Donald George

Clinical Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients Applying the GRADE System to Development of A.S.P.E.N. Clinical Guidelines

As an interdisciplinary organization dedicated to advancing the science and practice of nutrition support therapy, the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) works vigorously to support quality patient care, education, and research in the fields of nutrition and metabolic support in all healthcare settings. To promote safe and effective patient care by nutrition support practitioners, the A.S.P.E.N. Board of Directors published “Guidelines for the Use of Parenteral and Enteral Nutrition in Adult and Pediatric Patients” in 1993 and 2002. The format and methodology of the Clinical Guidelines (CG)s have changed over time, as a result of A.S.P.E.N.’s on-going efforts to improve the clarity and usefulness of the guidelines. The Institute of Medicine (IOM) has recently redefined Clinical Practice Guidelines as “statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options.” To be trustworthy, IOM states that CGs should be based on a systematic

Changes in Circulating Satiety Hormones in Obese Children: A Randomized Controlled Physical Activity-Based Intervention Study

The aims of this study are to examine in children: (i) obesity‐related alterations in satiety factors such as leptin, ghrelin, and obestatin; (ii) the link between satiety factors and cardiometabolic risk factors; and (iii) the impact of a physical activity‐based lifestyle intervention on the levels of these satiety factors in the obese. We studied a total of 21 adolescents (BMI percentile, 99.0 ± 0.6 for 15 obese and 56.2 ± 1.1 for 6 lean). The obese subjects underwent a 3‐month randomized controlled physical activity‐based lifestyle intervention. Leptin, soluble leptin receptor (sOB‐R), ghrelin, and obestatin levels were determined as the primary outcome measures. Other markers of cardiometabolic disease such as inflammation and insulin resistance were also determined. Body composition was measured by dual‐energy X‐ray absorptiometry. The concentrations of ghrelin, obestatin, and sOB‐R were significantly lower in the obese children compared to the lean controls, whereas that of leptin was higher (all P < 0.05). Although intervention led to a net increase in obestatin (P < 0.01) and no change in ghrelin levels, the balance between ghrelin and obestatin (ratio of ghrelin to obestatin, G/O) decreased (P < 0.02). Intervention reduced leptin and increased sOB‐R (P < 0.01 for both). Significant associations between satiety factors and other cardiometabolic risk factors were also observed. Taken together, alterations in the levels of satiety factors are evident early in the clinical course of obesity, but physical activity‐based lifestyle intervention either prevented their continued increase or normalized their levels. These beneficial effects appear to aid in the maintenance of body weight and reduction in cardiovascular risk.

A.S.P.E.N. Clinical Guidelines Nutrition Support of Neonates Supported with Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) utilizes a modified heart-lung machine with a membrane oxygenator in the setting of profound cardiorespiratory failure. ECMO has been used successfully in pediatric and adult applications, though the most frequent indication is neonatal respiratory failure in conditions such as persistent pulmonary hypertension, congenital diaphragmatic hernia, congenital heart disease, and meconium aspiration. ECMO use is associated with improved mortality, however the nutritional and metabolic burden in these children is considerable. ECMO does not provide a “metabolic rest.” Rather, neonates on ECMO have demonstrated some of the highest rates of protein catabolism reported. Appropriate provision of nutrition support in ECMO patients is predicated upon a clear understanding of the changes in their metabolism, metabolic reserves, and nutrition requirements. The purpose of this Clinical Guideline is to address the nutrition support of neonatal patients treated with ECMO.

Response of fractional synthesis rate (FSR) of fibrinogen, concentration of D-dimer and fibrinolytic balance to physical activity-based intervention in obese children

Summary.  Background: Physical activity‐induced reduction in obesity‐related hyperfibrinogenemia in children has been reported. The underlying mechanisms remain elusive. Further, the effect of such interventions on fibrinolysis in children is scarce. Objectives: To investigate in obese children, before and after a physical activity‐based intervention: (i) the mechanistic role of fractional synthesis rate (FSR) of fibrinogen in the reduction of hyperfibrinogenemia; and (ii) the changes in fibrinolytic factors. Methods: Subjects included 21 (age > 14 < 18 years; Tanner stage, IV–V) children (15 obese, BMI >95%tile for age and sex and six lean, BMI <85%tile). After baseline measurements of FSR of fibrinogen, and concentrations of fibrinogen, D‐dimer, PAI‐1 and t‐PA in all children, studies were repeated after a 3‐month randomized controlled physical activity‐based lifestyle intervention in obese children only. Results: FSR of fibrinogen was higher (P = 0.002) in the obese (vs. lean) group, which was reduced (P = 0.001) after intervention. This almost completely accounted for the reduction in obesity‐related hyperfibrinogenemia. High levels of D‐dimer decreased (P = 0.001) after intervention, whereas fibrinolysis was not enhanced. Conclusions: The direct reduction in the FSR of fibrinogen and the remarkable correlation between the magnitudes of reduction in fibrinogen FSR and concentration signify a mechanistic role for FSR in the regulation of physical activity‐induced reversal of hyperfibrinogenemia in obese children. The congruent reductions in the FSR of fibrinogen and the concentrations of fibrinogen and D‐dimer in response to intervention despite depressed fibrinolysis suggest an overall improvement in the hypercoagulable state in obese children with physical activity‐based lifestyle intervention.

Complications of retained internal bolster after pediatric percutaneous endoscopic gastrostomy

PURPOSE Percutaneous endoscopic gastrostomy (PEG) has been widely accepted as an efficacious means of nutritional support in the infant and child. A well-described technique uses the Gauderer-Ponsky tube (CR Bard Incorporated, Tewksbury, MA) drawn antegrade through the gastric wall and secured by an internal and external SILASTIC (Dow Corning; Midland, MI) bolster. The majority of reported complications attendant to its use occur secondary to insertion. This report details a less well-described complication of tube removal. METHODS Since 1992, 234 pediatric PEGs have been performed using a Gauderer-Ponsky tube. Approximately 6 weeks after the procedure, all catheters were removed and replaced with gastric buttons. The internal bolster was left within the stomach to pass spontaneously. RESULTS Five children (2.1%), ages 6 months to 5 years, failed to pass this crossbar. Three subsequently presented with dysphagia and drooling with the internal bolster wedged in the proximal esophagus. All were left with significant residual stricture after endoscopic removal of the crossbar. Two required dilatation and the third underwent operative stricturoplasty. A fourth child returned with intermittent gastric outlet obstruction. The internal bolster was retained in the stomach 4 months after catheter removal. Endoscopic retrieval resulted in resolution of the symptomatology. The final case was found to have an asymptomatic bolster in the stomach approximately 18 months after catheter removal. CONCLUSIONS These cases highlight a potential sequelae of pediatric percutaneous endoscopic gastrostomy not previously acknowledged. The significant complications associated with the retained bolster in four of these five children suggests that follow-up should be altered to monitor prompt passage of the crossbar after tube removal.

BILIARY INFUSION THERAPY IN THE INSPISSATED BILE SYNDROME OF CYSTIC FIBROSIS

A 3.5-month-old white boy was born with meconium ileus, peritonitis, and jejunal atresia from cystic fibrosis. He subsequently developed unrelenting and severe extrahepatic biliary obstruction as demonstrated by liver biopsy showing periportal inflammation, cholestasis, and fibrosis. Surgical exploration confirmed the diagnosis of extrahepatic biliary obstruction by severely inspissated bile. A cholecystostomy tube was left in place. The cholestasis remained unresponsive to conservative medical therapy. The obstruction was relieved by hydrostatic infusion of 2% N-acetylcysteine into the biliary tree over a 6-day period. The child also received concurrently four i.v. injections of synthetic cholecystokinin. This therapeutic modality was thought to be both safe and effective.

Vitamin D Status and Cardiovascular Risk in Obesity: Effect of Physical Activity in Nonvitamin D Supplemented Adolescents

BACKGROUND The relationship among inadequate vitamin D status, obesity, and cardiometabolic risk and the potential impact of physical activity-based interventions on vitamin D status are poorly characterized in children. This study aimed to address these issues. METHODS We studied a total of 21 adolescents (15 obese and 6 normal weight; age: 14-18 years; Tanner stage>IV). Adolescents with obesity (n = 15) underwent a randomized controlled (8 in the intervention group and 7 in the control group) 3-month physical activity-based lifestyle intervention. 25-Hydroxy vitamin D [25(OH)D] by mass spectrometry, adiponectin, leptin, high-sensitivity C-reactive protein (CRP), insulin, and glucose were measured and body composition was assessed by dual-energy x-ray absorptiometry (DXA). Analysis of covariance and mixed-effects model were used to compare mean change in 25(OH)D between intervention and nonintervention groups. Bootstrap method was used to validate the estimates and principle component analysis reduced the variables in the data for adjustment. RESULTS 25(OH)D was lower (P < 0.001) in the obese versus lean adolescents. Homeostasis model assessment-insulin resistance, CRP, fat mass (FM), and body mass index z-score were negatively correlated with baseline 25(OH)D, while adiponectin showed a positive correlation. After adjustment for baseline biomarkers of cardiometabolic risk, the concentration of 25(OH)D increased in the obese intervention group (P = 0.06), but not in the nonintervention group. Fat-free mass increased and FM decreased (P < 0.05 for both) in the intervention group. The magnitudes of increase in 25(OH)D and decrease in FM directly correlated (P < 0.05). CONCLUSIONS The increase in circulating 25(OH)D concentration by physical activity-based lifestyle-only intervention in adolescents with obesity, who did not receive vitamin D supplementation, suggests a putative independent role of physical activity-based interventions in the regulation of vitamin D status and potentially in the mitigation of risk factors of cardiovascular disease.

Novel Implementation of Genotype-Guided Proton Pump Inhibitor Medication Therapy in Children: A Pilot, Randomized, Multisite Pragmatic Trial

The efficacy of proton pump inhibitor (PPI) medications is highly dependent on plasma concentrations, which varies considerably due to cytochrome P450 (CYP2C19) genetic variation. We conducted a pragmatic, pilot study of CYP2C19 genotype‐guided pediatric dosing of PPI medications. Children aged 5–17 years old with gastric‐acid‐related conditions were randomized to receive either conventional dosing of a PPI or genotype‐guided dosing for a total of 12 weeks. Sixty children (30 in each arm) were enrolled and had comparable baseline characteristics. The mean daily omeprazole equivalent dose prescribed to participants across metabolizer phenotype groups was significantly different in the genotype‐guided dosing arm (P < 0.001), but not in the conventional dosing arm. Prescribers waited for the genotype result before prescribing the PPI medication for 90% of the participants in the genotype‐guided dosing arm. The number of participants who reported an infection was marginally lower in genotype‐guided dosing vs. conventional dosing (20% vs. 44%; P = 0.07). Sinonasal symptoms were higher in the conventional dosing arm as compared with genotype‐guided dosing arm: (2.6 (2.0, 3.4) vs. 1.8 (1.0, 2.3), P = 0.031). CYP2C19 genotype‐guided PPI therapy is feasible in a clinical pediatric setting, well accepted by providers, resulted in differential PPI dosing, and may reduce PPI‐associated infections. A future large scale randomized clinical trial of CYP2C19 genotype‐guided pediatric dosing of PPI medications in children is warranted.