nutrition and metabolism paper sessions - … · glutathione pathway metabolite) and hypoxanthine...

CLINICAL NUTRITION WEEK 2016 ABSTRACTS

January 16–19, 2016, Austin, Texas

Austin Convention Center

NUTRITION AND METABOLISM PAPER SESSIONS

Session Title Page

Premier Paper Session & Live Vars Award Competition 1

Parenteral Nutrition 8

Enteral Nutrition 14

Malnutrition, Obesity, Practice Concepts 22

Critical Care & Other Critical Health Issues 30

GI & Other Metabolic Issues 42

Pediatric and Neonatal 49

Premier Paper Session & Live Vars Award Competition

The Harry M. Vars award is given annually to the person presenting the highest-scoring qualified abstract for Clinical Nutrition Week (CNW). The candidates are also evaluated on a manuscript based on their abstract, as well as on their expertise and knowledge of the science as demonstrated during their oral presentation at the Premier Paper Session. CNW16 is January 16–19 in Austin, Texas. Vars Candidate

2371936—Preserved Gut Microbial Diversity Accompanies Upregulation of TGR5 and Hepatobiliary Transporters in Bile Acid–Treated Animals on Parenteral Nutrition

Ajay K. Jain, MD1; Abhineet Sharma2; Sumit Arora1; Keith S. Blomenkamp1; Ik Jun1; Robert Luong1; David Westrich1; Asyush Mittal3; John P. Long, PhD1; Jeffrey Teckman, MD1 1Pediatrics, Saint Louis University, St Louis, MO, USA; 2Pediatrics, Children’s Hospital of Wisconsin, Milwaukee, WI, USA; 3Wayne State University, Detroit, MI, USA

Purpose: Parenteral nutrition (PN) is a lifesaving therapy where essential nutrients are delivered via intravenous access. This therapy bypasses the enteric system in critically ill patients unable to tolerate enteral nutrition (EN). While the role of PN in clinical settings cannot be understated, the benefits of this lifesaving therapy tend to come at the cost of severe gut mucosal atrophy and gut inflammation. TGR5, a G-protein-coupled receptor, has been shown to modulate intestinal growth and immune responses. Recent evidence also indicates that the gut mucosal barrier is influenced by the gut microflora. Additionally, inflammation is known to downregulate hepatobiliary transporters bile salt export pump (BSEP) and sodium taurocholate cotransporting polypeptide (NTCP) involved in the normal enterohepatic circulation. We hypothesize that bile acid (BA) treatment regulates TGR5 and induces gut microbial changes contributing to improved pathology.

Methods: Based on our previously published ambulatory PN animal model, piglets (n = 12) were randomized to receive approximately 2 weeks of isocaloric enteral swine milk (EN), PN only, or PN with an enteral BA receptor agonist, oleanolic acid (OA). Tissue, serum, and feces were collected. Culture-independent identification of fecal bacterial populations was determined by 16S rRNA sequencing. Sequences were subjected to the unweighted UniFrac metric. Statistical analysis was performed with Jackknife sample clusters found in the UniFrac workflow. Additionally, sequences were classified up to the genus level via the RDP Classifier algorithm. Alpha diversity was calculated at the phylum level with Shannon’s diversity index.

Clinical Nutrition Week 2016 1

Results: PN resulted in marked gut atrophy when compared with EN animals. OA led to preservation of gut mass, demonstrated grossly and histologically. The mean gut density (g/cm, ± SD) was 0.31 ± 0.03 for EN, 0.18 ± 0.03 for PN (P < .05 EN vs PN), and 0.27 ± 0.01 for PN + OA (P < .05, PN + OA vs PN). OA preserved the markedly decreased villous:crypt ratio noted with PN. The mean ratio was 3.51 ± 0.59 for EN, 1.69 ± 0.10 for PN (P < .05, EN vs PN), and 2.90 ± 0.23 for PN + OA (P < .05, PN + OA vs PN). Gut TGR5 mRNA expression was significantly elevated with OA. When normalized for EN, mean TGR5 transcript value was 0.91 ± 0.14 for PN vs 2.27 ± 0.58 for OA. Additionally, there was a trend for NTCP and BSEP upregulation with OA. In subgroup analysis, clustering was noted with unweighted UniFrac metric based on the treatment. Branch points were supported by Jackknife analysis for PN vs other groups but not well supported for the other branches (>95% for PN). Additionally, a shift toward the proinflammatory phylum Bacteroidetes was noted with PN based on the RDP classifier algorithm. No statistical difference with the Bacteroidetes phylum was noted in EN or PN + OA animals (P = .4). Furthermore, the mean alpha diversity was significantly different among the groups (df = 2, F = 61.57, P < .0001) at 0.1351, 0.6403, 1.077 for PN, EN, and PN + OA, respectively.

Conclusions: We show that microbial communities diverge with PN. Such therapy leads to an overall reduced microbial diversity and gut atrophy. Additionally, a statistically significant expansion of the proinflammatory phylum Bacterioides occurs in PN animals. This study thus explores a potential novel relationship between gut microbiota and key mediators in the enterohepatic circulation. It provides direct evidence that treatment with BA receptor agonists, while upregulating TGR5, BSEP, and NTCP, also preserve gut growth and microbial diversity.

Financial support: American Society for Parenteral and Enteral Nutrition, North American Society for Pediatric Gastroenterology Hepatology and Nutrition. Vars Candidate

2367379—Plasma Metabolome Alteration in Critical Illness According to Nutrition Status: A Cohort Study

Kris Mogensen, MS, RD, LDN, CNSC1; Jessica Lasky-Su, PhD2; Angela Rogers, MD3; Rebecca Baron, MD4; Laura Fredenburg, MD4; James Rawn, MD 5; Malcolm Robinson, MD5; Anthony Massaro, MD4; Augustine Choi, MD6; Kenneth Christopher, MD7 1Department of Nutrition, Brigham and Women’s Hospital, Boston, MA, USA; 2Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 3Pulmonary and Critical Care Medicine, Stanford University Medical Center, Palo Alto, CA, USA; 4Pulmonary and Critical Care Division, Brigham and Women’s Hospital, Boston, MA, USA; 5Department of Surgery, Brigham and Women’s Hospital, Boston, MA, USA; 6New York–Presbyterian Hospital, New York, NY, USA; 7Renal Division, Brigham and Women’s Hospital, Boston, MA, USA

Purpose: Malnutrition is associated with increased mortality in critical illness. Loss of metabolic homeostasis is a common in critical illness and characterized by a severe disruption of a multitude of metabolic pathways. We hypothesize that circulating plasma metabolic profiles at intensive care unit (ICU) admission would differ in critically ill patients with malnutrition relative to those without malnutrition.

Methods: We performed a cohort study in a 20-bed medical ICU of a Boston teaching hospital. We generated metabolomics profiles in plasma collected at ICU admission in 85 adult patients with systemic inflammatory response syndrome or sepsis from 2008–2010. To identify metabolites and metabolite pathways, we performed an integrated discovery approach that included gas and liquid chromatography, mass spectroscopy, logistic regression, partial least squares–discriminant analysis, and metabolite set enrichment analysis where metabolite sets are ranked according to Holm P value. We removed metabolites with the lowest IQR of variability and those related to medications, leaving 281 metabolites. All raw metabolite concentrations were log2 transformed and normalized via cubic root transformation and Pareto scaling. Nutrition status was determined by a registered dietitian with data related to anthropometric measurements, biochemical indicators, clinical signs of malnutrition, malnutrition risk factors, and metabolic stress. Malnutrition was considered to be present if the patient was diagnosed by a registered dietitian at ICU admission with nonspecific protein-calorie malnutrition, specific (mild, moderate, or severe) protein-calorie malnutrition, or marasmus.

Results: Most patients were male (56%) and white (80%). The mean ± SD age at ICU admission was 55.0 ± 14.5 years; 38% of cohort patients were diagnosed with malnutrition; and 66% of cohort patients had sepsis. The mean APACHE II score was 25.7 ± 9.9. The 28-day mortality of the cohort was 33.3%. There were significant differences in age and malignancy status between patients with malnutrition and those without. In our cohort, pyroglutamine (a


glutathione pathway metabolite) and hypoxanthine (a purine metabolite) were identified as predictive of malnutrition in logistic regression analysis (Table 1). Pyroglutamine and hypoxanthine were also identified in partial least squares–discriminant analysis as having high importance for malnutrition classification (see Figure 1). Furthermore, quantitative metabolite set enrichment analyses show that increases in the glutathione pathway metabolites (cysteinylglycine, pyroglutamine, L-cysteine) and increases in purine metabolites (adenosine monophosphate, hypoxanthine, xanthine, and uric acid) were significantly associated with malnutrition. Furthermore, malnutrition was associated with 28-day mortality. When adjusted for age, sepsis, malignancy status, and APACHE II, patients diagnosed with malnutrition had a 3-fold odds of 28-day mortality (OR, 3.26; 95% CI, 1.12–9.52) relative to patients without malnutrition. Addition of metabolites associated with malnutrition to a 28-day mortality model including age, sepsis, malignancy status, and APACHE II improved model discrimination for mortality (area under the curve, 0.78–0.83).

Table 1. Top 10 Metabolites: Logistic Regression.

Metabolite Beta Regression Coefficienta

P Value Beta Regression Coefficientb

P Value Class

5-methylthioadenosine 0.71 .011 0.66 .018 Amino acid

1-palmitoylglycerophosphoethanolamine

–0.63 .018 –0.92 .002 Lipid

N-6-trimethyllysine 0.60 .024 0.82 .004 Amino acid

Nicotinamide –0.70 .024 –0.38 .21 Vitamin

N-acetylmethionine 0.51 .027 –0.07 .75 Amino acid

Pyroglutamine 0.49 .027 0.64 .007 Amino acid

Valerate –0.60 .030 –0.55 .048 Lipid

Hypoxanthine 0.46 .041 0.06 .76 Nucleotide

Kynurenine 0.53 .041 1.43 <.001 Amino acid

Phenyllactate 0.32 .049 0.91 <.001 Amino acid

aBeta and P values are for results using logistic regression for association with malnutrition. bBeta and P values are for results using logistic regression for association with 28-day mortality.


Figure 1. Partial least squares–discriminant analysis 2-dimensional score plot. Cross-validated score plot for 32 patients with malnutrition (+) and 53 patients without malnutrition (Δ) showing the separation achieved according to malnutrition status.

Conclusions: Malnutrition is associated with differential metabolic profiles early in critical illness. Common to all of our metabolome analyses, glutathione and purine metabolism—which play principal roles in cellular redox regulation and accelerated tissue ATP degradation, respectively—were significantly altered with malnutrition. Furthermore, the addition of metabolites related to malnutrition to mortality prediction models can improve the discrimination for 28-day mortality in the critically ill.

Financial support: This work was supported by the A.S.P.E.N. Rhoads Research Foundation. Vars Candidate and Trainee Award

2372373—Validation of Bedside Ultrasound of Muscle Layer Thickness of the Quadriceps in the Critically Ill Patient (VALIDUM Study): Preliminary Results

Michael Paris1; Marina Mourtzakis, PhD1; Andrew Day, MSc2; Roger Leung, MSc2; Snehal Watharkar, MSc1; Rosemary Kozar, MD, PhD3; Carrie Earthman, PhD, RD4; Adam Kuchnia, RD, MSc4; Rupinder Dhaliwal, RD2; Lesley Moisey, RD, MSc1; Charlene Compher, PhD, RD5; Niels Martin, MD6; Michele Nicolo, MSc7; Thomas White, MD8; Hannah Roosevelt, RD9; Sarah Peterson, RD9; Daren Heyland, MD2 1Kinesiology, University of Waterloo, Waterloo, Ontario, Canada; 2Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada; 3Surgery, University of Maryland, Baltimore, MD, USA; 4Food Science and Nutrition, University of Minnesota, St Paul, MN, USA; 5School of Nursing, University of Pennsylvania, Philadelphia, PA, USA; 6Surgery, University of Pennsylvania, Philadelphia, PA, USA; 7Clinical Nutrition Support Services, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; 8Surgery, Intermountain Medical Center, Murray, UT, USA; 9Food and Nutrition, Rush University Medical Center, Chicago, IL, USA|

Purpose: In critically ill patients, muscle atrophy is a strong predictor of morbidity, mortality, and long-term disability. While body mass index (BMI) has been commonly used to identify malnourished individuals, it cannot quantify specific lean tissues, such as skeletal muscle. Computed tomography (CT) can precisely quantify muscle


mass; however, it may not be practical or expedient. Ultrasound, which is available in most intensive care units (ICUs), is a potential tool to assess muscle atrophy. Comprehensive ultrasound protocols that assess multiple landmarks (ie, 9 sites) have been validated to quantify lean tissue in healthy individuals. These types of protocols are not feasible or practical in an ICU environment. While a quadriceps muscle layer thickness (QMLT) protocol may be easily applied at the ICU bedside, it has not been evaluated for its ability to identify ICU patients with low muscle mass. Thus, our objective was to validate QMLT derived by ultrasound by comparing with CT-based measures of muscle tissue.

Methods: In this multicenter (10 ICUs) prospective observational study, all patients were >18 years of age and had abdominal CT scans performed for clinical reasons <24 hours before or <72 hours after ICU admission. Moribund patients who were not expected to survive were excluded. CT scans were landmarked at the third lumbar vertebra and were analyzed for skeletal muscle cross-sectional area (CSA). Previously established cut points for identifying individuals with lower-than-normal muscularity were applied (<110 cm2 for females and <170 cm2 for males). The ultrasound assessment occurred <72 hours of the CT scan. The QMLT protocol for ultrasound assessed 2 sites on each quadriceps with maximal compression (depressing the underlying soft tissues by applying maximum force of the ultrasound probe against the landmarked sites).

Results: Of the 149 patients, 42% were females. Overall, patients were (mean ± SD) 50 ± 19 years old and had a BMI of 29 ± 8 kg/m2. Mean APACHE II and SOFA scores were 17 ± 8 and 5 ± 4, respectively. Median (Q1–Q3) Charlson Comorbidity Index was 1 (0–3) and ICU and hospital length of stay were 3 (2–7) and 8 (5–17) days, respectively, with 9% and 11% rates of mortality. Based on BMI, 3% of patients were classified as underweight and 68% overweight or obese, whereas CT data revealed that 57% of patients had lower-than-normal muscularity. Mean abdominal skeletal muscle CSA was 109 ± 25 cm2 for females and 168 ± 37 cm2 for males, suggesting that, on average, patients had low muscularity. Average ultrasound QMLT was significantly different between males (1.5 ± 0.6 cm) and females (1.1 ± 0.6 cm; P < .001). A significant positive correlation (r = 0.45) was found between QMLT and CSA (P < .0001). Area under the curve was 0.67 for an receiver operating characteristic curve that was created to predict CT-derived low-muscularity cut points based on QMLT (Figure 1). Notably, the area under the curve of the logistic model based on age, sex, BMI, Charlson Comorbidity Index, and admission type (surgical vs medical) as predictors was 0.72, and if ultrasound QMLT was added to the model, this increased to 0.76 (Table 1).

Conclusions: Although 68% of the patients in this study were overweight or obese and only 3% were underweight, more than half of the patients had lower-than-normal muscularity. CT imaging has been an important measure in identifying patients with low muscularity. Here, our preliminary results suggest that QMLT obtained from ultrasound along with additional predictors, including age, BMI, sex, Charlson Comorbidity index, and admission type, were valuable in predicting muscularity in this group of ICU patients.

Financial support: Government of Ontario Ministry of Research and Innovation Early Researcher Award.

Table 1. Ability of QMLT to Predict Low CT Skeletal Muscle Area by Logistic Regression.a

Predictors c P Value, Model P Value, QMLT

QMLT 0.665 .003 .003

Covariatesb 0.718 .006 NA

Covariates + QMLT 0.764 .001 .008

c, concordance index (also known as area under the receiver operating characteristic curve); CT, computed tomography; NA, not applicable (because QMLT was not included in this model); QMLT, quadriceps muscle layer thickness. aLow CT skeletal muscle area is defined as <170 cm2 for males and <110 cm2 for females. By this definition, 86 of 149 patients had low CT skeletal muscle area. Variance inflation factor for QMLT in model with all covariates is 1.2. bCovariates are age (linear), sex (binary), body mass index (linear), Charlson Comorbidity Index (linear), and admission type (binary).


Figure 1. Receiver operating characteristic curve of using QMLT to predict CT-based low muscle area (cm2). CT-based low muscle mass is defined as <170 cm2 for males and <110 cm2 for females. According to this definition, 49 of 86 (57%) males had low muscle mass and 37 of 63 (59%) females had low muscle mass. A selection of QMLT values is provided to show the corresponding sensitivity and specificity. CT, computed tomography; QMLT, quadriceps muscle layer thickness.

Vars Candidate

2373230—Differential Effects on Intestinal Adaptation Following Exogenous Glucagon-Like Peptide-2 Therapy With and Without Enteral Nutrition in Neonatal Short Bowel Syndrome

David Lim, MDCM, Med1; Diane Abdoulaye, PhD2; Mitsuru Muto, MD, PhD3; Donna Vine, PhD2; Patrick Nation, PhD4; Pamela Wizzard, BSc, RAHT3; David Bigam, MD, MSc, FRCSC1; Paul Pencharz, MB, ChB, PhD, FRCPC5,6; Justine Turner, MD, PhD2,3; Paul Wales, BSc, MD, MSc, FRCSC, FACS7 1Surgery, University of Alberta, Edmonton, Alberta, Canada; 2Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada; 3Pediatrics, University of Alberta, Edmonton, Alberta, Canada; 4Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada; 5Paediatrics, University of Toronto, Toronto, Ontario, Canada; 6Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada; 7Surgery, University of Toronto and The Hospital for Sick Children, Toronto, Ontario, Canada

Purpose: Our understanding of the efficacy of glucagon-like peptide-2 (GLP-2) therapy in pediatric short bowel syndrome (SBS) is limited. Many key questions remain unanswered: (1) Can GLP-2 stimulate adaptation in neonatal SBS? (2) If an adaptive effect is present, will it vary depending on anatomy? and (3) Will an adaptive effect be potentiated by the addition of enteral nutrition (EN)? We aim to study the efficacy of exogenously administered GLP-2 on structural and functional adaptation in 2 preclinical models of neonatal SBS representing the spectrum of disease and whether this adaptive effect can be potentiated with EN at a level reported to stimulate adaptation.

Methods: Piglets (3–5 days old) were block randomized to a 75% midintestinal resection (JI group; retains ileum), distal-intestinal resection (JC group; has no ileum), or no resection (sham control) and either GLP-2 treatment (11 nmol/kg/d) or saline control for 7 days. Piglets also received nutrition support at 100% parenteral nutrition (PN; n = 32 in total) or 80% PN + 40% EN (n = 28 in total). Structural adaptation was assessed by morphologic changes (in intestinal length and intestinal/mucosal weights) and histologic changes. Functional adaptation was assessed by qRT-PCR for the relative gene expression of nutrient transporters (SGLT1, GLUT5, CD36, FATP4) and epithelial

Area Under the Curve = 0.67

1 - Specificity

Sen

sitiv

ity


tight junction proteins (occludin and claudins 3, 7, and 15) as well as fecal fat absorption in pigs receiving 40% EN. Data are analyzed by 2-way analysis of variance for a 2 × 2 factorial design of surgery and treatment factors; post hoc testing was performed by Bonferroni’s method.

Results: Body weight gain: In pigs on 100% PN, there was no difference in the change in total body weight gain among groups. In the pigs receiving 40% EN, the JC group gained the least amount of weight vs the sham control (P < .01). Structural adaptation: In pigs receiving 100% PN (no EN), there was no difference in the change in intestinal length. GLP-2 therapy increased normalized bowel weight (P = .04) and jejunal mucosal weight (P < .01) in the JI but not the JC group. GLP-2 therapy increased villus height in the jejunum of the JC group and ileum of the JI group (P < .01). Jejunum crypt depth was increased in both groups with GLP-2 treatment (P < .01). In piglets receiving 40% EN, intestinal length increased in the JI group and did not change in the JC group, irrespective of GLP-2 treatment (P < .01). There was no difference in jejunal mucosal weight. Jejunum villus height increased in the JC group (P < .01), while ileum crypt depth was increased in the JI group (P < .01) with GLP-2 therapy. Functional adaptation: There was no difference in the relative expression of nutrient transporters or tight junction proteins as a function of either GLP-2 treatment or surgical anatomy or receiving EN. In pigs receiving 40% EN, GLP-2 treatment did not affect fecal fat absorption (P = .76).

Conclusions: In piglets receiving no EN on 100% PN, GLP-2 induced structural adaptation more robustly in the JI group than the JC group; the JC group nevertheless had histologic adaptation. However, while 40%–60% EN is reported in the literature as the minimum enteral requirement for adaptation in healthy piglets, our data suggest that, in the setting of SBS, 40% EN had differential effects on adaptation depending on anatomy. In the JI group, bowel lengthening occurred, while the JC group did not show evidence of enhanced adaptation. Together, our studies illustrate that even without EN, GLP-2 has an intestinotrophic effect. The optimal amount of EN necessary to potentiate the adaptive effect of GLP-2 in neonatal SBS may depend on remnant intestinal anatomy, which is relevant considering the heterogeneous nature of the human neonatal SBS population.

Financial support: Canadian Institutes of Health Research, SickKids Foundation. Vars Candidate

2372586—A Comparison of Fish Oil Sources for Parenteral Lipid Emulsions in a Murine Model

Gillian Fell, MD, PhD1; Bennet Cho, BA1; Amy Pan, BA1; Vania Nose, MD, PhD2; Lorenzo Anez-Bustillos, MD1; Duy Dao, MD1; Meredith Baker, MD1; Prathima Nandivada, MD3; Kathleen Gura, PharmD4; Mark Puder, MD, PhD1 1Vascular Biology Program and Department of Surgery, Boston Children’s Hospital, Boston, MA, USA; 2Department of Pathology, Massachusetts General Hospital, Boston, MA, USA; 3Department of Surgery, Beth Israel-Deaconess Medical Center, Boston, MA, USA; 4Department of Pharmacy, Boston Children’s Hospital, Boston, MA, USA

Purpose: Lipids in parenteral nutrition (PN) are administered as an emulsion of oil dispersed in an aqueous medium. They are important for preventing essential fatty acid deficiency, and they provide noncarbohydrate calories to prevent fatty liver disease that can result from high-carbohydrate feeding. Parenteral fat is also important in managing PN-associated liver disease (PNALD), a complication of long-term PN characterized by cholestasis and hepatic inflammation that can progress to cirrhosis and death if not treated. Fish oil (FO) lipid emulsions can reverse PN-induced cholestasis. FO is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—polyunsaturated omega-3 fatty acids that help prevent essential fatty acid deficiency and that are precursors of anti-inflammatory mediators that may contribute to treating PNALD. There are 2 FO monographs in the European Pharmacopeia. One is “Fish oil, rich in omega-3 fatty acids,” or natural FO (NFO), in which EPA and DHA constitute up to 30% of the fatty acids and virtually all fatty acids are in triglyceride form. The other is “Omega-3 acid triglycerides,” or purified FO (PFO), in which EPA and DHA constitute at least 45% of the fatty acids and the oil is a mixture of mono-, di-, and triglycerides. Use of PFO, by virtue of its high concentration of EPA and DHA, may be beneficial as compared with NFO, but use of intravenous (IV) emulsions containing PFO has not been previously reported. The purpose of this study is to compare the effects of IV lipid emulsions made with NFO or PFO in a murine model.

Methods: In the laboratory, lipid emulsions were generated containing different oils: United States Pharmacopeia–grade soybean oil (SO), NFO, or PFO. NFO and PFO met pharmacopeia standards of their respective monographs. All emulsions contained 20% oil in an aqueous dispersion (12% egg phospholipid, 2.5% glycerol, 0.03% sodium


oleate). Emulsions underwent PFAT5 and mean globule size analysis at a commercial laboratory (Micro Measurements, Wheeling, IL). Chow-fed C57BL/6 mice received saline, one of the above emulsions, or a commercial FO (Omegaven [OM]; Fresenius Kabi, Bad Homburg, Germany) by tail vein injection (2.4 g/kg/d) for 19 days. Effects after each dose were recorded. On day 19, animals were euthanized, and livers, spleens, and lungs were procured and fixed in 10% formalin for histologic analysis.

Results: All emulsions met the United States Pharmacopeia standard for mean globule size, and all except the NFO emulsion met the PFAT5 standard (NFO PFAT5 = 0.057). Animals administered OM, SO, and NFO tolerated injections well. Those administered PFO developed tachypnea and lethargy for ~5 minutes following injection. At euthanasia, PFO-treated animals had splenomegaly as compared with the other groups. On histologic analysis, the PFO groups had splenic fat-laden macrophages and hepatic sinusoidal lipid-laden Kupffer cells with no inflammation or necrosis. Lungs in this group had scattered fat deposits. All other groups had histologically normal livers, spleens, and lungs.

Conclusions: Use of PFO lipid emulsions is an attractive possibility for improving systemic inflammation in PN-dependent patients and optimizing management of PNALD. However, oils containing PFO were poorly tolerated and resulted in adverse end-organ sequelae. The presence of fat-laden macrophages in livers and spleens suggests attempts to clear physiologically incompatible fat molecules. Although PFO may meet pharmacopeia standards, it may not be safe for use in IV lipid emulsions, even when fatty acids in nontriglyceride form are present in small amounts.

Financial support: BASF, Boston Children’s Hospital Surgical Foundation, National Institutes of Health grant F32DK104525-01 (G.F.).

Nutrition and Metabolism Research Paper Session: Parenteral Nutrition

Abstract of Distinction

2369334—Failures of Fish Oil Therapy for Treatment of Parenteral Nutrition–Associated Liver Disease

Meredith A. Baker, MD1; Prathima Nandivada, MD2; Paul Mitchell, MSc3; Alison O’Loughlin, MEd1; Alexis K. Potemkin, RN, BSN1; Kathleen M. Gura, PharmD4; Gillian L. Fell, MD, PhD1; Lorenzo Anez-Bustillos, MD1; Duy T. Dao, MD1; Bennet S. Cho, BA1; Mark Puder, MD, PhD1 1Vascular Biology Program and Department of Surgery, Boston Children’s Hospital, Boston, MA, USA; 2Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA; 3Clinical Research Center, Biostatistics Core, Boston Children’s Hospital, Boston, MA, USA; 4Department of Pharmacy, Boston Children’s Hospital, Boston, MA, USA

Purpose: Parenteral fish oil (FO) therapy is a safe and effective treatment for parenteral nutrition–associated liver disease (PNALD), with successful resolution of cholestasis and avoidance of liver transplantation in 85% of infants. However, patients with PNALD who do not achieve resolution of cholestasis with parenteral FO therapy progress to end-stage liver disease requiring liver transplantation or resulting in death. The purpose of this study is to identify early patient factors associated with subsequent failure of parenteral FO therapy to guide prognostication and patient referral guidelines.

Methods: A retrospective review of prospectively collected data for children with PNALD treated with parenteral FO at Boston Children’s Hospital (BCH) between January 2004 and December 2014 was performed. PNALD was defined as a direct bilirubin (DB) >2 mg/dL. Resolution of cholestasis was defined as a sustained DB ≤2 mg/dL. Treatment failure was defined as undergoing liver or multivisceral transplantation or death while DB was >2 mg/dL as of July 31, 2015. Patient demographics, hospital transfer status, and laboratory values at initiation of therapy were compared between patients who achieved resolution of cholestasis with parenteral FO therapy and those who failed therapy. Comparisons are expressed as median (interquartile range [IQR]) and compared by Wilcoxon rank-sum test unless otherwise indicated.

Results: One hundred and eighty-eight patients with PNALD treated with parenteral FO at BCH were identified. Twelve patients were excluded because they transferred care or weaned off PN prior to resolution of cholestasis but did not fail FO therapy (ie, undergo transplant or die). Twenty-four patients (13.6%) failed therapy, with 8 of the children undergoing transplantation and 16 PNALD-associated deaths. Patients who failed therapy had lower birth


weight (1220 [731, 1800] vs 1760 [830, 2445] g, P = .03) and older age at FO therapy initiation (20.4 [10.4, 37.9] vs 11.7 [7.4, 24.0] weeks, P = .02) than patients whose cholestasis resolved. There was no significant difference in gestational age or age at starting PN between patients who responded to parenteral FO therapy and those who failed therapy. Patients who failed therapy had more advanced liver disease at the time of therapy initiation as evidenced by lower gamma-glutamyl transferase (54 [41, 98] vs 112 [76, 168] U/L, P < .0001), suggestive of a “burned out” liver. Moreover, patients who failed therapy had higher DB (10.4 [7.3, 15.4] vs 4.4 [3.1, 6.6] mg/dL, P < .0001), higher international normalized ratio (1.27 [1.16, 1.71] vs 1.12 [1.05, 1.21], P < .0001), lower platelet counts (67 [39, 104] vs 194 [131, 306] × 103/µL, P < .0001), and higher pediatric end-stage liver disease score (22.2 [17.0, 27.2] vs 14.1 [11.9, 17.5], P < .0001) at the time of FO therapy initiation than patients who did not fail therapy. A higher proportion of patients who transferred from outside hospitals failed parenteral FO therapy compared with patients who developed PNALD at BCH (20 of 114 [17.5%] vs 4 of 62 [6.5%], P = .04 by Pearson chi-square test).

Conclusions: Birth weight, age at FO therapy initiation, severity of biochemically measured liver disease at FO therapy initiation, and institutional transfer are factors that appear to impact resolution of cholestasis. These data suggest that liver disease progression at time of FO initiation may be a determinant of ultimate outcome, and they highlight the importance of early initiation of FO therapy once biochemical cholestasis is detected. Earlier referral of infants and children with PNALD at institutions without access to parenteral FO to centers where parenteral FO therapy is available may further improve response rates.

Financial support: None. A.S.P.E.N. Trainee Award

2371665—Aluminum Content in Parenteral Nutrition Negatively Affects Bile Acid Transporters

Amanda R. Hall, MD1; Gordon Zello, PhD2; Chris J. Arnold, MSc2; Jane Alcorn, DVMD, PhD2; Robert Bertolo, PhD3; Janet Brunton, PhD3; Grant G. Miller, MD1 1Surgery, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 2College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 3Biochemistry, Memorial University of Newfoundland, St John’s, Newfoundland, Canada

Purpose: Parenteral nutrition (PN) is an essential therapy available to hospitalized infants, but it is also hepatotoxic in cases of long-term exposure. The pathophysiology of PN-associated liver disease is unclear, although it is likely multifactorial. One contributing factor may be contaminants such as aluminum (Al). In this study, we assess the impact of Al contamination in PN to determine which bile acid transporters are affected and how they are altered, thereby gaining a better understanding of the disease pathophysiology. We hypothesize that Al in PN is capable of negatively affecting bile acid transporters, leading to cholestasis and eventual PN-associated liver disease.

Methods: This project was a randomized controlled trial using a newborn Yucatan miniature pig PN model. Fourteen piglets were placed into 2 groups of 7 animals each. The control group received standard PN, containing 38 μg/kg/d of Al. The treatment group received PN with a lower Al contamination (<2 μg/kg/d). After 3 weeks, the piglet livers were collected for analysis. We selected 4 bile acid transporters (Mrp2, Bsep, Ntcp, Oatp8), a stabilizer protein (radixin), and a nuclear receptor (FXR) as key components in the bile acid pathway. These targets were examined by real-time polymerase chain reaction (qPCR) to evaluate mRNA expression. Serum was collected to determine bile acid levels.

Results: qPCR for both apical transporters Mrp2 and Bsep showed fold differences of 1.8 (SD, 0.8) and 3.1 (SD 2.4), respectively, favoring the low Al vs the high Al group. The basal transporter Ntcp displayed a borderline fold difference of 1.4 (SD, 1.1) between the 2 groups, again with the low Al group being greater. qPCR for radixin did not show any significant difference between the groups, with a fold difference of 0.8 (SD, 0.2). Similarly, no significant difference in FXR mRNA levels (fold difference 1.0; SD, 0.4) or in Oatp8 levels (fold difference of 0.9; SD, 0.4) was apparent between the 2 groups. Serum bile acid levels between the 2 groups were also not significantly different (P = .07).

Conclusions: Al has a negative effect on the apical bile acid transporters Mrp2 and Bsep. If these transporters are downregulated, the hepatocyte is at higher risk of accumulating bile acids, potentially leading to cholestasis.

Financial support: Natural Sciences and Engineering Research Council; University of Saskatchewan, Department of Surgery; Children’s Hospital Foundation of Saskatchewan.


2372290—Impact of Intravenous Fat Emulsions on Risk of Bloodstream Infection in Patients Receiving Parenteral Nutrition Jennifer Isautier, APD1; Troy J. Cross, PhD1; Rizwan Sohail, MD2; Alan J. Wright, MD2; Erin M. Nystrom, PharmD3; Randy F. Wendt, BS4; John M. Miles, MD1 1Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA; 2Division of Infectious Diseases, Mayo Clinic, Rochester, MN, USA; 3Pharmacy, Mayo Clinic, Rochester, MN, USA; 4Information Technology, Mayo Clinic, Rochester, MN, USA Purpose: Whether intravenous fat emulsions (IVFEs) increase the risk of bloodstream infection (BSI) in patients receiving parenteral nutrition (PN) is controversial. The primary aim of this study was to investigate the effect of IVFE use on the risk of developing BSI during PN. A secondary aim was to assess whether a relationship exists between blood triglycerides and blood glucose on the risk of developing BSI.

Methods: We conducted a retrospective analysis of hospitalized patients who received PN from 2000 through 2014 in 2 large tertiary care hospitals (total beds = 2059). The primary outcome was the development of any BSI beginning 48 hours after initiation of PN and up to 48 hours after PN cessation. Patients were categorized into 2 groups: (1) those receiving IVFE for <50% of days (low lipid group) and (2) patients receiving IVFE for >50% of the time (high lipid group). Cox Proportional Hazards regression was used to examine differences in the incidence of BSI between these 2 groups after adjusting for patient age, body mass index, and sex. A subanalysis was performed to investigate the influence of blood triglycerides and glucose concentrations on the risk of developing BSI.

Results: A total of 14,998 patients received PN during the 15-year period of observation. The low lipid group (n = 963) received IVFE on 21 ± 1% of PN days, whereas the high lipid group (n=14,035) received IVFE on 94±1% of PN days. Patients in the low lipid group were younger (56±0.5 vs 60±0.1 years, p<0.001), had higher BMIs (27.9±0.2 vs 27.0±0.1 kg/m2, p<0.01) and received fewer PN calories (1188 ±10.9 vs 1485±2.6 kcal/day, p<0.001) than individuals in the high lipid group. Duration of PN administration was similar in the 2 groups (9.4± 0.4 days vs 9.0± 0.1 days, p = NS). The high lipid group had a higher occurrence of BSI than patients who received IVFE for <50% of the time, (p = 0.014), with absolute BSI incidence of 3.6% vs 2.2% in the respective groups. A subanalysis was performed on 3318 patients in whom both triglyceride and glucose concentrations were available. The low lipid group had higher triglyceride levels (268±10.9 vs 151±1.3 mg/dl, p<0.001), but glucose concentrations were similar between groups (135±0.4 vs 136±1.4 mg/dl, p = NS). In this subanalysis, there was no significant difference between the low lipid and high lipid groups in the incidence of BSI (3.2% vs 4.1%, respectively, p = NS); furthermore, the amount of time spent on IVFE did not predict risk of infection (p = NS). However, when adjusted for blood triglyceride and glucose concentrations, triglyceride concentrations were significantly associated with an increased risk of BSI (HR 1.002 per mg/dl, 95% CI 1.001–1.003, p <0.001). Thus, the risk of developing a BSI was 20% higher for every 100 mg/dl increase in triglycerides. Interestingly, women were 39% less likely to develop a BSI during PN than men (HR 0.61: 95% CI 0.427–0.872, p <0.01).

Conclusions: Our findings suggest that the risk of BSI during PN is increased when IVFEs are a near-daily component of PN, compared to when fat-free PN is given on most days. The subanalysis suggests that the BSI risk associated with PN use may more specifically relate to the patient’s triglyceride level rather than to IVFE use per se. A limitation of this study, due to its retrospective nature, is that not all patients receiving PN had a triglyceride measurement. Future studies should prospectively explore the relationship between triglyceride concentrations during PN and the effect of IVFE infusion on the risk of developing BSI. Financial support: Mayo Foundation.

2370073—Impact of Intravenous Omega-3 Fatty Acids on Hepatic Function in Advanced Oncology Patients on Home Parenteral Nutrition: A Prospective Consecutive Case Series Pankaj Vashi, MD1; Digant Gupta, MD, MPH1; Kim Gorsuch, RN1; Sadie Dahlk, MS, RD, CNSC1; Carolyn Lammersfeld, MS, RD, CNSC1 1Gastroenterology/Nutrition, Cancer Treatment Centers of America, Zion, IL, USA Purpose: Hepatic dysfunction is a known complication of (and a limiting factor for) long-term home parenteral nutrition (HPN) and affects 15–40% of adults and 40–60% of infants and neonates. Presence of Omega-6 (n-6) fatty acids in parenteral nutrition (PN) has been implicated as one factor that causes this dysfunction by promoting


steatohepatitis. Unfortunately, n-6 from soybean oil is the primary source of intravenous (IV) lipid in US. The clinical spectrum of hepatic dysfunction associated with PN ranges from steatosis, cholestasis, gallbladder stones, fibrosis and cirrhosis with significant overlap. Omega-3 (n-3) fatty acids have been shown to reverse this process in animal models and children, however, their impact on reversing hepatic dysfunction in adult oncology patients receiving HPN has not yet been studied. This study investigated whether IV n-3 fatty acids can improve parenteral nutrition induced hepatic injury in advanced cancer patients undergoing HPN.

Methods: A prospective compassionate use study under an IND was IRB approved for use in patients who developed parenteral nutrition induced hepatic injury. A mid-point analysis was conducted on a consecutive case series of 12 advanced cancer patients who received IV n-3 fatty acids for 4 weeks while undergoing HPN between June 2011 and July 2015. All patients had normal liver enzymes [alkaline phosphatase (ALKP), aspartate aminotransferase (AST), alanine transaminase (ALT)] before the start of HPN. The key inclusion criterion was an elevation of any one or more of the 3 liver enzymes (defined as a value at least 3 times the upper limit of normal range), not related to any other cause but HPN. All patients received IV n-3 fatty acids at the dose of 0.1 mg/kg on day one and 0.2 mg/kg from day 2 to day 30. The liver enzymes were monitored at day 1, 2, and 3 and then weekly from week 1 to week 4. Weekly clinical evaluation was done for any adverse effects of IV n-3 fatty acids. The non-parametric Wilcoxon signed-rank test was used to compare the baseline and 4-week levels of liver enzymes. All analyses were two-tailed, and a difference was considered to be statistically significant if the p value was ≤0.05.

Results: Of 12 patients, 3 were males and 9 females. The median age at the start of study was 58 years (range 32–64 years). Three patients were well-nourished, 7 moderately malnourished, and 2 severely malnourished. The cancer types were ovarian (n=6), colorectal (n=4), pancreas (n=1), and primary peritoneal (n=1). One patient expired from her primary cancer within 4 weeks of starting treatment with n-3 fatty acids and was not available for the 4-week assessment. Table 1 displays the change in mean levels of liver enzymes from baseline to week 4 for 11 patients. All liver enzymes showed a decline (improvement) at week 4 compared to the baseline levels (Wilcoxon signed rank test p value > 0.05 for all). The decline in ALKP levels reached marginal statistical significance (p = 0.07) despite such a small size. There were no adverse events related to n-3 fatty acid administration.

Conclusions: We present a small case series of patients with advanced cancer who showed clinical improvement in HPN-induced elevation of liver enzymes with the use of IV n-3 fatty acids for 4 weeks. The use of IV n-3 fatty acids, made it possible to meet the total calorie needs of our patients and continue HPN. While improvement in liver function did not reach statistical significance due to a small sample size, the clinical benefits of IV n-3 fatty acids without any adverse events in these patients look promising and worthy of future investigation using large prospective studies. Financial support: None.

Table 1. Change in Liver Enzymes From Baseline to 4 Weeks (n = 11).

Liver Enzyme Mean (Baseline)

Mean (4-Week)

Wilcoxon Test P value

ALKP 457.6 360.4 0.07 AST 88.7 69.9 0.53 ALT 133.6 101.4 0.48

The means are presented in the above table just to give an indication of how the scores changed over time. Please note that mean is the not the statistic generated by a Wilcoxon signed rank test. Mean is just more intuitive to understand, which is why it is reported in the table above.


2371194—Parenteral Nutrition Is Associated With a Decrease in Autophagy Leading to Decreased Epithelial Barrier Function Emma M. Tillman, PharmD, PhD1; Peihong Guan, BS1; Merrion G. Buckley, BS1; Daniel Teitelbaum, MD2; Radhakrishna K. Rao, PhD3 1Clinical Pharmacy, The University of Tennessee, Memphis, TN, USA; 2Pediatric Surgery, The University of Michigan, Ann Arbor, MI, USA; 3Physiology, The University of Tennessee Health Science Center, Memphis, TN, USA Purpose: The cellular process of autophagy is a defense mechanism utilized by many mammalian cell types to maintain homeostasis in response to stress. Starvation is a major cell stressor and is known to induce autophagy. However, the role of autophagy in loss of intestinal epithelial barrier function (EBF) associated with total parenteral nutrition (TPN) has not been well-defined. We hypothesize that autophagy is a key regulator of EBF homeostasis and when the intestinal epithelial cells are locally starved (lack of enteral nutrition) and TPN is administered, this defense pathway is unable to keep-up leading to barrier dysfunction. This may well contribute complications such as intestinal failure associated liver disease (IFALD) and central line associated blood stream infections (CLABSI). The objective of this study is to evaluate the role of autophagy in maintaining EBF homeostasis in the face of TPN and intestinal epithelial cell (IEC) starvation.

Methods: Two-month-old C57BL/6J mice had central venous catheter (CVC) placed into the superior vena cava and connected to a saline infusion. After 12 hours, mice randomized to two groups: (1) receiving standard chow also receive water ad libitum as well as saline infusion (5 mL/24 h) or (2) receiving TPN solution (7 mL/24 h). Mucosal permeability was evaluated by jejunal strips mounted to Using chambers and autophagy was evaluated by isolating protein from mucosal scrapings and immunoblotting for LC3-II and normalized to GAPDH. To further evaluate the role of autophagy in EBF, Caco-2 cells were grown on polycarbonate membranes in transwell inserts for 14 days. On day 1–13, cells were incubated with standard complete growth medium. On day 13, cells were treated with either standard complete medium (control) or Hank’s balanced salt solution (HBSS) (starvation). Paracellular permeability was evaluated from 1–7 hours by measuring unidirectional flux of FITC-inulin and transepithelial electrical resistance (TER). Concentrations of LC3 in Caco-2 cells were also measured by western blot. Additionally, EBF was evaluated in control and starvation conditions with and without the presence of the autophagy inhibitor bafilomycin.

Results: Intestinal permeability measured by TER (Ω.cm2) in control mice small intestine was 87.1 ± 6.8 (Ω.cm2), and TER was significantly decreased (p < .05) in mice receiving TPN 52.1 ± 5.3 (Ω.cm2). Additionally, concentrations of LC3-II were significantly decreased in mice that received TPN (p < .05). In the in vitro model, TER was decreased significantly in starved cells vs controls and ranged from 23% to 40% reduction across all time points (p < 0.05). Flux of FITC-inulin in starved cells increased by 400%, 700%, and 1000% at 1, 2, and 3 hours, respectively, as compared to control cells (p<0.05). These effects of starvation on both FITC-inulin flux and TER were attenuated by bafilomycin.

Conclusions: Intestinal EBF was decreased in both in vivo and in vitro models of TPN. Concentrations of the autophagy protein LC3-II was decreased after prolonged TPN or cellular starvation, which suggests that autophagy is a compensatory mechanism to maintain EBF in the normal fed intestine. Without enteral nutrition and nutrient provision by TPN, this mechanism is exhausted. This leads to disruption of EBF resulting in transit of luminal toxins from the intestine, which could lead to complication such as IFALD and CLABSI. Financial support: The University of Tennessee Health Science Center, College of Pharmacy.



2366160—Disaster Preparedness in Families With Parenteral Nutrition–Dependent Children: Can We Make a Difference?

Khadija T. Toor, MD1; Natalie Demeter, MPH2; Rita V. Burke, PhD, MPH2,3; Jeffrey S. Upperman, MD2,3; Russell J. Merritt, MD, PhD1,3; Catherine J. Goodhue, MN, RN, CPNP-PC2 1Pediatric Gastroenterology, Children’s Hospital Los Angeles, Los Angeles, CA, USA; 2Pediatric Surgery, Children’s Hospital Los Angeles, Los Angeles, CA, USA; 3Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA

Purpose: To improve disaster preparedness of families with parenteral nutrition (PN)–dependent children with education and distribution of a personalized disaster survival tool kit. Approximately 14.6 million children in the United States have special healthcare needs. Chronic conditions increase the risk of adverse outcomes following a disaster. Condition-specific disaster plans may limit the negative health outcomes of children with special healthcare needs. Families remain unprepared for a disaster in spite of significant special healthcare needs and concern about disasters. The American Academy of Pediatrics recommends a completed emergency information form (EIF) be provided to families with a summary of pertinent medical information and any special healthcare needs that their children have. Periods of normalcy are the best time to develop disaster preparedness plans. At Children’s Hospital Los Angeles, we care for many families with children receiving PN to maintain their hydration and nutrition. Power outages or lack of transportation after a disaster like an earthquake may have serious consequences for this vulnerable patient population.

Methods: After Institutional Review Board approval, families of PN-dependent children were approached during their intestinal rehabilitation clinic visit and agreed to participate. At the same clinic visit, we conducted a 5-question baseline survey and then distributed a personalized disaster toolkit. The same survey was conducted over the telephone at 2- and 4-month intervals. Unique identifiers were used to match baseline, 2-month, and 4-month follow-up survey results. The individualized disaster toolkit included (1) 4 D-cell batteries for use in PN pumps, (2) 150-W power inverter, (3) waterproof flash drive/USB preloaded with pertinent documents, and (4) physical paper documents including medical summary, list of medications, EIF, and supply lists.

Results: Thirty-four families agreed to participate in our study. Please review Tables 1 and 2 for results. At baseline, 68% of families did not have a family emergency plan, and 47% lacked a basic emergency supply kit. Ninety-one percent of families lacked a completed EIF. While all families had extra batteries at home for the PN pump, only 18% had backup generators. Median confidence level was 5 on a scale of 1–10. At the 2-month survey, 65% of families had a family emergency plan, and 76% had a basic emergency supply kit. Twenty-four percent of families had backup generators. Fifty-percent of families had a complete EIF. The median confidence level was 7. At the 4-month survey, 88% of families reported having a family emergency plan, and 91% had a basic emergency supply kit. Thirty-two percent of families had backup generators. Eighty-eight percent of families had a completed EIF with the help of their pediatricians. The median confidence level was 8.

Conclusions: In general, families with PN-dependent children did not feel prepared for a disaster. With individual disaster teaching, our PN families increased their home disaster preparations. We will continue to work toward refining the disaster survival toolkit, as it has effectively shown to improve the confidence level of the families. Our long-term goal is to standardize the disaster survival tool kits and establish preparedness guidelines.

Financial support: NAPNAP Foundation grant was awarded to C.J.G.


Table 1. Survey Results (in Percentages).

Questions Baseline 2 mo 4 mo

Yes No Yes No Yes No

Have you developed your family emergency plan? 32 68 65 35 88 12

Do you have a basic emergency supply kit? 53 47 76 24 91 9

Do you have a plan/supplies for an alternative power

source for your child’s infusion pump?

18 82 24 76 32 68

Do you have a completed emergency information form

from your child’s provider?

9 91 50 50 88 12

Table 2. Confidence Levels per Survey.

Confidence Level Baseline 2 mo 4 mo

Median 5 7 8

Nutrition and Metabolism Research Paper Session: Enteral Nutrition

2370598—Blenderized Enteral Nutrition Diet Study: Effects of a Blenderized Diet Provided Through a Gastrostomy Tube on Oral Intake and Gastrointestinal Symptoms Kelsey Gallagher, RD1,3; Marialena Mouzaki, MD, MSc3,2; Andrea Carpenter, RD1,2; Beth Haliburton, RD1,2; Louise Bannister, RD1,2; Holly Norgrove, RN4,3; Lisa Hoffman, OT5,3; Peggy Marcon, MD3,2 1Clinical Dietetics, The Hosptial for Sick Children, Toronto, Canada; 3Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada; 2Pediatrics, The Hospital for Sick Children, Toronto, Canada; 4Nursing, The Hospital for Sick Children, Toronto, Canada; 5Rehabilitation Services, The Hospital for Sick Children, Toronto, Canada Purpose: Increasing numbers of caregivers are looking to blenderized feeds as an alternative to commercial formula in children fed via gastrostomy tubes (G-tubes). Limited evidence suggests that blended feeds are better tolerated. The aim of this study was to address the impact of the BLenderized Enteral Nutrition Diet (BLEND) on gastrointestinal (GI) symptoms, progression to oral intake, and parental perception of G-tube feeds.

Methods: The BLEND study examines the feasibility of transitioning medically stable G-tube dependent children, receiving <25% caloric intake by mouth, from commercial formula to BLEND feeds over a 6-month period. Parents were given questionnaires at enrolment and 6 months to assess their overall satisfaction with feeding regimen; perception of GI symptoms; stool frequency and consistency (using Bristol Stool Scale); and their child’s oro-motor skills. Patients were followed by their primary care teams throughout the study and decisions regarding medical management were made irrespective of the study.

Results: Thirteen participants completed the BLEND study with a mean age of 3.6±2.1 years (female =9, male =4). Participants had complex medical histories and 92% had developmental delays. BMI z scores remained appropriate from enrolment to study exit (0.12 vs –0.32; p=0.054). On BLEND, prevalence of vomiting decreased from 69 to 46% (p=0.026) and gagging/retching from 77 to 54% (p=0.033). The majority of patients required antacids and promotility agents throughout the study, but antacid use decreased from 92% to 85% (p = 0.015) and promotility agent use increased from 54% to 62% (p=0.002). Stool softener/laxative use was 31% throughout the study. The frequency and consistency of bowel movements did not change significantly (p=0.107 & p=0.155). Overall, 23% of participants were unsafe on all textures by mouth. Despite this, BLEND was associated with an increased prevalence of oral feeding, with 54% of participants eating nothing by mouth at enrolment compared to 31% at study exit (p=0.026). A total of 54% of participants received ongoing oral therapy. Parental perception of feeding discomfort (measured using a 10 point Likert scale; 10=severe discomfort) improved from 5 to 1.8 (p=0.009) and overall satisfaction with tube feeding (10=extremely satisfied) improved from 5.4 to 9 (p=0.001).


Conclusions: BLEND was associated with a decreased prevalence of gagging/retching and vomiting and an increase in the prevalence of oral feeding. Despite this, the majority of participants still require antacids and promotility agents throughout the study. Bowel movement consistency and frequency did not significantly change with BLEND. Parental satisfaction with BLEND was superior to commercial formulas. Financial support: John Garfield Campbell Fund (Donations for GI Motility Research) account at the HSC Foundation and donation of blenders by Vita-Mix Corporation.

2371063—Slow Rate of Feeding Advancement After Early Initiation of Enteral Nutrition Might Be Associated With Reduced Requirement for Mechanical Ventilation at Hospital Discharge in Critically Ill, Underweight Patients Satomi Ichimaru, MS, RD, CNSC1; Maren Sono, MD2; Hidetoshi Fujiwara, PhC3; Ryutaro Seo, MD2; Koichi Ariyoshi, MD, PhD2; Teruyoshi Amagai, MD, PhD4 1Food Sciences and Nutrition Major, Graduate School of Human Environmental Sciences, Mukogawa Women’s University, Nishinomiya, Japan; 2Department of Emergency Medicine, Kobe City Medical Center General Hospital, Kobe, Japan; 3Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan; 4Department of Food Science and Nutrition, School of Human Environmental Sciences, Mukogawa Women’s University, Nishinomiya, Japan Purpose: Enteral nutrition (EN) is the preferred route for nutritional support in critically ill patients. Current clinical guidelines recommend that EN be initiated within 24 to 48 hours of admission. However, the optimal rate of feeding advancement after initiation of early EN (EEN) remains unclear. The aim of this study was to examine the impact of feeding advancement rate after the initiation of EEN on the mortality and morbidity of critically ill, underweight patients.

Methods: A retrospective chart review was conducted in an 8-bed emergency intensive care unit (EICU) of a tertiary teaching hospital. Consecutive patients admitted to the EICU from August 2011 to July 2014 were screened for eligibility. Critically ill adult patients with a BMI of <20.0 kg/m2 who were mechanically ventilated and initiated EN within the first 48 hours of admission and who stayed in the EICU for ≥72 hours were enrolled. An energy target of 25 kcal/kg/day was set as the energy requirement of the majority of critically ill patients. Patients were categorized into a rapid advancement group (Group R), which reached the energy target within 3 days of EEN initiation, or a slow advancement group (Group S), which reached the energy target 4 or more days after EEN initiation.

Results: Of the 1993 patients assessed for eligibility, 65 met the inclusion criteria and were enrolled. Demographics did not significantly differ between the two groups. Median patient age was 72.8 years and median BMI was 17.8 kg/m2. APACHE II score did not significantly differ between groups. Initial SOFA score was higher in Group R than in Group S (10 [9–13] vs. 9 [8–10]; P = .029). Median days to reach target energy intake from EEN initiation was 2 days in Group R and 5 days in Group S (Table 1). No significant differences were noted between the two groups for all-cause mortality, ICU-free days, or hospital-free days (Table 2). Further, no significant differences were noted in antibiotic-free days, serum level of CRP, development of pneumonia, incidence of liver or renal dysfunction, or glycemic control, or in the development of hypophosphatemia, lowest serum phosphorus (P) concentrations, or dose of P to treat hypophosphatemia. Ventilator-free days (VFDs) were significantly fewer in Group R than in Group S (18.0 [0.0–22.0] vs. 21.0 [16.3–24.8] days; P =.046), and the number of patients requiring mechanical ventilation (MV) at hospital discharge was significantly higher in group R than in S (29% vs. 2%; P=0.030) (Table 2). Multivariable analyses to adjust for confounders identified days required to reach target energy intake after EEN initiation as a significant factor independently associated with the requirement for MV at hospital discharge (Adjusted OR = 0.467, 95% CI = 0.245–0.889), but not with VFDs.

Conclusions: A slow rate of feeding advancement after initiation of EEN in critically ill patients with a BMI of <20.0 kg/m2 might be associated with a reduced requirement for MV at hospital discharge. These results should be confirmed in a large multicenter trial enrolling underweight, critically ill patients. Financial support: None.


Table 1. Demographics, Clinical Characteristics, and Nutritional Characteristics

Characteristic Group R Group S P

value n=41 n=24 Demographic

Age, years; median (IQR) 72.8 (64.1-83.0)

73.6 (61.9-81.0) .563

Sex .135 Female, n (%) 22 (54) 17 (71) Male, n (%) 19 (46) 7 (29)

BMI, kg/m2; median (IQR) 18.2 (16.4-19.2)

17.7 (16.1-19.1) .634

Clinical characteristic

APACHE II score (IQR) 21.0 (18.5-31.5)

22.0 (19.0-27.5) .563

Initial SOFA score (IQR) 10.0 (9.0-13.0) 9.0 (8.0-10.0) .029

Primary EICU diagnosis, n (%) .052 Cardiovascular or vascular disorder 6 (15) 1 (4) Respiratory disorder 7 (17) 3 (13) Gastrointestinal disorder 0 (0) 0 (0) Neurologic disorder 18 (44) 15 (63) Sepsis 6 (15) 0 (0) Trauma 0 (0) 3 (13) Metabolic disorder 2 (5) 2 (8) Burn 1 (2) 0 (0) Renal disorder 1 (2) 0 (0) Nutritional characteristic

Time to initiation of EEN from EICU admission, h; median (IQR) 14.5 (4.7-21.9)

24.7 (12.6-36.4) .010

Days to reach target energy intake from EEN initiation, day; median (IQR) 2.0 (2.0-3.0) 5.0 (4.0-7.0) <.001

EICU, emergency intensive care unit; EEN, early enteral nutrition; IQR, interquartile range. Data were provided as median and interquartile range for continuous variables and as number and percentage for categorical variables. Mann-Whitney U test was used for continuous data and Fisher’s exact test for categorical data.


Table 2. Clinical Outcomes

Outcome Group R Group S

P value n=41 n=24

All-cause mortality In EICU, n (%) 0 (0) 0 (0) 1.000 In hospital, n (%) 3 (7) 0 (0) .244 Length of stay ICU-free days, days; median (IQR) 19.0 (13.5-22.0) 20.5 (15.3-23.0) .309 Hospital-free days, days; median (IQR) 0 (0-0) 0 (0-0) .423 Mechanical ventilation Mechanical ventilation-free days, days; median (IQR) 18.0 (0.0-22.0) 21.0 (16.3-24.8) .046

Requirement for mechanical ventilation at hospital discharge, n (%) 12 (29) 2 (8) .030

Tracheostomy, n (%) In EICU 18 (44) 12 (50) .448 In hospital 26 (63) 17 (71) .422 Pneumonia Clinical diagnosis of pneumonia, n (%) 16 (39) 9 (38) .559 Development of VAP, n (%) 1 (2) 0 (0) .631

EEN, early enteral nutrition; EICU, emergency intensive care unit; IQR, interquartile range; ventilator associated pneumonia. Data presented as median and interquartile range for continuous variables and as number and percentage for categorical variables. Mann-Whitney U test was used for continuous data and Fisher’s exact test for categorical data.

2366298—Effectiveness of 5 Methods to Clear 4 Types of Occlusions in 10 French Feeding Tubes Marcia Brackbill, PharmD, BCPS1; Allyson Hunt, PharmD1; Jennifer Carter, RD2; Jeffery W. Spray, PharmD, MHA, BCPS3; David Newton, BSPharm, PhD4 1Department of Pharmacy Practice, Shenandoah University, Winchester, VA, USA; 2Department of Nutrition Therapy, Winchester Medical Center, Winchester, VA, USA; 3Department of Pharmacy, Winchester Medical Center, Winchester, VA, USA; 4Department of Biopharmaceutical Sciences, Shenandoah University, Winchester, VA, USA Purpose: An obstruction in a patient’s enteral tube can occur for a number of reasons, including improper flushing before or after administration of medications or enteral formula. When such problems arise, patients cannot receive essential nutrition or medications. Furthermore, if tubes are unable to be cleared, they may require replacement, which is both costly and uncomfortable. A number of methods have been proposed in the literature to resolve these obstructions. Traditional methods, with varying results and appropriateness, include flushes with water, juice, carbonated sodas and pancreatic enzymes. The American Society for Parenteral and Enteral Nutrition endorses water flushes. Newer tube clearing methods include food grade enzyme powders and mechanical devices that directly fracture and dislodge occlusions. We compared the efficacy of traditional and newer de-occlusion interventions for clearing occluded tubes in models created to simulate those encountered in the clinical setting.

Methods: This in-vitro study was conducted in two phases. Phase I involved the development of reproducible occluded 10 French small bore feeding tubes. The following types of enteral tube occlusions were developed. Model 1: occlusion using standard enteral tube feeding formula. Model 2: occlusion using standard enteral tube feeding formula and protein powder. Model 3: occlusion using medication (calcium carbonate tablet). Model 4: combination occlusion using enteral tube feeding and medication. Phase I was concluded and considered successful once reproducible occlusions of each model were created that were able to withstand aspiration with a 60 mL syringe followed by manual pressure with a 30 mL syringe filled with 10 mL of warm water. In Phase II of the study, each occlusion model was tested in triplicate with 5 different types of de-occlusion methods. The 5 de-occlusion methods


tested were flushes with water, carbonated soda (lemon citrus), fluid pancreatic enzyme, fluid enzymatic food grade powder, and a mechanical device. If the first attempt to clear each occlusion was not successful, then the method was repeated up to 3 times per product guidelines.

Results: In Phase I, four reproducible occlusion models were successfully created. In Phase II, results are presented for each of the following occlusion models. Model 1 (enteral formula occlusion): water, 0 of 3 tubes were cleared; carbonated soda, 2 of 3 tubes cleared; and 3 of 3 tubes were cleared using pancreatic enzyme, food grade enzymatic powder, and the mechanical clearing system. Model 2 (enteral formula plus protein occlusion): water, 0 of 3 tubes cleared; carbonated soda, 1 of 3 tubes cleared; and 3 of 3 tubes cleared using pancreatic enzyme, food grade enzymatic powder, and the mechanical clearing system. Model 3 (medication occlusion): 2 of 3 tubes cleared with water and soda, and 3 of 3 tubes cleared using pancreatic enzyme, food grade enzymatic powder, and the mechanical clearing system. Model 4 (enteral formula plus medication occlusion): 0 of 3 tubes cleared with water and carbonated soda, 1 of 3 tubes cleared with pancreatic enzyme, and 3 of 3 tubes cleared with food grade enzymatic powder and the mechanical clearing system.

Conclusions: Four in-vitro enteral feeding tube occlusion models were created, which served as simulation models for different types of enteral tube occlusions clinicians may encounter in patient care. Using these models, 5 different types of de-occlusion interventions commonly used in the hospital setting were tested. Food grade enzymatic therapies and mechanical de-occlusion interventions proved to be the most successful interventions for restoring tube patency.

Financial support: CORPAK MedSystems and Actuated Medical, Inc.

International Abstract of Distinction

2372067—Effect of Protein Type in Enteral Nutrition Formulas on Coagulation in the Stomach In Vivo: Post Hoc Analyses of a Randomized Controlled Trial With MRI

Marianne Klebach, MSc1; Zandrie Hofman, MSc1; Sena Bluemel, MD2; Jelena Curcic, PhD3; Andreas Steingoetter, PhD3 1Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, Netherlands; 2Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland; 3Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland

Purpose: Delayed gastric emptying is common in tube-fed patients. It is related to upper gastrointestinal complications, such as reflux and aspiration pneumonia, and reduced nutrition intake. Different types of protein have different gastric emptying times considered to be due to differences in coagulation of proteins in the stomach. In vitro digestion experiments have visualized the differences in coagulation, but no data are available in vivo. The current post hoc study investigated whether enteral formulas with different types of protein differ in coagulation in the human stomach as was previously demonstrated in vitro.

Methods: In a double-blind randomized 3-way crossover study in 21 healthy volunteers, 3 isocaloric (450 kcal) and isovolumetric (300 mL) enteral formulas—1 with a blend of 4 proteins (P4™: whey, casein, soy, and pea) and 2 with casein-dominant protein blends (C1 and C2)—showed different gastric emptying rates (P4 > C1 and C2). In this post hoc analysis, coagulation in the stomach was investigated by visual inspection of the homogeneity in MR signal intensity. Intragastric MR signal inhomogeneity—that is, the presence of varying contrasts (dark and light spots) in the stomach—was used as a surrogate marker for coagulation. Signal inhomogeneity at 50, 65, and 80 minutes was rated by 3 persons unaware of the product sequence. Pairwise comparisons among the 3 products were performed with a McNemar test.

Results: For P4, C1, and C2, inhomogeneity was scored “yes” in, respectively, 10%, 89%, and 80% of the MRI scans (P4 vs C1, P = .0003; P4 vs C2, P = .0005; and C1 vs C2, P = .688). “No” was scored for 43%, 0%, and 10%, and “uncertain” was scored for 48%, 11%, and 10%. See Figure 1.

Conclusions: The visual inspection of MR signal inhomogeneity in the stomach after intake of 3 protein-based enteral formulas indicated a lower degree of intragastric coagulation with the P4 protein blend as compared with casein-dominant enteral formulas. These results match with the differences in gastric emptying rate, validate in vitro findings, and support possible clinical benefits for tube-fed patients with gastrointestinal intolerance.

Financial support: The study was sponsored by Nutricia Research BV, Utrecht, Netherlands.


Figure 1. Representative MRI outlining the stomach at time point 80 minutes after administration of the P4, C1, and C2 formulae, respectively.

2366746—Assessment of Nutrition Education Among PGY1 Pharmacy Residency Programs Divya M. Daniel, PharmD1; Karrie Derenski, PharmD, BCNSP, CNSC1 1Pharmacy, CoxHealth, Springfield, MO, USA Purpose: Pharmacists have an important function in the care of patients receiving nutrition support (NS). The goal of the American Society of Health System Pharmacists (ASHP) post graduate year one (PGY1) residency program is to provide new or existing pharmacists with the training to become competent health care providers. We designed a survey to determine both the presence and magnitude of nutritional support training programs within the healthcare environment and the availability of ASHP accredited programs allowing for PGY1 residents to either receive on-site training or to pursue specialized training in NS.

Methods: The survey was created as a pdf file as well as an online document, using google docs, and was emailed out to the programs (see Figure 1). Selection of the institutions assessed was accomplished using the ASHP residency directory. Goals of the survey were to measure whether or not an institution provides residents with a nutritional/metabolic rotation and, based on the response, the survey was sub-divided into questions further assessing the program. Responses from the survey were declassified and respondents were kept anonymous.

Results: This survey was e-mailed a total of 895 residency program directors, and a total of 224(25%) responded to the survey. Out of the total responses, 90 hospitals (40%) offered a nutrition rotation: mandatory rotation in 38 hospitals (42%), an elective in 45 hospitals (50%), and as a longitudinal rotation in 7 hospitals (8%). When the NS rotations were offered as an elective, 100% of residents had alternative opportunities to work with NS in other rotations. Exposure to NS included compounding, electrolyte management, assessment of patient's nutritional requirements, assessment of patients’ requirements for receiving specialized NS, and ordering parenteral or enteral nutrition. Primary rotation preceptors were mostly board certified nutrition support pharmacists (BCNSP), 48 out of the 77 responses (62%). Other preceptors included dietitians, critical care trained pharmacists, general residency trained pharmacists, and pharmacists with clinical nutrition work experience. 112 hospitals responded that a multi-disciplinary nutrition support team existed in some capacity. Pharmacist involvement with metabolic teams was 93%, with 33 hospitals (29%) sometimes having a pharmacist on the team, and 71 hospitals (63%) always having a pharmacist on the team.

Conclusions: Results from this survey show multiple areas of improvement for current nutrition education among PGY1 pharmacy residency programs; 40% of the hospitals had a NS education offered and all lacked a standardized curriculum. Furthermore, with the survey response totaling 25%, there could be some preferential bias with respect to the responses given by hospitals having a NS team or rotation. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) has stated the function of a nutrition trained pharmacist to include compounding parenteral nutrition, management of teams, research, and educating other health care professionals. Furthermore, PN is considered a highly complex medication with the potential to cause harm and even death from medication error by both the institution of safe medication practices (ISMP) and A.S.P.E.N. The PN guidelines recommend NS education for practioners to improve PN ordering and reduce errors. The A.S.P.E.N. PN guideline recommendations can be incorporated as part of standardized NS education in the PGY1 curriculum. Financial support: None.


Figure 1. Survey questions for residency directors. Institution Maximum Patient Capacity (Approximate)

Number of Pharmacists (Approximate) Number of Pharmacy Residents (Approximate)

Does your institution have a multi-disciplinary nutrition/metabolic support team? Yes / No

If yes to the above questions:

If yes, 1) Is a BCNSP/CNSC pharmacist on staff? Yes / No

a. If yes, how many? Are any members of the nutrition/metabolic support team pharmacists? Yes / No

Does your institution offer a nutrition/metabolic rotation? Yes / No

If yes to the above questions:

1) Is this a required rotation? Yes / No 2) What is the duration of this rotation and how many hours of nutrition service are

requisite? 3) If the rotation is not required, are residents offered other opportunities to work with TPN

or tube-feed orders? Yes / No a. If yes, please describe these opportunities.

4) Do the rotation preceptors have a nutrition and/or critical-care PGY2 background? Yes / No

a. If yes, is their background in nutrition, critical-care or both? (Please circle one) 5) Are pharmacists routinely part of the nutrition/metabolic support team? Yes / No

a. If not, what is the background of the person that manages the nutrition/metabolic support team?

6) Are the PGY-1 residents offered a longitudinal experience in nutrition/metabolic support? Yes/No

7) Please check all Nutrition/Metabolic experiences the PGY-1 resident is exposed: a. Compounding UPS practice:

b. Electrolyte management c. Ordering electrolyte boluses

d. Assess patient for parenteral and/or enteral nutrition e. Assess patient’s nutritional requirements

f. Ordering parenteral nutrition patient orders g. Management patient’s parenteral nutrition h. Ordering enteral nutrition patient orders

i. Manage patient’s enteral nutrition

If no to the above questions:

1) Does your hospital have a nutrition/metabolic support staff? Yes / No 2) Are pharmacy residents offered the opportunity to take a metabolic/nutrition rotation at a

different institution? Yes / No 3) Does your institution provide other opportunities that allow pharmacy residents to work

with TPN and/or tube-feed orders? Yes / No 2370153—Influences of Ad Libitum and Isocaloric Feeding of Low Carbohydrate-High Fat Diet on Survival After Gut Ischemia Reperfusion in Mice Tomoki Watanabe, MD1,2; Kazuhiko Fukatsu, MD2; Satoshi Murakoshi, MD2; Tomoyuki Moriya, MD1; Junji Yamamoto, MD1; Kazuo Hase, MD1; Hiroshi Yasuhara, MD2 1Surgery, National Defense Medical College, Tokorozawa city, Japan; 2Surgical Center, The University of Tokyo, Tokyo, Japan Purpose: Low carbohydrate-high fat diets (LCHFDs) are expected to reduce the morbidity of metabolic syndrome. However, whether LCHFDs are also beneficial for host response to surgical insults is controversial. We previously reported that 5-day intragastric feeding of TPN solution with a high fat composition does not affect survival after gut


ischemia reperfusion (I/R) in mice. Herein, to examine the influences of LCHFD feeding for a longer period on outcomes after gut I/R, we performed 2 sets of experiments using ad libitum and isocaloric feeding models.

Methods: (Ad Lib Study) Six-week-old male ICR mice (n=29) were randomized to a normal diet group (NF-AD; 16.4% calories from fat, 18.8% from amino acids, 65.1% from carbohydrate) (n=15) or a LCHFD group (LCHFD-AD; 62.2% calories from fat, 18.2% from amino acids, 19.6% from carbohydrate) (n=14). The mice were fed the respective diets ad libitum for 3 weeks. The mice underwent 60 minutes of superior mesenteric artery occlusion for gut I/R. Survival was observed for 48 hours after reperfusion. (Isocaloric Study) Mice (n=25) were randomized to a normal diet group (NF-ISO) (n=13) or an isocaloric LCHFD diet group (LCHFD-ISO) (n=12). The mice were fed 15.5 kcal/day of the respective diets for 3 weeks. Survival was observed after gut I/R as in the Ad lib study.

Results: (Ad Lib Study) The average caloric intakes were 16.7 ± 0.5 kcal/day (NF-AD) vs. 19.1 ± 0.6 kcal/day (LCHFD-AD). Survival rates of the NF-AD and LCHFD-AD groups after reperfusion were 80% vs. 100% at 8 hours, 53% vs. 71% at 24 hours, and 27% vs. 50% at 48 hours, respectively. Ad libitum intake of LCHFD tended to be associated with better survival than that in the NF-AD group (Figure 1: log rank test; p=0.1). (Isocaloric Study) Survival rates of the NF-ISO and LCHFD-ISO groups were 54% vs. 58% at 8 hours, 31% vs. 25% at 24 hours, and 31% vs. 25% at 48 hours, respectively. There were no significant differences in survival times between the 2 groups (Figure 2: log rank test; p=0.78).

Conclusions: When mice received relatively long-term isocaloric LCHFD feeding, no marked influence of diet types on survival after gut I/R was observed, as in our previous short-term study. However, LCHFD might be more beneficial for gut I/R than normal diets during ad libitum feeding. Further studies are needed to clarify the reasons for these discrepant observations. Financial support: None.

Figure 1. Survival curves after gut I/R NF-AD vs LCHFD-AD.


Figure 2. Survival curves after gut I/R NF-ISO vs LCHFD-ISO.

Nutrition and Metabolism Research Paper Session: Malnutrition, Obesity, Practice Concepts


2373035—A Randomized Placebo-Controlled Clinical Trial of Readmission and Mortality in Malnourished Older Hospitalized Adults Treated With a Specialized Oral Nutrition Supplement

Nicolaas E. Deutz, MD, PhD1; Eric M. Matheson, MD2; Laura E. Matarese, PhD, RD3; Menghua Luo, MD, PhD4; Jeffrey Nelson, PhD4; Maria Geraldine E. Baggs, PhD4; Refaat Hegazi, MD, PhD4; Kelly A. Tappenden, PhD, RD5; Thomas Ziegler, MD6 1Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, TX, USA; 2Department of Family Medicine, Medical University of South Carolina, Charleston, SC, USA; 3Brody School of Medicine, East Carolina University, Greenville, NC, USA; 4Research and Development, Abbott Nutrition, Columbus, OH, USA; 5Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, USA; 6Department of Medicine, Emory University, Atlanta, GA, USA

Purpose: Hospitalized older adults are at high risk of malnutrition, which has a negative impact on subsequent clinical and economic outcomes, including a greater risk of mortality and a high rate of hospital readmission. We report the largest prospective randomized placebo-controlled trial in the United States of oral nutrition supplementation (ONS) therapy for up to 90 days postdischarge on clinical outcomes in malnourished hospitalized older adults (≥65 years).

Methods: The prospective multicenter NOURISH study (Nutrition Effect on Unplanned Readmissions and Survival in Hospitalized Patients) was a double-blind, placebo-controlled, parallel-group study conducted in the United States between May 2012 and October 2014 (ClinicalTrials.gov NCT01626742). Patients (n = 652) who were older (≥65 years), malnourished (Subjective Global Assessment [SGA] class B or C), and hospitalized for congestive heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease were randomized within 72 hours of hospitalization to receive medical and nutrition standard of care plus either the experimental ONS containing high protein (HP; 20 g/serving) and β-hydroxy-β-methylbutyrate (HMB; 1.5 g/serving) or a low-calorie protein-free placebo supplement. Two servings of HP-HMB or placebo ONS were given daily in the hospital and for up to 90 days postdischarge. A primary composite end point of 90-day postdischarge mortality or nonelective readmission was predefined before data unblinding and analysis. Other end points included 30- and 60-day rates of


readmission and/or death, SGA class, body weight, length of stay, activities of daily living, and serum concentration of 25-hydroxyvitamin D at 30 and 60 days. Efficacy analyses were performed with all available data from the intention-to-treat population (HP-HMB, n = 313; placebo, n = 309).

Results: Baseline characteristics were comparable between groups. The primary composite end point was similar between HP-HMB (26.8%) and placebo (31.1%). Individual components showed no differences between groups for 90-day readmission rate; however, 90-day mortality was significantly decreased with HP-HMB relative to placebo (4.8% vs 9.7%; relative risk = 0.49, 95% CI = 0.27–0.90, P = .018; Figure 1); the estimated number needed to treat was 20.3 (95% CI = 10.9–121.4) to prevent 1 death. Evaluation at 30 and 60 days postdischarge showed no significant difference between groups for the composite end point or for readmission, but mortality was significantly lower in the HP-HMB group relative to placebo at 30 and 60 days (respectively, 2.9% vs 6.2%, P = .049; 4.2% vs 8.7%, P = .020). Relative to placebo, HP-HMB administration resulted in significantly more patients with improved SGA nutrition class (OR = 2.04, 95% CI = 1.28–3.25, P = .009; Figure 2). At day 30, body weight was significantly increased by 0.55 ± 0.32 kg (LSM ± SD) with HP-HMB but decreased by 0.26 ± 0.34 kg in placebo (P = .035). Serum levels of 25-hydroxyvitamin D were significantly higher with HP-HMB treatment than placebo at days 30 and 60 (respectively, P = .035 and P = .008). Length of stay and activities of daily living were similar between treatments.

Conclusions: Although we did not observe a significant effect for the primary composite end point of nonelective readmission or death at 90 days in selective malnourished older adults, the HP-HMB formulation decreased mortality and improved indices of nutrition status during the observation period.

Financial support: Abbott Nutrition (Columbus, OH).

Figure 1. Composite primary efficacy end points and components. HMB, β-hydroxy-β-methylbutyrate; HP, high protein; NS, not significant.


Figure 2. Subjective Global Assessment (SGA) status. HMB, β-hydroxy-β-methylbutyrate; HP, high protein.

2369906—Rapid, Comprehensive Oral Nutritional Supplement Quality Improvement Program Reduces 30-Day Readmission in Malnourished Hospitalized Patients Krishnan Sriram, MD1; Suela Sulo, PhD1; Wm. Thomas Summerfelt, PhD1; Gretchen VanDerBosch, RD1; Sanja Nikolich, MD1; Josh Feldstein, BA3; Jamie Partridge, PhD2; Refaat Hegazi, MD2; Michael Ries, MD1 1James R. & Helen D. Russell Institute for Research & Innovation & eICU, Advocate Health Care, Oak Park, IL, USA; 3Center for Applied Value Analysis, Great Barrington, MA, USA; 2R&D, Abbott Nutrition, Columbus, OH, USA Purpose: Positive clinical and economic effects of oral nutritional supplements (ONS) on 30-day hospital readmissions (ReAdm) have been reported. The practical, programmatic aspects of implementing use of a validated malnutrition screening tool—together with developing and enforcing a sustained clinical environment of ONS consumption within the malnourished inpatient population—has not been studied. Nutrition-related initiatives are rarely considered in ReAdm reduction measures. The objective was to investigate the effect of the administration of a quality improvement program (QIP) integrating nutrition risk screening by nursing staff at the time of admission and ONS supplementation of hospitalized patients on non-elective 30-day ReAdm as compared to pre-QIP historical rate of ReAdm. An absolute difference of 4% reduction in 30-day ReAdm rates was targeted.

Methods: The ReAdm rate of historical comparison pre-QIP was 20%. In the QIP, 2 hospitals (a teaching hospital and a community hospital) from a 10-member system were selected where the electronic medical record (EMR) was upgraded to include Malnutrition Screening Tool (MST) and automatic condition-specific ONS administration to all patients at risk for malnutrition (MST ≥ 2). Dietitians assessed patients who screened positive to confirm the diagnosis of malnutrition and design the patient-specific nutrition plans. The enhanced QIP (QIP+) included 2 other hospitals (same mix as QIP), where in addition to the initiatives in QIP, aggressive nutrition-related procedures were implemented (faster administration of ONS, specific discharge instructions, coupons for purchase of ONS, and 4 follow-up/compliance telephone calls). More important, in the QIP+ hospitals, additional educational activities for nurses and dietitians were initiated, reinforcing patient and caregiver education about the importance of ONS. ReAdm data were obtained from the institution’s electronic data warehouse and reconfirmed by manual extraction and review by one or more blinded investigators.

Results: Data from 1269 patients enrolled between October 2014 and April 2015 were analyzed: QIP, n = 769; QIP+, n = 500. Between the 2 QIP groups, the demographic, clinical characteristics, and length of stay were comparable. The post-QIP 30-day ReAdm rate in the QIP+ was 15.6%, showing an absolute rate reduction of 4.4%, as compared to pre-QIP (22% relative risk reduction of readmission, P < .01). Similarly, an absolute reduction of 3.6% (18% relative risk reduction of readmission, P < .01) was seen in the QIP (post-QIP ReAdm rate = 16.4%), as


compared to pre-QIP. A negative correlation was observed between educational activities and errors in malnutrition risk identification using the MST (P < .01). Significant cost savings were estimated for both QIP groups.

Conclusions: Thirty-day unplanned hospital ReAdm can be significantly decreased among the malnourished inpatient population through a comprehensive QIP with a validated nurse-initiated nutrition screening tool incorporated into the EMR with multi-disciplinary team follow-up, immediate provision of ONS, ongoing patient education, and sustained provider and administrative programmatic support.

Financial support: Abbott Nutrition.


2373120—Phase Angle and Impedance Ratio: Bioimpedance Spectroscopy–Generated Reference Cut Points From National Health and Nutrition Examination Survey IV and V

Adam Kuchnia, MS, RD, LD, CNSC1; Levi Teigen, MS, RD1; Abigail Cole, PhD1; Urvashi Mulasi, PhD, RD1; Maria Cristina Gonzalez, MD, PhD2; Carrie Earthman, PhD, RD, LD1 1Food Science and Nutrition, University of Minnesota–Twin Cities, Minneapolis–St Paul, MN, USA; 2Postgraduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, Brazil

Purpose: Raw bioimpedance parameters—for example, 50-kHz phase angle (PA) and 200-kHz / 5-kHz impedance ratio (IR)—have been investigated as predictors of nutrition status and/or clinical outcomes. However, their validity as biomarkers depends on the availability of appropriate reference data. Previously, reference data have been categorized by age, sex, and/or body mass index (BMI) for German and Swiss (primarily Caucasian) populations. More limited data have been published for the U.S. population. Interstudy discrepancies, however, suggest that additional variables need to be accounted for to improve the accuracy of population reference values. Using a large and ethnically diverse data set, we aimed to identify additional variables and provide expanded bioimpedance reference data for the U.S. population.

Methods: The National Health and Nutrition Examination Survey (NHANES) is an ongoing compilation of studies conducted by the U.S. Centers for Disease Control and Prevention designed to monitor the nutrition status of the U.S. population. The NHANES IV and V data sets from 1999–2000, 2001–2002, and 2003–2004 were used for this analysis. A bioimpedance spectroscopy device (Hydra Model 4200; Xitron Technologies, San Diego, CA) was used for bioimpedance data collection only in persons aged 18–49 years. A subsample had dual-energy X-ray absorptiometry (DXA) data collected; in these individuals, PA and IR were further evaluated for their relationship to DXA-measured fat-free mass index (FFMI). Within ethnicity and sex, participants were further categorized by those falling ≤5th and within the 25th–50th percentiles for FFMI; mean PA and IR values were calculated for the FFMI groups. Available bioimpedance spectroscopy data were categorized by ethnicity; final groupings were Hispanic, white, black, and other.

Results: Multivariate analysis showed that PA and IR differed by BMI, age, sex, and ethnicity (n = 6237; R2 = 0.412, P < .0001). Suggested reference cut points for PA, stratified by age decade, ethnicity, and sex, are presented in Table 1, in a similar format to previously published population data. Mean BMI ± SD is also provided for each category, given that sample size limitations prevented further delineation of the data by BMI. Mean FFMI correlated with PA and IR measures (r = 0.55 and r = −0.58, respectively; P < .0001). Within all categories, PA was lower and IR higher in the ≤5th percentile FFMI group vs the 25th–50th percentile group (Table 2).

Conclusions: Ethnicity is an important variable that should be accounted for when determining population reference values for PA and IR. We have provided sex-, ethnicity-, and age decade–specific reference values for PA for use in future studies in U.S. populations. Interdevice differences are likely to be important contributors to variability across published population-specific reference data and, where possible, should be evaluated in future research. Ultimately, further validation with DXA-derived measures are necessary to determine if PA and IR are appropriate bedside diagnostic tools for the assessment of nutrition status in a clinical population.

Financial support: None.


Table 1.Cut Points Defining Low Phase Angle From NHANES IV and V Reference Data.a

Sex: Ethnicity Age Group, y 18–19 20–29 30–39 40–49 Males (n = 3253) Hispanic/black 6.42 6.47 6.68 6.13 n 441 477 404 465 Mean BMI 24.4 ± 5.1 26.5 ± 5.2 27.8 ± 4.7 28.1 ± 4.8 White/other 6.35 6.30 6.32 6.08 n 213 423 405 407 Mean BMI 24.6 ± 4.6 25.8 ± 4.7 27.0 ± 4.6 27.9 ± 4.6 Females (n = 3002) Hispanic/black 5.43 5.52 5.60 5.37 n 412 404 370 485 Mean BMI 26.0 ± 6.6 28.1 ± 6.9 29.7 ± 6.8 30.9 ± 6.4 White/other 5.29 5.47 5.38 5.11 n 172 350 403 406 Mean BMI 24.9 ± 6.2 26.0 ± 6.5 27.0 ± 6.9 27.4 ± 6.5

BMI, body mass index; NHANES, National Health and Nutrition Examination Survey; PA, phase angle (50 kHz). aLow phase angle defined as <5th percentile. Bioimpedence data measured by the Hydra 4200 bioimpedance spectroscopy device.

Table 2.Mean PA and IR Values Obtained From the ≤5th and 25th–50th Percentiles of DXA-Measured FFMI.a

Ethnicity: PA/IR Men, % of FFMI Women, % of FFMI ≤5th 25th–50th P Value ≤5th 25th–50th P Value White IR 0.78 ± 0.02 0.76 ± 0.02 <.0001 0.81 ± 0.02 0.79 ± 0.02 <.0001 PA 6.77 ± 0.76 7.35 ± 0.73 <.0001 5.79 ± 0.64 6.26 ± 0.63 <.0001 n 59 296 56 283 Black IR 0.78 ± 0.03 0.75 ± 0.02 <.0001 0.80 ± 0.02 0.78 ± 0.02 <.0001 PA 6.62 ± 1.02 7.53 ± 0.68 <.0001 5.92 ± 0.52 6.58 ± 0.66 <.0001 n 33 165 29 147 Hispanic IR 0.77 ± 0.02 0.75 ± 0.02 <.0001 0.80 ± 0.02 0.79 ± 0.02 <.0001 PA 6.97 ± 0.64 7.58 ± 0.70 <.0001 5.79 ± 0.61 6.48 ± 0.70 <.0001 n 50 250 47 231 Other IR 0.79 ± 0.02 0.76 ± 0.02 <.0001 0.82 ± 0.01 0.79 ± 0.01 .0013 PA 6.33 ± 0.56 7.28 ± 0.59 .0001 5.59 ± 0.37 6.48 ± 0.46 .0008 n 8 39 4 24

DXA, dual-energy X-ray absorptiometry; FFMI, fat-free mass index; IR, impedance ratio (ie, impedance at 200 kHz / 5 kHz); PA, phase angle (50 kHz). aBioimpedence data measured by the Hydra 4200 bioimpedance spectroscopy device. P values calculated with paired t tests.


2373138—Long-Term Follow-Up of Body Composition and Functional Status After Roux-en-Y Gastric Bypass Surgery Carrie Earthman, PhD, RD, LD1; Abigail Cole, PhD1; Adam Kuchnia, MS, RD, LD, CNSC1; Lauren Beckman, PhD, RD4; Cyrus Jahansouz, MD2; Jennifer Mager, PhD, RD5; Shalamar Sibley, MD, MPH3 1Food Science and Nutrition, University of Minnesota-Twin Cities, Minneapolis-St. Paul, MN, USA; 2Surgery, University of Minnesota-Twin Cities, Minneapolis-St. Paul, MN, USA; 3Medicine, University of Minnesota-Twin Cities, Minneapolis-St. Paul, MN, USA; 4Swedish Medical Center, Englewood, CO, USA; 5 Applied Nutrition LLC, Cleveland, MN, USA Purpose: The Roux-en-Y gastric bypass (RYGB) has been the most commonly performed bariatric surgery over the past decade. Fat mass (FM) and percent body fat have been observed to substantially decrease within the first year after RYGB; however, lean soft tissue (LST) also decreases after surgery, albeit to a lesser extent. Limited data exist regarding the long-term impacts of RYGB on body composition; therefore, our aim was to evaluate body composition and functional status changes in participants from a previous 1-year post-RYGB longitudinal study who had undergone RYGB approximately 8.5 years prior.

Methods: Five women from a previous larger cohort study were monitored pre-RYGB and at 1.5-months, 6-months, 1-year, and 8.7-years post-RYGB. Body composition was assessed using dual energy x-ray absorptiometry (DXA; GE Lunar iDXA, GE Healthcare, USA). Handgrip strength was measured using a digital isokinetic hand dynamometer (Takei Scientific Instruments, Ltd., Japan).

Results: Mean age was 47.2 ± 10.9 and 56.2 ± 10.9 years at 8.7-years post-RYGB. Significant weight loss was observed at 1-year post-RYGB (46.2 ± 10.2 kg, P=0.0005). Subjects regained 5.5 ± 6.7 kg of body weight between the 1-year and 8.7-year visits, although this was not significant. BMI decreased at each time point until 1-year (from 48.8 ± 9.7 to 32.6 ± 9.2 kg/m2, P<0.0001), and increased between 1-year and 8.7-years to 34.9 ± 8.8 kg/m2 (P<0.0001). Compared to baseline, 8.7-year mean LST decreased by 11.9 ± 5.6 kg (P<0.01). LST also decreased by 4.4 ± 3.0 kg between 1-year and 8.7-years post-RYGB (P<0.05). FM decreased from baseline to 1-year post-RYGB by 39.9 ± 8.32 kg (P<0.001), but then increased by 8.6 ± 7.0 kg between 1-year and 8.7-years post-RYGB (P=0.05). Mean handgrip strength decreased over the 8.7-year period from 31.9 ± 6.1 to 26.2 ± 4.5 kg of force (P<0.01). Loss of LST was correlated with loss of handgrip strength (r = 0.64, P<0.001). When controlling for the effect of age and repeated visits, the model containing LST, age, and repeated visits accounted for 84% of the variation in handgrip strength in this cohort.

Conclusions: In the long-term following RYGB our study participants exhibited a significant decrease in LST, which occurred in the background of weight regain, primarily as FM. The observed association between LST loss and diminished handgrip strength, accompanied by weight regain, is a concerning trend post-RYGB. This decrease in lean tissue and functional status, potentially masked by weight regain, carries particular implications for the aging bariatric population. These issues underscore the need for ongoing monitoring of body composition and functional status, in addition to body weight in the post-RYGB population. Financial support: A.S.P.E.N. Rhoads Research Foundation Grant. Grant M01-RR00400, NIH Grant 1UL1RR033183, National Center for Research Resources Grant 8 ULITR000114-02, National Center for Advancing Translational Sciences for the NIH to University of Minnesota CTSI.


2348835—Nutrition Assessment in Relation to Muscle Mass Assessment via CT Imaging in Cardiac Device Recipients Apameh Bashar, RD, CDE, CNSC2,1; Heather Danielson, RD2,1; Joan Wessels, MS, RD, CDE1; Jessica Bursey, MPH, RD1; Clint Jokerst, PhD3; Elizabeth Krupinski, PhD3; Kaitlin Callahan1; Lucille Cooke1; Ashley Luciano1; Jena Panebianco, RD1 1Nutrition Services, Banner University Medical Center Tucson, Tucson, AZ, USA; 2Nutrition Services, Aramark Healthcare, Tucson, AZ, USA; 3Radiology, University of Arizona, Tucson, AZ, USA Purpose: Patients who receive a left ventricular assist device (LVAD) or total artificial heart (TAH) represent a growing subset of heart failure (HF) patients. It is common practice for these patients to receive cross-sectional imaging of their torso throughout their course of care. Information generated from CT scans can be used as an objective measure of a patient’s total body muscle mass. Recent studies have shown that the term sarcopenia should be expanded to define the muscle wasting process that occurs with many chronic diseases such as HF. It is thought that sarcopenia increases the risk of morbidity and mortality in HF patients and ultimately may influence outcomes of cardiac device recipients. Muscle mass loss is among the criteria used for diagnosing both the presence and severity of malnutrition; however, identification of muscle mass loss through physical exam alone can be challenging in the HF population due to fluid retention. When used in conjunction with the 2012 AND/A.S.P.E.N. malnutrition criteria, CT imaging may assist the nutrition professional in diagnosing malnutrition by providing a more objective indicator of muscle mass loss.

Methods: In this retrospective study, the nutrition assessment and presence of sarcopenia identified by CT imaging were compared in 33 studies on 29 adult (>18 years) patients. Four patients had two CT images and corresponding nutritional assessments, therefore two separate statistical analyses were performed and included. Image analysis was performed using Slice-O-Matic software (Figure 1). Data analysis was performed using Analysis of Variance (ANOVA) statistical software. Inclusion criteria were placement of LVAD or TAH within the past 5 years, nutrition assessment prior to and/or during device placement admissions, and CT imaging at L3 within 3 months of device placement and/or nutritional assessment. An image at L3 (either MRI or CT) was analyzed for the cross-sectional area of skeletal muscle and normalized to the patient’s height, generating a skeletal muscle index (SMI) which was used to detect sarcopenia. Cut points for the diagnosis of sarcopenia were based on a CT-based sarcopenia study which determined that an SMI of ≤38.5 cm2/m2 for women and ≤52.4 cm2/m2 for men were considered sarcopenic.

Results: Thirteen of the studies showed normal SMIs, with 2 (15%) of the corresponding nutritional assessments identifying malnutrition. 20 studies showed abnormal SMIs, with 10 (50%) of the corresponding nutritional assessments identifying malnutrition.

Conclusions: CT imaging could be a useful tool in determining lean muscle composition and muscle mass loss in HF patients. Data obtained from imaging can support Registered Dietitian Nutritionists in assessing for malnutrition. This study did not show a significant correlation between SMI values and assessment of malnutrition using AND/A.S.P.E.N. criteria. Implications for current clinical practice include an ongoing improvement in conducting thorough physical exams with consideration of fluid status in this patient population. In addition, uniform and precise documentation of physical assessment will facilitate further study in cardiac device patients. Further research with a larger sample size is needed to explore the feasibility of using sarcopenia identified by CT imaging as an adjunct criterion in diagnosing malnutrition in this clinically complex population. Financial support: University of Arizona Seed Grant.


2372838—Determining the Relationship Between SGA Assessment of Functional Status and Handgrip Strength Kaleigh N. Brown, BS1; Sarah Peterson, PhD, RD, CNSC1; Anne Coltman, MS, RD, CNSC1; Molly DePrenger, MS, RD1; Diane Sowa, MBA, RD1 1Food and Nutrition, Rush University Medical Center, Chicago, IL, USA Purpose: Handgrip strength (HGS) has been used in assessing nutritional status of some hospitalized patients due to its objective nature. In contrast, another assessment tool, Subjective Global Assessment (SGA), subjectively inquire about changes in patient functional status. The purpose of this study was to describe the relationship between SGA assessment of functional status and handgrip strength.

Methods: A convenience sample of 208 patients admitted to a large, urban academic hospital was used. One registered dietitian completed SGA and asked patients about changes in functional status; results were categorized as no change versus decreased ability to complete ADLs and/or bedridden. In addition a Jamar dynamometer was used to assess HGS. Patients completed three consecutive readings with their dominant hand; the average of the three readings was used in these analyses. HGS adequacy was determined based on manufacturer guidelines for age and gender. A chi-square analysis was used to compare categorical variables. To determine comparisons between continuous variables such as age, BMI, average handgrip strength, with the dichotomous variable change in functional status (yes/no), an independent T-test was used. IRB consent was obtained.

Results: The sample was primarily female (56%, n=117), with a mean age of 58.0 ± 17.9 years, mean length of stay of 3.3 ± 3.0 days, and a mean BMI of 30.0± 8.6 kg/m2. A total of 131 (63%) patients reported no change in functional status when the SGA was completed; however, 71% (n=93) of those patients had inadequate HGS (Table 1). Significantly more patients that reported a change in functional status (n=73) had an inadequate HGS (93% versus 71%, p<0.001). Additionally, these patients also had a significantly lower HGS than those that reported no change in functional status (19.6±10.3 versus 30.1 ±11.6, p<0.001). Patients that reported a change in functional status were significantly older (64.5 ± 17.1 versus 54.5±17.5 years, p<0.001) and female (72% versus 48%, p<0.001). There were no significant differences in BMI of patients based on SGA assessment of functional status.


Conclusions: As expected, patients who reported no change in functional status had a higher HGS than those who did report a change in functional status. Nonetheless, a large proportion of patients reporting no functional change had inadequate HGS. This suggests that both reference standards should be reevaluated and/or SGA assessment of functional status may not be a sensitive marker in this population. Further research is needed to explore this relationship. Financial support: None.

Table 1. Subject Characteristics Compared to SGA Determination of Changes in Functional Status.

Characteristic SGA no reported change in functional status (n=131)

SGA reported change in functional status (n=73)

p-Value

Age, years (mean ± SD) 54.5 ± 17.5 64.5 ± 17.1

Female (n(%)) 64 (48%) 53 (72%)

HGS, kg (mean ± SD) 30.1 ± 11.6 19.6 ± 10.3

Inadequate HGS (n(%)) 93 (71%) 68 (93%)

Nutrition and Metabolism Research Paper Session: Critical Care & Other Critical Health Issues


2371640—ICU Microbiome Project: Critical Illness Is Associated With Loss of Microbial Diversity and Major Alterations in Bacterial Flora

Paul Wischmeyer, MD1; Daniel McDonald, PhD2; Daren Heyland, MD3; Ludmila Khailova, MS1; Christine Baird, BS1; Rob Knight, PhD4 1Anesthesiology and Pediatrics (Nutrition Section), University of Colorado School of Medicine, Aurora, CO, USA; 2BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO, USA; 3Medicine, Queens University, Kingston, Ontario, Canada; 4Pediatrics, University of California–San Diego, San Diego, CA, USA

Purpose: Alterations and loss of diversity in gut and oral bacterial flora (dysbiosis) are thought to be associated with infectious complications and mortality in ICU patients. However, to date, evaluations of microbial ecology in ICU patients have been restricted to small culture-based studies. With the evolution of 16s rRNA microbiome techniques, large-scale prospective trials of the ICU microbiome are needed. Thus, we conducted a multicenter prospective trial of the effect of critical illness on gut, oropharynx, and skin microbiome via 16s sequencing and metagenomics versus healthy controls.

Methods: Fecal, oral, and skin samples were collected in 149 mixed ICU patients in 4 centers from the United States and Canada at 2 time points: within 48 hours of ICU admission and discharge or day 10 (whichever came first). Sample collection and processing were performed in accordance with Earth Microbiome Project protocols. Results were compared with samples from self-reported healthy individuals (ie, no antibiotic use in last year; n = 1242 [American Gut Registry]). Diverse clinical outcomes were collected, including mortality, key infections, antibiotic use, and all nutrition delivery data.

Results: Regardless of time point, fecal, oral, and skin ICU samples were significantly different from American Gut healthy samples within principal coordinates space, a separation predominantly explained by a decreased ratio of firmicute abundance (see Figure 1). Correlations were observed with changes in microbiome signatures from all sites with adverse outcomes, including mortality, ARDS, and length of stay. A significant “crash” in taxon diversity was observed in fecal/oral samples, with only a few (1 to <5 taxa) making up 95% of entire bacterial population in


many ICU patients (Figure 2, showing rank abundance of most abundant operational taxonomic unit in ICU and healthy control patients). As an example, reduced microbiome diversity was associated with longer ICU length of stay (Mann U, P = .008). Many operational taxonomic units significantly depleted in ICU patients have been identified as “health-promoting species” in studies of other diseases states (ie, IBD), such as Faecalibacterium prausnitzii.

Conclusions: These initial data suggest that significant changes in the gut, oral, and skin microbiome occur in ICU patients, including significant loss of bacterial diversity. This loss of diversity can be extreme, with very few taxa making up a significant portion of the fecal and oral microbiome of ICU patients. This loss of diversity appears to be correlated with worsened clinical outcomes. Characterizing these changes opens the door to asking focused questions to understand why these differences arise, and it forms the basis for the development of diagnostic and therapeutic interventions, such as probiotics, prebiotics, and stool transplants utilizing microbiome signatures to guide therapy.

Financial support: National Institutes of Health (R01 GM078312).

Figure 1. Critical illness leads to reduced firmicute bacterial abundance. Light-colored spheres, low firmicute abundance; dark-colored spheres, high firmicute abundance; large spheres, ICU patients; small spheres, healthy subjects.


Figure 2. Rank abundance of most abundant operational taxonomic unit in each sample.


2371651—Safety and Effect of Enteral Glutamine Administration in Burn Patients on Plasma Glutamine Levels

Paul Wischmeyer, MD1; Christine Baird, BS1; Olav Rooijackers, PhD2; Daren Heyland, MD3 1University of Colorado School of Medicine, Aurora, CO, USA; 2Anesthesiology and Intensive Care, Karolinska Institutet and University Hospital, Huddinge, Sweden; 3Critical Care Medicine and Clinical Evaluation Research Unit, Queens University–Public Health, Kingston, Ontario, Canada

Purpose: Glutamine (GLN) given in standard accepted doses (0.3–0.5 g/kg/d) has shown signals of reduced mortality and improved outcomes in burn injury in a number of small randomized trials of intravenous and enteral GLN supplementation. However, in trials (REDOXS) of patients with multiorgan failure at admit, high-dose GLN (>0.5 g/kg/d) is associated with a signal of increased mortality. Secondary analysis indicates that much of this increased mortality occurred in renal failure patients at intensive care unit admit not undergoing dialysis. Previous research by other groups and our REDOXS data suggest that admission GLN levels >930 μmol/L may be associated with increased mortality and that renal failure may correlate with increased GLN levels. We observed GLN levels >930 μmol /L in REDOXS in 10% of patients at admit. A major multicenter trial planned to examine GLN’s effect on burn mortality. Prior to launching this large initiative, we conducted a multicenter randomized pilot trial to assess feasibility of larger trial, including an analysis of GLN levels.

Methods: A multicenter double-blind randomized pilot trial was conducted in 8 burn centers in Canada and the United States to demonstrate the feasibility of our larger planned trial. We included patients with deep second- and/or third-degree burns at moderate to high risk of death. For patients aged 18–59 years, we required a total burn surface area (TBSA) ≥20% or, in the presence of an inhalation injury, a minimum TBSA of 15%. For patients ≥60 years, we required a TBSA ≥10%. We excluded patients admitted >48 hours before screening and patients with


advanced liver and kidney disease. Patients were randomized to receive either GLN via feeding tube every 4 hours for a total of 0.5 g/kg/d or maltodextrin (control). Study intervention continued until 7 days post–last graft. Patients were followed for 6 months to document survival. A substudy of patients had blood draws done at baseline and weekly thereafter to measure plasma GLN levels and other laboratory measures.

Results: In first 18 patients in which GLN levels were analyzed, significant GLN deficiency was noted overall and in both GLN and control groups (<420 μmol/L; see Figures 1 and 2). Mean plasma GLN levels were consistently higher in the GLN group at 2 and 3 weeks post–burn injury, although this was/was not statistically significant (see Figure 2). A few mild elevations of GLN >930 μmol/L were observed in the GLN and control groups at weeks 3 (n = 1) and week 4 (n = 4). The highest level was 1026 μmol/L. These mild elevations of GLN were not associated with increased blood urea nitrogen or creatinine levels at time of sample collection. No elevated GLN levels were observed at admission or in first 2 weeks post–burn injury. No deaths were observed in any patient with an elevated GLN level. Further patients are currently being analyzed.

Conclusions: Burn injury is associated with significant GLN deficiency that can persist for ≥2 weeks without GLN treatment. Unlike in REDOXS, we observed no marked elevations of GLN level at admission or in the first 2 weeks post–burn injury. Late mild elevations of GLN levels were seen in both GLN and control groups. Furthermore, none of the deaths observed in this subgroup were associated with an elevated GLN level. We hypothesize that these elevations may be related to a number of factors, including the large total protein load that burn patients receive in feeding, the potential for massive weight loss in burn injury over time leading to need for GLN and protein redosing at weekly intervals, and reduced GLN/protein losses when burn wound is closed and/or as it is debrided and covered. We feel that these data indicate that the full 2700-patient RE-ENERGIZE trial can be initiated safely, with proper exclusions for renal and liver failure.

Financial support: Department of Defense / American Burn Association Clinical Trial Grant.

Figure 1. Glutamine levels in all burn patients.

Glu

tam

ine

μM

Week Post-Admit

930 μM


Figure 2. Glutamine (GLN) levels by group. Circle inside box, means; band inside box, medians; bottom and top edges of box, 25th and 75th percentiles (IQR); ends of whiskers, minimum and maximum values. Cont, control.

2373199—Early Nutritional Inadequacy Is Associated With Worse Outcomes in the Chronically Critically Ill Daniel D. Yeh, MD1; Eva Fuentes, MD1; Sadeq A. Quraishi, MD, MHA, MMSc2; Jarone Lee, MD, MPH1; Haytham Kaafarani, MD, MPH1; Kathryn Butler, MD1; George Velmahos, MD, PhD1 1Surgery, Massachusetts General Hospital, Boston, MA, USA; 2Anesthesia, Massachusetts General Hospital, Boston, MA, USA Purpose: Recent studies suggest that underfeeding is not inferior to full feeding in ICU patients. However, appropriate patient selection is important, as low-risk, less severely ill patients generally have good outcomes regardless of nutritional interventions. Surgical patients are often younger and have less co-morbid diseases than their medical counterparts and surgical intensive care units (ICU) often admit patients for a short course of postoperative monitoring or for an easily reversible cause. We hypothesized that early nutritional inadequacy is more impactful on clinical outcomes in those requiring longer surgical ICU (>=14 d) stay compared to those requiring shorter ICU stay (<14 d).

Methods: We performed a retrospective analysis of an ongoing prospective registry of adult SICU patients. Data collected included age, body mass index (BMI), Charlson Comorbidity Index (CCI), Injury Severity Score (ISS), Acute Physiology and Chronic Health Evaluation (APACHE II) score, and clinical outcomes such as mortality, length of stay (LOS) and ventilator free-days (VFD). Subjects were divided into shortICU (<14d) and longICU (>= 14d) groups. Cumulative nutritional deficits at ICU day 3 and 7 and were calculated as well as at ICU discharge, initiation of oral intake, or death. Variables between groups were compared using independent two-tailed Student's t test, or Mann U Whitney, depending on the distribution of the data and proportions were compared with chi-squared test. To investigate whether early nutrient deficit was associated with ICU length of stay (LOS), hospital LOS, 28 day VFD, and favorable discharge disposition (home/rehab vs. death/SNF), we performed linear and logistic regression analyses, while controlling for age, sex, BMI, and APACHE II score. All tests were two-tailed and a p value of <0.05 was considered statistically significant.

Results: 213 subjects were included. While the shortICU (n=118) and longICU (n=95) groups were similar in age, APACHE II, ISS, calorie/protein prescription, and enteral nutrition (EN) initiation within 48 h, longICU patients were less commonly female (19% vs. 36%, p=0.004) and had higher weight (73kg vs. 68kg, p=0.001) and BMI (29 vs. 26, p=0.008). Despite similar calorie and protein prescription, Day 3, 7, and total calorie and protein deficits were significantly greater in the longICU group compared to the shortICU group (TABLE). In shortICU patients, regression analysis did not show any association between any nutritional deficits and ICU LOS, mortality, or discharge disposition, while 28-VFD was associated with day 3, 7, and cumulative calorie deficit. In longICU patients, day 3, 7, and cumulative total calorie and protein deficits were associated with ICU LOS, hospital LOS, 28-VFD, mortality, and unfavorable discharge disposition (death/SNF).

Glu

tam

ine

μM

Week Post-Admit

700μM

420μM


Conclusions: Chronically critically ill patients accumulate greater early macronutrient deficits in the surgical ICU despite similar initiation and prescription. Nutritional deficits accumulating in the first 3 and 7 ICU days are more strongly correlated with clinical outcomes in patients requiring longer ICU stays (>=14 d) compared to shorter ICU stays (<14 d). Efforts to maximize early nutrient delivery should be focused on patients expected to stay in the surgical ICU >= 14 days. Financial support: None.

APACHE, Acute Physiology and Chronic Health Evaluation; BMI, body mass index; CCI, Charlson Comorbidity Index; EN, enteral nutrition; ISS, Injury Severity Score; LOS, length of stay; SNF, skilled nursing facility; VFD, ventilator free-days.



2373237—Effect of High-Dose Cholecalciferol Supplementation on Perioperative Vitamin D Status in Colorectal Surgery Patients: A Randomized Placebo-Controlled Pilot Trial

Sadeq A. Quraishi, MD1; Caitlin M. McCarthy, BA1; Joseph Needleman, BS, BA1; Erica Herzog, RN1; David Berger, MD1; Carlos A. Camargo, MD, DrPH1 1Massachusetts General Hospital, Boston, MA, USA

Purpose: Low vitamin D status is associated with various undesirable perioperative outcomes, such as healthcare-associated infections, cardiovascular events, and in-hospital mortality. However, very little is known about strategies to optimize perioperative vitamin D status. Therefore, our goal was to conduct a randomized placebo-controlled trial to determine the effect of high-dose cholecalciferol (vitamin D3) supplementation on perioperative vitamin D status in patients scheduled for elective colorectal surgery.

Methods: The experimental protocol was registered on ClinicalTrials.gov (NCT01689779). We planned on recruiting a total of 80 patients with an interim analysis once 60 patients had completed the study. Patients scheduled for elective colorectal surgery received either a single oral dose of cholecalciferol (100,000 IU) or a matched placebo 5–7 days before surgery. Blood samples were assessed at baseline, on the day of surgery, on postoperative day 1, and during follow-up on postoperative days 12–14 for (1) 25-hydroxyvitamin D (25OHD), (2) albumin and vitamin D binding protein to calculate bioavailable 25OHD (b25OHD), (3) the endogenous antimicrobial peptide cathelicidin (LL-37), and (4) levels of inflammatory markers high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), and IL-10. Percentage change (Δ) in biomarkers relative to baseline, day of surgery, postoperative day 1, and postoperative days 12–14 were compared between groups via 2-way repeated-measures analysis of variance tests. Simple linear regression modeling was used to test the relationship between Δ25OHD/Δb25OHD and ΔLL-37.

Results: Demographic and clinical information related to the placebo (n = 32) and cholecalciferol (n = 28) groups at interim analysis is shown in Table 1. All biomarkers were similar between groups at baseline. Changes in 25OHD and b25OHD over time are shown in Figure 1. Analysis of variance testing demonstrated a difference in Δ25OHD, Δb25OHD, and ΔLL-37 levels between groups (F = 16.7, P = .001; F = 7.7, P = .007; and F = 2.08, P = .005, respectively) and over time (F = 66.5, P < .001; F = 3.2, P = .04; and F = 10.47, P = .001, respectively). Δb25OHD (r = 0.42, P = .01) but not Δ25OHD (r = 0.32, P = .11) was found to correlate with ΔLL-37. ΔhsCRP and ΔIL-6 were not different between groups (F = 0.01, P = .9; F = 1.05, P = .41, respectively) but were different over time (F = 15, P < .001; F = 11.44, P < .001). However, ΔIL-10 was different between groups (F = 1.66, P = .02) and over time (F = 7.17, P = .001). There were no adverse effects related to cholecalciferol supplementation noted throughout the duration of the study. The trial was closed following the interim analysis due to a significant improvement in vitamin D status in the cholecalciferol group versus the placebo group. Further enrollment was not expected to materially change these results.

Conclusions: In our cohort of patients, a single dose of cholecalciferol (100,000 IU) given 5–7 days before elective colorectal surgery was safe and resulted in significant improvement in perioperative vitamin D status. Moreover, our data suggest that preoperative vitamin D supplementation may influence postoperative cytokine levels and influence expression of endogenous antimicrobial peptides. Future trials are needed to build on our findings and to determine whether preoperative vitamin D status optimization can influence important clinical outcomes, such as postoperative complications, length of stay, and mortality.

Financial support: Massachusetts General Hospital.


Table 1. Characteristics of the Study Cohort (n = 60).a

Placebo (n = 32)

Vitamin D (n = 28)

P Value

Age, y 61 ± 13 56 ± 13 .14 Sex, % Female 63 50 .04 Male 37 50 BMI, kg/m2 29 ± 6 29 ± 6 1.00 ASA physical status 2 ± 1 2 ± 1 .99 Type of surgery, % .77 Laparoscopic/assisted 66 64 Open abdominal 34 36 Vitamin D supplementation,b % .48 No 59 54 Yes 41 46 25OHD, ng/mL Baseline 29 ± 11 28 ± 12 .73 DOS 27 ± 11 36 ± 12 .004 POD1 23 ± 9 31 ± 11 .004 POSTOP 28 ± 13 39 ± 13 .002 b25OHD, ng/mL Baseline 3.7 ± 2.5 3.7 ± 2.3 .99 DOS 3.5 ± 2.1 4.8 ± 2.6 .04 POD1 3.3 ± 2.2 4.7 ± 2.4 .02 POSTOP 3.3 ± 2.3 5.1 ± 2.9 .01 hsCRP, mg/L Baseline 10 ± 26 9 ± 18 .86 DOS 7 ± 10 7 ± 12 .99 POD1 106 ± 55 90 ± 57 .38 POSTOP 41 ± 55 33 ± 42 .53 Cathelicidin, ng/mL Baseline 84 ± 54 97 ± 92 .52 DOS 79 ± 52 87 ± 75 .64 POD1 74 ± 40 84 ± 65 .48 POSTOP 82 ± 48 103 ± 91 .25 IL-6, pg/mL Baseline 8.4 ± 9.8 11.8 ± 23.4 .47 DOS 10.6 ± 17.7 17.4 ± 38.5 .40 POD1 121.5 ± 88.8 85.6 ± 100.7 .15 POSTOP 11.3 ± 23.2 49.2 ± 150.1 .20 IL-10, pg/mL Baseline 11.2 ± 11.6 10.8 ± 9.6 .88 DOS 12.2 ± 12.6 17.5 ± 36.7 .48 POD1 26.8 ± 27.4 17.5 ± 16.4 .11 POSTOP 9.7 ± 10.0 13.8 ± 23.2 .39

25OHD, 25-hydroxyvitamin D; ASA, American Society of Anesthesiologists; b25OHD, bioavailable 25-hydroxyvitamin D; BMI, body mass index; DOS, day of surgery; hsCRP, high-sensitivity C-reactive protein; IL, interleukin; POD1, postoperative day 1; POSTOP, postoperative days 12–14. aData are reported as mean ± SD or proportions and compared with t tests or chi-square tests, respectively. Statistically significant P values are shown in bold. bSupplementation ranged from 400–2000 IU.


Figure 1. Data in the figures represent percentage (%) change in vitamin D status (1A, 1B) and inflammation (1C) as compared with baseline. In the placebo group, a postoperative drop in 25OHD is accompanied by a drop in b25OHD. In supplemented patients, postoperative b25OHD is maintained despite an apparent drop in 25OHD. 25OHD, 25-hydroxyvitamin D; b25OHD, bioavailable 25OHD; DOS, date of surgery; hsCRP, high-sensitivity C-reactive protein; POD1, postoperative day 1; POSTOP, postoperative days 12–14.

A

B

C

Placebo Cholecalciferol



DOS POD1 POSTOP

DOS POD1 POSTOP

DOS POD1 POSTOP

% c

hang

e in

25O

HD

%

cha

nge

in b

25O

HD

%

cha

nge

in h

sCR

P



2372022—Early Parenteral Nutrition Does Not Worsen Intestinal Barrier Function: A Pilot RCT

Katri Typpo, MD, MPH1,2; Claire Larmonier, PhD3; Jendar Deschenes, MPH4; Daniel Laubitz, PhD1,2; Christy Harrison, BS3; Kareem W. Shehab, MD1; Pawel Kiela, PhD2,3; Fayez Ghishan, MD1,2 1Pediatrics, University of Arizona, Tucson, AZ, USA; 2Immunology, University of Arizona, Tucson, AZ, USA; 3Steele Children’s Research Center, University of Arizona, Tucson, AZ, USA; 4Department of Orthopaedics and Rehabilitation, University of New Mexico, Albuquerque, NM, USA

Purpose: Multiple retrospective studies associate parenteral nutrition (PN) with mortality in critically children. Putative mechanisms for this increased mortality are via intestinal barrier dysfunction and/or loss of intestinal microbiome diversity when PN is provided in the absence of enteral nutrition (EN). We sought to understand if early PN provided with EN worsens intestinal barrier function and microbiome diversity during pediatric critical illness.

Methods: Single-center pilot RCT of early (day 1) vs late PN (day 5) to supplement early EN, for children admitted to Diamond Children’s Medical Center, Tucson, AZ, with acute respiratory distress syndrome (ARDS) from August 2012 to December 2014. Block randomization was stratified by age and body mass index z score to early or standard care PN. All patients had early EN initiated and advanced according to our standard early EN guideline. For patients in the early PN arm, PN began within 4 hours of randomization and was titrated to deliver 100%–120% of measured resting energy expenditure in combination with advancing EN. We examined repeated plasma biomarkers at baseline and throughout the first 7 days of pediatric intensive care unit hospitalization to reflect intestinal barrier function (FABP2, epithelial integrity; citrulline, functional enterocyte mass; claudin 3, tight junction integrity). We examined fecal microbiome composition and diversity daily during the 1-week study period in 2 twin-study patients. DNA was purified with phenol-chloroform protocol with bead beating. Microbiota taxonomic analysis was performed by sequencing V4 fragment of 16S rRNA gene on MiSeq Illumina, followed by bioinformatic analysis with MacQiime (v. 1.9.1).

Results: We enrolled 10 study subjects in this pilot RCT. Median age was 2.0 years (range, 0.12–13.6 years). Patients had elevated baseline FABP2 (median, 467 pg/mL; IQR, 387–1151 pg/mL) and below-normal citrulline (median, 7.1 µmol/L; IQR, 4.6–10 µmol/L) concentrations at time of randomization, indicative of poor intestinal epithelial integrity and low functional enterocyte mass, respectively. Patients in the early PN arm had a nonsignificant trend for improved FABP2 concentrations (P > 0.05). Patients exposed to early PN did not have a trend for worse claudin 3 or citrulline concentrations. Exposure to PN was associated with predominance of Clostridiales (67–73.4%) rather than Bifidobacteriales (47.7%–65.6%) on days 1–2 of the study protocol. Lactobacillales had low abundance (1.4%–5.5%) in both patients on study days 1–2 but increased abundance (87%–99.6%) on days 3–7. Weighted UniFrac differences for β diversity demonstrated differences between patients on study days 1–2 but not on study days 3–7 (Figure 1). Both patients were treated with intravenous antimicrobials throughout the 7-day study period.

Conclusions: Patients randomized to early PN as a supplement to EN in this pilot RCT did not demonstrate worsened intestinal barrier function. Trends in our data indicate that early EN may prevent PN-associated loss of intestinal barrier function in children with ARDS. Exposure to antimicrobials may dominate PN effects on intestinal microbial population diversity. Further studies are needed to understand if early PN might improve intestinal barrier function for children with ARDS and which aspects of intensive care unit care most alter intestinal microbiome composition and diversity.

Financial support: National Institutes of Health, Eunice Kennedy Shriver National Institute for Child Health and Human Development.


Figure 1. Principal coordinate analysis of twin intestinal microbiome samples. Fecal samples were collected from twin siblings (p125 and p126) daily for 7 consecutive days after admission to the intensive care unit. Weighted UniFrac analysis, followed by principal coordinate analysis, of microbiota from the patients over the time indicates that patients exposed to parenteral nutrition differ in microbial β diversity, but over time it is likely that factors such as antimicrobial use dominate parenteral nutrition effects on microbial population β diversity.

A.S.P.E.N. Trainee Award

2372756—Nutrition Risk in Critically Ill (NUTRIC) and Nutrition Risk Screening 2002 (NRS 2002) Scores as Predictors of Protein and Caloric Deficit in Critically Ill Patients

Cecilia Canales, MPH1,2; Caitlin M. McCarthy, BS2,3; D. Dante Yeh, MD4,5; Nalin Chokengarmwong, MD4,5; Donna Belcher, RD, MS6; Anna Nakayama, RD6; Sadeq A. Quraishi, MD, MHA, MMSc2,5 1University of California–Irvine, Irvine, CA, USA; 2Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA; 3Tufts University School of Medicine, Boston, MA, USA; 4Department of Surgery, Massachusetts General Hospital, Boston, MA, USA; 5Harvard Medical School, Boston, MA, USA; 6Department of Nutrition and Food Services, Massachusetts General Hospital, Boston, MA, USA

Purpose: Nutrition status is strongly associated with clinical outcomes in critically ill patients. Nonetheless, patients in the intensive care unit (ICU) are typically undernourished and consequently are at risk for becoming malnourished during their hospitalization. Although several screening tools are available to assess nutrition status during the course of acute care (eg, Nutrition Risk Screening 2002 [NRS 2002]), their use in the ICU setting has not been rigorously studied. Recently, the Nutrition Risk in Critically Ill (NUTRIC) score was developed and validated for use in ICU patients; however, it is unclear whether the NUTRIC score is superior to existing screening tools to predict nutrition deficits in critically ill patients. Therefore, our goal was to compare NUTRIC vs NRS 2002 scores in terms of their association with protein as well as caloric deficit in ICU patients.


Methods: We performed a retrospective analysis of data from a prospective observational cohort study of nutrition in critically ill adults. Only patients who had both a calculated NUTRIC score and a NRS 2002 score were included in the study. Protein and caloric deficit over the course of ICU admission was determined by subtracting actual nutrient delivery from the estimated nutrient requirements (based on the American Society for Parenteral and Enteral Nutrition guidelines). To investigate the association of NUTRIC/NRS2002 scores with protein/caloric deficit, we first performed linear regression analyses, while controlling for age, sex, race, body mass index, and ICU length of stay. We then dichotomized the nutrition risk scores as low vs high risk for malnutrition (NUTRIC: ≤4 vs >4; NRS 2002: <3 vs ≥3). We also dichotomized nutrient deficit as low vs high risk for suboptimal outcomes (protein deficit: <300 g vs ≥300 g; caloric deficit: <6000 kcal vs ≥6000 kcal). Using the dichotomized nutrition risk scores and nutrient-deficit thresholds, we performed logistic regression analyses, while controlling for age, sex, race, body mass index, and ICU length of stay.

Results: A total of 312 adult ICU patients composed the analytic cohort (Table 1). Linear regression modeling demonstrated that for each increment in NUTRIC score, the protein deficit was likely to increase by 49 g (β = 48.70, 95% CI = 29.23–68.17; P < .001), and the caloric deficit was likely to increase by 752 kcal (β = 751.95, 95% CI = 447.80–1056.09; P < .001). Logistic regression modeling demonstrated that patients with NUTRIC scores >4 were more than twice as likely to develop a protein deficit ≥300 g (adjusted OR = 2.35, 95% CI = 1.43–3.85; P < .001) as compared with patients with NUTRIC scores ≤4. Similarly, patients with NUTRIC scores >4 were almost 3 times as likely to develop a caloric deficit ≥6000 kcal (adjusted OR = 2.73, 95% CI = 1.66–4.50; P < .001) as compared with patients with NUTRIC scores ≤4. Neither linear regression modeling nor logistic regression modeling demonstrated an association between NRS 2002 scores and nutrient deficit. Further adjusting for APACHE II (Acute Physiology and Chronic Health Evaluation) scores in these models did not materially affect the association of NRS 2002 scores and nutrient deficit in the ICU.

Conclusions: Our data suggest that NUTRIC scores are strongly associated with both protein and caloric deficits in critically ill patients. While the NRS 2002 is commonly used in the clinical setting to predict risk of malnutrition in hospitalized patients, it may not be appropriate for ICU patients. Future studies are needed to determine whether early nutrition intervention in the ICU, based on NUTRIC scores, can improve patient outcomes.



Table 1. Characteristics of Adult Intensive Care Unit Patients (n = 312) to Investigate the Association of Nutrition Risk in Critically Ill Score With Protein and Caloric Deficit.

Protein Deficit, ≥300 g

(n = 141)

Protein Deficit, <300 g

(n = 171)

P Value

Caloric Deficit, ≥6000 kcal (n =

137)

Caloric Deficit, <6000 kcal (n =

175)

P Value

Age, y 60 ± 15 62 ± 19 .30 60 ± 15 61 ± 19 .60 Sex, % .49 .68 Female 14 20 14 20 Male 32 34 30 36 Race, % .54 .60 Nonwhite 8 7 8 8 White 38 47 36 48 BMI, kg/m2 28 ± 6 27 ± 7 .18 28 ± 6 27 ± 7 .18 APACHE II 20 ± 9 16 ± 8 <.001 21 ± 8 16 ± 8 <.001 NUTRIC 5 ± 2 4 ± 2 <.001 5 ± 2 4 ± 2 <.001 NRS 2002 4 ± 1 4 ± 1 .99 4 ± 1 4 ± 1 .99 Deficit Protein, g 637 ± 325 93 ± 151 <.001 625 ± 345 114 ± 175 <.001 Caloric, kcal 10,982 ± 5590 3016 ± 2192 <.001 11,609 ± 2708 2708 ± 1801 <.011 Length of stay, d

ICU 15 (8–25) 10 (7–16) <.001 15 (8–25) 10 (7–16) <.011 Hospital 25 (15–39) 21 (12–32) .03 25 (14–38) 21 (12–33) .10

APACHE II, Acute Physiology and Chronic Health Evaluation; BMI, body mass index; ICU, intensive care unit; LOS, length of stay; NRS, Nutrition Risk Screening; NUTRIC, Nutrition Risk in Critically Ill. aData are presented as mean ± standard deviation, median (interquartile range), or proportions and compared with t tests, long-rank tests, and chi-square tests, respectively. Statistically significant P values are shown in bold.

Nutrition and Metabolism Research Paper Session: GI & Other Metabolic Topics


2371464—Event Rate and Delta Inflation When Evaluating Mortality as a Primary Outcome From Randomized Controlled Trials of Nutrition Interventions During Critical Illness: A Systematic Review

Matthew J. Summers, BSc, MDiet1; Lee-anne S. Chapple, BMSc, MND2; Stephen McClave, MD3; Adam Deane, MBBS, PhD1,4 1Department of Critical Care Services, Royal Adelaide Hospital, Adelaide, Australia; 2Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia; 3Department of Medicine, University of Louisville, Louisville, KY, USA; 4Centre for Research Excellence in Translating Nutritional Science to Good Health, National Health and Medical Research Council of Australia, Adelaide, Australia

Purpose: There is a lack of high-quality evidence to inform nutrition practices for critically ill patients. Accordingly, current guidelines for the provision of nutrition therapy in the critically ill include predominately lower grades of recommendations (B to E). Mortality is frequently chosen as the primary outcome for randomized controlled trials of nutrition therapy in the critically ill. However, a grade A recommendation requires that a statistically significant difference is observed with respect to the primary outcomes, and randomized controlled trials of nutrition interventions may be underpowered to detect a statistical difference in mortality, but this concept has


been somewhat neglected. Power calculations use estimated baseline event rate (ie, mortality during control group) and predicted delta (ie, predicted difference between mortality during control and intervention) from previous data, which may be either inadvertently or systematically overestimated. Such overestimations reduce power of the study and increase the risk of a false-negative result. The objective of this review was to evaluate whether power calculations for studies of nutrition interventions that had mortality as the primary end point were realistic and, if overestimation was systematic in the studies identified, to determine if this was due to event rate inflation or delta inflation.

Methods: A systematic review of the literature was performed to identify all randomized controlled trials (published between January 1, 2005, to June 30, 2015, in any of 19 prominent peer-reviewed journals selected because of their focus on general medicine, critical care, or nutrition) of a nutrition intervention administered to critically ill adults that had mortality as the primary outcome. Two reviewers independently extracted data utilizing a standardized form. Predicted event rate (predicted mortality during control), predicted mortality during intervention, predicted delta (predicted difference between mortality during control and intervention), actual event rate (observed mortality during control), observed mortality during intervention, and actual delta (difference between observed mortality during control and intervention) were recorded. The event rate gap (predicted event rate minus observed event rate) and delta gap (predicted delta minus observed delta) and the predicted number needed to treat were calculated. Event rate inflation and delta inflation were defined as positive event rate gap and delta gap, respectively, that would lead to an underpowered study. Summary statistics are presented as median (range).

Results: Fourteen manuscripts were extracted, and of these a power calculation for mortality was provided for 10 studies. The predicted event rate was 29.9% (20.0%–52.4%), and the predicted mortality during intervention was 21.5% (12.5%–32.4%) with a predicted delta of 7.9% (3.0%–20.0). If the study hypothesis was proven correct, then based on the power calculations, the predicted number needed to treat would have been 12.7 (5.0–33.3) patients. The actual event rate was 25.3% (6.1%–50.0%), and the observed mortality during intervention was 24.4% (6.3%–39.7%), with an actual delta 0.5% (–10.2% to 10.3%), such that the event rate gap was 2.6% (–3.9% to 23.7%) and delta gap was 7.5% (3.2%–25.2%).

Conclusions: Delta inflation occurs frequently in randomized controlled trials of nutrition interventions in the critically ill that are powered to determine a mortality benefit, whereas the predicated event rate was closer to the actual event rate. It appears that delta inflation contributes considerably to the number of “negative” studies in this field of research. Future studies should be powered according to a smaller delta, but this will increase sample sizes.

Financial support: A.M.D. is supported by a National Health and Medical Research Council Early Career Fellowship.

2370477—Aryl Hydrocarbon Receptor Activation Attenuates the Loss of Intestinal Barrier Function by Up-Regulating TJ Proteins in a Mouse Model of DSS-Induced Colitis Min Yu1; Yuan Qiu1; Weidong Xiao1; Hua Yang1 1Xinqiao Hospital, Third Military Medical University, Department of General Surgery, Chongqing, China Purpose: The aryl hydrocarbon receptor (AhR) is a cytoplasmic transcription factor activated by a large variety of environmental agents. Activation of the AhR is involved in the control of intestinal mucosal homeostasis and thought to suppresses inflammatory bowel disease (IBD). The goal of this study was to investigate the role of AhR activation in the maintenance of intestinal barrier function by regulating tight junction (TJ) proteins in intestinal epithelial cells.

Methods: Adult C57BL/6 mice were treated with dextran sulfate sodium (DSS) for 7 days, segments of colon were harvested for immunofluorescent staining of AhR and TJ proteins (ZO-1, claudin-1 and occludin). Caco-2 intestinal epithelial cells were treated with TNF-α/ IFN-γ for 24 hours, with or without 6-formylindolo (3,2-b) carbazole (Ficz), a ligand of AhR, and TJ proteins expression were detected by western blot analysis and qRT-PCR. Additionally, Caco-2 cells were treated with AhR siRNA, altered expressions of TJ proteins were studied with western blot analysis and qRT-PCR.

Results: Western blot analysis showed significant decreased expressions of AhR, ZO-1, claudin-1 and occludin in the colons of mice with DSS-induced colitis and TNF-α/ IFN-γ treated Caco-2 cells. Confocal microscopy also showed a loss of staining in TJ proteins in DSS-induced mouse colon mucosa. Administration of Ficz to mice with DSS-induced colitis resulted a significant increase in AhR detected by western blot analysis and qRT-PCR.


Interestingly, Ficz ameliorated morphological disruption of tight junction in DSS-induced mouse colon mucosa. Ficz also inhibited TNF-α/ IFN-γ-induced decreases of TJ proteins expression in Caco-2 cells. Furthermore, Interfering with AhR expression by siRNA promoted the sensitivity of Caco-2 cells to TNF-α/ IFN-γ. Conclusions: Ficz induced AhR activation could up-regulate TJ proteins expression and attenuate injury of intestinal epithelial barrier function both in vivo and in vitro models. AhR-activating factors might be the potential therapeutic methods for the treatment of patients with IBD. Financial support: Supported by the National Natural Science Foundation of China (NSFC 81330013 and NSFC 81272078 to H. Yang, NSFC 81270451 to W.D. Xiao) and the Program for Changjiang Scholars and Innovative Research Team in University (IRT 13051) to H. Yang.

2371660—GSNOR Is Involved in the Intestinal Epithelial Barrier Modulation of Enteric Glial Cells Through Regulating GSNO Metabolism Under Acute Intestinal Ischemia Reperfusion Injury Weidong Xiao1; Ke Peng1; Yuan Qiu1; Hua Yang1 1Xinqiao Hospital, Chongqing, China Purpose: Acute intestinal ischemia reperfusion (IR) injury is often associated with intestinal epithelial barrier (IEB) dysfunction. Our previous study demonstrated the important role of the enteric glial cells (EGCs) in IEB regulation in response to IR challenge. S-nitrosoglutathione (GSNO) was a key barrier-protective molecule synthesized and released by EGCs; while GSNO reductase (GSNOR) play a central role in intracellular GSNO metabolism. The objective of this study is to investigate the potential role of GSNO as well as GSNOR in the mechanisms of IEB regulation of EGCs under IR stimulation, further clarify the IEB dysfunction mechanism in intestinal IR injury. Also, the potential benefit of GSNO pretreatment in IEB protection in the acute IR mouse model was evaluated

Methods: EGCs were co-cultured with the Caco-2, subjected to hypoxia with 1% oxygen for 6h and the following re-oxygenation for 4h. A mouse model of IR was established by temporarily occluding superior mesenteric artery for 30min followed by 6h reperfusion. The immunofluorescence staining as well as western blot analysis of tight junction(TJ) proteins including occludin and ZO-1 were used to observe IEB functions. The intestinal epithelial permeability was evaluated with transepithelial resistance measurements (TER) (in vitro) as well as ussing chamber measurements (in vivo) respectively. GSNO was determined by high performance liquid chromatography (HPLC) in EGCs. Mice received saline or GSNO(10mg/kg) via abdominal injection 30min prior to surgery. The expression of GSNOR in EGCs was knocked down using lentivirus carrying GSNOR shRNA.

Results: Compared with normoxia(Nx) group, the concentration of GSNO in EGCs exposed to HR was decline by 37.7% (P<0.05). HR stimulation reduced the TER values of the Caco-2 monolayers to 31.8%(P<0.05) compare with Nx group, accompanied with the down-regulation of TJ proteins occludin and ZO-1 by 49.1% and 43.2% (P<0.05). GSNO pretreatment induced not only a 1.2-fold increase of the TER values, but also 1.3- and 1.4-fold increases in the expression of occludin and ZO-1(P<0.05)in HR group as well. Meanwhile, HR treatment led to the up-regulation of GSNOR expression in EGCs by 39.7% and 43.4% at the mRNA and protein levels respectively when compared to Nx group(P<0.05). The GSNO content was increased by 32.6%(P<0.05) in GSNOR-/- EGCs under HR treatment when compared with control EGCs. The TER values of Caco-2 co-cultured with GSNOR-/- EGCs increased by 28.2% (P<0.05) as compared to the group co-cultured with control EGCs under HR treatment. Correspondingly, co-culture with GSNOR-/- EGCs also induced to 1.35- and 1.39-fold increases of the expression of occludin and ZO-1 proteins respectively in Caco-2 cells exposed to HR when compared to the co-cultured with control EGCs. Acute IR induced significant increase of mucosal permeability as compared to the sham group(156±28.5Ω.cm2 vs 304±29.5Ω.cm2,P<0.05); while GSNO pretreatment led to a 1.5-fold increase of the TER of the intestinal mucosa when compared to saline-pretreatment group(P<0.05).

Conclusions: This study shows the relationship between GSNO metabolism and the barrier-inducing capability of EGCs under IR/HR stimulation: the overexpression of GSNOR in EGCs induced by IR/HR stimulation leads to the acceleration of intracellular GSNO metabolism, which may partially account for EGCs dysfunction in IEB protection in response to IR challenge. In addition, GSNO may be a potential promising strategy for preventing IEB damage from acute intestinal IR and reducing intestinal IR-associated high morbidity and mortality. Financial support: National Natural Science Foundation of China (NSFC 81270451, 81470803).



2371963—Effects of Vitamin D Supplements on Muscle Mass, Muscle Strength, and Muscle Function in the Elderly in Shanghai, China

Jianqin Sun, MD, MPS1; Huijing Bai,MD, PhD1; Min Chen, MD, MPH1; Danfeng Xu, PhD1; Hua Xie, MD, PhD1; Jiemin Gan,MD2; Yiru Pan,MD2; Ru Li, RN3; Zhenghui Gao, MD3; Xiangling Lv, RD3; Jie Chen, MD, MS4; Zhijun Bao, MD, PhD4 1Clinical Nutrition Center, Fudan University Affiliated Hua Dong Hospital, Shanghai, China; 2Clinical Laboratory, Fudan University Affiliated Hua Dong Hospital, Shanghai, China; 3Health Management Center, Fudan University Affiliated Hua Dong Hospital, Shanghai, China; 4Shanghai Key Laboratory of Clinical Geriatric Medicine, Shanghai, China

Purpose: To investigate the impact of vitamin D supplements on serum 25(OH)D level and skeletal muscle mass, strength, and function in the elderly population in China.

Methods: The study was a randomized double-blind controlled study. Eight-five subjects (serum vitamin levels <20 ng/mL) were randomly divided into an intervention group (vitamin D, 800 IU; n = 41 people) and placebo group (n = 44 people). Intervention time was 12 months (48 weeks). Lifestyle remained unchanged during the intervention period. The subjects accepted the comprehensive assessment at 0, 6, and 12 months during the study. The assessment included change of skeletal muscle mass, dominant hand grip strength (HGS), and Short Physical Performance Battery (SPPB). Secondary end points were the changes in the quality of life, inflammatory cytokines (IL-6, IL-10), weight, BMI, waist, serum calcium, and phosphorus levels. Appendicular skeletal muscle mass (ASM) were measured by bioelectrical impedance analysis. The ASM index (ASM/height2) was calculated. Muscle strength was assessed by HGS. Muscle function was assessed by measuring SPPB. Serum 25(OH)D levels, IL-6, and IL-10 were measured by electrochemiluminescence immunoassay. The quality of life was evaluated by EuroQol Group–5D (EQ-5D) and EuroQol visual analog scale (EQVAS).

Results: There was no difference in serum 25(OH)D level between the 2 groups at baseline (13.6 ± 3.6 vs 14.1 ± 3.7, P > .05). However, serum 25(OH)D levels in the intervention group was significantly higher than the placebo group at 6 months (35.9 ± 5.7 vs 27.5 ± 6.3 ng/mL, P < .05) and 12 months (24.0 ± 6.4 vs 14.6 ± 5.1 ng/mL, P < .05; see Table 1). HGS and SPPB in the intervention group were increased significantly as compared with the control group at 12 months (P < .05). But there was no statistical difference in the skeletal muscle mass (P > .05) between the 2 groups (see Table 1). After the intervention, EQ-5D and EQVAS were significantly higher in the intervention group than in the control group (P < .05), but IL-6 and IL-10 were not statistically different between 2 groups before and after the intervention. BMI, weight, and waist circumference did not change in both groups before and after the intervention (P > .05; see Table 2). In the multivariable linear regression models, adjusted for sex, age, protein intake, and regular exercise, VD supplements were significantly associated with HGS and SPPB (P < .05).

Conclusions: Vitamin D supplements were observed to increase serum 25(OH)D levels in the elderly (serum vitamin levels <20 ng/mL). Muscle strength, muscle function, and quality of life were also raised by vitamin D supplementation.

Financial support: Chinese Nutrition Society–Dutch State Mining (CNS2013-034) Specialized Research Fund and Groupe Danone SA Nutritional Research and Education Fund (DIC2012-07).


Table 1. Comparison of Observed Indicators Between Intervention Group and Control Group at Different Time Points.

Indicators Baseline 24 wk 48 wk

VD Placebo P VD Placebo P VD Placebo P

Serum 25(OH)D, ng/mL

13.6 ± 3.6

14.1 ± 3.7

.490 35.9 ± 5.7

27.5 ± 6.3

<.001 24.0 ± 6.4

14.6 ± 5.1

<.001

UMM, kg 4.1 ± 1.22

4.9 ± 1.29

.629 4.7 ± 1.32

4.3 ± 1.27

.732 4.1 ± 1.31

4.9 ± 1.20

.645

LMM, kg 12.60 ± 3.63

12.30 ± 3.23

.758 12.90 ± 3.25

13.00 ± 2.98

.798 12.50 ± 3.33

12.90 ± 3.54

.689

ASM, kg 15.6 ± 4.36

16.50 ± 4.72

.375 16.08 ± 3.85

16.72 ± 4.92

.509 15.53 ± 3.62

16.94 ± 4.14

.116

ASM/height2, kg/m2

6.43 ± 0.94

6.62 ± 0.97

.377 6.48 ± 0.98

6.46 ± 1.07

.922 6.26 ± 0.90

6.16 ± 0.80

.782

SMM, kg 21.6 ± 4.15

22.7 ± 4,8

.257 21.5 ± 4.5

22.7 ± 5.01

.241 21.09 ± 4.32

22.4 ± 4.9

.214

SMM/height2, kg/m2

8.68 ± 1.04

8.92 ± 1.07

.316 8.68 ± 1.20

8.62 ± 1.01

.860 8.78 ± 1.03

8.39 ± 0.93

.411

SPPB 9.61 ± 1.12

9.80 ± 1.13

.449 10.54 ± 1.36

10.66 ± 1.61

.707 11.07 ± 1.82

10.31 ± 2.01

.028

Balance test 3.98 ± 0.16

3.91 ± 0.29

.197 3.98 ± 0.12

3.90 ± 0.21

.210 3.96 ± 0.16

3.95 ± 0.22

.533

Gait speed, m/s 0.96 ± 0.24

0.98 ± 0.26

.320 1.03 ± 0.34

0.92 ± 0.21

.162 1.10 ± 0.19

0.97 ± 0.27

.025

Chair stand 2.51 ± 0.91

3.09 ± 0.60

.010 2.85 ± 0.16

3.05 ± 0.90

.365 3.46 ± 0.71

3.17 ± 0.14

.109

HGS, kg 28.2 ± 1.60

29.3 ± 1.40

.608 28.0 ± 1.60

27.0 ± 1.4

.861 33.9 ± 1.4

30.2 ± 1.3

.048

ASM, appendicular skeletal muscle mass; HGS, hand grip strength; LMM, lower limb muscle mass; SMM, skeletal muscle mass; SPPB, Short Physical Performance Battery; UMM, upper limb muscle mass; VD, vitamin D.


Table 2. Comparison of Observed Indicators Between Intervention Group and Control Group at Different Time Points.

Indicators Baseline 48 wk

VD Placebo P VD Placebo P

IL-6, ng/L 16.4 ± 7.6 18.1 ± 8.0 .532 17.5 ± 6.5 18.9 ± 9.0 .321

IL-10, ng/L 50.8 ± 19.0 48.8 ± 20.6 .423 51.8 ± 19.0 47.6 ± 19.5 .267

CRP, ng/L 8.4 ± 3.0 8.5 ± 2.8 .235 6.9 ± 3.0 8.5 ± 2.8 .044

EQ-5D 0.56 ± 0.08 0.58 ± 0.09 .257 0.65 ± 0.08 0.58 ± 0.09 .023

EQVAS 73.5 ± 11.9 76.4 ± 11.6 .235 80.4 ± 11.9 76.5 ± 11.7 .002

TF, pmol/L 34.7 ± 13.2 34.9 ± 13.3 .633 34.8 ± 13.2 35.1 ± 13.3 .786

Ca, mmol/L 2.3 ± 0.1 2.4 ± 0.1 .334 2.3 ± 0.1 2.4 ± 0.1 .258

P, mmol/L 1.4 ± 0.1 1.2 ± 0.2 .625 1 .4 ± 0.1 1.2 ± 0.2 .467

BMI, kg/m2 24.9 ± 3.4 24.7 ± 3.3 .375 24.0 ± 4.1 23.9 ± 4.2 .752

Weight, kg 59.3 ± 3.4 62.5 ± 3.3 .253 60.1 ± 3.4 59.3 ± 4.2 .476

Waistline, cm 89.6 ± 9.5 88.7 ± 9.1 .542 87.6 ± 8.4 89.3 ± 8.0 .642

Protein intake, g/kg 1.01 ± 0.4 1.05 ± 0.3 .625 1.00 ± 0.8 1.10 ± 0.4 .654

Regular exercise 20/41 23/44 .798 20/41 23/44 .798

2373080—Enhanced Recovery After Surgery Protocol Improves Time to Post-Operative Diet Advancement Hannah Roosevelt, MS, RD, CNSC1; Anne Coltman, MS, RD, CNSC1; Sarah Peterson, RD, PhD1; Diane Sowa, RD, MBA1 1Rush University Medical Center, Chicago, IL, USA Purpose: Enhanced recovery after surgery (ERAS) is proposed as a bundle approach to improving outcomes after surgery. A component of this bundle includes early diet advancement after surgery including clears on post-operative day zero and advancement to solid food on post-operative day one. The purpose of this quality improvement project was to describe differences in diet advancement, post-operative days to clears and post-operative days to solids, before and after ERAS implementation.

Methods: A convenience sample of 165 patients admitted to a large urban academic medical center admitted for colorectal surgery was utilized. Patients were classified as pre-ERAS implementation (December 2012 to July 2013, n=70) and post-ERAS implementation (December 2014 to July 2015, n=95). Demographic data were collected from the medical record including age, gender, body mass index (BMI). Post-operative days to clears was defined as days from the date of operation until patients were started on clears days and post-operative days to solids was defined as days from date of operation until patient started on solid diet. Patients who received enteral and parenteral nutrition were excluded from this sample. Post-operative days to clears and post-operative days to solids were compared between pre-ERAS and post-ERAS patients utilizing a Student’s t-test. Differences in demographic data were compared with Student’s t-test and Chi-square analysis.

Results: Demographic data were similar between groups. Post-operative days to clear liquids were significantly shorter for post-ERAS versus pre-ERAS patients (0.4±0.9 days vs 0.9±2.7 days, p<0.001). Post-operative days to solids were also significantly shorter for post-ERAS versus pre-ERAS patients (2.2±1.3 days vs 4.2±3.5 days, p<0.001).

Conclusions: Post-ERAS patients receive an oral diet in a significantly fewer days than non-ERAS patients. This data suggests that after implementation of ERAS protocol, a clear liquid diet is started on post-operative day zero;


however, some improvement is needed to meet the ERAS goal of advancement to solids foods on post-operative day one. More data are needed to determine if advancement of post-operative oral diet is effective in improving post-surgical outcomes including infections, rates of ileus, and days until discharge. Financial support: None.

2369226—Home Parenteral and Enteral Nutrition Consumer and Caregiver Causes of Non-Adherence Abigail E. Brogan1; Ann Weaver1; Deborah Pfister, MS, RD, CNSC1 1ThriveRx, Boston, MA, USA Purpose: There is concern in the medical community that noncompliance among home parenteral and enteral nutrition (HPEN) consumers may impact clinical outcomes. Researchers have explored compliance among a variety of chronic diseases with results consistently showing that complex medical regimens often result in lower compliance rates. While some centers have examined HPEN consumers’ compliance, causes of non-compliance have not been published. To better understand from a consumer/caregiver perspective, reasons for noncompliance with prescribed therapy, we conducted a survey of HPEN consumers/caregivers.

Methods: An electronic survey was created and distributed via social media. Respondents on nutrition support were asked if they adhered to the regime developed by their medical team. Additionally, consumers were asked about adherence to specific aspects of their HPEN therapy. Respondents were queried about volume adjustments, rate adjustments, alterations in schedule and line care, line submersion, oral intake, and use of alternative medications against advice or recommendation of their team. Respondents were asked to indicate reasons for non-adherence.

Results: 338 respondents (169 caregivers and 169 consumers) were surveyed. 80% were on HPN and 20% were home enteral nutrition (HEN) only. Of the 44% of respondents who indicated that they had not adhered to the care plan defined by their medical team; 48% were consumers and 52% were caregivers. 54% of respondents indicated actions that maybe considered noncompliant with their HPN infusions. Of these, 53% (66% consumers 34% caregivers) reported under infusing the prescribed volume of HPN. 37% (92% consumers, 8% caregivers) indicated they had skipped an entire prescribed HPN infusion. 40% (62% consumers, 38% caregivers) indicated they had shortened the prescribed infusion time of the HPN. 8% (33% consumers, 67% caregivers) of respondents reported altering prescribed line care technique, 15% (44% consumers, 56% caregivers) of respondents altered bathing protocols, 10% (35% consumer, 65% caregiver) of respondents altered swimming instructions. 51% (48% Consumers, 52% caregivers) of HEN respondents reported reducing the volume prescribed. The most common reasons for non-adherence among all respondents were: unpleasant side effects, interference with normal activities, and inconvenient schedule. HPEN consumers additionally reported feeling too sick (30%) and other medical challenges (23%) as reasons for non-adherence. Over 65% of caregivers indicated 3 or less reasons for non-adherence and 56% of consumers cited 6 or less reasons. More than half of respondents (61% consumers and 53% caregivers) who indicated they were adherent reported that they engaged in activities that could be considered noncompliant.

Conclusions: Despite the complexity of HPEN therapy, consumers and caregivers report an incidence of compliance which mirrors therapies for other chronic disease states. However discrepancies between responses indicate that consensus between consumers/caregivers and their medical teams as what constitutes non-compliance would be helpful. Our results further suggest that quality of life barriers frequently impact consumer/caregiver compliance. Further research is needed to determine if patient centered care, which integrates the consumers’ individual needs and concerns, would result in increased patient/caregiver compliance. Financial support: None.


Nutrition and Metabolism Research Paper Session: Pediatric and Neonatal

Best International Abstract

2357449—Baker’s Yeast Beta-Glucan Decreases Episodes of Common Childhood Illness in 1- to 4-Year-Old Children During Cold Season in China

Xia Zhou, MD1; Tiemin She, MD1; Yongmei Zhang, MD1; Naxin Yang, MD1; Chunyan Sun, MD1 1Chang Ping Women and Children Health Care Hospital, Beijing, China

Purpose: Infections, especially upper respiratory tract infections (URTIs), are common in early childhood, which creates a large economic burden on both the healthcare system and individual families. There are many foods and dietary supplement ingredients intended to improve children’s health status and immune function to decrease their susceptibility to common childhood illness. The ability of baker’s yeast beta-glucan (BYBG) to reduce the number of episodes of common childhood illness in 1- to 4-year old children was evaluated in a 12-week randomized, double-blinded, placebo-controlled study conducted in China.

Methods: A total of 174 subjects (12 to 48 months old) who had experienced at least 2 episodes of URTI in the previous 3 months were enrolled and randomized to 2 treatment groups (35 or 75 mg of BYBG per day) or placebo. The primary study outcome was the proportion of subjects that did not experience any confirmed common childhood infectious illness episodes during the study. Secondary outcomes included number of episodes and duration of both total infections and URTI.

Results: A total of 156 subjects (73 boys and 83 girls) completed the study and were included in full analysis set statistical analysis. All relevant characteristics in the 3 groups were comparable. Children in the BYBG groups were significantly healthier during the study period than those in the placebo group. During the 12-week course of the study, 85% of children in the placebo group experienced 1 or more episodes of infectious illness. By contrast, only 47% and 32% children in BYBG treatment groups experienced infectious illness, significantly less than placebo group (P < .001). The placebo group had significantly higher URTI incidence per child (P < .0001) and more days with URTI symptoms (P < .0001) compared with either BYBG group. There were no statistically significant differences between the 2 BYBG treatment groups for either primary or secondary outcomes. All reported adverse events (AEs) were mild to moderate, and no serious AEs were reported during the study. Only 1 AE (mild vomiting) in the BYBG 35-mg/d group was considered to have a doubtful relationship with the study product.

Conclusions: BYBG significantly decreased total episodes of common childhood infectious illness and episodes of URTI for children aged 12 to 48 months in a day care setting. Both dosages of BYBG were well tolerated.



2368637—Enhanced Documentation of Pediatric Malnutrition Increases Awareness and Revenue in the Hospital Setting

Katherine H. Bennett, MPH, RD, CLEC1; Caroline Steele, MS, RD, CSP, IBCLC1 1Clinical Nutrition and Lactation, Children’s Hospital of Orange County, Orange, CA, USA

Purpose: The impact of malnutrition on comorbidities and outcomes in the hospitalized patients, including length of stay and healthcare costs, has been well established. Older studies have indicated that up to 25% of hospitalized pediatric patients could be diagnosed with acute malnutrition. Therefore, proper identification and documentation in the hospital setting are critical to promote consistency in approach from the entire healthcare team and ensure that proper revenue is received to cover the additional resources malnourished patients need. In 2013, an interdisciplinary workgroup published comprehensive definitions for pediatric malnutrition. Their goal was to standardize definitions allowing for meaningful comparisons when evaluating outcomes and for use in future research. During fiscal year (FY) 2014, malnutrition was coded for 0.8% of all inpatient discharges, excluding the neonatal intensive care unit, at CHOC Children’s. Because this is a 279-bed regional tertiary medical center, it was suspected that this number did not reflect the actual number of malnourished patients or the care being provided.


There was also concern that without proper documentation and subsequent coding of malnutrition, appropriate hospital reimbursement was not being received. Therefore a project was initiated with the following objectives: (1) integrate the 2013 pediatric malnutrition definitions into the registered dietitian (RD) charting within the electronic medical record (EMR); (2) increase awareness among the medical team of the definitions and importance of properly identifying malnutrition to ensure optimal outcomes and appropriate reimbursement; and (3) ensure proper coding so that the diagnosis-related group generated resulted in the appropriate hospital reimbursement.

Methods: The RDs received comprehensive training on the new definitions as well as hands-on training for nutrition-focused physical assessment to assist in proper identification. The clinical nutrition note in the EMR was updated to include the standardized language (Figure 1) and the system updated so that the malnutrition portion of the note could be forwarded to the attending physician. Once the RD identified and documented malnutrition, the appropriate malnutrition diagnosis would be added to the problem and diagnosis list within the EMR and forwarded to the attending physician for review. The attending physician could then sign the malnutrition note and work with the RD and the team to implement and document appropriate interventions.

Results: Identification of malnutrition for discharged inpatients >30 days old (excluding the neonatal intensive care unit) increased from 0.8% at baseline (FY 14) to 3.8% for FY 15 to 4.5% for the first 2 months of FY 16 (Figure 2). This proper documentation has resulted in an estimated increase of $400,000 in revenue during the first 6 months of the project. In addition, there is increased awareness of malnutrition within the organization resulting in greater collaboration for earlier intervention. Malnutrition education has been provided to CHOC Children’s physicians and staff in many forums, including grand rounds, Resident Noon Conference, physician division meetings, and hospital department head meetings. Outreach to community physicians to ensure continuity of care upon discharge is also underway.

Conclusions: Adoption of the 2013 standardized definitions for pediatric malnutrition and creation of enhanced documentation within the EMR has resulted in increased awareness within the organization. We hope that this increased awareness will result in improved outcomes. In addition, the correct coding of malnutrition has assisted in improving revenue, which in turn has offset the cost of additional staffing allocated to the clinical nutrition department.


Figure 1. Malnutrition diagnosis charting in the electronic medical record.


Figure 2. Percentage of hospital discharges identified with malnutrition. FY, fiscal year.

2369922—Comparison of Macronutrient Content of Maternal and Donor Human Milk Using a Human Milk Analyzer Melanie Newkirk, MS, RDN, CSP, LD/N1; Fauzia Shakeel, MD2; Taymeyah Altoubah, BS3; Denise Martinez, MPH3 1Nutritional Services, All Children's Hospital Johns Hopkins Medicine, St. Petersburg, FL, USA; 2Neonatology, All Children's Hospital Johns Hopkins Medicine, St. Petersburg, FL, USA; 3Clinical and Translational Research, All Children's Hospital Johns Hopkins Medicine, St. Petersburg, FL, USA Purpose: Growth failure in Very Low Birth Weight (VLBW, <1500 grams) infants is common in the Neonatal Intensive Care Unit and is associated with poorer outcomes. It is well established that human milk is ideal for enteral feeding and donor milk (DM) is used when mother’s own milk (MM) is not available. However, neither has a nutrient composition to meet the requirements for growing premature infants. DM is associated with poorer growth and is hypothesized to have nutritional content below that of MM. Various strategies are available to increase the macronutrients in human milk however the baseline composition is unknown. It is important to determine if fortifiers added to human milk reach the target goals. The objective was to determine the baseline macronutrient content of MM compared to DM before fortifiers added.

Methods: This is a prospective observational study on 30 VLBW infants, completed gestational age ≤ 32 weeks with birth weight > 3rd percentile on the Fenton growth curve receiving MM and/or DM. Subjects were enrolled in a study evaluating the tolerance and outcomes of a new liquid protein fortifier (LP). Human milk was analyzed using the Calais Human Milk Analyzer at baseline (prior to fortification with LP) then twice weekly until study completion. Student's t-test was used to compare macronutrient content between MM and DM, with a p-value < 0.05 considered as statistically significant.

Results: A total of 195 milk samples (105 MM and 90 DM) from 24 subjects had completed analysis. There was a statistically significant difference between the calorie, fat, and protein content between MM and DM (Table 1). The calories/ounce was higher in MM (18.8) compared to DM (17.72) p = 0.009 while the mean fat content was also significantly higher 3.72 (MM) vs. 3.33 (DM) p = 0.011. Results were similar between groups for the total and true protein, however the small difference between the two groups was statistically significant: 1.07 (MM) vs. 1.04 (DM) for total protein, p = 0.01 and 0.87 (MM) vs. 0.76 (DM) for true protein, p < 0.001. All macronutrients were equally lower in MM and DM when compared with the standard reference for premature human milk especially the caloric content. There was no significant difference between the groups for lactose.

Conclusions: DM was significantly lower in calories, fat and protein when compared to MM. The mean calorie content was lower for both groups than the reference standard of 20 Cal/Oz indicating that current practice of


standard human milk fortification may fail to meet the goals for nutritional content that will support normal growth and development. Targeted fortification using milk analysis may help meet the increased calorie and protein needs of VLBW infants. Financial support: Abbott provided support for the fortifier part of the study, but did not support the milk analysis component.

Table 1.


2370831—Intestinal Adaptation in Children With Short Bowel Syndrome During Treatment With Teduglutide

Samuel Kocoshis, MD1; Beth A. Carter, MD, AGAF2; Susan Hill, MD3; Simon Horslen, MB, ChB, FRCPCH4; Benjamin Li, MS5; Sunita Goyal, MD6; Robert S. Venick, MD7 1Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 2Texas Children’s Hospital and Baylor College of Medicine, Houston, TX, USA; 3Great Ormond Street Hospital for Children, London, United Kingdom; 4Seattle Children’s Hospital, Seattle, WA, USA; 5NPS Pharmaceuticals, Inc, Bedminster, NJ, USA; 6Shire, plc, Lexington, MA, USA; 7Mattel Children’s Hospital UCLA, Los Angeles, CA, USA

Purpose: A percentage of children with short bowel syndrome (SBS) remain dependent on parenteral support (PS; parenteral nutrition and/or intravenous fluids) under current standards of care (SOC) for many months with little chance for adaptation. Teduglutide (TED), a GLP-2 analog, is an intestinal hormone that stimulates small bowel growth and mediates intestinal adaptation after resection. We sought to determine whether TED promotes intestinal adaptation in PS-dependent children with SBS for whom no significant advance in enteral nutrition (EN; oral and/or tube feeding) could be achieved.

Methods: This 12-week, open-label, multicenter, safety and pharmacodynamic study enrolled patients (pts) aged 1–17 years with SBS ≥12-month duration who required PS for ≥30% of caloric and/or fluid/electrolyte needs and who showed minimal/no advance in EN feeds for ≥3 months before baseline. Pts were enrolled sequentially into 3 TED cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received SOC (n = 5). Data presented are median (min, max).

Results: At baseline, 42 pts (age, 3.0 [1.0, 14.0] years) received 7.3 (4.0, 16.0) L/wk of PS and had been PS dependent for 3.7 (0.5, 12.2) years. Forty pts (95%) completed the study; 1 withdrew consent; and 1 discontinued because of protocol noncompliance. Weekly prescribed PS volume decreased between baseline and week 12 with TED 0.05 mg/kg/d (–1.3 [–11.0, 1.0] L/wk [–25%]) and 0.025 mg/kg/d (–2.3 [–6.9, 0.0] L/wk [–41%]) and was unchanged with TED 0.0125 mg/kg/d (0.0 [–2.5, 0.0] L/wk [0%]) and SOC (0.0 [–0.3, 1.4] L/wk [0%]). At week 12, prescribed PS calories decreased by 45% and 41% in the 0.05 and 0.025 mg/kg/d cohorts, respectively; in the 0.0125 mg/kg/d and SOC cohorts, PS calories changed by 0% and +4%, respectively. Based on pt diary data, EN volume increased by 0.6 (0.0, 3.9) (40%), 2.3 (–0.9, 8.8) (32%), and 1.1 (0.0, 12.5) L/wk (22%) in the 0.05, 0.025, and 0.0125 mg/kg/d cohorts, respectively, but by only 0.5 (0.0, 1.7) L/wk (11%) with SOC. EN calories increased by


62%, 28%, 9% and 46% in the 0.05, 0.025, and 0.0125 mg/kg/d and SOC cohorts, respectively. Four pts achieved PS independence with TED (0.05 mg/kg/d, n = 3 of 15; 0.025 mg/kg/d, n = 1 of 14), 2 of whom resumed PS 4 weeks after TED ended. Improvements in EN volume were maintained or increased from baseline at 4 weeks after stopping treatment (0.05 mg/kg/d, 0.8 [0.0, 3.5] L/wk [38%]; 0.025 mg/kg/d, 3.5 [–1.9, 8.7] L/wk [32%]; 0.0125 mg/kg/d, 3.2 [0.0, 10.5] L/wk [60%]; SOC, 0.9 [0.0, 1.7] L/wk [24%]). Levels of plasma citrulline, a biomarker of enterocyte mass, increased with TED (Table 1). All pts experienced ≥1 treatment-emergent adverse event (TEAE); most were mild (95% TED, 100% SOC) or moderate (57% TED, 60% SOC). The most common TEAEs in the combined TED group were vomiting (32% vs 0% SOC), upper respiratory tract infection (27% vs 40% SOC), catheter-related complications (24% vs 20% SOC), and pyrexia (24% vs 40% SOC). No serious TEAEs related to TED occurred. There were no reports of adverse events related to fluid overload, intestinal obstruction, hepatobiliary complications, or colon polyps. One pt tested positive for nonneutralizing anti-TED antibodies at week 16 but was negative at 3-month follow-up; no pt developed neutralizing antibodies to TED. Clinical/nutrition parameters were maintained (Table 2) despite PS reductions with the highest TED doses.

Conclusions: TED treatment reduced PS dependence while advancing EN in children with SBS whose intestinal rehabilitation had plateaued. TED 0.05 mg/kg/d achieved PS independence for some pts and decreased PS and increased EN overall; 4 weeks after TED, 2 pts remained PS independent, and PS reductions and EN improvements were maintained. TED was generally safe and well tolerated. ClinicalTrials.gov: NCT01952080, EudraCT: 201300458830.

Financial support: NPS Pharmaceuticals, Inc (Bedminster, NJ). Table 1. Plasma Citrulline Levels During TED Treatment in Pediatric Patients With SBS.a

TED, mg/kg/d

0.0125 (n = 8) 0.025 (n = 14) 0.05 (n = 15)

Baseline, µmol/L 14.7 (3.8, 25.3) 16.1 (6.4, 29.8) 16.8b (4.5, 30.6)

Week 12, µmol/L 18.6c (6.2, 48.2) 22.0d (7.8, 47.0) 16.7b (4.2, 72.9)

Change from baseline at week 12, µmol/Le 1.0c (‒0.8, 22.9) 5.4d (1.1, 17.2) 7.5d (‒13.9, 56.5)

Change from baseline at week 12, %e 11.6c (‒4.1, 90.5) 34.2d (10.1, 90.7) 78.2d (‒50.7, 344.5)

Week 16 (4 wk after end of study drug treatment), µmol/L

15.1c (6.5, 50.6) 17.5 (6.8, 35.8) 9.5b (2.9, 48.2)

Change from baseline at week 16, µmol/Le 1.0c (–4.2, 25.3) 1.9 (–2.4, 6.8) 0.4d (–19.1, 28.2)

Change from baseline at week 16, %e 8c (–30, 100) 12 (–21, 50) 5d (–67, 172)

SBS, short bowel syndrome; TED, teduglutide. aValues presented as median (min, max). bn = 14. cn = 7. dn = 13. eMedian value from individualized calculated values from baseline to week 12.


Table 2. Clinical/Nutrition Parameters at Baseline and Week 12 in Pediatric Patients With SBS.a

TED, mg/kg/d SOC (n = 5)

0.0125 (n = 8) 0.025 (n = 14) 0.05 (n = 15)

Weight, kg

Baseline 13.3 (10.1, 48.7) 17.4 (10.3, 44.3) 16.1 (10.5, 38.5) 12.3 (11.2, 14.8)

Week 12 16.0 (11.2, 50.4)b 17.2 (10.2, 53.4)c 16.1 (10.8, 35.8)d 13.1 (11.7, 15.7)

Albumin, g/L

Baseline 39.0 (37.0, 44.0) 38.5 (31.0, 44.0) 39.0 (35.0, 46.0) 39.0 (36.0, 40.0)

Week 12 39.0 (33.0, 44.0)b 38.0 (33.0, 43.0)d 38.0 (27.0, 44.0)d 36.0 (32.0, 40.0)

Blood urea nitrogen, mmol/L

Baseline 5.0 (1.4, 7.5) 5.2 (3.0, 7.8) 4.7 (2.9, 8.1) 4.0 (3.0, 5.9)

Week 12 4.4 (2.8, 6.7)b 4.9 (3.2, 6.2)d 4.5 (2.9, 6.4)d 3.7 (2.4, 6.7)

Creatinine, µmol/L

Baseline 34.0 (16.0, 57.0) 29.5 (19.0, 53.0) 27.0 (19.0, 43.0) 28.0 (23.0, 31.0)

Week 12 35.0 (16.0, 61.0)b 27.0 (19.0, 51.0)d 27.0 (19.0, 78.0)d 26.0 (21.0, 27.0)

Calcium, mmol/L

Baseline 2.4 (2.0, 2.7) 2.4 (2.1, 2.6) 2.3 (2.3, 2.5) 2.4 (2.2, 2.5)

Week 12 2.3 (2.1, 2.5)b 2.3 (2.2, 2.5)d 2.3 (2.1, 2.5)d 2.3 (2.1, 2.4)

Magnesium, mmol/L

Baseline 0.8 (0.6, 0.9) 0.8 (0.7, 1.0) 0.8 (0.7, 0.9) 0.8 (0.8, 0.8)

Week 12 0.8 (0.8, 0.9)b 0.8 (0.6, 0.9)d 0.8 (0.5, 0.9)d 0.8 (0.7, 0.8)

Phosphate, mmol/L

Baseline 1.7 (1.3, 1.8) 1.5 (1.1, 1.9) 1.6 (1.2, 1.9) 1.6 (1.6, 1.8)

Week 12 1.6 (1.1, 1.7)b 1.6 (0.9, 1.9)d 1.6 (0.9, 1.9)d 1.7 (1.5, 1.7)

SBS, short bowel syndrome; TED, teduglutide. aValues presented as median (min, max). bn = 7. cn = 12. dn = 13.

2373056—Whole Body Protein Turnover After Thoracic Surgery in Children—A Simplified Enterally Administered Stable-Isotope (15N Glycine) Protocol With Ammonia Enrichment Eric A. Sparks, MD1; Brenna S. Fullerton, MD1; Faraz A. Khan, MD1; Jeremy Fisher, MD1; Michael Scoville, CPhT3; David D. Bowling, CPhT3; Rocky Anzaldi, RPh3; Yong-Ming Yu, MD, PhD4; David A. Wagner, PhD5; Tom Jaksic, MD, PhD1; Nilesh M. Mehta, MD2 1Department of Surgery, Boston Children's Hospital, Boston, MA, USA; 2Division of Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, MA, USA;


3Department of Pharmacy, Boston Children's Hospital, Boston, MA, USA; 4Department of Surgery, Shriners Hospital for Children, Boston, MA, USA; 5Metabolic Solutions, Inc., Nashua, NH, USA Purpose: The metabolic stress response to surgical insult in humans is characterized by breakdown of skeletal and visceral protein stores to release free amino acids to be utilized for tissue repair, immune response, and acute-phase responses. Unless optimal protein intake is ensured, children recovering from surgery manifest a net negative protein balance resulting in a loss of lean body mass during a vulnerable phase of convalescence. A better understanding of protein turnover after major surgery in the modern era will help guide perioperative protein provision. The purpose of this study was to quantify whole body protein turnover, including protein flux, synthesis and breakdown following thoracic surgery, using a stable-isotope (15N glycine) enrichment protocol.

Methods: In a pilot prospective cohort study, we enrolled children ages 1 to 18 years undergoing elective thoracic surgery with expected hospital stay of at least 3 days. Patients with known metabolic disorders, renal insufficiency, contraindications to enteral nutrition, and perioperative hemodynamic instability were excluded. On post-operative day 1, baseline 15N enrichment of ammonia in urine was measured. A single standardized enteral dose of 15N glycine was then administered and a 24-hour urine collection was initiated. 15N enrichment of ammonia was measured in the 10-hour urine collection and urinary urea nitrogen (UUN) was measured by Kjeldahl method in the 24-hour urine collection. Protein flux, breakdown and synthesis were determined based on enrichment data. Protein balance was calculated as the difference between protein intake and protein excretion, obtained using the UUN and the 15N glycine enrichment methods.

Results: Data from the first eight patients, including 5 thoracoscopic and 3 thoracotomy procedures were included in this analysis. Median (IQR) age was 14 (9.1, 15.6) months and weight was 40.9 (34.7, 60) kg. Table 1 shows demographic, clinical and nutritional variables for this cohort. Protein synthesis, breakdown and flux measurements by 15N enrichment method for each patient are shown in Figure 1. The comparison between the protein balance values by the two methods for each subject is shown in Figure 2. Both protein synthesis and breakdown were elevated, with a net negative balance demonstrated in all patients. Median (IQR) net protein balance values determined by the UUN method and 15N glycine method were -0.07 (-0.09, -0.05) and -0.09 (-0.09, -0.07) grams/kg/day, respectively. There was no significant difference between these values (p=0.37, Mann Whitney U test).

Conclusions: Our results show the feasibility of a non-invasive stable-isotope protocol where a single-dose enteral 15N glycine administration was followed by measurement of 15N enrichment of ammonia (end product) in urine collected over 10 hours. This simple protocol allowed measurement of whole body protein turnover in pediatric patients, and the protein balance values were comparable with those from the commonly used 24-hour urinary urea nitrogen method. Children in the post-operative phase following elective thoracic surgery manifest elevated whole body protein turnover, and protein breakdown that is greater than protein synthesis. Future studies must examine the impact of optimal protein intake on protein balance after surgery. Financial support: The study was supported by the Anesthesia Trailblazer Grant (awarded to N.M.M.) by the Department of Anesthesiology, Preoperative and Pain Medicine at Boston Children's Hospital.


Table 1. Demographic variables for children undergoing thoracic surgery (N = 8)

Figure 1. Protein synthesis, breakdown and flux measurements by isotope enrichment method using single dose enteral 15N glycine.


Figure 2. Comparison between the protein balance values by 15N enrichment and urinary urea nitrogen methods after pediatric thoracic surgery.


2372887—Processes for Ruling Out Central Line–Associated Bloodstream Infections in Parenteral Nutrition–Dependent Pediatric Patients

Bennet S. Cho, BA1; Kathleen M. Gura, PharmD2; Alexis K. Potemkin, BSN, RN1; Alison O’Loughlin, MEd1; Prathima Nandivada, MD3; Lorenzo Anez-Bustillos, MD1; Meredith A. Baker, MD1; Duy T. Dao, MD1; Mark Puder, MD, PhD1; Gillian L. Fell, MD, PhD1 1Vascular Biology Program and Department of Surgery, Boston Children’s Hospital, Boston, MA, USA; 2Department of Pharmacy, Boston Children’s Hospital, Boston, MA, USA; 3Department of Surgery, Beth Israel-Deaconess Medical Center, Boston, MA, USA

Purpose: Parenteral nutrition (PN) is a life-sustaining therapy in pediatric patients with intestinal failure (IF) who are unable to absorb nutrients enterally. Patients who require long-term PN have central venous catheters for delivery of home PN (HPN). Central line–associated bloodstream infection (CLABSI) is the most common complication of HPN. Delays in diagnosis and treatment of CLABSI can result in sepsis, multisystem organ failure, and death. Given the potential gravity of CLABSI, there is a low threshold to admit and empirically treat HPN patients who present with concern for CLABSI. Certain CLABSI rule-out practices, such as obtaining microbial blood cultures, are evidence based, while other practices, such as length of inpatient admission for CLABSI rule-out, are not. The purpose of this study is to assess CLABSI rule-out practices at pediatric IF and HPN programs in the United States to determine what information would be nationally applicable to aide in defining and refining best CLABSI rule-out practices.

Methods: A 5-question electronic survey of CLABSI rule-out practices for pediatric HPN patients was sent to directors of 42 pediatric HPN or IF programs in the United States. Survey questions asked about the presence of an institutional protocol for managing CLABSI evaluation, admission practices and laboratory values obtained, and the top 3 presenting signs and symptoms felt to be most concerning for CLABSI based on institutional experience. Responses were not linked to particular institutions.

Results: Twenty-two of 42 programs responded. Fifteen (68%) have a protocol for CLABSI evaluation, while the remaining 7 (32%) have no specific protocol but general agreement among physicians on CLABSI rule-out management (Figure 1A). Twelve programs (55%) always admit patients with suspected CLABSI; 9 (41%) usually admit patients; and 1 (4%) usually does not admit patients (Figure 1B, left). Of the 21 programs that usually or always admit patients to rule-out CLABSI, 19 (90%) admit for 48 hours, and 2 (10%) admit for longer than 48 hours (Figure 1B, right). At presentation for CLABSI evaluation, all programs obtain microbial blood cultures and complete blood counts; 18 (82%) obtain blood chemistries; 14 (64%) obtain liver panels; and 11 (50%) obtain C-reactive protein levels (Figure 2A). All programs reported fever among the top 3 signs or symptoms most


concerning for CLABSI. Respondents reported other signs and symptoms among the top 3 most concerning for CLABSI at variable frequencies, including leukocytosis (48%), fatigue (38%), tachycardia (33%), elevated C-reactive protein (29%), thrombocytopenia (14%), elevated liver function tests (14%), changes in ostomy output (5%), leukopenia (5%), and respiratory distress (5%; Figure 2B).

Conclusions: Based on responses from 22 of 42 pediatric IF and HPN programs in the United States, it appears that while some CLABSI rule-out practices, including obtaining microbial blood cultures and complete blood count values, are widely agreed on, the majority of CLABSI rule-out practices, as well as perceptions of signs and symptoms most concerning for CLABSI, are variable among institutions. This study highlights a need for data-driven evidence to guide admission practices and define laboratory values, presenting signs, and patient symptoms important for risk-stratifying HPN patients at presentation for CLABSI evaluation. Development of an evidence-based standard of care may improve the quality of care and safety for this patient population.

Financial support: National Institutes of Health grant T35 HL 110843 (B.S.C.), National Institutes of Health grant F32DK104525-01 (G.L.F.).

Figure 1. A, Presence of an institutional protocol for ruling out CLABSI among 22 pediatric intestinal failure and home parenteral nutrition programs in the United States. B, Admission practices for CLABSI rule-out among the programs in A. The left chart shows whether or not programs admit patients to the hospital for CLABSI rule-out. The right chart shows admission length typically used for CLABSI rule-out. CLABSI, central line–associated bloodstream infection.


Figure 2. A, Laboratories obtained at presentation for CLABSI rule-out among 22 pediatric intestinal failure and home parenteral nutrition programs in the United States. X-axis denotes the percentage of programs that obtain the laboratory values along the y-axis. B, Programs in A were asked to report the 3 signs or symptoms felt to be most concerning for CLABSI when patients present at their institutions. X-axis denotes the percentage of programs that rated the signs and symptoms along the y-axis within their top 3 most concerning. CLABSI, central line–associated bloodstream infection.

These abstracts have not been copyedited. Any errors contained within the abstracts are the sole responsibility of the authors. A.S.P.E.N. does not assume liability for any errors herein. This content does not constitute medical or other professional advice. These and all of the Clinical Nutrition Week 2016 abstracts can be accessed online at http://pen.sagepub.com/supplemental.


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