 4 laparotomies, 3 facial reconstructions, and 2 craniotomies. The average length of stay was nearly 4 days, with 60% of the children requiring intensive care admission. There were no deaths. One child was discharged to rehab, the rest were sent home. CONCLUSIONS In our experience, more than one third of the children admitted after sustaining injuries in horse-related sports required surgical interventions. Children participating in equestrian activities are at risk for substantial injury, and pediatric care providers must maintain a high index of suspicion when evaluating these children.